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[ "2901565", "8582220", "6390057", "2676343", "3906280" ]

[ "Effects of prolonged naloxone infusion in septic shock.", "[Clinical effects of naloxone on hemorrhagic shock].", "Naloxone and methylprednisolone sodium succinate enhance sympathomedullary discharge in patients with septic shock.", "Prospective, controlled, randomized trial of naloxone infusion in early hyperdynamic septic shock.", "Naloxone fails to reverse blood pressure in shock: a double blind study in man." ]

[ "Fourteen patients suffering sixteen episodes of septic shock requiring inotrope and/or vasopressor support were randomised to receive a 30 micrograms/kg naloxone intravenous bolus followed by a 30 micrograms/kg/h infusion or an equivalent volume placebo bolus and infusion for 8-16 h in a double-blind study. pH and pulmonary wedge pressure were kept constant, and inotrope and/or vasopressor were titrated to maintain a preselected mean blood pressure. Inotrope/vasopressor requirements in the naloxone-treated group were significantly lower than those in the control group at 8 h (eight patients in each group, p less than 0.005) and at 16 h (five patients in each group, p less than 0.02). Late but significant improvements in stroke volume (p less than 0.02) and heart rate (p less than 0.05) were also noted in the eight naloxone-treated patients.", "In order to study the clinical effects of naloxone on hemorrhagic shock, 21 patients with moderate hemorrhagic shock were randomly divided into two groups. The naloxone group (NLX group) was infused normal saline (200ml) and naloxone (0.02mg/kg) via central vein while the control group was infused normal saline (200ml) only. Mean arterial pressure (MAP), central vein pressure (CVP), cardiac output (CO), cardiac index (CI), peripheral vascular resistance (PVR), levels of lactic acid in both artery and vein, and levels of catecholamine in artery were measured before and after the administration of naloxone or normal saline. The results showed that naloxone significantly increased blood level of catecholamine and MAP (P < 0.01), the effects sustained for more than 15 minutes with an increased PVR (P < 0.05). After infustion of normal saline, blood level of lactic acid in artery and vein decreased slightly (P > 0.05), yet comparatively lower in artery. On the contrary, after administration of naloxone, the blood level of lactic acid markedly decreased in both artery and vein (P < 0.01), but higher in artery. It is suggested that naloxone improve tissue oxygen supply temporarily with enhancement of tissue lactic acid metabolism.", "Naloxone and methylprednisolone sodium succinate (MPSS) may act in synergy to improve hemodynamics in patients with septic shock by enhancement of sympathomedullary discharge. This randomized double-blind study describes the effect of various dosing regimens of naloxone and MPSS upon hemodynamics and plasma catecholamines in patients with septic shock (n = 57). Consecutive bolus doses of naloxone were given 30 minutes apart (10 micrograms/kg;-100 micrograms/kg) and a single dose of MPSS (30 mg/kg); bolus doses of 5% dextrose in water solution plus single dose of MPSS as above; bolus dose of naloxone (30 micrograms/kg) followed by continuous infusion (30 micrograms/kg/hr for 1 hour) with single dose of MPSS as above; a bolus and continuous infusion of naloxone as above without MPSS; MPSS alone and standard therapy alone. In patients treated with bolus doses of naloxone in combination with MPSS, plasma levels of epinephrine and norepinephrine were increased approximately five-to tenfold. In patients treated with bolus plus continuous infusion of naloxone given with or without MPSS, only plasma epinephrine levels were increased. Systolic blood pressure and left ventricular stroke work index were improved within 15 minutes in groups which received naloxone and corticosteroids regardless of dose. In those groups, there were no changes in heart rate or filling pressure. Systemic vascular resistance improved significantly only in the group which received low dose bolus and continuous infusion of naloxone and MPSS. Naloxone and MPSS quickly improved cardiac function in patients with septic shock by enhanced sympathomedullary discharge and may be useful as an adjunct in the therapy of this disorder.", "To determine whether naloxone infusion is efficacious in severe hyperdynamic septic shock, we conducted a prospective study of 22 patients randomly assigned to a naloxone or placebo group. Patients were treated 12 +/- 2 h (SEM) after the onset of shock, with a mean arterial pressure (MAP) of 63 +/- 3 mm Hg. All patients had clinical evidence of an infectious process and required dopamine 20 +/- 2 micrograms/kg.min. Five (46%) of 11 patients in the naloxone group and one (9%) of the other 11 patients in the placebo group responded clinically. The MAP among the five responders increased from 62 +/- 5 to 89 +/- 4 mm Hg within 20 min of naloxone treatment (p less than .01). This favorable hemodynamic response was sustained throughout the patients' clinical course. In contrast, the MAP did not change significantly in the nonresponders who received naloxone, nor did it change in the placebo group. More patients in the naloxone group than in the placebo group received steroids concurrently. Survival rate was 100% in those who responded to naloxone clinically. However, overall survival rate in each group was essentially the same. No adverse effects were observed, except for mild agitation in some of the patients receiving naloxone. We conclude that naloxone infusion is clinically efficacious in improving the hemodynamic profile of a subgroup of patients with severe early hyperdynamic septic shock, but does not appear to improve the overall survival rate.", "nan" ]

[ "18728266" ]

[ "Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial." ]

[ "Hyperuricemia is a predictor for the development of hypertension and is commonly present in new-onset essential hypertension. Experimentally increasing uric acid levels using a uricase inhibitor causes systemic hypertension in animal models.\n To determine whether lowering uric acid lowers blood pressure (BP) in hyperuricemic adolescents with newly diagnosed hypertension.\n Randomized, double-blind, placebo-controlled, crossover trial (September 2004-March 2007) involving 30 adolescents (aged 11-17 years) who had newly diagnosed, never-treated stage 1 essential hypertension and serum uric acid levels > or = 6 mg/dL. Participants were treated at the Pediatric Hypertension Clinic at Texas Children's Hospital in Houston. Patients were excluded if they had stage 2 hypertension or known renal, cardiovascular, gastrointestinal tract, hepatic, or endocrine disease.\n Allopurinol, 200 mg twice daily for 4 weeks, and placebo, twice daily for 4 weeks, with a 2-week washout period between treatments. The order of the treatments was randomized.\n Change in casual and ambulatory blood pressure.\n For casual BP, the mean change in systolic BP for allopurinol was -6.9 mm Hg (95% confidence interval [CI], -4.5 to -9.3 mm Hg) vs -2.0 mm Hg (95% CI, 0.3 to -4.3 mm Hg; P = .009) for placebo, and the mean change in diastolic BP for allopurinol was -5.1 mm Hg (95% CI, -2.5 to -7.8 mm Hg) vs -2.4 (95% CI, 0.2 to -4.1; P = .05) for placebo. Mean change in mean 24-hour ambulatory systolic BP for allopurinol was -6.3 mm Hg (95% CI, -3.8 to -8.9 mm Hg) vs 0.8 mm Hg (95% CI, 3.4 to -2.9 mm Hg; P = .001) for placebo and mean 24-hour ambulatory diastolic BP for allopurinol was -4.6 mm Hg (-2.4 to -6.8 mm Hg) vs -0.3 mm Hg (95% CI, 2.3 to -2.1 mm Hg; P = .004) for placebo. Twenty of the 30 participants achieved normal BP by casual and ambulatory criteria while taking allopurinol vs 1 participant while taking placebo (P < .001).\n In this short-term, crossover study of adolescents with newly diagnosed hypertension, treatment with allopurinol resulted in reduction of BP. The results represent a new potential therapeutic approach, although not a fully developed therapeutic strategy due to potential adverse effects. These preliminary findings require confirmation in larger clinical trials.\n clinicaltrials.gov Identifier: NCT00288184." ]

[ "15244227", "12725547", "15841774", "6898112", "15060238", "21297814", "7383488", "7094857", "7633137", "1392359", "842335", "10910653", "19614878", "16874601", "20179657", "7418513", "15740818", "15177863", "892242", "640231", "14565739", "16519083" ]

[ "Randomized controlled trial of skin-to-skin contact from birth versus conventional incubator for physiological stabilization in 1200- to 2199-gram newborns.", "Skin-to-skin contact may reduce negative consequences of \"the stress of being born\": a study on temperature in newborn infants, subjected to different ward routines in St. Petersburg.", "Mother-infant skin-to-skin contact after delivery results in early recognition of own mother's milk odour.", "A comparison of skin-to-skin contact and radiant heaters in promoting neonatal thermoregulation.", "The effect of skin-to-skin contact (kangaroo care) shortly after birth on the neurobehavioral responses of the term newborn: a randomized, controlled trial.", "The importance of immediate postnatal contact: its effect on breastfeeding.", "Effects of early mother-infant contact following cesarean birth.", "The effect of early contact on maternal perception of infant behavior.", "Separation distress call in the human neonate in the absence of maternal body contact.", "Temperature, metabolic adaptation and crying in healthy full-term newborns cared for skin-to-skin or in a cot.", "Long-term effect on mother-infant behaviour of extra contact during the first hour post partum. I. First observations at 36 hours.", "[Influence of immediate newborn care on infant adaptation to the environment].", "A pilot study of a nursing intervention protocol to minimize maternal-infant separation after Cesarean birth.", "[Effect of very early kangaroo care on extrauterine temperature adaptation in newborn infants with hypothermia problems].", "Skin-to-skin contact after cesarean delivery: an experimental study.", "Mother-infant \"bonding\": failure to generalize.", "A randomised controlled trial in the north of England examining the effects of skin-to-skin care on breast feeding.", "The value of a pilot study in breast-feeding research.", "Defining the limits of the maternal sensitive period.", "Effects of amount of contact between mother and child on the mother's nursing behavior.", "Mother-newborn contact in a randomized trial of kangaroo (skin-to-skin) care.", "Effect of early mother-baby close contact over the duration of exclusive breastfeeding." ]

[ "Conventional care of prematurely born infants involves extended maternal-infant separation and incubator care. Recent research has shown that separation causes adverse effects. Maternal-infant skin-to-skin contact (SSC) provides an alternative habitat to the incubator, with proven benefits for stable prematures; this has not been established for unstable or newborn low-birthweight infants. SSC from birth was therefore compared to incubator care for infants between 1200 and 2199 g at birth.\n This was a prospective, unblinded, randomized controlled clinical trial; potential subjects were identified before delivery and randomized by computerized minimization technique at 5 min if eligible. Standardized care and observations were maintained for 6 h. Stability was measured in terms of a set of pre-determined physiological parameters, and a composite cardio-respiratory stabilization score (SCRIP).\n 34 infants were analysed in comparable groups: 3/18 SSC compared to 12/13 incubator babies exceeded the pre-determined parameters (p < 0.001). Stabilization scores were 77.11 for SSC versus 74.23 for incubator (maximum 78), mean difference 2.88 (95% CI: 0.3-5.46, p = 0.031). All 18 SSC subjects were stable in the sixth hour, compared to 6/13 incubator infants. Eight out of 13 incubator subjects experienced hypothermia.\n Newborn care provided by skin-to-skin contact on the mother's chest results in better physiological outcomes and stability than the same care provided in closed servo-controlled incubators. The cardio-respiratory instability seen in separated infants in the first 6 h is consistent with mammalian \"protest-despair\" biology, and with \"hyper-arousal and dissociation\" response patterns described in human infants: newborns should not be separated from their mothers.", "To evaluate how different delivery-ward routines influence temperature in newborn infants.\n A total of 176 newborn mother-infant pairs were included in a randomized study. The babies were kept skin-to-skin on the mother's chest (Skin-to-skin group), held in their mother's arms, being either swaddled or clothed (Mother's arms group), or kept in a cot in the nursery, being either swaddled or clothed (Nursery group). Temperature was measured in the axilla, on the thigh, back and foot at 15-min intervals at from 30 to 120 min after birth.\n During this time period the axilla, back and thigh temperatures rose significantly in all the treatment groups. The foot temperature displayed a significant fall in the babies in the Nursery group and this decrease was greatest in the swaddled babies. In contrast, foot temperature rose in the babies in the Mother's arms group and in particular in babies in the Skin-to-skin group. Foot temperature remained high in the Skin-to-skin group, whereas the low temperature observed in the Nursery group gradually increased and two days after birth the difference was no longer significant.\n The results show that delivery-ward routines influence skin temperature in infants in the postnatal period. Allowing mother and baby the ward routine of skin-to-skin contact after birth may be a \"natural way\" of reversing stress-related effects on circulation induced during labour.", "To determine the effects of mother-infant skin-to-skin contact immediately after birth on infant recognition of their own mother's milk odour and breastfeeding duration until 1 y of age.\n Sixty healthy, full-term neonates were randomly assigned to group A with skin-to-skin contact and group B without. One and 4 d after birth, infant responses to the following odour stimuli were observed: own mother's milk, another mother's milk, formula, orange juice and distilled water. Infant facial action was videotaped and the frequency of mouthing movements was evaluated for each stimulus. Nutritional assessment, focused particularly on breastfeeding, was performed every 3 mo on participating infants. Statistical analysis comparing the frequency of mouthing movements with the aforementioned five different odour exposures was performed by ANOVA with Fisher's PLSD. Kaplan-Meier analysis with a log-rank test was used to compare breastfeeding rates between groups.\n Infants in both groups responded differently to mother's milk odour (either their own or another mother's milk) compared to the other stimuli on days 1 and 4. However, infants in group A demonstrated a larger difference in mouthing movements between their own and another mother's milk odour at 4 d of age (2.6 +/- 1.6) compared to infants in group B (0.9 +/- 2.0, p = 0.01). Infants in group A were breastfed an average of 1.9 mo longer than the others.\n Our study provides evidence that mother-infant skin-to-skin contact for more than 50 min immediately after birth results in enhanced infant recognition of their own mother's milk odour and longer breastfeeding duration.", "nan", "The method of skin-to-skin contact (kangaroo care [KC]) has shown physiologic, cognitive, and emotional gains for preterm infants; however, KC has not been studied adequately in term newborns.\n To evaluate the effect of KC, used shortly after delivery, on the neurobehavioral responses of the healthy newborn.\n A randomized, controlled trial using a table of random numbers. After consent, the mothers were assigned to 1 of 2 groups: KC shortly after delivery or a no-treatment standard care (control group).\n Included were 47 healthy mother-infant pairs. KC began at 15 to 20 minutes after delivery and lasted for 1 hour. Control infants and KC infants were brought to the nursery 15 to 20 and 75 to 80 minutes after birth, respectively.\n During a 1-hour-long observation, starting at 4 hours postnatally, the KC infants slept longer, were mostly in a quiet sleep state, exhibited more flexor movements and postures, and showed less extensor movements.\n KC seems to influence state organization and motor system modulation of the newborn infant shortly after delivery. The significance of our findings for supportive transition from the womb to the extrauterine environment is discussed. Medical and nursing staff may be well advised to provide this kind of care shortly after birth.", "Breastfeeding is said to be the ideal form of infant nutrition, but promoting it is thought to be difficult. The results of this study show that success is more likely when breastfeeding and skin-to-skin contact begin in the delivery room. The procedure is simple and the contact period need to be of only 15-20 minutes duration. The primiparas in this study seemed contented, happy or excited with the experience. Possibly it is most beneficial to those mothers who have not asked to hold their infants at birth.", "This study investigated the effects of early mother-infant contact on the perceptions, attitudes, and behavior of mothers following cesarean birth. Forty mothers who delivered infants by cesarean section were randomly assigned to the control group or the study group. Mothers in the control group received the traditional procedures following a cesarean birth, which allowed only brief contact with their infant during the first 12 hours. Mothers in the study group participated in a program designed to provide early contact between mothers and infants during the first 12 hours after the cesarean section. The results of the study suggest that there is a time following birth in which contact between the mother and infant significantly affects mothering. This research provides direct implications that hospitals should adopt routines that encourage early mother-infant contact following cesarean birth.", "The effect of extra maternal-infant contact during the first postpartum hour on maternal perception of infant behavior one month after delivery was measured by the Broussard Neonatal Perception Inventories and the attachment questions of Klaus and colleagues. All mothers were indigent primiparas who vaginally delivered normal, term infants. 60 mother-infant dyads were randomly assigned to either an extra contact or routine contact group. 49 mothers were available 1 month later for home visits. Scores on the Neonatal Perception Inventories were not significantly affected by either degree of contact or the sex of the child. There was also no difference between contact groups in the maternal response to the attachment questions. Infant behaviors recorded by 24 mothers during the 4 days following home visits were similar in the 2 contact groups. Mothers reported significantly more negative behaviors for female than for male infants. Any effects of extra contact during the first hour after birth on maternal-infant interaction are unlikely to result from changes in maternal perception of infant behavior.", "Few studies have used the baby's cry as a means of evaluating the quality of neonatal care. In this randomized trial the newborn's cry was registered during the first 90 min after birth when infants were cared for either: (a) skin-to-skin with the mother; (b) in a cot; or (c) in a cot for the first 45 min of the 90-min observation period and then skin-to-skin with the mother. The results suggested that human infants recognize physical separation from their mothers and start to cry in pulses. Crying stops at reunion. The observed postnatal cry may be a human counterpart to the \"separation distress call\" which is a general phenomenon among several mammalian species, and serves to restore proximity to the mother. Our results suggest that in human newborns this cry is not dependent on earlier social experience and may be a genetically encoded reaction to separation. The findings are compatible with the opinion that the most appropriate position of the healthy full-term newborn baby after birth is in close body contact with the mother.", "The aim of the present study was to compare temperatures, metabolic adaptation and crying behavior in 50 healthy, full-term, newborn infants who were randomized to be kept either skin-to-skin with the mother or next to the mother in a cot \"separated\". The babies were studied during the first 90 min after birth. Axillary and skin temperatures were significantly higher in the skin-to-skin group; at 90 min after birth blood glucose was also significantly higher and the return towards zero of the negative base-excess was more rapid as compared to the \"separated\" group. Babies kept in cots cried significantly more than those kept skin-to-skin with the mother. Keeping the baby skin-to-skin with the mother preserves energy and accelerates metabolic adaptation and may increase the well-being of the newborn.", "The immediate post partum period may be particularly important for the developing relationship between mother and infant; little is as yet known, however, of the long-term effects of hospital practice during this period. This study examines the effect of extra contact during the first hour following delivery. An extra skin to skin contact and suckling contact was given to 22 primiparous mothers and their infants. One control group of 20 primiparous mothers and infants and a second one of 20 multiparous mothers and infants was given routine care immediately after birth. All mothers and infants were healthy with normal pregnancies and deliveries. At 36 hours a first observation was made of maternal and infant behaviour during breast feeding in all three groups. At this stage primiparae with extra contact showed behaviour much more like the behaviour of multiparae with routine care. Infants of primiparae with routine care cried most frequently. The behaviour of mothers of boys differed more from group to group than did that of mothers of girls.", "The indicators of newborns' adaptation during 75 min after birth were compared in three randomised groups of full-term newborns: skin-to-skin contact (group I), swaddled newborns beside the mother (group II), swaddled and separated from the mother (group III). The changes in skin temperature, blood glucose, pH, heart rate, respiration rate and crying time were studied. All the above characteristics but pH were significantly the most favourable for infants in the skin-to-skin group. The analysis of individual trends of changes in skin temperature indicated that for all but two newborns not separated from the mother (skin-to-skin or lying besides) the temperature was growing during the observation period, whereas in the separated group, six newborns (27%) had unstable not growing temperature. The mean level of blood glucose was the highest in skin-to-skin group (60.1 mg/dl), lower in group of swaddled and lying beside mother (52.5 mg/dl) and the lowest (49.6 mg/dl) in the separated group. The mean duration of crying time in the skin-to-skin contact was a little shorter than in the group of newborns lying besides the mother and more than three times shorter than in the separated group. The observed number of episodes of crying were 7, 17 and 38 in the three groups respectively. All results indicated that skin-to-skin contact is optimal for newborns', adaptation after birth especially as a protection against hypothermia and hypoglycaemia.", "To pilot test a standardized intraoperative and postoperative nursing intervention protocol to minimize maternal-infant separation after Cesarean.\n Randomized-controlled trial.\n A 250-bed acute care community hospital labor/delivery/recovery/postpartum unit with approximately 150 repeat Cesarean deliveries per year.\n Fifty women having a live, term, singleton, repeat Cesarean delivery and their newborns.\n A standardized nursing intervention protocol was designed and administered to minimize the amount of maternal-infant spatial, tactile, olfactory, auditory, and visual separation post-Cesarean.\n Maternal outcomes included maternal pain, anxiety, and childbirth perception. Infant outcomes included respiratory rate, temperature, stress (infant salivary cortisol), and breastfeeding rates.\n Compared with the control group, the intervention group experienced earlier first physical contact and feedings and a longer interval until the infant first bath. Differences were found between treatment groups for infant temperatures and respiratory rates. Three infants in the control group experienced suboptimal temperatures. Infants in the intervention group had significantly higher salivary cortisol levels but were within the normal upper level range. No differences were noted in maternal pain, maternal anxiety, or perception of birth experience among treatment groups.\n The pilot was valuable in examining intervention feasibility, appropriate outcome measures, and data collection strategies. The standardized intervention protocol shows promise for positively affecting maternal-infant outcomes after Cesarean delivery and merits further testing.", "Increased morbidity and mortality has been associated with neonates admitted with body temperatures below 36 degrees C. We employed an experimental design in a randomized control trial to compare the effectiveness of using early kangaroo care (KC) for extrauterine temperature adaptation against that of using radiant warmers. Trial subjects included 78 consecutive cesarean newborn infants with hypothermia problems. The KC group received skin-to-skin contact with their mothers in the post-operative room, while infants in the control group received routine care under radiant warmers. The mean temperature of the KC group was slightly higher than that of the control group (36.29 degrees C vs. 36.22 degrees C, p = .044). After four hours, 97.43% of KC group infants had reached normal body temperatures, compared with 82.05% in the radiant warmer group. Results demonstrate the positive effects of KC for extrauterine temperature adaptation in hypothermia infants. In the course of evidence-based practice, KC could be incorporated into the standard care regimen in order to improve hypothermia care.", "The effectiveness of skin-to-skin contact (SSC) after vaginal delivery has been shown. After cesarean births, SSC is not done for practical and medical safety reasons because it is believed that infants may suffer mild hypothermia.\n The aim of this study was to compare mothers' and newborns' temperatures after cesarean delivery when SSC was practiced (naked baby except for a small diaper, covered with a blanket, prone on the mother's chest) with those when routine care was practiced (dressed, in the bassinet or in the mother's bed) in the 2 hours beginning when the mother returned from the operating room.\n An experimental, noninferiority adaptive trial was designed with four levels of analysis: 34 pairs of mothers and newborns, after elective cesarean delivery, were randomized to SSC (n = 17) or routine care (n = 17). Temporal artery temperature was taken with an infrared ray thermometer at half-hour intervals.\n Compared with newborns who received routine care, SSC cesarean-delivered newborns were not at risk for hypothermia. The mean temperatures of both groups were almost identical: after 30 min, 36.1 degrees C for both groups (+/-0.4 degrees C for SSCs and +/-0.5 degrees C for the controls), and after 120 min, 36.2 degrees C +/- 0.3 degrees C for SSCs versus 36.4 degrees C +/- 0.7 degrees C for the controls (no significant differences). Time from delivery to the mothers' return to their room was 51 +/- 10 min. The SSC newborns attached to the breast earlier (nine SSC newborns and four controls after 30 min) were breast-fed (exclusively or prevalently) at discharge (13 SSCs and 11 controls) and at 3 months (11 SSCs and 8 controls), and the SSC mothers expressed high levels of satisfaction with the intervention.\n Cesarean-delivered newborns who experienced SSC within 1 hour of delivery are not at risk for hypothermia.", "Animal studies on the biological basis of mother-to-infant attachment have led to the hyphothesis that human mother-infant contact shortly after delivery may be crucial for the facilitation of such attachment. However, existing data do not clearly substantiate the influence of early contact on human maternal behavior. The present study was designed with procedural and methodological controls which were not always adequate in earlier studies and tested the hypothesis that early and enhanced contact facilitates maternal attachment behavior. 15 healthy primiparous mothers had their infants 1 hour at delivery and 90 min at each feeding; 15 received the usual hospital routine--brief contact at delivery and 30 min at each feeding. No differences in maternal behavior were obtained on 28 discrete response measures or on pooled sets of individual measures. A modest sex effect between contact conditions was found. Maternal behavior did not differ as a function of age. Factors that may account for differences obtained between this and other studies are discussed.", "to examine the effect of early skin-to-skin contact between mothers and their healthy full-term babies on initiation and duration of breast feeding.\n a randomised controlled trial comparing skin-to-skin with routine care.\n Warrington Hospital, Cheshire, UK.\n 204 mother and baby pairs; 102 randomised to each group.\n success of first breast feed, maternal satisfaction with skin-to-skin care and preference for future post-delivery care, baby-body temperature 1 hr after birth, partial or exclusive breast feeding at 4 months.\n in the skin-to-skin group, 89 out of 98 (91%) babies had a successful first feed compared with 82 out of 89 (83%) in the routine care group. The difference in the success rate was 8%, 95% confidence interval (CI) (-1.6%, 17.6%); chi(2)=2.7; df=1; P=0.10. Forty-two out of 97 (43%) babies given skin-to-skin were partially or exclusively breast feeding at 4 months compared with 40 out of 100 (40%) of babies in the routine care group. The difference in breast-feeding rate at 4 months was 3.3%, 95% CI (-10.3%, 16.7% ); chi(2)=0.22; df=1; P=0.64. The mean temperature 1 hr after birth was higher with skin-to-skin than routine care. The difference in means was 0.15 degrees C; 95% CI (0.03, 0.28); P=0.02. A larger proportion of mothers (87/97 [90%]) were very satisfied with skin-to-skin care, compared with 60 out of 102 (59%) in the control group; 83 out of 97 (86%) of the mothers in the intervention group said that they would prefer to receive the same care in the future compared with 31 out of 102 (30%) mothers in the control group.\n the difference between the groups in the success rate for the first breast feed and rates at 4 months was not statistically significant. However, mothers who had skin-to-skin contact enjoyed the experience, and most reported that they would choose to have skin-to skin care in the future. In this, the largest trial to date, previous concerns about baby-body temperature after skin-to-skin care were dispelled.", "To test the integrity of a protocol for a randomised controlled trial (RCT) to examine the effectiveness of skin-to-skin care compared to routine care on the initiation and duration of breast feeding and to provide data to be used in the power calculation for a proposed trial.\n Randomised pilot study.\n Warrington Hospital, Cheshire, UK.\n Women at 36 weeks' gestation with healthy singleton pregnancies, who intended to breast feed, who had 'booked' for care at Warrington Hospital and had given informed consent to participate. Twenty-eight women were randomised in the pilot study.\n Women were randomly allocated to receive either routine or skin-to-skin care following birth. The first breast feed was assessed using the Breast-feeding Assessment Tool (BAT). Mothers were followed up at discharge from hospital and again at four months to provide details of duration of breast feeding.\n 66 women were approached to participate in the trial and 44 consented (67% consent rate). Twenty-eight women were randomised in the study and 26 breast feeds were observed (93%). The pilot study identified procedural changes that were required in the design of the main study, provided an estimate of recruitment rates and confirmed the previously calculated sample size.\n The pilot study demonstrated that a large RCT of skin-to-skin versus routine care was feasible. This is an example of how a pilot study has the ability to identify unforeseen challenges in the conduct of the trial as well as allowing necessary changes to be made to the design that will increase the quality of the subsequent research.", "nan", "Short-term effects of different amounts of body contact between mother and newborn on human nursing behavior were studied. Extended contact immediately after parturition was related to an increase in affective components of maternal nursing behavior observed on postpartum Days 2 and 4.", "To describe the type and percent time of contact 0-48 hours postbirth for mother-preterm newborn (infant) dyads given kangaroo care (skin-to-skin) or standard care (controls).\n Randomized controlled trial with assignment by computerized minimization to kangaroo care (n = 48) or control (n = 43).\n Postpartum units and neonatal intensive-care units (NICU).\n Preterm infants 32 to less than 37 weeks gestation and their mothers.\n Kangaroo (skin-to-skin, SS) care (KC).\n Type and percent time of mother-infant contact (SS versus holding wrapped in blankets).\n Analyses were based on four groups: assignment for infants in each group to postpartum or NICU. For KC dyads, SS postpartum was 22.0%; SS NICU was 7.5%. KC wrapped holding postpartum was 11.6%; NICU was 1.8%. For control dyads, wrapped holding postpartum was 13.9%; NICU was 6.1%.\n Amount of SS was much less than expected. Reasons include unavailability of infants or mothers and hospital staff interrupting contact. However, KC postpartum dyads were held wrapped almost as often as control postpartum dyads. Total contact time for KC dyads (SS plus wrapped) was more than double that of controls. These data suggest that hospital and social supports for families are needed to facilitate early initiation of SS, prolonged periods of mother-infant SS contact, and reduction of maternal stress.", "This is a prospective study involving ninety-two lactating mother- infant pairs in the first six months of birth. They were followed-up up to six months for various perinatal factors determining the duration of exclusive breastfeeding. Early postpartum mother-baby skin-to-skin contact had a powerful influence (P<0.001) over the duration of exclusive breastfeeding up to 4-6 months and was found to be more significant than early initiation of breastfeeding (P<0.05). Mode of delivery did not have any significant effect (P<0.5) over the duration of exclusive breastfeeding. Thus health care centers can easily adopt a policy to allow few minutes of early postpartum mother-baby skin-to-skin contact and early initiation of breastfeeding to all vaginal as well as caesarian deliveries to promote breastfeeding." ]

[ "14663474", "9697781", "10647664", "12559281", "1383816", "8684407", "12824459", "12350480", "12526285", "8911291", "9703292", "14681504" ]

[ "A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.", "Treatment with finasteride preserves usefulness of prostate-specific antigen in the detection of prostate cancer: results of a randomized, double-blind, placebo-controlled clinical trial. PLESS Study Group. Proscar Long-term Efficacy and Safety Study.", "A prospective study of the natural history of hematuria associated with benign prostatic hyperplasia and the effect of finasteride.", "Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial.", "The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group.", "The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group.", "The influence of finasteride on the development of prostate cancer.", "Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia.", "Comparison of tamsulosin and finasteride for lower urinary tract symptoms associated with benign prostatic hyperplasia in Korean patients.", "Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study.", "The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels.", "The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia." ]

[ "In this multicentre, double-blind study, patients with LUTS/BPH were randomised to 26 weeks with finasteride 5 mg once daily (n=204) or tamsulosin 0.4 mg once daily (n=199). Double-blind treatment was continued for another 26 weeks (total treatment duration: 1 y). The primary efficacy parameter was the difference in mean change in total Symptom Problem Index (SPI) from baseline to end point at week-26 in the intention-to-treat (ITT) and per protocol (PP) populations. Tamsulosin induced a greater improvement in total SPI (-5.2 points or -37%) compared to finasteride (-4.5 points or -31%) at week-26 (P=0.055 in ITT and P=0.032 in PP). Tamsulosin improved urinary symptoms (particularly the more bothersome storage symptoms) and flow more quickly than finasteride. The difference was statistically significant for the SPI from week-1 (reduction, respectively, -2.5 vs -1.8 points, P=0.043) to week-18 and for Qmax from week-1 (increase, respectively, 2.3 vs 0.7 ml/s, P=0.0007) to week-12. Both treatments were well tolerated with a comparable incidence of adverse events, including urinary retention.", "To evaluate prostate cancer detection and prostate-specific antigen (PSA) among men with benign prostatic hyperplasia treated with finasteride.\n Three thousand forty men 45 to 78 years of age with PSA less than 10 ng/mL and no history of prostate cancer were randomized in a double-blind, placebo-controlled trial to finasteride (n = 1524) or placebo (n = 1516) for up to 4 years. A prerandomization biopsy negative for prostate cancer was obtained in 98% of patients with a screening PSA of 4.0 ng/mL or more, and an end-of-study biopsy was requested of all such patients without a recent second negative biopsy or a prostate cancer diagnosis.\n Overall, 644 patients (21%) underwent biopsy and 201 (6.6%) underwent transurethral resection of the prostate. Prostate cancer was diagnosed in 4.7% of men on finasteride and 5.1% on placebo (P = 0.7). Elevated PSA prompted diagnosis in 35% of cases on finasteride and 34% on placebo. The area under the receiver operating characteristic curve for last PSA was 0.84 on finasteride and 0.79 on placebo (P = 0.07). Use of an upper limit of normal for last PSA of 2.0 ng/mL for finasteride and 4.0 ng/mL for placebo yielded similar sensitivity (66% versus 70%, P = 0.6), higher specificity (82% versus 74%, P < 0.0001), and a higher likelihood ratio (3.6 versus 2.7, P < 0.05) for finasteride than for placebo.\n In men treated with finasteride, multiplying PSA by 2 and using normal ranges for untreated men preserves the usefulness of PSA for prostate cancer detection.", "We prospectively studied the effect of finasteride on chronic hematuria associated with benign prostatic hyperplasia.\n We prospectively evaluated 57 patients with chronic intermittent hematuria who were randomized to a finasteride treated or a control arm.\n In the untreated control group hematuria recurred in 17 patients (63%) within a year but in only 4 (14%) in the finasteride group, which was a statistically significant difference (p <0.05). Surgery was required for bleeding in 7 controls (26%), while no patient on finasteride required surgery.\n Hematuria secondary to prostatic bleeding may be significant if not treated. Finasteride appears to be effective for suppressing hematuria caused by benign prostatic hyperplasia and should be considered as treatment.", "To evaluate the efficacy and tolerability of the selective alpha(1)-adrenergic antagonist doxazosin and the 5-alpha-reductase inhibitor finasteride, alone and in combination, for the symptomatic treatment of benign prostatic hyperplasia.\n In a prospective, double-blind, placebo-controlled trial, 1095 men aged 50 to 80 years were randomized to treatment for 52 weeks with doxazosin, finasteride, the combination of doxazosin and finasteride, or placebo. The dose of finasteride (or its matched placebo) was 5 mg/day. Doxazosin (or its matched placebo) was initiated at 1 mg/day, and titrated up to a maximum of 8 mg/day over approximately 10 weeks according to the response of the maximal urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS). The IPSS and Qmax were assessed at baseline and at weeks 10, 14, 26, 39, and 52 or at the endpoint.\n An intent-to-treat analysis of 1007 men showed doxazosin and doxazosin plus finasteride combination therapy produced statistically significant improvements in total IPSS and Qmax compared with placebo and finasteride alone (P <0.05). Finasteride alone was not significantly different statistically from placebo with respect to total IPSS and Qmax. All treatments were generally well tolerated.\n Doxazosin was effective in improving urinary symptoms and urinary flow rate in men with benign prostatic hyperplasia, and was more effective than finasteride alone or placebo. The addition of finasteride did not provide further benefit to that achieved with doxazosin alone.", "Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction.\n In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period.\n As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups.\n The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.", "Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared.\n We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year.\n The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups.\n In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone.", "Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer.\n In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal. It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary end point was the prevalence of prostate cancer during the seven years of the study.\n Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis (18.4 percent) and 1147 of the 4692 men in the placebo group who had such data (24.4 percent), for a 24.8 percent reduction in prevalence over the seven-year period (95 percent confidence interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors [37.0 percent], or 6.4 percent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005 for the comparison between groups). Sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo.\n Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.\n Copyright 2003 Massachusetts Medical Society", "To study the efficacy and safety of dutasteride, a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II.\n A total of 4325 men (2951 completed) with clinical benign prostatic hyperplasia, moderate to severe symptoms (American Urological Association-Symptom Index score of 12 points or greater), a peak flow rate of 15 mL/s or less, a prostate volume of 30 cm3 or greater (as measured by transrectal ultrasonography), and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL (inclusive) were enrolled into three identical clinical trials and randomized to 0.5 mg dutasteride daily or placebo. After a 1-month, single-blind, placebo lead-in, patients were followed up for 24 months in a double-blind trial with multiple interval assessments.\n At 24 months, serum dihydrotestosterone was reduced from baseline by a mean of 90.2% (median -93.7%; P <0.001), and the total prostate and transition zone volumes were reduced by a mean of 25.7% and 20.4%, respectively (P <0.001). The symptom score was improved by as early as 3 months, with pooled significance from 6 months onward (P <0.001) and a reduction of 4.5 points (21.4%) at 24 months (P <0.001). The maximal flow rate improved significantly from 1 month (P <0.01), with an increase of 2.2 mL/s reported at 24 months (P <0.001). Hence, the risk reduction of acute urinary retention was 57% and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48% compared with placebo. The drug was well tolerated.\n Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms, flow rate improvement, and the reduction of the risk of acute urinary retention and surgery during a 24-month study period.", "Tamsulosin (0.2 mg) and finasteride (5 mg) once daily for 24 weeks were compared in a single-blind, randomized study as initial treatments for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH) in 205 Korean patients. Symptom and quality of life (QOL) assessment by the International Prostatic Symptom Score (I-PSS), maximum urinary flow rate (Qmax) and adverse events were analysed at 4 weeks and 24 weeks. On intention-to-treat analysis, both drugs showed similar efficacy at endpoint (decreased I-PSS, increased Qmax and improved QOL score; 34.7%, 23.9% and 34.1% for tamsulosin, and 30.5%, 22.2% and 23.1% for finasteride, respectively). However, tamsulosin produced significant improvements in I-PSS and Qmax at 4 weeks compared with finasteride (17.6% versus 10.0% and 10.9% versus 3.1%, respectively), and a superior QOL score improvement during the study. Adverse events were observed significantly more frequently among finasteride than tamsulosin patients (23 versus four). Both were equally effective in long-term treatment of urinary outflow obstruction symptoms associated with BPH in Korean patients, but tamsulosin was more effective for short-term treatment, with a better safety profile.", "To evaluate the efficacy and safety of 2 years' treatment of moderate benign prostatic hyperplasia (BPH) with finasteride.\n Double-blind, parallel-group, placebo-controlled, multicentre, prospective randomized study.\n Outpatient care in 28 centres across Canada.\n Men aged 45 to 80, in good health, with moderate BPH and no evidence of prostate cancer. A total of 613 men were entered into the study; 472 completed the 2 years of treatment.\n After 1 month of receiving a placebo (run-in period), patients were given either finasteride (5 mg/d) or a placebo for 2 years.\n Efficacy: changes from baseline in BPH symptom scores, maximum urinary flow rates and prostate volume. Safety: onset, course and resolution of all adverse events during the treatment period.\n In the efficacy analyses the mean BPH symptom scores decreased 2.1 points (from 15.8 to 13.7) in the finasteride group, as compared with a decrease of 0.7 points (from 16.6 to 15.9) in the placebo group (P < or = 0.01). The maximum urinary flow rate increased by a mean of 1.4 mL/s (from 11.1 to 12.5 mL/s) in the finasteride group, as compared with an increase of 0.3 mL/s (from 10.9 to 11.2 mL/s) in the placebo group (p < or = 0.01). The mean prostate volume decreased by 21% (from a mean volume of 44.1 cm3 at baseline) in the treatment group; it increased by 8.4% (from a mean volume of 45.8 cm3 at baseline) in the placebo group (p < or = 0.01). In the safety analysis, the proportion of patients who experienced any adverse event was similar in the two groups (81.0% in the treatment group and 81.2% in the placebo group). However, the incidence of adverse events related to sexual dysfunction were significantly higher in the finasteride group than in the placebo group (ejaculation disorder 7.7% v. 1.7% and impotence 15.8% v. 6.3%; p < or = 0.01 for both parameters).\n Finasteride is a well-tolerated and effective alternative to watchful waiting in the treatment of moderate BPH.", "Prostate cancer is a disease associated with androgens. It has been hypothesized that reducing the conversion of testosterone (T) to dihydrotestosterone (DHT) in the prostate by the use of the drug finasteride, a 5alpha-reductase inhibitor, will reduce the incidence of prostate cancer. We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gland of men with elevated serum prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were randomized to receive finasteride 5 mg day(-1) (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months. The biopsies were evaluated for the presence of cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen (PCNA). Serum blood samples were drawn at baseline and after 1, 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the finasteride group, PSA decreased 48% (P < 0.001), DHT decreased 67% (P < 0.001) and T increased 21% (P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the finasteride group had a 30% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002), although this decrease was not statistically significantly different between the finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with finasteride treatment. Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with finasteride, eight (30%) had adenocarcinoma of the prostate detected on the 12-month biopsy, compared with one (4%) of the control patients (P = 0.025). In the treatment group, six cancers occurred in the eight patients with PIN on the prestudy biopsy; in the observation group no cancers were detected in the five patients with PIN on the prestudy biopsy (P = 0.021). Two cancers occurred in the 19 men in the treatment group with no evidence of PIN on the prestudy biopsy, compared with one cancer in the 20 men in the observation group with no evidence of PIN on the prestudy biopsy (P = 0.60). This study, using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high risk of prostate cancer, provides little evidence that finasteride is an effective chemopreventive agent for prostate cancer in men with elevated PSA.", "Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown.\n We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia.\n The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone.\n Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.\n Copyright 2003 Massachusetts Medical Society" ]

[ "10390266", "9707853", "12508081", "15864643", "16452355", "10470576", "8816210", "10585975", "9310536", "17568152", "2199642", "7936832", "11150359", "10699107", "2196355", "9469999", "15329742", "10023787", "8984701", "8692619", "9462187", "10484801", "15161992", "15870666", "8653433", "15574629" ]

[ "A three-day course of dexamethasone therapy to prevent chronic lung disease in ventilated neonates: a randomized trial.", "Role of early postnatal dexamethasone in respiratory distress syndrome.", "Pulmonary effects of triiodothyronine (T3) and hydrocortisone (HC) supplementation in preterm infants less than 30 weeks gestation: results of the THORN trial--thyroid hormone replacement in neonates.", "Early neonatal dexamethasone treatment for prevention of bronchopulmonary dysplasia. Randomised trial and meta-analysis evaluating the duration of dexamethasone therapy.", "A double-blind, randomized, controlled study of a \"stress dose\" of hydrocortisone for rescue treatment of refractory hypotension in preterm infants.", "Early postnatal dexamethasone for the prevention of chronic lung disease in high-risk preterm infants.", "Influence of early postnatal dexamethasone therapy on ventilator dependency in surfactant-substituted preterm infants.", "Prophylaxis against early adrenal insufficiency to prevent chronic lung disease in premature infants.", "Early postnatal dexamethasone therapy for the prevention of chronic lung disease in preterm infants with respiratory distress syndrome: a multicenter clinical trial.", "Early low-dose hydrocortisone in very preterm infants: a randomized, placebo-controlled trial.", "Early postnatal dexamethasone therapy in premature infants with severe respiratory distress syndrome: a double-blind, controlled study.", "Two doses of early intravenous dexamethasone for the prevention of bronchopulmonary dysplasia in babies with respiratory distress syndrome.", "Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.", "Early dexamethasone-attempting to prevent chronic lung disease.", "Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis: a controlled trial.", "The effect of early dexamethasone administration on bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome.", "A randomized-controlled trial of prophylactic hydrocortisone supplementation for the prevention of hypotension in extremely low birth weight infants.", "Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy.", "Measurement of pulmonary status and surfactant protein levels during dexamethasone treatment of neonatal respiratory distress syndrome.", "A controlled trial of dexamethasone to prevent bronchopulmonary dysplasia in surfactant-treated infants.", "Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants.", "A single very early dexamethasone dose improves respiratory and cardiovascular adaptation in preterm infants.", "Effect of dexamethasone on tracheobronchial aspirate fluid cytology and pulmonary mechanics in preterm infants.", "Pretreatment cortisol values may predict responses to hydrocortisone administration for the prevention of bronchopulmonary dysplasia in high-risk infants.", "Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome.", "Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial." ]

[ "Although several trials of early dexamethasone therapy have been completed to determine if such therapy would reduce mortality and chronic lung disease (CLD) in infants with respiratory distress, optimal duration and side effects of such therapy remain unknown.\n The purpose of this study was: 1) to determine if a 3-day course of early dexamethasone therapy would reduce CLD and increase survival without CLD in neonates who received surfactant therapy for respiratory distress syndrome and 2) to determine adverse effects associated with such therapy.\n This was a prospective multicenter randomized trial comparing a 3-day course of dexamethasone therapy beginning at 24 to 48 hours of life to placebo therapy. Two hundred forty-one neonates (dexamethasone n = 118, placebo n = 123), who weighed between 500 g and 1500 g, received surfactant therapy, and were at significant risk for CLD or death using a model to predict CLD or death at 24 hours of life, were enrolled in the trial. Infants randomized to receive early dexamethasone were given 6 doses of dexamethasone at 12-hour intervals beginning at 24 to 48 hours of life. The primary outcomes compared were survival without CLD and CLD. CLD was defined by the need for supplemental oxygen at the gestational age of 36 weeks. Complication rates and adverse effects of study drug therapy were also compared.\n Neonates randomized to early dexamethasone treatment were more likely to survive without CLD (RR: 1.3; 95% CI: 1.03, 1.7) and were less likely to develop CLD (RR: 0.6; CI: 0.3, 0. 98). Mortality rates were not significantly different. Subsequent dexamethasone therapy use was less in early dexamethasone-treated neonates (RR: 0.8; CI: 0.7, 0.96). Very early (</=7 days of life) intestinal perforations were more common among dexamethasone-treated neonates (8% vs 1%).\n We conclude that an early 3-day course of dexamethasone therapy increases survival without CLD, reduces CLD, and reduces late dexamethasone therapy in high-risk, low birth weight infants who receive surfactant therapy for respiratory distress syndrome. Potential benefits of early dexamethasone therapy at the dosing schedule used in this trial need to be weighed against the risk for early intestinal perforation.", "To study the effect of early postnatal dexamethasone therapy on severity of hyaline membrane disease.\n Prospective, randomized, controlled, unblinded study.\n Neonatal Intensive Care Unit.\n 19 babies who had hyaline membrane disease were included in this study. The inclusion criteria were clinical and radiographic diagnosis of RDS, requiring mechanical ventilation and FiO2 > 0.3. Ten babies received injection dexamethasone 0.5 mg/kg/dose 12 hourly for 3 days starting within 6 hours of birth. The control group did not receive any drug. Babies with active infection, bleeding tendency and congenital malformation were excluded. None of the babies received surfactant. The duration of ventilation and AaDO2 and FiO2 requirements from day one to five were calculated.\n The initial AaDO2 were similar in both the groups but on day 3, 4, 5 AaDO2 were low in study group (201, 85, 70) compared to control group (236, 209, 162). The initial FiO2 were 0.66 and 0.63 in dexamethasone and control groups, respectively and remained high till day 2 and came down in study group on days 3, 4 and 5 (0.41, 0.27, 0.27) compared to control group (0.53, 0.34, 0.42). The mean duration of ventilation was shorter in dexamethasone group (87 hours) vs control group (120 hours).\n Early use of postnatal dexamethasone reduces the disease severity and oxygen requirement in RDS and hence would be useful in the Indian context.", "The THORN trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial to test the hypothesis that administration of triiodothyronine (T(3)) and hydrocortisone would decrease mortality and respiratory morbidity in preterm infants of less than 30 wk gestation. Two hundred fifty-three infants were randomized to receive either 6 micro g.kg(-1).d(-1) of T(3) with 1 mg.kg(-1).d(-1) of hydrocortisone or 5% dextrose (placebo) as a continuous i.v. infusion for 7 d. The dose was halved on d 5. Our first primary outcome was death or ventilator dependence at 1 wk, and the second was death or oxygen dependence at 2 wk. The overall mortality rate for both groups was 11.4%. Relative risk of death or ventilator dependence at 1 wk, treated versus placebo, was 0.87, p = 0.2, and death or oxygen dependence at 2 wk, 1.00, p = 0.9. We examined the relationship between free T(3) (FT(3)) and free thyroxine (FT(4)) levels in the first 7 d and the primary outcome death or ventilator dependence at 1 wk in all 253 babies. We found significant positive correlations of p = 0.05 for FT(3) and p = 0.002 for FT(4). Thus the higher the FT(3) and FT(4) levels, the better the outcome. No beneficial effects of T(3) and hydrocortisone were shown. In this study, although FT(3) levels were doubled by the treatment infusion, FT(4) levels were significantly suppressed. The lack of any beneficial effect of T(3) in our study may be explained by suppression of FT(4) in the treatment group.", "The aim of the aborted trial was to determine whether the short early dexamethasone (DX) given after the birth improves the early outcome. We also reviewed the evidence (meta-analysis) to determine whether the duration of early DX treatment influences the early outcome, particularly in terms of bronchopulmonary dysplasia (BPD). The participants of the randomised multicentre, double-blinded placebo-controlled trial had a birth weight 500-999 g, gestation < or = 31.0 weeks, and respiratory failure by the age of 4 h. The infants received either four doses of DX (0.25 mg/kg at 12 h intervals) or placebo. The meta-analysis was performed to determine the beneficial and adverse effects of early short (<96 h duration) versus early prolonged (>96 h) DX treatment. The trial was discontinued after 109 infants had been enrolled. There was a non-significant improvement in the outcome (survival without BPD, severe intracranial haemorrhage or periventricular leukomalacia; RR 1.27; 95% CI 0.87-1.85). The risks for gastrointestinal perforation and hyperglycaemia tended to increase. A total of 15 trials were included in the meta-analysis: 10 involved prolonged (i.e. >96 h; 1594 infants) and five short interventions (1069 infants). Early prolonged DX decreased the RR for BPD to 0.72 (95% CI 0.61-0.87), whereas early short DX course did not significantly decrease the risk (RR 0.82; 95% CI 0.64-1.05). Gastrointestinal haemorrhages and perforations were significantly increased only in the early prolonged DX group.\n The dosage and duration of early corticosteroid given to small premature infants influences the risk of the side-effects and the early outcome.", "To assess the effectiveness of a \"stress dose\" of hydrocortisone for rescue treatment of refractory hypotension and adrenocortical insufficiency of prematurity in very low birth weight (VLBW) infants. We hypothesized that significantly more VLBW infants who were receiving dopamine > or =10 microg/kg per min could wean off vasopressor support 72 hours after treatment with hydrocortisone.\n A double-blind, randomized, controlled study was conducted in a university neonatal center. Forty-eight VLBW infants who had refractory hypotension and required dopamine > or =10 microg/kg per min were randomly assigned to receive a stress dose of hydrocortisone (1 mg/kg every 8 hours for 5 days; n = 24) or an equivalent volume of the placebo solution (isotonic saline; n = 24).\n The baseline clinical characteristics were similar between the groups. Serum cortisol concentrations were very low immediately before randomization in both groups of infants. Significantly more VLBW infants who were treated with hydrocortisone weaned off vasopressor support 72 hours after starting treatment. The use of volume expander, cumulative dose of dopamine, and dobutamine were significantly less in hydrocortisone-treated infants compared with control infants. In addition, the median duration of vasopressor treatment was halved in hydrocortisone-treated patients. Two versus 11 infants in the hydrocortisone and control groups required a second vasopressor for treatment of refractory hypotension. The trend (linear and quadratic) of the mean arterial blood pressure was also significantly and consistently higher in hydrocortisone-treated infants.\n A stress dose of hydrocortisone was effective in treating refractory hypotension in VLBW infants. Although routine and prophylactic use of systemic corticosteroids could not be recommended because of their potential adverse effects, this relatively low dose of hydrocortisone would probably be preferable to high-dose dexamethasone for treatment of refractory hypotension in emergency and life-threatening situations.", "The purpose of this study was to evaluate the effect of early administration of dexamethasone on the incidence of chronic lung disease (CLD) in high risk preterm infants and to evaluate the side effects of the early steroid administration.\n Randomised clinical trial.\n Neonatal intensive care unit.\n 50 infants at high risk of CLD were randomly assigned after 72 h of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg per day for the first 3 days, 0.25 mg/kg per day for the next 3 days and 0.125 mg/kg per day on the 7th day). The control group received no steroid treatment.\n The incidence of CLD at 28 days of life and at 36 weeks' postconceptional age was significantly lower in the dexamethasone group than in the control group (p < 0.001). Moreover, infants in the dexamethasone group remained intubated and required oxygen therapy for a shorter period than those in the control group (p < 0.001). Hyperglycaemia, hypertension, growth failure and mainly hypertrophy of the left ventricle were the transient side effects associated with early steroid administration.\n Early dexamethasone administration may be useful in preventing CLD, but its use should prudently be restricted to preterm infants at high risk of CLD.", "We examined 26 preterm infants with respiratory distress syndrome in a randomized controlled prospective study to determine whether early postnatal dexamethasone therapy (< 2 h; 0.5 mg/kg per day) over 5 days in addition to substitution of surfactant (100 mg/kg) facilitates extubation and the course of RDS. Control (n = 12) and treated (n = 14) groups were comparable in birthweight (mean +/- SD: 1219 +/- 292 versus 1446 +/- 442 g), gestational age (29.3 +/- 2.2 versus 30.6 +/- 2.7 weeks), prenatal characteristics and initial respiratory and blood gas parameters. In both groups one infant died. Infants in the dexamethasone group responded better to surfactant (12/14 versus 3/12; p < 0.01), were extubated earlier (6.6 versus 14.2 days; p < 0.02) and required less time on supplemental oxygen (4.2 versus 12.5 days; p < 0.02). Pulmonary complications tended to be lower in the dexamethasone group (1/14 versus 4/12), as was the frequency of retinopathy (2/14 versus 6/12; p < 0.05). We conclude that early postnatal dexamethasone therapy improves response to surfactant therapy resulting in better weaning and earlier extubation in premature infants.", "BACKGROUND. Many extremely low birth weight infants (<1000 g) show biochemical evidence of adrenal insufficiency in the first week of life, correlating with subsequent development of chronic lung disease (CLD).\n We conducted a randomized, double-masked, placebo-controlled pilot study to test whether early treatment with low-dose hydrocortisone for 12 days (1 mg/kg/day for 9 days followed by.5 mg/kg/day for 3 days), begun before 48 hours of life, would increase the likelihood of survival without CLD.\n Forty patients were enrolled at two centers. Birth weight and gestation were similar for treatment and placebo groups: 732 +/- 135 g versus 770 +/- 135 g and 25.2 +/- 1.3 weeks versus 25.4 +/- 1.5 weeks. More infants treated with hydrocortisone achieved study success, defined as survival without supplemental oxygen at 36 weeks' postconception (12/20 [60%] vs 7/20 [35%]). Lower birth weight, histologic chorioamnionitis, and preeclampsia were significant risk factors, whereas study center, prenatal steroids, sex, and ethnicity were not significant. Hydrocortisone treatment decreased days on >40% oxygen, days on >25% oxygen, days on ventilator, and oxygen at discharge. Among infants exposed to chorioamnionitis, hydrocortisone treatment also was associated with increased enteral intake during the first month of life and with increased weight at 36 weeks' postconception. Five treated infants and 6 placebo infants developed sepsis; 3 in each group died.\n First, early treatment with low-dose hydrocortisone in this population of extremely low birth weight infants increased the likelihood of survival without CLD. Second, the benefit was particularly apparent in infants with chorioamnionitis. Third, a larger multicenter trial is needed to verify the primary outcome and to better evaluate risks and benefits.", "To study whether early postnatal (<12 hours) dexamethasone therapy reduces the incidence of chronic lung disease in preterm infants with respiratory distress syndrome.\n A multicenter randomized, double-blind clinical trial was undertaken on 262 (saline placebo, 130; dexamethasone, 132) preterm infants (<2000 g) who had respiratory distress syndrome and required mechanical ventilation shortly after birth. The sample size was calculated based on the 50% reduction in the incidence of chronic lung disease when early dexamethasone is used, allowing a 5% chance of a type I error and a 10% chance of a type II error. For infants who received dexamethasone, the dosing schedules were: 0.25 mg/kg/dose every 12 hours intravenously on days 1 through 7; 0.12 mg/kg/dose every 12 hours intravenously on days 8 through 14; 0.05 mg/kg/dose every 12 hours intravenously on days 15 through 21; and 0. 02 mg/kg/dose every 12 hours intravenously on days 22 through 28. A standard protocol for respiratory care was followed by the participating hospitals. The protocol emphasized the criteria of initiation and weaning from mechanical ventilation. The diagnosis of chronic lung disease based on oxygen dependence and abnormal chest roentgenogram was made at 28 days of age. To assess the effect of dexamethasone on pulmonary inflammatory response, serial tracheal aspirates were assayed for cell counts, protein, leukotriene B4, and 6-keto prostaglandin F1alpha. All infants were observed for possible side effects, including hypertension, hyperglycemia, sepsis, intraventricular hemorrhage, retinopathy of prematurity, cardiomyopathy, and alterations in calcium homeostasis, protein metabolism, and somatic growth.\n Infants in the dexamethasone group had a significantly lower incidence of chronic lung disease than infants in the placebo group either judged at 28 postnatal days (21/132 vs 40/130) or at 36 postconceptional weeks (20/132 vs 37/130). More infants in the dexamethasone group than in the placebo group were extubated during the study. There was no difference between the groups in mortality (39/130 vs 44/132); however, a higher proportion of infants in the dexamethasone group died in the late study period, probably attributable to infection or sepsis. There was no difference between the groups in duration of oxygen therapy and hospitalization. Early postnatal use of dexamethasone was associated with a significant decrease in tracheal aspirate cell counts, protein, leukotriene B4, and 6-keto prostaglandin F1alpha, suggesting a suppression of pulmonary inflammatory response. Significantly more infants in the dexamethasone group than in the placebo group had either bacteremia or clinical sepsis (43/132 vs 27/130). Other immediate, but transient, side effects observed in the dexamethasone group are: an increase in blood glucose and blood pressure, cardiac hypertrophy, hyperparathyroidism, and a transient delay in the rate of growth.\n In preterm infants with severe respiratory distress syndrome requiring assisted ventilation shortly after birth, early postnatal dexamethasone therapy reduces the incidence of chronic lung disease, probably on the basis of decreasing the pulmonary inflammatory process during the early neonatal period. Infection or sepsis is the major side effect that may affect the immediate outcome. Other observable side effects are transient. In view of the significant side effects and the lack of overall improvement in outcome and mortality, and the lack of long term follow-up data, the routine use of early dexamethasone therapy is not yet recommended.", "Several reports indicate a decreased cortisol response to adrenocorticotropic hormone in preterm infants developing chronic lung disease and in preterm infants with refractory hypotension. Low-dose hydrocortisone (HC) may allow for beneficial effects.\n Our aim was to assess whether HC is able to increase survival without chronic lung disease.\n We performed a double-blind, randomized, placebo-controlled trial. Fifty mechanically ventilated infants (birth weight: 500-1,249 g) were randomized to receive treatment (HC 0.5 mg/kg/12 h for 9 days, then HC 0.5 mg/kg/24 h for 3 days) or placebo. Major outcome was survival without oxygen dependence at 36 weeks of postconceptional age (O(2)-free survival).\n The basic characteristics were similar between the two groups. O(2)-free survival was higher in the HC group (64 vs. 32%). The advantage was particularly evident among infants without antenatal steroids. The mortality rate was 16% in the HC group versus 40% in the control group (difference not significant). Hypotension after recruitment was reduced by HC (0 vs. 30%). The incidence of gastrointestinal perforation and other adverse effects was similar between the two groups.\n HC prophylaxis improved O(2)-free survival and early cardiocirculatory function in our population, without important short-term effects. The neurodevelopmental outcome will be assessed at 2 years.\n Copyright (c) 2007 S. Karger AG, Basel.", "To determine whether early (less than or equal to 12 hours) postnatal dexamethasone therapy would facilitate removal of the endotracheal tube and improve outcome in premature infants with severe respiratory distress syndrome, we conducted a double-blind, controlled study of 57 infants whose birth weights were less than 2000 gm. The placebo (n = 29) and treated (n = 28) groups were comparable in birth weight (mean +/- SD: 1273 +/- 323 vs 1318 +/- 359 gm), gestational age (30.1 +/- 2.1 vs 30.8 +/- 2.7 weeks), postnatal age (8.7 +/- 3.1 vs 8.5 +/- 3.1 hours), and pulmonary function at the start of the study. The dose of dexamethasone was 1.0 mg/kg/day for 3 days and then was progressively decreased for 12 days. Infants in the dexamethasone group had significantly higher pulmonary compliance, tidal volume, and minute ventilation, and required lower mean airway pressure for ventilation than infants in the placebo group. The endotracheal tube was successfully removed from more infants in the dexamethasone group (16/28 vs 8/29; p less than 0.025). Nineteen infants (65%) in the placebo group and 11 (39%) in the dexamethasone group (p less than 0.05) had lung injuries. Dexamethasone therapy was associated with a temporary increase in blood pressure and plasma glucose concentration and a delay in somatic growth. We conclude that early postnatal dexamethasone therapy improves pulmonary status, facilitates removal of the endotracheal tube, and minimizes lung injuries in premature infants with severe respiratory distress syndrome.", "Bronchopulmonary dysplasia is an important complication of ventilation in babies for which treatment with steroids has been advocated. We report the results of a phase I study of early i.v. dexamethasone to prevent the development of bronchopulmonary dysplasia in a high-risk population of ventilated premature babies, < 30 wk gestation, with surfactant-treated respiratory distress syndrome. This study used a limited dexamethasone dosing regimen to minimize toxicity but used administration early in the course of acute lung disease to interrupt the injury cycle. Forty babies were enrolled; 19 were randomized to receive dexamethasone (0.5 mg/kg birth weight at 12-18 h of age and a second dose 12 h later) and 21 were randomized to receive placebo (i.v. saline). The dexamethasone group required less ventilatory support (mean airway, peak inspiratory and end expiratory pressures, and intermittent mandatory ventilation) and supplemental oxygen after study d 4 (all p < 0.05, repeated measures analysis of variance). Improved tidal volume in the dexamethasone group, as measured by pulmonary function testing of infants who remained intubated, was seen on study d 7 (p = 0.02, t test). The dexamethasone group required shorter hospitalizations (median of 95 d versus 106 d, p = 0.01) (proportional hazards regression). Survival in the dexamethasone group was 89% versus 67% in the placebo group (p = 0.08, chi 2 analysis). Survival without bronchopulmonary dysplasia, diagnosed at 36 wk corrected gestational age, was 68% in the dexamethasone group versus 43% in the placebo group (p = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)", "Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known.\n We randomly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia. The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days. The primary outcome was death or chronic lung disease at 36 weeks' postmenstrual age.\n The relative risk of death or chronic lung disease in the dexamethasone-treated infants, as compared with those who received placebo, was 0.9 (95 percent confidence interval, 0.8 to 1.1). Since the effect of dexamethasone treatment did not vary according to the ventilatory approach, the two dexamethasone groups and the two placebo groups were combined. The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth (P=0.004) or open-label dexamethasone (P=0.01), were more likely to have hypertension (P<0.001), and were more likely to be receiving insulin treatment for hyperglycemia (P=0.02). During the first 14 days, spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group (13 percent, vs. 4 percent in the placebo group; P=0.02). The dexamethasone-treated infants had a lower weight (P=0.02) and a smaller head circumference (P=0.04) at 36 weeks' postmenstrual age.\n In preterm infants, early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth.", "We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome. (1) A multicenter, randomized, double-blind trial was undertaken to confirm these results.\n Infants <30 weeks' gestation were eligible if they had respiratory distress syndrome, required mechanical ventilation at 12 to 18 hours of age, and had received at least 1 dose of exogenous surfactant. Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present. A total of 384 infants were enrolled-189 randomized to dexamethasone (.5mg/kg birth weight at 12-18 hours of age and a second dose 12 hours later) and 195 to an equal volume of saline placebo.\n No differences were found in the dexamethasone versus placebo groups, respectively, regarding the primary outcomes of survival (79% vs 83%), survival without oxygen at 36 weeks' corrected gestational age (CGA; both 59%), and survival without oxygen at 36 weeks' CGA and without late glucocorticoid therapy (46% vs 44%). No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen (50 vs 56 days), ventilation (20 vs 27 days), days to regain birth weight (15.5 vs 14 days), or length of stay (LOS; 88 vs 89 days). Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization (27% vs 35%). No clinically significant side effects were noted in the dexamethasone group, although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10. Among infants who died (40 vs 33), there were no differences in the median days on oxygen, ventilation, nor LOS. However, in survivors (149 vs 162), the following were observed: median days on oxygen 37 versus 45 days, ventilation 14 versus 19 days, and LOS 79 versus 81 days, for the dexamethasone versus placebo groups, respectively.\n This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks' CGA and survival was not improved. However, early dexamethasone reduced the use of later prolonged dexamethasone therapy, and among survivors, reduced the median days on oxygen and ventilation. We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dysplasia.", "To determine whether prenatal corticosteroid therapy would reduce the incidence of neonatal necrotizing enterocolitis (NEC), we assigned a total of 466 women admitted in premature labor either to receive placebo (group A, n = 256), if delivery was expected to occur within 24 hours of admission, or to receive betamethasone (group B, n = 210) if delivery was expected to take place more than 24 hours after admission. All women were free of severe medical complications or drug therapy; cases of intrauterine growth retardation or premature rupture of the membranes were excluded. Their newborn infants, excluding malformed, congenitally infected, and growth-retarded infants, were enrolled in the study unless they had died before the age of 10 postnatal days. Babies born to group A mothers (n = 248) were further assigned to a treatment group (group A1, n = 130) receiving dexamethasone, 2 mg/kg/day by intravenous injection during the first 7 days of life, or to a control group (group A2, n = 118) receiving 10% dextrose solution placebo. Group B infants (prenatal betamethasone, n = 205) received neither treatment nor placebo. The incidence of NEC in group A1 was 6.9% (9/130), and in group A2 it was 14.4% (17/118) (p less than 0.05). In group B the incidence was 3.4% (7/205); this was much lower than in group A2 (p less than 0.01) and lower than in group A combined (10.4%) (p less than 0.01). There was no death from NEC and no surgical intervention among group B patients. The mortality rate for group A1 (11%) was lower than for group A2 (56%) (p less than 0.02). There were fewer indications for surgical intervention for NEC in group A1 than in group A2. Histologic studies confirmed bowel ischemia in all specimens analyzed. These data support the hypothesis that the incidence of NEC is significantly reduced after prenatal steroid treatment. Although postnatal therapy with steroids does not decrease the incidence as effectively as prenatal therapy, it improves clinical outcome of NEC.", "This study was carried to evaluate the effect of early administration of dexamethasone on the incidence of bronchopulmonary dysplasia (BPD) and/or death in surfactant-treated preterm infants with respiratory distress syndrome (RDS).\n In a multicenter, double-blind, placebo-controlled trial, 109 preterm infants with RDS and birth weights between 700 and 1600 gm, who were treated with mechanical ventilation and surfactant, were randomly assigned before 36 hours of life to receive dexamethasone (n = 55) or placebo (n = 54) for 12 days.\n There were no differences in the incidence of BPD and/or death between groups. However, fewer patients in the dexamethasone group were oxygen-dependent at 36 weeks after conception (8% vs 33%, p < 0.05). The dexamethasone group had a lower incidence of necrotizing enterocolitis (0% vs 9%, p < 0.05). The incidence of arterial hypertension, hyperglycemia, and sepsis was not affected by the treatment. Basal and poststimulation serum cortisol levels did not differ between groups.\n The administration of dexamethasone early in the course of RDS does not decrease the incidence of BPD and/or death in preterm infants. However, dexamethasone may reduce oxygen dependency at 36 weeks after conception.", "Extremely low birth weight (ELBW) infants are at risk for hypotension. Abnormal adrenal function may play a role in the pathogenesis of hypotension, and therefore, the administration of hydrocortisone (HC) may be an effective treatment for hypotension in some infants. However, the efficacy of prophylactic HC to prevent the use of vasopressors for a defined hypotensive state has not been studied. We conducted a randomized-controlled trial to determine the potential role on adrenal insufficiency in early neonatal hypotension and to determine the effectiveness of prophylactic HC in reducing treatment of hypotension in ELBW infants.\n Infants were assigned to receive either HC or placebo within the first 3 hours of life. Therapy was continued for 5 days. The presence of hypotension was based on an operational definition and treatment with vasopressors (VP) was standardized based on an a priori protocol.\n A total of 34 patients were enrolled. Baseline characteristics were similar between groups. Of the HC group 25% received VP at 24 hours of age compared to 44% of the placebo group. On day of life 2, only 7% of the HC group received VP compared to 39% of the placebo group (p<0.05).\n Prophylactic treatment with HC reduces the incidence of hypotension, defined by treatment with VP, among ELBW infants during the first 2 days of life. However, the mounting evidence that prophylactic administration of glucocorticoids in the first days of life is harmful to ELBW infants makes HC prophylaxis unwise until the efficacy of treatment relative to safety can be clearly established.", "Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome (RDS). To investigate whether early (<12 hr) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease (CLD), a randomized, double-blind, controlled trial was conducted in 40 infants (birth weights from 500 to 1,999 gm) who had severe RDS and required mechanical ventilation within 6 hr of birth. All infants received one dose of Survanta before they were randomly assigned to control (saline placebo) or dexamethasone-treated groups (0.5 mg/kg/d for 1 week, then tapered over 3 weeks). Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28. Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment. Among the survivors, 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study. Infants in the treated group had transient hyperglycemia and hypertension. There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage. We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants. To substantiate our result, large randomized controlled trials are needed and warranted.", "Early postnatal use of dexamethasone in infants with respiratory distress syndrome (RDS) has been shown effectively to improve pulmonary status and to allow early weaning off mechanical ventilation. However, the mechanisms to explain the beneficial effects of dexamethasone in ventilatory dependent preterm infants remain unclear.\n A double blind, placebo controlled study was performed to determine the change in pulmonary ventilation of premature infants with RDS as a result of dexamethasone treatment, and to evaluate the effect of dexamethasone on the levels of surfactant-associated proteins A (SP-A) and D (SP-D) in the tracheal fluid from 34 premature infants with RDS and 29 control subjects.\n Dexamethasone treatment decreased fractional inspired oxygen concentration (FIO2), arterial carbon dioxide tension (PCO2), mean airway pressure (MAP), and facilitated successful weaning from mechanical ventilation. SP-A concentrations in the tracheal aspirates were increased at days 7 and 14, and SP-D concentrations were increased during the period from days 3 to 14 in the dexamethasone treated group compared with the control group. However, albumin levels in the tracheal aspirate samples were decreased after dexamethasone treatment over the period from days 3 to 14. There was an inverse correlation between PCO2 values and SP-A concentrations.\n These results suggest that early use of dexamethasone can improve pulmonary status and also increase SP-A and SP-D levels in the tracheal fluid in premature infants with RDS.", "Surfactant therapy now has a well-established role in the treatment of neonates with respiratory distress syndrome but has failed to reduce the incidence of bronchopulmonary dysplasia (BPD). We conducted a double-blind, placebo-controlled trial to test the hypothesis that dexamethasone therapy given during the first 12 days of life to very low birth weight infants would be synergistic to surfactant in preventing BPD.\n Seventy surfactant-pretreated infants (700-1500 g) who had severe respiratory distress syndrome (a/A ratio, 0.18 +/- 0.10; mean airway pressure, 11.1 +/- 1.9 cm H2O; fraction of inspired oxygen, 0.81 +/- 0.22) were enrolled to receive a 12-day course of dexamethasone (n = 36) or saline placebo (n = 34) starting within the first 12 hours after birth. The starting dose of dexamethasone was 0.5 mg/kg per day, and it was tapered progressively.\n Ventilator variables at 5 to 14 days were significantly improved in those infants who received dexamethasone compared with those who received the placebo. The effect seem to be more marked in infants weighting less than 1250 g at birth. Significantly more infants could be extubated by 14 days of age in the dexamethasone group (26 of 32 vs 14 of 32). Dexamethasone therapy reduced the incidence of BPD at 28 days (odds ratio, 0.1; 95% confidence interval, 0.03 to 0.3) and eliminated BPD at 36 weeks' postconceptional age. Dexamethasone-treated infants had greater weight loss at 14 days (12.9 +/- 6.4% vs 3.7 +/- 8.6%, respectively) and higher blood pressures from days 3 to 10. However, no differences were seen in time to regain birth weight, hypertension (1 infant in each group), or incidence of intraventricular hemorrhage.\n We found an additive effect between dexamethasone and surfactant in improving pulmonary status and reducing the incidence of BPD. Compared with the placebo, dexamethasone therapy was more effective in reducing the incidence of BPD in surfactant-pretreated very low birth weight infants.", "To determine whether treatment with inhaled nitric oxide (NO) and/or dexamethasone reduces the incidence of chronic lung disease (CLD) and/or death in high risk preterm infants.\n Infants below 32 weeks of gestation were recruited at 96 hours of age if they were deemed to be at high risk of developing CLD. Infants were randomly assigned to one of four treatment groups using a factorial design: (1) 5-20 parts per million inhaled NO for 72 hours; (2) 0.5-1 mg/kg/day intravenous dexamethasone for 6 days; (3) both drugs together; (4) continued conventional management.\n Forty two infants were randomised: 10 infants received inhaled NO alone; 11 dexamethasone alone; 10 both treatments; and 11 neither treatment. There was no difference in the combined incidence of CLD and/or death before discharge from hospital between either infants treated with inhaled NO and controls (RR 1.05, 95% CI 0.84-1.25), or those treated with dexamethasone and controls (RR 0.95, 95% CI 0.79-1.18).\n At 96 hours of age, neither treatment with inhaled NO nor dexamethasone prevented CLD or death.", "To test the hypothesis that a single dose of dexamethasone given soon after delivery to infants <28 weeks' gestation leads to improved cardiopulmonary adaptation in the first week and lowers the risk of significant intraventricular hemorrhage.\n In a prospective, blinded, placebo-controlled study, we randomly assigned 70 infants <28 weeks' gestation who were born in the hospital to receive dexamethasone (0.2 mg/kg) (n = 37) or normal saline solution (n = 33) within 2 hours of delivery. After an interim analysis showed that the incidence of intraventricular hemorrhage was much lower than expected, enrollment was stopped and we limited our analysis to a comparison of ventilator settings, blood pressure, and pressor use during the first 7 days.\n Clinical characteristics of the groups were comparable at study entry. Ventilator weaning occurred more rapidly in the patients who received dexamethasone: their intermittent mandatory ventilation rate was significantly lower on days 1 through 6, and their peak inspiratory pressure was lower on days 3 through 7 compared with the control group. Mean blood pressures were higher in the dexamethasone group within 12 hours and remained higher through day 5, but the use of pressors was not different. Fewer infants in the dexamethasone group received indomethacin to treat a patent ductus arteriosus (22% vs 47%, P <.03).\n Dexamethasone given within 2 hours of delivery to preterm infants <28 weeks' gestation resulted in lower ventilator settings and higher mean blood pressures during the first 7 days. Fewer infants required indomethacin to treat a patent ductus arteriosus.", "The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid (TAF) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease (CLD) were reported in this clinical trial designed in two phases. The first phase of the study included 20 neonates with birth weight < or = 1,250 g and gestational age < or = 32 weeks, who were oxygen and ventilator dependent on the 10th day of life. They were randomly assigned to the moderately early dexamethasone (MED) group or to the control group. The second phase of the study included 20 neonates with the same characteristics, oxygen and ventilator dependent on the 4th day of life, randomly assigned to the early dexamethasone (ED) group or to the control group. Both treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the last day of treatment). The control groups received no steroid treatment. A significantly lower absolute cell count and percentage of neutrophils (PMN) in the TAF and significantly higher dynamic lung compliance (Cdyn) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group. Moreover these changes were more precocious in the ED Group compared to the MED Group. Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier.\n Copyright 2004 S. Karger AG, Basel", "To investigate the effect of hydrocortisone treatment on survival without bronchopulmonary dysplasia (BPD) and to study whether serum cortisol concentrations predict the response.\n We performed a randomized, placebo-controlled trial on infants with gestation < or =30 weeks, body weight of 501 to 1250 g, and respiratory failure. Hydrocortisone was started before 36 hours of age and given for 10 days at doses from 2.0 to 0.75 mg/kg per day. Shortly before hydrocortisone treatment, basal and stimulated (ACTH, 0.1 microg/kg) serum cortisols were measured.\n The study was discontinued early, because of gastrointestinal perforations in the hydrocortisone group (4/25 vs 0/26, P = .05); 3 of the 4 had received indomethacin/ibuprofen. The incidence of BPD (28% vs placebo 42%, P = 0.28) tended to be lower, and patent ductus arteriosus (36% vs 73%, P = .01) was lower in the hydrocortisone group. The hydrocortisone-treated infants with serum cortisol concentrations above the median had a high risk of gastrointestinal perforation. In infants with cortisol values below the median, hydrocortisone treatment increased survival without BPD.\n Serum cortisol concentrations measured shortly after birth may identify those very high-risk infants who may benefit from hydrocortisone supplementation.", "To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome.\n A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities.\n The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered.\n These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants.", "Infants developing bronchopulmonary dysplasia (BPD) show decreased cortisol response to adrenocorticotropic hormone. A pilot study of low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed improved survival without BPD at 36 weeks' postmenstrual age, particularly in infants exposed to histologic chorioamnionitis.\n Mechanically ventilated infants with birth weights of 500 to 999 g were enrolled into this multicenter, randomized, masked trial between 12 and 48 hours of life. Patients received placebo or hydrocortisone, 1 mg/kg per day for 12 days, then 0.5 mg/kg per day for 3 days. BPD at 36 weeks' postmenstrual age was defined clinically (receiving supplemental oxygen) and physiologically (supplemental oxygen required for O2 saturation > or =90%).\n Patient enrollment was stopped at 360 patients because of an increase in spontaneous gastrointestinal perforation in the hydrocortisone-treated group. Survival without BPD was similar, defined clinically or physiologically, as were mortality, head circumference, and weight at 36 weeks. For patients exposed to histologic chorioamnionitis (n = 149), hydrocortisone treatment significantly decreased mortality and increased survival without BPD, defined clinically or physiologically. After treatment, cortisol values and response to adrenocorticotropic hormone were similar between groups. Hydrocortisone-treated infants receiving indomethacin had more gastrointestinal perforations than placebo-treated infants receiving indomethacin, suggesting an interactive effect.\n Prophylaxis of early adrenal insufficiency did not improve survival without BPD in the overall study population; however, treatment of chorioamnionitis-exposed infants significantly decreased mortality and improved survival without BPD. Low-dose hydrocortisone therapy did not suppress adrenal function or compromise short-term growth. The combination of indomethacin and hydrocortisone should be avoided." ]

[ "9292855", "11462230", "2729214", "2206479" ]

[ "Outcomes of a nursing intervention for siblings of chronically ill children: a pilot study.", "Supportive groups for siblings of pediatric oncology patients: impact on anxiety.", "Evaluation of a camp program for siblings of children with cancer.", "The effects of group therapy on siblings of pediatric oncology patients." ]

[ "To evaluate the outcomes of a structured, educational, and support group intervention (ISEE, Intervention for Siblings: Experience Enhancement) for siblings of children with chronic illness (cancer, cystic fibrosis, diabetes, and spina bifida), including a session with parents about sibling needs; and to describe sibling and parent perceptions of sibling experiences at home.\n One-group, pretest-posttest pilot study.\n A convenience sample of 22 siblings and parents.\n A Midwestern university medical center.\n Knowledge of Illness Test, parent ratings on a global, single item, 10-point scale.\n Sibling test scores increased significantly after intervention, compared to baseline. Parents' average evaluation rating was 9 on a 10-point scale. Parents supported their positive ratings with verbatim descriptions. Sibling and parent perceptions of sibling experiences were congruent, suggesting the sources of potential adjustment problems in siblings, and were consistent with the literature.\n A randomized, clinical trial with a larger sample size is needed to evaluate the intervention further.", "Childhood cancer can have a substantial emotional impact on the siblings of the sick child. In order to help these siblings adjust to the illness, supportive groups were started in 1994 at our medical center. The program is based on a model of psychosocial support; the aim of the group is to enhance control strategies and, thus, to reduce anxiety. It consists of five sessions and is offered to siblings aged 7-18. The study objective is to evaluate the effect of group participation on sibling anxiety. The State Trait Anxiety Inventory for Children was administered to 24 siblings before and after group participation. Results showed that siblings experience less anxiety after participating in the group. Before group participation, a majority of the siblings were more anxious compared with normal peers. The sibling's age and sex, whether the ill child is in treatment, survival perspective, and time since diagnosis were not related to anxiety reduction. The continuation of the group is supported by its positive impact on siblings. Results must nevertheless be interpreted cautiously, considering the small number of siblings participating in the study, the lack of a control group and the restriction to one outcome measure.\n Copyright 2001 John Wiley & Sons, Ltd.", "In recent years, specialized camping programs for chronically ill children, members of their family, or both have proliferated. Although these programs are popular, little systematic evaluation of risk-benefit has been undertaken. In a naturalistic study we evaluated the effect of a 5-day residential camping program to determine the effect of the program on the level of medical knowledge, on the perceptions of how the cancer experience affected the individual, and on the participant's mood state. Analysis of questionnaire data from 90 campers before and after their participation in the program revealed that desirable changes occurred in each of these areas and were sustained for at least 3 months after the program. Siblings reported by parents to have behavioral problems with onset since the diagnosis of the cancer seemed to benefit particularly from this type of program. No substantial negative effects were found regardless of the camper age, adaptational status, or previous camp experience.", "The stress and psychological difficulties of siblings of children with cancer is well documented. Siblings must cope with a myriad of emotions, isolation from the family, and many changes in daily life. Therefore, a need exists to determine the effects of psychosocial interventions on siblings of cancer patients. The support group is one psychosocial intervention that has been suggested as a method to relieve stress and enhance coping. A quasi-experimental design was selected to determine the effects of participation in a support group on the social adjustment of siblings of children with cancer. Conclusions suggest that a support group provides siblings with the opportunity to decrease their sense of isolation, ventilate negative feelings, and learn from each other. Additionally, descriptive data suggest a need for ongoing follow-up with siblings to help them manage the stresses emerging from the impact of the diagnosis and treatment on the family. Implications of this study suggest that nurses should organize support groups for siblings and/or refer them to existing groups. Also, this study suggests the need to work with siblings and educate parents regarding sibling concerns." ]

[ "11198705" ]

[ "Thiamin treatment and working memory function of alcohol-dependent people: preliminary findings." ]

[ "Wernicke-Korsakoff syndrome (WKS) is most often seen in people who are alcohol dependent. Treatment with thiamin may rapidly resolve acute symptoms. However, much evidence suggests that identification of WKS on clinical examination is relatively insensitive when compared with diagnosis at postmortem. No study has investigated the therapeutic effect of thiamin in a sample of alcohol-dependent people without the clinical triad of acute WKS.\n We conducted a randomized, double-blind, multidose study of thiamin treatment in 107 subjects who were detoxifying from alcohol. Five groups of subjects were assessed with the Mini-Mental State Examination and were examined for the presence of neurological signs. Subjects were given different doses of intramuscular thiamin for two consecutive days. The posttreatment performance of these groups then was examined on a test of working memory derived from comparative neuropsychology, namely, the delayed alternation task. This test has been established as sensitive to the neuropathology of WKS.\n Pretreatment measures of mental status and neurological signs were equivalent across groups. Groups were equated with respect to the background variables of age, education, typical daily alcohol consumption, and years of drinking. On the posttreatment measure, a superior performance was found in the group that received the highest dose of thiamin, compared with the other four treatment groups.\n A therapeutic relationship between dose and working memory performance was indicated. These results have important implications for the management and prevention of WKS, but further investigations are needed to substantiate the nature of the therapeutic relationship." ]

[ "12383805", "3828273", "7493231", "3855337", "3220672", "2275355", "6371649", "15642809", "3341973", "1882922", "10571351", "10340983", "7936562", "2618634", "8540545", "19920476", "9727511", "8155044" ]

[ "The Advanced Glaucoma Intervention Study (AGIS): 11. Risk factors for failure of trabeculectomy and argon laser trabeculoplasty.", "Laser trabeculoplasty as supplementary treatment for primary open angle glaucoma.", "Primary argon laser trabeculoplasty vs pilocarpine. IV. Long-term effects on optic nerve head.", "Argon laser trabeculoplasty or trabeculectomy a prospective randomised block study.", "Argon laser trabeculoplasty in primary open-angle glaucoma--results in black Jamaican population.", "Argon laser trabeculoplasty with standard and long duration.", "Argon laser trabeculoplasty: comparison of bichromatic and monochromatic wavelengths.", "Bronchial reactivity in healthy individuals undergoing long-term topical treatment with beta-blockers.", "Peripheral anterior synechiae formation after trabeculoplasty.", "Diode laser compared with argon laser for trabeculoplasty.", "Early Manifest Glaucoma Trial: design and baseline data.", "Selective laser trabeculoplasty v argon laser trabeculoplasty: a prospective randomised clinical trial.", "Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma.", "The immediate pressure response to primary laser trabeculoplasty--a comparison of one- and two-stage treatment.", "The Glaucoma Laser Trial (GLT) and glaucoma laser trial follow-up study: 7. Results. Glaucoma Laser Trial Research Group.", "Influence of treatment protocol on the long-term efficacy of argon laser trabeculoplasty.", "Five-year results of a randomized, prospective, clinical trial of diode vs argon laser trabeculoplasty for open-angle glaucoma.", "Initial argon laser trabeculoplasty to the inferior vs superior half of trabecular meshwork." ]

[ "To investigate the association of pre-intervention and post-intervention patient and eye characteristics with failure of argon laser trabeculoplasty (ALT) and trabeculectomy.\n Cohort study of participants in the Advanced Glaucoma Intervention Study.\n This multicenter study took place between 1988 and 2001. Between 1988 and 1992, 789 eyes of 591 patients aged 35 to 80 years with advanced glaucoma were randomized into one of two surgical treatment sequences: argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy or trabeculectomy-ALT-trabeculectomy. Upon study-defined failure (based on maximum medications, sustained intraocular pressure (IOP) elevation, visual field defect, and disk rim deterioration) of each intervention, patients were offered the subsequent intervention. Potential follow-up was 8 to 13 years. This report is based on data from 779 eyes that had at least 3 months of follow-up. The main outcome measures are failure of ALT and trabeculectomy, whether as first or second interventions. Effect size is measured by the hazard ratio (HR) and its corresponding 95% confidence interval (CI) obtained from Cox multiple regression analysis, where HR corresponds to the coefficient of change in risk associated with a unit increase in a factor. For binary factors, this corresponds to the change in risk in eyes with the factor relative to the risk in eyes without the factor.\n Pre-intervention factors associated with failure of ALT are younger age (HR = 0.98, CI = 0.96-0.99, P =.009) and higher IOP (1.11, 1.08-1.15, P <.001). Pre-intervention factors associated with failure of trabeculectomy are younger age (HR = 0.97, CI = 0.95-0.99, P =.005) and higher IOP (1.04, 1.01-1.06, P =.002), as well as diabetes (2.86, 1.88-4.36, P <.001) and any postoperative complication (1.99, 1.35-2.93, P <.001). Individual postoperative complications significantly associated with increased risk of failure of trabeculectomy are elevated IOP (3.4, 1.9-6.1, P <.001) and marked inflammation (2.4, 1.3-4.6, P =.006).\n In this study, ALT failure was associated with younger age and higher pre-intervention IOP. Trabeculectomy failure was associated with younger age, higher pre-intervention IOP, diabetes, and one or more postoperative complications, particularly elevated IOP and marked inflammation.", "A prospective trial was conducted of laser trabeculoplasty randomly assigned to one eye of a group of elderly patients with bilateral primary phakic open angle glaucoma who were already taking the maximum medical treatment that they could tolerate. With a minimum follow-up of 2 1/2 years (mean 35 months) a significant fall in mean intraocular pressure of over 7 mmHg (30%) at the time of the patient's last visit was noted in the treated eye.", "In a prospective, randomized study on primary argon laser trabeculoplasty vs piloparpine in 82 newly detected open-angle glaucomas the progress of optic nerve head damage is presented. In 70 patients reliable stereo photographs could be analysed. In the laser treated group a progression of glaucoma damage after 24 months was seen in 6/37 eyes (16%) and in the pilocarpine-treated group 16/33 (49%) (p = 0.0048). There was a statistically significant favourable outcome if intraocular pressure was regulated in terms of peak and range of pressure, but not average pressure. This was even more pronounced in capsular glaucoma, but not significant for simple glaucoma. Pilocarpine increased the risk for further damage to the optic nerve head 6.4 times compared to laser trabeculoplasty. Thus, laser is recommended as the primary therapy in high tension glaucoma, especially in capsular glaucoma.", "A prospective randomised block study of treatment by either argon laser trabeculoplasty or trabeculectomy was undertaken in patients with chronic open angle glaucoma not controlled by medication. The study was undertaken in two centres in the United Kingdom where the regimes of medical treatment prior to interference were different. Regression analysis showed that in both populations laser trabeculoplasty was effective in reducing the intraocular pressure but it was less effective than trabeculectomy in permanently reducing the intraocular pressure to within normal limits. Laser trabeculoplasty was most effective in those patients whose intraocular pressure was initially high but many of these required post-operative medication or surgery. Laser trabeculoplasty is a useful adjunct to the therapy of open angle glaucoma but it is not a substitute for trabeculectomy as a method of permanently reducing the intraocular pressure to normal. Because of the effectiveness of both these methods of treatment we feel it no longer justified to use anything other than simple local medication to control the intraocular pressure before proceeding to active therapy.", "A controlled, randomised, prospective trial of Argon laser trabeculoplasty (ALT) was carried out on 48 eyes of 30 black Jamaican patients with primary open-angle glaucoma. All eyes had uncontrolled intra-ocular pressures (greater than or equal to 22 mm Hg) despite medical therapy. Treatment was successful in controlling intraocular pressure in 68% of eyes after 12 months follow-up (p = 0.004). The average drop in intraocular pressure attributable to ALT was 6.6 mmHg. Argon laser trabeculoplasty is an effective adjunct in managing to control intraocular pressure in black Jamaican glaucoma patients.", "A prospective study of 0.1 sec and 0.2 sec duration argon laser trabeculoplasty was undertaken in 33 patients with chronic simple glaucoma. Patients were randomly allocated to receive 0.1 sec trabeculoplasty to the eye and 0.2 sec trabeculoplasty to the other. No difference was found in the fall in intra-ocular pressure or in glaucoma control between the two durations over the six months of the study. However, 0.2 sec argon laser trabeculoplasty was reported to be more uncomfortable of 60% of patients.", "A randomized prospective study was undertaken to examine the effects of bichromatic argon laser therapy and monochromatic argon laser therapy when used for trabeculoplasty in chronic open angle glaucoma. Fifty patients underwent laser trabeculoplasty with the continuous wave argon laser emitting wavelengths of multiple lines (454.5 nm to 528.7 nm) in the bichromatic spectrum (blue and green). Fifty additional patients underwent laser trabeculoplasty using a continuous-wave argon laser emitting a monochromatic (green) wavelength at 514.5 nm. Patients treated with the bichromatic laser had an average decrease in their intraocular pressure of -7.1 +/- 5.2 mmHg and patients treated with the monochromatic laser had an average decrease of -8.0 +/- 6.2 mmHg. The length of the follow-up was 2 to 13 months with an average of 10 months. For each group, this decrease in intraocular pressure from the pretreatment values was statistically significant (P less than 0.001). However, there was no statistically significant difference in the decrease in the intraocular pressure between the two groups (P = 0.34). No differences were noted in the postoperative course or in the complication rate between the two groups.", "To assess the impact of long-term treatment with topical timolol on bronchial reactivity in healthy individuals.\n Twenty-one otherwise healthy individuals with high-pressure primary open-angle glaucoma were enrolled in a randomized controlled clinical trial. Eleven patients underwent 3 years of topical 0.5% timolol treatment followed by a 1-year washout period; 10 patients underwent primary argon laser trabeculoplasty. Functional variables and bronchial reactivity (forced expiratory volume in 1 second and metacholine challenge test results) were assessed in both groups at enrollment and after 3 and 4 years of follow-up.\n After 3 years, a measurable response to metacholine challenge was recorded in 6 of 11 otherwise symptom-free individuals treated with 0.5% timolol twice daily. A detectable response to metacholine challenge was still present in half of these individuals (3 of 6) when further washed out for 1 year from the topical beta-blocker. No significant variation in bronchial reactivity was measured in the laser-treated group during 4 years of follow-up.\n Healthy individuals who undergo long-term topical application of a nonselective beta-blocker (0.5% timolol) can develop a subclinical increase in bronchial reactivity. This phenomenon may not be completely reversible on withdrawal of the beta-blocker.", "Argon laser trabeculoplasty (ALT) was performed on 60 eyes with primary open angle glaucoma and 59 eyes with capsular (pseudoexfoliation) glaucoma. Laser applications of four different power levels (500, 600, 700, and 800 mW) were directed either at the anterior trabecular meshwork or at the posterior trabecular meshwork. Gonioscopic examination to reveal peripheral anterior synechiae (PAS) formation was performed before and six months after ALT. Peripheral anterior synechiae were found in 26 (22%) of the eyes. With 500-mW laser power and anterior trabecular meshwork burns, no PAS developed. With 800-mW posterior trabecular meshwork burns, PAS developed in 12 (40%) of the eyes. No correlation between PAS formation and sex, age, glaucoma type, preoperative antiglaucoma medication, pigmentation of the chamber angle, and visible burn effect was found. Intraocular pressure decrease after ALT was significantly smaller in eyes with PAS.", "A randomized prospective study on two groups of ten patients compared the efficacy of diode laser and argon laser trabeculoplasty. In the diode laser group the intraocular pressure was 23.0 +/- 3.97 mm Hg before the treatment, 20.2 +/- 4.49 mm Hg at two hours, 16.3 +/- 3.13 at six months, and 16.9 +/- 2.80 mm Hg at one year. The differences from baseline were statistically significant at six months (P = .0001) and at one year (P = .0001) but not at two hours. In the argon laser group the intraocular pressure was 23.4 +/- 3.6 mm Hg before the treatment, 22.7 +/- 4.35 mm Hg at two hours, and 17.6 +/- 4.53 mm Hg at six months. One patient had uncontrolled mean high intraocular pressure and underwent surgery. In the nine patients who completed the study the intraocular pressure at one year was 16.7 +/- 3.00 mm Hg. The differences from baseline were significant at six months (N = 10; P = .0001) and 12 months (N = 9; P = .0001) but not at two hours. Differences between the two groups were not significant at two hours, six months, and one year. Laser trabeculoplasty may be effectively with a diode laser.", "The Early Manifest Glaucoma Trial (EMGT) will evaluate the effectiveness of reducing intraocular pressure (IOP) in early, previously untreated open-angle glaucoma. Its secondary aims are to explore factors related to glaucoma progression and to study the natural history of the disease. This article describes the EMGT design and presents baseline data.\n Randomized, clinical trial.\n Newly diagnosed patients 50 to 80 years of age with early glaucomatous visual field defects were mainly identified from a population-based screening of more than 44,000 residents of Malmö and Helsingborg, Sweden. Exclusion criteria were advanced visual field loss; mean IOP greater than 30 mmHg or any IOP greater than 35 mmHg; visual acuity less than 0.5; and inability to complete follow-up protocols.\n After informed consent, patients were randomized to treatment or no initial treatment with close follow-up. Treated patients had laser trabeculoplasty and started receiving topical betaxolol twice daily in eligible eyes. Follow-up visits include computerized perimetry and tonometry every 3 months and fundus photography every 6 months. Decisions to change or begin treatment are made jointly with the patient when EMGT progression occurs and also later if clinically needed.\n The EMGT progression is defined by sustained increases of visual field loss in three consecutive C30-2 Humphrey tests, as determined from computer-based analyses, or by optic disc changes, as determined from flicker chronoscopy and side-by-side comparisons of fundus photographs performed by masked, independent graders.\n A total of 255 patients were randomized between 1993 and 1997 and will be followed for at least 4 years. All had generally good health status; mean age was 68.1 years, and 66% were women. At baseline, mean IOP was 20.6 mmHg and 80% of eyes had IOP less than 25 mmHg.\n The Early Manifest Glaucoma Trial is the first large randomized, clinical trial to evaluate the role of immediate pressure reduction, as compared to no initial reduction, in patients with early glaucoma and normal or moderately elevated IOP. Its results will have implications for: (1) the clinical management of glaucoma; (2) understanding the role of IOP and the natural history of glaucoma; and (3) evaluating the rationale for glaucoma screening.", "To compare the effectiveness of selective laser trabeculoplasty (SLT, a 532 nm Nd:YAG laser) with argon laser trabeculoplasty (ALT) in lowering the intraocular pressure (IOP) in patients with medically uncontrolled open angle glaucoma.\n A prospective randomised clinical trial was designed. Patients were randomised to treatment with either SLT or ALT and were evaluated at 1 hour, 1 week, 1, 3, and 6 months post-laser.\n There were 18 eyes in each group. Baseline characteristics were similar in both groups. In the SLT group the mean IOP at baseline, 1, 3, and 6 months was 22.8 (SD 3.0), 20.1 (4.6), 19.3 (6.0), and 17.8 (4.8) mm Hg, respectively. In the ALT group, the mean IOP at baseline, 1, 3, and 6 months was 22.5 (3.6), 19.5 (4.7), 19.6 (5.6), and 17.7 (3.3) mm Hg, respectively. There was a greater anterior chamber reaction, 1 hour after SLT v ALT (p< 0.01). Patients with previous failed ALT had a better reduction in IOP with SLT than with repeat ALT (6.8 (2. 4) v 3.6 (1.8) mm Hg; p = 0.01).\n SLT appears to be equivalent to ALT in lowering IOP during the first 6 months after treatment. There is a slightly greater anterior chamber reaction 1 hour after SLT. Patients with previous failed ALT had a significantly greater drop in IOP when treated with SLT v ALT. These results need to be confirmed with a larger sample size.", "This randomly allocated prospective clinical study was designed to assess the relative efficacy of laser trabeculoplasty, medical therapy, and trabeculectomy used as the primary treatment in open-angle glaucoma, with particular regard to the level of intraocular pressure control and the amount of visual field decay. No patient had received any antiglaucoma treatment before entry into the trial.\n One hundred sixty-eight patients were entered into the trial and randomly allocated into one of the three treatment groups--laser, medicine, or surgery. Follow-up was for a minimum of 5 years. The patients were monitored in the standard way, including intraocular pressure estimations and visual field tests (initially using the Friedmann analyzer and later including Humphrey automated perimetry).\n Despite similar initial composition of the three treatment groups, primary surgery resulted in the lowest mean intraocular pressures. The perimeter Friedmann visual fields were shown to have deteriorated in patients in the medicine-treated group and to a lesser extent in patients in the laser-treated group, but not in patients in the surgery-treated group. Multivariate linear regression analysis showed that the difference in field changes between laser and surgical treatments could be explained entirely by the difference between the intraocular pressure values at 6 months between the two groups. The same was not true for the medicine-treated group.\n Primary trabeculectomy appears to have the desired effect in preserving visual function in patients with high-tension glaucoma. This may be related to laser treatment might be expected to have the same effect.", "The immediate pressure response to primary LTP was studied prospectively in 40 eyes randomised to one- and two-stage treatment in 360 degrees of the trabecular meshwork. There were 26 eyes with glaucoma capsulare and 14 with glaucoma simplex. Mean prelaser IOP was 32.8 mmHg in the former, and 35.5 mmHg in the latter group. The frequency and magnitude of postlaser pressure increase were the same in both groups when taking into consideration the pressure spikes in both 180 degrees sessions. The pressure increase was higher than in earlier reports on LTP in presurgical glaucoma patients on maximum medication. Almost all IOP elevations appeared during the first 2 h following laser treatment. The results were the same in both groups 6 months after LTP.", "To determine differences between the two treatment groups of the Glaucoma Laser Trial with respect to intraocular pressure, visual fields, optic disk cupping, and therapy for primary open-angle glaucoma.\n The Glaucoma Laser Trial was a multicenter, randomized clinical trial designed to assess the efficacy and safety of starting treatment for primary open-angle glaucoma with argon laser trabeculoplasty vs starting with topical medication. The Glaucoma Laser Trial Follow-up Study was a follow-up study of 203 of the 271 patients who enrolled in the Glaucoma Laser Trial. By the close of the Glaucoma Laser Trial Follow-up Study, median duration of follow-up since diagnosis of primary open-angle glaucoma was seven years (maximum, nine years).\n Over the course of the Glaucoma Laser Trial and Glaucoma Laser Trial Follow-up Study, the eyes treated initially with argon laser trabeculoplasty had lower intraocular pressure and better visual field and optic disk status than their fellow eyes treated initially with topical medication. As compared to eyes initially treated with medication, eyes initially treated with laser trabeculoplasty had 1.2 mm Hg greater reduction in intraocular pressure (P < .001) and 0.6 dB greater improvement in the visual field (P < .001) from entry into the Glaucoma Laser Trial. The overall difference between eyes with regard to change in ratio of optic cup area to optic disk area from entry into the Glaucoma Laser Trial was -0.01 (P = .005), which indicated slightly more deterioration for eyes initially treated with medication.\n Initial treatment with argon laser trabeculoplasty was at least as efficacious as initial treatment with topical medication.", "Forty-five phakic eyes of 36 patients with open-angle glaucoma and uncontrolled intraocular pressure despite maximally tolerated medication underwent initial argon laser trabeculoplasty (ALT) in 1981 and 1982 as part of a prospective, randomized study to evaluate the effectiveness of different treatment standards. Each eye had been randomly assigned to receive either 100 laser applications over 360 degrees of trabecular meshwork, 50 applications over 180 degrees , or 50 applications over 360 degrees in a single session. Further treatment in each group was based on clinical standards prevailing at the time. The long-term results were analyzed using Kaplan-Meier survival analyses. By 4 years after initial ALT, six of the 15 remaining eyes in group 1 (40%), one of 14 eyes in group 2 (7%), and two of 13 eyes in group 3 (15%) had undergone filtration surgery, and one eye in group 1 (7%), three eyes in group 2 (21%), and three eyes in group 3 (23%) had received further ALT. By 7 years after initial ALT, seven of the nine remaining eyes in group 1 (78%), one of 12 eyes in group 2 (8%), and four of 12 eyes in group 3 (33%) received filtration surgery, and two eyes in group 1 (22%), three eyes in group 2 (25%), and four eyes in group 3 (33%) had received further ALT. Kaplan-Meier survival curves predict the following probabilities of avoiding either repeat ALT or filtration surgery at 4 years after an initial ALT: group 1, 54 +/- 12%; group 2, 76 +/- 12%; and group 3, 62 +/- 11%. Our results suggest that performing 50 rather than 100 burns at initial ALT may significantly delay the need for additional surgical or repeat laser intervention.", "To evaluate the safety and efficacy of laser trabeculoplasty (LTP) with a semiconductor diode laser (810 nm, [DLT]) vs an argon blue-green laser (488 to 514 nm, [ALT]).\n In a prospective, randomized clinical trial, 50 eyes of 46 patients with uncontrolled open-angle glaucoma on maximally tolerated medical therapy were treated and followed at regular intervals for 5 years. Fifty laser spots were applied over 180 degrees using either maximal laser power or sufficient power to produce blanching or a small bubble (570 to 850 mW, DLT; 400 to 1,100 mW, ALT). We performed DLT using a 100-microm spot size, a 0.5-second exposure, and a Ritch lens; we conducted ALT with a 50-microm spot, a 0.1-second exposure, and a Goldmann lens. Patients in the study were followed until trabeculectomy was required.\n The mean follow-up times +/- SD for all eyes were 38.6 +/- 5.4 months, DLT (n = 22; range, 1 to 68 months) and 35.5 +/- 4.8 months, ALT (n = 28; range, 1 to 66 months). Those in the diode laser group (n = 16) who had more than 1 year of follow-up were tracked for 49.4 months, and those in the argon laser group (n = 21) were tracked for 45.8 months. There were no significant differences in the mean pretreatment intraocular pressures (IOPs): 21.2 mm Hg, DLT (n = 22) and 21.5, ALT 21.5 mm Hg (n = 28); P = .81] or in mean final IOPs (15.7 mm Hg, DLT and 17.1 mm Hg, ALT; P = .19). Time to surgical failure showed no significant differences, with 50% of the DLT eyes and 58% of the ALT eyes surviving at 5 years (P = .59).\n In eyes with open-angle glaucoma and unsatisfactory IOP control on maximally tolerated medical therapy, DLT and ALT are equally effective in lowering IOP over a 5-year period.", "nan" ]

[ "12599083", "12729289", "2773844", "8988907", "11694611", "17522609", "10721929", "16920862", "7115656", "6511008", "3414574", "6668226", "15321815", "17691591", "8816034", "4595583", "19675104", "11360125", "3981699", "9192196", "7678046", "9310602", "17928808", "604260", "15473523", "2773847", "8375881", "15735107", "15303996", "12003652", "3348161", "11355564", "14652364", "10989766", "11395986", "15514272", "20889877", "11916762", "12354473", "16413877", "12736400", "8237843", "16306925", "12499347", "3751561", "8169656", "16837718", "9094893", "15164114", "2644855", "12756979", "12788572", "9039270", "10694769", "8594693", "16630383", "11814373", "2471448", "3836201", "17468087", "15613506", "2134529", "11053508" ]

[ "Randomized, controlled trial of daily iron supplementation and intermittent sulfadoxine-pyrimethamine for the treatment of mild childhood anemia in western Kenya.", "The effect of iron therapy on the growth of iron-replete and iron-deplete children.", "Effects of iron deficiency on attention and learning processes in preschool children: Bandung, Indonesia.", "Zinc supplementation reduced morbidity, but neither zinc nor iron supplementation affected growth or body composition of Mexican preschoolers.", "Multivitamin-multimineral and iron supplementation did not improve appetite of young stunted and anemic Beninese children.", "The efficacy of micronutrient supplementation in reducing the prevalence of anaemia and deficiencies of zinc and iron among adolescents in Sri Lanka.", "Efficacy and acceptability of two iron supplementation schedules in adolescent school girls in Lima, Peru.", "Iron and zinc supplementation improved iron and zinc status, but not physical growth, of apparently healthy, breast-fed infants in rural communities of northeast Thailand.", "Behavioural responses of young anaemic Indian children to iron-folic acid supplements.", "An effective intervention to reduce the prevalence of anaemia in children.", "Hematological effect of supplementing anemic children with vitamin A alone and in combination with iron.", "The relative effectiveness of iron and iron with riboflavin in correcting a microcytic anaemia in men and children in rural Gambia.", "A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development.", "Effect of oral supplementation with iron(III)-hydroxide polymaltose complex on the immunological profile of adolescents with varying iron status.", "Does iron therapy benefit children with severe malaria-associated anaemia? A clinical trial with 12 weeks supplementation of oral iron in young children from the Turiani Division, Tanzania.", "Effect of iron and folate supplementation on haematocrit levels of school children in a rural area of Central Thailand.", "Multiple micronutrients including iron are not more effective than iron alone for improving hemoglobin and iron status of Malian school children.", "Impact of iron supplementation and deworming on growth performance in preschool Beninese children.", "Haemopoietic response of Nigerian village children to iron, folate supplementation and malaria prophylaxis.", "Weekly iron supplementation is as effective as 5 day per week iron supplementation in Bolivian school children living at high altitude.", "Reversal of developmental delays in iron-deficient anaemic infants treated with iron.", "Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants.", "The effect of weekly iron and vitamin A supplementation on hemoglobin levels and iron status in adolescent schoolgirls in western Kenya.", "The Balwadi as an outlet for anaemia prophylaxis programme.", "A randomized placebo-controlled trial of iron supplementation in breastfed young infants initiated on complementary feeding: effect on haematological status.", "Preliminary findings on iron supplementation and learning achievement of rural Indonesian children.", "Growth performance in anemia and following iron supplementation.", "Efficacy of a foodlet-based multiple micronutrient supplement for preventing growth faltering, anemia, and micronutrient deficiency of infants: the four country IRIS trial pooled data analysis.", "Weekly iron supplements given by teachers sustain the haemoglobin concentration of schoolchildren in the Philippines.", "A randomised trial in Mali of the effectiveness of weekly iron supplements given by teachers on the haemoglobin concentrations of schoolchildren.", "Iron supplementation and physical growth of rural Indonesian children.", "The effect of different anthelmintic treatment regimens combined with iron supplementation on the nutritional status of schoolchildren in KwaZulu-Natal, South Africa: a randomized controlled trial.", "Simultaneous weekly supplementation of iron and zinc is associated with lower morbidity due to diarrhea and acute lower respiratory infection in Bangladeshi infants.", "Effect of daily and intermittent iron supplementation on iron status of high school girls.", "School-administered weekly iron supplementation--effect on the growth and hemoglobin status of non-anemic Bolivian school-age children. A randomized placebo-controlled trial.", "Low-dose daily iron supplementation for 12 months does not increase the prevalence of malarial infection or density of parasites in young Zanzibari children.", "A comparison of iron and folate with folate alone in hematologic recovery of children treated for acute malaria.", "Treatment of iron deficiency in goitrous children improves the efficacy of iodized salt in Côte d'Ivoire.", "Intermittent administration of iron and sulfadoxine-pyrimethamine to control anaemia in Kenyan children: a randomised controlled trial.", "Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial.", "Anemia prophylaxis in adolescent school girls by weekly or daily iron-folate supplementation.", "Decreased rate of stunting among anemic Indonesian preschool children through iron supplementation.", "Efficacy of combined iron and zinc supplementation on micronutrient status and growth in Vietnamese infants.", "Iron supplementation improves iron status and reduces morbidity in children with or without upper respiratory tract infections: a randomized controlled study in Colombo, Sri Lanka.", "Mild anaemia in African school children: effect on running performance and an intervention trial.", "Iron supplementation improves appetite and growth in anemic Kenyan primary school children.", "Zinc and iron supplementation and malaria, diarrhea, and respiratory infections in children in the Peruvian Amazon.", "Effective community intervention to improve hemoglobin status in preschoolers receiving once-weekly iron supplementation.", "Effectiveness of weekly vitamin A (10,000 IU) and iron (60 mg) supplementation for adolescent boys and girls through schools in rural and urban East Java, Indonesia.", "The effect of iron therapy on malarial infection in Papua New Guinean schoolchildren.", "Use of microencapsulated iron(II) fumarate sprinkles to prevent recurrence of anaemia in infants and young children at high risk.", "Effect of intermittent treatment with amodiaquine on anaemia and malarial fevers in infants in Tanzania: a randomised placebo-controlled trial.", "The effect of oral iron therapy during treatment for Plasmodium falciparum malaria with sulphadoxine-pyrimethamine on Malawian children under 5 years of age.", "Effect of daily iron supplementation on iron status, cell-mediated immunity, and incidence of infections in 6-36 month old Togolese children.", "Iron, but not folic acid, combined with effective antimalarial therapy promotes haematological recovery in African children after acute falciparum malaria.", "Failure of twice-weekly iron supplementation to increase blood haemoglobin and serum ferritin concentrations: results of a randomized controlled trial.", "Weekly vs daily iron and folic acid supplementation in adolescent Nepalese girls.", "Iron-deficiency anaemia and its response to oral iron: report of a study in rural Gambian children treated at home by their mothers.", "Prophylactic iron supplementation for underprivileged school boys. I. Two levels of dosing and efficacy of teacher-distributions.", "Zinc-iron, but not zinc-alone supplementation, increased linear growth of stunted infants with low haemoglobin.", "Haematological effect of iron supplementation in breast fed term low birth weight infants.", "Improvements in growth following iron supplementation in young Kenyan school children.", "Supplemental vitamin A improves anemia and growth in anemic school children in Tanzania." ]

[ "A randomized, placebo-controlled treatment trial was conducted among 546 anemic (hemoglobin concentration, 7-11 g/dL) children aged 2-36 months in an area with intense malaria transmission in western Kenya. All children used bednets and received a single dose of sulfadoxine-pyrimethamine (SP) on enrollment, followed by either intermittent preventive treatment (IPT) with SP at 4 and 8 weeks and daily iron for 12 weeks, daily iron and IPT with SP placebo, IPT and daily iron placebo, or daily iron placebo and IPT with SP placebo (double placebo). The mean hemoglobin concentration at 12 weeks, compared with that for the double-placebo group, was 1.14 g/dL (95% confidence interval [CI], 0.82-1.47 g/dL) greater for the IPT+iron group, 0.79 g/dL (95% CI, 0.46-1.10 g/dL) greater for the iron group, and 0.17 g/dL (95% CI, -0.15-0.49 g/dL) greater for the IPT group. IPT reduced the incidence of malaria parasitemia and clinic visits, but iron did not. The combination of IPT and iron supplementation was most effective in the treatment of mild anemia. Although IPT prevented malaria, the hematological benefit it added to that of a single dose of SP and bednet use was modest.", "This prospective, double-blind, placebo-controlled trial was designed to study the effect of iron therapy on the growth of iron-replete and iron-deficient children, and to study the change in iron status in iron-deficient children with iron therapy. One hundred and fifty children (aged 6-24 months) were included in the study. After an informed written consent, 100 healthy children, who were iron replete (group I) according to preset criteria, were randomly allocated to receive iron supplements 2 ng/kg/day (group IA) or placebo (group IB). Fifty iron-deficient children (group II) were administered iron syrup 6 mg/kg/day. Growth parameters (weight, length and head-circumference) and hematological parameters were studied for 4 months. Iron therapy, as compared with placebo, produced a significant improvement of mean monthly weight gain (p < 0.001) and linear growth (p < 0.001) in the iron-deficient children. However, it significantly decreased the weight gain (p < 0.001) and linear growth (p < 0.001) of iron-replete children. Caution should therefore be exercised while supplementing iron to children with apparently normal growth and when the iron status of the child is not known.", "A double-blind clinical trial was conducted in Indonesia to assess effects of iron supplementation on performance of iron-depleted and iron-deficient anemic children in discrimination and oddity learning tasks. Half these children received elemental Fe for 8 wk; the others received a placebo. There were significant changes from pre- to postintervention evaluations in ferritin, transferrin saturation, free erythrocyte protoporphyrin, and hemoglobin among the anemic and iron-depleted children; no changes were observed among the placebos or any of the iron-replete children. The magnitude of hematological changes in anemic children treated with iron was small; yet, after treatment the children's mean ferritin, transferrin saturation, and hemoglobin values were above the cutoff points used for the definition of iron-deficiency anemia (IDA). Pre- and posttreatment psychological test data show that IDA produces alterations in cognitive processes related to visual attention and concept acquisition, alterations reversed with iron treatment.", "In rural Mexico and in many developing countries micronutrient deficiencies, growth stunting, and morbidity from infectious diseases are highly prevalent in young children. We assessed the extent to which growth stunting could be reversed and the number of infectious disease episodes reduced by zinc and/or iron supplementation. In a double-blind, randomized community trial 219 Mexican preschoolers were supplemented with either 20 mg Zn as zinc methionine, 20 mg Fe as ferrous sulfate, 20 mg Zn + 20 mg Fe, or a placebo. After 12 mo, plasma zinc increased significantly in the two zinc-treated groups, and plasma ferritin was significantly higher in the two iron-treated groups. There was no effect of treatments on growth velocity or body composition. Children in both zinc-supplemented groups had fewer episodes of disease (zinc alone, 3.9 +/- 0.3; zinc+iron, 3.7 +/- 0.4; placebo, 4.6 +/- 0.5; P < 0.03), including diarrhea (zinc alone, 0.7 +/- 0.1; zinc+iron, 0.8 +/- 0.1; placebo, 1.1 +/- 0.2; P < 0.01). Zinc and zinc+iron supplements reduced morbidity but had no effect on growth or body composition.", "In developing countries, low food intake is often reported in children < 5 y old. Reduced appetite may be a contributing factor. We investigated whether a combination of a multivitamin-multimineral supplement and additional iron treatment improved appetite and growth of 18- to 30-mo-old stunted and anemic Beninese children. The study was placebo-controlled using VITALIA tablets (11 vitamins and 10 minerals) and ferrous fumarate tablets (66 mg of iron). One hundred fifty stunted (height-for-age Z score < -2) and anemic children (hemoglobin < 110 g/L) were randomly assigned to one of four groups: group 1, multivitamin-multimineral plus iron; group 2, multivitamin-multimineral plus placebo; group 3, placebo plus placebo; and group 4, placebo plus iron. Supplementation was daily and supervised for 6 wk. Appetite, knee-heel length, dietary intakes and morbidity were assessed before and after supplementation. Length, weight, arm circumference and hemoglobin concentration were assessed before, just after supplementation and 4 mo after the intervention. Appetite was assessed by means of an appetite test using a test food, riz-au-gras, eaten ad libitum after an overnight fast. Dietary intakes were assessed during three consecutive days in a subsample by means of the observed weighed record method. Energy intake from the habitual breakfast was significantly correlated with that from the test food (r = 0.49, n = 38, P = 0.002). There were no differences among groups in changes in appetite and growth performance. The habitual diet of the children was monotonous and contained only small amounts of animal products. The morbidity status of the children was comparable in all study groups, before as well as after supplementation. We conclude that the 6-wk multivitamin-multimineral supplementation with additional iron treatment failed to improve the appetite and growth of the children.", "To determine the effectiveness of combined iron and zinc over the iron or zinc-only supplementation in correcting deficiency and possible interactive effects in a group of adolescent school children.\n Schoolchildren (n=821) of 12-16 years of age were randomized into four groups and supplemented with iron (50 mg/day), zinc (14 mg/day), iron+zinc or placebo capsules 5 days per week for 24 weeks. Anthropometry, and haemoglobin (Hb), serum zinc (SZn) and serum ferritin (SF) concentrations were determined before and after the intervention.\n There were no significant effects between-groups in their weight, height and Hb concentrations with the intervention when compared with the placebo group. Iron-only and combination-supplemented groups had reached mean SF concentrations of 55.1 microg/l with no difference between them (P=0.99). The zinc-only group had a mean change of 4.3 micromol//l whereas the combine-supplemented group had a mean change of 4.0 micromol/l (P=0.82). The prevalence of anaemia was found to be 70.3% in the iron group at baseline; this was reduced to 14.5% after the supplementation. In the combine-supplemented group anaemia, prevalence was reduced from 64.8 to 19.3%.\n Zinc alone or in combination with iron has not shown a significant improvement in growth in adolescence. Severe and moderate forms of anaemia were successfully treated in children who received iron supplementation. Initial high prevalence of low SZn and iron stores was significantly improved with micronutrient supplementation.", "To assess the efficacy and acceptability of a daily and intermittent iron supplementation, a double-blind, placebo-controlled trial was conducted in a public school located in periurban Lima, Peru. Adolescent girls (n = 312), 12-18 y old, were randomly assigned to one of the following three groups: 1) 60 mg iron as ferrous sulfate daily from Monday to Friday; 2) 60 mg iron as ferrous sulfate 2 d/wk and 3 d placebo (intermittent); 3) placebo, from Monday to Friday. Field workers gave the girls supplements during school hours for 17 wk; 296 girls completed the trial. Girls took 94% of the expected dose of 85 pills. Few side effects were reported. Postintervention, hemoglobin (Hb), serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) were improved significantly in the iron-supplemented groups compared with placebo (P<0.05). Daily supplements led to higher Hb increases than intermittent supplements (P<0.05), but SF and FEP were similar between the two groups. Thus, both iron supplementation schedules were efficacious in preventing iron deficiency in adolescent girls through the school system, and the daily schedule was better than the intermittent schedule at increasing Hb values and reducing anemia.", "Iron deficiency is prevalent in children and infants worldwide. Zinc deficiency may be prevalent, but data are lacking. Both iron and zinc deficiency negatively affect growth and psychomotor development. Combined iron and zinc supplementation might be beneficial, but the potential interactions need to be verified. In a randomized, placebo-controlled trial using 2 x 2 factorial design, 609 Thai infants aged 4-6 mo were supplemented daily with 10 mg of iron and/or 10 mg of zinc for 6 mo to investigate effects and interactions on micronutrient status and growth. Iron supplementation alone increased hemoglobin and ferritin concentrations more than iron and zinc combined. Anemia prevalence was significantly lower in infants receiving only iron than in infants receiving iron and zinc combined. Baseline iron deficiency was very low, and iron deficiency anemia was almost nil. After supplementation, prevalence of iron deficiency and iron deficiency anemia were significantly higher in infants receiving placebo and zinc than in those receiving iron or iron and zinc. Serum zinc was higher in infants receiving zinc (16.7 +/- 5.2 micromol/L), iron and zinc (12.1 +/- 3.8 micromol/L) or iron alone (11.5 +/- 2.5 micromol/L) than in the placebo group (9.8 +/- 1.9 micromol/L). Iron and zinc interacted to affect iron and zinc status, but not hemoglobin. Iron supplementation had a small but significant effect on ponderal growth, whereas zinc supplementation did not. To conclude, in Thai infants, iron supplementation improved hemoglobin, iron status, and ponderal growth, whereas zinc supplementation improved zinc status. Overall, for infants, combined iron and zinc supplementation is preferable to iron or zinc supplementation alone.", "1. Behavioural responses of young anaemic Indian children to iron-folic acid supplements were assessed in two separate studies using the Indian adaptation of Wechsler's (1967) intelligence scale for children (WISC). 2. The first study was an exploratory study in which the cognitive behaviour of 5-8-year-old children of both sexes was assessed before and after supplementation with 20 mg elemental Fe and 0.1 mg folic acid given daily for a period of 60 d. 3. The supplemented children showed a significant improvement in haemoglobin (Hb) as well as the WISC scores while the control children who did not receive any supplements failed to show an improvement either in Hb or in the WISC scores. However, within the supplemented group when the initially-anaemic children were compared with the initially-non-anaemic ones, only the 7-year-old anaemic children performed significantly poor in the tests than the non-anaemic group of the same age. The study raised the possibility that in addition to increasing the blood Hb levels, Fe-folic acid supplements may have additional benefits in improving the cognitive performance of children. 4. In the second study, cognitive behaviour of fourteen matched pairs of anaemic children in the age-range of 5-6 years was assessed before and after supplementation with 40 mg Fe and 0.2 mg folic acid given daily in two divided doses or sugar placebos for a period of 60 d. The tester did not know the groups to which each child belonged. 5. The supplemented children showed a significant improvement in Hb as well as in the verbal and performance IQ of WISC. The control children showed no improvement in Hb but their verbal IQ improved significantly. However, there was no significant improvement in their performance IQ. 6. The results indicated that Fe-folic acid supplements to anaemic children not only raised Hb levels but also improved intelligence test results, particularly in the performance section.", "nan", "Ninety-nine anemic children aged 1-8 y were divided into four groups. Each group was supplemented for 2 mo with vitamin A, iron, vitamin A plus Fe, or a placebo. Clinical, hematological, and Fe biochemical evaluations were performed at the beginning and end of the study. Vitamin A supplementation produced significant elevations in the serum levels of retinol, blood hemoglobin, hematocrit, erythrocytes, serum Fe, and percent transferrin saturation (%TS) and had no effect on total Fe binding capacity (TIBC) or serum ferritin. Fe supplementation did not affect serum retinol. However, it improved hematological and Fe nutrition indicators, including TIBC and serum ferritin. The simultaneous administration of vitamin A and Fe resulted in a better response of serum Fe and %TS than when the supplement consisted only of vitamin A or Fe alone. Vitamin A benefits hematological condition and Fe metabolism.", "Adult males and children between 4 and 12 years in a subsistence farming community in The Gambia were screened for haematological status. 80 men and 80 children with initially poor status were identified and allocated to three treatment groups comprising: a placebo, ferrous sulphate, and ferrous sulphate with riboflavin. Over a period of 6 weeks of supplementation there was a general improvement in haematological status in the two supplemented groups. The inclusion of riboflavin in the supplement enhanced recovery, particularly in those individuals with strikingly low levels of haemoglobin at the outset.", "Deficiencies of iron and zinc are associated with delayed development, growth faltering, and increased infectious-disease morbidity during infancy and childhood. Combined iron and zinc supplementation may therefore be a logical preventive strategy.\n The objective of the study was to compare the effects of combined iron and zinc supplementation in infancy with the effects of iron and zinc as single micronutrients on growth, psychomotor development, and incidence of infectious disease.\n Indonesian infants (n = 680) were randomly assigned to daily supplementation with 10 mg Fe (Fe group), 10 mg Zn (Zn group), 10 mg Fe and 10 mg Zn (Fe+Zn group), or placebo from 6 to 12 mo of age. Anthropometric indexes, developmental indexes (Bayley Scales of Infant Development; BSID), and morbidity were recorded.\n At 12 mo, two-factor analysis of variance showed a significant interaction between iron and zinc for weight-for-age z score, knee-heel length, and BSID psychomotor development. Weight-for-age z score was higher in the Zn group than in the placebo and Fe+Zn groups, knee-heel length was higher in the Zn and Fe groups than in the placebo group, and the BSID psychomotor development index was higher in the Fe group than in the placebo group. No significant effect on morbidity was found.\n Single supplementation with zinc significantly improved growth, and single supplementation with iron significantly improved growth and psychomotor development, but combined supplementation with iron and zinc had no significant effect on growth or development. Combined, simultaneous supplementation with iron and zinc to infants cannot be routinely recommended at the iron-to-zinc ratio used in this study.", "To assess the effects of iron supplementation on immunological parameters of adolescents with varying iron status.\n Adolescents of both sexes with varying iron status were allocated to four treatment groups by using inclusion criteria. Three of the four groups received iron(III)-hydroxide polymaltose complex (IPC, Maltofer) containing 100 mg of iron 6 days a week for 8 months. The fourth group was given a placebo. Immunological parameters were assessed at baseline and after 4 and 8 months of supplementation.\n Increases from baseline to 4 months and from 4 to 8 months of supplementation were observed for Bactericidal Capacity of Neutrophils (BCA), NitroBlue Tetrazolium Reduction Test (NBT), and phytohaemagglutinin (PHA) in all three supplemented groups. No increase was found in the control placebo group except for PHA. No side effects were noted in any participants.\n IPC supplementation for eight months led to significant improvements of immunological parameters in iron deficient adolescents with and without anemia.", "Oral iron supplementation is often routinely given to children with malaria-associated anaemia, but its contribution to recovery is controversial. A randomized clinical trial, evaluating such routine, was carried out among 100 children, who had a haemoglobin of < or = 5 g/dl and a positive blood smear for malaria parasites. All children received malaria therapy (chloroquin + fansidar) and were randomly allocated to two groups, one receiving additional oral iron treatment, the other being the control. In the 12-week follow-up period the haemoglobin level and malaria indices were measured at 2, 4, 8, and 12 weeks. There was a 100 per cent compliance during the follow-up period. In each group 20 children (40 per cent) required a blood transfusion. In the remaining 60 children, after 2 weeks the haemoglobin had risen 3.7 g/dl in the ferrous-supplemented group compared to 3.5 g/dl in the non-ferrous group. Thereafter, the increase in haemoglobin in both groups was steady. At follow-up measurements, the groups did not differ for haemoglobin levels. The mean haemoglobin at 12 weeks was 9.2 and 9.0 g/dl, respectively. It was concluded that iron supplementation did not have any effect on the rate of parasitaemia and on parasite density during the 12 weeks. However, the iron-supplemented group had a significantly increased morbidity from other causes than malaria. It appears that iron does not have an effect on the recovery of haemoglobin level in children with malaria-associated anaemia. This study provides no evidence supporting routine iron supplementation to these children.", "nan", "Iron deficiency and anemia remain among the most important global public health problems facing school children. Helminth infections often peak at school age and aggravate nutritional risks. We conducted a 12-wk randomized controlled trial in 406 Malian anemic schoolchildren infected with Schistosoma hematobium to examine the effects of 2 doses of praziquantel (P) (40 mg/kg body weight), P + 60 mg/d iron (Fe), and/or a multiple micronutrient supplement (MM) that included 18 mg/d Fe. Supplements were administered to the children each school day (5 d/wk) throughout the study. Changes in hemoglobin (Hb), serum ferritin (SF), and serum transferrin receptors (s-TfR) were followed. We also examined interactions between Fe and MM supplements on Hb and SF concentrations and malaria incidence. The effects of Fe on Hb and SF concentrations were greater than the effects of P alone and MM with or without added Fe at 6 and 12 wk (P < 0.001). In all groups, s-TfR decreased at 6 and 12 wk compared with baseline. The decrease was most pronounced in the P + Fe group compared with the other 3 groups at wk 6 (P = 0.05). Fe and MM interacted negatively at wk 6 and 12 to affect Hb (beta = -0.43, 95% CI = -0.77, -0.09; P = 0.01 and beta = -0.47, 95% CI = -0.83, -0.11; P = 0.01, respectively) and SF (beta = -0.42, 95% CI = -25.60, 12.31; P < 0.001, and beta = -0.37, 95% CI = -0.63, -0.12; P = 0.004, respectively). Malaria incidence was higher in the groups treated with added Fe (relative risk: 1.66; 95% CI: 0.75, 3.67). In this context, MM with added iron were not more effective than Fe without MM. Fe supplementation of schoolchildren with 60 mg/d for anemia control should be considered carefully.", "To assess the effects of iron and deworming on linear growth performance of preschoolers.\n Three-month randomized, double-blind and placebo-controlled trial. The children were allocated to four treatments: iron (60 mg elemental iron/day) + albendazole (200 mg/day for 3 consecutive days, repeated 1 month later), iron + albendazole-placebo, albendazole + iron-placebo or placebos. The supplementation was supervised.\n A group of 177 children aged 3-5 y was selected from low-income households in a rural area in southern Bénin. A complete data set was analysed for 140 subjects. Many children were stunted (58% had height-for-age Z-score <-2), none were wasted (2% had weight-for-height Z-score < -2) and 76% were anemic (Hb < 110 g/l).\n Anthropometric parameters, hemoglobin and eggs per gram feces.\n No significant difference in changes in anthropometric parameters was observed between study groups, and also not in a sub-sample of stunted and anemic subjects. Changes in hemoglobin were highest in the iron-treated subjects at the end of the 3-month intervention period (P = 0.032). The difference between the iron and the placebo groups remained significant even 7 months later (P = 0.022). The difference was 5 g/l in both periods. Ascaris lumbricoides and hookworm infections decreased significantly in albendazole-treated subjects (P < 0.05).\n In addition to recurrent parasitic infection burden, the children may have multiple micronutrient deficiencies. Therefore, it may be interesting to study appetite and food intake of young toddlers in relation to health and linear growth performance in poor environments.", "nan", "To compare the efficacy of a daily and a weekly iron supplementation on the hematological status of anemic children living at high altitude.\n Double blind iron supplementation trial including a placebo control group.\n A socioeconomically disadvantaged district of La Paz, Bolivia (altitude of 4000 m).\n Anemic (hemoglobin concentration < or = 144 g/L), 3.3-8.3 y old children of both sexes.\n Children received a placebo (n = 57) or a dose of 3-4 mg of elemental iron per kg body weight (FeSO4 tablets) 1 d per week (n = 58) or 5 d per week (n = 58) for 16 weeks.\n Hemoglobin and zinc erythrocyte protoporphyrin concentrations improved significantly in supplemented groups but not in the placebo group. Changes in hemoglobin during the study were not significantly different between supplemented groups (weekly group: 15.2 +/- 6.9 g/L and daily group: 18.6 +/- 11.1 g/L) but were different from the placebo group (0.5 +/- 7.1 g/L, P < 0.001). At the end of the supplementation period, the hemoglobin distribution was Gaussian, and similar in both supplemented groups. Adjusting for the initial hemoglobin concentration, final hemoglobin and its changes were similar in both supplemented groups.\n Weekly iron supplementation is as efficacious as daily iron supplementation in improving iron status and correcting moderate iron deficiency anemia in Bolivian school children living at high altitude.\n Program supported in part by ORSTROM, the French Ministry of Foreign Affairs and the National Secretary's Office of Health, Bolivia.", "Iron-deficient anaemic infants perform worse in tests of mental and motor development than do iron-sufficient infants of a comparable age. A randomised, double-blind trial was done to monitor the effects of iron supplementation on performance in the Bayley scales of mental and motor development among 12-18-month-old infants in Indonesia. Iron-deficient anaemic infants (n = 50) were assigned randomly to receive dietary ferrous sulphate or placebo for 4 month. Similar treatment randomisation was done among nonanaemic iron-deficient (n = 29) and iron-sufficient (n = 47) infants. Before intervention, the mean mental and motor scores of the iron-deficient anaemic infants were significantly (p < 0.01) lower than those of the nonanaemic iron-deficient and iron-sufficient classes. After intervention, developmental delays were reversed among iron-deficient anaemic infants who had received iron but they remained the same among placebo-treated iron-deficient anaemic infants. Neither ferrous sulphate nor placebo had significant effects on the scores of the other two iron-status classes. The poor performance of 12-18-month-old iron-deficient anaemic infants in the Bayley scales of mental and motor development can be improved to the level of performance of iron-sufficient infants by treatment with ferrous sulphate.", "Malaria and anaemia, especially that due to iron deficiency, are two leading causes of morbidity worldwide. Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas. We undertook a randomised comparison of different strategies for control of anaemia and malaria in infants, including an assessment of the effect of iron supplementation on malaria susceptibility.\n 832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October, 1995, were randomly assigned to group DI, receiving daily oral iron (2 mg/kg daily) plus weekly Deltaprim (3.125 mg pyrimethamine plus 25 mg dapsone); group IP, receiving iron plus weekly placebo; group DP, receiving daily placebo plus weekly Deltaprim; or group PP. supplementation was given from 8 to 24 weeks of age, and the weekly chemoprophylaxis from 8 to 48 weeks. The frequency of severe anaemia (packed-cell volume < 25%) and malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys.\n The groups that received iron supplementation had a lower frequency of severe anaemia than those that did not receive iron (0.62 vs 0.87 cases per person-year; protective efficacy 28.8% [95% CI 6.3-45.8). Iron supplementation had no effect on the frequency of malaria (0.87 vs 1.00 cases per person-year; protective efficacy 12.8% [-12.8 to 32.5]). The groups that received malaria prophylaxis had lower frequencies of both severe anaemia (0.45 vs 1.04 episodes per person-year; protective efficacy 57.3% [43.0-67.9]) and malaria (0.53 vs 1.34 episodes per person-year; protective efficacy 60.5% [48.2-69.9]) than the groups that did not receive prophylaxis. After the end of the intervention period, children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups (relative risks 2.2 [1.3-3.7] and 1.8 [1.3-2.6]).\n Malaria chemoprophylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity. Iron supplementation was effective in preventing severe anaemia without increasing susceptibility to malaria. Our findings support iron supplementation of infants to prevent iron-deficiency anaemia, even in malaria-endemic areas.", "Iron deficiency anemia is a major public health problem in developing countries and may affect school performance and physical work capacity in nonpregnant adolescents, and may increase the risk of anemia during subsequent teenage pregnancies. We assessed the effect of weekly iron (120 mg elemental iron) and vitamin A (25 000 IU) supplementation on hemoglobin, iron status and malaria and nonmalaria morbidity in adolescent schoolgirls.\n A total of 279 schoolgirls aged 12-18 years from public primary schools in Kisumu, western Kenya. Double-blind randomized placebo-controlled trial using a factorial design.\n Five months of iron supplementation was associated with a 0.52 g dl(-1) (0.21, 0.82) greater increase in hemoglobin relative to iron placebo. The effect was only observed in girls with iron deficiency on enrollment (1.34 g dl(-1) (0.79, 1.88)), but not in iron-replete girls (-0.20 g dl(-1) (-0.59, 0.18)). Similar differences in treatment effect were seen between menstruating and nonmenstruating girls. The effect of iron was independent of vitamin A. The baseline prevalence of vitamin A deficiency was low (6.7%) and no sustained increase in hemoglobin was seen with weekly vitamin A (-0.07 g dl(-1) (-0.38, 0.25)). Incidence of malaria parasitemia was higher in the iron than iron-placebo groups (Rate ratio 1.33 (0.94, 1.88)).\n Weekly iron supplementation results in substantial increases in hemoglobin concentration in adolescent schoolgirls in western Kenya, which may outweigh possible risks caused by malaria, but only in iron-deficient or menstruating girls and not in iron-replete and nonmenstruating girls.", "nan", "To combat iron deficiency manifesting around six months of age, iron-fortified complementary feeding has been recommended. In developing countries, in view of the poor bioavailability of iron from predominantly cereal-based diets and the high cost of fortification, medicinal iron supplementation is an alternative intervention. This double-blind randomized placebo-controlled trial was conducted from April 1999 to March 2000 in the Out-patient Department of a tertiary hospital in New Delhi, India, to evaluate the haematological effects of medicinal iron supplementation to breastfed young infants initiated on complementary feeding. One hundred healthy non-low birth-weight, predominantly breastfed infants aged 4-6 months were randomized into two groups to receive either iron (2 mg/kg/day) (IS group; n=49) or placebo drops (P group; n=51) beginning with the initiation of home-based non-fortified complementary feeding. Haematological parameters and anthropometry of mothers and infants were measured at baseline and repeated for infants after four and eight weeks of recruitment. Seventy-one subjects (35 in the IS group and the 36 in P group) came for the first follow-up, and of these, 43 (19 in the IS group and 24 in the P group) reported for the second visit. The adjusted (for maternal and baseline infant ferritin) serum ferritin levels were significantly higher in the IS group at both the follow-ups (p=0.006). The adjusted (for maternal ferritin and baseline infant ferritin) change in haemoglobin was significantly higher only at the second follow-up (0.7 g/dL; 95% confidence interval [CI] 0.3-1.0 g/dL). The adjusted rise in haemoglobin was higher in initially anaemic infants (at second follow-up by 1 g/dL; 95% CI 0.5-1.6 g/dL). Medicinal iron supplementation, at the time of initiating complementary feeding, to breastfed young infants resulted in an elevation of serum ferritin and haemoglobin. The response was higher in initially anaemic infants. From a programmatic perspective, evidence needs to be generated on the relative merits of selective (anaemic) versus general supplementation and daily versus weekly supplementation.", "The effects of oral iron supplementation on blood iron levels and learning achievement in 130 rural Indonesian school children were assessed in this double-blind study. The children were classified into anemic and nonanemic groups according to their initial hemoglobin and transferrin saturation levels and were randomly assigned to either iron or placebo treatment for 3 mo. Hematological, anthropometric, and learning-achievement data were collected before (T1) and after (T2) the treatment period and 3 mo later. The means and standard deviations suggest that supplementation with 10 mg ferrous sulfate per kilogram body weight per day for 3 mo resulted in an apparent improvement in anemic subjects' hematological status and learning-achievement scores. No tests of statistical comparisons are reported.", "The growth status of anemic (n = 117, Hb 7-10 g/dl) and normal (n = 53, H > or = 11 g/dl) children 3-5 years of age living under similar environmental and socio-economic conditions was evaluated. The dietary intake was assessed on a random subsample of the anemic and normal children. The anemic children had a poorer growth status than normal children as indicated by their significantly (p < 0.001) lower body weight, height and weight for age and significantly (p < 0.001) larger number in Grades II and III malnutrition. Iron supplementation (40 mg elemental iron/day) for six months produced a significant (p < 0.001) increase in Hb levels of both groups (1.6 g/dl in the anemic and 0.8 g/dl in the non-anemic) compared to their respective controls who received sugar placebos. The growth performance of the anemic children supplemented with iron was superior to that of anemic placebo treated children as indicated by a better weight gain and a significantly higher weight for height (p < 0.05). Weight for age was a good differentiator of the anemic from normal while weight for height was a good indicator of the impact of iron supplements on growth.", "Diets of infants across the world are commonly deficient in multiple micronutrients during the period of growth faltering and dietary transition from milk to solid foods. A randomized placebo controlled trial was carried out in Indonesia, Peru, South Africa, and Vietnam, using a common protocol to investigate whether improving status for multiple micronutrients prevented growth faltering and anemia during infancy. The results of the pooled data analysis of the 4 countries for growth, anemia, and micronutrient status are reported. A total of 1134 infants were randomized to 4 treatment groups, with 283 receiving a daily placebo (P), 283 receiving a weekly multiple micronutrient supplement (WMM), 280 received a daily multiple micronutrient (DMM) supplement, and 288 received daily iron (DI) supplements. The DMM group had a significantly greater weight gain, growing at an average rate of 207 g/mo compared with 192 g/mo for the WMM group, and 186 g/mo for the DI and P groups. There were no differences in height gain. DMM was also the most effective treatment for controlling anemia and iron deficiency, besides improving zinc, retinol, tocopherol, and riboflavin status. DI supplementation alone increased zinc deficiency. The prevalence of multiple micronutrient deficiencies at baseline was high, with anemia affecting the majority, and was not fully controlled even after 6 mo of supplementation. These positive results indicate the need for larger effectiveness trials to examine how to deliver supplements at the program scale and to estimate cost benefits. Consideration should also be given to increasing the dosages of micronutrients being delivered in the foodlets.", "To examine the effectiveness of weekly iron supplements given for 10 weeks by teachers to children in rural schools in the Philippines.\n Forty-nine rural primary schools took part in the study and were randomly assigned to two groups: children in 25 schools received a weekly tablet providing 108 mg iron while children in 24 schools acted as controls. All children were dewormed before the start of the iron supplementation. The haemoglobin concentration of a systematic sample of one in three children in two classes in each school was estimated before and 5-17 weeks after the end of the iron supplementation.\n A total of 1510 children aged 7-12 years were studied at both surveys. The mean haemoglobin concentration of children in the intervention group did not change significantly; in the untreated group it fell by 3.8 g/l and the prevalence of anaemia rose from 14.3% to 25.6%. The difference between study groups was significantly larger amongst the younger children (7-8 years), and was observed in both anaemic and non-anaemic children.\n Even where anaemia is only a mild public health problem, weekly iron supplements given by teachers may prevent a fall in the haemoglobin concentration, and can benefit both anaemic and non-anaemic children.", "To assess the effect on the haemoglobin concentrations of schoolchildren of weekly iron tablets administered by teachers.\n Sixty schools were randomly assigned to two groups: in 30 schools children were given weekly for 10 weeks a tablet providing 65 mg of iron and 0.25 mg of folic acid; in the other 30 schools no iron tablets were given. All children were dewormed and given vitamin A before the study began. The haemoglobin concentration of up to 20 randomly selected children in each school was estimated before and 2 weeks after the end of treatment.\n Rural community schools in Kolondieba district of Mali.\n Some 1113 schoolchildren aged 6-19 years with a mean of 11.4 years.\n The haemoglobin concentration of treated children rose on average by 1.8 g l(-1) and the prevalence of anaemia fell by 8.2%; in untreated children the haemoglobin concentration fell by an average of -2.7 g l(-1) and the prevalence of anaemia rose by 9.4%. The fall in haemoglobin concentration among untreated girls of -4.0 g l(-1) was greater than in untreated boys (-0.3 g l(-1) ).\n Weekly iron tablets given by teachers prevented a general fall in the haemoglobin concentrations of untreated children, and led to a small but statistically significant rise among treated children. Young children benefited more than children aged >or=12 years, and girls benefited more than boys.", "The effect of oral iron supplementation on blood Fe levels and physical growth in 119 rural Indonesian school children was assessed in this double-blind study. The children were classified into anemic and normal groups according to their initial hemoglobin and transferrin saturation levels and were randomly assigned to either Fe or placebo treatment for 12 wk. Hematological, anthropometric, and morbidity data were collected before and after the treatment period. Before treatment, anemic subjects were smaller and had higher morbidity than normal subjects. Treatment with 10 mg ferrous sulfate.kg-1.d-1 for 12 wk resulted in a significant improvement in anemic subjects' hematological status, growth velocity, and level or morbidity.", "A randomized controlled trial in KwaZulu-Natal (South Africa) of 428 primary-school pupils (stratified into 6 groups by age, sex and intervention) measured the effect of different anthelmintic treatments and iron supplementation regimens provided twice at 6-monthly intervals for 1 year (1996/97). Half the pupils received iron supplementation (ferrous fumarate 200 mg weekly for 10 weeks). Pupils received 2 anthelmintic regimens, either (i) albendazole 400 mg plus praziquantel 40 mg/kg or (ii) albendazole 400 mg on 3 consecutive days plus praziquantel 40 mg/kg or (iii) placebo. Baseline prevalences of Ascaris 55.9%, Trichuris 83.6%, hookworm spp. 59.4%, were reduced after 12 months for single-dose albendazole treatment to Ascaris 17.4% (P < 0.005), Trichuris 61.5% (NS), hookworm spp. 0% (P < 0.005), and for triple-dose albendazole treatment to Ascaris 14.8% (P < 0.005), Trichuris 25.0% (P < 0.01), hookworm 0% (P < 0.005). Schistosoma haematobium 43.4% was reduced among treated groups to 8.3% (P < 0.005). There were no significant changes in the anthropometry of the different treatment groups at either 6 or 12 months post treatment. Twelve months after treatment there was a significant increase in haemoglobin levels (P = 0.02) among pupils receiving triple-dose albendazole, praziquantel and ferrous fumarate; pupils receiving no anthelmintic treatment showed a significant decrease as did pupils who received triple-dose albendazole and praziquantel but no iron. Regular 6-monthly anthelmintic treatment significantly reduced the prevalence of Ascaris, hookworm spp. and S. haematobium infections (P < 0.05). Triple-dose treatment for Trichuris was significantly more effective than a single dose of albendazole 400 mg (P = 0.002). In areas with schistosomiasis, hookworm infection and high prevalence of Trichuris infection, combination treatment with praziquantel, triple-dose albendazole, plus iron supplementation, is likely to improve pupils' health and haemoglobin levels.", "Given the high prevalence of micronutrient deficiencies and infectious diseases in infants in developing countries, an evaluation of the efficacy of different micronutrient formulations on infant morbidity is a priority. The efficacy of weekly supplementation of four different micronutrient formulations on diarrhea and acute lower respiratory infection (ALRI) morbidity was evaluated in Bangladeshi infants. In a double-blind, randomized, controlled community trial, 799 infants aged 6 mo were randomly assigned to one of the following 5 groups: 1) 20 mg elemental iron with 1 mg riboflavin, 2) 20 mg elemental zinc with 1 mg riboflavin, 3) 20 mg iron and 20 mg zinc with 1 mg riboflavin, 4) a micronutrient mix (MM) containing 20 mg iron, 20 mg zinc, 1 mg riboflavin along with other minerals and vitamins and 5) a control treatment, 1 mg riboflavin only. Health workers visited each infant weekly until age 12 mo to feed the supplement and to collect data on diarrhea and ALRI morbidity. Hemoglobin, serum ferritin and serum zinc levels of a sample of infants were measured at 6 and 12 mo. Compared with the control group, at 12 mo, serum ferritin levels were higher in the iron + zinc group, and serum zinc levels were higher in the zinc and iron + zinc groups. Simultaneous supplementation with iron + zinc was associated with lower risk of severe diarrhea, 19% lower in all infants and 30% lower in less well-nourished infants with weight-for-age Z-score below -1. Iron + zinc supplementation was also associated with 40% lower risk of severe ALRI in less well-nourished infants. MM supplementation was associated with a 15% higher risk of diarrhea in all infants and 22% higher risk in less well-nourished infants. Intermittent simultaneous supplementation with iron + zinc seems promising; it will be useful to determine whether higher doses would provide greater benefits.", "This experimental study was designed to investigate the effects of daily versus intermittent iron supplementation on iron status of high school girls in Zahedan and Rasht cities in 1996-1997. The subjects were selected randomly from among students of grades 1-3 of four high schools in each city. Anemia was determined by measuring hematological indices. 260 anemic and a similar number of non-anemic subjects of 4 high schools were selected and allocated randomly to 4 treatment groups. During a 3-month period, the test groups were given 150 mg ferrous sulfate tablets (50 mg Fe). Subjects in group 1 received a daily dose, groups 2 & 3 received twice or once weekly doses respectively. The control group received no iron supplement. For these subjects, in addition to hematological indices biochemical iron indices were measured in the beginning and at the end of the study. The increases in hemoglobin concentration in anemic subjects were not significantly different among supplemented groups but were different from the control group (p < 0.00001). Among anemic subjects, changes in serum ferritin levels in 3 supplemented groups were significantly different from the control group. Serum ferritin in Group 1 was also increased to a greater extent than groups 2 and 3 (P < 0.00001). It is concluded that over the study period a weekly iron dose was as effective as a daily dose in treating anemia but the daily dose was more effective in improving iron stores than a weekly dose in the short run.", "Recent data suggest that daily iron supplementation of iron-replete children could impair their growth. If verified for weekly iron supplementation these results would markedly complicate targeting and implementing school-based weekly iron supplementation programs.\n To ascertain the effect of weekly iron supplementation on the growth and hemoglobin status of non-anemic school-age children.\n 73 Bolivian non-anemic school-age children randomly assigned to the treatment group (n = 37; receiving supplements containing FeSO4 during 18 weeks) or the control group (n = 36; receiving a placebo during the same period). Hemoglobin concentration and anthropometric measures were determined for each child at the beginning (T0) and the end (T18) of the study.\n The treatment group did not show any significant variation in hemoglobin concentration between T0 and T18 (-1.6 +/- 10.4 g/L; P = 0.40) whereas the control group showed a significant decrease in hemoglobin concentration (-4.6 +/- 10.9 g/L; P = 0.03). Anthropometric changes were not significantly different between the treatment and the control groups for weight, (1.63 +/- 1.11 kg vs 1.88 +/- 0.79 kg; P = 0.30), height (2.35 +/- 0.94 cm vs 2.11 +/- 1.03 cm; P = 0.34) or mid-upper arm circumference (0.29 +/- 0.57 cm vs 0.22 +/- 0.54 cm; P = 0.64).\n In our study, weekly iron supplementation of non-anemic school-age children had no negative effect on their growth while having a positive effect in preventing significant decreases in hemoglobin concentration. These results suggest that in regions where iron deficiency anemia (IDA) is prevalent, a simple and cost-effective way to control IDA in school-age children is to give weekly iron supplements to all children at school.", "Conflicting evidence exists on the possible role of iron supplementation in the predisposition to malaria infection or the enhancement of its clinical severity. Where anemia prevalence is >40%, current guidelines are to provide low-dose daily iron to young children for up to 18 mo. Earlier studies used doses higher than the current guidelines, intermittent doses, or have supplemented for durations < or = 4 mo. We aimed to assess the effect of low-dose, long-term iron supplementation on malaria infection using a double-blind, placebo-controlled, randomized design, and to examine possible subgroup effects by season and child age. The study was conducted in Pemba Island, Zanzibar, where Plasmodium falciparum malaria has year-round high transmission. A community-based sample of 614 children 4-71 mo old was randomly allocated to 10 mg/d iron or placebo for 12 mo. Outcome measures were the prevalence and density of malaria infection, which was assessed by blood films at monthly intervals. At baseline, 94.4% were anemic (hemoglobin < 110 g/L), 48.1% were stunted (height-for-age Z-score less than -2) and >80% had malaria-positive blood films. No significant differences in malariometric indices were observed between children in the iron-supplemented and placebo groups. Parasite density was higher in certain months and in younger children, but iron supplementation was not associated with any malarial infection outcome in any season or age subgroup. We conclude that in this environment of high malaria transmission, daily oral low-dose supplementation of iron for 12 mo did not affect the prevalence of malaria infection or parasite density.", "Concern has been raised that iron supplementation for treatment of acute malaria may worsen the severity of malaria. We compared the effect of iron and folate with folate alone on hematologic recovery in children treated for acute malaria. We randomized 82 children 6-60 months of age from Nigeria with smear-positive malaria and anemia (hematocrit < 33%) to receive iron (2 mg/kg/day) plus folate (5 mg/day) or folate alone in addition to antimalarial drugs. The mean ± SD hematocrit at baseline was 28.5% ± 2.9%. At four weeks, the mean hematocrit increased by 2.5% ± 1.6% in the iron plus folate group and by 1.4% ± 1.0% in the folate alone group (P = 0.001). Baseline hematocrit, iron supplementation, weight for height, and weekly meat intake were significant predictors of final hematocrit. The effect of iron was not significantly modified by baseline hematocrit, weekly meat intake, nutritional status, mother's education, sex, or age of the child. Iron supplementation improved hematologic recovery in children with malarial anemia.", "In many developing countries, children are at high risk of both goiter and iron deficiency anemia. Iron deficiency adversely affects thyroid metabolism and may reduce the efficacy of iodine prophylaxis in areas of endemic goiter.\n The aim of this study was to determine whether iron supplementation in goitrous, iron-deficient children would improve their response to iodized salt.\n We conducted a randomized, double-blind, placebo-controlled trial in 5-14-y-old children in Côte d'Ivoire. Goitrous, iron-deficient children (n = 166) consuming iodized salt (10-30 mg I/kg salt at the household level) were supplemented with either iron (60 mg Fe/d, 4 d/wk for 16 wk) or placebo. At 0, 1, 6, 12, and 20 wk, we measured hemoglobin, serum ferritin, serum transferrin receptor, whole-blood zinc protoporphyrin, thyrotropin, thyroxine, urinary iodine, and thyroid gland volume (by ultrasonography).\n Hemoglobin and iron status at 20 wk were significantly better after iron treatment than after placebo (P < 0.05). At 20 wk, the mean reduction in thyroid size in the iron-treated group was nearly twice that in the placebo group (x +/- SD percentage change in thyroid volume from baseline: -22.8 +/- 10.7% compared with -12.7 +/- 10.1%; P < 0.01). At 20 wk, goiter prevalence was 43% in the iron-treated group compared with 62% in the placebo group (P < 0.02). There were no significant differences between groups in whole-blood thyrotropin or serum thyroxine at baseline or during the intervention.\n Iron supplementation improves the efficacy of iodized salt in goitrous children with iron deficiency. A high prevalence of iron deficiency among children in areas of endemic goiter may reduce the effectiveness of iodine prophylaxis.", "Iron supplementation is recommended for children at high risk of anaemia, but its benefits may not outweigh the associated risk of malaria in areas of seasonal transmission. We investigated the effect on haemoglobin concentrations of intermittent administration of iron supplements and sulfadoxine-pyrimethamine in symptom-free children under intense health surveillance.\n In a trial of two by two factorial design, 328 anaemic Kenyan children were randomly assigned either iron or placebo and sulfadoxine-pyrimethamine or placebo (82 to each group). Primary outcomes were haemological indicators of iron status and inflammation at the end of the follow-up, and occurrence of malaria attacks. Morbidity surveillance consisted of medical examinations every 4 weeks, continuous passive case detection, and visits twice a week to community health-workers. Analyses were by intention to treat.\n After 12 weeks, the groups assigned iron plus sulfadoxine-pyrimethamine, iron alone, or sulfadoxine-pyrimethamine alone had higher haemoglobin concentrations than the group assigned placebo (treatment effect adjusted for prognostic factors at baseline: 11.1 g/L [95% CI 7.5 to 14.7]; 10.7 g/L [7.1 to 14.3]; and 3.1 g/L [-0.5 to 6.7]). Administration of iron plus sulfadoxine-pyrimethamine also lowered the proportion with anaemia from 100% at baseline to 36% at 12 weeks, and of iron deficiency from 66% at baseline to 8% at 12 weeks. Survival analysis showed no evidence of substantially increased risk of malaria after iron supplementation.\n Iron supplementation gives substantial health benefits, which may outweigh possible inherent risks caused by malaria. A larger study than ours is needed to assess benefits and risks of intermittent administration of sulfadoxine-pyrimethamine in reducing the incidence of malaria attacks in areas of seasonal malaria transmission.", "Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa. However, there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful.\n We did a randomised, placebo-controlled trial, of children aged 1-35 months and living in Pemba, Zanzibar. We assigned children to daily oral supplementation with: iron (12.5 mg) and folic acid (50 mug; n=7950), iron, folic acid, and zinc (n=8120), or placebo (n=8006); children aged 1-11 months received half the dose. Our primary endpoints were all-cause mortality and admission to hospital. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59549825.\n The iron and folic acid-containing groups of the trial were stopped early on Aug 19, 2003, on the recommendation of the data and safety monitoring board. To this date, 24 076 children contributed a follow-up of 25,524 child-years. Those who received iron and folic acid with or without zinc were 12% (95% CI 2-23, p=0.02) more likely to die or need treatment in hospital for an adverse event and 11% (1-23%, p=0.03) more likely to be admitted to hospital; there were also 15% (-7 to 41, p=0.19) more deaths in these groups.\n Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death. In the presence of an active programme to detect and treat malaria and other infections, iron-deficient and anaemic children can benefit from supplementation. However, supplementation of those who are not iron deficient might be harmful. As such, current guidelines for universal supplementation with iron and folic acid should be revised.", "To examine the benefits of anemia prophylaxis in adolescent school.girls by weekly or daily iron-folate supplementation.\n Prospective study.\n Government girl schools of northeast Delhi.\n 2088 subjects (with hemoglobin greater than 7.9 g/dL), including 702 on daily and 695 on weekly iron-folate administration; 691 girls served as controls.\n About 85% girls were iron deficient out of which 49.3% were anemic. Weekly administration took longer time to raise hemoglobin but was effective as well as practical. Plasma ferritin estimation in girls showed rise in level in both the treated groups.\n Weekly administration of iron-folate was a practical and effective strategy for anemia prophylaxis in adolescent school girls.", "Effects of iron supplementation on growth and hematological status of Indonesian anemic preschool children with low weight-for-age were investigated. A treatment group (n = 39) received daily supplements of 30 mg Fe and 20 mg vitamin C, whereas a control group (n = 37) received 20 mg vitamin C only for a period of 2 mo. Supplement allocation was double blind. At the start and finish of the study, body weight, height, food intake, and hemoglobin and serum ferritin concentrations were determined. Only the treatment group showed a significant increase in all hematological values (P < 0.001). Height and weight of all children increased (P < 0.01). Increases in height and height-for-age Z score in the treatment group were larger (P = 0.001) than the increase in the control group. The positive effect of iron supplementation on linear growth was not caused by increased food intake, but seems to be influenced by decreased morbidity. Iron supplementation may be a relatively inexpensive way to help decrease the high prevalence of stunting.", "To evaluate the effect of combined iron-zinc supplementation on micronutrient status, growth and morbidity.\n Randomized, double-masked, placebo-controlled supplementation trial.\n Rural district of Que Vo, in the Red River Delta in Vietnam.\n A total of 915 breast-fed infants aged 4-7 months were included and 784 completed the study.\n The Fe-group received daily and for a 6-month period 10 mg of iron, the Zn-group 10 mg zinc, the Fe-Zn group 10 mg iron+10 mg zinc and the placebo group a placebo. Hemoglobin (Hb), serum ferritin (SF) and zinc (SZn), and anthropometry were measured before and at the end of the intervention. Morbidity was recorded daily.\n Changes of Hb and SF were higher in both Fe and Fe+Zn groups (respectively 22.6 and 20.6 g/l for Hb; 36.0 and 24.8 microg/l for SF) compared to Zn and placebo groups (Hb: 6.4 and 9.8 g/l; SF: -18.2 and -16.9 microg/l, P<0.0001). SZn increased more in Zn group (10.3 micromol/l) than in Fe+Zn group (8.0 micromol/l, P=0.03) and more in these groups compared to Fe and placebo groups (1.6 and 1.2 micromol/l, P<0.0001). Weight gain was higher in the Zn group. No significant effects of supplementations on growth in length or morbidity.\n Combined iron-zinc supplementation had a positive effect on iron and zinc status in infants. However, the positive effect of zinc alone on SZn and weight would indicate a negative interaction of iron when added to zinc supplements.\n UNICEF New York.", "Iron deficiency anemia and recurrent infections are common among children of low socioeconomic status.\n The objective was to evaluate the effects of iron supplementation on iron status and morbidity in children with or without infection.\n Children aged 5-10 y were recruited for a randomized, controlled, double-blind study from outpatients attending the Children's Hospital, Colombo, Sri Lanka. Clinical, inflammatory, nutritional, and iron statuses were determined at baseline and after the intervention. Children with a history of recurrent upper respiratory tract infections (URTIs) and with laboratory and clinical evidence of a current URTI constituted the infection group (n = 179), and children without infection constituted the control group (n = 184). Subjects in both groups were supplemented with ferrous sulfate (60 mg Fe) or placebo once daily for 8 wk. Morbidity from URTIs, the number of gastrointestinal infections, and compliance were recorded every 2 wk.\n The overall prevalence of anemia was 52.6%. Iron supplementation significantly improved iron status by increasing hemoglobin (P < 0.001) and serum ferritin (P < 0.001) concentrations from baseline values in the children with or without infection. There was no significant improvement in iron status in the children who received placebo. In both the infection group and the control group, the mean number of URTI episodes and the total number of days sick with an URTI during the period of intervention were significantly lower (P < 0.005 and P < 0.001, respectively) in the children who received iron supplements than in those who received placebo.\n Iron supplementation significantly improves iron status and reduces morbidity from URTIs in children with or without infection.", "Blood haemoglobin concentrations and reticulocyte counts were determined in 430 school children in grades 1, 3 and 5 in a small township in rural Zambia at the end of the rainy season. Running capacity was estimated by the 12-min running test. Age, sex, height, weight, social and nutritional indicators were recorded. Mean haemoglobin was 125.3 g/1 +/- 12.3 SD. Low haemoglobin was associated with indicators of a traditional way of life. After a controlled trial of iron, folic acid, tetrachlorethylene and chloroquine lasting for 6 weeks, mean haemoglobin in all the children was 128.8 g/1 +/- 10.0 SD. The mean haemoglobin was significantly higher in the 218 children who received iron than in the 212 children who did not receive iron. There were no other significant differences among the treatment groups. In a subgroup of 377 children who completed two running tests, those with lower haemoglobin ran significantly shorter distances, even when possible confounding factors were partialled out. The effect was reduced by excluding 12 children with haemoglobin less than 100 g/1 or 48 children with reticulocyte counts of 15% or more, but remained statistically significant.", "A randomized, double-blind, placebo-controlled iron supplementation trial was conducted in Kenya to examine the effect of iron supplements on appetite and growth in 87 primary school children. Sustained-release ferrous sulfate (150 mg) or placebo tablets were provided daily at school for 14 wk. Prior to tablet administration, baseline anthropometry, iron nutritional status (hemoglobin and serum ferritin), parasitic infections and clinical indicators of morbidity were measured. A baseline appetite test was conducted twice on each child by quantitatively measuring the ad libitum consumption of a midmorning snack. In addition, each child was asked for a subjective assessment of his or her appetite. Follow-up exams and appetite tests were identical to those at baseline. Findings indicated that provision of iron supplements resulted in improved growth and improved appetite (in terms of both energy intake of the snack and child report of appetite) as compared with children receiving the placebo. The increased energy intake from the snack was 10% of the daily estimated energy intake for children of this same age group living elsewhere in Kenya. Further research into the underlying physiological mechanisms may shed light on the relationship between iron nutritional status and appetite.", "Iron and zinc deficiencies are common in developing countries and supplementation is one way of reversing these deficiencies. The objective of this randomized, placebo-controlled clinical trial was to identify the effect of daily supplementation with iron, zinc, and iron plus zinc on the morbidity experience of 855 children 0.5-15 years of age in Peru. Single nutrient supplementation with zinc reduced diarrhea morbidity by 23% in all children. In older children (more than five years of age), iron supplementation increased morbidity due to Plasmodium vivax and diarrhea. In younger children, iron combined with zinc provided protection against P. vivax malaria, but also interfered with some of the diarrhea protection associated with zinc supplementation. No statistically significant effect was observed of either supplement on incidence of respiratory infection or anthropometric indices. Iron and zinc deficiencies should be remedied, and combined supplementation may be a good option, particularly in younger children in P. vivax malaria-endemic areas, although local endemicity and species-specific prevalence should be considered carefully when designing any supplementation program involving iron in a malaria-endemic area.", "The effect of weekly iron supplementation with and without deworming on hemoglobin was investigated in a double-masked, placebo-controlled field trial. Subjects were 289 preschoolers who were randomly divided into three groups. Groups 1 and 2 received 30 mg Fe once weekly and group 3 received a placebo. Group 1 additionally received anthelminthic treatment. Supplements were administered by the mothers, who were educated about iron deficiency beforehand. In the iron-supplemented groups prevalence of anemia decreased from 37.2% to 16.2% (P < 0.001). Hemoglobin increased by an average of 6.9 +/- 9.8 g/L in the two iron-supplemented groups (n = 191), which was greater (P < 0.001) than the increase of 1.9 +/- 8.0 g/L in the placebo group. None of the subjects had hookworm, and anthelminthic treatment did not have an additional effect. Iron supplements administered once weekly by mothers reduced anemia without major involvement of health staff.", "High prevalences of vitamin A deficiency and anaemia among adolescents warrant interventions. This study evaluated the effectiveness of school-based supplementation to reduce anaemia and improve vitamin A status.\n School-based, grade-randomized, intervention.\n In all, 1757 girls and 1859 boys, aged 12-15 y, in 24 Junior High Schools.\n Weekly supplementation for 14 weeks with 60 mg iron and 250 microg folate (Fe group; n=978), 10 000 IU vitamin A (VA group; n=970) or both (VAFe group; n=1042) to subjects in 15 schools, compared to subjects in nine other schools not receiving supplements (control; n=626).\n The baseline anaemia prevalence (Hb <120 g/l) in girls was 20% (prepubertal) and 26% (pubertal), and in boys 24% (pre-pubertal) and 11% (pubertal). Serum retinol concentrations were low (<1.05 micromol/l) in 41% of boys and 45% of girls. The interventions did not increase haemoglobin concentrations. Serum retinol concentration of boys, but not girls, in the VA group increased (0.33 vs 0.07 micromol/l in controls; P<0.01). The risk factors for low serum retinol concentration were lower baseline serum retinol concentration (OR 0.02-0.03) with, for girls, nightblindness at baseline (OR 5.88), and for boys, not receiving vitamin A (OR control: 1.00; VA: 0.37; Fe: 0.77; VAFe: 0.34) and maternal illiteracy (OR mother never attended school 1.00, mother received any formal education 0.17-0.33).\n Supplementation with vitamin A increased serum retinol concentration of boys. Iron supplementation did not change Hb. This appeared to be due to poor compliance, and partly related to side effects.", "The effect of iron therapy on malarial infection was investigated in Papua New Guinea, where malaria is endemic. Prepubescent schoolchildren with hemoglobin levels of 8-12 g/dl were randomly assigned to receive either 200 mg ferrous sulfate or a placebo twice daily for 16 weeks. Iron status and malarial infection were assessed at baseline, after 6 and 16 weeks of therapy, and 8 weeks after therapy was discontinued. Iron status was significantly improved by the treatment. The treatment did not significantly affect parasite rate, parasite density, or levels of anti-malarial IgG. No changes in spleen size were observed in either group. Furthermore, there was no significant difference between the groups in reported episodes of suspected malaria during the therapy. These results suggest that, in malaria endemic areas, oral treatment for iron deficiency can be carried out in semi-immune or immune schoolchildren without adverse consequences.", "To compare the effectiveness of microencapsulated iron(II) fumarate sprinkles (with and without vitamin A), iron(II) sulfate drops, and placebo sprinkles in preventing recurrence of anaemia and to determine the long-term haematological outcomes in children at high risk of recurrence of anaemia 12 months after the end of supplementation.\n A prospective, randomized, placebo-controlled design was used to study 437 Ghanaian children aged 8-20 months who were not anaemic (haemoglobin > or = 100 g/l). Four groups were given microencapsulated iron(II) fumarate sprinkles, microencapsulated iron(II) fumarate sprinkles with vitamin A, iron(II) sulfate drops or placebo sprinkles daily for six months. Primary outcome measures were change in haemoglobin and anaemic status at baseline and study end. Non-anaemic children at the end of the supplementation period were reassessed 12 months after supplementation ended.\n Overall, 324 children completed the supplementation period. Among the four groups, no significant changes were seen in mean haemoglobin, ferritin or serum retinol values from baseline to the end of the supplementation period. During the trial, 82.4% (267/324) of children maintained their non-anaemic status. Sprinkles were well accepted without complications. At 12 months post-supplementation, 77.1% (162/210) of children with no intervention remained non-anaemic. This proportion was similar for children among the four groups.\n In most children previously treated for anaemia, further supplementation was not needed to maintain their non-anaemic status. These results may have important implications for community intervention programmes in which initial high-dose treatment is needed because of a high prevalence of anaemia.", "Malaria is a major cause of infant morbidity and mortality in sub-Saharan Africa, and is often complicated by severe anaemia. Resistance of Plasmodium falciparum to most affordable antimalarial drugs is an impediment to intermittent chemotherapy. We investigated the effect of presumptive intermittent treatment with amodiaquine and daily iron supplementation in infants on malarial fevers and anaemia, in a holoendemic area of Tanzania where malaria is largely resistant to chloroquine and sulfadoxine/ pyrimethamine.\n 291 infants aged 12-16 weeks who attended three clinics were randomised to receive amodiaquine, iron supplementation, amodiaquine plus iron supplementation, or placebo. Over 6 months, we gave amodiaquine three times with intervals of 60 days; oral iron supplementation was given daily. Malarial fevers and anaemia were monitored at bimonthly treatment visits and by self-reporting to health centres.\n The protective efficacy of intermittent amodiaquine treatment in prevention of malarial fevers and anaemia was 64.7% (95% CI, 42.4-77.2) and 67.0% (95% CI, 34.5-83.4), respectively. Protective efficacy was similar in the group receiving amodiaquine plus iron supplementation. Infants receiving iron supplementation only were partly protected against anaemia (protective efficacy 59.8%; 95% CI, 23.4-78.9), but not against malarial fevers. 4 months' follow-up did not show rebound morbidity. We noted no haematological or clinical adverse effects.\n Presumptive intermittent treatment for malaria with amodiaquine reduced malarial fevers and anaemia in infants, in an area with high resistance to other antimalarials. Intermittent treatment strategies for malaria in highly endemic areas could be of great benefit to public health.", "In sub-Saharan countries, although malaria and malaria-associated anaemia are major public health problems, the usefulness of supplementary iron treatment for children with malaria-associated anaemia is unknown. In a 6-week period during the 1995 rainy season, 222 Malawian children aged < 5 years, who sought treatment for malaria, had > or = 500 parasites/microliter blood and at least 5 g haemoglobin (HB)/dl blood and whose parents gave consent, were randomized into a prospective study comparing the efficacy of sulphadoxine- pyrimethamine only (SP), SP plus daily iron (SPD) and SP plus weekly iron (SPW) as treatment for malaria-associated anaemia. The patients had their HB concentrations measured on enrollment (day 0), just before antimalarial treatment, and on days 3, 7, 14, 21 and 28; 215 (96.8%) completed the 28-day study. Among the children with 5-8 g HB/dl on enrolment, HB gain by the end of the study was significantly greater than in the children with > 8 g HB/dl initially (4.1 v. 2.2 g/dl; P < 0.05), and those in the SPD group gained significantly more HB by days 21 and 28 (3.6 and 4.9 g/dl, respectively) than those in either the SPW (2.7 and 3.7 g/dl, respectively) or the S2 groups (2.6 and 3.5 g/dl, respectively); there was no difference in HB gain between the SP and SPW groups. Type of treatment had no apparent effect, at any time during the study, on HB gains in those patients who had > 8 g HB/dl on enrolment. Thus the children with 5-8 g HB/dl on enrolment benefited from daily iron therapy whereas those with > 8 g HB/dl derived no significant benefit; improvement in HB depended most on whether enrolment HB was < or = 8.0 g/dl. As treatment with an effective antimalarial drug resulted in HB gains, irrespective of treatment group or HB concentration at enrolment, the anaemia observed may be mostly related to malaria. However, as a larger proportion of the iron-treated patients failed to clear their parasitaemias than of those given SP alone, oral iron may inhibit SP action. It is therefore recommended that, for children with both malaria and malaria-associated anaemia, the malaria should first be cleared with an effective antimalarial drug, such as SP, before the anaemia, if it still persists, is treated with iron.", "To assess the impact of a daily oral iron supplementation on hematological status, cell-mediated immunity and susceptibility to infections in children living in an environment where iron deficiency, malaria and other infections are frequent.\n Randomized, double-blind iron supplementation including a placebo group.\n A village in Togo, West Africa.\n Of the 229 6-36-month-old children of both sexes recruited, 197 with hemoglobin concentration >/=80 g/l were included and 163 completed the study.\n Children received daily a placebo (n=79) or a dose of 2-3 mg of elemental iron per kg of body weight (n=84) for 3 months. Hematological, nutritional and immune status were assessed at the beginning and at the end of the supplementation period, and 6 months later. Morbidity was recorded throughout the study.\n Iron supplementation had a significant and positive effect on iron status of children and no impact on the incidence of infections, especially malaria. Its probable effect on immune status was masked by interference of infections and their treatment, which contributed to improve hematological and immune status in both groups.\n According to the negative consequences of anemia and iron deficiency on global child development, control of iron deficiency by oral iron supplementation in young children has to be conducted, associated with prophylaxis and treatment of malaria and repeated deworming.\n Program supported by IRD. European Journal of Clinical Nutrition (2000) 54, 29-35", "Whether children with malarial anaemia should receive supplementation with iron or folic acid is uncertain. Therefore, the effects of supplementary treatment with iron or folic acid, given together with chloroquine or pyrimethamine-sulfadoxine (Fansidar), has been assessed in 600 Gambian children with uncomplicated falciparum malaria. After one month, haematological recovery was significantly better in the group treated with Fansidar than in the chloroquine-treated group (difference in mean haemoglobin level = 0.54 g/dL, P = 0.01). Children who received iron had a significantly better response than those given placebo (differences in mean haemoglobin level after one month and at dry season follow-up = 0.70 g/dL, P = 0.006, and 0.81 g/dL, P = 0.001, respectively). Iron supplementation was not associated with increased prevalence of malaria. Supplementation with folic acid did not improve the haematological response but, among children who received Fansidar, the treatment failure rate was significantly higher among those given folic acid than among those given placebo. Thus, supplementation with iron, but not folic acid, improves haematological recovery without increasing susceptibility to malaria.", "In order to increase the intestinal absorption of iron whilst simultaneously minimising the side-effects and thus increasing compliance, once- or twice-weekly, instead of daily, iron supplementation has been widely recommended. In a randomized, placebo-controlled, double-blind study in western Kenya, a tablet of ferrous dextran (containing 60 mg elemental iron) or an identical-looking placebo tablet was provided twice-weekly for 12 months to each child or adult investigated. At baseline each subject had a moderately low blood concentration of haemoglobin (Hb). Initial Hb and serum ferritin (SF) concentrations were determined and each subject was tested for malarial and helminth infection and treated, if necessary, with the appropriate anthelminthic drug(s). Overall, 200 children (aged 4-15 years) and 129 adults (aged 16-63 years) completed the 12-month study. At baseline, 47.5% of the children and 58.1% of the adults were anaemic, hookworm (detected in 60.0% of the children and 69.9% of the adults) was the most common helminth infection, and malaria was endemic. The results of bivariate analyses indicated that twice-weekly iron supplementation had no significant effect on blood Hb or SF concentrations, either in the children or the adults investigated. The results were confirmed in multiple linear-regression analyses, which revealed that the predictors of the final Hb concentration in the children investigated were age and infection, after enrollment, with Ascaris lumbricoides. Gender and the serum concentration of alpha-1-antichymotrypsin (ACT) at final follow-up were predictors of the final SF concentration in the children. In adults, the predictors of the final Hb concentration were gender and HIV infection, and the predictors of the final SF concentration were age and the serum concentration of ACT at the final follow-up. Twice-weekly iron supplementation did not increase Hb or iron stores in children or adults. Since compliance appeared to be high, this lack of effect may be the result of an inadequate dose of iron or of subjects who have deficiencies in micronutrients other than iron.", "To compare the effectiveness of weekly vs daily iron and folic acid supplementation for control of anemia in adolescent Nepalese girls.\n Randomized controlled trial.\n A Government Girl School in Dharan, Nepal, an urban foothill town that is 305 m above sea level.\n Consecutive healthy adolescent girls (n = 209, median age 15 years) randomized to 3 groups matched for age, anthropometry, and personal and sociodemographic characteristics. Of 209 subjects, 181 completed the trial. Two girls had adverse reactions to treatment and were excluded.\n Group A (n = 70) received a 350-mg ferrous sulfate and 1.5-mg folic acid combination once daily for 90 to 100 days. Group B (n = 67) received the tablet under supervision once a week for 14 weeks. Group C (n = 72) did not receive any drugs.\n Presupplementation and postsupplementation differences in prevalence of anemia and change in hematocrit.\n Prevalence of anemia (defined as hematocrit <36%) declined from 68.6% and 70.1% in groups A and B to 20% and 13.4%, respectively, postsupplementation (P<.001), whereas the prevalence in group C changed little (68.1% to 65.3%, P =.81). There was a significant rise in the mean hematocrit of both supplemented groups (group A, 32.9% +/- 3.5% to 41.0% +/- 5.6%, P<.001; group B, 33.2% +/- 3.6% to 40.4% +/- 4.9%, P<.001) but no appreciable change in controls (34.2% +/- 2.9% to 34.1% +/- 3.3%, P =.91). Net change in mean hematocrit in both the supplementation groups was comparable (P =.57).\n The prevalence of anemia in adolescent Nepalese girls is high. Supervised iron and folic acid therapy once a week is an effective alternative to daily administration and helps lower the prevalence of anemia in adolescent girls.", "Haematological and iron parameters, measured in 907 children aged from 6 months to 5 years in rural Gambia at the start of the rainy season, differed from those in American reference populations as follows: mean haemoglobin levels were much lower at ages 1 and 2 years and mean levels of mean corpuscular volume (MCV) were lower at all ages (at age 1 year mean haemoglobin was 11.2 g/dl and mean MCV 68.2 fl); in a sample of 249 children randomly selected from the whole study population, mean serum iron levels were similar but mean transferrin saturation and mean serum ferritin levels were lower, especially at ages 1-3 years (at age 1 year mean serum iron was 11.1 mumol/l, mean transferrin saturation 16.9%, and geometric mean serum ferritin 8.8 ng/ml. A total of 213 children (23%) whose haemoglobin and mean corpuscular volume were both less than the 3rd percentile of the reference population received oral iron or placebo from their mothers during the rainy season when malaria transmission is maximal. Mean levels of haemoglobin, mean corpuscular volume, serum iron, transferrin saturation and serum ferritin rose in the iron-treated group and fell in the placebo group at all ages, except under 1 year for serum ferritin, to produce significant differences between the groups by the end of the study. Total iron-binding capacity showed no significant changes during the study. We concluded that oral iron given by the mother during the rainy season can be used to treat iron-deficiency anaemia in Gambian children who would otherwise become more anaemic.", "nan", "Zinc supplementation has been shown to benefit linear growth. However the effect may depend on whether zinc is the most limiting nutrient. This study aims to investigate the effect of supplementation with zinc-given alone or with iron and vitamin-A in improving infantsf micronutrient status and linear growth. The study was a double-blind-community-intervention study involving 800 infants aged 3-6 months in rural East Lombok, West Nusa Tenggara. Syrup consisting of zinc-alone, Zn (10 mg/d), zinc+iron, Zn+Fe (10 mg/d of each), zinc+iron+vitamin-A, Zn+Fe+vit.A (10 mg/d of each zinc and iron plus 1,000 IU vitamin-A), or placebo were given daily for six months. Outcomes measured were length, weight, and micronutrient status (haemoglobin, se-rum zinc, ferritin and retinol). Zn+Fe and Zn+Fe+vit.A supplementations benefit zinc and iron status of the sub-jects, while Zn-alone supplementation disadvantaged haemoglobin and iron status. The highest increment in vi-tamin A and haemoglobin status was shown in Zn+Fe+vit.A group. An effect on linear growth was observed among initially-stunted subjects in Zn+Fe and Zn+Fe+vit.A groups who grew 1.1-1.5 cm longer than placebo. On the other hand, in the Zn-alone group, mean height-for-age Z-score decreased to a greater extent than placebo. The between-group difference in HAZ among initially-stunted subjects was significant after four months sup-plementation. While the difference was not significant in follow-up after 6 months, the pattern remained the same where means height-for-age Z-score in Zn+Fe+vit.A and Zn+Fe groups were higher than placebo and Zn-alone groups. Given the low haemoglobin/iron status of the subjects, zinc supplementation would have positive effect on growth if the low haemoglobin/iron status is also addressed and corrected.", "To determine the haematological effects of iron supplementation in predominantly breast fed term low birth weight (LBW) infants.\n Seventy three healthy term LBW (<2500 g), predominantly breast fed infants aged 50-80 days were randomised into two groups to receive either iron (3 mg/kg/day) (iron supplemented (IS) group; n = 37) or placebo drops (placebo (P) group; n = 36). Haematological parameters and anthropometry were measured at baseline and repeated after four and eight weeks.\n A total of 62 subjects (32 in the IS group and 30 in the P group) came for the first follow up and 26 (13 in the IS group and 13 in the P group) reported for the second visit. There were no significant differences in serum ferritin and anthropometry. However, covariates (infant age, haemoglobin, and ferritin, and maternal haemoglobin) adjusted haemoglobin change was significantly higher in the IS group after four weeks (4.6 g/l; 95% CI 0.5 to 8.8) and eight weeks (8.6 g/l; 95% CI 1.8 to 15.4).\n Iron supplementation in a therapeutic dose in term breast fed LBW infants results in a marginal increase in haemoglobin. The functional benefit of this haemoglobin rise requires further evaluation.", "The study was conducted to determine whether provision of oral supplementary iron to primary school children in Kenya would improve their growth. Children in the two lowest grades who satisfied study criteria were allocated to either an iron-supplementation group (n = 29) or a placebo group (n = 26). At the baseline before intervention the groups did not differ significantly in age, sex ratio, prevalence and intensity of intestinal helminthic infections, most anthropometric measurements or hemoglobin levels. Although the study lasted for 32 weeks, children only took iron or placebos on school days thus omitting weekends and school holidays. Examination at the end of the study showed that the iron-supplemented children had grown significantly more in terms of weight, weight for height, arm circumference and skinfold thickness compared with the placebo group. Hemoglobin levels had also improved significantly. We conclude that where iron deficiency anemia and undernutrition are prevalent in children, iron supplementation will improve growth and hemoglobin levels.", "We conducted a randomized controlled trial of the effects of dietary supplements on anemia, weight and height in 136 anemic school children from a low socioeconomic background in Bagamoyo District schools in Tanzania. The aim of the current study was to investigate the impact of dietary supplements on anemia and anthropometric indices of anemic school children. The supplements were vitamin A alone, iron and vitamin A, iron alone or placebo, administered in a double-blinded design for 3 mo. All supplements were provided with local corn meals. Hemoglobin concentration, body weight and height were measured at baseline and at follow-up after supplementation. Vitamin A supplementation increased the mean hemoglobin concentration by 13.5 g/L compared with 3.5 g/L for placebo [P < 0.0001, 95% confidence interval (CI) 6.19-13.57), the mean body weight by 0.6 kg compared with 0.2 kg for placebo (P < 0.0001, 95% CI 0.19-0.65) and the mean height by 0.4 cm compared with 0.1 cm for placebo (P = 0.0009, 95% CI 0.08-0.42). However, the group of children who received combined vitamin A and iron supplementation had the greatest improvements in all indicators compared with placebo (18.5 g/L, P < 0.0001, 95% CI 14.81-22.23; 0.7 kg, P < 0. 0001, 95% CI 0.43-0.88 and 0.4 cm, P < 0.0001, 95% CI 0.22-0.56 for hemoglobin, weight and height, respectively). It is likely that vitamin A supplementation may have a useful role in combating the problems of vitamin A deficiency and anemia, as well as in improving children's growth, in developing countries." ]

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[ "Effects of human recombinant growth hormone on donor-site healing in burned adults.", "Recombinant human growth hormone treatment in pediatric burn patients and its role during the hepatic acute phase response.", "[Effectiveness of recombinant human growth hormone treatment for severe burn injury].", "Effects of recombinant human growth hormone on the development of burn scarring.", "Effects of recombinant human growth hormone on donor-site healing in severely burned children.", "[The effect of growth hormone on wound healing rate in adult burns].", "Recombinant human growth hormone accelerates wound healing in children with large cutaneous burns.", "[The influence of combined supplementation of glutamine and recombinant human growth hormone on the protein metabolism in severely burned patients].", "Beneficial effects of extended growth hormone treatment after hospital discharge in pediatric burn patients.", "Growth hormone effects on hypertrophic scar formation: a randomized controlled trial of 62 burned children.", "Comparison of the anabolic effects and complications of human growth hormone and the testosterone analog, oxandrolone, after severe burn injury.", "[Effect of recombinant growth hormone on wound healing in severely burned adults. A placebo controlled, randomized double-blind phase II study]." ]

[ "Patients suffering severe burns have an accelerated catabolism with a highly negative nitrogen balance that may worsen their prognosis. Somatropin treatment has been shown to improve this balance in different hypercatabolic situations. Moreover, in children with extensive burns it also reduces the healing time of the skin graft donor site and shortens the hospital stay. In the existing literature there are no controlled prospective clinical trials in adult patients that confirm these data. Our aim was to demonstrate the efficacy of recombinant growth hormone (somatropin) in reducing the healing time of the skin graft donor sites and the length of stay in the burn unit in adult patients with severe burns. A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 adult patients with severe burns (more than 40% of the total body surface burned or more than 15% full-thickness burns). Patients received placebo (n = 11) or somatropin (n = 13) at a dosage of 0.15 mg/kg/day divided into two equal doses (every 12 hours) via intramuscular injection. Treatment was initiated the day the first autograft was performed and terminated the day the patient was discharged from the burn unit. The mean number (+/- SD) of skin grafts per patient was similar between the two groups (4.2 +/- 1.8 vs 3.4 +/- 1.8 in the placebo and somatropin groups, respectively). No reduction in the healing time of the skin graft donor site was observed in the somatropin group compared to the placebo group. Likewise, the time admitted to the burn unit was not significantly different, either in the absolute number of days (36.2 +/- 19.7 vs 30.1 +/- 16.8 days in the placebo and somatropin groups, respectively) or in relation to the percentage of the total body surface burned or the body surface with full-thickness burns. Growth hormone and insulin-like growth factor I (IGF-I) levels were three and five times higher, respectively, in the somatropin group than in the placebo group. Ten of the patients treated with somatropin experienced hyperglycemia, and seven of them required insulin treatment. No other adverse side effect was observed. One patient in the placebo group died as a result of sepsis and multiple organ failure. Somatropin, with the treatment regimen and dosage used in these studies, did not reduce the healing time of the skin graft donor sites or the length of hospitalization in the burn unit in adult patients with severe burns.", "Recombinant human growth hormone (rHGH) has been shown to increase mortality in adult trauma patients; however, little has been reported on its side effects in children. The acute phase response has been suggested to be a contributing factor to trauma mortality. Therefore, the purpose of this study was to examine the effects of exogenous rHGH on the acute phase response in pediatric bum patients.\n Prospective, randomized, double-blind study.\n Shriners Hospital for Children.\n Thermally injured pediatric patients, ranging in age from 0.1 to 16 yrs.\n Twenty-eight thermally injured children received either 0.2 mg/kg/day of rHGH or saline (placebo) within 3 days of admission and for at least 25 days.\n Measurements were patient demographics, incidence of sepsis, inhalation injury, mortality, serum constitutive proteins, acute phase proteins, proinflammatory cytokines and insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3. No differences could be demonstrated in age, gender, burn size, incidence in sepsis (20% vs. 26%), inhalation injury (46% vs. 27%), or mortality (8% vs. 7%) between those receiving rHGH or placebo. Serum IGF-I and IGFBP-3 increased with rHGH treatment, whereas serum IGFBP-1 decreased compared with placebo (p < .05). Burned children treated with rHGH required significantly less albumin substitution to maintain normal levels compared with placebo (p < .05). Those receiving rHGH demonstrated a decrease in serum C-reactive protein and serum amyloid-A and an increase in serum retinol-binding protein compared with placebo (p < .05). rHGH decreased serum tumor necrosis factor-alpha and interleukin (IL)-1beta, whereas no changes were found for serum IL-1alpha, IL-6, and IL-10 compared with placebo (p < .05). Free fatty acids were elevated in burned children who received rHGH (p < .05).\n Data indicate that rHGH does not increase mortality. rHGH decreased acute phase proteins, tumor necrosis factor-alpha, and IL-1beta, which is associated with increases in constitutive hepatic proteins and IGF-I.", "In order to investigate the effectiveness and safety of recombinant human growth hormone(rhGH) treatment for severe burn injury, we designed a randomized prospective study. The patients in rhGH group were given rhGH in a dose of 0.5 IU/(kg.d) subcutaneously between days 3-17 post-burn. Indices about protein metabolism, wound healing, hepatic and renal function and blood were measured regularly. Patients were monitored until their wound healed sufficiently so that they could be discharged for rehabilitation. The results showed: all patients survived; the rhGH group had less weight loss, increased level of serum albumin and shorter healing time of deep partial-thickness burn and donor site. The hospital stay time decreased from the control value of 45 +/- 17 days to 37 +/- 12 days for rhGH treated patients, i.e. a significant improvement. Resistant hyperglycemia was present in 2 patients in the rhGH group and disappeared after transient insulin administration. This study demonstrates that rhGH treatment for severe burn injury has obvious beneficial effects with slight side-effects.", "Anabolic agents, such as recombinant human growth hormone (rhGH), have been used effectively to ameliorate the catabolic response to burn injury and to improve wound-healing. However, in experimental animal models, growth hormone has also been associated with increased renal scarring. The effect of rhGH on the development of human scarring is unknown. Therefore, the purpose of this study was to assess the effect of rhGH on the scarring of human skin after burn injury. A series of 94 patients was studied in a prospective randomized double-blind clinical trial. Patients receiving 0.2 mg/kg/day subcutaneous rhGH during their acute hospital stays presented with the same quality and intensity of scarring as patients receiving a placebo. Similar reconstructive needs also resulted. The treatment of severely burned children with recombinant human growth hormone during the acute-phase hospital course did not increase scarring of the burn wound.", "The beneficial effects of growth hormone on wound healing in severely burned children were studied. Forty patients who were 2 to 18 years old, with 40% or more total body surface area (TBSA) and 20% or more TBSA full-thickness flame or scald burns, were randomized in a double-blind study to receive placebo or 0.1 mg/kg/day recombinant human growth hormone (rHGH) until the first donor site healed or to receive 0.2 mg/kg/day rHGH or placebo from admission throughout hospitalization. Patients receiving 0.2 mg/kg/day rHGH demonstrated significantly higher serum IGF-1 levels at 4.8 +/- 1.7 U/mL compared to placebos at 1.6 +/- 0.4 U/mL (p less than 0.05) and a significant decrease in donor-site healing times compared to placebo (p less than 0.05). Length of hospital stay (LOS/%TBSA) was decreased from 0.80 +/- 0.10 days/%TBSA burned in the placebo group to 0.54 +/- 0.04 days/%TBSA burned in the 0.2 mg/kg/day treatment group (p less than 0.05). This translates, for the average 60% TBSA burned patient, to a decrease in LOS from 46 to 32 days.", "To determine the wound healing effect of rHGH in adult burn patients.\n 16 patients with burn wounds covering over 60% of total body surface (TBSA) were enrolled in this placebo controlled prospective study. They were comparable in nutrient intake, TBSA, and full thickness burn area. rHGH group patients were given rHGH subcutaneously in the dose of 0.3u.Kg-1 at 8 am each morning for 10 days beginning from POD 1. The control group patients were given normal saline as placebo. All the patients received scar excision within 4 days postburn, and the excision wounds were covered with autologous skin pulp grafting. Serum amino acid profile was analyzed at day 1 and day 20 post burn. Healing time of burn wound area and donor site was recorded. Wound healing rate was assessed at day 30 after day.\n 1. The healing time of autologous skin pulp grafting and donor site, and the length of hospital stay were significantly shorter in GH group patients than control group. 2. The amino acid profile showed no difference between two groups at day 1 and was significantly better in GH group at day 20.\n rHGH could enhance the wound healing rate, improve amino acid profile, and reduce the length of hospital stay of severe burn patients.", "Two forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated.\n Growth hormone has been shown to reduce wound healing times in burned pediatric patients. Through genetic engineering, several different forms have been synthesized; however, not all are marketed currently. Two forms of growth hormone were used in these studies, Protropin (Genentech, Inc., San Francisco, CA), a commercially available product that possesses a N-terminal methionine residue not found in the second form Nutropin (Genentech, Inc., San Francisco, CA), which, as yet, is not commercially available. Through the use of recombinant human growth hormone, rapid wound healing may reduce the hypermetabolic period, the risk of infection, and accelerate the healing of donor sites used for grafting onto burned areas. The two structurally different forms of growth hormone were tested for their efficacy in healing donor sites in severely burned children.\n Forty-six children, with a > 40% total body surface area and > 20% total body surface area full-thickness burn were entered in a double-blind, randomized study to receive rhGH within 8 days of injury. Twenty received (0.2 mg/kg/day) Nutropin or placebo by subcutaneous or intramuscular injection beginning on the morning of the initial excision. Eighteen patients who failed the entry criteria for receiving Nutropin received Protropin therapeutically (0.2 mg/kg/day). Donor sites were harvested at 0.006 to 0.010 inches in depth and dressed with Scarlet Red impregnated fine mesh gauze (Sherwood Medical, St. Louis, MO). The initial donor site healing time, in days, was reached when the gauze could be removed without any trauma to the healed site.\n Donor sites in patients receiving Nutropin (n = 20) or Protropin (n = 18) healed at 6.8 +/- 1.5 and 6.0 +/- 1.5 (mean +/- SD) days, respectively, whereas those receiving placebo (n = 26) had a first donor site healing time of 8.5 +/- 2.3 days. Both groups receiving rhGH showed a significant reduction in donor site healing time compared with placebo at p < 0.01. When subgroups were compared, no difference in healing times could be shown with regards to age or time of admission after injury.\n Our results indicate that both forms of rhGH are effective in reducing donor site healing time compared with placebo and suggest that accelerating wound healing is of clinical benefit because the patients' own skin becomes rapidly available for harvest and autografting. With this increase in the rate of wound healing, the total length of hospital stay can be reduced by more than 25%.", "To investigate the influence of combined supplementation of glutamine (Gln) and recombinant human growth hormone (rhGH) on the protein metabolism in severely burned patients.\n Sixty severely burned patients were enrolled in the study and were randomly divided into control (C, n = 20) and Gln with rhGH (Gln + rhGH, n = 20) groups. The patients in C group received glycine as the placebo, while those in Gln group took Gln orally in dose of 0.5 g kg(-1) d(-1) during 1-14 postburn days (PBDs). For the patients in Gln + rhGH group rhGH was administered subcutaneously in dose of 0.2 U kg(-1) d(-1) in addition to glutamine in same dosage beginning on the 7 PBD for 7 days. The plasma Gln concentration in the 3 groups of patients was determined on the 1st, 7th and 14th PBD and the plasma albumin level was determined on 14th and 21st PBD. The wound healing rate of the patients within 30 PBSs and the total hospital stay days were recorded.\n The plasma Gln concentration in Gln + rhGH group of patients was evidently higher than that in C group after 7 PBD[(452.28 +/- 21.72) micromol/L vs(325.12 +/- 25.34) micromol/L, P < 0.05]. The plasma albumin level in Gln + rhGH group was obviously higher than that in C and Gln groups on the 21st PBD (P < 0.05). The wound healing rate in Gln + rhGH group was evidently higher than that in Gln and C groups on the 30th PBD (P < 0.05). The total hospital stay days in Gln + rhGH group were obviously less than that in C and Gln groups (P < 0.05 or 0.01).\n Combined administration of Gln and rhGH could be beneficial to the elevation of plasma Gln level in severely burned patients and the systemic protein synthesis was therefore enhanced and the wound healing rate was improved.", "To study the efficacy of growth hormone given to severely burned children from discharge to 12 months after burn and for 12 months after the drug was discontinued.\n We have previously shown that low-dose recombinant human growth hormone (rhGH), given to children after a severe thermal injury, successfully improved lean muscle mass, bone mineral content, and growth. The aim of the present study was to investigate long-term functional improvements after treatment.\n Forty-four pediatric patients with over 40% total body surface area burns were studied for 24 months after burn. Patients were randomized to receive either rhGH (0.05 mg/kg body weight) or placebo. Height, weight, body composition, serum hormones, resting energy expenditure, cardiac function, muscle strength, and number of reconstructive procedures performed were measured during rhGH treatment and for 12 months after treatment was discontinued. Statistical analysis used Tukey's multiple comparison test. Significance was accepted at P < 0.05.\n Height, weight, lean body mass, bone mineral content, cardiac function, and muscle strength significantly improved during rhGH treatment compared with placebo (P < 0.05). This treatment significantly increased GH, IGF-I, and IGFBP-3, whereas serum cortisol decreased (P < 0.05). The number of operative reconstructive procedures was significantly lower with rhGH (P < 0.05). Improvements in height, bone mineral content, and IGF-1 concentrations persisted after rhGH treatment (P < 0.05). No side effects with rhGH were observed.\n Administration of rhGH for 1 year after burn was safe and improved recovery. These salutary effects continued after rhGH treatment was discontinued.", "The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.", "This study compared the anticatabolic and wound healing effects of the anabolic agents human growth hormone, HGH, and the testosterone analogue, oxandrolone, after severe burn injury. A randomized prospective study design was used. Patients were given HGH at a dose of 0.1 mg/kg/day (n = 20) or oxandrolone, 20 mg/day (n = 16), beginning between days 7-10 post-burn. Data was compared to burn patients not placed on either agent (n = 24). Patients were monitored until they were sufficiently healed to be transferred to a rehabilitation center. The results of our study were as follows. All patients survived. Net weight loss was 8 +/- 2.1 kg in the control group compared with 4 +/- 1.8 kg with HGH and 3 +/- 1.2 kg with oxandrolone, a significant decrease. Net daily nitrogen loss was 12 +/- 3 g in non-treated compared to 3 g or less for each of the anabolic groups, a significant decrease. The metabolic rate in untreated burns was 155 + 25% of predicted normal, compared to 178 +/- 28% for HGH and 156 +/- 20% for oxandrolone treated patients. The complete healing time of a standardized donor site, decreased from the control value of 14 +/- 2 days to 10 +/- 3 days for HGH and 10 +/- 2 days for oxandrolone treated patients, a significant improvement. Hyperglycemia (glucose over 225 mg/dl 12.5 mM) was present in 100% of HGH patients compared to 55% for control and 50% for oxandrolone treated. We found that both anabolic agents significantly decreased weight and nitrogen loss and increased healing with nearly identical benefits. However HGH resulted in the significant complications of hyperglycemia and accentuated hypermetabolism. We noted no side effects with oxandrolone.", "Recombinant growth hormone (rGH) has been used successfully in burned children with a shortened donor-site healing time and length of hospital stay as well as a protein-sparing effect. In adult burn patients, no comparable study exists to date.\n The study was performed on 49 adults, aged 18-60, with an Abbreviated Burn Severity Index (ABSI) score of 7-I1 as a randomized, placebo-controlled, double-blind study. The treatment period was 28 days and follow-up period 1 year. rGH was administered subcutaneously at a dose of 0.5 lU/kg per day in 26 patients, 23 patients were in the placebo group. Wound-closure assessment was performed on the day of admission and on each day of dressing change. A wound-closure index (WCI) was calculated.\n Thirty-seven patients, 19 in the rGH group and 18 in the placebo group, survived and were available for primary efficacy analysis. The mean total body surface area (TBSA) burned was 41.5% (rGH) versus 36.7% (placebo); the average ABSI score was 8.27 (rGH) versus 7.9 (placebo). The wound-closure index was not significantly different in patients treated with rGH (1.92) compared with patients treated with placebo (1.72). WCI for partial thickness-loss burn wounds did not significantly differ from rGH (0.9) to placebo (0.69). The donor site healing time in rGH-treated patients (12 days) was not significantly different compared to placebo patients (10.4 days).\n In severely burned adult patients rGH has no positive effect on burn wound or donor-site healing." ]

[ "7618972", "9339943", "9494004", "9038665", "8200238", "15286958", "9351723", "15869128", "8951516" ]

[ "Is early oral feeding safe after elective colorectal surgery? A prospective randomized trial.", "Immediate postoperative enteral feeding results in impaired respiratory mechanics and decreased mobility.", "Early feeding after elective open colorectal resections: a prospective randomized trial.", "Influence of postoperative enteral nutrition on postsurgical infections.", "Must early postoperative oral intake be limited to laparoscopy?", "Randomized clinical trial of the effects of preoperative and postoperative oral nutritional supplements on clinical course and cost of care.", "A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy.", "The economic impact of early enteral feeding in gastrointestinal surgery: a prospective survey of 51 consecutive patients.", "Early postoperative feeding after elective colorectal surgery is not a benefit unique to laparoscopy-assisted procedures." ]

[ "The routine use of a nasogastric tube after elective colorectal surgery is no longer mandatory. More recently, early feeding after laparoscopic colectomy has been shown to be safe and well tolerated. Therefore, the aim of our study was to prospectively assess the safety and tolerability of early oral feeding after elective \"open\" abdominal colorectal operations.\n All patients who underwent elective laparotomy with either colon or small bowel resection between November 1992 and April 1994 were prospectively randomized to one of the following two groups: group 1: early oral feeding--all patients received a clear liquid diet on the first postoperative day followed by a regular diet as tolerated; group 2: regular feeding--all patients were treated in the \"traditional\" way, with feeding only after the resolution of their postoperative ileus. The nasogastric tube was removed from all patients in both groups immediately after surgery. The patients were monitored for vomiting, bowel movements, nasogastric tube reinsertion, time of regular diet consumption, complications, and length of hospitalization. The nasogastric tube was reinserted if two or more episodes of vomiting of more than 100 mL occurred in the absence of bowel movement. Ileus was considered resolved after a bowel movement in the absence of abdominal distention or vomiting.\n One hundred sixty-one consecutive patients were studied, 80 patients in group 1 (34 males and 46 females, mean age 51 years [range 16-82 years]), and 81 patients in group 2 (43 males and 38 females, mean age 56 years [range 20-90 years]). Sixty-three patients (79%) in the early feeding group tolerated the early feeding schedule and were advanced to regular diet within the next 24 to 48 hours. There were no significant differences between the early and regular feeding groups in the rate of vomiting (21% vs. 14%), nasogastric tube reinsertion (11% vs. 10%), length of ileus (3.8 +/- 0.1 days vs. 4.1 +/- 0.1 days), length of hospitalization (6.2 +/- 0.2 days vs. 6.8 +/- 0.2 days), or overall complications (7.5% vs. 6.1%), respectively, (p = NS for all). However, the patients in the early feeding group tolerated a regular diet significantly earlier than did the patients in the regular feeding group (2.6 +/- 0.1 days vs. 5 +/- 0.1 days; p < 0.001).\n Early oral feeding after elective colorectal surgery is safe and can be tolerated by the majority of patients. Thus, it may become a routine feature of postoperative management in these patients.", "The authors set out to determine whether immediate enteral feeding minimizes early postoperative decreases in handgrip and respiratory muscle strength.\n Muscle strength decreases considerably after major surgical procedures. Enteral feeding has been shown to restore strength rapidly in other clinical settings.\n A randomized, controlled, nonblinded clinical trial was conducted in patients undergoing esophagectomy or pancreatoduodenectomy who received immediate postoperative enteral feeding via jejunostomy (fed, n = 13), or no enteral feeding during the first 6 postoperative days (unfed, n = 15). Handgrip strength, vital capacity, forced expiratory volume in one second (FEV1), and maximal inspiratory pressure (MIP) were measured before surgery and on postoperative days 2, 4, and 6. Fatigue and vigor were evaluated before surgery and on postoperative day 6. Mobility was assessed daily after surgery using a standardized descriptive scale. Postoperative urine biochemistry was evaluated in daily 24-hour collections.\n Postoperative vital capacity (p < 0.05) and FEV1 (p = 0.07) were consistently lower (18%-29%) in the fed group than in the unfed group, whereas grip strength and maximal inspiratory pressure were not significantly different. Postoperative mobility also was lower in the fed patients (p < 0.05) and tended to recover less rapidly (p = 0.07). Fatigue increased and vigor decreased after surgery (both p < or = 0.001), but changes were similar in the fed and unfed groups. Intensive care unit and postoperative hospital stay did not differ between groups.\n Immediate postoperative jejunal feeding was associated with impaired respiratory mechanics and postoperative mobility and did not influence the loss of muscle strength or the increase in fatigue, which occurred after major surgery. Immediate postoperative enteral feeding should not be routine in well-nourished patients at low risk of nutrition-related complications.", "A period of starvation after colorectal resections to allow for resolution of the clinical evidence of ileus has been an unchallenged surgical doctrine until recent times. A prospective randomized trial comparing early feeding to traditional management in patients undergoing open elective colorectal resections is reported.\n Patients undergoing elective intraperitoneal colorectal resections without stoma formation were randomized to either an early feeding or control group. The early feeding group were allowed free fluids from 4 h postoperatively progressing to a solid diet from the first postoperative day as they tolerated it. The control group remained nil orally until passage of flatus or bowel motion and were then commenced on fluids progressing to solids over 24-48 h.\n There were 40 patients in each group well matched for age, sex, type and duration of operation, method of analgesia and mobilization. Thirty-two patients (80%) in the early feeding group tolerated a diet within 48 h. There was no significant difference in the rate of vomiting, nasogastric reinsertion or complications. The early feeding group tolerated a diet, passed flatus, used their bowels, and were discharged from hospital significantly earlier than the control group.\n Early feeding after elective open colorectal resections is successfully tolerated by the majority of patients, leading to earlier resolution of ileus and hospital discharge.", "This study was undertaken to test the hypothesis that early enteral nutrition might reduce the incidence of serious complications after major abdominal surgery.\n In a randomised double blind prospective trial 30 patients received Nutri-drink and 30 patients received placebo through a nasoduodenal feeding tube. On the day of operation the patients were given median 600 ml of either nutrition or placebo, 60 ml per hour. On the first postoperative day the patients received either 1000 ml (median) of nutrition or placebo, on day 2 1200 ml (median) nutrition, 1400 ml placebo, on day 3 1000 ml (median) nutrition, 1150 ml placebo, and on day 4 1000 ml (median) nutrition, 800 ml placebo. All patients were followed up for 30 days by the same investigator.\n The two groups were similar with regard to nutritional status and type of operation. The rate of postoperative infectious complications was significantly lower in the nutrition group, two of 30 compared with 14 of 30 in the placebo group (p = 0.0009).\n Early enteral nutrition given to patients after major abdominal surgery results in an important reduction in infectious complications.", "This prospective, randomized study was designed to evaluate whether or not early postoperative feeding (claimed as a unique benefit of laparoscopic surgery) is possible after laparotomy and colorectal resection.\n The trial was performed between July 1, 1992 and October 31, 1992 and included all 64 consecutive patients who underwent laparotomy with either a colonic or an ileal resection. In all cases the nasogastric tube was removed immediately after the operation. Group 1 consisted of 32 patients (age range, 15-81 years; mean, 52 years) who received a regular diet on the first postoperative morning. Group 2 consisted of 32 patients (age range, 15-87 years; mean, 52 years) who were fed in a traditional manner. Regular food was permitted after resolution of ileus as defined by resumption of bowel movements in the absence of abdominal distention, nausea, or vomiting.\n The rate of nasogastric tube reinsertion for distention with persistent vomiting was 18.7 percent (six patients) in Group 1 and 12.5 percent (four patients) in Group 2. Although vomiting was experienced more frequently by patients in Group 1 (44 percent vs. 25 percent, respectively), there was no difference between the two groups with regard to the duration of postoperative ileus (3.6 vs. 3.4 days, respectively). In the 26 patients from Group 1 who did not require nasogastric tube reinsertion, there was a trend toward shorter hospitalization (6.7 vs. 8.0 days, respectively).\n Early oral intake is possible after laparotomy and colorectal resection. Thus, the laparoscopic surgeon's claim of early tolerated oral intake may not be unique to laparoscopy.", "Postoperative oral nutritional supplementation has been shown to be of clinical benefit. This study examined the clinical effects and cost of administration of oral supplements both before and after surgery.\n This was a randomized clinical trial conducted in three centres. Patients undergoing lower gastrointestinal tract surgery were randomized to one of four groups: group CC received no nutritional supplements, group SS took supplements both before and after surgery, group CS received postoperative supplements only, and group SC were given supplements only before surgery. Preoperative supplements were given from the time it was decided to operate to 1 day before surgery. Postoperative supplements were started when the patient was able to take free fluids and continued for 4 weeks after discharge from hospital. Data collected included weight change, complications, length of stay, nutritional intake, anthropometrics, quality of life and detailed costings covering all aspects of care.\n Some 179 patients were randomized, of whom 27 were withdrawn and 152 analysed (CC 44, SS 32, CS 35, SC 41). Dietary intake was similar in all four groups throughout the study. Mean energy intake from preoperative supplements was 536 and 542 kcal/day in the SS and SC groups respectively; that 2 weeks after discharge from hospital was 274 and 361 kcal/day in the SS and CS groups respectively. There was significantly less postoperative weight loss in the SS group than in the CC and CS groups (P < 0.050), and significantly fewer minor complications in the SS and CS groups than the CC group (P < 0.050). There were no differences in the rate of major complications, anthropometrics and quality of life. Mean overall costs were greatest in the CC group, although differences between groups were not significant.\n Perioperative oral nutritional supplementation started before hospital admission for lower gastrointestinal tract surgery significantly diminished the degree of weight loss and incidence of minor complications, and was cost-effective.\n Copyright 2004 British Journal of Surgery Society Ltd.", "The purpose of the study was to determine whether early postoperative enteral feeding with an immune-enhancing formula (IEF) decreases morbidity, mortality, and length of hospital stay in patients with upper gastrointestinal (GI) cancer.\n Early enteral feeding with an IEF has been associated with improved outcome in trauma and critical care patients. Evaluable data documenting reduced complications after major upper GI surgery for malignancy with early enteral feeding are limited.\n Between March 1994 and August 1996, 195 patients with a preoperative diagnosis of esophageal (n = 23), gastric (n = 75), peripancreatic (n = 86), or bile duct (n = 11) cancer underwent resection and were randomized to IEF via jejunostomy tube or control (CNTL). Tube feedings were supplemented with arginine, RNA, and omega-3 fatty acids, begun on postoperative 1, and advanced to a goal of 25 kcal/kg per day. The CNTL involved intravenous crystalloid solutions. Statistical analysis was by t test, chi square, or logistic regression.\n Patient demographics, nutritional status, and operative factors were similar between the groups. Caloric intake was 61% and 22% of goal for the IEF and CNTL groups, respectively. The IEF group received significantly more protein, carbohydrate, lipids and immune-enhancing nutrients than did the CNTL group. There were no significant differences in the number of minor, major, or infectious wound complications between the groups. There was one bowel necrosis associated with IEF requiring reoperation. Hospital mortality was 2.5% and median length of hospital stay was 11 days, which was not different between the groups.\n Early enteral feeding with an IEF was not beneficial and should not be used in a routine fashion after surgery for upper GI malignancies.", "Early postoperative oral feeding has been demonstrated to be safe and not increase postoperative morbidity. There are conflicting reports about its effect on postoperative length of stay. Some patients will fail attempts at early postoperative feeding and may be relegated to a longer postoperative course. Few studies to date have attempted to identify cost savings associated with early oral support, and those identified address nasoenteric support only. Fifty-one consecutive patients were randomized into either a traditional postoperative feeding group or an early postoperative feeding group after their gastrointestinal surgery. Length of hospital stay, hospital costs (excluding operating room costs), morbidity, and time to tolerance of a diet were compared. There was a tendency toward increased nasogastric tube use in the early feeding arm, but the morbidity rates were similar. Length of hospital stay and costs were similar in both arms. Early postoperative enteral support does not reduce hospital stay, nursing workload, or costs. It may come at a cost of higher nasogastric tube use, however, without an increase in postoperative morbidity.", "Previous analyses of non-prospectively randomized trials have suggested that early oral postoperative feeding might be a benefit unique to laparoscopic surgery. However, some authors have indicated that early feeding can be tolerated by the majority of patients after elective open surgery.\n This prospective randomized study was undertaken to assess whether the time prior to oral intake of food after laparoscopy-assisted surgery is shorter than that after standard laparotomy.\n This trial included 40 patients who were divided randomly into two groups before operation. Group I included 20 patients (mean age, 52 years; range, 15-77 years) who underwent a laparoscopy-assisted colon or rectal procedure (LAP). Group II consisted of 20 patients (mean age, 56 years, range, 41-74 years) who underwent surgery with a standard midline incision (SMI). On the evening after surgery, patients were allowed clear liquids ab libitum. This regimen was continued until the first postoperative day at which time they could elect to start eating a regular diet. If a patient had two episodes of vomiting, a nasogastric tube was inserted.\n Five laparoscopic procedures were converted to SMI because of adhesions (25%) and an equal number of patients was excluded from the group that was treated in the traditional manner. Therefore, only 30 patients were included in the analysis. There were no deaths in this trial. Complications appeared in four of the patients in the LAP group and in two of the patients in the SMI group (no significant difference). There were no statistically significant differences between the two groups in terms of the ability to tolerate the early oral intake of food, in the frequency of vomiting or in the incidence of insertion of a nasogastric tube. The time to the first bowel movement was 5.4 days in LAP and 5.5 days in SMI, and the difference was not significant.\n This study invalidates the claim by laparoscopic surgeons that earlier oral intake of food is tolerated by their patients than by patients who undergo standard procedures." ]

[ "1887473", "2177041", "12558620", "9024895", "17586452", "7677218", "15696988", "12243707", "16780497", "10487452", "7591417", "12856053", "1909469", "15237267", "15701249", "7872446", "15649196", "16961529", "17376205", "16863518", "17178983", "8561269", "15757817", "10487453", "17466071", "8678570", "15090013", "15485530", "1567264", "1663089", "15791515", "17175700", "12207774", "9499605", "11907288", "9071622", "12745852", "12121563", "9579209" ]

[ "A double-blind study on the efficacy of oral dapsone in cutaneous leishmaniasis.", "Cutaneous leishmaniasis in India. Clinical experience with itraconazole (R51 211 Janssen).", "Treatment of cutaneous leishmaniasis with either topical paromomycin or intralesional meglumine antimoniate.", "Itraconazole and leishmaniasis: a randomised double-blind trial in cutaneous disease.", "Comparison of miltefosine and meglumine antimoniate for the treatment of zoonotic cutaneous leishmaniasis (ZCL) by a randomized clinical trial in Iran.", "A randomized, placebo-controlled trial in Tunisia treating cutaneous leishmaniasis with paromomycin ointment.", "Intralesional injection of 2% zinc sulfate solution in the treatment of acute old world cutaneous leishmaniasis: a randomized, double-blind, controlled clinical trial.", "Comparative study of the efficacy of oral ketoconazole with intra-lesional meglumine antimoniate (Glucantime) for the treatment of cutaneous leishmaniasis.", "Comparison between the efficacy of photodynamic therapy and topical paromomycin in the treatment of Old World cutaneous leishmaniasis: a placebo-controlled, randomized clinical trial.", "Weekly vs. fortnightly intralesional meglumine antimoniate in cutaneous leishmaniasis.", "Ketoconazole in the treatment of cutaneous leishmaniasis in Kuwait.", "Treatment of cutaneous leishmaniasis with aminosidine (paromomycin) ointment: double-blind, randomized trial in the Islamic Republic of Iran.", "A randomized trial comparing a pentavalent antimonial drug and recombinant interferon-gamma in the local treatment of cutaneous leishmaniasis.", "Comparison of intralesionally injected zinc sulfate with meglumine antimoniate in the treatment of acute cutaneous leishmaniasis.", "Efficacy of paromomycin ointment in the treatment of cutaneous leishmaniasis: results of a double-blind, randomized trial in Isfahan, Iran.", "A randomized, double-blind, clinical trial of topical clotrimazole versus miconazole for treatment of cutaneous leishmaniasis in the eastern province of Saudi Arabia.", "A randomized, double-blind, placebo-controlled clinical trial of itraconazole in the treatment of cutaneous leishmaniasis.", "Comparison of intralesional meglumine antimoniate, cryotherapy and their combination in the treatment of cutaneous leishmaniasis.", "Efficacy of local heat therapy by radiofrequency in the treatment of cutaneous leishmaniasis, compared with intralesional injection of meglumine antimoniate.", "Effect of combination therapy with systemic glucantime and pentoxifylline in the treatment of cutaneous leishmaniasis.", "Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis: a randomized assessor-blind controlled trial.", "A randomized, placebo-controlled trial of a two-week regimen of aminosidine (paromomycin) ointment for treatment of cutaneous leishmaniasis in Iran.", "Comparison of topical paromomycin sulfate (twice/day) with intralesional meglumine antimoniate for the treatment of cutaneous leishmaniasis caused by L. major.", "A double-blind randomized clinical trial of a topical herbal extract (Z-HE) vs. systemic meglumine antimoniate for the treatment of cutaneous leishmaniasis in Iran.", "Effect of topical honey application along with intralesional injection of glucantime in the treatment of cutaneous leishmaniasis.", "Treatment of cutaneous leishmaniasis with itraconazole. Randomized double-blind study.", "Comparative study of the efficacy of combined cryotherapy and intralesional meglumine antimoniate (Glucantime) vs. cryotherapy and intralesional meglumine antimoniate (Glucantime) alone for the treatment of cutaneous leishmaniasis.", "Evaluation of CO laser efficacy in the treatment of cutaneous leishmaniasis.", "Local application of diminazene aceturate: an effective treatment for cutaneous leishmaniasis?", "Cutaneous leishmaniasis in Kuwait. Clinical experience with itraconazole.", "Efficacy of thermotherapy to treat cutaneous leishmaniasis caused by Leishmania tropica in Kabul, Afghanistan: a randomized, controlled trial.", "A double blind, randomised placebo controlled trial of rifampicin with omeprazole in the treatment of human cutaneous leishmaniasis.", "Evaluating the efficacy of allopurinol and meglumine antimoniate (Glucantime) in the treatment of cutaneous leishmaniasis.", "A comparative controlled trial of intralesionally-administered zinc sulphate, hypertonic sodium chloride and pentavalent antimony compound against acute cutaneous leishmaniasis.", "Fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major.", "A randomized clinical trial of topical paromomycin versus oral ketoconazole for treating cutaneous leishmaniasis in Turkey.", "Treatment of cutaneous leishmaniasis with ketoconazole cream.", "Treatment of cutaneous leishmaniasis with a combination of allopurinol and low-dose meglumine antimoniate.", "Treatment of cutaneous leishmaniasis with antimony: intramuscular versus intralesional administration." ]

[ "One hundred and twenty patients with localized cutaneous leishmaniasis were randomly allocated to receive tablets of dapsone (100 mg) or matching placebo tablets every 12 h for 6 weeks. No topical medication was used. Demonstration of Leishmania from skin lesions by the slit smear technique was mandatory for inclusion. Before, periodically during, and one month after completion of therapy an overall clinical assessment, haemoglobin determination, leucocyte count, and liver function tests were performed. 49 patients (82%) of those receiving dapsone were assessed as cured by clinical and parasitological criteria. Oral dapsone has certain advantages over other current forms of treatment: it is economical and widely available in countries where cutaneous leishmaniasis is common, and it is effective by mouth and well tolerated.", "Fifteen patients with cutaneous leishmaniasis were randomly selected for clinical trials with itraconazole. A single daily itraconazole dose of approximately 4 mg per 1 kg of body weight was administered to each patient with breakfast for 6 weeks. Five patients served as controls. On completion of therapy, ten cases in the study group (66.6%) were considered to be cured. No major adverse effects were reported. No significant changes were seen in the controls at the end of the study. The possibility of spontaneous recovery will be discussed in this report even though it is considered to be unlikely. Itraconazole has promising potential in cutaneous leishmaniasis therapy.", "Ninety-six patients with a clinical and parasitological diagnosis of cutaneous leishmaniasis were recruited to a comparative randomized clinical trial evaluating the efficacy of topical paromomycin vs. weekly intralesional injections of meglumine antimoniate. The patients were randomly divided into two treatment groups: one group was treated with topical paromomycin ointment and the other with intralesional meglumine antimoniate. Treatment was continued in both groups until complete recovery occurred (defined as healing in less than 2 months with no residual scar or relapse for up to 1 year post treatment). Treatment failure was defined as an increase in the number and size of pre-existing lesions or untoward side-effects. The maximum treatment period was 3 months. The patients were followed up for 1 year. The results showed that intralesional meglumine antimoniate led to 41.7% complete recovery, However, topical paromomycin gave a lower cure rate of 16.6% (P < 0.05). Treatment failure was observed in 39.7% of the group receiving intralesional meglumine and in 72.9% of those on topical paromomycin (P < 0.05). This study indicates that intralesional meglumine antimoniate is superior to topical paromomycin in the treatment of cutaneous leishmaniasis.", "Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease of the skin. Previous open controlled studies with oral itraconazole suggest that it was effective for CL in India. Twenty patients with localised CL participated in this trial. Patients were allocated randomly to receive capsule itraconazole and matching placebo for 6 weeks. No topical medicines were used. Demonstration of Leishmania by slit smear was mandatory. Prior to, periodically during and 3 months after completion of therapy an overall clinical assessment, liver function tests and urinalysis were performed. On decoding, out of the 10 cases receiving drug itraconazole, 7 were declared cured by clinical and parasitological criteria. No major side-effects were noted. Spontaneous remission was observed in 1 case in the placebo group at 3 months follow up. Oral itraconazole has a promising antileishmanial thus secure CL patient from the hazards of antimonials.", "This study was a randomized, open label comparison that was designed to determine efficacy and safety of miltefosine as the first oral drug for the treatment of zoonotic cutaneous leishmaniasis caused by Leishmania major in comparison with meglumine antimoniate. Complete clinical response was defined as 100% re-epithelialization of the lesion. Definitions of lesion cure and failure were based on both clinical and parasitological criteria two weeks after the end of treatment and clinical recovery three months after this period. Of 32 patients enrolled for miltefosine treatment 28 patients completed treatment, of which 26 were cured at three months, corresponding to a cure rate of 92.9% on a per protocol analysis, and 81.3% according to intention to treat analysis. There was one failure (3.1%), one relapse (3.1%) and four dropouts due to lack of tolerability (12.5%) during the first week of treatment. Of 31 patients who received intramuscular meglumine antimoniate (20mgSb(5)/kg body weight daily for 14 days) 25 were cured (83.3% on a per protocol basis, 80.6% on intention to treat basis), five failed (16.1%) and one was lost (3.2%) at 3-month follow-up. At 6-month follow-up after the end of treatment, no relapse was observed. Both regimens were tolerated but averages of nausea (32.2%) and vomiting (21.5%) were observed in patients during two weeks after initiation of miltefosine treatment. Other gastrointestinal, musculoskeletal, and total adverse events were not statistically different in the two groups during one to four weeks after therapy initiation. No relevant changes were observed in levels of liver enzymes, creatinine and hematological tests before and after end of treatment in both groups. In conclusion, miltefosine is apparently at least as good as meglumine antimoniate for the treatment of cutaneous leishmaniasis caused by L. major in Iran, based on parasitological as well as clinical criteria two weeks, three months, and six months after end of treatment.", "A randomized, placebo-controlled, double-blind trial was carried out in 1992 in central Tunisia to assess the tolerability and efficacy of paromomycin ointment against zoonotic cutaneous leishmaniasis caused by Leishmania major. One hundred fifteen patients, 2--60 years of age, with a single lesion of parasitologically confirmed cutaneous leishmaniasis, were included in the trial. The ointment was applied twice a day from day 1 through day 14. Clinical and parasitologic evaluations of lesions were done at days 0, 15, 45, and 105. Fifty-seven patients were allocated the treatment and 58 the placebo. Based on local toxicity and laboratory evaluation, there was no difference in tolerability between the two groups. Parasitologic evaluation at day 15 showed that 74.5% of the treated group had negative smears compared with 56.4% among controls (P = 0.06). This difference was no longer apparent at days 45 and 105. Clinical evaluation at days 15, 45, and 105 did not indicate any difference between the two groups. The clinical evaluation at day 15 was a good predictor of the final prognosis of the lesion in the two groups when analyzed separately, suggesting no clinical relapse in either group. These findings suggest that paromomycin ointment should not be used in the present formulation as a treatment for zoonotic cutaneous leishmaniasis in Tunisia.", "Several in vitro and in vivo studies have shown inhibitory effects of zinc sulfate (ZnSO4) on Leishmania parasites. The objective of this study was to compare the efficacy of intralesional injections of 2% ZnSO4 solution with meglumine antimonate (Glucantime) in the treatment of acute Old World cutaneous leishmaniasis (CL). Seventy-two patients with CL lesions less than 8 weeks were recruited in a randomized, double-blind, clinical trial in an area endemic for Leishmania major after giving written informed consent. They were treated with 6 weekly intralesional injections of either drug. Among 36 patients with 53 lesions treated with ZnSO4 and 36 patients with 53 lesions treated with Glucantime, 13 patients with 19 lesions and 22 patients with 31 lesions completed the trial, respectively. Inadequacy of treatment was the main reason for drop-out in 12 (33.3%) and 2 (5.5%) patients in ZnSO4 and Glucantime groups, respectively (P < .05). Complete re-epithelialization was observed in 2 (10.5%) and 19 (61.3%) lesions 1 week after the end of treatment in the ZnSO4 and Glucantime groups, respectively (P < .05). In conclusion a 6-week course of weekly intralesional injections of 2% ZnSO4 solution was less effective than Glucantime in the treatment of acute Old World CL.", "Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease caused by a range of Leishmania species. Many treatment modalities have been proposed, although pentavalent antimonials are still considered to be the first-line treatment of CL. However, due to the high cost and adverse effects of antimonials, as well as an increase in the number of resistant strains of CL to antimonials, this study was conducted to compare the efficacy of oral ketoconazole with intralesional meglumine antimoniate (Glucantime, Specia, Paris, France) for the treatment of CL.\n A total of 96 patients with CL were enrolled in the study. The diagnosis of CL was confirmed parasitologically using direct skin smears or skin biopsies. The patients were randomly allocated to two treatment groups. Group A (64 patients) was treated with ketoconazole 600 mg/day for adults and 10 mg/kg per day for children for 30 days. Group B (32 patients) was treated with 6-8 biweekly intra-lesional injections of meglumine antimoniate (Glucantime). Both groups were followed for 6 months after termination of treatment.\n The results showed complete clinical cure in 89% of cases in Group A (treated with oral ketoconazole) and 72% of cases in Group B (treated with intra-lesional Glucantime). This difference was statistically significant (p < 0.05). No significant side effects were observed in either treatment group.\n Oral ketoconazole can be an effective treatment modality in CL, especially in children afflicted with this disease.", "The optimal treatment for cutaneous leishmaniasis (CL) is not known. Topical paromomycin is one of the many drugs that have been suggested for the treatment of CL caused by Leishmania major. Recently, topical photodynamic therapy (PDT) has been reported to be effective in the treatment of CL.\n To compare the parasitological and clinical efficacy of PDT vs. topical paromomycin in patients with Old World CL caused by L. major in Iran.\n In this trial, 60 patients with the clinical and parasitological diagnosis of CL were recruited and were randomly divided into three treatment groups of 20 subjects each. Group 1 was treated with weekly topical PDT, and groups 2 and 3 received twice-daily topical paromomycin and placebo, respectively. The duration of treatment was 4 weeks for all groups. These groups were followed for 2 months after the end of treatment.\n In total, 57 patients with 95 lesions completed the study. At the end of the study, complete improvement was seen in 29 of 31 (93.5%), 14 of 34 (41.2%) and 4 of 30 lesions (13.3%) in groups 1, 2 and 3, respectively (P<0.001). At the same time point, 100%, 64.7% and 20% of the lesions had parasitological cure in group 1, 2 and 3, respectively (P<0.001).\n Topical PDT can be used safely as a rapid and highly effective alternative treatment choice for Old World CL in selected patients.", "nan", "nan", "To compare the parasitological and clinical efficacy of four weeks versus two weeks of treatment with aminosidine (paromomycin) ointment in patients with cutaneous leishmaniasis caused by Leishmania major in the Islamic Republic of Iran.\n Double-blind, randomized trial of four weeks of aminosidine ointment (n = 108) vs two weeks of aminosidine ointment and two weeks of placebo (n = 108). Patients were assessed on days 15, 29, 45, and 105 for clinical cures and clinical and parasitological cures.\n Four weeks' treatment gave significantly better cure rates than two weeks' treatment: on day 29, there were 80/108 (74%) vs 64/108 (59%) clinical cures (P = 0.05) and 47 (44%) vs 26 (24%) clinical and parasitological cures (P = 0.005). By day 45, fewer patients who received four weeks' treatment had required rescue treatment with antimonials than those who received two weeks' treatment: 20 (19%) vs 36 (33%) (P = 0.02). On day 105, the results still favoured those who had been allocated four weeks of active treatment, but the differences were no longer as clearly significant. No side-effects were observed or reported.\n Approximately two-thirds of patients given ointment for four weeks were cured clinically. Although about half of those cured might have recovered spontaneously even without treatment, four weeks of aminosidine ointment could become the first-line treatment for uncomplicated cutaneous leishmaniasis due to L. major, with antimonials needed in only the one-third of patients not cured by the end of treatment with aminosidine. This would considerably reduce the costs and side-effects associated with antimonial drugs.", "In a randomized prospective trial N-methyl-glucamine antimoniate (Glucantime) and human recombinant interferon-gamma were infiltrated around lesions of cutaneous leishmaniasis caused by Leishmania tropica in Syria. A previous trial had shown that intradermal application of interferon-gamma promoted the healing of similar lesions in the study area. Twenty patients with 38 lesions received 1-3 ml Glucantime and 20 patients with 37 lesions received 25 micrograms of interferon-gamma intradermally once weekly for 5 consecutive weeks. While all lesions treated with Glucantime were free of parasites after the third injection, only 69% of those treated with interferon-gamma were parasitologically cured by week 10. Within 10 weeks, lesions treated with Glucantime healed completely in 29/38, and partially in 9/38, cases, whereas 1/37 and 13/37 lesions treated with interferon-gamma healed completely and partially, respectively. Perilesional application of Glucantime was highly effective and superior to interferon-gamma for treatment of cutaneous leishmaniasis caused by L. tropica.", "Cutaneous leishmaniasis is an endemic disease in developing countries. The first-line drugs for its treatment are the pentavalent antimony compounds such as meglumine antimoniate (MA). High cost, side effects, multiple injections and incomplete efficacy are limitations of this therapy. Zinc sulfate (ZS) has been reported to be effective in the treatment of cutaneous leishmaniasis.\n To compare the efficacy of intralesional injections of ZS 2% with those of MA in the treatment of cutaneous leishmaniasis.\n This was a prospective, double-blind, case-control clinical study. 104 patients with typical lesions of acute cutaneous leishmaniasis (ACL) were included. The duration of treatment was 6 weeks. Improvement was evaluated by clinical examination and direct smear.\n The study was completed in only 66 patients: 35 patients received MA and 31 received ZS. The cure rates were 60% for MA and 83.8% for ZS. After the second and fourth weeks, the efficacy of treatment with ZS was higher than that with MA (p < 0.01), but after 6 weeks no significant differences were observed between the two groups (p > 0.05).\n On the basis of this trial and despite the high number of drop-outs, we consider that the intralesional injection of ZS 2% is an alternative treatment in ACL.\n Copyright 2004 S. Karger AG, Basel", "Although pentavalent antimonials are often used in the first-line treatment of cutaneous leishmaniasis (CL), they have several adverse effects. Intralesional administration of antimonials and other antileishmanial drugs can be painful. In the present, double-blind, randomized study, to determine if topical treatment with paromomycin is effective in the treatment of CL, 35 cases of CL were treated, twice daily for 30 days, with a commercial skin-care lotion containing 10% urea (the placebo) and another 30 were similarly treated with the same lotion to which paromomycin sulphate had been added (to give a concentration of 15%). Each case was assessed clinically 7, 14, 21 and 30 days after treatment began, and parasitologically 30 and 60 days after the initiation of treatment. Five (17%) and five (17%) of the cases treated with paromomycin showed complete healing, with the apparent clearance of amastigotes from their lesions, 30 and 60 days after treatment began, respectively. At the same time-points, however, the lesions on six (17%) and seven (20%) of the cases in the placebo group, respectively, also appeared to have healed completely. Ointment containing 15% paromomycin therefore appears ineffective in the treatment of CL, at least when applied twice daily for 30 days to the lesions of cases from an endemic area of Isfahan, Iran.", "The parenteral treatment currently available for cutaneous leishmaniasis (CL) is painful and potentially exposes patients to serious side effects. Thus, effective, topical therapy would be valuable. We assessed the efficacy of topical 1% clotrimazole and 2% miconazole creams in relation to early healing of lesions in CL in a randomized, double-blind clinical trial in 54 patients with 151 lesions treated for 30 consecutive days. Response to treatment was assessed at two weeks and 30 days and classified as fully healed, size reduced, no change, and size increased or worse. Of 89 lesions treated with clotrimazole, 14 (15.7%) healed fully, 42 (47.2%) were reduced in size, 20 (22.5%) showed no change, and 13 (14.6%) got worse. Correspondingly, in the 62 lesions treated with miconazole, none healed fully, 22 (35.5%) were reduced in size, 16 (25.8%) showed no change, and 24 (38.7%) got worse. The differences were statistically significant (P < 0.001). No side effects were observed. It is concluded that clotrimazole was the more effective of the two imidazoline compounds and is recommended as initial treatment for simple lesions.", "Several modalities have been used for the treatment of cutaneous leishmaniasis (CL) with various results. In vitro and in vivo studies have shown inhibitory effects of azole drugs on Leishmania parasites.\n To evaluate the efficacy and tolerability of oral itraconazole in the treatment of CL caused by L. major.\n A total of 200 patients with parasitologically confirmed CL with a duration of less than 45 days from a well known L. major endemic area were included in a randomized, double-blind, placebo-controlled clinical trial. The patients received either itraconazole 200 mg daily (100 patients) or placebo (100 patients) for 8 weeks. The primary outcome measures were clinical cure (complete re-epithelization of all lesions) and parasitological cure at the end of the treatment.\n Eighty-three patients in the itraconazole and 75 patients in the placebo group completed the treatment course. After 8 weeks of treatment, clinical cure was observed in 59% and 53% and parasitological cure was observed in 83% and 76% of patients in the itraconazole and placebo groups, respectively, which were not significantly different. There was no difference in the rate of adverse events.\n An 8-week course of oral itraconazole was not more effective than placebo in the treatment of CL.", "nan", "Cutaneous leishmaniasis (CL) is a serious public health problem in many tropical and subtropical regions of the world. Treatment of CL can prevent disfiguring scars.\n The efficacy of local heat therapy by radiofrequency (RF) was compared with intralesional injection of meglumine antimoniate in the treatment of CL.\n This was a randomized clinical trial. Patients with antroponotic cutaneous leishmaniasis (ACL) in the Isfahan province of Iran were enrolled in the study if the examination of a smear from a suspected CL lesion was confirmed positive for Leishmania. Patients were randomly allocated to one of two treatment groups. Group A was treated by heat therapy by RF at 50 degrees C for 30 s once weekly for 4 weeks, and group B was treated with intralesional injection of meglumine antimoniate once weekly for 4 weeks. Follow-up lasted 6 months. Response to treatment was classified as complete (lesions flattened, no induration, and epidermal creases had appeared), partial (reduction in lesion size, but without the appearance of epidermal creases) and poor (no reduction in lesion size).\n Of 117 participants, 57 patients with 83 lesions in group A and 60 patients with 94 lesions in group B completed the study and were followed up for 6 months. Complete, partial and poor response to treatment were 80.7%, 12% and 7.3% in group A, and 55.3%, 21.27% and 23.40% in group B, respectively (P = 0.001). In both groups, there was no relapse in patients with complete response after 6 months of follow-up.\n Heat therapy with thermogenerator RF can be used as an efficacious treatment in the lesions of CL. It is more effective than the conventional treatment with intralesional meglumine antimoniate injection.", "Cutaneous leishmaniasis is a common parasitic disease in Iran, especially in Isfahan. First line treatment for this disease is antimonial compounds; however, owing to the intermittent failure of this treatment and its significant side-effects alternative therapeutic measures have been advocated.\n Evaluating the efficacy of pentoxifylline plus glucantime in the treatment of cutaneous leishmaniasis.\n This double-blind, randomized, controlled clinical trial with simple sampling was performed on 64 patients with cutaneous leishmaniasis referred to the Skin Diseases & Leishmaniasis Research Center from an endemic foci of L. major in Isfahan. The patients randomly were divided into two groups. One group was treated with systemic Glucantime (20 mg pentavalent antimony/kg/day) combined with pentoxifylline (400 mg three times daily) and the other group were treated with Glucantime (20 mg pentavalent antimony/kg/day) plus placebo (three tablets daily) for 20 days. Follow up lasted 3 months. Response to treatment was grouped as complete improvement (lesions had been flattened, no induration, and epidermal creases had appeared), partial improvement (reduction in lesion size, but without the appearance of epidermal creases) and poor response (no reduction in lesion size).\n Of 64 participants, 32 patients in the trial group and 31 patients in the control group were followed for 3 months. One patient in group B discontinued withdrew. After this time, complete improvement, partial improvement and poor response to treatment were 81.3%, 12.5% and 6.2% in the trial group and 51.6%, 29% and 19.4% in the control group, respectively. We also observed no adverse effect resulting from pentoxifylline.\n The result obtained by two therapeutic methods indicates that combined therapy with Glucantime and pentoxifylline is more effective than Glucantime alone (P < 0.05).", "To determine the efficacy and safety of imiquimod in combination with meglumine antimoniate in treating cutaneous leishmaniasis.\n Prospective, randomized, assessor-blind, parallel-design, placebo-controlled trial.\n Two primary care health clinics.\n One hundred nineteen patients (59 patients in the imiquimod group and 60 in the placebo group) were included in the study.\n Patients were randomly assigned to receive a combined 4-week course of imiquimod or placebo with meglumine antimoniate treatment (20 mg/kg of pentavalent antimony daily for 2 weeks) in an endemic area of Leishmania tropica.\n The primary end point was clinical cure, defined as more than 75% reduction in the size of lesions compared with baseline at week 8.\n At the end of the 4-week treatment period, clinical cure was similar in both groups (11 patients [18.6%] in the imiquimod-treated group vs 18 patients [30.0%] in the placebo group) (P = .15). Four weeks after the end of treatment, 26 patients (44.1%) and 29 patients (48.3%) in the imiquimod-treated and placebo groups, respectively, were cured (P = .64). Pruritus and burning sensation were reported by 3 patients treated with imiquimod and by no patients treated with placebo.\n This study showed no beneficial effect of combining a 4-week course of treatment with 5% imiquimod cream and a standard course of treatment with meglumine antimoniate in patients with cutaneous leishmaniasis in an endemic area of L tropica.\n isrctn.org Identifier:ISRCTN77659407 and Cochrane Skin Group Identifier: CSG Trial No. 32.", "The effect of a two-week regimen of topical aminosidine was investigated in a randomized, double-blind, placebo-controlled trial of 251 selected Iranian patients with zoonotic cutaneous leishmaniasis. Patients underwent clinical and parasitologic assessment before and 15 (end of therapy), 45, and 105 days after starting the treatment. Aminosidine ointment was safe and well-tolerated, and produced significant reductions in the prevalence of parasitologically positive smears on days 15 and 105 (but not day 45) after treatment compared with placebo. However, there was no clear clinical benefit at any stage after treatment. We conclude that this twice a day two-week regimen of aminosidine was inadequate to accelerate the recovery of most cases of cutaneous leishmaniasis. However, the ointment did show some clear evidence of parasitologic efficacy and should now be studied in longer or more frequent regimens in an effort to prevent parasitologic relapse and thus promote clinical improvement.", "This is an open study to compare the cure rate of cutaneous leishmaniasis caused by L. major and treated with either paromomycin sulfate or intralesional injection of meglumine antimoniate. Sixty parasitologically proven cases with 1-3 lesions were included and divided randomly into two equal groups; one group received 1 ml of meglumine antimonate intradermally every other day for 20 days, the other group received the ointment containing 15% parmomycin sulfate in urea twice daily for 20 days. The patients were clinically evaluated at 1 and 6 weeks after treatment was completed. The results of clinical evaluation at 1 week after treatment completed showed a cure rate of 18 out of 27 (66%) in the meglumine antimonate injected group and 20 out of 29 (68%) in the paromomycin sulfate treated group. The chi square test was used to compare the cure rate between the two groups and showed no significant difference (p = 0.85).", "nan", "Leishmaniasis is an endemic disease in Iran. Although many treatments have been suggested for this disease, there hasn't been an effective and safe treatment yet. Regarding the healing effect of honey in the chronic ulcers and its reported therapeutic effect in cutaneous leishmaniasis, we performed a study to better evaluate the efficacy of honey in cutaneous leishmaniasis and its final scar.\n In a prospective clinical trial, 100 patients with confirmed cutaneous leishmaniasis were selected and randomized into 2 groups. Group A were treated with topical honey twice daily along with intralesional injection of glucantime once weekly until complete healing of the ulcer or for maximum of 6 weeks. Group B were treated with intralesional injection of glucantime alone until complete healing of the ulcer or for a maximum of 6 weeks, too. The patients were followed for 4 months. The collected data were analyzed statistically using statistical tests including Chi-square, Mann Whitney and Kaplan-Mayer tests.\n In this study, 45 patients that had cutaneous leishmaniasis were treated with intralesional glucantime alone and 45 patients were treated with topical honey and glucantime. Ten patients left out the study. In the glucantime alone treated group, 32 patients (71.1%) had complete cure whereas in the group treated with both glucantime & topical honey, 23 patients (51.1%) achieved complete cure. This difference was significant statistically (p = 0.04).\n Further studies to better clarify the efficacy of honey in cutaneous leishmaniasis is needed. We suggest that in another study, the efficacy of honey with standardized level of antibacterial activity is evaluated against cutaneous leishmaniasis.", "To compare the efficacy of itraconazole with placebo in the treatment of cutaneous leishmaniasis caused by Leishmania major.\n Double-blind placebo-controlled study.\n Patients were selected from volunteers wit cutaneous leishmaniasis who lived in a hyperendemic area.\n One hundred forty patients were randomly selected for this double-blind study. Exclusion criteria were pregnancy, gestation, age younger than 12 years, and duration of disease of more than 4 months.\n Each patient received itraconazole (7 mg/kg per day) or placebo for a 3-week period. The patients were kept under observation for an additional 30-day period. OUTCOME. The study was completed as planned in 131 patients.\n Complete healing occurred in 59% of the itraconazole group in comparison with 44.3% of the patients who were treated with placebo capsules. No difference was found between the 2 groups with respect to adverse effects.\n Although itraconazole has the advantage of being an oral agent that is used in the treatment of cutaneous leishmaniasis, the low response rate in patients receiving itraconazole indicates that itraconazole cannot be used as the single agent in the treatment of patients with cutaneous leishmaniasis caused by L. major.", "Cutaneous leishmaniasis (CL) is a parasitic disease caused by Leishmania species. There is a need for more effective and less time-consuming therapeutic methods for this condition.\n To evaluate the efficacy of combined cryotherapy and intralesional meglumine antimoniate (MA) (Glucantime, Specia, Paris, France) for the treatment of CL.\n Patients were divided into three groups: Group 1, 100 patients with 149 lesions were treated with cryotherapy plus intralesional MA; Group 2, 200 patients with 230 lesions were treated with cryotherapy; Group 3, 100 patients with 160 lesions were treated with intralesional MA. These groups were followed for 6 months after the end of treatment.\n The results showed complete cure in 90.9% of cases in Group 1, 57.15% of cases in Group 2, and 55.63% of cases in Group 3. The difference between Group 1 and the other groups was statistically significant (P < 0.05).\n Combined cryotherapy and intralesional MA is more effective than either cryotherapy or intralesional MA alone for the treatment of CL.", "Cutaneous leishmaniasis is a common disease in Iran, especially in the north-east, central and southern parts of the country. Many treatments have been suggested for this disease but none is completely effective and without side-effects such as pain, arthralgia and renal or cardiac complications. Lasers have been used for treatment of several skin diseases since 1970, and CO(2) lasers are now being used for treatment of leishmaniasis. In this study, a CO(2) laser (Sonic 500 machine) was used as a source of a continuous CO(2) laser wave.\n A total of 123 patients (68 female and 55 male) with 183 lesions were treated with the CO(2) laser. The maximum power was 100 W and the pulse width was 0.5-5 s. For the control group, 110 patients (with 250 lesions) were treated with glucantime 50 mg/kg/day for 15 days and, after 15 days of rest, this treatment was repeated (Glucantime Amps, 1.5 g in a 50-mL solution, was used). For follow-up, the patients were visited 1, 3, 4, 8, 12 and 24 weeks after treatment and any complications, recurrences or other wound characteristics were recorded. In the second group, Finally, all collected data were analyzed statistically.\n Statistical analysis with the chi(2) test showed that treatment with the CO(2) laser was more effective than treatment with glucantime (P = 0.0007). Complications were also seen less often with the laser treatment than with glucantime and were limited to the ulcer site. The CO(2) laser was more effective in treating cutaneous leishmaniasis than glucantime (1.12 times), had fewer side-effects (4.5% vs. 24%) and resulted in a shorter healing time (1 month vs. 3 months), and treatment could be applied in a single session.\n The results of this and previous studies suggest that cutaneous leishmaniasis can be treated effectively with CO(2) laser if those providing the treatment are sufficiently experienced. Laser treatment is more cost-effective than other treatments and can be used as first-line therapy for cutaneous leishmaniasis (wet and dry types).", "In a controlled clinical trial we tested the effect of diminazene aceturate (Berenyl, Bayer) in local application against cutaneous leishmaniasis. The study was performed among schoolchildren in Nyala, West-Sudan in 1988 during a major outbreak of cutaneous leishmaniasis in this region. Sixty-six schoolchildren with cutaneous leishmaniasis were enrolled in the study. The children were randomly assigned to either diminazene aceturate (Berenil) or cetrimide 15% + chlorhexidine 1.5% (Savlon) treatment. The study results show a significant faster healing of the ulcers in the children treated with diminazene aceturate (chi-square 7.31, p less than 0.01). We conclude that diminazene aceturate should be considered as a potential topical drug in the treatment of cutaneous leishmaniasis.", "Twenty-four patients suffering from single or multiple lesions of cutaneous leishmaniasis were included in this study. Most of the lesions were on the extremities. The patients were randomly divided into two groups. Most of the patients in the first group who were given oral itraconazole for a period of 6-8 weeks showed excellent clinical response. On the other hand, only one patient in the second control group who was given placebo showed good clinical improvement. Systemically administered itraconazole may prove to be a valuable modality for the treatment of cutaneous leishmaniasis.", "Pentavalent antimony is the agent recommended for treatment of cutaneous leishmaniasis (CL). Its use is problematic, because it is expensive and because of the potential for drug-associated adverse effects during a lengthy and painful treatment course.\n We tested the efficacy of thermotherapy for the treatment of CL due to Leishmania tropica in a randomized, controlled trial in Kabul, Afghanistan. We enrolled 401 patients with a single CL lesion and administered thermotherapy using radio-frequency waves (1 treatment of >or=1 consecutive application at 50 degrees C for 30 s) or sodium stibogluconate (SSG), administered either intralesionally (a total of 5 injections of 2-5 mL every 5-7 days, depending on lesion size) or intramuscularly (20 mg/kg daily for 21 days).\n Cure, defined as complete reepithelialization at 100 days after treatment initiation, was observed in 75 (69.4%) of 108 patients who received thermotherapy, 70 (75.3%) of 93 patients who received intralesional SSG, and 26 (44.8%) of 58 patients who received intramuscular SSG. The OR for cure with thermotherapy was 2.80 (95% confidence interval [CI], 1.45-5.41), compared with intramuscular SSG treatment (P=.002). No statistically significant difference was observed in the odds of cure in comparison of intralesional SSG and thermotherapy treatments. The OR for cure with intralesional SSG treatment was 3.75 (95% CI, 1.86-7.54), compared with intramuscular SSG treatment (P<.001). The time to cure was significantly shorter in the thermotherapy group (median, 53 days) than in the intralesional SSG or intramuscularly SSG group (median, 75 days and >100 days, respectively; P=.003).\n Thermotherapy is an effective, comparatively well-tolerated, and rapid treatment for CL, and it should be considered as an alternative to antimony treatment.", "This study was conducted on 50 patients of Anthroponotic cutaneous leishmaniasis (oriental sore) to assess the efficacy of rifampicin and omeprazole through a double blind, randomised placebo control study.\n The diagnosis of Anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica was done by demonstration of Leishmania tropica (LT) bodies from the painless, dry ulcerative lesion. Each patient was assessed clinically in the beginning of the study, at the end of 2,4 and 6 weeks and all observations were compared in both the groups. Twenty-five patients received rifampicin with omeprazole (Group A) whereas other 25 patients received placebo (Group B) for a period of six weeks.\n Altogether 23 cases in group Aand 21 cases in group B completed the study. About 16 (69.7%) cases in group A and 3 (14.29%) cases in group B had complete healing, whereas 3 patients (13.04%) of group A and 4 patients (19.05%) of group B had partial response and 4 patients (17.93%) of group A and 14 patients (66.67%) of group B had no response at the end of study. The difference of two groups was statistically highly significant (p < 0.00025). All patients tolerated the drug and placebo very well and no side effect was reported.\n In our opinion rifampicin and omeprazole is a highly effective, less toxic and cheaper alternative for the management of cutaneous leishmaniasis.", "Cutaneous leishmaniasis is a common disease in Iran, particularly in Kerman province. It usually occurs via the bite of an infected sandfly.\n One hundred and fifty patients suffering from cutaneous leishmaniasis were included in this study in Kerman. The patients were randomly divided into three groups. They were matched with regard to age, sex, duration of the disease, and type, number, and site of the lesions. For each group, one of the following therapeutic methods was applied: (i) oral allopurinol (15 mg/kg/day) for 3 weeks; (ii) intramuscular injection of Glucantime (30 mg/kg/day), corresponding to 8 mg/kg/day of pentavalent antimony, for 2 weeks; (iii) combined therapy. The lesions were re-examined at the end of treatment and 2 and 4 weeks later. The response to treatment was graded as excellent (reduction in the size of the lesion by at least 80% or complete clearance), good (reduction in the size of the lesion by 50%), and poor (minimal or no change in the lesion).\n The overall results indicated that 18% of patients showed excellent response, 6% good response, and 76% poor response in the first group. In the second group, 24% of patients showed excellent response, 6% good response, and 70% poor response. In the third group, 46% of patients showed excellent response, 8% good response, and 46% poor response.\n The results obtained by the three therapeutic methods indicated that combined therapy with allopurinol plus Glucantime was much more effective than that obtained by each of the two drugs when used alone (P < 0.05).", "A comparative clinical trial between two newly introduced intralesional treatments for acute leishmaniasis and the established treatment of intralesionally-administered pentavalent antimony compounds was performed. Treatments were allocated randomly to a total of 63 patients who received 2% zinc sulphate, 7% sodium chloride solutions or sodium stibogluconate intralesionally. A number of patients were left without treatment as controls. Patients were followed-up for 45 days, the results showing that the three treatments gave comparable cure rates by the end of the follow-up period. However, zinc sulphate gave a high cure rate (94.8%) usually with a single injection.", "Whereas certain oral antifungal azoles are well documented to have activity against leishmania, data on the efficacy of fluconazole for leishmaniasis are limited. We conducted a controlled trial in Saudi Arabia of fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major.\n This randomized, double-blind, placebo-controlled trial assessed the efficacy of oral fluconazole, in a dose of 200 mg daily for six weeks, in the treatment of parasitologically confirmed cutaneous leishmaniasis. The primary outcome measure was the time to the complete healing of all lesions.\n A total of 106 patients were assigned to receive fluconazole, and 103 patients were assigned to receive placebo. Follow-up data were available for 80 and 65 patients, respectively. At the three-month follow-up, healing of lesions was complete for 63 of the 80 patients in the fluconazole group (79 percent) and 22 of the 65 patients in the placebo group (34 percent; relative risk of complete healing, 2.33 [95 percent confidence interval, 1.63 to 3.33]). According to an intention-to-treat analysis, the rates of healing were 59 percent and 22 percent, respectively (relative risk, 2.76 [95 percent confidence interval, 1.84 to 4.12]). Sodium stibogluconate was offered to 11 patients in the fluconazole group who returned for follow-up (14 percent) and 33 of those in the placebo group (51 percent) in whom oral treatment was judged to have failed. According to a Kaplan-Meier analysis, the time to healing was shorter for the fluconazole group (median, 8.5 weeks, as compared with 11.2 weeks in the placebo group; P<0.001 by the log-rank test). Side effects were mild and similar in both groups.\n A six-week course of oral fluconazole is a safe and useful treatment for cutaneous leishmaniasis caused by L. major.", "An open-labeled, randomized clinical trial to evaluate the efficacy of paromomycin ointment as compared with ketoconazole was conducted on seventy-two patients of both sexes and different ages with the confirmed diagnosis of cutaneous leishmaniasis (CL). All patients had a complete clinical evaluation for other diseases. Patients were excluded if they were pregnant or nursing or if they had serious concomitant diseases. Patients were divided randomly into two treatment groups: in the first group 40 patients were treated with an ointment containing 15% paromomycin sulfate and 12% methylbenzothonium chloride in white soft paraffin (labeled as p-ointment by El-On1) twice daily for 15 days. Treated lesions were left uncovered. The second group consisted of 32 patients who received ketoconazole 400 mg/day orally for 30 days. This dosage was reduced to 200 mg/day for patients below 12 years of age. In all cases the diagnosis was based on positive smear and/or culture. Direct smears were prepared from the exudate obtained by a small incision made at the edge of the lesion with a sterile surgical blade or lancet and stained using the Giemsa method for leishmania bodies (Fig 1). In smear negative and suspected cases aspirates taken by puncturing the lesions were inoculated onto NNN (Novy, McNeal, Nicolle) medium for culture. The cultures were incubated at 28 degrees C and the development of motile promastigotes was observed. Clinical and parasitological evaluations of the patients were performed at the end of the treatment period and 4 weeks post-treatment. A cure was defined as complete healing and disappearance of the lesion or reversible hypopigmentation at the site of lesion. Incomplete or partial improvement was defined as a reduction in the size of a lesion and the absence of parasites on smear or culture. A treatment failure was defined as the absence of any changes in the lesion and persistence of parasites on smear or culture.", "Cutaneous leishmaniasis (CL) is endemic in many countries. It has been recognized as a major public health problem in Iran. Many drugs have been suggested for the treatment of CL but most of them used intramuscularly or intravenously. Recently, a ketoconazole tablet has been used for the treatment of CL.\n To compare the efficacy of ketoconazole cream with placebo in the treatment of CL.\n The study was a double-blind, placebo-controlled trial. Patients with proven CL were treated with ketoconazole cream or placebo cream. The duration of treatment was 21 days and the patients were visited on days 7, 14 and 21. Follow-up was for 1 month after the end of treatment.\n The study was completed in 73 patients (45 male, 28 female). The mean age of the patients was 19.9 years. A total of 38 patients received ketoconazole and 35 patients were treated with the placebo cream. At the end of treatment (day 21), complete healing had occurred in 15.7% of the ketoconazole group in comparison with 14.3% of the patients who were treated with the placebo cream (p=0.86). One month after the end of treatment the lesions in 28.9% of the ketoconazole group and 22.8% of the placebo group were healed (p=0.55).\n Although the ketoconazole tablet has been reported to be effective in the treatment of some cases of CL, the low response rate in patients receiving ketoconazole cream indicates that it cannot be used as the single agent in the treatment of CL patients.", "The objective of this study was to compare the efficacy of a combination of allopurinol (AL) and low-dose meglumine antimoniate (MA) with standard-dose MA in cutaneous leishmaniasis caused by Leishmania major. An open, controlled study was performed. Seventy-two patients were randomly selected from volunteers with cutaneous leishmaniasis living in a hyperendemic area. Exclusion criteria included pregnancy, nursing vs. gestation, age less than 5 years, and duration of disease of more than 4 months. Each patient received MA (60 mg/kg/day) or AL (20 mg/kg/day) plus low-dose MA (30 mg/kg/day) for 20 days, and was followed up for 30 days after cessation of treatment. The study was completed as planned in 66 patients. Complete healing occurred in 74.2% of patients in the MA group and in 80.6% of patients in the MA + AL group. No difference was found between the two groups with respect to side-effects. The combination of AL and MA increases the anti-leishmanial effects of antimoniate. In this study, it was confirmed that low-dose MA plus AL is as effective as high-dose MA in the treatment of cutaneous leishmaniasis caused by L. major.", "The various methods used to treat cutaneous leishmaniasis (CL) have not given consistent results. The aim of the present study was to compare the efficacy of a solution of meglumine antimoniate (MA; 85 mg Sb/ml) given intralesionally (i.l.) with that of the same solution given intramuscularly (i.m.). Eighty CL patients, with a total of 147 lesions, were randomly allocated into the two treatment groups. Forty were injected i.m. with MA (15 mg Sb/kg.day) on 6 days/week until 12 injections had been given to each. The lesions of the other 40 patients were infiltrated with MA (0.2-0.8 ml/lesion) every other day for 30 days. After 15 days' therapy, none of the lesions on those treated i.m. had fully healed (although five lesions showed some improvement) whereas two lesions on those treated i.l. had fully healed and 10 showed good improvement. After 30 days, 46 (68%) of the 68 lesions on those treated i.m. had healed completely, 11 (16%) had improved, and five (8%) worsened. The corresponding values for the 66 lesions on those treated i.l. were 48 (73%), 10 (15%) and three (5%). There was no statistically significant difference between the two treatment groups, either in terms of satisfactory response (lesions fully healed or improved) or unsatisfactory response (lesions unchanged or advanced), when assessed on day 30 (P > 0.5). Intralesional antimony is a rapidly effective, safe and economical method of treating simple CL, particularly in patients with cardiac, liver or renal disease, for whom antimonials are contra-indicated." ]

[ "14735178", "7656956", "9014795", "1359262", "8100289", "8630595", "14694916" ]

[ "A double-blind, randomised, controlled Phase II trial of Heliox28 gas mixture in lung cancer patients with dyspnoea on exertion.", "Ambulatory oxygen therapy in stable kyphoscoliosis.", "Contribution of peripheral chemoreceptors to ventilation and the effects of their suppression on exercise tolerance in chronic heart failure.", "Ambulatory oxygen in chronic heart failure.", "Effects of oxygen on dyspnoea in hypoxaemic terminal-cancer patients.", "Does oxygen help dyspnea in patients with cancer?", "A randomized controlled trial of supplemental oxygen versus air in cancer patients with dyspnea." ]

[ "Helium has a low density and the potential of reducing the work of breathing and improving alveolar ventilation when replacing nitrogen in air. A Phase II, double-blind, randomised, prospective, controlled trial was undertaken to assess whether Heliox28 (72% He/28% O(2)) compared with oxygen-enriched air (72% N(2)/28% O(2)) or medical air (78.9% N(2)/21.1% O(2)) could reduce dyspnoea and improve the exercise capability of patients with primary lung cancer and dyspnoea on exertion (Borg >3). A total of 12 patients (seven male, five female patients, age 53-78) breathed the test gases in randomised order via a facemask and inspiratory demand valve at rest and while performing 6-min walk tests. Pulse oximetry (SaO(2)) was recorded continuously. Respiratory rate and dyspnoea ratings (Borg and VAS) were taken before and immediately post-walk. Breathing Heliox28 at rest significantly increased SaO(2) compared to oxygen-enriched air (96+/-2 cf. 94+/-2, P<0.01). When compared to medical air, breathing Heliox28 but not oxygen-enriched air gave a significant improvement in the exercise capability (P<0.0001), SaO(2) (P<0.05) and dyspnoea scores (VAS, P<0.05) of lung cancer patients.", "Patients with chronic obstructive pulmonary disease (COPD) may benefit from ambulatory oxygen; however, the effect of exercise on arterial oxygen saturation (Sa,O2) in patients with kyphoscoliosis and of correction with ambulatory oxygen have not been previously reported. Twelve patients with stable kyphoscoliosis (mean (SD) Cobb angle 79 (26) degrees) were studied, with mean (SD) arterial oxygen tension (Pa,O2) 8.96 (0.93) kPa, arterial carbon dioxide tension (Pa,CO2) 6.52 (0.66), forced expiratory volume in one second (FEV1) 0.90 (0.15) L, forced vital capacity (FVC) 1.34 (0.46) L. Six-minute walking tests with oximetry and visual analogue scores (VAS) for breathlessness were performed on air (baseline), and with cylinders containing air and oxygen at 2 L-min-1. Cylinder walks were in random order, with patients blinded to cylinder content. Patients showed oxygen desaturation at each stage of the study. At baseline, oxygen desaturation during exercise was correlated with deterioration in VAS breathlessness scores. Ambulatory oxygen produced significant improvements in desaturation, breathlessness scores and recovery time compared to baseline and air cylinder walks. There was no relationship between baseline desaturation and changes in walking distance. Although exercise desaturation, breathlessness and recovery times were significantly improved with ambulatory oxygen at 2 L.min-1, walking distance was unaffected. We conclude that patients with moderate to severe kyphoscoliosis have significant oxygen desaturation on exercise and should thus routinely receive oximetry on exercise and assessment for ambulatory oxygen therapy.", "To assess the contribution of peripheral chemoreceptors to ventilation and the effects of continuous inspired oxygen on exercise tolerance in chronic heart failure patients. The role of peripheral chemoreceptors in mediating hyperpnoea in chronic heart failure is unknown. Hyperoxia is known to suppress the peripheral chemoreceptor drive. The magnitude of decrease in ventilation with transient inhalations of oxygen thus provides a measure of the contribution of the peripheral chemoreceptors to ventilation.\n Tertiary specialist hospital.\n Three breaths of 100% oxygen were given at rest and also during cycle ergometry at 25 W to 8 healthy controls (age 52.0 (4.7) (SEM) years) and 13 patients with chronic heart failure (age 60.5 (2.1) years (P = NS); radionuclide left ventricular ejection fraction 25.5 (4.3)%). The peripheral chemoreceptor sensitivity was also measured by assessing the ventilatory response to hypoxia using transient inhalations of pure nitrogen. Another group of 12 patients with chronic heart failure (age 65.5 (1.5) years; left ventricular ejection fraction 21.3 (3.0)%) underwent treadmill exercise testing on 2 occasions, breathing air or 100% oxygen in a randomised single-blind manner, to examine the effects of continuous inspired oxygen on exercise tolerance.\n The reduction in ventilation with transient hyperoxia was 18.1 (2.9)% v 17.9 (2.6)% (P = NS) at rest and 20.4 (2.8)% v 21.0 (1.6)% (P = NS) during cycle ergometry, for controls and patients respectively. The hypoxic chemosensitivity was higher in patients (0.232 (0.022) v 0.572 (0.082) 1/min/%SaO2; P = 0.002). Continuous inspired oxygen increased exercise time (517 (31) v 455 (27) seconds; P = 0.003), and a trend towards a reduction in the ventilatory response to exercise, characterised by the regression slope relating ventilation to carbon dioxide output, was evident (31.27 (2.60) v 34.19 (2.35); P = 0.08).\n Despite an increased peripheral chemoreceptor sensitivity, the proportionate contribution of peripheral chemoreceptors to ventilation remained similar in heart failure patients (about 20%). This suggests that the peripheral chemoreceptors are not the main mediator of increased ventilation and there are other non-peripheral chemoreceptor-mediated mechanisms involved. Hyperoxia reduced ventilation at rest and during cycle ergometry. The increase in exercise duration with continuous inspired oxygen that was associated with a reduction in exercise ventilatory response suggests that suppression of the peripheral chemoreceptors may improve exercise tolerance; the effects of possible reduced skeletal muscle anaerobiosis cannot be excluded, however.", "Ambulatory oxygen therapy may be of benefit in bicycle exercise tests. We have assessed the effects of ambulatory oxygen during walk tests in 12 patients with chronic heart failure. In 6 min walks with the patient breathing air, mean (SD) arterial oxygen saturation (SaO2) fell from 94.4 (3.7)% at rest to 90.1 (6.1)% (p = 0.014) on exercise. 21/min oxygen increased resting SaO2 from 93.7 (4.0)% (air cylinder) to 96.5 (3.0)% (p < 0.001) with no effect on minimum SaO2, distance, or breathlessness. During endurance walks, 4 l/min oxygen increased minimum SaO2 from 90.4 (5.6)% to 93.5 (4.7)% (p = 0.011) but also had no effect on breathlessness or distance. Ambulatory oxygen in currently available cylinders cannot be recommended for patients with chronic heart failure.", "Dyspnoea is a frequent and devastating symptom of advanced cancer. The purpose of this prospective, double-blind, crossover trial was to assess the effects of supplemental oxygen on the intensity of dyspnoea. 14 patients with hypoxaemic dyspnoea due to advanced cancer were randomised to receive either oxygen or air; the gases were delivered at 5 L/min by mask. After 5 min of stable oxygen saturation (pulse oximetry), patients were crossed over to receive the other treatment. The crossover was repeated twice. Dyspnoea was assessed with a visual analogue scale (O = no dyspnoea, 100 = worst dyspnoea). Mean difference in dyspnoea visual analogue scale between air and oxygen treatment was 20.5 (95% confidence interval 13.5 to 27.6). 12 patients consistently preferred oxygen to air; similarly, the investigator consistently chose oxygen for the same 12 patients. In a global rating questionnaire, patients reported little or no benefit during the air phase compared with moderate to much benefit during the oxygen phase. We conclude that oxygen is beneficial to patients with hypoxia and dyspnoea at rest.", "Dyspnea in patients with advanced cancer is a common symptom that is difficult to treat. This study investigated whether oxygen helps to relieve rest dyspnea in patients with advanced cancer. In a single-blind controlled trial, oxygen and air were administered in random order to hospice patients reporting dyspnea at rest. Measurements of arterial oxygen saturation, lung function, and dyspnea (using a visual analogue scale [VAS] and Borg score) were made before and after each gas had been given for 15 min. Data from 38 patients were used: analysis of variance revealed that mean VAS levels during baseline conditions, breathing room air (59 mm), were significantly reduced after administration of either air (48 mm; p < 0.001) or oxygen (45 mm; p < 0.001); there was no significant difference for the mean VAS scores between oxygen and air administration. There was no statistically significant order of treatment effect. There was no difference in the response to oxygen or air in patients with a history of cardiopulmonary disease. The improvement in dyspnea with oxygen could not be predicted from a subject's initial level of hypoxia. Results suggested that benzodiazepines may potentiate the effect of oxygen. The overall conclusion is that oxygen and air can have a significant effect in reducing dyspnea at rest in patients with advanced cancer.", "The symptomatic benefits of oxygen in patients with cancer who have nonhypoxic dyspnea are not well defined.\n To determine whether or not oxygen is more effective than air in decreasing dyspnea and fatigue and increasing distance walked during a 6-minute walk test.\n Patients with advanced cancer who had no severe hypoxemia (i.e., had an O2 saturation level of > or = 90%) at rest and had a dyspnea intensity of > or = 3 on a scale of 0-10 (0 = no shortness of breath, 10 = worst imaginable shortness of breath) were recruited from an outpatient thoracic clinic at a comprehensive cancer center. This was a double-blind, randomized crossover trial. Supplemental oxygen or air (5 L/min) was administered via nasal cannula during a 6-minute walk test. The outcome measures were dyspnea at 3 and 6 minutes, fatigue at 6 minutes, and distance walked. We also measured oxygen saturation levels at baseline, before second treatment phase, and at the end of study.\n In 33 evaluable patients (31 with lung cancer), no significant differences between treatment groups were observed in dyspnea, fatigue, or distance walked (dyspnea at 3 minutes: P = 0.61; dyspnea, fatigue, and distance walked at 6 minutes: P = 0.81, 0.37, and 0.23, respectively).\n Currently, the routine use of supplemental oxygen for dyspnea during exercise in this patient population cannot be recommended." ]

[ "8707741", "16505651", "8923071", "16307824", "9265425", "9265424", "17624052", "11815983", "8790170", "9878638", "12473479", "16026898", "11029566", "9468157", "10397217", "8967579", "8712561", "18593746", "8825113", "10199530", "12544993", "16041209", "3046351", "2016833", "8878569", "15278273", "7048839", "16230723", "17334256", "11125233", "7789897", "15060765", "15549302", "14722639", "15537696", "9253572", "15284269", "11886196", "9364263", "8805887", "9437382", "10378561", "16301258", "20711070", "21926583", "19443078", "8437326", "15834740", "14514774", "14572489", "10379447", "10460558", "9403542", "11025176" ]

[ "Retention of antibacterial activity and bacterial colonization of antiseptic-bonded central venous catheters.", "A prospective, randomized trial of rifampicin-minocycline-coated and silver-platinum-carbon-impregnated central venous catheters.", "Retention of the antibiotic teicoplanin on a hydromer-coated central venous catheter to prevent bacterial colonization in postoperative surgical patients.", "Efficacy of antiseptic-impregnated catheters on catheter colonization and catheter-related bloodstream infections in patients in an intensive care unit.", "Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. The Texas Medical Center Catheter Study Group.", "Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. A randomized, controlled trial.", "Use of heparin-coated central venous lines to prevent catheter-related bloodstream infection.", "Catheter-related infection and thrombosis of the internal jugular vein in hematologic-oncologic patients undergoing chemotherapy: a prospective comparison of silver-coated and uncoated catheters.", "No difference in catheter sepsis between standard and antiseptic central venous catheters. A prospective randomized trial.", "A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group.", "Comparison of bacterial colonization rates of antiseptic impregnated and pure polymer central venous catheters in the critically ill.", "Impact of central venous catheter type and methods on catheter-related colonization and bacteraemia.", "A central venous catheter coated with benzalkonium chloride for the prevention of catheter-related microbial colonization.", "Antimicrobial durability and rare ultrastructural colonization of indwelling central catheters coated with minocycline and rifampin.", "The ex vivo antimicrobial activity and colonization rate of two antimicrobial-bonded central venous catheters.", "Central venous line sepsis in the intensive care unit. A study comparing antibiotic coated catheters with plain catheters.", "Failure of antiseptic bonding to prevent central venous catheter-related infection and sepsis.", "Central venous catheterization: a prospective, randomized, double-blind study.", "Prevention of catheter-related infections by silver coated central venous catheters in oncological patients.", "Efficacy of silver-coating central venous catheters in reducing bacterial colonization.", "Impact of oligon central venous catheters on catheter colonization and catheter-related bloodstream infection.", "Comparison of antimicrobial impregnation with tunneling of long-term central venous catheters: a randomized controlled trial.", "An attachable silver-impregnated cuff for prevention of infection with central venous catheters: a prospective randomized multicenter trial.", "Reduced intravascular catheter infection by antibiotic bonding. A prospective, randomized, controlled trial.", "Gamma radiation-sterilized, triple-lumen catheters coated with a low concentration of chlorhexidine were not efficacious at preventing catheter infections in intensive care unit patients.", "Benefits of minocycline and rifampin-impregnated central venous catheters. A prospective, randomized, double-blind, controlled, multicenter trial.", "Material thrombogenicity in central venous catheterization. I. A comparison between uncoated and heparin-coated, long antebrachial, polyethylene catheters.", "Effect of a second-generation venous catheter impregnated with chlorhexidine and silver sulfadiazine on central catheter-related infections: a randomized, controlled trial.", "Comparison of silver-impregnated with standard multi-lumen central venous catheters in critically ill patients.", "Efficacy of a benzalkonium chloride-impregnated central venous catheter to prevent catheter-associated infection in cancer patients.", "A prospective randomized comparison of an attached silver-impregnated cuff to prevent central venous catheter-associated infection.", "Prevention of intravascular catheter-related infection with newer chlorhexidine-silver sulfadiazine-coated catheters: a randomized controlled trial.", "Reduction of catheter-related infections in neutropenic patients: a prospective controlled randomized trial using a chlorhexidine and silver sulfadiazine-impregnated central venous catheter.", "Evaluation of a triple-lumen central venous heparin-coated catheter versus a catheter coated with chlorhexidine and silver sulfadiazine in critically ill patients.", "Reduced colonization and infection with miconazole-rifampicin modified central venous catheters: a randomized controlled clinical trial.", "Antiseptic-impregnated central venous catheters reduce the incidence of bacterial colonization and associated infection in immunocompromised transplant patients.", "Long-term silicone central venous catheters impregnated with minocycline and rifampin decrease rates of catheter-related bloodstream infection in cancer patients: a prospective randomized clinical trial.", "Contamination of central venous catheters in immunocompromised patients: a comparison between two different types of central venous catheters.", "Evaluation of chlorhexidine and silver-sulfadiazine impregnated central venous catheters for the prevention of bloodstream infection in leukaemic patients: a randomized controlled trial.", "Central venous catheters revisited--infection rates and an assessment of the new Fibrin Analysing System brush.", "Influence of triple-lumen central venous catheters coated with chlorhexidine and silver sulfadiazine on the incidence of catheter-related bacteremia.", "Decreasing catheter colonization through the use of an antiseptic-impregnated catheter: a continuous quality improvement project.", "Central venous catheter colonization in critically ill patients: a prospective, randomized, controlled study comparing standard with two antiseptic-impregnated catheters.", "Anti-infective external coating of central venous catheters: a randomized, noninferiority trial comparing 5-fluorouracil with chlorhexidine/silver sulfadiazine in preventing catheter colonization.", "Comparison of Oligon catheters and chlorhexidine-impregnated sponges with standard multilumen central venous catheters for prevention of associated colonization and infections in intensive care unit patients: a multicenter, randomized, controlled study.", "Double-lumen central venous catheters impregnated with chlorhexidine and silver sulfadiazine to prevent catheter colonisation in the intensive care unit setting: a prospective randomised study.", "A prospective randomized trial comparing the silver-impregnated collagen cuff with the bedside tunneled subclavian catheter.", "Chlorhexidine and silver-sulfadiazine coated central venous catheters in haematological patients--a double-blind, randomised, prospective, controlled trial.", "Prevention of catheter related bloodstream infection by silver iontophoretic central venous catheters: a randomised controlled trial.", "A prospective, randomized study in critically ill patients using the Oligon Vantex catheter.", "Reduced rates of catheter-associated infection by use of a new silver-impregnated central venous catheter.", "Antiseptic-bonded central venous catheters and bacterial colonisation.", "A prospective randomized trial of an antibiotic- and antiseptic-coated central venous catheter in the prevention of catheter-related infections.", "Evaluation of antiseptic-impregnated central venous catheters for prevention of catheter-related infection in intensive care unit patients." ]

[ "We determined how long antiseptic impregnation with silver sulphadiazine and chlorhexidine (SCC) on polyurethane central venous double- or triple-lumen catheters is retained in vivo. A total of 116 antiseptic catheters were tested for antibacterial activity in an in-vitro bioassay after various periods of iv catheterization. Segments from the subcutaneous (sc) and intravenous (iv) portions of the catheters were cultured. The results of test antiseptic catheters were compared with those from 117 noncoated control (c) catheters. Retention of antibacterial activity followed an exponential curve and lasted for up to 520 h after catheter insertion. Significant differences (P = 0.0001) between SSC and C catheters were noticed with regard to the quantitative level of bacterial colonization (SSC-sc 87 +/- 34 vs C-sc 584 +/- 122; SSC-iv 52 +/- 17 vs C-iv 286 +/- 57; all values are given as mean cfu +/- S.E.M.), and the frequency of bacterial colonization (SSC-sc 20.7% vs C-sc 38.5%, P = 0.0047; SSC-iv 18.1% vs C-iv 30.8%, P = 0.0361). There was no significant difference between the incidence of catheter-related bacteraemia in the test (n = 0) and control groups (n = 3) (P = 0.2573). Further prospective studies are required to delineate the role of antiseptic catheters in preventing catheter-related infections.", "Central venous catheters are the predominant cause of nosocomial bacteremia; however, the effectiveness of different antimicrobial central venous catheters remains uncertain. We compared the infection rate of silver-platinum-carbon (SPC)-impregnated catheters with rifampicin-minocycline (RM)-coated catheters.\n A large, single-center, prospective randomized study.\n Twenty-two-bed adult general intensive care unit in a large tertiary metropolitan hospital in Brisbane, Australia (2000-2001).\n Consecutive series of all central venous catheterizations in intensive care unit patients.\n Randomization, concealment, and blinding were carefully performed. Catheter insertion and care were performed according to published guidelines. Blood cultures were taken at central venous catheter removal, and catheter-tip cultures were performed by both roll-plate and sonication techniques. Pulsed field gel electrophoresis was used to establish shared clonal origin for matched isolates.\n Central venous catheter colonization and catheter-related bloodstream infection were determined with a blinded technique using the evaluation of the extensive microbiological and clinical data collected and a rigorous classification system. Six hundred forty-six central venous catheters (RM 319, SPC 327) were inserted, and 574 (89%) were microbiologically evaluable. Colonization rates were lower for the RM catheters than SPC catheters (25 of 280, 8.9%; 43 of 294, 14.6%; p=.039). A Kaplan-Meier analysis that included catheter time in situ did not quite achieve statistical significance (p=.055). Catheter-related bloodstream infection was infrequent for both catheter-types (RM 4, 1.4%; SPC 5, 1.7%).\n The SPC catheter is a clinically effective antimicrobial catheter; however, the RM catheter had a lower colonization rate. Both catheter types had low rates of catheter-related bloodstream infection. These results indicate that future studies will require similar rigorous methodology and thousands of central venous catheters to demonstrate differences in catheter-related bloodstream infection rates.", "Antibiotic-coated intravascular catheters may be an effective means of decreasing bacterial colonization and subsequent catheter-related infection. The present study was designed to investigate the retention of the antibiotic teicoplanin on a hydromer-coated intravenous catheter and the effect of this antibiotic coating on catheter bacterial colonization.\n A prospective, randomized pilot study.\n Operating rooms (ORs) and an intensive care unit (ICU) at a university hospital.\n A consecutive group of 20 male patients undergoing major abdominal surgery.\n Control (C; n = 10) or teicoplanin-coated (T; n = 10) single-lumen central venous catheters were inserted before surgery in the OR. Catheters were withdrawn at the discretion of the physicians in the ICU after various periods.\n The teicoplanin content of the catheter material was assessed using a bioassay with Bacillus subtilis after complete elution of the antibiotic from the catheter. Bacterial colonization was measured using a quantitative culture technique after the catheter lumen had been flushed and the catheter segments sonicated.\n Nearly three-quarters of the initial teicoplanin coating (374 +/- 103 micrograms; mean +/- SD) were released during the first day of catheterization, and after 36 h of intravenous catheterization, no antibiotic was retained on the catheter. No significant difference could be found either in the incidence of bacterial colonization between test (n = 3) and control (n = 4) catheters or in the number of colony-forming units (CFU) on the catheter segments (T, 263 +/- 104 CFU/cm; C, 372 +/- 294 CFU/cm; mean +/- SEM).\n The retention of teicoplanin antibiotic coating on hydromer catheters is only short term if catheters are inserted intravenously. This may limit clinical antibacterial efficacy.", "This study was conducted to evaluate the impact of central venous catheters impregnated with chlorhexidine and silver sulphadiazine on the incidence of colonization and catheter-related bloodstream infection in critically ill patients. One hundred and thirty-three patients requiring central venous catheterization were chosen at random to receive either an antiseptic-impregnated triple-lumen catheter (N=64) or a standard triple-lumen catheter (N=69). The mean (SD) durations of catheterization for the antiseptic and standard catheters were 11.7 (5.8) days (median 10; range 3-29) and 8.9 (4.6) days (median 8.0; range 3-20), respectively (P=0.006). Fourteen (21.9%) of the antiseptic catheters and 14 (20.3%) of the standard catheters had been colonized at the time of removal (P=0.834). Four cases (6.3%) of catheter-related bloodstream infection were associated with antiseptic catheters and one case (1.4%) was associated with a standard catheter (P=0.195). The catheter colonization rates were 18.7/1000 catheter-days for the antiseptic catheter group and 22.6/1000 catheter-days for the standard catheter group (P=0.640). The catheter-related bloodstream infection rates were 5.3/1000 catheter-days for the antiseptic catheter group and 1.6/1000 catheter-days for the standard catheter group (P=0.452). In conclusion, our results indicate that the use of antiseptic-impregnated central venous catheters has no effect on the incidence of either catheter colonization or catheter-related bloodstream infection in critically ill patients.", "Central venous catheters are a principal source of nosocomial bloodstream infections, which are difficult to control.\n To determine the efficacy of catheters coated with minocycline and rifampin in preventing catheter-related colonization and bloodstream infections.\n Multicenter, randomized clinical trial.\n Five university-based medical centers.\n 281 hospitalized patients who required 298 triple-lumen, polyurethane venous catheters.\n 147 catheters were pretreated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin. Untreated, uncoated catheters (n = 151) were used as controls.\n Quantitative catheter cultures, blood cultures, and molecular typing of organisms to determine catheter-related colonization and bloodstream infections.\n The group with coated catheters and the group with uncoated catheters were similar with respect to age, sex, underlying diseases, degree of immunosuppression, therapeutic interventions, and risk factors for catheter infections. Colonization occurred in 36 (26%) uncoated catheters and 11 (8%) coated catheters (P < 0.001). Catheter-related bloodstream infection developed in 7 patients (5%) with uncoated catheters and no patients with coated catheters (P < 0.01). Multivariate logistic regression analysis showed that coating catheters with minocycline and rifampin was an independent protective factor against catheter-related colonization (P < 0.05). No adverse effects related to the coated catheters or antimicrobial resistance were seen. An estimate showed that the use of coated catheters could save costs.\n Central venous catheters coated with minocycline and rifampin can significantly reduce the risk for catheter-related colonization and bloodstream infections. The use of these catheters may save costs.", "Bloodstream infection related to short-term use of noncuffed central venous catheters is a common and serious problem. Technologic innovations to reduce the risk for these infections are needed.\n To determine 1) the efficacy of a novel antiseptic catheter in preventing central venous catheter-related infection, 2) patient tolerance of this catheter, and 3) the sources of bloodstream infection originating from noncuffed, multilumen central venous catheters.\n Randomized, controlled clinical trial.\n Medical-surgical intensive care unit of a 450-bed university hospital.\n 158 adults scheduled to receive a central venous catheter; 403 catheters were studied.\n Participants received either a standard triple-lumen polyurethane catheter or a catheter that was indistinguishable from the standard catheter and was impregnated with chlorhexidine and silver sulfadiazine.\n Catheters were studied for colonization and catheter-related bloodstream infection at removal; local and systemic effects of catheters were assessed. The origin of each catheter-associated bloodstream infection was sought by culturing all potential sources (skin, catheter segments, hubs, and infusate) and confirmed by restriction-fragment DNA subtyping.\n Antiseptic catheters were less likely to be colonized at removal than control catheters (13.5 compared with 24.1 colonized catheters per 100 catheters; relative risk, 0.56 [95% CI, 0.36 to 0.89]; P = 0.005) and were nearly fivefold less likely to produce bloodstream infection (1.0 compared with 4.7 infections per 100 catheters; 1.6 compared with 7.6 infections per 1000 catheter-days; relative risk, 0.21 [CI, 0.03 to 0.95]; P = 0.03). In the control group, 8 catheter-related bloodstream infections were caused by Staphylococcus aureus, gram-negative bacilli, enterococci, or Candida species; no infections with these organisms occurred in the antiseptic catheter group (P = 0.003). No adverse effects from the antiseptic catheter were seen, and none of the 122 isolates obtained from infected catheters in either group showed in vitro resistance to chlorhexidine-silver sulfadiazine. Cost-benefit analysis indicated that the antiseptic catheter should prove cost-beneficial if an institution's rate of catheter-related bacteremia with noncuffed central venous catheters is at least 3 infections per 1000 catheter-days).\n The chlorhexidine-silver sulfadiazine catheter is well tolerated, reduces the incidence of catheter-related infection, extends the time that noncuffed central venous catheters can be safely left in place for the short term, and should allow cost savings.", "Bloodstream infections related to the use of central venous catheters are an important cause of patient morbidity, mortality, and increased health care costs. Catheter-related infection may be due to fibrin deposition associated with catheters. Interventions designed to decrease fibrin deposition have the potential to reduce catheter-related infections. This study was a randomized, controlled trial in which 246 patients with nontunneled central venous catheters were randomly assigned to receive a heparin-coated catheter with 50 mL/d of normal saline solution as a continuous infusion (heparin-coated group) or a noncoated catheter with a continuous infusion of low-dose unfractionated heparin (control group: continuous infusion of 100 U/kg/d). Catheter-related bloodstream infection occurred in 2.5% (3/120 catheters) in the heparin-coated group (0.9 events per 1,000 days) and in 9.1% (11/120 catheters) in the control group (3.5 events per 1,000 days; P = 0.027). No other risk factors were found for the development of catheter-related bloodstream infection. Six and seven patients experienced severe bleeding in the heparin-coated and control groups, respectively (P = 1.00). We did not observe heparin-induced thrombocytopenia. The use of heparin-coated catheters can be a safe and effective approach to the prevention of catheter-related bloodstream infection in patients with hematooncologic disease.", "Catheter-related venous thrombosis is one of the most frequent complications of central venous catheters (CVCs). This complication occurs in 4- 40% of patients with hematologic malignancies receiving conventional chemotherapy after placement of CVCs.\n The objective of this prospective study was to assess whether a silver-coated CVC poses an additional risk in the development of catheter-related thrombosis in hematologic-oncologic patients. Patients were randomized to receive either silver-coated polyurethane catheters (BactiGuard; Metacot, Stockholm, Sweden) or uncoated standard polyurethane catheters (Cavatheter, Fresenius AG, Bad Homburg, Germany) for central venous access. Silver-coated catheters (n = 120) and standard catheters (n = 113) were inserted into the jugular vein in 233 consecutive patients. Variables that may be significant for the development of thrombosis were comparable in the two groups. After removal of the CVC, the patency of both jugularian veins internal as well as external was assessed with real-time ultrasound (Sonolayer-SAL-35A; Toshiba, Tokyo, Japan).\n Four of 233 patients (1.5%) were found to have venous thrombosis. Incomplete occlusion of the internal jugular vein occurred in 2 patients (0.75%, parietal thrombosis), and complete thrombosis, although clinically silent, was found in 2 patients (0.75%). There was no difference between patients with silver-coated and uncoated CVCs.\n The authors concluded that this novel silver-coated CVC does not cause a higher rate of central venous thrombosis compared with standard CVCs. The low overall incidence of central venous thrombosis might be attributed to the routine application of low-dose heparin in our patients during chemotherapeutic treatment.\n Copyright 2002 American Cancer Society.", "To determine the efficacy of antiseptic compared with standard triple lumen central venous catheters (CVCs) in reducing the incidence of catheter sepsis and catheter site infection in patients with CVCs for total parenteral nutrition.\n A prospective, randomized, controlled trial.\n Truman Medical Center, the public teaching hospital for University of Missouri, Kansas City, School of Medicine.\n Seventy-two inpatients on the Metabolic Support Service received a CVC for the infusion of total parenteral nutrition. Diagnoses included pancreatic disease, cancer, bowel obstruction, and intestinal surgery, among others. Patients who had a higher risk for contamination during insertion, such as those with a catheter placed through an introducer, inserted in the emergency department, or changed over a guidewire were excluded from the study.\n The control group received a standard CVC without antiseptics. The treatment group received a CVC with a coating of silver sulfadiazine and chlorhexidine gluconate. Each CVC was inspected for infection or malfunction by the Metabolic Support Service 5 times per week. A transparent occlusive dressing was changed every 7 days or more often if there were signs of infection or nonocclusion. When the CVC was removed, the catheter tip, the blood, and the insertion site were cultured.\n Although 88 catheters were inserted, only 72 catheters were evaluable. There were 40 patients in the standard group and 32 in the antiseptic group. There were no statistically significant differences between the 2 groups for diagnosis, sex, age, length of stay, days with a CVC, or catheter location. The catheter sepsis rate in the standard group was 8% and in the antiseptic group it was 6%. There were no statistically significant differences between the 2 groups in frequency of site infections or catheter sepsis.\n In this study, there were no statistically significant differences in the incidence of catheter-related sepsis or catheter site infections between the standard and antiseptic groups. Future prospective, randomized controlled trials with a larger number of antiseptic catheters are encouraged to confirm or refute these results.", "The use of central venous catheters impregnated with either minocycline and rifampin or chlorhexidine and silver sulfadiazine reduces the rates of catheter colonization and catheter-related bloodstream infection as compared with the use of unimpregnated catheters. We compared the rates of catheter colonization and catheter-related bloodstream infection associated with these two kinds of antiinfective catheters.\n We conducted a prospective, randomized clinical trial in 12 university-affiliated hospitals. High-risk adult patients in whom central venous catheters were expected to remain in place for three or more days were randomly assigned to undergo insertion of polyurethane, triple-lumen catheters impregnated with either minocycline and rifampin (on both the luminal and external surfaces) or chlorhexidine and silver sulfadiazine (on only the external surface). After their removal, the tips and subcutaneous segments of the catheters were cultured by both the roll-plate and the sonication methods. Peripheral-blood cultures were obtained if clinically indicated.\n Of 865 catheters inserted, 738 (85 percent) produced culture results that could be evaluated. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters impregnated with minocycline and rifampin were 1/3 as likely to be colonized as catheters impregnated with chlorhexidine and silver sulfadiazine (28 of 356 catheters [7.9 percent] vs. 87 of 382 [22.8 percent], P<0.001), and catheter-related bloodstream infection was 1/12 as likely in catheters impregnated with minocycline and rifampin (1 of 356 [0.3 percent], vs. 13 of 382 [3.4 percent] for those impregnated with chlorhexidine and silver sulfadiazine; P<0.002).\n The use of central venous catheters impregnated with minocycline and rifampin is associated with a lower rate of infection than the use of catheters impregnated with chlorhexidine and silver sulfadiazine.", "A study was performed on critically ill patients to evaluate the rate of colonization and catheter-related sepsis using antiseptic bonded (Arrowguard Arrow International) versus smooth pure polymer (Infectguard MedexMedical Ltd) central venous catheters. Two hundred and thirty-two catheters were inserted into 181 patients. Indications for removal included local or systemic infection, the catheter was no longer required and patient death. No statistical difference in colonization rate was found between the two types of catheter.\n Copyright 2002 The Hospital Infection Society", "A prospective, randomized, controlled, multi-centre clinical trial was performed to test the effectiveness of an antimicrobial central venous catheter (CVC) made of polyurethane integrated with silver, platinum and carbon black (Vantex). Adults expected to require a CVC for more than 60 h were eligible, and were randomized to receive the test or control catheter. All CVCs were inserted with new venipunctures using full aseptic technique. Following catheter removal, the distal tip and an intracutaneous segment were removed and cultured using semiquantitative and quantitative methods. Peripheral blood samples were obtained and cultured to confirm cases of catheter-related bloodstream infection (CRBSI). Bacterial and fungal organisms were identified by standard microbiological methods. Catheter placement was performed primarily in the intensive care unit (50%) or operating theatre (42%). Complete data could be evaluated for 539 patients (77%). The mean duration of CVC placement was 149.3h (six days). There were no significant differences in colonization or bacteraemia rates between the test and control catheters. The overall colonization rate was not particularly low (24.5%), and yet CVC-related bacteraemia occurred in only 1.4% of patients, and CRBSI occurred in only one patient from the control group (0.2%). Insertion site and dressing change frequency were significantly associated with the colonization rate. Although CVCs with antimicrobial features have been associated with a decrease in catheter-related colonization and bacteraemia, this study demonstrated that infection rates may depend more on non-catheter-related factors, such as adherence to infection control standards, selection of insertion site, duration of CVC placement, and dressing change frequency. As microbial resistance increases, clinicians should make maximal use of these processes to reduce catheter-related infections.", "In an attempt to overcome infections associated with central venous catheters, a new antiseptic central venous catheter coated with benzalkonium chloride on the internal and external surfaces has been developed and evaluated in a clinical trial. Patients (235) randomly received either a triple-lumen central venous catheter coated with benzalkonium chloride (117) or a polyurethane non-antiseptic catheter (118). The incidence of microbial colonization of both catheters and retained antiseptic activity of the benzalkonium chloride device following removal were determined. The benzalkonium chloride resulted in a significant reduction of the incidence of microbial colonization on both the internal and external catheter surfaces. The reduction in colonization was detected at both the intradermal (21 benzalkonium chloride catheters vs. 38 controls, P = 0.0016) and distal segments of the antiseptic-coated catheters. Following catheter removal retained activity was demonstrated in benzalkonium chloride catheters which had been in place for up to 12 days. No patients developed adverse reactions to the benzalkonium chloride catheters. The findings demonstrate that the benzalkonium chloride catheter significantly reduced the incidence of catheter-associated colonization.", "To determine the duration of antimicrobial activity and the efficacy of indwelling catheters coated with minocycline and rifampin in preventing ultrastructural colonization.\n Multicenter, prospective, randomized, clinical trial.\n Five university-based medical centers.\n Cohort 1 consisted of 40 randomized patients in whom an equal number of minocycline- and rifampin-coated and uncoated catheters were inserted and studied using scanning electron microscopy. Cohort 2 consisted of 118 patients who received coated catheters that were tested for the antimicrobial activity and levels of the antibiotics at the time of removal.\n Catheters pretreated with tridodecylmethylammonium chloride and subsequently coated with minocycline and rifampin; uncoated catheters (control).\n Quantitative scanning electron microscopy was utilized to determine both the ultrastructural colonization in biofilm on coated and uncoated catheters. The zones of inhibition of coated catheters from studied patients against Staphylococcus epidermidis was used to determine the antimicrobial durability. High-performance liquid chromatography was used to determine antibiotic levels on indwelling coated catheters and in serum. Mild-to-heavy ultrastructural colonization was detected in 7 (35%) of 20 coated catheters and in 16 (80%) of 20 uncoated catheters (p = .004). Significant antimicrobial inhibitory activity against S. epidermidis was maintained for 16 days. Rifampin and minocycline continued to be detected on the surfaces of coated catheters for at least 2 wks after placement. Neither antibiotic was detected in the 60 serum samples obtained from 15 patients during catheterization.\n Coating catheters with minocycline and rifampin inhibits ultrastructural colonization of indwelling catheters and maintains effective antimicrobial activity for at least 2 wks.", "Catheter-related sepsis is an important complication associated with the use of central venous catheters. Recent studies have suggested that antimicrobial-bonded catheters may reduce catheter colonization and catheter-related sepsis. The aim of this study was to determine the relationship between the antimicrobial activity and the colonization rate of two commercially available antimicrobial-bonded central venous catheters.\n Prospective, randomized, controlled, nonblinded study.\n Medical intensive care unit of a university-affiliated teaching hospital.\n One hundred twenty consecutive medical intensive care unit patients requiring new central venous catheters (fresh stick).\n Patients were randomized to receive a) a Standard Arrow; b) an ARROWgard; or c) a Cook Bio-Guard Spectrum central venous catheter. Central venous catheters were removed when they were no longer required or when catheter-related sepsis was suspected. Under aseptic conditions, the distal 12 cm of the removed catheters were cut into six 2-cm segments. Semiquantitative culture was performed (by roll technique) on the distal segment. Colonization was defined as >15 colony-forming units. Using a modified Kirby-Bauer technique, the zone of inhibition of the remaining five segments was determined against the following organisms: methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Enterococcus faecalis, Acinetobacter baumannii, and Candida albicans Catheters that were removed within 24 hrs of insertion were excluded from the analysis.\n Seven patients were not assessable. The baseline clinical and demographic characteristics were similar among the three groups of patients. Eleven Standard Arrow (28%), seven ARROWgard (19%), and four Bio-Guard (11%) catheters were colonized (p = .05 for Bio-Guard vs. control). Staphylococci were the most common colonizing organisms. Two patients with Standard Arrow catheters (5%) and one patient with an ARROWgard catheter (3%) developed catheter-related sepsis. Antibiotic-coated catheters significantly inhibited the growth of all test organisms except C. albicans (p < or = .05). Zones of inhibition were significantly larger for the Bio-Guard compared with the ARROWgard catheter when tested against MRSA, S. epidermidis, and E. faecalis (p < or = .002).\n The Bio-Guard central venous catheter had greater ex vivo antimicrobial activity against MRSA, S. epidermidis, and E. faecalis compared with the ARROWgard catheter, and this was associated with a significantly lower rate of catheter colonization.", "A randomized controlled clinical trial was undertaken to evaluate the efficacy of antibiotic bonded lines in the reduction of central venous catheter infection. One hundred and seventy-six plain and bonded catheters were inserted into one hundred and ten patients in an intensive care unit, many of whom were admitted with evidence of sepsis. The catheters used in the study group, which had been pre-treated by the manufacturers with the cationic surfactant tridodecylmethylammonium chloride, were bonded with vancomycin 1 g made up in 10 ml of water immediately prior to insertion. The catheters used in the control group were neither pre-treated nor bonded with vancomycin. Eighty percent of control group catheters were infected compared with 62% of study catheters (p = 0.01). The most common organism isolated was coagulase negative staphylococcus. We conclude that antibiotic bonding can reduce central venous catheter infection even in a patient population with a high incidence of sepsis.", "Infection associated with the use of triple lumen catheters in hospitals is a frequent and serious complication. The prevailing hypothesis for the origin of catheter-related infection (CRI) is bacterial colonization and subsequent infection of the skin insertion site and catheter interface. The recently released ARROWgard catheter contains a bonded synergistic combination of silver sulfadiazine and chlorhexidine, which is thought to render the catheter resistant to bacterial colonization and subsequent sepsis. The purpose of this study is to compare the incidence of CRI and catheter-related sepsis (CRS) between a standard triple lumen catheter and ARROWgard antiseptic coated catheter in patients receiving total parenteral nutrition (TPN). A randomized, prospective clinical trial was conducted at a community referral center from January 1993 through April 1994. One-hundred-ninety-one patients with need for TPN were randomized to receive either the ARROWgard or a standard triple lumen catheter placed under a strict sterile protocol. CRI was defined as >/= 15 colony forming units by semiquantitative culture technique of the catheter tip or intracutaneous segment. CRS was defined as growth of the same organism on the catheter and at least one peripheral blood culture. All catheters were cultured. Ninety-two patients received the ARROWgard catheter, and 99 patients received the standard catheter. There were no differences between the average age, sex, length of hospital stay, days on TPN, number of catheters/patient, indications for TPN, primary diagnoses, or duration of the central line between the two groups. The overall rate of CRI was 11.5 per cent, and CRS was 8.4 per cent in this study. The rate of CRI for the ARROWgard was 10.9 per cent, compared with 12.9 per cent for the standard catheter (P = NS). The rate of CRS for the ARROWgard was 8.7 per cent, compared with 8.1 per cent for the standard catheter (P = NS). The coating of central venous catheters with silver sulfadiazine and chlorhexidine does not reduce the rate CRI or CRS when compared with standard central venous catheters in patients receiving TPN.", "Central venous catheters (CVCs) are extensively used worldwide. Mechanical, infectious and thrombotic complications are well described with their use and may be associated with prolonged hospitalization, increased medical costs and mortality. CVCs account for an estimated 90% of all catheter-related bloodstream infections (CRBSI) and a host of risk factors for CVC-related infections have been documented. The duration of use of CVCs remains controversial and the length of time such devices can safely be left in place has not been fully and objectively addressed in the critically ill patient. Antimicrobial-impregnated catheters have been introduced in an attempt to limit catheter-related infection (CRI) and increase the time that CVCs can safely be left in situ. Recent meta-analyses concluded that antimicrobial-impregnated CVCs appear to be effective in reducing CRI. The authors conducted a prospective, randomized, double-blind study at Johannesburg Hospital over a 4-year period. The study entailed a comparison of standard triple-lumen versus antimicrobial impregnated CVCs on the rate of CRI. Our aim was to determine whether we could safely increase the duration of catheter insertion time from our standard practice of seven days to 14 days, to assess the influence of the antimicrobial impregnated catheter on the incidence of CRI, and to elucidate the epidemiology and risks of CRI. One hundred and eighteen critically ill patients were included in the study which spanned 34 951.5 catheter hours (3.99 catheter years). It was found that antimicrobial catheters did not provide any significant benefit over standard catheters, which the authors feel can safely be left in place for up to 14 days with appropriate infection control measures. The most common source of CRI was the skin. The administration of parenteral nutrition and the site of catheter insertion (internal jugular vein vs subclavian vein) were not noted to be risk factors for CRI. There was no clinical evidence of thrombotic complication in either of the study groups. This study offers direction for the use of CVCs in critically ill patients and addresses many of the controversies that exist.", "Catheter-related infection (CRI) is a serious complication of central venous catheterization. We have investigated the efficacy of a silver-coated polyurethane catheter (Pellethane, Fresenius AG, Germany) in preventing CRI in oncological patients receiving chemotherapy in a phase II study. From November 1992 through April 1994, 266 patients were assigned to receive single lumen catheters, either standard uncoated catheters (UC, n = 113) or silver-coated ones (SC, n = 120). Catheters were inserted into the internal jugular vein after institutional approval and informed consent. Duration of catheterization (UC vs. SC = 13.3 vs. 12.7 days) and leukopenia (< 1.0 x 10(9) WBC/l; 4.3 vs. 3.6 days) were similar in both groups demonstrating a comparable risk for infections. Skin reactions at the catheter entry site were recorded daily. CRI and colonization rates were studied by semiquantitatively culturing intradermal and intravascular segments. CRI were confirmed by blood cultures obtained via catheter and from peripheral veins in cases of suspected sepsis or at the end of catheterization. No adverse effects from the silver-coated catheter could be observed. The bacteriological results showed that SC were colonized (> 15 CFU) in 45.1% and UC in 44.2%. CRI developed in 21.2% of the UC patients but only in 10.2% of the SC patients (p = 0.011). We conclude that this new silver-coated central venous catheter is biocompatible and effective in reducing the incidence of catheter-related infections in oncological patients.", "To compare silver-coated and uncoated central venous catheters regarding bacterial colonization. To assess the relative contribution of catheter hub and skin colonization to catheter tip colonization.\n Prospective, randomized clinical trial.\n Intensive care unit in a university hospital.\n Patients after cardiac surgery who required a central venous double-lumen catheter (DLC).\n Sixty-seven adult patients were prospectively randomized to receive either a silver-coated (S group, n = 34) or an uncoated control (C group, n = 33) DLC. Blood cultures were drawn at catheter removal, and removed catheters were analyzed with quantitative cultures. Typing of microorganisms included DNA fingerprinting.\n Catheters were removed if no longer necessary and aseptically divided into three segments: segment A, the catheter tip; segment B, an intermediate section; and segment C, the subcutaneous portion. Bacterial catheter colonization was quantitatively measured using sonication to detach adherent bacteria from the catheter segments in the broth and subsequent culture of an aliquot. Selected isolates of coagulase-negative staphylococci and other bacteria from catheter segments were examined by means of pulsed-field gel electrophoresis (PFGE) after macrorestriction digestion of bacterial DNA to study colonization pathogenesis. Quantitatively lower bacterial colonization could be demonstrated on the silver-coated catheters (200 +/- 550 colony forming units [CFUs]/cm catheter segment; mean +/- SD). The difference in the control catheters (1120 +/- 5350 CFUs/cm catheter segment; mean +/- SD) was not, however, significant (p = .25). The frequency of colonization of at least one catheter segment was 52.9% for the silver-coated catheters and 57.6% for the control catheters (p= .44), without any significant differences in the colonization of corresponding catheter segments. The rate of significant catheter colonization (i.e., > or = 10(3) CFUs/cm catheter by quantitative catheter culture or > or = 10(3) CFUs/mL by luminal flush) was nine in the silver group and seven in the control group, a difference that failed to reach significance (p = .41). Two patients in both groups developed catheter-related bacteremia. Pattern analysis after PFGE demonstrated that about 70% of the isolates found on the catheter tip were identical with those on the skin at the insertion site, whereas about 75% were identical with those recovered from the hub. In 29% of colonized catheters, identical bacteria were found on the hub and the skin at the insertion site.\n Silver-coating of DLCs did not significantly reduce bacterial catheter colonization compared with the control catheters. PFGE analysis of coagulase-negative staphylococci and other bacteria demonstrated various pathogenic routes of catheter-related colonization, whereby the microorganisms of the skin flora around the insertion site must be regarded as the main source of catheter-related infections.", "To evaluate a new antimicrobial treatment for central venous catheters in comparison with a traditional treatment, by assessing the catheter colonization and catheter-related bloodstream infection rates in two groups of patients.\n Multiple-center, prospective randomized study.\n The medical and surgical departments of ten institutions.\n Patients requiring a central venous catheter for medical or surgical pathologies between June 2000 and November 2001.\n Patients in the control group received a conventional benzalkonium-treated double-lumen central venous catheter, while patients in the oligon group received an oligon-treated (polyurethane combined with silver, carbon, and platinum) catheter with the same characteristics. Data collection included demographics, preexisting clinical conditions, main pathology, catheter insertion, and management data. Catheter colonization was defined as the growth of > or = 15 colony-forming units in culture of catheter segments by the roll-plate method, or > or = 1000 colony-forming units for the sonication method, and catheter-related bloodstream infection was defined as isolation of the same organism from the colonized catheter and from the peripheral blood of a patient with clinical signs of bloodstream infection.\n Data were obtained from 545 catheters. Of these, 132 catheters (24.2%) were positive for colonization. Patients in the oligon group demonstrated a lower risk for catheter colonization in the overall population (relative risk, 0.63; 95% confidence interval, 0.46-0.86; p = .003) and in the surgical subgroup (relative risk, 0.5; 95% confidence interval, 0.33-0.76;p = .001). Significant differences between groups were detected for coagulase-negative staphylococci and Gram-negative bacilli colonization rates. Twenty-one patients (3.8%) were positive for catheter-related bloodstream infection, without significant differences between control and oligon groups.\n Oligon treatment is effective in limiting the catheter colonization rate. Due to the limited amount of events, this study lacked the power to detect significant differences in terms of catheter-related bloodstream infection rate.", "We sought to compare the impact of antimicrobial impregnation to that of tunneling of long-term central venous catheters on the rates of catheter colonization and catheter-related bloodstream infection.\n Tunneling of catheters constitutes a standard of care for preventing infections associated with long-term vascular access. Although antimicrobial coating of short-term central venous catheters has been demonstrated to protect against catheter-related bloodstream infection, the applicability of this preventive approach to long-term vascular access has not been established.\n A prospective, randomized clinical trial in 7 university-affiliated hospitals of adult patients who required a vascular access for > or = 2 weeks. Patients were randomized to receive a silicone central venous catheter that was either impregnated with minocycline and rifampin or tunneled. The occurrence of catheter colonization and catheter-related bloodstream infection was determined.\n Of a total of 351 inserted catheters, 346 (186 antimicrobial-impregnated and 160 tunneled) were analyzed for catheter-related bloodstream infection. Clinical characteristics were comparable in the 2 study groups, but the antimicrobial-impregnated catheters remained in place for a shorter period of time (mean, 30.2 versus 43.8 days). Antimicrobial-impregnated catheters were as likely to be colonized as tunneled catheters (7.9 versus 6.3 per 1000 catheter-days). Bloodstream infection was 4 times less likely to originate from antimicrobial-impregnated than from tunneled catheters (0.36 versus 1.43 per 1000 catheter-days).\n Antimicrobial impregnation of long-term central venous catheters may help obviate the need for tunneling of catheters.", "Percutaneously inserted central venous catheters are widely used. Catheter-related bacteremia or fungemia is the most frequent serious complication of these catheters. In an attempt to reduce the frequency of such infections, a subcutaneous cuff constructed of a biodegradable collagen matrix impregnated with bactericidal silver was developed. Our goal was to assess, in a multicenter clinical trial, the effectiveness of this cuff in preventing catheter-related infection.\n Central venous catheters needed for fluid or drug therapy, hemodynamic monitoring, or hyperalimentation in patients in three centers were randomly assigned to be inserted with or without the cuff. Patients and catheters in the two groups were comparable in terms of risk factors predisposing to infection, including colonization of skin about the insertion site.\n The results with 234 catheters inserted into a new site showed that catheters inserted with the cuff were threefold less likely to be colonized on removal (more than 15 colony-forming units) than were control catheters (28.9 percent versus 9.1 percent, p = 0.002) and were nearly fourfold less likely to produce bacteremia (3.7 percent versus 1.0 percent). Adverse effects from the cuff were not seen. The cuff did not confer protection, however against infection with catheters inserted over a guidewire into old sites. Most of the catheter-related infections identified in this study, including four of the six bacteremias, appear to have been caused by microorganisms colonizing skin about the insertion site, affirming the pathogenetic basis for benefit seen with the cuff in this clinical trial; two may have derived from contamination of the catheter hub.\n This novel, silver-impregnated, attachable cuff can substantially reduce the incidence of catheter-related infection with most percutaneously inserted central venous catheters, can extend the time catheters can be left in place safely, and can prove cost-beneficial.", "We report a prospective, randomized, controlled clinical trial to evaluate the efficacy of antibiotic-bonded catheters in reducing the incidence of intravascular catheter-related infections. Ninety-three central venous catheters and 85 arterial catheters were studied in the surgical intensive care unit. Study catheters were pretreated with the cationic surfactant tridodecylmethylammonium chloride. The anionic antibiotic, cefazolin, was bonded before insertion of the catheters by immersing them in a 50-mg/mL solution. Fourteen percent of the 81 catheters in the control group were infected, compared with 2% of the 97 antibiotic-bonded catheters. Staphylococcus epidermidis was the most common organism obtained. There was no significant difference in the number of colonized or clinically inflamed catheter insertion sites. None of the 100 antibiotic immersion solutions yielded anything on microbiologic culture. We conclude that antibiotic bonding is an efficient, safe, and cost-effective method of reducing intravascular catheter infection in patients who are in intensive care units.", "In a randomized, double-blind trial, gamma radiation-sterilized, chlorhexidine-coated triple-lumen catheters were compared with uncoated control catheters for their ability to prevent catheter infection in 254 intensive care unit patients. The chlorhexidine coating was not efficacious, and a rabbit model demonstrated that reduction of chlorhexidine activity by gamma radiation sterilization was the likely explanation for the failure.", "To determine the efficacy of minocycline and rifampin-impregnated catheters compared to non-impregnated catheters in critically ill patients.\n Prospective, randomized, double-blind, controlled, multicenter trial.\n Intensive care units of seven acute-care teaching hospitals in Spain. PATIENTS. Intensive care unit patients requiring triple-lumen central venous catheter for more than 3 days.\n At catheter insertion, 228 patients were randomized to minocycline and rifampin-impregnated catheters and 237 to non-impregnated catheters. Skin, catheter tip, subcutaneous segment, hub cultures, peripheral blood and infusate cultures were performed at catheter withdrawal. The rate of colonization, catheter-related bloodstream infection (CRBSI) and catheter-related clinical infectious complications (purulence at the insertion site or CRBSI) were assessed.\n In the intention-to-treat analysis (primary analysis), the episodes per 1000 catheter days of clinical infectious complications decreased from 8.6 to 5.7 (RR =0.67, 95% CI 0.31-1.44), CRBSI from 5.9 to 3.1 (RR =0.53, 95% CI 0.2-1.44) and tip colonization from 24 to 10.4 (RR =0.43, 95% CI 0.26-0.73). Antimicrobial-impregnated catheters were associated with a significant decrease of coagulase-negative staphylococci colonization (RR =0.24, 95% CI 0.13-0.45) and a significant increase of Candida spp. colonization (RR =5.84, 95% CI 1.31-26.1).\n The use of antimicrobial-impregnated catheters was associated with a significantly lower rate of coagulase-negative staphylococci colonization and a significant increase in Candida spp. colonization, although a decrease in CRBSI, increase in 30-day survival or reduced length of stay was not observed.", "In order to evaluate a new method of heparinization, uncoated (22) and heparin-coated (27) central venous polyethylene catheters were inserted in 49 patients via basilic and cephalic veins punctured at the fossa cubiti. The means duration of catheterization was 5.7 (1-11) days. One-third of the patients with heparin-coated catheters, and one sixth with uncoated catheters developed clinical thrombophlebitis, with a maximum incidence between 4 and 8 days after catheterization. A higher risk of developing thrombophlebitis in the first 4 days after catheterization was found in the patients with heparin-coated polyethylene catheters. After 8 days of catheterization, it seems that there is a lower risk of new cases of thrombophlebitis appearing both in patients with uncoated and those with heparin-coated polyethylene catheters. Radiological thrombosis, regardless of duration of catheterization and heparin-coating, was demonstrated in all 22 patients investigated by \"pull-out\" phlebography. The heparin-coating did not decrease the rate of thrombotic complications. Location of the catheter tip in subclavian veins was associated with a significantly higher incidence of large, parietal thrombi and catheter occlusion than when the tip was situated in anonymous veins, the superior vena cava, or the right atrium. Cannulation by heparin-coated, polyethylene tubing did not reduce the rate of catheter occlusion.", "Central venous catheter-related infections are a significant medical problem. Improved preventive measures are needed.\n To ascertain 1) effectiveness of a second-generation antiseptic-coated catheter in the prevention of microbial colonization and infection; 2) safety and tolerability of this device; 3) microbiology of infected catheters; and 4) propensity for the development of antiseptic resistance.\n Multicenter, randomized, double-blind, controlled trial.\n 9 university-affiliated medical centers.\n 780 patients in intensive care units who required central venous catheterization.\n Patients received either a standard catheter or a catheter coated with chlorhexidine and silver sulfadiazine.\n The authors assessed catheter colonization and catheter-related infection, characterized microbes by molecular typing, and determined their susceptibility to antiseptics. Patient tolerance of the catheter was monitored.\n Patients with the 2 types of catheters had similar demographic features, clinical interventions, laboratory values, and risk factors for infection. Antiseptic catheters were less likely to be colonized at the time of removal compared with control catheters (13.3 vs. 24.1 colonized catheters per 1000 catheter-days; P < 0.01). The center-stratified Cox regression hazard ratio for colonization controlling for sampling design and potentially confounding variables was 0.45 (95% CI, 0.25 to 0.78). The rate of definitive catheter-related bloodstream infection was 1.24 per 1000 catheter-days (CI, 0.26 to 3.62 per 1000 catheter-days) for the control group versus 0.42 per 1000 catheter-days (CI, 0.01 to 2.34 per 1000 catheter-days) for the antiseptic catheter group (P = 0.6). Coagulase-negative staphylococci and other gram-positive organisms were the most frequent microbes to colonize catheters. Noninfectious adverse events were similar in both groups. Antiseptic susceptibility was similar for microbes recovered from either group.\n The antiseptic catheter was not compared with an antibiotic-coated catheter, and no conclusion can be made regarding its effect on bloodstream infection.\n The second-generation chlorhexidine-silver sulfadiazine catheter is well tolerated. Antiseptic coating appears to reduce microbial colonization of the catheter compared with an uncoated catheter.", "To evaluate a new silver-impregnated multi-lumen central venous catheter for reducing catheter-related colonization in intensive care patients.\n Multicenter, prospective, randomized, controlled clinical study.\n Ten adult intensive care units (multidisciplinary, medical and surgical, university and nonuniversity hospitals) in eight institutions.\n A total of 577 patients who required 617 multi-lumen central venous catheters between November 2002 and April 2004 were studied.\n Intensive care adult patients requiring multi-lumen central venous catheters expected to remain in place for >or=3 days were randomly assigned to undergo insertion of silver-impregnated catheters (silver group) or standard catheters (standard group). Catheter colonization was defined as the growth of >or=1,000 colony-forming units in culture of the intravascular tip of the catheter by the vortexing method. Diagnosis of catheter-related infection was performed by an independent and blinded expert committee.\n A total of 320 catheters were studied in the silver group and 297 in the standard group. Characteristics of the patients, insertion site, duration of catheterization (median, 11 vs. 10 days), and other risk factors for infection were similar in the two groups. Colonization of the catheter occurred in 47 (14.7%) vs. 36 (12.1%) catheters in the silver and the standard groups (p = .35), for an incidence of 11.2 and 9.4 per 1,000 catheter days, respectively. Catheter-related bloodstream infection was recorded in eight (2.5%) vs. eight (2.7%) catheters in the silver and the standard groups (p = .88), for an incidence of 1.9 and 2.1 per 1,000 catheter days, respectively.\n The use of silver-impregnated multi-lumen catheters in adult intensive care patients is not associated with a lower rate of colonization than the use of standard multi-lumen catheters.", "This study was performed to determine the efficacy of a benzalkonium chloride-impregnated central venous catheter (CVC) in preventing catheter-related infection in patients suffering from malignant diseases and undergoing chemotherapy.\n A randomized, prospective clinical trial was carried out to compare the incidence of catheter-related colonization and catheter-related bacteremia using an antiseptic-impregnated CVC (n = 25) with that using a standard triple-lumen CVC (n = 25).\n All patients were treated with intensive chemotherapy for acute leukemia (n = 28), lymphoma (n = 17) or solid tumors (n = 5). Both study groups presented with similar data in regards to age, insertion site, duration of catheterization and neutropenia period during catheterization, demonstrating a comparable risk for catheter-related colonization. Suspicion of infection led to explantation in 14 versus 15 cases. Catheter-related colonization was proven in 4 cases (16%) and catheter-related bacteremia was observed only once (4%) in both groups. Statistical testing showed no significant differences between the study and control group.\n The rate of catheter-related colonization was lower than suspected in this high-risk patient group. The use of benzalkonium chloride-impregnated CVC failed to decrease the incidence of catheter-related colonization and bacteremia in patients with a high risk of infectious complications.\n Copyright 1999 S. Karger AG, Basel", "The VitaCuff catheter, a specialized central venous catheter (CVC) with an attached silver-impregnated cuff, is designed to permit percutaneous placement and prolonged venous access. A prospective randomized study was undertaken comparing the VitaCuff with standard triple lumen catheters to determine if the VitaCuff reduces infection during extended use. All consenting patients underwent percutaneous placement of subclavian lines. By study design, control and VitaCuff catheters could remain in site for up to 7 and 14 days, respectively. Cultures were obtained from the preinsertion skin site, and upon removal, from the skin, hubs, infusates, CVC tip, and cuff. Statistical methods included chi 2, the Student t test, and the log-rank test on Kaplan-Meier estimates. Of 133 patients completing this study, 64 patients (48.1%) underwent VitaCuff placement and 69 patients (51.8%) served as controls. In 124 patients (93.2%), the indication for catheter placement was for perioperative care. Overall, 67 patients (50.4%) required central venous access > 7 days, necessitating > or = 1 additional line in 29 patients (21.8%). The incidence of pneumothorax per patient from the initial central line insertion was 4/104 (3.85%), significantly lower than the 4/29 (13.8%) incidence during secondary catheter placement (P = 0.046). Culture results upon catheter removal demonstrated a reduction in colonization of skin sites and hubs for the VitaCuff patients, but not for catheter tips or infusates. Regardless of the type of catheter used, colonization was dependent upon duration of insertion. The incidence of catheter-related sepsis was 6.8%, and did not differ significantly between the study groups. Multiple CVC insertions increase the incidence of pneumothorax. Because VitaCuff catheters permit extended access up to 14 days without increasing the incidence of sepsis, we recommend their use in patients who require prolonged CVC access.", "The indication of antiseptic-coated catheters remains debated.\n To test the ability of the new generation of chlorhexidine-silver and sulfadiazine-coated catheters, with enhanced antiseptic coating, to reduce the risk of central venous catheter (CVC)-related infection in ICU patients.\n Multicentre randomized double-blind trial.\n A total of 397 patients from 14 ICUs of university hospitals in France.\n Patients were randomized to receive an antiseptic-coated catheter (ACC) or a standard non-coated catheter (NCC).\n Incidence of CVC-related infection.\n Of 367 patients having a successful catheter insertion, 363 were analysed (175 NCC and 188 ACC). Patients had one (NCC=162, ACC=180) or more (NCC=13, ACC=11) CVC inserted. The two groups were similar for insertion site [subclavian (64 vs 69)] or jugular (36 vs 31%)], and type of catheters (single-lumen 18 vs 18%; double-lumen 82 vs 82%), and mean (median) duration of catheterisation [12.0+/-11.7 (9) vs 10.5+/-8.8 (8) days in the NCC and ACC groups, respectively]. Significant colonisation of the catheter occurred in 23 (13.1%) and 7 (3.7%) patients, respectively, in the NCC and ACC groups (11 vs 3.6 per 1000 catheter-days; p=0.01); CVC-related infection (bloodstream infection) occurred in 10 (5) and 4 (3) patients in the NCC and CC groups, respectively (5.2 vs 2 per 1000 catheter days; p=0.10).\n In the context of a low baseline infection rate, ACC were associated with a significant reduction of catheter colonisation and a trend to reduction of infection episodes, but not of bloodstream infection.", "Antiseptic coating of intravascular catheters may be an effective means of decreasing catheter-related colonization and subsequent infection. The purpose of this study was to assess the efficacy of chlorhexidine and silver sulfadiazine (CH-SS)-impregnated central venous catheters (CVCs) to prevent catheter-related colonization and infection in patients with hematological malignancies who were subjected to intensive chemotherapy and suffered from severe and sustained neutropenia. Proven CVC-related bloodstream infection (BSI) was defined as the isolation of the same species from peripheral blood culture and CVC tip (Maki technique). This randomized, prospective clinical trial was carried out in 106 patients and compared catheter-related colonization and BSI using a CH-SS-impregnated CVC (n=51) to a control arm using a standard uncoated triple-lumen CVC (n=55). Patients were treated for acute leukemia (n=89), non-Hodgkin's lymphoma (n=10), and multiple myeloma (n=7). Study groups were balanced regarding to age, sex, underlying diseases, insertion site, and duration of neutropenia. The CVCs were in situ a mean of 14.3+/-8.2 days (mean+/-SD) in the study group versus 16.6+/-9.7 days in the control arm. Catheter-related colonization was observed less frequently in the study group (five vs nine patients; p=0.035). CVC-related BSI were significantly less frequent in the study group (one vs eight patients; p=0.02). In summary, in patients with severe neutropenia, CH-SS-impregnated CVCs yield a significant antibacterial effect resulting in a significantly lower rate of catheter-related colonization as well as CVC-related BSI.", "To compare the incidence of catheter colonization and catheter-related bloodstream infections between heparin-coated catheters and those coated with a synergistic combination of chlorhexidine and silver sulfadiazine.\n Randomized, controlled clinical trial.\n A 20-bed medical-surgical intensive care unit.\n A total of 180 patients requiring the insertion of a trilumen central venous catheter. INTERVENTIONS. Patients were randomized to receive either a trilumen heparin or chlorhexidine and silver sulfadiazine-coated catheter.\n Catheter colonization was defined by a semiquantitative catheter tip culture yielding 15 or more colony-forming units or quantitative culture of 1,000 or more colony-forming units/ml. Catheter-related bloodstream infection as the isolation of the same microorganism from a peripheral blood culture and catheter tip.\n A total of 260 catheters were cultured. Out of 132 heparin-coated catheters, 29 were colonized and out of 128 chlorhexidine and silver sulfadiazine-coated catheters, 13 were colonized ( p=0.03), relative risk RR=2.16 (1.18-3.97). This represents an incidence of 23.5 and 11.5 episodes of catheter colonization per 1,000 catheter-days, respectively ( p=0.0059), RR=2.04 (1.05-3.84). Microorganisms isolated in catheter colonization from heparin-coated catheters were gram-positive cocci 23, gram-negative bacilli 7, and Candida spp 4. In chlorhexidine and silver sulfadiazine-coated catheters were gram-positive cocci 6 and gram-negative bacilli 11 ( p=0.009). The incidence of catheter-related bloodstream infections per 1,000 catheter-days was 3.24 in heparin-coated catheters and 2.6 in chlorhexidine and silver sulfadiazine-coated catheters ( p=0.79), RR=1.22 (0.27-5.43).\n In critically ill patients the use of trilumen central venous catheters coated with chlorhexidine and silver sulfadiazine reduced the risk of catheter colonization due to prevention of gram-positive cocci and Candida spp.", "Central venous catheters (CVC) are a major cause of nosocomial bloodstream infections. Catheters modified with miconazole and rifampicin that constantly and slowly release antimicrobial substances are assumed to be beneficial in reducing rates of colonization and catheter-related infections.\n Prospective controlled non-blinded randomized clinical trial in two German university hospitals.\n 223 adult inpatients with CVC between October 2000 and February 2002. Baseline characteristics, APACHE II score and therapeutic interventions were comparable.\n Randomization to receive either a miconazole and rifampicin modified catheter (n=118) or a standard triple-lumen CVC (n=105). MEASUREMENTS, DEFINITIONS: Microbiological evaluation was done after CVC removal. A catheter was considered colonized if growth of > or =15 cfu was found by semi-quantitative roll-plate technique from a proximal or distal catheter segment. A catheter-related infection (CRI) was defined as a colonized catheter with local signs of inflammation. A catheter-related bloodstream infection (CR-BSI) was defined as a colonized catheter with isolation of the same organism from the patient's blood with accompanying clinical signs of infection.\n A colonization of CVC was observed in six patients (5.1%) with a modified catheter and 38 patients (36.2%) with a standard catheter (P < 0.001). Five patients in the modified group (4.2%) and 18 in the standard group (17.1%) developed CRI (P=0.002). One assumed CR-BSI was detected in the standard group, with none in the modified group. No adverse effects related to the modified catheters and no antimicrobial resistance were observed.\n CVC supersaturated with miconazole and rifampicin were associated with a significantly lower risk for catheter colonization and catheter-related infections compared to standard catheters.", "The incidence of bacterial colonization of central venous catheters using a standard polyurethane catheter was compared with that using an antiseptic (silver sulphadiazine and chlorhexidine) impregnated catheter in a group of patients with thoracic organ transplantation. Colonization was reduced from 25 of 35 standard catheters to 10 of 44 study catheters (P < 0.002), a 68% reduction. Similarly, the incidence of concomitant infection, by the same organism at another site was reduced from 10 of 35 standard catheters to 4 of 44 study catheters (P < 0.03), a 63% reduction.", "To evaluate the efficacy of long-term nontunneled silicone catheters impregnated with minocycline and rifampin (M-R) in reducing catheter-related bloodstream infections.\n This prospective, randomized, double-blind clinical trial was conducted at M.D. Anderson Cancer Center, a tertiary care hospital in Houston, TX. All patients in the trial had a malignancy.\n Between September 1999 and May 2002, 356 assessable catheters were used: 182 M-R and 174 nonimpregnated. The patients' characteristics were comparable between the two study groups. The mean (+/- standard deviation) duration of catheterization with M-R catheters was comparable to that of nonimpregnated catheters (66.21 +/- 30.88 v 63.01 +/- 30.80 days). A total of 17 catheter-related bloodstream infections occurred during the course of the study. Three were associated with the use of M-R catheters and 14 were associated with the nonimpregnated catheters, with a rate of catheter-related bloodstream infection of 0.25 and 1.28/1,000 catheter-days, respectively (P = .003). Gram-positive cocci accounted for the majority of the organisms causing the infections. There were no allergic reactions associated with M-R catheters.\n Long-term nontunneled central venous catheters impregnated with minocycline and rifampin are efficacious and safe in reducing catheter-related bloodstream infections in cancer patients.\n Copyright 2004 American Society of Clinical Onocology", "Catheters impregnated with silver have been proposed as a means of reducing catheter-related infection. We therefore performed a prospective randomized study to compare a new silver-impregnated central venous catheter (CVC) with a commercially available CVC in a cohort of immunocompromised patients. We studied 157 patients of whom 97 could be analysed. The median indwelling time in the study group (SC) was 10.5 days and 11 days in the control group (CC). The incidence of contamination in the SC group was 15.6 vs 24.6 in the CC group referring to 1000 catheter days. In both groups, we found 6% of catheter-related infections according to the definitions of a published scoring system. The differences between the two groups were not significant. We conclude that the SC decrease the incidence of catheter contamination and may have a positive effect on the reduction of CVC-related infections.\n Copyright 2002 The Hospital Infection Society.", "It has been suggested that central venous catheters impregnated with antiseptics such as chlohexidine and silver-sulfadiazine reduce the risk of catheter-related bacteraemia in intensive care patients. Patients suffering from haematologic malignancy treated by chemotherapy through a central venous catheter are at even greater risk of catheter-related bacteraemia. A prospective double-blind randomized controlled trial was performed in order to investigate the effectiveness of chlorhexidine and silver-sulfadiazine impregnated catheters (CH-SS) in these patients. A total of 680 catheters (13,826 catheter days) were inserted, of which 338 were antiseptic impregnated. Bloodstream infection was observed in 105 cases with an overall risk of 7.6 per 1000 catheter days. Thirty-two infections (30.5%) were catheter-related, corresponding to a risk of 2.3 per 1000 catheter days. There was no statistically significant different between the overall rates of bloodstream infection for impregnated and non-impregnated catheters (14.5 vs. 16.3%). The incidence of catheter-related infection was also similar in both groups (5 vs. 4.4%) and there was no difference in the time of the onset of bacteraemia in the two groups. It is concluded that the use of CH-SS catheters in patients with haematologic malignancy reduces neither the overall risk of bloodstream infection, nor the catheter-related infection rate, nor the delay for the occurrence of infection.", "Sixty-one consecutive patients in the Intensive Care Unit requiring central venous lines (CVC) for five or more days were randomized to receive either a standard triple lumen CVC (STD/CVC) or a silver sulphadiazine and chlorhexidine impregnated CVC (SSD/CVC). Data from the 54 patients who completed the trial show a reduced infection rate (positive tip culture) in the SSD/CVC group (4 out of 28) compared to the STD/CVC group (10 out of 26) (P < 0.05). In addition, the new Fibrin Analysing System (FAS) brush was evaluated and used to determine the presence of infection in all the CVCs (STD/CVC and SSD/CVC combined, n = 54) at day 3 (i.e. early warning of CVC colonization/infection) and at the time of removal of the CVC. The FAS brush was able to detect an infected CVC on only one occasion on day 3 out of the 14 CVC tips which were later found to be colonized/infected at the time of removal. The sensitivity of the FAS brush in detecting colonized/infected CVCs at the time of CVC removal compared with CVC tip culture was 21% with a specificity of 100%. These findings would currently not support the routine use of the FAS brush in determining CVC infection/colonization.", "To evaluate the efficacy of triple-lumen central venous catheters coated with a combination product of chlorhexidine and silver sulfadiazine (CSS) in reducing the incidence of local catheter infection and catheter-related bacteremia.\n Randomized, controlled trial.\n The surgical intensive care units in a university hospital.\n All patients who needed central venous catheterization were randomized to receive either an uncoated triple-lumen catheter (n = 157) or a catheter coated with CSS (n = 151).\n Catheters were removed when no longer needed or suspected as a cause of infection. The tip and a 5-cm segment of the intradermal portion of the catheter were cultured semiquantitatively. Blood cultures were obtained when clinically indicated. The remaining segment of catheters coated with CSS were cut and incubated on an agar plate with strains of Staphylococcus aureus and Enterococcus. Zone of inhibition was determined 24 hours later. Data were analyzed by survival and logistic multivariate regression methods.\n Catheters coated with CSS were effective in reducing the rate of significant bacterial growth on either the tip or intradermal segment (40%) compared with control catheters (52%; P = .04). However, there was no difference in the incidence of catheter-related bacteremia (3.8% [uncoated] vs 3.3% [coated]; P = .81). In vitro activity of catheters with CSS against S aureus was evident up to 25 days but activity against Enterococcus dissipated more quickly over time and was absent by day 4. The most common colonizing organisms were coagulase-negative staphylococcus and enterococcus. Variables that were associated with a significant amount of growth on the tip or intradermal segment were a duration of catheterization of longer than 7 days, jugular insertion site, and the absence of a CSS coating. The use of a guidewire when the catheter was removed was associated with a lower risk of significant bacterial growth.\n The use of CSS reduces the incidence of significant bacterial growth on either the tip or intradermal segments of coated triple-lumen catheters but has no effect on the incidence of catheter-related bacteremia. In this patient population, catheters coated with CSS provide no additional benefit over uncoated catheters.", "To evaluate the use of an antiseptic-impregnated (chlorhexidine and silver sulfadiazine) catheter for the prevention of catheter colonization and catheter-related bloodstream infection (CR-BSI). Then, based on these findings, to implement changes in hospital policy and to assess their effect on a hospital service.\n Prospective, randomized, controlled (phase I); prospective, concurrent data collection (phase II).\n Tertiary referral hospital with level 1 trauma center.\n Patients > 12 years of age with central venous catheters placed while they were in the emergency room, neurotrauma ICU, or medical/surgical ICU from May through December, 1995 (phase I). All patients > 12 years of age on the trauma service admitted from November 16, 1996, through November 15, 1997 (phase II).\n Randomization table determined whether the patient would receive an antiseptic-impregnated catheter (AIC) or nonimpregnated catheter (NIC) (phase I). All removed or exchanged catheters were sent for semiquantitative culture. In phase II, only AICs were used; \"length of time\" and \"fever\" were discouraged as reasons for catheter exchange or removal; and only the tip was sent for culture.\n In phase I, there were 139 catheters placed in 60 patients in the NIC group and 98 catheters placed in 55 patients in the AIC group. Two catheters (2.0/100 catheters) in the AIC group were found to be colonized, compared with 25 (18.0/100 catheters) in the NIC group (p = 0.001). The catheter colonization rates were 2.27/1,000 catheter days (AIC) and 24.68/1,000 catheter days (NIC) (p < 0.001), while the CR-BSI rates were 1.14/1,000 catheter days (AIC) and 3.9.5/1,000 catheter days (NIC) (p = 0.31). The reason for each catheter removal/exchange was noted, and only \"positive blood culture\" was statistically significant overall. The tip segment was found to be positive more often than the intracutaneous segment. In phase II, there were 213 AICs placed in 101 patients. The colonization rate was 3.8/100 catheters (4.52/1,000 catheter days), and CR-BSI rate was 1.0/100 catheters (0.6/1,000 catheter days). The colonization rate for catheters left in place remained low for catheters left in place < 14 days (1.6/100 catheters). Only 11% of catheters were exchanged/removed for reason of \"fever,\" as compared with 23% in phase I.\n AICs significantly reduce the rate of central venous catheter colonization. In addition, the apparent protective effects of the catheter over time permit less frequent exchanges or removals of the catheters, decreasing both patient risk and hospital cost.", "In this prospective, randomized, controlled, unblinded study, we compared colonization rates of a standard, unimpregnated central venous catheter (CVC) with rates for silver-coated and chlorhexidine-silversulfadiazine (CH-SS)-impregnated CVC. Patient characteristics, CVC insertion site, indwelling time, and colonization detected by semiquantitative and quantitative microbiologic techniques were documented. Two-hundred-seventy-five critically ill patients were included into the study protocol. One-hundred-sixty standard, 160 silver (S)-coated, and 165 externally impregnated CH-SS CVC were inserted. There was a significant difference in CVC colonization rates among study groups (P = 0.029). There was no difference in the colonization rate and the colonization per 1000 catheter days between standard and S-coated (P = 0.564; P = 0.24) or CH-SS-coated CVC (P= 0.795; P = 0.639). When comparing antiseptic CVC with each other, colonization rates were significantly less with CH-SS-impregnated than with S-coated CVC (16.9% versus 7.3%; P = 0.01; 18.2 versus 7.5 of 1000 catheter days; P = 0.003; relative risk, 0.43; 95% confidence interval, 0.21-0.85). Whereas standard and S-coated CVC were first colonized 2 and 3 days after insertion, respectively, CH-SS CVC were first colonized only after 7 days. In conclusion, antiseptic-impregnated CVC could not prevent catheter colonization when compared with standard polyurethane catheters in a critical care setting with infrequent catheter colonization rates and CVC left in place for >10 days.", "The antimetabolite drug, 5-fluorouracil, inhibits microbial growth. Coating of central venous catheters with 5-fluorouracil may reduce the risk of catheter infection. Our objective was to compare the safety and efficacy of central venous catheters externally coated with 5-fluorouracil with those coated with chlorhexidine and silver sulfadiazine.\n Prospective, single-blind, randomized, active-controlled, multicentered, noninferiority trial.\n Twenty-five US medical center intensive care units.\n A total of 960 adult patients requiring central venous catheterization for up to 28 days.\n Patients were randomized to receive a central venous catheter externally coated with either 5-fluorouracil (n = 480) or chlorhexidine and silver sulfadiazine (n = 480).\n The primary antimicrobial outcome was a dichotomous measure (<15 colony-forming units or ≥ 15 colony-forming units) for catheter colonization determined by the roll plate method. Secondary antimicrobial outcomes included local site infection and catheter-related bloodstream infection. Central venous catheters coated with 5-fluorouracil were noninferior to chlorhexidine and silver sulfadiazine coated central venous catheters with respect to the incidence of catheter colonization (2.9% vs. 5.3%, respectively). Local site infection occurred in 1.4% of the 5-fluorouracil group and 0.9% of the chlorhexidine and silver sulfadiazine group. No episode of catheter-related bloodstream infection occurred in the 5-fluorouracil group, whereas two episodes were noted in the chlorhexidine and silver sulfadiazine group. Only Gram-positive organisms were cultured from 5-fluorouracil catheters, whereas Gram-positive bacteria, Gram-negative bacteria, and Candida were cultured from the chlorhexidine and silver sulfadiazine central venous catheters. Adverse events were comparable between the two central venous catheter coatings.\n Our results suggest that central venous catheters externally coated with 5-fluorouracil are a safe and effective alternative to catheters externally coated with chlorhexidine and silver sulfadiazine when used in critically ill patients.", "To evaluate silver-impregnated (Oligon) central venous catheters and chlorhexidine-gluconate-impregnated sponges for reducing catheter-related colonization and infection, nonbacteremic or bacteremic.\n Multicenter, prospective, randomized, controlled study.\n Five general intensive care units in Greece.\n Intensive care unit patients requiring a multilumen central venous catheter between June 2006 and May 2008.\n Patients were randomly assigned to receive a standard catheter (standard group), a standard catheter plus chlorhexidine-gluconate-impregnated sponge (chlorhexidine-gluconate-impregnated sponge group), or an Oligon catheter (Oligon group). Catheter colonization was defined as a positive quantitative tip culture (≥10 colony-forming units/mL), catheter-related infection was defined by the previous criterion plus clinical evidence of sepsis, and bacteremia catheter-related infection as catheter-related infection plus a positive peripheral blood culture with the same micro-organism as in the catheter tip.\n Data were obtained from 465 patients, 156 in the standard-group, 150 in the chlorhexidine-gluconate-impregnated sponge group, and 159 in the Oligon-group. Colonization occurred in 24 (15.4%) standard catheters, 21 (14%) in the chlorhexidine-gluconate-impregnated sponge group, and 25 (15.7%) in the Oligon catheters (p = .35) (20.9, 19.9, 21.8/1000 catheter-days, respectively). Catheter-related infections were recorded in nine (5.8%) standard catheters, six (4%) in the chlorhexidine-gluconate-impregnated sponge group, and seven (4.4%) in the Oligon catheters (p = .58) (7.8/1,000, 5.7/1,000, 6.1/1,000 catheter-days, respectively). No difference was observed between the chlorhexidine- gluconate-impregnated sponge group and the standard group regarding catheter colonization (hazard ratio 1.21; 95% confidence interval 0.56-2.61; p = .64) and catheter-related infections (hazard ratio 0.65; 95% confidence interval 0.23-1.85; p = .42). The Oligon catheter did not reduce colonization or catheter-related infections when compared with the standard catheter (colonization: hazard ratio 1.0; 95% confidence interval 0.46-2.21; p = .98; catheter-related infection: hazard ratio 0.72; 95% confidence interval 0.27-1.95; p = .52). Seven patients (1.5%, 2.09/1,000 catheter-days) presented bacteremic catheter-related infections. Central venous catheters inserted either in the internal jugular or the femoral vein had greater risk to be colonized than catheters inserted in the subclavian vein (internal jugular vs. subclavian: hazard ratio 3.29; 95% confidence interval 1.26-8.61; p = .01; femoral vs. subclavian: hazard ratio 3.36; 95% confidence interval 1.17-9.65; p = .02). Acinetobacter baumannii was the predominant pathogen (37.1% episodes of colonization, 36.4% catheter-related infections, 57.1% bacteremic catheter-related infections).\n For short-term (median duration 7 days) central venous catheters in intensive care units with high prevalence of multiresistant Gram-negative bacteria, chlorhexidine-impregnated sponges and Oligon catheters as single preventive measures did not reduce catheter colonization or catheter-related infections. As a result of the limited amount of events, no conclusion could be reached regarding bacteremic catheter-related infections. The femoral site was the most frequently colonized insertion site in all types of catheters.", "Antimicrobial- and antiseptic-impregnated catheters are strategies recommended to prevent central venous catheter (CVC) colonisation. Few data regarding chlorhexidine/silver sulfadiazine-impregnated catheters in intensive care unit (ICU) patients have been reported. We performed a prospective, randomised study comparing the colonisation rates of chlorhexidine/silver sulfadiazine-impregnated CVCs (group 1) against standard CVCs (group 2). In order to assess catheter colonisation rates, a 4cm segment from the tips of aseptically removed catheters was cultured by the roll-plate method. In all, 109 patients were enrolled with successful catheter insertion, 51 of them in group 1 and 58 in group 2. There were no statistically significant differences between the two groups with regards to age, Sequential Organ Failure Assessment (SOFA) score, ICU admission diagnosis, infection risk, catheter insertion sites or catheter length of stay. The colonisation rates were 29.4% (15 catheters) for group 1 and 34.5% (20 catheters) for group 2 (P=0.50). Double-lumen CVCs impregnated with chlorhexidine and silver sulfadiazine were not effective in reducing the incidence of catheter colonisation in ICU patients.", "A prospective study was undertaken to compare the silver-impregnated collagen cuff (Vitacuff) with the bedside tunneled catheter. Fifty patients were randomly assigned to three groups: group I received triple-lumen catheters with Vitacuff application and a semiocclusive dressing material; group II received triple-lumen tunneled catheters with a semiocclusive dressing; and group III received triple-lumen tunneled catheters with collodion as a dressing material. In patients suspected of having central venous catheter sepsis, blood cultures were obtained through the catheter, the catheter was removed, and the tip was cultured semiquantitatively. Central venous catheter sepsis was defined as a positive catheter-tip culture and blood culture for the same organism. No catheter-related sepsis was seen in either the Vitacuff or the tunneled catheters with collodion dressing. In the tunneled catheters with semiocclusive dressing, there was one case of catheter-related sepsis and one case of insertion-site infection. There was also one insertion-site infection in the Vitacuff group, but there was no statistical difference in infection rates between the three groups.", "Central venous catheters (CVCs) are essential for the intensive care of patients with haematological illness. Catheter-related infections (CRI) are an important problem in modern medicine, which may lead to life-threatening situations, to prolonged hospitalisation and increased cost. In immunocompromised patients suffering from haemato-oncological diseases, CRI is a significant factor for adverse outcome. Several clinical studies have shown that CVCs coated with antiseptics such as chlorhexidine and silver-sulfadiazine (CHSS) reduce the risk of catheter-related bacteraemia. Most studies, however, were performed on intensive care patients not suffering from chemotherapy-induced immunosuppression.\n A prospective double-blind, randomised, controlled trial was performed to investigate the effectiveness of CHSS-coated catheters in haemato-oncological patients. A total number of 184 catheters (median duration of placement, 11 days) were inserted into 184 patients (male 115, female 69), of which 90 were antiseptically coated. After removal, all catheters were investigated for bacterial growth.\n Catheters coated with CHSS were effective in reducing the rate of significant bacterial growth on either the tip or subcutaneous segment (26%) compared to control catheters (49%). The incidence of catheter colonisation was also significantly reduced (12% coated vs 33% uncoated). Data obtained show a significant reduction of catheter colonisation in CHSS catheters. There was no significant difference in the incidence of catheter-related bacteraemia (3% coated vs 7% uncoated). However, due to the overall low rate of CRI, we could not observe a significant reduction in the incidence of catheter-related bacteraemia.\n Our data show that the use of CHSS catheters in patients with haematological malignancy reduces the overall risk of catheter colonisation and CRI, although the incidence of catheter-related bacteremia was similar in both groups.", "To evaluate the efficacy of silver iontophoretic central venous catheters in preventing catheter related colonisation and bloodstream infection among high risk patients in a tertiary hospital.\n Patients requiring central venous access for a period greater than seven days were stratified into two groups according to systemic inflammatory response syndrome criteria before being randomly assigned to receive either silver iontophoretic or control catheters. The incidence of catheter colonisation and catheter related bloodstream infection (CRBSI) was recorded.\n Three hundred and four single lumen study catheters were inserted into 268 patients. Total duration of catheterisation was 5449 days (median, 12 days/catheter). Complete data could be evaluated in 270 catheters: 128 silver iontophoretic catheters and 140 untreated catheters. Forty seven silver iontophoretic catheters (36.7%) were colonised compared with 48 control catheters (33.8%). Seven cases (5.5%) of CRBSI occurred in patients who received silver iontophoretic catheters, compared with 11 cases (7.7%) in patients receiving control catheters. There was no significant difference in the incidence of catheter colonisation or CRBSI between silver iontophoretic and control catheters. When the duration of catheter placement was taken into consideration, Kaplan-Meier analysis showed no significant difference in the risk of CRBSI between the silver iontophoretic catheters and the untreated catheters (p = 0.77).\n There was no significant difference in the incidence of catheter colonisation or CRBSI among high risk patients between silver iontophoretic catheters and control catheters. Future prospective, randomised studies with a larger number of catheters are encouraged to confirm or refute these results.", "Microbial colonization and the incidence of catheter-related bloodstream infections (CR-BSI) associated with Oligon Vantex silver central venous catheters (CVC) in critically ill patients were determined. A prospective, randomized, controlled 17-month trial was carried out in an intensive care unit (ICU). All patients requiring a triple-lumen CVC for four days or longer were enrolled. Patients were randomized to receive a standard polyurethane CVC or an Oligon Vantex silver CVC. Before removal of the catheter either due to discharge from the ICU or suspected infection, blood for cultures was taken via the CVC and a peripheral site. Skin and hub swabs and catheter-tips were also cultured. Two hundred and six catheters, 103 in both groups, were evaluated. In the control group (CG) 45/103 (44%) and in the silver group (SG) 30/103 (29%) were colonized or had a CR-BSI (P=0.04). The SG was less likely to be colonized than the CG when the catheter remained in situ for eight days or less (P=0.03) or over 15 days (P=0.01); a second or subsequent catheter was present in the same patient (P=0.002), or if the CVC was placed in the internal jugular vein (P=0.05). Multivariate logistic-regression showed predisposing factors for catheter colonization were jugular and femoral sites, second or subsequent catheter, and being a member of the CG. CR-BSI occurred in five cases (four in CG). Rates of CR-BSI per 1000 catheter-days in the CG were 2.8 and in the SG, 0.8 (P<0.001). The Oligon Vantex silver catheter reduced the incidence of catheter-colonization and may decrease the risk of CR-BSI.", "A central venous catheter with a new form of silver impregnation of the internal and external surfaces was investigated for antimicrobial activity and tolerance in patients in a controlled comparative, prospective and randomized clinical study. Commercially available catheters with no antimicrobial activity were used as controls. One hundred sixty-five catheters were included in the final evaluation. All catheters were percutaneously inserted for the first time with a duration of > or = 5 days and a microbiological examination of the catheter tip. Catheter location (> 90% internal jugular vein), mean duration of catheterization (8-9 days), patients' age and diagnosis were comparable in both groups. Silver-impregnated catheter tips showed an incidence of colonization in 14.2/1000 catheter days and control catheters in 22.8/1000 catheter days. This represents a reduction of 37.7%. Catheter-associated infections were diagnosed in the silver group in 5.26/1000 catheter days and 18.34/1000 catheter days in the control group, indicating a reduction rate of 71.3% (P < 0.05, chi 2-test). No complications or side effects were documented in either group.", "This study was undertaken to evaluate the impact of chlorhexidine/silver sulphadiazine-bonded catheters on the incidence of colonisation and catheter-related sepsis in critically ill patients. Threehundred and fifty-one catheters were inserted into 228 patients during the study period, 174chlorhexidine/silver sulphadiazine-bonded catheters and 177 standard catheters. Indications for catheter removal were: death, clinical redundancy and clinical evidence of local or systemic infection. All catheter tips were sent to the microbiology laboratory for semiquantitative analysis of bacterial colony count. Seventy-one (40.2%) of the standard catheters and 47 (27.2%) of the antiseptic-bonded catheters were found to be colonised on removal (p < 0.01). Eight cases (4.7%) of catheter-related sepsis were associated with standard catheters and three cases (1.7%) with antiseptic-bonded catheters, however, this reduction was not statistically significant. Our results indicate that the use of antiseptic-bonded catheters in critically ill patients significantly reduces the incidence of bacterial colonisation.", "To test the efficacy of the ARROWgard (Arrow International Inc, Reading, Pa) central venous catheter (CVC) coated with silver sulfadiazine and chlorhexidine (A-CVC) in the prevention of CVC-related infections.\n Prospective, randomized trial.\n A tertiary care medical center.\n Two hundred eighty-two patients who required CVC placement were evaluated in this study. Patients were prospectively randomized to receive either a standard CVC (S-CVC) or the A-CVC. Only fresh-stick double- and triple-lumen catheters were studied.\n Patients were evaluated for catheter site inflammation, catheter site colonization, local catheter-related infection, and catheter-related septicemia.\n The 2 groups were matched for age, percentage in the intensive care unit, percentage receiving total parenteral nutrition, percentage with triple-lumen catheters, and duration of catheterization. Rates of catheter site inflammation in the 2 groups were similar (12% vs 10%, S-CVC group and A-CVC group, respectively). The A-CVC was associated with a significantly decreased catheter site colonization rate (49% vs 28%; 43% reduction; P<.001) and local catheter-related infection rate (22.4% vs 5.8%; 74% reduction; P<.001). Rates of catheter-related septicemia were reduced by 41% in the A-CVC group (6.4% vs 3.8%, S-CVC group and A-CVC group, respectively), but this was not statistically significant.\n Despite a marked decrease in catheter site colonization and catheter-related infection rates, the A-CVC did not significantly reduce the incidence of catheter-related septicemia. This may be due to a greater pathogenic dependence on catheter hub contamination rather than catheter site colonization or local catheter-related infection, or the relatively short (5.2 days) duration of catheterization in this study.", "Central venous catheterization represents a significant medical advancement, particularly in the treatment of critical ill. However, there is a high risk of central venous catheters-related infection. A novel antiseptic central venous catheter, made of polyurethane and impregnated with chlorhexidine and silver sulfadiazine, was developed to reduce the risk of catheters-related infection. In this study, we did a randomized clinical study to determine the efficacy by using antiseptic catheters for the prevention of central venous catheters-related infection in the intensive care units. A total of 204 patients with 235 central venous catheters were studied at the surgical intensive care units at National Taiwan University Hospital between November 1998 and June 1999. Participants received either a standard triple-lumen polyurethane catheter or an antiseptic catheter (Arrow International, Reading, Pennsylvania, USA). Both were indistinguishable from each other. Compared to standard polyurethane catheters, antiseptic catheters were less likely to be colonized by microorganisms when they were cultured at the removal (8.0 versus 20.0 colonized catheters per 100 catheters; relative risk 0.34 [95% CI, 0.15 to 0.74]; p<0.01). There was no significant differences between both groups in catheter-related infections (0.9 versus 4.9 infections per 100 catheters; relative risk 0.17 [95% CI, 0.03 to 1.15]; p = 0.07). Gram-positive cocci and fungi were more likely to colonize in the standard polyurethane catheters (p = 0.06 and 0.04, compared to antiseptic catheters respectively). Two of our cases in the control group died directly due to catheter-related candidemia. No adverse reactions such as hypersensitivity or leukopenia were found in the antiseptic catheter group. Our study showed that central venous catheters with antiseptic coating were safe and had less risk of colonization of bacteria and fungi than standard catheters in the critically ill patients." ]

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[ "Efficacy and safety of tonabersat, a gap-junction modulator, in the acute treatment of migraine: a double-blind, parallel-group, randomized study.", "Oral sumatriptan compared with placebo in the acute treatment of migraine.", "A double-blind placebo-controlled study assessing the efficacy and tolerability of 50 mg sumatriptan tablets in the acute treatment of migraine. Sumatriptan Tablets S2CM07 Study Group.", "Crossover comparison of rizatriptan 5 mg and 10 mg versus sumatriptan 25 mg and 50 mg in migraine. Rizatriptan Protocol 046 Study Group.", "Comparative study of a combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the treatment of migraine.", "2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the Spectrum Study.", "Pain-free efficacy after treatment with sumatriptan in the mild pain phase of menstrually associated migraine.", "Pain free efficacy of sumatriptan in the early treatment of migraine.", "Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast-disintegrating/rapid-release formulation of sumatriptan tablets.", "Efficacy of naratriptan tablets in the acute treatment of migraine: a dose-ranging study. Naratriptan S2WB2004 Study Group.", "Valdecoxib for treatment of a single, acute, moderate to severe migraine headache.", "Efficacy and tolerability of sumatriptan in the treatment of multiple migraine attacks.", "A comparison of visual analog scale and categorical ratings of headache pain in a randomized controlled clinical trial with migraine patients.", "Sumatriptan in the treatment of acute migraine with aura.", "Oral almotriptan vs. oral sumatriptan in the abortive treatment of migraine: a double-blind, randomized, parallel-group, optimum-dose comparison.", "Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg.", "Pain-free results with sumatriptan taken at the first sign of migraine pain: 2 randomized, double-blind, placebo-controlled studies.", "A comparative trial of zolmitriptan and sumatriptan for the acute oral treatment of migraine.", "Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early treatment of migraine: results from the ASSET trial.", "Comparison of the efficacy of zolmitriptan and sumatriptan: issues in migraine trial design.", "Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs.", "Rizatriptan vs sumatriptan in the acute treatment of migraine. A placebo-controlled, dose-ranging study. Dutch/US Rizatriptan Study Group.", "Sumatriptan and naproxen sodium for the acute treatment of migraine.", "Oral sumatriptan for the acute treatment of migraine: evaluation of three dosage strengths.", "A study to compare oral sumatriptan with oral aspirin plus oral metoclopramide in the acute treatment of migraine. The Oral Sumatriptan and Aspirin plus Metoclopramide Comparative Study Group.", "Eletriptan vs sumatriptan: a double-blind, placebo-controlled, multiple migraine attack study.", "Comparison of rizatriptan 5 mg and 10 mg tablets and sumatriptan 25 mg and 50 mg tablets.", "Efficacy of sumatriptan tablets in migraineurs self-described or physician-diagnosed as having sinus headache: a randomized, double-blind, placebo-controlled study.", "Efficacy of 1,000 mg effervescent acetylsalicylic acid and sumatriptan in treating associated migraine symptoms.", "Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks.", "Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study.", "Efficacy and tolerability of sumatriptan tablets in a fast-disintegrating, rapid-release formulation for the acute treatment of migraine: results of a multicenter, randomized, placebo-controlled study.", "Treatment with sumatriptan 50 mg in the mild phase of migraine attacks in patients with infrequent attacks: a randomised, double-blind, placebo-controlled study.", "Almotriptan is an effective and well-tolerated treatment for migraine pain: results of a randomized, double-blind, placebo-controlled clinical trial.", "Sumatriptan-naproxen for acute treatment of migraine: a randomized trial.", "Eletriptan in acute migraine: a double-blind, placebo-controlled comparison to sumatriptan. Eletriptan Steering Committee.", "Clinical experience with oral sumatriptan: a placebo-controlled, dose-ranging study. Oral Sumatriptan Dose-defining Study Group.", "Tolfenamic acid rapid release versus sumatriptan in the acute treatment of migraine: comparable effect in a double-blind, randomized, controlled, parallel-group study.", "High efficacy and low frequency of headache recurrence after oral sumatriptan. The Oral Sumatriptan Italian Study Group.", "Prevalence of migraine and response to sumatriptan in patients self-reporting tension/stress headache.", "Efficacy and safety of sumatriptan 50 mg in patients not responding to standard care, in the treatment of mild to moderate migraine. The Sumatriptan 50 mg Italian Study Group.", "Acute treatment of migraine attacks: efficacy and safety of a nonsteroidal anti-inflammatory drug, diclofenac-potassium, in comparison to oral sumatriptan and placebo. The Diclofenac-K/Sumatriptan Migraine Study Group.", "Zolmitriptan versus sumatriptan for the acute oral treatment of migraine: a randomized, double-blind, international study.", "Efficacy and safety of sumatriptan tablets (25 mg, 50 mg, and 100 mg) in the acute treatment of migraine: defining the optimum doses of oral sumatriptan.", "Sumatriptan--an oral dose-defining study. The Oral Sumatriptan Dose-Defining Study Group.", "Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group.", "A randomized, double-blind comparison of sumatriptan and Cafergot in the acute treatment of migraine. The Multinational Oral Sumatriptan and Cafergot Comparative Study Group.", "The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine.", "Oral sumatriptan is effective and well tolerated for the acute treatment of migraine: results of a multicenter study.", "Almotriptan increases sustained pain-free outcomes in acute migraine: results from three controlled clinical trials." ]

[ "The ability of tonabersat to relieve the symptoms of migraine attacks with or without aura was evaluated in a randomized, double-blind, placebo-controlled, multicentre, parallel-group study. Patients received 20 or 40 mg of tonabersat, or 50 mg of sumatriptan (positive control), or placebo at the onset of a moderate or severe attack. Headache intensity, relief and recurrence were recorded for 24 h after dosing. On the basis of primary or secondary efficacy measures, tonabersat did not provide a clinically or statistically significant advantage over placebo. Tonabersat generally was well tolerated and had no effect on vital signs, electrocardiogram recordings or laboratory values. The lack of efficacy may be a function of the slow absorption of tonabersat. As a consequence of slow absorption, daily administration of tonabersat as prophylaxis for migraine attacks is under investigation in ongoing studies.", "This multicentre, double-blind, parallel-group study compared the efficacy, safety and tolerability of oral sumatriptan, given as a new film-coated tablet, with placebo in the acute treatment of migraine. Patients were randomised unequally (1:2) to receive placebo or sumatriptan. Eighty-eight patients received placebo (plus an optional dose 2 h later if the headache persisted plus a further optional dose for recurrence within 24 h) and 162 patients received sumatriptan 100 mg (plus an optional 100 mg dose at 2 h and an optional 100 mg dose within 24 h). Sumatriptan was significantly more effective than placebo at relieving headache (defined as reduction in severity from severe or moderate pain to mild or no pain) at 2 h (51% versus 31%, P = 0.003) and 4 h (71% versus 35%, P < 0.001). Fewer sumatriptan-treated patients required a second dose compared with placebo-treated patients (49% versus 74%, P < 0.001). More sumatriptan-treated patients were completely pain free compared with placebo-treated patients at both 2 h (24% versus 12%) and 4 h (48% versus 18). Patients receiving sumatriptan reported earlier onset of headache relief than patients receiving placebo. Headache relief in sumatriptan-treated patients was similar, irrespective of the type of migraine (with or without aura) or the time of treatment < or = 4 h or > 4 h after onset of migraine). Sumatriptan was more effective than placebo at relieving nausea, vomiting and photophobia/phonophobia. Few patients were evaluable for treatment of headache recurrence, and statistical analysis was not possible.(ABSTRACT TRUNCATED AT 250 WORDS)", "Oral sumatriptan 50 mg has been found to have good efficacy and tolerability in the acute treatment of migraine but has been less well studied than the 100 mg dose.\n This was a double-blind, parallel-group study (Glaxo Wellcome protocol number S2CM07) comparing the efficacy and safety of sumatriptan 50 mg tablets with placebo in the acute treatment of migraine. Patients treated three migraine attacks with study medication; a second, optional dose was available for treating recurrent headache. Of the 560 patients randomized, 485 treated at least one attack, 411 at least two attacks, and 362 three attacks. The primary efficacy measure was the proportion of patients who had obtained complete or almost complete headache relief at 4 h after dosing.\n For all attacks, a significantly greater proportion of patients experienced headache relief at 4 h with sumatriptan 50 mg tablets than with placebo (59% to 62% versus 32% to 42%; P = 0.005). The same was true at 3 h across all attacks, and at 2 h for attacks 1 and 2 (49% versus 23% and 45% versus 29%, respectively). Although sumatriptan and placebo were associated with similar incidences of recurrence, sumatriptan was associated with a longer time to recurrence. The incidence of adverse events with sumatriptan was similar to that with placebo, and there was no increase in adverse events associated with use of a second dose to treat recurrence.\n Sumatriptan 50 mg tablets are well tolerated and efficacious in relieving migraine headache.", "Rizatriptan is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This double-blind, placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients were allocated to one of five groups for treatment of two attacks: rizatriptan 5 mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10 mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For each attack, patients rated headache severity, presence of associated symptoms, and functional disability prior to dosing and at intervals through 4 hours thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively. The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication. All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing. All active treatments were well-tolerated and showed comparable safety profiles.", "To compare the safety and efficacy of isometheptene mucate, dichloralphenazone with acetaminophen to sumatriptan succinate for the treatment of mild-to-moderate migraine, with or without aura, when taken at the first sign of an attack.\n The Food and Drug Administration approved sumatriptan succinate and the combination of isometheptene mucate, dichloralphenazone with acetaminophen for the treatment of migraine. As part of the stratified treatment of migraine, those patients whose headaches are mild or moderate may benefit from nontriptan medications. Additionally, early treatment of acute migraine before the headache has become moderate or severe may improve response to treatment.\n This was a multicenter, double-blind, randomized, parallel-group study to assess the safety and efficacy of the combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the early stages of a single migraine attack. Patients diagnosed with migraine, with or without aura, as defined by the International Headache Society diagnostic criteria were enrolled.\n One hundred thirty-seven patients were enrolled in the study. Data for efficacy were available for 126 patients; safety data were available for 128 patients. No statistically significant difference between the two active agents in the patient's response to treatment was demonstrated. Headache recurrence was not significantly different over the 24-hour evaluation period for those patients responding in the first 4 hours. In those with headache recurrence, it was statistically significantly more severe in those patients treated with sumatriptan succinate. Improvement in functional disability was, in general, better among those treated with isometheptene mucate, dichloralphenazone with acetaminophen. Global analysis of efficacy was similar in the two active groups. Patients treated with sumatriptan succinate were somewhat more likely to have adverse effects than the isometheptene mucate, dichloralphenazone with acetaminophen group.\n Both isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate are safe and effective when used early in the treatment of an acute migraine. Several parameters suggest that isometheptene mucate, dichloralphenazone with acetaminophen may have a slight advantage compared with sumatriptan succinate in the early treatment of mild-to-moderate migraine.", "Migraineurs experience a spectrum of headaches: migraine, migrainous, and episodic tension-type as defined by the International Headache Society (IHS).\n To evaluate the effectiveness of sumatriptan, 50-mg tablets, in treating the spectrum of headaches in IHS-diagnosed migraineurs.\n Migraineurs with severe disability (Headache Impact Questionnaire score 250 or greater) were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients treated up to 10 headaches with sumatriptan, 50 mg, or placebo (4:1). Headache features, recorded prior to treatment, were used to classify each headache using IHS criteria. Headache response (moderate or severe pain reduced to mild or no pain) and pain-free response were recorded at 2 and 4 hours postdose (primary endpoint). Because patients treated multiple attacks, statistical methods controlling for within-subject correlation were used.\n Two hundred forty-nine migraineurs treated 1576 moderate or severe headaches: migraine (n = 1110), migrainous (n = 103), and tension-type (n = 363). Sumatriptan was superior to placebo for headache response 4 hours postdose (primary endpoint) across all headache types (migraine, 66% versus 48%; P<.001; migrainous, 71% versus 39%; P<.01; tension-type, 78% versus 50%, P<.001). Sumatriptan was also superior to placebo for pain-free response 4 hours postdose for migraine (41% versus 24%, P<.001) and tension-type headaches (56% versus 36%, P =.001). Sumatriptan provided superior pain-free response 2 hours postdose for migraine (18% versus 7%, P<.0001) and tension-type headache (28% versus 14%, P =.0005) compared with placebo.\n Sumatriptan, 50-mg tablets, are effective for the full spectrum of headaches experienced by patients with disabling migraine due to a sumatriptan-responsive mechanism.", "To estimate the efficacy of sumatriptan 50-mg and 100-mg tablets in menstrually associated migraine when treatment is administered during the mild pain phase.\n A randomized, double-blind, placebo-controlled, single-attack study was conducted. Menstrually associated migraine was defined as any migraine beginning on or between day -2 and day 4, with day 1 = first day of flow. Patients had at least a 1-year history of migraine as defined by International Headache Society criteria and reported regularly occurring menstrually associated migraines typically having a mild pain phase. Patients treated attacks within 1 hour of the onset of pain but only if the pain was mild at onset and while the pain was still mild.\n In the 349 women with menstrually associated migraine, sumatriptan was significantly more effective than placebo: 61% and 51% of patients who used sumatriptan 100 mg and 50 mg, respectively, were pain-free 2 hours after treatment compared with 29% of patients who used placebo (P <.001 for both comparisons). At 2 hours, 51% and 45% of patients who used sumatriptan 100 mg and 50 mg were free of pain and associated symptoms (photophobia, phonophobia, nausea, vomiting) compared with 25% of placebo patients (P <.001 for both comparisons). Adverse events were low for sumatriptan 100 and 50 mg, and both doses were generally well tolerated.\n Sumatriptan 50-mg and 100-mg tablets are generally well tolerated and effective in providing pain-free relief and relief of the associated symptoms of menstrually associated migraine when administered in the mild pain phase.", "There is evidence that headache response rates may be higher if triptans are used early when a migraine attack is still mild, as compared to when it is treated after pain has reached moderate or severe intensity.\n In this randomized, double blind, placebo controlled, parallel group clinical trial, 361 patients took either placebo, sumatriptan 50 mg, or sumatriptan 100 mg in a single attack study. The primary outcome measure was pain-free status at two hours.\n In the intention to treat group, two hour pain free rates were 16%, 40%, and 50% in the placebo group, sumatriptan 50 mg group, and the sumatriptan 100 mg group respectively (p < 0.001, active treatment groups vs. placebo).\n Both sumatriptan 50 mg and 100 mg were significantly superior to placebo for the pain-free end point at two hours. The pain-free response rates in this trial where sumatriptan was taken while the headache was still mild were generally higher than in older clinical trials where headache was treated after reaching a moderate or severe intensity.", "The gastric stasis that commonly accompanies migraine headache may impair absorption of conventional oral tablets in the stomach. A fast-disintegrating/rapid-release formulation of sumatriptan has been developed to enhance tablet disintegration and drug dispersion and potentially improve absorption.\n Two studies were conducted comparing the time to onset of relief from moderate or severe migraine pain with the fast-disintegrating/rapid-release formulation of sumatriptan tablets 50 and 100 mg and placebo.\n These were 2 identically designed randomized, double-blind, parallel-group studies. Sumatriptan 50 or 100 mg or placebo was taken on an outpatient basis to treat a single moderate or severe migraine attack. Using a personal digital assistant, patients recorded the time of dosing and the time at which pain severity reached none or mild (ie, pain relief) or none (ie, pain free) in real time so that the time to onset of relief could be measured as a continuous variable. Onset of relief was defined as the earliest time point at which a statistically significant difference in pain relief compared with placebo was achieved and maintained through 2 hours after dosing. Before dosing and at pre-determined time points after dosing, patients also provided an assessment of migraine pain as none, mild, moderate, or severe. At a clinic visit within 1 week after treatment of the migraine attack, patients were queried about adverse events. For each adverse event, investigators recorded whether study medication was considered the cause. Data analyses were undertaken for each study individually and, in post hoc analyses of the primary and key secondary end points, on pooled data from both studies.\n The 2 studies comprised 2696 patients: 902 received sumatriptan 50 mg, 902 received sumatriptan 100 mg, and 892 received placebo. Patients' mean age ranged from 40.2 to 40.8 years across treatment groups, and most patients were female (83%-87%) and white (92%-93%). In the analysis of pooled data, sumatriptan tablets provided significantly more effective pain relief compared with placebo as early as 20 minutes after dosing with the 100-mg dose and as early as 30 minutes after dosing with the 50-mg dose (P < or = 0.05). Similar results were observed for the individual studies: in study 1, sumatriptan tablets were significantly more effective than placebo at 25 minutes with the 100-mg dose and at 50 minutes with the 50-mg dose; in study 2, sumatriptan tablets were significantly more effective than placebo at 17 minutes for the 100-mg dose and at 30 minutes for the 50-mg dose (P < or = 0.05). In the pooled data, the cumulative percentages of patients with pain relief by 2 hours after dosing were 72% for the 100-mg dose and 67% for the 50-mg dose, compared with 42% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). The cumulative percentages of patients with a pain-free response by 2 hours were 47% for the 100-mg dose, 40% for the 50-mg dose, and 15% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). In the individual studies, significantly more patients receiving either sumatriptan dose were migraine free 2 hours after dosing and had sustained pain relief and a sustained pain-free response over 24 hours compared with placebo (P < or = 0.001, both sumatriptan doses vs placebo). The only drug-related adverse events reported in >2% of patients in any treatment group in either study were nausea (both studies: 3% sumatriptan 100 mg, 2% sumatriptan 50 mg, 1% placebo) and paresthesia (study 1: <1% sumatriptan 100 mg, <1% sumatriptan 50 mg, 0% placebo; study 2: 3% sumatriptan 100 mg, 1% sumatriptan 50 mg, <1% placebo).\n In these studies, sumatriptan tablets in a fast-disintegrating/rapid-release formulation were effective for the acute treatment of moderate to severe migraine pain, were generally well tolerated, and achieved an onset of pain relief as early as 20 minutes for 100 mg and as early as 30 minutes for 50 mg.", "This study sought to compare the efficacy of several doses of naratriptan tablets with that of sumatriptan tablets and placebo in the acute treatment of a single migraine attack.\n This was a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study. Patients received either naratriptan tablets (1, 2.5, 5, 7.5, or 10 mg), sumatriptan tablets (100 mg), or placebo.\n A total of 643 patients took part in the study. Two hours after dosing, headache relief was reported by significantly more patients treated with any dose of naratriptan (52%-69%) or sumatriptan (60%) than with placebo (31%) (P < 0.05). Four hours after dosing, headache relief was reported by significantly more patients treated with any dose of naratriptan (63%-80%) or sumatriptan (80%) than with placebo (39%) and by significantly more patients treated with sumatriptan 100 mg (80%) than with naratriptan 1 mg (64%), 2.5 mg (63%), or 5 mg (65%) (P < 0.05). Twenty-four-hour overall efficacy (headache relief maintained through 24 hours postdose with no worsening, no use of rescue medication, and no recurrence) was reported by more patients treated with any dose of naratriptan (39%-58%) or sumatriptan (44%) than with placebo (22%). Headache recurrence was reported in 17% to 32% of naratriptan-treated patients, 44% of sumatriptan-treated patients, and 36% of placebo recipients. The overall incidence of adverse events was similar in patients treated with naratriptan 1 mg (20%), naratriptan 2.5 mg (21%), and placebo (23%). For naratriptan 5, 7.5, and 10 mg, the incidence of adverse events was 32%, 37%, and 35%, respectively, and for sumatriptan 100 mg it was 26%.\n Our results suggest that the 2.5-mg dose of naratriptan tablets offers the optimal efficacy-to-tolerability ratio at the dose range between 1 and 10 mg. Although naratriptan 2.5 mg was less effective than sumatriptan 100 mg at 4 hours after dosing, the 2 medications showed similar efficacy at 24 hours.", "To evaluate the analgesic efficacy and safety of a single 20- or 40-mg dose of valdecoxib compared with placebo in treatment of a single, acute, moderate or severe migraine headache, with or without aura.\n Valdecoxib, an oral COX-2 specific inhibitor, is indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis and treatment of primary dysmenorrhea. This study assessed the optimal dose of valdecoxib for treatment of a single, acute, moderate to severe migraine headache.\n This was a double-blind, randomized, placebo- and active-controlled, multicenter, single-dose (primary end point) and multiple-dose (secondary end point), 56-day study of valdecoxib in the treatment of a single, acute, moderate or severe migraine headache, with or without aura. Migraine headaches were diagnosed according to International Headache Society (IHS) criteria. The primary efficacy end point was headache response (defined as reduction of headache pain intensity from moderate or severe to mild or none) at 2 hours postdose. Patients assessed their headache pain intensity and presence or absence of migraine-associated nausea, vomiting, phonophobia, and photophobia at intervals from 0 to 24 hours postdose. Sumatriptan 50 mg (encapsulated, in standard method, to maintain blinding) was included as a positive control for assay sensitivity. No statistical comparisons were performed between active treatment arms (valdecoxib 20 mg, valdecoxib 40 mg, and sumatriptan 50 mg). Adverse events and safety parameters were monitored throughout the study.\n In the intent-to-treat population of 570 patients (135 valdecoxib 20 mg, 151 valdecoxib 40 mg, 143 sumatriptan, and 141 placebo), no significant differences in baseline demographics among treatment groups were observed. The headache response rate with valdecoxib 40 mg and sumatriptan 50 mg was significantly greater than that with placebo at all time points from 2 to 24 hours postdose. With valdecoxib 20 mg, headache response rate was significantly greater than placebo from 2 to 4 hours. Significantly fewer patients treated with valdecoxib 40 mg, compared with placebo, experienced nausea, vomiting, and phonophobia at 2 hours postdose.\n A single 40-mg dose of valdecoxib is effective and well tolerated in treatment of migraine headache pain and associated symptoms.", "This cross-over, double blind, randomized, multicentre study evaluated the consistency of efficacy and safety of oral sumatriptan in 233 migraneurs. The patients received 50 mg oral sumatriptan or placebo for the treatment of 12 migraine attacks. Within each group of 4 attacks, three were treated with sumatriptan and one with placebo, according to a randomization list. Over all the attacks, the efficacy rate was statistically significant for sumatriptan against placebo at 2 or 4 hours (2 hours: sumatriptan 60%, PLO 38%, p < 0.001; 4 hours sumatriptan 79%, PLO 47%, p < 0.001). Oral sumatriptan was similarly effective at relieving the associated symptoms and at reducing clinical disability in most attacks. The incidence of adverse events did not differ between treatment groups. All the events recorded were mild to moderate as intensity and resolved spontaneously.", "A visual analog scale (VAS) method of assessing headache pain was compared with a standard categorical four-grade scale (4GS) in a randomized, placebo-controlled, double-blind, clinical trial involving 792 treated migraine outpatients who received oral rizatriptan 5 mg, sumatriptan 50 mg, or placebo for a moderate or severe headache. The VAS and 4GS were equally useful in demonstrating that the active drugs were superior to placebo at reducing headache pain, and in showing that the active drugs were similarly effective. For both rizatriptan and sumatriptan, slightly larger effect sizes were observed with the 4GS compared with the VAS. In analyses using data combined across all treatment groups, VAS and 4GS scores were highly correlated. Use of the VAS imposed additional administrative burdens. These findings suggest that the 4GS may be the preferred scale for assessing headache pain in clinical trials involving adult migraineurs.", "The efficacy of the selective 5HT1-like agonist sumatriptan in acute treatment of classical migraine (i.e. migraine with aura) was assessed in a double-blind, placebo-controlled, parallel group randomized trial. An oral dose of 200 mg was chosen on the basis of the efficacy rates achieved (70-85%) with 70-280 mg in open studies (1, 2). The dose of 200 mg was also chosen for the study because preliminary data from an oral pilot study indicated that efficacy increased with increasing dose up to 200 mg. Each patient was treated for a maximum of three separate attacks of migraine with aura within a three months' period. Three attacks were treated so that we could examine consistency of response across more than one attack. For attack 1, 200 mg sumatriptan was significantly more effective, safe and well tolerated than placebo at relieving headache 2 h after treatment was given (p = 0.023). In subsequent attacks, i.e. in attacks 2 and 3, there was no such significant effect of sumatriptan compared with placebo in relieving headache. This reduced efficacy of sumatriptan in the second and third attacks may be due to a high incidence of vomiting induced by the high dose of dispersible formulation and also by the bitter taste of the tablets. In addition, there was an increase in placebo response in attacks 2 and 3 compared to the first attack.", "Almotriptan malate is a novel, selective serotonin(1B/D) agonist, or triptan, developed for the abortive treatment of migraine. In double-blind, placebo-controlled studies, it has been shown to be effective, well tolerated, and safe.\n To compare the efficacy, tolerability, and safety of almotriptan with that of the \"standard triptan,\" sumatriptan succinate. The power calculation of the study was based on 24-hour headache recurrence, an efficacy measure in the abortive treatment of migraine, and on the occurrence of adverse events.\n Subjects, aged between18 and 65 years, with migraine with or without aura but otherwise healthy, were randomized to take orally either almotriptan malate, 12.5 mg, or sumatriptan succinate, 50 mg. The medications were provided in identical-looking capsules to ensure blinding and were taken for the treatment of moderate or severe headache. Efficacy was determined in terms of (1) headache relief-a decrease in pain intensity to mild or no pain; (2) headache freedom-a decrease to no pain; (3) use of rescue medications, allowed after 2 hours; and (4) headache recurrence-moderate or severe pain returning within 24 hours after headache relief at 2 hours. Adverse events were collected for 96 hours after treatment and for safety evaluation, vital signs, blood tests, and electrocardiograms were performed at the screening and exit visits.\n Seventy-five investigators enrolled 1255 subjects of whom 1173 were treated (591 with almotriptan and 582 with sumatriptan). At 2 hours, almotriptan treatment provided headache relief in 58.0% of the subjects and sumatriptan treatment in 57.3%; headache freedom was provided by the medications in 17.9% and 24.6%, respectively (P =.005). Rescue medications were taken by 36.7% of the subjects in the almotriptan-treated group and by 33.2% in the sumatriptan-treated group; headaches returned to moderate or severe intensity in 27.4% and 24.0%, respectively. Treatment-emergent adverse events occurred in 15.2% of the subjects in the almotriptan-treated group and in 19.4% in the sumatriptan-treated group (P =.06); treatment-related adverse events occurred in 9.1% and 15.5% of the subjects, respectively (P =.001), including chest pain, which occurred in 0.3% and 2.2%, respectively (P =.004).\n Almotriptan and sumatriptan are similarly effective in the abortive treatment of moderate or severe migraine headache; they are also similarly well tolerated and safe.", "To confirm the efficacy advantage of eletriptan 40 mg over sumatriptan 100 mg. Background.-Eletriptan 80 mg has demonstrated significantly greater efficacy when compared to both sumatriptan 50 mg and 100 mg in two studies. Eletriptan 40 mg demonstrated significantly greater efficacy than sumatriptan 100 mg in one previous trial.\n Two thousand one hundred thirteen patients with a diagnosis of migraine according to International Headache Society criteria were randomized using a double-blind, double-dummy, parallel-group design, and treated for a single migraine attack with either eletriptan 40 mg, sumatriptan 100 mg, or placebo. The primary endpoint was 2-hour headache response. Secondary endpoints included headache response rates at 1 hour, pain-free rates, absence of associated symptoms, functional response at 1 and 2 hours, and sustained headache response.\n Headache response rates at 2 hours postdose were significantly higher for eletriptan 40 mg (67%) than for sumatriptan 100 mg (59%; P <.001) and placebo (26%; P <.0001). Eletriptan 40 mg consistently showed significant (P <.01) efficacy over sumatriptan 100 mg across secondary clinical outcomes, including 1-hour headache response; 2-hour pain-free response; absence of nausea, photophobia, and phonophobia; functional improvement; use of rescue medication; treatment acceptability; and sustained headache response (P <.05). Overall, treatment-related adverse events were low, nausea being the only adverse event with an incidence of 2% or higher (4.9% with eletriptan, 4.2% sumatriptan, 2.8% placebo).\n This trial confirmed that eletriptan 40 mg offers superior efficacy in treating migraine pain and associated symptoms and in restoring patient functioning when compared with sumatriptan 100 mg.", "To evaluate the efficacy and tolerability of sumatriptan, 50-mg and 100-mg tablets, compared with placebo for treatment of migraine at the first sign of pain.\n Two identical multicenter randomized, double-blind, placebo-controlled, single-attack studies were conducted from May through November 2000 in adults (aged 18-65 years). Patients treated migraine at the first sign of pain, while pain was mild, but not more than 2 hours after onset with oral sumatriptan, 50 mg or 100 mg, or matching placebo. The primary end point was pain-free relief at 2 hours after treatment with 50 mg of sumatriptan compared with placebo.\n There were 354 patients in study 1 and 337 patients in study 2. Significantly more patients treated with sumatriptan, 50 mg and 100 mg, were completely free from pain 2 and 4 hours after treatment vs patients treated with placebo (at 2 hours, 50% and 57% vs 29%; at 4 hours, 61% and 68% vs 30%; for both, P < .001). Also, significantly more patients treated with sumatriptan, 50 mg and 100 mg, were migraine-free (no pain or associated symptoms) vs those treated with placebo at 2 and 4 hours after treatment (at 2 hours, 43% and 49% vs 24%; at 4 hours, 54% and 63% vs 28%; for both, P < .001). The incidence of overall adverse events was low with the 50- and 100-mg dose of sumatriptan (placebo, 7%; sumatriptan at 50 mg, 14%; sumatriptan at 100 mg, 16%).\n Treatment of migraine at the first sign of pain with sumatriptan, 50-mg and 100-mg tablets, provides superior pain-free relief at 2 and 4 hours after treatment compared with placebo. Results of these studies suggest that sumatriptan at 100 mg may be more efficacious than at 50 mg when used in the early treatment paradigm. Because these studies were not powered to detect statistical differences between active doses, studies to investigate this finding are warranted.", "This randomized, double-blind, parallel group multicenter study compared response rates and tolerability of zolmitriptan with sumatriptan in the acute treatment of migraine.\n A sample consisting of 1445 outpatients with an established diagnosis of migraine was randomized to zolmitriptan, 2.5 mg or 5 mg, or sumatriptan, 25 mg or 50 mg. Patients took 1 tablet for moderate/severe migraine and a second identical tablet, if necessary, for recurrent headache of moderate/severe intensity 4 to 24 hours after the initial dose. Up to six attacks were treated during a 6-month period. The primary outcome measure was headache response 2 hours after the initial dose. Secondary end points included 1-hour and 4-hour headache response and pain relief over 24 hours.\n A headache response at 2 hours was noted in 67.1% of patients taking zolmitriptan, 2.5 mg, and 64.8% of those taking zolmitriptan, 5 mg, versus 59.6% of patients taking sumatriptan, 25 mg, and 63.8% of those taking sumatriptan, 50 mg. At 2 and 4 hours, the differences between zolmitriptan, 2.5 mg, and sumatriptan, 25 mg, were statistically significant (odds ratio=1.49 and 1.67, respectively; both P<.001). Statistically significant differences between zolmitriptan, 2.5 mg, and sumatriptan, 50 mg, were seen at 2 and 4 hours post dose (odds ratio=1.21 and 1.23, respectively; both P<.05). At 1 hour post dose, the headache response rate for zolmitriptan, 2. 5 mg, was numerically higher than response rates for sumatriptan, 25 mg and 50mg (odds ratio=1.16, odds ratio=1.06, though they failed to reach statistical significance; P=.061, P=.461 respectively). Differences between zolmitriptan, 5 mg, and sumatriptan, 25 mg, were statistically significant at 1, 2, and 4 hours (odds ratio=1.43, 1. 46, and 1.78, respectively; all P<.001) and at 1 and 4 hours versus sumatriptan, 50 mg (odds ratio=1.28, P=.002; odds ratio=1.29, P=.012, respectively). Although not statistically significant at 2 hours, more patients responded to zolmitriptan, 5 mg, than to sumatriptan, 50 mg (odds ratio=1.16, P=.064). Patients receiving zolmitriptan, 2. 5 mg or 5 mg, achieved more pain relief over 24 hours than patients receiving sumatriptan, 25 mg (odds ratio=1.47, and 1.54 respectively, both P<.001) or sumatriptan, 50 mg (odds ratio=1.17, P=.021; odds ratio=1.22, P=.005, respectively). All treatments were well tolerated.\n Zolmitriptan, 2.5 mg and 5 mg, was at least as effective as sumatriptan, 25 mg or 50 mg, for all parameters studied. Zolmitriptan, 2.5 mg, was significantly more effective than sumatriptan, 50 mg, in terms of headache response at 2 and 4 hours. Patients taking zolmitriptan were significantly more likely to have pain relief over 24 hours than those taking sumatriptan.", "To address the need for a rigorous, direct comparison of prescription and over-the-counter (OTC) migraine drugs and to expand the database on early treatment of migraine.\n Most people who experience migraine use OTC medications to treat their symptoms, but no head-to-head clinical trials comparing these agents with prescription migraine therapies have been published. In addition, even though most migraineurs treat early in the attack, few studies have been conducted to reflect this treatment pattern.\n We compared a combination of nonprescription migraine medication (acetaminophen 500 mg, aspirin 500 mg, and caffeine 130 mg) with a prescription migraine product (50 mg sumatriptan) in a randomized, controlled clinical trial in which subjects treated at the first sign of a migraine attack. Subjects who reported vomiting during more than 20% of migraine episodes or who required bedrest during more than 50% of migraine episodes were excluded from the study. Of the 188 subjects randomized, 171 took study medication and were included in the analysis.\n The combination of acetaminophen, aspirin, and caffeine was significantly more effective (P > .05) than sumatriptan in the early treatment of migraine, as shown by superiority in summed pain intensity difference, pain relief, pain intensity difference, response, sustained response, relief of associated symptoms, use of rescue medication, disability relief, and global assessments of effectiveness. An additional, larger clinical trial is needed to confirm these results.", "In this international, multicentre, double-blind, placebo-controlled, single attack study, 'triptan naive' migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated analysis included 1058 patients who took study medication. The primary endpoint, complete headache response, was reported by 39%, 38% and 32% of patients treated with zolmitriptan, sumatriptan and placebo, respectively, with no significant difference between treatment groups. In patients with moderate headache at baseline, complete response was significantly greater following zolmitriptan than after placebo (48% vs. 27%; P=0.01); there was no significant difference between sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline headache (where a greater reduction in headache intensity is required for a headache response), there was no significant difference between any groups in complete headache response rates. For secondary endpoints, active treatment groups were significantly superior to placebo for: 1-, 2- and 4-h headache response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%; placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h; alleviation of nausea and vomiting; use of escape medication and restoration of normal activity. The incidence of adverse events was similar between zolmitriptan and sumatriptan groups but was slightly lower in the placebo group. The lack of difference between active treatments and placebo for complete response probably reflects the high placebo response obtained, which is probably a result of deficiencies in trial design. For example, the randomization ratio may result in high expectation of active treatment. Thus, while ethically patient exposure to placebo should be minimized, this must be balanced against the scientific rationale underpinning study design.", "We evaluated the effectiveness of combination treatment using sumatriptan plus metoclopramide versus sumatriptan alone for the treatment of acute migraine. The patients who were treated had failed to respond to triptans in the past despite adequate doses on at least 2 separate trials of the same triptan or 2 trials involving different triptans.\n There is limited evidence that dopaminergic antagonists may benefit the migraineur by relieving migraine pain and associated symptoms. The exact mechanism of action in migraine is unknown. The postulated action is the inhibition of dopaminergic overactivity. A dopaminergic antagonist, metoclopramide, may improve the efficacy of a 5-HT1B/1D agonist, sumatriptan.\n In this double-blind, randomized, crossover study, 16 adult migraineurs fulfilling International Headache Society (IHS) criteria for migraine with or without aura who had failed to receive adequate relief from triptans treated one migraine with each treatment: sumatriptan 50 mg plus metoclopramide 10 mg or sumatriptan 50 mg plus placebo to match metoclopramide. Patients treated their migraines when they were moderate or severe in intensity and recorded pain severity and symptoms prior to treatment and 30, 60, 90, and 120 minutes and 24 hours after treatment.\n Thirteen women and 3 men (mean age, 40 years) completed the study; ie, treated 2 migraines (a total of 32 migraines), one attack with each treatment. Meaningful relief was attained in 10 (63%) of 16 migraines treated with the combination of sumatriptan 50 mg plus metoclopramide 10 mg compared with 5 (31%) of 16 migraines treated with sumatriptan 50 mg plus placebo. Headache response (moderate or severe to mild or no pain at 2 hours) was achieved in 7 (44%) of 16 migraines with the combination of sumatriptan 50 mg plus metoclopramide 10 mg compared with 5 (31%) of 16 migraines treated with sumatriptan 50 mg plus placebo. There did not appear to be a difference between treatment groups with respect to associated symptoms. The combination of sumatriptan 50 mg plus metoclopramide 10 mg was well tolerated.\n Combining sumatriptan with metoclopramide provided relief in some migraineurs who failed to achieve adequate relief with a triptan alone. It remains unknown whether initiating therapy when pain was mild or using a higher dose of sumatriptan (ie, 100 mg) would have provided additional benefit. Further studies are indicated.", "Rizatriptan (MK-462) is a new 5-hydroxytryptamine1D (serotonin1D; 5-HT1D) receptor agonist for the acute treatment of migraine that has improved pharmacokinetic properties compared with sumatriptan succinate.\n To assess the efficacy and tolerability of 10-, 20-, and 40-mg doses of oral rizatriptan vs a 100-mg dose of oral sumatriptan succinate and placebo for the acute treatment of migraine.\n Randomized, double-blind, parallel-group, placebo-controlled, outpatient trial.\n Ten US and 4 Dutch investigator centers.\n Patients who had migraine with or without aura (N = 449).\n The proportion of patients whose conditions improved from severe or moderate headache immediately before dosing to mild or no headache at 2 hours after drug administration (ie, headache relief).\n The proportion of patients with headache relief was 18% for placebo; 46% for sumatriptan; and 52% for 10-mg, 56% for 20-mg, and 67% for 40-mg rizatriptan. All differences with placebo were statistically significant (P < .001), and 40-mg rizatriptan was superior to sumatriptan (P = .01). The proportion of patients who became free of pain at 2 hours was 3% for the placebo-treated group; 22% for the sumatriptan-treated group; and 26%, 35%, and 47% for the group of patients who took the 10-, 20-, and 40-mg doses of rizatriptan, respectively (all differences with placebo, P < .005; 40-mg rizatripan vs sumatriptan, P = .001). The recurrence of headache within 24 hours was found to be equal across all treatment groups-approximately 40%. Adverse events (most commonly short-lasting mild or moderate dizziness and drowsiness) occurred more frequently after a 40-mg dose of rizatriptan was given than after the other treatments.\n The antimigraine effect of 10- and 20-mg rizatriptan was superior to placebo, and comparable with that of 100-mg sumatriptan succinate; the efficacy of 40-mg rizatriptan was superior to that of both placebo and 100-mg sumatriptan succinate, although it was associated with a high frequency of adverse events.", "To evaluate the efficacy and tolerability of treatment with a combination of sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg administered concurrently in the acute treatment of migraine.\n The pathogenesis of migraine involves multiple peripheral and central neural mechanisms that individually have been successful targets for acute (abortive) and preventive treatment. This suggests that multi-mechanism therapy, which acts on multiple target sites, may confer improved efficacy and symptom relief for patients with migraine.\n This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, four-arm study. Participants (n = 972) treated a single moderate or severe migraine attack with placebo, naproxen sodium 500 mg, sumatriptan 50 mg, or a combination of sumatriptan 50 mg and naproxen sodium 500 mg. In the latter two treatment arms, the sumatriptan tablets were encapsulated in order to achieve blinding of the study.\n In the sumatriptan plus naproxen sodium group, 46% of subjects achieved 24-hour pain relief response (primary endpoint), which was significantly more effective than sumatriptan alone (29%), naproxen sodium alone (25%), or placebo (17%) (P < .001). Two-hour headache response also significantly favored the sumatriptan 50 mg plus naproxen sodium 500 mg therapy (65%) versus sumatriptan (49%), naproxen sodium (46%), or placebo (27%) (P < .001). A similar pattern of between-group differences was observed for 2-hour pain-free response and sustained pain-free response (P < .001). The incidence of headache recurrence up to 24 hours after treatment was lowest in the sumatriptan plus naproxen sodium group (29%) versus sumatriptan alone (41%; P = .048), versus naproxen sodium alone (47%; P= .0035), and versus placebo (38%; P= .08). The incidences of the associated symptoms of migraine were significantly lower at 2 hours following sumatriptan 50 mg plus naproxen sodium 500 mg treatment versus placebo (P < .001). The frequencies and types of adverse events reported did not differ between treatment groups, with dizziness and somnolence being the most common.\n This is among the first prospective studies to demonstrate that multi-mechanism acute therapy for migraine, combining a triptan and an analgesic, is well tolerated and offers improved clinical benefits over monotherapy with these selected standard antimigraine treatments. Specifically, sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg resulted in significantly superior pain relief as compared to monotherapy with either sumatriptan 50 mg (encapsulated) or naproxen sodium 500 mg for the acute treatment of migraine. Because encapsulation of the sumatriptan for blinding purposes may have altered its pharmacokinetic profile and thereby decreased the efficacy responses, additional studies are warranted that do not involve encapsulation of the active treatments and assess the true onset of action of multi-mechanism therapy in migraine. This study did show that the combination of sumatriptan and naproxen sodium was well tolerated and that there was no significant increase in the incidence of adverse events compared to monotherapy.", "This randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy and tolerability of oral sumatriptan (Imitrex tablets) in 259 migraineurs. In the clinic, patients received oral sumatriptan 25 mg, 50 mg, or 100 mg, or placebo for the treatment of a migraine attack. The results indicate that by 2 hours post-dose, 50 to 56% of patients treated with any of the three doses, compared with 26% of patients treated with placebo, achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). By 4 hours postdose, 68 to 71% of sumatriptan-treated patients, compared with 38% of placebo-treated patients, achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). Oral sumatriptan was similarly effective at relieving nausea and photophobia and at reducing clinical disability. The pattern and incidence of adverse events did not differ between treatment groups. All doses--25 mg, 50 mg, and 100 mg--of sumatriptan were effective and generally well tolerated. Dosing should be individualized according to the needs of the patient.", "In a double-blind, placebo-controlled study, the efficacy, safety and tolerability of 100 mg oral sumatriptan, given as a dispersible tablet, was compared with that of 900 mg oral aspirin plus 10 mg oral metoclopramide in the acute treatment of migraine. A total of 358 patients treated up to three migraine attacks within 3 months, recording clinical information on a diary card. In attack 1, headache relief after 2 h, defined as a reduction in severity from severe or moderate pain to mild or no pain, was recorded in 56% (74/133) of patients who took sumatriptan and 45% (62/138) of patients who took aspirin plus metoclopramide (p = 0.078). This analysis of the primary efficacy end point was not statistically significant. However, for attacks 2 and 3 (secondary end points), headache relief was achieved in 58 versus 36% of patients (p = 0.001) and 65 versus 34% of patients (p less than 0.001), respectively. Relief from nausea, vomiting, photophobia and phonophobia was similar in both treatment groups. Rescue medication was required by fewer patients treated with sumatriptan than by those who received aspirin plus metoclopramide (attack 1, 34 versus 56%, p less than 0.001; attack 2, 32 versus 51%, p = 0.001, and attack 3, 35 versus 54%, p = 0.001). Sumatriptan also produced a faster improvement and resolution of migraine attacks. Comparing the sumatriptan and aspirin plus metoclopramide treatment groups, complete resolution of the attack occurred within 6 h in 32 versus 19% (attack 1), 35 versus 23% (attack 2) and 32 versus 20% of patients (attack 3).(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare the efficacy of oral eletriptan, 40 mg and 80 mg, and oral sumatriptan, 50 mg and 100 mg, in the acute treatment of migraine.\n Patients with a history of migraine (n = 1,008) were randomly assigned to receive placebo, 40 mg of eletriptan, 80 mg of eletriptan, 50 mg of sumatriptan, or 100 mg of sumatriptan to treat up to three attacks. Early headache response (at 1 hour) was the primary endpoint, in addition to the standard endpoint, 2-hour headache response.\n Headache response rates were 12% at 1 hour and 31% at 2 hours for placebo; 24% at 1 hour and 50% at 2 hours for sumatriptan 50 mg; 27% at 1 hour and 53% at 2 hours for sumatriptan 100 mg; 30% at 1 hour and 64% at 2 hours for eletriptan 40 mg; and 37% at 1 hour and 67% at 2 hours for eletriptan 80 mg. More patients receiving eletriptan 80 mg achieved a 1-hour headache response than did patients receiving sumatriptan 50 mg (p < 0.05). All doses of eletriptan were superior to sumatriptan at 2 hours for headache response and complete pain relief (p < 0.05). Significantly more patients on eletriptan 80 mg achieved headache response in all attacks than did patients receiving either sumatriptan dose. Eletriptan 40 mg was superior to both sumatriptan doses in functional improvement (p < 0.005). The superior efficacy of both eletriptan doses was associated with higher rates of patient acceptability than sumatriptan 50 mg (p < 0.05). Eletriptan and sumatriptan were well tolerated.\n Oral eletriptan (40 mg and 80 mg) is effective, safe, and tolerable in the acute treatment of migraine and yields a consistent response.", "This randomized, double-blind, two-attack, placebo-controlled, crossover study explored the efficacy and tolerability of rizatriptan 10 mg compared with sumatriptan 50 mg as well as rizatriptan 5 mg compared with sumatriptan 25 mg in the acute treatment of migraine. Following randomization to one of six possible treatment sequences, patients (n = 1447) treated two sequential attacks, of moderate or severe intensity, separated by at least 5 days. Patients assessed pain severity, migraine-associated symptoms, and functional disability at 0.5, 1, 1.5, and 2 h post treatment. Compared with placebo, all treatments were effective. On the primary endpoint of time to pain relief, rizatriptan 10 mg was not statistically different from sumatriptan 50 mg [odds ratio (OR) 1.10, P = 0.161], and rizatriptan 5 mg was statistically superior to sumatriptan 25 mg (OR 1.22, P = 0.007). In general, rizatriptan 10 mg and 5 mg treatment resulted in improvement compared with the corresponding doses of sumatriptan on measures of pain severity, migraine symptoms, and functional disability and the 5-mg dose reached statistical significance on almost all measures. All treatments were generally well tolerated.", "Many patients and physicians interpret episodic headache in the presence or absence of nasal symptoms as \"sinus' headache, while ignoring the possible diagnosis of migraine.\n The purpose of this study was to assess the efficacy and tolerability of sumatriptan succinate 50-mg tablets in patients with migraine presenting with \"sinus\" headache.\n A randomized, double-blind, placebo-controlled, multicenter study was conducted in adult (aged 18-65 years) migraine patients presenting with self-described or physician-diagnosed \"sinus\" headache. From November 2001 to March 2002, patients meeting International Headache Society criteria for migraine (with > or =2 of the following: unilateral location, pulsating quality, moderate or severe intensity, aggravation by moderate physical activity; and > or =1 of: phonophobia and phonophobia, nausea and/or vomiting) and with no evidence of bacterial rhinosinusitis were enrolled and randomized in a 1:1 ratio via computer-generated randomization schedule to receive either 1 sumatriptan 50-mg tablet or matching placebo tablet. The primary efficacy end point was headache response (moderate or severe headache pain reduced to mild or no headache pain) at 2 hours after administration. The presence or absence of migraine-associated symptoms and sinus and nasal symptoms was also measured. Tolerability was assessed through patient-reported adverse events (AEs).\n Two hundred sixteen patients with self-described or physician-diagnosed \"sinus\" headache received a migraine diagnosis and treated 1 migraine attack with sumatriptan 50 mg. The efficacy (intent-to-treat) analysis included 215 patients treated with sumatriptan 50 mg (n = 108; mean [SD] age, 39.6 [12.3] years; mean [SD] weight, 77.7 [17.7] kg; sex, 71% female; race, 69% white) or placebo (n = 107; mean [SD] age, 41.0 [11.3] years; mean [SD] weight 80.7 [20.9] kg; sex, 69% female; race, 64% white). Significantly more patients treated with sumatriptan 50 mg achieved a positive headache response at 2 and 4 hours after administration compared with those treated with placebo (69% vs 43% at 2 hours and 76% vs 49% at 4 hours, respectively; both, P < 0.001). Significantly more sumatriptan-treated patients were free from sinus pain compared with placebo recipients at 2 hours (63% vs 49% placebo, P = 0.049) and 4 hours (77% vs 55%, P = 0.001). All treatments were generally well tolerated. The most common drug-related AEs reported in the sumatriptan and placebo groups, respectively, were dizziness (5% vs < 1%), nausea (3% vs 2%), other pressure/tightness (defined as sense of heaviness; heaviness of upper body, upper extremities; jaw tension; neck tension) (4% vs 0%), and temperature sensations (defined as warm feeling of back of neck, or flushing) (2% vs 0%). No patients experienced any serious AEs.\n Sumatriptan 50-mg tablets were effective and generally well tolerated in the treatment of these patients presenting with migraine headaches that were self-described or physician-diagnosed as sinus headaches.", "Recently a new effervescent acetylsalicylic acid (ASA) tablet with high buffering capacity has been developed. In this double-blind, 3-arm, multicenter, parallel-group study, 433 patients were treated either with 1,000 mg effervescent ASA or 50 mg encapsulated sumatriptan or placebo. The primary endpoint was the percentage of patients with complete remission of the 3 accompanying symptoms nausea, photophobia and phonophobia within 2 h after intake of the study drug. 43.8% of patients treated with ASA, 43.7% of patients treated with sumatriptan and 30.9% of patients treated with placebo showed complete remission of all 3 accompanying symptoms (p < 0.05 for ASA and sumatriptan vs. placebo). Both active treatments were superior to placebo regarding the individual symptoms photophobia and phonophobia, but not for nausea. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (secondary objective) was 49.3% for ASA, 48.8% for sumatriptan and 32.9% for placebo. All active treatments were superior to placebo (p < 0.05). 25.3, 24.4 and 14.5% of patients treated with ASA, sumatriptan or placebo were pain free at 2 h. Drug-related adverse events were reported in 3.9, 4.7 and 6.7% of patients treated with placebo, ASA or sumatriptan. The study showed that administration of effervescent ASA leads to remission of the migraine symptoms nausea, photophobia and phonophobia, reduces migraine headache and is comparable to sumatriptan.\n Copyright 2004 S. Karger AG, Basel", "Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.", "In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets.\n Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57-1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82-1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated.\n The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf.", "Sumatriptan tablets have been developed in a fast-disintegrating, rapid-release formulation designed to facilitate tablet disintegration and drug dispersion and to potentially mitigate the effects of gastric stasis that can accompany migraine.\n This study was conducted to evaluate the efficacy and tolerability of sumatriptan 50- and 100-mg tablets in a fast-disintegrating, rapid-release formulation compared with those of placebo in patients with migraine.\n This clinical trial had a randomized, double-blind, placebo-controlled, parallel-group design. Exclusion criteria included >6 migraines monthly during either of the 2 months before screening; uncontrolled hypertension; suspected or confirmed cardiovascular or cerebrovascular disease; and ophthalmic, basilar, or hemiplegic migraine. Sumatriptan 50 and 100 mg and placebo were taken on an outpatient basis during the mild-pain phase of a single migraine attack. Patients recorded details of the treated migraine on a diary card and rated pain severity immediately before dosing and 30 minutes, 45 minutes, 1 hour, and 2 hours after dosing using a 4-point scale (from 0 = none to 3 = severe). The primary efficacy end point was the proportion of patients who were pain free 2 hours after dosing. Additional efficacy end points were the proportion of patients who were pain free at 30 minutes, 45 minutes, and 1 hour after dosing; the proportion who were migraine free through 2 hours after dosing; and the proportion with a sustained pain-free response.\n Patients' mean age ranged from 39.7 to 41.5 years across the 3 groups, and the majority were women (79.7%-85.9%) and white (98.7%-100%). One hundred thirty-seven patients received sumatriptan 50 mg, 142 sumatriptan 100 mg, and 153 placebo. In the intent-to-treat population (n = 432), 51.1% of patients who received sumatriptan 50 mg and 66.2% of patients who received sumatriptan 100 mg were pain free 2 hours after dosing, compared with 19.6% of the placebo group (P < 0.001, each sumatriptan dose vs placebo). In an exploratory analysis, the 2-hour pain-free rate with sumatriptan 100 mg was significantly better than that with sumatriptan 50 mg (P = 0.007). Significantly more patients who received sumatriptan 100 mg were pain free compared with placebo at 30 minutes (P < 0.01), 45 minutes (P < 0.001), and 1 hour after dosing (P < 0.001); similar pain-free results were observed in patients who received sumatriptan 50 mg at 45 minutes (P < 0.05) and 1 hour (P = 0.01). In the per-protocol population (n = 313), pain-free efficacy 2 hours after dosing was 52.7% with sumatriptan 50 mg and 74.8% with sumatriptan 100 mg, compared with 21.0% with placebo (P < 0.001, each sumatriptan dose vs placebo). These rates were greater than those in the overall study population, approximately 12.0% of whom treated moderate or severe pain. The only drug-related adverse events reported in >/=3% of patients in any treatment group were nausea and vomiting (<1%, 5%, and 2% in the sumatriptan 50 and 100 mg and placebo groups, respectively), chest symptoms (2%, 3%, and 0%), and malaise and fatigue (1%, 3%, and <1%). No serious adverse events were reported.\n In this study, sumatriptan tablets in a fast-disintegrating, rapid-release oral formulation provided pain-free efficacy in the acute treatment of migraine. Efficacy was maximized with the 100-mg dose compared with the 50-mg dose, and by treating early when pain was mild. In the intent-to-treat population, 51.1% of patients who received sumatriptan 50 mg and 66.2% of those who received sumatriptan 100 mg were pain free 2 hours after dosing. In the per-protocol population, 3 of 4 patients taking the 100-mg tablets for mild pain within 1 hour of its onset were pain free at 2 hours. Sumatriptan tablets were generally well tolerated.", "Most migraine patients with infrequent attacks are currently not treated with migrainespecific medication such as triptans. The response of these patients to triptans is unknown. The objective of this study was to investigate the efficacy and tolerability of sumatriptan 50 mg vs. placebo in migraine patents with infrequent migraine attacks when medication is taken during the mild phase of an attack. The study design was double-blind, placebocontrolled, parallel-group and randomised. Migraine patients were recruited by general practitioners and referred to one of 4 study centres. Additional patients were recruited by advertising. The patients were eligible for the study if they had between 6 and 12 migraine attacks with or without aura per year. The patients were instructed to take the medication during the mild phase of a single attack. The primary efficacy measure was the percentage of patients pain-free after 2 h. Fortysix percent of treated attacks were moderate or severe. In the intention-to-treat analysis, sumatriptan was superior (20/51 patients were pain-free) to placebo (8/47 patients pain-free) (p=0.03). Adverse events (AEs) occurred more frequently after sumatriptan (40%) than after placebo (13%) (p=0.003) and most AEs were mild or moderate. In this migraine population with infrequent attacks, sumatriptan was superior to placebo and was generally well tolerated.", "Almotriptan is a novel and specific serotonin 5-HT1B/1D agonist for the acute treatment of migraine. This randomized, single-dose, double-blind, multicentre, study assessed the efficacy and safety of oral almotriptan (12.5 mg and 25 mg) in patients with migraine, and compared it with the standard treatment (sumatriptan 100 mg) and placebo. A total of 668 patients treated one migraine attack of moderate or severe intensity with study medication. The primary efficacy assessment was migraine pain relief, improvement from severe or moderate pain to mild or no pain, at 2 h after treatment. Response rates, stratified for variation in baseline pain levels, for both almotriptan doses were equivalent to sumatriptan and significantly better than placebo. Other efficacy assessments confirmed the equivalence of the almotriptan groups with the sumatriptan group. Almotriptan 12.5 mg was as well tolerated as placebo (P=0.493) and significantly better tolerated than sumatriptan (P<0.001), in terms of the overall incidence of adverse events. There was no statistically significant difference in the incidence of adverse events between almotriptan 25 mg and sumatriptan 100 mg (P=0.376). The results from this large clinical study indicate that the new, specific 5-HT1B/1D agonist, almotriptan, is an effective and well-tolerated treatment for migraine pain.", "Multiple pathogenic mechanisms may be involved in generating the migraine symptom complex, and multimechanism-targeted therapy may confer advantages over monotherapy.\n To evaluate the efficacy and safety of a fixed-dose tablet containing sumatriptan succinate and naproxen sodium relative to efficacy and safety of each monotherapy and placebo for the acute treatment of migraine.\n Two replicate, randomized, double-blind, single-attack, parallel-group studies conducted among 1461 (study 1) and 1495 (study 2) patients at 118 US clinical centers who were diagnosed as having migraine and received study treatment for a moderate or severe migraine attack.\n Patients were randomized in a 1:1:1:1 ratio to receive a single tablet containing sumatriptan, 85 mg, and naproxen sodium, 500 mg; sumatriptan, 85 mg (monotherapy); naproxen sodium, 500 mg (monotherapy); or placebo, to be used after onset of a migraine with moderate to severe pain.\n Primary outcome measures included the percentages of patients with headache relief 2 hours after dosing, absence of photophobia, absence of phonophobia, and absence of nausea for the comparison between sumatriptan-naproxen sodium and placebo, and the percentages of patients with sustained pain-free response for the comparison between sumatriptan-naproxen sodium and each monotherapy.\n Sumatriptan-naproxen sodium was more effective than placebo for headache relief at 2 hours after dosing (study 1, 65% vs 28%; P<.001 and study 2, 57% vs 29%; P<.001), absence of photophobia at 2 hours (58% vs 26%; P<.001 and 50% vs 32%; P<.001), and absence of phonophobia at 2 hours (61% vs 38%; P<.001 and 56% vs 34%; P<.001). The absence of nausea 2 hours after dosing was higher with sumatriptan-naproxen sodium than placebo in study 1 (71% vs 65%; P = .007), but in study 2 rates of absence of nausea did not differ between sumatriptan-naproxen sodium and placebo (65% vs 64%; P = .71). For 2- to 24-hour sustained pain-free response, sumatriptan-naproxen sodium was superior at P<.01 (25% and 23% in studies 1 and 2, respectively) to sumatriptan monotherapy (16% and 14% in studies 1 and 2), naproxen sodium monotherapy (10% and 10% in studies 1 and 2), and placebo (8% and 7% in studies 1 and 2). The incidence of adverse events was similar between sumatriptan-naproxen sodium and sumatriptan monotherapy.\n Sumatriptan, 85 mg, plus naproxen sodium, 500 mg, as a single tablet for acute treatment of migraine resulted in more favorable clinical benefits compared with either monotherapy, with an acceptable and well-tolerated adverse effect profile.\n clinicaltrials.gov Identifiers: NCT00434083 (study 1); NCT00433732 (study 2).", "To compare the efficacy, safety, and tolerability of oral eletriptan (20 mg, 40 mg, and 80 mg) with that of oral sumatriptan (100 mg) and placebo for the acute treatment of migraine.\n Eletriptan is a potent and selective agonist at human recombinant 5HT1B/1D receptors, with efficacy in animal models that predict antimigraine activity. In healthy volunteers, the pharmacokinetics of eletriptan are characterized by linear and rapid oral absorption.\n Randomized, double-blind, parallel-group study conducted in 857 outpatients with a diagnosis of migraine according to the International Headache Society (IHS) criteria. Of these, 692 took study medication for one acute migraine attack and provided on-drug efficacy data. Subjects received either placebo, 100 mg of sumatriptan or 20 mg, 40 mg, or 80 mg of eletriptan for the treatment of an acute migraine attack. The primary endpoint was the percentage of patients with a headache response (improvement in pain intensity from moderate or severe to mild or none) at 2 hours after treatment.\n At the primary endpoint (2 hours after dosing), headache response rates were 24% (30/126) for placebo; 55% (63/115) for sumatriptan, 100 mg; 54% (70/129) for eletriptan, 20 mg; 65% (76/117) for eletriptan, 40 mg; and 77% (91/118) for eletriptan, 80 mg. There was a difference compared with placebo (p<0.001) for all doses of eletriptan, and at 2 hours there was a difference between sumatriptan, 100 mg, and eletriptan, 80 mg (p<0.001). Headache-free rates at 2 hours were superior to placebo (6%; p<0.001) for both the 80-mg dose of eletriptan (37%) and the 40-mg dose (29%), with the 80-mg dose also being superior to 100 mg of sumatriptan (23%; p<0.05). Eletriptan and sumatriptan were well tolerated, and the majority of adverse events were mild or moderate in intensity and transient.\n In this placebo-controlled trial, eletriptan, at selected doses, demonstrated superior efficacy, onset of action and patient acceptability in the acute treatment of migraine when compared with oral sumatriptan and placebo.", "A double-blind, placebo-controlled multicentre study was carried out to evaluate the efficacy and tolerability of 100, 200 and 300 mg sumatriptan, a selective 5-hydroxytryptamine (5-HT)1-like receptor agonist, given in an oral dispersible form in the acute treatment of migraine attacks. A total of 1130 patients were recruited from 51 centres in eight countries and the efficacy results are presented from an interim analysis of 538 cases. Tolerability was evaluated in 227 patients. At 2 h, an improvement in headache severity from moderate or severe to mild or none was reported by 67% of patients who received 100 mg sumatriptan, 75% receiving 200 mg and 69% of patients receiving 300 mg sumatriptan, compared with 22% of patients who received placebo (P less than 0.001 all doses sumatriptan vs placebo). Adverse events were generally mild and transient, and appeared to be dose-related; the adverse event profile of 100 mg sumatriptan was similar to that of placebo. Overall, nausea/vomiting and \"bitter taste\" were the most common complaints. The proportion of patients withdrawn due to adverse events was similar in the placebo and 100 mg sumatriptan treatment groups (2% and 3%, respectively). It is concluded that 100 mg sumatriptan given orally is well tolerated with an anti-migraine efficacy comparable to that provided by the two higher doses.", "The efficacy and safety of tolfenamic acid and oral sumatriptan in the acute treatment of migraine was studied at five neurological centers in Finland. One hundred forty-one patients experiencing 289 migraine attacks, fulfilling the diagnostic criteria for migraine with or without aura as defined by the International Headache Society, were randomized. For first attacks, 77% of patients receiving tolfenamic acid experienced a reduction of the initial severe or moderate headache to mild or no headache after 2 hours, as compared to 79% in the sumatriptan group and 29% in the placebo group. No significant difference was found between active treatments (P = 0.85, 95% CI [-22%, 18%]), however, both active treatments were significantly better than placebo; P = 0.001, 95% CI (26%, 69%) for tolfenamic acid and P = 0.001, 95% CI (28%, 71%) for sumatriptan. For second attacks, results were similar with 70% of patients receiving tolfenamic acid experiencing relief, as compared to 64% in the sumatriptan group and 39% in the placebo group. No significant differences were observed in accompanying symptoms. Both drugs were well tolerated with the frequency of adverse events; 30% for tolfenamic acid and 41% for sumatriptan, a nonsignificant difference. In this study, tolfenamic acid and oral sumatriptan are comparably effective in the acute treatment of migraine. When comparably effective, factors like individual effect, tolerance, and cost of treatment should be considered when prescribing migraine medication.", "This multicentre, double-blind study compared (100 mg) sumatriptan administered orally with placebo in treating an acute attack of migraine; 238 patients were studied over a 48-h period. Four hours after treatment, 92 of the 142 evaluable sumatriptan patients (65%) showed significant reductions (P < 0.001) in headache severity, clinical disability and accompanying symptoms compared with 32 of the 80 evaluable placebo-treated patients (40%). The duration of attack prior to taking medication and the history of persistent migraine do not influence the observed difference between the two treatment regimens (sumatriptan and placebo), which remained statistically significant (P < 0.001) in both cases. The incidence of headache recurrence in patients who experienced relief 4 h after initial treatment was low, occurring in 16 (17%) and 4 (13%) of the sumatriptan- and placebo-treated patients, respectively. Only patients with a history of migraine attacks lasting longer than 24 h suffered headache recurrences, and these recurrences were not consistent with the International Headache Society definition of migraine. Treatment with sumatriptan was well tolerated.", "This study was conducted to evaluate the prevalence of migraine and its responsiveness to migraine-specific therapy in patients with self-reported tension-type headache.\n Patients were adults (n = 423) consulting one of 54 North American study sites including primary care clinics, neurology clinics, and headache clinics. The study comprised an initial diagnosis phase to determine the headache diagnosis of patients entering the study with self-reported tension/stress headache, including that previously diagnosed by a health care provider. Patients reporting tension/stress headache were evaluated and diagnosed as having migraine with or without aura, probable migraine, tension-type headache, or another headache type. Exclusion criteria included prior diagnosis of migraine or probable migraine and the presence of headache for at least 15 days monthly during either of the 2 months before screening. The initial phase was followed by a randomized, double-blind treatment phase to evaluate the efficacy of sumatriptan 100 mg tablets for the treatment of a single migraine attack in those meeting International Headache Society (IHS) criteria for migraine during the diagnosis phase.\n Of 423 patients reporting tension/stress headache at study entry, 84% (n = 357) were diagnosed at the clinic visit as fulfilling IHS criteria for migraine without aura or migraine with aura, and 65% (n = 276) were diagnosed with migraine only (i.e., with no other concurrent headache diagnosis). Three hundred thirty-two (332) patients entered the double-blind treatment phase. Headache relief rates 2h post-dose, the primary efficacy endpoint, did not significantly differ between sumatriptan and placebo (p = 0.099). However, improvements were significantly (p < 0.05) greater with sumatriptan than placebo on several other headache-related efficacy measures.\n Migraine headache may go unrecognized in patients with self-reported tension headache. Among patients having self-reported tension headache and diagnosed with migraine during the study, response to acute treatment with sumatriptan was inconclusive. Improvement with sumatriptan versus placebo was observed for some measures and not for others. The results should be interpreted in the context of study limitations including use of patient self-reports to assess headache diagnosis and possible lack of representativeness arising from the predominantly white sample.", "The tolerability and efficacy of oral sumatriptan 50 mg for the treatment of mild to moderate migraine attacks were assessed in a double-blind, multicenter placebo-controlled study on a group of patients who had not responded sufficiently to analgesic preparations. Three-hundred-and-twenty-eight migraine sufferers treated a first migraine attack with a nontriptan standard care medication: a mixture containing phenazone, butalbital and caffeine (optalidon) or indomethacin plus prochlorperazine plus caffeine (difmetre) or paracetamol 100 mg (tachipirine), depending on their habits. Of these patients, 32.6% reported headache relief with this treatment and were not included in phase II of the study. The 219 patients not reporting relief during the first phase of the study entered the second phase and were randomized to sumatriptan 50 mg or to placebo; 167 of these patients treated a second attack according to the protocol and were evaluated for efficacy. Of the patients with migraine taking sumatriptan, 58% reported headache relief compared with 35% of placebo-treated patients (p = 0.008). The reduction of nausea and vomiting was significantly better in the sumatriptan group. No differences were detected for the recurrence rate, while rescue medication was used more by the placebo group. The safety profile of sumatriptan 50 mg was confirmed. This study demonstrates the usefulness of this dose of oral sumatriptan against the pain and the accompanying symptoms of mild and moderate migraine.", "Migraine attacks are often treated with simple analgesics or with ergotamine-containing preparations alone or in combination with anti-emetics. Although also sometimes used to treat migraine, nonsteroidal anti-inflammatory drugs (NSAIDs) have not been systematically evaluated in controlled clinical trials, particularly in comparison with the newer drug sumatriptan. Sumatriptan is a specific migraine treatment which has recently become among the most widely prescribed acute migraine therapies. However, while effective, it has low oral bioavailability and some problematic adverse effects. Diclofenac-potassium is a potent NSAID available as a fast-acting oral tablet, which has been shown to be safe and effective in several other acute pain indications. In the clinical trial reported here, the efficacy and safety of diclofenac-potassium in the acute treatment of migraine attacks has been tested in comparison with oral sumatriptan and placebo.\n Single oral doses of 50 mg and 100 mg diclofenac-potassium were compared to a single oral dose of 100 mg sumatriptan and placebo in a double-blind randomized crossover trial in 156 adult patients suffering from migraine attacks, with or without aura, selected according to the International Headache Society diagnostic criteria. The primary efficacy criterion was migraine headache pain recorded on a visual analog scale at 2 h after dosing. Secondary endpoints included pain at other time points up to 8 h and the presence of accompanying symptoms (nausea, vomiting, photophobia, phonophobia).\n Diclofenac-potassium was more effective than placebo in reducing migraine headache pain at 2 h after dosing, which was the primary endpoint. Secondary analyses showed that diclofenac-potassium provided significant pain relief from 60 min after dosing and for all remaining endpoints in the 8-h observation period. Both 50 and 100 mg doses of diclofenac-potassium were similarly effective. A similar effect was shown with sumatriptan; however, significant superiority to placebo was seen only from the 90-min time point. Diclofenac-potassium was generally superior to placebo or sumatriptan in reducing accompanying symptoms, particularly nausea. Diclofenac-potassium seemed to be as well tolerated as placebo, with fewer adverse events reported than after sumatriptan treatment and with more patients assessing the overall tolerability of diclofenac-potassium better than that of sumatriptan.\n Compared with placebo and the reference therapy sumatriptan, diclofenac-potassium is an effective, fast-acting, and well-tolerated acute oral therapy for migraine attacks, with advantages over oral sumatriptan in terms of onset of analgesic effect, reduction of accompanying symptoms, and tolerability profile. It may therefore be useful as an alternative oral therapy for migraine attacks.", "This randomized, double-blind, parallel-group study compared the efficacy and tolerability of zolmitriptan (2.5 or 5 mg) and sumatriptan (50 mg) in the acute oral treatment of up to six moderate-to-severe migraine attacks. The intention to treat (ITT) population comprised of 1522 patients: 500 treated with zolmitriptan 2.5 mg (2671 attacks), 514 with zolmitriptan 5 mg (2744 attacks) and 508 with sumatriptan 50 mg (2693 attacks). Overall, the 2-h headache response rates in these groups were 62.9, 65.7 and 66.6%, respectively. There were no statistically significant differences between sumatriptan 50 mg and zolmitriptan 2.5 mg (P = 0.12) or 5 mg (P = 0.80). Approximately 40% of patients in each group reported a 2-h headache response in > or = 80% of attacks. There were no statistically significant differences between the groups in the rates of headache response at 1 h (zolmitriptan 2.5 mg 36.9%, zolmitriptan 5 mg 39.5% and sumatriptan 50 mg 38.0%) or 4 h (70.3, 72.9 and 72.2%, respectively) or in the rates of meaningful migraine relief at 1, 2 or 4 h or sustained (24-h) pain relief. All treatments were well tolerated. In conclusion, zolmitriptan (2.5 or 5 mg) proved similarly efficacious compared with sumatriptan (50 mg), both in terms of response rates and consistency across attacks.", "That sumatriptan tablets are effective and well tolerated in the acute treatment of migraine has been established, but the relationship between dose and efficacy has not been adequately defined to date in clinical trials. This multinational double-blind trial (N = 1003) in which patients treated up to three migraine attacks with sumatriptan 25 mg, 50 mg, 100 mg, or placebo, with a second independently randomized dose for headache recurrence, evaluated the efficacy and tolerability of three doses of sumatriptan. The results demonstrate that all doses of sumatriptan were superior (P < 0.05) to placebo in reducing moderate or severe predose headache to mild or no headache 4 hours postdose for each of the three treated attacks; sumatriptan 50 mg and 100 mg were each superior (P < 0.05) to sumatriptan 25 mg 4 hours postdose for two of three attacks. Sumatriptan (all doses) was similarly effective at relieving nausea and photophobia or phonophobia or both and at reducing clinical disability. Headache recurrence was experienced by similar proportions of patients across treatment groups (35% to 48% after placebo; 26% to 39% after sumatriptan). Relief of recurrent headache 2 hours after the second dose of study medication occurred in greater percentages of patients using any dose of sumatriptan compared with patients using placebo to treat recurrence. The incidence of adverse events with 25-mg and 50-mg sumatriptan tablets was similar to the incidence with placebo and lower than the incidence with 100-mg sumatriptan tablets. These data provide the first demonstration from a large well-controlled clinical trial that both the 50- and 100-mg doses are more effective than the 25-mg dose and that the 50-mg dose is associated with a lower incidence of adverse events than the 100-mg dose.", "Three oral doses of sumatriptan, 100, 200 and 300 mg, given as dispersible tablets, were compared in the acute treatment of migraine in a double-blind, placebo-controlled, parallel-group study of 1,130 patients from 51 centres in eight countries. Patients treated up to three migraine attacks at home over a 3-month period and recorded the results on a diary card. Safety follow-ups were performed monthly at a clinic. All doses of sumatriptan were significantly (p less than 0.001) more effective than placebo at relieving headache within 2 h of treatment. Response rates, scored on a 4-point scale, were: placebo 27%; 100 mg sumatriptan 67%; 200 mg sumatriptan 73%; and 300 mg sumatriptan 67%. The proportion of patients who required rescue medication within 2 h of treatment was significantly (p less than 0.001) lower in all active treatment groups when compared with placebo. Response rates to sumatriptan were the same irrespective of the type of migraine (with or without aura) or the duration of symptoms prior to treatment (less than or equal to 4 or greater than 4 h). Sumatriptan also provided significant (p less than 0.001) relief from nausea and photophobia as compared with placebo. The majority of adverse events reported were mild to moderate in severity and were transient. The overall incidence of adverse events was dose-related, the percentage of patients reporting adverse events in the first attack treated being 36, 47 and 53% for 100-, 200- and 300-mg doses of sumatriptan, respectively, compared to 17% of placebo patients (p less than 0.001 for each treatment dose compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)", "Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.", "The efficacy and safety of oral sumatriptan as a 100-mg dispersible tablet was compared with oral Cafergot (2 mg ergotamine tartrate, 200 mg caffeine) in a multicentre, randomized, double-blind, double-dummy, parallel-group trial. In the trial, 580 patients were treated from 47 investigating centres in nine European countries. Sumatriptan was significantly more effective than Cafergot at reducing the intensity of headache from severe or moderate to mild or none; 66% (145/220) of those treated with sumatriptan improved in this way by 2 h, compared with 48% (118/246) of those treated with Cafergot (p less than 0.001). The onset of headache resolution was more rapid with sumatriptan, whereas recurrence of migraine headache within 48 h was lower with Cafergot. Sumatriptan was also significantly more effective at reducing the incidence of nausea (p less than 0.001), vomiting (p less than 0.01) and photophobia/phonophobia (p less than 0.001) 2 h after treatment, and fewer patients on sumatriptan (24%) than on Cafergot (44%, p less than 0.001) required other medication after 2 h. The overall incidence of patients reporting adverse events was 45% after sumatriptan and 39% after Cafergot; the difference was not significant. The most commonly reported events in the sumatriptan-treated patients were malaise or fatigue and bad taste; these were generally mild and transient. Nausea and/or vomiting, abdominal discomfort, and dizziness or vertigo were reported by a greater proportion of Cafergot-treated patients. It is concluded that oral sumatriptan was well tolerated and is a more effective acute treatment for migraine than Cafergot.", "Aspirin is commonly used to treat migraine attacks, although sumatriptan, a much more expensive treatment, is also effective. We compared a combination of lysine acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg metoclopramide (LAS+MTC) with oral sumatriptan (100 mg) and placebo in 421 patients with migraine. LAS+MTC was as effective as sumatriptan with a decrease of headache from severe or moderate to mild or none of 57% and 53%, respectively, for the first migraine attack treated. Both treatments were better than placebo (success rate 24%, p < 0.0001). LAS+MTC was significantly more effective in the treatment of nausea than sumatriptan (p < 0.0001) and was better tolerated (adverse events in 18% and 28%, respectively, p < 0.05). LAS+MTC is as effective as sumatriptan in the treatment of migraine attacks. It is also much cheaper.", "The efficacy and tolerability of oral sumatriptan (Imitrex tablets) were assessed in 187 migraineurs enrolled in a randomized, double-blind, parallel-group, placebo-controlled study. In the clinic, patients received oral sumatriptan 25 mg, 50 mg, or 100 mg, or placebo, for the treatment of a migraine attack. The results demonstrate that by 2 hours postdose, 52 to 57% of patients treated with sumatriptan 25 mg, 50 mg, 100 mg compared with 17% of patients treated with placebo achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). By 4 hours postdose, 65 to 78% of sumatriptan-treated patients compared with 19% of placebo-treated patients achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). Oral sumatriptan also effectively relieved nausea and photophobia and improved clinical disability. No serious or unusual adverse events were reported, and the pattern and incidence of adverse events did not vary among the sumatriptan doses. Each dose--25 mg, 50 mg, or 100 mg--of sumatriptan was effective and generally well tolerated.", "Evaluate the effect of almotriptan on sustained pain-free outcome in patients with acute migraine.\n Three randomized, double-blind, placebo-controlled trials of almotriptan for the treatment of acute migraine were examined. Two trials evaluated almotriptan 6.25 mg and 12.5 mg, and the third evaluated almotriptan 12.5 mg and sumatriptan 100 mg. Patients aged 18 to 65 years were instructed to take 1 dose of study medication at the onset of a moderate-to-severe migraine headache. A second dose was allowed for relapse. Sustained pain-free was defined as a decrease in pain severity from moderate or severe at baseline to no pain at 2 hours postdose and without relapse or the use of escape medication between 2 and 24 hours.\n A total of 1791 adult migraine sufferers were studied. The proportion of patients achieving a sustained pain-free state was significantly (P<.05) higher in the almotriptan 6.25-mg (21.7% to 22.5%) and 12.5-mg (24.6% to 27.6%) groups than in the placebo group (7.5% to 12.1%). The proportion of patients achieving a sustained pain-free state was comparable between almotriptan 12.5 mg (24.6%) and sumatriptan 100 mg (28.5%) and significantly (P<.05) greater than with placebo (12.1%). Among patients with severe baseline pain, a sustained pain-free state was achieved in significantly more patients (P<.05) with almotriptan 12.5 mg (17.3% to 20.9%) than with placebo (3.1% to 3.2%). Among those with moderate baseline pain, a sustained pain-free state was achieved in significantly more patients (P<.01) with almotriptan 12.5 mg (31.3% to 32.0%) than with placebo (10.2% to 16.1%).\n Almotriptan 12.5 mg is significantly better than placebo and comparable to sumatriptan 100 mg for achieving a sustained pain-free state." ]

[ "6869493" ]

[ "Effectiveness of cognitive skill remediation in acute stroke patients." ]

[ "The purpose of this study was to determine whether a cognitive skills remediation program could help acute stroke patients regain important thinking skills. Patients in a community hospital stroke program were pre-tested in three skill areas--visual scanning, visual-spatial orientation, and time judgment--and randomly assigned to a treatment (n = 16) or control (n = 17) group. The treatment group received cognitive skill retraining on a one-to-one basis for 30 minutes per day, 3 days per week, for 3 weeks. The retraining involved the use of paper and pencil tasks, simple cuing procedures, positive reinforcement, and immediate feedback. Although the control group did not receive this treatment, conventional therapies continued for both groups. Patients receiving treatment had overall and separate skill improvement scores that were significantly higher than those for control patients. The implications of this type of treatment program are discussed." ]

[ "8469324", "2044501", "1944909" ]

[ "Felbamate: a double-blind controlled trial in patients undergoing presurgical evaluation of partial seizures.", "Felbamate: a clinical trial for complex partial seizures.", "Felbamate for partial seizures: results of a controlled clinical trial." ]

[ "We studied the efficacy and safety of felbamate, an investigational antiepileptic drug, in a unique, double-blind, placebo-controlled trial. Sixty-four patients with refractory partial-onset seizures who completed a routine evaluation for epilepsy surgery met seizure frequency entry criteria. Each patient received felbamate or placebo in addition to the anticonvulsant regimen present at the conclusion of the presurgical evaluation. The treatment phase consisted of an 8-day inpatient period and a 21-day outpatient period. The efficacy variable was time to fourth seizure. The difference in time to fourth seizure was statistically significant (p = 0.028) in favor of felbamate. Eighty-eight percent of the patients in the placebo group had a fourth seizure during the treatment phase compared with 46% of the patients in the felbamate group (p = 0.001). Adverse experiences with felbamate were generally mild or moderate in severity. This trial demonstrated the ability of felbamate to quickly and safely reduce the occurrence of frequent partial-onset seizures and maintain effective seizure control following reductions in the dosages of standard antiepileptic drugs.", "We performed a randomized, double-blind, three-period cross-over study of felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate: Carter-Wallace 554) in patients with complex partial seizures. Patients continued carbamazepine (CBZ) throughout the study and were observed in the hospital for the entire trial period. The entry criteria required at least six seizures in a 3-week baseline period (and no more than 1 week with a single seizure) with CBZ alone. Thirty subjects were randomized. Two left the study after randomization, 1 owing to seizure exacerbation, and 1 owing to hyponatremia, which may have been related to CBZ therapy. The daily dosage of 50 mg/kg (maximum 3,000 mg) FBM per day was well tolerated by all 28 patients who completed the study. Only mild adverse experience were observed during the trial. FBM reduced CBZ level (p less than 0.0001; 95% confidence interval -28%, -20%). There was no significant difference in seizure frequency between placebo and FBM periods (one-sided p = 0.172), but when a correction was made for the lower CBZ level noted during FBM periods, the data suggested a strong antiseizure effect of FBM.", "Felbamate (2-phenyl-1,3-propanediol dicarbamate) has a favorable preclinical profile in animal models of epilepsy. We present the results of a double-blind, randomized, placebo-controlled clinical trial in patients with partial seizures. Criteria for entry included a requirement for four or more partial seizures per month despite concomitant therapeutic blood levels of phenytoin and carbamazepine. Fifty-six patients (mean age, 31.4 years; 32 men, 24 women) completed the trial. The mean seizure frequencies for the 8-week periods analyzed were felbamate = 34.9, placebo = 40.2. Felbamate was statistically superior to placebo in seizure reduction, percent seizure reduction, and truncated percent seizure reduction. The mean felbamate dosage was 2,300 mg/d. Plasma felbamate concentrations ranged from 18.4 to 51.9 mg/l, mean = 32.5 mg/l. Adverse experiences during felbamate therapy were minor and consisted primarily of nausea and CNS effects. This trial indicates that felbamate is safe and effective in the treatment of comedicated patients with severely refractory epilepsy." ]

[ "7600753", "12242455", "8590781", "11815493", "2974778", "11375359", "11815494", "2904532", "10394695" ]

[ "Evaluation of a structured teaching and treatment programme for type 2 diabetes in general practice in a rural area of Austria.", "Lifestyle intervention by group care prevents deterioration of Type II diabetes: a 4-year randomized controlled clinical trial.", "Evaluation of the effectiveness of an ambulatory teaching/treatment programme for non-insulin dependent (type 2) diabetic patients.", "Culturally competent diabetes self-management education for Mexican Americans: the Starr County border health initiative.", "Group education for obese patients with type 2 diabetes: greater success at less cost.", "Group visits improve metabolic control in type 2 diabetes: a 2-year follow-up.", "Assessment of group versus individual diabetes education: a randomized study.", "Evaluation of a structured treatment and teaching programme on non-insulin-dependent diabetes.", "[The education of type-2 diabetics: why not in groups?]." ]

[ "The efficacy of a treatment and teaching programme for non-insulin-treated Type 2 diabetic patients in general practice was evaluated in a prospective, controlled study. In a rural area in southern Austria, 53 patients from seven general practices participated in a structured programme (intervention group) and 55 patients from seven general practices without the programme served as the control group. After 6 months the weight reduction in the intervention group was 2.6 kg (1.6-3.7 kg, p < 0.001) and the difference in HbA1c between the groups was 0.92% (0.23-1.61%, p < 0.01) at follow-up. Systolic (-16.6 mmHg) and diastolic (-11.1 mmHg) blood pressure, serum triglycerides (-0.63 mmol I-1), and serum cholesterol (-0.40 mmol I-1) were reduced significantly in the intervention group (p < 0.006). The number of patients with callus formation and poor nail care decreased significantly after participating in the teaching programme (p < 0.001). In the control group no reduction in body weight, metabolic control or in risk factors for diabetic foot complications were observed. Calculated health care costs per patient and year decreased in the intervention group (-33 pounds) and increased in the control group (+ 30 pounds) mainly due to changes in prescription of oral hypoglycaemic agents in both groups. This programme may be an efficient and helpful model to increase overall quality of diabetes care according to the St Vincent Declaration.", "Metabolic control worsens progressively in Type II (non-insulin-dependent) diabetes mellitus despite intensified pharmacological treatment and lifestyle intervention, when these are implemented on a one-to-one basis. We compared traditional individual diabetes care with a model in which routine follow-up is managed by interactive group visits while individual consultations are reserved for emerging medical problems and yearly checks for complications.\n A randomized controlled clinical trial of 56 patients with non-insulin-treated Type II diabetes managed by systemic group education and 56 control patients managed by individual consultations and education.\n Observation times were 51.2+/-2.1 months for group care and 51.2+/-1.8 for control subjects. Glycated haemoglobin increased in the control group but not in the group of patients ( p<0.001), in whom BMI decreased ( p<0.001) and HDL-cholesterol increased ( p<0.001). Quality of life, knowledge of diabetes and health behaviours improved with group care ( p<0.001, all) and worsened among the control patients ( p=0.004 to p<0.001). Dosage of hypoglycaemic agents decreased ( p<0.001) and retinopathy progressed less ( p<0.009) among the group care patients than the control subjects. Diastolic blood pressure ( p<0.001) and relative cardiovascular risk ( p<0.05) decreased from baseline in group patients and control patients alike. Over the study period, group care required 196 min and 756.54 US dollars per patient, compared with 150 min and 665.77 US dollars for the control patients, resulting in an additional 2.12 US dollars spent per point gained in the quality of life score.\n Group care by systemic education is feasible in an ordinary diabetes clinic and cost-effective in preventing the deterioration of metabolic control and quality of life in Type II diabetes without increasing pharmacological treatment.", "The aim of this study was to evaluate the effect of a structured teaching/treatment programme on the clinical and metabolic control of non-insulin-dependent (type 2) diabetic patients. The programme was aimed at improving the overall treatment quality in these patients through measures involving self-care, diet, exercise and weight reduction. Four theoretical-practical teaching units were given once a week to group of 5-8 ambulatory patients by previously trained general practitioners. Clinical and biochemical parameters were recorded at the beginning of the course and 1 year after its completion in 40 patients attending the programme and in 39 patients of similar clinical characteristics under conventional diabetes treatment, but receiving no structured teaching before or during the survey period (control group). The drop-out percentage in the intervention group (25%) was significantly lower than in the control group (45%, P < 0.05), suggesting an incentive toward greater compliance in the former. At the end of the 1-year follow-up, the mean differences observed in the control and in the intervention groups were: body weight loss -2.4 +/- 0.5 kg vs -0.4 +/- 0.5 (P < 0.001); haemoglobin HbA1 -0.2% +/- 0.4% vs +0.8% +/- 0.4% (NS); number of daily oral hypoglycaemic agent intake -1.4 +/- 0.2 vs +0.9 +/- 0.2 tablets (P < 0.001). Our results strongly suggest that this programme, applied through family doctors, may constitute an efficient tool to improve the compliance and clinico-metabolic control of type 2 patients at the primary health care level.", "To determine the effects of a culturally competent diabetes self-management intervention in Mexican Americans with type 2 diabetes.\n A prospective, randomized, repeated measures study was conducted on the Texas-Mexico border in Starr County. A total of 256 randomly selected individuals with type 2 diabetes between 35 and 70 years of age, diagnosed with type 2 diabetes after 35 years of age, and accompanied by a family member or friend were included. The intervention consisted of 52 contact hours over 12 months and was provided by bilingual Mexican American nurses, dietitians, and community workers. The intervention involved 3 months of weekly instructional sessions on nutrition, self-monitoring of blood glucose, exercise, and other self-care topics and 6 months of biweekly support group sessions to promote behavior changes. The approach was culturally competent in terms of language, diet, social emphasis, family participation, and incorporation of cultural health beliefs. Outcomes included indicators of metabolic control (HbA(1c) and fasting blood glucose), diabetes knowledge, and diabetes-related health beliefs.\n Experimental groups showed significantly lower levels of HbA(1c) and fasting blood glucose at 6 and 12 months and higher diabetes knowledge scores. At 6 months, the mean HbA(1c) of the experimental subjects was 1.4% below the mean of the control group; however, the mean level of the experimental subjects was still high (>10%).\n This study confirms the effectiveness of culturally competent diabetes self-management education on improving health outcomes of Mexican Americans, particularly for those individuals with HbA(1c) levels >10%.", "It has been suggested that much effort expended in teaching diabetic diets is ineffective and wasteful. We have tested a different system by randomly allocating 75 newly diagnosed obese Type 2 diabetic patients to usual 'unstructured' clinic care or to group education by diabetes specialist nurses and a dietitian. Patients allocated to group education attended five 90-min group sessions during the first 6 months. Six months after diagnosis they had lost more weight (median (95% Cl), 7 (5.5-9) vs 2(1-5)kg, p less than 0.002) and were better controlled (HbA1:7.5 (7.0-8.1) vs 9.5 (8.7-10.4)%, p less than 0.001) than those randomized to the usual clinic system. At 1 year (after no further visits) the difference in weight loss was less (5.5 (4-6.5) vs 3 (2-4) kg, p less than 0.05) and diabetic control was similar (HbA1:9.0(8.2-9.8) vs 9.9(8.9-10.9)%. At 1 year only 14(39%) of the education group and 9(23%) of those attending the clinic had a fasting blood glucose less than 7.0 mmol l-1.", "To evaluate whether group visits, delivered as routine diabetes care and structured according to a systemic education approach, are more effective than individual consultations in improving metabolic control in non-insulin-treated type 2 diabetes.\n In a randomized controlled clinical trial of 112 patients, 56 patients were allocated to groups of 9 or 10 individuals who participated in group consultations, and 56 patients (considered control subjects) underwent individual visits plus support education. All visits were scheduled every 3 months.\n After 2 years, HbA(1c) levels were lower in patients seen in groups than in control subjects (P < 0.002). Levels of HDL cholesterol had increased in patients seen in groups but had not increased in control subjects (P = 0.045). BMI (P = 0.06) and fasting triglyceride level (P = 0.053) were lower. Patients participating in group visits had improved knowledge of diabetes (P < 0.001) and quality of life (P < 0.001) and experienced more appropriate health behaviors (P < 0.001). Physicians spent less time seeing 9-10 patients as a group rather than individually, but patients had longer interaction with health care providers.\n Group consultations may improve metabolic control in the medium term by inducing more appropriate health behaviors. They are feasible in everyday clinical practice without increasing working hours.", "The current study was conducted to compare the effectiveness of delivering diabetes education in either a group or individual setting using a consistent, evidence-based curriculum.\n A total of 170 subjects with type 2 diabetes were randomly assigned to either group (n = 87) or individual (n = 83) educational settings. Subjects received education in four sequential sessions delivered at consistent time intervals over a 6-month period. Outcomes included changes in knowledge, self-management behaviors, weight, BMI, HbA(1c), health-related quality of life, patient attitudes, and medication regimen. Changes were assessed at baseline and after the 2-week, 3-month, and 6-month education sessions.\n Both educational settings had similar improvements in knowledge, BMI, health-related quality of life, attitudes, and all other measured indicators. HbA(1c) decreased from 8.5 +/- 1.8% at baseline to 6.5 +/- 0.8% at 6 months (P < 0.01) in the study population as a whole. Subjects assigned to the individual setting had a 1.7 +/- 1.9% reduction in HbA(1c) (P < 0.01), whereas subjects assigned to the group setting had a 2.5 +/- 1.8% reduction in HbA(1c) (P < 0.01). The difference in HbA(1c) improvement was marginally greater in subjects assigned to group education versus individualized education (P = 0.05).\n This study demonstrates that diabetes education delivered in a group setting, when compared with an individual setting, was equally effective at providing equivalent or slightly greater improvements in glycemic control. Group diabetes education was similarly effective in delivering key educational components and may allow for more efficient and cost-effective methods in the delivery of diabetes education programs.", "A structured treatment and teaching programme for non-insulin-treated non-insulin-dependent (type 2) diabetes was evaluated prospectively in general practice. The four group sessions were mainly conducted by paramedical personnel. 65 patients from five general practices were assessed at the start of the programme and 50 (mean age 65 years, diabetes duration 7 years) completed the 1 year follow-up (intervention group). The control group consisted of 49 patients (mean age 63 years, diabetes duration 7 years) from three other general practices without the programme. In the intervention group the percentage of patients receiving sulfonylureas fell from 68% at the start of the study to 38% after 1 year (mean difference 30%, 95% confidence interval [CI] 16-44%); the mean weight loss was 2.7 kg (95% CI 1.6-3.8 kg), and non-fasting triglycerides were reduced by 0.77 mmol/1 (95% CI 0.35-1.19 mmol/l); and glycosylated haemoglobin remained unchanged (7.1% of total haemoglobin). In the control group none of these indices was changed during the study year, and 10% of patients started insulin treatment. The structured treatment and teaching programme improved the overall quality of patient care in elderly non-insulin-dependent diabetic patients treated by general practitioners.", "To evaluate the efficacy of a programme of group education for diabetics, which succeeded in reducing base glucaemia, body mass index and glycosylated haemoglobin, stimulating insulin-treated patients' self-monitoring of glucaemia, improving their understanding of the disease, and bringing into group education 75% of the target population.\n A controlled clinical trial with paired samples, lasting two years.\n \"Las Fuentes Norte\" Health Centre, Zaragoza.\n 243 type-2 diabetics, distributed at random, with 120 in the intervention group and 123 in the control group. All patients with no history of group education in the previous two years and with no restrictions on their attending talks and monitoring were included. No-one gave up in the first year; 9 did in the second year.\n Group health education workshop for two days in the first and second years.\n In the intervention group, at the end of the study, success in the survey increased by 4.2; base glucaemia dropped by 17.1 mg/dl, glycate haemoglobin went down by 0.5, and self-analysis went up by 14.2%, all with significant differences (p < 0.005 and CI 95%). The body mass index went down by 0.3 without significant differences. Knowledge was lost between the first and second year, with worse metabolic control. In the control group there were no significant differences in any variable.\n A stable programme of group education may be effective, especially because of the increase in knowledge of the disease, fostering excellent conditions for a change to a healthier life-style." ]

[ "17628562", "7825081", "12635758", "15121569", "3103663", "15141801" ]

[ "A randomized comparison of different methods of analgesia in abortion using manual vacuum aspiration.", "Is ward evacuation for uncomplicated incomplete abortion under systemic analgesia safe and effective? A randomised clinical trial.", "Pain relief using paracervical block in patients undergoing manual vacuum aspiration of uterus.", "Paracervical block in incomplete abortion using manual vacuum aspiration: randomized clinical trial.", "Anaesthesia for evacuation of retained products of conception. Comparison between alfentanil plus etomidate and fentanyl plus thiopentone.", "Bolus application of remifentanil with propofol for dilatation and curettage." ]

[ "To estimate the effectiveness of different methods of analgesia among women treated with manual vacuum aspiration for spontaneous abortion.\n The 113 patients diagnosed with incomplete abortion and considered candidates for manual vacuum aspiration were randomly assigned to 3 groups of analgesic administration: diclofenac plus paracervical block; meperidine plus diclofenac; and meperidine alone. Pain levels were evaluated using the Wong Scale of Pain.\n The mean pain scores for the three groups were: diclofenac and paracervical block 5.4; meperidine plus diclofenac 5.0; meperidine 5.7 (P=0.57). Analysis of pain using the levels mild (0-3), moderate (4-6), and severe (7-10) showed no statistical significance among the 3 groups of analgesics. Adverse effects were more common in the groups using analgesia containing meperidine.\n There was no significant difference between the analgesics used among the 3 groups. Most of the patients, regardless of the analgesic used, reported moderate pain.", "To compare evacuation under systemic analgesia (fentanyl and midazolam) in a treatment room (ward group) with evacuation under general anaesthesia in theatre.\n A prospective randomised clinical trial.\n A tertiary medical centre serving a black urban population.\n One hundred and forty-two patients with uncomplicated incomplete abortions.\n Randomisation into two groups, those for evacuation under systemic analgesia and those for evacuation under general anaesthesia.\n Both groups were compared in terms of safety, efficacy, acceptability, blood consumption and time delay between admission and evacuation.\n Significantly less blood was used in the ward group (37 units for 13 patients) than in the theatre group (65 units for 24 patients) (P < 0.03). Significantly less time was taken between admission and evacuation in the ward group (median 7 hours 15 minutes) than in the theatre group (median 12 hours 38 minutes) (P < 0.0003). Evacuation under fentanyl and midazolam was safe, effective and acceptable for the majority of patients compared with evacuation under general anaesthesia.\n Patients with uncomplicated incomplete abortions (uterine size equivalent to a pregnancy of 14 weeks' duration or less) can undergo evacuation safely and effectively under fentanyl and midazolam and have a significantly smaller chance of requiring a blood transfusion.", "To evaluate pain relief using paracervical nerve block with 1% lignocaine injection in patients undergoing uterine evacuation by Manual Vacuum Aspiration (MVA) for the treatment of incomplete abortion.\n A randomized double blind clinical trial.\n Marie Stopes Health Centre, Nairobi.\n One hundred and forty two patients were recruited between September and October 1997. The intervention was random assignment to the study group (paracervical block with 1% lignocaine) or the placebo group (paracervical block with sterile water for injection). Intra and post operative assessment of pain was made using McGills and facial expression scales.\n The untreated group experienced significantly more pain than the treated group, especially lower abdominal pain and backache. The pain was especially marked intraoperatively, less so 30 minutes post-operatively.\n Based on the findings of this study, any patient going for manual vacuum aspiration for the treatment of incomplete abortion should be given Paracervical block as it is cost effective, easy to perform and with less side effects.", "To estimate the effectiveness of paracervical block in controlling pain among women treated with manual vacuum aspiration for an incomplete abortion\n A randomized clinical trial was conducted at Nuestra Señora de Altagracia, a maternal and perinatal referral hospital in the Dominican Republic. The sample size was based on a clinical difference of 1.5 points in the level of pain measured with the visual analog scale using 90% power and a sampling error of 0.04. Women who were at 12 weeks of gestation or less with an incomplete abortion were eligible to participate. They were randomly assigned to receive either the standard treatment of care (manual vacuum aspiration for uterine evacuation with psychological support but no paracervical block) or manual vacuum aspiration treatment with psychological support and paracervical block using 1.0% lidocaine. Patients with active infections, severe illnesses, psychiatric disorders, or allergies to lidocaine were excluded. Intraoperative pain as reported by the women and as documented by an external observer was measured.\n Although the paracervical block technique used showed a slight reduction in severe pain, there were no clinically or statistically significant differences in intraoperative pain between the 2 groups (relative risk 0.73; 95% confidence interval 0.43, 1.23) with 50% of all patients registering 7 or higher score on a visual analog pain scale of 0-10. However, statistically significant differences were found in each group when comparing the level of preoperative and intraoperative pain described by the patient (P <.001). The manual vacuum aspiration technique and the paracervical block were not accompanied by complications.\n The paracervical block technique used in this study along with psychological support was comparable with pain control using psychological support alone; neither pain management regimen provided sufficient pain control. It is recommended that randomized comparative studies be designed to determine the effectiveness of other paracervical block techniques and the efficacy of the use of analgesics in patients suffering from incomplete abortion treated with manual vacuum aspiration.", "Forty-four patients presenting for evacuation of retained products of conception were anaesthetized with either fentanyl and thiopentone, or alfentanil with etomidate, along with 70% nitrous oxide in oxygen. There was no difference between the two techniques in indices of immediate recovery (time to opening eyes and obeying a simple command), but the rate of return of higher mental functions (assessed by a coin counting test) was significantly better using the alfentanil-etomidate technique. There was no statistically significant difference between the techniques for apnoea or abnormal movements during anaesthesia, but alfentanil with etomidate was associated with significantly more pain on injection and a higher frequency of postoperative vomiting (40%).", "This study was designed to determine which single bolus dose of remifentanil in combination with propofol and nitrous oxide is best to control the haemodynamic, autonomous and somatic responses in patients scheduled for dilatation and curettage of the uterine cervix. We evaluated the adequacy of different bolus doses of remifentanil, associated with propofol and nitrous oxide, for dilatation and curettage in a prospective double-blind study.\n After institutional approval and informed consent, 34 healthy females undergoing curettage to remove material from the uterus after spontaneous abortion were randomized to receive remifentanil 0.5 microg kg(-1) intravenously (i.v.) (Group A; n = 4), 1 microg kg(-1) i.v. (Group B; n = 15) or 1.5 microg kg(-1) i.v. (Group C; n = 15), with propofol 2 mg kg (-1) i.v. in all groups. Anaesthesia was maintained with 60% nitrous oxide in oxygen. Haemodynamic, somatic and autonomic signs of light anaesthesia were registered to assess the response to surgical stress. Recovery times and Aldrete score were recorded at the end of the procedure.\n The groups were similar with regard to biometric data and duration of surgery. The poor results using the lowest dose of remifentanil obliged us to abandon this dose. The total dose of remifentanil was larger in Group C (100 +/- 5.7 microg vs. 65 +/- 4.1 microg in Group B; P < 0.05), but more patients required extra bolus injections in Group B (69% vs. 38% in Group C; P < 0.01). Recovery times were significantly shorter in Group C. Aldrete scores when leaving the operation room was similar.\n Remifentanil 1.5 microg kg(-1) i.v. with propofol 2 mg kg(-1) i.v. and 60% nitrous oxide in oxygen provided the best anaesthetic control with the fastest recovery times." ]

[ "7966789", "2284533", "8201695" ]

[ "Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited: long-term results of a controlled prospective study and further clinical experience.", "Adjuvant chemotherapy following cystectomy benefits patients with deeply invasive bladder cancer.", "Adjuvant cisplatin chemotherapy following cystectomy for bladder cancer: results of a prospective randomized trial." ]

[ "A total of 83 patients with nonorgan-confined bladder cancer with or without lymph node metastases (tumor stages pT3b, pT4a and/or pN1, pN2) was evaluated in November 1993 for relapse-free and overall survival. All patients underwent radical cystectomy between 1987 and 1991, 38 underwent adjuvant polychemotherapy with methotrexate, vinblastine and cisplatin plus doxorubicin (M-VAC) or epirubicin (M-VEC). Of the 83 patients 49 had entered a prospective randomized trial comparing adjuvant to no adjuvant treatment. The protocol was activated in May 1987. Patient recruitment was concluded in December 1990 because an interim analysis of the 49 randomized patients revealed a significant prognostic advantage in favor of the 26 patients randomized to the chemotherapy group compared to 23 in the control group (p = 0.0015, log-rank test for relapse-free survival curves). Preliminary data were published in 1992. Of the 26 patients randomized for adjuvant chemotherapy 18 were treated with M-VAC or M-VEC, 7 refused chemotherapy before or during cycle 1 and 1 received chemotherapy without cisplatin because of impaired renal function. The update of patient followup obtained in November 1993 continues to demonstrate a significant improvement in progression-free survival in favor of patients randomized for adjuvant chemotherapy (p = 0.0005). Followup of patients living free of disease ranged from 38 to 78 months. In a second analysis of actual treatment, the total collective of 83 patients treated from 1987 to 1991 was reviewed: 38 who had actually undergone adjuvant M-VAC/M-VEC (18 during the prospective trial and 20 in 1991 as the routinely recommended therapy) were compared with 45 without adjuvant M-VAC/M-VEC (7 refused to participate in the adjuvant trial, 8 randomized for but did not undergo adjuvant M-VAC/M-VEC, 23 belonged to the control group of the trial, and 7 underwent cystectomy in 1991 and remained without adjuvant treatment). This analysis again revealed a significant prognostic advantage in favor of the patients treated with adjuvant M-VAC/M-VEC. We conclude that adjuvant chemotherapy with M-VAC/M-VEC leads to a significant prolongation of relapse-free survival and to an improvement of the definitive cure rates after radical cystectomy for locally advanced transitional cell carcinoma of the bladder.", "nan", "Between April 1984 and May 1989, 77 eligible patients with invasive, nonmetastatic (stage M0) transitional cell carcinoma of the bladder were stratified after radical cystectomy and pelvic lymph node dissection on the basis of nodal status (stage pN0 versus pN1-2) and were randomly assigned to either observation or postoperative cisplatin chemotherapy (3 courses of 90 mg./m.2 cisplatin given for 3 consecutive days at monthly intervals). Patient eligibility included a creatinine clearance of greater than 60 ml. per minute. There were 40 eligible patients in the control group (median age 61 years) and 37 in the cisplatin group (median age 64 years). In regard to postoperative tumor stage and nodal status, there was no statistical difference between the 2 patient groups. In the cisplatin group 21 patients received the full dose, 9 required dose reduction and 7 refused treatment. Median followup was 5 years 9 months (range 3 to 8 years). Survival analysis showed no significant difference (log rank p = 0.65) between the 40 patients in the control group and the 37 in the cisplatin group. The survival rate at 5 years was 54% (95% confidence interval 39 to 69%) in the control group and 57% (95% confidence interval 40 to 74%) in the treatment group. Patients with cancer confined to the bladder wall (stage pT3a or less) had a 5-year overall survival rate of 70% and those with tumor growth in the perivesical fat or into the prostate (stages pT3b plus pT4a) had a 5-year overall survival rate of 40%. This difference in survival between the low stage subgroup (stages pT3a or less) and the high stage subgroup (pT3b plus pT4a) is highly significant (p = 0.0043). However, no difference between the controls and the cisplatin group was found within either the low or high stage subgroups. The reasons for failing to show a survival benefit from adjuvant high dose cisplatin monotherapy after radical cystectomy are discussed." ]

[ "15327804", "11842864", "20216107", "11889661", "17030096", "2099487", "11203735", "15134414", "1812146", "8811136" ]

[ "Treatment of painful temporomandibular joints with a cyclooxygenase-2 inhibitor: a randomized placebo-controlled comparison of celecoxib to naproxen.", "A randomized double-blind clinical trial of the effect of chondroitin sulfate and glucosamine hydrochloride on temporomandibular joint disorders: a pilot study.", "Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study.", "The effectiveness of adding pharmacologic treatment with clonazepam or cyclobenzaprine to patient education and self-care for the treatment of jaw pain upon awakening: a randomized clinical trial.", "Analgesic action of gabapentin on chronic pain in the masticatory muscles: a randomized controlled trial.", "[Piroxicam, diazepam and placebo in the treatment of temporomandibular joint dysfunction. Double blind study].", "Topical application of capsaicin for the treatment of localized pain in the temporomandibular joint area.", "Use of Theraflex-TMJ topical cream for the treatment of temporomandibular joint and muscle pain.", "Administration of clonazepam in the treatment of TMD and associated myofascial pain: a double-blind pilot study.", "Diclofenac sodium as an alternative treatment of temporomandibular joint pain." ]

[ "To compare the efficacy and adverse effects of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, with naproxen, a non-steroidal anti-inflammatory drug, and placebo in the treatment of painful temporomandibular joints (TMJs). In this randomized, double-blind, placebo-controlled trial, 68 subjects with painful TMJs secondary to disc-displacement with reduction, received celecoxib 100 mg twice a day; naproxen, 500 mg twice a day; or placebo for 6 weeks. Subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analogue scale, maximal comfortable mandibular opening, and quality of life (SF-36), at baseline (1 week after discontinuing previous analgesic therapy) and again after 6 weeks of drug treatment. Naproxen significantly reduced the symptoms of painful temporomandibular joint disc-displacement (TMJ DD) with reduction as determined by most efficacy measures. Significant improvement in pain intensity occurred within 3 weeks of treatment, and was sustained throughout the 6-week study. Clinically significant improvement in mandibular range of motion was observed for naproxen compared to celecoxib and placebo. Celecoxib showed slightly better pain reduction than placebo, but was not significantly effective for temporomandibular disorder pain. Celecoxib and naproxen were well tolerated, with similar number of reported adverse effects. Dual COX-1 and COX-2 inhibition with naproxen was demonstrated to be effective for the treatment of painful TMJs, as seen by significant improvement in clinical signs and symptoms of TMJ DD with reduction compared to celecoxib and placebo. Inhibition of both COX isozymes is needed to achieve effective analgesia for this type of musculoskeletal pain.", "Previous studies have shown chondroitin sulfate and glucosamine hydrochloride have beneficial effects on symptoms of osteoarthritis of the knee. Our aim was to study the effect of a daily dose of 1500 mg of glucosamine hydrochloride (GH) and 1200 mg of chondroitin sulfate (CS) taken for twelve weeks on subjects diagnosed with capsulitis, disk displacement, disk dislocation, or painful osteoarthritis of the temporomandibular joint (TMJ). Forty-five subjects were enrolled in the study and were randomly assigned to either an active medication group or a placebo group. Eleven subjects were lost from the study for various reasons, resulting in fourteen subjects remaining in the active medication group and twenty subjects remaining in the placebo group. Subjects taking CS-GH had improvements in their pain as measured by one index of the McGill Pain Questionnaire, in TMJ tenderness, in TMJ sounds, and in the number of daily over-the-counter medications needed. Subjects taking the placebo medication had improvements in their pains as measured by the visual analog scale and by four indices of the McGill Pain Questionnaire. Additional studies are required to evaluate the clinical effectiveness of CS-GH and to determine the exact mechanism by which CS-GH affects the articular cartilage of synovial joints.", "Three common haplotypes in the gene encoding catechol-O-methyltransferase (COMT) have been associated with pain modulation and the risk of developing chronic musculoskeletal pain, namely temporomandibular disorder (TMD). Haplotypes coding for higher enzymatic activity were correlated with lower pain perception. Rodent studies showed that COMT inhibition increases pain sensitivity through beta2/3-adrenergic receptors. We hypothesized that the nonselective beta-adrenergic antagonist propranolol will reduce clinical and experimental pain in TMD patients in a manner dependent on the individuals' COMT diplotype.\n Forty Caucasian female participants meeting the Research Diagnostic Criteria for TMD were genotyped for COMT polymorphisms and completed a randomized, double-blind, placebo-controlled, two-period crossover pilot study. Each period consisted of a baseline assessment week followed by an intervention week (propranolol or placebo). Changes in clinical pain ratings, psychological status, and responses to heat and pressure stimuli between baseline and intervention weeks were compared across periods.\n The number of patients reporting a reduction in pain intensity rating was greater during propranolol treatment (P=0.014) compared with placebo. Propranolol significantly reduced a composite pain index (P=0.02) but did not decrease other clinical and experimental pain ratings. When stratified by the COMT high activity haplotype, a beneficial effect of propranolol on pain perception was noted in patients not carrying this haplotype, a diminished benefit was observed in the heterozygotes, and no benefit was noted in the homozygotes.\n COMT haplotypes may serve as genetic predictors of propranolol treatment outcome, identifying a subgroup of TMD patients who will benefit from propranolol therapy.", "To compare the relative effectiveness of a benzodiazepine (clonazepam), a muscle relaxant (cyclobenzaprine), and a placebo for the treatment of jaw pain upon awakening, when each is combined with the recommended nonpharmacological components of initial medical management.\n Forty-one subjects were recruited with a diagnosis of myofascial pain based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). All subjects were given education about TMD and a self-care program. Subjects were randomized into 1 of 3 groups: clonazepam (0.5 mg/night), cyclobenzaprine (10 mg/night), or placebo. The primary outcome measure was the subjects' average intensity of jaw pain upon awakening over the prior week. This was recorded with a visual analog scale at pretreatment and at the completion of the 3-week trial. A secondary outcome measure was sleep quality based on the Pittsburg Sleep Quality Index.\n Within-group changes showed a statistically significant (P < .001) decrease in jaw pain upon awakening for all 3 groups. Between-group differences demonstrated a statistically significant difference (P < .016) between cyclobenzaprine and placebo, and between cyclobenzaprine and clonazepam. There was no significant effect on sleep quality in any group.\n This study suggests that cyclobenzaprine is statistically superior to either placebo or clonazepam when added to self-care and education for the management of jaw pain upon awakening. Based on the subjects' report of sleep quality, these medications failed to significantly improve sleep in the short term.", "Chronic masticatory myalgia (CMM) can be defined as constant pain in the masticatory muscles for more than 6 months and is influenced by the central nervous system. The antiepileptic agent gabapentin acts centrally and is used for managing different types of chronic pain conditions. The objective of this study was to evaluate the analgesic action of gabapentin on CMM. In this 12-week randomized controlled clinical trial 50 patients were randomly allocated into two study groups: 25 received gabapentin and 25 received placebo. The outcome measures utilized were pain reported on a VAS (VAS-pain), Palpation Index (PI) and impact of CMM on daily functioning reported on a VAS (VAS-function). Thirty-six patients completed the study. Gabapentin showed to be clinically and statistically superior to placebo in reducing pain reported by patients (gabapentin=51.04%; placebo=24.30%; P=0.037), masticatory muscle hyperalgesia (gabapentin=67.03%; placebo=14.37%; P=0.001) and impact of CMM on daily functioning (gabapentin=57.70%; placebo=16.92%; P=0.022). It can be concluded from this study that gabapentin is effective for the management of CMM.", "The effects of Piroxicam, Diazepam, and a Placebo on patients of different degrees of Stomatognathic System Dysfunction were studied. No statistically significant differences were found between the therapeutic effects of Piroxicam, Diazepam and a placebo.", "To determine the effectiveness of topical capsaicin cream application on localized pain in the temporomandibular joint (TMJ) area.\n A randomized, double-blind, placebo-controlled study was conducted on 30 patients suffering from unilateral pain in the TMJ area. Patients were randomly divided into experimental and placebo groups; they were instructed to apply 0.025% capsaicin cream or its vehicle to the painful TMJ area 4 times daily for 4 weeks. Subjective parameters of present pain, most severe pain, effect of pain on daily activities, and pain relief were assessed each week on a visual analog scale. Muscle and joint sensitivity to palpation on the painful and contralateral joints and maximal mouth opening (assisted/passive and non-assisted/active) were examined weekly by the same experienced examiner.\n Capsaicin cream produced no statistically significant influence on measured variables when compared to placebo. Both experimental and placebo groups showed statistically significant improvement in most variables during the experiment.\n The factor of time had a major effect in the non-specific improvement of the parameters assessed. The placebo effect played an important role in the treatment of patients with pain in the TMJ area.", "This randomized, double-blind study was designed to evaluate the effectiveness of the topical cream Theraflex-TMJ (NaBob/Rx, San Mateo, CA) in patients with masseter muscle pain and temporomandibular joint (TMJ) pain. Fifty-two subjects (5 males and 47 females) were instructed to apply a cream over the afflicted masseter muscle(s) or over the jaw joint(s) twice daily for two weeks. Theraflex-TMJ cream was used by the experimental group, while a placebo cream was used by the control group. The means of pain ratings were calculated prior to the application of the cream (baseline), after ten days of tx (period 1), and 15 days of tx (period 2) days of treatment and five days after stopping the treatment (follow-up). There was a significant decrease in reported pain levels from baseline in the experimental group for period 1 (p < 0.01), period 2 (p < 0.001), and follow-up (p < 0.01). For the control group, no significant differences were found between the different time periods (p > 0.05). There was evidence of minor side effects such as skin irritation and/or burning on the site of the application in two subjects in the experimental as well as two subjects in the control groups. The data strongly suggest that Theraflex-TMJ topical cream is safe and effective for reducing pain in the masseter muscle and the temporomandibular joint.", "A double-blind pilot study was undertaken to test the administration of low doses of the long-acting benzodiazepine drug clonazepam in the management of chronic intractable temporomandibular disorder/myofascial pain patients who were not responsive to occlusal splint, behavioral, and physical therapy. Clonazepam was selected for its long duration and its cholinergic/GABA-ergic/serotonergic, anxiolytic, muscle relaxant, and sedative properties. Clonazepam appears to be effective when compared to a placebo. However, caution must be observed with long-term administration of clonazepam because of potential side effects such as depression and liver dysfunction. Indiscriminate administration of clonazepam may be harmful to the patient.", "In a double-blind study, diclofenac sodium (Voltaren), 50 mg two or three times a day, was compared with placebo in 32 patients with pain localized to the temporomandibular joint (TMJ). The patients were allocated into two equally large groups. A visual analog scale was used to estimate the pretreatment degree of pain. The treatment effect was assessed as the frequency of joint and muscle pain and by the patients' own evaluation of improvement. The change in the clinical condition was assessed by tenderness to palpation of the TMJ and masticatory muscles and by mandibular mobility. The frequency of TMJ pain showed a greater reduction in the diclofenac group than in the placebo group, and there was a significant reduction of daily TMJ pain in the diclofenac group. The diclofenac group also showed a significant decrease in tenderness to palpation of the masticatory muscles in comparison with the placebo group. The patients with short duration of pain showed the best response to diclofenac. There was no evidence in this study to prove that diclofenac should be used as a primary treatment of TMJ pain, but it could be used as a complement to other treatments of acute TMJ pain." ]

[ "3553986", "9066350", "2893583", "6150321" ]

[ "Guillain-Barré syndrome: quantitative measurement of plasma exchange therapy.", "Appropriate number of plasma exchanges in Guillain-Barré syndrome. The French Cooperative Group on Plasma Exchange in Guillain-Barré Syndrome.", "Efficiency of plasma exchange in Guillain-Barré syndrome: role of replacement fluids. French Cooperative Group on Plasma Exchange in Guillain-Barré syndrome.", "Beneficial effects of plasma exchange in acute inflammatory polyradiculoneuropathy." ]

[ "A prospective, controlled study with quantitative measurement of hand muscle-force for plasma exchange treatment in acute Guillain-Barré polyradiculitis was done. Of the 29 patients with severe symptoms, every second patient was selected to the plasma exchange group and all others to the control group. The muscle forces increased and CSF protein decreased significantly more in the plasma exchange group than in the control group, but there were no differences in hospitalization or recovery periods.", "Plasma exchange (PE) is the standard treatment in Guillain-Barré syndrome (GBS) patients who have lost the ability to walk. The effect of exchanges before this stage and the optimal number of exchanges for the other patients are still unknown. We randomized 556 GBS patients according to severity and number of exchanges as follows: Zero versus 2 PEs for patients who could walk-with or without aid-but not run, or who could stand up unaided (mild group); 2 versus 4 PEs for patients who could not stand up unaided (moderate group); and 4 versus 6 PEs for mechanically ventilated patients (severe group). In the mild group, 2 PEs were more effective than none for time to onset of motor recovery (median, 4 vs 8 days, respectively). In the moderate group, 4 PEs were more beneficial than 2 for time to walk with assistance (median, 20 vs 24 days) and for 1-year full muscle-strength recovery rate (64% vs 46%). Six PEs were no more beneficial than 4 in the severe cases. Patients with mild GBS on admission should receive 2 PEs. Patients with moderate and severe forms should benefit from 2 further exchanges.", "The goals of this multicenter controlled trial were: (1) to study the short-term effect of plasma exchange in the Guillain-Barré syndrome when applied alone within 17 days of onset of the disease; and (2) to compare two replacement fluids, diluted albumin and fresh frozen plasma (FFP) with regard to efficacy and morbidity. Two hundred twenty patients were included, 111 in the control group, 109 in the plasma exchange group, 57 of whom were assigned to receive albumin and 52 to receive fresh frozen plasma. Treatment consisted of four plasma exchanges of two plasma volumes each, initiated on the day of randomization and repeated on alternate days. Significant short-term benefits appeared in the group that received plasma exchange as demonstrated by the reduction in the proportion of patients who required assisted ventilation after randomization, and the decrease in time before beginning weaning from ventilator, time to onset of motor recovery, and time to walk with and without assistance. No statistically significant difference was found between the group that received albumin and the group that received fresh frozen plasma. Incidents during exchanges and complications related to the plasma exchange were more frequent in patients who received fresh frozen plasma. Plasma exchange is beneficial in Guillain-Barré syndrome when it is carried out early in the course of the disease. Given its risks and the lack of its clear superiority over albumin, however, we recommend that fresh frozen plasma be abandoned in the treatment of Guillain-Barré syndrome.", "The results of a controlled trial in which 38 patients with severe acute inflammatory polyradiculoneuropathy took part indicate that plasma exchange favourably influenced the course of the disease. Significant benefits were seen in time until onset of improvement, course of muscular weakness, improvement in disability grades over the first 2 months, and working capacity after 1 month. Cost-benefit analysis showed that the exchange treatment resulted in net financial savings. The results suggest that plasma exchange may have a role in the treatment of severe acute inflammatory polyradiculoneuropathy." ]

[ "8523357", "8478852", "7837158" ]

[ "The treatment of osteoarthritis of the knee with pulsed electrical stimulation.", "A double-blind trial of the clinical effects of pulsed electromagnetic fields in osteoarthritis.", "The effect of pulsed electromagnetic fields in the treatment of osteoarthritis of the knee and cervical spine. Report of randomized, double blind, placebo controlled trials." ]

[ "The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis (OA) of the knee.\n A multicenter, double blind, randomized, placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients' pain, patients' function, and physician global evaluation of patients' condition, and 6 secondary variables that included duration of morning stiffness, range of motion, knee tenderness, joint swelling, joint circumference, and walking time. Measurements were recorded at baseline and during the 4 week treatment period.\n Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment (p < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one primary efficacy variable in 50% of the active device group, in 2 variables in 32%, and in all 3 variables in 24%. In the placebo group improvement of > or = 50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group (p < 0.05). No statistically significant differences were observed for tenderness, swelling, or walking time.\n The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.", "Further evaluation of pulsed electromagnetic fields (PEMF), which have been observed to produce numerous biological effects, and have been used to treat delayed union fractures for over a decade.\n In a pilot, double-blind randomized trial, 27 patients with osteoarthritis (OA), primarily of the knee, were treated with PEMF. Treatment consisted of 18 half-hour periods of exposure over about 1 month in a specially designed noncontact, air-coil device. Observations were made on 6 clinical variables at baseline, midpoint of therapy, end of treatment and one month later; 25 patients completed treatment.\n An average improvement of 23-61% occurred in the clinical variables observed with active treatment, while 2 to 18% improvement was observed in these variables in placebo treated control patients. No toxicity was observed.\n The decreased pain and improved functional performance of treated patients suggests that this configuration of PEMF has potential as an effective method of improving symptoms in patients with OA. This method warrants further clinical investigation.", "We conducted a randomized, double blind clinical trial to determine the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee and cervical spine.\n A controlled trial of 18 half-hour active or placebo treatments was conducted in 86 patients with OA of the knee and 81 patients with OA of the cervical spine, in which pain was evaluated using a 10 cm visual analog scale, activities of daily living using a series of questions (answered by the patient as never, sometimes, most of the time, or always), pain on passive motion (recorded as none, slight, moderate, or severe), and joint tenderness (recorded using a modified Ritchie scale). Global evaluations of improvement were made by the patient and examining physician. Evaluations were made at baseline, midway, end of treatment, and one month after completion of treatment.\n Matched pair t tests showed extremely significant changes from baseline for the treated patients in both knee and cervical spine studies at the end of treatment and the one month followup observations, whereas the changes in the placebo patients showed lesser degrees of significance at the end of treatment, and had lost significance for most variables at the one month followup. Means of the treated group of patients with OA of the knee showed greater improvement from baseline values than the placebo group by the end of treatment and at the one month followup observation. Using the 2-tailed t test, at the end of treatment the differences in the means of the 2 groups reached statistical significance for pain, pain on motion, and both the patient overall assessment and the physician global assessment. The means of the treated patients with OA of the cervical spine showed greater improvement from baseline than the placebo group for most variables at the end of treatment and one month followup observations; these differences reached statistical significance at one or more observation points for pain, pain on motion, and tenderness.\n PEMF has therapeutic benefit in painful OA of the knee or cervical spine." ]

[ "14651538", "17768157", "9386657", "21094951", "12014386", "18561728", "7616831", "12549803", "10625080", "10586177", "16547381", "9175948", "17937843", "22284563", "16219273", "22089267", "22809601", "17484080", "10974130", "22147286", "18458658", "14700149", "19047225" ]

[ "Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants.", "Comparison of ibuprofen and indometacin for early-targeted treatment of patent ductus arteriosus in extremely premature infants: a randomised controlled trial.", "Comparative evaluation of the effects of indomethacin and ibuprofen on cerebral perfusion and oxygenation in preterm infants with patent ductus arteriosus.", "Efficacy and safety of oral versus intravenous ibuprofen in very low birth weight preterm infants with patent ductus arteriosus.", "Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial.", "Comparison of oral ibuprofen and indomethacin on closure of patent ductus arteriosus in preterm infants.", "Ibuprofen treatment of patent ductus arteriosus.", "Oral ibuprofen and indomethacin for treatment of patent ductus arteriosus in premature infants: a randomized trial at Ramathibodi Hospital.", "Randomized double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus.", "Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus.", "[Comparison of the efficacy of ibuprofen and indomethacin in the treatment of patent ductus arteriosus in prematurely born infants].", "Treatment of patent ductus arteriosus with ibuprofen.", "Comparison of oral ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants.", "Timing of patent ductus arteriosus treatment and respiratory outcome in premature infants: a double-blind randomized controlled trial.", "[Ibuprofen versus indomethacin in the treatment of patent ductus arteriosus in preterm infants].", "High-dose ibuprofen for patent ductus arteriosus in extremely preterm infants: a randomized controlled study.", "[Therapeutic effect of early administration of oral ibuprofen in very low birth weight infants with patent ductus arteriosus].", "Oral Ibuprofen and ductus arteriosus in premature infants: a randomized pilot study.", "A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus.", "Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a randomised controlled trial in extremely low birthweight infants.", "Ibuprofen versus continuous indomethacin in premature neonates with patent ductus arteriosus: is the difference in the mode of administration?", "A comparison of oral ibuprofen and intravenous indomethacin for closure of patent ductus arteriosus in preterm infants.", "Randomized pilot study comparing oral ibuprofen with intravenous ibuprofen in very low birth weight infants with patent ductus arteriosus." ]

[ "Patent ductus arteriosus (PDA) is commonly found in very low-birthweight (VLBW) infants. The presence of respiratory distress syndrome (RDS) is also associated with increased frequency of significant PDA. Intravenous indomethacin has been used to treat and to prevent PDA in premature infants since 1976. However, concern remains regarding the safety of indomethacin, which affects renal, gastrointestinal and cerebral perfusion. Intravenous ibuprofen has recently been used to treat and to prevent PDA premature infants with PDA without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. The aim of the present study is to compare intravenous ibuprofen and indomethacin with regard to efficacy and safety for the early treatment of PDA in preterm infants.\n A total of 63 preterm infants with RDS who had a birthweight of < or =1500 g and gestational age of < or =32 weeks, were enrolled in the present study. All patients were treated with nasal continuous positive airway pressure with additional oxygen supply in inspired air>30%, or with mechanical ventilation. The patients' serum platelet counts were>100,000/uL, and serum creatinine values were <1.5 mg/dL. There were no 3-4 grade intraventricular hemorrhages before randomization, and all patients were aged 2-7 days and had echo-cardio-graphic evidence of significant PDA. Patients were randomized into two groups: the first group of neonates (group A, n = 32) received intravenous ibuprofen lysine 10 mg/kg, followed by 5 mg/kg after 24 and 48 h; the second group (group B, n = 31) received intravenous indomethacin 0.2 mg/kg every 12 h for three doses.\n Patent ductus arteriosus closed in 27 patients from the ibuprofen group (84.4%) and in 25 patients from the indomethacin group (80.6%). PDA reopened in three patients from the ibuprofen group (9.4%) and in three patients from the indomethacin group (9.7%). One patient in the ibuprofen group and two patients in the indomethacin group required ductal ligation. Serum creatinine and blood urea nitrogen (BUN) concentrations were lower in the ibuprofen group than in the indomethacin group. Urine output and creatinine clearance values were higher in the ibuprofen group than in the indomethacin group.\n Ibuprofen therapy is as efficacious as indomethacin for the treatment of PDA in preterm infants. Infants treated with ibuprofen have higher creatinine clearance and urine output and lower serum creatinine and BUN values than infants treated with indomethacin.", "To date there is no firm conclusion as to the efficacy and safety of ibuprofen compared with indometacin for patent ductus arteriosus (PDA) closure in extremely premature infants.\n To conduct a randomised controlled trial to better address this problem.\n 119 infants (gestational age < or =28 weeks) with respiratory distress syndrome and PDA confirmed by echocardiography were randomly assigned to receive either indometacin (0.2 mg/kg) or ibuprofen (10 mg/kg), starting at <24 hours of life, followed by half these first doses within 48 hours at 24-hour intervals if indicated by echocardiographic PDA flow pattern.\n The PDA closure rate and the doses of drug (mean (SD)) were similar in both groups: 53/60 (88.3%) and 1.9 (1.5) mg/kg in infants given ibuprofen, and 52/59 (88.1%) and 1.9 (1.7) mg/kg in infants given indometacin. No significant difference was found in the numbers of infants requiring surgical ligation, and the levels of post-treatment serum creatinine and urea nitrogen between the two groups. Although not significantly different, more infants (9/59 (15.3%)) treated with indometacin tended to develop oliguria (<1 ml/kg/h) than those treated with ibuprofen (4/60 (6.7%)). There were no significant differences in side effects or complications between the two groups.\n Ibuprofen is as effective as indometacin for the early-targeted PDA treatment in extremely premature infants, without increasing the incidence of complications. When the echocardiographic PDA flow pattern was used as a guide for PDA treatment, fewer doses of drugs were needed to achieve acceptable closing rates.", "To compare the effects on cerebral perfusion and oxygenation of intravenous ibuprofen and indomethacin as treatment for patent ductus arteriosus in preterm infants.\n Sixteen infants receiving mechanical ventilation (< 31 weeks gestation) with patent ductus arteriosus received either 0.2 mg/kg indomethacin (n = 8) or 10 mg/kg ibuprofen (n = 8) infused over 1 minute. Near-infrared spectroscopy was used to measure changes in cerebral blood volume and in oxidized cytochrome oxidase concentration. Cerebral blood flow velocity in the pericallosal artery was measured using Doppler ultrasonography.\n Indomethacin caused a significant reduction of CBV (maximal changes in cerebral blood volume: -320 +/- 171 microL/100 gm) and, in four of eight patients, a fall in oxidized cytochrome oxidase concentration (maximal change in oxidized cytochrome oxidase concentration in the eight patients: -0.68 +/- 0.98 mumol/L, NS). Cerebral blood flow velocity fell significantly. Ibuprofen caused no significant reduction of cerebral blood volume, oxidized cytochrome oxidase concentration, or cerebral blood flow velocity, whereas a significant increase of cerebral blood volume (+207 +/- 200 microL/100 gm) was observed after 60 minutes. Ductus closure was seen in six of eight infants after the first dose of indomethacin and in five of eight infants after the first dose of ibuprofen. The therapeutic cycle involved administration of a second and third dose, provided no side effects occurred. Treatment was effective in all infants.\n Compared with indomethacin, treatment with ibuprofen does not significantly reduce cerebral perfusion and oxygen availability; the observed increase in cerebral blood volume requires further investigation.", "To compare oral ibuprofen with intravenous ibuprofen for closure of patent ductus arteriosus in very low birth weight (VLBW) preterm infants.\n In a prospective, randomized study, 102 VLBW preterm infants with patent ductus arteriosus received either intravenous or oral ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours. The success rate and evaluation of renal tolerance using cystatin-C were the major outcomes.\n Patent ductus arteriosus closure rate was significantly higher with oral ibuprofen (84.6% versus 62%) after the first course of the treatment (P = .011). The cystatin-C level increased significantly after treatment in the oral group (P = .001), but did not change with intravenous ibuprofen (P = .4).\n Oral ibuprofen is more effective than intravenous ibuprofen for ductal closure in VLBW infants. The increase in the cystatin-C level with oral treatment suggests that patients with borderline renal function should be evaluated and followed closely.\n Copyright © 2011 Mosby, Inc. All rights reserved.", "Indomethacin (INDO) and, more recently, ibuprofen (IBU) have been used to treat haemodynamically significant patent ductus arteriosus (PDA) in preterm infants. Both are cyclo-oxygenase blockers, but seem to have a different influence on regional circulation. In a prospective, randomised, controlled study, we compared INDO and IBU with regard to efficacy and safety for the early non-invasive treatment of PDA. Doppler echocardiography was used to study 232 preterm infants (gestational age 23-34 weeks) with respiratory distress syndrome of whom 175 had persistent, haemodynamically significant PDA at 48-72 h of life. They were randomised to receive three intravenous doses of either INDO (0.2 mg/kg, at 12 h intervals) or IBU (a first 10 mg/kg dose followed by two doses of 5 mg/kg at 24 h intervals), recording rate of ductal closure, need for additional treatment, side-effects and clinical course. The efficacy of the pharmacological treatment was similar in the two groups (56/81, 69% INDO; 69/94, 73% IBU). Patients treated with INDO showed a significant increase in serum creatinine (89 +/- 24 versus 82 +/- 20 mmol/l, P = 0.03) and a near-significant tendency for a lower fractional excretion of sodium (3 +/- 3 versus 4 +/- 2%, P = 0.08); moreover, 12/81 (15%) INDO patients versus 1/94 (1%) IBU patients became oliguric (< 1 ml/kg per h) during treatment (P = 0.017).\n Our findings confirm that, by comparison with indomethacin, ibuprofen has fewer effects on renal function in terms of urine output and fluid retention, with much the same efficacy and safety in closing patent ductus arteriosus in preterm infants with respiratory distress syndrome. In particular, no increased incidence of intracranial haemorrhage was observed after ibuprofen treatment.", "Although intravenous indomethacin and ibuprofen are widely used for closure of patent ductus arteriosus in premature infants, these formulations are unavailable in the Islamic Republic of Iran. In this study of the therapeutic effects of oral treatments, 20 preterm infants were randomized to oral ibuprofen (1 x 10 mg/kg, then 2 x 5 mg/kg at 24-hour intervals) or oral indomethacin (3 x 0.2 mg/kg at 24-hour intervals). Complete ductal closure was seen in 7/10 of the indomethacin and 8/10 of the ibuprofen group. The difference was not significant. There was no reopening after the ductal closure during the hospital stay or in the follow-up visits in either group and no excessive increases in the blood urea nitrogen or serum creatinine levels were observed.", "nan", "Ibuprofen given intravenously to premature newborn infants is a proven treatment for patent ductus arteriosus (PDA). The efficacy of ibuprofen is comparable to indomethacin in many clinical trials with fewer renal side effects. However, the intravenous form of ibuprofen is not available in Thailand, whereas, the oral suspension form is widely used for antipyretic treatment in children. Therefore, the authors investigated the possibilities of using oral ibuprofen for the treatment of PDA in premature newborn infants.\n To assess whether oral ibuprofen at 10 mg/kg/dose daily for 3 days was as effective as indomethacin to treat symptomatic PDA in premature infants and to compare the side effects of oral ibuprofen to indomethacin.\n Eighteen premature infants with gestational ages less than 34 weeks born at Ramathibodi Hospital who developed symptomatic PDA were randomly assigned to receive three doses of either indomethacin (oral or intravenous administration 0.2 mg/kg/dose for three doses given at 12 hourly intervals or oral ibuprofen (10 mg/kg/dose for three doses given at 24 hourly intervals). The rates of ductal closure, infants' clinical courses, side effects and complications were recorded.\n Birth weight, gestational age, gender, age onset and number of infants who had respiratory distress syndrome were similar in both groups, PDA was closed in 7 of 9 infants given ibuprofen (78%) and in 8 of 9 infants given indomethacin (89%) (p > 0.05). The mean plasma concentration of ibuprofen was 28.05 microg/ml at 1 hour after the third dose. Neonates in the ibuprofen group had more urine output. However, the increment of serum BUN and creatinine were not significantly different in both groups. There were no significant differences in duration of ventilator support as well as number of patients with bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis and death in both groups.\n Oral ibuprofen therapy is as effective as indomethacin for the treatment of PDA in premature infants and seems to have fewer renal side effects.", "A prospective randomized controlled trial was performed to compare the effects of ibuprofen with indomethacin on cerebral hemodynamics measured using near infrared spectroscopy in preterm infants during treatment for patent ductus arteriosus. Infants were randomly assigned to three intravenous doses of either indomethacin (0.20-0.25 mg/kg, 12 hourly) or ibuprofen (5-10 mg/kg, 24 hourly) and also received a dose of saline. The primary end points of the study were the effects of the first dose on cerebral blood flow (CBF) and cerebral blood volume. Fifteen infants received indomethacin and 18 received ibuprofen. The group mean (SD) values for CBF (mL x 100 g(-1) x min(-1)) before and after the first dose of indomethacin were 13.6 (4.1) and 8.3 (3.1), respectively, the change being significant (p<0.001). In contrast, no significant changes in CBF were observed with the first dose of ibuprofen, the respective before and after values being 13.3 (3.2) and 14.9 (4.7) mL x 100 g(-1) x min(-1). The median (interquartile range) value for change in cerebral blood volume (mL/100 g) after the first dose in the indomethacin group was -0.4 (-0.3 to -0.6) and in the ibuprofen group was 0.0 (0.1 to -0.1), the difference between the two groups being significant (p<0.001). Cerebral oxygen delivery changed significantly after the first dose in the indomethacin group but not in the ibuprofen group. Significant reductions in CBF, cerebral blood volume, and cerebral oxygen delivery also occurred after the 24-h dose of indomethacin, but there were no significant changes after the 48-h dose of saline in the indomethacin group or after the 24- and 48-h doses of ibuprofen. The patent ductus arteriosus closure rates after indomethacin and ibuprofen were 93 and 78%, respectively. We conclude that ibuprofen, unlike indomethacin, has no adverse effects on cerebral hemodynamics and appears to mediate patent ductus arteriosus closure.", "To evaluate the effect of intravenous ibuprofen and indomethacin for treatment of patent ductus arteriosus (PDA) on mesenteric and renal blood flow velocity in preterm infants.\n Seventeen mechanically ventilated preterm infants (<33 weeks' gestation) with PDA received either 0.2 mg/kg indomethacin (n = 8) or 10 mg/kg ibuprofen (n = 9), infused over 15 minutes. Mesenteric and renal blood flow velocity were measured by using Doppler ultrasonography.\n Indomethacin caused a significant reduction in mesenteric and renal blood flow velocity 30 minutes after drug administration; mesenteric and renal blood flow velocity did not return to the pretreatment values by 120 minutes. Ibuprofen did not alter blood flow 30 minutes after treatment, and blood flow increased 120 minutes after treatment. Mesenteric and renal blood flow velocity changes were significantly different between the 2 treatment groups.\n Compared with indomethacin, ibuprofen did not significantly reduce mesenteric and renal blood flow velocity.", "To assess the efficacy and safety of early treatment with ibuprofen (IBU) and indomethacin (INDO) of patent ductus arteriosus in preterm infants. Prospective study with blind trial.\n We studied 35 preterm infants (19 treated with INDO, 16 IBU) (gestation age <33 and birth weight < 1500 g), who had an echocardiographicaly confirmed patent ductus arteriosus (PDA). The infants were randomly assigned in two groups to receive INDO (0.2-0.2-0.2 mg/kg) or IBU (10-5-5 mg/kg) in first 72 hours of life (average 2 days of life). The rate of ductal closure, the need for surgical ligation, side effects, complications, and the infants clinical course were recorded.\n The rate of ductal closure was similar in two groups (15/19, 80% INDO; 11/16, 69% IBU). 27 infants (15 INDO, 12 IBU) were treated per protocol (3 doses). For remaining 8 infants we stopped treatment due to side effects. In the IBU group the main reason to stop treatment was pulmonary hemorrhage (3/16, 19%) and pulmonary hypertension (1/16, 6%), but in the INDO group it was increased serum creatinine and urea nitrogen concentrations (3/19, 16%) and intraventricular hemorrhage (IVH IV) grade (1/19 5%). In IBU group vs. INDO, urine output decreased (p=0.02), but never before below the level of oliguria (defined as urine output below 1 ml/kg/h). Risk of necrotizing enterocolitis (NEC) grade II was similar in two groups, but only patients treated with INDO showed intestinal perforations (p=ns). They received also postnatal hydrocortisone and we showed near significant tendency (p=0.06) for intestinal perforation in patients treated with INDO and hydrocortisone. There were no significant differences with respect to IVH or PVL between the groups.\n The efficacy of ibuprofen and indomethacin in PDA treatment is similar. Treatment of ibuprofen and indomethacin may cause transient renal dysfunction: diminished urine output and increase of serum creatinine and urea nitrogen concentrations. Indomethacin, especially with concomitant treatment with hydrocortisone, may increase the risk of intestinal perforation.", "To evaluate the efficiency and side effects of ibuprofen for the early treatment of patent ductus arteriosus (PDA) and compare it with indomethacin.\n Forty preterm infants with gestational ages of less than 33 weeks, with respiratory distress syndrome (RDS) and echocardiographically confirmed PDA, were randomly assigned at days 2 to 3 of life to receive either intravenous indomethacin 3 x 0.2 mg/kg at 12 hour intervals or intravenous ibuprofen 1 x 10 mg/kg, followed by 5 mg/kg 24 and 48 hours later.\n PDA closed in 15 of 20 patients from the indomethacin group (75%) and in 16 of 20 (80%) from the ibuprofen group. Seven patients (three indomethacin, four ibuprofen) required a second treatment with indomethacin and in five (three in the indomethacin group and two in the ibuprofen group) the duct was ultimately ligated. Ibuprofen patients had a better urinary output and showed no increase in serum creatinine concentrations compared with the indomethacin group. Ibuprofen was not associated with any other side effect.\n Ibuprofen treatment seems to be as efficient as indomethacin in closing PDA on the third day of life in preterm infants with respiratory distress syndrome and seems to have fewer renal side effects.", "Intravenous indomethacin is the conventional treatment for patent ductus arteriosus (PDA) in preterm infants; however its use is associated with various side effects such as oliguria, gastrointestinal bleeding and reduction of cerebral perfusion. Intravenous ibuprofen has recently been used to treat PDA in preterm infants without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. Intravenous forms of indomethacin and ibuprofen are not available in Iran. This study aimed to examine and compare the efficacy and safety of oral ibuprofen and oral indomethacin for the treatment of PDA in preterm infants.\n Thirty-six infants (gestational age less than 34 weeks) who had echocardiographically confirmed PDA were enrolled in this study. The patients were randomly administered with three oral doses of either indomethacin (0.2 mg/kg, at an interval of 24 hrs) or ibuprofen (a first dose of 10 mg/kg, followed at an interval of 24 hrs by two doses of 5 mg/kg each) (n=18 each group). The rate of ductal closure, side effects, complications, and the infants' clinical course were recorded.\n The ductus was closed in all of 18 patients (100%) in the ibuprofen group and in 15 (83.3%) patients in the indomethacin group (P > 0.05). There were no significant differences in the levels of serum blood urea nitrogen and creatinine between the two groups before and after treatment. Necrotizing enterocolitis (NEC) occurred in 3 patients in the indomethacin group and none in the ibuprofen group (P < 0.05). The survival rate at 1 month after treatment was 94% (17/18) in both groups. One infant in the ibuprofen group died from sepsis and one in the indomethacin group died as a result of NEC.\n Oral ibuprofen is as effective as oral indomethacin for the treatment of PDA in preterm infants. Oral ibuprofen therapy is associated with a lower incidence of NEC.", "To determine whether \"early\" ibuprofen treatment, at the onset of subtle patent ductus arteriosus (PDA) symptoms, would improve respiratory outcome in premature infants compared with \"expectant\" management, with ibuprofen treatment only when the PDA becomes hemodynamically significant (HS).\n We conducted a randomized double-blind controlled trial of infants with gestational ages 23 to 32 weeks and birth weights 500 to 1250 g who had echocardiography for subtle PDA symptoms (metabolic acidosis, murmur, bounding pulses). Infants were then randomized to \"early\" treatment (blinded ibuprofen; n = 54) or \"expectant management\" (blinded placebo, n = 51). If the PDA became HS (pulmonary hemorrhage, hypotension, respiratory deterioration), infants received open label ibuprofen. Infants with HS PDA at enrollment were excluded from the study. Respiratory outcomes and mortality and major morbidities were determined.\n \"Early\" treatment infants received ibuprofen at median age of 3 days; infants in the \"expectant group\" in whom HS symptoms developed (20%) received ibuprofen at median of 11 days. A total of 49% of \"expectant\" infants never required ibuprofen or ligation. No significant differences were found in the primary outcome (days on oxygen [O(2)] during the first 28 days), death, O(2) at 36 weeks, death or O(2) at 36 weeks, intestinal perforation, surgical necrotizing enterocolitis, grades III and IV intracranial hemorrhage, periventricular leukomalacia, sepsis or retinopathy of prematurity.\n Infants with mild signs of PDA do not benefit from early PDA treatment compared with delayed treatment.\n Copyright © 2012 Mosby, Inc. All rights reserved.", "Persistent patent ductus arteriosus (PDA) is a common entity in preterm infants. The most commonly used pharmacological treatment to close the ductus is indomethacin but it can affect cerebral, renal and mesenteric blood flow. Ibuprofen has recently been shown to be effective in closing PDA with fewer hemodynamic effects. In this study we compared the safety and efficacy of ibuprofen and indomethacin in the treatment of PDA in preterm infants.\n A randomized trial was performed. Premature infants with symptomatic PDA confirmed by echocardiography in the first week of life and who required respiratory support were included. The patients were randomly assigned to receive either intravenous indomethacin or ibuprofen. The rate of ductal closure, need for additional treatment, complications, and clinical course were evaluated.\n Twenty-four patients were treated with indomethacin and 23 with ibuprofen. The clinical characteristics before treatment were similar in both groups. Both treatments were effective in closing PDA (87.5% in the indomethacin group and 82.6% in the ibuprofen group). The two cohorts did not differ in the rate of reopening, need for a second pharmacologic treatment, or surgical ductal ligation. No patient in the ibuprofen group developed gastrointestinal adverse effects, but two infants in the indomethacin group had isolated bowel perforation and one had necrotizing enterocolitis. Transient renal dysfunction developed in seven patients (29%) in the indomethacin group versus two (9%) in the ibuprofen group. Transient renal insufficiency was found in one patient in the indomethacin group and in none in the ibuprofen group. The rate of other complications was similar in both groups.\n In our trial ibuprofen was as effective as indomethacin in closing PDA. No significant differences were found in the incidence of complications but fewer renal complications and no gastrointestinal complications were found in the ibuprofen group.", "Our aim was to assess the hypothesis that a high-dose regimen of ibuprofen is more effective than the standard-dose regimen in closing patent ductus arteriosus (PDA) without increasing adverse effects. Infants of gestational age <29 weeks, with respiratory distress syndrome (RDS) and echocardiographic evidence of significant PDA at 12-24 h of life, were randomized to receive a standard (10-5-5 mg/kg/day) or high-dose (20-10-10 mg/kg/day) course of ibuprofen. We studied 70 infants, 35 of whom received the standard dose of ibuprofen and the other 35 the high dose. Of the infants treated with the standard-dose regimen, 37% had persistent PDA as compared with 14% of those treated with the high-dose regimen (P = 0.03). No differences in the occurrence of adverse effects were observed between the two groups. The high-dose ibuprofen regimen is more effective than the standard-dose regimen in closing PDA in preterm infants <29 weeks of gestation without increasing the adverse effect rate.", "To study therapeutic effect and safety of early administration of oral ibuprofen in very low birth weight infants (VLBWIs) with patent ductus arteriosus (PDA).\n A total of 64 symptomatic VLBWIs (within 24 hours after birth) with PDA confirmed by bedside Color Doppler ultrasound were randomly divided into two groups: treatment and control (n=32 each). The treatment group was orally administered ibuprofen within 24 hours after birth at 10 mg/kg, followed 24 hours later by a second dose of 5 mg/kg and 48 hours later by a third dose of 5 mg/kg. The control group was treated with placebo (normal saline) at 1 mL/kg, followed 24 hours later by a second dose of 0.5 mL/kg and 48 hours later by a third dose of 0.5 mL/kg. The therapeutic efficacies and adverse effects in both groups were observed.\n The treatment group showed a significantly higher closure rate of ductus arterious than the control group after one course of treatment (84% vs 41%; P<0.01). The incidence rates of periventricular leukomalacia and bronchopulmonary dysplasia were significantly lower in the treatment group than in the control group (P<0.05). The duration of mechanical ventilation and mean hospitalization time were significantly shorter in the treatment group than in the control group (P<0.05). There were no significant differences in the incidence rates of intraventricular hemorrhage, early pulmonary hemorrhage and necrotizing enterocolitis between the two groups (P>0.05). No obvious adverse effects were observed in both groups.\n Early administration of oral ibuprofen for treatment of PDA in VLBWIs can decrease the incidence rates of some early complications and shorten hospitalization time, but causes no significant adverse effects.", "The purpose of this study was to evaluate the feasibility of the use oral ibuprofen suspension (OIS) in the treatment of patent ductus arteriosus (PDA) in premature infants. Premature infants (</= 35 weeks) age 2 to 7 days who suffered from respiratory distress and had been diagnosed with PDA were included in this study. Color Doppler echocardiography (ECHO) was used to measure the internal ductal diameter, pressure gradient, and the ratio of left atrial to aortic root diameters (La/Ao). Infants were randomly assigned to one of two groups: group I received three doses of intravenous (IV) indomethacin (0.2 mg/kg at 12-hour intervals) and group O received an initial dose of OIS (10 mg/kg), followed by two doses of 5 mg/kg each, after 24 and 48 hours. A follow-up ECHO was done after treatment by the same pediatric cardiologist who was blinded to the assignment of the study groups. Changes in blood platelet count, hematocrit, blood urea nitrogen, and creatinine were compared between groups. In total, 78 premature infants were screened: 21 had been diagnosed with PDA. Infants in group I (n = 9) and group O (n = 12) did not differ in birthweight (1884 +/- 485 versus 1521 +/- 398 g [mean +/- SD]; P = 0.13), gestational age (32.9 +/- 1.6 versus 31.2 +/- 2.5 weeks; P = 0.07), internal diameter of PDA (2.3 +/- 0.5 versus 2.1 +/- 0.5 mm; P = 0.34), pressure gradient across PDA (12.83 +/- 6.46 versus 11.11 +/- 4.5 mm Hg; P = 0.48), and La/Ao ratio (1.26 +/- 0.21 versus 1.17 +/- 0.12; P = 0.25). Closure of PDA was achieved in 78% (seven of nine) of infants in group I and in 83% (10 of 12) of infants in group O. Comparisons of laboratory changes following treatment in group I and group O were as follows: decrease in hematocrit (-6.5 +/- 6.6 versus -1.2 +/- 4.2; P = 0.04) and in platelet count (-54 +/- 67 versus -1 +/- 53 x 10 (3)/muL; P = 0.24), and increase in blood urea nitrogen (16.4 +/- 16.4 versus 2.1 +/- 17.4 mg/dL; P = 0.06) and serum creatinine (0.12 +/- 0.22 versus -0.06 +/- 0.19 mg/dL; P = 0.13). Two infants in group I had severe pulmonary hemorrhage, whereas there were none in the group O. Oral ibuprofen could be an easy-to-administer and efficacious alternative in the treatment of PDA.", "Indomethacin is the conventional treatment for hemodynamically important patent ductus arteriosus in preterm infants. However, its use is associated with various side effects. In a prospective study, we compared ibuprofen and indomethacin with regard to efficacy and safety for the early treatment of patent ductus arteriosus in preterm infants.\n We studied 148 infants (gestational age, 24 to 32 weeks) who had the respiratory distress syndrome and an echocardiographically confirmed, hemodynamically important patent ductus arteriosus. The infants were randomly assigned at five neonatal intensive care centers to receive three intravenous doses of either indomethacin (0.2 mg per kilogram of body weight, given at 12-hour intervals) or ibuprofen (a first dose of 10 mg per kilogram, followed at 24-hour intervals by two doses of 5 mq per kilogram each), starting on the third day of life. The rate of ductal closure, the need for additional treatment, side effects, complications, and the infants' clinical course were recorded.\n The rate of ductal closure was similar with the two treatments: ductal closure occurred in 49 of 74 infants given indomethacin (66 percent), and in 52 of 74 given ibuprofen (70 percent) (relative risk, 0.94; 95 percent confidence interval, 0.76 to 1.17; P=0.41). The numbers of infants who needed a second pharmacologic treatment or surgical ductal ligation did not differ significantly between the two groups. Oliguria occurred in 5 infants treated with ibuprofen and in 14 treated with indomethacin (P=0.03). There were no significant differences with respect to other side effects or complications.\n Ibuprofen therapy on the third day of life is as efficacious as indomethacin for the treatment of patent ductus arteriosus in preterm infants with the respiratory distress syndrome and is significantly less likely to induce oliguria.", "To compare the efficacy and safety of oral versus intravenous ibuprofen for the pharmacological closure of patent ductus arteriosus (PDA) in less mature preterm infants.\n Prospective, randomised controlled study.\n Tertiary neonatal intensive care unit.\n The study enrolled 80 preterm infants with gestational age ≤28 weeks, birth weight <1000 g, postnatal age 48 to 96 h, and had echocardiographically confirmed significant PDA. Seventy extremely low birthweight (ELBW) preterm infants received either intravenous or oral ibuprofen randomly as an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h.\n The success rate and the safety of the drugs in ELBW preterm infants were the major outcomes.\n PDA closure rate was significantly higher with oral ibuprofen (83.3% vs 61.7%) after the first course of the treatment (p=0.04). Although the primary closure rate was marginally higher in the oral ibuprofen group, the need for a second course of ibuprofen during the whole hospitalisation was similar between groups: 11 of 36 in oral versus 15 of 34 in intravenous groups (p=0.24) because of a higher reopening rate in the oral group. In addition to no increase in side effects with oral ibuprofen use, the need for postnatal steroid use for chronic lung disease was significantly lower in oral ibuprofen group (p=0.001).\n Oral ibuprofen is as effective as intravenous ibuprofen for PDA closure even in ELBW infants.", "Ibuprofen has been proposed as a preferential alternative to indomethacin in treating patent ductus arteriosus (PDA), because it is purported to have less renal, mesenteric, and cerebral vasoconstrictive effects. However, short and long-term safety concerns regarding ibuprofen remain. Continuous slow infusion of indomethacin also eliminates peripheral vasoconstriction and may thus offer similar benefits to ibuprofen without safety concerns. In this study, our objective was to show that treating a PDA with continuous indomethacin is similar to ibuprofen in its effect on urine output, renal function, and blood flow velocities in the renal, superior mesenteric, and anterior cerebral arteries. Sixty four prematures with PDA were randomly, prospectively assigned to either treatment. PDA closure rates were similar (74 versus 59%; p = 0.123). Nine indomethacin-treated babies (29%) versus twelve ibuprofen babies (38%) underwent repeated therapy (p = 0.656). Two indomethacin and four ibuprofen infants required surgical ligation (p = 0.672). Serum creatinine, oliguria, estimated glomerular filtration rate, and fractional excretion of sodium were similar in both groups, as were blood flow velocity parameters in the vessels studied. There were no differences in necrotizing enterocolitis, BPD, intraventricular hemorrhage, and/or retinopathy of prematurity. In conclusion, PDA treatment with either continuous indomethacin infusion or ibuprofen was equally devoid of adverse renal effects and/or peripheral vasoconstrictive effects.", "Indomethacin is widely accepted as the treatment for patent ductus arteriosus (PDA) in preterm infants but it has various side effects. Ibuprofen is the alternative treatment and believed to be less likely to induce side effects.\n To compare efficacy and side effects of ibuprofen versus indomethacin treatment for symptomatic patent ductus arteriosus (PDA) in preterm infants.\n The authors studied 30 infants (gestational age < or = 35 weeks, aged < or = 10 days) who were diagnosed as having symptomatic PDA confirmed by echocardiogram. The infants were randomly assigned to receive three intravenous doses of indomethacin given at 12-hour intervals or three doses of ibuprofen given at 24-hour intervals, starting within ten days of life. The demographic data, rate of clinical closure, need for additional treatment, side effects, complications and the infants' clinical course were recorded within 28 days.\n The rate of ductal closure was similar with the two treatment regimes. Ductal closure occurred in 7 of 15 infants given ibuprofen (46.67%) and 10 of 15 infants given indomethacin (66.67%). (Relative risk 0.669; 95% confidence interval, 0.328 to 1.364; p = 0.462) The number of infants who needed a second pharmacologic treatment was not significantly different between the two groups, (6 cases in the ibuprofen group, 5 cases in the indomethacin group) but surgical ligation was performed in two cases in the indomethacin group. There was a significant difference in using the diuretic drug (furosemide) in the indomethacin group (11 cases), compared to the ibuprofen group (3 cases), (p = 0.009). More cases of necrotizing enterocolitis were seen in the indomethacin group (66.67% compared to 40% in the ibuprofen group) but there was no statistically significant difference.\n Ibuprofen has the same efficiency as indomethacin for the treatment of symptomatic patent ductus arteriosus in preterm infants and less likely to induce necrotizing enterocolitis and renal toxicity than indomethacin.", "We conducted a prospective, randomized, single-masked pilot study with the principal aim of comparing efficacy and tolerance between oral and intravenous ibuprofen in early closure of patent ductus arteriosus in very low birth weight infants. The possibility of ductal closure with only 1 or 2 doses of treatment was a secondary objective.\n Sixty-four very low birth weight patients with echocardiographically confirmed patent ductus arteriosus and respiratory distress were studied. The patients were randomly assigned to receive either oral (group O, n=32) or intravenous (group I, n=32) ibuprofen starting on the third day of life. After the first dose of treatment in both groups, echocardiographic evaluation was performed to determine the need for a second or third dose. The rate of ductal closure, adverse effects, complications, and the patient's clinical course were recorded.\n In each group, 24 (75%) patients were born after 28 weeks' gestation. The rate of ductal closure tended to increase in group O (84.3% vs 62.5%). Closure of the ductus was obtained after 1 or 2 doses of treatment in 19 (70.3%) of 27 patients in group O and 14 (70%) of 20 patients in group I. The adverse effects were increased in group I (31.2% vs 9.3%). There were no significant differences with respect to complications during the stay. Adverse effects were significantly fewer when closure was achieved after an incomplete course of treatment (23.1% vs 76.9%).\n In very low birth weight infants, the rate of early ductal closure with oral ibuprofen is at least as good as with the intravenous route. Ductal closure may be obtained with an incomplete course of ibuprofen. Oral ibuprofen is associated with fewer adverse effects. However, a larger sample is needed for more definitive conclusions." ]

[ "11160464", "14966716", "8619521", "9869251", "11990874", "9921849" ]

[ "Controlled randomised crossover trial of the effects of physiotherapy on mobility in chronic multiple sclerosis.", "The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis.", "Impact of aerobic training on fitness and quality of life in multiple sclerosis.", "A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study.", "Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis.", "Physical rehabilitation has a positive effect on disability in multiple sclerosis patients." ]

[ "To determine whether physiotherapy can improve mobility in chronic multiple sclerosis and whether there is a difference between treatment at home and as a hospital outpatient?\n A randomised controlled crossover trial was undertaken in patients with chronic multiple sclerosis who had difficulty walking and were referred from neurology clinics: allocation was to one of six permutations of three 8 week treatment periods separated by 8 week intervals: treatments consisted of physiotherapy at home, as an outpatient, or \"no therapy\". The main outcome measures were based on independent assessments at home and included mobility related disability (primary outcome: the Rivermead mobility index), gait impairments, arm function, mood, and subjective patient and carer ratings. Therapy was assessed by recording delivery, achievement of set targets, patient and carer preference, and cost.\n On the Rivermead mobility index (scale 0-15) (primary outcome) there was a highly significant (p<0.001) treatment effect of 1.4-1.5 units favouring hospital or home based therapy over no therapy: this was supported by other measures of mobility, gait, balance, and the assessor's global \"mobility change\" score: there was no major difference between home and hospital. Carers preferred home treatment but neither they nor patients discerned greater benefit there. Estimated costs of home physiotherapy were 25 pounds/session and those at hospital were 18 pounds (including 7 pounds patient travel costs).\n A course of physiotherapy is associated with improved mobility, subjective wellbeing, and improved mood in chronic multiple sclerosis compared with no treatment but benefit may only last a few weeks: there is little to choose between home and hospital based therapy but the first is more costly, mainly due to skilled staff travelling time.", "To examine the effects of an 8-week home-based resistance exercise program on balance, power, and mobility in adults with multiple sclerosis.\n Experimental group design.\n General community.\n Twenty-nine women (age, 50.3+/-8.5 y) and 8 men (age, 51.1+/-7.1 y) were stratified by disability level and age and were randomized into exercise (n=19) and control (n=17) groups.\n The exercise group had lower-extremity resistance training 3 times a week. The control group maintained current level of physical activity.Main outcome measures Primary outcome measures included balance, as measured by anteroposterior sway, mediolateral sway, and sway velocity using the AccuSway(PLUS) force platform; mobility as assessed with the Up and Go test; and leg power as assessed with the Leg Extensor Power Rig.\n Leg extensor power improved significantly in the exercise group (pretest, 3.19+/-1.36 W/kg; posttest, 3.95+/-1.23 W/kg; P=.004), although measures of balance and mobility did not change.\n The home-based resistance program was well tolerated by participants and offered a practical means to improve leg extensor power in a short period of time.", "Fifty-four multiple sclerosis (MS) patients were randomly assigned to exercise (EX) or nonexercise (NEX) groups. Before and after 15 weeks of aerobic training, aspects of fitness including maximal aerobic capacity (VO2max), isometric strength, body composition, and blood lipids were measured. Daily activities, mood, fatigue, and disease status were measured by the Profile of Mood States (POMS), Sickness Impact Profile (SIP), Fatigue Severity Scale (FSS), and neurological examination. Training consisted of 3 x 40-minute sessions per week of combined arm and leg ergometry. Expanded Disability Status Scale (EDSS) scores were unchanged, except for improved bowel and bladder function in the EX group. Compared with baseline, the EX group demonstrated significant increases in VO2max, upper and lower extremity strength, and significant decreases in skinfolds, triglyceride, and very-low-density lipoprotein (VLDL). For the EX group, POMS depression and anger scores were significantly reduced at weeks 5 and 10, and fatigue was reduced at week 10. The EX group improved significantly on all components of the physical dimension of the SIP and showed significant improvements for social interaction, emotional behavior, home management, total SIP score, and recreation and past times. No changes were observed for EX or NEX groups on the FSS. Exercise training resulted in improved fitness and had a positive impact on factors related to quality of life.", "To use a pilot study to compare two physiotherapy approaches to improve walking in patients with gait disturbance due to multiple sclerosis (MS).\n Patients were assessed and then randomly assigned to one of two groups using a block randomization technique. They were treated by the research physiotherapist for a minimum of 15 treatments over a 5-7-week period and then reassessed by an independent therapist one week after treatment.\n Both assessment and treatment were undertaken at a specialist rehabilitation centre.\n Outpatients with clinically stable MS (chronic progressive or relapsing-remitting types) who were referred for physiotherapy to improve their mobility.\n Comparison was between a facilitation (impairment-based) approach and a task-oriented (disability-focused) approach.\n Mobility was assessed using four measures: the 10-metre timed walk, the Rivermead Mobility Index, stride length and the Rivermead Visual Gait Assessment. Balance was assessed using the Berg Balance Test.\n Twenty-three patients were entered, and 10 in each group completed the study. The groups were similar on all measured items both before and after treatment. There was no significant difference in improvement between the two approaches. Following treatment, patients in both groups showed a significant overall improvement (p < 0.05) in both impairment and disability measures.\n No significant differences in effectiveness between the two methods were demonstrated. Both a task-oriented approach and a facilitation approach to the treatment of MS outpatients were associated with improved mobility.", "Multiple sclerosis (MS) patients of an inpatient rehabilitation program have been randomly assigned to an exercise training (MS-ET) or nontraining group (MS-NI). Before and after 4 weeks of aerobic exercise training, a graded maximal exercise test with measurement of gas exchange and a lung function test was administered to all 26 patients fulfilling the inclusion criteria. Activity level, fatigue and health perception were measured by means of questionnaires. Twenty-six healthy persons served as control group and were matched in respect of age, gender and activity level. Training intervention consisted of 5x30 min sessions per week of bicycle exercise with individualised intensity. Compared with baseline, the MS training group demonstrated a significant rightward placement of the aerobic threshold (AT) (VO2+13%; work rate [WR])+11%), an improvement of health perception (vitality+46%; social interaction+36%), an increase of activity level (+17%) and a tendency to less fatigue. No changes were observed for the MS-NI group and the control groups. Maximal aerobic capacity and lung function were not changed by either training or nontraining in all four groups. Overall compliance to the training program was quite low (65%), whereas incidence of symptom exacerbation by physical activity has been lower than expected (6%).", "Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established.\n We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial.\n Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician.\n No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001).\n Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks." ]

[ "14861680", "14162138", "8677772", "392622" ]

[ "The use of intramuscular ergometrine at the end of the second stage of normal labour.", "OXYTOCIC DRUGS IN FOURTH STAGE OF LABOR.", "A placebo-controlled trial of oral ergometrine to reduce postpartum hemorrhage.", "The effect of prostaglandin F2 alpha on third stage labor." ]

[ "nan", "nan", "Active management with oral ergometrine 0.4 mg was compared with expectant management for the control of blood loss in the third stage of labor in women at low risk of postpartum hemorrhage (PPH).\n A three-arms randomized trial in which 0.4 mg ergometrine (2 tablets of 0.2 mg) was set off against placebo, both groups allowing comparison with a standard oxytocin regimen of 5 IU. Women at low risk for PPH. Of 367 parturients, 146 were randomised to ergometrine 0.4 mg, 143 to placebo and 78 to intramuscular oxytocin in a 2:2:1 design.\n Compared with placebo, ergometrine reduced blood loss with 5% (-5%; Confidence interval: -20% to +13%). Oxytocin reduced blood loss with 9% (-9%; Confidence interval: -26% to +12%) versus placebo.\n Oral ergometrine has too little effect on blood loss after childbirth in order to be a good alternative to parenteral prophylactic management.", "The effects of intramyometrially injected PGF2 alpha intravenous Ergometrin and no treatment were compared during 3rd stage labor in 140 patients. In comparison with Ergometrin or no treatment, PGF2 alpha significantly reduced the duration of 3rd stage labor, blood loss, incidence of subinvolution and subfebrility." ]

[ "17447865", "15172083", "19169167", "15536539", "17486470", "18551087" ]

[ "Physical activity and mental health outcomes during menopause: a randomized controlled trial.", "Vasomotor symptoms and quality of life in previously sedentary postmenopausal women randomised to physical activity or estrogen therapy.", "Physical activity, menopause, and quality of life: the role of affect and self-worth across time.", "Physical training and hormone replacement therapy reduce the decrease in bone mineral density in perimenopausal women: a pilot study.", "Training or EPT in perimenopause on balance and flushes.", "A randomized, placebo-controlled trial of the effects of physical exercises and estrogen therapy on health-related quality of life in postmenopausal women." ]

[ "Many women experience detriments in mental health during the menopausal transition. Physical activity may attenuate these adverse outcomes but few studies investigating such effects exist.\n This study examined the effects of a 4-month randomized controlled exercise trial on mental health outcomes in 164 previously low-active middle-aged women (M age = 49.9; SD = 3.6).\n Participants completed body composition and fitness assessment and a battery of psychological measures at the beginning and end of a 4-month randomized controlled exercise trial with three arms: walking, yoga, control. The results indicated that walking and yoga were effective in enhancing positive affect and menopause-related QOL and reducing negative affect. Women who experienced decreases in menopausal symptoms across the trial also experienced improvements in all positive mental health and QOL outcomes and reductions in negative mental health outcomes. Whether menopausal symptoms increased or decreased across the trial appeared to be determined in part by whether there were increases or decreases in cardiorespiratory fitness.\n Physical activity appears to enhance mood and menopause-related QOL during menopause, however, other aspects of mental health may be affected only as a result of reduction in menopausal symptoms. Increasing cardiorespiratory fitness could be one way to reduce menopausal symptoms.", "To assess if regular physical exercise or oral oestradiol therapy decreased vasomotor symptoms and increased quality of life in previously sedentary postmenopausal women.\n A prospective, randomised trial at a University Hospital.\n 75 postmenopausal, sedentary women with vasomotor symptoms were randomised to: exercise three-times weekly over 12 weeks (15 women), oral oestradiol therapy for 12 weeks (15 women) and 45 women to three other treatment arms. Results from the exercise and oestradiol groups are presented here. The effects on vasomotor symptoms and wellbeing were assessed with logbooks and validated questionnaires.\n Ten women fulfilled 12 weeks of exercise. The number of flushes was rather unchanged in five women and decreased to 28% (range 18-42%) of baseline in the other five women. Five of the ten women continued to exercise another 24 weeks, thus in all 36 weeks. The mean number of flushes decreased by about 50% in these five women (from 6.2/24 to 3.2 flushes/24 h at 36 weeks). In the same group a score made as the product of reduction in number and severity of flushes decreased by 92% at 12 weeks, 75% at 24 weeks and 72% at 36 weeks compared with baseline. In the estrogen group flushes decreased from 8.4 to 0.8 (P<0.001) after 12 weeks of therapy and remained at this level after 36 weeks. Well-being according to different measurements improved significantly in both groups, albeit more markedly in the estrogen group.\n Apart from many other health benefits regular physical exercise may decrease vasomotor symptoms and increase quality of life in postmenopausal women, but this has to be further evaluated scientifically. Exercise should be introduced gradually to ensure compliance.", "Physical activity has been shown to enhance quality of life (QOL); however, few investigations of these effects exist in women undergoing the menopausal transition. The present study examined the long-term effects of physical activity on menopause-related QOL and tested the mediating effects of physical self-worth and positive affect in this relationship.\n Middle-aged women previously enrolled in a 4-month randomized controlled trial involving walking and yoga, and a control group completed a follow-up mail-in survey 2 years after the end of the trial. The survey included a battery of psychological and physical activity measures, including measures of menopausal symptoms and menopause-related QOL. Longitudinal linear panel analysis was conducted within a covariance modeling framework to test whether physical self-worth and positive affect mediated the physical activity-QOL relationship over time.\n At the end of the trial, physical activity and menopausal symptoms were related to physical self-worth and positive affect, and in turn, greater levels of physical self-worth and positive affect were associated with higher levels of menopause-related QOL. Analyses indicated that increases in physical activity and decreases in menopausal symptoms over the 2-year period were related to increases in physical self-worth (betas = 0.23 and -0.52, physical activity and menopausal symptoms, respectively) and, for symptoms, also to decreased positive affect (beta = -0.47), and both physical self-worth (beta = 0.34) and affect (beta = 0.43) directly influenced enhancements in QOL (R = 0.775).\n The findings support the position that the effects of physical activity on QOL are mediated, in part, by intermediate psychological outcomes and that physical activity can have long-term benefits for women undergoing the menopausal transition.", "The effects of physical training and hormone replacement therapy (HRT) on bone mineral density in perimenopausal women were studied. Sixty perimenopausal women were randomized to either physical training (n = 20), HRT (n = 20), or control group (n = 20). The study period was 18 months. Bone mineral density (BMD) in the femoral neck and lumbar spine was measured using dual-energy X-ray absorptiometry (DXA). DXA was performed before treatment and after 6 and 18 months. Blood samples for analysis of the bone markers U-deoxypyridinoline and osteocalcin were collected at the same time points. After 18 months, BMD in the spine had not decreased in either the training group or in the HRT group. In the control group, spine BMD had significantly decreased (p = 0.0014). U-Deoxypyridinoline and osteocalcin were increased significantly in the control group (p = 0.0198, p = 0.0295, respectively). No significant changes in bone marker levels were found in the training group or the HRT group. We found that both HRT and physical training can prevent loss of spine BMD in perimenopausal women over a period of 18 months. HRT remains a cornerstone in the treatment of vasomotor symptoms and preservation of BMD. However, HRT can only be used for limited periods of time due to the potential serious adverse effects. This study indicates a beneficial effect of physical activity on spine BMD in the perimenopausal period, and highlights its potential as an alternative to HRT during this period.", "With advancing age, the postural balance function deteriorates as a consequence of decreased functional capacity. Deteriorating balance is a risk factor for bone fractures due to increased risks of falls. It has been suggested that the loss of estrogen, which occurs in relation to the menopause, may be associated with loss of balance. Regular physical exercise without balance training has, in some studies, been shown to have positive effects on the postural balance. The aim of the present study was to examine balance function during the perimenopausal period, and evaluate the effect of estrogen plus progesterone therapy (EPT) or aerobic training on balance. Sixty perimenopausal women were recruited to the study. The subjects were then randomised to either physical training (n=20), EPT (n=20), or to a control group (n=20). The study period was 18 months. Postural stability was measured every third month using a custom-made force platform. The women using EPT achieved better results in 3 of 6 parameters, after 18 months.", "The purpose of this study was to evaluate the isolated and associated effects of estrogen therapy (estradiol valerate 1 mg/d orally) and physical exercise (moderate aerobic exercise, 3 h/wk) on health-related quality of life (HRQOL) and menopausal symptoms among women who had undergone hysterectomy.\n A 6-month, randomized, double-blind, placebo-controlled clinical trial with 44 postmenopausal women who had undergone hysterectomy. The interventions were physical exercise and hormone therapy (n = 9), being sedentary and hormone therapy (n = 14), physical exercise and placebo (n = 11), and being sedentary and placebo (n = 10). HRQOL was assessed by a Brazilian standard version of the Medical Outcome Study Short-Form Health Survey and symptoms by Kupperman Index at baseline and after 6 months.\n There was a decrease in symptoms in all groups, but only groups who performed physical exercise showed an increase in quality of life. Analysis of variance showed that changes in physical functioning (P = 0.001) and bodily pain (P = 0.012) scores over the 6-month period differed significantly between women who exercised and women who were sedentary, regardless of hormone therapy. Hormone therapy had no effect, and there was also no significant association between physical exercise and hormone therapy in HRQOL.\n Physical exercises can reduce menopausal symptoms and enhance HRQOL, independent of whether hormone therapy is taken." ]

[ "11424099", "8743353" ]

[ "Ultrasound-guided testicular sperm aspiration in azoospermic patients: a new sperm retrieval method for intracytoplasmic sperm injection.", "Microsurgical epididymal sperm aspiration versus epididymal micropuncture with perivascular nerve stimulation for intracytoplasmic sperm injection to treat unreconstructable obstructive azoospermia." ]

[ "We investigated the technique of ultrasound-guided testicular sperm aspiration (USTSA) and compared it with \"blind\" testicular sperm aspiration (TSA) in patients with nonobstructive azoospermia.\n Thirty-nine consecutive azoospermic men underwent TSA, 16 under sonographic guidance (USTSA group) and 23 with no imaging guidance (TSA group). Clinical and hormonal evaluation and sonography of the scrotum and testes were performed 1-2 days before the procedure. The aspiration was done using short-term general anesthesia. Follow-up consisted of sonographic reexamination of the scrotum and testes immediately and 1 month after the procedure.\n Intraoperative sonography with power Doppler imaging enabled good visualization of the testicular parenchyma, easy sampling, and avoidance of prominent vessels. Sufficient material was retrieved in 15 USTSA patients (94%) and 19 TSA patients (83%). No patients needed more than 4 hours' ambulatory hospitalization after the procedure. In the remaining 5 patients, aspiration failed to yield sperm, so open biopsy was performed. In those patients, postaspiration surgical exploration revealed subtunical bleeding in 3 patients after TSA but none after USTSA. Late minor complications occurred in 2 patients (13%) in the USTSA group and 7 (30%) in the TSA group. No difference was found between the 2 groups in pregnancy rate in the patients' female partners.\n USTSA is a safe and accurate method for sperm retrieval in azoospermic patients.\n Copyright 2001 John Wiley & Sons, Inc.", "A novel sperm collection method by epididymal micropuncture combined with perivascular nerve stimulation has been developed to obtain as many clean sperm as possible for IVF for patients with surgically irreparable vasal obstruction. To assess whether the new technique could improve the fertilization and pregnancy rates obtained when attempting microsurgical epididymal sperm aspiration (MESA) to retrieve epididymal sperm from such patients, a prospective randomized comparative study was conducted. Twenty-nine cycles of conventional MESA with ICSI were performed on 25 couples with congenital bilateral absence of the vas deferens (CBAVD) and four failed vasovasostomy cases (group 1). Thirty cycles of epididymal micropuncture with nerve stimulation with ICSI were performed on 28 couples with CBAVD and two failed epididymovasostomy cases (group 2). The mean volume of epididymal fluid and sperm motility in group 2 was significantly higher than that in group 1 (p < .001). Both fertilization and pregnancy rates in group 2 were significantly higher than those in group 1 (p < .001 and p < .03). This novel epididymal sperm collection method for ICSI can provide significantly higher fertilization and pregnancy rates than conventional MESA for ICSI." ]

[ "19078008", "8598501", "9313387", "9782813", "8971229", "10048521", "9598884", "7794984", "10914845", "2285755", "8728664", "9295454", "8994013", "1581367", "8945112", "7234956" ]

[ "Can foot orthoses prevent hallux valgus deformity in rheumatoid arthritis? A randomized clinical trial.", "Impacts of foot orthoses on pain and disability in rheumatoid arthritics.", "Commercial wrist extensor orthoses: a descriptive study of use and preference in patients with rheumatoid arthritis.", "A comparison of the Futuro wrist orthosis with a synthetic ThermoLyn orthosis: utility and clinical effectiveness.", "Finger dexterity and hand function: effect of three commercial wrist extensor orthoses on patients with rheumatoid arthritis.", "Splinting in the treatment of arthritis of the first carpometacarpal joint.", "The effect of a static wrist orthosis on hand function in individuals with rheumatoid arthritis.", "Use of commercially produced elastic wrist orthoses in chronic arthritis: a controlled study.", "Metatarsalgia and rheumatoid arthritis--a randomized, single blind, sequential trial comparing 2 types of foot orthoses and supportive shoes.", "Elastic wrist orthoses. Reduction of pain and increase in grip force for women with rheumatoid arthritis.", "Soft versus hard resting hand splints in rheumatoid arthritis: pain relief, preference, and compliance.", "Off-the-shelf orthopedic footwear for people with rheumatoid arthritis.", "Evaluation of the effectiveness of a metacarpophalangeal ulnar deviation orthosis.", "Effect of the arthritis health professional on compliance with use of resting hand splints by patients with rheumatoid arthritis.", "Immediate and short-term effects of three commercial wrist extensor orthoses on grip strength and function in patients with rheumatoid arthritis.", "Use of resting splints by patients with rheumatoid arthritis." ]

[ "Hallux valgus deformity is the most commonly observed forefoot deformity in patients with rheumatoid arthritis. This 5-year, double-blind, randomized clinical trial compared treatment orthoses with placebo orthoses for the prevention of hallux valgus deformity in the rheumatoid arthritic foot.One hundred and two subjects with active rheumatoid arthritis and with foot pain and minimal radiographic changes of the feet participated in the study. They were recruited from five arthritis clinics in the Chicago metropolitan area that are affiliated with or are teaching clinics of area medical schools. Patients were followed for 3 years.Eighty-one subjects completed the study. In a logistic regression analysis, the treatment group was 73% less likely to develop hallux valgus deformity compared with the control group (adjusted odds ratio 0.27, 95% confidence interval 0.078, 0.916 p = .04). These findings suggest that foot orthoses can prevent or slow the progression of hallux valgus deformity.", "Rheumatoid arthritis (RA) frequently causes foot pain and swelling that affect ambulation. Pharmaceutical management of pain and disability is standard in clinical practice. The use of functional posted foot orthoses, as an adjunct to pharmaceutical treatment, is a promising treatment for managing foot pain and disability in RA. Its effectiveness, however, has not been rigorously evaluated. We performed a double-blind clinical trial using foot orthoses vs. placebo orthoses in the management of the rheumatoid arthritic foot, while subjects continued customary treatment. On the basis of findings of no effect on disability and pain measures, this study indicates no benefit of functional posted foot orthoses over placebos.", "To describe patients' functional uses of 3 commercial wrist orthoses, to describe patients' preference patterns for the orthoses, and to clarify orthotic attributes that are viewed positively and negatively.\n Using a cross-over design, 42 patients with definite rheumatoid arthritis used each of 3 commercial orthoses for one week. There was a one-week wash-out between each week of use. At the end of the study, private semi-structured interviews were conducted with each participant. Data from close-ended questions were tabulated. Open-ended data were analyzed using qualitative methods.\n Patients reported that the 3 commercial wrist orthoses reduced wrist pain similarly, but that comfort and a sense of security during functional tasks were only found if the orthoses were comfortable and well-fitting. Most subjects preferred the padded, short forearm orthosis, though a small number found it uncomfortably warm, and many complained that it was difficult to use when wearing long-sleeved garments. Common complaints about the two elastic orthoses included chafing at the thumb webspace and chafing at the proximal closures. Longer forearm length was often perceived as providing unnecessarily high levels of wrist support.\n No single orthosis suited all subjects. Satisfaction with an orthosis appears to be based not only on its therapeutic effect, but also the comfort and ease of its use. To maximize patient satisfaction and improve the likelihood of appropriate fit and comfort, several styles of commercial orthoses should be available. The current trend toward restricted clinic stocks appears contrary to both therapeutic goals and patient satisfaction.", "To compare the short-term utility and clinical effectiveness of the commercial-made Futuro wrist orthosis with a newly developed, custom-made ThermoLyn wrist orthosis.\n Using a randomized cross-over trial, 10 patients with rheumatoid arthritis used each of the two orthoses for two weeks. Outcome measures were patients' judgments with respect to different statements about utility and clinical assessments including pain and swelling of the wrist and finger joints, range of motion of the wrist, and grip strength. At the end of the study the patients were asked which of the two orthoses they preferred and why.\n Patients tended to favor the Futuro wrist orthosis with respect to pain relief and to handling the orthosis. The visual analog scale score of the appearance of the ThermoLyn wrist orthosis was a little higher than that of the Futuro wrist orthosis, but the difference was not statistically significant. Clinical parameters such as pain in the wrist, swelling of the wrist and finger joints, and movements of the wrist showed that the Futuro orthosis tended to be more effective than the ThermoLyn orthosis. None of the differences reached statistical significance. At the end of the study, 5 patients preferred the Futuro and 5 patients the ThermoLyn wrist orthosis. Arguments in favor of the ThermoLyn orthosis were better hygiene, stability, and no need to remove the orthosis during dirty and wet conditions. Arguments in favor of the Futuro orthosis were greater suppleness and freedom of movement.\n The ready-made fabric Futuro wrist orthosis appears to be as good as the more expensive individually made synthetic ThermoLyn wrist orthosis with respect to short-term utility and clinical effectiveness. The conditions under which the orthosis will be worn will help to decide which orthosis is the best for the patient. In the event that the patient wants to use the orthosis in wet and dirty conditions, the ThermoLyn wrist orthosis is a good alternative to the Futuro wrist orthosis.", "To investigate the effect of 3 commercial wrist orthoses on finger dexterity and hand function of patients with rheumatoid arthritis (RA).\n Forty-two patients with definite RA participated in the cross-over study comparing 3 styles of commercial wrist orthoses. Finger dexterity and hand function of the dominant hand were assessed while splinted and unsplinted, at the initial session and after 1 week of intermittent orthosis use. Finger dexterity was assessed using two subtests from the Purdue Pegboard Test (Purdue) and hand function was assessed using the Jebsen-Taylor Hand Function Test (Jebsen-Taylor).\n Both finger dexterity and hand function were reduced by splinting; men and women were affected similarly. There was no difference in finger dexterity or hand function afforded by the 3 orthoses. Results on both the Purdue and Jebsen-Taylor tests showed a significant learning effect across time.\n The 3 commercial wrist orthoses studied reduce dexterity similarly and significantly. When commercial wrist orthoses are to be used during tasks that require maximum dexterity, this reduction should be weighed against the known benefits of splinting.", "Although much has been written about surgical treatment of arthritis of the first carpometacarpal joint, no literature exists on splinting as a conservative treatment. One hundred fourteen patients (130 thumbs) were retrospectively reviewed to determine the efficacy of splinting. Patients were grouped according to their stage of disease and whether they had carpometacarpal joint surgery. Seventy-six percent of patients with stage I and II disease and 54% of patients with stage III and IV disease had improvement in their symptoms with splinting. There was no significant difference in the degree of improvement between the 2 groups. All patients who had initial improvement in their symptoms with splinting had between 54% and 61% average improvement in symptom severity 6 months after splinting. All groups were found to be equally tolerant of the splinting protocol and no group had a significantly higher rate of activity modification. Overall, splinting was found to be a well-tolerated and effective conservative treatment to diminish, but not completely eliminate, the symptoms of carpometacarpal joint arthritis and inflammation.", "To determine the effect of a wrist orthosis on work performance, hand dexterity, and pain during task performance, 40 individuals with rheumatoid arthritis were studied using a 2 period, crossover design.\n Each patient was fitted with a Futuro wrist orthosis. Dexterity was measured with and without the orthosis using the Jebsen Hand Function Test. Work performance was assessed using 2 tasks (one simulating the use of shears, the other the use of a screwdriver) on a work simulator. All tasks were performed both with and without the orthosis, with the order of orthosis versus no orthosis randomly assigned. Pain before and after performing tasks was assessed using a 10 cm horizontal visual analog scale.\n While on the screwdriver task work performance was less with the orthosis (p = 0.0002); on the shears task there was no significant difference in work performance with and without the orthosis. The average pain after performing both tasks was significantly less with the orthosis on. A 2 factor analysis of variance model with repeated measures suggested that taking into account the reduced work performance during splint wear, pain was still significantly reduced with splint wear. The average time to complete all 7 tasks on the Jebsen Hand Function Test was longer when the subjects wore the splint compared to when they did not (62.0 vs 57.6 s, respectively; p = 0.0086).\n The results suggest that the effect of splint wear on work performance is highly task specific, and thus the ergonomic demands of the individual's daily life must be considered if a splint is to provide maximal effectiveness.", "To examine the efficacy of wrist orthoses on pain, motion, and function of the wrist.\n Consecutive patients were randomized to a treatment group using wrist orthoses or to a control group using no wrist orthoses, in a prospective, controlled, 6-month study.\n Changes in wrist joint variables and general disease activity variables were not statistically different between the orthosis group (n = 36) and the control group (n = 33). Patients in the orthosis group had 25% and 12% improvements in grip strength and pinch grip and 50% reduction in pain while using the wrist orthosis.\n Use of wrist orthoses improves function and reduces pain, but has no effects after 6 months, compared to a control group, on measures of local or general disease activity.", "To compare the effects of semi-rigid and soft orthoses worn in supportive shoes, and supportive shoes worn alone, on metatarsal phalangeal (MTP) joint pain. MTP joint synovitis, and lower extremity function in patients with rheumatoid arthritis.\n Twenty-eight subjects referred to occupational therapy received in random order 3 interventions for 12 week trials, separated by 2 week washouts. A crossover design compared effectiveness of interventions.\n Twenty-four subjects completed the study. A reduction in mean pain scores from baseline to final visits showed that semi-rigid orthoses had a highly significant effect on pain. Soft orthoses did not show a significant effect on pain from baseline to final visit, nor did shoes worn alone. None of the interventions had a significant effect on synovitis or function.\n Semi-rigid orthoses worn in supportive shoes were an effective treatment for metatarsalgia. Supportive shoes worn alone or worn with soft orthoses did not provide pain relief for metatarsalgia.", "The aim of this study was to investigate effects of elastic wrist orthoses on pain, grip strength, and function. Twenty-two women with seropositive rheumatoid arthritis (mean age, 53 years) registered their pain on a visual analogue scale both with and without orthosis on the wrist of the dominant hand in three standardized activities of daily living (ADL) situations. Grip force at onset of pain was measured on an electronic instrument (Grippit) with three different grips. Pain was decreased by 39%, 42%, and 52% when using an orthosis in the three ADL situations. Anecdotally, the women noted that the splints provided support and decreased pain both in home, at work, and during leisure activities. Orthoses improved grip force at onset of pain by 26%, 22%, and 29%. All subjects showed reduced strength (20%-25%) when compared to grip strength in a group of women without rheumatoid arthritis.", "This study compared soft versus hard resting hand splints on pain and hand function in 39 persons with rheumatoid arthritis. Splint preference was also evaluated to determine its effects on splint wear compliance.\n A repeated measures research design was used to compare the two experimental conditions, wearing a soft splint versus a hard splint on the dominant hand for 28 days at night only, and an unsplinted control period of 28 days.\n Arthritis pain was considerably less during both splinted periods when compared with the pretest. Subjects identified fewer joints as being painful during the soft splint condition than during the unsplinted condition. There were no significant differences among conditions on hand function measures. Splint preference was 57% for the soft splint, 33% for the hard splint, and 10% for no splint. Splint wear compliance was significantly better with the soft splint (82%) than with the hard splint (67%).\n The findings indicate that resting hand splints are effective for pain relief and that persons with rheumatoid arthritis are more likely to prefer and comply with soft splint use for this purpose. Individualized splint prescription that focuses on client comfort and preference may enhance splint wear compliance.", "To assess the effectiveness of off-the-shelf orthopedic footwear for people with rheumatoid arthritis (RA) reporting chronic foot pain, in terms of self-reported pain and physical function, as well as objectively measured gait variables using an electric footswitch walkway.\n A small, randomized, controlled trial followed by a larger repeated measures analysis was used.\n The control group (n = 15) demonstrated no significant changes over a 2-month period in pain, physical function, or gait scores. In contrast, after supply of the footwear both the original footwear group (n = 15) and the control group demonstrated significant improvements, with small to large effect sizes, in weight-bearing pain scores, physical function, gait velocity, and gait stride length without increases in use of arthritis medications or walking aids.\n These data suggest that off-the-shelf orthopedic footwear is beneficial for people with RA even when subjects were unselected on basis of age, sex, disease duration, or disability as measured by the Stanford Health Assessment Questionnaire.", "Rheumatoid arthritis (RA) causes structural damage that precipitates joint deformity, including metacarpophalangeal (MCP) joint ulnar drift (UD). Orthoses have been designed in order to maintain hand function by improving joint alignment, restoring biomechanical balance and reducing stress on supporting diseased tissues. This study investigated the impact an MCP UD (MUD) splint had on: pain, hand function, grip strength, and passive correction of UD when worn for function by RA patients. Twenty seven hands (26 subjects) were evaluated and performances compared with and without the splint. Results showed anatomic alignment improved significantly in all except the index finger. The mean difference for all fingers combined was 10 degrees. Observable correction of subluxation was identified from x-ray film and noted in 14.8% of index fingers, 18.5% of middle fingers, 33.3% of ring fingers, and 48.1% of little fingers. Three point pinch showed a statistically significant change, the mean difference being an improvement of 15% while wearing the splint. There was no significant change in hand function score, pain score, gross grip strength, and lateral pinch. Subjects' perceptions of the MUD splint gained from a questionnaire showed a high acceptance: 79.2% reporting minimal interference in ADL, 95.8% satisfied with cosmesis, 87.5% satisfied with comfort, and 95.8% reported continued use of the orthosis.", "This study examined the effects of an occupational therapist's approach during the initial splinting session on the subsequent use of resting hand splints by patients with rheumatoid arthritis. Forty subjects were randomly assigned either to a standard treatment (control) group or to a compliance-enhancement (experimental) group, for whom the use of learning principles, sharing of expectations, use of a positive affective tone and behaviors by the therapist, and the assumption of responsibility by the patient were emphasized. During the 28-day period after splinting, patients in the experimental and control groups wore their splints an average of 23.3 and 18.1 days, respectively (p = 0.056). Nine subjects in the experimental group, but only four in the control group used their splints every day (p = 0.035). Knowledge of splint use correlated with actual use, regardless of the group assignment (p = 0.035). Change in the amount of wrist and hand pain was not significant in either group; however, the experimental group experienced a decrease in the duration of morning stiffness (p = 0.013). This intervention provides health professionals with a pragmatic and effective method to enhance compliance.", "To investigate the immediate and short-term effects of 3 commercial wrist orthoses on grip strength and function.\n Thirty-six patients with definite rheumatoid arthritis participated in the randomized, controlled, cross-over design study of 3 commercial wrist extensor orthoses. Dominant-hand dynamometric grip strength was assessed at both initial and followup sessions while splinted and nonsplinted. Functional impact was assessed using a written questionnaire.\n All 3 commercial orthoses reduced grip strength when first donned. After a 1-week adjustment period, one orthosis, the Smith and Nephew Roylan D-Ring (Roylan), afforded splinted grip strength equal to that of the nonsplinted grip strength. The other 2 orthoses continued to reduce grip strength, and afforded splinted grip strength significantly below that of the Roylan. The Roylan was deemed comfortable by more subjects than the other orthoses.\n The belief that commercial orthotic use increases grip strength, either immediately or after 1 week, is not supported by this study's data. Different styles of commercial wrist orthoses appear to have differing influence on splinted grip strength.", "A follow-up evaluation of 50 patients with rheumatoid arthritis who were fitted with full bilateral wrist and hand resting splints revealed that 62 percent wore them most or all of the prescribed time. Patients deviated from the prescribed splint program when their symptoms remitted or diminished, and adhered more closely to the program when they experienced persistent inflammation. Patients splinted during a hospital stay were somewhat more compliant than those splinted as outpatients. Patients judged to be noncompliant discontinued splint usage because of a decrease of joint pain or stiffness, or both. Their decision did not appear detrimental, since, during the course of the study, there was no significant difference between compliant and noncompliant patients in range of motion of hand or wrist joints at followup evaluation and, when range of motion at the time of initial evaluation was compared with that at the follow-up examination, a higher proportion of noncompliant (37%) than compliant patients (16%) showed improvement." ]

[ "3379696", "10872909", "8971536", "7048776", "922458" ]

[ "Results of carbon dioxide laser therapy and topical 5-fluorouracil treatment for subclinical condyloma found by magnified penile surface scanning.", "Management of intravaginal warts in women with 5-fluorouracil (1%) in vaginal hydrophilic gel: a placebo-controlled double-blind study.", "Treatment of men with flat (FC) or acuminata (CA) condylomata with interferon alpha-2a.", "[Treatment of condyloma acuminatum with 0.5% 5-fluorouracil-solution, A double-blind clinical trial].", "5-Fluorouracil in the treatment of penile and urethral condylomata acuminata." ]

[ "Previously we demonstrated a 68 per cent recurrence rate for subclinical penile human papillomavirus infections found by magnified penile surface scanning and treated with the carbon dioxide laser. In this report it is shown that the addition of a regimen of adjuvant topical 5-fluorouracil does not lower the recurrence rate. This knowledge combined with the evidence for a subclinical urethral reservoir of human papillomavirus implies that any strictly topical therapy will fail at 4 months of followup and that improved systemic therapy may be needed.", "The purpose of this placebo-controlled, double-blind study was to determine the safety, tolerability and clinical efficacy of 5-fluorouracil (1%) in a vaginal hydrophilic gel (hydroxyethylcellulose, 1%) to cure intravaginal papillomas in women. Pre-selected, 60 women ranging between 18 and 50 years of age (mean 24.6), having 312 vaginal condylomas (mean 5.2) joined the study. The diagnosis of human papillomavirus (HPV) was established with clinical, histopathological and polymerase chain reaction (PCR) techniques. Subjects were randomized into 2 parallel groups. Each patient was allocated a pre-coded tube 15 g (active or placebo) with graduated vaginal applicators (disposable), and instructions how to insert 4 g of the trial medication deep into the vagina once at bedtime on every other day (1, 3 and 5) per week, to visit the clinic on day 7 for clinical evaluations and to receive the same pre-coded replacement to continue the regimen for another week. A maximum 12 applications were to be used in 4 weeks. Cure was defined as absence of clinical signs of infection, re-confirmed by PCR and Southern blot hybridization negative HPV DNA. By the end of the treatment 48.4% patients and 51.9% lesions were cured. Breaking the code revealed that 5-fluorouracil (1%) gel had cured 83.3% patients and 87% intravaginal warts. Placebo resolved 13.3% patients and 14% condylomas; (active gel versus placebo; P < 0.001). Twelve patients (20%) mostly in the active gel experienced mild erythema, erosion and oedema, with no drop-outs. Among cured patients 3 had a relapse after 16 months. In conclusion, the clinical results of the study demonstrate that 5-fluorouracil (1%) in a vaginal hydrophilic gel is safe, tolerable and significantly more effective than placebo to cure intravaginal warts in women.", "This study was undertaken to assess the effect of CO2 laser vaporization, 5-fluorouracil 5% (5-FU) topical application and Interferon alpha-2a (IFA alpha-2a) in the treatment of C.A. or F.C. of the male genital tract. From March 1986 to September 1991, 1372 men, sexual partners of women with F.C. or C.A. or cervical intraepithelial neoplasia, were submitted to peoscopy. One thousand and nineteen (74.27%) men presented with various penile lesions caused by HPV (histologically confirmed); of these 505 were treated for C.A. or F.C. or a combination of F.C. and C.A. The best treatment modalities, irrespective of the kind of lesion, were found to be the combination of 5-FU plus IFN alpha-2a (high dose) (98.27%), the combination of CO2 laser vaporization plus 5-FU plus IFN alpha-2a (high dose) (93.93%) and the combination of CO2 laser vaporization plus 5-FU (87.23%). In conclusion we believe that IFN alpha-2a can be used with excellent results as first line treatment in combination with CO2 laser vaporization or/plus 5-FU in patients with C.A. or F.C. or combined condylomata.", "30 males and 29 females with condyloma acuminatum took part in a double-blind randomized trial with 0,5% 5-fluorouracil (5-FU) salicylic acid containing varnish for warts versus the varnish without 5-FU. The females were treated twice weekly at the clinic, the males were treated once daily at home by themselves. The 5-FU solution was found significantly superior to placebo (P less than 0,01). 60% of the 5-FU treated patients were healed with a median healing time of two weeks in the males and three weeks in the females. In the placebo group 27,6% healed with a median healing time of 2,5 weeks (males) an 3,5 weeks (females). Blood tests obtained before and after the trial were normal. Patch tests with 0,5% 5-FU revealed no sensitization after the therapy.", "5-Fluorouracil (5-FU) cream was compared with podophyllin 25 percent in alcohol for treating genital and urethral condylomata acuminata. The cure rate after four weeks was found to be 6 of 18 patients treated with 5-FU and 10 of 19 treated with podophyllin. By changing the treatment for those not cured, warts regressed after four weeks in four more patients in each group. Patients were followed up for four to nine months; 10 of 27 treated with 5-FU and 14 of 31 treated with podophyllin remained in remission. It is not possible to support earlier reports on the successful treatment of meatal warts using 5-FU cream. More than half of the patients given 5-FU reported side effects after 10 to 14 days' treatment, which in some cases led them to stop using the cream. Twenty-one men considered to be treatment failures or relapses were examined by urethroscopy. No intraurethral condylomata were found but three cases of warts in the fossa navicularis were doscovered; this prompted us to introduce an instrument to examine the urethral meatus and the fossa navicularis." ]

[ "18036873", "19530976", "11336929", "10532441", "15824216", "18166408" ]

[ "Verteporfin therapy of subfoveal occult choroidal neovascularization in AMD using delayed light application: one-year results of the VALIO Study.", "Verteporfin PDT for subfoveal occult CNV in AMD: two-year results of a randomized trial.", "Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization--verteporfin in photodynamic therapy report 2.", "Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials--TAP report. Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group.", "Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial.", "Randomized multicenter trial of more intense and standard early verteporfin treatment of neovascular age-related macular degeneration." ]

[ "To compare photodynamic therapy (PDT) with verteporfin (Visudyne; Novartis Pharma AG, Basel, Switzerland) using either standard or delayed light application.\n Phase II, multicenter, masked, randomized clinical trial.\n Sixty patients with occult with no classic choroidal neovascularization (CNV) resulting from age-related macular degeneration were assigned randomly (1:1) to verteporfin infusion followed by light application either at 15 minutes (standard light) or 30 minutes (delayed light) after the start of the infusion. The assigned treatment was repeated every three months if fluorescein leakage was detected.\n At month 12, patients lost a mean of 15.7 letters and 11.4 letters from baseline in the standard and delayed light groups, respectively (P = .38). Twelve (52%) of 23 patients in the standard light group and 11 (42%) of 26 in the delayed light group lost at least 15 letters of visual acuity (P = .57).\n There were no statistically significant differences between verteporfin therapy using the delayed light regimen of 30 minutes or the standard light regimen of 15 minutes in eyes with occult with no classic CNV.", "To determine whether verteporfin photodynamic therapy (PDT) can safely reduce the risk of vision loss in patients with subfoveal occult with no classic choroidal neovascularization (CNV) due to age-related macular degeneration.\n Eligible patients were > or =50 years of age with lesion size < or =6 disc areas and best-corrected vision 20/40-20/200. A total of 364 patients with occult with no classic CNV were randomly assigned 2 : 1 to verteporfin PDT (n = 244) or placebo (n = 120). The primary outcome measures were loss of > or =15 and > or =30 letters of visual acuity (VA) from baseline at 12 and 24 months.\n This study was registered with ClinicalTrials.gov on 20 July 2005. ClinicalTrials.gov identifier: NCT00121407.\n A total of 37% and 47% of verteporfin-treated patients versus 45% and 53% of placebo recipients lost > or =15 letters of VA at month 12 and month 24, respectively; 16% and 23% of verteporfin-treated patients versus 17% and 25% of placebo recipients lost > or =30 letters at month 12 and month 24, respectively. These differences were not statistically significant. Four (1.6%) verteporfin-treated patients and one placebo patient (who received verteporfin in error) experienced an acute severe VA decrease; all five patients recovered some degree of vision. No unexpected ocular or systemic adverse events were identified.\n Verteporfin PDT in the treatment of occult with no classic CNV was safe and well-tolerated. The differences between the two groups in the primary efficacy variables were not significant. Baseline characteristics and patient selection methods may have contributed to the small treatment effect.", "To determine if photodynamic therapy with verteporfin (Visudyne; Novartis AG, Bülach, Switzerland), termed verteporfin therapy, can safely reduce the risk of vision loss compared with a placebo (with sham treatment) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration who were identified with a lesion composed of occult with no classic choroidal neovascularization, or with presumed early onset classic choroidal neovascularization with good visual acuity letter score.\n This was a double-masked, placebo-controlled (sham treatment), randomized, multicenter clinical trial involving 28 ophthalmology practices in Europe and North America. The study population was patients with age-related macular degeneration, with subfoveal choroidal neovascularization lesions measuring no greater than 5400 microm in greatest linear dimension with either 1) occult with no classic choroidal neovascularization, best-corrected visual acuity score of at least 50 (Snellen equivalent approximately 20/100), and evidence of hemorrhage or recent disease progression; or 2) evidence of classic choroidal neovascularization with a best-corrected visual acuity score of at least 70 (better than a Snellen equivalent of approximately 20/40); assigned randomly (2:1) to verteporfin therapy or placebo therapy. Verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) was administered by means of intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50 J/cm(2) by application of an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the choroidal neovascularization lesion on the retina. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fluorescein leakage. The main outcome measure was at least moderate vision loss, that is, a loss of at least 15 letters (approximately 3 lines), adhering to an intent-to-treat analysis with the last observation carried forward to impute for missing data.\n Two hundred ten (93%) and 193 (86%) of the 225 patients in the verteporfin group compared with 104 (91%) and 99 (87%) of the 114 patients in the placebo group completed the month 12 and 24 examinations, respectively. On average, verteporfin-treated patients received five treatments over the 24 months of follow-up. The primary outcome was similar for the verteporfin-treated and the placebo-treated eyes through the month 12 examination, although a number of secondary visual and angiographic outcomes significantly favored the verteporfin-treated group. Between the month 12 and 24 examinations, the treatment benefit grew so that by the month 24 examination, the verteporfin-treated eyes were less likely to have moderate or severe vision loss. Of the 225 verteporfin-treated patients, 121 (54%) compared with 76 (67%) of 114 placebo-treated patients lost at least 15 letters (P =.023). Likewise, 67 of the verteporfin-treated patients (30%) compared with 54 of the placebo-treated patients (47%) lost at least 30 letters (P =.001). Statistically significant results favoring verteporfin therapy at the month 24 examination were consistent between the total population and the subgroup of patients with a baseline lesion composition identified as occult choroidal neovascularization with no classic choroidal neovascularization. This subgroup included 166 of the 225 verteporfin-treated patients (74%) and 92 of the 114 placebo-treated patients (81%). In these patients, 91 of the verteporfin-treated group (55%) compared with 63 of the placebo-treated group (68%) lost at least 15 letters (P =.032), whereas 48 of the verteporfin-treated group (29%) and 43 of the placebo-treated group (47%) lost at least 30 letters (P =.004). Other secondary outcomes, including visual acuity letter score worse than 34 (approximate Snellen equivalent of 20/200 or worse), mean change in visual acuity letter score, development of classic choroidal neovascularization, progression of classic choroidal neovascularization and size of lesion, favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire study group and the subgroup of cases with occult with no classic choroidal neovascularization at baseline. Subgroup analyses of lesions composed of occult with no classic choroidal neovascularization at baseline suggested that the treatment benefit was greater for patients with either smaller lesions (4 disc areas or less) or lower levels of visual acuity (letter score less than 65, an approximate Snellen equivalent of 20/50(-1) or worse) at baseline. Prospectively planned multivariable analyses confirmed that these two baseline variables affected the magnitude of treatment benefit. (ABSTRACT TRUNCATED)", "To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) can safely reduce the risk of vision loss in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD).\n Two multicenter, double-masked, placebo-controlled, randomized clinical trials.\n Twenty-two ophthalmology practices in Europe and North America.\n Patients with subfoveal CNV lesions caused by AMD measuring 5400 microm or less in greatest linear dimension with evidence of classic CNV and best-corrected visual acuity of approximately 20/40 to 20/200.\n Six hundred nine patients were randomly assigned (2: 1) to verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) administered via intravenous infusion of 30 mL over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50J/cm2 at an intensity of 600 mW/cm2 over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the CNV lesion. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fuorescein leakage. The primary outcome was the proportion of eyes with fewer than 15 letters lost (approximately <3 lines of loss), adhering to an intent-to-treat analysis.\n In each group, 94% of patients completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month-12 examination, 246 (61%) of 402 eyes assigned to verteporfin compared with 96 (46%) of 207 eyes assigned to placebo had lost fewer than 15 letters of visual acuity from baseline (P<.001). In subgroup analyses, the visual acuity benefit (< 15 letters lost) of verteporfin therapy was clearly demonstrated (67% vs 39%; P<.001) when the area of classic CNV occupied 50% or more of the area of the entire lesion (termed predominantly classic CNV lesions), especially when there was no occult CNV. No statistically significant differences in visual acuity were noted when the area of classic CNV was more than 0% but less than 50% of the area of the entire lesion. Few ocular or other systemic adverse events were associated with verteporfin treatment, compared with placebo, including transient visual disturbances (18% vs 12%), injection-site adverse events (13% vs 3%), transient photosensitivity reactions (3% vs 0%), and infusion-related low back pain (2% vs 0%).\n Since verteporfin therapy of subfoveal CNV from AMD can safely reduce the risk of vision loss, we recommend verteporfin therapy for treatment of patients with predominantly classic CNV from AMD.", "To compare the treatment effect and safety of photodynamic therapy with verteporfin using a standard (SF) or reduced (RF) light fluence rate with that of placebo therapy in patients with subfoveal minimally classic choroidal neovascularization (CNV) with age-related macular degeneration.\n Phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial.\n Nineteen ophthalmology practices in North America and Europe.\n Patients with initial best-corrected visual acuity of at least 20/250 and a lesion size of no greater than 6 Macular Photocoagulation Study (MPS) disc areas.\n We randomly assigned 117 patients (1:1:1) to verteporfin infusion (6 mg/m(2)) and light application with an RF rate (300 mW/cm(2)) for 83 seconds (light dose of 25 J/cm(2)) or an SF rate (600 mW/cm(2)) for 83 seconds (light dose of 50 J/cm(2)) or to placebo infusion with RF or SF. Treatment was repeated every 3 months if the treating physician noted fluorescein leakage from CNV on angiography. Patients in whom a predominantly classic lesion developed could receive open-label standard verteporfin treatment. Best-corrected visual acuity was measured every 3 months, and angiographic changes were assessed by the Photograph Reading Center through the 3-month examination unless an ocular adverse event or conversion to a predominantly classic lesion was identified by an investigator. Safety was assessed throughout the study. All outcomes were on an intent-to-treat basis.\n One hundred three (88%) of 117 patients completed the 24-month examination. Twelve (30%) of 40 patients assigned to placebo received open-label standard verteporfin treatment after confirmation of presence of predominantly classic CNV. At month 12, a loss of at least 3 lines of visual acuity occurred in 5 (14%) of 36 eyes assigned to RF and 10 (28%) of 36 eyes assigned to SF, compared with 18 (47%) of 38 eyes assigned to placebo (RF, P = .002; SF, P = .08; RF + SF, P = .004). At month 24, this loss occurred in 9 (26%) of 34 eyes assigned to RF and 17 (53%) of 32 assigned to SF, compared with 23 (62%) of 37 eyes assigned to placebo (RF, P = .003; SF, P = .45; RF + SF, P = .03). Progression to predominantly classic CNV by 24 months was more common in the placebo group (11 [28%] of 39 patients compared with 2 [5%] of 38 in the RF group [P = .007] and 1 [3%] of 37 in the SF group [P = .002]). No unexpected ocular or systemic adverse events were identified. Treatment-related, usually transient visual disturbances were 13% with SF, 10% with placebo, and 5% with RF.\n Verteporfin therapy safely reduced the risks of losing at least 15 letters (> or =3 lines) of visual acuity and progression to predominantly classic CNV for at least 2 years in individuals with subfoveal minimally classic lesions due to age-related macular degeneration measuring 6 MPS disc areas or less. Based on the overall evidence available on verteporfin therapy for these lesions, the VIM Study Group would consider recommending verteporfin therapy for relatively small minimally classic lesions similar to those enrolled in the VIM Trial.", "To compare efficacy and safety of a more intense regimen versus a standard one for retreatment of neovascular age-related macular degeneration (AMD) during the early period of verteporfin therapy (VT).\n Prospective, randomized, multicenter clinical trial.\n Two hundred three patients with predominantly classic choroidal neovascularization (CNV) secondary to AMD.\n During the first 6 months of VT, patients underwent retreatment every 2 (group A) or 3 (group B) months. After 6 months, both groups underwent retreatment every 3 months for as long as CNV activity was documented.\n Best-corrected visual acuity (BCVA) measured every 6 months, mean number of treatments per patient during 24 months' follow-up, proportions of patients in each group losing at least 3 lines of vision or gaining at least 1 line, greatest linear dimension (GLD) of the lesion as documented by fluorescein angiography every 6 months, and relationship between initial lesion size and BCVA.\n At all follow-up times, mean BCVAs were similar for groups A and B. Mean numbers of photodynamic therapy treatments were similar for both groups (4.07 vs. 4.36; P = 0.451, paired t test). A lower proportion (51.9% vs. 56.7%) of patients in group A had lost at least 3 lines of vision at 24 months. Groups A and B had similar increases in mean lesion size from baseline to 24 months (2104-3056 microm and 2179-3020 microm). At 24 months, patients in group A with a baseline lesion GLD of < or =2000 microm had significantly less mean loss of vision than patients in group A with a GLD of >2000 microm (P = 0.032); differences also were significant for group A with GLD of < or =2000 microm versus group B with GLD of < or =2000 microm (P = 0.041) or GLD of >2000 microm (P = 0.045); and mean vision losses from baseline were 8, 17, 15, and 14 letters, respectively.\n Overall outcomes regarding visual benefit, lesion anatomic features, and number of retreatments after 6 months were similar for patients receiving more intense or standard early therapy. An unplanned retrospective analysis showed that there was significantly less vision loss when the more intense regimen was used to treat smaller lesions." ]

[ "2901947", "4585770", "140827", "8050380", "10591711", "792861", "4936362", "8854297", "13960004", "4923928", "2192383", "14015397", "3279023", "353872", "4606452", "1629383", "2643356", "9590668", "8018452", "508127", "5326793", "4940219", "9165379", "4922592", "10460069", "6338987", "4940167", "1276560", "3127845", "7440519", "3927356", "7609861", "3519096", "4905242", "10441239" ]

[ "A double blind controlled clinical trial of benzoctamin (Tacitin) and imipramine (Tofranil) in the treatment of 'internal heat' and its association symptoms.", "Amitriptyline in anxious-depressed outpatients: a controlled study.", "Tofranil in the treatment of low back pain.", "[Controlled study of treatment of residual depression by clomipramine versus placebo].", "Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks.", "Mianserin in the treatment of depression in general practice.", "[Double-blind clinical study with a new psychotropic agent: doxepin versus placebo].", "A double-blind placebo-controlled study of clomipramine in depressed patients with Alzheimer's disease.", "A trial of imipramine (Tofranil) in depressed patients with chronic physical disease.", "Controlled trial of amitriptyline in general practice.", "The Nottingham Study of Neurotic Disorder: relationship between personality status and symptoms.", "Effects of amitriptyline on depressive and anxiety states in penitentiary inmates.", "Plasma levels and therapeutic response with trimipramine treatment of endogenous depression.", "Doctor-patient concordance in a placebo-controlled trial of limbitrol versus its components [proceedings].", "Doxepin: is a single daily dose enough?", "A double-blind clinical trial of alprazolam, imipramine, or placebo in the depressed elderly.", "Double-blind trial of imipramine in Alzheimer's disease patients with and without depression.", "Buspirone and imipramine for the treatment of major depression in the elderly.", "The effect of low dose lofepramine in depressed elderly patients in general medical wards.", "Amitriptyline in migraine prophylaxis.", "[Comparative evaluation of the antidepressive properties of opipramol, imipramine and placebo in neurotic depression].", "Amytriptyline and chlordiazepoxide (Limbitrol) in depressive states in Nigerians--a double-blind study.", "Amisulpride versus imipramine and placebo in dysthymia and major depression. Amisulpride Study Group.", "Amitriptyline in emotional states at the menopause.", "Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Danish University Antidepressant Group (DUAG).", "Amitriptyline for depressed women with young children in general practice.", "Chronic tension headache--treated with amitriptyline--a double-blind study.", "A clinical evaluation of depressives found in a rural survey in India.", "Antidepressive effect of amitriptyline treatment with plasma drug levels controlled within three different ranges.", "Trazodone in the treatment of neurotic depression.", "Cianopramine and amitriptyline in the treatment of depressed patients--a placebo-controlled study.", "Comparative effects of amitriptyline and amineptine in patients affected by anxious depression.", "Trimipramine in rheumatoid arthritis: a randomized double-blind trial in relieving pain and joint tenderness.", "Drug treatment in depressive illness.", "Imipramine and diet counseling with psychological support in the treatment of obese binge eaters: a randomized, placebo-controlled double-blind study." ]

[ "nan", "nan", "This report describes a double-blind between-group comparison of Tofranil and placebo in fifty-nine patients admitted to the Joint Service Medical Rehabilitation Unit suffering from low back pain. Patients were given 25 mg of either Tofranil or placebo three times a day for four weeks. Fifteen patients were not included in the analysis, nine dropping out for non-trial related reasons, two dropping out complaining of lost libido and four not taking the tablets, or taking additional drugs. One of the patients complaining of lost libido was taking Tofranil and the other was taking placebo. Over the whole sample there was no significant benefit for Tofranil over placebo as regards physical measurements. Both Tofranil and placebo groups showed a significant improvement during the trial on straight leg raise and backward flexion. For lateral flexion the Tofranil group was significantly worse than the placebo group on entering the trial, and during the trial the Tofranil group improved to match the placebo group. The clinician's pain and stiffness assessments and the patients' pain and stiffness assessments show a significant improvement for both the Tofranil and placebo groups during the trial. However, no difference is shown between Tofranil and placebo. The psychological tests show no difference between Tofranil and placebo and only a marinal improvenmet over initial condition. Further analysis according to initial diagnosis showed nothing conclusive. Numerically, the use of Tofranil produced a marked improvement in pain and stiffness in patients with 'disc lesion only' diagnoses, whereas placebo did not produce an improvement. However, this observation was far from reaching statistical significance. Side-effects were not severe for either drug. Additional medication was rarely used.", "The choice of a new treatment strategy for a patient suffering from residual depression in sometimes difficult; in reality, any change in the prescription involves a risk of losing any benefit, even partial, that has recently been obtained; consequently, can one be sure that a new antidepressant treatment will be beneficial? To attempt to find the answer to this question, the Laboratories Ciba-Geigy have conducted a controlled study versus placebo to evaluate the efficacy of clomipramine in residual depression which has been progressing for more than a year. 207 patients were pre-included in the 7-day wash-out phase and treated with placebo. During this period, a clinical examination and laboratory work-up made it possible to exclude patients with a curable cause of partial resistance to antidepressants (e.g., hypothyroidism) or who were \"placebo-responders\". After this run-in, 181 patients were included if they complied with the criteria characterizing a major depressive episode in partial remission (according to the DSM III-R), present for at least one year and treated throughout this period with at least two antidepressants at effective dosages. In addition, these patients had to have a score between 15 and 25 on the Montgomery and Asberg Depression Rating Scale (MADRS). The patients included were randomized into two groups, receiving either an clomipramine 75 tablet or a placebo tablet for two weeks; the dosage could be increased to two tablets as at D14 if necessary and maintained for the next six weeks. The only authorized concomitant treatments were tranquillizers (lorazepam or bromazepam) and/or non-barbiturate hypnotics (zopiclone or flunitrazepam).(ABSTRACT TRUNCATED AT 250 WORDS)", "To assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression.\n Randomised, double blind, multicentre, parallel group trial for 8 weeks.\n Trained panel of 18 general practitioners from four German states: Bavaria, Berlin, Rhineland Palatinate, and Saxony.\n 263 patients (66 men, 197 women) with moderate depression according to ICD-10 (international classification of diseases, 10th revision) codes F32. 1 and F33.1.\n 1050 mg hypericum extract (350 mg three times daily), 100 mg imipramine (50 mg, 25 mg, and 25 mg daily), or placebo three times daily.\n Change from baseline score on the 17 item version of the Hamilton depression scale, the Hamilton anxiety scale, the clinical global impressions scale, Zung's self rating depression scale, and SF-36, and adverse events profile.\n Hypericum extract was more effective at reducing Hamilton depression scores than placebo and as effective as imipramine (mean -15.4 (SD 8.1), -12.1 (7.4), and -14.2 (7.3) respectively). Comparable results were found for Hamilton anxiety and clinical global impressions scales and were most pronounced for the Zung self rating depression scale. Quality of life was more improved in the standardised mental component scale of the SF-36 with both active treatments than with placebo but in the physical component scale was improved only by hypericum extract compared with placebo. The rate of adverse events with hypericum extract was in the range of the placebo group but lower than that of the imipramine group (0.5, 0.6, and 1.2 events per patient respectively).\n At an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life.", "In a double-blind study in general practice, both mianserin ('Bolvidon') in an average dose of 40 mg a day, and imipramine, in an average dose of 100 mg a day, were found to be significantly more effective than placebo after two to three weeks' treatment. No significant differences in antidepressant effect could be demonstrated between mianserin and imipramine. There was no significant difference in side-effects between the three treatments.", "nan", "Twenty-one depressed patients with probable Alzheimer's disease (AD) were randomized to receive a 6-week treatment with clomipramine or placebo in a study with a double-blind crossover design. Main outcome measures were Hamilton Depression, Mini-Mental State (MMSE), and Functional Independence Measure (FIM) scores. Mood improved significantly on both clomipramine and placebo, but clomipramine was significantly more effective than placebo during the first 6-week treatment period. Patients started on clomipramine maintained improvement during the washout and placebo periods, whereas patients started on placebo worsened during the washout period. However, patients on clomipramine showed significantly lower MMSE scores overall than patients on placebo. No significant drug effects were found on FIM scores. Clomipramine proved to be a useful treatment of depression in patients with probable AD.", "nan", "A controlled double-blind trial of amitriptyline at two dosage levels (75 and 150 mg/day), amylobarbitone (150 mg/day), and an inert substance for a period of four weeks was conducted on four matched groups of women attending their general practitioners and suffering from a depressive illness. Improvement at 7 and 28 days was noted on several measures of depression and anxiety in all treatment groups. Of these treatments amitriptyline 150 mg/day was the most consistent in relieving depression and anxiety. Troublesome side effects were equally distributed among the four treatments.", "Two hundred and ten psychiatric patients with one of three DSM-III diagnoses, generalized anxiety disorder (N = 71), panic disorder (N = 74) or dysthymic disorder (N = 65), were included in a clinical trial in which diazepam, dothiepin or placebo tablets, cognitive and behaviour therapy, or a self-help package were given over ten weeks. Personality status was assessed independently using a structured interview, the Personality Assessment Schedule. One hundred and ninety-eight patients had personality assessments, 89% with a close informant. Thirty-six per cent had a personality disorder and these patients had more severe psychopathology than those with no personality disorder. Personality disorder was more common in patients with dysthymic disorder and this group responded less well to treatment. The category of personality disorder had no apparent influence on symptoms.", "nan", "In a 6-week, double-blind study involving 34 endogenously depressed patients, plasma trimipramine levels of two dosage groups, 75-mg/day and 150-mg/day, were compared with regard to clinical efficacy as determined by scores on the Hamilton Rating Scale for Depression, the Clinical Global Impressions scale, and the Zung Self-Rating Depression Scale. Both dosage levels of trimipramine produced prompt, consistent, and progressive antidepressant effects. No correlation between plasma levels and clinical efficacy was found.", "nan", "nan", "The efficacy and safety of alprazolam as compared to imipramine or a placebo added to weekly interpersonal psychotherapy was compared in a 6-week double-blind randomized clinical trial of 35 ambulatory elderly patients with major depression. The average maximum dosage of alprazolam was 2.2 mg and the average maximum dosage of imipramine was 97.5 mg. The findings showed a rapid onset of action of alprazolam within 1 week on symptoms of depression and anxiety. The effects for imipramine were seen later in the study. There were no serious side effects that interfered with treatment. The anticholinergic effects of imipramine were the ones that most commonly interfered with treatment. Alprazolam produced the greatest number of symptoms with discontinuation, most of which were alleviated within a week. We conclude that alprazolam may be useful as an antidepressant for the elderly. More clinical trials are needed to test its efficacy in the depressed elderly with concomitant medical problems, using plasma levels. A double-blind discontinuation study of alprazolam is needed to determine the degree of symptom return.", "The authors divided 61 subjects with primary degenerative dementia of the Alzheimer's type into a group who also met DSM-III criteria for depression (N = 28) and a group who did not (N = 33). Both groups were randomly assigned to an 8-week double-blind trial of imipramine or placebo. Scores on the Hamilton Rating Scale for Depression, administered at baseline and weeks 2, 4, 6, and 8, indicated significant improvement in both groups. Two measures of cognitive function yielded differing results. The results suggest that moderate depression is a treatable condition in patients with Alzheimer's disease.", "The current study was designed to assess the safety and efficacy of imipramine and buspirone in the treatment of major depression in elderly depressed attendees of primary care practices.\n 177 patients aged 65 and over (mean age = 72 years; range, 65-89) who met DSM-III-R criteria of unipolar major depression with a minimum Hamilton Rating Scale for Depression score of 18 were randomly assigned to 8 weeks of double-blind, placebo-controlled treatment with flexible doses of either imipramine or buspirone.\n Moderate to marked global improvement after 8 weeks of treatment (LOCF analysis) occurred in 70% of patients treated with imipramine, 61% of patients treated with buspirone, and 42% of patients treated with placebo (chi2 = 9.1, df = 2, p < .02). Drug treatment was well tolerated, with 77% of imipramine- and 61% of buspirone-treated patients completing 8 weeks of therapy. Imipramine/placebo differences were present from week 2 on, but buspirone/placebo differences occurred only at week 8. The presence of comorbid medical illness or concomitant use of nonpsychiatric prescription medications was not associated with poorer antidepressant response, increased adverse effects, or study attrition.\n Imipramine and to a lesser extent buspirone were found to be effective and well tolerated in the treatment of elderly depressed outpatients.", "A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression.", "In a controlled trial of amitriptyline hydrochloride in migraine prophylaxis, 100 patients received placebo for a four-week baseline period and then were randomized in double-blind fashion to therapy with amitriptyline (47 subjects) or placebo (53 subjects) for another four to eight weeks. Subjects received up to four 25-mg tablets of amitriptyline hydrochloride or identical placebo per day. Comparing the first and second four-week periods for each patient, the conditions of 55.3% of amitriptyline subjects as opposed to 34.0% of placebo subjects were greater than or equal to 50% improved and the difference between amitriptyline and placebo response rates was significant (P less than .05). Nondepressed subjects with severe migraine and depressed subjects with less severe migraine responded best to amitriptyline, whereas depressed subjects with severe migraine had little headache relief. Amitritryline is an effective antimigraine agent and the antimigraine effect seems relatively independent of antidepressant activity.", "nan", "nan", "Amisulpride, a selective antagonist of D2 and D3 dopamine receptors, acts preferentially on presynaptic receptors increasing dopaminergic transmission at low doses. In a multicentre, 6 months, placebo-controlled trial, amisulpride (50 mg/daily) was compared to imipramine (100 mg/daily) in the treatment of patients with DSM-III-R criteria for primary dysthymia, dysthymia with major depression or major depression in partial remission. A total of 219 patients were included. Both analyses (intention-to-treat and \"per protocol' analysis) detected significant differences between groups (active treatment vs. placebo) on all main rating scales (CGI, MADRS, ERD, and SANS). The number of patients reporting at least one adverse event was higher in the imipramine group than in the two other, mainly due to anticholinergic effects. Endocrine symptoms were more frequent in female patients treated with amisulpride. These results confirm the interest of a drug acting on dopaminergic transmission such as amisulpride in the treatment of depressed patients.", "nan", "To examine the problems of establishing dose-effect and concentration-effect relationships of antidepressant therapy with clomipramine.\n This randomized double-blind study compared five fixed doses of clomipramine hydrochloride: 25, 50, 75, 125, and 200 mg/day in hospitalized or day patients at nine clinical centers in Denmark. A 1-week washout period was followed by 6 weeks of active treatment and weekly depression ratings. In total, 151 patients (100 women and 51 men) with major depression scoring > or =18 on the Hamilton Depression Scale (HDS) or > or =9 on the Hamilton Depression subscale (HDSS) before and after the washout period were randomized. The treatment groups (n = 29 to 32) were well balanced with respect to sex, age, and depression rating. Serum concentrations of clomipramine plus metabolites were measured at weekly intervals. A sparteine test was performed before and during drug treatment.\n There was pronounced interpatient variability in response and kinetics at each dose. Drop-outs attributable to adverse events increased with rising doses, whereas drop-outs caused by worsening or lack of effect or nonresponse declined with increasing dose. Completer analyses showed a moderate and statistically significant relationship between depression rating and dose at all ratings after 1 to 6 weeks of treatment (trend analysis). HDS items representing core symptoms of depression showed a particularly consistent dose-effect relationship. Early sustained response occurred more frequently with the two highest doses. Serum levels of clomipramine and desmethylclomipramine showed weak correlation with depression ratings (Rs = -0.18 to -0.27; P < .05 to P < .01). A few blood pressure measurements and a few typical side-effect ratings showed a statistically significant dose-effect and concentration-effect relationship. Serum concentration of clomipramine and desmethylclomipramine showed a pronounced disproportionate increase with increasing dose. Clomipramine inhibited in a dose-dependent fashion CYP2D6 (sparteine oxidation).\n The dose-effect curves, indicating the probability of a certain outcome at a given dose, were flat and overlapping suggesting a narrow therapeutic range. This pattern is similar to that observed with newer antidepressants.", "nan", "nan", "Those who were labelled as depressives in a rural survey were randomly divided into a Medicine group (who received antidepressive drug treatment), a Placebo group (who received placebo) and a Natural Process group (who received no treatment). The depth of their depression was assessed by Hamilton's Depressive Rating Scale before the beginning of the trial, on the 14th day and on the 28th day of trial. They were compared with a matched group of healthy controls and again with a matched group of depressives who attended an urban clinic for treatment. The results indicate that the rural depressives who never sought treatment voluntarily were not different from those who sought treatment in clinics, so far as their response to treatment is concerned.", "Seventy-four depressed patients were treated with amitriptyline for 4-6 weeks. Their doses were individually adjusted to maintain the sum of the plasma levels of amitriptyline (AT) and nortriptyline (NT) within one of three different ranges, randomly allocated. Allowance was made for individual plasma binding of the drugs. In the 50 patients between 25 and 65 years of age, the antidepressive response at low plasma drug levels was somewhat poorer than at medium or high levels, which were equally effective. In this age group an association was found between outcome and the individual rate of AT metabolism, expressed as \"reciprocal clearance\" (RC), the steady-state plasma concentration of AT plus NT divided by the daily AT dose. Good antidepressive outcome was associated with high RC. The implications of these findings for patient treatment and for the interpretation of other studies are discussed. The 18 patients between 65 and 80 years of age showed no significant differences between the effectiveness of treatment at different plasma drug levels, and no significant associations between outcome and RC.", "A double-blind study was conducted to determine the efficacy and safety of trazodone vs. amitriptyline and placebo in 184 patients suffering from neurotic depression. All patients were evaluated for safety and 127 patients who completed 12 to 42 days' therapy were evaluated for efficacy. Trazodone was found to be significantly better than placebo on almost every rating scale, particularly on those items or factors related to depression and associated anxiety. Trazodone was superior to amitriptyline in some patients while amitriptyline was only occasionally better than placebo. Significant improvement was noted in trazodone patients within the first seven days of therapy. Trazodone produced a low level of side effects compared to amitriptyline.", "3-Cyano-imipramine (cianopramine) is a potent and selective inhibitor of serotonin uptake into synaptosomes. In a double-blind trial, 60 patients with various types of depression fulfilling the DSM-III criteria of depressive episodes were treated with either cianopramine (n = 20, mean daily dose 3.3 +/- 0.6 mg) amitriptyline (n = 20, mean daily dose 86.4 +/- 21 mg) or placebo (n = 20) orally. According to the ratings of the Hamilton Scale of Depression and clinical global evaluations, both active drugs showed statistical superiority over placebo (P less than 0.02). The frequencies of anticholinergic side effects in the cianopramine group were comparable to those of the placebo group and were less than in the amitriptyline group. The findings suggest that cianopramine is a promising new antidepressant.", "In a double-blind, placebo-controlled study, the therapeutic efficacy of two antidepressants with different neurochemical mechanisms of action, amitriptyline and amineptine, was investigated in patients affected by anxious depression. Sixty-six patients with the primary diagnosis of major depression or bipolar affective disorder (DSM-III-R) and meeting additional operational clinical criteria such as anxiety, trepidation, restlessness, early and/or late insomnia, impulsivity, hostility, dysphoria, compulsivity, hyperperspiration, palpitation, pollakiuria and phobias were included. They were randomly assigned to three groups (n = 22) and treated either with placebo, amitriptyline (up to 100 mg/day) or amineptine (up to 200 mg/day) for 6 weeks. Patients showed better response to amitriptyline, a preferential inhibitor of serotonin reuptake, than to amineptine, a selective inhibitor of dopamine reuptake. The present results suggest that alterations in serotonergic rather than dopaminergic transmission contribute to the pathophysiology of anxious depression.", "The effect of low-dose trimipramine (25 to 75 mg/day) on joint pain and tenderness in 36 patients with rheumatoid arthritis was studied in a randomized double-blind trial carried out over a period of 12 weeks. The patients were pre-selected to include only patients who were depressed on a 'self-rating depression scale' but had no evidence of fibrositic 'trigger-points'. The results showed that joint pain and tenderness were significantly reduced with trimipramine, but depression scores remained unchanged.", "nan", "This study with 31 obese binge eaters (body mass index [BMI] 39.5+/-8.6 kg/m(2) [SD]) was designed to assess whether diet counseling with psychological support and imipramine or placebo has an effect on the frequency of binge eating, body weight, and depression during an 8-week treatment phase. This was followed by an open medication-free phase of 6 months of continuous diet counseling with psychological support.\n Randomized double-blind placebo-controlled study of 8 weeks followed by an open phase of 6 months. Patients were evaluated in medical visits by a semistructured videotaped interview, psychometric questionnaires, and hematochemical parameters.\n From Week 0 to 8, a significant reduction in binge frequency occurred in both treatment conditions (7.1+/-4.1 to 2.8+/-3.0 binges per week [imipramine] vs. 7.1+/-4.1 to 5.4+/-5.1 [placebo], p<.01). Patients on imipramine lost -2.2+/-1.8 kg compared to placebo-treated subjects (+0.2+/-3.3 kg, p<.001). On follow-up, only the patients initially treated with imipramine continued to lose weight (-5.1+/-2.8 kg [imipramine] vs. 2.2+/-6.8 kg [placebo], p<.001 [differences to Week 0]). While both treatment conditions were associated with significant improvements on a rater's measure of depressive symptoms (Hamilton Depression Scale) at Week 8, only the patients treated with imipramine still showed a significant improvement at Week 32. Scores on the Self Depression Rating Scale did not show a group difference but a significant reduction at Weeks 8 and 32, compared to baseline.\n These results suggest that adding low-dose imipramine to diet counseling with psychological support helps patients losing weight even for at least 6 months off medication. The effect might include a psychological priming of weight loss during the double-blind phase that continues at least for half a year after stopping the drug.\n Copyright 1999 by John Wiley & Sons, Inc." ]

[ "17655723", "17439514", "21420555" ]

[ "Pilot study of two new injectable bulking agents for the treatment of faecal incontinence.", "Elastomer implants in faecal incontinence: a blind, randomized placebo-controlled study.", "Efficacy of dextranomer in stabilised hyaluronic acid for treatment of faecal incontinence: a randomised, sham-controlled trial." ]

[ "The use of injectable bulking agents for passive faecal incontinence appears to provide reasonable short-term results. However experience with different agents is limited. We report on the outcome of injections with new bulking agents.\n Each patient received injections of either Bulkamid (hydrogel cross-linked with polyacrylamide) or Permacol (porcine dermal collagen). Assessment included clinical evaluation, anorectal physiological testing, endoanal ultrasonography and questionnaires including the St Mark's Incontinence Score, one week bowel diary card, the Faecal Incontinence Quality of Life Scale and the Short Form-36 (SF-36) health survey. Follow up was at 6 weeks and 6 months, with a further telephone review at a median of 19 months (range 14-22).\n Ten patients (nine female), median age 68 years (range 45-79), were enrolled. St Mark's incontinence score (0 = best, 24 = worst) was 15 (range 11-24) at baseline, 12.5 (range 3-18) at 6 weeks and 14 (range 6-22) at 6 months. A 1-week bowel diary and SF-36 forms also showed temporary improvement but this was not sustained beyond 6 weeks.\n Bulkamid and Permacol injections did not have a major effect on faecal incontinence.", "To test efficacy and safety of polydimethylsiloxane elastomer implants, a silicone biomaterial, in patients with severe faecal incontinence related to an impaired internal anal sphincter.\n Subjects were randomized to receive three injections of 2.5 mL of either physiological saline or polydimethylsiloxane elastomer. After local anaesthesia, an 18 gauge, 2.5-in needle was inserted through the perianal skin and laid down into the intersphincteric space. Treatment (saline or polydimethylsiloxane elastomer) was administered by means of a ratchet gun. Three injections of 2.5 mL each were performed in the area of the internal anal sphincter at 3, 7 and 11 o'clock positions. Main end point was the percentage of subjects in each treatment arm experiencing a successful treatment, defined as a Cleveland Clinic Florida-Faecal Incontinence score <8, 3 months after treatment. Secondary end points were quality of life scores, weekly number of faecal incontinence episodes, subject acceptance and adverse events rate. Both patients and end point assessments were blinded to treatment. Results: 44 women (64.3 +/- 9 years) with a baseline Cleveland Clinic Florida-Faecal Incontinence score > or =8 were enrolled prospectively; 22 received polydimethylsiloxane elastomer and 22 saline treatment. Treatment was well tolerated. At 3 months, the percentage of subjects experiencing a successful treatment was not different between polydimethylsiloxane elastomer and saline groups (23% vs. 27%, respectively, P = 0.73). Moreover, Cleveland Clinic Florida-Faecal Incontinence score was not significantly different between polydimethylsiloxane elastomer and saline groups (11.7 +/- 4.7 vs. 11.4 +/- 4.5, respectively, P = 0.79).\n Polydimethylsiloxane elastomer implants cannot be recommended for treatment of severe faecal incontinence related to impaired internal anal sphincter.", "Injection of a bulking agent in the anal canal is an increasingly used treatment for faecal incontinence, but efficacy has not been shown in a controlled trial. We aimed to assess the efficacy of injection of dextranomer in stabilised hyaluronic acid (NASHA Dx) for treatment of faecal incontinence.\n In this randomised, double-blind, sham-controlled trial, patients aged 18-75 years from centres in USA and Europe were randomly assigned (2:1) to receive either transanal submucosal injections of NASHA Dx or sham injections. Randomisation was stratified by sex and region in blocks of six, and managed with a computer generated, real-time, web-based system. Patients and investigators were masked to assignment for 6 months when the effect on severity of faecal incontinence and quality of life was assessed with a 2-week diary and clinical assessments. The primary endpoint was response to treatment based on the number of incontinence episodes. A response to treatment was defined as a reduction in number of episodes by 50% or more. Patients in the active treatment group are still being followed up. This trial was registered with ClinicalTrials.gov, number NCT00605826.\n 278 patients were screened for inclusion, of whom 206 were randomised assigned to receive NASHA Dx (n=136) or sham treatment (n=70). 71 patients who received NASHA Dx (52%) had a 50% or more reduction in the number of incontinence episode, compared with 22 patients who received sham treatment (31%; odds ratio 2·36, 95% CI 1·24-4·47, p=0·0089). We recorded 128 treatment-related adverse events, of which two were serious (1 rectal abscess and 1 prostatic abscess).\n Anal injection of NASHA Dx is an effective treatment for faecal incontinence. A refinement of selection criteria for patients, optimum injected dose, ideal site of injection, and long-term results might further increase the acceptance of this minimally invasive treatment.\n Q-Med AB.\n Copyright © 2011 Elsevier Ltd. All rights reserved." ]

[ "14760660", "11727073", "11084131", "11988802", "11961622", "11961623", "10376458", "17236859", "12163963", "14752633", "17512301", "17122975", "11928017", "18027030", "17377238", "12368674", "17968168", "12184901" ]

[ "Randomized clinical trial of virtual reality simulation for laparoscopic skills training.", "Skill transfer from virtual reality to a real laparoscopic task.", "A comparison between randomly alternating imaging, normal laparoscopic imaging, and virtual reality training in laparoscopic psychomotor skill acquisition.", "The transfer of basic skills learned in a laparoscopic simulator to the operating room.", "Does training in a virtual reality simulator improve surgical performance?", "Evaluation of structured and quantitative training methods for teaching intracorporeal knot tying.", "Virtual reality training in laparoscopic surgery: a preliminary assessment of minimally invasive surgical trainer virtual reality (MIST VR).", "Virtual-reality training improves angled telescope skills in novice laparoscopists.", "Practice distribution in procedural skills training: a randomized controlled trial.", "Laparoscopic virtual reality and box trainers: is one superior to the other?", "Proficiency-based virtual reality training significantly reduces the error rate for residents during their first 10 laparoscopic cholecystectomies.", "Prospective randomized controlled trial of laparoscopic trainers for basic laparoscopic skills acquisition.", "Comparison of video trainer and virtual reality training systems on acquisition of laparoscopic skills.", "Transfer validity of laparoscopic knot-tying training on a VR simulator to a realistic environment: a randomized controlled trial.", "Skills acquired on virtual reality laparoscopic simulators transfer into the operating room in a blinded, randomised, controlled trial.", "Virtual reality training improves operating room performance: results of a randomized, double-blinded study.", "Proving the effectiveness of virtual reality simulation for training in laparoscopic surgery.", "Training in laparoscopic suturing skills using a new computer-based virtual reality simulator (MIST-VR) provides results comparable to those with an established pelvic trainer system." ]

[ "This study examined the impact of virtual reality (VR) surgical simulation on improvement of psychomotor skills relevant to the performance of laparoscopic cholecystectomy.\n Sixteen surgical trainees performed a laparoscopic cholecystectomy on patients in the operating room (OR). The participants were then randomized to receive VR training (ten repetitions of all six tasks on the Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR)) or no training. Subsequently, all subjects performed a further laparoscopic cholecystectomy in the OR. Both operative procedures were recorded on videotape, and assessed by two independent and blinded observers using predefined objective criteria. Time to complete the procedure, error score and economy of movement score were assessed during the laparoscopic procedure in the OR.\n No differences in baseline variables were found between the two groups. Surgeons who received VR training performed laparoscopic cholecystectomy significantly faster than the control group (P=0.021). Furthermore, those who had VR training showed significantly greater improvement in error (P=0.003) and economy of movement (P=0.003) scores.\n Surgeons who received VR simulator training showed significantly greater improvement in performance in the OR than those in the control group. VR surgical simulation is therefore a valid tool for training of laparoscopic psychomotor skills and could be incorporated into surgical training programmes.\n Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "To validate the usefulness of virtual reality surgical simulators, we investigated the transfer of skills achieved by their use to real tasks.\n Thirty medical students underwent a pretest using a real laparoscopic trainer. They were then randomized to the following three groups: group I received no training; group II received training using the Minimal Invasive Surgical Trainer in Virtual Reality (MIST-VR); and group III received training using conventional training exercises. Each group then underwent a posttest. Using the Imperial College Surgical Assessment Device (ICSAD), scores were generated for time taken, distance traveled, number of movements made, and speed of instrument movement.\n Significant changes between the MIST-VR group (group II) and the conventionally trained group (group III), were observed in the speed of movement of the left hand and the numbers of movements taken by each hand, when compared to the untrained group (group I).\n The training of novices using MIST-VR yields quantifiable changes in skill that are transferable to a simple real task and are similar to the results achieved with conventional training.", "To evaluate virtual reality as a laparoscopic training device in helping surgeons to automate to the \"fulcrum effect\" by comparing it to time-matched training programs using randomly alternating images (ie, y-axis inverted and normal laparoscopic) and normal laparoscopic viewing conditions.\n Twenty-four participants (16 females and 8 males), were randomly assigned to minimally invasive surgery virtual reality (MIST VR), randomly alternating (between y-axis inverted and normal laparoscopic images), and normal laparoscopic imaging condition. Participants were requested to perform a 2-minute laparoscopic cutting task before and after training.\n In the test trial participants who trained on the MIST VR performed significantly better than those in the normal laparoscopic and randomly alternating imaging conditions.\n The results show that virtual reality training may provide faster skill acquisition with particular reference to automation of the fulcrum effect. MIST VR provides a new way of training laparoscopic psychomotor surgical skills.", "The aim of the study was to evaluate whether basic surgical skills achieved by training in LapSim, a computerbased laparoscopic simulator, could be transferred to the operating room.\n For this study, 24 medical students undergoing courses in surgery were randomly assigned to train with LapSim or to serve as control subjects. After they had undergone simulator training 2 h per week for 5 weeks, their basic skills in laparoscopic surgery were assessed in a porcine model. The time to perform each task was measured, and four senior surgeons independently graded the overall performance on a 9-step differential rating scale.\n The participants randomized to train with LapSim showed significantly better results for all tasks in both parts of the study than the untrained participants, according to the expert evaluation. Time consumption was accordingly lower in the training group in the control group.\n The results show that basic skills achieved by systematic training with a laparoscopic simulator such as LapSim can be transferred to the operating room.", "The development of computerized surgical simulators in a virtual reality environment demands models for proper validation. Recent investigations have shown that a virtual reality simulator (MIST-VR) is a reliable tool for the assessment of laparoscopic psychomotor skills and that it improves the automation of the so-called fulcrum effect. Therefore, we set out to determine whether training with the MIST-VR would improve the surgical performance of surgically inexperienced medical students and to see if results obtained in the simulator would correlate with surgical performance.\n A total of 29 medical students were randomized into two groups. One group received preoperative MIST-VR training. Both groups then performed a simulated laparoscopic appendectomy in a pig. The operations were videotaped and examined by three independent observers.\n There was no significant difference in performance between the two groups. The performance with the MIST-VR correlated with the results in surgery.\n A method that can measure surgical skill, based on the scoring of independent observers who view videotaped performances, seems to be reliable. MIST-VR did not improve the surgical skills of the subjects, but the results with MIST-VR did predict surgical outcome.", "We evaluated the effectiveness of five training methods-four structured and one unstructured-for teaching intracorporeal knot tying.\n Forty-three graduate students without prior laparoscopic experience were randomly assigned to one of five training groups, and their performance in 10 intracorporeal knot tying trials was evaluated, using time to complete a knot as the outcome measure.\n The average knot tying times for the four structured groups were significantly faster than the unstructured group (p < 0.0001). Among the four structured groups, the minimally invasive surgical trainer-virtually reality (MIST-VR) and the box trainer drills showed the most rapid improvements. The MIST-VR improved average suturing time from trial one to trial two (P = 0.05), the box trainer drills group improved from trial one to trial four (P = 0.01), and the other two groups showed slower improvements. Statistically significant correlations were observed between scores on MIST-VR tasks and average knottying times (R > 0.7, p < 0.05).\n Structured training can be useful for the development of laparoscopic skills. MIST-VR is a valuable part of this training, particularly in the objective evaluation of performance.", "The \"fulcrum effect\" of the body wall on surgical instrument manipulation is a major hurdle for novice endoscopic surgeons. Virtual reality training has not previously been evaluated as a means to overcome this problem.\n 16 participants with no experience of endoscopy were required to make multiple defined incisions under laparoscopic laboratory conditions within 2-minute periods. Half of the subjects were randomized to receive initial training on the Minimally Invasive Surgical Trainer, Virtual Reality (MIST VR) computer programme.\n Participants with MIST VR training made significantly more correct incisions (P = 0.0001) than the control group on test trial 1, and even after extended practice by both groups (P = 0.0001). They were also significantly more likely to actively use both hands to perform the endoscopic evaluation task (P = 0.01).\n Virtual reality training represents a potential, viable solution for junior endoscopists, for overcoming the \"fulcrum effect\", in a replicable, safe learning environment which allows objective and reliable quantification of skill levels by trainers.", "Based on prior success of virtual-reality (VR) trainers in imparting surgical skills, a randomized and controlled study was designed to determine whether VR training improves angled-telescope operative performance.\n Third-year medical students received instruction on the use of an angled laparoscope and subsequently underwent performance assessment of angled telescope navigational tasks in an anesthetized porcine model. Subjects were then randomized to objective-based training with an angled-telescope simulator (EndoTower; Verefi Technologies, Elizabethtown, PA) versus no training, followed by reassessment of performance.\n Initially, there were no significant differences between VR-trained (n = 9) and control (n = 10) groups. After training, object visualization, scope orientation, and horizon error scores were significantly better in VR-trained than control groups; subject-matched improvement in orientation score was 50.9% versus 10.8% (P < .05).\n VR training in angled laparoscope use improves operative performance of novices. These data support growing evidence that VR training is highly effective in improving surgical skills outside of the clinical setting.", "\"Massed\" and \"distributed\" practice are important concepts in the acquisition of fine motor skills, and may be important in training in procedural skills.\n A total of 41 novice subjects were recruited and randomized to three groups to receive training on the MIST VR surgical trainer. There were 14 subjects in each of groups A and B and 13 subjects in group C. Training comprised 20 min of massed practice for group A, 20 min of distributed practice in 5 min blocks for group B, and 15 min of distributed practice in 5-min blocks for group C. Following the training period, all groups had a 5-min rest period, followed by a 5-min retention test. Comparisons were made between groups A and B, and groups A and C.\n There was a statistically significant difference between groups A and B (p = 0.023) on the retention test, with group B performing better. The increment between the groups was 19% for the overall score on MIST VR. There were also significant differences in the time taken to complete the task during the training phase (p = 0.023, training blocks 3 and 4). Graphical representation suggests no effect between groups A and C, and statistical analysis confirms that the observed difference in median score is not significant.\n This study demonstrates a benefit for distributed practice over massed practice in learning laparoscopic surgical skills on the MIST VR surgical trainer. This finding has potential implications for skills training in all areas of medicine.", "Virtual reality (VR) simulators now have the potential to replace traditional methods of laparoscopic training. The aim of this study was to compare the VR simulator with the classical box trainer and determine whether one has advantages over the other.\n Twenty four novices were tested to determine their baseline laparoscopic skills and then randomized into the following three group: LapSim, box trainer, and no training (control). After 3 weekly training sessions lasting 30-min each, all subjects were reassessed. Assessment included motion analysis and error scores. Nonparametric tests were applied, and p < 0.05 was deemed significant.\n Both trained groups made significant improvements in all parameters measured ( p < 0.05). Compared to the controls, the box trainer group performed significantly better on most of the parameters, whereas the LapSim group performed significantly better on some parameters. There were no significant differences between the LapSim and box trainer groups.\n LapSim is effective in teaching skills that are transferable to a real laparoscopic task. However, there appear to be no substantial advantages of one system over the other.", "Virtual reality (VR) training has been shown previously to improve intraoperative performance during part of a laparoscopic cholecystectomy. The aim of this study was to assess the effect of proficiency-based VR training on the outcome of the first 10 entire cholecystectomies performed by novices.\n Thirteen laparoscopically inexperienced residents were randomized to either (1) VR training until a predefined expert level of performance was reached, or (2) the control group. Videotapes of each resident's first 10 procedures were reviewed independently in a blinded fashion and scored for predefined errors.\n The VR-trained group consistently made significantly fewer errors (P = .0037). On the other hand, residents in the control group made, on average, 3 times as many errors and used 58% longer surgical time.\n The results of this study show that training on the VR simulator to a level of proficiency significantly improves intraoperative performance during a resident's first 10 laparoscopic cholecystectomies.", "Laparoscopic surgery requires a different set of skills than traditional open surgery. The acquisition of basic laparoscopic skills may help novices when learning laparoscopic procedures. This study tested the hypothesis that the combination of virtual reality and box trainers leads to better basic laparoscopic skill acquisition than either method alone or no training.\n A randomized control trial involving preclinical medical students with no prior operative experience was performed. The students were grouped according to four training methods: virtual reality training, inanimate box training, a combination of both, and no training (control). The pre- and posttraining scores for four skills in the porcine laboratory were the metrics chosen for this study.\n A total of 65 students participated in this study. There were no differences among any of the pretraining scores (p > 0.05). The posttraining times differed between the four groups. Post hoc analyses showed statistically significant differences (p < 0.05) between the participants trained with both trainers and the control subjects.\n Our data demonstrate that the combination of virtual reality training and inanimate box training leads to better laparoscopic skill acquisition than either training method alone or no training at all. Optimal preclinical laparoscopic training should incorporate both virtual reality trainers and inanimate box trainers.", "Training on a video trainer or computer-based minimally invasive surgery trainer leads to improved benchtop laparoscopic skill. Recently, improved operative performance from practice on a video trainer was reported. The purpose of this study was three fold: (a) to compare psychomotor skill improvement after training on a virtual reality (VR) system with that after training on a video-trainer, (VT) (b) to evaluate whether skills learned on the one training system are transferable to the other, and (c) to evaluate whether VR or VT training improves operative performance. For the study, 50 junior surgery residents completed baseline skill testing on both the VR and VT systems. These subjects then were randomized to either a VR or VT structured training group. After practice, the subjects were tested again on their VR and VT skills. To assess the effect of practice on operative performance, all second-year residents (n = 19) were evaluated on their operative performance during a laparoscopic cholecystectomy before and after skill training. Data are expressed as percentage of improvement in mean score/time. Analysis was performed by Student's paired t-test. The VR training group showed improvement of 54% on the VR posttest, as compared with 55% improvement by the VT group. The VR training group improved more on the VT posttest tasks (36%) than the VT training group improved on the VR posttest tasks (17%) (p <0.05). Operative performance improved only in the VR training group (p <0.05). Psychomotor skills improve after training on both VR and VT, and skills may be transferable. Furthermore, training on a minimally invasive surgery trainer, virtual reality system may improve operative performance during laparoscopic cholecystectomy.", "Laparoscopic suturing is one of the most difficult tasks in endoscopic surgery, requiring extensive training. The aim of this study was to determine the transfer validity of knot-tying training on a virtual-reality (VR) simulator to a realistic laparoscopic environment.\n Twenty surgical trainees underwent basic eye-hand coordination training on a VR simulator (SIMENDO, DelltaTech, Delft, The Netherlands) until predefined performance criteria were met. Then, they were randomized into two groups. Group A (the experimental group) received additional training with the knot-tying module on the simulator, during which they had to tie a double laparoscopic knot ten times. Group B (controls) did not receive additional manual training. Within a week the participants tied a double knot in the abdominal cavity of an anaesthetized porcine model. Their performance was captured on digital video and coded. Objective analysis parameters were: time taken to tie the knot and number of predefined errors made. Subjective assessments were also made by two laparoscopic surgeons using a global rating list with a five-point Likert scale.\n Trainees in group A (n = 9) were significantly faster than the controls (n = 10), with a median of 262 versus 374 seconds (p = 0.034). Group A made a significantly lower number of errors than the controls (median of 24 versus 36 errors, p = 0.030). Subjective assessments by the laparoscopic experts did not show any significant differences in economy of movement and erroneous behavior between the two groups.\n Surgical trainees who received knot-tying training on the VR simulator were faster and made fewer errors than the controls. The VR module is a useful tool to train laparoscopic knot-tying. Opportunities arose to improve simulator-based instruction that might enhance future training.", "Virtual reality surgical simulators have proven value in the acquisition and assessment of laparoscopic skills. In this study, we investigated skill transfer from a virtual reality laparoscopic simulator into the operating room, using a blinded, randomised, controlled trial design. Surgical trainees using the LapSim System performed significantly better at their first real-world attempt at a laparoscopic task than their colleagues who had not received similar training, as measured independently by a number of expert surgical observers using four criteria.", "To demonstrate that virtual reality (VR) training transfers technical skills to the operating room (OR) environment.\n The use of VR surgical simulation to train skills and reduce error risk in the OR has never been demonstrated in a prospective, randomized, blinded study.\n Sixteen surgical residents (PGY 1-4) had baseline psychomotor abilities assessed, then were randomized to either VR training (MIST VR simulator diathermy task) until expert criterion levels established by experienced laparoscopists were achieved (n = 8), or control non-VR-trained (n = 8). All subjects performed laparoscopic cholecystectomy with an attending surgeon blinded to training status. Videotapes of gallbladder dissection were reviewed independently by two investigators blinded to subject identity and training, and scored for eight predefined errors for each procedure minute (interrater reliability of error assessment r > 0.80).\n No differences in baseline assessments were found between groups. Gallbladder dissection was 29% faster for VR-trained residents. Non-VR-trained residents were nine times more likely to transiently fail to make progress (P <.007, Mann-Whitney test) and five times more likely to injure the gallbladder or burn nontarget tissue (chi-square = 4.27, P <.04). Mean errors were six times less likely to occur in the VR-trained group (1.19 vs. 7.38 errors per case; P <.008, Mann-Whitney test).\n The use of VR surgical simulation to reach specific target criteria significantly improved the OR performance of residents during laparoscopic cholecystectomy. This validation of transfer of training skills from VR to OR sets the stage for more sophisticated uses of VR in assessment, training, error reduction, and certification of surgeons.", "The aim of this study was to compare learning curves for laparoscopic cholecystectomy (LC) after training on a proficiency based virtual reality (VR) curriculum with that of a traditionally trained group.\n Simulator-based training has been shown to improve technical performance during real laparoscopic procedures, although research to date has not proven the persistence of this effect over subsequent cases.\n Twenty novice surgeons underwent baseline laparoscopic skills testing followed by a 1-day didactic training session. Control subjects (n = 10) performed 5 cadaveric porcine LCs each; VR-trained subjects (n = 10) completed a VR training curriculum followed by 3 porcine LCs each. A further 10 experienced laparoscopic surgeons (>100 LCs) performed 2 porcine LCs each to define benchmark levels. Technical skill assessment was by motion analysis and video-based global rating scores (out of 35).\n There were no intergroup differences in baseline skill. The first LC revealed significant differences between control and VR groups for time (median 4590 seconds vs. 2165 seconds, P = 0.038), path length (169.2 meters vs. 86.8 meters, P = 0.009), number of movements (2446 vs. 1029, P = 0.009), and video scores (17 vs. 25, P = 0.001). The VR group, although not a control, achieved video and dexterity scores equivalent to expert levels of performance.\n A proficiency based VR training curriculum shortens the learning curve on real laparoscopic procedures when compared with traditional training methods. This may be a more cost- and time-effective approach, and supports the need for simulator-based practice to be integrated into surgical training programs.", "We hypothesized that the Minimally Invasive Surgery Trainer (MIST-VR; VP Medical R, London, U.K.) would be as effective as the Yale Laparoscopic Skills Course in improving laparoscopic intracorporeal suturing skills.\n Each student made six attempts to tie a knot laparoscopically. Students were then randomized to train on the MIST-VR for five sessions (six skills/session) or the Yale Skills for five sessions (three skills/session) over 5 days. On completion of training, all students were evaluated by a test consisting of six attempts to tie a laparoscopic knot.\n The percentage improvement in knot tying time did not differ significantly in the pelvic trainer group (30 +/- 21%) (from 443 +/- 135 to 311 +/- 137 seconds) and the MIST-VR group (39 +/- 21%) (from 409 +/- 109 to 256 +/- 140 seconds) (P = 0.308).\n The MIST-VR is equivalent to the Yale Skills Course for training in the advanced laparoscopic skill of intracorporeal suturing." ]

[ "10850749", "9543326", "10818549", "9298634", "8880694", "9329701", "2135708", "10609697" ]

[ "Propentofylline treatment for Alzheimer disease and vascular dementia: an economic evaluation based on functional abilities.", "Propentofylline enhances cerebral metabolic response to auditory memory stimulation in Alzheimer's disease.", "Investigating the natural course and treatment of vascular dementia and Alzheimer's disease. Parallel study populations in two randomized, placebo-controlled trials.", "A 12-month, randomized, placebo-controlled trial of propentofylline (HWA 285) in patients with dementia according to DSM III-R. The European Propentofylline Study Group.", "Propentofylline improves regional cerebral glucose metabolism and neuropsychologic performance in vascular dementia.", "Clinical trials in dementia with propentofylline.", "Propentofylline in adult-onset cognitive disorders: double-blind, placebo-controlled, clinical, psychometric and brain mapping studies.", "Clinical trials of propentofylline in vascular dementia. European/Canadian Propentofylline Study Group." ]

[ "A Canadian economic evaluation of propentofylline (a therapy shown to be effective for patients with mild to moderate Alzheimer disease and/or vascular dementia) versus standard care was conducted. Patients were categorized by functional abilities according to the Alberta Resident Classification System by translating measures that were originally captured through the Gottfries-Bråne-Steen scale. The Alberta Resident Classification System was then linked to a community dataset of home care costs for a population with dementia. Cost and cost-effectiveness analyses were performed from the perspective of the Ministry of Health, the caregiver, and society using an intent-to-treat analysis for propentofylline versus placebo. Results, limited to the 48-week clinical trial duration, indicated that propentofylline improved health outcomes of persons with dementia as statistically significant treatment effects were found. However, although an incremental cost for the propentofylline intervention was incurred from the Ministry of Health perspective, home care and, to a larger extent, caregiver costs were reduced. Savings in these areas may have partially offset annual treatment medication costs because a non-statistically significant cost difference was observed from a societal perspective.", "To evaluate efficacy, safety, metabolic and clinical effects of propentofylline in Alzheimer's disease (AD), a prospective, randomized, double-blind, placebo-controlled trial was performed in 30 patients with mild to moderate AD who underwent pretreatment and posttreatment 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography under resting conditions and during stimulation with an auditory memory paradigm. Twenty-eight subjects completed the 3-month study. The drug was well tolerated. In the active treatment group, a significant increase of cerebral metabolic response to the memory task was observed (multiple measurement ANOVA P = 0.02). The placebo group showed a significantly decline in the MMSE score (P = 0.02) while there was no change in the treatment group. This suggests a protective role for propentofylline in slowing the progression of AD.", "nan", "Alzheimer's disease (AD) and vascular dementia (VaD) share several features such as overactivation of microglial cells, damage induced by free radicals, glutamate and calcium overload. Propentofylline (HWA 285) has shown beneficial effects on all of these common elements, thus favouring its use in both subtypes of dementia. In a multinational, randomized, 12-month, double-blind, parallel-group study 260 out-patients with mild to moderate AD or VaD received 300 mg propentofylline (n = 129) or placebo (n = 131) three times daily 1 h before meals. The efficacy was tested at four independent rater levels (physician, psychologist, relative and patient) with assessments covering three major domains of dementia (global function, cognitive function and activities of daily living). After 12 months, the total patient population showed statistically significant treatment differences in favour of propentofylline for the global measures of dementia (Gottfries-Bråne-Steen scale, GBS, p = 0.001; Clinical Global Impressions, CGI, item I: p = 0.004, item II: p = 0.072) as well as for the cognitive measures (Syndrome Short Test, SKT, p = 0.002) and Mini-Mental State Examination (p = 0.001). The activities of daily living also showed a significant treatment difference in favour of propentofylline (p = 0.002). No significant treatment differences were found for rating scales performed by the patients. At month 12, VaD patients showed treatment differences in favour of propentofylline for the GBS total score (p = 0.006), CGI item I (p = 0.004), GGI item II (p = 0.044) and SKT (p = 0.028). Treatment differences for AD patients were all in favour of propentofylline and reached statistical significance for the SKT (p = 0.018). Propentofylline showed a good safety profile with respect to adverse events, vital signs, ECG and laboratory changes.", "In a double-blind, placebo-controlled trial in thirty patients with mild to moderate vascular dementia (VD) according to DSM-III-R criteria, the effects of the adenosine uptake blocker propentofylline (HWA 285) on regional cerebral glucose metabolism (rCMRGl) was studied using positron emission tomography of 2-[18F]fluoro-2-deoxy-D-glucose (FDG). 25 subjects completed the 3-months study. Propentofylline significantly improved relative rCMRGl in the motor cortex, while relative rCMRGl in the placebo treated group worsened significantly. Neuropsychologically, visual information processing was improved in the propentofylline group and we observed a trend towards a slowing of the progression of cognitive deterioration in patients with VD. The results of the longitudinal analysis showed further that neuropsychological and metabolic changes are closely related. These findings justify a large-scale clinical trial to prove therapeutic efficacy.", "The mode of action of propentofylline (a xanthine derivative) suggested that it would have beneficial effects in patients with Alzheimer's disease or vascular dementia. In four double-blind, placebo-controlled, randomized studies, 901 patients with mild to moderate Alzheimer's disease and 359 patients with mild to moderate vascular dementia were treated for up to 12 months (daily dose of propentofylline: 3 x 300 mg taken 1 hr before food). Patients were assessed at regular intervals for efficacy and safety of the drug. Efficacy variables covered cognitive and global functions as well as activities of daily living. Propentofylline showed statistically significant, clinically relevant improvements over placebo in efficacy assessments, both in patients with Alzheimer's disease and in patients with vascular dementia. The drug was also well tolerated. It had no significant effects on laboratory findings and the adverse events that were considered to be related to the study medication were mostly minor, transient, and affected the digestive and nervous systems.", "In a double-blind, placebo-controlled parallel group trial, the therapeutic efficacy and central effects of propentofylline (HWA 285) - a xanthine derivative with neuroprotective, metabolic, hemorheologic and antithrombotic action - were studied in 190 elderly outpatients with mild to moderate chronic cognitive disturbances (mild dementia, DSM-III-R). They received after a 2-week run-in period (placebo) for 12 weeks either 3 x 300 mg propentofylline or 3 x 1 tablet placebo (given at least 1 h before meals). The verum group (n = 96, age 68 +/- 9) was comparable to the placebo group (n = 94, age 69 +/- 8) in regard to age, height, smoking, consumption of stimulating alcoholic drinks, family and living status. Clinical evaluation by the Gottfries-Brane-Steen (GBS) scale demonstrated a significant superiority of propentofylline over placebo in the total score and the four GBS factors (motor, intellectual, emotional functions and other symptoms) as well as in the clinical global impression and Mini-Mental State. Psychometric measures showed slight and significant improvement in both groups but no intergroup differences. EEG brain mapping was carried out before and after 12 weeks' treatment in the Viennese subsample involving 24 propentofylline and 24 placebo patients. Propentofylline-treated patients exhibited, as compared with placebo-treated ones, a trend towards augmentation of total power, furthermore an increase in relative delta and beta and a decrease in alpha power, an acceleration of the dominant frequency as well as a slowing of the centroid of the combined delta/theta band. The total centroid tended towards acceleration, while the centroid deviation increased significantly. These alterations reflect vigilance changes of the dissociative type and differ from those of the classical nootropics. Clinical and psychometric evaluations demonstrated changes in the same direction as in the total sample, but interdrug differences were not significant. Thus, EEG brain mapping seems to be more sensitive in objectivating central drug effects.", "The neuroprotective glial cell modulator propentofylline has been used in clinical trials involving more than 800 patients with vascular dementia (VaD). These data derive from two sources: a pooled group of VaD patients from four early phase III European trials, and a multinational European/Canadian phase III study (MN 305) that features a combined randomized withdrawal/delayed onset of progression design to evaluate the effect of propentofylline on disease progression. In the pooled studies, DSM-III-R criteria, Hachinski Ischemia Scores, computed tomography (CT), and magnetic resonance imaging (MRI) were used to select subjects with mild-to-moderate disease; in MN 305, National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria and neurologic examinations (including CT and MRI scans) were used to select patients with possible or probable VaD. The use of a central rater to assess cerebrovascular disease in neuroradiologic examinations for study MN 305 was considered to be a key feature for reducing the heterogeneity of the VaD patient population. In addition, the inclusion of patients with possible VaD in this trial greatly increased the number of eligible patients; subgroup analyses revealed no substantial differences between patients with probable versus possible VaD, justifying their inclusion in the study. VaD patients exhibited a more pronounced placebo response in global assessments compared with the Alzheimer disease population in a parallel study. In addition, they experienced less deterioration over time with respect to cognitive and global assessments. Beneficial effects of propentofylline were consistently demonstrated in the domains of cognitive and global function for both VaD populations; however, no treatment benefits could be demonstrated for activities of daily living, possibly due to factors relating to the study population/design, the lack of a validated test instrument for such patients, the caregiver-related phenomenon of \"tutoring,\" or the nature of the disease itself." ]

[ "10534584", "2149565", "6210751", "17414235", "6228015", "140827", "9718247", "1833813", "11110112", "16202958" ]

[ "Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity.", "A randomized, double-blind, placebo-controlled trial of trazodone hydrochloride in chronic low back pain syndrome.", "Controlled trial of imipramine for chronic low back pain.", "Efficacy of noradrenergic and serotonergic antidepressants in chronic back pain: a preliminary concentration-controlled trial.", "Amitriptyline and chronic low-back pain. A randomized double-blind crossover study.", "Tofranil in the treatment of low back pain.", "A placebo-controlled randomized clinical trial of nortriptyline for chronic low back pain.", "[Prospective study of the analgesic action of clomipramine versus placebo in refractory lumbosciatica (68 cases)].", "The relationship between pain and depression in a trial using paroxetine in sufferers of chronic low back pain.", "A randomized, placebo-controlled trial of bupropion sustained release in chronic low back pain." ]

[ "To understand the relative efficacy of noradrenergic and serotonergic antidepressants as analgesics in chronic back pain without depression, we conducted a randomized, double-blind, placebo-control head-to-head comparison of maprotiline (a norepinephrine reuptake blocker) and paroxetine (a serotonin reuptake blocker) in 103 patients with chronic low back pain. Of these 74 completed the trial; of the 29 who did not complete, 19 were withdrawn because of adverse effects. The intervention consisted of an 8-week course of maprotiline (up to 150 mg daily) or paroxetine (up to 30 mg daily) or an active placebo, diphenhydramine hydrochloride (up to 37.5 mg daily). Patients were excluded for current major depression. Reduction in pain intensity (Descriptor Differential Scale scores) was significantly greater for study completers randomized to maprotiline compared to placebo (P=0.023), and to paroxetine (P=0.013), with a reduction of pain by 45% compared to 27% on placebo and 26% on paroxetine. These results suggest that at standard dosages noradrenergic agents may provide more effective analgesia in back pain than do selective serotonergic reuptake inhibitors.", "A 6-week placebo-controlled trial evaluated the efficacy of trazodone hydrochloride for the relief of chronic low back pain. Forty-two subjects (22 trazodone, 20 placebo) with a 20.3-year average history of back pain were titrated to an average dose of trazodone 201 mg or placebo 238 mg and evaluated daily on a Visual Analogue Scale of pain intensity, at 2-week intervals on an observer rating of pain behavior while walking, and before and after the trial on the Beck Depression Inventory, the Sickness Impact Profile, and a solid state microcomputer (Vitalog) that measured physical activity. Trazodone blood levels and urine toxicology screens were also obtained. There were no significant differences between groups in treatment effect. The results of this study require confirmation by longer trials with larger, less chronic, more homogeneous samples at higher doses with follow-up assessments.", "Chronic low back pain is a common problem that has been noted in several studies to exist as a component of masked depression. To determine the usefulness of imipramine in the treatment of chronic low back pain, either by a direct action or indirectly via resolution of a depressive equivalent, 50 consecutive patients were entered into a controlled trail that employed serum imipramine and desipramine levels and Beck depression questionnaires. Forty-one patients completed the study, and 48 were used in the statistical analysis. Imipramine had a statistically significant effect over placebo in most, but not all, of the clinical parameters that were measured. A linear relationship between serum drug levels and reported symptoms was not noted. Only 10 of the 50 patients entered into the study were judged clinically depressed and, of these, 7 were depressed according to standard criteria. There was no statistically significant difference noted in either the initial or the change in Beck depression scores between those on imipramine and those on placebo. However, among those on the active drug, the patients with a greater symptomatic response had a simultaneous change in the total Beck depression scores (toward less depression) that approached statistical significance when compared with those with a less symptomatic response. Although the results are not conclusive, imipramine may possibly be useful in the treatment of chronic low back pain, especially so when it exists as a component of masked depression.", "Although antidepressants are widely prescribed as analgesics in chronic back pain, their clinical pharmacology is not well established. Norepinephrine transporter blockade seems to be essential for analgesia, but optimal concentrations are unknown. Fixed-dose studies of serotonin reuptake inhibitors are generally negative, but such studies cannot be interpreted clearly because efficacy might be detected if concentration-response relationships were known. We evaluated (1) the feasibility of conducting a controlled-concentration study of a norepinephrine (desipramine) and a serotonin reuptake (fluoxetine) inhibitor and (2) the relationship between achieved concentrations and analgesic response.\n This single-center, 12-week, double-blind, prospective, controlled-concentration study randomized 121 chronic back pain patients without major depression to active placebo (benztropine mesylate) or to predetermined low, medium, or high concentrations of desipramine (targets were 50, 110, and 150 ng/mL, respectively) or fluoxetine (targets were 100, 200, and 400 ng/mL, respectively). Of these, 83 completed the trial: 38 withdrew primarily due to side effects.\n Manipulation check revealed significant overlap of assigned and achieved concentrations related to drug intolerability. Completers' analysis of achieved concentrations revealed reduction in pain intensity was significantly greater for low-concentration desipramine (<60 ng/mL, mean Descriptor Differential Scale [DDS], 4.5) compared with placebo (DDS 6.2), higher concentrations of desipramine (>60 ng/mL, DDS 7.9), and all concentrations of fluoxetine (P < 0.05, DDS 7.1). Significant improvement in everyday function mirrored findings for pain intensity.\n Preliminary evidence for a low-concentration \"therapeutic window\" for noradrenergic analgesia may warrant additional study.", "The effect of antidepressant medication on chronic low-back pain patients was studied in a randomized blind crossover study. Among those patients who completed the study, there was a 46% decrease in the use of analgesics while on amitriptyline when compared to placebo (P less than 0.005). There was also improvement in affect, but no measurable change in activity level. The MMPI profile of those patients who were unable to comply with the study protocol differed from that of patients who completed the study. The noncompliers demonstrated an elevation of the F, Pd, Pt (P less than 0.05) and Mf (P less than 0.01) scales. Although the interpretation of such a profile is left open to speculation, it may serve as an indicator of noncompliant individuals.", "This report describes a double-blind between-group comparison of Tofranil and placebo in fifty-nine patients admitted to the Joint Service Medical Rehabilitation Unit suffering from low back pain. Patients were given 25 mg of either Tofranil or placebo three times a day for four weeks. Fifteen patients were not included in the analysis, nine dropping out for non-trial related reasons, two dropping out complaining of lost libido and four not taking the tablets, or taking additional drugs. One of the patients complaining of lost libido was taking Tofranil and the other was taking placebo. Over the whole sample there was no significant benefit for Tofranil over placebo as regards physical measurements. Both Tofranil and placebo groups showed a significant improvement during the trial on straight leg raise and backward flexion. For lateral flexion the Tofranil group was significantly worse than the placebo group on entering the trial, and during the trial the Tofranil group improved to match the placebo group. The clinician's pain and stiffness assessments and the patients' pain and stiffness assessments show a significant improvement for both the Tofranil and placebo groups during the trial. However, no difference is shown between Tofranil and placebo. The psychological tests show no difference between Tofranil and placebo and only a marinal improvenmet over initial condition. Further analysis according to initial diagnosis showed nothing conclusive. Numerically, the use of Tofranil produced a marked improvement in pain and stiffness in patients with 'disc lesion only' diagnoses, whereas placebo did not produce an improvement. However, this observation was far from reaching statistical significance. Side-effects were not severe for either drug. Additional medication was rarely used.", "To assess the efficacy of nortriptyline, a tricyclic antidepressant, as an analgesic in chronic back pain without depression, we conducted a randomized, double-blind, placebo-controlled, 8-week trial in 78 men recruited from primary care and general orthopedic settings, who had chronic low back pain (pain at T-6 or below on a daily basis for 6 months or longer). Of these 57 completed the trial; of the 21 who did not complete, four were withdrawn because of adverse effects. The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression (50-150 ng/ml). The main outcome endpoints were pain (Descriptor Differential Scale), disability (Sickness Impact Profile), health-related quality of life (Quality of Well-Being Scale), mood (Beck Depression Inventory, Spielberger State Anxiety Inventory, Hamilton Anxiety/Depression Rating Scales), and physician rated outcome (Clinical Global Impression). Reduction in pain intensity scores was significantly greater for participants randomized to nortriptyline (difference in mean change 1.68, 95%-0.001, CI -3.36, P = 0.050), with a reduction of pain by 22% compared to 9% on placebo. Reduction in disability marginally favored nortriptyline (P = 0.055), but health-related quality of life, mood, and physician ratings of overall outcome did not differ significantly between treatments. Subgroup analyses of study completers supported the intent-to-treat analysis. Also, completers with radicular pain on nortriptyline (n = 5) had significantly (P < 0.05) better analgesia and overall outcome than did those on placebo (n = 6). The results suggest noradrenergic mechanisms are relevant to analgesia in back pain. This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression.", "The authors sought to determine the analgesic activity of clomipramine (CMP) versus placebo, efficacy and side-effects according to the time of administration, long term clinical results and the relationship between plasma levels and analgesic effect. This double-blind randomised trial involved the infusion of 250 ml of glucose solution morning and evening versus placebo. CMP was administered at progressive doses for 8 days (maximum dosage 75 mg), either in the morning at 8 a.m. or in the evening at 6 p.m. Sixty eight patients accepted to be treated, all suffering from low back pain with or without sciatica. Maintenance treatment at the dose of 75 mg/day was then administered. CMP had a statistically significant analgesic action independent (rapidity of action) of its antidepressant activity. CMP was more effective and better tolerated (sedative and tranquilizer effect) in the evening. Long term results were poor (75% of cases). There was no link between plasma levels and clinical response. The authors noted that the analgesic activity of CMP was rapid, but for a duration limited to the short term and that this efficacy compared with the quite good results obtained with the placebo could be explained by a possible methodological bias (patients hospitalised and treated by intravenous infusions). The finding that CMP was better tolerated in the evening, without any loss of efficacy, is a positive feature (chronotherapeutic trial). Poor long term results could be partially explained by side-effects (66%). There was no relationship between analgesic effect and plasma levels.", "Previous studies have shown a positive association between pain and depression, though evidence supporting a direct link between these two variables is less robust. Using a placebo-controlled trial, the authors examined the analgesic and antidepressant efficacy of paroxetine (20 mg) in chronic low back pain sufferers. The authors examined the associations among pain, depression, disability, and illness attitudes. Paroxetine showed no effects on pain or depression compared with placebo; however, subjects randomized to paroxetine were more likely to reduce concomitant analgesic medication. The cross-sectional association of depression and pain at baseline (r = 0.2, P = 0.02) was weaker than the association between depression and disability (r = 0.3, P = 0.004). Similarly, the association of change in depression scores with change in pain (r = 0.25, P = 0.016) was weaker than change between depression and disability (r = 0.49, P<0.0005). Whereas the relationship between pain and depression became nonsignificant when disability and illness attitudes were controlled, the relationship between depression and disability remained highly significant when pain and illness attitudes were controlled. These data are consistent with the association between pain and depression being wholly modulated by disability and illness attitudes, with no direct relationship between pain and depression.", "Clinical trials of the efficacy of antidepressant drugs in patients with chronic low back pain have had mixed results, possibly because of the different mechanisms of action of the drugs that have been studied. Because bupropion has a mechanism of action that differs from other antidepressants and has shown efficacy in neuropathic pain, a randomized, placebo-controlled, 2-period crossover trial was conducted to evaluate its efficacy in subjects with chronic low back pain. The primary efficacy variable was mean daily diary pain intensity ratings, and secondary pain intensity and relief outcomes included weekly pain intensity ratings, the McGill Pain Questionnaire (MPQ) Present Pain Intensity scale, pain relief ratings, and satisfaction with pain relief ratings. Adverse events were also assessed throughout the trial. Analyses were performed of an intention-to-treat sample of 44 patients, only 3 of whom met criteria for neuropathic low back pain. Daily and weekly pain intensity ratings, the MPQ Present Pain Intensity scale, and pain relief ratings were not significantly different following treatment with bupropion sustained release (SR) vs. placebo. These results suggest that bupropion SR was not significantly better than placebo in the treatment of patients with non-neuropathic chronic low back pain.\n Antidepressant medications that have both noradrenergic and serotonergic effects appear to have greater efficacy in patients with chronic low back pain than those with only serotonergic activity. We studied bupropion because it inhibits the reuptake of both norepinephrine and dopamine, but found no evidence of efficacy in patients with non-neuropathic chronic low back pain." ]

[ "661262", "5925525", "7865920", "10515518", "9113858", "9630259", "3724113", "11407566", "1118271", "14145958", "3974209", "8084191", "9113855", "7680731", "1739321", "11030677", "13839775", "9130202", "8227504", "13915131", "5006954", "8028316", "8959612", "903408" ]

[ "Assessment of parent-administered listening training for preschool children with articulation deficits.", "The effectiveness of group and individual therapy.", "Parental-based intervention with pre-school language-delayed children.", "Effects of treatment on linguistic and social skills in toddlers with delayed language development.", "The influence of peer models on the play scripts of children with specific language impairment.", "Effectiveness of speech intervention for phonological disorders: a randomized controlled trial.", "Direct language instruction and interactive language instruction with language delayed preschool children: a comparison study.", "The effect of target-selection strategy on phonological learning.", "Speech remediation of children involved in two different physical education programs.", "EFFECTS OF MATERNAL ATTITUDES UPON IMPROVEMENT IN ARTICULATION WHEN MOTHERS ARE TRAINED TO ASSIST IN SPEECH CORRECTION.", "Facilitating word combination in language-impaired children through discourse structure.", "Effects of grammar facilitation on the phonological performance of children with speech and language impairments.", "Two models of grammar facilitation in children with language impairments: phase 2.", "Two approaches to the facilitation of grammar in children with language impairment: an experimental evaluation.", "Trial of intensive compared with weekly speech therapy in preschool children.", "Randomised controlled trial of community based speech and language therapy in preschool children.", "Effectiveness of trained parents as speech therapists.", "Effects of lexical intervention on the phonology of late talkers.", "The use of different service delivery models for children with phonological disorders.", "Factors in the effectiveness of mothers trained to aid in speech correction.", "Utilization of parents in a speech correction program.", "Speech perception training can facilitate sound production learning.", "Interactive focused stimulation for toddlers with expressive vocabulary delays.", "Generalization of an operant remediation program for syntax with language delayed children." ]

[ "Two studies concerning preschool misarticulating children are reported. The first study was concerned with direct effects of two varieties of parent-administered listening training. The second study focused on the influence of that same training on children's responses to sound-production training. Subjects were assigned to one of three conditions: listening, reading-talking, and control. Children in the first group were provided training by their parents that was intended to focus the child's attention on consonants in syllables or words and to teach discrimination between correctly and incorrectly articulated consonants. Parents of children in the second group read to and talked with them about the material. Neither treatment group surpassed the control group in gains made on any auditory processing or articulatory measure employed, and some parents found the listening training frustrating. In the second study, a subset of the children in each of the three groups was given sound-production training. The data obtained did not show any effect from earlier listening experiences on sound-production performance.", "nan", "Mothers of children randomly allocated to an experimental group attended fortnightly group parental language training sessions, over a 6-month period. Mothers of children allocated to a matched no intervention control group received no special attention. The results showed significantly greater gains in the expressive language skills of the experimental group compared to the control group. A second experiment was designed to compare the parental involvement approach with direct, individual treatment and to clarify the role of non-specific 'Hawthorne-type' effects. The experimental group mothers attended parental language training sessions, as above. The parental control group mothers also attended training sessions, with the emphasis on general learning skills rather than language. A third group of children received individual, direct speech and language therapy. Results showed significantly greater language gains in the parental language training group and in the individual group in comparison with the non-specific training group. The two former groups did not differ significantly, indicating that, for these groups and this methodology, parental language training is as effective as individual speech and language therapy. The results also indicate that the effectiveness of the parental involvement approach cannot be accounted for by non-specific factors. The research findings are discussed, together with the professional implications of the study and recommendations for further research.", "This study investigated the effects of early language intervention on various linguistic and social skills of late-talking toddlers. The 21 children who participated in the investigation were randomly assigned to an experimental group (n = 11) or a control (delayed-treatment) group (n = 10). The experimental group participated in a 12-week clinician-implemented language intervention program. Groups were compared at pretest and posttest on five linguistic variables: Mean Length of Utterance, Total Number of Words, Number of Different Words, Lexical Repertoire, and Percentage of Intelligible Utterances, as well as on Socialization and Parental Stress. Significant group differences were found for each of the variables, indicating facilitative effects of the treatment. Notably, increases were observed in areas that were not specifically targeted by the intervention. Implications of these results are discussed with respect to considerations regarding clinical management decisions for toddlers with delayed language development.", "This investigation included two phases of inquiry that examined the effects of peer modeling upon the play scripts of children with specific language impairment (SLI). The first study employed a pretest-posttest control group design involving two groups of children with SLI (10 who participated in the experimental treatment and 10 controls) and a group of peer models (10 children with normal language development). The treatment involved dyadic play sessions in which children with SLI were paired with a normal language peer model. Significant differences were found between the play script reports of the experimental (SLI-E) and control groups (SLI-C) of children with specific language impairment. The second study, utilizing single-case methodology, involved 6 children with SLI who participated in the control group of Study 1, plus 2 peer models. Play dyads consisted of either two children with SLI or one child with SLI and a normal language peer. Results of this study provided support for the contention that play interactions with normal language peers facilitates increases in the play-script reports of children with SLI.", "Thirty children of preschool age with severe phonological disorders were randomly assigned to two treatment groups. Group 1 received treatment for 4 months followed by 4 months without treatment while group 2 underwent 4 months without treatment followed by 4 months of treatment. The outcome measures used were the Assessment of Phonological Processes-Revised (APP-R), the Goldman-Fristoe Test of Articulation (GFTA), the Percentage Consonants Correct (PCC), and Mean Length of Utterance (MLU). Group 1 showed significant differences on scores of phonological measures (APP-R, GFTA, and PCC) after the first 4 months of the study. At the 8-month assessment point the measures for conversational speech intelligibility continued to be significantly different, with group 1 scores higher than those of group 2. The expressive language measure did not detect a difference between groups at any time; however group 1 scores were consistently higher than group 2 scores.", "Direct language instruction and interactive language instruction are based on highly distinct theoretical positions and incorporate very different behavioral techniques. A purpose of the present study was to evaluate the relative effectiveness of direct and interactive language instruction in promoting a variety of language skills. A second purpose was to determine if an aptitude and treatment interaction influenced the outcome of intervention. Forty-four children of preschool age were randomly assigned to classrooms using either direct instruction or interactive instruction. After 8 months, children in both settings improved significantly and substantially on syntactic and semantic measures. There were no differences between the two groups at posttest, nor were there any significant aptitude by treatment interactions for either cognitive or language pretest measures. The results of this study, and a careful examination of previously reported interactions, suggest that such an interaction has yet to be demonstrated.", "In this study, 48 children with moderate or severe delays in phonological ability received treatment for four phonemes, selected in accordance with either traditional or nontraditional target-selection criteria. Children who received treatment for phonemes that are early developing and associated with greater productive phonological knowledge showed greater progress toward acquisition of the target sounds than did children who received treatment for late-developing phonemes that were associated with little or no productive phonological knowledge. Between-group differences in generalization learning were not observed. Child enjoyment of therapy did not differ between groups, but parental satisfaction with treatment progress was greater for children in the traditional group than for children in the nontraditional group.", "25 children with severe speech defects and receiving specialized therapy in a camp were randomly assigned to either a physical education program with an emphasis on recreational games or perceptual-motor instruction. All children were administered 6 pre- and posttests of language and speech proficiency. The recreation games group achieved slightly more statistically significant improvements.", "nan", "The influence of an adult-child discourse structure on the production of early word combinations was examined in language-impaired children. The subjects were 10 children (2:8-3:4) at the single-word utterance level. Eight of the children were engaged in 10 experimental sessions utilizing vertical structures (e.g., Adult: \"Who's this?\" Child: \"Daddy.\" Adult: \"What's Daddy throwing?\" Child: \"Ball.\" Adult: \"Yeah, Daddy's throwing the ball.\"), while the remaining children, serving as controls, were engaged in an alternate activity. Examination of pretest and posttest data as well as session data revealed a substantial increase in the number of multiword productions for most of the children in the experimental group but not for the children serving as controls. These findings indicate that vertical structures have a facilitating effect on the multiword productions of language-impaired children comparable to that found in an identical procedure with normally developing children. The use of a naturally occurring adult-child discourse structure as an intervention procedure is discussed.", "Although there is a great deal of evidence for a significant developmental relationship between grammar and phonology, the nature of this relationship and its implications for the intervention of children with impairments in both grammar and phonology are unclear. The purpose of this investigation was to determine whether two approaches to grammar facilitation that placed no emphasis on phonology would have indirect effects on the phonological output of preschoolers with speech and language impairments. All 26 subjects, ages 44-70 months, had impairments both in grammar and in phonology. Ten subjects took part in a clinician-administered intervention program, eight subjects received a similar intervention program implemented by their parents, and eight children served as delayed intervention controls (Fey, Cleave, Long, & Hughes, 1993). The results indicated that despite a strong effect for the intervention on the children's grammatical output, there were no indirect effects on the subjects' phonological production. It is concluded that despite a close relationship between the development of grammar and phonology, language intervention approaches for children approximately 4 to 6 years of age should address phonological problems directly if significant effects on phonology are to be expected.", "Fey, Cleave, Long and Hughes (1993) demonstrated the effectiveness of two 5-month interventions for preschoolers with problems in expressive grammar. This article reports the results of an additional 5-month intervention phase for 18 of the original participants. Results indicated that although participants improved during Phase 2, improvements generally were not as strong as those noted for Phase 1. Gains were larger and more consistent for children who received the relatively costly clinician-administered approach than for those who received a less expensive parent-administered intervention. The parent intervention was successful in helping parents to use sentence recasts, and especially so for parents of children at relatively early stages of grammatical development, Finally, children who were dismissed after a highly successful treatment Phase 1 generally exhibited no gains over the no-treatment Phase 2.", "Two approaches to grammar facilitation in preschool-age children with language impairment were evaluated. One approach was administered by a speech-language pathologist and the other was presented by the subjects' parents, who were trained by the speech-language pathologist. Both treatment packages ran for 4 1/2 months and made use of focused stimulation procedures and a cyclical goal-attack strategy. Subjects were 30 children between the ages of 3:8 and 5:10 (years:months) who had marked delays in grammatical development. Children who served in a delayed-treatment control group averaged no gains over their no-treatment period. In contrast, large treatment effects were observed for both treatment groups on three of four measures of grammatical expression. However, closer inspection of the data revealed that the effects for the clinician treatment were more consistent across treatment administrations than were those for the parent treatment. Although the specific contributions of the focused stimulation procedures and the cyclical goal attack strategy were not evaluated, the results support the viability of these components as parts of larger treatment packages. The results also support the participation of parents as primary intervention agents in grammar facilitation programs. When parents take such a large role in the intervention process, however, it is imperative that the children's progress be monitored carefully and that program adjustments be made whenever gains are smaller than expected.", "Forty two preschool children referred to a speech therapy department were randomly allocated to receive intensive individual speech therapy or the more traditional once weekly approach. Boys and minority ethnic groups were referred most frequently. Speech therapy improved expression more than comprehension, as measured on Reynell scales. The mean improvements were 0.5 SDs (95% confidence intervals (CI) 0.3 to 0.7) and 0.3 (95% CI 0.1 to 0.5) respectively. There was a greater improvement in children receiving intensive compared with weekly therapy in the expression scores (0.8 SDs (95% CI 0.5 to 1.1) v 0.2 SDs (95% CI -0.1 to 0.5]. White and non-white children had similar improvements in comprehension scores but white children had greater improvement in expression scores (1.1 SDs v 0.3 SDs). This difference was seen in both therapy groups. Randomised trials are useful in the evaluation of speech therapy in children.", "To compare routine speech and language therapy in preschool children with delayed speech and language against 12 months of \"watchful waiting.\"\n Pragmatic randomised controlled trial. Setting: 16 community clinics in Bristol.\n 159 preschool children with appreciable speech or language difficulties who fulfilled criteria for admission to speech and language therapy.\n Four quantitative measures of speech and language, assessed at 6 and 12 months; a binary variable indicating improvement, by 12 months, on the trial entry criterion.\n Improvement in auditory comprehension was significant in favour of therapy (adjusted difference in means 4.1, 95% confidence interval 0.5 to 7.6; P=0.025). No significant differences were observed for expressive language (1.4, -2.1 to 4.8; P=0.44); phonology error rate (-4.4, -12.0 to 3.3; P=0.26); language development (0.1, -0.4 to 0.6; P=0.73); or improvement on entry criterion (odds ratio 1.3, 0.67 to 2.4; P=0.46). At the end of the trial, 70% of all children still had substantial speech and language deficits.\n This study provides little evidence for the effectiveness of speech and language therapy compared with watchful waiting over 12 months. Providers of speech and language therapy should reconsider the appropriateness, timing, nature, and intensity of such therapy in preschool children. Continued research into more specific provision to subgroups of children is also needed to identify better treatment methods. The lack of resolution of difficulties for most of the children suggests that further research is needed to identify effective ways of helping this population of children.", "nan", "The purpose of this investigation is to determine whether a focused stimulation intervention focusing on lexical training has indirect, secondary effects on children's phonological abilities. Twenty-five toddlers with expressive vocabulary delays and their mothers were randomly assigned to intervention and control groups. The children were between 23 and 33 months of age at entry into the study and were at the single-word stage of language development. Parents of late talkers in the experimental group were trained to employ frequent, highly concentrated presentations of target words without requiring responses. Two measures of phonological diversity (i.e., syllable structure level and consonant inventory) and one measure of accuracy of production (i.e., percent consonants correct) were measured prior to and following intervention within the context of mother-child interactions. The toddlers who received intervention made treatment gains in two areas of phonological ability. They used a greater variety of complex syllable shapes and expanded their speech sound inventories to include more consonant sounds in both initial and final position. In contrast, there were no effects of language treatment on the accuracy of correct production when compared to the adult phonological system.", "A group of 12 preschool children with phonological process errors was selected, and individual subjects were randomly assigned to one of two treatments that differed in relation to service delivery. Group I received a treatment that was administered exclusively by the clinician. Group II received a combination that included clinician administered treatment and parent administered instruction with the Speech Viewer system. Results indicate that both groups improved significantly, but they did not differ significantly from each other in the degree of change. Implications with respect to the service delivery options and their respective components are discussed.", "nan", "nan", "This study examined the role of speech perception training in the correction of phonological errors. Twenty-seven preschoolers with phonological impairment who misarticulated /integral of/ were randomly assigned to one of three groups: Group 1 children listened to a variety of correctly and incorrectly produced versions of the word \"shoe\"; Group 2 children listened to the words \"shoe\" and \"moo\"; Group 3 children listened to the words \"cat\" and \"Pete.\" A computer game was used to provide reinforcement for correct identification of the words. All children received the same traditional sound production training program for correction of their /integral of/ error, concurrently with speech perception training, during six weekly treatment sessions. On post-testing, Group 1 and 2 children demonstrated a superior ability to articulate the target sound in comparison to Group 3 children. The results are interpreted in relation to previous research on this topic.", "This study explores the effects of training parents to administer focused stimulation intervention to teach specific target words to their toddlers with expressive vocabulary delays. Twenty-five mothers and their late-talking toddlers were randomly assigned to treatment and delayed-treatment (control) groups. Vocabulary targets were individually selected for each toddler based on the child's phonetic repertoire and parent report of vocabulary development. Following treatment, mothers' language input was slower, less complex, and more focused than mothers in the control group. Concomitantly, their children used more target words in naturalistic probes, used more words in free-play interaction, and were reported to have larger vocabularies overall as measured by parent report. In addition, the treatment had an effect on language development-children in the experimental group used more multiword combinations and early morphemes than children in the control group. The implications of these results are discussed with regard to the role of focused stimulation intervention for children with expressive vocabulary delays.", "Generalization of the Monterey Behavioral Sciences Institute operant language program was assessed. Six male and three female children (4 years, 4 months to 6 years, 3 months) receiving language remediation were randomly assigned to (I) the Monterey program for the syntactic structure \"is interrogative\" (including the home carryover phase) plus an extended transfer program devised by the investigators (II) the Monterey \"is interrogative\" program alone (including the home carryover), or (III) a control activity (articulation training). Language samples evoked by a variety of language tasks were collected outside the treatment settling preceding and following treatment. Standard within-clinic measures indicated that groups I and II improved a significant, equal amount. However, the extraclinic language measures showed that group I demonstrated significantly greater improvement than group II; neither group II nor group III showed significant extraclinic improvement. Extraclinic generalization occurred, therefore, only for the group receiving the special extended transfer training." ]

[ "10721594", "16117821" ]

[ "[Orbit decompression surgery in patients with exophthalmos caused by Graves-Basedow disease].", "Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves' ophthalmopathy? A randomized controlled trial." ]

[ "To evaluate in a prospective trial two surgical technique routinely used for orbital decompression in Graves' disease ophthalmopathy.\n Patients with Graves' disease exophthalmus (greater than 22 mm) that was euthyroid for at least six months after treatment were admitted to the study and randomly assigned to two groups, twenty six orbits in 17 patients were surgically decompressed with the Walsh and Ogura technique (group I) and 18 orbits in 18 patients were decompressed with Kennedy's surgical approach (group II).\n Both surgical techniques were equally effective in reducing the exophthalmus (p < 0.05). Morbility was significantly greater in terms of diplopia and infraorbital nerve lesion with Walsh and Ogura surgical approach.\n Due to reduced morbility, orbital surgical decompression with Kennedy's technique is recommended in patients with Graves' disease exofthalmus.", "Only a small percentage of Graves' ophthalmopathy (GO) patients develop optic neuropathy with impending loss of visual acuity. Therapy with methylprednisolone pulses is the treatment of first choice in severe and active GO patients. When the effect is insufficient, patients are usually treated with surgical decompression. We investigated whether surgery could become the first-line treatment, thus preventing treatment with steroids.\n We performed a randomized trial in 15 patients with very active GO and optic neuropathy. Six patients were treated with surgical decompression, and nine with methylprednisolone i.v. pulses for 2 weeks, followed by oral prednisone for 4 months. The primary outcome was determined by changes in visual acuity. If the eye disease deteriorated despite treatment or did not improve sufficiently, patients were switched to the other treatment arm.\n The severity and activity of GO in both groups were similar at baseline. The Clinical Activity Score (CAS) was 6.3+/- 0.8 in the surgical group vs. 6.0+/- 0.5 in the steroids group and the Total Eye Score was 24+/- 6 vs. 25+/- 6. In the surgery group, 5/6 patients (82%) did not respond because of insufficient improvement in vision (n=3) or persistent chemosis (n=2), and all needed further immunosuppression. In the steroids group, 4/9 patients (45%) did not improve in visual acuity (P=0.132 vs. surgery group), and these needed decompressive surgery. All patients in whom therapy failed were switched to the other treatment arm and visual acuity improved in almost all patients. Visual acuity improved from 0.36 (0.02--0.40) to 0.90 (0.63--1.0) in the surgery group and from 0.50 (0.32--0.63) to 0.75 (0.32--1.0) in the steroids group at 52 weeks. At long-term follow-up in the surgery group 3/6 patients required squint surgery and 5/9 patients in the steroids group. Eyelid surgery was performed in 5/6 patients in the surgery group and in 4/9 patients in the steroids group.\n Immediate surgery does not result in a better outcome and therefore methylprednisolone pulse therapy appears to be the first-choice therapy." ]

[ "18167048", "19145637", "18424099" ]

[ "Effect of sugar cane policosanol on lipid profile in primary hypercholesterolemia.", "A randomized, multicentre, open-label, parallel-group trial to compare the efficacy and safety profile of daming capsule in patients with hypercholesterolemia.", "Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: a randomized, double blind placebo controlled trial." ]

[ "Policosanol, a mixture of long-chain aliphatic primary alcohols, is used as a cholesterol-lowering supplement. The effectiveness of policosanol is still questionable. To determine the lipoprotein-lowering effects of Cuban sugar cane-derived policosanol a double-blind, randomized, placebo controlled trial was performed. Sixty-eight primary hypercholesterolemic subjects were enrolled and randomly assigned to the treatment or to the control group. The first group received sugar cane policosanol 20 mg daily for 8 weeks, while the control group was treated with placebo. All subjects followed a normocaloric diet. The content of policosanol in the supplement tablets was assessed by gas chromatography. A total of 32 subjects in the policosanol group and 31 subjects in the control group completed the study. Body mass index, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride plasma levels did not change significantly in either group. In conclusion, sugar cane policosanol at doses of 20 mg daily showed no lipid lowering effects in subjects with primary hypercholesterolemia.", "To study the efficacy and tolerability of Daming capsule (DMC) in Chinese patients with hyperlipidemia, a randomized, multi-centre, open-label, parallel-group trial was conducted. Sixty enrolled patients with hyperlipidemia allocated to six medical centers were randomly divided into two groups of 30 individuals each. One group received DMC 2 g b.i.d. for 6 weeks, and the other received pravastatin 10 mg o.d. for 6 weeks. For efficacy assessment, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured before and after drug treatment. Serum TC and LDL-C levels in the DMC-treatment group were significantly decreased compared with those before treatment (p < 0.05), while TG and HDL-C levels did not change much. Tolerability was assessed by heart rate (HR), blood pressure (BP), body mass index (BMI), alanine aminotransferase (ALT) and creatinine (Cr), which were not changed in either the DMC or pravastatin groups at 3 and 6 weeks (p > 0.05). Besides, eight patients experienced diarrhea during DMC treatment and two experienced myalgia and epigastric discomfort during pravastatin treatment. Based on the above results, it was concluded that DMC may be a good candidate for the treatment of hyperlipidemia and further clinical trials are warranted.\n Copyright 2009 John Wiley & Sons, Ltd.", "Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p=0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response." ]

[ "7675964", "9695999", "8977350", "7590022", "8276366", "12644958", "7480556", "11515632", "9347201", "7600138" ]

[ "Benzodiazepine receptor antagonism improves reaction time in latent hepatic encephalopathy.", "Flumazenil for hepatic encephalopathy grade III and IVa in patients with cirrhosis: an Italian multicenter double-blind, placebo-controlled, cross-over study.", "Evaluation of the efficacy and safety of flumazenil in the treatment of portal systemic encephalopathy: a double blind, randomised, placebo controlled multicentre study.", "Flumazenil therapy for hepatic encephalopathy. A double-blind cross over study.", "Flumazenil in cirrhotic patients in hepatic coma: a randomized double-blind placebo-controlled crossover trial.", "The efficacy of flumazenil in subclinical to mild hepatic encephalopathic ambulatory patients. A prospective, randomised, double-blind, placebo-controlled study.", "Differential effects of flumazenil in alcoholic and nonalcoholic cirrhotic patients.", "Flumazenil in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double blind randomized placebo controlled study.", "The effect of flumazenil on subclinical psychometric or neurophysiological alterations in cirrhotic patients: a double-blind placebo-controlled study.", "Flumazenil therapy for hepatic encephalopathy in cirrhotic patients: a double-blind pragmatic randomized, placebo study." ]

[ "Endogenous benzodiazepine-like substances are thought to play a role in the development of hepatic encephalopathy (HE). Ten patients with sub-clinical or latent hepatic encephalopathy (LHE) and ten normal controls were cognitively assessed pre- and post-infusion of 0.2 mg of the benzodiazepine (BZ) antagonist flumazenil in a placebo-controlled, cross-over, double-blind design. Flumazenil infusion resulted in a significant improvement in simple reaction time in patients, but not in controls. Saline infusion had no effect on any of the cognitive measures in either group. Flumazenil appeared to have a particular enhancing effect on the cognitive, as opposed to the motor, component of the reaction time task. This finding supports the view that the benzodiazepine/GABA system is implicated in the bradyphrenia that is characteristic of chronic liver disease, even before hepatic encephalopathy is apparent. We conclude that benzodiazepine receptor antagonism may improve cognitive function, particularly speed of information processing, in patients with latent hepatic encephalopathy.", "The rationale for use of benzodiazepine receptor antagonists is based on the so-called benzodiazepine pathogenetic hypothesis of hepatic encephalopathy (HE). To assess the efficacy of flumazenil, a specific benzodiazepine receptor antagonist, in a large and selected population of cirrhotic patients with severe HE, we conducted a double-blind, placebo-controlled, cross-over trial on 527 cirrhotic patients with HE grade III and IVa admitted to Intensive Care Units over a 5-year period; among them, 265 (132 of grade III and 133 of grade IVa) received flumazenil, whereas 262 (130 of grade III and 132 of grade IVa) received placebo. Treatment was begun within 15 minutes of randomization; the response to treatment was assessed by neurological score and by continuous electroencephalographic (EEG) recordings. Improvement of the neurological score was documented in 17.5% of grade III patients treated with flumazenil and in 14.7% of grade IVa patients, compared, respectively, with 3.8% and 2.7% of the patients of both groups treated with placebo. Improvements in EEG tracings were observed in 27.8% of grade III patients and in 21.5% of grade IVa patients, compared, respectively, with 5% and 3.3% of the patients of both groups treated with placebo. Benzodiazepines were detected in the serum of 10 patients (4 in grade III group and 6 in grade IVa group). Flumazenil is beneficial only in a selected subset of cirrhotic patients with severe HE; the applicability of this treatment to unselected patients with severe HE still remains to be determined.", "Portal systemic encephalopathy (PSE) is a complex neuropsychiatric syndrome associated with hepatic failure. Small scale studies have shown the benzodiazepine receptor antagonist flumazenil to be effective in ameliorating PSE.\n To determine the efficacy of flumazenil in patients with non-comatous mild to moderate PSE (stages I to III) due to severe chronic liver disease.\n 49 male and female adults without symptoms of severe bleeding and sepsis and who screened negative for benzodiazepine in both blood and urine, were included in the study.\n Patients were randomised to receive either three sequential bolus injections of flumazenil (0.4, 0.8, and 1 mg) or placebo at one minute intervals, followed by intravenous infusions of either flumazenil (1 mg/h) or placebo for three hours. Clinical PSE grading and vital signs were assessed hourly during baseline and post-treatment periods and half hourly during treatment. The main outcome measures were improvement in group average PSE score and reduction of two points in individual PSE score (clinically relevant improvement).\n The mean average improvement in the PSE score in the subjects treated with flumazenil was not statistically significantly different from placebo. However, for patients showing clinically relevant improvement, the difference between flumazenil and placebo was statistically significant (seven of 28 v none of 21; p = 0.015). Flumazenil was well tolerated.\n A subgroup of patients with PSE resulting from chronic liver disease may benefit from the administration of flumazenil.", "Thirty-one patients with acute or chronic liver disease were included in the study to investigate the effect of flumazenil on hepatic encephalopathy. After screening for recent benzodiazepine use or non-hepatic causes of encephalopathy, 18 patients entered a double-blind cross-over study. The 13 remaining patients, most of them with renal failure or recent use of benzodiazepines, were given flumazenil in an open study. In the controlled study, flumazenil (1.0 mg) or placebo was given in a single injection on two separate days to study the immediate effect; half the patients received a continuous infusion of flumazenil (0.25 mg/h) or placebo for two 3-day periods to study a potential steady state effect. In the open study, a single bolus of flumazenil (1.0 mg) was given.\n In the controlled study, fifteen minutes after bolus injection, the clinical grade of hepatic encephalopathy decreased in 6 patients after injection of flumazenil, whereas a decrease was found in 2 after the placebo (P = 0.06). However, the EEG grade did not change in any of the patients, and the changes in the mean dominant frequency as measured by spectral analysis did not differ between flumazenil and the placebo. Furthermore, patients on flumazenil did not differ significantly from those on placebo during the infusion period. Subgroup analysis of underlying liver disease and the causes of encephalopathy revealed a trend for clinical improvement only in the patients with chronic liver disease, but without significant changes in the mean dominant frequency. In the open study, the clinical grade of encephalopathy decreased in 3 patients and, in contrast to the controlled study, the EEG also improved in 2 patients and the mean dominant frequency increased significantly. Responders had previously used benzodiazepines.\n Our study does not support a major therapeutic effect of flumazenil on hepatic encephalopathy.", "Previous reports have suggested that \"endogenous\" benzodiazepines could contribute to neural inhibition in hepatic encephalopathy. RO 15-1788 (flumazenil), a specific antagonist of brain benzodiazepine receptors, could thus reverse the neurological symptoms of hepatic encephalopathy. To test this possibility, we conducted a double-blind, placebo-controlled crossover trial of the efficacy of flumazenil in cirrhotic patients in hepatic coma. Seventy-seven cirrhotic patients in hepatic coma were evaluated. Fifty-six were excluded from the trial because of multiorgan failure or because coma was precipitated by prior use of benzodiazepines, and 21 patients were randomly assigned to the flumazenil group (11 patients) or the placebo group (10 patients). Treatment was administered intravenously as a 20-ml solution (placebo or 2 mg flumazenil); seven patients were crossed over. Clinical status was assessed blindly by two observers, using a modified Glasgow scale, every 15 min for 6 hr. Electroencephalogram tracings obtained before and after drug administration were evaluated blindly by two independent observers. Serum concentrations of benzodiazepines before treatment were measured by means of a fluorescence polarization immunoassay. Improvement in neurological symptoms was observed in six patients treated with flumazenil, whereas none in the placebo group showed improvement (p < 0.05; Fisher's exact test). Improvements in electroencephalogram tracings were demonstrated in four patients treated with flumazenil, compared with two patients in the placebo group (p = NS). Benzodiazepines were found in the serum of four patients treated with flumazenil (two responders and two nonresponders); all of these patients had received pharmaceutical benzodiazepines 4 to 6 days before the trial.(ABSTRACT TRUNCATED AT 250 WORDS)", "Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with fulminant hepatic failure and chronic liver disease. Its pathogenesis is unclear. One of the factors implicated is enhanced GABA-ergic tone, which is probably related to increased concentrations of cerebral benzodiazepine (BNZ). In the present study, we tested flumazenil, a cerebral BNZ antagonist, in cirrhosis patients with hepatic encephalopathy.\n Out of 47 patients, 7 were excluded prior to randomization for various reasons. Twenty patients were included in the flumazenil group and 20 in the placebo group in a prospective, randomized, double-blind, placebo-controlled study. Patients were given flumazenil (1 mg/h, continuous IV infusion) or an equal volume of saline solution for 5 hours. Before and after treatment, portosystemic encephalopathy (PSE) stage and number connection test (NCT) scores were checked every half hour for 5 hours. EEG was recorded 15 minutes before and 1 hour after treatment.\n While significant improvements were determined in PSE stage and NCT score in the flumazenil group, there were no such improvements in the placebo group. There was no statistically significant difference between pre- and post-treatment EEGs in either group.\n It was concluded that continuous IV infusion of flumazenil had beneficial and safe effects in the treatment of hepatic encephalopathy patients.", "Ligands to the benzodiazepine receptor (BZR) accumulate in hepatic encephalopathy; the benzodiazepine antagonist flumazenil can reverse some manifestations of this condition. This study was designed to explore the effects of flumazenil on cognitive function and anxiety levels in cirrhotic patients without hepatic encephalopathy. Twenty such patients--ten alcoholic, ten nonalcoholics--and ten normal volunteers matched for age and sex were randomly allocated to treatment order (flumazenil or placebo first) in a double-blind cross-over trial. Cognitive function was evaluated with a battery of psychological tests shown previously to be sensitive to the impairment induced by liver disease. Cirrhotic patients performed worse than controls on several tests: digit cancellation, digit symbol substitution, key tapping and Reitan's trail B test. Flumazenil did not reverse these cognitive impairments but it did induce anxiety in nonalcoholic cirrhotics. On one index of memory--delayed word recall--alcoholics performed worse than nonalcoholic cirrhotics. Flumazenil reversed this memory impairment in the alcoholic cirrhotic group. These results suggest that alcohol consumption induces changes at the BZR that are different from changes induced solely by liver impairment.", "The aim of this study was to evaluate the effects of flumazenil on hepatic encephalopathy in patients with liver cirrhosis.\n . In the double blind randomized, placebo controlled study, 54 patients with hepatic encephalopathy grade III-IV were randomly assigned to receive either flumazenil 2 mg iv (group A) or placebo (group B); conventional treatment with branched-chain amino acid, saline, glucose, and lactulose was administered in both groups. A 24-hour observation period was established. Clinical improvement was defined as a 3 point decrease in the Glasgow coma score at any time within 24 hours.\n Clinical improvement was obtained in 22/28 patients in group A and in 14/26 in group B (p<0.05); improvement was observed within the first six hours in 21/22 patients in group A and only in 3/14 in group B. Mortality rate was not different between group A and B; however, all 6 non-responders in group A and only 5 out of 12 in group B died within 24 hours. Among patients with post-bleeding encephalopathy, 11 out of 17 in group A and only 2 out of 14 in group B improved (p<0.001).\n Flumazenil may exert a beneficial effect in a subset of patients with acute hepatic encephalopathy; encephalopathy associated with bleeding is more likely to respond to flumazenil; responders to the treatment usually improve within the first 6 hours while lack of response usually represents a bad prognostic sign.", "It is not yet clear if benzodiazepine receptor ligands, implicated in the pathophysiology of hepatic coma, also have a role in subclinical cognitive or neurophysiological alterations in cirrhotic patients. Therefore, we carried out a double-blind, placebo-controlled study to evaluate the effectiveness of flumazenil, a benzodiazepine antagonist, on brainstem auditory evoked responses and on the number connection test in cirrhotic patients with subclinical neurophysiological or cognitive alterations. Thirteen cirrhotic subjects with subclinical neurophysiological or cognitive alterations were studied. A total of 3 mg of flumazenil or saline was infused intravenously. Before and after the infusion, the number connection test was administered and brainstem auditory evoked responses recorded. After 72 h, patients were crossed over. Flumazenil did not influence brainstem auditory evoked responses or the number connection test. A screening test for benzodiazepines was negative in all subjects. We conclude that benzodiazepine receptor ligands have a negligible role, if any, in the pathophysiology of subclinical neurophysiological or cognitive alterations of cirrhotic patients.", "To evaluate the effects of flumazenil on hepatic encephalopathy in patients with cirrhosis.\n Double-blind randomized study.\n Liver intensive care unit over a 2-year period.\n Fourteen patients with cirrhosis (median age 54 years, range 41-73 years), comprising 10 men and four women enrolled during 18 episodes of hepatic encephalopathy.\n Placebo or flumazenil (1 mg at 0.1 mg/min infusion rate) was infused in coded vials. The patients' hepatic encephalopathy was graded clinically and by electroencephalography (EEG).\n In eight episodes of hepatic encephalopathy the placebo was infused first and no improvement occurred (0%). During 12 episodes of hepatic encephalopathy, flumazenil was administered and the EEG recording improved within 7 min (range 4-47 min; 12 out of 18 cases; 66 versus 0% for flumazenil versus placebo, respectively; P < 0.01); a modest clinical improvement in hepatic encephalopathy was observed within 83 min (range 30-340 min). The amount of flumazenil infused averaged 0.7 mg (range 0.4-1 mg).\n The infusion of 0.4-1 mg flumazenil results in a modest but rapid improvement in the EEG grading of hepatic encephalopathy and to a moderate but delayed improvement in the clinical grade of hepatic encephalopathy." ]

[ "19724045", "12660062", "20679560", "19907043", "11027928", "18640445", "18757621", "18389392", "15161896", "16921045", "12164983", "19435763", "14703540", "15451835", "16227797", "19901314" ]

[ "Comparison of registered and published primary outcomes in randomized controlled trials.", "Role of a research ethics committee in follow-up and publication of results.", "Outcome reporting among drug trials registered in ClinicalTrials.gov.", "Outcome reporting in industry-sponsored trials of gabapentin for off-label use.", "Reporting the study populations of clinical trials. Clear transmission or static on the line?", "Selective reporting in clinical trials: analysis of trial protocols accepted by The Lancet.", "Clinical research projects at a German medical faculty: follow-up from ethical approval to publication and citation by others.", "Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee.", "Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.", "Adverse event reporting in publications compared with sponsor database for cancer clinical trials.", "Investigation of within-study selective reporting in clinical research: follow-up of applications submitted to a local research ethics committee.", "Reporting of sample size calculation in randomised controlled trials: review.", "Bad reporting does not mean bad methods for randomised trials: observational study of randomised controlled trials performed by the Radiation Therapy Oncology Group.", "Outcome reporting bias in randomized trials funded by the Canadian Institutes of Health Research.", "Eligibility criteria for HIV clinical trials and generalizability of results: the gap between published reports and study protocols.", "Undisclosed changes in outcomes in randomized controlled trials: an observational study." ]

[ "As of 2005, the International Committee of Medical Journal Editors required investigators to register their trials prior to participant enrollment as a precondition for publishing the trial's findings in member journals.\n To assess the proportion of registered trials with results recently published in journals with high impact factors; to compare the primary outcomes specified in trial registries with those reported in the published articles; and to determine whether primary outcome reporting bias favored significant outcomes.\n MEDLINE via PubMed was searched for reports of randomized controlled trials (RCTs) in 3 medical areas (cardiology, rheumatology, and gastroenterology) indexed in 2008 in the 10 general medical journals and specialty journals with the highest impact factors.\n For each included article, we obtained the trial registration information using a standardized data extraction form.\n Of the 323 included trials, 147 (45.5%) were adequately registered (ie, registered before the end of the trial, with the primary outcome clearly specified). Trial registration was lacking for 89 published reports (27.6%), 45 trials (13.9%) were registered after the completion of the study, 39 (12%) were registered with no or an unclear description of the primary outcome, and 3 (0.9%) were registered after the completion of the study and had an unclear description of the primary outcome. Among articles with trials adequately registered, 31% (46 of 147) showed some evidence of discrepancies between the outcomes registered and the outcomes published. The influence of these discrepancies could be assessed in only half of them and in these statistically significant results were favored in 82.6% (19 of 23).\n Comparison of the primary outcomes of RCTs registered with their subsequent publication indicated that selective outcome reporting is prevalent.", "Follow-up of clinical trials is a commitment rarely fulfilled by research ethics committees (RECs). We assessed the output of clinical trials submitted in 1997 to our REC, and talked to principal investigators, sponsors, contract research organisations, or a combination of these. During 1997, our REC reviewed 166 clinical trials, and approved 158. The recruitment rate was lower than expected in 45% (64/143) of all initiated clinical trials; 64% (92/143) were finished in accordance with protocol. 3 years after, the results of only 21% (26/123) of finished clinical trials were published in peer-reviewed journals, rising to 31% (38/123) if in-press articles were included. RECs should devote more effort and resources to assess public dissemination of results of clinical trials.", "Clinical trial registries are in widespread use to promote transparency around trials and their results.\n To describe characteristics of drug trials listed in ClinicalTrials.gov and examine whether the funding source of these trials is associated with favorable published outcomes.\n An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006.\n ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999.\n Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations.\n Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization-funded trials (P < 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or nonfederal organization-funded trials without industry contributions (P = 0.005 across groups).\n The publication status of a trial could not always be confirmed, which could result in misclassification. Additional information on study protocols and comprehensive trial results were not available to further explore underlying factors for the association between funding source and outcome reporting.\n In this sample of registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources.\n National Library of Medicine and National Institute of Child Health and Human Development, National Institutes of Health.", "There is good evidence of selective outcome reporting in published reports of randomized trials.\n We examined reporting practices for trials of gabapentin funded by Pfizer and Warner-Lambert's subsidiary, Parke-Davis (hereafter referred to as Pfizer and Parke-Davis) for off-label indications (prophylaxis against migraine and treatment of bipolar disorders, neuropathic pain, and nociceptive pain), comparing internal company documents with published reports.\n We identified 20 clinical trials for which internal documents were available from Pfizer and Parke-Davis; of these trials, 12 were reported in publications. For 8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol. Sources of disagreement included the introduction of a new primary outcome (in the case of 6 trials), failure to distinguish between primary and secondary outcomes (2 trials), relegation of primary outcomes to secondary outcomes (2 trials), and failure to report one or more protocol-defined primary outcomes (5 trials). Trials that presented findings that were not significant (P > or = 0.05) for the protocol-defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome. The primary outcome was changed in the case of 5 of 8 published trials for which statistically significant differences favoring gabapentin were reported. Of the 21 primary outcomes described in the protocols of the published trials, 6 were not reported at all and 4 were reported as secondary outcomes. Of 28 primary outcomes described in the published reports, 12 were newly introduced.\n We identified selective outcome reporting for trials of off-label use of gabapentin. This practice threatens the validity of evidence for the effectiveness of off-label interventions.\n 2009 Massachusetts Medical Society", "In contrast to attempts that have been made to measure the clarity of reporting of the methods of clinical trials in journal articles, we report here an attempt to measure the accuracy of methods reporting. We focus in this article on eligibility criteria as a test case for the reporting of clinical trial methods. We examined the reporting of eligibility criteria in the protocol, methods paper (if applicable), journal article, and Clinical Alert for articles appearing in print between January 1988 and September 1994 for which a Clinical Alert had been issued. Eligibility criteria were further classified into five categories in order to examine the content of information loss, if any. On average, 82% of protocol eligibility criteria were reported in methods papers. Journal articles and Clinical Alerts fared somewhat worse: 63% of criteria were reported in journal articles, 19% in Clinical Alerts. In all three categories of medical communication, the reporting of criteria that defined the study disease tended to be complete; reporting of criteria relating to trial precision, patient safety, legal and ethical concerns, and administrative considerations, was not complete. We found that criteria for clinical trial eligibility are frequently under-reported in medical communications. Moreover, some of the criteria omitted are of considerable clinical importance. We suggest that in the design phase of clinical trials, proposed eligibility criteria be scrutinized closely. Those criteria that survive this scrutiny and that have clinical import must be reported upon fully and accurately when communicating trial results.", "nan", "Only data of published study results are available to the scientific community for further use such as informing future research and synthesis of available evidence. If study results are reported selectively, reporting bias and distortion of summarised estimates of effect or harm of treatments can occur. The publication and citation of results of clinical research conducted in Germany was studied.\n The protocols of clinical research projects submitted to the research ethics committee of the University of Freiburg (Germany) in 2000 were analysed. Published full articles in several databases were searched and investigators contacted. Data on study and publication characteristics were extracted from protocols and corresponding publications.\n 299 study protocols were included. The most frequent study design was randomised controlled trial (141; 47%), followed by uncontrolled studies (61; 20%), laboratory studies (30; 10%) and non-randomised studies (29; 10%). 182 (61%) were multicentre studies including 97 (53%) international collaborations. 152 of 299 (51%) had commercial (co-)funding and 46 (15%) non-commercial funding. 109 of the 225 completed protocols corresponded to at least one full publication (total 210 articles); the publication rate was 48%. 168 of 210 identified publications (80%) were cited in articles indexed in the ISI Web of Science. The median was 11 citations per publication (range 0-1151).\n Results of German clinical research projects conducted are largely underreported. Barriers to successful publication need to be identified and appropriate measures taken. Close monitoring of projects until publication and adequate support provided to investigators may help remedy the prevailing underreporting of research.", "Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results.\n We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models.\n 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication.\n In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.", "Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected, but direct evidence of such bias is currently limited to case reports.\n To study empirically the extent and nature of outcome reporting bias in a cohort of randomized trials.\n Cohort study using protocols and published reports of randomized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg, Denmark, in 1994-1995. The number and characteristics of reported and unreported trial outcomes were recorded from protocols, journal articles, and a survey of trialists. An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta-analysis. Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias. Protocols and published articles were also compared to identify discrepancies in primary outcomes.\n Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes; consistency between primary outcomes defined in the most recent protocols and those defined in published articles.\n One hundred two trials with 122 published journal articles and 3736 outcomes were identified. Overall, 50% of efficacy and 65% of harm outcomes per trial were incompletely reported. Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy (pooled odds ratio, 2.4; 95% confidence interval [CI], 1.4-4.0) and harm (pooled odds ratio, 4.7; 95% CI, 1.8-12.0) data. In comparing published articles with protocols, 62% of trials had at least 1 primary outcome that was changed, introduced, or omitted. Eighty-six percent of survey responders (42/49) denied the existence of unreported outcomes despite clear evidence to the contrary.\n The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention. To ensure transparency, planned trials should be registered and protocols should be made publicly available prior to trial completion.", "Prospectively planned collection and analysis of adverse event (AE) data are essential parts of well-conducted clinical trials. The AE data in a trial sponsor's database should be comparable with what is stipulated in the protocol and with the AE data published. We examined whether the published AE data differ from those in the sponsor's database and from the data collection requirements stated in study protocols.\n We searched the National Cancer Institute (NCI) Clinical Data Update System (CDUS) for studies that used the Common Toxicity Criteria version 2.0 and for which a final study publication was available. We extracted from the protocols information pertaining to AE collection and reporting methods and compared it with the methods cited in the article. We also compared the AE data in the trial publication with the AE data submitted by the investigators to CDUS.\n We identified 22 studies meeting the criteria for this review. There was considerable inconsistency between AE collection and reporting methods cited in the protocols versus final publications. AE data in the article and CDUS were not identical. Twenty-seven percent of article high-grade AEs could not be matched to agent-attributable AEs in the CDUS. Twenty-eight percent of CDUS high-grade AEs could not be matched to AEs in the corresponding article. In 14 of 22 articles, the number of high-grade AEs in CDUS differed from the number in the articles by 20% or more.\n Lack of consistency in and reporting of AEs are associated with NCI database and trial publication AE data discrepancy.", "Within-study selective reporting is widely believed to exist, although to date there have been no empirical studies to assess the extent of the problem in clinical research. The present study aimed to examine this process.\n We undertook a pilot study, involving a single local research ethics committee (LREC), in which we compared the outcomes, analysis and sample size proposed in the original approved study protocol with the results presented in the subsequent study report.\n We received 41 (73%) replies from lead researchers of 56 projects, which were a complete cohort of clinical research applications approved in a particular time period by the LREC. Fifteen of these projects, which were completed and published at the time of our study, were further investigated. Only six (40%) stated which outcome variables were of primary interest and four (67%) of these showed consistency in the reports. Eight (53%) of the 15 studies mentioned an analysis plan. However, seven (88%) of these eight studies did not follow their prescribed analysis plan: the analysis of outcome variables or associations between certain variables were found to be missing from the report.\n Our pilot study has shown that within-study selective reporting may be examined qualitatively by comparing the study report with the study protocol. Our results suggest that it might well be substantial; however, the bias can only be broadly identified as protocols are not sufficiently precise.", "To assess quality of reporting of sample size calculation, ascertain accuracy of calculations, and determine the relevance of assumptions made when calculating sample size in randomised controlled trials.\n Review.\n We searched MEDLINE for all primary reports of two arm parallel group randomised controlled trials of superiority with a single primary outcome published in six high impact factor general medical journals between 1 January 2005 and 31 December 2006. All extra material related to design of trials (other articles, online material, online trial registration) was systematically assessed. Data extracted by use of a standardised form included parameters required for sample size calculation and corresponding data reported in results sections of articles. We checked completeness of reporting of the sample size calculation, systematically replicated the sample size calculation to assess its accuracy, then quantified discrepancies between a priori hypothesised parameters necessary for calculation and a posteriori estimates.\n Of the 215 selected articles, 10 (5%) did not report any sample size calculation and 92 (43%) did not report all the required parameters. The difference between the sample size reported in the article and the replicated sample size calculation was greater than 10% in 47 (30%) of the 157 reports that gave enough data to recalculate the sample size. The difference between the assumptions for the control group and the observed data was greater than 30% in 31% (n=45) of articles and greater than 50% in 17% (n=24). Only 73 trials (34%) reported all data required to calculate the sample size, had an accurate calculation, and used accurate assumptions for the control group.\n Sample size calculation is still inadequately reported, often erroneous, and based on assumptions that are frequently inaccurate. Such a situation raises questions about how sample size is calculated in randomised controlled trials.", "To determine whether poor reporting of methods in randomised controlled trials reflects on poor methods.\n Observational study.\n Reports of randomised controlled trials conducted by the Radiation Therapy Oncology Group since its establishment in 1968.\n The Radiation Therapy Oncology Group. Outcome measures Content of reports compared with the design features described in the protocols for all randomised controlled trials.\n The methodological quality of 56 randomised controlled trials was better than reported. Adequate allocation concealment was achieved in all trials but reported in only 42% of papers. An intention to treat analysis was done in 83% of trials but reported in only 69% of papers. The sample size calculation was performed in 76% of the studies, but reported in only 16% of papers. End points were clearly defined and alpha and beta errors were prespecified in 76% and 74% of the trials, respectively, but only reported in 10% of the papers. The one exception was the description of drop outs, where the frequency of reporting was similar to that contained in the original statistical files of the Radiation Therapy Oncology Group.\n The reporting of methodological aspects of randomised controlled trials does not necessarily reflect the conduct of the trial. Reviewing research protocols and contacting trialists for more information may improve quality assessment.", "The reporting of outcomes within published randomized trials has previously been shown to be incomplete, biased and inconsistent with study protocols. We sought to determine whether outcome reporting bias would be present in a cohort of government-funded trials subjected to rigorous peer review.\n We compared protocols for randomized trials approved for funding by the Canadian Institutes of Health Research (formerly the Medical Research Council of Canada) from 1990 to 1998 with subsequent reports of the trials identified in journal publications. Characteristics of reported and unreported outcomes were recorded from the protocols and publications. Incompletely reported outcomes were defined as those with insufficient data provided in publications for inclusion in meta-analyses. An overall odds ratio measuring the association between completeness of reporting and statistical significance was calculated stratified by trial. Finally, primary outcomes specified in trial protocols were compared with those reported in publications.\n We identified 48 trials with 68 publications and 1402 outcomes. The median number of participants per trial was 299, and 44% of the trials were published in general medical journals. A median of 31% (10th-90th percentile range 5%-67%) of outcomes measured to assess the efficacy of an intervention (efficacy outcomes) and 59% (0%-100%) of those measured to assess the harm of an intervention (harm outcomes) per trial were incompletely reported. Statistically significant efficacy outcomes had a higher odds than nonsignificant efficacy outcomes of being fully reported (odds ratio 2.7; 95% confidence interval 1.5-5.0). Primary outcomes differed between protocols and publications for 40% of the trials.\n Selective reporting of outcomes frequently occurs in publications of high-quality government-funded trials.", "Applicability of randomized controlled clinical trial (RCT) results to 'real world' situations is dependent on the comparability of trial participants to general patient populations. A full disclosure of criteria employed for trial enrollment is necessary for clinicians to assess generalizability. We sought to assess both the impact on generalizability and the disclosure rate of enrollment criteria for 32 major HIV RCTs in the AIDS Clinical Trial Group (ACTG) and Community Programs for Clinical Research on AIDS (CPCRA) trial networks.\n Eligibility criteria were compared in complete protocols to criteria listed in publications from these 32 NIH-funded HIV RCTs. We then applied these criteria to the Women's Interagency HIV Study (WIHS), the largest cohort study of HIV-infected women in the US.\n When applied to WIHS, eligibility criteria from protocols excluded 0-67.6% (median 42%) of WIHS participants (50.6% excluded from ACTG trials). Eligibility criteria in publications excluded 0-62% (median 19.6%) of WIHS (21.2% excluded from ACTG trials). The number of women in WIHS seemingly ineligible for trial participation per enrollment criteria listed in publications averaged only 60% of those actually excluded based on the protocols.\n We found that HIV RCT eligibility criteria excluded a large proportion of a representative cohort of HIV-infected women from trial participation. Furthermore, trial publications are not fully reflective of protocols in terms of disclosing eligibility criteria. Standardization and full disclosure of trial methodology will allow clinicians and researchers to more fully assess the generalizability of findings to their patient populations.", "We wanted to investigate the frequency of undisclosed changes in the outcomes of randomized controlled trials (RCTs) between trial registration and publication.\n Using a retrospective, nonrandom, cross-sectional study design, we investigated RCTs published in consecutive issues of 5 major medical journals during a 6-month period and their associated trials registry entries. Articles were excluded if they did not have an available trial registry entry, did not have analyzable outcomes, or were secondary publications. The primary outcome was the proportion of publications in which the primary outcome of the trial was, without disclosure, changed between that recorded in the trial registry and that reported in the final publication. The secondary outcome was the proportion of publications in which the secondary outcome was changed without disclosure.\n We reviewed 158 reports of RCTs and included 110 in the analysis. In 34 (31%), a primary outcome had been changed, and in 77 (70%), a secondary outcome had been changed.\n There are substantial and important undisclosed changes made to the outcomes of published RCTs between trial registration and publication. This finding has important implications for the interpretation of trial results. Disclosure and discussion of changes would improve transparency in the performance and reporting of trials." ]

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[ "Effects of regular salmeterol on lung function and exercise capacity in patients with chronic obstructive airways disease.", "Efficacy of salmeterol xinafoate in the treatment of COPD.", "Effects of formoterol and ipratropium bromide in COPD: a 3-month placebo-controlled study.", "Symptoms are an important outcome in chronic obstructive pulmonary disease clinical trials: results of a 3-month comparative study using the Breathlessness, Cough and Sputum Scale (BCSS).", "Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium.", "Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease.", "Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow-release theophylline in the treatment of COPD.", "Salmeterol & fluticasone 50 microg/250 microg bid in combination provides a better long-term control than salmeterol 50 microg bid alone and placebo in COPD patients already treated with theophylline.", "The addition of salmeterol 50 microg bid to anticholinergic treatment in patients with COPD: a randomized, placebo controlled trial. Chronic obstructive pulmonary disease.", "The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD.", "An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD)", "Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus device in the treatment of chronic obstructive pulmonary disease.", "Efficacy of inhaled salmeterol in the management of smokers with chronic obstructive pulmonary disease: a single centre randomised, double blind, placebo controlled, crossover study." ]

[ "The aim of this study was to evaluate the effects of single and chronic dosing with salmeterol on exercise capacity and lung function in patients with chronic obstructive pulmonary disease.\n Twenty nine patients of mean (SE) age 64 (1.5) years, forced expiratory volume in one second (FEV1) 42(3)% of predicted, and 5-15% reversibility to salbutamol 200 micrograms were randomised to receive four weeks treatment with salmeterol 50 micrograms twice daily or placebo in a double blind crossover fashion with a one week washout period in between. Measurements of spirometric parameters, static lung volumes, and exercise capacity were made one and six hours after a single dose, and six hours after the final dose of salmeterol or placebo.\n Salmeterol produced a small increase in FEV1 at one and six hours after a single dose, and this was maintained after chronic dosing (mean difference and 95% CI versus placebo): single dosing at one hour 0.07 (95% CI 0.02 to 0.11) 1, single dosing at six hours 0.16 (95% CI 0.09 to 0.22) 1, chronic dosing at six hours 0.11 (95% CI 0.03 to 0.19) 1. The increase in forced vital capacity (FVC) was greater with salmeterol than with placebo six hours after single but not chronic dosing: single dosing at six hours 0.17 (95% CI 0.04 to 0.29) 1, chronic dosing at six hours 0.02 (95% CI -0.18 to 0.22) 1. Slow vital capacity was increased after treatment with salmeterol compared with placebo one and six hours after single but not after chronic dosing. There were no significant differences in static lung volumes or exercise capacity after single or chronic dosing with salmeterol compared with placebo. Patients reported a significantly lower Borg score for perceived exertion following the six minute walk after chronic treatment with salmeterol compared with placebo.\n Salmeterol produced a small improvement in spirometric values compared with placebo consistent with the degree of reversibility originally shown by the subjects to salbutamol 200 micrograms. This was not associated with improvements in static lung volumes or exercise capacity, but there was some symptomatic benefit in that patients were able to walk the same distance in six minutes with less perceived exertion.", "To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD.\n A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial.\n Multiple sites at clinics and university medical centers throughout the United States.\n Four hundred eleven symptomatic patients with COPD with FEV1 < or = 65% predicted and no clinically significant concurrent disease. Interventions: Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks.\n Salmeterol xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects were similar among the three treatments.\n These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.", "The aim of this study was to compare the effects of formoterol, ipratropium bromide and a placebo on walking distance, lung function, symptoms and quality of life (QoL) in chronic obstructive pulmonary disease (COPD) patients. A total of 183 patients (mean age 64 yrs, 86 female) with moderate-to-severe nonreversible COPD participated in this randomised, double-blind, parallel-group study. After a 2-week placebo run-in, patients were randomised to formoterol Turbuhaler 18 microg b.i.d. (delivered dose), ipratropium bromide 80 microg t.i.d. via a pressurised metered dose inhaler, or placebo for 12 weeks. Inhaled short-acting beta2-agonists were allowed as relief medication and inhaled glucocorticosteroids were allowed at a constant dose. The primary variable was walking distance in the shuttle walking test (SWT). Baseline mean SWT distance was 325 m, mean forced expiratory volume in one second (FEV1) was 40% predicted. Clinically significant improvements in SWT (>30 m) were seen in 41, 38 and 30% of formoterol, ipratropium and placebo patients, respectively (not significant). Mean increases from run-in were 19, 17 and 5 m in the formoterol, ipratropium and placebo groups, respectively. Both active treatments significantly improved FEV1, forced vital capacity, peak expiratory flow and daytime dyspnoea score compared with placebo. Formoterol reduced relief medication use compared with placebo. Neither active treatment improved QoL. Formoterol and ipratropium improved airway function and symptoms, without significant improvements in the shuttle walking test.", "The need to manage the key symptoms of chronic obstructive pulmonary disease (COPD) (breathlessness, cough and sputum) is an important treatment objective. Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, which combines conventional bronchodilatory activity with the sensory nerve modulation afforded by dopamine agonism. The efficacy of this agent in relieving patient symptoms has been determined in a series of large-scale clinical studies; the results of a 3-month, placebo-controlled multi-centre study are reported. Effect on patient symptoms was determined using a novel patient-reported assessment instrument, the Breathlessness, Cough and Sputum Scale (BCSS). Patients with smoking-related COPD were required to complete a 2-week baseline period before being randomized to one of three treatment groups; sibenadet (500 microg three times daily) plus placebo (twice daily); salmeterol (50 microg twice daily) plus placebo (three times daily); placebo (twice daily) plus a second placebo (three times daily). All treatments were delivered via pressurized metered dose inhaler (pMDI) for 12 weeks. From enrolment, patients were required to complete daily diary cards to record symptoms of breathlessness, cough and sputum, medication use and adverse events. The primary outcome measure was the difference between the mean BCSS total score measured over the baseline period and the mean BCSS total score in the final 4 weeks of the treatment period. Secondary measures included assessment of lung function, rescue medication use, exacerbations, health-related quality of life, opinion of efficacy and safety. Although an initial reduction in BCSS total score (indicating symptom improvement) was seen with sibenadet therapy, this effect was not maintained for the study duration. Salmeterol therapy, however, resulted in a sustained reduction in BCSS total score. No notable benefit over placebo was seen in lung function, exacerbations or health-related quality of life with either active treatment. While the results of this study failed to demonstrate sustained efficacy with sibenadet therapy, they do indicate the value of symptom assessment in the clinical evaluation of new drugs for the treatment of COPD.", "The efficacy and safety of salmeterol alone was compared with the combination of salmeterol plus ipratropium and with placebo during long-term treatment in patients with stable chronic obstructive pulmonary disease. In addition, the single-dose effect in response to the first dose of treatment was studied over 12 h. The patients (n=144; age 64+/-7 yrs, forced expiratory volume in one second (FEV1) 44+/-11% pred) participated in a three-centre double-blind double-placebo parallel group study and were randomized after a run-in period of 2 weeks to receive either salmeterol 50 microg b.i.d., salmeterol 5 microg b.i.d. plus ipratropium 40 microg q.i.d. or placebo for a period of 12 weeks. The single-dose study demonstrated that salmeterol produced a significant increase in FEV1 (peak of 7% pred) and specific airway conductance (sGaw) (maximum of 60% baseline) for > or =12 h. The combination of salmeterol plus ipratropium elicited a greater bronchodilator response (11% and 94% increases respectively) than salmeterol alone during the first 6 h after inhalation. During treatment there were significant improvements in daytime symptom scores and morning peak expiratory flow in both the salmeterol and the salmeterol plus ipratropium groups (p<0.001), with an associated decrease in the use of rescue salbutamol. Improvements in FEV1 and sGaw were greater in the salmeterol plus ipratropium group than in the patients receiving only salmeterol. Thirty-five patients had an exacerbation; 11 (23%) in the salmeterol group (versus placebo NS), six (13%) in the salmeterol plus ipratropium group (versus placebo p<0.01) and 18 (36%) in the placebo group. In conclusion, in patients with severe stable chronic obstructive pulmonary disease, long-term treatment with either salmeterol alone or salmeterol plus ipratropium is safe and effective. There was added benefit from the combination therapy in terms of improvement in airways obstruction, but not for improvement in symptom control or need for rescue salbutamol.", "Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a beta-agonist bronchodilator with a duration of action substantially longer than that of short-acting beta-agonists, compared with ipratropium, an anticholinergic bronchodilator, and placebo in patients with COPD. Four hundred and five patients with COPD received either salmeterol 42 microg twice daily, ipratropium bromide 36 microg four times daily, or placebo for 12 wk in this randomized, double-blind, parallel-group study. Patients were stratified on the basis of bronchodilator response to albuterol (> 12% and > 200-ml improvement) and were randomized within each stratum. Bronchodilator response was measured over 12 h four times during the treatment period. Salmeterol provided similar maximal bronchodilatation to ipratropium but had a longer duration of action and a more constant bronchodilatory effect with no evidence of bronchodilator tolerance. Both active treatments were well tolerated. Salmeterol was an effective bronchodilator with a consistent effect over this 12-wk study in patients with COPD, including those \"unresponsive\" to albuterol. The long duration of action of salmeterol offers the advantage of twice daily dosing compared with the required four times a day dosing with ipratropium.", "To compare the efficacy, tolerability, and safety of therapy with formoterol and oral slow-release theophylline (THEO) in patients with COPD.\n A randomized, parallel-group study, with double-blind arms for formoterol and placebo (PL) and an open arm for oral slow-release THEO administered in individual doses on the basis of plasma concentrations.\n Eighty-one centers worldwide.\n Eight hundred fifty-four patients with symptomatic COPD.\n Comparison of twice-daily inhaled formoterol dry powder (12 or 24 microg), PL, and THEO (individualized doses) over 12 months.\n Compared to PL, doses of formoterol and THEO both significantly improved the area under the curve for FEV(1) measured over a period of 12 h following the morning dose of study medication at 3 and 12 months (p < 0.001 for all comparisons). Therapy with formoterol, 12 microg, was significantly more effective than that with THEO (p < or = 0.026). Formoterol significantly reduced the percentage of \"bad days\" (i.e., days with at least two individual symptom scores > or = 2 and/or a reduction in peak expiratory flow from a baseline of > 20%; p < or = 0.035 vs. PL and THEO), and the use of salbutamol rescue medication (p < or = 0.003 vs PL) over the whole treatment period, while the effect of THEO was similar to that of PL. Therapy with formoterol and THEO was more effective than PL at improving quality of life for > 12 months (p < or = 0.030). Treatment-related adverse events and discontinuations were more frequent among patients receiving THEO than among those receiving formoterol.\n Long-term treatment with inhaled formoterol dry powder is more effective and better tolerated than treatment with therapeutically appropriate doses of oral slow-release THEO in symptomatic patients with COPD.", "Bronchodilator agents are central to the symptomatic management of Chronic Obstructive Pulmonary Disease (COPD), and long-acting inhaled bronchodilators are regarded as more convenient. The role of inhaled corticosteroids still remains controversial, but there is increasing evidence that they may improve FEV(1) and symptoms in the long-term.\n of the present small pilot study was to compare Salmeterol & Fluticasone (SM&FP) 50/250 microg bid via a single Diskus inhaler with SM 50 microg bid alone, and with placebo (P) in the treatment of moderate COPD.\n Eighteen moderate COPD patients (53-77 yr, mean basal FEV(1)=49.1% pred.+/-5.0 s.d.; mean FEV(1) reversibility=3.6% bsln+/-3.8 s.d.) treated with theophylline 400 mg/day and beta(2) short acting prn, were divided into three matched groups of six subjects according to a double-blind design, and treated with SM&FP 50/250 microcg, or SM 50 microcg alone, or P via Diskus inhaler bid for 52 weeks. In bsln, after 4, 12, 24, 36 and 52 weeks, FEV(1) (% pred), morning PEF (l/s), the daily symptom score, and the number of exacerbations (compared with the previous year) were considered. Statistics. t-test, anova in each treatment group, and anova among basal values and among the 52 week values were used, being p<0.05 accepted. Also changes (DeltaFEV(1)) from baseline were compared at different control times.\n The mean number of exacerbations/yr decreased from 3.5+/-0.8 to 1.16+/-0.75 s.d. exacerbation/yr in the SM&FP group (t-test p<0.001); from 3.0+/-0.89 to 2.3+/-0.81 s.d. in the SM group (t-test p=ns); and from 3.16+/-1.16 to 4.16+/-0.75 s.d. in the P group (t-test p=ns). Patients receiving SM&FP showed the highest mean improvement in FEV(1) (+7.3%+/-3.3 s.d.) over the baseline pre-treatment value after 36 weeks of treatment (anova p<0.001), being FEV(1) unchanged after 52 weeks of treatment in SM group (+0.33%+/-2.4 s.d.) and with a substantial decrease following P (-2.6%+/-1.2 s.d.) (anova p<0.001). Morning PEF (l/min) increased in subjects treated with SM&FP (anova p<0.001), while it remained unchanged in SM and P group (in both, anova p=ns). After 52 weeks of treatment, only subjects treated with SM&FP showed a reduction of the daily symptoms score from 3.6+/-0.7 to 2.0+/-0.2 s.d. (anova p=0.008). Daily beta(2) short acting prn consumption was reduced only in SM&FP group from 4.2+/-0.81 to 2.2+/-1.2 s.d. after 52 weeks (anova p<0.001).\n SM&FP 50/250 microcg regularly assumed in combination via a single Diskus inhaler for a 52 week period improves respiratory function (such as FEV(1), morning PEF), and and symptom score significantly in moderate COPD previously treated with theophylline, and at an higher extent than SM alone or P. The use of beta(2) short acting prn is also reduced, together with the number of exacerbations.", "In the past, the role of long-acting beta(2-) agonists in chronic obstructive pulmonary disease (COPD) relative to other agents has been unclear.\n To compare the effect of adding salmeterol (50 microg bid) or placebo to concurrent anticholinergic therapy on symptom scores, quality of life, prebronchodilator lung function and exacerbations in patients with moderately severe COPD.\n This was a double-blind, randomized, parallel-group study in patients aged 40 years or older receiving anticholinergic medication. Patients were randomly assigned to treatment with placebo (n=207) or salmeterol (n=201) via a Diskus/Accuhaler inhaler for 24 weeks.\n The morning trough (prestudy drug) forced expiratory volume in 1 s (FEV(1)) increased significantly above baseline levels among the salmeterol-treated patients. Improvement in FEV(1) was greater in the salmeterol group than in the placebo group at four weeks (difference 0.06 L, P<0.005), eight weeks (0.06 L, P<0.005) and 16 weeks (0.05 L, P<0.05) after the start of treatment. There was a nonsignificant trend in favour of salmeterol after 24 weeks of treatment (P=0.198). Improvements in morning peak flow were significantly greater in the salmeterol group over 24 weeks (P<0.01). Although symptom scores were numerically higher in the salmeterol group than in the placebo group and there was less requirement for rescue bronchodilator use, these differences were not statistically significant. In the salmeterol group, fewer patients had exacerbations of COPD, and there was a trend toward an improved quality of life. The safety profile of the two groups was similar.\n Salmeterol has a beneficial effect when added to existing anticholinergic therapy in patients with COPD. The regular use of salmeterol for six months was not associated with worsening of the underlying airflow obstruction; rather, there was a tendency for the trough FEV1 to improve above the baseline levels over the treatment period.", "To compare the efficacy and safety of the inhaled corticosteroid fluticasone propionate (FP) and the inhaled long-acting beta(2)-agonist salmeterol (SM), when administered together in a single device (Diskus; GlaxoSmithKline, Inc; Research Triangle Park, NC), with that of placebo and the individual agents alone in patients with COPD.\n Randomized, double-blind, multicenter, placebo-controlled study.\n Seventy-six investigative sites in the United States.\n Seven hundred twenty-three patients > or =40 years of age with COPD and a mean baseline FEV(1) of 42% predicted.\n FP (250 microg), SM (50 microg), FP plus SM combined in a single inhaler (FSC), or placebo administered twice daily through the Diskus device for 24 weeks.\n Primary efficacy measures were morning predose (ie, trough FEV(1)) for FSC compared with SM and 2-h postdose FEV(1) for FSC compared with FP. Other efficacy measures were as follows: morning peak expiratory flow rate (PEF); transition dyspnea index; chronic respiratory disease questionnaire; chronic bronchitis symptom questionnaire; exacerbations; and other symptomatic measures.\n At Endpoint (ie, the last on-treatment, post-baseline assessment), treatment with FSC significantly (p < or = 0.012) increased the morning predose FEV(1) (165 mL) compared with SM (91 mL) and placebo (1 mL), and significantly (p < or = 0.001) increased the 2-h postdose FEV(1) (281 mL) compared with FP (147 mL) and placebo (58 mL). Improvements in lung function with FSC compared with FP and SM, and with FP and SM compared with placebo, as measured by the average daily morning PEF, was observed within approximately 24 h after the initiation of treatment, indicating an early onset of effect (p < or = 0.034). Compared with placebo, FSC significantly improved dyspnea, quality of life, and symptoms of chronic bronchitis. The incidence of adverse effects (except for an increase in oral candidiasis with FSC and FP) were similar among the treatment groups.\n Treatment with FSC (FP, 250 microg, and SM, 50 microg) twice daily substantially improved morning lung function and sustained these improvements for over a period of 24 weeks compared with FP or SM treatment alone in patients with COPD, with no additional safety concerns for the combination treatment vs that with the individual components.", "The objectives of this study were to compare the efficacy and safety of salmeterol xinafoate (50 and 100 microg b.i.d.) with that of placebo, when added to existing therapy, in the treatment of patients with chronic obstructive pulmonary disease (COPD). Six hundred and seventy four patients were randomized to receive either salmeterol 50 microg b.i.d., salmeterol 100 microg b.i.d., or placebo treatment for a period of 16 weeks. The results showed a significant improvement in daily symptom scores noted for patients taking either 50 microg (p=0.043) or 100 microg b.i.d. salmeterol (p=0.01) compared with placebo, with a corresponding decrease in additional daytime salbutamol requirements for both salmeterol groups. The same pattern was reflected for night-time symptoms and additional salbutamol use. During treatment, forced expiratory volume in one second (FEV1) measurements improved significantly in each salmeterol group, with up to a 7% improvement observed at the end of the study. Although no difference was observed between treatment groups for the distance walked in 6 min, patients treated with salmeterol 50 microg b.i.d. were significantly less breathless than those treated with placebo after their 6 min walk, after 8 weeks (p=0.024) and 16 weeks (p=0.004) of therapy. Adverse events were similar in all three groups except for tremor, which was significantly higher in the 100 microg b.i.d. salmeterol group (p=0.005) compared both with 50 microg b.i.d. salmeterol and placebo. Salmeterol offered further positive improvement to the effect of therapy in patients with chronic obstructive pulmonary disease when added to their existing regimens. This clinical improvement was similar both with 50 and 100 microg b.i.d. dosage, although the group receiving 50 microg b.i.d. tolerated the drug better than those receiving 100 microg b.i.d. salmeterol.", "This randomized controlled trial examined the benefits of combining an inhaled corticosteroid, fluticasone propionate (F), with an inhaled long-acting beta(2)-agonist, salmeterol (S), to treat the inflammatory and bronchoconstrictive components of chronic obstructive pulmonary disease (COPD). A total of 691 patients with COPD received the combination of F and S (FSC), S (50 mcg), F (500 mcg), or placebo twice daily via the Diskus device for 24 weeks. A significantly greater increase in predose FEV(1) at the endpoint was observed after FSC (156 ml) compared with S (107 ml, p = 0.012) and placebo (-4 ml, p < 0.0001). A significantly greater increase in 2-hour postdose FEV(1) at the endpoint was observed after treatment with FSC (261 ml) compared with F (138 ml, p < 0.001) and placebo (28 ml, p < 0.001). There were greater improvements in the Transition Dyspnea Index with FSC (2.1) compared with F (1.3, p = 0.033), S (0.9, p < 0.001), and placebo (0.4, p < 0.0001). The incidence of adverse effects (except for an increase in oral candidiasis with FSC and F) was similar among the treatment groups. We conclude that FSC improved lung function and reduced the severity of dyspnea compared with individual components and placebo.", "The acute response to bronchodilators in patients with chronic obstructive pulmonary disease (COPD) is modest; it has, however, been suggested that these patients may benefit from long term treatment.\n To investigate the efficacy of salmeterol in smokers with moderate to severe COPD a double blind, randomised, crossover comparison was performed between salmeterol (50 micrograms twice daily) and placebo in 63 patients with stable COPD (mean age 65 years). Prior to inclusion, all patients had a forced expiratory volume in one second (FEV1) of < 60% of predicted and an improvement in FEV1 of < 15% following 400 micrograms inhaled salbutamol. Patients received four weeks of therapy with each of the treatment regimens. Assessment of efficacy was made with recording of morning and evening peak expiratory flow rates (PEF), respiratory symptoms, and use of rescue salbutamol. FEV1 was measured before and after nebulised salbutamol prior to randomisation and at the end of each treatment period.\n Morning PEF values were higher during the salmeterol than during the placebo period, although the mean treatment difference was small (12 l/min (95% confidence limits 6 to 17)). No difference in mean evening PEF values was found. Diurnal variation in PEF, assessed as the difference between the morning PEF and that of the previous evening, was more pronounced during the placebo than during the salmeterol period. The mean spirometric values (including reversibility in FEV1) obtained at the end of the two treatment periods were similar. Compared with placebo, treatment with salmeterol was associated with lower daytime and night time symptom scores and less use of rescue salbutamol both during the day and the night. The patients rated the treatment with salmeterol better than treatment with placebo.\n This study shows that, compared with placebo, treatment with salmeterol produces an improvement in respiratory symptoms and morning PEF values in patients with moderate to severe COPD. Treatment with long acting beta agonists may therefore result in an improvement in functional status, even in patients suffering from apparently nonreversible obstructive pulmonary disease." ]

[ "10844161", "18386255", "19916788", "16959685", "19083426", "14659974", "18570266", "15363656", "11081989", "15641632", "17015282" ]

[ "Pycnogenol in chronic venous insufficiency.", "Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects.", "Pycnogenol improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy.", "Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol.", "Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation.", "Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients.", "Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis.", "Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II.", "PYCNOGENOL in chronic venous insufficiency.", "Pycnogenol as an adjunct in the management of childhood asthma.", "Effect of polyphenolic extract, Pycnogenol, on the level of 8-oxoguanine in children suffering from attention deficit/hyperactivity disorder." ]

[ "Forty patients with chronic venous insufficiency (CVI) and varices of the legs were selected and double-blindly randomly assigned to a treatment with Pycnogenol (French maritime pine bark extract), 100 mg x 3/day or a placebo for 2 months, according to a double-blind experimental design. The effects of the treatment were evaluated by scoring the symptomatology with a semi-quantitative scale, and the venous blood flow by means of a hand-held Doppler ultrasound. The tolerability was evaluated by recording the adverse effects and by means of hematology and blood chemistry parameters, before and at the end of the treatment. Pycnogenol treatment induced a significant reduction in subcutaneous edema as well as heaviness and pain in the legs, on both after 30 and 60 days, the evaluation time periods. Approximately 60% of patients treated with Pycnogenol(R) experienced a complete disappearance of edema (the most rapidly disappearing symptom) and pain at the end of the treatment, while almost all the patients reported a reduction in leg heaviness which disappeared in approximately 33% of patients. These changes were statistically significant. No effect was observed in the placebo-treated subjects. No effect on the venous blood flow was observed in either of the experimental groups.", "The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of 100 mg Pycnogenol daily (oral capsules) in a 3 month study in patients with osteoarthritis (OA). OA symptoms were evaluated by WOMAC scores, mobility by recording their walking performance (treadmill). Treatment (77 patients) and placebo group (79) were comparable for age, sex distribution, WOMAC scores, walking distances and use of antiinflammatory drugs. The global WOMAC score decreased by 56% (p < 0.05) in the treatment group versus 9.6% in the placebo group. Walking distance in the treadmill test was prolonged from 68 m at the start to 198 m after 3 months treatment (p < 0.05), under placebo, from 65 m to 88 m (NS). The use of drugs decreased by 58% in the treatment group (p < 0.05) versus 1% under placebo. Gastrointestinal complications decreased by 63% in the treatment group, but only 3% under placebo. Overall, treatment costs were reduced significantly compared with placebo. Foot edema was present in 76% of the patients of the treatment group at inclusion and in 79% of the controls. After 3 months edema decreased in 79% of Pycnogenol patients (p < 0.05) vs 1% in controls. In conclusion, Pycnogenol offers an option for reduction of treatment costs and side effects by sparing antiinflammatory drugs.\n (c) 2008 John Wiley & Sons, Ltd.", "The growing numbers of diabetes cases in the developed world are followed by increasing numbers of people diagnosed with diabetic complications. Diabetic microangiopathies in the eye lead to the development of retinopathy involving gradual loss of vision. Previous studies with Pycnogenol showed effectiveness for stopping progression of preproliferative stages of retinopathy. The aim of our study was to show protective effects of Pycnogenol in early stages of retinopathy, characterized by mild to moderate retinal edema in the absence of hemorrhages or hard exudates in the macula center.\n Following treatment with Pycnogenol (24 patients) for 3 months, retinal edema score (dilated ophthalmology) and retinal thickness (high resolution ultrasound) showed statistically significant improvement as compared to the placebo group (22 patients), which showed negligible changes to baseline. Laser Doppler flow velocity measurements at the central retinal artery showed a statistically significant increase from 34 to 44 cm/s in the Pycnogenol group as compared to marginal effects in the control group.\n The major positive observation of this study is the visual improvement, which was subjectively perceived by 18 out of 24 patients in the Pycnogenol group. Testing of visual acuity using the Snellen chart showed a significant improvement from baseline 14/20 to 17/20 already, after 2 months treatment, whereas no change was found in the control group.\n Pycnogenol taken at this early stage of retinopathy may enhance retinal blood circulation accompanied by regression of edema, which favorably improves vision of patients.", "Diabetic microangiopathy leads to lower limb ulcers that are very slow to heal. Pycnogenol was evaluated on diabetic ulcers in a controlled trial. Ulcer medications were used in 4 groups (30 patients): (1) systemic Pycnogenol and local application; (2) local Pycnogenol only; (3) oral Pycnogenol; and (4) medications only (control group). Ulcerated areas and symptom scores were more reduced with the combined oral and local treatment (P < .05). Oral and local treatment were less effective, but still improved compared with the controls. Combined treatment produced 89% complete healing at 6 weeks versus 84% with local treatment and 85% with oral treatment; healing in controls was 61%. The combined treatment group and oral only group had better microcirculation after the combined treatment. Combined local and systemic application of Pycnogenol may offer a new treatment of diabetic ulcers. Local treatment also speeds ulcer healing.", "Patients with type 2 diabetes are at considerable risk of excessive morbidity and mortality from cardiovascular disease (CVD). We investigated the clinical effectiveness of Pycnogenol, a flavonoid-rich dietary supplement, in reducing antihypertensive medication use and CVD risk factors in subjects with type 2 diabetes. Forty-eight individuals were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. Patients were diagnosed with both type 2 diabetes and mild to moderate hypertension and were undergoing treatment with angiotensin-converting enzyme (ACE) inhibitors. Subjects were randomly assigned to receive either Pycnogenol pill (125 mg daily) or matched placebo for 12 weeks. According to the values of blood pressure (BP) measured at 2-week intervals, the pretrial ACE inhibitor dosage was left unchanged, reduced by 50%, or brought back to the pretrial dosage until a stable BP was obtained. Fasting plasma glucose, low-density lipoprotein (LDL) cholesterol, glycosylated hemoglobin (HbA1c), serum endothelin-1, and urinary albumin were evaluated monthly. Pycnogenol treatment achieved BP control in 58.3% of subjects at the end of the 12 weeks with 50% reduction in individual pretrial dose of ACE-inhibitors (P <.05). Plasma endothelin-1 decreased by 3.9 pg/mL in Pycnogenol-treated group vs 0.5 pg/mL increase in control group (P < .001). Mean HbA1c dropped by 0.8% in Pycnogenol-treated group (P < .05), whereas it decreased by 0.1% in control group. Fasting plasma glucose declined by 23.7 mg/dL in Pycnogenol-treated group vs 5.7 mg/dL in control group (P < .0001). Low-density lipoprotein cholesterol improved significantly in Pycnogenol-treated group, declining by 12.7 mg/dL (P < .001). A significant decrease in urinary albumin level was observed at week 8 compared with the control group (P < .05). However, this reduction was not significant at 12th week. After 12 weeks of supplementation, Pycnogenol resulted in improved diabetes control, lowered CVD risk factors, and reduced antihypertensive medicine use vs controls.", "A placebo-controlled, double-blind, parallel group study was performed with 58 patients to investigate effects of French maritime pine bark extract, Pycnogenol, on patients with hypertension. Supplementation of the patients with 100 mg Pycnogenol over a period of 12 weeks helped to reduce the dose of the calcium antagonist nifedipine in a statistically significant manner. The intake of Pycnogenol decreased endothelin-1 concentrations significantly compared to placebo while concentrations of 6-keto prostaglandin F1a in plasma were significantly higher compared to placebo. Values for nitric oxide (NO) in plasma increased in both groups, but the differences were not significant. Angiotensin II concentrations in plasma were lowered in the placebo group to a larger extent than in the Pycnogenol group. Heart rate, electrolytes and blood urea nitrogen were not changed during treatment in both groups of patients. Unwanted effects observed in both groups were of mild and transient nature, such as gastrointestinal problems, vertigo, headache and nausea. Differences in rate of side effects were not statistically significant between the two groups. Study results support a supplementation with Pycnogenol for mildly hypertensive patients.", "The safe and efficacious use of Pycnogenol (French maritime pine bark extract) in other inflammatory diseases prompted this study of its antiinflammatory effects in patients with osteoarthritis (OA). The aim of the study was to evaluate whether Pycnogenol reduces the symptoms of OA in a double-blind, placebo-controlled, randomly allocated trial with patients suffering from knee osteoarthritis stages I and II.\n 100 patients were treated for 3 months either by 150 mg Pycnogenol per day at meals or by placebo. Patients had to report any change of use of previously prescribed antiinflammatory medication during the study period. Patients filled the Western Ontario and Mc Masters University (WOMAC) questionnaire for osteoarthritis every 2 weeks and evaluated weekly pain symptoms using a visual analogue scale for pain intensity.\n Following treatment with Pycnogenol patients reported an improvement of WOMAC index (p < 0.05), and a significant alleviation of pain by visual analogue scale (p < 0.04), the placebo had no effect. The use of analgesics diminished in the verum group but increased under the placebo. Treatment with Pycnogenol was well tolerated.\n Results show that Pycnogenol in patients with mild to moderate OA improves symptoms and is able to spare NSAIDs.", "A double-blind, placebo-controlled, randomized, multi-center study was performed with 77 diabetes type II patients to investigate anti-diabetic effects of the French maritime pine bark extract, Pynogenol. Supplementation with 100 mg Pycnogenol for 12 weeks, during which a standard anti-diabetic treatment was continued, significantly lowered plasma glucose levels as compared to placebo. HbA1(c) was also lowered; however, the difference as compared to placebo was statistically significant only for the first month. In the Pycnogenol-group endothelin-1 was significantly decreased, while 6-ketoprostaglandin F(1a) in plasma was elevated compared to placebo. Nitric oxide levels in plasma increased during treatment in both groups, but, differences did not reach statistical significance. Pycnogenol was well-tolerated with ECG, electrolytes, creatinine and blood urea nitrogen remaining unchanged in both groups. Mild and transient unwanted effects were reported for both groups without significant differences. Supplementation of Pycnogenol to conventional diabetes treatment lowers glucose levels and improves endothelial function.", "The aim of out study was to investigate the efficacy of Pycnogenol - a French maritime pine bark extract - in the treatment of chronic venous insufficiency (CVI). The study consisted of a double-blind phase - in which 20 patients were recruited and randomly treated with placebo or Pycnogenol (100 mg 2 3/day for 2 months) - and an open phase - in which other 20 patients were treated with Pycnogenol at the same dose schedule. In total, 40 patients were enrolled; 30 of them were treated with Pycnogenol and 10 with placebo. Pycnogenol significantly improved the legs' heaviness and subcutaneous edema; the venous pressure was also significantly reduced by the Pycnogenol treatment, thus adding further clinical evidence to its therapeutic efficacy in patients with CVI. Pycnogenol was effective, probably by either stabilizing the collagenous subendothelial basal membrane or scavenging the free radicals, or by a combination of these activities. Clinically, capillary leakage, perivascular inflammation and subcutaneous edema were all reduced. The safety of use of Pycnogenol is demonstrated by the lack of side effects or changes in blood biochemistry and hematologic parameters. Pycnogenol can be therefore recommended both for prevention and treatment of CVI and related veno-capillary disturbances.", "A randomized, placebo-controlled, double-blind study involving 60 subjects, aged 6-18 years old, was conducted over a period of 3 months to determine the effect of Pycnogenol (a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine) on mild-to-moderate asthma. After baseline evaluation, subjects were randomized into two groups to receive either Pycnogenol or placebo. Subjects were instructed to record their peak expiratory flow with an Assess Peak Flow Meter each evening. At the same time, symptoms, daily use of rescue inhalers (albuterol), and any changes in oral medications were also recorded. Urine samples were obtained from the subjects at the end of the run-in period, and at 1-, 2-, and 3-month visits. Urinary leukotriene C4/D4/E4 was measured by an enzyme immunoassay. Compared with subjects taking placebo, the group who took Pycnogenol had significantly more improvement in pulmonary functions and asthma symptoms. The Pycnogenol group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group. There was also a significant reduction of urinary leukotrienes in the Pycnogenol group. The results of this study demonstrate the efficacy of Pycnogenol as an adjunct in the management of mild-to-moderate childhood asthma.", "The purpose of this randomized, double-blind and placebo controlled study was to test the effect of polyphenolic extract of pine bark Pycnogenol (Pyc) on the level of oxidized purines represented by 8-oxo-7,8-dihydroguanine (8-oxoG) and on the total antioxidant status (TAS) in children with attention deficit/hyperactivity disorder (ADHD).We have found significantly increased damage to DNA in ADHD children when compared to controls. 8-oxoG was significantly lower after 1 month of Pyc administration in comparison to the beginning state and to placebo group. TAS in ADHD children was lower in comparison to controls. After Pyc administration, TAS was elevated but statistically significant increase was recorded after 1 month of termination of Pyc application. Improvement of DNA damage and TAS after Pyc administration is associated with the improvement of attention in ADHD children. In conclusion, Pycnogenol(R) administration reduces oxidative damage to DNA, normalizes TAS and improves attention of ADHD children. Explanation of mutual relation between oxidative damage to DNA, TAS and symptoms of ADHD and mechanism of Pyc's action needs further investigations." ]

[ "3302916", "11255901", "16968847", "15972565", "2123239", "11978254", "9116551", "11159657", "1905799" ]

[ "Adverse and beneficial effects of immediate treatment of Group A beta-hemolytic streptococcal pharyngitis with penicillin.", "A randomised controlled trial of delayed antibiotic prescribing as a strategy for managing uncomplicated respiratory tract infection in primary care.", "Wait-and-see prescription for the treatment of acute otitis media: a randomized controlled trial.", "Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial.", "Lack of impact of early antibiotic therapy for streptococcal pharyngitis on recurrence rates.", "Do delayed prescriptions reduce the use of antibiotics for the common cold? A single-blind controlled trial.", "Open randomised trial of prescribing strategies in managing sore throat.", "Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media.", "Immediate vs. delayed treatment of group A beta-hemolytic streptococcal pharyngitis with penicillin V." ]

[ "One hundred forty-two children with presumed Group A beta-hemolytic streptococcal (GABHS) pharyngitis were enrolled in a randomized double blind prospective study comparing the consequences of immediate penicillin treatment with treatment delayed for 48 to 56 hours. One hundred fourteen of the enrolled patients were culture-positive. An adverse impact of early antibiotic therapy was noted; the incidence of subsequent infections with GABHS was significantly greater in those treated at the initial office visit with penicillin. In the month following documented evaluation of GABHS, a recurrence occurred 2 times more frequently in those treated with penicillin immediately compared with those for whom treatment was delayed 48 to 56 hours. Late recurrences (beyond 1 month but in the same streptococcal season) occurred 8 times more frequently (P less than 0.035). Delay in penicillin treatment did not increase GABHS intrafamilial spread. Symptoms of both groups were assessed for 2 days following the initiation of treatment. Both placebo-treated and penicillin-treated groups used aspirin or acetaminophen ad libitum. Penicillin was shown to reduce fever and relieve sore throat, dysphagia, headache, abdominal pain, lethargy and anorexia significantly beyond that achieved with aspirin or acetaminophen alone. Penicillin had no effect on culture-negative cases.", "Despite evidence that uncomplicated lower respiratory tract infection (cough) does not respond appreciably to antibiotics and that bacterial resistance is increasing, general practitioners (GPs) still prescribe frequently.\n To assess delayed antibiotic prescribing as a strategy for reducing the unnecessary use of antibiotics for cough in primary care.\n Open randomised controlled trial of delayed versus immediate prescribing of antibiotics.\n One hundred and ninety-one adult patients with uncomplicated cough in 22 Scottish practices who would have received antibiotics under the GP's usual practice were randomised to receive either an immediate prescription (92 patients) or a delayed prescription (99 patients).\n Delayed subjects were asked to wait a week before deciding whether to collect their prescription. Outcome measures included symptom duration, prescription uptake, patient satisfaction, patient enablement, and subsequent consultation rates. The 48 GPs who recruited patients were surveyed six months after the trial to see whether they used delayed prescribing as a part of their normal practice.\n Study and control groups were similar at baseline. Of the subjects in the delayed arm, 55% did not pick up their prescription. Although most patients were satisfied, more patients in the immediate arm were very satisfied with the treatment (P = 0.001) and the consultation (P = 0.03). The patients in the immediate arm were also more enabled (3.3 versus 2.4; P = 0.04), although more of them intended to consult for similar complaints in the future (85% versus 69%, P = 0.02). We were unable to detect any difference in actual consulting behaviour in the follow-up period (mean = 15 months [SD = 5 months]). Subsequently, 68% of GPs used delayed prescribing at least monthly; all gave the prescription to the patient.\n Delayed prescribing is effective at reducing the use of antibiotics for self-limiting cough; however, patients are less satisfied and enabled as a result. Patients may be deterred from consulting rather than becoming enabled.", "Acute otitis media (AOM) is the most common diagnosis for which antibiotics are prescribed for children. Previous trials that have evaluated a \"wait-and-see prescription\" (WASP) for antibiotics, with which parents are asked not to fill the prescription unless the child either is not better or is worse in 48 hours, have excluded children with severe AOM. None of these trials were conducted in an emergency department.\n To determine whether treatment of AOM using a WASP significantly reduces use of antibiotics compared with a \"standard prescription\" (SP) and to evaluate the effects of this intervention on clinical symptoms and adverse outcomes related to antibiotic use.\n A randomized controlled trial conducted between July 12, 2004, and July 11, 2005. Children with AOM aged 6 months to 12 years seen in an emergency department were randomly assigned to receive either a WASP or an SP. All patients received ibuprofen and otic analgesic drops for use at home. A research assistant, blinded to group assignment, conducted structured phone interviews 4 to 6, 11 to 14, and 30 to 40 days after enrollment to determine outcomes.\n Filling of the antibiotic prescription and clinical course.\n Overall, 283 patients were randomized either to the WASP group (n = 138) or the SP group (n = 145). Substantially more parents in the WASP group did not fill the antibiotic prescription (62% vs 13%; P<.001). There was no statistically significant difference between the groups in the frequency of subsequent fever, otalgia, or unscheduled visits for medical care. Within the WASP group, both fever (relative risk [RR], 2.95; 95% confidence interval [CI], 1.75 - 4.99; P<.001) and otalgia (RR, 1.62; 95% CI, 1.26 - 2.03; P<.001) were associated with filling the prescription.\n The WASP approach substantially reduced unnecessary use of antibiotics in children with AOM seen in an emergency department and may be an alternative to routine use of antimicrobials for treatment of such children.\n clinicaltrials.gov Identifier: NCT00250900.", "Acute lower respiratory tract infection is the most common condition treated in primary care. Many physicians still prescribe antibiotics; however, systematic reviews of the use of antibiotics are small and have diverse conclusions.\n To estimate the effectiveness of 3 prescribing strategies and an information leaflet for acute lower respiratory tract infection.\n A randomized controlled trial conducted from August 18, 1998, to July 30, 2003, of 807 patients presenting in a primary care setting with acute uncomplicated lower respiratory tract infection. Patients were assigned to 1 of 6 groups by a factorial design: leaflet or no leaflet and 1 of 3 antibiotic groups (immediate antibiotics, no offer of antibiotics, and delayed antibiotics).\n Three strategies, immediate antibiotics (n = 262), a delayed antibiotic prescription (n = 272), and no offer of antibiotics (n = 273), were prescribed. Approximately half of each group received an information leaflet (129 for immediate antibiotics, 136 for delayed antibiotic prescription, and 140 for no antibiotics).\n Symptom duration and severity.\n A total of 562 patients (70%) returned complete diaries and 78 (10%) provided information about both symptom duration and severity. Cough rated at least \"a slight problem\" lasted a mean of 11.7 days (25% of patients had a cough lasting > or =17 days). An information leaflet had no effect on the main outcomes. Compared with no offer of antibiotics, other strategies did not alter cough duration (delayed, 0.75 days; 95% confidence intervals [CI], -0.37 to 1.88; immediate, 0.11 days; 95% CI, -1.01 to 1.24) or other primary outcomes. Compared with the immediate antibiotic group, slightly fewer patients in the delayed and control groups used antibiotics (96%, 20%, and 16%, respectively; P<.001), fewer patients were \"very satisfied\" (86%, 77%, and 72%, respectively; P = .005), and fewer patients believed in the effectiveness of antibiotics (75%, 40%, and 47%, respectively; P<.001). There were lower reattendances within a month with antibiotics (mean attendances for no antibiotics, 0.19; delayed, 0.12; and immediate, 0.11; P = .04) and higher attendance with a leaflet (mean attendances for no leaflet, 0.11; and leaflet, 0.17; P = .02).\n No offer or a delayed offer of antibiotics for acute uncomplicated lower respiratory tract infection is acceptable, associated with little difference in symptom resolution, and is likely to considerably reduce antibiotic use and beliefs in the effectiveness of antibiotics.", "To determine whether recurrence rates for group A beta-hemolytic streptococcal (GABHS) pharyngitis are related to the time of initiation of antibiotic therapy, we randomly assigned 113 patients with GABHS pharyngitis either to a group that began a 10-day course of penicillin V at the time of diagnosis or to a group that began the same antibiotic regimen after a dealy of 48 hours. Follow-up throat culture specimens were obtained 4 days, 2 months, and 4 months after the completion of antibiotic therapy, as well as during any interim episodes of acute pharyngitis. Serotyping of all GABHS isolates was performed to distinguish between recurrences with homologous serotypes and new acquisitions with heterologous serotypes. There was no significant difference between the two treatment groups in age, gender, duration of illness before enrollment in the study, initial clinical presentation, or compliance. Of the 50 patients in the immediate-treatment group, 6 (12%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. Of the 63 patients in the delayed-treatment group, 9 (14%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. These data indicate that a 48-hour delay in the initiation of penicillin therapy for GABHS pharyngitis does not reduce the recurrence rate.", "To test the use of a delayed prescription compared with instructions to take antibiotics immediately in patients presenting to family physicians with upper respiratory tract infections (common colds).\n Randomized controlled single-blind study.\n Subjects were 129 patients presenting with the common cold who requested antibiotics or whose physicians thought they wanted them. All patients were in a family practice in Auckland, New Zealand, consisting of 15 physicians (9 male, 6 female) who had completed medical school between 1973 and 1992.\n Outcomes were antibiotic use (taking at least 1 dose of the antibiotic), symptom scores, and responses to the satisfaction questions asked at the end of the study.\n Patients in the delayed-prescription group were less likely to use antibiotics (48%, 95% CI, 35%-60%) than were those instructed to take antibiotics immediately (89%, 95% CI, 76%-94%). Daily body temperature was higher in the immediate-prescription group. The lack of difference in the symptom score between the 2 groups suggests that there is no danger in delaying antibiotic prescriptions for the common cold.\n Delayed prescriptions are a safe and effective means of reducing antibiotic consumption in patients with the common cold. Clarification of patient expectations for antibiotics may result in a lower prescription rate. When the patient demands a prescription, delaying its delivery has the potential to provide gentle education.", "To assess three prescribing strategies for sore throat.\n Randomised follow up study.\n 11 general practices in the South and West region.\n 716 patients aged 4 years and over with sore throat and an abnormal physical sign in the throat; 84% had tonsillitis or pharyngitis. Patients were randomised to three groups: prescription for antibiotics for 10 days (group 1,246 patients); no prescription (group 2,230 patients); or prescription for antibiotics if symptoms were not starting to settle after three days (group 3; 238 patients).\n Duration of symptoms; satisfaction and compliance with and perceived efficacy of antibiotics; time off school or work. Outcomes were documented in 582 subjects (81%).\n Median duration of antibiotic use differed significantly in the three groups (10 v 0 v 0 days, P < 0.001); 69% of patients in group 3 did not use their prescription. The proportion of patients better by day 3 did not differ significantly (37% v 35% v 30%, P = 0.28), nor did the duration of illness (median 4 v 5 v 5 days, P = 0.39), days off work or school (median 2 v 2 v 1, P = 0.13), or proportion of patients satisfied (96% v 90% v 93%, P = 0.09), although group 1 had fewer days of fever (median 1 v 2 v 2 days, P = 0.04). More patients in group 1 thought the antibiotics were effective (87% v 55% v 60%, P < 0.001) and intended coming to the doctor in future attacks (79% v 54% v 57%, P < 0.001). \"Legitimation\" of illness-to explain to work or school (60%) or family or friends (37%)-was an important reason for consultation. Patients who were more satisfied got better more quickly, and satisfaction related strongly to how well the doctor dealt with patient's concerns.\n Prescribing antibiotics for sore throat only marginally affects the resolution of symptoms but enhances belief in antibiotics and intention to consult in future when compared with the acceptable strategies of no prescription or delayed prescription. Psychosocial factors are important in the decision to see a general practitioner and in predicting the duration of illness.", "To compare immediate with delayed prescribing of antibiotics for acute otitis media.\n Open randomised controlled trial. Setting: General practices in south west England.\n 315 children aged between 6 months and 10 years presenting with acute otitis media.\n Two treatment strategies, supported by standardised advice sheets-immediate antibiotics or delayed antibiotics (antibiotic prescription to be collected at parents' discretion after 72 hours if child still not improving).\n Symptom resolution, absence from school or nursery, paracetamol consumption.\n On average, symptoms resolved after 3 days. Children prescribed antibiotics immediately had shorter illness (-1.1 days (95% confidence interval -0.54 to -1.48)), fewer nights disturbed (-0.72 (-0.30 to -1.13)), and slightly less paracetamol consumption (-0.52 spoons/day (-0.26 to -0.79)). There was no difference in school absence or pain or distress scores since benefits of antibiotics occurred mainly after the first 24 hours-when distress was less severe. Parents of 36/150 of the children given delayed prescriptions used antibiotics, and 77% were very satisfied. Fewer children in the delayed group had diarrhoea (14/150 (9%) v 25/135 (19%), chi(2)=5.2, P=0.02). Fewer parents in the delayed group believed in the effectiveness of antibiotics and in the need to see the doctor with future episodes.\n Immediate antibiotic prescription provided symptomatic benefit mainly after first 24 hours, when symptoms were already resolving. For children who are not very unwell systemically, a wait and see approach seems feasible and acceptable to parents and should substantially reduce the use of antibiotics for acute otitis media.", "Three hundred six children with probable Group A beta-hemolytic streptococcal pharyngitis were enrolled in a randomized double blind trial to compare the effects of immediate vs. delayed treatment with oral penicillin V. Among the 229 culture-positive patients, 111 were randomly assigned to receive penicillin V immediately and 118 to receive a placebo for 48 to 52 hours followed by penicillin V. Patients were evaluated clinically for 48 to 52 hours following initiation of treatment. The Streptozyme test was used to measure acute to convalescent antibody titer. Both regimens resulted in a greater than 92% cure rate. Early treatment was associated with significantly fewer and milder signs and symptoms on Day 3 and a significantly lower rise in the antibody titer. On the other hand we found 8 (7%) relapses and 18 (16%) early and 14 (13%) late recurrences in this group; all were significantly higher than the corresponding numbers of 2 (2%), 6 (5%) and 4 (3%), respectively, in the late treatment group. This study shows the beneficial effect of early treatment with penicillin V on the clinical course of Group A beta-hemolytic streptococcal pharyngitis. This study also shows that delayed penicillin treatment may be associated with a lower incidence of subsequent Group A beta-hemolytic streptococcal pharyngitis." ]

[ "17132719", "1985161", "1793154", "2173470", "9324339", "6338381", "4574467", "766905" ]

[ "Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients.", "High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children.", "High-dose cyclophosphamide-high-dose methotrexate with coordinated intrathecal therapy for advanced nonlymphoblastic lymphoma of childhood: results of a Pediatric Oncology Group study.", "Specific transfer factor with activity against Epstein-Barr virus reduces late relapse in endemic Burkitt's lymphoma.", "Fractionated cylophosphamide and back to back high dose methotrexate and cytosine arabinoside improves outcome in patients with stage III high grade small non-cleaved cell lymphomas (SNCCL): a randomized trial of the Pediatric Oncology Group.", "Childhood non-Hodgkin's lymphoma. The results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2).", "Intensive chemotherapy in patients with generalized Burkitt's lymphoma.", "Failure of BCG immunostimulation to affect the clinical course of Burkitt's lymphoma." ]

[ "A previous study (LMB89) of the French Society of Pediatric Oncology for childhood mature B-cell lymphoma (B-NHL) demonstrated a 92% 3-year event-free survival (EFS) for intermediate-risk group B defined as \"non-resected\" stage II/I and CNS-negative advanced-stage IIV/IV (70% of cases). We performed the FAB/LMB96 trial to assess the possibility of reducing treatment in children/adolescents with intermediate-risk B-NHL without jeopardizing survival. \"Early responding\" patients (tumor response > 20% at day 7) were randomized in a factorial design between 4 arms, 2 receiving half-dose of cyclophosphamide in the second induction course with cyclophosphamide, Oncovin (vincristine), prednisone, Adriamycin (doxorubicin), methotrexate (COPADM) and 2 not receiving the maintenance course M1. A total of 657 patients were randomized (May 1996 to June 2001) and 637 were analyzed. The analysis showed no significant effect of any of the treatment reductions on EFS and survival. The 4-year EFS was 93.4% and 90.9% in the groups with full-dose and half-dose of cyclophosphamide (RR = 1.3, P = .40) and 91.9% and 92.5% in the groups with and without M1 (RR = 1.01, P = .98). There was no interaction between the 2 treatment reductions or between each treatment reduction and LDH level or histologic subtypes (Burkitt/Burkitt-like or large B-cell). Children/adolescents with intermediate-risk B-NHL who have an early response and achieve a complete remission after the first consolidation course can be cured with a 4-course treatment with a total dose of only 3.3 g/m2 cyclophosphamide and 120 mg/m2 doxorubicin.", "From April 1984 to December 1987, the French Pediatric Oncology Society (SFOP) organized a randomized trial for advanced-stage B-cell lymphoma without CNS involvement to study the possibility of reducing the length of treatment to 4 months. After receiving the same three intensive six-drug induction courses based on high-dose fractionated cyclophosphamide, high-dose methotrexate (HD MTX), and cytarabine in continuous infusion, patients were evaluated for remission. Those who achieved complete remission (CR) were randomized between a long arm (five additional courses with two additional drugs; 16 weeks of treatment) and a short arm (two additional courses; 5 weeks). For patients in partial remission (PR), intensification of treatment was indicated. Two hundred sixteen patients were registered: 15 stage II nasopharyngeal and extensive facial tumors, 167 stage III, and 34 stage IV, 20 of the latter having more than 25% blast cells in bone marrow. The primary sites of involvement were abdomen in 172, head and neck in 30, thorax in two, and other sites in 12. One hundred sixty-seven patients are alive in first CR with a minimum follow-up of 18 months; four are lost to follow-up. Eight patients died from initial treatment failure, 14 died from toxicity or deaths unrelated to tumor or treatment, and 27 relapsed. The event-free survival (EFS), with a median follow-up of 38 months, is 78% (SE 3) for all the patients, 73% (SE 11) for the stage II patients, 80% (SE 3) for the stage III patients, and 68% (SE 8) for the stage IV and acute lymphoblastic leukemia (ALL) patients. One hundred sixty-six patients were randomized: 82 in the short arm and 84 in the long arm. EFS is, respectively, 89% and 87%. Statistical analysis confirms equivalence of both treatment arms with regard to EFS. Moreover, morbidity was lower in the short arm. This study confirms the high survival rate obtained in the previous LMB 0281 study without radiotherapy or debulking surgery and demonstrates the effectiveness of short treatment.", "The Pediatric Oncology Group (POG) investigated a high-dose cyclophosphamide (CPM) high-dose methotrexate (MTX) regimen to determine therapeutic efficacy in confirmed advanced nonlymphoblastic non-Hodgkin's lymphoma (NHL) (stages III and IV) and B-cell acute lymphatic leukemia (B-ALL) in children. Another goal was to determine the comparative effectiveness of shortened maintenance treatment (2 versus 6 courses) in the study population. Systemic induction therapy included vincristine, prednisone, cyclophosphamide, and intermediate-dose MTX with leucovorin rescue. Superimposed intrathecal (IT) therapy included cytosine arabinoside for 2 successive days followed on day 3 by MTX. Intrathecal MTX was given 3 times during induction. At the end of induction, 2 days of triple (hydrocortisone, MTX, and cytosine arabinoside) therapy were given intrathecally (TIT). All patients then received a consolidation course of 4 doses of TIT, 2 doses of cyclophosphamide, and 4 more courses of vincristine and MTX with leucovorin rescue. Patients were then randomized to receive either 2 or 6 cycles of vincristine plus MTX with leucovorin rescue. The TIT was given with each cycle. Complete response rates by histology and Murphy stage (1) were as follows: undifferentiated lymphoma (DUL) stage III, 84/105 (80%): stage IV, 5/12 (42%); and other NHL [primarily large cell lymphoma (LCL)] stage III, 21/28 (75%); stage IV, 2/3 (67%). Event-free survival (EFS) at greater than 2 years was similar for patients with DUL and LCL, i.e., 65 and 61%, respectively. No significant difference in outcome was noted between patient groups receiving 2 or 6 maintenance treatments (p = .76). Treatment was notable for its modest toxicity following the early change to single-dose CPM therapy.(ABSTRACT TRUNCATED AT 250 WORDS)", "Twenty-seven children with abdominal Burkitt's lymphoma (stage III), who had achieved complete remission, were entered into a prospective controlled trial of adjunct treatment with Epstein-Barr virus (EBV)-specific transfer factor (TF). Two patients treated with TF and 2 controls relapsed early (less than or equal to 12 weeks). Two out of 12 TF-treated patients and 5 out of 11 controls subsequently suffered relapses. Time to first late relapse was longer among TF-treated patients (p = 0.08), and no late relapse occurred while a patient was receiving TF treatment. Thus it seems that specific TF might be useful in the management of endemic Burkitt's lymphoma and also in the treatment of other virus-associated cancers and diseases.", "The Pediatric Oncology Group (POG) conducted a two-arm, randomized study for the treatment of children and adolescents with stage III small, non-cleaved cell lymphoma (SNCCL). Regimen A, based on the group's previous best treatment for this group of patients, included cyclophosphamide (CTX) and high-dose methotrexate (MTX), as well as vincristine (VCR), prednisone (PRED), and intrathecal (IT) chemoprophylaxis. Regimen B, based on a single institution pilot study (Total B therapy), consisted of two rapidly alternating chemotherapy combinations (CTX, VCR, doxorubicin; MTX, and cytarabine (Ara-C) plus coordinated IT chemotherapy.\n One hundred thirty-four consecutive patients were entered on this study. Seventy patients were randomized to Regimen A, and 64 patients to Regimen B. One hundred and twenty-two patients are eligible for response.\n Complete remission (CR) was achieved by 81% (52/64) of patients on Regimen A, and 95% (55/58) of patients on Regimen B (p=0.014 one-sided). The two-year event-free survival (EFS) is 64% (SE=6%) on Regimen A, and 79% (SE=6%) on Regimen B (p=0.027 by one-sided logrank test). No patient has relapsed on either regimen after a year from diagnosis, although one patient had a second malignancy at day 371. Severe, but manageable, hematologic toxicity was seen in the majority of patients on both regimens, but was more frequent on Regimen B.\n We conclude that the cure rate in stage III SNCCL is significantly improved with the use of a short, six-month chemotherapy regimen of fractionated CTX alternated with coordinated MTX and Ara-C. Results suggest that drug schedule, not simple drug selection, influences outcome.", "Members of the Childrens Cancer Study Group treated 234 eligible patients in a randomized trial designed to study the relative effectiveness of two therapy programs for the treatment of childhood and adolescent non-Hodgkin's lymphoma. Two chemotherapeutic strategies were compared: a 4-drug regimen (COMP) and a 10-drug regimen (modified LSA2-L2). Failure-free survival for all patients was 60 per cent at 24 months. In patients with disseminated disease treatment success was influenced by both the histologic subtype of disease and the therapeutic regimen followed. The 10-drug program was more effective than the 4-drug program in patients with disseminated lymphoblastic disease (two-year failure-free survival rate, 76 vs. 26 per cent, respectively; P = 0.0002), whereas the 4-drug program was more effective than the 10-drug program in those with nonlymphoblastic disease (57 vs. 28 per cent, respectively, P = 0.008). The less toxic, more easily administered 4-drug regimen was as effective as the 10-drug regimen in patients with localized disease (89 vs. 84 per cent, respectively).", "nan", "A controlled randomised trial was carried out to evaluate the efficacy of BCG immunotherapy in preventing relapse in patients with Burkitt's lymphoma in whom remission had been induced with cyclophosphamide. Twenty-one patients were treated with BCG, and 19 were controls. Eleven patients in each group relapsed during a follow-up period long enough to make it unlikely that further relapses would occur. There were no significant differences in the length of remission or the site of relapse that could be attributed to treatment. Eleven patients died: of these none of the six patients in the BCG group but all of the five in the control group had stage D lymphomas. BCG treatment increased the rate of recovery from tumour-induced immunosuppression, but within the BCG group immunocompetence improved most rapidly in the patients who relapsed-a finding that appears to contradict the tenet retionalising the use of immunological adjuvants as treatment." ]

[ "1439601", "15879805" ]

[ "Cost effectiveness of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for medium-sized kidney stones. A randomised clinical trial.", "Prospective, randomized trial comparing shock wave lithotripsy and ureteroscopy for lower pole caliceal calculi 1 cm or less." ]

[ "To evaluate percutaneous nephrolithotomy (PNL) and extracorporeal shock wave lithotripsy (ESWL) for their clinical effects, their cost effectiveness, their complication rates, and the patients' experiences, 55 consecutive patients were randomised to have one or other operation between October 1986 and October 1988. Six patients were excluded, 21 were treated with PNL and 28 with ESWL as primary treatment. Mean hospital stay and length of treatment were longer for PNL than for ESWL. Since 1 July 1987 all patients having ESWL have been treated without anaesthesia (n = 15), whereas epidural anaesthesia was used for all PNL. Slightly more of the ESWL patients experienced some pain during treatment. Minor complications or pain were more common after ESWL during the first 10 days after discharge from hospital. If patients with stone fragments of 4 mm or less were regarded as having a successful outcome, the success rates after one year were 94% for PNL and 77% for ESWL. The overall total cost was lower for ESWL than for PNL, the cost per successfully treated patient being 2172 pounds for PNL and 1810 pounds for ESWL. Medium sized kidney stones (6-30 mm, or 2-3 stones of 20 mm or less) can be efficiently and cheaply treated by both PNL and ESWL, though the cost of ESWL is lower. Even if effects other than cost (such as complications and patients' experience) are borne in mind, ESWL was superior to PNL for this group of patients.", "The optimal management of lower pole renal calculi is controversial. We compared shock wave lithotripsy (SWL) and ureteroscopy (URS) for the treatment of patients with small lower pole stones in a prospective, randomized, multicenter trial.\n A total of 78 patients with 1 cm or less isolated lower pole stones were randomized to SWL or URS. The primary outcome measure was stone-free rate on noncontrast computerized tomography at 3 months. Secondary outcome parameters were length of stay, complication rates, need for secondary procedures and patient derived quality of life measures.\n A total of 67 patients randomized to SWL (32) or URS (35) completed treatment. The 2 groups were comparable with respect to age, sex, body mass index, side treated and stone surface area. Operative time was significantly shorter for SWL than URS (66 vs 90 minutes). At 3 months of followup 26 and 32 patients who underwent SWL and URS had radiographic followup that demonstrated a stone-free rate of 35% and 50%, respectively (p not significant). Intraoperative complications occurred in 1 SWL case (unable to target stone) and in 7 URS cases (failed access in 5 and perforation in 2), while postoperative complications occurred in 7 SWL and 7 URS cases. Patient derived quality of life measures favored SWL.\n This study failed to demonstrate a statistically significant difference in stone-free rates between SWL and URS for the treatment of small lower pole renal calculi. However, SWL was associated with greater patient acceptance and shorter convalescence." ]

[ "16294814", "15734771", "16923414", "19770739", "19007597" ]

[ "[Impact of the intra-aortic balloon pump in the mortality due to cardiogenic shock secondary to acute myocardial infarction].", "Randomized comparison of intra-aortic balloon support with a percutaneous left ventricular assist device in patients with revascularized acute myocardial infarction complicated by cardiogenic shock.", "A randomized multicenter clinical study to evaluate the safety and efficacy of the TandemHeart percutaneous ventricular assist device versus conventional therapy with intraaortic balloon pumping for treatment of cardiogenic shock.", "Intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: the prospective, randomized IABP SHOCK Trial for attenuation of multiorgan dysfunction syndrome.", "A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction." ]

[ "To determine the impact of the intra-aortic balloon pump in the mortality due to cardiogenic shock post-acute myocardial infarction.\n In a two-year period, 292 patients with acute myocardial infarction were admitted to the coronary intensive care unit, 40 were included in the study. Afterwards, patients were divided in two groups: early cardiogenic and late cardiogenic shock, and they were assigned randomly and blind to treatment with inotropics and inotropics plus intra-aortic balloon pump.\n There were significant differences in the measurements of pulmonary wedge pressure (20.4 +/- 1.6 vs 24.4 +/- 1.50, p = 0.0004) and the cardiac index (2.06 +/- 0.7 vs 1.65 +/- 0.18, p = 0.0002) between the two groups. The late cardiogenic shock group showed an increased mortality (25.9% vs 61.5%, p < 0.05). Patients treated with inotropics + balloon, in both early and late shock groups, showed a reduction in mortality of 66% and 69%, respectively.\n The use of the intra-aortic balloon pump in the treatment of cardiogenic shock post acute myocardial infarction reduces the mortality when associated with the use of inotropics and reperfusion.", "Mortality in cardiogenic shock (CS) following acute myocardial infarction (AMI) remains unacceptably high despite percutaneous coronary intervention (PCI) of the infarcted artery and use of intra-aortic balloon pump (IABP) counterpulsation. A newly developed percutaneous left ventricular assist device (VAD) (Tandem Heart, Cardiac Assist, Pittsburgh, PA, USA) with active circulatory support might have positive haemodynamic effects and decrease mortality.\n Patients in CS after AMI, with intended PCI of the infarcted artery, were randomized to either IABP (n=20) or percutaneous VAD support (n=21). The primary outcome measure cardiac power index, as well as other haemodynamic and metabolic variables, could be improved more effectively by VAD support from 0.22 [interquartile range (IQR) 0.19-0.30] to 0.37 W/m2 (IQR 0.30-0.47, P<0.001) when compared with IABP from 0.22 (IQR 0.18-0.30) to 0.28 W/m2 (IQR 0.24-0.36, P=0.02; P=0.004 for intergroup comparison). However, complications like severe bleeding (n=19 vs. n=8, P=0.002) or limb ischaemia (n=7 vs. n=0, P=0.009) were encountered more frequently after VAD support, whereas 30 day mortality was similar (IABP 45% vs. VAD 43%, log-rank, P=0.86).\n Haemodynamic and metabolic parameters can be reversed more effectively by VAD than by standard treatment with IABP. However, more complications were encountered by the highly invasive procedure and by the extracorporeal support.", "Despite major advances in the treatment of heart failure, cardiogenic shock (CGS) remains associated with substantial mortality. Recent data suggest that the TandemHeart percutaneous ventricular assist device (pVAD) may be useful in the management of CGS. The aim of this prospective randomized study was to test the hypothesis that the TandemHeart (pVAD) provides superior hemodynamic support compared with intraaortic balloon pumping (IABP).\n Forty-two patients from 12 centers presenting within 24 hours of developing CGS were included in the study and treated in an initial roll-in phase (n = 9) or randomized to treatment with IABP (n = 14) or TandemHeart pVAD (n = 19). Thirty patients (71%) had persistent CGS despite having an IABP in place at the time of study enrollment.\n Cardiogenic shock was due to myocardial infarction in 70% of the patients and decompensated heart failure in most of the remaining patients. The mean duration of support was 2.5 days. Compared with IABP, the TandemHeart pVAD achieved significantly greater increases in cardiac index and mean arterial blood pressure and significantly greater decreases in pulmonary capillary wedge pressure. Overall 30-day survival and severe adverse events were not significantly different between the 2 groups.\n In patients presenting within 24 hours of the development of CGS, TandemHeart significantly improves hemodynamic parameters, even in patients failing IABP. Larger-scale studies are required to assess the influence of improved hemodynamics on survival.", "Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction with cardiogenic shock (CS) are often treated with intra-aortic balloon pump counterpulsation (IABP), even though the evidence to support this is limited. We determined whether IABP as an addition to PCI-centered therapy ameliorates multiorgan dysfunction syndrome (MODS) in patients with acute myocardial infarction complicated by CS.\n A prospective, randomized, controlled, open-label clinical trial recruiting patients between March 2003 and June 2004 (ClinicalTrials.gov ID NCT00469248).\n Tertiary care university hospital.\n Forty-five consecutive patients with AMI and CS undergoing PCI were randomized to treatment with or without IABP.\n Acute Physiology and Chronic Health Evaluation (APACHE) II scores (primary outcome measure), hemodynamic values, inflammatory markers, and plasma brain natriuretic peptide (BNP) levels (secondary outcomes) were collected over 4 days from randomization. The prospective hypothesis was that adding IABP therapy to \"standard care\" would improve CS-triggered MODS. The addition of IABP to standard therapy did not result in a significant improvement in MODS (measured by serial APACHE II scoring over 4 days). IABP use had no significant effect on cardiac index or systemic inflammatory activation, although BNP levels were significantly lower in IABP-treated patients. Initial and serial APACHE II scoring correlated with mortality better than cardiac index, systemic inflammatory state, and BNP levels in this group of patients. Nonsurvivors had significantly higher initial APACHE II scores (29.9 +/- 2.88) than survivors (18.1 +/- 1.66, p < .05). Nevertheless, discrepancies among patients within the groups cannot be ruled out and might interfere with our results.\n In this randomized trial addressing addition of IABP in CS patients, mechanical support was associated only with modest effects on reduction of APACHE II score as a marker of severity of disease, improvement of cardiac index, reduction of inflammatory state, or reduction of BNP biomarker status compared with medical therapy alone. However, the limitations of our present trial preclude any definitive conclusion, but request for a larger prospective, randomized, multicentered trial with mortality as primary end point.", "The aim of this study was to test whether the left ventricular assist device (LVAD) Impella LP2.5 (Abiomed Europe GmbH, Aachen, Germany) provides superior hemodynamic support compared with the intra-aortic balloon pump (IABP).\n Cardiogenic shock caused by left ventricular failure is associated with high mortality in patients with acute myocardial infarction (AMI). An LVAD may help to bridge patients to recovery from left ventricular failure.\n In a prospective, randomized study, 26 patients with cardiogenic shock were studied. The primary end point was the change of the cardiac index (CI) from baseline to 30 min after implantation. Secondary end points included lactic acidosis, hemolysis, and mortality after 30 days.\n In 25 patients the allocated device (n = 13 IABP, n = 12 Impella LP2.5) could be safely placed. One patient died before implantation. The CI after 30 min of support was significantly increased in patients with the Impella LP2.5 compared with patients with IABP (Impella: DeltaCI = 0.49 +/- 0.46 l/min/m(2); IABP: DeltaCI = 0.11 +/- 0.31 l/min/m(2); p = 0.02). Overall 30-day mortality was 46% in both groups.\n In patients presenting with cardiogenic shock caused by AMI, the use of a percutaneously placed LVAD (Impella LP 2.5) is feasible and safe, and provides superior hemodynamic support compared with standard treatment using an intra-aortic balloon pump. (Efficacy Study of LV Assist Device to Treat Patients With Cardiogenic Shock [ISAR-SHOCK]; NCT00417378)." ]

[ "19299681", "16235871", "11527868", "10143452", "17277011", "16602835", "6429905" ]

[ "A multifaceted intervention to improve health worker adherence to integrated management of childhood illness guidelines in Benin.", "The effect of two models of supervision on selected outcomes.", "The impact of supervision on stock management and adherence to treatment guidelines: a randomized controlled trial.", "Improving primary health care through systematic supervision: a controlled field trial.", "Improving adherence to family planning guidelines in Kenya: an experiment.", "Participatory supervision model: building health promotion capacity among health officers and the community.", "Quarterly versus monthly supervision of CBD family planning programs: an experimental study in northeast Brazil." ]

[ "We evaluated an intervention to support health workers after training in Integrated Management of Childhood Illness (IMCI), a strategy that can improve outcomes for children in developing countries by encouraging workers' use of evidence-based guidelines for managing the leading causes of child mortality.\n We conducted a randomized trial in Benin. We administered a survey in 1999 to assess health care quality before IMCI training. Health workers then received training plus either study supports (job aids, nonfinancial incentives, and supervision of workers and supervisors) or usual supports. Follow-up surveys conducted in 2001 to 2004 assessed recommended treatment, recommended or adequate treatment, and an index of overall guideline adherence.\n We analyzed 1244 consultations. Performance improved in both intervention and control groups, with no significant differences between groups. However, training proceeded slowly, and low-quality care from health workers without IMCI training diluted intervention effects. Per-protocol analyses revealed that workers with IMCI training plus study supports provided better care than did those with training plus usual supports (27.3 percentage-point difference for recommended treatment; P < .05), and both groups outperformed untrained workers.\n IMCI training was useful but insufficient. Relatively inexpensive supports can lead to additional improvements.", "To evaluate the effect of training in two different supervisory models on the supervision itself, the quality of care, and job satisfaction of nurses in different service settings in a district health service (DHS) in South Africa.\n As part of a larger health systems study, the results of supervision training were evaluated. The quantitative study was done in three health districts in South Africa.\n The modified matrix (MM) model of supervision was taught and implemented in District A, the Centre for Health and Social Studies (CHESS) model in District B, and the control was District C. Checklists based on direct observation and record reviews were used to measure quality of care (quality of hand-over between shifts, nursing records, management of chronic diseases, and implementation of universal precautions). Questionnaires were used to measure perception of supervision and patient satisfaction. Chi-square analysis was done.\n Supervision ratings before and after the interventions differed significantly in the total sample, but not by district. In the district with the MM model, care for people with chronic diseases improved significantly, but other measures did not. The supervision training had some influence, but more measures of effectiveness of supervision training are needed.", "Ensuring the availability of essential drugs and using them appropriately are crucial if limited resources for health care are to be used optimally. While training of health workers throughout Zimbabwe in drug management (including stock management and rational drug use) resulted in significant improvements in a variety of drug use indicators, these achievements could not be sustained, and a new strategy was introduced based on the supervision of primary health care providers. This was launched in 1995 with a training course in supervisory skills for district pharmacy staff. In order to evaluate the impact of the supervision and the effectiveness of the training programme, adherence to standard treatment guidelines (STG) and stock management protocols was evaluated in a randomized controlled trial. The study compared three different groups of health facilities: those that received supervision for either use of STG (n = 23) or stock management (n = 21) - each facility acting as control for the other area of supervision - and a comparison group of facilities which received no supervision (n = 18). On-the-spot supervision by a specially trained pharmacy staff, based around identified deficiencies, took place at the start of the study and 3 months later. The evaluation compared performance on a variety of drug management indicators at baseline and 6-8 months after the second supervisory visit. The results of the study showed that, following supervision, overall stock management improved significantly when compared with the control and comparison groups. Similar improvements were demonstrated for adherence to STG, although the effect was confounded by other interventions. The study also showed that supervision has a positive effect on improving performance in areas other than those supervised, and demonstrated that pharmacy technicians with limited clinical skills can be trained to influence primary health care workers to positively improve prescribing practices. Allocating resources to supervision is likely to result in improved performance of health workers with regard to the rational use of essential drugs, resulting in improved efficiency and effectiveness.", "Most primary health care services in developing countries are delivered by staff working in peripheral facilities where supervision is problematic. This study examined whether systematic supervision using an objective set of indicators could improve health worker performance. A checklist was developed by the Philippine Department of Health which assigned a score from 0 to 3 on each of 20 indicators which were clearly defined. The checklist was implemented in 4 remote provinces with 6 provinces from the same regions serving as a control area. In all 10 provinces, health facilities were randomly selected and surveyed before implementation of the checklist and again 6 months later. Performance, as measured by the combined scores on the 20 indicators, improved 42% (95% Cl = 29% to 55%) in the experimental group compared to 18% (95% Cl = 9% to 27%) in the control group. In the experimental, but not in the control facilities, there was a correlation between frequency of supervision and improvements in scores. The initial cost of implementing the checklist was US $ 19.92 per health facility and the annual recurrent costs were estimated at $ 1.85. Systematic supervision using clearly defined and quantifiable indicators can improve service delivery considerably, at modest cost.", "QUALITY PROBLEM: Research in Kenya in the mid-1990s suggested poor quality family planning services and limited access to services. Clinical guidelines for family planning and reproductive health were published in 1991 and updated in 1997, but never widely distributed.\n Managers and trainers chose intensive, district-level training workshops to disseminate guidelines and update health workers on guideline content and best practices.\n Training workshops were held in 41 districts in 1999. Trainees were instructed to update their untrained co-workers afterwards. As a reinforcement, providers in randomly selected areas received a 'cascade training package' of instructional materials and training tips. Providers in 15 randomly selected clinics also received 'supportive supervision' visits as a second reinforcement.\n A cluster-randomized experiment in 72 clinics assessed the overall impact of the training and the marginal benefits of the two reinforcing activities. Researchers and trainers created several dozen indicators of provider knowledge, attitudes, beliefs and practices. Binomial and multivariate analyses were used to compare changes over time in indicators and in aggregated summary scores. Data from patient interviews were analysed to corroborate provider practice self-reports. Cost data were collected for an economic evaluation.\n Post-test data collected in 2000 showed that quality of care and access increased after the intervention. The cascade training package showed less impact than supportive supervision, but the former was more cost-effective.\n Service delivery guidelines, when properly disseminated, can improve family planning practices in sub-Saharan Africa.", "The Thai traditional health supervision model has been developed since 1991. However, many supervisors lack supervisory knowledge and skills. This study aimed to compare and identify the strengths and challenges of two different supervision models, in order to determine their effects on enhancing the health promotion capacity of health officers in two primary care units (PCU) in Chiang Mai Province, northern Thailand.\n The two models were implemented at two PCU in one semi-district, Chiang Mai Province, over a six-month period. The first model involved supervisors from the district level, with the full participation of health officers at the sub-district level. The second model was designed with the addition of community involvement in the supervision process. Before implementing the models, the district supervisors attended a retraining course to enhance their supervisory knowledge and ability. Questionnaires were used to assess health officers' job satisfaction, clients' perceived service quality and care satisfaction. Semi-structured interviews and qualitative observations were used to explore the involvement of health officers and the community, and to determine the strengths and challenges of each supervisory model.\n Both before and after the intervention, the PCU health officers appeared to have good and comparable job satisfaction levels. Bivariate analysis indicated that after the intervention, both supervisory models appeared effective in terms of clients' perceived service quality and satisfaction with care, among those who utilized the PCU. However, the second model, which allowed the community to participate in the supervision process, achieved better results. The qualitative findings suggested that the involvement of health officers caused a rapid change and improvement after the supervision. The involvement of the community helped the community itself to identify problems and formulate alternatives to meet the community's needs.\n This study shows positive outcomes for two forms of participatory supervision in a rural setting. There appear to be additional positive outcomes for the model that involved community participation. To ensure successful implementation, several issues, such as the supervisor's knowledge and ability, health officer workload and supervisory communication skills, need to be improved.", "The cost-effectiveness of reducing the frequency of routine supervision from monthly to quarterly was evaluated in a closely controlled field experiment conducted in a community-based distribution program in Piaui State in northeast Brazil. The results demonstrated substantial potential savings in supervisors' salaries and travel at no cost to program performance (new acceptors, revisits, distributor turnover). A possible reason for this finding was that most supervisory visits were primarily concerned with collecting inventory and service statistics, which probably contributed little to post performance. It was suggested that the number of supervisors and the frequency of supervision should be linked to productive rather than routine supervisory activities." ]

[ "1729065", "7259512", "2153475", "7710569", "6716222" ]

[ "Calcium inhibits the cardiac stimulating properties of dobutamine but not of amrinone.", "Ionized calcium concentration and cardiovascular function after cardiopulmonary bypass.", "Calcium attenuates epinephrine's beta-adrenergic effects in postoperative heart surgery patients.", "Effects of single dose calcium gluconate infusion in hypocalcemic preterm infants.", "Effect of calcium therapy in the sick premature infant with early neonatal hypocalcemia." ]

[ "To contrast the effect of increasing blood calcium concentrations on the cardiovascular actions of intravenous beta-adrenergic agonists and phosphodiesterase inhibitors, 46 patients recovering from aortocoronary bypass surgery received either dobutamine or amrinone both in the presence and absence of a calcium infusion. Cardiac output, systemic arterial pressure, pulmonary arterial pressure, central venous pressure, pulmonary artery occlusion pressure, heart rate, and blood ionized calcium concentration were measured before and during infusions of dobutamine (2.5 and 5.0 micrograms/kg/min) and amrinone (0.75 mg/kg bolus + 10 micrograms/kg/min or 2.25 mg/kg bolus + 20 micrograms/kg/min). After the initial dobutamine infusion period, patients were randomly and blindly assigned to receive either a calcium or placebo infusion, and the dobutamine infusions were repeated. Because of the long duration of amrinone's actions, the amrinone maintenance infusion was continued while randomized, blinded infusion of either calcium or placebo was added. Dobutamine (5 micrograms/kg/min) increased cardiac output from 7.1 +/- 0.3 L/min to 9.1 +/- 0.4 L/min, and increased heart rate from 93 +/- 4 beats/min to 107 +/- 4 beats/min. Systemic vascular resistance decreased and stroke volume increased. Dobutamine had no significant effects on other hemodynamic values. Amrinone (2.25 mg/kg bolus + 20 micrograms/kg/min) increased cardiac output from 5.6 +/- 0.4 L/min to 6.9 +/- 0.5 L/min, and increased heart rate from 87 +/- 3 beats/min to 98 +/- 3 beats/min. Amrinone decreased mean arterial pressure, systemic vascular resistance, pulmonary artery occlusion pressure, central venous pressure, and pulmonary artery pressure. Calcium infusion increased arterial pressure (8 to 13 percent) but had no significant effects on any other hemodynamic parameters. Calcium reduced the increase in cardiac output produced by dobutamine by 30 percent, but it did not alter the cardiotonic actions of amrinone. Thus, calcium inhibits the cardiotonic actions of certain beta-adrenergic agonists, most likely by interfering with signal transduction through the beta-adrenergic receptor complex.", "Patients who required cardiopulmonary bypass were studied to determine the postoperative incidence of hypocalcemia and to quantify the effects of intravenous (IV) calcium chloride on ionized calcium (Ca++) concentration in blood and on cardiac function. Patients either received no calcium chloride postoperatively (control), or received it as an intermittent IV bolus (5 mg/kg) or as a constant infusion (0.5 mg/kg/min) whenever Ca++ concentration was less than 1.8 mEq/L. Hemodynamic profiles were determined every 15 minutes during the first two postoperative hours. Regardless of Ca++ concentration and therapy, cardiac indices, stroke indices, and vascular resistances of all patients never differed significantly. No variable changed consistently, other than Ca++ concentration, in those patients receiving calcium chloride. We conclude that postoperative hypocalcemia occurs frequently after cardiopulmonary bypass surgery, but not to the degree that would be expected to cause cardiovascular depression, and is readily corrected with IV calcium chloride. Myocardial depression occurred in all patients, but likely resulted from other causes.", "Epinephrine and calcium possess both cardiac inotropic and vasopressor activity. In addition, epinephrine's cardiovascular effects are mediated via increases in intracellular calcium. As a result, many clinicians administer the two agents together in an attempt to augment their effects. Although this approach seems rational, it has never been proven effective. We evaluated the cardiovascular and hyperglycemic actions of epinephrine (10 and 30 ng/kg/min), with and without calcium chloride administration (10 mg/kg bolus followed by 2 mg/kg/hr infusion), in a prospective, randomized, blinded, crossover designed study. Twelve adult patients were studied 1 day after aortocoronary bypass surgery. Calcium chloride raised ionized calcium levels from 1.06 +/- 0.03 (mean +/- SEM) to 1.44 +/- 0.05 mM (p less than 0.05). Calcium raised mean arterial pressure from 85 +/- 1 to 94 +/- 2 mm Hg (p less than 0.05) but had no significant effect on cardiac index. Epinephrine alone at 10 and 30 ng/kg/min significantly raised cardiac index from 2.7 +/- 0.2 to 3.0 +/- 0.2 (p less than 0.05) and 3.6 +/- 0.3 (p less than 0.05) l/min/m2. After calcium, epinephrine failed to significantly increase cardiac index. Epinephrine at 30 ng/kg/min significantly increased mean arterial pressure from 87 +/- 1 to 95 +/- 2 mm Hg (p less than 0.05). After calcium, epinephrine had no significant effect on blood pressure. In addition, epinephrine's hyperglycemic effect was blunted by calcium. Plasma epinephrine levels were similar during control and calcium infusions. We conclude that calcium blunts epinephrine's beta-adrenergic actions in postoperative cardiac surgery patients.", "We conducted a prospective, double-blind study of 43 preterm infants to examine the effect of a single calcium gluconate infusion as therapy for neonatal hypocalcemia on serum calcium concentrations and hypocalcemic signs in preterm infants with low total serum calcium concentrations. Total and ionized serum calcium was measured and signs of irritability, jitteriness, and twitching were scored (scale 0-9) by blinded observers before and after receiving one dose of either calcium gluconate (100 mg/kg) or placebo (normal saline). Total and ionized serum calcium increased 3 to 6 hours following the calcium, but not the placebo, infusion. Of the infants with hypocalcemic signs, the average score of hypocalcemic signs decreased in the 11 calcium-treated infants; the 12 infants with hypocalcemic signs showed no change of hypocalcemic signs following treatment with placebo. We conclude from this study that a single dose of calcium gluconate (100 mg/kg) in hypocalcemic preterm infants raise total and ionized serum calcium and decrease clinical signs of hypocalcemia.", "Twenty-seven sick premature infants with serum calcium concentrations less than 6.0 mg/dl during the first day of age were enrolled in a prospective controlled study involving two treatment regimens--calcium given as a bolus or a drip--or no treatment. Mean total calcium concentration was 5.5 +/- 0.8 mg/dl, and ionized calcium was 3.1 +/- .3 mg/dl, with no significant difference between treatment groups. By 24 hours, in all groups total calcium had increased to greater than 6.0 mg/dl (bolus 6.5 +/- 1.1, drip 7.0 +/- 0.4, control 6.6 +/- 0.4) and ionized calcium to greater than 3.5 mg/dl (bolus 3.9 +/- 0.3, drip 3.6 +/- 0.6, control 3.6 +/- 0.3). Ionized and total calcium concentrations were significantly correlated (r = 0.562; P less than 0.001), but total calcium did not predict ionized calcium in any group. These data support the concept that, even in sick infants, early neonatal hypocalcemia is a physiologic phenomenon that may not require treatment." ]

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[ "Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates.", "A long-term study on the effect of spontaneous consumption of reduced fat products as part of a normal diet on indicators of health.", "A randomized trial of a low fat high fibre diet in the recurrence of colorectal polyps. Toronto Polyp Prevention Group.", "Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction (from The Heart Institute of Spokane Diet Intervention and Evaluation Trial).", "Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS)", "The effect of diet on bile acid kinetics and biliary lipid secretion in gallstone patients treated with ursodeoxycholic acid.", "Low fat, low cholesterol diet in secondary prevention of coronary heart disease.", "Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.", "Effect of dietary intervention and lipid-lowering treatment on brachial vasoreactivity in patients with ischemic heart disease and hypercholesterolemia.", "Better dietary adherence and weight maintenance achieved by a long-term moderate-fat diet.", "Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial.", "Long-term effects of ad libitum low-fat, high-carbohydrate diets on body weight and serum lipids in overweight subjects with metabolic syndrome.", "Weight loss with high and low carbohydrate 1200 kcal diets in free living women.", "Methods to increase fruit and vegetable intake with and without a decrease in fat intake: compliance and effects on body weight in the nutrition and breast health study.", "Prospective comparison of modified fat-high-carbohydrate with standard low-carbohydrate dietary advice in the treatment of diabetes: one year follow-up study.", "The Mediet Project.", "Long-term effects of a reduced fat diet intervention on cardiovascular disease risk factors in individuals with glucose intolerance.", "[Long-term effects of nutrition with fat-reduced foods on energy consumption and body weight].", "Comparison of high-fat and high-protein diets with a high-carbohydrate diet in insulin-resistant obese women.", "Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey.", "Long-term effects of linoleic-acid-enriched diet on albuminuria and lipid levels in type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion.", "Effect of a low-fat diet on the incidence of actinic keratosis.", "Comparison of 3 ad libitum diets for weight-loss maintenance, risk of cardiovascular disease, and diabetes: a 6-mo randomized, controlled trial.", "Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART).", "Effect of diet or very long chain omega-3 fatty acids on progression of atherosclerosis, evaluated by carotid plaques, intima-media thickness and by pulse wave propagation in elderly men with hypercholesterolaemia.", "Unsaturated fats and progression of diabetic retinopathy.", "Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women's Healthy Eating and Living (WHEL) randomized trial.", "Change in women's diet and body mass following intensive intervention for early-stage breast cancer.", "The polyp prevention trial I: rationale, design, recruitment, and baseline participant characteristics.", "Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy.", "Hypercholesterolaemia in treated hypertensives: a controlled trial of intensive dietary advice.", "A 9-mo randomized clinical trial comparing fat-substituted and fat-reduced diets in healthy obese men: the Ole Study.", "Long term metabolic effects of two dietary methods of treating hyperlipidaemia.", "A randomized trial of a low-fat dietary intervention in women at high risk for breast cancer.", "Dietary Counseling for High Blood Cholesterol in Families at Risk of Coronary Disease.", "Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study.", "Effects of a diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on postmeal triglyceride concentrations and other cardiovascular risk factors in type 1 diabetes.", "Randomized controlled trial of changes in dietary carbohydrate/fat ratio and simple vs complex carbohydrates on body weight and blood lipids: the CARMEN study. The Carbohydrate Ratio Management in European National diets.", "Lipoprotein lipid response to the National Cholesterol Education Program step II diet by hypercholesterolemic and combined hyperlipidemic women and men." ]

[ "The possible advantage for weight loss of a diet that emphasizes protein, fat, or carbohydrates has not been established, and there are few studies that extend beyond 1 year.\n We randomly assigned 811 overweight adults to one of four diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the four diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The diets consisted of similar foods and met guidelines for cardiovascular health. The participants were offered group and individual instructional sessions for 2 years. The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content.\n At 6 months, participants assigned to each diet had lost an average of 6 kg, which represented 7% of their initial weight; they began to regain weight after 12 months. By 2 years, weight loss remained similar in those who were assigned to a diet with 15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respectively); in those assigned to a diet with 20% fat and those assigned to a diet with 40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbohydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg, respectively) (P>0.20 for all comparisons). Among the 80% of participants who completed the trial, the average weight loss was 4 kg; 14 to 15% of the participants had a reduction of at least 10% of their initial body weight. Satiety, hunger, satisfaction with the diet, and attendance at group sessions were similar for all diets; attendance was strongly associated with weight loss (0.2 kg per session attended). The diets improved lipid-related risk factors and fasting insulin levels.\n Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize. (ClinicalTrials.gov number, NCT00072995.)\n 2009 Massachusetts Medical Society", "The growing public concern with the adverse effects on health of a high fat intake has led to a proliferation on the market of reduced fat products. However, no consensus exists on the effectivity of reduced fat products to decrease energy intake. The studies that have investigated this topic have included small numbers of subjects, studied under laboratory conditions and over a relatively short period of time. Therefore, we have executed a long-term study in which volunteers had free access to both reduced fat, commercially available products in the laboratory as well as to products obtained from regular shops. We here report the feasibility of such a type of study and the effects of consumption of reduced fat products on blood levels of cholesterol, haemostasis variables, antioxidants and parameters of the immune system. The study was a multicentre parallel comparison trial of six months (so-called MSFAT-study). 241 volunteers received either reduced fat products or full-fat products and the products were clearly labelled as such. Two months before the start of the study, a 1 month adaptation period was executed to optimize the experimental procedures. Food intake was recorded before the start of the adaptation period and 2-4 weeks, 3 months and 6 months after the start of the study. Blood samples were taken before, after 2, 4 and 6 months of the study. In addition, a selection of the reduced fat and full-fat products was sensorically evaluated three times during the study by a subgroup of the volunteers. 220 volunteers completed the study. The reduced fat group consumed on average 46% less fat from the so-called MSFAT-products obtained from the shop at the laboratory than the control group and consumption of these MSFAT-products did not decrease in either of the groups during the time course of the study. The palatability of the reduced fat and full-fat products was similar and as expected, the perceived fattiness of the full-fat products was higher than that of the reduced fat products. No effects were found on blood levels of cholesterol, haemostasis variables, parameters of antioxidant status and immune system characteristics. In conclusion, the experimental manipulation of the fat content of the diet that was achieved and that remained stable throughout the 6 months of the study indicates that this type of set-up is feasible to assess the effects of long-term nutritional intervention in large groups of volunteers under semi-controlled conditions. The regular use of reduced fat products did not positively but also not adversely affect blood cholesterol levels, antioxidant status, haemostasis factors and the body's immune system.", "After polypectomy for adenomatous colorectal polyps, 201 persons were randomized to receive counselling on a diet low in fat (the lesser of 50 g/day or 20% of energy) and high in fibre (50 g/day) (LFHF), or to follow a normal western diet (ND), high in fat and low in fibre. After 12 months of counselling, fat consumption was about 25% of energy in the LFHF group and 33% in the ND group; fibre consumption was 35 g and 16 g respectively. After an average of two years of follow-up, an intention to treat analysis led to a ratio of cumulative incidence rates of 1.2 (95% CL 0.6-2.2) for recurrence of neoplastic polyps, a finding which suggests no significant difference between dietary groups over the period of observation. An exploratory analysis conducted among 142 persons with substantial diet counselling indicated a reduced risk of neoplastic polyp recurrence in women (RR = 0.5), associated with reduced concentrations of faecal bile acids while on the LFHF diet, but indicated an increased risk of recurrence in men (RR = 2.1), associated with increased faecal bile acids. Although a larger study would be needed to rule out the role of chance, these findings of gender-specific associations between diet counselling and both faecal bile acid concentrations and recurrence of colorectal neoplasia are consistent with recently published evidence of differences between genders.", "Whether a Mediterranean-style diet reduces cardiovascular events and mortality more than a low-fat diet is uncertain. The objectives of this study were to actively compare low-fat and Mediterranean-style diets after first myocardial infarction (MI) in a randomized, controlled clinical trial and to compare dietary intervention per se with usual care in a case-control analysis. First MI survivors were randomized to a low-fat (n = 50) or Mediterranean-style (n = 51) diet. The 2 diets were low in saturated fat (< or =7% kcal) and cholesterol (< or =200 mg/day); the Mediterranean-style diet was distinguished by greater omega-3 fat intake (>0.75% kcal). Participants received individual dietary counseling sessions, 2 within the first month and again at 3, 6, 12, 18, and 24 months, along with 6 group sessions. Combined dietary intervention groups (cases, n = 101) were compared with a usual-care group (controls, n = 101) matched for age, gender, MI type and treatment, and status of diabetes mellitus and hypertension. Primary-outcome-free survival (a composite of all-cause and cardiac deaths, MI, hospital admissions for heart failure, unstable angina pectoris, or stroke) did not differ between low-fat (42 of 50) and Mediterranean-style (43 of 51) diet groups over a median follow-up period of 46 months (range 18 to 72; log-rank p = 0.81). Patients receiving dietary intervention had better primary-outcome-free survival (85 of 101) than usual-care controls (61 of 101) (log-rank p <0.001), with unadjusted and adjusted odds ratios of 0.33 (95% confidence interval 0.18 to 0.60, p <0.001) and 0.28 (95% confidence interval 0.13 to 0.63, p = 0.002), respectively. In conclusion, active intervention with either a low-fat or a Mediterranean-style diet similarly and significantly benefits overall and cardiovascular-event-free survival after MI.", "To assess the effect of dietary reduction of plasma cholesterol concentrations on coronary atherosclerosis, we set up a randomised, controlled, end-point-blinded trial based on quantitative image analysis of coronary angiograms in patients with angina or past myocardial infarction. Another intervention group received diet and cholestyramine, to determine the effect of a greater reduction in circulating cholesterol concentrations. 90 men with coronary heart disease (CHD), who had a mean (SD) plasma cholesterol of 7.23 (0.77) mmol/l were randomised to receive usual care (U, controls), dietary intervention (D), or diet plus cholestyramine (DC), with angiography at baseline and at 39 (SD 3.5) months. Mean plasma cholesterol during the trial period was 6.93 (U), 6.17 (D), and 5.56 (DC) mmol/l. The proportion of patients who showed overall progression of coronary narrowing was significantly reduced by both interventions (U 46%, D 15%, DC 12%), whereas the proportion who showed an increase in luminal diameter rose significantly (U 4%, D 38%, DC 33%). The mean absolute width of the coronary segments (MAWS) studied decreased by 0.201 mm in controls, increased by 0.003 mm in group D, and increased by 0.103 mm in group DC (p less than 0.05), with improvement also seen in the minimum width of segments, percentage diameter stenosis, and edge-irregularity index in intervention groups. The change in MAWS was independently and significantly correlated with LDL cholesterol concentration and LDL/HDL cholesterol ratio during the trial period. Both interventions significantly reduced the frequency of total cardiovascular events. Dietary change alone retarded overall progression and increased overall regression of coronary artery disease, and diet plus cholestyramine was additionally associated with a net increase in coronary lumen diameter. These findings support the use of a lipid-lowering diet, and if necessary of appropriate drug treatment, in men with CHD who have even mildly raised serum cholesterol concentrations.", "Effects of specific dietary alterations in patients with radiolucent gallstones treated with ursodeoxycholic acid (UDCA, 750 mg at bedtime) were investigated. Patients were allocated randomly to one of four diets: standard (500 mg cholesterol/day), low-cholesterol (250 mg/day), added-bran (30 g/day), or substituted medium-chain triglycerides (MCT) oil (20% of fat). Dietary intake and good compliance were verified by computerized analysis of dietary diaries. Bile-acid kinetics (26 patients) or secretion of biliary lipids (23 other patients) were determined at enrollment and at 6 and 9 mo, respectively, during treatment. Although MCT further decreased the UDCA-induced decrease in the synthesis of chenodeoxycholic acid, it did not lessen desaturation of bile. Otherwise, compared to the standard diet, no experimental diet significantly altered the UDCA-induced increase of the pools of total bile acids and UDCA or the UDCA-induced decrease in synthesis of bile acids and in biliary secretion or saturation of cholesterol. If these dietary manipulations facilitate dissolution of gallstones by UDCA, they do so by other mechanisms.", "nan", "Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.\n To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.\n Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.\n Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.\n Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).\n By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.\n Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.\n ClinicalTrials.gov Identifier: NCT00000611.", "The \"Mediterranean\" diet and statin treatment have both independently been shown to improve survival and reduce the risk of cardiovascular events in patients with ischemic heart disease (IHD), but no studies have evaluated the effect of this combination on endothelial function. We therefore sought to evaluate the effect of the combination dietary intervention and lipid-lowering treatment on brachial vasoreactivity.\n A total of 131 consecutive patients with documented IHD and a serum cholesterol level > or =5 mmol/L (193 mg/dL) were randomized to receive Mediterranean dietary advice (n = 68) or no specific dietary advice (n = 63). Endothelial function was assessed at baseline and after 12 months with noninvasive ultrasound scanning vessel-wall tracking of brachial artery flow-mediated vasodilatation (FMD). All patients started statin treatment with Fluvastatin (40 mg once daily) at baseline.\n A total of 115 patients completed the study. At baseline, FMD was 4.30% +/- 4.89% in the control group versus 4.32% +/- 6.15% in the intervention group (P = not significant). After 12 months of follow-up, FMD was significantly higher in the intervention group (control group 5.72% +/- 4.87% vs intervention group 8.62% +/- 6.60%, P <.01). This was accompanied by a larger intake of fatty fish and a significant decrease in triglyceride levels. In multivariate analysis, randomization status was a significant predictor of FMD after adjustment for classic cardiovascular risk factors and vessel size (P =.02; beta = -2.66 [-4.91; -0.41]).\n Dietary intervention with the Mediterranean diet and statin treatment improve FMD in the brachial artery in patients with IHD and hypercholesterolemia to a greater degree than statin treatment alone.", "The objective of the present study was to determine the effects of a long-term moderate-fat diet (30 % energy from fat) v. a low-fat one (20 % energy from fat) on metabolic risks. The study was a randomised, prospective 14-month trial on overweight and obese patients (eighty-nine overweight and obese men and women). The intervention was a moderate-fat diet (30 % energy) or a low-fat diet (20 % energy). The main outcome measurements were change in body weight, waist circumference, LDL-cholesterol, HDL-cholesterol, total cholesterol, TAG, and systolic and diastolic blood pressure. Forty-five subjects on the moderate-fat diet and forty-four subjects on the low-fat one were studied. Characteristics of all randomised participants were similar in both groups. After 7 months, the moderate- and low-fat diets had similar effects on cardiovascular risks. The moderate-fat diet was more successful after 14 months in reducing weight ( -5.0 (SD 2.5) kg in the moderate-fat group v. -1.2 (SD 1.1) kg in the low-fat one; P < 0.0001), waist circumference (-5.5 (SD 2.4) cm in the moderate-fat group v. - 2.3 (SD 1.3) cm in the low-fat one; P < 0.0001), and other cardiovascular risk factors as well (LDL, TAG, total cholesterol and systolic blood pressure). In conclusion, a moderate-fat energy-restricted diet in the long term might have more beneficial effects on weight maintenance and cardiovascular risk factors compared with a low-fat diet. Better dietary adherence with the moderate-fat diet may be the reason for its successful effects.", "Weight loss, sodium reduction, increased physical activity, and limited alcohol intake are established recommendations that reduce blood pressure (BP). The Dietary Approaches to Stop Hypertension (DASH) diet also lowers BP. To date, no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations.\n To determine the effect on BP of 2 multicomponent, behavioral interventions.\n Randomized trial with enrollment at 4 clinical centers (January 2000-June 2001) among 810 adults (mean [SD] age, 50 [8.9] years; 62% women; 34% African American) with above-optimal BP, including stage 1 hypertension (120-159 mm Hg systolic and 80-95 mm Hg diastolic), and who were not taking antihypertensive medications.\n Participants were randomized to one of 3 intervention groups: (1) \"established,\" a behavioral intervention that implemented established recommendations (n = 268); (2) \"established plus DASH,\"which also implemented the DASH diet (n = 269); and (3) an \"advice only\" comparison group (n = 273).\n Blood pressure measurement and hypertension status at 6 months.\n Both behavioral interventions significantly reduced weight, improved fitness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Across the groups, gradients in BP and hypertensive status were evident. After subtracting change in advice only, the mean net reduction in systolic BP was 3.7 mm Hg (P<.001) in the established group and 4.3 mm Hg (P<.001) in the established plus DASH group; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg (P =.43). Compared with the baseline hypertension prevalence of 38%, the prevalence at 6 months was 26% in the advice only group, 17% in the established group (P =.01 compared with the advice only group), and 12% in the established plus DASH group (P<.001 compared with the advice only group; P =.12 compared with the established group). The prevalence of optimal BP (<120 mm Hg systolic and <80 mm Hg diastolic) was 19% in the advice only group, 30% in the established group (P =.005 compared with the advice only group), and 35% in the established plus DASH group (P<.001 compared with the advice only group; P =.24 compared with the established group).\n Individuals with above-optimal BP, including stage 1 hypertension, can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk.", "Overweight individuals with metabolic syndrome are at increased risk of type 2 diabetes and coronary vascular disease. Weight gain and features of the syndrome may be ameliorated by dietary intervention.\n We investigated the effects of replacing one-quarter of daily fat intake by complex or simple carbohydrate on body weight and intermediary metabolism.\n Forty-six subjects with > or =3 metabolic syndrome risk factors were randomly assigned to receive a control diet; a low-fat, complex carbohydrate diet (LF-CC); or a low-fat, simple carbohydrate diet (LF-SC) for 6 mo. Thirty-nine subjects completed the trial. About 60% of daily dietary intake was provided free of charge through a grocery store. Energy intake was ad libitum. Body weight, body mass index (BMI), blood pressure, and blood lipids were measured at months 0, 2, 4, and 6.\n There was a significant diet x time interaction on body weight and BMI (P < 0.001). Weight loss was greatest with the LF-CC diet [change in body weight: control diet, 1.03 kg (NS); LF-CC diet, -4.25 kg (P < 0.01); LF-SC diet, -0.28 kg (NS)]. Total cholesterol decreased by 0.33 mmol/L, 0.63 mmol/L, and 0.06 mmol/L in subjects consuming the control, LF-CC, and LF-SC diets, respectively (difference between the LF-CC and LF-SC groups: P < 0.05). There were no significant changes in LDL cholesterol, whereas HDL cholesterol decreased over time in all 3 groups (P < 0.0001). Triacylglycerol concentrations were higher in the LF-SC group than in the other 2 groups (P < 0.05).\n A low-fat, high-polysaccharide diet in overweight individuals with abnormal intermediary metabolism led to moderate weight loss and some improvement in serum cholesterol. Increasing simple carbohydrates did not promote weight gain, but nor was there improvement in body weight or lipid profile.", "This randomised controlled trial examined anthropometric changes and cardiovascular benefits of six months of weight management in 110 free living women, aged 18-68 y and BMI 25-50 kg/m2, who received 1200 kcal/d diet treatments of either high (58% energy, n = 57) or low (35% energy, n = 53) carbohydrate (CHO) content. Body weight, plasma total, HDL and LDL cholesterol, triglyceride and blood pressure were measured. Examination at three months showed women on high CHO lost (mean +/- s.e.m) 4.3 +/- 0.5 kg and those on low CHO lost 5.6 +/- 0.6 kg of body weight. Changes in risk factors did not significantly differ between the two diet treatments throughout the study. However those on high CHO diets significantly lowered their plasma total cholesterol by 0.33 mmol/l (95% CI: 0.10, 0.55), LDL cholesterol by 0.23 mmol/l (0.02, 0.43) and HDL cholesterol by 0.05 mmol/l (0.03, 0.10), while women on low CHO diets lowered only plasma triglyceride by 0.28 mmol/l (0.08, 0.48). Blood pressure did not change significantly on either diet. After six months, women on high CHO lost 5.6 +/- 0.8 kg and those on low CHO lost 6.8 +/- 0.8 kg. On the high CHO diet, total cholesterol remained significantly below the baseline value at 0.34 mmol/l (0.13, 0.56), triglyceride was significantly lowered by 0.27 mmol/l (0.10, 0.45), and HDL cholesterol returned to the baseline value. On the low CHO diet, triglyceride remained the only risk factor to be significantly improved. A subgroup of 46 postmenopausal women lost significantly (P < 0.05) more weight on the low CHO diet than high CHO diet. In conclusion, these results provided some support for preferring a high CHO diet to a lower CHO approach in weight management, from the point of view of risk reduction, but do not indicate a consistently more rapid weight loss with either diet.", "Dietary patterns that involve a decrease in fat and an increase in fruit and vegetable (FV) intake have been suggested to decrease cancer risks. In this study, intervention methods to selectively modify dietary fat and/or FV intakes were developed. Compliance to the diets and the effects on body weight are shown, because both of these dietary changes can impact on and be confounded by changes in energy intake. A total of 122 women with a family history of breast cancer were randomized onto one of four diets for 12 mo. Counseling methods were devised to increase amount and variety of FV consumed with or without a decrease in fat intake using modified exchange list diets. Women on the low-fat and combination low-fat/high-FV diet arms decreased their fat intakes to approximately 16% of energy. Women on the high-FV and the combination low-fat/high-FV diet arms increased FV intakes to approximately 11 servings/day. Despite counseling efforts to maintain baseline energy intakes, mean body weight increased significantly by 6 pounds in women in the high-FV diet arm and decreased significantly by 5 pounds in women in the low-fat diet arm. Percent body fat also was increased in the high-FV diet arm and decreased in the low-fat diet arm. Body weight and percent body fat in the combination diet arm did not change significantly. Control of energy intake, therefore, appears to have been achieved only when the addition of FV to the diet was balanced by a decrease in fat intake and both dietary components were enumerated daily. Maintenance of energy intake, therefore, did not appear to be attained intrinsically when individuals were counseled to make changes in the composition of their diets.", "1. A prospective randomized study of two dietary regimens has been started in newly-diagnosed diabetics to determine their effect on circulating metabolites and on diabetic complications. 2. During the first year of treatment the fasting plasma glucose concentrations on both the low-carbohydrate diet and the high-carbohydrate, modified-fat (MF) diet showed a similar decrease. 3. Plasma cholesterol showed a sustained decrease only in patients recommended a MF diet. Transient changes in plasma triglyceride concentrations occurred in patients on both dietary regimens. 4. Increased plasma cholesterol levels are associated with atheromatous disease which is common in diabetics in Europe and North America. A MF diet may therefore have an advantage in that it lowers the plasma cholesterol as well as being effective in lowering the plasma glucose.", "Preliminary evidence from a case control study of healthy postmenopausal women living in Palermo, Sicily, is presented to investigate the potential impact of a traditional Mediterranean diet on the risk of developing breast cancer. Of the 230 women who fulfilled specific eligibility criteria, 115 were enrolled in the study based on serum testosterone values equal to or greater than the median population value (0.14 microg/ml). Women were then individually randomized into a diet intervention (n = 58) and a control (n = 55) group. Women in the intervention group attended a weekly \"cooking course\" for 1 year, being trained by professional chefs in the correct use of the natural ingredients of the traditional Mediterranean diet, including whole cereals, legumes, seeds, fish, cruciferous vegetables, and many others. The intervention group was subsequently instructed to follow the learned diet at home, while the control group was only advised to increase the consumption of fruits and vegetables, as recommended by WHO. The following measures were taken at the beginning, middle, and end of the study: (a) fasting blood and 12-hour urine samples to assay defined hormonal endpoints; (b) height, weight, and circumference of the waist and hip; and (c) a food frequency and computerized 24-hour dietary recall questionnaire. After 1 year, both the control and the intervention groups showed satisfactory compliance rates (81 and 85%, respectively). In addition, preliminary results so far obtained reveal an unequivocal trend towards weight loss, a strong reduction in cholesterol levels, and a psychophysical feeling of well-being by women adopting the Mediterranean diet. The study is currently ongoing to verify the association of changes in serum and urine hormone levels and breast cancer risk in the intervention group.", "The long-term effects on cardiovascular disease risk factors of a reduced fat (RF), ad libitum diet were compared with usual diet (control, CD) in glucose intolerance individuals. Participants were 136 adults aged > or =40 years with 'glucose intolerance' (2h blood glucose 7-11.0 mmol/l) detected at a Diabetes Survey who completed at 1 year intervention study of reduced fat, ad libitum diet versus usual diet. They were re-assessed at 2, 3 and 5 years. Main outcome measures were blood pressure, serum concentrations of total cholesterol, HDL and LDL cholesterol, total cholesterol:HDL ratio, triglycerides and body weight. The reduced fat diet lowered total cholesterol (P<0.01), LDL cholesterol (P< or =0.05), total cholesterol:HDL ratio (P< or =0.05), body weight (P<0.01) and systolic blood pressure (P< or =0.05) initially and diastolic blood pressure (P<0.01) long-term. No significant changes occurred in HDL cholesterol or triglycerides. In the more compliant 50% of the intervention group, systolic and diastolic blood pressure levels and body weight were lower at 1, 2 and 3 years (P<0.05). It was concluded that a reduced fat ad libitum diet has short-term benefits for cholesterol, body weight and systolic blood pressure and long-term benefits for diastolic blood pressure without significantly effecting HDL cholesterol and triglycerides despite participants regaining their lost weight.", "In a 3-month intervention study 70 women (40 < age < 60; 24 < BMI < 29), randomized into two groups, were supplied ad libitum and free of charge with 1) customary fat-reduced foods (D group) or 2) products with normal fat content (K group). After 6 months without any contact to the volunteers food intake and body weight were controlled. Results: During the intervention period fat intake (by 22 g/d) and total energy intake (by 266 kcal/d) of the volunteers in the D group were significantly lower than in the K group. Fat reduction was not accompanied by a compensative increase in the intake of other nutrients. The weight loss was significant in the D group (1.5 kg) and not significant in the K group (0.7 kg). Between the two groups the difference in weight reduction was not significant. In the follow-up a lowered fat and energy intake had been voluntarily retained in the D group and adopted by most of the individuals in the K group. Conclusion: The consumption of low-fat products lowers the energy and fat intake and may be useful for a long-term weight control and health support.", "A diet low in saturated fatty acids and rich in wholegrains, vegetables and fruit is recommended in order to reduce the risk of obesity, cardiovascular disease and type 2 diabetes mellitus. However there is widespread interest in high-fat (\"Atkins Diet\") and high-protein (\"Zone Diet\") alternatives to the conventional high-carbohydrate, high-fibre approach. We report on a randomised trial that compared these two alternative approaches with a conventional diet in overweight insulin-resistant women.\n Ninety-six normoglycaemic, insulin-resistant women (BMI >27 kg/m(2)) were randomised to one of three dietary interventions: a high-carbohydrate, high-fibre (HC) diet, the high-fat (HF) Atkins Diet, or the high-protein (HP) Zone Diet. The experimental approach was designed to mimic what might be achieved in clinical practice: the recommendations involved advice concerning food choices and were not prescriptive in terms of total energy. There were supervised weight loss and weight maintenance phases (8 weeks each), but there was no contact between the research team and the participants during the final 8 weeks of the study. Outcome was assessed in terms of body composition and indicators of cardiovascular and diabetes risk.\n Body weight, waist circumference, triglycerides and insulin levels decreased with all three diets but, apart from insulin, the reductions were significantly greater in the HF and HP groups than in the HC group. These observations suggest that the popular diets reduced insulin resistance to a greater extent than the standard dietary advice did. When compared with the HC diet, the HF and HP diets were shown to produce significantly (p<0.01) greater reductions in several parameters, including weight loss (HF -2.8 kg, HP -2.7 kg), waist circumference (HF -3.5 cm, HP -2.7 cm) and triglycerides (HF -0.30 mmol/l, HP [corrected] -0.22 mmol/l). LDL cholesterol decreased in individuals on the HC and HP diets, but tended to fluctuate in those on the HF diet to the extent that overall levels were significantly lower in the HP group than in the HF group (-0.28 mmol/l, 95% CI 0.04-0.52, p=0.02). Of those on the HF diet, 25% showed a >10% increase in LDL cholesterol, whereas this occurred in only 13% of subjects on the HC diet and 3% of those on the HP diet.\n In routine practice a reduced-carbohydrate, higher protein diet may be the most appropriate overall approach to reducing the risk of cardiovascular disease and type 2 diabetes. To achieve similar benefits on a HC diet, it may be necessary to increase fibre-rich wholegrains, legumes, vegetables and fruits, and to reduce saturated fatty acids to a greater extent than appears to be achieved by implementing current guidelines. The HF approach appears successful for weight loss in the short term, but lipid levels should be monitored. The potential deleterious effects of the diet in the long term remain a concern.", "The Minnesota Coronary Survey was a 4.5-year, open enrollment, single end-time double-blind, randomized clinical trial that was conducted in six Minnesota state mental hospitals and one nursing home. It involved 4393 institutionalized men and 4664 institutionalized women. The trial compared the effects of a 39% fat control diet (18% saturated fat, 5% polyunsaturated fat, 16% monounsaturated fat, 446 mg dietary cholesterol per day) with a 38% fat treatment diet (9% saturated fat, 15% polyunsaturated fat, 14% monounsaturated fat, 166 mg dietary cholesterol per day) on serum cholesterol levels and the incidence of myocardial infarctions, sudden deaths, and all-cause mortality. The mean duration of time on the diets was 384 days, with 1568 subjects consuming the diet for over 2 years. The mean serum cholesterol level in the pre-admission period was 207 mg/dl, falling to 175 mg/dl in the treatment group and 203 mg/dl in the control group. For the entire study population, no differences between the treatment and control groups were observed for cardiovascular events, cardiovascular deaths, or total mortality. A favorable trend for all these end-points occurred in some younger age groups.", "We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and 200 micrograms/min). Thirty-eight patients were randomly assigned to increase dietary polyunsaturated:saturated fatty acids ratio to 1.0 by replacement of saturated fat with linoleic-acid-rich products (n = 18, two dropouts, analysis was performed in n = 16) or to continue their usual diet (n = 20). The total fat and protein content of the diet was unaltered. Clinical characteristics, albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7 +/- 4 to 11 +/- 2 energy % and polyunsaturated:saturated fatty acids ratio rose from 0.60 +/- 0.28 to 0.96 +/- 0.16 (p less than 0.001 compared to usual diet group). The median increase albuminuria was 58% (95% confidence interval, 13 to 109) during the first year (p less than 0.02) and 55% (95% confidence interval, 11 to 127) (p less than 0.01) during the second year. Glomerular filtration rate remained unaltered and filtration fraction tended to rise (p less than 0.05 compared to usual diet group). In the usual diet group, albuminuria did not significantly increased by 16% (95% confidence interval, -17 to 38) and glomerular filtration rate declined during the second year. Blood pressure tended to rise similarly in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "Actinic keratoses are premalignant lesions and are a sensitive and important manifestation of sun-induced skin damage. Studies in animals have shown that dietary fat influences the incidence of sun-induced skin cancer, but the effect of diet on the incidence of actinic keratosis in humans is not known.\n We randomly assigned 76 patients with nonmelanoma skin cancer either to continue their usual diet (control group) or to eat a diet with 20 percent of total caloric intake as fat (dietary-intervention group). For 24 months, the patients were examined for the presence of new actinic keratoses by physicians unaware of their assigned diets.\n At base line, the mean (+/- SD) percentage of caloric intake as fat was 40 +/- 4 percent in the control group and 39 +/- 3 percent in the dietary-intervention group. After 4 months of dietary therapy the percentage of calories as fat had decreased to 21 percent in the dietary-intervention group, and it remained below this level throughout the 24-month study period. The percentage of calories as fat in the control group did not fall below 36 percent at any time. The cumulative number of new actinic keratoses per patient from months 4 through 24 was 10 +/- 13 in the control group and 3 +/- 7 in the dietary-intervention group (P = 0.001).\n In patients with a history of nonmelanoma skin cancer, a low-fat diet reduces the incidence of actinic keratosis.", "The optimal dietary content and type of fat and carbohydrate for weight management has been debated for decades.\n The objective was to compare the effects of 3 ad libitum diets on the maintenance of an initial weight loss of >or=8% and risk factors for CVD and diabetes during a 6-mo controlled dietary intervention.\n Nondiabetic overweight or obese [mean +/- SD body mass index (in kg/m(2)): 31.5 +/- 2.6] men (n = 55) and women (n = 76) aged 28.2 +/- 4.8 y were randomly assigned to a diet providing a moderate amount of fat (35-45% of energy) and >20% of fat as monounsaturated fatty acids (MUFA diet; n = 54), to a low-fat (20-30% of energy) diet (LF diet; n = 51), or to a control diet (35% of energy as fat; n = 26). Protein constituted 10-20% of energy in all 3 diets. All foods were provided free of charge from a purpose-built supermarket.\n More subjects dropped out of the MUFA (28%) group than out of the LF group (16%) and control group (8%) (MUFA compared with control: P < 0.05). All groups regained weight (MUFA: 2.5 +/- 0.7 kg; LF: 2.2 +/- 0.7 kg; and control: 3.8 +/- 0.8 kg; NS). Body fat regain was lower in the LF (0.6 +/- 0.6%) and MUFA (1.6 +/- 0.6%) groups than in the control group (2.6 +/- 0.5%) (P < 0.05). In the MUFA group, fasting insulin decreased by 2.6 +/- 3.5 pmol/L, the homeostasis model assessment of insulin resistance by 0.17 +/- 0.13, and the ratio of LDL to HDL by 0.33 +/- 0.13; in the LF group, these variables increased by 4.3 +/- 3.0 pmol/L (P < 0.08) and 0.17 +/- 0.10 (P < 0.05) and decreased by 0.02 +/- 0.09 (P = 0.005), respectively; and in the control group, increased by 14.0 +/- 4.3 pmol/L (P < 0.001), 0.57 +/- 0.17 (P < 0.001), and 0.05 +/- 0.14 (P = 0.036), respectively. Dietary adherence was high on the basis of fatty acid changes in adipose tissue.\n Diet composition had no major effect on preventing weight regain. However, both the LF and MUFA diets produced less body fat regain than did the control diet, and the dropout rate was lowest in the LF diet group, whereas fasting insulin decreased and the homeostasis model assessment of insulin resistance and ratio of LDL to HDL improved with the MUFA diet. This trial was registered at clinicaltrials.gov as NCT00274729.", "A randomised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infarction (MI). 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors: a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat, an increase in fatty fish intake, and an increase in cereal fibre intake. The advice on fat was not associated with any difference in mortality, perhaps because it produced only a small reduction (3-4%) in serum cholesterol. The subjects advised to eat fatty fish had a 29% reduction in 2 year all-cause mortality compared with those not so advised. This effect, which was significant, was not altered by adjusting for ten potential confounding factors. Subjects given fibre advice had a slightly higher mortality than other subjects (not significant). The 2 year incidence of reinfarction plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens. A modest intake of fatty fish (two or three portions per week) may reduce mortality in men who have recovered from MI.", "This randomized study targeted a comparison of the effect of 3-year diet counselling or omega-3 polyunsaturated fatty acid (PUFA) supplementation (2.4 g/day) on the progression of atherosclerosis in carotid arteries and on finger pulse wave propagation.\n Measurements were assessed by high-resolution B-mode ultrasound and a photopletysmographic finger pulse-sensor, respectively. Altogether, 563 elderly men with long-standing hyperlipidaemia were randomized into four groups: controls (no dietary counselling and placebo); dietary counselling (and placebo); omega-3 PUFA supplementation (no dietary counselling); dietary counselling and omega-3 PUFA supplementation.\n In the diet only group, the carotid intima-media thickness increase (0.929 to 0.967 mm) was significantly less than in the control group (0.909 to 0.977 mm), (P = 0.018). Significant increase in carotid plaques score and plaques area were observed in all four groups, but without between group differences. Changes in carotid intima-media thickness and in high-density lipoprotein-cholesterol were negatively correlated (adjusted P < 0.001). Pulse wave propagation time decreased significantly in the control group (206 to 198 ms; P = 0.002), reflecting reduced arterial elasticity. In the group receiving omega-3 PUFA only, pulse wave propagation time increased significantly when compared with the control group (P = 0.013).\n Reduced progression in carotid intima-media thickness was observed after dietary counselling, whereas omega-3 PUFA supplementation imposed a favourable effect on arterial elasticity.", "Two groups of adult-onset diabetics, matched according to 10 different criteria, were followed, biochemically and fluorescein-angiographically, over a period of 6 years. One group used a saturated-fat diet, and the other group of patients were on an unsaturated-fat diet, particularly rich in linoleic acid. Statistically significant differences were found in biochemical data and in the progression of diabetic microangiopathy between the two groups. The conclusion is warranted that a linoleic acid-rich diet, administered over an extended period of time, may inhibit the development of microangiopathy, or the deterioration of diabetic retinopathy.", "Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival.\n To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer.\n Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006.\n The intervention group (n = 1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n = 1551) was provided with print materials describing the \"5-A-Day\" dietary guidelines.\n Invasive breast cancer event (recurrence or new primary) or death from any cause.\n From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, -13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80-1.14; P = .63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72-1.15; P = .43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment.\n Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period.\n clinicaltrials.gov Identifier: NCT00003787.", "To determine the effectiveness of an intensive dietary intervention on diet and body mass in women with breast cancer.\n Randomized clinical trial.\n 172 women aged 20 to 65 years with stage I or II breast cancer.\n A 15-session, mainly group-based and dietitian-led nutrition education program (NEP) was compared to a mindfulness-based stress reduction clinic program (SRC); or usual supportive care (UC).\n Dietary fat, complex carbohydrates, fiber, and body mass were measured.\n In addition to descriptive statistics, analysis of variance was conducted to test for differences according to intervention group.\n Of the 157 women with complete dietary data at baseline, 149 had complete data immediately postintervention (at 4 months) and 146 had complete data at 1 year. Women randomized to NEP (n = 50) experienced a large reduction in fat consumption (5.8% of energy as fat) at 4 months and much of this reduction was preserved at 1 year (4.1% of energy) (both P < .0002) vs no change in either SRC (n = 51) or UC (n = 56). A 1.3-kg reduction in body mass was evident at 4 months in the NEP group (P = .003) vs no change in the SRC and UC groups. Women who had higher-than-average expectations of a beneficial effect of the intervention experienced larger changes.\n Dietitians' use of group nutrition interventions appear to be warranted. Increasing their effectiveness and maintaining high levels of adherence may require additional support, including the involvement of significant others, periodic individual meetings, or group booster sessions.", "The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial examining the effect of a low-fat (20% of total energy intake), high-fiber (18 g/1000 kcal), high-vegetable and -fruit (5-8 daily servings) dietary pattern on the recurrence of adenomatous polyps of the large bowel, precursors of most colorectal malignancies. Eligibility criteria include one or more adenomas removed within 6 months of randomization; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy: age 35 years of more; no history of colorectal cancer, inflammatory bowel disease, or large bowel resection; and satisfactory completion of a food frequency questionnaire and 4-day food record. Of approximately 38,277 potential participants with one or more polyps recently resected, investigators at eight clinical centers randomized 2,079 (5.4%; 1,037 in the intervention and 1,042 in the control arm) between June 1991 and January 1994, making the PPT the largest adenoma recurrence trial ever conducted. Of PPT participants, 35% are women and 10% are minorities. At study entry, participants averaged 61.4 years of age; 14% of them smoked, and 22% used aspirin. At the baseline colonoscopy, 35% of participants had two or more adenomas, and 29% had at least one large (> of = 1 cm) adenoma. Demographic, behavioral, dietary, and clinical characteristics are comparable across the two study arms. Participants have repeat colonoscopies after 1 (T(1)) and 4 (T(4)) years of follow-up. The primary end point is adenoma recurrence; secondary end points include number, size, location, and histology of adenomas. All resected lesions are reviewed centrally by gastrointestinal pathologists. The trial provides 90% power to detect a reduction of 24% in the annual adenoma recurrence rate. The primary analytic period, on which sample size calculations were based is 3 years (T(1) to T(4)), which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T(1), given that at least 10-15% of polyps may be missed at baseline. The final (T(4)) colonoscopies are expected to be completed in early 1998.", "21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.", "We evaluated dietary counselling by dietitians in hypercholesterolaemic hypertensives over 6 months. A total of 141 patients were randomly assigned to intensive advice or usual care. Body weight fell significantly in the intervention group, but did not in the controls. There was a modest but significant fall in total cholesterol from 7.1 to 6.8 and 7.1 to 6.9 mmol/l in the diet and the control groups, respectively (4 and 3%). A similar pattern emerged from the triglyceride measurements. Low-density lipoprotein fell in both groups, but only achieved significance (P less than 0.05) in the intervention group. High-density lipoprotein did not change. There was a more marked change in cholesterol when serum levels during the study were compared with the previous annual review. These falls occurred after selection for the study but before random allocation to groups. They are unlikely to reflect regression to the mean as the lipids were stable for 2 or more years before the study, but may reflect spontaneous changes in diet after the patients were labelled hypercholesterolaemic. Dietary advice can lower total cholesterol but the magnitude of this decrease is small. Additional approaches are likely to be required to reduce plasma cholesterol to a normal range.", "Dietary fat has been implicated as a risk factor for cardiovascular disease and obesity.\n We evaluated the effect on body weight, body fat, lipids, glucose, and insulin of replacing dietary fat with olestra in moderately obese men.\n Forty-five healthy overweight men were randomly assigned to 1 of 3 diets: control diet (33% fat), fat-reduced diet (25% fat), or fat-substituted diet (one-third of dietary fat replaced by olestra to achieve a diet containing 25% metabolizable fat). Body fat was measured by dual-energy X-ray absorptiometry and visceral and subcutaneous abdominal fat by computed tomography.\n Thirty-six men completed the 9-mo study. Body weight and body fat in the fat-substituted group declined by a mean (+/- SEM) of 6.27 +/- 1.66 and 5.85 +/- 1.34 kg, respectively, over 9 mo compared with 3.8 +/- 1.34 and 3.45 +/- 1.0 kg in the control group and 1.79 +/- 0.81 and 1.68 +/- 0.75 kg in the fat-reduced diet group. At 9 mo, the mean difference in body fat between the fat-reduced and fat-substituted groups was -4.19 +/- 1.19 kg (95% CI: -6.57, -1.81), that between the control and fat-substituted groups was -2.55 +/- 1.21 kg (-0.13, -4.97), and that between the control and fat-reduced groups was 1.63 +/- 1.18 kg (3.96, -0.70). The men eating the fat-reduced diet asked for almost no extra foods, in contrast with the significantly higher requests (P < 0.05) from both of the other 2 groups.\n Replacement of dietary fat with olestra reduces body weight and total body fat when compared with a 25%-fat diet or a control diet containing 33% fat.", "To compare the long term metabolic effects of two diets for treating hyperlipidaemia.\n Randomised controlled study: after three weeks of normal (control) diet, subjects were randomly allocated to one of two test diets and followed up for six months.\n Lipid clinic of tertiary referral centre in Naples.\n 63 subjects with primary type IIa and IIb hyperlipoproteinaemia entered the study, and 44 completed it. Exclusion criteria were taking drugs known to influence lipid metabolism, evidence of cardiovascular disease, homozygous familial hypercholesterolaemia, and body mass index over 30.\n Two test diets with reduced saturated fat (8%) and cholesterol (approximately 200 mg/day): one was also low in total fat and rich in carbohydrate and fibre, and the other was low in carbohydrate and fibre and rich in polyunsaturated and monounsaturated fats.\n Fasting plasma lipid and lipoprotein concentrations; blood glucose, insulin, and triglyceride concentrations before and after a test meal.\n In comparison with the control diet, both test diets induced significant and similar decreases in low density lipoprotein cholesterol concentrations (by a mean of 0.72 (SE 0.15) mmol/l, P < 0.001, for low total fat diet; by 0.49 (0.18) mmol/l, P < 0.05, for high unsaturated fat diet) and plasma triglyceride concentrations (by 0.21 (0.09) mmol/l, P < 0.05, for low total fat diet; by 0.39 (0.15) mmol/l, P < 0.05, for high unsaturated fat diet), while high density lipoprotein cholesterol concentrations after fasting and plasma glucose and insulin concentrations during test meals were not modified by either diet.\n Both test diets are suitable (alone or in combination) for treatment of hypercholesterolaemia.", "A randomized intervention trial of dietary fat reduction to 15% of total calories was initiated in 1987 for women at high risk for breast cancer to determine the feasibility of recruiting and maintaining them on a low-fat diet. The study has enrolled 194 women between the ages of 18 and 67 years who met at least one of three eligibility criteria: 1) a first-degree relative with breast cancer, 2) a P2 or DY Wolfe mammographic pattern, and 3) a prior breast biopsy demonstrating epithelial hyperplasia with or without atypia. Eligible women must also have had diets that contained > or = 30% of calories from fat at entry. Women were randomized to a nonintervention usual diet vs. a 15% low-fat diet. Recruitment was sought through physicians, personal mailings, breast cancer patients, and the news media. Two study sites participated: a large urban hospital affiliated with a university medical center and a community oncology private practice. The results from both institutions were similar and demonstrated that a low-fat dietary plan could be effectively conducted in private as well as academic settings with recruitment tailored to the community where the trial is being conducted. Reduction in dietary fat intake was maximal during the first three months of the dietary intervention and remained stable throughout 12 months of follow-up. Reductions in total calories, weight loss, and percent body fat were minimal. The nonintervention group experienced no major change in their diet. We conclude that it is feasible to recruit women who are at high risk for breast cancer into a dietary intervention trial and with sufficient dietary counseling and motivation on the part of participants, reduction in dietary fat intake can be achieved and maintained. More in-depth analyses of these data will be presented in subsequent reports.", "A positive family history of coronary heart disease alone confers an increased risk, which may be affected by untreated hypercholesterolemia. Dietary counseling is a first-line treatment approach. To determine whether nurse counseling can provide additional benefits over usual physician efforts to lower dietary fat in high-risk persons, 117 apparently healthy adult siblings of persons with premature coronary heart disease were counseled by a registered nurse using adapted national guidelines. Reductions in total fat, saturated fat, and cholesterol were significantly greater in the nurse group compared to those in the usual care group. Total fat intake decreased by 14 g in the nurse group, compared with an increase of 5 g in the usual care group (p=0.0001). Assignment to the nurse group was also a significant predictor of a greater reduction in the percentage of total fat calories (p=0.008). The authors conclude that a registered nurse may serve as a complement to usual care in efforts to lower dietary fat and cholesterol in high-risk families. (c)2001 CHF, Inc.", "Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management.\n A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided.\n Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 [95% confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7], respectively; P<.001), corresponding to a statistically significant (P = .005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status.\n A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment.", "To compare the effects of a eucaloric diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on postmeal triglyceride (TG) concentrations and other cardiovascular disease risk factors in nonobese subjects with type 1 diabetes and in good glycemic control.\n In a parallel group design study, 30 subjects were randomly assigned and completed one of the two eucaloric diets. Assessments included: BMI, blood pressure, A1C, plasma lipids, and markers of oxidation, thrombosis, and inflammation. At 6 months, subjects were hospitalized for 24 h to measure plasma TG excursions.\n There were no significant differences between groups other than decreased plasminogen activator inhibitor 1 (PAI-1) levels and weight gain in the lower-carbohydrate/higher-monounsaturated fat group. During the 24-h testing, the lower-carbohydrate/higher-monounsaturated fat group had a lower plasma TG profile.\n A diet lower in carbohydrate/higher in monounsaturated fat could offer an appropriate choice for nonobese type 1 diabetic individuals with good metabolic and weight control.", "To investigate the long-term effects of changes in dietary carbohydrate/fat ratio and simple vs complex carbohydrates.\n Randomized controlled multicentre trial (CARMEN), in which subjects were allocated for 6 months either to a seasonal control group (no intervention) or to one of three experimental groups: a control diet group (dietary intervention typical of the average national intake); a low-fat high simple carbohydrate group; or a low-fat high complex carbohydrate group.\n Three hundred and ninety eight moderately obese adults.\n The change in body weight was the primary outcome; changes in body composition and blood lipids were secondary outcomes.\n Body weight loss in the low-fat high simple carbohydrate and low-fat high complex carbohydrate groups was 0.9 kg (P < 0.05) and 1.8 kg (P < 0.001), while the control diet and seasonal control groups gained weight (0.8 and 0.1 kg, NS). Fat mass changed by -1.3kg (P< 0.01), -1.8kg (P< 0.001) and +0.6kg (NS) in the low-fat high simple carbohydrate, low-fat high complex carbohydrate and control diet groups, respectively. Changes in blood lipids did not differ significantly between the dietary treatment groups.\n Our findings suggest that reduction of fat intake results in a modest but significant reduction in body weight and body fatness. The concomitant increase in either simple or complex carbohydrates did not indicate significant differences in weight change. No adverse effects on blood lipids were observed. These findings underline the importance of this dietary change and its potential impact on the public health implications of obesity.", "The beFIT study tested whether teaching the NCEP step II diet (< 30% of calories from total fat and < 7% from saturated fat) is an effective therapy in hypercholesterolemic women and men with or without elevated triglycerides after 6 months. Hypercholesterolemic subjects had two LDL cholesterol measurements above the age- and sex-specific 75th percentile, and combined hyperlipidemic subjects additionally had similarly elevated triglyceride. Subjects were randomized to receive dietary intervention (eight weekly classes) immediately or 6 months later. Follow-up visits were quarterly, with lipid measurements and 4-day food records. Subjects randomized to delayed intervention did not report diet changes or experience lipid changes; the immediate intervention group significantly reduced fat and cholesterol intake, resulting in significant LDL cholesterol lowering. Six months after diet instruction, 178 women and 231 men reported total and saturated fat intakes of approximately 25% and 7.5% kcal LDL cholesterol was significantly reduced in women (7.6% and 8.1%) and men (8.8% and 8.1%) with hypercholesterolemia and combined hyperlipidemia, respectively, but was not different by sex or lipid disorder. Candidates for drug therapy were reduced from between 27% and 37% to 20%. HDL cholesterol was significantly decreased in women (-6.4% and -4.7%) but not in men (-1.3% and -2.7%). The 6.4% reduction in hypercholesterolemic women was significantly different from that of men. The significance of the HDL cholesterol reduction in women is unknown. LDL cholesterol response was similar between women and men and between hypercholesterolemic and combined hyperlipidemic subjects. LDL cholesterol lowering by diet can significantly reduce the number of hyperlipidemic persons requiring drug therapy." ]

[ "6437476", "11005114", "8355740", "8179545", "1345870", "8105165", "3113566" ]

[ "Screening for small for dates fetuses: a controlled trial.", "Routine ultrasound fetal examination in pregnancy: the 'Alesund' randomized controlled trial.", "Effect of prenatal ultrasound screening on perinatal outcome. RADIUS Study Group.", "A randomized controlled trial in a hospital population of ultrasound measurement screening for the small for dates baby.", "Routine ultrasonography in utero and school performance at age 8-9 years.", "Effects of frequent ultrasound during pregnancy: a randomised controlled trial.", "Third trimester placental grading by ultrasonography as a test of fetal wellbeing." ]

[ "In the hope of reducing perinatal risks associated with retardation of intrauterine growth a previously described two stage ultrasound screening schedule was evaluated by a controlled trial in 877 women with low risk single pregnancies. The two stages of ultrasound examination were an assessment of gestational age during early pregnancy followed by measurement of length from crown to rump and area of trunk at between 34 and 36 weeks' gestation. The product of crown to rump length and trunk area was calculated. The sensitivity of this schedule in identifying in advance 94% of babies who were small for dates at birth, with 90% specificity, and the speed and simplicity of measurement confirmed the accuracy and feasibility of two stage ultrasonography as a screening procedure. The controlled trial did not, however, show any benefit from its routine application in these low risk pregnancies.", "To evaluate the possible benefits of the routine use of ultrasound screening in pregnancy.\n A randomized controlled trial was designed to detect a 50% difference in the incidence of induction for apparent post-term pregnancies between women who were screened with ultrasound and unscreened women. A total of 1628 pregnant women from the general population were included. Eight hundred and twenty-five were allocated to an ultrasound examination at the 18th and 32nd week of pregnancy in addition to receiving routine antenatal care. The remaining 803 women received standard antenatal care, but could only be referred for ultrasound examination on clinical indication.\n The incidence of induced labor due to apparent post-term pregnancies was approximately 70% lower in the ultrasound-screened group. Inductions from all causes were also less frequent among ultrasound-screened women. There were six perinatal deaths among the screened and seven among the controls after excluding three lethal malformations among the controls. There was no difference in Apgar score after 1 min, but the proportion with Apgar score less than 8 after 5 min was lower among the screened group (P = 0.04). The need for positive pressure ventilation for more than 1 min was lower among the screened group (P = 0.02). Birth weight was slightly higher in the screened group (39 g), but the difference was not statistically significant. Among the controls three pairs of twins remained undiagnosed until the mothers were admitted to the hospital in labor at between 36 and 38 weeks gestation.\n These results suggest that for women who were screened with ultrasound, obstetricians were less likely to induce labor due to apparent post-term pregnancy, than for women who were not screened. All 10 pairs of twins in the screened group were diagnosed at the routine examination. These data also suggest that perinatal morbidity might be slightly lower in the screened group.", "Many clinicians advocate routine ultrasound screening during pregnancy to detect congenital anomalies, multiple-gestation pregnancies, fetal growth disorders, placental abnormalities, and errors in the estimation of gestational age. However, it is not known whether the detection of these conditions through screening leads to interventions that improve perinatal outcome.\n We conducted a randomized trial involving 15,151 pregnant women at low risk for perinatal problems to determine whether ultrasound screening decreased the frequency of adverse perinatal outcomes. The women randomly assigned to the ultrasound-screening group underwent one sonographic examination at 15 to 22 weeks of gestation and another at 31 to 35 weeks. The women in the control group underwent ultrasonography only for medical indications, as identified by their physicians. Adverse perinatal outcome was defined as fetal death, neonatal death, or neonatal morbidity such as intraventricular hemorrhage.\n The mean numbers of sonograms obtained per woman in the ultrasound-screening and control groups were 2.2 and 0.6, respectively. The rate of adverse perinatal outcome was 5.0 percent among the infants of the women in the ultrasound-screening group and 4.9 percent among the infants of the women in the control group (relative risk, 1.0; 95 percent confidence interval, 0.9 to 1.2; P = 0.85). The rates of preterm delivery and the distribution of birth weights were nearly identical in the two groups. The ultrasonographic detection of congenital anomalies had no effect on perinatal outcome. There were no significant differences between the groups in perinatal outcome in the subgroups of women with post-date pregnancies, multiple-gestation pregnancies, or infants who were small for gestational age.\n Screening ultrasonography did not improve perinatal outcome as compared with the selective use of ultrasonography on the basis of clinician judgment.", "Poor fetal growth is an important cause of perinatal mortality and morbidity. Based on the hypothesis that early diagnosis of fetal growth problems leads to more appropriate management and therefore, improved outcome, a randomized controlled trial of ultrasound measurement was performed on 1,528 women booked through a hospital antenatal clinic. This compared a number of perinatal outcomes between the group who had a routine 2-stage examination (early dating and 34-week scan) and a group who had only a dating scan and then additional scans as generated by their clinical situations. No significant differences could be found between the groups when these perinatal outcomes were considered. These results mirror previously published randomized controlled trials. Selection of women for third trimester ultrasound examination for suspected fetal growth problems should be based on careful clinical assessment and should not be routine.", "Most fetuses in developed countries are exposed in utero to diagnostic ultrasound examination. Many pregnant women express concern about whether the procedure harms the fetus. Since most routine ultrasound examinations are done at weeks 16-22, when the fetal brain is developing rapidly, effects on neuronal migration are possible. We have sought an association between routine ultrasonography in utero and reading and writing skills among children in primary school. At the age of 8 or 9 years, children of women who had taken part in two randomised, controlled trials of routine ultrasonography during pregnancy were followed-up. The women had attended the clinics of 60 general practitioners in central Norway during 1979-81. The analysis of outcome was by intention to treat: 92% of the \"screened\" group had been exposed to ultrasound screening at weeks 16-22, and 95% of controls had not been so exposed, but there was some overlap. 2428 singletons were eligible for follow-up, and the school performance of 2011 children (83%) was assessed by their teachers on a scale of 1-7; the teachers were unaware of ultrasound exposure status. A subgroup of 603 children underwent specific tests for dyslexia. There were no statistically significant differences between children screened with ultrasound and controls in the teacher-reported school performance (scores for reading, spelling, arithmetic, or overall performance). Results from the dyslexia test sample showed no differences between screened children and controls in reading, spelling, and intelligence scores, or in discrepancy scores between intelligence and reading or spelling. The test results classified 21 of the 309 screened children (7% [95% confidence interval 3-10%]) and 26 of the 294 controls (9% [4-12%]) as dyslexic. The risk of having poor skills in reading and writing was no greater for children whose mothers had been offered routine ultrasonography than for those whose mothers had not been offered the procedure.", "Despite widespread application of ultrasound imaging and Doppler blood flow studies, the effects of their frequent and repeated use in pregnancy have not been evaluated in controlled trials. From 2834 women with single pregnancies at 16-20 weeks gestation, 1415 were selected at random to receive ultrasound imaging and continuous-wave Doppler flow studies at 18, 24, 28, 34, and 38 weeks gestation (the intensive group) and 1419 to receive single ultrasound imaging at 18 weeks (the regular group). Outcome data was obtained from 99% of women who entered the study. The only difference between the two groups was significantly higher intrauterine growth restriction in the intensive group, when expressed both as birthweight < 10th centile (relative risk 1.35; 95% confidence interval 1.09 to 1.67; p = 0.006) and birthweight < 3rd centile (relative risk 1.65; 95% confidence intervals 1.09 to 2.49; p = 0.020). While it is possible that this finding was a chance effect, it is also plausible that frequent exposure to ultrasound may have influenced fetal growth. Repeated prenatal ultrasound imaging and Doppler flow examinations should be restricted to those women to whom the information is likely to be of clinical benefit.", "In a study of 2000 unselected pregnant women the development of a mature placental appearance (grade 3) on ultrasonography by 34-36 weeks' gestation, observed in 15% of cases, was associated with maternal smoking, low parity, low maternal age, and being white. These women had an increased risk of problems during labour and their babies had an increased risk of low birth weight, poor condition at birth, and perinatal death. The women were randomly allocated to two groups: in one group the result of the placental grading was reported to the clinician responsible for care; in the second the result was noted but not reported. There was a significant decrease in the risk of perinatal death in the group where the grading was known. This reduction was responsible for a difference in the principal outcome index, a heterogeneous group of measures of mortality and morbidity, but this difference was not significant. This study alone does not justify routine late scanning, and further, larger trials are required. Nevertheless, the results do provide a basis for the reporting of placental grading when ultrasound examination is performed during the third trimester." ]

[ "8642881", "7633704", "17218570", "11115443", "19213769", "12358325", "1741532" ]

[ "Efficacy of nocturnal nasal ventilation in stable, severe chronic obstructive pulmonary disease during a 3-month controlled trial.", "Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.", "Effects of nocturnal noninvasive mechanical ventilation on heart rate variability of patients with advanced COPD.", "Long-term controlled trial of nocturnal nasal positive pressure ventilation in patients with severe COPD.", "Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial.", "The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients.", "Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease." ]

[ "To evaluate the efficacy of nocturnal nasal ventilation (NNV) in patients with rigidly defined, severe but stable chronic obstructive pulmonary disease (COPD) and hypercapnia.\n By randomization, eligible patients were assigned to an active or a sham treatment arm. Data from these two groups were analyzed statistically.\n Initially, 35 patients with severe COPD (forced expiratory volume in 1 second [FEV1] of less than 40% predicted) and daytime hypercapnia (arterial carbon dioxide tension [PaCO2] of more than 45 mm Hg) were enrolled in a 3-month NNV trial. After a minimal observation period of 6 weeks, 13 patients were judged to be clinically stable and were randomized to NNV (N = 7) or sham (N = 6) treatment, consisting of nightly use of a bilevel positive airway pressure (PAP) device set to deliver an inspiratory pressure of either 10 or 0 cm of water (H2O). The device was used in the spontaneous or timed mode and set to a minimal expiratory pressure of 2 cm H2O. Patients underwent extensive physiologic testing including polysomnography and were introduced to the bilevel PAP system during a 2.5-day hospital stay.\n The NNV and sham treatment groups were similar in mean age (71.0 versus 66.5 years), PaCO2 (54.7 versus 48.5 mm Hg), and FEV1 (0.62 versus 0.72 L). Only four of seven patients in the NNV group were still using the bilevel PAP device at the completion of the trial, as opposed to all six patients in the sham group. Only one patient had a substantial reduction in PaCO2 - from 50 mm Hg at baseline to 43 mm Hg after 3 months of NNV. He declined further NNV treatment with bilevel PAP. Sham treatment did not lower PaCO2. Lung function, nocturnal oxygen saturation, and sleep efficiency remained unchanged in both groups.\n Disabled but clinically stable patients with COPD and hypercapnia do not readily accept and are unlikely to benefit from NNV.", "Non-invasive ventilation has been used in chronic respiratory failure due to chronic obstructive pulmonary disease (COPD), but the effect of the addition of nasal positive-pressure ventilation to long-term oxygen therapy (LTOT) has not been determined. We report a randomized crossover study of the effect of the combination of nasal pressure support ventilation (NPSV) and domiciliary LTOT as compared with LTOT alone in stable hypercapnic COPD. Fourteen patients were studied, with values (mean +/- SD) of Pao2 of 45.3 +/- 5.7 mm Hg, PaCO2 of 55.8 +/- 3.6 mm Hg, and FEV1 of 0.86 +/- 0.32 L. A 4 wk run-in period (on usual therapy) was followed by consecutive 3-mo periods of: (1) oxygen therapy alone, and (2) oxygen plus NPSV in randomized order. Assessments were made during run-in and at the end of each study period. There were significant improvements in daytime arterial PaO2 and PaCO2, total sleep time, sleep efficiency, and overnight PaCO2 following 3 mo of oxygen plus NPSV as compared with run-in and oxygen alone. Quality of life with oxygen plus NPSV was significantly better than with oxygen alone. The degree of improvement in daytime PaCO2 was correlated with the improvement in mean overnight PaCO2. Nasal positive-pressure ventilation may be a useful addition to LTOT in stable hypercapnic COPD.", "Cardiovascular comorbidities have a negative impact on the health status and prognosis of patients with COPD. We determined whether nocturnal noninvasive (positive) mechanical ventilation (NIMV) can improve heart rate variability (HRV), decrease circulating natriuretic peptide levels, and improve functional performance of patients with very advanced COPD.\n A randomized, double-blind, parallel controlled trial was conducted in 23 participants with stable but advanced COPD. Participants received standard medical therapy plus nocturnal NIMV or standard medical therapy plus sham NIMV for 3 months.\n After 3 months of NIMV therapy, the 24-h triangular interpolation of N-N intervals increased from 322 to 473 ms (p = 0.034), the 24-h HRV index (HRVI) increased from 21.8 to 29.9 ms (p = 0.035), nocturnal HRVI increased from 6.1 to 8.0 ms (p = 0.026), and the SD of the average N-N interval increased from 37 to 41 ms (p = 0.020). None of these indexes changed significantly in the control group. Additionally, compared with the control group, the pro-atrial natriuretic peptide levels declined significantly in the NIMV group (p = 0.013).\n NIMV applied nocturnally over 3 months may improve HRV, reduce circulating natriuretic peptide levels, and enhance the functional performance of patients with advanced but stable COPD. While not definitive due to small sample size, these data suggest that nocturnal NIMV may reduce the impact of cardiac comorbidities in COPD patients.", "To determine the 1-year efficacy of noninvasive positive pressure ventilation (NPPV) added to long-term oxygen therapy (LTOT) in patients with stable severe COPD. PATIENT SELECTION AND METHODS: We prospectively randomized 52 patients with severe COPD (FEV(1) < 45%) to either NPPV plus \"standard care\" (96% patients with LTOT) or to standard care alone (93% patients with LTOT). The outcomes measured included the following: rate of acute COPD exacerbations; hospital admissions; intubations; and mortality at 3 months, 6 months, and 12 months. The patients were also evaluated at 3 months and 6 months for dyspnea using the Medical Research Council and Borg scales, gas exchange, hematocrit, pulmonary function, cardiac function with echocardiogram, and neuropsychological performance.\n One-year survival was similar in both groups (78%). The number of acute exacerbations was similar at all time points in patients receiving NPPV, compared with control subjects. The number of hospital admissions was decreased at 3 months in the NPPV group (5% vs 15% of patients, p < 0.05), but this difference was not seen at 6 months (18% vs 19%, respectively). The only beneficial differences were observed in the Borg dyspnea rating, which dropped from 6 to 5 (p < 0.039), and in one of the neuropsychological tests (psychomotor coordination) for the NPPV group at 6 months.\n Our study indicates that over 1 year, NPPV does not affect the natural course of the disease and is of marginal benefit in outpatients with severe COPD who are in stable condition.", "Sleep hypoventilation has been proposed as a cause of progressive hypercapnic respiratory failure and death in patients with severe chronic obstructive pulmonary disease (COPD). A study was undertaken to determine the effects of nocturnal non-invasive bi-level pressure support ventilation (NIV) on survival, lung function and quality of life in patients with severe hypercapnic COPD.\n A multicentre, open-label, randomised controlled trial of NIV plus long-term oxygen therapy (LTOT) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD (forced expiratory volume in 1 s (FEV1.0) <1.5 litres or <50% predicted and ratio of FEV1.0 to forced vital capacity (FVC) <60% with awake arterial carbon dioxide tension (PaCO2) >46 mm Hg and on LTOT for at least 3 months) and age <80 years. Patients with sleep apnoea (apnoea-hypopnoea index >20/h) or morbid obesity (body mass index >40) were excluded. Outcome measures were survival, spirometry, arterial blood gases, polysomnography, general and disease-specific quality of life and mood.\n 144 patients were randomised (72 to NIV + LTOT and 72 to LTOT alone). NIV improved sleep quality and sleep-related hypercapnia acutely, and patients complied well with therapy (mean (SD) nightly use 4.5 (3.2) h). Compared with LTOT alone, NIV (mean follow-up 2.21 years, range 0.01-5.59) showed an improvement in survival with the adjusted but not the unadjusted Cox model (adjusted hazard ratio (HR) 0.63, 95% CI 0.40 to 0.99, p = 0.045; unadjusted HR 0.82, 95% CI 0.53 to 1.25, p = NS). FEV1.0 and PaCO2 measured at 6 and 12 months were not different between groups. Patients assigned to NIV + LTOT had reduced general and mental health and vigour.\n Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival, but this appears to be at the cost of worsening quality of life.\n ACTRN12605000205639.", "Chronic obstructive pulmonary disease (COPD) patients with chronic ventilatory failure (CVF) are more likely to develop exacerbations, which are an important determinant of health-related quality of life (HRQL). Long-term noninvasive positive-pressure ventilation (NPPV) has been proposed in addition to long-term oxygen therapy (LTOT) to treat CVF but little information is available on its effects on HRQL and resource consumption. Therefore, the current authors undertook a 2-yr multicentric, prospective, randomised, controlled trial to assess the effect of NPPV+ LTOT on: 1) severity of hypercapnia; 2) use of healthcare resources, and 3) HRQL, in comparison with LTOT alone. One hundred and twenty-two stable hypercapnic COPD patients on LTOT for > or = 6 months were consecutively enrolled. After inclusion and 1-month run-in, 90 patients were randomly assigned to NPPV+LTOT (n=43) or to LTOT alone (n=47). Arterial blood gases, hospital and intensive care unit (ICU) admissions, total hospital and ICU length of stay and HRQL were primary outcome measures; survival and drop-out rates, symptoms (dyspnoea and sleep quality) and exercise tolerance were secondary outcome measures. Follow-up was performed at 3-month intervals up to 2 yrs. Lung function, inspiratory muscle function, exercise tolerance and sleep quality score did not change over time in either group. By contrast the carbon dioxide tension in arterial blood on usual oxygen, resting dyspnoea and HRQL, as assessed by the Maugeri Foundation Respiratory Failure Questionnaire, changed differently over time in the two groups in favour of NPPV+LTOT. Hospital admissions were not different between groups during the follow-up. Nevertheless, overall hospital admissions showed a different trend to change in the NPPV+LTOT (decreasing by 45%) as compared with the LTOT group (increasing by 27%) when comparing the follow-up with the follow-back periods. ICU stay decreased over time by 75% and 20% in the NPPV+LTOT and LTOT groups, respectively. Survival was similar. Compared with long-term oxygen therapy alone, the addition of noninvasive positive-pressure ventilation to long-term oxygen therapy in stable chronic obstructive pulmonary disease patients with chronic ventilatory failure: 1) slightly decreased the trend to carbon dioxide retention in patients receiving oxygen at home and 2) improved dyspnoea and health-related quality of life. The results of this study show some significant benefits with the use of nocturnal, home noninvasive positive-pressure ventilation in patients with chronic ventilatory failure due to advanced chronic obstructive pulmonary disease patients. Further work is required to evaluate the effect of noninvasive positive-pressure ventilation on reducing the frequency and severity of chronic obstructive pulmonary disease exacerbation.", "Intermittent positive pressure ventilation administered nocturnally via a nasal mask has been associated with improvements in pulmonary function and symptoms in patients with restrictive ventilatory disorders. We hypothesized that nocturnal nasal ventilation (NNV) would bring about similar improvements in patients with severe chronic obstructive pulmonary disease (COPD). The study used a randomized, crossover design, with subjects undergoing NNV or \"standard care\" for sequential 3-month periods. Of 23 patients with obstructive lung disease and a FEV1 less than 1 L who were initially enrolled, 4 were excluded because of obstructive sleep apnea prior to randomization. Among the remaining 19 patients, 7 withdrew because of intolerance of the nose mask, 5 were withdrawn because of intercurrent illnesses, and 7 completed both arms of the protocol. These latter 7 patients used the ventilator for an average of 6.7 h/night, and 3 of the 7 had partial relief of dyspnea during ventilator use. However, in comparison with studies performed upon initiation or after the standard care arm of the study, studies performed after 3 months of NNV revealed no improvements in pulmonary function, respiratory muscle strength, gas exchange, exercise endurance, sleep efficiency, quality or oxygenation, or dyspnea ratings. The only improvements observed were in neuropsychological function, possibly related to a placebo effect or another unknown mechanism. Despite the small sample size, our study indicates that NNV is not well tolerated by and brings about minimal improvements in stable outpatients with severe COPD." ]

[ "4599883", "331502", "6750282" ]

[ "Voltaren in the treatment of rheumatoid arthritis.", "Bumadizone calcium in the treatment of rheumatoid arthritis.", "Effectiveness of tolmetin in rheumatoid arthritis: evaluation by means of a new method." ]

[ "nan", "A double-blind crossover trial of bumadizone calcium (Eumotol), a non-steroidal anti-inflammatory drug, has been carried out in 56 patients with rheumatoid arthritis. On both objective and subjective criteria bumadizone was superior to placebo and paracetamol at a statistically highly significant level (P less than 0,01). When tested against acetylsalicylic acid, bumadizone was more effective in 13 patients and less effective in 4 patients. Although this does not represent a statistically significant difference it does suggest that its anti-inflammatory and analgesic qualities are at least equal to those of salicylate in high dosages. There were no serious side-effects in the patients who received bumadizone and the drug was better tolerated than either acetylsalicylic acid or paracetamol.", "Twelve patients with rheumatoid arthritis were treated in a random double-blind crossover study with Tolmetin (1,200 mg/day) and Paracetamol (2,000 mg/day). Each drug was administered for 4 days. A three-days wash-out period was fixed between the administrations of the first drug and that of the second one. The efficacy of the treatments was investigated by self-evaluation of the grip strength expressed as mmHg.h during the day. Tolmetin proved significantly more effective than Paracetamol and induced a significant increase of grip strength, as compared to the baseline values, from the first day of administration. The self-evaluation of the grip strength proved a simple and useful method to evaluate, within an extremely short time and on few groups of patients, the effectiveness of non-steroidal anti-inflammatory drugs in rheumatoid arthritis." ]

[ "9831059" ]

[ "The comparative efficacy of aceclofenac and ibuprofen in postoperative pain after third molar surgery." ]

[ "The aim of the present placebo-controlled, double-blind study was to evaluate the comparative efficacy of single doses of aceclofenac 150 mg and ibuprofen 400 mg in 217 patients with postoperative pain after third molar surgery. Outcome of primary efficacy was judged by overall assessment of the area under the curve (AUC) of graphs for pain intensity (AUC pain) pain relief (AUC relief), both measured from serial visual analogue scales over a 6 h investigation period. Other measures of efficacy included the rate of pain reduction in the first hour, the number of patients who took 'escape' analgesics and the time before they did, and an overall assessment of pain relief score on a five-point categorical scale. Ibuprofen 400 mg was significantly superior to placebo for pain relief (P < 0.01), degree of pain reduction in the first hour (P = 0.005), and the number of patients who required escape analgesia (P < 0.001), and the time before they did (P < 0.001). The outcome for patients treated with aceclofenac 150 mg was not significantly different from that of patients treated with placebo (P > 0.05). A single dose of ibuprofen 400 mg provided significant pain relief in the early postoperative period after third molar surgery, whereas a single dose of aceclofenac 150 mg was not effective in the management of postoperative pain after this operation." ]

[ "9058296", "12191671", "9840118", "10912666", "7843700", "12698083", "10470605", "7712308", "9246043", "9563925", "9034935", "10192613", "7847298" ]

[ "Efficacy of combination therapy of interferon-alpha with ursodeoxycholic acid in chronic hepatitis C: a randomized controlled clinical trial.", "A controlled randomised trial of t-UDCA as adjuvant to interferon for treatment of chronic hepatitis C: an interferon sparing effect of t-UDCA.", "Tauroursodeoxycholic acid for the treatment of HCV-related chronic hepatitis: a multicenter placebo-controlled study.", "Randomized trial of interferon-alpha plus ursodeoxycholic acid versus interferon plus placebo in patients with chronic hepatitis C resistant to interferon.", "Interferon and ursodeoxycholic acid combined therapy in the treatment of chronic viral C hepatitis: results from a controlled randomized trial in 80 patients.", "Effects of ursodeoxycholic acid (ursodiol) treatment on chronic viral hepatitis in heart transplant patients: results of a prospective, double-blind, placebo-randomized study.", "Effect of tauroursodeoxycholic acid on ALT, GGT and viral load in patients with hepatitis C virus-related chronic hepatitis with reference to the genotype.", "Effects of ursodeoxycholic acid on serum liver enzymes in patients with hepatitis C virus-related chronic liver disease.", "Long-term efficacy of interferon-alpha and ursodeoxycholic acid in treatment of chronic type C hepatitis.", "Treatment of chronic hepatitis C with interferon with or without ursodeoxycholic acid: a randomized prospective trial.", "Efficacy of ursodeoxycholic acid in combination with interferon-alpha in treating chronic hepatitis C: results of a long-term follow-up trial.", "Effect of ursodeoxycholic acid in acute viral hepatitis.", "Recombinant interferon-alpha and ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic hepatitis C: a randomized clinical trial with long-term follow-up." ]

[ "The efficacy of interferon-alpha therapy in the treatment of chronic hepatitis C is still limited. A combination therapy of interferon-alpha with ursodeoxycholic acid (UDCA) was tested for its efficacy in the treatment of chronic hepatitis C by a randomized controlled study. Eighty consecutive Japanese patients with chronic hepatitis C were randomly divided into two groups: one group was treated with interferon-alpha (group A, n = 40) and the other with a combination of interferon-alpha and UDCA (group B, n = 40). In both groups, human interferon-alpha (6 million units per day) was intramuscularly injected daily for 2 weeks and then three times a week for 22 weeks: this 24-week period was followed by 24 weeks of observation. In group B, UDCA was also administered, daily at a dose of 600 mg orally, from the beginning of the interferon therapy and administration was continued for 48 weeks. The rates for ALT normalization and clearance of hepatitis C virus (HCV) viremia at the end of the 24-week interferon therapy were similar for groups A and B (58% vs 60% and 55% vs 48%, respectively). At the end of the 24-week follow-up, the sustained normalization rates for ALT levels for the two groups were not different (35% vs 43%), while the rate of clearance was higher in group B (40%) than in group A (23%), but the difference was not significant (P = 0.14). The sustained complete response, i.e., HCV RNA negativity at the end of the follow-up, as well as the maintenance of ALT normalization during the follow-up period, was more frequent in group B (38%) than in group A (18%) although the difference was not significant (P = 0.08). The rate of HCV reactivation after interferon was discontinued was significantly lower in group B (16%) than in group A (59%) (P < 0.01). Although this combination therapy did not lead to a sufficiently sustained complete response, it could serve as adjuvant antiviral therapy when a suitable dosage and administration period are determined.", "BACKGROUND: Combination of the cytoprotective effect of tauro-ursodeoxycholic acid (t-UDCA) with the antiviral effect of interferon may be more effective than interferon alone for treatment of chronic hepatitis C. METHODS: We randomised 106 patients with chronic hepatitis C to interferon 3 MU/m(2)/3 times per week given alone (regimen A, n=51) or in combination with t-UDCA 10 mg/kg/day (regimen B, n=55) for 6 months followed by IFN dose tapering for further 6 months. Control liver biopsies were obtained 6 months after stopping treatment. RESULTS: At the end of the trial a similar proportion of patients had normal serum alanine aminotransferase activity (ALT) levels (41 and 44%) and negative viremia (42 and 43%) with regimens A and B, respectively. The effect on liver histology was also similar, and the Knodell score decreased by 2.9+/-0.4 points with both regimens. During the dose tapering phase, the cumulative interferon dose to maintain ALT activity within the normal range was significantly lower for regimen B (142+/-4 million units, MU) than for regimen A (180+/-12 MU, P<0.005). CONCLUSIONS: Adjuvant t-UDCA exerts an 'interferon sparing effect' that may be of value for patients intolerant to high dose interferon.", "Tauroursodeoxycholic acid is a promising drug for the treatment of chronic cholestatic liver diseases since it has more favourable physicochemical and metabolic properties than ursodeoxycholic acid. Tauroursodeoxycholic acid may be of benefit also for necroinflammatory liver disease, especially for HCV-related chronic hepatitis in which bile duct damage and some degree of cholestasis are frequently seen at histology.\n One hundred and fifty patients with chronic hepatitis were randomly assigned to receive tauroursodeoxycholic acid at daily doses of 500 mg or 750 mg, or a placebo for 6 months.\n A consistent decrease in aminotransferase serum levels was observed in patients treated with tauroursodeoxycholic acid compared with placebo (p<0.001) and a progressive improvement with time was also found (p<0.05; linear time effect).\n Tauroursodeoxycholic acid improves the biochemical expression of chronic hepatitis. Long-term studies with clinically relevant end-points are warranted.", "Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the efficacy of IFN with that of a combination of IFN and UDCA.\n Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44) plus interferon (3 MU three times weekly) for 6 months and were then followed up for 6 additional months.\n At entry 30% of patients had cirrhosis, and 70% had HCV genotype 1. Five and four patients withdrew from the combination and the monotherapy groups, respectively. At 6 months alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities were significantly lower (P < 0.001) in the combination group than in the monotherapy group; the differences were no longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8 patients in the combination and the monotherapy groups, respectively (P = 0.67). In 10 of them (5 in each group) HCV RNA levels became undetectable. At 1 year four versus one patient had a sustained normalization of ALAT, and in one patient the HCV RNA became negative. There was no difference in the histologic progression. In this setting, in contrast to chronic cholestasis, UDCA administration induced an increase in total serum bile acids and did not change primary bile acids.\n An IFN plus UDCA combination is more effective than IFN alone in terms of ALAT but not in terms of the virologic response. These results favor the hypothesis that UDCA has an effect on the biochemical indices of cellular injury independent of a change in primary bile acids.", "Because 70% to 75% of patients with chronic hepatitis C either do not respond to or relapse after interferon (IFN) therapy, and because ursodeoxycholic acid (UDCA) has been shown to reduce aminotransferase levels in patients with chronic hepatitis, we undertook a prospective controlled randomized trial of IFN (group I) versus IFN plus UDCA (group II) in 80 patients with chronic hepatitis C. IFN was administered in both groups for 6 months (3 to 5 million units [MU] three times a week), and in group II UDCA (10 mg/kg/d) was administered with IFN and then alone for 3 additional months. Response to therapy was defined as the normalization of alanine transaminase (ALT) levels. The results showed that 6 months after cessation of IFN, 59% of responders had relapsed in group I but only 27% had relapsed in group II (P = .03). There was no difference between the two groups for the initial (month 6) and the late (months 15 and 18) response rates to IFN. There was no virological effect or significant histological improvement attributable to the addition of UDCA to IFN treatment. In conclusion, the results of this study show that the addition of UDCA to IFN therapy significantly prolongs the period for which serum ALT remain, within the normal range after discontinuation of IFN. Further studies would be required to determine whether UDCA has any potential for long-term amelioration of the histological severity of liver disease caused by hepatitis C virus (HCV) infection, and, therefore, whether it could be advocated as an adjunct to antiviral therapy.", "Chronic viral hepatitis averages 15% to 20% in heart transplant patients. Several studies have shown that ursodiol may improve liver biochemistry in patients with chronic hepatitis. We used a double-blind randomized controlled trial to evaluate the effect of ursodiol in heart transplant patients with chronic viral hepatitis.\n Thirty heart patients with chronic viral hepatitis B, C, or non-A-G received ursodiol, 800 mg per day (group 1), and 30 received placebo (group 2) for 12 months. Endpoints were improvement in liver biochemical tests and in total Knodell score. Intent-to-treat and per-protocol analyses were performed.\n At entry, both groups were comparable for all of the studied parameters. During the study period, serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase variations were not different between group 1 and group 2 patients. Knodell score improved in 20% of group 1 patients and in 43% of group 2 patients (NS). Adverse events or mortality were not different in the two groups during the study period. Similar results were observed by intent-to-treat and per-protocol analyses.\n A 12-month course of ursodiol therapy had no effect on liver enzymes or liver histology in heart transplant patients with chronic hepatitis.", "nan", "To study the effect of ursodeoxycholic acid (UDCA) on serum liver enzyme levels [alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT)] in 101 patients with hepatitis C virus-related chronic liver disease.\n Forty-nine patients were assigned to receive UDCA (450 mg/day) over a period of 6 months and 52 to receive no treatment.\n In the UDCA group, serum ALT and GGT levels significantly improved. ALT values decreased from pre-treatment levels of 157.0 +/- 62.6 IU/l to 82.5 +/- 46.4 IU/l (P < 0.05), and GGT fell from 141.3 +/- 86.2 IU/l to 66.0 +/- 49.5 IU/l (P < 0.001). No significant change occurred in the mean ALT and GGT levels in the control group.\n Although our encouraging preliminary results must be validated by double-blind histological trials, UDCA may be an alternative treatment for patients who fail to respond to interferon therapy.", "Interferon-alpha (IFN) and ursodeoxycholic acid (UDCA) combined have a controversial role in the treatment of chronic type C hepatitis. We studied the long-term efficacy of both drugs alone or in combination. In a three-year period, 108 patients were randomized into three treatment arms: (1) IFN alone 3 MU three times a week (N = 49), (2) IFN 3 MU three times a week + UDCA 250 mg twice a day (N = 45), and (3) UDCA alone 250 mg twice a day (N = 14). Response was defined as complete normalization of serum ALT. For the responders at the end of six months, the treatment was run to 12 months. Nonresponders (NRs) of the first group were crossed over to combination and NRs of the combination received 6 MU three times a week IFN+UDCA for the next six months. The enrollment to the UDCA alone arm was stopped early, since only 1/14 normalized serum ALT at the end of third month. However, 12/14 completed six months and 11 NRs received IFN 3 MU three times a week alone for the next six months. Twelve discontinued treatment due to side effects. Responders were followed-up untreated for 18 months. Sustained response (SR) was defined as persistence of normal serum ALT levels in this period. At the end of six months, 22/45 (48%) from the IFN-alone and 23/39 (58%) from the combination group responded. Twenty NRs from former and 15 of latter group were crossed over. While none of the 20 from the IFN-alone group responded to the combination, 1/15 NRs of the combination group responded to dose escalation. SR was achieved in 9/45 (20%) of the IFN alone and 7/39 (18%) of the combination group. The mean time form the end of the treatment to the relapse was not different between the groups. Five of 11 UDCA NRs responded to IFN with SR in 2. It was concluded that UDCA as a single agent is ineffective in achieving response in the treatment of chronic type C hepatitis. Combined with IFN, it increases response rate insignificantly although this is not sustained.", "The only effective and approved therapy for chronic hepatitis C is interferon-alpha. Because sustained response rates with interferon alone are disappointingly low, multidrug treatment regimens are currently being investigated. Ursodeoxycholic acid has been used in other chronic liver diseases and can limit hepatocyte injury. To evaluate the potential benefit of ursodeoxycholic acid in combination with interferon-alpha for the treatment of chronic hepatitis C, we conducted a prospective, double-blinded, randomized, placebo-controlled trial comparing the combination therapy of interferon-alpha 2b and ursodeoxycholic acid with interferon alone. Thirty-one patients with chronic hepatitis C were randomized to receive 3 million units of interferon-alpha 2b subcutaneously three times per week and either 13 to 15 mg/kg/day ursodeoxycholic acid or placebo orally for 6 months. The 6-month treatment period was followed by 6 months of observation. Biochemical normalization at the end of treatment occurred in 5 of 14 (36%) patients receiving monotherapy versus 8 of 15 (53%) patients (p = 0.34) receiving combination therapy. No patient treated with interferon alone had a sustained biochemical response 6 months after therapy; however, 3 of 12 patients (25%) treated with combination interferon and ursodeoxycholic acid maintained biochemical normalization at 6 months after therapy (p = 0.08). No difference in liver histology or clearance of hepatitis C viral RNA was noted 6 months after treatment. We conclude that combination therapy with ursodeoxycholic acid and interferon-alpha 2b was no more effective than interferon monotherapy in inducing a biochemical response in previously untreated patients with chronic hepatitis C. Ursodeoxycholic acid, however, may be useful in prolonging the biochemical response to interferon therapy.", "Ursodeoxycholic acid (UDCA) has recently been combined with interferon (IFN) in the treatment of individuals with chronic hepatitis C. However, whether its addition results in a long-term favourable response to IFN remains unclear. A prospective randomized trial of IFN alone versus IFN plus UDCA was therefore undertaken in 52 patients with chronic hepatitis C. All patients received a 24 week course of IFN-alpha (6 x 10(6) U/day for 2 weeks and then three times a week for 22 weeks) and half also received UDCA (600 mg/day) with IFN and then alone for 48 additional weeks. Normalization of serum alanine transaminase (ALT) concentrations at 0, 24 and 48 weeks after cessation of IFN therapy was apparent in 77, 42 and 42% of patients in the IFN-alone group and in 77, 54 and 42% of patients in the IFN plus UDCA group, respectively. There was no significant difference between the two groups with regard to response rate to IFN and the addition of UDCA to IFN treatment had no significant effect on hepatitis C virus (HCV) viraemia. During the follow-up period, 10 of 20 patients with normal serum ALT at the end of IFN treatment relapsed in the IFN-alone group compared with 11 of 20 patients in the IFN plus UDCA group. Among these relapsed patients, serum ALT concentration was significantly lower in the IFN plus UDCA group than in the IFN-alone group during the follow-up period. Twenty-four weeks after cessation of IFN therapy, the percentage of patients with HCV-RNA in their serum who showed a normalization of serum ALT concentrations was significantly higher in the IFN plus UDCA group than in the IFN-alone group (44 vs 6%). Thus, although the addition of UDCA was not associated with a favourable long-term response to HCV viraemia, it did reduce the risk and the severity of relapse following the cessation of IFN therapy.", "In previously published studies ursodeoxycholic acid (UDCA) showed beneficial effect on the course of chronic hepatitis. We investigated the effect of UDCA on the course of acute viral hepatitis in a prospective double-blind study. Seventy-eight consecutive patients were randomly assigned either to the UDCA group or to placebo. At 12 months of follow-up 76 patients were available for the final assessment. The analysis of all cases and of the patients with hepatitis B (n = 59) showed a comparable rate of decline of the alanine aminotransferase and other liver function tests in the treatment group and in the placebo group. However, the elevation of alanine aminotransferase persisted more frequently in the placebo group (all cases, p = 0.05; hepatitis B group, p = 0.03). Persistence of the hepatitis B virus infection, measured by the presence of hepatitis B early antigen and hepatitis B virus DNA (polymerase chain reaction and hybridization) at 12 months of follow-up, was observed in I of 33 patients in the UDCA group and in 6 of 25 patients in the placebo group (p = 0.02). Gallstones detected by entry ultrasound dissolved in four of eight cases in the UDCA group and in none of six in the placebo group. We conclude that UDCA has a beneficial effect on the course of the acute viral hepatitis. It may enhance the clearance of the hepatitis B virus and thus prevent the development of chronic hepatitis.", "The purpose of this study was to compare, within a randomized controlled trial, the efficacy of recombinant interferon-alpha in combination with ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic HCV hepatitis.\n Forty anti-HCV positive chronic hepatitis patients with ALT levels persistently greater than 3 times the upper normal level were randomized to receive either interferon-alpha (6 million units three times/wk for 6 months) plus ursodeoxycholic acid (10 mg/kg/day for 9 months) (n = 20) or interferon-alpha (6 million units three times/wk for 6 months) alone (n = 20). Disease activity was monitored monthly by ALT measurement until 18 months after interferon-alpha cessation. Serum HCV-RNA was measured at baseline and after 6, 9, and 24 months. Liver biopsies (basal and at the 9th month) were evaluated blindly and scored by Knodell's criteria.\n The probability of full or partial response during interferon-alpha treatment was similar in the two groups. The probability of biochemical relapse (i.e, any persistent return of ALT above normal) after 18-month of posttreatment follow-up was 75% in both the combination and the monotherapy group. Relapse, however, occurred significantly later in the combination than in the monotherapy group (6.6 +/- 5.4 [SD] months and 1.8 +/- 1.6 months after IFN-alpha cessation, respectively, p < 0.02). Severe biochemical relapse (i.e., a persistent ALT elevation greater than 3 times normal) occurred more frequently and earlier (p = 0.05) in patients treated with interferon-alpha (58.3%) than in those receiving the combination therapy (27.3%). The cumulative duration of normalized ALT periods during and after treatment was significantly greater (p = 0.005, chi 2) in patients treated with IFN-alpha + UDCA than with monotherapy (189/354 months vs 136/323 months. Lobular necrosis improved in both groups (p = 0.056 and p = 0.001, respectively), whereas portal inflammation improved (p = 0.009) only in the combination therapy group. Among the 30 patients who were viremic at entry, plasma HCV-RNA was no longer detectable after 6 months in four from the combination group and in five from the monotherapy group, yet all patients but one returned HCV-RNA positive 3 months after interferon-alpha cessation and were still viremic after 18 months. Cox's multiple regression identified the histological degree of posttreatment portal inflammation as the sole positive indicator of relapse.\n The combination of interferon-alpha and ursodeoxycholic acid prolongs the efficacy of interferon-alpha alone in chronic hepatitic C by delaying the probability of biochemical relapse and/or by reducing its severity, without affecting HCV viremia." ]

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[ "Haemodilutional effect of standard fluid management limits the effectiveness of acute normovolaemic haemodilution in AAA surgery--results of a pilot trial.", "Hemodynamic effects of hypertonic hydroxyethyl starch 6% solution and isotonic hydroxyethyl starch 6% solution after declamping during abdominal aortic aneurysm repair.", "Comparison of hemodynamic, pulmonary, and renal effects of use of three types of fluids after major surgical procedures on the abdominal aorta.", "The preservation of renal function by isovolemic hemodilution during aortic operations.", "Randomized controlled trial of the effect of mannitol on renal reperfusion injury during aortic aneurysm surgery.", "Gastric intramucosal pH changes after volume replacement with hydroxyethyl starch or crystalloid in patients undergoing elective abdominal aortic aneurysm repair.", "The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution.", "Hypertonic sodium lactate versus lactated ringer's solution for intravenous fluid therapy in operations on the abdominal aorta.", "Randomized study comparing the effects of hydroxyethyl starch solution with Gelofusine on pulmonary function in patients undergoing abdominal aortic aneurysm surgery.", "Crystalloid vs. colloid resuscitation: is one better? A randomized clinical study.", "[Effect of infusion of hypertonic-hyperoncotic solution on cardiovascular function in surgery of the abdominal aorta during the perioperative period].", "Cardiac response is greater for colloid than saline fluid loading after cardiac or vascular surgery.", "Safety of HES 130/0.4 (Voluven(R)) in patients with preoperative renal dysfunction undergoing abdominal aortic surgery: a prospective, randomized, controlled, parallel-group multicentre trial.", "Effect of preoperative normovolemic hemodilution on left ventricular segmental wall motion during abdominal aortic surgery.", "Hemodynamic and cardiometabolic effects of infrarenal aortic and common iliac artery declamping in man--an approach to optimal volume loading.", "Extracellular fluid and colloid osmotic pressure in abdominal vascular surgery. A study of volume changes.", "Effects of a hemoglobin-based oxygen carrier (HBOC-201) on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery.", "Effect of hypertonic saline dextran on acid-base balance in patients undergoing surgery of abdominal aortic aneurysm.", "Haemodynamic effects of diaspirin crosslinked haemoglobin (DCLHb) given before abdominal aortic aneurysm surgery.", "Haemodynamics and 'optimal' hydration in aortic cross clamping.", "Effect of bicarbonated Ringer's solution on the acid-base balance in patients undergoing abdominal aortic aneurysm repair.", "[Use of a hypertonic solution of 7.5% NaCl in preventing post-declamping hypotension of the abdominal aorta].", "Splanchnic oxygenation in patients undergoing abdominal aortic aneurysm repair and volume expansion with eloHAES.", "[Comparative study of the intraoperative effectiveness of 5% human albumin or 10% hydroxyethyl starch (HAES-steril) on hemodynamics and oxygen transport in 40 patients].", "Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study.", "Optimal fluid management after aortic reconstruction: a prospective study of two crystalloid solutions.", "A prospective trial of diaspirin cross-linked hemoglobin solution in patients after elective repair of abdominal aortic aneurysm.", "Comparison of hetastarch to albumin for perioperative bleeding in patients undergoing abdominal aortic aneurysm surgery. A prospective, randomized study.", "Intraoperative glucose infusion and blood lactate: endocrine and metabolic relationships during abdominal aortic surgery.", "Gastric intramucosal pH-guided therapy in patients after elective repair of infrarenal abdominal aneurysms: is it beneficial?", "The effects of increased doses of bovine hemoglobin on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery.", "Randomized trial of albumin vs. electrolyte solutions during abdominal aortic operations.", "Randomized clinical trial comparing the effects on renal function of hydroxyethyl starch or gelatine during aortic aneurysm surgery.", "Low molecular weight hydroxyethyl starch 6% compared to albumin 4% during intentional hemodilution." ]

[ "To evaluate the impact of standard fluid management on the effectiveness of ANH as a blood conservation method in elective open AAA repair.\n Prospective randomised controlled study.\n Thirty-four patients undergoing elective AAA repair were randomised to have ANH (16) or act as controls (18). Intra-operative cell salvage was permitted in both groups. Haemoglobin (Hb) concentrations were determined at variable intervals peri-operatively. Blood loss and the use of heterologous blood were recorded.\n The pre- and post-operative Hb concentrations, surgical blood loss and the use of cell salvage were similar in both groups. Hb concentration (median, range) decreased significantly from pre-operative to aortic clamping (with blood loss <100 ml) in ANH patients from 8.8 (7.5-10.2) to 5.7 (4.2-6.6)mmol/l following ANH but also in controls from 8.6 (7.5-9.7) to 7.0 (4.5-9.0)mmol/l due to fluid infusion (P<0.01 for every comparison). Bank blood requirements were similar: median 2 units in ANH and 2.5 units in control patients (P=0.68).\n Large volumes of fluids infused during AAA repair already conserve blood by the mechanism of hypervolaemic haemodilution. When cell salvage is used with standard fluid management during AAA repair, additional ANH is ineffective in saving blood.", "Fluid resuscitation with hypertonic hydroxyethyl starch solutions (HES) is effective in haemorrhagic shock due to the rapid mobilisation of fluids into the intravascular compartment. Declamping of the abdominal aorta with acute redistribution of blood into the vessels of the lower body half causes declamping-induced hypotension. Usually large amount of fluids or vasopressors are necessary to restore hemodynamic stability. Therefore, infusion of a hypertonic colloid solution may be an attractive option to achieve hemodynamic stability. This study was conducted to determine the amount of fluid of either hypertonic HES (HES 6%;7.2% NaCl) or isotonic HES (HES 6%;0.9% NaCl) needed to attain best wedge pressure (PCWP) cardiac index (CI) relation after declamping. Thirty-two high-risk patients undergoing elective abdominal aneurysm resection were enrolled in a prospective, randomised, double blinded study. The individual optimised PCWP/CI relation was determined after induction of anaesthesia. After declamping, both solutions were titrated in small boluses of 100 mL until the previously determined best wedge was reached. The amount of fluid after declamping was significantly reduced in the hypertonic HES- group 162 mL vs. 265 mL in the control group (P < 0.05). Resuscitation time was shortened, and cardiac index was slightly higher in the treatment group. The use of hypertonic HES-solution after aortic declamping led to a significant reduction of fluids necessary to attain optimised PCWP/CI relation. In this clinical trial with moderate blood loss in high-risk patients, hypertonic HES applied in a titrated fashion restored hemodynamic stability faster and without volume overload.", "Hemodynamic, pulmonary, and renal variables were measured in 24 patients scheduled for major abdominal aortic operations. Control values were obtained before preoperative medications were given. All patients received 5% dextrose in Lactated Ringer's solution intraoperatively. Postoperatively, group 1 patients received 5% dextrose in water plus albumin, group 2 received 5% dextrose in 0.45 sodium chloride solution, and group 3 received 5% dextrose in lactated Ringer's solution. There were significant increases in Qs/Qt and AaDO2, 48 hours after operation in group 3. Oxygen consumption and cardiac output increased in all groups 24 hours after operation. Twenty-four hours later, these two variables returned to control values in group 1 but continued to rise in the other two groups. Significant diuresis occurred in group 1, 48 hours postoperatively, whereas the other two groups continued to retain water. Use of albumin and 5% dextrose in water in the postoperative period seemed to produce less deviations from control values of most measured variables, than the other two groups.", "In an investigation of the effects of isovolemic hemodilution, 39 consecutive patients undergoing elective infrarenal aortic operation had detailed measurements of renal function, renal artery blood flow, and cardiac hemodynamics.\n The patients were randomly allocated to receive acute preoperative isovolemic hemodilution to a hematocrit of 28%, with 20 patients receiving hemodilution and 19 being control subjects.\n Twelve (63%) of the control group had renal impairment, compared with only four (20% in the group receiving hemodilution (p < 0.01). Hemodilution also prevented the fall in cardiac output induced by cross-clamping (p < 0.01) and significantly reduced the need for transfusion of donor blood (p < 0.01).\n Acute isovolemic hemodilution is clearly a useful adjunct in the management of patients undergoing elective aortic operation.", "The effects of mannitol on renal impairment following infrarenal aortic aneurysm repair were studied. Patients received either mannitol 0.3 g/kg (n = 15) or saline (n = 13) as a rapid intravenous infusion before aortic cross-clamping. One patient in the control group developed fatal postoperative renal failure but there was no renal failure in the mannitol group. Two patients treated with mannitol died from perioperative myocardial infarction. There were no significant differences in postoperative blood urea level, serum creatinine concentration or creatinine clearance between mannitol and control groups. In patients who had mannitol there was a significant diuresis on the first day after operation (mean urine output 2250 ml) compared with before operation (1557 ml) (P = 0.007). Compared with controls, patients treated with mannitol had lower mean (s.e.m.) postoperative levels of urinary albumin (160(32) versus 500(140) mg per mmol creatinine; P = 0.036) and N-acetyl glucosaminidase (143(34) versus 271(70) mumol per mmol creatinine; P = 0.04) indicating a reduced level of subclinical glomerular and renal tubular damage. These data demonstrate that mannitol reduces subclinical renal injury following infrarenal aortic aneurysm repair.", "Gastric intramucosal pH (pHi), a surrogate marker of tissue oxygenation, falls following abdominal aorta aneurysm (AAA) repair. We tested the hypothesis that volume replacement with a hydroxyethyl starch solution would result in better preserved splanchnic oxygenation than would volume replacement with crystalloid solutions.\n This was a prospective, randomized, nonblinded study set in a university-affiliated community hospital. Thirty patients undergoing elective AAA repair were studied. Patients were randomly selected to receive intraoperative and postoperative fluid replacement with either hetastarch or crystalloid. According to the study protocol, patients could not receive in excess of 3,000 mL of hetastarch. Tissue oxygenation was assessed indirectly by measuring pHi using a nasogastric tonometer. Hemodynamic, oxygenation, and pHi data were collected preoperatively, preclamp, before unclamping, at the end of the procedure and postoperatively for 24 hours. Coagulation parameters were determined preoperatively and postoperatively for 24 hours.\n Fifteen patients were randomized to each group. There were 18 male and 12 female patients, whose mean age was 66 +/- 9 years. The intraoperative fluid balance was significantly greater in the crystalloid compared with the hetastarch group (4,194 +/- 1,500 mL v 2,949 +/- 1,123 mL; P = .05, 95% confidence interval [C] 23 to 2,519 mL). There were no significant differences in the amount of intraoperative blood loss or postoperative transfusion requirements between the two groups. The difference between the preoperative pHi and nadir was 0.07 +/- 0.03 in the hetastarch group compared with 0.13 +/- 0.04 in the crystalloid group (P = .001, Cl 0.03 to 0.09). By multivariate analysis the only variable that influenced the fall in pHi was the type of resuscitation fluid (F ratio of 7.63; P = .01). There were no significant differences in hemodynamic- and oxygenation-derived variables or coagulation parameters between the two groups of patients. The length of mechanical ventilation, intensive care unit, and hospital stay was comparable between the two groups of patients.\n In patients undergoing major surgery, volume resuscitation with hydroxyethyl starch solutions may improve microvascular blood flow and tissue oxygenation.", "Because of allogenic red blood cell (RBC) availability and infection problems, novel alternatives, including hemoglobin-based oxygen-carrying solutions (HBOC), are being explored to minimize the perioperative requirement of RBC transfusions. This study evaluated HBOC-201, a room-temperature stable, polymerized, bovine-HBOC, as a substitute for allogenic RBC transfusion in patients undergoing elective infrarenal aortic operations.\n In a single blind, multicenter trial, 72 patients were prospectively randomized two-to-one to HBOC (n = 48) or allogenic RBC (n = 24) at the time of the first transfusion decision, either during or after elective infrarenal aortic reconstruction. Patients randomized to the HBOC group received 60 g of HBOC for the initial transfusion and had the option to receive three more doses (30 g each) within 96 hours. In this group, any further blood requirement was met with allogenic RBCs. Patients randomized to the allogenic RBC group received only standard RBC transfusions. The efficacy analysis was a means of assessing the ability of HBOC to eliminate the requirement for any allogenic RBC transfusions from the time of randomization through 28 days. Safety was evaluated by means of standard clinical trial methods.\n The two treatment groups were comparable for all baseline characteristics. Although all patients in the allogenic RBC group required at least one allogenic RBC transfusion, 13 of 48 patients (27%; 95% CI, 15% to 42%) in the HBOC group did not require any allogenic RBC transfusions. The only significant changes documented were a 15% increase in mean arterial pressure and a three-fold peak increase in serum urea nitrogen concentration after HBOC. The complications were similar in both groups, with no allergic reactions. There were two perioperative deaths (8%) in the allogenic RBC group and three perioperative deaths (6%) in the HBOC group (P = 1.0).\n HBOC significantly eliminated the need for any allogenic RBC transfusion in 27% of patients undergoing infrarenal aortic reconstruction, but did not reduce the median allogenic RBC requirement. HBOC transfusion was well tolerated and did not influence morbidity or mortality rates.", "Fifty-eight patients who were to undergo aortic reconstruction were prospectively randomized into two groups to compare the effects of perioperative fluid replacement with isotonic and hypertonic crystalloid solutions. Blood loss was replaced with packed red blood cells, and additional fluid was given as either Ringer's lactate solution (RL, 130 mEq sodium/L, 274 mOsm/L) or a hypertonic balanced salt solution (HSL, 250 mEq sodium/L, 514 mOsm/L). Fluid was administered to maintain the cardiac filling pressure within 3 torr of the preoperative level and the cardiac output (CO) at or above the preoperative level. The groups were similar with respect to age, preexisting disease, duration of operation, and operative blood loss. During the operation, the RL group required 9.5 +/- 0.8 L of fluid, whereas the HSL group required 4.5 +/- 0.3 L (P less than 0.001). Pulmonary, cardiac, and renal functions were adequately maintained in both groups. There were no significant differences between the groups with regard to CO, urine output, or creatinine clearance during the operation and early postoperative period. Postoperatively, the intrapulmonary shunt was 20 +/- 1% in the RL group and it was 16 +/- 1% in the HSL group (P less than 0.05). The amount of sodium infused and the cumulative sodium balance at the completion of the study period were similar in both groups. Serum sodium and osmolarity were significantly greater in the HSL group (P less than 0.001), reaching a maximum of 151 +/- 1 mEq/L and 305 +/- 2 mOsm/L, respectively. Two patients in the HSL group had a persistent elevation in serum osmolarity (greater than 320 mOsm/L) during operation, for which they received RL for the balance of the resuscitation. There were no complications that could be attributed to the hypertonicity of the solution. HSL is effective for resuscitation of patients with extracellular fluid deficit and is safe provided that the serum sodium and osmolarity are monitored during periods of large volume administration.", "Restoring blood flow to ischaemic tissue can cause lung damage with pulmonary oedema. Hydroxyethyl starch (HES) solution, when used for volume replacement, may modify and reduce the degree of ischaemia-reperfusion injury. We compared the effects of HES solution with those of Gelofusine solution on pulmonary function, microvascular permeability and neutrophil activation in patients undergoing elective infrarenal abdominal aortic aneurysm surgery.\n Forty patients were randomized into two groups. The anaesthetic technique was standardized. Lung function was assessed with the PO(2)/FI(O(2)) ratio, respiratory compliance, chest x-ray and a score for lung injury. Microvascular permeability was determined by measuring microalbuminuria. Neutrophil activation was determined by measurement of plasma elastase.\n Four hours after surgery, the median (quartile values) PO(2)/FI(O(2)) ratio was 40.3 (37.8, 53.1) kPa for the HES-treated patients compared with 33.9 (31.2, 40.9) kPa for the Gelofusine-treated patients (P<0.01, Mann-Whitney test). The respiratory compliance was 80 (73.5, 80) ml cm(-1) H(2)O in the HES-treated patients compared with 60.1 (50.8, 73.3) ml cm(-1) H(2)O in the Gelofusine-treated patients (P<0.01, Mann-Whitney test). The lung injury score 4 h after surgery was less for the patients treated with HES compared with the patients treated with Gelofusine (0.33 vs 0.71, P=0.01, Wilcoxon rank sum test). Mean (SD) plasma elastase was less in the HES-treated patients on the first postoperative day (1.96 (0.17) vs 2.08 (0.24), P<0.05). The log mean microalbuminuria was less in the HES-treated patients (0.41 vs 0.91 mg mmol(-1), P<0.05). This difference in microvascular permeability was associated with different volumes of colloid required to maintain stable cardiovascular measurements in the two groups of patients studied (3000 vs 3500 ml, P<0.01, Mann-Whitney test).\n Compared with Gelofusine, the perioperative pulmonary function of patients treated with HES after abdominal aortic aneurysm surgery was better.", "The effects of hemodynamic resuscitation with protein-containing or balanced salt solution were studied prospectively in 29 patients undergoing abdominal aortic surgery. Blood loss was replaced with packed red cells and extracellular volume with either Ringer's Lactate (RL) or 5% albumin in Ringer's lactate (ALB). Fluids were given to maintain the pulmonary capillary wedge pressure (PCWP) equal to or within 5 torr above preoperative (PO) levels, the cardiac output (CO) equal to or greater than preoperative values, and the urine output at least 50 ml/hr. Serum colloid osmotic pressure (COP), CO, PCWP, the gradient between COP and PCWP (COP-PCWP), and intrapulmonary shunt (Qs/Qt) were measured PO, intraoperatively (IO), and daily for 3 days. The measured variables were similar PO in both groups. Operation time, estimated blood loss, and transfusions were similar. Total fluids received for resuscitation (day of operation) was 11.3 +/- 0.8 liters (RL) and 6.2 +/- 0.4 liters (ALB). Fluid balance at the end of resuscitation was 8.4 +/- 0.8 liters (RL) and 3.4 +/- 0.5 liters (ALB). Maximum decrease in COP was 40% (P less than 0.001) in the RL group and was insignificant in the ALB group. The COP-PCWP decreased from 11 +/- 1 to 2 +/- 1 in RL (P less than 0.001) and insignificantly in ALB. Qs/Qt increased slightly in both groups following operation but was not different between groups. Fluid balance, total fluid infused, sodium balance, total sodium infused, COP, or COP-PCWP did not significantly correlate with Qs/Qt. Two patients in the ALB group experienced pulmonary edema associated with normal COPs and elevated PCWPs. There were no cases of pulmonary edema associated with low COPs and normal PCWPs in the crystalloid group. These data seriously question the necessity to maintain COP by using protein-containing solutions during acute hemodynamic resuscitation. When titrated to physiological end points, even large volumes of balanced salt solutions are tolerated well.", "When blood flow is decreased, as in prolonged hypovolaemia and hypotension, or in the course of transversal clamping of the aorta during aortic reconstruction, nutritive tissue perfusion can also fall below the critical level.\n The objective of this study was to analyse the effects of hypertonic-hyperoncotic solution on cardiovascular function during reconstruction of the abdominal aorta.\n This prospective randomised study included 40 patients. All patients underwent surgery of the abdominal aorta under general endotracheal anaesthesia. Based on the type of solution infused from the time of clamping to the moment of the removal of the transversal aortic clamp, the patients were divided into two groups of 20. The study group was infused with a small volume of hypertonic-hyperoncotic solution, while the controls were administered infusions of isotonic solution. Patients with a preoperative creatinine level over 130 micromol L(-1) and an ejection fraction of less than 40% were excluded from the study.\n Cardiac output increased from 5.67 +/- 2.95 to 7.05 +/- 3.39 L min(-1) in the study group, in comparison to the controls, where it increased from 4.98 +/- 2.06 to 5.99 +/- 3.02 L min(-1) (p = 0.004). Central venous pressure increased from 8.75 +/- 3.67 to 9.30 +/- 2.77 mm Hg in the study group, in comparison to the controls, where the values decreased from 6.84 +/- 2.73 to 6.45 +/- 2.50 mm Hg (p = 0.022). Diastolic pulmonary artery pressure increased from 15.92 +/- 5.61 to 16.65 +/- 6.53 mm Hg in the study group, in comparison to the controls, where it decreased from 12.65 +/- 4.28 to 11.85 +/- 3.91 mm Hg (p = 0.021). The amount of given crystalloids 24 hours after the removal of the aortic clamp totalled 2562.5 +/- 485.82 mL in the study group, versus 3350 +/- 727.29 mL in the control group (p = 0.000). The amount of given human albumins 24 hours after the removal of the aortic clamp totalled 30 +/- 49.74 mL in the study group versus 100 +/- 4.34 mL in the control group (p = 0.001). CONCLUSION Haemodynamic stability of patients and adequate organ perfusion during surgery are achieved through the infusion of hypertonic-hyperoncotic solution, which maintains optimal values of: cardiac output, mixed venous oxygen saturation, and delivery of oxygen, while reducing alveolo-arterial oxygen difference. The balance of fluids, 24 hours after the removal of the aortic clamp, was maintained with the aid of hypertonic-hyperoncotic solution, while isotonic solution produced an excess of over 1000 mL of fluid in the control patients. Hypertonic-hyperoncotic solution increases cardiac output considerably more than does isotonic solution, and its application significantly reduces the accumulation of crystalloid solutions and human albumins.", "To study the effects on volume expansion and myocardial function of colloids or crystalloids in the treatment of hypovolaemic hypotension after cardiac and major vascular surgery.\n A single-centre, single-blinded, randomized clinical trial at the intensive care unit of a university hospital.\n Patients (n=67) were subjected to a 90-min filling pressure-guided fluid challenge with saline 0.9% or the colloids gelatin 4%, hydroxyethyl starch 6% or albumin 5%. Biochemical variables and haemodynamics (transpulmonary thermodilution) were measured.\n An amount of 1800 (1300-1800) ml of saline or 1600 (750-1800) ml of colloid solution (P< 0.005) was infused. Colloid osmotic pressure (COP) decreased in the saline group and increased in the colloid groups (P< 0.001). Plasma volume increased by 3.0% (-18 to 24) in the saline versus 19% (-11 to 50) in the colloid groups (P< 0.001). Cardiac index increased by median 13% (ns) in the saline group and by 22% in the colloid groups (P<0.005). The rise in left ventricular stroke work index was greater in the colloid than in the saline groups. The different colloids were equally effective. The rise in cardiac index related to the rise in plasma volume and global end-diastolic volume, confirming plasma volume and preload augmentation by the fluid loading.\n After cardiac or major vascular surgery, the pressure- and time-guided fluid response is dependent on the type of fluid used. Colloid fluid loading leads to a greater increase in preload-recruitable cardiac and left ventricular stroke work indices than that with saline, because of greater plasma volume expansion following an increase in plasma COP.", "Patients with impaired renal function are at risk of developing renal dysfunction after abdominal aortic surgery. This study investigated the safety profile of a recent medium-molecular-weight hydroxyethyl starch (HES) preparation with a low molar substitution (HES 130/0.4) in this sensitive patient group.\n Sixty-five patients were randomly allocated to receive either 6% hydroxyethyl starch (Voluven); n = 32) or 3% gelatin (Plasmion); n = 33) for perioperative volume substitution. At baseline, renal function was impaired in all study patients as indicated by a measured creatinine clearance < 80 mL min(-1). The main renal safety parameter was the peak increase in serum creatinine up to day 6 after surgery.\n Both treatment groups were compared for non-inferiority (pre-defined non-inferiority range hydroxyethyl starch < gelatin + 17.68 micromol L(-1) or 0.2 mg dL(-1). Other renal safety parameters included minimum postoperative creatinine clearance, incidence of oliguria and adverse events of the renal system. Baseline characteristics, surgical procedures and the mean total infusion volume were comparable. Non-inferiority of hydroxyethyl starch vs. gelatin could be shown by means of the appropriate non-parametric one-sided 95% CI for the difference hydroxyethyl starch-gelatin [-infinity, 11 micromol L(-1)]. Oliguria was encountered in three patients of the hydroxyethyl starch and four of the gelatin treatment group. One patient receiving gelatin required dialysis secondary to surgical complications. Two patients of each treatment group died.\n As we found no drug-related adverse effects of hydroxyethyl starch on renal function, we conclude that the choice of the colloid had no impact on renal safety parameters and outcome in patients with decreased renal function undergoing elective abdominal aortic surgery.", "Preoperative normovolemic hemodilution (PNH) has been proposed for patients scheduled to undergo aortic surgery. Coronary artery disease is frequent in these patients. The aim of the study was to assess the effect of PNH on hemodynamics and segmental wall motion (SWM) evaluated by transesophageal echocardiography in such patients. Twenty patients with coronary artery disease were allocated randomly to either PNH or no PNH; PNH was performed after anesthetic induction using dextran 60,000. Patients were operated on under general anesthesia and monitored intraoperatively with electrocardiographic lead CM5, radial and pulmonary artery catheters, and transesophageal echocardiography positioned to obtain a short-axis view. Hemodynamic and transesophageal echocardiographic data were collected after anesthetic induction and after PNH, before and 5 min after aortic clamping, after unclamping, and at the end of surgery. Aortic clamping induced a significant increase in systemic vascular resistance and arteriovenous difference in oxygen and a decrease in cardiac index (P < 0.05), but the effect of aortic clamping was inversely related to hemodilution. The SWM score (graded from 1 = normal to 5 = dyskinesia) was significantly increased after aortic clamping, mainly in the anterior segment (P < 0.05). Four patients in the control (no PNH) group and one in the PNH group developed new SWM abnormalities indicative of myocardial ischemia during surgery (P = NS). This study suggests that PNH may improve hemodynamic tolerance to aortic clamping in patients with coronary artery disease. The observed changes in SWM indicate that PNH may not worsen myocardial ischemia in patients scheduled to undergo aortic surgery.", "Nineteen patients undergoing abdominal aortic aneurysm surgery were randomly assigned to two groups and investigated to elucidate the mechanisms of declamping hypotension. The control group of nine patients was kept at an average mean pulmonary artery occlusion pressure (MPAOP) of 11 mmHg (1.46 kPa) before declamping. The other group was volume loaded to a MPAOP of 16 mmHg (2.13 kPa) shortly before declamping. Following declamping there was a significantly greater decrease in mean arterial pressure in the control group, with the same reduction of MPAOP in both groups. In parallel, cardiac and stroke volume indices decreased in the control patients, but remained unchanged in the volume-loaded patients. In the control group there was a reduction in myocardial substrate utilization which was not seen in the volume-loaded patients. No signs of myocardial ischemia could be demonstrated in any of the groups. The results indicate that mismatching between intravascular volume and blood volume is the main cause of infrarenal aortic or common iliac artery declamping hypotension. Volume loading before declamping to a slightly elevated MPAOP can effectively prevent hypotension, while a normal MPAOP does not guarantee a stable hemodynamic situation after declamping.", "nan", "We conducted a pilot study to evaluate the effects of HBOC-201, a bovine hemoglobin-based oxygen carrier, on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. After induction of anesthesia and isovolemic hemodilution with 1 L of lactated Ringer's solution, 13 patients were randomly assigned to receive, within 30 min, 3 mL/kg of either HBOC-201 or 6% hydroxyethyl starch (HES). Monitored variables included invasive arterial and pulmonary artery pressures, arterial and mixed venous blood gases, and calculations of cardiac index (CI), systemic and pulmonary vascular resistance indices, oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER). Thirty minutes after HBOC-201 infusion, mean arterial pressure, systemic vascular resistance index, and CI were 149% (P = 0.028), 169% (P = 0.046), and 75% (P = 0.46) of the preinfusion values, respectively. No significant changes were noticed in heart rate and pulmonary vascular resistance index. DO2I and VO2I, 30 min after the infusion of HBOC-201, were 79% (P = 0.046) and 76% (P = 0.028) of the preinfusion values, respectively, whereas CaO2 and O2ER remained unaffected. We conclude that HBOC-201, at a dose of 3 mL/kg, impairs oxygen delivery because of adverse effects on cardiac output.", "To evaluate the magnitude and cause of metabolic acidosis after infusion of 7.5% sodium chloride 6% dextran 70.\n Randomized, prospective clinical study.\n University hospital.\n Two groups of 14 patients each, undergoing repair of abdominal aortic aneurysm.\n Patients were randomly assigned to receive either 250 mL of hypertonic saline dextran (HSD) or a conventional fluid regimen with 250 mL of hydroxyethyl starch in normal saline solution (H-NS) during the period of aortic clamping. Additionally, normal saline was used in both groups to reach a target pulmonary artery occlusion pressure of 15-18 mmHg. pH, Paco2, and serum concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured. Strong ion difference was calculated as (sodium + potassium + magnesium + calcium) - (chloride + lactate). The amount of weak plasma acid was calculated.\n The infusion of HSD resulted in an immediate large increase in serum sodium (19 mmol/L) and chloride (22 mmol/L), whereas the infusion of H-NS led only to mild increases in serum sodium (3 mmol/L) and chloride (6 mmol/L). Both HSD and H-NS caused concomitant and equal decreases in the amount of weak plasma acid, strong ion difference, and pH (7.28-7.30). The reduction of bicarbonate was also identical and proportional to the extent of dilution due to infusion of HSD and H-NS. This induced metabolic acidosis was corrected spontaneously in both groups 24 hrs after surgery.\n Both the intravenous administration of 7.5% sodium chloride and the conventional fluid regimen with saline-based 6% hydroxyethyl starch solution resulted in a metabolic acidosis of equal extent. This suggests dilution of plasma buffers or a decrease in strong ion difference to be the primary cause of metabolic acidosis.", "We studied 34 patients undergoing elective repair of an abdominal aortic aneurysm under combined general anaesthesia and epidural block to evaluate the acute effects of diaspirin crosslinked haemoglobin (DCLHb) 50, 100 and 200 mg kg-1 i.v. Haemodynamic variables were measured continuously using pulmonary and radial artery catheters, and oxygen delivery and consumption were calculated at regular intervals. DCLHb was shown to be vasoactive, producing an increase in mean arterial pressure of approximately 25% with each dose, with small decreases in cardiac index and calculated oxygen delivery. These effects persisted beyond the end of infusion and provided a degree of cardiovascular stability during the operative procedure. The effects of DCLHb on oxygen consumption at these doses were minimal.", "The effect of optimal hydration on haemodynamics and renal function during infrarenal aortic cross clamping was studied in 26 consecutive patients operated on because of an infrarenal aortic aneurysm. The patients were randomly divided over two groups. The patients of group B (n = 13) were optimally hydrated before the operation. The Starling curve was used as standard. Patients of group A (n = 13) served as control. The pre-operative and postoperative renal functions of both groups were compared, as were the haemodynamic parameters. The haemodynamic parameters were measured at five minutes intervals during the entire procedure. During aortic clamping the heart rate was significantly lower in patients of group B, indicating a lower myocardial oxygen consumption. Neither the haemodynamic parameters nor the renal function showed other beneficial effects on optimal hydration.", "The present study was designed to assess whether prophylactic use of bicarbonated Ringer's solution ameliorates metabolic acidosis in patients undergoing aortic surgery.\n Twenty patients undergoing elective infrarenal aortic aneurysm repair were randomly assigned to receive either bicarbonated Ringer's solution or acetated Ringer's solution. The pH, PaCO(2), and base excess (BE) were measured before surgical incision (T0), 5 min before reperfusion (T1), 5 min after reperfusion (T2), and 30 min after reperfusion (T3). Data were compared between the two groups.\n Both pH and BE initially showed a slight decrease in both groups during clamping. After unclamping of the aorta, an additional decrease in pH was observed in both groups (T0 to T2, and T3). There were no significant differences in pH between the groups throughout the study period.\n Aortic cross-clamping leads to the development of metabolic acidosis, with a decrease in pH and BE. The effect of administration of bicarbonated infusion fluid during elective abdominal aortic surgery had not significant compared with that of acetated Ringer's solution with respect to acid-base homeostasis.", "nan", "Gastric intramucosal pH (pHi), a surrogate marker of splanchnic oxygenation, falls following abdominal aortic aneurysm surgery.\n To investigate the effects of volume expansion with hydroxyethyl starch (eloHAES) on splanchnic perfusion compared to another colloid such as gelofusine.\n Twenty-two consecutive patients undergoing AAA repair were randomised to receive either eloHAES or gelofusine as plasma expanders. Tissue oxygenation was monitored (10 gelofusine and 12 eloHAES) indirectly by measuring pHi using a nasogastric tonometer.\n Compared to the eloHAES group, the fall in pHi was significantly greater in the gelofusine group at clamp release (7.29 vs 7.33, P=0.003) and at 4 h following clamp release (7.29 vs 7.33, P=0.03). There was a good inverse correlation between the lowest pHi and the peak serum interleukin-6 (r(s)= -0.47, P=0.03). By multivariate analysis, the only factor that influenced the pHi was the type of colloid used (F=5.54, P=0.005). The eloHAES treated patients required significantly less colloid on the first postoperative day (3175 +/- 175 vs 4065 +/- 269 ml, P=0.01).\n In patients undergoing abdominal aortic aneurysm repair, plasma expansion with eloHAES improves microvascular perfusion and splanchnic oxygenation.", "In 40 patients, whose expected hemodynamic instability during surgery necessitated invasive monitoring (Swan-Ganz catheter) and arterial pressure monitoring the hemodynamic and oxygen transport parameters in conditions of hypervolemic hemodilution were investigated in randomized tests. After insertion of an arterial catheter (arteria radialis) as well as Swan-Ganz pulmonary arterial catheter via the vena jugularis interna, one of the two volume substitutes selected at random was infused in quantities of 125 ml/5 min and the hemodynamic changes were measured after infusion of 500 ml and finally after a wedge pressure of 18 mmHg was reached. Using either solution, the measurements indicated significant increases in mean arterial pressure as well as in central venous pressure (ZVD) and wedge pressure. The cardiac index, left ventricular stroke work index, and stroke output rose consecutively and pulmonary vascular resistance went down in both test groups. In the case of both volume substitutes, there was an improvement in oxygen availability. The hemoglobin content decreased in both groups, though to different degrees in each group. Although the hydroxyethyl starch group registered a greater improvement in the cardiac index, a bigger decrease in pulmonary vascular resistance, a higher rise in the left ventricular stroke work index and a more significant improvement in stroke output, smaller quantities of the volume substitute were required in this group than in the group in which volume substitution was carried out with human albumin 5%.(ABSTRACT TRUNCATED AT 250 WORDS)", "Metabolic acidosis and changes in serum osmolarity are consequences of 0.9% normal saline (NS) solution administration. We sought to determine if these physiologic changes influence patient outcome. Patients undergoing aortic reconstructive surgery were enrolled and were randomly assigned to receive lactated Ringer's (LR) solution (n = 33) or NS (n = 33) in a double-blinded fashion. Anesthetic and fluid management were standardized. Multiple measures of outcome were monitored. The NS patients developed a hyperchloremic acidosis and received more bicarbonate therapy (30 +/- 62 mL in the NS group versus 4 +/- 16 mL in the LR group; mean +/- SD), which was given if the base deficit was greater than -5 mEq/L. The NS patients also received a larger volume of platelet transfusion (478 +/- 302 mL in the NS group versus 223 +/- 24 mL in the LR group; mean +/- SD). When all blood products were summed, the NS group received significantly more blood products (P = 0.02). There were no differences in duration of mechanical ventilation, intensive care unit stay, hospital stay, and incidence of complications. When NS was used as the primary intraoperative solution, significantly more acidosis was seen on completion of surgery. This acidosis resulted in no apparent change in outcome but required larger amounts of bicarbonate to achieve predetermined measurements of base deficit and was associated with the use of larger amounts of blood products. These changes should be considered when choosing fluids for surgical procedures involving extensive blood loss and requiring extensive fluid administration.\n Predominant use of 0.9% saline solution in major surgery has little impact on outcome as assessed by duration of mechanical ventilation, intensive care unit stay, hospital stay, and postoperative complications, but it does appear to be associated with increased perioperative blood loss.", "To determine optimal fluid management after elective aortic surgery we compared postoperative administration of 5% dextrose Ringer's lactate solution (102 patients) with 5% dextrose half-normal saline solution (80 patients). For 72 hours after operation, intravenous fluids were titrated to maintain urine output between 50 and 100 ml/hr. The group receiving 5% dextrose Ringer's lactate required less intravenous volume per day (2005 +/- 138 ml [mean +/- standard error of the mean] vs. 2701 +/- 145 ml, p less than 0.05), gained less weight (0.8 +/- 0.2 kg vs. 3.2 +/- 0.2 kg, p less than 0.05), and sustained less hyponatremia (serum sodium reduction, 0.1 mEq/L vs. 4.5 mEq/L, p less than 0.05). The group receiving 5% dextrose Ringer's lactate exhibited consistently lower pulmonary capillary wedge pressure (7.3 +/- 1.0 mm Hg vs. 11.4 +/- 1.9 mm Hg) and required treatment for fluid overload in 9 of 102 instances compared with 30 of 80 instances with hypotonic saline solution (p less than 0.05). The patients receiving 5% dextrose Ringer's lactate maintained higher arterial PO2 at 40% forced inspiratory oxygen (PaO2, 83 +/- 3 torr vs. PaO2, 67 +/- 5 torr, p less than 0.05). Optimal fluid management was approached by the use of 5% dextrose Ringer's lactate solution postoperatively. The use of hypotonic saline solution after aortic surgery offered no advantage and predisposed the patient to volume overload.", "We evaluated the safety, pharmacokinetics, and pharmacodynamics of diaspirin cross-linked hemoglobin (DCLHb) solution in patients after repair of abdominal aortic aneurysm. We performed a randomized, single-blind controlled study with 10 patients in the surgical intensive care unit of a tertiary care facility. Within 24 hours after repair of an abdominal aortic aneurysm, each patient received an infusion of DCLHb (50 mg/kg or 35 mL for a 70-kg patient) or an equal volume of hetastarch. Variables were measured before infusion, at 15 and 30 minutes postinfusion, and at hourly intervals up to 72 hours. Compared with controls, the experimental group had significantly greater mean pulmonary artery pressure at 30 minutes (mean +/- SD, 26.4 +/- 3.18 vs. 22.8 +/- 2.86 mm Hg), greater mean arterial pressure through 30 minutes (100.8 +/- 8.67 vs. 81.6 +/- 13.8 mm Hg), and greater plasma hemoglobin through 2 hours (69.3 +/- 6.08 vs. 1.8 +/- 0 g/dL). Cardiac output was significantly less in the DCLHb group at 2 hours (5.34 +/- 7.92 vs. 6.18 +/- 0.54 L/minute), levels of serum bilirubin were significantly less at 24 and 48 hours (94 +/- 0.26 vs. 1.56 +/- 0.73 mg/dL), and platelet counts were significantly greater at 24 hours (128 +/- 35.8 vs. 101 +/- 55.7 mg/dL). The two groups did not differ in oxygen delivery or consumption. One patient treated with DCLHb had a myocardial infarction 36 hours postinfusion. No patient had antibodies to DCLHb. At this dosage, DCLHb was well tolerated without severe organ dysfunction or toxicity. However, its use may lead to decreases in cardiac output because of increases in afterload, which may pose serious problems with left ventricular function.", "The effects of hetastarch and human albumin solutions on perioperative bleeding and coagulation parameters during abdominal aortic aneurysm repair were compared. In two randomized groups of 20 patients, albumin 5% (group 1) or hetastarch 6% (group 2) 1 g/kg was given during surgery. The remaining perioperative fluids consisted of lactated ringers and packed red blood cells. Perioperative coagulation measurements included partial thromboplastin time, prothrombin time, activated clotting time, platelet count, and bleeding time. Estimated blood loss and the total amount of crystalloid and blood infused were also measured. The surgeon, blind to the colloid used, subjectively rated bleeding on a scale of 1 to 10. There was no significant difference between groups for any measured parameter at any time. Measurements of coagulation function were within normal limits for both groups. Hetastarch does not cause clotting disorders in patients undergoing abdominal aortic aneurysm repair, at least if the quantities used in this study are not exceeded.", "The hypothesis that increased intraoperative blood lactate depends both on intraoperative glucose supply and inadequate tissue oxygenation occurring during surgery was tested in anesthetized patients undergoing infrarenal abdominal aortic surgery. Twenty surgical patients received either Ringer's solution or 5% glucose solution for intraoperative volume loading. Arterial blood lactate, arterial glucose, hemodynamic variables, insulin, glucagon, cortisol, epinephrine, and norepinephrine were determined preoperatively and intraoperatively. There were no significant changes in hemodynamic values, glucagon, norepinephrine, and epinephrine compared with control values in both groups. Oxygen consumption decreased only during aortic clamping. Cortisol and lactate increased significantly 10 min after aortic clamping until the end in both groups. Glucose 5% solution infusion resulted in significantly greater blood lactate accumulation and significantly greater blood glucose and insulin levels, whereas there were no changes in the patients receiving Ringer's solution. From control until aortic clamping, lactate and glucose were significantly correlated with each other in both groups; after aortic clamping until the end of the procedure, the correlation remained constant in patients in the Ringer's group, whereas no relationship could be demonstrated in those in the glucose group. The authors conclude that intraoperative glucose administration increases intraoperative blood lactate and that blood lactate accumulation depends both on glucose supply and tissue oxygen deficit. Furthermore, none of the hemodynamic metabolic and endocrine factors were reliable for assessing tissue perfusion and metabolic demands during surgery.", "To determine if gastric intramucosal pH (pHi)-guided therapy reduces the number of complications and length of stay in the intensive care unit (ICU) or the hospital after elective repair of infrarenal abdominal aortic aneurysms.\n Prospective, randomized study.\n Surgical intensive care unit (SICU) of a University Hospital.\n Fifty-five consecutive patients randomized to group 1 (pHi-guided therapy) or to group 2 (control).\n Patients of group 1 with a pHi of lower than 7.32 were treated by means of a prospective protocol in order to increase their pHi to 7.32 or more.\n pHi was determined in both groups on admission to the SICU and thereafter at 6-h intervals. In group 2, the treating physicians were blinded for the pHi values. Complications, APACHE II scores, duration of endotracheal intubation, fluid and vasoactive drug treatment, treatment with vasoactive drugs, length of stay in the SICU and in the hospital and hospital mortality were recorded. There were no differences between groups in terms of the incidence of complications. We found no differences in APACHE II scores on admission, the duration of intubation, SICU or hospital stay, or hospital mortality. In the two groups the incidence of pHi values lower than 7.32 on admission to the SICU was comparable (41% and 42% in groups 1 and 2, respectively). Patients with pHi lower than 7.32 had more major complications during SICU stay (p < 0.05), and periods more than 10 h of persistently low pHi values (< 7.32) were associated with a higher incidence of SICU complications (p < 0.01).\n Low pHi values (< 7.32) and their persistence are predictors of major complications. Treatment to elevate low pHi values does not improve postoperative outcome. Based on these data, we cannot recommend the routine use of gastric tonometers for pHi-guided therapy in these patients. Further studies are warranted to determine adequate treatment of low pHi values that results in beneficial effects on the patient's postoperative course and outcome.", "In two consecutive studies (Study A and Study B), we evaluated the effects of increasing doses of HBOC-201, a bovine hemoglobin-based oxygen carrier, on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. After the induction of anesthesia and the exchange of 1 L of blood for 1 L of lactated Ringer's solution, 24 patients (12 in each study) were randomly assigned to receive, within 30 min, a predetermined volume of either HBOC-201 or 6% hydroxyethyl starch (Study A 6.9 mL/kg; Study B 9.2 mL/kg). Monitored variables included systemic and pulmonary arterial pressures, arterial and mixed venous blood gases, and calculations of cardiac index (CI), systemic (SVRI) and pulmonary (PVRI) vascular resistance indices, oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER). In both studies, the infusion of HBOC-201 was associated with increases in SVRI (Study A 121%; Study B 71%) and PVRI (Study A 70%; Study B 53%) and with a decrease in CI (29% both studies). Hemodilution with HBOC-201 maintained the arterial oxygen content at levels higher than hemodilution with hydroxyethyl starch, but the advantage of a greater oxygen-carrying capacity was offset by the increase in SVRI, with a resulting net decrease in both CI and DO2I (Study A 30%; Study B 28%); VO2I was maintained by increased O2ER. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch. Implications: Bovine hemoglobin in doses ranging between 55 and 97 g of hemoglobin increased vascular resistance and decreased cardiac output in anesthetized surgical patients. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch.", "In a prospective randomized trial of 16 patients undergoing abdominal vascular reconstructive procedures, changes in plasma volume, serum oncotic pressure (pis), serum albumin and total protein concentration, alveolar to arterial oxygen tension differences (AaDO2, FIO2 = 1.0), creatinine clearance, body weight, and fluid and sodium intake were examined. By random assignment patients received either an albumin- or a sodium-rich intraoperative fluid regimen. Pulmonary arteriovenous admixture was significantly less in the albumin group (n = 7) than in the electrolyte group (n = 9) on the first postoperative day. The change in AaDO2 correlated positively with the total sodium intake in the electrolyte group. Despite the larger fluid load and significantly greater gain of body weight, patients in the electrolyte group had a postoperative plasma volume significantly lower than the preoperative value. Postoperative values of albumin concentration, circulating albumin mass and pis were significantly greater in the albumin group in comparison to the electrolyte group. Creatinine clearance values were not different between the two groups. The change in pis correlated significantly with sodium intake and circulating albumin mass. Pulmonary shunting and expansion of the extracellular fluid volume may be minimized without adverse effects on renal function by administration of fluids rich in albumin in preference to sodium.", "The optimal colloid for renal protection during abdominal aortic aneurysm (AAA) surgery is not known. This study compared the effects of two hydroxyethyl starch (HES) solutions and gelatine on perioperative renal function.\n Sixty-two patients undergoing AAA surgery were randomized to 6 per cent HES of molecular weight 200/0.62 kDa or 130/0.4 kDa, or 4 per cent gelatine for plasma expansion. Measurements were taken of serum urea and creatinine to mark glomerular filtration, urinary immunoglobulin G : creatinine ratio to mark glomerular membrane function and alpha(1)-microglobulin : creatinine ratio to mark tubular dysfunction before, and for 5 days after, surgery.\n Serum urea was lower in both HES groups than the gelatine group. Serum creatinine was lower with HES 130/0.4 compared with gelatine at days 1, 2 and 5 after surgery (P = 0.020, P = 0.045 and P = 0.045 respectively). Urinary alpha(1)-microglobulin : creatinine ratio was lower with HES 200/0.62 compared with gelatine at 4 and 8 h (P < 0.050) and lower with HES 130/0.4 compared with gelatine at 4 to 24 h, and on days 4 and 5 (P < 0.050). Urinary immunoglobulin G : creatinine was lower in both HES groups compared with gelatine. There was no difference between the two starch groups.\n Compared with gelatine, volume expansion with both types of HES during AAA surgery improved renal function and reduced renal injury.", "Intentional normovolemic hemodilution was chosen as the model to compare a 6% low molecular weight hydroxyethyl starch (LMW HES) to 4% albumin. The study ran over the plasma exchange period for 24 h. Nine patients, scheduled for abdominal aortic surgery, were included in each group. After basal measurements, blood was withdrawn and simultaneously replaced by either 4% albumin (Group 1) or 6% LMW HES (Group 2) to achieve a final hematocrit of approximately 30%. Hemodynamic blood oxygen gas and hormonal plasma levels were determined before hemodilution then at 30 min, 1, 2, 3, and 24 h after the end of hemodilution. Basal value for total blood volume was 4377 +/- 162 ml in group 1 and 4138 +/- 315 ml in group 2. As in both groups the decrease in blood cell volume was exactly compensated by the increase in plasma volume, no significant change in total blood volume (respectively 4432 +/- 159 and 4305 +/- 267 ml) was observed. Throughout the study, in both groups, no significant change in mean arterial and right atrial pressures was observed. In group 2 (LMW HES), a significant increase of pulmonary capillary wedge pressure was noted 120 min after hemodilution. After hemodilution, despite a significant decrease in arterial oxygen O2 content, systemic oxygen transport did not significantly vary until 24 h in relation to the increased cardiac index. An increase in O2 extraction was observed after the exchange but no further increase was observed until the 24 h. No significant changes either in global O2 consumption or in lactate concentration were detected.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "11932085", "10530535", "7726351", "18434457", "12473699" ]

[ "Comparative study of intra-articular lidocaine and intravenous meperidine/diazepam for shoulder dislocations.", "Anesthetic methods for reduction of acute shoulder dislocations: a prospective randomized study comparing intraarticular lidocaine with intravenous analgesia and sedation.", "Intraarticular lidocaine versus intravenous analgesic for reduction of acute anterior shoulder dislocations. A prospective randomized study.", "Intra-articular lidocaine versus intravenous meperidine/diazepam in anterior shoulder dislocation: a randomised clinical trial.", "Comparison of intra-articular lidocaine and intravenous sedation for reduction of shoulder dislocations: a randomized, prospective study." ]

[ "The purpose of this study was to compare the analgesic effectiveness of intra-articular lidocaine versus intravenous meperidine and diazepam during the reduction of anterior shoulder dislocations. Patients were randomized to one of the two methods before the reduction of shoulder dislocations. Patients marked a visual analog pain scale at baseline, after anesthesia just before reduction, and at the time of discharge. Interference with the procedure caused by pain or lack of muscle relaxation, perception of adequacy of analgesia by the patient, adverse effects, and time to discharge from the Emergency Department (ED) were measured. Differences of outcomes, relative risks (RR), and 95% confidence intervals (CIs) were derived. Fifty-four patients with anterior shoulder dislocations presenting from May 21, 1998 through January 21, 1999 were included in this study; 29 were randomly assigned to receive intra-articular lidocaine (IAL) and 25 to receive intravenous meperidine/diazepam (IVMD). IAL was less effective than IVMD in relieving pre-reduction pain (p = 0.045) but equally effective in overall pain relief (p = 0.98). IAL was more effective than IVMD in shortening recovery time (p = 0.025). There was an indication favoring IVMD in terms of physician-perceived muscle relaxation and patient's perception of analgesia adequacy. In conclusion, although the IVMD method appears to have some clinically and statistically significant advantages, IAL possesses some favorable features that render it to be an analgesia alternative in shoulder dislocation reduction.", "A prospective, randomized, nonblinded clinical trial was undertaken to evaluate whether local intraarticular lidocaine injection (IAL) is equally effective in facilitating reduction of acute anterior shoulder dislocations (AASD) as intravenous analgesia/sedation (IVAS). The setting was an urban, Level 1, trauma center. Patients enrolled presented to the emergency department (ED) with radiographically confirmed AASD and were randomized either to the IVAS group or the IAL group. Ease of reduction and pain associated with reduction were measured subjectively using a 10-point scale. There were 49 patients entered into the study, 20 in the IVAS group and 29 in the IAL group. There was no statistically significant difference between mean +/- SD pain scores of 3.32+/-2.39 in the IVAS group and 4.90+/-2.34 in the IAL group (P = .18), or mean +/- SD ease of reduction scores of 3.32+/-2.36 in the IVAS group and 4.45+/-2.46 in the IAL group (P = .12). Although IVAS tended to have a higher success rate (20 of 20) than IAL (25 of 29) in this study, Kaplan-Meier estimates for delayed time-events curves applying the log-rank test showed that this difference was not statistically significant overall (P = .16). However, with reduction rate evaluated as a function of time delay in seeking treatment, patients presenting 5.5 hours after dislocation were more likely to fail treatment with IAL (P = .00001). Additionally, half of the patients in the IAL group who had experience with IVAS did not favor IAL. Emergency physicians should be aware of IAL as an alternative technique that may be considered in patients when there are reasons to avoid systemic analgesia or sedation.", "We performed a prospective, randomized study to evaluate the use of injected lidocaine as an anesthetic for closed reduction of acute anterior shoulder dislocations. Thirty consecutive patients who presented at the emergency department with acute anterior shoulder dislocations were randomly placed in one of two groups. One group received an intraarticular injection of 20 ml of 1% lidocaine and the other group, intravenous injections of morphine sulfate and midazolam. The groups were compared regarding time of reduction maneuver, difficulty of reduction, subjective pain, complications, and total time spent in the emergency department. The lidocaine provided adequate anesthesia and secondary relief of muscle spasm in 15 of 15 (100%) patients. When compared with the intravenous sedation group, the lidocaine group showed no statistically significant difference in time for reduction maneuver, difficulty of reduction, or subjective pain. The lidocaine group had no complications and had a statistically significant shorter emergency department visit when compared with the intravenous sedation group (mean, 78 minutes versus 186 minutes; P = 0.004). Lidocaine provides excellent anesthesia for patients with uncomplicated anterior shoulder dislocations and can be very beneficial when sedation is contraindicated. Lidocaine injections also proved to be cost effective in our institution, reducing total costs by as much as 62%.", "Anterior shoulder dislocation is one of the most common complaints of patients referred to emergency departments. Intravenous opiates and benzodiazepines are traditionally prescribed in order to relieve the pain in this group of patients; however, complications always pose a problem.\n To compare the pain relief and complications following intra-articular lidocaine and intravenous meperidine/diazepam in patients with anterior shoulder dislocation.\n 48 patients with non-habitual traumatic anterior dislocation of the glenohumoral joint admitted to Imam Khomeini hospital emergency department were enrolled in this randomised clinical trial. They were divided into two groups: one group of patients received intra-articular lidocaine 1%, while the other received intravenous meperidine and diazepam. Closed reduction using the countertraction-traction method was performed by a single person in all the patients. Utilising a 100 mm visual analogue scale, each patient's pain was recorded before injection, before reduction, and after reduction.\n Mean pain (mm) recorded before injection, before reduction, and after reduction in the intra-articular lidocaine group was 84.3 (95% confidence interval (CI) 79.8 to 88.8), 52.6 (95% CI 45.2 to 60.1), and 27.3 (95% CI 19.9 to 34.7), respectively. The corresponding rates in the intravenous meperidine/diazepam group were 83.2 (95% CI 79.2 to 87.2), 57.9 (95% CI 53.8 to 62.0), and 23.9 (95% CI 18.9 to 28.8), respectively. Both groups demonstrated a similar significant decline in pain after injection (p<0.005). No severe complications were reported in either of the groups.\n Intra-articular injection of lidocaine before closed reduction of anterior shoulder dislocation produces the same pain relief as intravenous meperidine and diazepam.", "Acute anterior glenohumeral dislocations have been commonly treated with closed reduction and the use of intravenous sedation. Recently, the use of intra-articular lidocaine has been advocated as an alternative to sedation, since intravenous access and patient monitoring are not required. The purpose of this study was to evaluate the value of local anesthesia compared with that of the commonly used intravenous sedation during the performance of a standardized reduction technique.\n In a prospective, randomized study, skeletally mature patients with an isolated glenohumeral joint dislocation and no associated fracture were randomized to receive either intravenous sedation or intra-articular lidocaine to facilitate reduction of the dislocation. Reduction was performed with the modified Stimson method. The two groups were compared with regard to the rate of successful reduction, pain as rated on a visual analog scale, time required for the reduction, time from the reduction until discharge from the emergency department, and cost.\n Thirty patients were enrolled in the study. Five (two in the lidocaine group and three in the sedation group) required scapular manipulation in addition to the Stimson technique to reduce the dislocation. The lidocaine group spent significantly less time in the emergency department (average time, seventy-five minutes compared with 185 minutes in the sedation group, p < 0.01). There was no significant difference between the two groups with regard to pain (p = 0.37), success of the Stimson technique (p = 1.00), or time required to reduce the shoulder (p = 0.42). The cost of the intravenous sedation was $97.64 per patient compared with $0.52 for use of the intra-articular lidocaine.\n Use of intra-articular lidocaine to facilitate reduction with the Stimson technique is a safe and effective method for treating acute shoulder dislocations in an emergency room setting. Intra-articular lidocaine requires less money, time, and nursing resources than does intravenous sedation to facilitate reduction with the Stimson technique." ]

[ "6499689", "4028625", "6466260", "4876723", "6873137", "3044323", "3539128", "7009021", "15354005" ]

[ "[Prevention of motion sickness with a transdermal therapeutic system containing scopolamine. A randomized, comparative double-blind study in the German Federal Navy].", "Influence of transdermal scopolamine on motion sickness during 7 days' exposure to heavy seas.", "Drug treatment of motion sickness: scopolamine alone and combined with ephedrine in real and simulated situations.", "Side-effects of 1-hyoscine and cyclizine studied by objective tests.", "Psychomotor, physiological and cognitive effects of scopolamine and ephedrine in healthy man.", "The Republic of Singapore Navy's Scopoderm TTS study: results after 2,200 man-days at sea.", "[Comparative in-flight study of a scopolamine-containing membrane plaster versus dimenhydrinate under defined acceleration conditions].", "Transdermal scopolamine in the prevention of motion sickness at sea.", "Stimulation of the semicircular canals via the rotary chair as a means to test pharmacologic countermeasures for space motion sickness." ]

[ "To test the prophylactic value of anti-motion sickness drugs, a randomized double-blind trial was undertaken on 46 young, healthy, male volunteer marines. Comparison was made between a transdermal therapeutic system (TTS) containing as the effective agent scopolamine (TTS-scopolamine) and proprietary meclozine tablets. An artificial \"sea voyage\" served to produce motion sickness, each subject sitting by himself on an artificially tilting \"island\", on two days for 30 minutes. Without treatment, 19 of the 46 subjects developed symptoms of motion sickness requiring treatment. After administration of TTS-scopolamine or meclozine tablets (double-dummy technique) the motion sickness score was reduced by 89% and 59%, respectively. There was a reduction on the visual analog scale of 98% and 59%, respectively. Probability of error (Fisher's exact probability test) for assuming therapeutic advantage of TTS-scopolamine over meclozine tablets was 13.5%. A pre-set significance level of 5% was thus not reached. This trial shows that TTS-scopolamine, even in a brief exposure, has at least the same effectiveness as meclozine, in addition to avoiding the gastrointestinal tract and maintaining with certainty a constant blood level over three days.", "We conducted a double-blind, placebo-controlled study to evaluate the efficacy and tolerability of transdermal scopolamine in the prevention of motion sickness (MS) aboard a frigate during 7 days of continuously moderate or heavy seas. Forty-nine healthy sailors with a previous history of MS were randomly assigned to receive a transdermal therapeutic system of scopolamine (TTS-S) or transdermal placebo (TD-P). Patches were placed behind the ears at least 4 hours before departure and were removed 72 hours later. Subjects were observed on days 1 to 4 and 6. In the TTS-S group, both subjective feeling of MS and the incidence of nausea were reduced during the first 2 days. Because of adaptation, differences in signs and symptoms of MS between subjects receiving TTS-S and TD-P disappeared after the second day. During the first 3 days, vomiting occurred less often in the TTS-S group. On day 6, 3 days after removal of the patch, vomiting occurred in 23% of the TTS-S group, probably due to delay in adaptation, but none of the subjects in the TD-P group vomited. Concentration was not adversely influenced, since the ability to work increased in the TTS-S group. During prolonged continuous exposure to heavy and moderate seas, 2.5 cm2 TTS-S discs proved to be efficacious in preventing MS, with xerostomia as a tolerable side effect and no significant ocular side effects.", "In two placebo-controlled, double-blind, randomized trials scopolamine (0.3 mg) alone or combined with ephedrine (25 mg) was tested for its effectiveness in the prevention of seasickness during 24 h at sea and of motion sickness in rotating chair tests in a laboratory. Scopolamine was effective both alone and in combination with ephedrine, which supports the hypothesis on central cholinergic overactivity in the pathogenesis of motion sickness. Ephedrine did not markedly increase the effectiveness of scopolamine. Side-effects were slight and did not disturb the operating ability of the volunteers.", "nan", "Three placebo-controlled double-blind studies in healthy volunteers were performed to reveal the psychophysiological effects of scopolamine, ephedrine and their combination. Single intravenous dose of scopolamine 6 micrograms/kg (scopolamine hydrobromide 7.4 micrograms/kg) impaired various psychomotor functions both subjectively and objectively. It caused sedation, impairment of coordinative and reactive skills, visual disturbances and impairment of shortterm memory. Oral scopolamine hydrobromide in single doses of 0.3 mg and 0.9 mg, or 0.9 mg b.d. for 3 days, had few effects. A slight impairment of shortterm memory and a decrease in the flicker fusion threshold were seen. The visual nearpoint and pupil diameter were increased and some subjects reported blurred vision and dizziness during treatment with scopolamine 0.9 mg b.d. Scopolamine showed clear cardiovascular effects in all studies: it decreased heart rate and systolic blood pressure. Ephedrine alone and in combination with scopolamine had no deleterious effects. On the contrary, it antagonized the scopolamine-induced impairment in the flicker fusion test and the decrease in blood pressure and heart rate. In sufficient doses scopolamine impairs various psychomotor and cognitive skills. An oral dose of scopolamine hydrobromide 0.9 mg on average has few effects, although they may be very striking in certain individuals. To avoid unwanted effects and diminution in performance by scopolamine, doses less than 0.9 mg should be used.", "Most clinical trials investigating prevention of seasickness with transdermal scopolamine have been short-term, and little information regarding long-term use is available. We report here a double-blind trial conducted on board a flat-bottomed Republic of Singapore Navy vessel of 2,490 tons, sailing in the South China Sea. The trip lasted 26 d, but self-assessment by the 122 adult male participants (using a simplified scale quantifying the level of seasickness) was confined to the 18 d spent at sea. We found that the protection rate with transdermal scopolamine was 46-57%, with maximum benefits to inexperienced participants, during the early preadaptation phase, or in rough seas even after adaptation. Unwanted effects were few and generally minor. We concluded that the benefits of Scopoderm were worth exploiting even for long trips in moderate-to-rough seas.", "The efficacy and tolerability of Scopoderm TTS (SCOTTS), a transdermal system containing scopolamine, were compared with those of the oral antiemetic dimenhydrinate (double-dummy technique) in a controlled, double-blind, within-patient study including 20 test persons with proven motion sickness. During a 1-h test flight, SCOTTS proved to be as effective as dimenhydrinate. The efficacy and tolerability of both SCOTTS and dimenhydrinate were assessed as to be equally good. Due to its galenic properties, SCOTTS is effective over a 72-h period and therefore is useful in the prevention of motion sickness during long-distance flights, where it is superior to dimenhydrinate.", "Studies were conducted to evaluate the efficacy of scopolamine, absorbed through intact skin, in preventing motion sickness at sea. Efficacy of transdermal scopolamine was compared with oral dimenhydrinate and placebo. Transdermal applications were made 4 to 16 hr before exposure to motion. Dimenhydrinate or placebo was given 1.5 hr before motion and again 2.5 hr after motion began. Comparison with placebo indicated that transdermal scopolamine provided protection against motion sickness at a significance level of p = 0.0001 and oral dimenhydrinate at a level of p = 0.05. Dry mouth, drowsiness, and blurred vision associated with transdermal scopolamine therapy were minimal.", "Space motion sickness is currently treated pharmacologically with the empiric use of the H1 antihistamine promethazine, but use of this intervention is limited by the side effect of significant sedation. This creates a dilemma, as full cognition is particularly important during the same conditions likely to exacerbate the symptoms of space motion sickness. Using overstimulation of the semicircular canals with a rotary chair as a paradigm for space motion sickness, we evaluated four medications, commonly used for the treatment of terrestrial motion sickness and vertigo, for their efficacy in alleviating the simulated symptoms of space motion sickness.\n Randomized, prospective, double-blind study.\n Tertiary referral center.\n Healthy male and female volunteers, 18 years of age or older, without history of neurologic or psychiatric disorders, and with no known allergies or any previous adverse reactions to the drugs used.\n Lorazepam 1 mg, meclizine 25 mg, promethazine 25 mg, scopolamine 0.4 mg, or placebo.\n The ability of each treatment to control the nausea and vomiting associated with our paradigm for space motion sickness was evaluated by measuring time of rotation pre- and posttreatment and time of symptom onset pre-and posttreatment.\n Only scopolamine effected a mean change in duration of rotation that reached statistical significance when compared with placebo (p <0.008), with a greater than 40% increase in rotation time. Results with promethazine were not statistically significant.\n Results showed a rank order of efficacy of scopolamine > promethazine > placebo > meclizine > lorazepam. Scopolamine significantly increased rotation time, but none of the treatments resulted in a significant delay to onset of symptoms." ]

[ "1679154" ]

[ "Heparin treatment in sinus venous thrombosis." ]

[ "Treatment of sinus venous thrombosis (SVT) is controversial. Although heparin has been used for this condition, many investigators have opposed its use because of the frequent occurrence of intracranial haemorrhage (ICH) and SVT. Therefore we have evaluated anticoagulation with adjusted-dose intravenous heparin for treatment of aseptic SVT in a randomised, blinded (patient and observer), placebo-controlled study in 20 patients (10 heparin, 10 placebo). The clinical course of the two groups, as judged by a newly designed SVT-severity scale, started to differ in favour of the heparin group after 3 days of treatment (p less than 0.05, Mann-Whitney U-test) and the difference remained significant (p less than 0.01) after 8 days of treatment. After 3 months, 8 of the heparin-treated patients had a complete clinical recovery and 2 had slight residual neurological deficits. In the placebo group, only 1 patient had a complete recovery, 6 patients had neurological deficits, and 3 patients died (p less than 0.01, modified Fisher's exact test). An additional retrospective study on the relation between heparin treatment and ICH in SVT patients was based on 102 patients, 43 of whom had an ICH. 27 of these patients were treated with dose-adjusted, intravenous heparin after the ICH. Of these 27 patients, 4 died (mortality 15%), and 14 patients completely recovered. Of the 13 patients that did not receive heparin after ICH, 9 died (mortality 69%) and only 3 patients completely recovered. We conclude that anticoagulation with dose-adjusted intravenous heparin is an effective treatment in patients with SVT and that ICH is not a contraindication to heparin treatment in these patients." ]

[ "12480612", "9516091", "1679870" ]

[ "Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis.", "Placebo-controlled, double-blind, randomized study of aerosolized tobramycin for early treatment of Pseudomonas aeruginosa colonization in cystic fibrosis.", "Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment." ]

[ "We conducted a double-blind, placebo-controlled, multicenter, randomized trial to test the hypothesis that 300 mg of tobramycin solution for inhalation administered twice daily for 28 days would be safe and result in a profound decrease in Pseudomonas aeruginosa (Pa) density from the lower airway of young children with cystic fibrosis. Ninety-eight subjects were to be randomized; however, the trial was stopped early because of evidence of a significant microbiological treatment effect. Twenty-one children under age 6 years were randomized (8 active; 13 placebo) and underwent bronchoalveolar lavage at baseline and on Day 28. There was a significant difference between treatment groups in the reduction in Pa density; no Pa was detected on Day 28 in 8 of 8 active group patients compared with 1 of 13 placebo group patients. We observed no differences between treatment groups for clinical indices, markers of inflammation, or incidence of adverse events. No abnormalities in serum creatinine or audiometry and no episodes of significant bronchospasm were observed in association with active treatment. We conclude that 28 days of tobramycin solution for inhalation of 300 mg twice daily is safe and effective for significant reduction of lower airway Pa density in young children with cystic fibrosis.", "In chronic Pseudomonas aeruginosa pulmonary infection of patients with cystic fibrosis (CF), antibiotic therapy generally fails to eradicate the bacterial pathogen. The mucoid bacterial phenotype, high sputum production by the host, and low airway levels of antibiotics seem to be responsible for the observed decrease in antibiotic efficacy. We hypothesized that early antibiotic treatment by inhalation in CF patients may be able to prevent or at least delay airway infection. In a prospective placebo-controlled, double-blind, randomized multicenter study, 22 CF patients received either 80 mg b.i.d. of aerosolized tobramycin or placebo for a period of 12 months shortly after the onset of P. aeruginosa pulmonary colonization. Two patients in the tobramycin and six patients in the placebo group stopped inhalation before the 12 month treatment period. Using life table analysis, the time to conversion from a P. aeruginosa-positive to a P. aeruginosa-negative respiratory culture was significantly shorter in the tobramycin-treated group than in the placebo group (P < 0.05, log rank test). Lung function parameters and markers of inflammation did not change in either group during treatment. The results of this study suggest that early tobramycin inhalation may prevent and/or delay P. aeruginosa pulmonary infection in CF patients.", "To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable, 26 patients who had never received anti-pseudomonas chemotherapy were randomly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks, whenever Ps aeruginosa was isolated from routine sputum cultures. During the 27 months of the trial, infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects (2 [14%] vs 7 [58%]; p less than 0.05) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group (49/214 [23%] vs 64/158 [41%]; p = 0.0006). Thus, chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy." ]

[ "12468166", "1495689", "7779245", "9228499", "9241004", "18344730", "10418540", "15385695", "17035933", "17107257", "12220761", "10530636", "11952025", "18517289", "9109106", "14754784", "9307345", "9378691", "9501889", "7739706", "9790157", "2071558", "16098854" ]

[ "Efficacy of intermittent, luteal phase sertraline treatment of premenstrual dysphoric disorder.", "Treatment of premenstrual syndrome with fluoxetine: a double-blind, placebo-controlled, crossover study.", "The serotonin reuptake inhibitor paroxetin is superior to the noradrenaline reuptake inhibitor maprotiline in the treatment of premenstrual syndrome.", "Fluoxetine in the treatment of premenstrual syndrome.", "Comparison of fluoxetine, bupropion, and placebo in the treatment of premenstrual dysphoric disorder.", "Escitalopram administered in the luteal phase exerts a marked and dose-dependent effect in premenstrual dysphoric disorder.", "Luteal phase sertraline treatment for premenstrual dysphoric disorder. Results of a double-blind, placebo-controlled, crossover study.", "Paroxetine controlled release for premenstrual dysphoric disorder: a double-blind, placebo-controlled trial.", "Placebo-controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder.", "Low-dose sertraline in the treatment of moderate-to-severe premenstrual syndrome: efficacy of 3 dosing strategies.", "Premenstrual daily fluoxetine for premenstrual dysphoric disorder: a placebo-controlled, clinical trial using computerized diaries.", "Differential response to antidepressants in women with premenstrual syndrome/premenstrual dysphoric disorder: a randomized controlled trial.", "Weekly luteal-phase dosing with enteric-coated fluoxetine 90 mg in premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled clinical trial.", "Luteal phase administration of paroxetine for the treatment of premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled trial in Canadian women.", "Fluoxetine in the treatment of premenstrual dysphoria.", "Continuous or intermittent dosing with sertraline for patients with severe premenstrual syndrome or premenstrual dysphoric disorder.", "Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group.", "Intermittent luteal phase sertraline treatment of dysphoric premenstrual syndrome.", "Treatment of premenstrual dysphoric disorder with sertraline during the luteal phase: a randomized, double-blind, placebo-controlled crossover trial.", "Fluoxetine in the treatment of premenstrual dysphoria. Canadian Fluoxetine/Premenstrual Dysphoria Collaborative Study Group.", "Citalopram in premenstrual dysphoria: is intermittent treatment during luteal phases more effective than continuous medication throughout the menstrual cycle?", "Fluoxetine in the treatment of late luteal phase dysphoric disorder.", "Luteal phase dosing with paroxetine controlled release (CR) in the treatment of premenstrual dysphoric disorder." ]

[ "Premenstrual dysphoric disorder is a menstrually related disorder that intermittently causes disabling emotional, behavioral, and physical symptoms. The goal of the current study was to evaluate the efficacy and tolerability of sertraline for premenstrual dysphoric disorder when treatment was limited to the luteal phase.\n Two hundred eighty-one women who met Diagnostic and Statistical Manual of Mental Disorders (4th edition) criteria for premenstrual dysphoric disorder and who completed two prospective screening cycles and one single-blind placebo cycle were randomized to three cycles of double-blind, luteal phase treatment with either a placebo or sertraline in a flexible daily dose of 50-100 mg. Outcome measures included the Daily Record of Severity of Problems and the Clinical Global Impression Severity and Improvement scales.\n Luteal phase treatment with sertraline was significantly superior to the placebo, as demonstrated by end- point analysis of Clinical Global Impression Improvement scale scores (sertraline, 2.3 +/- 1.1, versus placebo, 2.7 +/- 1.1; P <.001), and cycle 3 Daily Record of Severity of Problems change scores (sertraline, 27.6 +/- 26.8, versus placebo, 17.6 +/- 23.3; P <.002). A significant difference was also noted in responder rates in favor of sertraline (50%) versus placebo (26%, P <.001) by cycle 1 (with responder defined as a Clinical Global Impression Improvement scale score of 1 or 2). Quality of life and functioning outcomes were also significantly improved. Intermittent luteal administration of sertraline was well tolerated, with only approximately 8% of patients on sertraline and less than 1% on placebo discontinuing because of adverse events.\n Sertraline was significantly more effective than a placebo and was well tolerated as a treatment for premenstrual dysphoric disorder when administered intermittently during the luteal phase of the menstrual cycle.", "Although its etiology is unknown, it has been hypothesized that premenstrual syndrome (PMS) is linked to a deficiency of central serotoninergic activity. In the present study, we evaluated the effect of fluoxetine, a specific serotonin uptake inhibitor, on PMS symptoms.\n Following extensive screening, including several psychological inventories, eight women with severe persistent PMS participated in a 6-month double-blind, placebo-controlled, crossover study which included three months each of daily fluoxetine 20 mg or placebo, administered in a randomized order. Symptoms were evaluated using the Calendar of Premenstrual Experiences and other psychometric measures.\n Compared with placebo, treatment with fluoxetine was associated with an improvement in PMS symptoms as judged by highly significant decreases in behavioral (P less than .005), physical (P less than .05), and total (P less than .005) Calendar of Premenstrual Experiences scores; Beck Depression Inventory scores (P less than .005); Profile of Mood States subscales scores including depression (P less than .005), tension (P less than .005), and anger (P less than .01); and State-Trait Anxiety Inventory scores. The use of fluoxetine was associated with a greater mean reduction in behavioral (75%) than in physical scores (40%), with a mean decrease in total Calendar of Premenstrual Experiences scores of 62%, which rendered these scores similar to follicular phase values. Thus, the luteal phase symptomatology of PMS was effectively abolished. At this dose, no significant side effects or complications were noted during treatment.\n Fluoxetine appears to be a highly effective, well-tolerated treatment for the psychological and physical symptoms accompanying severe PMS.", "Recent studies indicate that antidepressant drugs with potent serotonin reuptake inhibiting properties are effective in reducing the symptoms of premenstrual syndrome (PMS). In order to elucidate whether all antidepressant drugs are equally effective in the treatment of PMS or whether potent serotonin reuptake inhibition is a prerequisite for reducing premenstrual complaints, women suffering from severe PMS were treated daily for three menstrual cycles with a selective serotonin reuptake inhibitor, paroxetine (n = 22), or with a selective noradrenaline reuptake inhibitor, maprotiline (n = 21); in addition, a placebo group was included (n = 22). Six symptoms (irritability, depressed mood, tension/anxiety, increased appetite/craving for carbohydrates, bloating, and breast tenderness) were rated by the participants daily throughout the study. With respect to all outcome measurements, the symptom reduction obtained with paroxetine was significantly superior to that obtained with placebo; with respect to irritability, increased appetite/carbohydrate craving, bloating, and breast tenderness, as well as global self-rating, paroxetine was significantly superior also to maprotiline. The clear-cut superiority of paroxetine over maprotiline indicates that not all antidepressant drugs are equally effective in the treatment of PMS; rather, like panic disorder and obsessive compulsive disorder, but in contrast to depression, PMS apparently responds better to serotonin reuptake inhibitors than to antidepressants with a noradrenergic profile.", "Premenstrual syndrome (PMS) is defined as the disabling and cyclic occurrence of emotional and behavioral symptom complex during the latter half of the menstrual cycle. Although its etiology is unknown, it has been speculated that premenstrual syndrome is linked to a deficiency of central serotoninergic activity.\n The study consisted of a double-blind, placebo controlled trial of fluoxetine at a dose of 20 mg/day or placebo for three menstrual cycles. The 440 women who appeared to meet the eligibility criteria were instructed to record the 'Calendar of Premenstrual Experiences' (CPE) scale for two complete menstrual cycles. Of 410 women who successfully completed two cycles of recording their symptoms daily only 35 met the criteria for PMS. These criteria included psychiatric interviews which were made before treatment. Thirty-five PMS patients were randomized into placebo or fluoxetine treatment groups.\n Our study suggests that fluoxetine at a dose of 20 mg per day was significantly superior to placebo in alleviating the symptoms of PMS. The most common side effects were gastrointestinal irritability (15%), insomnia (11%) and sexual dysfunction (8.5%).\n Fluoxetine is an effective and well-tolerated drug and appears to have considerable promise in treating a range of symptoms in women with PMS.", "Serotonergic antidepressants have been shown to be effective treatments for premenstrual dysphoric disorder (PMDD). The efficacy of nonserotonergic antidepressants is less well studied. This study was a two-center, parallel design, placebo-controlled, randomized trial of fluoxetine, bupropion, and placebo in women with PMDD. Thirty-four women with PMDD completed 1 month of single-blind placebo and 2 months of fluoxetine 20 mg/day (N = 10), bupropion 100 mg three times daily (N = 12), or placebo (N = 12). Clinical Global Impressions (CGI) Scale, an expanded form of the Hamilton Rating Scale for Depression (HAM-D), and Global Assessment Scale (GAS) ratings were obtained premenstrually in each of the three treatment cycles. The three treatment groups differed significantly in efficacy by CGI ratings. Fluoxetine was superior to both bupropion and placebo. Comparison of posttreatment to pretreatment HAM and GAS scores demonstrated significant superior efficacy of fluoxetine compared with placebo. Posttreatment HAM and GAS scores for bupropion were intermediate between but not significantly different from fluoxetine or placebo. In summary, fluoxetine was significantly superior to bupropion and placebo as an effective treatment for PMDD. Although some improvement with bupropion was noted, and both medications were well tolerated, patient satisfaction was far greater with fluoxetine.", "This is the first placebo-controlled trial evaluating the efficacy of the selective serotonin reuptake inhibitor (SSRI), escitalopram, in the treatment of premenstrual dysphoric disorder (PMDD). Women with PMDD (intention-to-treat population, n = 151) were treated intermittently for 3 months, during luteal phases only, with 10 mg/d escitalopram, 20 mg/d escitalopram, or placebo. Escitalopram was found to exert a marked and a dose-dependent symptom-reducing effect, 20 mg/d being clearly superior to 10 mg/d. Although the primary outcome parameter, that is, the sum of the symptoms irritability, depressed mood, tension, and affective lability, was decreased by 90% with 20 mg/d escitalopram, the effect of active treatment on breast tenderness, food craving, and lack of energy was more modest and not significantly different from that of placebo; this outcome supports our previous assumption that the former symptoms are more inclined to respond to intermittent administration of an SSRI than are the latter. Although the placebo response was high, the difference between the placebo group and the 20-mg/d escitalopram group with respect to the percentage of subjects displaying 80% or greater reduction in the rating of the cardinal symptom of PMDD, that is, irritability, was considerable: 30% versus 80%. Adverse events were those normally reported in SSRI trials, such as nausea and reduced libido, and were not more common in patients given 20 mg/d of escitalopram than in patients given the lower dose. This study supports the usefulness of escitalopram for the treatment of PMDD and sheds further light on how different components of this syndrome are differently influenced by intermittent administration of an SSRI.", "To test the efficacy of late-luteal phase dosing of sertraline hydrochloride in women with moderate-to-severe premenstrual dysphoric disorder. This highly prevalent disorder often causes significant psychosocial impairment.\n Double-blind, crossover trial of each 2-menstrual cycle of baseline, sertraline treatment, and placebo. Randomization to sertraline treatment vs placebo occurred after a 2-cycle, drug-free period.\n A large outpatient multispecialty clinic in central Texas.\n Fifty-seven women aged 19 to 49 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of premenstrual dysphoric disorder.\n Late-luteal phase treatment with sertraline hydrochloride in daily doses of 50 mg (cycle 1) followed by 100 mg (cycle 2) vs placebo.\n The 22-item calendar of premenstrual experiences was completed daily and constituted the primary outcome measure, consisting of a total score and behavioral and physical factor scores.\n A repeated-measures analysis of variance for crossover designs found a significant beneficial effect from sertraline treatment in improving the calendar of premenstrual experiences total (P < .01), behavioral factor (P < .01), and physical factor (P < .04) scores. Most women improved when taking sertraline, 50 mg, although a dose increase to 100 mg yielded further improvement in approximately 25% of women. Use of sertraline was extremely well tolerated; the only adverse event reported by 10% or more of women was insomnia in 8 (14%) of them.\n Luteal phase treatment with sertraline was a safe and effective treatment for moderate-to-severe premenstrual dysphoric disorder. Further controlled studies are needed to confirm the results of this preliminary study.", "Better characterization of safety and efficacy of multiple doses of selective serotonin reuptake inhibitors for the treatment of a wider range of symptoms of premenstrual dysphoric disorder (PMDD) will provide clinicians with flexibility to provide symptom relief along with acceptable tolerability. This study was designed to assess the efficacy and tolerability of multiple doses of paroxetine controlled release (CR) in PMDD.\n In a multicenter (43 outpatient U.S. sites), placebo-controlled trial, 327 females aged 18 to 45 years, with regular menstrual cycles, meeting DSM-IV criteria for PMDD, were randomly assigned to receive paroxetine CR 12.5 mg; paroxetine CR 25 mg; or placebo, once daily, for up to three treatment cycles. The primary efficacy outcome was change from baseline to end point in mean luteal phase Visual Analogue Scale-Mood (irritability, tension, affective lability, depressed mood) score.\n At end point, subjects treated with paroxetine CR (12.5 mg and 25 mg) demonstrated significant improvement in VAS-Mood scores compared with those who received placebo (paroxetine CR 12.5 mg mean treatment difference vs. placebo, -8.7 mm; 95% CI, -15.7, -1.7; p =.015; paroxetine CR 25 mg mean treatment difference vs. placebo, -12.1 mm; 95% CI, -18.9, -5.3; p <.001). Results were also significant across measures of physical symptoms and social functioning. Paroxetine CR was well tolerated; 9.5% of subjects treated with 12.5 mg and 13.5% of subjects treated with 25 mg withdrew from the trial due to adverse events, compared with 6.5% of subjects in the placebo group.\n Both doses of paroxetine CR 12.5 mg and 25 mg daily are effective and well tolerated in patients who suffer from PMDD. Efficacy with both doses affords greater flexibility to the prescribing physician.", "Serotonin reuptake inhibitors (SRIs) do not have to be administered continuously to be effective for premenstrual dysphoric disorder (PMDD), but can be given during luteal phases only. This is of practical importance, but also of theoretical interest since it suggests that the onset of action of SRIs is shorter in PMDD than in, for example depression. In this study, both continuous and intermittent SRI administration was compared with placebo, with the special purpose of analyzing if different PMDD symptoms respond differently depending on the treatment regimen. To this end, women meeting slightly modified DSM-IV criteria for PMDD (mean+/-SD age, 37+/-6.3 years) were treated for three menstrual cycles with paroxetine continuously, paroxetine during the luteal phase only, or placebo, the population completing at least one treatment cycle comprising 55-56 subjects per group. Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%. The effect size was highest for irritability (1.4) and lowest for lack of energy (0.5). Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms. The study indicates that the response rate when treating PMDD with SRIs is high, and that irritability is a key target symptom. Symptoms such as irritability, affect lability, and mood swings appear to be more inclined to respond rapidly to SRIs, enabling intermittent treatment, than are, for example, the somatic symptoms.", "Many studies have demonstrated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of premenstrual dysphoric disorder, but few studies have investigated the efficacy of SSRIs in the treatment of premenstrual syndrome (PMS). The objective of this study was to evaluate the safety and efficacy of sertraline in the treatment of moderate-to-severe PMS using 3 different dosing strategies: luteal phase (2 cycles), followed by continuous dosing throughout the month (1 cycle), followed by dosing begun at the first onset of PMS symptoms, or \"symptom-onset\" dosing (1 cycle).\n 314 women with PMS from 22 U.S. sites were randomly assigned to fixed-dose treatment with sertraline (25 or 50 mg/day) or placebo for 4 menstrual cycles after a single-blind, placebo lead-in cycle. Assessments included the Daily Symptom Report (DSR), the Clinical Global Impressions-Severity of Illness and -Improvement scales, the Patient Global Evaluation scale, the Quality of Life Enjoyment and Satisfaction Questionnaire, and the Social Adjustment Scale-Self Report.\n Intermittent luteal-phase dosing with low doses of sertraline (25 and 50 mg/day) produced significant improvement across 2 menstrual cycles, based on total DSR scores, compared with placebo. Continuous and symptom-onset dosing were also effective in treating PMS symptoms, particularly at the lower dose of 25 mg/day.\n The results of the current study suggest that low doses of sertraline may be a safe, effective, and well-tolerated treatment for moderate-to-severe PMS.", "To evaluate premenstrual daily dosing with fluoxetine for treatment of premenstrual dysphoric disorder.\n After a two-cycle screening and one-cycle single-blind placebo period, 260 women were randomized to fluoxetine 10 mg, fluoxetine 20 mg, or placebo (dosed daily from 14 days before next expected menses through the first full day of bleeding) for three cycles. Women recorded premenstrual dysphoric disorder symptoms daily using a computerized version of the Daily Record of Severity of Problems.\n Premenstrual daily fluoxetine 20 mg demonstrated significant improvement in mean Daily Record of Severity of Problems luteal scores compared with placebo (P =.005); premenstrual daily fluoxetine 10 mg did not (P =.100). Daily Record of Severity of Problems total scores were statistically significantly improved by the first treatment cycle for both active treatment groups. However, only fluoxetine 20 mg remained statistically significantly superior to placebo throughout the active treatment phase of the trial. Both fluoxetine groups showed significant treatment advantage over placebo for mood-related symptoms (P <.05). Only premenstrual daily fluoxetine 20 mg showed significant treatment advantage over placebo for physical symptoms of breast tenderness (P <.001), bloating (P =.001), and joint/muscle pain (P =.037). Treatment was well tolerated; discontinuations due to adverse events did not differ among the three groups (P =.316).\n Premenstrual daily dosing with fluoxetine effectively treats mood, physical, and social functioning symptoms associated with premenstrual dysphoric disorder. Fluoxetine 20 mg appears to have comparable tolerability with, and better efficacy than, fluoxetine 10 mg.", "Studies show that selective serotonin reuptake inhibitors are effective for severe premenstrual syndrome and premenstrual dysphoric disorder. This study compares the efficacy of a selective serotonin reuptake inhibitor with that of a tricyclic antidepressant to determine whether efficacy for premenstrual syndrome/premenstrual dysphoric disorder is a general or more serotonergic effect of antidepressants.\n After 3 screening months, 189 subjects were randomized to sertraline hydrochloride, desipramine hydrochloride, or placebo for 3 months of double-blind treatment. The flexible dosage range was 50 to 150 mg/d. The outcome measures included the Penn Daily Symptom Report (DSR), the Hamilton Depression Rating Scale, the Clinical Global Impressions-Severity Scale, the Quality of Life Scale, and Patient Global Ratings of Functioning and Improvement. Analyses included all subjects with treatment data, with the last observation carried forward.\n Sertraline was significantly more effective than placebo or desipramine; desipramine was not better than placebo (F2,163 = 12.47, P<.001). All DSR factors were more improved with sertraline compared with desipramine and placebo; the factors for mood (P<.001) and pain (P = .05) were significant, and the results of all outcome measures were consistent. A history of depression, postmenstrual symptom levels, and other diagnostic variables added individually as covariates did not alter the treatment results. At end point analysis, DSR symptoms had decreased by more than 50% in 40 subjects (65%) in the sertraline group, 18 subjects (36%) in the desipramine group, and 16 subjects (29%) in the placebo group (P<.001).\n The comparison of 2 classes of antidepressants strongly favored the serotonergic drug, which effectively reduced symptoms and improved functioning and was well tolerated by women with severe premenstrual syndrome. A history of depression did not alter the treatment results.", "Because the symptoms of premenstrual dysphoric disorder (PMDD) are limited to the luteal phase of the menstrual cycle, the potential benefit of luteal-phase dosing has been hypothesized.\n This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluated the efficacy and tolerability of enteric-coated fluoxetine 90 mg given once or twice during the luteal phase for the treatment of PMDD.\n Study drug was given 14 and 7 days before expected menses during the luteal phase of 3 menstrual cycles. After a screening period and single-blind placebo lead-in period, eligible women were randomized to I of 3 treatment groups: enteric-coated fluoxetine 90 mg on both days (LPWDx2); placebo 14 days before menses and enteric-coated fluoxetine 90 mg 7 days before menses (LPWDx1); or placebo on both days (PLC). The primary efficacy measure was change from baseline in mean luteal-phase scores on the Daily Record of Severity of Problems (DRSP). Secondary efficacy measures included scores on the Rating Scale for Premenstrual Tension Syndrome, Clinician-Rated (PMTS-C); the Clinical Global Impression (CGI)-Severity scale; and the Patient Global Impression (PGI)-Improvement scale. Quality of life was assessed using the Sheehan Disability Scale.\n Two hundred fifty-seven women were randomized to treatment. At the end of the study, the LPWDx2 group had statistically significant improvements in DRSP total, DRSP mood subtotal, DRSP social functioning subtotal, PMTS-C, CGI-Severity, PGI-Improvement, and Sheehan Disability Scale work and family life scores compared with LPWDx1 and PLC (each measure, P < 0.05). There was also a statistically significant improvement in the score on the social life section of the Sheehan Disability Scale with LPWDx2 compared with PLC (P = 0.037). Across all treatment groups, 5 patients discontinued due to nonserious adverse events. Rates of discontinuation for any reason did not differ between the 3 treatment groups.\n The findings of this study support the efficacy and tolerability of enteric-coated fluoxetine 90 mg given twice during the luteal phase of the menstrual cycle for the treatment of PMDD.", "To evaluate the efficacy and safety of intermittent, luteal phase-only administration of paroxetine (10 mg and 20 mg) in the treatment of premenstrual dysphoric disorder (PMDD).\n In this multicenter trial, female outpatients (aged 18-45 years) from 4 Canadian health centers meeting DSM-IV criteria for PMDD were asked to perform daily ratings of their premenstrual symptoms for 2 consecutive menstrual cycles. Those displaying the symptoms of irritability and/or depressed mood in the luteal phases but not in the follicular phases of their menstrual cycles were randomly assigned to intermittent, luteal phase-only treatment with paroxetine 10 mg or 20 mg or placebo for 4 additional cycles. The primary efficacy endpoint was the percent change from baseline at study endpoint on the visual analog scale irritability score. Treatment differences were tested using analysis of covariance ad hoc. Estimated treatment mean differences and their associated 95% confidence intervals were also calculated. Data were collected from May 1999 to November 2002.\n Ninety-nine patients were included in the intention-to-treat population. When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects.\n Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD. These results are consistent with previous studies suggesting that PMDD may be treated effectively by luteal phase-only administration of a selective serotonin reuptake inhibitor.\n clinicaltrials.gov Identifier: NCT00620581.", "We performed a double-blind, placebo-controlled, crossover trial of fluoxetine in 17 women with prospectively confirmed PMS who also met criteria for premenstrual dysphoric disorder (PMDD). A subset of 10 women with PMDD and an additional 10 controls participated in a single-dose m-chlorophenylpiperazine (m-CPP) challenge during the follicular and luteal phases of the menstrual cycle. We evaluated the ability of the acute behavioral response to luteal phase m-CPP administration to predict therapeutic response to fluoxetine. compared with baseline, fluoxetine, but not placebo, treatment significantly improved both emotional and physical symptoms. We identified 11 (65%) fluoxetine responders who no longer met diagnostic criteria for PMDD during fluoxetine but remained symptomatic during placebo treatment. In addition, acute symptomatic improvement also occurred following m-CPP administration in 7 of 10 women with PMDD. The small number of m-CPP nonresponders did not respond to fluoxetine either. Our findings confirm that fluoxetine is an effective treatment of PMDD.", "The authors compared the efficacy and acceptability of continuous versus intermittent treatment with a selective serotonin reuptake inhibitor in women with severe premenstrual syndrome and determined the effects of postmenstrual symptom severity and depression history as covariates of the treatment response.\n Patients who met symptom criteria and reported impaired functioning after three screening cycles were randomly assigned to three cycles of double-blind, placebo-controlled treatment with continuous (full-cycle dosing) or intermittent (luteal-phase dosing) sertraline. The design was stratified for severity of postmenstrual symptoms and history of major depression. Flexible sertraline dose was 50-100 mg/day. Outcome measures were the Daily Symptom Rating Form score and patient global ratings of functioning.\n Both sertraline groups improved significantly more than the placebo group as assessed by total premenstrual Daily Symptom Rating Form scores for 3 treatment months. Daily Symptom Rating Form factors that were significantly more improved in the sertraline groups were mood and physical symptoms. Sertraline improvement occurred swiftly in the first month of treatment. Gradual placebo improvement was similar to sertraline in the third month. Subjects with higher postmenstrual symptoms before treatment remained more symptomatic regardless of the dosing regimen. A history of major depression was not associated with treatment response. More sertraline-treated subjects reported improved functioning in the domains of family relationships, social activities, and sexual activity.\n Premenstrual dosing does not differ from continuous dosing with sertraline in premenstrual syndrome treatment. Higher levels of postmenstrual symptoms limit treatment response and are important to define in treatment of premenstrual syndrome.", "Premenstrual dysphoric disorder is an important cause of symptoms and functional impairment in menstruating women.\n To evaluate the efficacy of sertraline hydrochloride for treatment of premenstrual dysphoria by measuring changes in symptom expression and functional impairment.\n Two screening cycles followed by 1 single-blind placebo cycle and 3 cycles of randomized, double-blind, placebo treatment.\n Twelve university-affiliated outpatient psychiatry and gynecology clinics.\n Of the 447 women who requested participation, 243 met criteria for premenstrual dysphoric disorder and were randomized; 200 women completed the study.\n A flexible (50-150 mg) daily dose of sertraline hydrochloride.\n The Daily Record of Severity of Problems, Hamilton Rating Scale for Depression, Clinical Global Impression Scale, and Social Adjustment Scale.\n Mean (+/-SD) total daily symptom scores decreased significantly (P<.001) in the sertraline-treated (64+/-22 to 44+/-19) compared with the placebo-treated (62+/-22 to 54+/-24) groups. Significant improvement (P<.05) was found for all clinically derived symptom clusters (depressive, physical, and anger/irritability symptoms). Hamilton Rating Scale for Depression scores decreased by 44% and 29% in the sertraline and placebo groups, respectively (P<.002). End-point global ratings showed much or very much improvement in 62% of the active treatment group and 34% of the placebo treatment group (P<.001). Reported functional impairment was substantial at baseline. Improvement in psychosocial functioning with treatment was similar to what is found in studies of major depression.\n Sertraline was significantly better than placebo for treatment of premenstrual dysphoria as reflected by symptomatic improvement and change in reported functional impairment. Serotonin reuptake inhibitors such as sertraline are useful therapeutic options for women with premenstrual dysphoria.", "Dysphoric premenstrual syndrome (PMS) has been associated with serotonergic dysregulation, and serotonergic medications have been reported to alleviate the symptoms of PMS. We investigated the effects of the serotonin reuptake inhibitor sertraline given during only the luteal phase in women with dysphoric PMS.\n After baseline ratings were obtained during two menstrual cycles, 15 women with dysphoric PMS who also met DSM-IV criteria for premenstrual dysphoric disorder (PMDD) entered single-blind treatment with sertraline 100 mg/day for one full menstrual cycle. Women who responded to this treatment were randomly assigned to a four-cycle double-blind placebo-controlled crossover study in which sertraline 100 mg/day or placebo was each given only during luteal phases of two consecutive menstrual cycles.\n Eleven (79%) of fourteen women responded to single-blind full-cycle treatment with sertraline and were randomly assigned to the double-blind crossover study. Three patients dropped out of the study while taking placebo owing to nonresponse. For the remaining patients, sertraline given during the luteal phase produced significant improvements in depression, impairment, and global ratings compared with placebo and was equivalent in efficacy to sertraline given during the entire menstrual cycle.\n Women with dysphoric PMS who responded to continuous sertraline treatment responded equally well to sertraline treatment that was restricted to the luteal phase. Luteal phase treatment may have advantages in side effect burden and costs. Larger controlled trials are warranted to confirm this finding.", "The authors designed a randomized, double-blind, crossover study to assess the efficacy of sertraline in the treatment of premenstrual dysphoric disorder (PMDD) when given only during the luteal phase of the menstrual cycle.\n Thirty-one subjects were selected for a 7-month study period that included an initial 2 months of screening, 2 months of treatment with placebo or sertraline, 1 washout month, and 2 months of crossover treatment with either placebo or sertraline. Eleven subjects completed the study. Symptoms were monitored with daily reports using the Calendar of Premenstrual Experience (COPE). For each study phase, premenstrual COPE scores (7 days prior to menses) were examined using repeated measures analysis of variance. Scores were logarithmically transformed. Comparison of baseline scores between the luteal and follicular phases was examined using the paired t test.\n Analysis of COPE results during the treatment periods of the luteal phase showed a significant treatment effect, with higher scores during the placebo cycles compared with the sertraline-treated cycles (p = .0052 behavioral, p = .014 physical).\n This study is the first to demonstrate a significant response to a serotonin selective reuptake inhibitor used only during the luteal phase. The authors point out the importance of this finding both in terms of economic cost of patients as well as how it may add to the growing understanding of the etiology of PMDD.", "Premenstrual dysphoria shares certain features with depression and anxiety states, which have been linked to serotonergic dysregulation. We evaluated the efficacy and safety of fluoxetine (which selectively inhibits the reuptake of serotonin) in the treatment of premenstrual dysphoria.\n The trial consisted of a single-blind, placebo washout period lasting two menstrual cycles, followed by a randomized, double-blind, placebo-controlled trial of fluoxetine at a dose of either 20 mg or 60 mg per day or placebo for six menstrual cycles. Healthy women meeting criteria for what was then called late-luteal-phase dysphoric disorder were recruited at seven university-affiliated women's health clinics in Canada. The primary outcome measure consisted of visual-analogue scales for tension, irritability, and dysphoria during the late luteal phase of each cycle.\n Of 405 women enrolled in the placebo washout period, 313 subsequently entered the randomized phase of the study, which lasted six menstrual cycles, and 180 completed it. Fluoxetine at a dose of 20 or 60 mg per day was significantly superior to placebo in reducing symptoms of tension, irritability, and dysphoria, as measured by the visual-analogue scales (P < 0.001). The women who received 60 mg of fluoxetine per day reported significantly more side effects than those who received 20 mg per day or placebo (P < 0.001).\n Fluoxetine is useful in the treatment of premenstrual dysphoria. Treatment with fluoxetine at a dose of 20 mg per day reduces the potential for side effects while maximizing therapeutic efficacy.", "In a double-blind trial, the selective serotonin reuptake inhibitor citalopram was administered to women with severe irritability and/or depressed mood in the luteal but not in the follicular phase of the menstrual cycle (premenstrual dysphoria). Treatment continued for three consecutive menstrual cycles. One group (N = 17 completers) was administered citalopram continuously at a constant dosage (20+/-10 mg/day) throughout the menstrual cycle. A second group (N = 17) also received citalopram continuously throughout the cycle, but at a lower dosage in the follicular phases (5 mg/day) than in the luteal phases (20+/-10 mg/day) (semi-intermittent treatment). A third group (N = 18) received citalopram (20+/-10 mg/day) in the luteal phase only and placebo during the follicular phase (intermittent treatment). A fourth group (N = 17) received placebo throughout the cycles. The side effects of active treatment were generally mild and transient. Intermittent administration of citalopram was clearly more effective than placebo with respect to both reduction in self-rated irritability and self-rated global improvement; it is of interest that intermittent treatment with citalopram also seemed more effective than continuous or semi-intermittent administration of the drug.", "Despite many associations between late luteal phase dysphoric disorder (LLPDD) and major depression, there have been no placebo-controlled trials of an antidepressant in this disorder.\n The authors conducted a double-blind, randomized, placebo-controlled trial of fluoxetine in the treatment of LLPDD. The diagnosis of LLPDD was based on daily, prospective self-rating forms that subjects completed over two menstrual cycles. Subjects with other psychiatric disorders, determined by the Schedule for Affective Disorders and Schizophrenia interview, were excluded from the study. Women who continued to meet criteria for LLPDD after a single-blind trial of placebo were randomly assigned to treatment for two menstrual cycles with either fluoxetine 20 mg/day (N = 10) or placebo (N = 10).\n Nine of the 10 subjects receiving fluoxetine responded to treatment, whereas only 2 of the 10 receiving placebo did (p less than .0003). Symptoms decreased significantly in all 10 LLPDD diagnostic categories in the fluoxetine-treated group. All subjects taking fluoxetine elected to continue with this treatment after completion of the study.\n These results suggest that fluoxetine is an effective and well-tolerated treatment for LLPDD.", "This clinical trial evaluated luteal phase dosing with paroxetine controlled release (CR) (12.5 mg and 25 mg) in the treatment of premenstrual dysphoric disorder (PMDD).\n A multicenter, randomized, double-blind, placebo-controlled, 3-arm, fixed-dose study of luteal phase dosing with paroxetine CR in the treatment of PMDD. Three hundred seventy-three patients with PMDD were randomly assigned into the study. The primary measure of efficacy was the change from baseline in the mean luteal visual analogue scale (VAS)-Mood score. Secondary efficacy measures included disorder-specific evaluations, global assessments of disease severity, and assessments of functional impairment. Adverse events were recorded throughout the trial.\n Patients treated with either dose of paroxetine CR demonstrated significantly greater improvements on the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood scores) and on the majority of secondary efficacy measures compared with patients randomly assigned to placebo.\n For the treatment of PMDD, luteal phase dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well tolerated." ]

[ "17396040", "16911173" ]

[ "Effects of a step-by-step inpatient rehabilitation programme on quality of life in breast cancer patients. A prospective randomised study.", "Efficacy of comprehensive group rehabilitation for women with early breast cancer in South Korea." ]

[ "The aim of this study was to compare a conventional oncological inpatient rehabilitation programme with an inpatient step-by-step rehabilitation programme with regard to quality of life in breast cancer patients.\n Women with the diagnosis of breast cancer were randomly assigned to either the step-by-step programme (group A: 3-week rehabilitation plus 4 and 8 months later a 1-week sojourn each time) or the conventional rehabilitation programme (group B: 4- week stay and no further interventions afterwards). Quality of life was assessed with the QLQ-C30 of the EORTC at t0 (beginning of the study), t1 (end of 3- or 4-week stay) and t2 (12 months after t0, end of study).\n Between t0 and t1, a tendency (0.1 > p = 0.05) could be shown in group B towards better improvement in global quality of life and emotional function. In the subgroup of patients that had impaired functions of quality of life at t0, superiority in group B reached significance (p < 0.05) for emotional and cognitive function at t1. Between t1 and t2, cognitive function improved further in group A, but diminished in group B. For the subgroup of patients with impaired cognitive function at t0, this difference between both groups became significant (p = 0.0098).\n Although not generally superior to conventional inpatient rehabilitation programmes, the analysed step-by- step rehabilitation provided marked benefits for patients with cognitive impairments.", "The purpose of this study was to evaluate the effects of a comprehensive group rehabilitation program on the range of motion of the shoulder joint, psychosocial adjustment, and the quality of life for early breast cancer patients. Fifty-five women with early breast cancer were assigned to an intervention group or a control group. Intervention was provided three times per week for 10 weeks. The results showed an increased range of motion of the shoulder joint, and psychosocial adjustment and quality of life were shown to be significantly higher in the intervention group than in the control group. The rehabilitation program comprised psychology-based education, exercise, and peer support group activity to promote recovery of the affected shoulder joint range of motion, alleviate physical symptoms, and improve psychosocial adjustment and quality of life for early breast cancer patients in South Korea." ]

[ "15015606", "20026830", "18322873", "21398178" ]

[ "Palliative management of malignant rectosigmoidal obstruction. Colostomy vs. endoscopic stenting. A randomized prospective trial.", "Endolaparoscopic approach vs conventional open surgery in the treatment of obstructing left-sided colon cancer: a randomized controlled trial.", "Early closure of a multicenter randomized clinical trial of endoscopic stenting versus surgery for stage IV left-sided colorectal cancer.", "Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre randomised trial." ]

[ "Colostomy was the palliative treatment of choice in patients with malignant unresectable rectosigmoid obstruction. Palliative endoscopic treatment of malignant rectosigmoid obstruction by endoluminal self-expanding metallic stents is nowadays a well-established procedure.\n Twenty-two patients, referred for treatment with diagnosis of malignant obstruction of the rectosigmoid region presenting an advanced unresectable stage, were enrolled. Patients were randomly assigned into two treatment groups (endoscopic stenting vs colostomy) according to random-number tables. The length of procedure, morbidity and mortality rate, canalization of the gastrointestinal tract, restoration of oral intake and hospital stay were assessed.\n Endoscopic group: The median length of procedure was 36 minutes. No death was observed. None of the patients reported complications. All patients resumed bowel function within 24 hours. The restoration of oral intake was achieved one day after stent placement. The median hospital stay was 2.6 days. Colostomy group: The median length of the operation was 75.4 minutes. No mortality was reported. In 1 patient (9.1%) stoma prolapse was observed 3 days after the operation. Canalization of the gastrointestinal tract was restored when colostomy was opened (on postoperative day 3). All patients were able to resume oral feedings on postoperative day 3. The median hospital stay was 8.1 days.\n There were no statistically significant differences between the 2 groups concerning morbidity and mortality. Endoscopic stenting was significantly more effective concerning operative time, restoration of bowel function and oral intake and median hospitalization. Our results would suggest that endoscopically placed metal stents offer an effective alternative to surgical palliation in patients suffering from unresectable malignant rectosigmoid obstruction.", "To compare self-expanding metal stents with emergency open surgery in the treatment of obstructing left-sided colon cancer.\n A randomized controlled trial.\n An acute care hospital.\n Adult patients with an obstructing tumor between the splenic flexure and rectosigmoid junction.\n Successful 1-stage operation, cumulative operative time, blood loss, hospital stay, pain score, and postoperative complications.\n Forty-eight patients were analyzed. Twenty-four underwent endoluminal stenting followed by laparoscopic resection and 24 underwent emergency open surgery. The 2 groups were matched for age, sex, body mass index, and disease staging. Patients in the endolaparoscopic group had significantly less cumulative blood loss and lower pain, incidence of anastomotic leak, and wound infection. Significantly more patients in the endolaparoscopic group had a successful 1-stage operation performed (16 vs 9, P = .04). None of the patients in the endolaparoscopic group had a permanent stoma compared with 6 patients in the emergency open surgery group (P = .03).\n Self-expanding metal stents serve as a safe and effective bridge to subsequent laparoscopic surgery in patients with obstructing left-sided colon cancer. This endolaparoscopic approach makes a 1-stage operation more feasible, is associated with reduced incidence of stoma creation, and allows patients with malignant large-bowel obstruction to enjoy the full benefit of minimally invasive surgery. Trial Registration clinicaltrials.gov Identifier: NCT00654212.", "The introduction of self-expandable metal stents has offered a promising alternative for palliation of malignant left-sided colonic obstruction. This randomized clinical trial aimed to assess whether a nonsurgical policy, with endoluminal stenting, is superior to surgical treatment in patients with stage IV left-sided colorectal cancer and imminent obstruction.\n Patients with incurable left-sided colorectal cancer who fulfilled the study criteria were randomly assigned to nonsurgical or surgical treatment. The primary outcome measure was survival in good health out of hospital (World Health Organization performance scores 0 or 1).\n A high number of serious adverse events in the nonsurgical arm led to premature closure of the trial. Ten patients were allocated to surgical treatment and 11 patients to nonsurgical palliation. The median survival in good health out of hospital during the first year was 56 days (interquartile range 7.5 - 338.5 days) in the surgical arm vs. 38 days (interquartile range 5.25 - 288.75 days) in the nonsurgical arm (P = 0.68). Eleven adverse events (six perforations) occurred in the nonsurgical arm vs. one adverse event in the surgical arm (P < 0.001). Of the six perforations, two were stent-related because they occurred at the proximal edge of the stent by erosion through a normal colon wall; one was probably stent-related (it was located in the region of the proximal half of the stent); one was a colon blowout; and two were late tumor perforations in patients on chemotherapy.\n The unexpected high rate of perforation in the nonsurgical arm might be specifically WallFlex-related or enteral stent-related in patients on chemotherapy and warrants attention.", "Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction, but its benefits are uncertain. We aimed to establish whether colonic stenting has better health outcomes than does emergency surgery.\n Patients with acute obstructive left-sided colorectal cancer were enrolled from 25 hospitals in the Netherlands and randomly assigned (1:1 ratio) to receive colonic stenting as a bridge to elective surgery or emergency surgery. The randomisation sequence was computer generated with permuted blocks and was stratified by centre; treatment allocation was concealed by use of a web-based application. Investigators and patients were unmasked to treatment assignment. The primary outcome was mean global health status during a 6-month follow-up, which was assessed with the QL2 subscale of the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30). Analysis was by intention to treat. This study is registered, number ISRCTN46462267.\n Between March 9, 2007, and Aug 27, 2009, 98 patients were assigned to receive colonic stenting (n=47 patients) or emergency surgery (n=51). Two successive interim analyses showed increased 30-day morbidity in the colonic stenting group, with an absolute risk increase of 0.19 (95% CI -0.06 to 0.41) in analysis of the first 60 patients (14 of 28 patients receiving colonic stenting vs 10 of 32 receiving emergency surgery), and an absolute risk increase of 0.19 (-0.01 to 0.37) in analysis of the first 90 patients (23 of 47 patients vs 13 of 43). In accordance with the advice of the data safety monitoring committee, the study was suspended on Sept 18, 2009, and ended on March 12, 2010. At the final analysis of 98 patients, mean global health status during follow-up was 63.0 (SD 23.8) in the colonic stenting group and 61.4 (SD 21.9) in the emergency surgery group; after adjustment for baseline values, mean global health status did not differ between treatment groups (-4.7, 95% CI -14.8 to 5.5, p=0.36). No difference was recorded between treatment groups in 30-day mortality (absolute risk difference -0.01, 95% CI -0.14 to 0.12, p=0.89), overall mortality (-0.02, -0.17 to 0.14, p=0.84), morbidity (-0.08, -0.27 to 0.11, p=0.43), and stoma rates at latest follow-up (0.09, -0.10 to 0.27, p=0.35). However, the emergency surgery group had an increased stoma rate directly after initial intervention (0.23, 0.04 to 0.40, p=0.016) and a reduced frequency of stoma-related problems (between-group difference -12.0, -23.7 to -0.2, p=0.046). The most common serious adverse events were abscess (three in the colonic stenting group vs four in the emergency surgery group), perforations (six vs none), and anastomotic leakage (five vs one), and the most common adverse events were pneumonia (three vs one) and wound infection (one vs three).\n Colonic stenting has no decisive clinical advantages to emergency surgery. It could be used as an alternative treatment in as yet undefined subsets of patients, although with caution because of concerns about tumour spread caused by perforations.\n None.\n Copyright © 2011 Elsevier Ltd. All rights reserved." ]

[ "7923966", "3255485", "12671829", "15663548", "9734615", "6243528", "15528944", "11045316", "9808143", "11818704", "9623560", "1552999", "2128383", "16797393", "17269594", "11689389", "15187195", "14708413", "8052367", "8261678", "3982576", "1419378", "8704116", "9697664", "6786673", "3536232", "11076106", "15785941", "9426846", "17533024", "1565181", "16282676", "7566580", "205382", "7933819", "9708607", "10749297", "11961400", "10620210", "9375818", "16792136", "10977787", "7894000", "12631365", "7899583", "7503139", "11576883" ]

[ "Comparisons between oral and intraperitoneal 1,25-dihydroxyvitamin D3 therapy in children treated with peritoneal dialysis.", "Renal osteodystrophy in children on CAPD: a prospective trial of 1-alpha-hydroxycholecalciferol therapy.", "Effect of oral calcitriol pulse therapy on the lipid, calcium, and glucose homeostasis of hemodialysis-patients: its safety in a combination with oral calcium carbonate.", "Dose-response study of 22-oxacalcitriol in patients with secondary hyperparathyroidism.", "Intermittent calcitriol therapy in secondary hyperparathyroidism: a comparison between oral and intraperitoneal administration.", "Controlled trial of the effects of 1,25-dihydroxycholecalciferol in patients treated with regular dialysis.", "Intravenous vitamin D therapy reduces PTH-(1-84)/large C fragments ratio in chronic hemodialysis patients.", "Pulse oral versus pulse intraperitoneal calcitriol: a comparison of efficacy in the treatment of hyperparathyroidism and renal osteodystrophy in peritoneal dialysis patients.", "Suppression of parathyroid hormone secretion in hemodialysis patients by a novel vitamin D analogue: 19-nor-1,25-dihydroxyvitamin D2.", "Comparative effect of oral pulse and intravenous calcitriol treatment in hemodialysis patients: the effect on serum IL-1 and IL-6 levels and bone mineral density.", "Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a randomized trial.", "Prevention of hyperparathyroidism in patients on maintenance dialysis by intravenous 1-alpha-hydroxyvitamin D3 in association with Mg(OH)2 as sole phosphate binder. A randomized comparative study with the association CaCO3 +/- Mg(OH)2.", "Low calcium dialysate and high-dose oral calcitriol in the treatment of secondary hyperparathyroidism in haemodialysis patients.", "Initial dosing of paricalcitol based on PTH levels in hemodialysis patients with secondary hyperparathyroidism.", "Prospective comparison of the effects of maxacalcitol and calcitriol in chronic hemodialysis patients with secondary hyperparathyroidism: a multicenter, randomized crossover study.", "Paricalcitol dosing according to body weight or severity of hyperparathyroidism: a double-blind, multicenter, randomized study.", "Comparison of the effects of calcitriol and maxacalcitol on secondary hyperparathyroidism in patients on chronic haemodialysis: a randomized prospective multicentre trial.", "Comparative efficacy of oral and intravenous calcitriol treatment in haemodialysis patients: effects on serum biochemistry and cytokine levels.", "Comparison of intermittent and continuous oral administration of calcitriol in dialysis patients: a randomized prospective trial.", "Comparison of intermittent oral and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism.", "Comparison of 1 alpha-OH-vitamin D3 and high doses of calcium carbonate for the control of hyperparathyroidism and hyperaluminemia in patients on maintenance dialysis.", "Assessment of combined 24,25(OH)2D3 and 1 alpha (OH)D3 therapy for bone disease in dialysis patients.", "Pharmacokinetics and efficacy of pulse oral versus intravenous calcitriol in hemodialysis patients.", "19-Nor-1-alpha-25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis.", "Double-blind trial of oral 1,25-dihydroxy vitamin D3 versus placebo in asymptomatic hyperparathyroidism in patients receiving maintenance haemodialysis.", "Controlled trial of calcitriol in hemodialysis patients.", "A controlled trial of the early treatment of secondary hyperparathyroidism with calcitriol in hemodialysis patients.", "Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis.", "Comparison of the efficacy of two injectable forms of vitamin D3 and oral one-alpha in treatment of secondary hyperparathyroidism in patients on maintenance hemodialysis.", "Intravenous paricalcitol for treatment of secondary hyperparathyroidism in children on hemodialysis.", "Effect of 24,25-dihydroxycholecalciferol on intestinal absorption of calcium and phosphate and on parathyroid hormone secretion in chronic renal failure.", "Inhibition of parathyroid hormone: a dose equivalency study of paricalcitol and doxercalciferol.", "Effect of the mode of calcitriol administration on PTH-ionized calcium relationship in uraemic patients with secondary hyperparathyroidism.", "Calcitriol in dialysis patients.", "Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD.", "Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism.", "Twice versus thrice weekly administration of intravenous calcitriol in dialysis patients: a randomized prospective trial. Gruppo Italiano di Studio dell'Osteodistrofia Renale.", "Clinical effect of intravenous calcitriol administration on secondary hyperparathyroidism. A double-blind study among 4 doses.", "Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Durham Renal Osteodystrophy Study Group.", "'Pulse oral' versus intravenous calcitriol therapy in chronic hemodialysis patients. A prospective and randomized study.", "A randomized trial of intermittent versus continuous oral alfacalcidol treatment of hyperparathyroidism in end-stage renal disease.", "Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism.", "A comparison of oral and intravenous alfacalcidol in the treatment of uremic hyperparathyroidism.", "Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism.", "Treatment of secondary hyperparathyroidism with intermittent oral high doses of 1-alpha-OHD3 plus pharmacological dose of 24,25(OH)2D3.", "The effect of peroral calcitriol in small doses on mild secondary hyperparathyroidism in patients on hemodialysis.", "A placebo-controlled trial to evaluate immunomodulatory effects of paricalcitol." ]

[ "Recent studies in adults have suggested that parenteral 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may have advantages over oral therapy in the management of renal osteodystrophy. The purpose of this study was to determine whether there were clear differences between oral and IP 1,25(OH)2D3 treatments in children who did not pose a treatment problem. Seven children (5 males, 2 females, aged 1.8 to 16 years, median 4.8 years) undergoing peritoneal dialysis were initially treated with oral 1,25(OH)2D3 for a one month equilibration period They were randomly assigned to 3 months of either oral or intraperitoneal (IP) therapy with 1,25(OH)2D3 followed by 3-months-treatment using the alternative route. No significant differences in serum creatinine, phosphate, or parathyroid hormone concentrations were found between the different routes of administration in the patients. No significant differences in height standard deviation scores or renal osteodystrophy scores were found over the six-month study. Paired oral and IP pharmacokinetic studies were performed on these 7 patients and 2 other children who had been treated for at least 2 months using either oral or IP 1,25(OH)2D3. Serum was taken prior to one of the usual 1,25(OH)2D3 doses and 0.5, 1.5, 3, 6, and 24 h afterward. The highest measured concentrations of 1,25(OH)2D3 were found at 1.5 h for both oral and IP treatments (mean Cmax [SD]: oral 116 [23] pmol/l, IP 121 [24] pmol/l, p > 0.05). The AUC's for oral and IP therapy were similar (1701 [276] and 1645 [301] pmol/h/l, respectively). In the paired pharmacokinetic studies no significant differences were found between oral and IP treatments for the serum half life (27.4 [11.6] h and 19.2 [8.1] h, respectively) and total body clearance (15.3 [2.1] h and 18.4 [3.3] h, respectively) of 1,25(OH)2D3. In children who respond appropriately to oral 1,25(OH)2D3 there is no biological advantage to the use of IP 1,25(OH)2D3.", "The efficacy of 1 alpha-hydroxycholecalciferol in the prevention of renal osteodystrophy in children commencing continuous ambulatory peritoneal dialysis was studied in 12 patients, 0.8-17 years of age, who were randomly assigned to either group I receiving standard therapy or to group II receiving in addition 10-20 ng/kg body weight/day of 1 alpha-hydroxycholecalciferol. Calcium carbonate compounds were used to control hyperphosphataemia. Mean plasma calcium (total and ionised) and phosphate levels were not significantly different between the two groups. All group I patients continued to have elevated plasma immunoreactive parathyroid hormone levels at 6 months compared to only 1 patient in group II (p less than 0.05). Four patients in group I developed subperiosteal erosions on radiography compared to the healing of mild lesions in 2 patients in group II. Bone histomorphometry on iliac crest needle biopsy specimens revealed a significant reduction in osteoid index and seam width in group II. Serum aluminum levels decreased during the course of continuous ambulatory peritoneal dialysis, and the significant staining for bone aluminum in 6 patients at the beginning of the study was no longer present in 5 patients at 6 months. Our data demonstrate that 1 alpha-hydroxycholecalciferol is beneficial in the prevention and treatment of bone disease in children on continuous ambulatory peritoneal dialysis.", "To more clearly elucidate the conflicting results that have been obtained after oral calcitriol pulse therapy on lipid, glucose, and calcium levels in hemodialysis (HD) patients, and to determine safety of oral calcitriol pulse therapy in a combination with calcium carbonate.\n A randomized, crossover, placebo-controlled study.\n HD centers in 3 teaching university hospitals.\n Forty-eight chronic HD patients.\n HD patients were randomized into 2 groups. Each group (n = 24), in addition to 4.5 g calcium carbonate daily, received either oral calcitriol pulse therapy or placebo twice weekly at the end of HD, sessions for 3 months, after which the 2 therapeutic groups were crossed-over, and for an additional 3 months, the calcitriol group received placebo, and the placebo group was put on calcitriol. Serum triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), total calcium, alkaline phosphatase, proteins, phosphorus, parathyroid hormone (PTH), blood pH, and glucose were measured at random and at the end of 3 and 6 months of the trial.\n After calcitriol therapy, triglyceride, serum PTH, total alkaline phosphatase, and fasting blood sugar significantly decreased, but total serum calcium significantly increased, whereas other examined parameters remained unchanged compared with the other groups. Calcium, phosphorus, calcium x phosphorus product, PTH levels, and all of these parameters were optimized in 18 (37.5%), 22 (45.8%), 34 (70.8%), 30 (62.5%), and 12 (%25) cases, respectively, in the calcitriol groups. No significant side effect was seen during the trial.\n Our findings indicate that short-term oral calcitriol pulse therapy in combination with calcium carbonate is safe and beneficial for metabolic abnormalities of HD patients; however, its safety for prolonged therapy is yet to be proved.\n Copyright 2003 by the National Kidney Foundation, Inc.", "The dose-response relationships and the safety of administering 22-oxacalcitriol (OCT) to patients with secondary hyperparathyroidism (2HPT) under regular three-times-weekly hemodialysis (HD) were evaluated by double-blind parallel group design. A total of 203 patients with 2HPT were randomly allocated into four groups, and 5 microg (Group L), 10 microg (Group M), or 15 microg (Group H) OCT, or placebo (Group P) was administrated at the end of every HD for 12 weeks. Reductions of intact-parathyroid hormone (iPTH) concentration greater than 30% from baseline were observed in 7.7% of Group P as compared to 77.3% of the pooled OCT groups after 12 weeks of treatment (Mantel test: P < 0.001). Time-trends (slopes) of log-iPTH concentration calculated by least-squares line fitting to each patient's data during treatment differed between Group P and the pooled OCT groups (t-test: P < 0.001) and these iPTH slopes decreased dose-dependently (linear trend by t-test: P < 0.001). Slopes of serum calcium corrected for albumin (corrected-sCa) concentrations also differed between Group P and the pooled OCT groups (t-test: P < 0.001), and increased dose-dependently (linear trend by t-test: P < 0.0001). Serum phosphorus and Ca x P product increased significantly only in high dose groups. Slopes of log(iPTH) and corrected-sCa concentrations were reciprocally related. Most adverse events were hypercalcemia and dose-related, but occasionally comprised pruritus or increased serum creatinine phosphokinase. These results indicate that OCT produced a strong and dose-dependent suppression of PTH and an increase of corrected-sCa concentration in patients with 2HPT. The recommended initial dosages of OCT would appear to be 5 microg when pretreatment iPTH concentrations are less than 500 pg/mL, and 10 microg when greater than 500 pg/mL for safe and effective treatment. As in the case of PTH, calcium and phosphorus showed dose-dependent increases. It is therefore essential to take precautions as to possible increases in calcium and phosphorus.", "Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism (secondary HPT). This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis (CCPD).\n Forty-six patients aged 12.5+/-4.8 years on CCPD for 22+/-25 months were randomly assigned to treatment with oral (p.o.) or i.p. calcitriol for 12 months; 17 subjects given p.o. calcitriol and 16 subjects given i.p. calcitriol completed the study. Bone biopsies were performed at the beginning and at the end of the study, while determinations of serum and total ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and calcitriol levels were done monthly.\n Serum total and ionized calcium levels were higher in subjects treated with i.p. calcitriol, P < 0.0001, whereas serum phosphorus levels were higher in those given p.o. calcitriol, P < 0.0001. For the i.p. group, serum PTH levels decreased from pre-treatment values of 648+/-125 pg/ml to a nadir of 169+/-57 pg/ml after nine months. In contrast, serum PTH levels did not change from baseline values of 670+/-97 pg/ml in subjects given p.o. calcitriol, P < 0.0001 by multiple regression analysis. Serum alkaline phosphatase levels were also lower in patients treated with i.p. calcitriol, P < 0.0001, but there was no difference between groups in the average dose of calcitriol given thrice weekly. The skeletal lesions of secondary HPT improved in both groups, 33% of patients developed adynamic bone lesion.\n Differences in the bioavailability of calcitriol and/or in phosphorus metabolism may account for the divergent biochemical response to p.o. and i.p. calcitriol.", "In a double-blind controlled study, 15 patients received 1,25-dihydroxycholecalciferol (1,25[OH]2D3) (0.5-1.5 microgram/day) and 16 patients received vitamin D3 (D3) (400-1,200 IU/day). The patients receiving 1,25(OH)2D3 had a rise in mean serum calcium concentration from 9.05 +/- 0.15 to 10.25 +/- 0.20 mg/dl (p less than .001) with a return to 9.37 +/- 0.16 (p less than .001) in the post-control period; however, hypercalcemia (greater than 11.5 mg/dl) occurred in 5 of 15 patients. Likewise, patients who received 1,25(OH)2D3 but not those given D3 had a reversible decrease in immunoreactive parathyroid levels. 9 of 12 patients given D3 had serial iliac crest bipsies showing histologic deterioration, while 6 of 7 patients who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium content decreased in patients on D3 (p less than .05) but not in those on 1,25(OH)2D3. We conclude that the administration of 1,25(OH)2D3 to dialysis patients: (1) has a calcemic effect. (2) decreases levels of immunoreactive parathyroid hormone, and (3) is associated with histologic improvement in bone disease.", "Renal osteodystrophy is one of the major complications in patients with chronic renal failure. Large C-PTH fragments are secreted from the parathyroid glands and exert antagonistic actions against PTH-(1-84). The PTH-(1-84)/large C-PTH fragments ratio reflects both biosynthesis and processing of PTH; however the alteration of the ratio under vitamin D therapy has not been investigated.\n Seventeen hemodialysis patients with intact PTH levels of >300 pg/ml were enrolled. Calcitriol or maxacalcitol were administered intravenously for 78 weeks. Intact PTH, PTH-(1-84), and the PTH-(1-84)/large C-PTH fragments ratio were measured at 0, 13, 26, 52 and 78 weeks.\n Intact PTH and PTH-(1-84) levels, which were 492.0 +/- 115.7 and 303.4 +/- 105.4 pg/ml, respectively, at baseline, significantly decreased at the end of the study to 268.9 +/- 121.9 (p < 0.0001) and 190.7 +/- 106.9 pg/ml (p = 0.0008), respectively. In contrast, large C-PTH fragments, which were 152.7 +/- 53.5 pg/ml at baseline, did not significantly change at 78 weeks (144.5 +/- 72.2 pg/ml, p = 0.7612). Consequently, the PTH-(1-84)/large C-PTH fragments ratio was significantly reduced from 2.25 +/- 1.31 to 1.47 +/- 0.89 (p = 0.0004).\n The PTH-(1-84)/large C-PTH fragments ratio reflects the change of PTH biosynthesis, processing and secretion from the parathyroid glands, and it may be a beneficial marker to evaluate the overall biological PTH action and predict bone turnover status in hemodialysis patients under intravenous vitamin D therapy.\n Copyright (c) 2004 S. Karger AG, Basel.", "Controversy exists among various studies in regard to the efficacy of oral (p.o.) versus parenteral calcitriol. Some studies suggest that intravenous (i.v.) calcitriol is superior to p.o. calcitriol for treating renal osteodystrophy in hemodialysis patients; others suggest that these routes of administration are equivalent. To our knowledge, no large, prospective, randomized study compares intraperitoneal (i.p.) to p.o. calcitriol in adult peritoneal dialysis patients. We conducted a prospective randomized study in 76 patients (38 on i.p. calcitriol and 38 on p.o. calcitriol), whom we followed for 48 months. Of the 76 patients, 34 (18 in the i.p. group and 16 in the p.o. group) completed the 48-month study period. Calcitriol dosing was similar in both groups (3-6 micrograms per week in three divided doses). Dose adjustments were made depending on levels of parathyroid hormone (PTH), serum calcium, phosphorus, and calcitriol. No significant difference was seen between the groups in regard to age, sex, race, body mass index, dialysis duration, or cause of ESRD. Neither was any difference in the incidence of peritonitis seen between the groups. In the first 3-6 months, PTH decreased equivalently in both groups. The PTH level remained suppressed in the i.p. group throughout the remainder of the study, but, in the p.o. group, PTH returned to its pretreatment level after 3-6 months. Mean serum calcium was not different in the two groups. In the p.o. group, a considerably higher mean follow-up phosphorus level (6.8 +/- 2.3 mg/dL versus 4.7 +/- 1.4 mg/dL, p = 0.008), PTH level (384 +/- 146 pg/mL versus 162 +/- 64 pg/mL; p = 0.005), and alkaline phosphatase level (178 +/- 37 IU/L versus 72 +/- 21 IU/L, p = 0.02) were seen as compared to the i.p. group. In the i.p. group, resolution of osteodystrophy occurred in all patients at the end of the study; in the p.o. group, 5 patients maintained or developed osteodystrophy by the end of the study (p = 0.016). We conclude that i.p. calcitriol is more effective than pulse p.o. calcitriol in lowering PTH and alkaline phosphatase levels and in resolving renal osteodystrophy, and that i.p. calcitriol is associated with a lower incidence of hyperphosphatemia and elevated Ca x PO4 byproduct.", "In this double-blind, placebo-controlled, randomized, multicenter study, 35 patients with end-stage renal disease undergoing maintenance hemodialysis were treated three times weekly for 4 weeks with either 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) intravenously at doses ranging from 0.04 to 0.24 microg/kg or placebo. Eligible patients with secondary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] level > 300 pg/mL) were initially withdrawn from any existing vitamin D therapy over a 4-week washout period and then randomized to treatment for 4 weeks with either paricalcitol or placebo. Overall, there was a clinically and statistically significant reduction in iPTH level for patients receiving paricalcitol compared with placebo (P = 0.006). The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH level for 75% of the patients receiving paricalcitol per dosing group. The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH for 75% of patients receiving paricalcitol per dosing group. Sixty-eight percent (15 of 22) of patients receiving paricalcitol attained this efficacy end point regardless of dosage received (0.04, 0.08, 0.16, and 0.24 microg/kg). Eighty-three percent (5 of 6) of the patients in each of the paricalcitol groups receiving 0.16- and 0.24-microg/kg dosages attained the efficacy end point. Only two patients receiving placebo attained the iPTH end point. There were no clinically relevant differences in serum calcium (Ca) or phosphorus (P) levels between the group treated with paricalcitol and that treated with placebo. Although there was a statistically significant difference between the change from baseline to final-visit Ca levels in the paricalcitol group and the placebo group (P < 0.001), the final-visit mean Ca level in the paricalcitol group was within the normal range (9.44 mg/dL). There was no statistically significant difference between groups for the change from baseline in P level (P = 0.625). Only one patient treated with paricalcitol developed hypercalcemia before or coincident with the iPTH end point. Three other patients receiving paricalcitol experienced elevated serum Ca levels subsequent to reaching the iPTH end point, with iPTH reductions of 83% to 98%. There were no significant differences between patients treated with paricalcitol and patients treated with placebo in adverse reactions. These results show that paricalcitol safely and effectively reduces iPTH levels in hemodialysis patients with secondary HPT.", "Increased serum levels of bone-resorptive cytokines such as interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) have been implicated for changes in bone remodeling in hemodialysis patients. In this prospective randomized study, we aimed to compare the effect of oral and intravenous (IV) pulse calcitriol on serum levels of IL-1 beta and IL-6.\n Twenty-eight hemodialysis patients were included and consecutively randomized to receive either oral (n = 14, M/F = 7/7, mean age 42 +/- 15 years) or IV pulse (n = 14, M/F = 6/8, mean age 38 +/- 14 years) calcitriol treatment. No difference was found between groups for age, sex distribution, primary renal disease, mean time on hemodialysis and baseline biochemical parameters including serum levels of IL-1 beta and IL-6.\n The percent fall of intact parathyroid hormone (iPTH) was significantly less with oral compared to IV calcitriol between 0 and the 3rd month (32 +/- 21 vs. 56 +/- 28%, p = 0.03). However, the percent fall in iPTH at the 6th month of the therapy was not different in the oral group compared to the IV group (57 +/- 22 vs. 73 +/- 24%, p = 0.12). The increase in bone mineral densities was higher in the IV group than the oral group. Oral and IV calcitriol caused a significant fall in IL-1 beta (p = 0.02 and p = 0.03, respectively) and IL-6 levels (p = 0.02 and p < 0.001, respectively) at the 6th month of treatment. The percent fall in serum IL-6 levels at the 6th month was significantly greater in the IV compared to the oral group (61 +/- 18 vs. 36 +/- 33%, p = 0.04), while the percent changes in serum IL-1 beta levels were similar.\n IV calcitriol therapy has a greater suppression of PTH at the 3rd month of the therapy. Despite no difference in serum PTH levels at the 6th month, IV therapy has a greater increase in bone mineral densities and a greater decrease in serum IL-6 levels. These findings suggest IV calcitriol treatment has a superior effect on bone remodeling by influencing the levels of bone-resorptive cytokines as compared to the oral therapy group, beyond its suppressive effect on iPTH.\n Copyright 2002 S. Karger AG, Basel", "Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism. Oral administration of calcitriol is necessary in CAPD patients, but no studies have directly compared different routes of administration in this patient population.\n To determine if the peak serum calcitriol level (pulse therapy) is more important than the total delivered dose, we randomized CAPD patients with mild to moderate secondary hyperparathyroidism to receive either pulse (3.0 microg twice a week, n = 10) or daily (0.75 microg a day, n = 8) oral calcitriol in comparable weekly doses. The main comparison was the rate of decline of serum intact parathyroid hormone (PTH) levels to reach the desired end-point of 100 pg/ml. The patients were dialysed with low-calcium dialysate and received only calcium-containing phosphate binders.\n Pharmacokinetic analysis after a single dose of 3.0 microg (pulse) vs 0.75 microg (daily) revealed 1,25(OH)2-vitamin D levels to be higher in the pulse group at 3 and 6 h, but equivalent by 12 h. The area under the curve for 1 week of daily and 1 week of pulse therapy was equal. The patients in the 2 arms had equivalent basal serum levels of PTH (pulse = 562 +/- 291 vs daily = 454 +/- 113 pg/ml), calcium (pulse = 2.32 +/- 0.20 vs daily = 2.32 +/- 0.12 mmol/l) and phosphorus (pulse = 1.32 +/- 0.52 vs daily = 1.35 +/- 0.26 mmol/l). The time required for the PTH to decrease to 100 pg/ml and the rate of decline in PTH were similar (time: pulse = 14.2 +/- 6.8 weeks, daily = 12.2 +/- 7 weeks; rate: pulse = 7.4 +/- 4.2 vs daily = 8.4 +/- 4.2% PTH/week; P = NS). The serum calcium increased similarly in both groups. Hypercalcaemia (> 2.9 mmol/l) was rare (pulse = 3, daily = 2 episodes).\n This study demonstrates that pulse and daily calcitriol are similarly effective and safe for the treatment of mild to moderate secondary hyperparathyroidism in CAPD patients despite higher peak levels of 1,25(OH)2-vitamin D with pulse therapy.", "The purpose of this study is to evaluate the place of intravenous 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) in the prevention of radiologically obvious hyperparathyroidism (HPT) in patients on maintenance dialysis while excluding aluminium phosphate binder and using a dialysate calcium concentration of 1.62 mmol which keeps the intradialytic calcium balance neutral. Therefore, 47 patients without subperiosteal resorption and previously treated by oral CaCO3 and if necessary Mg(OH)2 as phosphate binder while their dialysate calcium had a Ca level of 1.62 and a Mg level of 0.2 mmol/l were randomized into a control group of 24 who were maintained on the same treatment and an experimental group of 23. This group discontinued CaCO3 and received intravenous 1 alpha-OH-D3 after each dialysis at increasing doses up to 4 micrograms and increased Mg(OH)2 as their sole phosphate binder. When plasma Ca increased above 2.7 mmol/l, the dose of 1 alpha-OH-D3 was decreased. When plasma PO4 increased above 2 mmol/l, the dose of Mg(OH)2 was increased to the highest dose not inducing diarrhea, hypermagnesemia (less than 2 mmol/l) or hyperkalemia (less than 6 mmol/l). In case of persistent hyperphosphatemia, the dose of 1 alpha-OH-D3 was decreased. Since mean plasma alkaline phosphatase was normal, HPT was monitored on the plasma concentration of 1-84 PTH for which a previous histological study showed that frank osteitis fibrosa was present only when they were above 70 pg/ml, i.e. (about twice the upper limit of the normal value). Before the study, plasma PTH was below this limit in 16 patients of the CaCO3 group and in 14 patients of the 1 alpha-OH-D3 group. After 6 months, they remained below this limit in all patients except 2 of each group. Plasma PTH was initially above 70 pg/ml in 8 of the CaCO3 and did not change significantly throughout the study, 2 patients having at 6 months a PTH level below 70 pg/ml. In contrast with intravenous 1 alpha-OH-D3, all the 9 patients with initial frank HPT decreased their PTH levels after 2 months, the levels being below 70 pg/ml in 6 cases. However, because of hypercalcemia and/or of hyperphosphatemia in spite of a highest tolerable dose of Mg(OH)2, 1 alpha-OH-D3 doses had to be decreased down to 0.4 microgram per dialysis at the 6th month so that at 6 months 6 of 9 patients had their PTH levels above 70 pg/ml, a number comparable to that of patients treated with CaCO3 (6 of 8).(ABSTRACT TRUNCATED AT 400 WORDS)", "We treated nineteen haemodialysis patients with secondary hyperparathyroidism with increasing oral doses of 1,25 dihydroxycholecalciferol (calcitriol) over a 12-week period and used low calcium dialysate (1.0 mmol/l) to prevent hypercalcaemia. Nine patients received daily calcitriol and ten received calcitriol thrice weekly, and at the end of the study the mean doses were 2.0 micrograms daily and 2.6 micrograms thrice weekly respectively. The regimen was well tolerated with nine episodes of mild hypercalcaemia, none of which were symptomatic. Mean PTH and alkaline phosphatase concentrations decreased from 62.0 pmol/l (15-125) to 22.0 pmol/l(1-70) (P less than 0.01), and 144 IU/l (48-461) to 123 IU/l (61-346) (P less than 0.05) respectively. Mean serum calcium increased from 2.33 mmol/l (2.05-2.55) to 2.52 mmol/l (2.26-2.67) (P less than 0.01). There were no significant changes in serum phosphate, magnesium, or aluminium concentrations and there were no significant differences in outcome between patients receiving daily therapy compared to those receiving it thrice weekly. A combination of high-dose oral calcitriol and low calcium dialysate can reverse secondary hyperparathyroidism without causing hypercalcaemia and these results suggest a benefit over conventional low-dose calcitriol.", "Adjustment of the initial dose of paricalcitol in hemodialysis patients with secondary hyperparathyroidism (SHPT) on the basis of severity of SHPT generally is preferred in current practice. Whether the proposed dose, based on the formula baseline intact parathyroid hormone (iPTH [picograms per milliliter]) divided by 80, is the most appropriate has not been assessed adequately.\n A double-blind randomized trial comparing iPTH/80 dose with the immediately lower iPTH/120 dose was undertaken. Forty-three hemodialysis patients with iPTH levels between 300 and 900 pg/mL (300 and 900 ng/L) were followed up for 12 weeks. The primary outcome was control of iPTH levels within a target range between 150 and 300 pg/mL (150 and 300 ng/L).\n No difference between the 2 dose groups was noted in time to achieve target iPTH levels of 150 to 300 pg/mL (150 to 300 ng/L). More episodes of excessive decrease in iPTH levels occurred in the iPTH/80 group compared with the iPTH/120 group (P = 0.003). Nine patients in the iPTH/80 group (45%) versus 2 patients in the iPTH/120 group (10%) had iPTH levels less than 150 pg/mL (<150 ng/L) in at least half the measurements performed during the second half of the study (P = 0.034). Increases in calcium levels were greater in the iPTH/80 group at all times during the study (P < 0.05 at weeks 4 and 10). The number of required dose reductions was significantly greater in the iPTH/80 group compared with the iPTH/120 group (P = 0.008).\n In hemodialysis patients with SHPT, a lower initial dose of iPTH/120 shows efficacy similar to that of the already widely used iPTH/80 scheme in reaching target iPTH levels (150 to 300 pg/mL [150 to 300 ng/L]), with less required dose adjustments, lower increase in calcium levels, and lower cost. In addition, the initial dose of paricalcitol based on the iPTH/80 formula leads significantly more patients to excessive suppression of iPTH (<150 pg/mL [<150 ng/L]) than the iPTH/120 dose.", "Maxacalcitol is a vitamin D analogue, which is administered intravenously for secondary hyperparathyroidism in dialysis patients as well as calcitriol. However, few dose-comparison clinical studies have been reported for these drugs. The present multicenter, randomized crossover study was conducted to determine the equivalence of maxacalcitol and calcitriol doses.\n Subjects comprised 31 patients on chronic hemodialysis with secondary hyperparathyroidism who had not received maxacalcitol or calcitriol in the previous 3 months. Patients were randomly divided into two groups, and maxacalcitol or calcitriol was administered in a crossover design for 12 weeks each. Maxacalcitol and calcitriol doses were adjusted based on serum levels of calcium and intact parathyroid hormone.\n After the 12-week maxacalcitol/calcitriol administration, there were no significant differences in levels of calcium (maxacalcitol 2.40+/-0.22 mmol/1 (9.6+/-0.9 mg/dl), calcitriol 2.42 + 0.25 mmol/l (9.7+/-1.0 mg/dl), p = 0.71), phosphate (maxacalcitol 1.97 + 0.42 mmol/l (6.1+/-1.3 mg/dl), calcitriol 2.00+/-0.48 mmol/l (6.2+/-1.5 mg/dl), p = 0.64), intact parathyroid hormone (maxacalcitol 267+/-169 pg/ml, calcitriol 343+/-195 pg/ml, p = 0.11) in serum or other bone-metabolic parameters such as serum alkaline phosphatase. The doses ofmaxacalcitol and calcitriol were 49.3+/-23.7 microg/month and 9.0+/-3.8 microg/month, respectively, and maxacalcitol : calcitriol dose ratio was 5.5: 1. No severe adverse reactions were seen for either maxacalcitol or calcitriol during the study period.\n Comparable therapeutic efficacy can be obtained in the treatment of secondary hyperparathyroidism using either maxacalcitol or calcitriol at a dose ratio of 5.5 : 1.", "Vitamin D therapy for patients with end-stage renal disease (ESRD) on hemodialysis therapy has relied on patient dry weight to determine the initial dose of medication. Obtaining a patient's dry weight can be difficult, and no correlation has been established between a patient's body weight and severity of secondary hyperparathyroidism. We conducted a double-blind, double-dummy, randomized, 12-week, multicenter trial to compare the incidence of hypercalcemia (single occurrence) between two dosing regimens: one regimen based on baseline intact parathyroid hormone (iPTH; PTH/80) level, and the other regimen based on patient body weight (0.04 microgram/kg). One hundred twenty-five adult patients with ESRD on maintenance hemodialysis therapy were enrolled at multiple sites. Before treatment, all patients were required to have PTH levels of 300 pg/mL or greater, calcium levels of 8.0 mg/dL or greater and 10.5 mg/dL or less, and a calcium x phosphorus (Ca x P) product of 70 or less. Patients were randomized to one of two regimens: the nonrandomized treatment was also administered as a placebo dummy. No incidence of hypercalcemia occurred in either treatment group during the study. Patients treated according to the formula iPTH/80 required fewer dose adjustments and achieved the first of four consecutive reductions from baseline PTH level of 30% or greater more rapidly than patients treated based on body weight (P = 0.0306). Incidences of elevated Ca x P product levels were similar between treatment groups. Treatment with paricalcitol injection based on degree of secondary hyperparathyroidism incurred no greater risk for hypercalcemia and achieved meaningful therapeutic results with fewer dose adjustments than dosing based on patient body weight.", "To identify differences between the effects of calcitriol and the calcitriol analogue, maxacalcitol, on parathyroid hormone (PTH) and bone metabolisms, we conducted a randomized prospective multicentre study on patients on chronic haemodialysis.\n We randomly assigned 91 patients with secondary hyperparathyroidism [intact PTH (iPTH) > or =150 pg/ml] to have either calcitriol (47 patients) or maxacalcitol (44 patients) therapy, for 12 months after a 1 month control period. Serum electrolytes, bone alkaline phosphatase (bAP), iPTH, total PTH and PTH(1-84) (whole PTH) levels were measured periodically. The first end point was a serum iPTH of <150 pg/ml, the second was the iPTH levels obtained.\n Treatment was discontinued for various reasons in nine patients in each group, but no serious side effects were observed in either group. The numbers of cases reaching the first end point were not significantly different between the two groups. Serum calcium concentration was significantly higher in the maxacalcitol than the calcitriol group during early treatment, but not at the end of treatment. Throughout the treatment period there were no significant differences between the two groups in serum iPTH, inorganic phosphate, the product of the serum calcium and inorganic phosphorus concentrations, bAP, or the ratio of whole PTH to total PTH minus whole PTH. Nor were the changes in these parameters significantly different between the two groups comparing the patients with moderate to severe hyperparathyroidism (basal iPTH > or =500 pg/ml).\n Calcitriol and maxacalcitol are equally effective on PTH and bone metabolism.", "This study compared the effects of oral and intravenous calcitriol on serum biochemistry parameters and levels of bone-resorptive cytokines in haemodialysis patients. Patients were randomized to receive oral (n = 18) or intravenous (n = 16) calcitriol treatment for 6 months. Serum levels of total calcium, ionized calcium, intact parathyroid hormone (iPTH), magnesium, alkaline phosphatase, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and IL-6 were measured at baseline and after 3 and 6 months of treatment. After treatment, serum levels of iPTH, total calcium, ionized calcium, TNF-alpha, IL-1 and IL-6 were not significantly different from baseline. The intravenous calcitriol treatment group showed significant decreases in levels of iPTH, TNF-alpha, IL-1 and IL-6 and a significant increase in total calcium level after 3 and 6 months. There was no significant change in serum ionized calcium levels. Significantly decreased serum alkaline phosphatase and magnesium levels were found in both treatment groups after 3 and 6 months. In conclusion, intravenous calcitriol treatment has a significant depressive effect on iPTH and bone-resorptive cytokines in patients undergoing haemodialysis.", "Intermittent bolus administration of calcitriol--i.e., 1,25-dihydroxycholecalciferol or 1,25-(OH)2D3--is highly efficacious in dialysis patients. In experimental studies, intermittent administration of calcitriol is superior to continuous administration in suppressing preproparathyroid hormone (PTH) mRNA and circulating PTH concentrations. In a randomized, prospective, open multicenter trial 45 dialysis patients with elevated 1,84-iPTH (> or = 20 pmol/l, normal 1-6 pmol/l) levels were randomly allocated to daily administration of 0.75 microgram calcitriol (continuous) or twice weekly administration (intermittent); the two protocols provided an identical total weekly doses of 5.25 micrograms calcitriol. Patients were dialyzed with a dialysate Ca concentration of 1.75 mmol/l and had oral CaCO3 or Ca acetate. 1,84-iPTH (immunoradiometric assay) and serum Ca and Pi levels were measured weekly. At the beginning of the study, the median 1,84-iPTH value was 37 pmol/l (range 20-115) in the intermittent versus 36 pmol/l (range 21-72) in the continuous calcitriol group. After 2 weeks, the median 1,84-iPTH level was 18.5 pmol/l (range 1.4-106) versus 18 pmol/l (range 1.2-48). After 12 weeks, 11 of 21 of the patients in the intermittent and 18 of 24 patients in the continuous group had reached the treatment goal, i.e., 1,84-iPTH < or = 10 pmol/l without hypercalcemia or hyperphosphatemia. There were seven episodes of hypercalcemia (> 2.7 mmol/l) in the intermittent versus two in the continuous group; the mean peak Ca level was 2.8 mmol/l (range 2.76-3.0) versus 2.9 mmol/l (range 2.74-3.06). There were 21 versus 17 episodes, respectively, of hyperphosphatemia (> 2.2 mmol/l).", "Both intermittent intravenous and intermittent oral calcitriol have been shown to be effective in the treatment of secondary hyperparathyroidism in hemodialysis patients and it has been claimed that intravenous calcitriol causes less hypercalcemia. However, there has been no published systematic comparison of the two routes of administration of intermittent calcitriol. Therefore in a prospective crossover study 11 (9 male) patients on maintenance hemodialysis were randomized to receive intravenous followed by oral calcitriol for 4 months each, or oral followed by intravenous calcitriol, commencing at 2 micrograms postdialysis three times per week. Initial serum immunoreactive parathyroid hormone (PTH) was 446 +/- 111 (normal < 65) pg/ml. Calcium-containing phosphate binders were not used. Calcitriol was ceased if hypercalcemia developed and restarted at 2 micrograms or 1 microgram when calcium returned to normal. Hypercalcemia was frequent (11 episodes in 8 patients on intravenous calcitriol and 10 episodes in 7 patients on oral calcitriol) and dose reduction to 1 microgram was necessary in 7 patients on intravenous and on 6 patients on oral. Serum PTH fell during both treatments. Parathyroid enlargement was seen in 10 glands from 4 patients, but no size reduction was demonstrated with treatment. There was no reduction in activity on quantitative metabolic bone scan. In summary, intermittent oral calcitriol and intermittent intravenous calcitriol were equally effective in reducing serum parathyroid hormone levels and at a dose of 2 micrograms postdialysis caused hypercalcemia with equal frequency.", "27 patients on hemodialysis (dialysate aluminium less than 0.7 mumol/l for 2 years, and 2 mumol/l before) whose plasma Ca and PO4 were adequately controlled for already 6 months by high doses of CaCO3 alone (mean +/- SD: 9 +/- 5 g/day), were randomly divided into 2 groups, a control group (c group) which was kept on the same treatment, and a group in which CaCO3 was reduced to 3 g/day but in which plasma Ca was kept normal due to 1 alpha-OH-vitamin D3 administration (1 microgram/day at the beginning, 0.3 microgram/day after 6 months; 1 alpha group) whereas plasma phosphate was kept below 6.0 mg/dl because of Al(OH)3 (2.7-5 g/day). Initially, the 2 groups were comparable as regards the plasma concentrations of total and ionized Ca, phosphate, alkaline phosphatases, medium and C-terminal parathyroid hormone (PTH) and aluminium, but the control group had lower plasma 25-OH-vitamin D (25-OHD.) After 6 months, the same difference in plasma 25-OHD was found with comparable plasma concentrations of total and ionized calcium as well as of medium and C-terminal PTH (beta error 1%). However, plasma concentration of phosphate and the plasma Ca phosphate product, as well as the plasma aluminium were higher in the 1 alpha group whereas their PCO3H- was lower. Although the alkaline phosphatase values were not significantly different between the 2 groups, they increased only in the control group because of 1 patient who developed a vitamin-D-deficient osteomalacia (plasma 25-OHD 3 ng/ml), which was subsequently cured by physiological doses of 25-OHD3. The incidence of transient hypercalcemia (15 vs. 21 episodes) and worsening of soft tissue calcifications (3 in each group) was the same in the 2 groups.", "An increasing body of experimental data suggests a role for 24,25(OH)2D3 in bone metabolism. The present study was carried out to assess a possible therapeutic role of this vitamin D metabolite in renal osteodystrophy. Twenty-two chronic dialysis patients, most of whom were previously maintained on 1 alpha (OH)D3 therapy, received additional treatment with 10 micrograms/day 24,25(OH)2D3 and were compared to 19 patients receiving 1 alpha (OH)D3 alone. Analysis of transiliac bone biopsies obtained at study entry and following 10-16 months of treatment revealed that the combined therapy produced a decrease in bone turnover. Specifically, the addition of 24,25(OH)2D3 inhibited an increase in trabecular bone volume (BV/TV) and suppressed osteoclastic parameters. Thus BV/TV increased from 26.2 +/- 8.6 to 32.1 +/- 7.5% (p < 0.01) in the 1 alpha (OH)D3 group, but it remained unchanged in the combined therapy group. In contrast, the eroded surface (ES/BS), the osteoclast surface (Oc.S/BS), and the osteoclast numbers were significantly suppressed in patients receiving both 24,25(OH)2D3 and 1 alpha (OH)D3, as compared with those receiving 1 alpha (OH)D3 alone (p < 0.01, p < 0.01, and p < 0.001, respectively). These improvements were independent of changes in 1 alpha (OH)D3 dosage. The extent of bone aluminium deposits was unrelated to the administration of 24,25(OH)2D3 or to its effect. 24,25(OH)2D3 therapy was not associated with any adverse effects.", "Because intravenous (iv) calcitriol has greater bioavailability than oral calcitriol, it may be more efficacious in suppressing parathyroid hormone (PTH) secretion. In this study, the pharmacokinetics and efficacy of pulse oral and i.v. calcitriol were compared. Patients were randomized to receive 2 micrograms of i.v. or oral calcitriol after each dialysis. Two pharmacokinetic studies (PK1, PK2) were performed 10 days apart, during which the patients received calcitriol after each dialysis. Calcitriol bioavailability was determined from the area under the curve (AUCtime interval (hours) in pg/mL per h). After the PK phase, PTH was lowered to < 200 pg/mL by titrating calcitriol to a maximum of 12 micrograms/wk over 4 wk. Calcitriol was then maintained for another 18 wk unless serum calcium exceeded 11.5 mg/dL or Ca x P product exceeded 70; when these limits were reached, calcitriol was held and then restarted at a lower dose. After i.v. administration, peak serum calcitriol exceeded that achieved orally but by 1 h, calcitriol levels were similar. The AUC0-0.5 (105 +/- 12, i.v.; 9 +/- 4, oral) and AUC0.5-1 (68 +/- 6, i.v.; 30 +/- 7, oral) were higher with i.v. (P < 0.05), but cumulative AUC0-48 did not differ. Individual t1/2 values ranged from 10 to 129 h for PK1 and from 10 to 50 h for PK2. The t1/2 for oral calcitriol was 38 +/- 14 h for PK1 and 30 +/- 4 h for PK2 (not significant (NS)). The t1/2 for i.v. calcitriol was 26 +/- 5 h for PK1 and 19 +/- 3 h for PK2 (NS, PK1 versus PK2 and oral versus i.v.). When the PK1 oral and i.v. data were combined, the mean t1/2 was 32 +/- 7 h whereas the t1/2 for PK2 (oral and i.v.) was 22 +/- 3 h (P < 0.05). Baseline PTH levels were 510 +/- 90 pg/mL and 499 +/- 79 pg/mL, oral and i.v., respectively. Serum PTH level at 22 wk was not different between oral and i.v. groups, 153 +/- 38 pg/mL and 214 +/- 124 pg/mL in i.v. (NS). The percentage of PTH suppression was 66 +/- 7.4% in the oral group and 69 +/- 12% in the i.v. group (NS). A major degree of serum iPTH suppression occurred during the initial 4 wk of treatment, concomitant with a rise in serum calcium levels. Adverse effects were similar between groups, as were the average dosages of calcitriol and phosphate binders. In conclusion, the efficacy of intravenous and pulse oral calcitriol were similar in hemodialysis patients with secondary hyperparathyroidism. The early rise in serum calcium levels observed with treatment may have contributed significantly to the suppression of serum iPTH levels. The difference in bio-availability between the different routes does not have a clinically apparent effect. The t1/2 varied widely among individuals, whereas exposure to calcitriol may decrease the t1/2.", "Paricalcitol (19-nor-1alpha-25-dihydroxyvitamin D2), a new vitamin D analog developed for the treatment of secondary hyperparathyroidism, was evaluated in three double-blind, placebo-controlled, dose-escalating, randomized multicenter trials. A total of 78 patients (40 Paricalcitol injection, 38 placebo) achieved treatment phase eligibility, which included intact parathyroid hormone (iPTH) > or = 400 pg/ml, normalized serum calcium levels between 8.0 and 10.0 mg/dl, and calcium x phosphorus product values less than 75. Study end points included a decrease in iPTH of at least 30% or a maximum of five dose escalations. After a 4-wk washout, paricalcitol or placebo was administered intravenously three times per week after dialysis for 12 wk. Study drug was started at a dose of 0.04 microg/kg and was increased by 0.04 microg/kg every 2 wk to a maximal allowable dose of 0.24 microg/kg or until at least a 30% decrease in serum iPTH was achieved. The dose of paricalcitol that decreased iPTH by at least 30% became the maintenance dose. Of 40 patients receiving paricalcitol, 27 (68%) had at least a 30% decrease in serum iPTH for 4 consecutive weeks, compared with three of 38 patients (8%) receiving placebo (P < 0.001). For patients who received 12 wk of treatment with paricalcitol, the levels of iPTH decreased significantly from 795+/-86 to 406+/-106 pg/ml (P < 0.001), whereas the values for PTH were 679+/-41 pg/ml before and 592+/-41 pg/ml after 12 wk of therapy in patients receiving placebo (P=NS). Also, there was a significant difference between treatment groups for the change from baseline PTH levels (P < 0.001). Paricalcitol treatment resulted in a significant reduction in serum alkaline phosphatase from 148+/-23 U/L to 101+/-14 U/L (P < 0.001) in patients treated for 12 wk compared with 120+/-9 U/L to 130+/-11 U/L (P=NS) in patients receiving placebo for 12 wk. Importantly, hypercalcemia did not occur before achieving target serum iPTH levels in any of the paricalcitol-treated patients. There was no significant difference for the change from baseline in serum phosphorus within or between treatment groups. There was no significant difference in adverse events between the paricalcitol and placebo-treated groups. These studies demonstrate that paricalcitol safely and effectively suppresses iPTH levels in hemodialysis patients. This second generation vitamin D analog may have a wider therapeutic window than current vitamin D preparations, and thus may allow reduction in PTH with less hypercalcemia.", "Fifty-seven patients who had been receiving maintenance haemodialysis for a mean of 4.6 years were given 0.25-0.5 microgram oral 1,25-dihydroxy (1,25-(OH)2) vitamin D3 or a placebo in a double-blind manner for one to two years. In patients with normal radiographs (mean plasma parathyroid hormone concentration 205 microliterEq/ml) 1,25-(OH)2 vitamin D3 prevented the development of the radiological appearances of hyperparathyroidism. In patients with abnormal radiographs (mean plasma parathyroid concentration 709 microliterEq/ml) 1,25-(OH)2 vitamin D3 arrested or reversed the radiological changes of hyperparathyroidism. Nevertheless, the response was slow and the concentration of the hormone remained considerably raised (mean 445 microliterEq/ml). It is concluded from these results that giving 1,25-(OH)2 vitamin D3 to patients receiving maintenance haemodialysis who have normal hand radiographs or minimal erosions is beneficial. In patients with more advanced hyperparathyroidism parathyroidectomy should be considered unless there is a rapid response.", "We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation.", "Calcitriol is widely used in conjunction with phosphorus-binders containing calcium to treat secondary hyperparathyroidism in dialysis patients. Its efficacy in patients with severe hyperparathyroidism is diminished, in part, due to glandular hyperplasia associated with decreased calcitriol and calcium receptors.\n We, therefore, developed a prospective, randomized trial comparing i.v. calcitriol plus calcium carbonate (CaCO3) compared to CaCO3 alone (control) in patients with mild to moderate hyperparathyroidism who were within the first year of initiating hemodialysis. Patients underwent calcium (Ca) suppression/stimulation testing at baseline and after six and twelve months of treatment to indirectly assess parathyroid gland hyperplasia.\n In the calcitriol group, the amino-terminal parathyroid hormone (N-PTH) decreased significantly from a baseline value of 70 +/- 12 pg/ml at month zero to 22 +/- 7 and 19 +/- 6 pg/ml at months 6 and 12, respectively (the conversion factor of amino-terminal PTH to intact PTH is 6, i.e., 10 pg/ml N-PTH equals 60 pg/ml intact PTH). In contrast, the N-PTH levels in the CaCO3 alone group did not change. The change in nadir N-PTH levels at month 12 compared to month zero decreased by 14 +/- 7% in the calcitriol group but increased by 96 +/- 59% in the control group (p < 0.05). In addition, the increment in N-PTH levels during hypocalcemic stimulation decreased by 68 +/- 6% at month 12 compared to month zero but increased by 61 +/- 42% in the control group. Although total calcium and phosphorus levels were not different between the two groups, ionized calcium values were higher in the calcitriol group. The incidence of hypercalcemia was the same in both groups and the episodes were asymptomatic.\n Pulse calcitriol therapy is effective in preventing progression of secondary hyperparathyroidism in hemodialysis patients with mild to moderate disease. Based on Ca suppression/stimulation tests, calcitriol was more successful in preventing gland growth than CaCO3 alone. Further studies are needed to determine if the strategy of early treatment of mild to moderate hyperparathyroidism by pulse calcitriol is safe and effective in hemodialysis in patients.", "This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (i.v.) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (secondary HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD). After a 2 to 6-week washout period of all vitamin D compounds, patients with two consecutive PTH values > 400 pg mL(-1), calcium levels < or = 10.5 mg dL(-1) and calcium x phosphorus product values < or = 70 mg2 dL(-2) were eligible for the treatment phase. Patients received a bolus injection of calcitriol or placebo three times a week, immediately after dialysis for up to 12 weeks. Initial doses (0.5-1.5 microg) were based on the severity of secondary HPT. The dose was increased every two weeks by 0.25 microg until there was at least a 30% decrease in PTH from baseline, or Ca > 11.0 mg dL(-1), or Ca x P > 75 mg2 dL(-2). Overall, 11/21 (52%) patients in the calcitriol group had two consecutive > or = 30% decreases from baseline in serum PTH compared with 5/26 (19%) patients in the placebo group (P=0.03). The mean total alkaline phosphatase decreased from 274 to 232 IU L(-1) in the calcitriol group and increased from 547 to 669 IU L(-1) in the placebo group (P=0.002). The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 microg L(-1) in the calcitriol group and increased from 105.3 to 148.5 microg L(-1) in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium x phosphorus (Ca x P > 75 mg2 dL(-2)) product was higher in the calcitriol group than in the placebo group (P=0.01). Two consecutive occurrences of phosphorus > 6.5 mg dL(-1) occurred in 71% of the calcitriol group and 46% of the placebo group (P=0.14). Calcium levels > 10.5 mg dL(-1) were more common in the calcitriol group than in the placebo group (P=0.01). There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group (r=0.46; P<0.0001) and the placebo group (r=0.21; P=0.0005). This study demonstrates that i.v. calcitriol, at initial doses of 0.5-1.5 microg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca x P product.", "In the present study, we compared the efficacy of two intravenous forms of vitamin D3[Calcijex: 1,25(OH)2D3 and One-Alpha: 1(OH)D3] and that of oral One-Alpha in the treatment of secondary hyperparathyroidism in patients receiving maintenance hemodialysis. Twenty patients were assigned to 1 of 2 treatment groups (A and B) which were matched for age, sex, and duration of maintenance hemodialysis. None of the patients included had chronic liver disease or had received drugs known to interfere with hepatic enzymes. All patients had received a stable dose of oral calcium and One-Alpha for a minimum period of 1 year, which maintained corrected serum calcium at the upper limit of the normal range. At the start of the study, oral One-Alpha was replaced by Calcijex in group A and injectable One-Alpha in group B. Treatment was maintained for 3 months (phase I). Subsequently, injectable vitamin D3 was discontinued and all patients received their previous dose of oral One-Alpha for a period of 1 month. Finally, oral One-Alpha was discontinued again and the injectable forms of vitamin D3 were crossed over in the 2 treatment groups for another 3 months (phase II). The results showed that the serum concentrations of 1,25(OH)2D3, measured 48 h after intravenous injection of One-Alpha, were not different from that produced by an equivalent dose of Calcijex in the same group of patients. Furthermore, overall analysis of intact parathyroid levels during the cross-over, using ANOVA with repeated responses, indicated that the two analogues were equipotent as regards suppression of PTH secretion. In our study, treatment with intravenous vitamin D3 led to significant suppression of PTH secretion. These results were achieved by a lower drug dosage of vitamin D3 and at lower trough blood levels of 1,25(OH)2D3 as compared to those of oral One-Alpha. Our findings are in favor of the early use of either forms of injectable vitamin D3 in the treatment of secondary hyperparathyroidism.", "Secondary hyperparathyroidism is a common complication in children receiving hemodialysis. Active vitamin D is an effective therapy, but its use is often limited by hypercalcemia and increased calcium x phosphorus (Ca x P) product. Paricalcitol, a selective vitamin D receptor activator, causes less sustained hypercalcemia and increase in Ca x P product than calcitriol and has been used effectively in adult hemodialysis patients.\n Double blind, placebo-controlled.\n Hemodialysis units and pediatric subjects receiving hemodialysis.\n After a washout period of 2 to 6 weeks, 29 subjects aged 5 to 19 years received either paricalcitol or placebo for up to 12 weeks (0.04 mug/kg if initial intact parathyroid hormone [iPTH] level < 500 pg/mL [ng/L]; 0.08 mug/kg if initial iPTH level > 500 pg/mL [ng/L]). The dose was increased by 0.04 mug/kg every 2 weeks until there was a 30% decrease in iPTH level from baseline or calcium level greater than 11 mg/dL (>2.74 mmol/L) or Ca x P product greater than 75 mg(2)/dL(2) (>6.04 mmol(2)/L(2)).\n Two consecutive 30% decreases from baseline in iPTH levels and safety of paricalcitol, including hypercalcemia and increase in Ca x P product.\n 60% of the paricalcitol group had 2 consecutive 30% decreases from baseline iPTH levels compared with 21% in the placebo group (P = 0.06). The paricalcitol group had a mean decrease in iPTH level of 164 pg/mL (ng/L), whereas the placebo group had a mean increase of 238 pg/mL (ng/L; P = 0.03). There was no difference from baseline to final visit in calcium, phosphorus, or Ca x P product values in either group.\n Low power to detect differences in safety between groups and a short-term study.\n Paricalcitol decreased iPTH levels in children receiving hemodialysis with no significant changes in serum calcium, phosphorus, or Ca x P product values during the course of the study.", "Twelve patients with chronic renal failure (CRF) requiring dialysis, 7 of whom were hypercalcaemic, were treated with 24,25-dihydroxycholecalciferol [24,25(OH)2D3; 10 micrograms daily for 3 months] or placebo and the treatment then crossed over for a further 3 months. Treatment with 24,25(OH)2D3 was associated with small but significant increments in the fractional rates of absorption of calcium (p less than 0.01) and phosphate (p less than 0.05) measured by a combined radioisotope test, but even during treatment, the absorption of both calcium and phosphate remained subnormal. A significant fall in immunoreactive parathyroid hormone (i-PTH) levels occurred during treatment (p less than 0.05) in the absence of significant changes in plasma ionised calcium and plasma phosphate levels. In 7 patients, treatment with 24,25(OH)2D3 converted parathyroid glands which were non-suppressible by calcium infusion before treatment to suppressible ones (greater than 50% suppression of i-PTH levels) at similar levels of ionised calcium. 24,25(OH)2D3 may have a role in the treatment of renal osteodystrophy, especially in patients with hypercalcaemic hyperparathyroidism.", "Paricalcitol and doxercalciferol are effective in reducing parathyroid hormone PTH concentrations in patients with secondary hyperparathyroidism. The purpose of this study was to determine the relative dose of doxercalciferol (compared to paricalcitol) required to maintain equivalent PTH concentrations in dialysis patients.\n Chronic hemodialysis patients treated with a stable dose of paricalcitol for at least 3 months were randomized to receive doxercalciferol at either 35, 50, or 65% of the paricalcitol dose for 6 weeks. Serum iPTH, calcium, phosphorus, and albumin were determined at baseline and monitored every 2 weeks. A linear regression analysis of percent change in iPTH values by dose group was performed to determine the conversion factor.\n 27 patients were enrolled. Initial iPTH, adjusted serum calcium, serum phosphorus, and CaxP were similar among the treatment groups. Linear regression analysis demonstrated a conversion factor of 0.57 for the dose of doxercalciferol relative to paricalcitol resulting in equivalent suppression of iPTH. Corrected serum calcium, phosphorus, CaxP product, as well as incidence of hypercalcemia, hyperphosphatemia and CaxP >50 were similar for all groups.\n In patients on a maintenance dose of paricalcitol, dosing doxercalciferol at 55-60% of the paricalcitol dose results in comparable inhibition of PTH.", "To assess the effect of the different modes of calcitriol administration on PTH-ionized calcium relationship we conducted a prospective clinical trial in 33 patients on chronic haemodialysis with secondary hyperparathyroidism (four times upper normal limit intact PTH) who were randomly assigned, with stratification to PTH levels, to receive daily oral, intermittent oral, or intermittent intravenous calcitriol at the same dose of 0.045 micrograms/kg/weekly. PTH-iCa curves were generated by inducing hypo- or hypercalcaemia in sequential haemodialysis 1 week apart, before and after 10 weeks on treatment. All patients were dialysed against a dialysate calcium concentration of 2.5 mEq/l throughout the study period. After drop-outs, 26 patients completed the study: 11 on intravenous calcitriol (mean basal PTH +/- SD: 666 +/- 280 pg/ml), eight on intermittent oral calcitriol (mean basal PTH: 831 +/- 361), and seven on daily oral calcitriol (mean basal PTH: 719 +/- 280). Serum ionized calcium and phosphorus significantly increased in intravenous and daily oral groups after calcitriol treatment, but not in the intermittent oral group. Basal PTH did not significantly change in the three groups after 10 weeks on treatment. Maximal PTH significantly decreased in intravenous group (1449 +/- 660 versus 1122 +/- 691 pg/ml, P = 0.0085) and at the limit of statistical significance in the intermittent oral group (1701 +/- 774 versus 1445 +/- 634, P = 0.12), but it did not change in the daily oral group. Minimal PTH did not modify in the three groups. In all three groups, a shift to the right in the PTH-iCa relationships were observed, with significant changes in the set point of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)", "We conducted a 7-month randomized, single, double, single-blind comparison of calcitriol (1,25(OH)2D3) with vitamin D3 in 22 hemodialysis patients to study the effects on the biochemical abnormalities associated with osteodystrophy. Calcitriol was given for 3 mo. All patients had initial prestudy calcium values less than or equal to 9.5 mg/100 ml, and phosphate values less than or equal to 4.5 mg/100 ml. Data were analyzed using the Normalized Trend Index (NTI). Calcitriol induced a rise in calcium (8.7 to 10.25 mg/100 ml) (p less than 0.001) and a fall in alkaline phosphatase (p less than 0.005), while D3 had no appreciable effect. The mean dose of calcitriol during treatment was 0.579 microgram/day while that for D3 was 706 IU/day. The effect on serum phosphate concentration was variable. Hypercalcemia as high as 13.2 mg/100 ml occurred in 2 of 13 patients on 1,25(OH)2D3, but in every instance promptly returned to normal with dose reduction. No other adverse effects were noted with therapy. We conclude that calcitriol reverses the biochemical abnormalities of osteodystrophy. Since its effects are rapidly reversed with discontinuation, the drug is probably safe as well as effective.", "To examine the most effective route (intravenous vs. \"pulse\" oral), dose (physiologic vs. pharmacologic) and long-term efficacy of calcitriol therapy for secondary hyperparathyroidism in patients with end-stage renal disease (ESRD), we randomized 19 hemodialysis patients with severe hyperparathyroidism to receive over a 36-week study period either pulse orally administered calcitriol and intravenous placebo (pulse oral group; N = 9) or intravenous calcitriol and oral placebo (intravenous group; N = 10). Calcitriol was given intermittently in a double-blinded fashion at an initial dose of 2 micrograms thrice weekly and increased as tolerated up to a maximum dose of 4 micrograms per treatment. All patients received similar daily calcium supplementation (2.5 g of elemental calcium) and low dialysate calcium (1.25 mmol/liter) throughout the study period. At the maximum tolerated calcitriol dose, serum 1,25-dihydroxyvitamin D levels were significantly greater 60 minutes following intravenous (389 pmol/liter) compared to oral administration (128 pmol/liter). In spite of the different pharmacologic profiles, intravenous and oral administered calcitriol resulted in similar reductions of serum PTH over the 36 week period of observation (P = 0.300), achieving an overall maximum average PTH reduction of 43% (P = 0.016). Long-term intensive calcitriol therapy (independent of administration route), however, failed to decrease parathyroid gland size as assessed by high resolution ultrasound and/or magnetic resonance imaging. Calcitriol therapy also failed to alter the calcium sensitivity as assessed by serial PTH measurements in response to calcium loading. Increases in serum calcium, but not calcitriol dose or parathyroid gland size, predicted decrements in serum PTH, whereas hyperphosphatemia and the level of PTH suppression derived from the PTH/ionized calcium response curves predicted refractoriness to calcitriol therapy. Episodes of hypercalcemia and hyperphosphatemia were similar in both treatment groups and limited the dose of calcitriol that could be administered. These data indicate that intermittent intensive calcitriol therapy, regardless of administration route, is poorly tolerated, fails to correct parathyroid gland size and functional abnormalities, and has a limited ability to achieve sustained serum PTH reductions in end-stage renal failure patients with severe hyperparathyroidism.", "Active vitamin D3 is extensively used for the treatment of secondary hyperparathyroidism in hemodialysis patients. But it is often impossible to administer enough dose to suppress parathyroid hormone (PTH) level, because of hypercalcemia and hyperphosphatemia. New modalities with higher specificity for PTH suppression are desirable. We conducted a crossover comparative study of falecalcitriol, an active vitamin D3 analog, and alfacalcidol (1alpha[OH]D3). In this study, 25 hemodialysis patients with moderate to severe secondary hyperparathyroidism who had normal serum calcium levels were enrolled. They received daily oral doses of alfacalcidol during an 8-week observation period. Based on serum calcium levels and intact PTH, the subjects were allocated into two groups, and a comparative study was conducted using unmasked crossover design of two drugs x two periods. The dosage of both drugs was adjusted to maintain the initial serum calcium levels, and the relative change (%change) of serum biochemical parameters were compared. Comparison of two drugs in period 1 was taken as primary efficacy evaluation. Reproducibility of drug action was confirmed by comparing the effect of falecalcitriol between period 1 and 2. The percent change of PTH of falecalcitriol was lower than that of alfacalcidol: Those were, respectively, -7.89% and +30.42% for c-terminal PTH (P = 0.022), -4.39% and +38.88% for i-PTH (P = 0.077), and +3.68% and +30.52% for midregion PTH (P = 0.099). The similar changes were observed in the falecalcitriol group during period 2, confirming the reproducibility. Falecalcitriol was found to be superior to alfacalcidol in suppression of PTH levels in patients with moderate to severe secondary hyperparathyroidism when it is administered in equivalent doses that might maintain similar serum calcium levels.", "Administration of intravenous (i.v.) calcitriol three times weekly effectively controls the synthesis and secretion of PTH in most uremic patients. Administration of a single dose of 1.25(OH)2D3 reduces synthesis of PTH-mRNA for 6 days in rats. Moreover, it can lower PTH levels for up to 4 days in chronic hemodialysis patients. Therefore, a good response to the administration of i.v. calcitriol two times weekly can be expected. We studied - in a multicenter randomized study in patients with moderate to severe secondary hyperparathyroidism - the effects of the same doses of intravenous calcitriol, administered two or three times weekly.\n Twenty-two hemodialysis patients were randomized into two frequencies of treatment groups: two times (G-2/w) and three times weekly (G-3/w). Both groups were treated with increasing doses of intravenous calcitriol for 3 months (first month 3 microg, second month 4 microg, third month 6 microg weekly).\n After 12 weeks of therapy with intravenous calcitriol the G-2/w group showed a significant reduction in serum PTH levels (from 821 +/- 392 to 350 +/- 246 pg/ml; mean reduction = 57.4%) comparable to the decrease observed in the G-3/w group (from 632 +/- 116 to 246 +/- 190 pg/ml; mean reduction = 61.2%). Ionized calcium (G-2/w from 1.13 +/-0.10 to 1.14 +/- 0.08 and G-3/w 1.21 +/- 0.13 to 1.26 +/- 0.18 mmol/l) and phosphate levels (G-2/w from 4.99 +/- 1.01 to 5.99 +/- 1.78 and G-3/w 5.31 +/- 0.73 to 5.81 +/- 1.18 mg/dl) did not change significantly and phosphate binders were not modified during the study.\n This study confirms that intravenous calcitriol is an effective therapy for moderate to severe secondary hyperparathyroidism. The administration of two doses per week of intravenous calcitriol is as efficacious as three doses per week in suppressing PTH secretion.", "Although the PTH-suppressive effect of intravenous calcitriol has already been demonstrated by various studies, the precise dose-response to calcitriol has not been fully determined for uremic secondary hyperparathyroidism (2HPT). In order to investigate in detail the dose-response of intravenous calcitriol and the adequate initial dose against 2HPT, a randomized prospective double-blind study was conducted.\n One-hundred and sixty-two patients with 2HPT undergoing hemodialysis three times per week were randomly assigned to four calcitriol (Ro21-5535) treatment groups, 0 (placebo), 1, 1.5 or 2 microg. Calcitriol or placebo was given intravenously after each dialysis for 12 weeks under double-blind conditions.\n Calcitriol dose-dependently reduced both intact-PTH and high-sensitivity assay mid-terminal (HS)-PTH levels. The rate of per-week change in intact-PTH was 0.0% in the placebo group, -7.8% in the 1-microg group, -18.9% in the 1.5-microg group and -24.1% in the 2-microg group. Calcitriol dose-dependently increased the rate of increase in serum Ca adjusted by albumin level. The per-week increases in adjusted serum Ca were -0.01, 0.08, 0.23 and 0.35 mg/dl in the placebo, 1-, 1.5- and 2-microg groups, respectively. Although the degree of PTH suppression was correlated with the adjusted serum Ca increase, by-patients investigation revealed that the number of patients with suppression of PTH despite of no or slight elevation of adjusted serum Ca level was largest in the 1-microg group among the three calcitriol groups.\n Intravenous calcitriol was found to have a clear dose-dependent effect on PTH reduction in patients with 2HPT, and the appropriate initial dose of this agent was determined to be 1 microg per dialysis session.\n Copyright 2002 S. Karger AG, Basel", "Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients.\n In the management of patients with mild secondary hyperparathyroidism, it is not known whether calcium supplementation alone is sufficient to correct abnormalities in bone and mineral metabolism or if calcitriol is needed in either physiologic oral or intravenous pharmacologic doses.\n This was a 40-week prospective nonmasked trial of 52 patients [parathyroid hormone (PTH) 150 to 600 pg/mL] who were randomized to receive escalating doses of either calcium carbonate (CaCO3) alone (calcium group, N = 11), daily oral calcitriol (oral group, N = 20), or intermittent intravenous calcitriol (IV group, N = 21). The groups were compared with regard to changes in serum intact PTH, serum bone-specific alkaline phosphatase (BAP), incidence of hypercalcemia (>10.5 mg/dL), and hyperphosphatemia (>6.5 mg/dL).\n PTH levels decreased in all groups (P < 0.01, paired t-test). In the calcium group, PTH (mean +/- SEM) decreased from 325 +/- 46.2 to 160 +/- 44.5 pg/mL. In the oral group, it decreased from 265 +/- 26.4 to 125 +/- 23.7 pg/mL, and in the IV group, it decreased from 240 +/- 27.7 to 65 +/- 10.0 pg/mL. Upon analysis of covariance, controlling for the initial PTH level, we found no differences in the PTH response between the groups (P > 0.10). In contrast, the BAP concentration increased from 20.7 +/- 7.6 to 27.5 +/- 7.0 microg/L in the calcium group (P = 0.17), decreased from 20. 6 +/- 3.9 to 17.8 +/- 4.5 microg/L in the oral group (P = 0.26), and from 19.1 +/- 2.6 to 10.6 +/- 1.1 microg/L in the IV group (P = 0. 007). Serum calcium increased significantly in all groups from 8.4 +/- 0.25 to 9.0 +/- 0.28, 8.5 +/- 0.16 to 9.2 +/- 0.27, and 8.7 +/- 0.16 to 9.4 +/- 0.18 mg/dL in the calcium, oral, and IV groups, respectively (P = NS difference between groups). Serum phosphorus was significantly lower in the calcium group throughout the study (P = 0.02). Hypercalcemic episodes were 2.0 +/- 0.8, 3.0 +/- 0.6, and 3. 4 +/- 0.6 per patient-year (P > 0.10), and hyperphosphatemic episodes were 0.9 +/- 0.56, 4.2 +/- 0.79 and 4.9 +/- 0.84 in the calcium, oral, and IV groups, respectively (P < 0.01).\n In mild secondary hyperparathyroidism, all three strategies are effective. High-dose CaCO3 alone may be sufficient to control PTH with a favorable side-effect profile, but calcitriol appears to have additional suppressive effects on bone that are greater following the intravenous route of administration and may increase the risk of adynamic bone disease.", "The aim of this prospective and randomized study was to compare the efficacy, side effects, and costs of 'pulse oral' versus intravenous calcitriol in the treatment of secondary hyperparathyroidism in hemodialysis (HD) patients. A total of 20 patients were randomized to receive over a 4-month period pulse orally administered calcitriol (pulse oral group; n = 10) or intravenous calcitriol (intravenous group; n = 10). All patients used standard dialysate calcium (1.75 mmol/l) throughout the study period. In accordance with the study design calcium dialysate concentrations were reduced when this was necessary to avoid hypercalcemic crises. The patients were stratified into two subgroups according to their initial serum PTH levels: patients with mild or moderate degree of hyperparathyroidism (17 patients) and patients with severe hyperparathyroidism (3 patients). Intravenous and pulse oral cacitriol did not significantly reduce serum PTH concentrations in patients with severe hyperparathyroidism (1,157 +/- 156 vs. 807 +/- 228 pg/ml [corrected], p = 0.09). Intermittent calcitriol, administered by intravenous or oral route, significantly reduced serum PTH levels (326 +/- 119 vs. 109 +/- 79 pg/ml [corrected], p = 0.0001) in patients with mild or moderate hyperparathyroidism. In patients with mild or moderate hyperparathyroidism, intravenous calcitriol significantly reduced PTH concentrations at the end of the 1st month, before the increase of serum ionized calcium levels, whereas 'pulse oral' calcitriol significantly suppressed parathyroid activity at the end of the 2nd month. Calcium dialysate concentration was reduced in 9 out of 10 (90%) patients of the pulse oral group and in all patients (10/10) of intravenous group. The incidence of hypercalcemic crises was 24% (39/160) in the pulse oral group and 14% (27/160) in the intravenous group. Analysis of costs showed that intravenous calcitriol was more expensive compared to pulse oral calcitriol. These data indicate that intermittent intensive calcitriol therapy, regardless of the route of administration, is effective in suppressing parathyroid activity in HD patients with mild or moderate hyperparathyroidism. In contrast, intermittent calcitriol therapy has a limited ability to achieve sustained serum PTH reductions in HD patients with severe hyperparathyroidism. Intravenous calcitriol was more expensive than pulse oral calcitriol, and we recommend the use of pulse oral calcitriol in HD patients with mild or moderate secondary hyperparathyroidism.", "Secondary hyperparathyroidism, a major clinical problem in patients with chronic renal failure, develops in response to phosphate retention and impaired calcitriol [1,25-dihydroxyvitamin D3] synthesis. Vitamin D therapy, particularly alfacalcidol [1 alpha-hydroxyvitamin D3], has been shown to be effective in the treatment of secondary hyperparathyroidism. The aim of this study was to compare the effect of a 12-week course of continuous versus intermittent oral alfacalcidol therapy on parathyroid hormone suppression.\n 34 patients were selected and randomly divided into 2 groups to receive either intermittent or continuous oral alfacalcidol. Baseline data were obtained on serum calcium, phosphorus, alkaline phosphatase and PTH. All but the PTH were monitored monthly. PTH levels were measured again until the end of the protocol. The intervention was 2 microg of alfacalcidol given after each dialysis session (intermittent group) or 1 microg given 6 days/week (continuous group).\n Serum calcium and phosphorus showed a tendency to increase from baseline levels in both groups. Mean PTH levels for both groups showed a progressive reduction over time during the study period. This decrement showed no significant difference with regard to the schedule of alfacalcidol administration when comparing the 2 groups. There also was no difference in the incidence of side effects--hypercalcemia and hyperphosphatemia--between the intermittent and continuous intervention.\n Feedback regulation of PTH with oral alfacalcidol therapy is efficient in the treatment of hyperparathyroidism. However, intermittent and continuous oral administration are equally effective in suppressing an elevated PTH level in hemodialysis patients, with similar safety margins.", "Hypercalcemia and hyperphosphatemia frequently necessitate vitamin D withdrawal in hemodialysis patients with secondary hyperparathyroidism. In short-term trials, doxercalciferol (1alpha-hydroxyvitamin D(2) [1alphaD(2)]) suppressed intact parathyroid hormone (iPTH) effectively with minimal increases in serum calcium and phosphorus (P) levels. This modified, double-blinded, controlled trial examined the efficacy and safety of 1alphaD(2) use in 138 hemodialysis patients with moderate to severe secondary hyperparathyroidism by using novel dose titration; 99 patients completed the study. Hemodialysis patients with secondary hyperparathyroidism were enrolled onto this study, consisting of washout (8 weeks), open-label 1alphaD(2) treatment (16 weeks), and randomized, double-blinded treatment with 1alphaD(2) or placebo (8 weeks). Oral 1alphaD(2) was administered at each hemodialysis session, with doses titrated to achieve target iPTH levels of 150 to 300 pg/mL. Baseline iPTH levels (897 +/- 52 [SE] pg/mL) decreased by 20% +/- 3.4% by week 1 (P: < 0.001) and by 55% +/- 2.9% at week 16; iPTH levels returned to baseline during placebo treatment but remained suppressed with 1alphaD(2) treatment. In 80% of the patients, iPTH level decreased by 70%, reaching the target level in 83% of the patients. Grouping patients by entry iPTH level (<600, 600 to 1,200, and >1,200 pg/mL) showed rapid iPTH suppression in the group with the lowest level; greater doses and longer treatment were required in the group with the highest level. During open-label treatment, serum calcium and P levels were 9.2 +/- 0.84 (SD) to 9.7 +/- 1.05 mg/dL and 5.4 +/- 1.10 to 5.9 +/- 1.55 mg/dL, respectively. During double-blinded treatment, serum calcium levels were slightly greater with 1alphaD(2) than placebo, but P levels did not differ. During double-blinded treatment, 3.26% and 0.46% of serum calcium measurements exceeded 11.2 mg/dL with 1alphaD(2) and placebo, respectively (P: < 0.01); median level was 11.6 mg/dL during hypercalcemia. Intermittent oral 1alphaD(2) therapy effectively suppresses iPTH in hemodialysis patients with secondary hyperparathyroidism, with acceptable mild hypercalcemia and hyperphosphatemia.", "The i.v. bolus administration of 1 alpha hydroxylated vitamin D derivatives is effective in the treatment of uremic hyperparathyroidism. However, few of the published studies of this mode of treatment have been adequately controlled, and recent reports have suggested that p.o. bolus administration may be just as effective. In this study, 16 hemodialysis patients with mild to moderate hyperparathyroidism were assigned, after a 4-wk run-in period, to receive a 6-wk course of either thrice-weekly i.v. or p.o. alfacalcidol (initial dose, 4 micrograms). Then, after a further control period, they received a second 6-wk course, with either p.o. or i.v. alfacalcidol (whichever was not given in the first treatment period). Plasma parathyroid hormone (PTH) was measured weekly by the use of an intact hormone assay. Both routes of therapy resulted in a significant suppression of plasma PTH (P = 0.005) and an elevation in plasma ionized calcium (P = 0.01). The magnitude of the responses was similar for the two treatment phases, as was the relationship between the increment in calcium and the decrement in PTH. The most complete suppression of PTH was seen in those with the greatest increment in plasma calcium. The incidence of hypercalcemia and the mean dose reductions necessary were also similar in the two treatment phases. Oral bolus therapy and i.v. bolus therapy with alfacalcidol are equally effective in suppressing hyperparathyroidism. The postulated advantages of i.v. over p.o. therapy with 1 alpha hydroxylated vitamin D derivatives remain to be confirmed by controlled studies.", "Management of secondary hyperparathyroidism has included the use of active vitamin D or vitamin D analogs for the suppression of parathyroid hormone (PTH) secretion. Although, these agents are effective, therapy is frequently limited by hypercalcemia, hyperphosphatemia, and/or elevations in the calcium-phosphorus (Ca x P) product. In clinical studies, paricalcitol was shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia as compared to placebo. A comparative study was undertaken in order to determine whether paricalcitol provides a therapeutic advantage to calcitriol.\n A double-blind, randomized, multicenter study comparing the safety and effectiveness of intravenous paricalcitol and calcitriol in suppressing PTH concentrations in hemodialysis patients was performed. A total of 263 randomized patients were enrolled at domestic and international sites. Following the baseline period, patients with serum Ca x P < 75, and a PTH level > or =300 pg/mL were randomly assigned to receive either paricalcitol or calcitriol in a dose-escalating fashion for up to 32 weeks. Dose adjustments were based on laboratory results for PTH, calcium, and Ca x P. The primary end point was the greater than 50% reduction in baseline PTH. Secondary end points were the occurrence of hypercalcemia and elevated Ca x P product.\n Paricalcitol-treated patients achieved a > or =50% reduction from baseline PTH significantly faster than did the calcitriol-treated patients (P = 0.025) and achieved a mean reduction of PTH into a desired therapeutic range (100 to 300 pg/mL) at approximately week 18, whereas the calcitriol-treated patients, as a group, were unable to achieve this range. Moreover, paricalcitol-treated patients had significantly fewer sustained episodes of hypercalcemia and/or increased Ca x P product than calcitriol patients (P = 0.008).\n Paricalcitol treatment reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased Ca x P product than calcitriol therapy.", "The present study examined the effect of intermittent oral high doses of 1-alpha-OHD3 in combination with a pharmacological dose of 24,25(OH)2D3 on parathyroid hormone (PTH) secretion. Twenty hemodialysis (HD) patients (10 males, aged 26-72 years, on regular hemodialysis for 7-128 months) with secondary hyperparathyroidism resistant to long-term low-dose 1-alpha-OHD3 therapy were studied for 24 weeks. At the outset of the study they were randomly divided into two groups: group 1 received high-dose 1-alpha-OHD3 plus 24,25(OH)2D3 (2 x 5 micrograms/day) and group 2 was on monotherapy with 1-alpha-OHD3. 1-alpha-OHD3 was given three times a week in the evening before each HD in gradually increased doses from 1 to 4 micrograms adjusted to keep serum calcium levels below 2.6 mmol/L. During the therapy mean serum calcium and ionized calcium levels increased but remained in the normal ranges without differences between the two groups. However, the frequency of hypercalcemia episodes was different in the two groups. In the first 12 weeks the number of hypercalcemia episodes was significantly lower in group 1 than in group 2 (6 vs. 12; p < .05), allowing the use of significantly higher 1-alpha-OHD3 doses in group 1. In the second 12 weeks of the study the 1-alpha-OHD3 dose in group 1 had to be reduced due to more frequent appearance of hypercalcemia. So, the 1-alpha-OHD3 doses became similar in the two groups during the second 12 weeks of the study.(ABSTRACT TRUNCATED AT 250 WORDS)", "Our prospective 1-year study comprises 93 patients of both sexes, various ages and various dialysis duration. Among them, 31 patients with a concentration of Ca in blood under 2.7 mmol/l, a concentration of P under 1.8 mmol/l and a concentration of PTHi over 65 pg/ml (group 0) received calcitriol 0.25 microgramx418p4The control group consisted of patients not receiving calcitriol and having normal Ca and P metabolism (group 1). The rest of the patients had a concentration of P over 1.8 mmol/l and could not be given calcitriol. A comparison of the dynamics of average plasmic concentrations of Ca, P, AP, PTHi and X-ray changes in group 0 and 1 at the beginning of the investigation and 1 year later was carried out. At the termination of the 1-year treatment, when compared to the initial state, a statistically significant increase in the concentration of Ca (p < 0.005) and in the concentration of P (p < 0.005) was noted in group 0. The average concentration of PTHi decreased to the desired level, the X-ray changes characteristic of secondary hyperparathyroidism progressed more slowly in group 0.", "Calcitriol has shown a benefit in various small uncontrolled studies of ex vivo immune function. We hypothesized that paricalcitol, a new vitamin D derivative, will have a positive effect on the immune system with minimal adverse effects on calcium homeostasis. Thirty-one hemodialysis patients not administered vitamin D because of low intact parathyroid hormone (PTH) levels were randomized to placebo or 4 microg of paricalcitol intravenously with the hemodialysis session three times weekly for 12 weeks. Effects on in vivo and ex vivo assessments of immune function were evaluated. All patients achieved the target dose of paricalcitol. Twenty patients were anergic at the start of the study; 4 of 11 patients in the paricalcitol group and 0 of 9 patients in the placebo group converted to reactive (P = 0.09). The in vivo response to standard hepatitis B booster vaccine and in vitro proliferation and release of interleukin-2 (IL-2), IL-6, tumor necrosis factor-alpha, and interferon-gamma from stimulated lymphocytes were not different between the groups. In contrast to clinical immune effects, paricalcitol increased serum calcium levels and decreased PTH and bone alkaline phosphatase levels (all P < 0.05). However, hypercalcemia was infrequent. In vitro experiments showed that paricalcitol led to greater dose-dependent thymidine uptake than calcitriol in lymphocytes isolated from either dialysis patients or control subjects. Paricalcitol has a tendency toward improving delayed hypersensitivity reactions, but did not have other proimmune effects. However, as expected, paricalcitol had significant effects on calcium homeostasis compared with placebo. Thus, patients with low PTH levels are unlikely to experience the proimmune effects of vitamin D therapy without more profound and potentially adverse oversuppression of PTH." ]

[ "8026290" ]

[ "Clinical evaluation of a semipermeable polymeric membrane dressing for the treatment of chronic diabetic foot ulcers." ]

[ "To evaluate the utility of a semipermeable polymeric membrane dressing for the treatment of chronic diabetic foot ulcers.\n Nineteen subjects with either insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) and foot ulcers were randomly assigned to the polymeric dressing or conventional wet-to-dry saline dressings. Subjects had foot ulcer site measurements performed every 3 weeks. The subjects using conventional therapy were allowed to cross over to polymeric dressing after 2 months.\n At the end of 2 months, in the patients using the polymeric dressing, ulcer size was reduced to 35 +/- 16% of baseline. The patients on conventional therapy had an ulcer size of 105 +/- 28% of baseline (P < 0.03, polymeric vs. conventional). Patients initially treated with wet-to-dry saline were crossed over into the polymeric membrane treatment and demonstrated a decrease to 35 +/- 11% of baseline size (p < 0.02) after an additional 2 months.\n The semipermeable polymeric membrane dressing is a useful therapeutic option for treating uncomplicated chronic diabetic foot ulcers." ]

[ "6781888", "8979563", "1864478", "8156961", "3928820", "1814875", "3919805", "8601999", "7823066" ]

[ "Comparison of sodium valproate and phenytoin as single drug treatment in epilepsy.", "Comparison of phenobarbitone, phenytoin with sodium valproate: randomized, double-blind study.", "Cognitive impairment in new cases of epilepsy randomly assigned to carbamazepine, phenytoin and sodium valproate.", "Impact of valproate and phenytoin on cognitive function in elderly patients: results of a single-blind randomized comparative study.", "A prospective study between carbamazepine, phenytoin and sodium valproate as monotherapy in previously untreated and recently diagnosed patients with epilepsy.", "Comparison of sodium valproate and phenytoin as single drug treatment in generalised and partial epilepsy.", "Which drug for the adult epileptic patient: phenytoin or valproate?", "Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy.", "Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial." ]

[ "Thirty-three epileptic patients were randomly divided into two treatment groups. One group of 18 patients was given sodium valproate; the other 15 patients were given phenytoin. Periods of treatment ranged from 9 t0 48 months (mean, 30 months). Any patient who developed a seizure while on the first drug was changed to the other drug, provided the serum level of the first drug was in the accepted therapeutic range. Six required the change from phenytoin to sodium valproate, and three from sodium valproate to phenytoin. Side effects were not a major problem with either drug during the trial period. Phenytoin has been widely prescribed alone; our results indicate that sodium valproate may also be used as a single drug in the treatment of several types of epilepsy.", "To compare the efficacy and side effects of phenobarbitone (PB), phenytoin (PHT) and sodium valproate (SVP) in controlling generalized tonic-clonic convulsions (GTC).\n Randomized, double blind clinical trial.\n Out-Patients in a tertiary care hospital.\n 151 children with GTC, aged 4-12 yrs, from Madras city were enrolled. At the end of 2 yrs, 127 children remained in the study.\n Each child was given one active drug and 2 placebo tablets. Clinical, hematological and biochemical evaluations were done every month. Serum drug levels were assessed periodically.\n Recurrence of convulsion and side effects.\n The proportion of children with recurrence did not differ among the 3 groups. More than one side effect was observed in 16 (32%) children on PB, 20 (40%) children on PHT and 9 (19%) children on SVP and this difference was statistically significant (p < 0.05). Hyperactivity was the major side effect of PB, observed in 22% of children.\n All 3 drugs were equally effective in controlling seizures. Side effects were minimal with SVP followed by PB. Though side effects were more frequent with PHT, most of them disappeared on adjusting drug dosage. Least expensive phenobarbitone may be preferred as the first drug of choice but, only for pre-school children. SVP is advised for school going children.", "Sixty-four new cases of childhood epilepsy were randomly assigned to either carbamazepine, phenytoin or sodium valproate, and were assessed with cognitive tests before medication and three subsequent times over a year. Carbamazepine in moderate dosage adversely affected memory, but sodium valproate and phenytoin did not.", "Thirty-eight patients (median age 77 years; range 62-88 years) with elderly-onset seizures were entered into a single-blind, randomized study designed to compare the impact of phenytoin (PHT) and valproate (VPA) on cognitive function. A stratified minimization program matched the two groups for age, sex, and seizure type. Attention, concentration, psychomotor speed, and memory were assessed twice before treatment (to minimize practice effects), at 6 weeks and (for patients remaining in the study) at 3 months, 6 months, and 1 year by an extensive battery of psychologic tests. Changes in cognitive function were minor, and some tended toward improvement. Contrary to expectation, there was little difference between PHT and VPA with regard to impact on cognitive function. Frequent noncognitive adverse effects were reported. Thus, we did not replicate the findings of previous literature. We conclude that antiepileptic drug (AED) monotherapy as used in our trial did not produce significant adverse cognitive effects. The choice of AED in the elderly may therefore be more influenced by consideration of other adverse effects.", "One hundred and eighty one patients with previously untreated epilepsy were randomised to sodium valproate, phenytoin or carbamazepine as monotherapy and followed up for a median period which ranged from 14 to 24 months. All three drugs were highly effective in the control of generalised seizures but less effective for partial seizures. Excellent or good control was achieved with therapeutic levels of sodium valproate and carbamazepine, but with subtherapeutic levels of phenytoin.", "Ninety four patients of generalised and partial epilepsy were randomly assigned to treatment with sodium valproate (49 cases) or phenytoin (45 cases). Serum levels were monitored. Cases were evaluated after 4, 12, 24 weeks of treatment. Both drugs were found to be equally effective in controlling generalised seizures. However, valproate is better in partial seizures. No correlation could be established. Side effects were minor with both the drugs.", "A series of 140 previously untreated patients with tonic-clonic or partial seizures were randomised to receive either phenytoin or sodium valproate. There was no difference between the treatment groups in pretreatment variables that might influence outcome. Sodium valproate and phenytoin in the treatment of tonic-clonic or partial seizures showed no difference in efficacy as regards time to two year remission or time to first seizure. When the possible prognostic factors were studied, including history and results of clinical examination and investigations before treatment; the only factor which influenced the proportion of patients achieving two year remission was type of seizure. Patients with a clinical history of partial seizures did significantly less well than those with a history of tonic-clonic seizures only. This study showed no major difference in efficacy between sodium valproate and phenytoin in adults with recent onset of epilepsy, irrespective of the type of seizures that the patient suffered.", "The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy.\n Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission.\n The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.", "Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs." ]

[ "1987395", "9692452", "11932655" ]

[ "A prospective randomized study of cerebrospinal fluid drainage to prevent paraplegia after high-risk surgery on the thoracoabdominal aorta.", "Reduction of neurologic injury after high-risk thoracoabdominal aortic operation.", "Cerebrospinal fluid drainage reduces paraplegia after thoracoabdominal aortic aneurysm repair: results of a randomized clinical trial." ]

[ "This article is concerned with the study of the effect of several variables, principally that of cerebrospinal fluid drainage, on the incidence of neurologic deficit in a prospective randomized series of patients with extensive aneurysms of the descending thoracic and abdominal aorta (thoracoabdominal type I and II). Forty-six patients had cerebrospinal fluid drainage, and 52 were controls, with a total of 98 available for study. Cerebrospinal fluid pressure was continuously monitored in the former group and pressure maintained less than or equal to 10 mm Hg in 20, less than or equal to 15 mm Hg in 20, and greater than 15 mm Hg in 6 patients during period of aortic clamping. The method of treatment including reattachment of intercostal and lumbar arteries (p = 0.2), temporary atriofemoral bypass during aortic occlusion (p = 0.3), and spinal fluid drainage (p = 0.8) were not statistically significant in reducing the incidence of neurologic deficits. Thus cerebrospinal fluid drainage as we used it, was not beneficial in preventing paraplegia. On appropriate statistical analysis we found that the only significant predictor of delayed deficits was postoperative hypotension (p = 0.006).", "Of all aortic operations, thoracoabdominal aortic repairs have the highest risk of spinal cord neurologic injury, manifest by lower limb paraplegia or paraparesis. Cerebrospinal fluid drainage combined with intrathecal papaverine (CSFDr + IP) may reduce the risk and severity of neurologic injury. The objective of this study was to evaluate the effect of CSFDr + IP to prevent neurologic injury after high-risk thoracoabdominal aneurysm repairs.\n We screened 64 patients before operation with descending thoracic or thoracoabdominal aneurysms for possible inclusion in a prospective, randomized study. Thirty-three patients with high-risk type I and II thoracoabdominal aneurysms met inclusion criteria and 17 were randomly assigned to CSFDr + IP and 16 to the control group. The study was terminated early after interim analysis revealed a significant difference.\n Of 64 patients screened, 2 patients died after operation (3.1%, 2/64); both were in the randomized study (6%, 2/33), and neither had a neurologic injury. Neurologic injury developed in 2 CSFDr + IP patients and 7 control patients (p = 0.0392). Control patients also had lower postoperative motor strength scores (p = 0.0340). On multivariate analysis, risk factors for neurologic injury included (p < 0.05) longer cross-clamp time, failure to actively cool with bypass, and postoperative hypotension, whereas CSFDr + IP was protective. Logistic regression showed that CSFDr + IP and active cooling significantly reduced the risk of injury and that the two combined modalities were additive. Of 64 patients screened, only 2 (3%) had a permanent neurologic deficit preventing ambulation.\n For high-risk thoracoabdominal aneurysms, CSFDr + IP was effective in reducing the incidence and severity of neurologic injury. Active cooling may be further additive to CSFDr + IP protection, although this needs to be confirmed in a larger study.", "Despite the use of various strategies for the prevention of spinal cord ischemia, paraplegia and paraparesis continue to occur after thoracoabdominal aortic aneurysm (TAAA) repair. Although cerebrospinal fluid drainage (CSFD) is often used as an adjunct for spinal cord protection, its benefit remains unproven. The purpose of this randomized clinical trial was to evaluate the impact of CSFD on the incidence of spinal cord injury after extensive TAAA repair.\n After randomization, 145 patients underwent extent I or II TAAA repairs with a consistent strategy of moderate heparinization, permissive mild hypothermia, left heart bypass, and reattachment of patent critical intercostal arteries. The repairs were performed with CSFD (n = 76) or without CSFD (n = 69). In the former group, CSFD was initiated during the operation and continued for 48 hours after surgery. The target CSF pressure was 10 mm Hg or less.\n The two groups had similar risk factors for paraplegia. Aortic clamp time, left heart bypass time, and number of reattached intercostal arteries were also similar in both groups. Thirty-day mortality rates were 5.3% (four patients) and 2.9% (two patients) for CSFD and control groups, respectively (P =.68). Nine patients (13.0%) in the control group had paraplegia or paraparesis develop. In contrast, only two patients in the CSFD group (2.6%) had deficits develop (P =.03). No patients with CSFD had immediate paraplegia. Overall, CSFD resulted in an 80% reduction in the relative risk of postoperative deficits.\n Perioperative CSFD reduces the rate of paraplegia after repair of extent I and II TAAAs." ]

[ "18948800", "17503161", "12814414", "16473379", "15141368", "20855414", "15644016", "11809253" ]

[ "Effects of a perioperative smoking cessation intervention on postoperative complications: a randomized trial.", "Strategies of smoking cessation intervention before hernia surgery--effect on perioperative smoking behavior.", "Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.", "A randomized controlled trial to assess the effectiveness of a letter from a consultant surgeon in causing smokers to stop smoking pre-operatively.", "Efficacy of a smoking-cessation intervention for elective-surgical patients.", "Brief smoking cessation intervention in relation to breast cancer surgery: a randomized controlled trial.", "A programme for reducing smoking in pre-operative surgical patients: randomised controlled trial.", "Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial." ]

[ "To determine whether an intervention with smoking cessation starting 4 weeks before general and orthopedic surgery would reduce the frequency of postoperative complications.\n Complications are a major concern after elective surgery and smokers have an increased risk. There is insufficient evidence concerning how the duration of preoperative smoking intervention affects postoperative complications.\n A randomized controlled trial, conducted between February 2004 and December 2006 at 4 university-affiliated hospitals in the Stockholm region, Sweden. The outcome assessment was blinded. The follow-up period for the primary outcome was 30 days. Eligibility criteria were active daily smokers, aged 18 to 79 years. Of the 238 patients assessed, 76 refused participating, and 117 men and women undergoing surgery for primary hernia repair, laparoscopic cholecystectomy, or a hip or knee prosthesis were enrolled.\n Smoking cessation therapy with individual counseling and nicotine substitution started 4 weeks before surgery and continued 4 weeks postoperatively. The control group received standard care. The main outcome measure was frequency of any postoperative complication.\n An intention-to-treat analysis showed that the overall complication rate in the control group was 41%, and in the intervention group, it was 21% (P = 0.03). Relative risk reduction for the primary outcome of any postoperative complication was 49% and number needed to treat was 5 (95% CI, 3-40). An analysis per protocol showed that abstainers had fewer complications (15%) than those who continued to smoke or only reduced smoking (35%), although this difference was not statistically significant.\n Perioperative smoking cessation seems to be an effective tool to reduce postoperative complications even if it is introduced as late as 4 weeks before surgery.", "Although it is now generally accepted that patients should be advised to quit smoking before surgery, the effect of low-intensive smoking cessation intervention, both on preoperative smoking behavior and on risk reduction, remains unclear. Our objective was to study the effect on perioperative smoking behavior and on postoperative wound infection of different types of low-intensive intervention before herniotomy.\n Between October 1998 and October 2000, 180 consecutive smokers scheduled for elective herniotomy were advised to quit smoking perioperatively and subsequently allocated randomly to three low-intensive smoking cessation groups: a standard (control) group, a telephone group, which was reminded by telephone, and an out-patient group, which was reminded by means of an out-patient talk and demonstration of nicotine replacement drugs. Spontaneous perioperative smoking behavior was recorded for 64 consecutive non-advised smokers. Postoperative wound infection was evaluated by independent assessors.\n Of the advised patients, 19% (29/149) stopped smoking before surgery compared with 2% (1/64) in the non-advised cohort (P < 0.01). In the standard group 13% (6/48) quit smoking compared with 23% (23/101) in the pooled telephone and outpatient group (NS). In the last group 64% (65/101) reduced or stopped smoking compared with 42% (20/48) in the standard group (P < 0.05). Predictors of failed perioperative cessation of smoking were a CO breath-test at inclusion above 20 ppm (OR: 0.11; 0.02-0-57) and low motivation to quit smoking (OR: 0.25; 0.09-0.70). Wound infection occurred in 6% (13/213) and there was no difference between the groups.\n Low-intensive smoking cessation intervention helps approximately one fifth of patients to stop smoking perioperatively. Patients who are reminded in addition to preoperative advice are more likely to stop or reduce smoking. Failure to stop smoking is greater if the patients are not motivated and if the CO breath test is high at the time of the preoperative advice.", "Smokers have a higher risk of complicated tissue and wound healing after surgery than nonsmokers. We tested the hypothesis that short-term pre-operative cessation of smoking in colorectal surgery decreases the incidence of postoperative tissue and wound complications.\n From February 1998 to March 2001, 60 patients, who smoked daily, undergoing colorectal resection were randomly assigned 2-3 weeks before scheduled surgery to either abstinence from smoking, counselling and nicotine replacement therapy or maintenance of daily smoking habits. Postoperative tissue and wound complications necessitating surgical or medical treatment were evaluated at discharge and 30 days after surgery by blinded outcome assessment.\n In the pre-operative period of 15 days (8-24) (median, interquartile range (IQR)), 89% of the patients in the intervention group vs. 13% in the control group abstained from smoking or reduced by more than half (P < 0.05). In the postoperative period of 11 days (10-13), the corresponding figures were 92% and 50%, respectively (P < 0.05). Postoperative tissue and wound complications occurred in 33% (9 of 27) of the patients in the intervention group compared to 27% (8 of 30) in the control group (NS). Likewise, no difference in overall postoperative complication rate was found between the groups.\n Short-term cessation of smoking does not reduce the risk of complicated tissue and wound healing or other complications in colorectal surgery.", "nan", "We tested an intervention to help smokers abstain (fast) from smoking before surgery, maintain abstinence postoperatively, and achieve long-term cessation. A randomized experiment included 237 patients admitted for presurgical assessment who smoked. The intervention included counseling and nicotine replacement therapy. Treatment group participants (73.0%) were more likely to fast than were controls (53.0%): chi(2)(1, N = 228) = 8.89, p =.003, and more likely to be abstinent 6 months after surgery (31.2% vs. 20.2%). There was no significant difference in the abstinence rates at 12 months after surgery, chi(2)(1, N = 169) <.001, p = 1.00. Encouraging patients to fast from smoking before surgery and postoperative support are efficacious ways to reduce preoperative and immediate post-operative tobacco use.\n Copyright 2004 Wiley Periodicals, Inc.", "Smokers are more prone to develop postoperative complications. Smoking cessation intervention beginning 4-8 weeks prior to surgery improves the postoperative outcome. Cancer patients, however, often undergo surgery less than 4 weeks after diagnosis. The primary objective of this study was therefore to examine if a brief smoking cessation intervention shortly before breast cancer surgery would influence postoperative complications and smoking cessation.\n A randomized controlled multicentre trial with blinded outcome assessment conducted at 3 hospitals in Denmark. One hundred and thirty patients were randomly assigned to brief smoking intervention (n = 65) or standard care (n = 65). The intervention followed the principles of motivational interviewing and included personalized nicotine replacement therapy aimed at supporting smoking cessation from 2 days before to 10 days after surgery.\n The overall postoperative complication rate (including seroma requiring aspiration) was 61% in both groups risk ratio (RR) 1.00 (95% CI 0.75-1.33). The wound complication rate was 44% versus 45%. The effect on perioperative smoking cessation was modest, 28% intervention versus 11% control group patients, RR 2.49 (95% CI 1.10-5.60). There was no effect on smoking cessation at 12 months, 13% versus 9%.\n Brief smoking intervention administered shortly before breast cancer surgery modestly increased self-reported perioperative smoking cessation without having any clinical impact on postoperative complications. The study adds to the body of evidence indicating that brief intervention has no clinical importance for surgical patients in regard to postoperative morbidity. Future studies should be designed to determine the optimal time of smoking cessation before surgery.", "We assessed the efficacy of a comprehensive programme for stopping smoking in 210 smokers scheduled for surgery, before admission and 3 months after attending a pre-operative clinic. Participants were randomly allocated to receive an intervention incorporating nicotine replacement therapy for patients smoking more than 10 cigarettes per day (\"dependent smokers\"), or to a control group to receive usual care. Dependent smokers allocated to the intervention group were more likely to report abstinence before surgery than those allocated to receive usual-care (63 (73%) vs. 29 (56%), respectively; OR 2.2 (95% CI 1.0-4.8)), and 3 months after attendance (16 (18%) vs. 3 (5%), respectively; OR = 3.9 (95% CI 1.0-21.7).", "Smokers are at higher risk of cardiopulmonary and wound-related postoperative complications than non-smokers. Our aim was to investigate the effect of preoperative smoking intervention on the frequency of postoperative complications in patients undergoing hip and knee replacement.\n We did a randomised trial in three hospitals in Denmark. 120 patients were randomly assigned 6-8 weeks before scheduled surgery to either the control (n=60) or smoking intervention (60) group. Smoking intervention was counselling and nicotine replacement therapy, and either smoking cessation or at least 50% smoking reduction. An assessor, who was masked to the intervention, registered the occurrence of cardiopulmonary, renal, neurological, or surgical complications and duration of hospital admittance. The main analysis was by intention to treat.\n Eight controls and four patients from the intervention group were excluded from the final analysis because their operations were either postponed or cancelled. Thus, 52 and 56 patients, respectively, were analysed for outcome. The overall complication rate was 18% in the smoking intervention group and 52% in controls (p=0.0003). The most significant effects of intervention were seen for wound-related complications (5% vs 31%, p=0.001), cardiovascular complications (0% vs 10%, p=0.08), and secondary surgery (4% vs 15%, p=0.07). The median length of stay was 11 days (range 7-55) in the intervention group and 13 days (8-65) in the control group.\n An effective smoking intervention programme 6-8 weeks before surgery reduces postoperative morbidity, and we recommend, on the basis of our results, this programme be adopted." ]

[ "16154062", "12092017", "16504907", "18695809", "9883917", "18669713", "18021143", "11375230" ]

[ "Midwifery care measures in the second stage of labor and reduction of genital tract trauma at birth: a randomized trial.", "Traditional care of the perineum during birth. A prospective, randomized, multicenter study of 1,076 women.", "A comparison of \"hands off\" versus \"hands on\" techniques for decreasing perineal lacerations during birth.", "The use of liquid petroleum jelly in the prevention of perineal lacerations during birth.", "A randomised controlled trial of care of the perineum during second stage of normal labour.", "Modified Ritgen's maneuver for anal sphincter injury at delivery: a randomized controlled trial.", "Perineal outcomes and maternal comfort related to the application of perineal warm packs in the second stage of labor: a randomized controlled trial.", "Perineal massage in labour and prevention of perineal trauma: randomised controlled trial." ]

[ "Genital tract trauma after spontaneous vaginal childbirth is common, and evidence-based prevention measures have not been identified beyond minimizing the use of episiotomy. This study randomized 1211 healthy women in midwifery care at the University of New Mexico teaching hospital to 1 of 3 care measures late in the second stage of labor: 1) warm compresses to the perineal area, 2) massage with lubricant, or 3) no touching of the perineum until crowning of the infant's head. The purpose was to assess whether any of these measures was associated with lower levels of obstetric trauma. After each birth, the clinical midwife recorded demographic, clinical care, and outcome data, including the location and extent of any genital tract trauma. The frequency distribution of genital tract trauma was equal in all three groups. Individual women and their clinicians should decide whether to use these techniques on the basis of maternal comfort and other considerations.", "To investigate the influence of the traditional hands-on versus the innovative hands-poised method on the risk of perineal trauma during vaginal delivery and on neonatal outcomes.\n In a prospective, randomized, multicenter study, 1,161 of 1,505 women giving birth at the Departments of Obstetrics and Gynecology of the University Hospital of Vienna and Semmelweis Women's Hospital, Vienna, between February and September 1999, were randomized into the trial. In the hands-on method, the left hand of the midwife puts pressure on the infant's head, and the right hand is placed against the perineum. In the hands-poised method, the midwife guides the parturient through the birth without touching the perineum, prepared to apply light pressure on the infant's head.\n One hundred eighty-seven of 574 women (32.5%) in the hands-on group and 180 of 502 women (35.8%) in the hands-poised group experienced perineal tears (P = .5). Sixteen women (2.7%) treated with the hands-on method developed third-degree perineal tears as compared with five women (0.9%) treated with the hands-poised method (P < .05). In the hands-on group, 103 women (17.9%) underwent episiotomy as compared with 51 cases (10.1%) in the hands-poised group (P < .01). No significant differences in neonatal outcomes were observed between the two groups.\n Our data suggest that a policy of hands-poised care is more suitable for preserving the perineum during birth and is a safe and effective birthing alternative for women.", "Our goal was to determine the frequency, degree, and location of perineal lacerations and the neonatal outcomes associated with the use of two techniques of perineal protection--expectant (\"hands off\") and interventionist (\"hands on\")--during childbirth. We conducted a randomized controlled trial to compare the effectiveness of two techniques for perineum protection during spontaneous delivery. Study participants included 70 nulliparous expectant mothers, who were divided equally between the \"hands off\" and \"hands on\" groups (n = 35 per group). Perineal laceration occurred in 81.4% of the women. Among these, first-degree lacerations were predominant (82.5%). Lacerations in the anterior and posterior regions of the perineum occurred with similar frequencies. Laceration rates did not differ between the \"hands off\" and \"hands on\" groups (P > .05). Neonatal outcomes were similar in both groups. The use of \"hands off\" technique of perineal protection does not alter the frequency or degree of perineal lacerations in childbirth, relative to a \"hands on\" technique.", "Most of vaginal births are accompanied by lacerations in the genital tract. This was a randomized study carried out in a Birth Center located in São Paulo city to evaluate the efficacy of liquid petroleum jelly in reducing perineal laceration. The sample was composed of 38 nulliparous women per group (experimental and control). In the experimental group was used 30 ml of the petroleum jelly in the perineal region during the expulsive period. The parturient were allowed to push spontaneously during the delivery and remained in the left side position. The frequency of perineal laceration was similar in both groups (experimental 63.2% versus control 60.5%). The posterior perineum region presented the highest frequency of trauma (53.2%). Of the total cases of perineal trauma, 72.3% were first-degree lacerations. The use of liquid petroleum jelly of perineal protection does not reduce the frequency neither the degree of lacerations in childbirth.", "To compare the effect of two methods of perineal management used during spontaneous vaginal delivery on the prevalence of perineal pain reported at 10 days after birth.\n Randomised controlled trial.\n Two English maternity care units.\n 5471 women who gave birth between December 1994 and December 1996.\n At the end of the second stage of labour women were allocated to either the 'hands on' method, in which the midwife's hands put pressure on the baby's head and support ('guard') the perineum; lateral flexion is then used to facilitate delivery of the shoulders, or the 'hands poised' method, in which the midwife keeps her hands poised, not touching the head or perineum, allowing spontaneous delivery of the shoulders.\n Perineal pain in the previous 24 hours reported by women in self-administered questionnaire 10 days after birth.\n Questionnaires were completed by 97% of women at 10 days after birth. 910 (34.1%) women in the 'hands poised' group reported pain in the previous 24 hours compared with 823 (31.1%) in the 'hands on' group (RR 1.10, 95% CI 1.01 to 1.18: absolute difference 3%, 0.5% to 5%, P = 0.02). The rate of episiotomy was significantly lower in the 'hands poised' group (RR 0.79, 99% CI 0.65 to 0.96, P = 0.008) but the rate of manual removal of placenta was significantly higher (RR 1.69, 99% CI 1.02 to 2.78; P = 0.008). There were no other statistically significant differences detected between the two methods.\n The reduction in pain observed in the 'hands on' group was statistically significant and the difference detected potentially affects a substantial number of women. These results provide evidence to enable individual women and health professionals to decide which perineal management is preferable.", "To investigate whether Ritgen's maneuver decreases the risk of third- to fourth-degree perineal tears compared with simple perineal support.\n A total of 1,623 nulliparous women in term labor, singleton pregnancy, and cephalic presentation were randomly assigned to Ritgen's maneuver or standard care. Ritgen's maneuver denotes extracting the fetal head, using one hand to pull the fetal chin from between the maternal anus and the coccyx, and the other on the fetal occiput to control speed of delivery. Ritgen's maneuver was performed during a uterine contraction, rather than, as originally recommended, between contractions. Our standard care entailed perineal support with one hand and control of the speed of crowning with the other, and use of Ritgen's maneuver only on specific indications. Women delivered by cesarean delivery (n=10) or instrumentally (n=142) were excluded, as well as 39 erroneously included women (parous or in preterm labor), six inaccurately assigned participants, one with missing data, and two participants who withdrew consent. For the remaining 1,423 women, the result was analyzed according to intention to treat.\n Ritgen's maneuver was performed in 554 (79.6%) of 696 women randomly assigned to this procedure and in 31 (4.3%) of 727 women randomly assigned to simple perineal support. The rate of third- to fourth-degree tears was 5.5% (n=38) in women assigned to Ritgen's maneuver and 4.4% (n=32) in those assigned to simple perineal support (relative risk 1.24; 95% confidence interval 0.78-1.96).\n Ritgen's maneuver does not decrease the risk of anal sphincter injury at delivery, at least not when performed during a contraction.", "Perineal warm packs are widely used during childbirth in the belief that they reduce perineal trauma and increase comfort during late second stage of labor. The aim of this study was to determine the effects of applying warm packs to the perineum on perineal trauma and maternal comfort during the late second stage of labor.\n A randomized controlled trial was undertaken. In the late second stage of labor, nulliparous women (n = 717) giving birth were randomly allocated to have warm packs (n = 360) applied to their perineum or to receive standard care (n = 357). Standard care was defined as any second-stage practice carried out by midwives that did not include the application of warm packs to the perineum. Analysis was on an intention-to-treat basis, and the primary outcome measures were requirement for perineal suturing and maternal comfort.\n The difference in the number of women who required suturing after birth was not significant. Women in the warm pack group had significantly fewer third- and fourth-degree tears and they had significantly lower perineal pain scores when giving birth and on \"day 1\" and \"day 2\" after the birth compared with the standard care group. At 3 months, they were significantly less likely to have urinary incontinence compared with women in the standard care group.\n The application of perineal warm packs in late second stage does not reduce the likelihood of nulliparous women requiring perineal suturing but significantly reduces third- and fourth-degree lacerations, pain during the birth and on days 1 and 2, and urinary incontinence. This simple, inexpensive practice should be incorporated into second stage labor care.", "To determine the effects of perineal massage in the second stage of labour on perineal outcomes.\n Randomised controlled trial. Participants: At 36 weeks' gestation, women expecting normal birth of a singleton were asked to join the study. Women became eligible to be randomised in labour if they progressed to full dilatation of the cervix or 8 cm or more if nulliparous or 5 cm or more if multiparous. 1340 were randomised into the trial.\n Massage and stretching of the perineum during the second stage of labour with a water soluble lubricant.\n Primary outcomes: rates of intact perineum, episiotomies, and first, second, third, and fourth degree tears.\n pain at three and 10 days postpartum and pain, dyspareunia, resumption of sexual intercourse, and urinary and faecal incontinence and urgency three months postpartum.\n Rates of intact perineums, first and second degree tears, and episiotomies were similar in the massage and the control groups. There were fewer third degree tears in the massage group (12 (1.7%) v 23 (3.6%); absolute risk 2.11, relative risk 0.45; 95% confidence interval 0.23 to 0.93, P<0.04), though the trial was underpowered to measure this rarer outcome. Groups did not differ in any of the secondary outcomes at the three assessment points.\n The practice of perineal massage in labour does not increase the likelihood of an intact perineum or reduce the risk of pain, dyspareunia, or urinary and faecal problems." ]

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[ "A randomized, double-blind, placebo-controlled clinical evaluation of a nicotine sublingual tablet in smoking cessation.", "Smoking cessation in women concerned about weight.", "Weight gain prevention and smoking cessation: cautionary findings.", "The effects of phenylpropanolamine on dietary intake, physical activity, and body weight after smoking cessation.", "Effectiveness of a transdermal nicotine system in smoking cessation studies.", "Effects of phenylpropanolamine on withdrawal symptoms.", "High-dose nicotine patch therapy. Percentage of replacement and smoking cessation.", "A placebo controlled randomized trial of the effects of phenylpropanolamine and nicotine gum on cessation rates and postcessation weight gain in women.", "The nicotine inhaler in smoking cessation.", "Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice.", "Cognitive-behavioral therapy to reduce weight concerns improves smoking cessation outcome in weight-concerned women.", "Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up.", "Efficacies of dexfenfluramine and fluoxetine in preventing weight gain after smoking cessation.", "Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial.", "Bupropion and cognitive behavioral therapy for weight-concerned women smokers.", "Individualizing nicotine replacement therapy for the treatment of tobacco dependence: a randomized trial.", "A comparison of the nicotine lozenge and nicotine gum: an effectiveness randomized controlled trial.", "The efficacy of exercise as an aid for smoking cessation in women: a randomized controlled trial.", "Effect of nicotine nasal spray on smoking cessation. A randomized, placebo-controlled, double-blind study.", "Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up.", "Efficacy of exercise counselling as an aid for smoking cessation: a randomized controlled trial.", "The effect of ephedrine plus caffeine on smoking cessation and postcessation weight gain.", "Efficacy of a nicotine lozenge for smoking cessation.", "A randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers.", "The efficacy of moderate-intensity exercise as an aid for smoking cessation in women: a randomized controlled trial.", "Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial.", "The transdermal nicotine patch: results of a randomised placebo-controlled trial.", "Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society.", "Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments.", "A double-blind trial of a nicotine inhaler for smoking cessation.", "Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers.", "A proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to prevent weight gain on smoking cessation.", "Smoking cessation for weight-concerned women: group vs. individually tailored, dietary, and weight-control follow-up sessions.", "Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.", "Weight suppression and weight rebound in ex-smokers treated with fluoxetine.", "Controlled trial of transdermal nicotine patch in tobacco withdrawal.", "Bupropion for smoking cessation: a randomized trial.", "A double-blind trial of a 16-hour transdermal nicotine patch in smoking cessation.", "The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: a randomized controlled trial.", "A randomized trial of smoking cessation. Medication versus motivation.", "Effects of nicotine gum dose by level of nicotine dependence.", "Sustained-release bupropion for hospital-based smoking cessation: a randomized trial.", "Bupropion SR vs placebo for smoking cessation in health care professionals.", "Open randomised trial of intermittent very low energy diet together with nicotine gum for stopping smoking in women who gained weight in previous attempts to quit.", "Effect of nicotine chewing gum in smoking cessation. A randomized, placebo-controlled, double-blind study.", "Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial.", "Double-blind placebo-controlled trial of fluoxetine in smoking cessation treatment including nicotine patch and cognitive-behavioral group therapy.", "Dose effects of nicotine gum.", "Efficacy of bupropion alone and in combination with nicotine gum.", "Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial.", "Participation in a population-based physical activity programme as an aid for smoking cessation: a randomised trial.", "A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation.", "Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: a randomized trial.", "A comparison of sustained-release bupropion and placebo for smoking cessation.", "Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.", "Double blind trial of repeated treatment with transdermal nicotine for relapsed smokers.", "Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation." ]

[ "Evaluation of the clinical efficacy and safety of a nicotine 2-mg sublingual tablet in smoking cessation.\n A randomized, double-blind, placebo-controlled study of smokers using the 2-mg tablet for 3-6 months with follow-up to 12 months. Dosing was established according to baseline nicotine dependence, scored on the Fagerström Tolerance Questionnaire (FTQ): FTQ > or = 7, two tablets/hour (maximum 40/day); FTQ < 7, one tablet/hour (maximum 20/day).\n Smoking cessation programme in a department of oral and maxillofacial surgery.\n A total of 247 adult smokers, smoking > or = 10 cigarettes/day for > or = 3 years, of whom 123 received active and 124 placebo treatment. The study was powered to detect difference at 6 months.\n Efficacy and safety were evaluated at 6 weeks and 3, 6 and 12 months. Self-reported abstinence was verified by exhaled CO < 10 p.p.m.\n Success rates for complete abstinence (no slips after 2 weeks) for active vs. placebo were 50% vs. 29% at 6 weeks, 42% vs. 23% at 3 months, 33% vs. 18% at 6 months and 23% vs. 15% at 12 months (p < 0.001, 0.001, 0.005 and p = 0.14), respectively. Craving during the first 8 days was significantly reduced among highly dependent smokers on active treatment compared to placebo. Baseline mucosal lesions among abstinent subjects were reduced during the treatment period and at the non-treatment follow-up. Adverse events were mild and tolerable, the most common being irritation and soreness in the mouth and throat.\n The nicotine sublingual tablet increased the smoking cessation rate compared to placebo, reduced craving in highly dependent smokers and was well tolerated.", "Weight gain after smoking cessation is often cited by women smokers as a primary reason for not attempting to quit smoking or for relapsing after a cessation attempt.\n A randomized trial of 417 women smokers was conducted to test the addition of two weight control strategies to a smoking cessation program. Participants received the standard smoking cessation program, the program plus nicotine gum, the program plus behavioral weight control, or the program plus both nicotine gum and behavioral weight control. Weight and smoking status were measured at the end of treatment and at 6 and 12 months posttreatment.\n Smoking cessation rates were highest in the group receiving the smoking cessation program plus nicotine gum. Weight gain did not vary by treatment condition, so its effect on relapse could not be examined by group. There was no significant relationship between weight gained and relapse in individuals.\n The added behavioral weight control program was attractive to the participants and did not reduce smoking cessation rates. However, it did not produce the expected effect on weight, thereby restricting our ability to examine the effect of weight control on smoking cessation and relapse.", "Weight gain is a consistent sequela of smoking cessation. A successful intervention might attract smokers who fear weight gain. If the gain causes smoking relapse, such an intervention might reduce smoking relapse risk.\n Using a sample of 158 smokers who completed a 2-week smoking treatment program, we compared an innovative weight gain prevention intervention with both a nonspecific treatment and standard treatment. Subjects were assessed on weight and smoking behavior and followed for 1 year.\n A disturbing, unexpected finding was that subjects in both the innovative and nonspecific conditions had a higher risk of smoking relapse than did standard treatment subjects. Some differences were observed between abstinent and smoking subjects in weight gain by treatment condition.\n Both active interventions may have been so complicated that they detracted from nonsmoking. Also, caloric restriction may increase the reinforcing value of nicotine, a psychoactive drug, thereby increasing smoking relapse risk. The magnitude of weight gain after smoking cessation may not merit interventions that increase smoking risk. Perhaps attitudinal modifications are the most appropriate.", "This investigation evaluated the effect of phenylpropanolamine on the weight gain associated with 2 weeks of abstinence from smoking. Subjects were 57 adult female cigarette smokers who were randomly assigned, in a double-blind procedure, to chew gum with phenylpropanolamine or placebo gum, or to chew no gum. After a baseline assessment, subjects were paid to quit smoking for a period of 2 weeks. Forty-one (72%) of the 57 subjects were successful in quitting smoking for the 2-week period. Results indicated that, relative to the other two conditions, abstinent subjects receiving phenylpropanolamine gained 1.5 to 1.9 pounds less weight (p less than 0.05). In addition, abstinence rates were higher (p less than 0.03) and dietary intake lower for subjects receiving phenylpropanolamine (p less than 0.05) relative to the other two conditions. No changes in physical activity were observed. It is concluded that phenylpropanolamine may help reduce weight gain associated with smoking abstinence and in this way may enhance smoking cessation efforts in certain individuals.", "To investigate the effectiveness and tolerability of a transdermal nicotine system (TNS) as an aid towards easing smoking cessation, two double-blind placebo-controlled randomized field studies were performed. The TNS was available in sizes of 10, 20 and 30 cm2, delivering 7, 14 and 21 mg of nicotine per 24 h. A first study was undertaken in general medical practice by a group of 21 doctors (Practitioner Study). This study involved 199 nicotine-dependent cigarette smokers of whom 100 were allocated to the nicotine group and 99 to the placebo group. The second trial was performed in 112 young people, 56 in each treatment group, at the Universities of Basle and Zurich (University Study). The placebo and the nicotine groups were comparable in both studies. Participants smoking more than 20 cigarettes a day were treated with the 30-cm2 system and the others with the 20-cm2 system. When abstinence, as verified by CO measurements, was achieved, the next smaller system was applied. In the Practitioner Study, the double-blind treatment phase lasted for 12 weeks with consultations every month and in the University Study the consultations during the 9-weeks' treatment period took place every 3 weeks. Abstainers in both studies will be followed up until 12 months after treatment was begun. After 1, 2 and 3 months of treatment 41%, 36% and 36% of the participants in the nicotine group of the Practitioner Study were abstinent. The corresponding figures in the placebo group were 19.4%, 20.4% and 22.5%. The differences were statistically significant for all three months (p = 0.001; p = 0.018 and p = 0.043). Body weight did not increase in the TNS group, but did in the placebo group (+ 4.4 kg). The craving for cigarettes and withdrawal symptoms decreased more under nicotine substitution. Abstinence rates in the University Study were initially higher with 51.8% in the nicotine group and 28.6% in the placebo group after 3 weeks of treatment, but then declined to 42.9% after 6 weeks and 39.3% after 9 weeks in the nicotine group and to 25% and 19.6%, respectively, in the placebo group. The differences between the groups were statistically significant on all 3 occasions, with p = 0.012, p = 0.046 and p = 0.023.(ABSTRACT TRUNCATED AT 250 WORDS)", "A prior report (Klesges et al. 1990) suggested that phenylpropanolamine (PPA) was successful in reducing the smoking withdrawal symptom of weight gain in a sample of women. The current investigation evaluates whether the effects of phenylpropanolamine (PPA; up to 10/day PPA gums) on withdrawal symptoms associated with smoking cessation are specific to weight and weight-related symptoms or whether PPA alleviates withdrawal in general. One hundred and seven adult smokers (56 men, 51 women) were randomly assigned, in this double-blind trial, to chew either 8.33 mg phenylpropanolamine gum or a placebo gum. Subjects were then aided to quit smoking for 4 weeks. PPA did not enhance cessation rates. Results from the 47 subjects who successfully quit smoking indicated that postcessation weight gain and ratings of hunger were significantly reduced in both men and women for those assigned to the PPA group relative to the placebo group. Overall, no effects of PPA relative to placebo were observed for other smoking-related withdrawal symptoms. Thus, although PPA appears to reduce weight gain and alleviate weight-related symptoms, no effects on other withdrawal symptoms were observed. Future research directions are suggested.", "To assess the level of nicotine replacement, evidence of nicotine toxicity, and withdrawal symptom relief with placebo and 11-, 22-, and 44-mg/d doses of transdermal nicotine. A secondary objective was to assess short- and long-term smoking cessation rates.\n Randomized, double-blind, placebo-controlled inpatient/outpatient trial.\n Seventy-one cigarette smokers stratified according to light (n = 23), moderate (n = 24), and heavy (n = 24) smoking rates.\n After baseline measures were obtained, subjects were randomly assigned to placebo or an 11-, 22-, or 44-mg/d dose of transdermal nicotine and admitted to a special hospital unit for intensive inpatient treatment of nicotine dependence. During the 6-day inpatient stay, daily nicotine and cotinine levels were determined from trough and peak blood samples. Outpatient patch therapy continued for 7 weeks following the hospital stay, and those initially assigned to placebo were randomly assigned to 11 or 22 mg/d. At week 4, the dosage of those initially assigned to 44 mg/d was reduced to 22 mg/d.\n Percentage of replacement of cotinine was calculated by dividing the steady-state levels attained during patch therapy by the corresponding baseline levels. Abstinence from smoking was verified by expired air carbon monoxide. Withdrawal symptoms and nicotine toxicity were assessed daily through questionnaires during the inpatient stay. Follow-up visits were at 3, 6, 9, and 12 months.\n There was a statistically significant relationship between baseline smoking rate and baseline trough and peak blood cotinine levels (rs = 0.39, rs = 0.45; P < .001 in both instances). A dose-response relationship was observed with higher patch doses, which produced a higher percentage of cotinine replacement and better withdrawal symptom relief. Only one subject (a light smoker assigned to the 44-mg dose) developed signs of nicotine toxicity. There was a positive association between the week 2 patch dose and the biochemically confirmed abstinence at the end of patch therapy (P = .007) but not for subsequent follow-up times. A higher percentage of cotinine replacement was associated with the higher 8-week smoking abstinence rate (P = .03), an association not found at long-term follow-up.\n A 44-mg/d dose of nicotine patch therapy appears to be safe for use in heavy smokers. Cigarette smoking rates can be used to estimate the initial nicotine patch dose. Monitoring blood cotinine levels at baseline and steady state can be used for assessing the adequacy of nicotine replacement. Withdrawal symptom relief can be improved with more complete nicotine replacement. Achieving a greater percentage of nicotine replacement may increase the efficacy of nicotine patch therapy.", "With smoking prevalence rates beginning to decline, studies designed to promote cessation in more challenging populations, like weight-concerned smokers, warrant attention. This study assessed the efficacy of two forms of pharmacotherapy [nicotine and phenylpropanolamine (PPA) gums] in addition to a 13-week cognitive behavioral smoking cessation program targeted for women. Participants were 439 females who met rigorous screening criteria and were randomized to one of the three treatment intervention groups (PPA gum, nicotine gum, or placebo gum). All participants attended a 13-week cognitive behavioral smoking cessation program and were given specific instructions on gum chewing. At posttest (13 weeks), and 6- and 12-month follow-ups, body weight and point prevalence abstinence were assessed. Analyses to determine potential differences between treatment groups on weight change and cessation rates were performed. Results indicated that neither change in body weight nor cessation rates significantly differed between groups. Attendance to sessions did appear to consistently increase the likelihood of quitting smoking at posttest and at each of the follow-ups. These results suggest that although the pharmacological interventions had no effect on cessation rates and postcessation weight gain, the behavioral component of the intervention was effective in increasing the odds of quitting smoking in weight-concerned women. Future efforts should focus on increasing adherence to behavioral program components, particularly session attendance.", "Nicotine replacement therapy has been shown to improve success rates in smoking cessation treatment. However, the available products cause adverse effects, which prevent some smokers from using them. A new method of delivering nicotine via inhaler supplies nicotine orally through inhalation from a plastic tube. This mode of delivering nicotine resembles smoking, as it includes handling and active inhalation.\n To assess the efficacy and safety of the nicotine inhaler as an aid in smoking cessation.\n A 1-year, randomized, double-blind, placebo-controlled study was conducted in a smoking cessation clinic. Two hundred forty-seven smokers who smoked at least 10 cigarettes per day and who had previously made a serious attempt to stop smoking using nicotine chewing gum were recruited through advertisements. Randomization to treatment or control conditions were made at the first group session, with 123 participants receiving nicotine inhalers and 124 receiving placebo inhalers. The inhalers were distributed at the second session and participants were allowed to use the inhalers for 6 months.\n Biochemically verified continuous abstinence from smoking after 2 and 6 weeks and at 3, 6, and 12 months.\n Significantly more participants who had used the nicotine inhalers were continuously abstinent compared with those who had used the placebo inhalers. The respective success rates after 12 months were 28% and 18% (P = .046). At 6 months, 20 participants (16%) in the nicotine group were still using the inhaler, compared with 4 (3%) in the control group (P < .001).\n The nicotine inhaler was an effective smoking cessation aid that produced a few mild and transient adverse effects.", "The transdermal nicotine patch has proved an effective aid to smoking cessation. The ease of securing good compliance gives it a potential advantage over nicotine gum as an adjunct to brief advice and support in primary care settings where the major public health impact is obtained. In a preliminary report of half the sample of a randomized placebo controlled trial, we showed the patch to be effective in a general practice setting. We report here the definitive results of the full sample, including dose effects, predictors of outcome and other issues of theoretical and practical interest. A total of 1200 heavy smokers (> or = 15 per day), attending 30 general practices in 15 English counties received brief GP advice, a booklet and 16 hours per day patch treatment for 18 weeks. Dose increase and abrupt vs. gradual reduction of patch dosage were also randomized and follow-ups conducted at 1, 3, 6, 12, 26 and 52 weeks. Outcome was measured by self-reported complete abstinence from week 3 to 52 with biochemical validation at all follow-up points. Nicotine patch treatment doubled the rate of continuous abstinence up to 1 year (nicotine 9.6%, placebo 4.8%, p < 0.01); it most likely worked by reducing withdrawal symptoms. It enhanced cessation during the first week and reduced relapse during the second week. The dose increase after week 1 produced no sustained increase in cessation. Gradual reduction was no better at preventing relapse than abrupt withdrawal of patches after week 12. Whether relapse would have increased by ending treatment at some point between weeks 3 and 12 was not tested. Although pre-treatment dependence on cigarettes was prognostic of failure, the patches were equally helpful to both highly and less dependent smokers. Patches were particularly helpful to smokers with pre-treatment subclinical dysthymic symptoms. All but one of the 96 subjects eventually achieving long-term abstinence in the study quit during the first week of cessation.", "Women smokers concerned about weight gain (N = 219) were randomly assigned to 1 of 3 adjunct treatments accompanying group smoking cessation counseling: (a) behavioral weight control to prevent weight gain (weight control); (b) cognitive-behavioral therapy (CBT) to directly reduce weight concern, in which dieting was discouraged; and (c) standard counseling alone (standard), in which weight gain was not explicitly addressed. Ten sessions were conducted over 7 weeks, and no medication was provided. Continuous abstinence was significantly higher at posttreatment and at 6 and 12 months of follow-up for CBT (56%, 28%, and 21%, respectively), but not for weight control (44%, 18%, and 13%, respectively), relative to standard (31%, 12%, and 9%, respectively). However, weight control, and to a lesser extent CBT, was associated with attenuation of negative mood after quitting. Prequit body mass index, but not change in weight or in weight concerns postquit, predicted cessation outcome at 1 year. In sum, CBT to reduce weight concerns, but not behavioral weight control counseling to prevent weight gain, improves smoking cessation outcome in weight-concerned women.", "Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control.\n A phase 2, multicenter, randomized, double-blind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n = 127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7 weeks.\n During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%). The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related increases occurred in adverse events for varenicline.\n Varenicline tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation.", "We tested whether 14 wk of dexfenfluramine (30 mg) or fluoxetine (40 mg) treatment would prevent weight gain after subjects quit smoking. Normal-weight women (n = 144) were randomly assigned to drug or placebo on a double-blind basis for 2 wk before quitting smoking and 12 wk thereafter. The fluoxetine group had more dropouts (28/49, 57.1%) than the dexfenfluramine group (17/47, 36.2%), with an intermediate number of dropouts from the placebo group (21/48, 43.8%). All groups gained weight during treatment, but their amount and pattern of weight gain differed. In the first month after quitting smoking, the placebo group gained more weight than either the dexfenfluramine or fluoxetine group (P < 0.05). By 2 mo postcessation, dexfenfluramine still suppressed weight gain in comparison with placebo (P < 0.05); weight gain with fluoxetine was not differentiable from either dexfenfluramine or placebo. By 3 mo postcessation, the dexfenfluramine group had gained 1.0 +/- 0.7 kg, significantly less than either the placebo (3.5 +/- 0.7 kg) or fluoxetine (2.7 +/- 0.5 kg) groups. Three months after drug discontinuation, formerly medicated, but not placebo patients, showed additional weight gain, eliminating differences between groups. Results indicate that weight gain, an adverse accompaniment of smoking cessation, can be minimized to some degree by serotoninergic drugs, although only for the duration of drug treatment.", "Nicotine replacement therapy is an effective treatment for nicotine-dependent smokers. However, cessation rates are modest, and preliminary studies suggest that combination therapy may be superior. We compared the efficacy of the nicotine inhaler plus nicotine patch vs nicotine inhaler plus placebo patch for smoking cessation.\n A double-blind, randomized, placebo-controlled trial was conducted in 400 subjects who had smoked 10 or more cigarettes per day for 3 years or longer. Group 1 (n = 200) received the nicotine inhaler plus nicotine patch (delivering 15 mg of nicotine per 16 hours) for 6 weeks, then inhaler plus placebo patch for 6 weeks, then inhaler alone for 14 weeks. Group 2 (n = 200) received the nicotine inhaler plus placebo patch for 12 weeks, then inhaler for 14 weeks. Inhaler was used at a rate of 6 to 12 cartridges per day ad libitum for 3 months and then tapered off. Main outcome measures were complete abstinence (self-reported) and expired carbon dioxide concentration less than 10 ppm.\n Group 1 vs group 2 complete abstinence rates were 60.5% and 47.5% at 6 weeks (P =.009), 42.0% and 31.0% at 12 weeks (P =.02), 25.0% and 22.5% at 6 months (P =.56), and 19.5% and 14.0% at 12 months (P =. 14). One-year survival analysis showed a significant association between abstinence and treatment with nicotine inhaler plus nicotine patch (P =.04). Mean nicotine substitution at week 6 was 60.1% (group 1) and 24.6% (group 2) (P<.001). At 12 months, the frequency of respiratory symptoms in abstinent subjects fell significantly and lung function showed a trend toward improvement. The most common adverse events were throat irritation (inhaler) and itching (patch).\n Treatment with the nicotine inhaler plus nicotine patch resulted in significantly higher cessation rates than inhaler plus placebo patch.", "We previously documented that cognitive behavioral therapy for smoking-related weight concerns (CONCERNS) improves cessation rates. However, the efficacy of combining CONCERNS with cessation medication is unknown. We sought to determine if the combination of CONCERNS and bupropion therapy would enhance abstinence for weight-concerned women smokers.\n In a randomized, double-blind, placebo-controlled trial, weight-concerned women (n = 349; 86% white) received smoking cessation counseling and were randomized to 1 of 2 adjunctive counseling components: CONCERNS or STANDARD (standard cessation treatment with added discussion of smoking topics but no specific weight focus), and 1 of 2 medication conditions: bupropion hydrochloride sustained release (B) or placebo (P) for 6 months. Rates and duration of biochemically verified prolonged abstinence were the primary outcomes. Point-prevalent abstinence, postcessation weight gain, and changes in nicotine withdrawal, depressive symptoms, and weight concerns were evaluated.\n Women in the CONCERNS + B group had higher rates of abstinence (34.0%) and longer time to relapse than did those in the STANDARD + B (21%; P = .05) or CONCERNS + P (11.5%; P = .005) groups at 6 months, although rates of prolonged abstinence in the CONCERNS + B and STANDARD + B groups did not differ significantly at 12 months. Abstinence rates and duration did not differ in the STANDARD + B group (21% and 19%) compared with the STANDARD + P group (10% and 7%) at 6 and 12 months, respectively. There were no differences among abstinent women in postcessation weight gain or weight concerns, although STANDARD + B produced greater decreases in nicotine withdrawal and depressive symptoms than did STANDARD + P.\n Weight-concerned women smokers receiving the combination of CONCERNS + B were most likely to sustain abstinence. This effect was not related to differences in postcessation weight gain or changes in weight concerns. Trial Registration clinicaltrials.gov Identifier: NCT00006170.", "Despite the well-documented efficacy and different pharmacokinetic and pharmacodynamic properties of different forms of nicotine replacement therapy, empirical data are insufficient to guide practitioners in selecting a particular form of treatment for individual patients with tobacco dependence.\n To evaluate the comparative efficacy of transdermal nicotine and nicotine nasal spray and identify predictors of treatment outcome.\n Randomized, open-label clinical trial with a 6-month follow-up period.\n 2 university-based smoking cessation research programs.\n 299 treatment-seeking smokers who were followed for 6 months after the target quit date.\n Behavioral group counseling and 8 weeks of therapy with nicotine nasal spray or transdermal nicotine.\n Demographic characteristics, smoking history, depression symptoms, and body mass index were measured at baseline. Smoking practices were biochemically verified at the end of treatment and at 6 months after the target quit date.\n Abstinence rates for the transdermal nicotine and nicotine nasal spray groups were not significantly different at 6-month follow-up (15.0% vs. 12.2%, respectively; P > 0.2). Interactions in abstinence rates for subgroups of smokers were statistically significant (P < 0.05). Smokers who had low to moderate dependence levels, were not obese, and were white achieved higher abstinence rates with transdermal nicotine, whereas smokers who were highly dependent, obese, or members of minority groups achieved higher abstinence rates with nasal spray.\n The subgroup findings need confirmation in additional large studies before they are routinely applied.\n Ethnicity, weight, and level of nicotine dependence may help identify smokers who have greater or lesser abstinence rates with either transdermal or nasal spray nicotine.", "Both the nicotine gum and nicotine lozenge have been shown to increase smoking cessation rates, but no published trials have directly compared the two. Higher dose nicotine gum has been recommended as a treatment that may reduce cessation-related weight gain. DESIGN/OUTCOME: In a diverse urban setting, 408 participants were randomized to receive either the lozenge or the gum for 8 weeks of treatment. Seven-day point prevalence of smoking abstinence was biochemically confirmed by exhaled carbon monoxide levels of less than 10 ppm measured at 8 weeks with follow-up at 6 and 12 months.\n At 8 weeks, the lozenge quit rate was 15.1% and the gum quit rate was 11.3%, with an odds ratio of 1.39, 95% confidence interval (0.78-2.49) P=0.26. These rates compare favorably to a historical spontaneous quit rate of 5%. Quit rate comparisons were similarly non-significant at 6 and 12 months. At 8 weeks, successful quitters in the lozenge group gained 3.0+/-6.3 lbs compared to the gum group, which gained 8.4+/-9.2 lbs with t=-2.4, P=0.02, but this finding was not sustained at 6 and 12 months.\n The gum and lozenge appear equally effective for smoking cessation; however, for patients concerned about preventing cessation related to immediate weight gain, the lozenge may be the better agent.", "Smoking prevalence rates among women are declining at a slower rate than among men.\n To determine if exercise, a healthful alternative to smoking, enhances the achievement and maintenance of smoking cessation.\n Two hundred eighty-one healthy, sedentary female smokers were randomly assigned to either a cognitive-behavioral smoking cessation program with vigorous exercise (exercise) or to the same program with equal staff contact time (control). Subjects participated in a 12-session, group-based smoking cessation program. Additionally, exercise subjects were required to attend 3 supervised exercise sessions per week and control subjects were required to participate in 3 supervised health education lectures per week. Abstinence from smoking was based on self-report, was verified by saliva cotinine level, and was measured at 1 week after quit day (week 5), end of treatment (week 12), and 3 and 12 months later (20 and 60 weeks after quit day, respectively).\n Compared with control subjects (n = 147), exercise subjects (n = 134) achieved significantly higher levels of continuous abstinence at the end of treatment (19.4% vs 10.2%, P = .03) and 3 months (16.4% vs 8.2%, P=.03) and 12 months (11.9% vs 5.4%, P=.05) following treatment. Exercise subjects had significantly increased functional capacity (estimated VO2 peak, 25+/-6 to 28+/-6, P<.01) and had gained less weight by the end of treatment (3.05 vs 5.40 kg, P = .03).\n Vigorous exercise facilitates short- and longer-term smoking cessation in women when combined with a cognitive-behavioral smoking cessation program. Vigorous exercise improves exercise capacity and delays weight gain following smoking cessation.", "Nicotine replacement therapies have proved to be of value in smoking cessation. However, not all smokers can use the nicotine gum or nicotine patch owing to side effects. In addition, the absorption of nicotine from these formulas is slow compared with smoking. A nicotine nasal spray delivers nicotine more rapidly. The objective of this study was to evaluate the efficacy and safety of the nicotine nasal spray for smoking cessation.\n Subjects were recruited through advertisements in newspapers and among patients referred to the smoking cessation clinic at Sahlgren's Hospital, Göteborg, Sweden. Two hundred forty-eight smokers were treated in small groups with eight counseling sessions over 6 weeks. At their first group session, subjects were randomized to a group receiving nicotine spray (n = 125), 0.5 mg of nicotine per single spray, or to a placebo group (n = 123). The procedure was double blind. Success rates were measured up to 12 months. The nonsmoking status was verified by expired carbon monoxide less than 10 ppm.\n Significantly more subjects in the nicotine group were continuously abstinent for 12 months than in the placebo group (27% vs 15%; odds ratio, 2.16; 95% confidence interval, 1.15 to 4.12). Ten of the 34 abstinent subjects in the nicotine group used the spray for 1 year. Mild or moderate side effects were rather frequent for both sprays, but they were significantly more for the nicotine spray. Subjects with high scores (> 7) on Fagerström's tolerance questionnaire had a significantly lower success rate with placebo than with the nicotine spray. For subjects with low scores, there was no difference.\n Nicotine nasal spray in combination with group treatment is an effective aid to smoking cessation.", "To evaluate the efficacy of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year.\n Placebo controlled, double blind trial.\n Reykjavik health centre.\n 237 smokers aged 22-66 years living in or around Reykjavik.\n Nicotine patch for 5 months with nicotine nasal spray for 1 year (n=118) or nicotine patch with placebo spray (n=119). Treatment with patches included 15 mg of nicotine for 3 months, 10 mg for the fourth month, and 5 mg for the fifth month, whereas nicotine in the nasal spray was available for up to 1 year. Both groups received supportive treatment.\n Sustained abstinence from smoking.\n Sustained abstinence rates for the patch and nasal spray group and patch only group were 51% v 35% after 6 weeks (odds ratio 1.97, 95% confidence interval 1.17% to 3.32; P=0.011(chi2), 37% v 25% after 3 months (1.76, 1.01 to 3.08; P=0.045), 31% v 16% after 6 months (2.40, 1.27 to 4.50; P=0.005), 27% v 11% after 12 months (3.03, 1.50 to 6.14; P=0.001), and 16% v 9% after 6 years (2.09, 0.93 to 4.72; P=0.08) [corrected].\n Short and long term abstinence rates show that the combination of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year is a more effective method of stopping smoking than using a patch only. The low percentage of participants using the nasal spray at 1 year, and the few relapses during the second year, suggest that it is not cost effective to use a nasal spray for longer than 7 months after stopping a patch.", "To examine whether exercise counselling increases smoking abstinence and reduces tobacco withdrawal and gains in weight and body fat.\n A randomized controlled trial.\n A community-based stop smoking clinic.\n Two hundred and ninety-nine male and female smokers.\n Participants were assigned randomly to a 7-week smoking cessation programme, including nicotine replacement therapy plus either (i) exercise counselling, or (ii) health education advice with equal contact time as for the exercise counselling condition.\n Six weeks of smoking abstinence was confirmed by expired carbon monoxide.\n There was no significant difference in smoking abstinence between the exercise group (n = 154) and the controls (n = 145) at 6 weeks (39.6% versus 38.6%), nor was there any difference in gains in weight or body fat, although those in the exercise group increased their exercise levels. Exercise participants reported less tension, anxiety and stress than the controls during the first week of smoking abstinence (P = 0.03, 0.01 and 0.04, respectively), less irritability throughout 2 weeks of abstinence (P = 0.03), and less restlessness throughout 3 weeks of abstinence (P = 0.04).\n Adding brief exercise counselling to a smoking cessation programme did not increase smoking abstinence or reduce gains in weight or body fat significantly, although exercise levels were raised and there were some beneficial effects on psychological symptoms.", "To evaluate the efficacy of a combination of ephedrine and caffeine on smoking cessation rates, postcessation weight gain, and withdrawal symptoms and to examine changes in glycosylated hemoglobin (HbA1c) after smoking cessation.\n This randomized double-blind placebo-controlled study with a 1-year follow-up period was carried out at the Department of Pulmonary Medicine in Denmark. Study subjects were 225 heavy smokers who wanted to quit smoking without gaining weight. Two-thirds of the subjects were randomized to receive 20 mg ephedrine plus 200 mg caffeine three times a day; one-third of the subjects received placebo treatment. The dosage was gradually decreased from week 12 to discontinuation at week 39. Group support and control were performed at entry and after 1, 3, 6, 12, 26, 39, and 52 weeks. Main outcome measures were (1) self-reported abstinence with validation by carbon monoxide in expired air and serum cotinine and (2) weight gain.\n The success rates after 1 year were 17% in the group treated with ephedrine plus caffeine and 16% in the group treated with placebo; the success rates were not significantly different at any time. The success rates for the four counseling physicians varied between 7% and 27% after 1 year (p < 0.05). The weight gain was significantly lower in the ephedrine plus caffeine-treated group during the first 12 weeks, but weight gains were similar after 1 year. No differences in the smoking withdrawal symptoms could be observed between the treatment groups. HbA1c was lower 6 weeks and 1 year after smoking cessation (p < 0.05).\n We found an effect of this combination of ephedrine and caffeine on weight gain during the first 12 weeks, but we found no effect on the success rates or craving for cigarettes.", "Since nicotine gum was introduced in the 1980s, nicotine replacement therapy has become the most widely used pharmacological smoking cessation treatment. Some smokers prefer acute oral forms, but many smokers reject chewing gum. We tested the safety and efficacy of a new nicotine polacrilex lozenge for smoking cessation.\n Double-blind, placebo-controlled, randomized clinical trial with parallel arms testing 2- and 4-mg nicotine lozenges. Smokers (n = 1818) were assigned to a lozenge dose on the basis of nicotine dependence, assessed by time to the first cigarette of the day. Low-dependence smokers were randomized to receive the 2-mg nicotine (n = 459) or placebo (n = 458) lozenge; high-dependence smokers, the 4-mg nicotine (n = 450) or placebo (n = 451) lozenge. We assessed abstinence at 6, 12, 24, and 52 weeks and analyzed craving and withdrawal symptoms.\n Treatment with the nicotine lozenge resulted in significantly greater 28-day abstinence at 6 weeks, for the 2-mg (46.0% vs. 29.7%; odds ratio [OR], 2.10; 95% confidence interval [CI], 1.59-2.79; P<.001) and the 4-mg (48.7% vs. 20.8%; OR, 3.69; 95% CI, 2.74-4.96; P<.001) lozenges, compared with placebo. Significant treatment effects were maintained for a full year. Smokers who used more lozenges achieved significantly better treatment effects. Use of the active lozenge also resulted in reduced craving and withdrawal. Most adverse events were moderate and resembled those seen with nicotine gum.\n The nicotine lozenge is a safe and effective new treatment for smoking cessation in low- and high-dependence smokers.", "Rates of smoking in East Asian men range from >35% to >60%, and are increasing in women and the young.\n This study evaluated the efficacy and tolerability of 1 mg BID varenicline, a novel alpha4beta2 nicotinic acetylcholine receptor partial agonist, for smoking cessation in smokers in Taiwan and Korea.\n A randomized, double-blind, placebo-controlled, 12-week treatment, 12-week follow-up trial was conducted at 5 sites each in Korea and Taiwan. Eligible subjects, smoking >or=10 cigarettes/d, received brief smoking-cessation counseling and were randomly assigned in a 1:1 ratio to varenicline 1 mg BID (titrated during the first week) or placebo. Smoking status was established by self-report and confirmed at clinic visits by end-expiratory carbon monoxide <or=10 ppm. The primary end point was continuous abstinence rate (CAR) during the last 4 weeks of treatment. Secondary end points included CAR from weeks 9 to 24 and 7-day point prevalence (PP) of abstinence at weeks 12 and 24. Craving, withdrawal, and smoking satisfaction were determined by the Minnesota Nicotine Withdrawal Scale, the Brief Questionnaire of Smoking Urges, and the modified Cigarette Evaluation Questionnaire. Observed or volunteered adverse-event data were recorded at clinic visits.\n Overall, 126 subjects (84.9% male) received varenicline, and 124 (92.7% male) received placebo, Subjects were aged 21 to 73 years (mean age, 39.7 and 40.9 years for varenicline and placebo groups, respectively), and the mean (range) body weights were 69.0 (44.8-110.0) kg and 71.4 (45.5-102.0) kg, respectively. Subjects had smoked for 3 to 52 years (mean, 20.2 and 22.1 years in the varenicline and placebo groups, respectively). Subjects had smoked a mean of 23 cigarettes/d over the past month, with 51.6% (varenicline) and 46.0% (placebo) having made 1 or more prior serious quit attempts. Smoking-cessation rates at the end of treatment were 59.5% with varenicline versus 32.3% with placebo (P < 0.001). CARs through 12 weeks post-treatment (weeks 9-24) were 46.8% with varenicline and 21.8% with placebo (P < 0.001). The 7-day PP was 67.5% with varenicline versus 36.3% with placebo at week 12, and 57.1% versus 29.0% with placebo at week 24 (both, P < 0.001). Treatment-emergent, all-causality adverse events with an incidence >or= 5% for varenicline were nausea (43.7% for varenicline vs 11.3% placebo), insomnia (15.1% vs 13.7%), increased appetite (7.9% vs 6.5%), constipation (7.1% vs 2.4%), anxiety (5.6% vs 2.4%), and abnormal dreams (5.6% vs 0.8%). Adverse events resulted in <10% treatment discontinuations overall.\n Varenicline was an efficacious and well-tolerated pharmacotherapy for smoking cessation in this group of Asian smokers over a 12-week treatment period, and its effects persisted for a further 12-week follow-up period.", "Evidence suggests that vigorous-intensity exercise interventions may be effective for smoking cessation among women; however, few studies have examined the efficacy of a moderate-intensity exercise program. The present study examined the efficacy of moderate-intensity exercise for smoking cessation among female smokers. Healthy, sedentary female smokers (N = 217) were randomly assigned to an 8-week cognitive-behavioral smoking cessation program plus moderate-intensity exercise (CBT+EX) or to the same cessation program plus equal contact (CBT). A subsample received nicotine replacement therapy. Results indicated that the CBT+EX and CBT groups were equally likely to attain smoking cessation at the end of treatment, as measured by cotinine-verified 7-day point-prevalence abstinence (20.2% for CBT+EX vs. 18.5% for CBT). The CBT+EX group was more likely to report smoking cessation, as measured by 7-day point prevalence at the 3-month follow-up (11.9% vs. 4.6%, p<.05), compared with the CBT group. No group differences were found at 12 months by either 7-day point prevalence (7.3% for CBT+EX vs. 8.3% for CBT) or continuous abstinence (0.9% for CBT+EX vs. 0.9% for CBT). Additionally, among participants in the CBT+EX group, those with higher adherence to the exercise prescription were significantly more likely to achieve smoking cessation at the end of treatment than were participants reporting lower adherence to exercise. Our findings indicate that the empirical support for moderate-intensity exercise as an adjunctive treatment to CBT for smoking cessation may be limited. Perhaps future studies could compare moderate- vs. vigorous-intensity physical activity to test their relative efficacy.", "Smoking is the most important risk factor for COPD and accelerates its progression. Despite the health implications, a large proportion of patients with COPD continue to smoke, so finding effective smoking cessation interventions for this population is paramount. To our knowledge, this is the first randomized clinical trial to compare the efficacy and safety of varenicline tartrate vs placebo in smokers with mild to moderate COPD.\n In a 27-center, double-blind, multinational study, 504 patients with mild to moderate COPD (postbronchodilator FEV1/FVC, <70%; FEV1 percent predicted normal value, ≥50%) and without known psychiatric disturbances were randomized to receive varenicline (n=250) or placebo (n=254) for 12 weeks, with a 40-week nontreatment follow-up. The primary end point was carbon monoxide-confirmed continuous abstinence rate (CAR) for weeks 9 to 12. A secondary end point was CAR for weeks 9 to 52.\n CAR for weeks 9 to 12 was significantly higher for patients in the varenicline group (42.3%) than for those in the placebo group (8.8%) (OR, 8.40; 95% CI, 4.99-14.14; P<.0001). CAR in the patients treated with varenicline remained significantly higher than in those treated with placebo through weeks 9 to 52 (18.6% vs 5.6%) (OR, 4.04; 95% CI, 2.13-7.67; P<.0001). Nausea, abnormal dreams, upper-respiratory tract infection, and insomnia were the most commonly reported adverse events (AEs) for patients in the varenicline group. Serious AEs were infrequent in both treatment groups. Two patients in the varenicline group and one patient in the placebo group died during the study. Reports of psychiatric AEs were similar for both treatment groups.\n Varenicline was more efficacious than placebo for smoking cessation in patients with mild to moderate COPD and demonstrated a safety profile consistent with that observed in previous trials. Trial registry: ClinicalTrials.gov; No.: NCT00285012; URL: www.clinicaltrials.gov.", "To evaluate the efficacy of the transdermal nicotine patch as an aid to smoking cessation when used as an adjunct to a cognitive-behavioural group intervention and to assess the effectiveness of the patch in ameliorating withdrawal symptoms.\n Double-blind placebo-controlled randomised trial with six months' follow-up of those who returned to the hospital-based outpatients smoking cessation clinic.\n Three hundred and thirteen smokers recruited from the local community. Mean age was 42 years, 48% were male, mean cigarette consumption was 29 per day and mean duration of smoking was 24 years.\n Cognitive-behavioural intervention delivered in a group context, two hours once a week over five weeks, self-help manual, and 24-hour daily nicotine patch treatment for 10 weeks.\n Point prevalence abstinence at three and six months, and sustained cessation from end of treatment to six months, with biochemical validation (expired carbon monoxide). We examined the effectiveness of the nicotine patch in ameliorating specific withdrawal symptoms by self-report of degree of severity.\n The active nicotine patch resulted in significantly higher biochemically confirmed abstinence rates when compared with placebo at three months (48% v. 21%) and at six months (33% v. 14%). Six-months' continuous abstinence rates were also significantly higher among the active nicotine group (25%) compared with placebo (12%). The most common adverse events among active patch users were sleep disturbance and local skin irritation. The nicotine patch reduced the severity of some withdrawal symptoms. A low level of dependence was the strongest predictor of three and six months' abstinence.\n The transdermal nicotine patch is effective when used as an adjunct to a group cognitive-behavioural intervention and it provides relief from withdrawal symptoms associated with nicotine dependence.", "The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus placebo, p<0.001, Chi-squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p< 0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates.", "To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments.\n Two independent randomized placebo-controlled double-blind trials.\n Smoking cessation clinic.\n Eighty-eight (study 1) and 112 (study 2) adult volunteers motivated to quit smoking.\n Eight weeks of 22-mg transdermal nicotine therapy with group counseling (study 1); 4 weeks of 22 mg followed by 2 weeks of 11-mg transdermal nicotine therapy with brief individual counseling (study 2).\n Modified point prevalence (7 consecutive days of nonsmoking) at the end of patch treatment and 6 months after treatment initiation was assessed by self-report and biochemically confirmed; survival analyses were also conducted for both studies to compare treatment efficacy. Also, we examined the impact of the nicotine patch on specific withdrawal symptoms (anger, anxiety, awakening, difficulty concentrating, depression, hunger, impatience, and craving).\n Transdermal nicotine treatment produced higher cessation rates at the end of treatment than did placebo with both adjuvant counseling interventions: 59 percent vs 40 percent (p < 0.05 in study 1) and 37 percent vs 20 percent (p < 0.05 in study 2), respectively. Smoking cessation efficacy was maintained 6 months after initiation of treatment: 34 percent vs 21 percent (p = 0.08 in study 1) and 18 percent vs 7 percent (p = 0.05 in study 2). Survival analyses also revealed significant group differences in efficacy in both studies. Nicotine patches also suppressed a variety of withdrawal symptoms, including craving in the first weeks after patients quit smoking.\n Transdermal nicotine effectively augments smoking cessation rates with two different types of counseling treatment. Overall, the nicotine patch approximately doubles the sustained rate of smoking cessation. Additionally, the nicotine patch provides relief from some tobacco withdrawal symptoms.", "To evaluate the efficacy of a new nicotine inhaler system for smoking cessation.\n A 1-year, randomized, double-blind, placebo-controlled study.\n Medical outpatient clinic with physicians experienced in smoking cessation assistance.\n A total of 286 volunteers who smoked at least 10 cigarettes daily recruited through a local newspaper.\n Subjects were randomly allocated to nicotine inhalers (n = 145) or placebo (n = 141) to be used for 3 months followed by tapering for 3 months in the context of minimal levels of advice and support.\n Continuous smoking abstinence at weeks 6, 12, 24, and 52, verified by measurements of carbon monoxide in expired air.\n Continuous smoking abstinence was significantly higher for the active nicotine inhaler group compared with the placebo inhaler group. The respective success rates were 28% and 12% after 6 weeks, 21% and 9% after 12 weeks, 17% and 8% after 6 months, and 15% and 5% after 1 year (P = .02 to .001). The mean nicotine substitution based on cotinine determinations after 2 weeks was 43% (SD, 45%) of smoking levels. The treatment was well tolerated, and no serious adverse events were reported.\n In this setting the nicotine inhaler appeared safe to use and increased success rates of smoking cessation attempts.", "Varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, has been developed specifically for smoking cessation. In Japan, 39.3% of men smoke and this is a major public health concern.\n The primary objective of this study was to evaluate the efficacy and dose-response relationship of varenicline in Japanese smokers.\n In this double-blind, placebo-controlled, randomized, parallel-group study, subjects were randomized to receive varenicline at 0.25 mg BID, 0.5 mg BID, 1 mg BID, or placebo for 12 weeks followed by a 40-week, nontreatment follow-up phase. The primary efficacy variable was the continuous abstinence rate (CAR), defined as no reported smoking (not even a puff) or other nicotine use and confirmed by end-expiratory carbon monoxide level <or=10 ppm, during the last 4 weeks of treatment (weeks 9-12). Secondary end points included CARs for weeks 9-24 and 9-52. Craving, withdrawal, and smoking satisfaction were determined by the Minnesota Nicotine Withdrawal Scale, the Brief Questionnaire on Smoking Urges, and the modified Cigarette Evaluation Questionnaire. The tolerability of varenicline was also evaluated.\n Of 618 subjects who received treatment, 515 (83.3%) were classified as nicotine dependent (scoring >or=5 on the Tobacco Dependence Screener), and constituted the primary analysis group. Of these, 385 (74.8%) subjects were male, and the mean age was within the range of 39.0 to 40.2 years. Across treatment groups, subjects claimed to have smoked a mean of 23.1 to 24.9 cigarettes per day in the preceding 30 days, and the mean score on the Fagerström Test for Nicotine Dependence was within the range from 5.4 to 5.7. The CAR for weeks 9-12 was significantly higher for all doses of varenicline compared with placebo (39.5% [51/129]). The highest CAR of 65.4% (85/130) was achieved with varenicline 1 mg BID (odds ratio [OR] [95% CI] = 2.98 [1.78-4.99]; P < 0.001). The CAR for weeks 9-52 was significantly greater for varenicline 1 mg BID than placebo (34.6% [45/130] vs 23.3% [30/129]; OR [95% CI] = 1.81 [1.04-3.17]; P = 0.036). The CARs for weeks 9-24 at 0.25, 0.5, and 1 mg BID were 33.6% (43/128), 35.2% (45/128), 37.7% (49/130), and for weeks 9-52 at 0.25 and 0.5 mg BID were 27.3% (35/128) and 28.9% (37/128) but failed to reach significance versus the placebo (29.5% [38/129] for weeks 9-24 and 23.3% [30/129] for weeks 9-52). Treatment-emergent adverse events (AEs) were more prevalent among varenicline-treated subjects (79.1% [121/153] at 0.25 mg BID, 80.6% [125/155] at 0.5 mg BID, and 80.1% [125/156] at 1 mg BID) than placebo subjects (71.4% [110/154]). The 3 most prevalent AEs at varenicline 1 mg BID were nasopharyngitis (35.9% [56/156]), nausea (24.4% [38/156]), and headache (10.3% [16/156]), all of which were of mild or moderate intensity. Nausea was the only AE that appeared dose related (7.2% [11/153] at 0.25 mg BID, 9.7% [15/155] at 0.5 mg BID, and 24.4% [38/156] at 1 mg BID) versus placebo (7.8% [12/154]).\n Varenicline was associated with dose-dependent improvement in smoking abstinence rates during the last 4 weeks of treatment and in the longer term over 40 weeks of nontreatment follow-up. The dose associated with the highest efficacy was varenicline 1 mg BID.", "St John's wort is an effective antidepressant that can reduce tobacco withdrawal symptoms, but it is not known whether it assists cessation. Chromium assists weight loss and might limit post cessation weight gain.\n In a factorial design, we randomised smokers stopping smoking to 900 mg St John's wort (SJW) active or placebo and also randomised them to 400 microm chromium or placebo daily. Treatment started 2 weeks prior to quit day and continued for 14 weeks. Participants and researchers were blind to treatment allocation. All participants received weekly behavioural support. The primary endpoints were biochemically confirmed prolonged abstinence and mean weight gain in abstinent smokers 4 weeks after quitting.\n 6/71 (8.5%) participants on active SJW and 9/72 (12.5%) on placebo achieved prolonged abstinence at 4 weeks, an odds ratio (OR) (95% confidence interval) of 0.65 (0.22-1.92). At 6 months, 3 (4.2%) SJW active and 6 (8.3%) SJW placebo participants were still abstinent, an OR of 0.49 (0.12-2.02). Among these participants, the mean difference in weight gain between active chromium and placebo was -0.8 1kg (-3.79 to 2.18) at 4 weeks and -3.88 kg (-12.13 to 4.38) at 6 months.\n Taking together the absolute quit rates, the small difference between active and placebo, and lack of effects on withdrawal shows that SJW is ineffective for smoking cessation. Insufficient people stopped smoking to properly test the efficacy of chromium in preventing weight gain, but the point estimate indicates a potentially worthwhile benefit.", "Postcessation weight gain is of concern to many female cigarette smokers. A multidisciplinary treatment combining psychological, dietary, and exercise components followed a 2-week smoking cessation program. Participants were randomly assigned to receive six follow-up relapse prevention sessions (in a group format or in an individually tailored format) directed by trained representatives from clinical psychology, dietary counseling, and exercise physiology. As predicted, abstinence rates were significantly higher among the individually tailored follow-up participants than among those assigned to the group follow-up condition at 3 and 6 months posttreatment. Differences between conditions in postcessation weight gain were not significant. However, the postcessation weight gain that did occur was significantly associated with subsequent smoking relapse in the group follow-up condition only.", "The alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel alpha4beta2 nAChR partial agonist, may be beneficial for smoking cessation.\n To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo.\n Randomized, double-blind, parallel-group, placebo- and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (> or =10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising.\n Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n = 352), bupropion SR titrated to 150 mg twice per day (n = 329), or placebo (n = 344) orally for 12 weeks, with 40 weeks of nondrug follow-up.\n Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52.\n For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P = .057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]).\n Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.\n clinicaltrials.gov Identifier: NCT00141206.", "Fluoxetine's effect (30 mg, 60 mg, and placebo) on postcessation weight gain was studied among participants from a randomized, double-blind 10-week smoking cessation trial who met strict criteria for abstinence and drug levels. It was hypothesized that (a) fluoxetine would dose-dependently suppress postcessation weight gain and (b) drug discontinuation would produce dose-dependent weight rebound. During the on-drug phase, placebo participants gained weight linearly (M = 2.61 kg). exceeding both fluoxetine groups (30-mg group M = 1.33 kg, 60-mg group M = 1.25 kg). Weight suppression was initially greater for 60 mg than 30 mg, but both were followed by weight gain. Six months off drug produced greater dose-dependent weight rebound for 60 mg than 30 mg or placebo. Considering both on- and off-drug phases, weight gain for 60 mg of fluoxetine (M = 6.5 kg) was comparable with that for placebo (M = 4.7 kg) but greater than that for 30 mg (M = 3.6 kg). Fluoxetine appears to forestall postcessation weight gain, allowing time for the weight-conscious smoker to focus on quitting smoking rather than on preventing weight gain.", "A transdermal nicotine patch, which delivers 0.7 mg/cm2 per 24 h and is available in sizes of 10, 20, and 30 cm2 was tested in subjects from 21 general medical practices in a 3-month, placebo-controlled randomised double-blind study. The nicotine group (n = 100) and the placebo group (n = 99) were similar at entry. Participants who smoked more than 20 cigarettes a day were treated with the 30 cm2 patch and the others with the 20 cm2 patch. When abstinence, defined as smoking 0-3 cigarettes per week and verified by CO measurement, was achieved, the next smallest patch was applied. After 1, 2, and 3 months of treatment 41, 36, and 36%, respectively, in the nicotine group were abstinent. The corresponding figures in the placebo group were 19, 20, and 23%. The differences were significant for all 3 months. Body weight did not increase in the nicotine group, but in the placebo group the mean increase was 4.4 kg. Craving and withdrawal symptoms decreased more with nicotine substitution for cigarettes. The patches were generally well tolerated, although 25% of subjects in the nicotine group and 13% in the placebo group had transient local erythema after application of the patch; 5 members of the nicotine group withdrew because of poor cutaneous tolerance.", "Bupropion hydrochloride is recommended for smoking cessation; however, there have been relatively few clinical trials examining its efficacy.\n A total of 244 current smokers were enrolled in an outpatient randomized blinded smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center, San Francisco, Calif. Of the 244 participants, 121 received a 7-week course of bupropion and 123 received placebo. All participants received 2 months of transdermal nicotine replacement therapy and 3 months of cognitive-behavioral counseling. We determined on-medication treatment, end-of-medication treatment, 3-month, 6-month, and 1-year quit rates.\n During treatment with bupropion vs placebo, there was a trend toward increased quit rates among participants randomized to bupropion; the self-reported end-of-medication treatment quit rates were 64% for the bupropion group vs 57% for the placebo group (P =.23). The trend favoring bupropion persisted at 3 months of follow-up (P =.12) but was not apparent at 6 months and 1 year of follow-up (both P>.78). The 12-month quit rates, validated by either saliva cotinine or spousal proxy, were 22% in the bupropion group and 28% in the placebo group (P =.31). Based on biochemical validation, 19% of the bupropion group vs 24% of the placebo group had quit smoking by 1 year (P =.36).\n In this randomized blinded trial of mostly veteran participants, the addition of a brief 7-week bupropion trial to treatment with nicotine replacement therapy and counseling did not significantly increase smoking cessation rates.", "The use of nicotine chewing gum combined with psychological support improves the success rate in quitting smoking. We studied the safety and efficacy of a transdermal nicotine patch in smoking cessation.\n We conducted a double-blind randomized study comparing the effects of a 16-hour nicotine patch (15 +/- 3.5 mg of nicotine in 16 hours) with those of a placebo patch. Of the 289 smokers (207 women and 82 men) enrolled in the study, 145 were treated with nicotine patches and 144 with placebo patches for 16 weeks.\n Rates of sustained abstinence were significantly better with active treatment than with placebo: 53, 41, 24, and 17 percent of those in the nicotine-patch group were abstinent after 6, 12, 26, and 52 weeks, respectively, as compared with 17, 10, 5, and 4 percent of those in the placebo-patch group (P less than 0.0001). Only two subjects with the nicotine patch and one with the placebo patch had to withdraw from the study because of side effects.\n The nicotine skin patch proved to be safe and effective, as demonstrated by a higher rate of abstinence than with placebo. However, the absolute rate of abstinence after one year was only 17 percent, which is lower than the rate in studies that have combined the use of nicotine chewing gum with behavioral therapy.", "To determine whether self-regulated flexible dosing with varenicline tartrate is safe and effective for smoking cessation.\n 320 healthy, motivated-to-quit smokers (> or =10 cigarettes/day) aged 18-65 years, entered a multicenter, randomized, double-blind, placebo-controlled study - conducted between December 26, 2001 and June 24, 2003 - with a 12-week treatment phase and 40-week, double-blind, non-treatment follow-up. Treatment consisted of varenicline or placebo in fixed doses (Week 1: titrated from 0.5 to 1.0 mg/day) followed by a self-regulated flexible schedule (Weeks 2-12: 0.5-2.0 mg/day).\n Primary outcomes included carbon monoxide-confirmed continuous abstinence rate (CAR) from smoking for Weeks 4 through 7, 9 through 12, and 9 through 52. Secondary outcomes included CAR from Weeks 9 through 24, 7-day point prevalence of abstinence, safety assessments, and measures of craving, withdrawal, and smoking reward.\n Superior CARs were observed in varenicline-treated (n = 157) versus placebo participants (n=155) for Weeks 4 through 7 (38.2 vs. 11.6%), 9 through 12 (40.1 vs. 11.6%), 9 through 24 (28.0 vs. 9.0%), and 9 through 52 (22.3 vs. 7.7%) (all p<0.001). Seven-day point prevalence was higher in varenicline-treated than placebo participants at Weeks 12 (46.5 vs. 14.2%; p<0.001), 24 (32.5 vs. 13.5%; p<0.001), and 52 (28.0 vs. 13.5%; p=0.001). Overall, medication compliance was high, although varenicline-treated, but not placebo, participants tended to taper down their dosage over time. Total treatment-emergent AEs were 77.1% (varenicline: 121/157) and 65.8% (placebo: 102/155). Few AEs led to treatment discontinuation (varenicline: 11/157, 7.0% and placebo: 7/155, 4.5%). Participants were primarily healthy Caucasians, so more research is necessary to determine how applicable these findings are to other populations.\n A self-regulated, flexible dosing regimen of varenicline is well tolerated, with superior effectiveness versus placebo for smoking cessation.", "A prospective randomized study was undertaken to assess the effectiveness and side effect profiles of nicotine patch and bupropion therapies for smoking cessation.\n Three hundred and fifty patients were referred to our smoking cessation program in the Department of Pulmonary Diseases, Gaziantep University between September 2002 and July 2003. Of these, only 131 patients fulfilled the trial criteria. We randomized the patients into nicotine patch (n=50), bupropion (n=50) and control groups (n=31). Cases were followed up for 24 weeks. Questionnaires including the Fagerstrom test for nicotine dependence and Beck Depression Inventory were carried out at initial evaluation. Declaration of quitting and exhaled carbon monoxide level less than 10 ppm was accepted as success criteria.\n Success rates were 26% for nicotine patch group, 26% for bupropion and 16% for control group at the end of the 24th week (p=0.56). Beck depression inventory scores did not differ significantly between the groups, however none of the cases with scores greater than 13 succeeded regardless of the group. Mean body weight at baseline and change at 6 months did not differ significantly between the groups. Sleep disturbance was significantly more common in nicotine patch and bupropion groups than the control group (p=0.008).\n The present study reinforces the role of medical doctors and importance of close follow up in smoking cessation, and directed counseling is quite as effective as pharmacologic therapy and is the sole approach without any adverse effects.", "We used the Heaviness of Smoking Index, a subset of the Fagerstrom Test for Nicotine Dependence, to classify 608 cigarette smokers planning a cessation attempt as low or high in nicotine dependence. Subjects within each level of dependence were then randomly assigned to placebo, 2-mg, or 4-mg nicotine gum treatment. Subjects were also provided brief (5-10 min per visit) behavioral counseling during a 1-year period of follow-up. At 1 year post-cessation, quit rates were 11.2, 19.5, and 18.4% for low-dependence smokers receiving placebo, 2-mg, and 4-mg gum, respectively (plinear trend = 0.20). For high-dependence smokers, quit rates at 1 year were 6.1, 15.7, and 20.7% for the placebo, 2-mg, and 4-mg gum conditions, respectively (plinear trend = 0.002). The interaction of nicotine-gum dose and dependence group was not significant (p = 0.42), nor did the 2-mg and 4-mg doses differ significantly in effectiveness, though both 2-mg and 4-mg gum were significantly more effective than placebo gum. We also found a significant dose-related effect for nicotine gum to moderate post-cessation heart-rate decline. Other variables related to abstinence at 1 year post-cessation were a longer period of abstinence on a prior quit attempt, being married, higher education level, and having a non-smoking spouse or significant other. Results indicate that nicotine gum is a significant aid to smoking cessation, more than doubling the odds of successful cessation compared to the odds for placebo-gum users. The 4-mg dose provided a non-significant increase in cessation rates for high-dependence smokers. Smoking history and demographic variables also have a significant impact on the outcome of a quit-smoking attempt.", "Bupropion is a first-line pharmacological aid for smoking cessation; however, no clinical trials have been conducted in a general population of hospitalized smokers.\n We enrolled 85 smokers in a hospital-based randomized smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center. A total of 42 participants received a 7-week course of sustained-release bupropion and 43 participants received placebo. All participants received cognitive-behavioral counseling. We screened 14,997 patients, of whom 25% were current smokers. Of the 536 smokers who met the entry criteria, 451 opted not to enroll. We determined on-medication, end-of-medication, 3-month, and 6-month smoking cessation rates.\n At the end of 7 weeks of drug treatment, self-reported quit rates were equivalent in the bupropion and placebo arms, 37% versus 33%, respectively (p = .82). The validated quit rates for the bupropion and placebo groups were 27% versus 29%, respectively (p = 1.00). At 6 months, the self-reported quit rates were 29% in the bupropion group and 41% in the placebo group (p = .36). In a comparison of 6-month quit rates, validated either by salivary cotinine or by spousal proxy, we found nonsignificantly higher quit rates in the placebo group than in the bupropion group, 31% versus 15% (p = .12).\n The addition of sustained-release bupropion to counseling did not increase quit rates, but the study was underpowered. Because of the secular trend toward shorter hospital stays, recruitment was very difficult, raising questions regarding the feasibility of future hospital-based smoking cessation trials and interventions.", "To evaluate bupropion SR for smoking cessation in physicians and nurses.\n This double-blind prospective 26-center, 12-country trial randomized 687 subjects to smoking cessation counselling with bupropion SR or placebo for 7 weeks. The participants were followed for 52 weeks.\n Bupropion SR was superior to placebo (50% vs 40%, P=0.013) on the 4-week primary outcome variable. Due to a high placebo response in this health care population, statistical differences were not maintained after treatment was discontinued.\n Bupropion SR is effective and well tolerated in health care professionals. Relapse prevention measures are needed to attain long-term abstinence.", "To determine whether attempts to prevent weight gain will increase success rates for stopping smoking.\n 16 week, open, randomised study with 1 year follow up.\n Obesity unit.\n 287 female smokers who had quit smoking before but started again because of weight concerns.\n Combination of a standard smoking cessation programme with nicotine gum and a behavioural weight control programme including a very low energy diet. A control group was treated with the identical programme but without the diet. Main outcome measure: Sustained cessation of smoking.\n After 16 weeks, 68/137 (50%) women had stopped smoking in the diet group versus 53/150 (35%) in the control group (P=0.01). Among these women, weight fell by mean 2.1 (95% confidence interval 2.9 to 1.3) kg in the diet group but increased by 1.6 (0.9 to 2.3) kg in the control group (P<0.001). After 1 year the success rates in the diet and control groups were 38/137 (28%) and 24/150 (16%) respectively (P<0.05), but there was no statistical difference in weight gain.\n Combining the smoking cessation programme with an intervention to control weight helped women to stop smoking and control weight.", "The effect of 2-mg nicotine chewing gum as an adjunct to group therapy for smoking cessation was studied in a placebo-controlled, double-blind, randomized trial. After one year, 29% of the 106 subjects treated with nicotine chewing gum had remained abstinent throughout the year compared with 16% of the 99 subjects treated with placebo. The results were confirmed by measurement of levels of expired CO. More subjects in the nicotine group (70/94 v 45/93) reported that the gum reduced the craving for smoking. The adverse effects were few and not serious. In the nicotine group, 3% were still using the nicotine gum after two years. No subjects in the placebo group used the chewing gum beyond six months. Nicotine chewing gum is effective in improving the success rates in smoking cessation based on group therapy.", "The majority of cigarette smokers who achieve abstinence relapse within the first year and require many attempts before achieving permanent abstinence. Evidence to support pharmacological treatment for relapse prevention is insufficient.\n To determine whether smokers who quit after 12 weeks of treatment with varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, maintain greater continuous abstinence rates (defined as not a single \"puff\" of a cigarette) than placebo controls during an additional 12 weeks of treatment and until 52 weeks after treatment initiation.\n Randomized controlled trial conducted at multiple medical clinics in 7 countries with follow-up to 52 weeks after study baseline. Of 1927 cigarette smokers recruited between April 2003 and February 2004 and treated for 12 weeks with open-label varenicline titrated to 1 mg twice per day, 1236 (64.1%) did not smoke, use tobacco, or use nicotine replacement therapy during the last week of treatment and 62.8% (n = 1210) were randomized to additional treatment or placebo.\n Participants were randomly assigned to receive either double-blind varenicline, 1 mg twice per day (n = 603), or placebo (n = 607) for an additional 12 weeks.\n Carbon monoxide-confirmed continued abstinence during weeks 13 to 24 and weeks 13 to 52 of the study.\n The carbon monoxide-confirmed continuous abstinence rate was significantly higher for the varenicline group than for the placebo group for weeks 13 to 24 (70.5% vs 49.6%; odds ratio [OR], 2.48; 95% confidence interval [CI], 1.95-3.16; P<.001) as well as for weeks 13 to 52 (43.6% vs 36.9%; OR, 1.34; 95% CI, 1.06-1.69; P = .02). Adverse events reported in the open-label period were mostly mild; no difference in adverse events between varenicline and placebo was observed during the double-blind period.\n Smokers who achieved abstinence for at least 7 days at the end of 12 weeks of open-label varenicline treatment and were randomized to receive an additional 12 weeks of varenicline treatment showed significantly greater continuous abstinence in weeks 13 to 24 compared with placebo. This advantage was maintained through the nontreatment follow-up to week 52. Varenicline may be an efficacious, safe, and well-tolerated agent for maintaining abstinence from smoking.\n clinicaltrials.gov Identifier: NCT00143286.", "Smoking cessation attempts are often complicated by dysphoria/depression, weight gain, craving, and other nicotine withdrawal symptoms. Fluoxetine's antidepressant and anorectant properties, along with its capacity to attenuate compulsive behavior, suggest that this medication might facilitate smoking cessation treatment. We examined the effect of fluoxetine on smoking cessation in the context of a program that included group cognitive-behavioral therapy (six weeks) and transdermal nicotine patch(ten weeks). In a double-blind randomized trial of fluoxetine for smoking cessation, 150 daily smokers were assigned to placebo (n=48), 20 mg (n=51), or 40 mg fluoxetine (n=51). Fluoxetine did not significantly improve smoking cessation rates, either for those with or without major depressive disorder(MDD)histories or elevated current depression. Our results suggest that fluoxetine may moderate withdrawal symptoms, even if that was not manifested in improved smoking cessation rates. Our results, however, clearly favor the use of fluoxetine if weight gain is a major clinical obstacle to smoking cessation.", "Nicotine gum has been shown to be effective in improving abstinence rates, and in reducing post-cessation withdrawal distress and weight gain. However, the dose effects of nicotine gum on these outcomes is not known. In the present study, we varied the amount of 2 mg nicotine gum prescribed to motivated quitters to explore the hypotheses (a) that motivated quitters would use more pieces of gum when coached and counseled to do so and (b) that there would be a dose-related effect of gum use on abstinence, withdrawal symptoms, and weight gain. One hundred seventy-seven volunteers were assigned to chew either 0, 7, 15, or 30, pieces per day of 2 mg nicotine gum. Biological verification of gum use and smoking abstinence were assessed in community volunteers who attended an intensive behavioral counseling program for smoking cessation while using nicotine gum for 3 months. In the survival analysis at 12 weeks, gum-group assignment was not related to successful abstinence. In the subset of 42 abstinent subjects, there was a strong positive relationship between pieces per day of nicotine gum used and saliva cotinine. However, there was substantial variability in groups of subjects reporting similar amounts of gum use. Withdrawal symptom reporting was not related to either gum use or cotinine levels. Weight gain was significantly related in a dose-dependent manner to salivary cotinine levels, but not to gum group assignment, with high and low cotinine subjects gaining on average, 4.0 and 6.6 pounds, respectively. Discussion of the use of high levels of nicotine gum is addressed. Consistent with earlier work, the study provided further support for the relationship between nicotine replacement level and post-cessation weight gain.", "In this double-blind, placebo-controlled smoking cessation treatment study, 608 participants were randomly assigned to receive active bupropion and active 4-mg gum (AA, n = 228), active bupropion and placebo gum (AP, n = 224), or placebo bupropion and placebo gum (PP, n = 156). Relative to the PP group, the AA and AP groups were each significantly more likely to be abstinent at 1 week, end of treatment, and 6 months but not at 12 months postquit. After the first week postquit there were no differences in abstinence rates between the AA and AP groups. We found no significant individual difference variables that moderated outcome beyond 1 week postquit.", "Smoking cessation is a key component of secondary cardiovascular disease prevention. Varenicline, a partial alpha4beta2 nicotinic acetylcholine receptor agonist, is effective for smoking cessation in healthy smokers, but its efficacy and safety in smokers with cardiovascular disease are unknown.\n A multicenter, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease. Participants received varenicline (1 mg twice daily) or placebo, along with smoking-cessation counseling, for 12 weeks. Follow-up lasted 52 weeks. The primary end point was carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 (last 4 weeks of treatment). The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 (47.0% versus 13.9%; odds ratio, 6.11; 95% confidence interval [CI], 4.18 to 8.93) and weeks 9 through 52 (19.2% versus 7.2%; odds ratio, 3.14; 95% CI, 1.93 to 5.11). The varenicline and placebo groups did not differ significantly in cardiovascular mortality (0.3% versus 0.6%; difference, -0.3%; 95% CI, -1.3 to 0.7), all-cause mortality (0.6% versus 1.4%; difference, -0.8%; 95% CI, -2.3 to 0.6), cardiovascular events (7.1% versus 5.7%; difference, 1.4%; 95% CI, -2.3 to 5.0), or serious adverse events (6.5% and 6.0%; difference, 0.5%; 95% CI, -3.1 to 4.1). As a result of adverse events, 9.6% of varenicline and 4.3% of placebo participants discontinued study drug.\n Varenicline is effective for smoking cessation in smokers with cardiovascular disease. It was well tolerated and did not increase cardiovascular events or mortality; however, trial size and duration limit definitive conclusions about safety. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov/ct2/show/NCT00282984. Unique identifier: NCT00282984.", "Exercise combined with nicotine therapy may help smoking cessation and minimise weight gain after quitting. Low participation in vigorous-intensity physical activity programmes precludes their population-wide applicability. In a randomised controlled trial, we tested whether a population-based moderate-intensity physical activity programme increases quit rates among sedentary smokers receiving nicotine therapy.\n Participants (n=481; 57% male; mean age, 42.2 years (SD 10.1); mean cigarette consumption, 27 (SD 10.2) per day) were offered a nine-week smoking cessation programme consisting of a weekly 15-minute counselling session and the prescription of nicotine replacement therapy. In addition, participants in the physical activity group (n=229) also took part in a programme of moderate-intensity physical activity implemented at the national level, and offering nine weekly 60-minute sessions of physical activity. To ensure equal contact conditions, participants in the control group (n=252) attended weekly 60-minute health behaviour education sessions unrelated to physical activity. The primary outcome was continuous CO-verified smoking abstinence rates at 1-year follow-up.\n Continuous smoking abstinence rates were high and similar in the physical activity group and the control group at the end of the intervention (47% versus 46%, p=0.81) and at 1-year follow-up (27% versus 29%, p=0.71). The mean weight gain after one year was 4.4 kg and 6.2 kg among sustained quitters of the physical activity and control groups, respectively (p=0.06).\n Participation in a population-based moderate-intensity physical activity programme for 9 weeks in addition to a comprehensive smoking cessation programme did not significantly increase smoking cessation rates. A non-significant reduction in weight gain was observed among participants who quit smoking in the physical activity group.\n ClinicalTrials.gov; US National Institutes for Health (available online at http://clinicaltrials.gov/; Clinical Trial Registration Number: NCT00521391).", "Many smokers remain refractory to current therapies, which only partially address weight gain after smoking cessation. Thus, this study evaluated whether naltrexone hydrochloride augmentation of nicotine patch therapy improves smoking abstinence and reduces postcessation weight gain more than nicotine patch therapy alone and at what dose.\n Six-week double-blind placebo-controlled trial with follow-up in an outpatient research center. Four hundred individuals who smoked 20 or more cigarettes daily were randomly assigned to treatment for 6 weeks with a 21-mg nicotine patch and oral naltrexone hydrochloride (0, 25, 50, or 100 mg/d) after equal random treatment assignment and followed up for 1 year after randomization. The a priori specified primary end points were prolonged 4-week cigarette abstinence after a 2-week grace period in the intent-to-treat sample and weight gain in these abstainers.\n We found no significant differences in prolonged 4-week abstinence (P = .49) or 6-week continuous abstinence after the quit date (P = .12) during treatment in the intent-to-treat analysis. Among 295 treatment completers, the 100-mg dose was associated with higher continuous abstinence rates (71.6%) compared with placebo (48%) (odds ratio, 2.73; 95% confidence interval, 1.39-5.39; P<.01). Among continuous abstainers, the 25-mg naltrexone hydrochloride group gained significantly less weight (mean +/- SEM, 0.7 +/- 0.31 kg) than the placebo group (mean +/- SEM, 1.9 +/- 0.33 kg; P<.01). Similar naltrexone dose effects on weight were found for those with prolonged abstinence and treatment completers, irrespective of abstinence.\n The 100-mg dose of naltrexone hydrochloride appears the most promising for augmenting the efficacy of the nicotine patch on smoking cessation outcomes but requires further study. The significant weight reduction with low-dose naltrexone therapy suggests that it may be useful as a second-line treatment for weight-concerned smokers.", "Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting.\n Smokers (N=172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post-quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date.\n The difference in weight at 26 weeks post-quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs ± 8.94 vs placebo: 9.7 lbs ± 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43).\n For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence.\n Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.", "Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or \"target quit date\") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less.\n At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups.\n A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.", "Varenicline, a partial agonist at the alpha4beta2 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine.\n To determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR).\n A randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study.\n Varenicline titrated to 1 mg twice daily (n = 344) or bupropion SR titrated to 150 mg twice daily (n = 342) or placebo (n = 341) for 12 weeks, plus weekly brief smoking cessation counseling.\n Continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52).\n During the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P<.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P<.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P<.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P = .003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P<.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P = .004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%).\n Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR.\n clinicaltrials.gov Identifier: NCT00143364.", "To assess the efficacy and safety of a repeat course of treatment with transdermal nicotine for cessation of smoking in a brief intervention setting.\n Randomised, double blind, placebo controlled trial with follow up for 26 weeks.\n 629 smokers who had unsuccessfully attempted to stop smoking by using active transdermal nicotine and brief behavioural counselling. Smokers were motivated to quit smoking for a second time and smoked > or = 15 cigarettes a day.\n Twelve weeks' treatment with active transdermal nicotine patches or placebo and brief counselling at monthly visits.\n Sustained smoking cessation for the 28 days before the visit at week 12 verified by expired carbon monoxide concentrations.\n At 12 weeks 21/315 (6.7%) subjects allocated to active treatment had stopped smoking compared with 6/314 (1.9%) allocated to placebo (absolute difference 4.7%; 95% confidence interval 1.6% to 7.9%; P = 0.003). At 26 weeks the rates were 20/315 (6.4%) and 8/314 (2.6%) (3.8%; 0.6% to 7.0%; P = 0.021). Difficulty in sleeping was reported by 43/179 (24.0%) on active treatment and 19/143 (13.3%) on placebo (P = 0.015). Severe reactions at the site of application were rare (6/322; 1.9%).\n Repeated treatment with transdermal nicotine together with brief counselling can improve the low success rates of smoking cessation in recently relapsed, moderate to heavy smokers. Questions remain about whether more intensive interventions or higher doses of nicotine could be more effective. The likelihood of severe reactions at the site of application with repeated treatment is low.", "The selective nicotinic acetylcholine receptor partial agonist, varenicline tartrate, represents a novel type of therapy for smoking cessation. This study evaluated the efficacy, safety, and tolerability of 4 varenicline dose regimens, 2 with progressive dosing over the first week (eg, titrated) and 2 with a fixed dosing schedule (eg, non-titrated), for promoting smoking cessation.\n This multicenter, double-blind, placebo-controlled study randomized healthy smokers (aged 18-65 years) to varenicline tartrate, 0.5 mg twice daily nontitrated (n = 129), 0.5 mg twice daily titrated (n = 130), 1.0 mg twice daily nontitrated (n = 129), 1.0 mg twice daily titrated (n = 130), or placebo (n = 129) for 12 weeks to aid in smoking cessation. A 40-week follow-up period assessed long-term efficacy. The primary efficacy measures were the carbon monoxide-confirmed 4-week continuous quit rates by pooled dosage group for weeks 4 through 7 and 9 through 12 and the continuous abstinence rates for weeks 9 through 52.\n Weeks 9 through 12 continuous quit rates were greater in the 1.0-mg group (49.4%) and the 0.5-mg group (44.0%) vs placebo (11.6%; P<.001 vs both doses). Weeks 9 through 52 abstinence rates were greater in the 1.0-mg group (22.4%; P<.001) and the 0.5-mg group (18.5%; P<.001) vs placebo (3.9%). Varenicline was generally well tolerated, with nausea occurring in 16% to 42% of varenicline-treated subjects. Reports of nausea were lower for the titrated vs nontitrated dosing and infrequently led to medication discontinuation.\n Varenicline tartrate, 0.5 mg and 1.0 mg twice daily, is efficacious for smoking cessation." ]

[ "6443376", "6725168", "6410266", "19586142", "15571443", "11772479", "9337499" ]

[ "Contingent methadone dose increases as a method for reducing illicit opiate use in detoxification patients.", "Contingency management interventions: effects on treatment outcome during methadone detoxification.", "Efficacy of psychotherapeutic counselling during 21-day ambulatory heroin detoxification.", "Facilitating outpatient treatment entry following detoxification for injection drug use: a multisite test of three interventions.", "Abstinence incentive effects in a short-term outpatient detoxification program.", "Voucher-based reinforcement of opiate abstinence during methadone detoxification.", "Effects of adding behavioral treatment to opioid detoxification with buprenorphine." ]

[ "nan", "We examined the effectiveness of a contingency management program in preventing relapse to illicit opiate use and increasing treatment retention during outpatient methadone detoxification treatment. Twenty male opiate addicts were randomly assigned to an experimental or control group. Following a 3-week methadone stabilization period, men in both groups received identical gradual methadone dose reductions during Weeks 4 through 9 and were maintained on placebo during Weeks 10 through 13. Beginning in Week 4, control patients received $5.00 for providing a specimen twice weekly. Experimental patients received $10.00 and a take home methadone dose for each opiate-free urine specimen but forfeited the incentives and participated in more intensive clinic procedures when specimens were opiate positive. The contingency management procedure slowed the rate of relapse to illicit opiate use. Experimental patients provided significantly more opiate-free urines during the methadone dose reduction in Weeks 4 through 9 than control patients, although the difference between groups was no longer significant during placebo administration in Weeks 10 through 13. In addition, the contingency management program improved treatment retention and reduced symptom complaints during the detoxification. The usefulness and limitations of contingency management procedures for outpatient methadone detoxification are discussed.", "Structured, psychotherapeutic counselling during 21-day heroin detoxification was evaluated by randomly assigning a group of 25 heroin addicts to a detoxification treatment regimen with mandatory counselling by a therapist and 25 to a control group who received only standard detoxification without counselling. There was no significant difference between groups in the number who successfully detoxified as measured by conversion of morphine positive urine to morphine negative urine. The counselling intervention group did, however, improve the attendance of subjects while in detoxification treatment, and significantly more patients entered long-term treatment following detoxification. Maximal use of a counselor during 21-day heroin detoxification may best be realized by directing therapy toward engaging patients in long-term care.", "A multisite, randomized trial within the National Drug Abuse Treatment Clinical Trials Network (CTN) was conducted to test 3 interventions to enhance treatment initiation following detoxification: (a) a single session, therapeutic alliance intervention (TA) added to usual treatment; (b) a 2-session, counseling and education, HIV/HCV risk reduction intervention (C&E), added to usual treatment; and (c) treatment as usual (TAU) only. Injection drug users (n=632) enrolled in residential detoxification at 8 community treatment programs were randomized to 1 of the 3 study conditions. TA participants reported entering outpatient treatment sooner and in greater numbers than TAU participants. Reported treatment entry for C&E fell between TA and TAU with no significant differences between C&E and the other conditions. There were no differences among the interventions in retention, as measured by weeks of outpatient treatment for all participants who reported treatment entry. Alliance building interventions appear to be effective in facilitating transfer from detoxification to outpatient treatment, but additional treatment engagement interventions may be necessary to improve retention.\n Copyright (c) 2009 APA, all rights reserved.", "Despite being widely available, outpatient detoxification has limited efficacy as a stand-alone treatment. This study examined whether abstinence-contingent incentives would improve outcomes for patients entering outpatient opiate detoxification. Participants (N = 211) received a 100 US dollars voucher on the last day of detoxification either contingent on opiate and cocaine abstinence or noncontingently. Urine samples were collected at intake, on Wednesday, Friday (the last day of detoxification), and the following Monday. Among contingent-voucher participants, 31% were drug-free on Friday compared with 18% of noncontingent controls (Z = 2.4, p < .05). Few (12-13%) participants tested negative on Monday. Results support the ability of vouchers to produce modest improvements in abstinence initiation rates during brief detoxification but suggest that additional interventions are needed to sustain improvements.\n Copyright 2004 APA.", "Methadone detoxification is often used in the treatment of opiate dependence. This procedure, however, is frequently associated with continued opiate use, and high rates of attrition and relapse. In this study, a 90-day methadone detoxification was enhanced by adding voucher-based reinforcement of opiate abstinence before, during and after the dose tapering schedule. After 4 weeks of standard methadone maintenance (baseline), subjects were randomized to either the abstinence (n=26), or attendance reinforcement (n=22) condition. During the remaining 22 weeks of the study, the abstinence reinforcement group could receive vouchers with monetary value three times per week for providing opiate-negative urine specimens, while subjects in the attendance reinforcement group received vouchers of equal value for attending the clinic, regardless of urinalysis results. Methadone maintenance continued during weeks 5-10, dose tapering was implemented during weeks 11-23, and during weeks 24-26 the voucher schedule remained in effect but no medication was provided. Fifty percent of clients in both groups completed dose tapering, and 40% completed the vouchers-only phase. Subjects in the abstinence as compared with the attendance reinforcement group had lower rates of opiate use during the maintenance and detoxification phases, and longer periods of opiate abstinence during the detoxification phase. Cocaine use was also lower in the abstinence than the attendance reinforcement group during the maintenance and detoxification phases. In addition, abstinence as compared with attendance reinforcement subjects reported significantly fewer intravenous injections during the detoxification phase. Voucher-based reinforcement procedures could be useful for successfully transitioning patients into opiate antagonist therapy, or drug-free treatments.", "This trial assessed whether behavioral treatment improves outcome during a 26-week outpatient opioid detoxification. Thirty-nine opioid-dependent adults were assigned randomly to a buprenorphine dose-taper combined with either behavioral or standard treatment. Behavioral treatment included (a) a voucher incentive program for providing opioid-free urine samples and engaging in verifiable therapeutic activities and (b) the community reinforcement approach, a multicomponent behavioral treatment. Standard treatment included lifestyle counseling. Fifty-three percent of the patients receiving behavioral treatment completed treatment, versus 20% receiving standard treatment. The percentage of patients achieving 4, 8, 12, and 16 weeks of continuous opioid abstinence were 68, 47, 26, and 11 for the behavioral group and 55, 15, 5, and 0 for the standard group, respectively. Behavioral treatment improved outcomes during outpatient detoxification." ]

[ "6360297", "9555556", "8903550", "7921936", "2729386", "2750828" ]

[ "A trial comparing the Stamey bladder neck suspension procedure with colposuspension for the treatment of stress incontinence.", "Comparative analysis of bladder neck suspension using Raz, Burch and transvaginal Burch procedures. A 3-year randomized prospective study.", "Burch colposuspension versus stamey endoscopic bladder neck suspension: a urodynamic appraisal.", "A prospective randomized trial comparing a modified needle suspension procedure with the vagina/obturator shelf procedure for genuine stress incontinence.", "Comparison of three different surgical procedures for genuine stress incontinence: prospective randomized study.", "Primary stress urinary incontinence and pelvic relaxation: prospective randomized comparison of three different operations." ]

[ "Fifty-one women with urodynamically proven genuine stress incontinence were alternately allocated to either colposuspension or a Stamey-type bladder neck suspension. One year after operation 89% of the patients who had had a colposuspension were subjectively cured and 73% were objectively normal. In the Stamey procedure group these figures were 76 and 40% respectively. The Stamey procedure is a quicker, simpler and a lesser procedure but has a higher incidence of post-operative voiding difficulties and residual urge symptoms. Colposuspension is to be preferred for the younger, healthier patient. The Stamey procedure is useful in the elderly, obese or unfit patient or the patient who has had multiple previous surgical attempts at a cure.", "Ever since Pereyra described needle suspension of the bladder neck for the treatment of stress urinary incontinence in women, numerous modifications have been presented. There were variations in the success reported by different authors. We report 3-year follow-up results in 146 women operated on for stress urinary incontinence using Raz, Burch and our own new procedures.\n During a 5-year period, 146 women were operated on for genuine stress urinary incontinence. Using the method of Raz, and transvaginal Burch as well as the Burch retropubic urethropexy, a modified bladder neck suspension was performed in 46 (32%), 44 (30%) and 56 (38%) patients, respectively. In all patients a prior gynecological or urological operation for urinary incontinence and a clear neuropathic condition had been excluded before surgery. The routine diagnostic procedure consisted of multichannel cystometry, voiding cystourethrography, infusion urography and cystoscopy. A pressure-flow electromyography study was done in patients with a residual volume greater than 50 ml following voiding. The operations were performed by the same surgeon (I.G.). Initial follow-up was done after 12 months and then every year.\n Urodynamic testing did not reveal significant differences between Burch and Raz (p = 0.2652), Raz and transvaginal Burch (p = 0.5745) as well as between Burch and transvaginal Burch procedures (p = 0.7602; Fisher's exact test). Three years after surgery, 50 of 56 (89.3%; Burch procedure), 37 of 46 (80.4%; Raz modification) and 38 of 44 patients (86.4%; transvaginal Burch) were continent.\n There is no reason (except patient condition) to prefer any of the numerous modifications of bladder neck suspension. We believe that the success of the operation lies in adequate mobilization of the bladder neck and urethra as well as in a surgeon's familiarity with the procedure.", "A total of 51 consecutive female patients with genuine stress incontinence who underwent a Burch or Stamey operation were clinically and urodynamically evaluated preoperatively at least 8 months postoperatively. Our study group consisted of 27 women who underwent the Burch colposuspension and 24 who had the Stamey endoscopic bladder neck suspension. The urodynamic parameters which were studied pre- and postoperatively were the maximum flow rate (Qmax), the residual urine (Vres), the first sensation (FS), the bladder capacity (BC), the maximum vesical pressure (Pves max), the detrusor pressure at maximum flow (Pdet/Qmax), the functional urethral length (Lfun) and the maximum closure pressure (Pclos max). The successful results of the operations were 89% for Burch and 83% for the Stamey procedure. As for differing objective urodynamic findings, the Qmax, Pclos max, Vres and Lfun for both groups were the only parameters which showed statistically significant difference after surgery. The statistical comparison of the postoperative urodynamic parameters of the two operative techniques showed that Lfun, Pves max and Pclos max had difference in favor of Burch colposuspension. There were not statistical differences in the other studied parameters. In conclusion, according to the differentiation in the values of Pclos max, Lfun and Pves max, the Burch technique seems to result in a higher increase of patient's urethral resistance.", "To compare two procedures for the treatment of genuine stress incontinence in patients selected randomly.\n Fifty patients with proven genuine stress incontinence were randomized prospectively over a 3 year period to be treated either by a modified needle suspension (MNS) (n = 26) or by a vagina/obturator shelf (VOS) (n = 24) procedure.\n In patients who had not undergone previous surgery for incontinence, the VOS procedure was superior with 12 of 14 patients achieving continence compared with eight of 15 patients in the MNS group (P < 0.05). In women who had undergone previous surgery seven of 11 were continent following MNS compared with five of 10 after a VOS procedure. Both techniques had a much lower continence rate when compared with a classical colposuspension operation which was reported in a previous series.\n As a primary procedure VOS was more successful than MNS. In patients who had undergone previous surgery for incontinence neither procedure gave acceptable results.", "One hundred seven consecutive patients with clinical and urodynamic findings of genuine stress incontinence not previously treated were prospectively allocated in a randomized manner to one of three surgical procedures: anterior colporrhaphy, revised Pereyra procedure, or Burch retropubic urethropexy. Randomization included the surgical procedure and choice of surgeon (one of the three authors). Clinical and urodynamic evaluations were repeated at 3 months and 1 year after surgery. Differences in cure rates among the three procedures at the 3-month postoperative evaluation were insignificant (82%, 84%, and 92% for the anterior colporrhaphy, Pereyra, and Burch respectively) but became statistically significant at the 1 year postoperative evaluation (cure rates of 65%, 72%, and 91% for the anterior colporrhaphy, Pereyra, and Burch respectively, p less than 0.05). In our hands the Burch procedure stabilized the urethrovesical junction and prevented its descent during straining (evaluated by a postoperative Q-tip test) more effectively than either the Pereyra or anterior colporrhaphy. No procedure resulted in severe postoperative voiding difficulties. The present prospective randomized study demonstrates that in our hands the abdominal retropubic operation for genuine stress incontinence in patients not previously operated on results in a higher cure rate when compared with anterior colporrhaphy or Pereyra procedure.", "There were 289 women with clinical and urodynamic diagnosis of primary stress urinary incontinence, stable bladder, and pelvic relaxation who underwent a single-stage surgical procedure because of incontinence and pelvic relaxation. Patients underwent one of three surgical procedures because of stress incontinence--anterior colporrhaphy, revised Pereyra procedure, or Burch retropubic urethropexy. Decisions with regard to the type of bladder neck suspension and the surgeon were made randomly with a randomization table. Each patient had a complete clinical and urodynamic evaluation before surgery and at 3 and 12 months after surgery. Cure rate as defined by strict clinical and urodynamic criteria was not significantly different among the three groups at the 3-month postsurgical evaluations; however, at the 12-month postsurgical evaluations, the cure rate among women who underwent Burch urethropexy (n = 101) was significantly higher than that of either Pereyra or anterior colporrhaphy (cure rates were 87%, 70%, and 69%, respectively; p less than 0.01). The Burch urethropexy was more effective than the Pereyra procedure or anterior colporrhaphy in the stabilization of the bladder base and resulted in a significantly better cure rate in women with primary stress urinary incontinence and pelvic relaxation." ]

[ "16317317" ]

[ "A double-blind, controlled study of sertindole versus risperidone in the treatment of moderate-to-severe schizophrenia." ]

[ "Sertindole is a non-sedating atypical antipsychotic effective in the management of schizophrenia and is associated with placebo-level incidence of extrapyramidal symptoms (EPS). In this randomized, double-blind, parallel-group, flexible-dose, multi-centre study, the efficacy and tolerability of sertindole was directly compared with another atypical antipsychotic in patients with schizophrenia. A total of 187 patients were randomly assigned to treatment with sertindole (12-24 mg/day, n=98) or risperidone (4-10 mg/day, n=89) for 12 weeks. Although early termination reduced the power of the study, some significant between-group differences were evident. Sertindole reduced the mean Positive and Negative Syndrome Scale total scores to a greater extent than risperidone, and the difference reached statistical significance at endpoint for the Observed Cases (OC) dataset. Moreover, sertindole was superior for the treatment of negative symptoms compared to risperidone (P<0.05, Last Observation Carried Forward and OC). Both treatment groups were similarly effective in improving Clinical Global Impression (Severity and Improvement), the Drug Attitude Inventory and Global Assessment of Functioning scores. Sertindole and risperidone were both well tolerated. Numerically, fewer patients in the sertindole group (19%) reported EPS-related adverse events than in the risperidone group (28%), although significantly more sertindole-treated patients reported QT prolongation and abnormal ejaculation volume (P<0.05). In conclusion, sertindole was well tolerated and demonstrated clinically relevant efficacy advantages over risperidone." ]

[ "8746985", "12457220", "9689974", "10917122", "9703597", "7482218", "9014675" ]

[ "A comparative study of laparoscopic extraperitoneal and transabdominal preperitoneal herniorrhaphy.", "Totally extraperitoneal endoscopic inguinal hernia repair (TEP).", "Laparoscopic transperitoneal versus extraperitoneal inguinal hernia repair: a prospective clinical trial.", "A multicentric comparison of transabdominal versus totally extraperitoneal laparoscopic hernia repair using PARIETEX meshes.", "Transabdominal or totally extraperitoneal laparoscopic hernia repair?", "Laparoscopic hernioplasty. TAPP vs TEP.", "Prospective randomized trial comparing postoperative pain and return to physical activity after transabdominal preperitoneal, total preperitoneal or Shouldice technique for inguinal hernia repair." ]

[ "Laparoscopic minimally invasive surgical procedures are gaining popularity. Laparoscopic hernia repair is now less controversial and more readily acceptable, with at present numerous technical modifications described in an attempt to define the best procedure. Between November 1992 and February 1995, a nonrandomized trial of laparoscopic inguinal herniorrhaphy was performed on 115 patients with a total of 120 hernias. Of these 58 patients with 60 hernias underwent the transabdominal preperitoneal patch repair (TAPP) without plug and 57 patients with a total of 60 hernias were offered the extraperitoneal (EXTRA) approach using a distension balloon. The average operative time was 55 min for the TAPP and 50 min for the EXTRA procedure. The overall recurrence rate was 1.7% with a follow up of 1-27 months. The recurrence rate was 3.4% for the TAPP and none for the EXTRA approach. All patients returned to their normal activity within 1 week of discharge. Patients undergoing the EXTRA repair consumed less amount of narcotic analgesic than did the group undergoing the TAPP repair. Of the EXTRA group 58% did not require any analgesic, compared to 22% of the TAPP group (p < 05). There were no intraoperative complications. A total of 8 (6.9%) postoperative complications occurred in 115 patients. Four complications (6.9%) occurred in the TAPP procedure: 2 transient urinary retentions, 1 pulmonary edema, and 1 Richter's type hernia. Four (6.9%) complications occurred in the EXTRA procedure: 1 urinary retention, 2 abdominal wall ecchymoses, and 1 thoracic pain. Hospital stay was shorter for the EXTRA group: 57% were discharged the same day and 98% were discharged within 24 h of their operations for the EXTRA group compared to 10 and 84%, respectively, for the TAPP (p < 0.05). Laparoscopic extraperitoneal hernia repair can be accomplished with shorter hospitalization and less analgesic requirement than the TAPP repair. The overall incidence of complications, the recurrence rate, and the return to normal activity were not different between the two types of repair.", "This report reviews our experience with 5,203 totally extraperitoneal (TEP) endoscopic hernia repairs performed in 3,868 patients over the 7.5-year period between May 1994 and December 2001, 34.5% of whom had bilateral hernias and 13% recurrent hernias.\n We performed TEP as the method of choice in more than 92% of all the patients presenting with inguinal hernia, including those with incarcerated, strangulated, or inguinoscrotal hernias. After reduction of the hernial sac and appropriate dissection of the preperitoneal space, we placed a slit-free 10 x 15-cm polypropylene mesh without the use of staple fixation.\n Altogether, 29 recurrent hernias (0.6%) were observed, more than 50% of which occurred during the first 2 years after the technique was introduced (1.8%). During subsequent years, the recurrence rate settled to approximately 0.3%. Regarding intraoperative complications, we observed eight injuries to the bladder. At this writing, no bowel injuries or damage to iliac vessels has been seen. Postoperatively, we noted only a single case of mesh infection. In 14 cases (0.4%), postoperative hemorrhage necessitated either inguinal or endoscopic reoperation. As a further major complication, a small bowel obstruction caused by inadequate closure of a peritoneal lesion occurred in two patients (0.05%). The overall reoperation rate for the 3,868 patients was 0.6%.\n We consider TEP to be a procedure that carries an acceptably low complication rate, combining the advantages of minor access surgery and mesh reinforcement of the groin. This approach is associated with early postoperative return to usual activities and a very low recurrence rate.", "A prospective series of 106 inguinal hernias in 91 patients is studied, comparing two methods of laparoscopic hernia repair: a transperitoneal technique with preperitoneal stapled mesh fixation (TransAbdominal PrePeritoneal or TAPP-technique) performed in 33 patients, and a totally extraperitoneal placement of non stapled mesh (Totally ExtraPeritoneal Approach or TEPA-technique) performed in 58 patients. Conversions to open repair were equally frequent (5% vs. 7% respectively) and were due to adhesions, haemorrhage, irreducible intestinal loop in the hernial sac or important subcutaneous emphysema. Minor postoperative complications included regional seroma or haematoma, testicular pain and meralgia paraesthetica. There was no mortality nor long lasting complication. Recurrence rates in both groups amounted 2.7% (TAPP) and 2.8% (TEPA) respectively after a mean follow-up of 15.8 months (TAPP) and 17.6 months (TEPA). In both groups early recovery of normal activities was noted, after a mean of respectively 13.6 days (TAPP) and 12.9 days (TEPA). It is concluded that the transabdominal route and the totally extraperitoneal approach for laparoscopic herniorrhaphy are both adequate techniques for inguinal hernia repair with similar complication and short-term recurrence rates.", "The authors report a series of 1972 inguinal hernias treated between 1993 and 1997 by the insertion of a PARIETEX mesh via either a transabdominal-preperitoneal (TAPP) (1,290 procedures) or a totally extraperitoneal TEP approach (682 procedures). Pain scores were equivalent in both groups, while the hospital stay and time to return to normal activity was lower in the TEP group than in the TAPP group (p<0.001). In both groups, the average incidence of the total reported events (complications) was around 10% with no statistical difference. This ratio seemed to compare favorably to previously published reports. Chronic pain was extremely rare (0.6% and 0.7% in the TAPP and TEP groups, respectively). Whatever the approach was, sepsis was also very rare (1/1,526 laparoscopic procedures). These findings illustrate the local tolerance of the mesh. Recurrence rates were below 1% with no statistical difference between groups. This retrospective study demonstrates the clinically apparent local tolerance of this type of mesh. Prospective and long-term clinical results will be necessary to demonstrate that the optimized short-term tolerance of PARIETEX mesh will influence the long term functional results.", "Laparoscopic repair of inguinal hernias follows some principles that have already proven its efficiency, as a posterior approach and the prosthetic repair that allows a \"tension-free\" repair with consequent early return to work and low recurrence rate. To determine the most appropriate laparoscopic repair, we compared the transabdominal preperitoneal (TAPP) and the totally extraperitoneal (TEP) approach. Patients undergoing TAPP and TEP were compared regarding technical feasibility and difficulties, time until return to work and follow-up, including intraoperative and postoperative complications. Seventy-eight patients (108 hernias) were submitted to TAPP and 67 (100 hernias) were repaired through TEP. All data were analyzed by Yates-corrected chi-square test to qualitative analysis of each group and p < or = 0.05 was considered significant. Both procedures were indicated mainly for bilateral and/or recurrent hernias (68%). The operative time was shorter in TAPP (not statistically significant). Surgeons complained of more technical difficulties while performing the TEP approach (70% complaints of difficulty in TEP--four conversions to TAPP). There was no difference in hospital stay (mean of 30 h) and return to work (TAPP 7 days and TEP 5.5 days). Regarding the complication rate (TAPP = 20.5% and TEP = 13.5%; not significant), none were related to the pneumoperitoneum technique or its systemic effects. In the TAPP approach, two trocar site hernias occurred, and in the TEP approach, one severe cellulitis occurred, which was managed without surgical intervention. The mean follow-up period for each procedure was not the same, so the recurrence rates are not comparable statistically (rate of 1.85% in TAPP and 0 in TEP). Both techniques are safe and have the same advantages, but TAPP is easier: a better view of the anatomy is achieved, shortening the learning curve. We suggest that TAPP can be an adequate laparoscopic approach to groin hernias. A longer follow-up period and more cases are needed to determine recurrence rates.", "This study compares the results of two laparoscopic hernioplasties: the transabdominal preperitoneal (TAPP) and the totally extraperitoneal (TEP). Over a 43-month period 1,115 laparoscopic hernioplasties, 733 TAPP and 382 TEP, were performed in 866 patients. There were 11 major complications in the TAPP group (2 recurrences, 6 trocar hernias, 1 small-bowel obstruction, 1 trocar, and 1 dissection injury of the small bowel) compared to 1 recurrence and no intraperitoneal complications in the TEP group. Five TEP procedures required conversion to the TAPP approach, resulting in one umbilical hernia. The median time to return to work did not vary with the approach, but was prolonged in patients compensated for time off, 16 vs 8 days for noncompensated patients. Results suggested that both techniques shortened recovery and eliminated most early failures, but the totally extraperitoneal approach reduced the potential for intraperitoneal complications and may be the procedure of choice in most situations.", "In a prospective randomized study postoperative pain, analgesic consumption, return to physical activity and work, cosmetic result and experience with the type of operation were assessed in 86 patients undergoing inguinal hernia repair by means of either the Shouldice technique (n = 34), the laparoscopic transabdominal preperitoneal (TAPP) (n = 28) or total preperitoneal (TPP) (n = 24) repair. Patients having TAPP repair had decreased visual analogue scale scores for pain on the day of operation compared with those undergoing TPP and Shouldice repair (4.8 versus 6.5 and 6.2 respectively, P = 0.02) and on the first postoperative day compared with TPP (4.0 versus 6.0, P = 0.01). There was no difference between the three groups for days 2, 3, 4, 5 and 30 after operation. Patient satisfaction with the operation, analgesic consumption, return to physical activity such as walking, driving, climbing stairs, running, bicycling and sexual intercourse, as well as return to work, was comparable in the three groups. There was a better cosmetic result after TAPP and TPP repair. This study failed to demonstrate significant benefits from laparoscopic hernia repair over the Shouldice technique." ]

[ "16719029", "10205352", "3364308", "15637216", "11108415", "1452950", "9550459", "15297095", "16770284", "9599191", "6989171", "3742182", "18407904", "16354710", "6416514", "1970070", "12880608", "15105027", "14512038" ]

[ "Nutritional supplementation and resistance training in nutritionally at risk older adults following lower limb fracture: a randomized controlled trial.", "Pressure sores and tube feeding in patients with a fracture of the hip: a randomized clinical trial.", "Thiamine status, vitamin supplements and postoperative confusion.", "Nightly enteral nutrition support of elderly hip fracture patients: a pilot study.", "Nutritional supplementation of elderly hip fracture patients. A randomized, double-blind, placebo-controlled trial.", "Benefits of oral protein supplementation in elderly patients with fracture of the proximal femur.", "Nightly enteral nutrition support of elderly hip fracture patients: a phase I trial.", "Effects of protein-rich supplementation and nandrolone in lean elderly women with femoral neck fractures.", "Nutritional supplementation decreases hip fracture-related complications.", "Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial.", "Treatment of osteoporosis with 1-alpha-hydroxycholecalciferol and calcium.", "Supplement feeds and nitrogen and calorie balance following femoral neck fracture.", "Effects of oral nutritional supplements in normally nourished or mildly undernourished geriatric patients after surgery for hip fracture: a randomized clinical trial.", "Using dietetic assistants to improve the outcome of hip fracture: a randomised controlled trial of nutritional support in an acute trauma ward.", "Benefits of supplementary tube feeding after fractured neck of femur: a randomised controlled trial.", "Dietary supplementation in elderly patients with fractured neck of the femur.", "A randomised, double-blind assessment of the effect of nutritional supplementation on the prevention of pressure ulcers in hip-fracture patients.", "Provision of high-protein supplement for patients recovering from hip fracture.", "Nutritional supplements after hip fracture: poor compliance limits effectiveness." ]

[ "To describe the independent and combined effects of oral nutrition supplementation and resistance training on health outcomes in nutritionally at risk older adults following lower limb fracture.\n Randomized controlled trial with 12-week masked outcome assessment.\n Teaching hospital.\n One hundred nutritionally at risk older adults hospitalized following a fall-related lower limb fracture.\n Commenced seven days after injury. Consisted of daily multinutrient energy-dense oral supplement (6.3 kJ/mL) individually prescribed for six weeks (n = 25), tri-weekly resistance training for 12 weeks (n = 25), combined treatment (n = 24) or attention control plus usual care and general nutrition and exercise advice (n = 26).\n Weight change, quadriceps strength, gait speed, quality of life and health care utilization at completion of the 12-week intervention.\n At 12 weeks, all groups lost weight: nutrition -6.2% (-8.4, -4.0); resistance training -6.3% (-8.3, -4.3); nutrition and resistance training -4.7% (-7.4, -2.0); attention control -5.2% (-9.0, -1.5). Those receiving resistance training alone lost more weight than those receiving the combined treatment (P= 0.029). Significant weight loss was prevented if supplement was consumed for at least 35 days. Groups were no different at 12 weeks for any other outcome.\n Frail, undernourished older adults with a fall-related lower limb fracture experience clinically significant weight loss that is unable to be reversed with oral nutritional supplements. Those receiving a programme of resistance training without concurrent nutrition support are at increased risk of weight loss compared with those who receive a combined nutrition and resistance training intervention. In this high-risk patient group it is possible to prevent further decline in nutritional status using oral nutritional supplements if strategies are implemented to ensure prescription is adequate to meet energy requirements and levels of adherence are high.", "Pressure sores are a frequent problem, especially in elderly patients. Nutritional status may influence the incidence, progression and severity of pressure sores, data, however, are contradictory (1). The purpose of this study was to determine the effect of supplemental feeding on the nutritional status and the development and severity of pressure sores. The effect of supplemental feeding overnight (tube +) on patients with a fracture of the hip and a high pressure-sore risk score, was studied in a randomized clinical trial. The control group (tube -) had no supplemental feeding. After informed consent, 140 patients were randomized, and 129 of these took part in the trial (62 tube +, and 67 tube -). Protein and energy intake, haemoglobin, serum albumin, total serum protein and pressure-sore grade were measured at admission and after 1 and 2 weeks. Of the 62 patients randomized for tube feeding (tube +), only 25 tolerated their tube for more than 1 week and 16 for 2 weeks. Nevertheless, energy and protein intake was significantly higher in the tube + group (P < 0.001). This, however, did not significantly influence total serum protein, serum albumin and development and severity of pressure sores after 1 and 2 weeks. Comparison of the actually tube fed group (n=25 at 1 week, n = 16 at 2 weeks) and the control group showed a 2-3 times higher protein and energy intake (P < 0.0001), and a significantly higher total serum protein and serum albumin after 1 and 2 weeks in the actually tube fed group (all P < 0.001). Pressure-sore development and severity were not significantly influenced in the actually tube fed group. We conclude that we were not able to show a significant decrease in development and severity of pressure sores, because the nasogastric tube for supplemental feeding was not well tolerated in this patient group. Nevertheless, tube feeding overnight does result in a significant higher protein and energy intake, and has a significant effect on nutritional status in the actually tube-fed group. Other means of supplemental feeding will have to be used in order to answer the question of whether supplemental feeding can decrease development and severity of pressure sores.", "In a prospective, randomized, controlled study an intravenous vitamin B complex and vitamin C preparation was administered pre- and post-operatively to 28 elderly patients with a fractured proximal femur and compared with 32 nonsupplemented postoperative controls. Vitamin supplementation significantly, though only transiently, improved postoperative thiamine status (P less than 0.001), but had no influence on mental state or outcome during the postsurgical period. Therefore, the use of parenteral vitamins for postoperative confusion cannot be justified on a routine basis.", "Assess whether postoperative nightly enteral nutrition support improves outcomes of elderly patients with an acute hip fracture\n Randomized controlled trial.\n A University and a Department of Veteran's Affairs Hospital\n Adults >64 years of age who underwent surgical repair of an acute hip fracture.\n Subjects randomized to the control (Ctrl) group received standard care while the treatment (Tx) group received standard care plus up to 1,375 Kcal [5,755 kJ/d] of nasoenteral tube feedings each night. When tube feedings had to be discontinued, Tx subjects were asked to drink an equivalent amount of the nutritional supplement each night. Measures of Outcome: Rate of postoperative complications and 6-month postoperative survival.\n Fifty-seven patients were randomized to the Tx (n = 27, mean age 75.9 +/- 7.4 yrs) or Ctrl groups (age 81.7 +/- 7.7 yrs). All subjects had reduced volitional nutrient intakes after surgery. During the first week subsequent to surgery, there was no difference between the treatment and control groups in the amount of nutrients that they volitionally consumed during the day. However, the treatment subjects had a greater total daily nutrient intake (Median 5,866 (IQR 5,024 to 7,335) kJ/d vs. 3,965 (IQR 2,968 to 4,664) kJ/d, p < 0.001). However, by the second postoperative week this difference was no longer statistically significant. Intolerance to the tube feedings developed commonly. There was no difference between the groups in the rate of postoperative life-threatening complications or mortality within six months subsequent to surgery.\n This study failed to confirm findings from a prior study of improved postoperative survival with nutrition support. However, it was conducted on multiple hospital wards which may have contributed to the higher rate of tube-related problems and less nutrient delivery signifying the need for further study.", "undernourishment is common in elderly hip fracture patients and has been linked to poorer recovery and increased post-operative complications.\n to determine whether a nutritional supplement may (i) help elderly patients return to pre-fracture functional levels 6 months post-fracture and (ii) decrease fracture-related complications and mortality.\n a double-blind, randomized, placebo-controlled clinical trial.\n a county hospital near Barcelona.\n 171 patients, aged 70 and older, hospitalized for hip fracture between July 1994 and July 1996.\n we randomized patients to intervention (n = 85) or control (n = 86) group. Patients received a nutritional supplement containing 20 g of protein and 800 mg of calcium or placebo for 60 days. We determined functional levels by the Barthel index, the mobility index and by the use of walking aids. We performed assessments during hospitalization and at 2 and 6 months post-fracture.\n the two groups were comparable at study entry. We observed no differences in return to functional status 6 months post-fracture (61% intervention group vs 55% in control group) nor in fracture-related mortality (13% in intervention group vs 10% in control group). The intervention group suffered fewer in-hospital [odds ratio 1.88 (95% CI 1.01 - 3.53), P = 0.05] and total complications [odds ratio 1.94 (95% CI 1.02-3.7), P = 0.04] than the control group.\n based on our results, we cannot recommend routine nutritional supplementation of all elderly hip fracture patients. While nutritional supplementation may be useful in decreasing complications, this reduction does not result in improvement in functional recovery and nor does it decrease fracture-related mortality. Selected patients may, however, benefit from nutritional supplementation.", "Malnutrition has been often suggested as contributing to both the high incidence of hip fracture in elderly people and its complications. In a recent prospective controlled randomized study, the clinical outcome of elderly patients with osteoporotic fracture of the proximal femur (hip fracture) improved by giving a simple oral dietary supplement. This study, however, did not prove that protein was responsible for the clinical improvement since the supplement also contained vitamins and minerals. We addressed this question by comparing the clinical outcome and bone mineral density (BMD) changes in elderly patients with hip fracture, receiving two different dietary supplements with different protein contents. Sixty-two patients (mean age 82) admitted into the orthopedic ward for fracture of the proximal femur were randomized into two groups. One group (n = 33) received 250 ml/day of an oral nutritional supplement containing protein (20.4 g), mineral salts (Ca: 0.525 g) and vitamins A = 750 IU; D3 = 25 IU) for a mean of 38 days. A control group (n = 29) received the same supplement dose, but with no protein, for the same period of time. The clinical course was significantly better in the group receiving protein, with 79% having a favorable course as compared to 36% (p less than 0.02) in the control group during the stay in the recovery hospital. The rate of complications and deaths was also significantly lower in the protein-supplemented vs the control group (52 vs 80%, p less than 0.05) 7 months after hip fracture. The median hospital stay was significantly lower in the protein-supplemented group (69 vs 102 days, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "This non-blinded randomized controlled trial was the first phase of a planned series of investigations designed to test the efficacy of aggressive post-operative enteral nutrition support to decrease the rate of post-operative complications or improve long-term outcomes in specifically defined subgroups of elderly patients who have sustained a hip fracture requiring surgery.\n Eighteen patients (17 males) were randomized to the treatment (eight male subjects) or control groups. The control group (mean age 76.5+/-6.1 years) received standard post-operative care. Subjects in the treatment group (mean age 74.5+/-2.1 years) received 125 cc/hour of nasoenteral tube feedings over 11 hours each night in addition to standard post-operative nutritional care.\n Both the treatment and control groups had reduced volitional nutrient intakes for the first 7 post-operative days (3,966+/-2,238 vs. 4,263+/-2,916 kJ/day [948+/-535 vs. 1019+/-697 kcal/day], p=0.815), but the treatment subjects had a greater total nutrient intake (7,719+/-2,109 vs. 4,301+/-2,858 kJ/day [1845+/-504 vs. 1028+/-683 kcal], p=0.012). On average, treatment subjects were tube fed for 15.8+/-16.4 days. There was no difference between the groups (treatment vs. controls) in the rate of post-operative life-threatening complications (25 vs. 30%, p=1.00) or in-hospital mortality (0 vs. 30%, p=0.216). Mortality within 6 months subsequent to surgery was lower in the treatment group compared to the controls (0 vs. 50%, p=0.036).\n We conclude that nightly enteral feedings are a safe and effective means of supplementing nutrient intake. The greatest impact of nutrition support may be to reduce mortality.", "To evaluate the effects of a protein-rich liquid supplementation, alone or in combination with the anabolic steroid nandrolone decanoate, on body composition, activities of daily living (ADL) status and the health-related quality of life (HRQoL) after a femoral neck fracture.\n Sixty women, aged 83 +/- 5 years (mean +/- SD), BMI < 24 kg/m2 (20.4 +/- 2 kg/m2 ) and capable of co-operating, with a femoral neck fracture treated with internal fixation, were randomised to open treatment during 6 months with a protein-rich liquid formula alone (PR, Fortimel, 200 ml/day, 20 g protein/day) or in combination with nandrolone decanoate (PR/N, Deca-Durabol 25 mg i.m./3 weeks) or to a control group (C). The patients were re-examined after 6 and 12 months regarding body weight (BW), lean body mass (LBM, DXA), ADL status according to Katz, HRQoL according to EQ 5-D and fracture healing.\n LBM decreased in the C (-1.2 +/- 2 kg) and PR groups (-1.2 +/- 1 kg) but remained the same in the PR/N group (0.3 +/- 1 kg) (P < 0.05 between groups). ADL remained at a high level in the two intervention groups but declined significantly in the C group (P < 0.005 between groups). The decline in HRQoL was least pronounced in the PR/N group at 6 months (P < 0.05 between groups). Patients with fracture healing complications lost more BW (P < 0.05) and LBM (P < 0.01) than patients with uneventful fracture healing.\n Protein-rich liquid supplementation in combination with nandrolone given for 6 months to lean elderly women after a femoral neck fracture may positively affect LBM, ADL and HRQoL.\n Copyright 2003 Elsevier Ltd.", "Protein energy malnutrition is an important determinant of clinical outcome in older patients after hip fracture, but the effectiveness of nutritional support programs in routine clinical practice is controversial. We performed a prospective, randomized, controlled clinical trial to determine if nutritional supplementation decreased fracture-related complications in a selection of otherwise healthy patients with hip fractures. Patients were randomized to intervention or control groups. The control group (n = 40) was given ordinary hospital food and beverage. The intervention group (n = 40) also was administered a 1000 kcal daily intravenous supplement for 3 days, followed by a 400 kcal oral nutritional supplement for 7 days. We recorded daily fluid and energy intake during the first 10 days of hospitalization and fracture-related complications up to 4 months. The total fluid and energy intake in the intervention group neared optimal levels. The control group received 54% and 64% of optimal energy and fluid intake, respectively. The risk of fracture- related complications was greater in the control group (70%) than in the intervention group (15%). Four patients in the control group died within 120 days postoperatively. The comprehensive balanced nutrition supplement resulted in lower complication rates and mortality at 120 days postoperatively.", "Elderly persons who have osteoporotic hip fracture are often undernourished, particularly with respect to protein. Protein malnutrition may contribute to the occurrence and outcome of hip fracture.\n To investigate whether oral protein supplements benefit bone metabolism in patients with recent hip fracture.\n 6-month, randomized, double-blind, placebo-controlled trial with a 6-month post-treatment follow-up.\n University orthopedic ward.\n 82 patients (mean age, 80.7 +/- 7.4 years) with recent osteoporotic hip fracture. Patients received calcium supplementation, 550 mg/d, and one dose of vitamin D, 200,000 IU (at baseline).\n Protein supplementation, 20 g/d, or isocaloric placebo (among controls).\n Bone mineral density, biochemical markers of bone remodeling, calciotropic hormone levels, biochemically evaluated nutritional and immunologic status, and muscle strength were measured every 6 months.\n Compared with controls, patients who received protein supplements had significantly greater increases in serum levels of insulin-like growth factor-I (85.6% +/- 14.8% and 34.1% +/- 7.2% at 6 months; difference, 51.5 percentage points [95% CI, 18.6 to 84.4 percentage points]; P = 0.003) and an attenuation of the decrease in proximal femur bone mineral density (-2.29% +/- 0.75% and -4.71% +/- 0.77% at 12 months; difference, 2.42 percentage points [CI, 0.26 to 4.59 percentage points]; P = 0.029). Seven and 13 new vertebral deformities were found among patients who received protein supplements and controls, respectively (P > 0.2). Median stay in rehabilitation wards was shorter for patients who received protein supplements than for controls (33 days [CI, 29 to 56 days] and 54 days [CI, 44 to 62 days]; difference, 21 days [CI, 4 to 25 days]; P = 0.018).\n Protein repletion after hip fracture was associated with increased serum levels of insulin-like growth factor-I, attenuation of proximal femur bone loss, and shorter stay in rehabilitation hospitals.", "A double-blind comparative study of 1 alpha-OHD3 and placebo was performed on 37 patients with osteoporotic hip fracture without clinical osteomalacia. 1 alpha-OHD3, in a dose of 1 microgram/day together with 2.5 g CaCO3, did not heal osteoporosis as judged from determinations of bone mineral density and histomorphometric analyses during four months of treatment. However, 1 alpha-OHD3 seemed to have an effect on fracture healing as concluded from the posttreatment alkaline phosphatase level. Hypercalcemia was common, occurring in six out of 19 patients treated with 1 alpha-OHD3. It is concluded that treatment of osteoporosis with 1 alpha-OHD3 and calcium is ineffective and potentially dangerous because it frequently causes hypercalcemia.", "A 10 day study of nitrogen and calorie balance has been undertaken in 61 women patients aged 65-96 years (mean age 81 years) with femoral neck fractures. All underwent fracture surgery with an inhalation anaesthetic lasting from 45 min to 2 h. Intake of ward food varied widely but was always low with a mean of 127 mg N kg-1 and 17 kcal kg-1 daily. Daily nitrogen production was 85-250 mg N kg-1 (mean 158 mg N kg-1) and calorie expenditure was 17-48 kcal kg-1 (mean 32 kcal kg-1). These were greatest in trochanteric fracture patients. Of the 61 patients, 90 per cent were in negative nitrogen balance with a mean 8 day deficit of 411 mg N kg-1 and all in negative calorie balance, mean 141 kcal kg-1. The deficits were greatest in trochanteric fracture patients. Sip feeding with supplementary enriched drinks raised protein and calorie intake substantially. Both nitrogen and calorie balance were significantly improved, but large calorie deficits remained; intolerance of the supplements proved to be a handicap in correcting the deficits in many patients.", "Oral nutritional supplements have been recommended after orthopedic surgery in geriatric patients to reduce postoperative complications. However, tolerability of supplements could be a limitation, and their universal use is not supported by the heterogeneity of previous studies, especially in patients without malnutrition.\n This study is a randomized, controlled, open, parallel, 3-arm clinical trial comparing supplementation with protein powder dissolved in liquids to aim at 36 g of protein per day, energy and protein supplements to aim at 37.6 g of protein and 500 kcal per day, or no intervention in normally nourished or mildly undernourished patients. Outcomes were serum albumin, prealbumin, retinol-binding globulin, and body mass index, among others. Postoperative complications were also recorded.\n Ninety patients aged 83.8 +/- 6.6 years were included. The mean ingested amount of supplements was 41.1% +/- 20.6% in the protein powder supplement group and 51.4% +/- 13.2% in the energy protein supplement group (t = 2.278, P = .027). Postoperative supplements had no effect on the nutrition status during in-hospital follow-up, as assessed by serum albumin (P = .251), prealbumin (P = .530), retinol-binding globulin (P = .552), or body mass index (P = .582). Multivariate analysis showed that length of hospital stay with an established complication until its resolution (beta = .230, P = .031), total hospital stay (beta = .450, P < .001), baseline body mass index (beta = .204, P = .045), and total daily ingested proteins per body weight (beta = .252, P = .018) were predictive variables on the change in serum albumin (R2 = 0.409, F = 11.246, P < .001).\n Oral nutritional supplements in normally nourished or only mildly undernourished geriatric patients with hip fracture submitted to surgery may be of interest for patients with postoperative complications and long hospital stays.", "To examine how improved attention to nutritional status and dietary intake, achieved through the employment of dietetic assistants (DAs), will affect postoperative clinical outcome among elderly women with hip fracture.\n Open prospective randomised controlled trial, comparing conventional nursing care with the additional nutritional support provided by DA.\n Thirty-eight bedded acute trauma ward in a teaching hospital.\n All but 11 of 344 consecutive admissions with acute nonpathological hip fracture were approached. Three hundred and eighteen (93%) agreed to inclusion. Sixteen were ineligible as they were immediately transferred to another acute ward, were managed conservatively or died preoperatively.\n Postoperative mortality in the acute trauma unit.\n Postoperative mortality at 4 months after fracture, length of stay, energy intake and nutritional status.\n DA-supported participants were less likely to die in the acute ward (4.1 versus 10.1%, P = 0.048). This effect was still apparent at 4 month follow-up (13.1 versus 22.9%, P = 0.036). DA-supported subjects had significantly better mean daily energy intake (1,105 kcal versus 756 kcal/24 h, 95% CI 259-440 kcal/24 h, P<0.001), significantly smaller reduction in mid-arm circumference during their inpatient stay (0.39 cm, P = 0.002) and nonsignificantly favourable results for other anthropometric and laboratory measurements.\n Dietetic or nutrition assistants are being introduced in units across the UK. This, the largest ever study of nutritional support after hip fracture, shows that their employment significantly reduced patients' risk of dying in the acute trauma unit; an effect that persisted at 4 month follow-up.", "A total of 744 elderly women with fractured neck of femur were classified into three groups according to anthropometric measurements on admission: group 1, well nourished; group 2, thin; group 3, very thin. Group 1 ate well and had a low mortality and a short rehabilitation time. The thinner the patients the lower their voluntary food intake, the higher their mortality and the longer their rehabilitation time. A series of 122 patients from groups 2 and 3 were entered postoperatively into a randomised controlled trial of overnight supplementary nasogastric tube feeding (4.2 MJ (1000 kcal), including 28 g protein) in addition to their normal ward diet. This treatment was associated with improvements not only in anthropometric and plasma protein measurements but also in clinical outcome, especially in the very thin group 3 patients. Rehabilitation time and hospital stay were shortened. Mortality in group 3 was less in the tube fed patients (8%) than in the controls (22%) but this difference did not reach statistical significance. One in five patients could not tolerate the nasogastric tube, but in the remainder the treatment caused no side effects and did not seriously diminish voluntary oral food intake by day.", "59 elderly patients (mean age 82) with femoral neck fractures were randomised into two groups. 27 patients received daily an oral nutrition supplement (250 ml, 20 g protein, 254 kcal) for a mean of 32 days; 32 patients acted as controls. On admission most patients had nutritional deficiencies. Despite being offered adequate quantities, nutritional requirements were not met during the hospital stay. Clinical outcome was significantly better in the supplemented group (56% favourable course vs 13% in controls) during the stay in the convalescent hospital. The rates of complications and deaths were also significantly lower in supplemented patients (44% vs 87%). 6 months after the fracture the rates of complications and mortality were significantly lower in supplemented patients (40% vs 74%). The median duration of hospital stay was significantly shorter in the supplemented group (24 vs 40 days). Thus the clinical outcome of elderly patients with femoral neck fracture can be improved by once daily dietary oral supplementation.", "Malnutrition is a risk factor for development of pressure ulcers (PU). Nutritional supplementation may thus reduce the incidence of PU. We investigated the effect of nutritional supplementation on incidence of PU in hip-fracture patients at risk of developing PU.\n Hip-fracture patients (n=103) were included in this double-blind, randomised, placebo-controlled trial. They received 400 ml daily of a supplement enriched with protein, arginine, zinc and antioxidants (n=51) or a non-caloric, water-based placebo supplement (n=52). Presence and stage of PU were assessed daily for 28 days or until discharge (median: 10 days during supplementation).\n Incidence of PU was not different between supplement (55%) and placebo (59%), but incidence of PU stage II showed a 9% difference (difference: 0.091; 95% CI: 0.07-0.25) between supplement (18%) and placebo (28%). Of patients developing PU 57% developed it by the second day. Time of onset (days) showed a trend (P=0.090) towards later onset of PU with supplement (3.6+/-0.9) than placebo (1.6+/-0.9).\n Hip-fracture patients develop PU at an early stage. Nutritional supplementation may not prevent PU at this stage, but contributes possibly to a delayed onset and progression of PU. Nutritional supplementation may be more effective if initiated earlier.", "We compared clinical outcomes with a standard (Ensure) or a high-protein (Boost HP) liquid nutritional supplement for older adults recovering from hip fracture surgery in a rehabilitation hospital.\n This randomized, double-blind, parallel-group study compared the clinical effectiveness of a standard (Ensure) with a high-protein (Boost HP) liquid nutritional supplement among patients (n = 46) 60 y or older who recently underwent surgical repair of a hip fracture. Patients were encouraged to drink at least two 8-oz cans (17.8 g/d protein for Ensure versus 30 g/d protein for Boost HP) per day for 28 d. Study measurements included change in Functional Independence Measure between rehabilitation admission and discharge, length of rehabilitation stay, laboratory measures (i.e., serum albumin, prealbumin, and C-reactive protein), physical activity energy expenditure by 7-d triaxial accelerometry, and dietary intake by three random, telephonic, 24-h dietary recalls.\n There were no significant group differences with respect to age, sex, acute hospital days, hip fracture assessment parameters, or surgical treatment. Consumption of supplement (260 oz/28 d of Ensure versus 239 oz/28 d of Boost HP) was comparable. There were no differences in complication or adverse event rates during the study. The Boost HP group consumed more protein than the Ensure group (63 versus 50 g, P < 0.048) and had a greater improvement in serum albumin over the 28-d supplementation period (+0.7 versus +0.2 g/dL, P < 0.019). The Boost HP group also consumed more fiber (12 versus 8 g), calcium (821 versus 639 mg), vitamin K (66 versus 45 microg), and phosphorus (1035 versus 833 mg) than did the Ensure group. Rehabilitation length of stay was shorter in the Boost HP than in the Ensure group, although this trend did not reach statistical significance (23 versus 28 d, P = 0.27). Outcome differences were not detected in the Functional Independence Measure.\n Supplementation was well tolerated in this population and contributed significantly to total dietary intake. Consumption of a high-protein liquid nutritional supplement may offer some benefits by improving visceral protein status.", "Undernutrition and weight loss are important determinants of clinical outcome in older patients after hip fracture but the effectiveness of nutritional support programs in routine clinical practice remains controversial. AIMS OF THE PROJECT: To determine if oral nutritional supplements given daily for 28 days after hip fracture surgery could prevent weight loss and/or lead to improved clinical outcomes (mortality rates, discharge destination, activities of daily living or length of hospital stay) in non-malnourished community-dwelling older women with hip fracture.\n One hundred and nine women with BMI range 20-30 kg/m(2) were allocated to either nutritional supplements (352 kcal/day) or usual hospital nutrition using a quasi-randomisation technique. Body weight changes were monitored at 4 and 8 weeks and clinical outcomes were recorded at discharge and at 6 months.\n No significant differences in weight change or clinical outcomes were seen between the two groups. Compliance with consuming the nutritional supplements was quite variable and there was a significant negative correlation between the amount of supplement consumed and subsequent weight change (r=-0.36, P=0.019).\n Poor compliance with oral nutritional supplements is an important determinant of the effectiveness of oral nutritional interventions in preventing weight loss after hip fracture. Whilst this may explain the lack of clinical improvements seen, our data do not support the routine use of oral nutritional supplements in non-malnourished hip fracture patients." ]

[ "20921836", "16750294", "16340597", "16864815" ]

[ "A double-blind, controlled, randomized trial to evaluate the efficacy of botulinum toxin for the treatment of lumbar myofascial pain in humans.", "Efficacy and safety of a single botulinum type A toxin complex treatment (Dysport) for the relief of upper back myofascial pain syndrome: results from a randomized double-blind placebo-controlled multicentre study.", "The effect of small doses of botulinum toxin a on neck-shoulder myofascial pain syndrome: a double-blind, randomized, and controlled crossover trial.", "A double-blind, controlled study of botulinum toxin A in chronic myofascial pain." ]

[ "Among all the causes of chronic low back pain, myofascial pain syndrome of the spinal stabilizer muscles is one of the most frequent, yet underconsidered sources of pain. The purpose of this prospective, randomized, double-blind, controlled trial was to evaluate the efficacy of type-A botulinum toxin (BTX-A) in relieving myofascial pain in patients experiencing mechanical low back pain due to bilateral myofascial pain syndrome involving the iliopsoas and/or the quadratus lumborum muscles.\n Each of the 27 enrolled patients received a bilateral, fluoroscopically guided injection in the affected muscle(s) to randomly deliver BTX-A in one side of the low back and a control drug (randomly constituted by NaCl 0.9% or bupivacaine 0.25%) in the opposite side. To evaluate the effects of treatment on daily life activities and psychologic status, 5 different questionnaires were administered (Hospital Anxiety and Depression scale [HAD-A and HAD-D], Lattinen, Oswestry, and Spielberger State-Trait Anxiety Index).\n BTX-A injection did not significantly reduce visual analog scale scores more than treatment with NaCl or bupivacaine in the contralateral side; furthermore, the treatments administered did not result in a significant improvement of patients' daily life activities or psychologic status. Although a trend toward a decrease in postintervention visual analog scale scores could be recognized in all low back sides, this trend was significant only in the sides treated with BTX-A.\n BTX-A seems to provide significant postintervention pain relief. However, considering its high cost and the small differences compared with control treatments, its use should be reserved only for patients with pain refractory to other invasive treatments.", "Botulinum type A toxin (BoNT-A) has antinociceptive and muscle-relaxant properties and may help relieve the symptoms of myofascial pain syndrome. In this study we evaluated the efficacy and tolerability of BoNT-A (Dysport) in patients with myofascial pain syndrome of the upper back. We conducted a prospective, randomized, double-blind, placebo-controlled, 12-week, multicentre study. Patients with moderate-to-severe myofascial pain syndrome affecting cervical and/or shoulder muscles (10 trigger points, disease duration 6-24 months) were randomized to Dysport or saline. Injections were made into the 10 most tender trigger points (40 units per site). The primary outcome was the proportion of patients with mild or no pain at week 5. Secondary outcomes included changes in pain intensity and the number of pain-free days per week. Tolerability and safety were also assessed. At week 5, significantly more patients in the Dysport group reported mild or no pain (51%), compared with the patients in the placebo group (26%; p=0.002). Compared with placebo, Dysport resulted in a significantly greater change from baseline in pain intensity during weeks 5-8 (p<0.05), and significantly fewer days per week without pain between weeks 5 and 12 (p=0.036). Treatment was well tolerated, with most side effects resolving within 8 weeks. In conclusion, in patients with upper back myofascial pain syndrome, injections of 400 Ipsen units of Dysport at 10 individualised trigger points significantly improved pain levels 4-6 weeks after treatment. Injections were well tolerated.", "Myofascial pain syndrome is a common cause of muscular pain in the shoulder-neck region. Injections of large amounts of botulinum toxin A have been found to be beneficial for the alleviation of myofascial pain, but large doses of this toxin may cause paresis of the muscle and other adverse events. The aim of this work was to determine the effect of small doses (5 U) of botulinum toxin A (BTA) injected directly into the painful trigger points of the muscles, using a double-blind crossover technique.\n On the basis of the empirical criteria proposed for diagnosis of myofascial pain syndrome, 31 patients suffering from myofascial pain in the neck-shoulder region were studied. The patients received either botulinum toxin A or physiological saline injections on 2 occasions 4 weeks apart. The total dose varied from 15 to 35 U of botulinum toxin A [28+/- 6 U (mean+/- SD)]. The follow-up measurements were carried out at 4 weeks after each treatment. Neck pain and result of treatment were assessed with questionnaires. The pressure pain threshold was determined using a dolorimeter.\n Neck pain values decreased from 4.3+/- 2.4 to 3.3+/- 2.0 after saline injections and from 4.1+/- 2.1 to 3.3+/- 2.2 after botulinum toxin A. The pressure pain threshold values increased from 5.2+/-1.6 to 5.9+/-1.5 and from 5.7+/-1.6 to 5.9+/-1.6 after injections with saline and botulinum toxin A, respectively. No statistically significant changes in the neck pain and pressure pain threshold values occurred between the botulinum toxin A and saline groups. After the first injections, the subjective result of treatment was significantly (P=0.008) in favor of botulinum toxin A, and after the second injections, the subjective result was better for saline, but the difference was not statistically significant (P=0.098). There was no significant difference in the prevalence of side effects between saline and botulinum toxin A.\n Our study shows that there was no difference between the effect of small doses of botulinum toxin A and those of physiological saline in the treatment of myofascial pain syndrome.", "Recent studies have reported a potential analgesic effect of botulinum toxin A (BTXA) in musculoskeletal pain. The present double-blind, randomized, placebo-controlled, parallel clinical trial studied the effect of BTXA on pain from muscle trigger points and on EMG activity at rest and during voluntary contraction.\n Thirty patients with trigger points in the infraspinatus muscles received either 50 units/0.25 mL of BTXA or 0.25 mL of isotonic saline. Baseline measures were determined during a run-in period of 1 week. Outcome measures including local and referred spontaneous pain, pain detection and tolerance thresholds to mechanical pressure, and shoulder movement were assessed at 3 and 28 days after injection. The interference pattern of the EMG during maximal voluntary effort of infraspinatus muscle was recorded and a standardized search for spontaneous electrical motor endplate activity at the trigger points was performed before and 28 days after BTXA or saline injection.\n BTXA reduced motor endplate activity and the interference pattern of EMG significantly but had no effect on either pain (spontaneous or referred) or pain thresholds compared with isotonic saline.\n The results do not support a specific antinociceptive and analgesic effect of botulinum toxin A." ]

[ "15545844", "16732007", "16513202", "12809451", "16715577", "16456680", "15642076" ]

[ "A comparison of bedtime insulin glargine with bedtime neutral protamine hagedorn insulin in patients with type 2 diabetes: subgroup analysis of patients taking once-daily insulin in a multicenter, randomized, parallel group study.", "A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes.", "Efficacy of conversion from bedtime NPH insulin to morning insulin glargine in type 2 diabetic patients on basal-prandial insulin therapy.", "Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A randomized, controlled trial.", "Therapy in type 2 diabetes: insulin glargine vs. NPH insulin both in combination with glimepiride.", "Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.", "Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes." ]

[ "Basal insulin is frequently administered once daily. This subgroup analysis of a multicenter, randomized, parallel study compared insulin glargine (Lantus Aventis Pharmaceuticals, Bridgewater, NJ) with neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes, evaluating only patients treated previously with once-daily NPH insulin.\n Patients received bedtime insulin glargine or NPH insulin, with preprandial regular insulin. One hundred patients (mean age, 57.9 years; mean glycohemoglobin, 8.4%; mean fasting blood glucose, 167 mg/dL) were treated for up to 28 weeks.\n Patients treated with insulin glargine (n = 52) and NPH insulin (n = 48) achieved similar reductions from baseline in glycohemoglobin (-0.41% versus -0.46%) and fasting blood glucose (-22 mg/dL versus -22 mg/dL) at week 28. The proportion of patients reaching target fasting blood glucose (<120 mg/dL) at 28 weeks was 34.2% with insulin glargine and 24.4% with NPH insulin. Similar proportions of patients achieved glycohemoglobin less than 7% and less than 8% in both groups. Baseline and week-28 mean daily doses of insulin glargine (27.3 IU versus 36.4 IU) were similar to NPH insulin doses (25.5 IU versus 30.2 IU). However, significantly fewer patients reported one or more episodes of hypoglycemia with insulin glargine (46.2%) versus NPH insulin (60.4%; P < 0.05). Significantly fewer patients also reported one or more symptomatic episodes confirmed by blood glucose less than 50 mg/dL with insulin glargine (17.3%) versus NPH insulin (31.3%; P < 0.005).\n Bedtime insulin glargine is as effective as bedtime NPH insulin in improving glycemic control, with significantly less hypoglycemia.", "To assess efficacy and tolerability of insulin detemir or NPH insulin added to oral therapy for type 2 diabetes in a treat-to-target titration protocol.\n Individuals (n = 476) with HbA(1c) (A1C) 7.5-10.0% were randomized to addition of twice-daily insulin detemir or NPH insulin in a parallel-group, multicenter trial. Over 24 weeks, insulin doses were titrated toward prebreakfast and predinner plasma glucose targets of < or =6.0 mmol/l (< or =108 mg/dl). Outcomes assessed included A1C, percentage achieving A1C < or =7.0%, risk of hypoglycemia, and body weight.\n At 24 weeks, A1C had decreased by 1.8 and 1.9% (from 8.6 to 6.8 and from 8.5 to 6.6%) for detemir and NPH, respectively (NS). In both groups, 70% of participants achieved an A1C </= 7.0%; [corrected] there was a trend towards [corrected] the proportion achieving this without hypoglycemia being [corrected] higher with insulin detemir than with NPH insulin (34% [corrected] vs. 25[corrected]%, P = 0.052[corrected]). Compared with NPH insulin, the risk for all hypoglycemia with insulin detemir was reduced by 47% (P < 0.001) and nocturnal hypoglycemia by 55% (P < 0.001). Mean weight gain was 1.2 kg with insulin detemir and 2.8 kg with NPH insulin (P < 0.001), and the difference in baseline-adjusted final weight was -1.58 (P < 0.001).\n Addition of basal insulin to oral drug therapy in people with suboptimal control of type 2 diabetes achieves guideline-recommended A1C values in most people with aggressive titration. Insulin detemir compared with NPH insulin achieves this with reduced hypoglycemia and less weight gain.", "In normal subjects, approximately half of the daily insulin requirement constitutes basal insulin. We investigated whether increasing the dose of insulin glargine up to half of the total insulin requirement could lead to better glycemic control in type 2 diabetic patients who were treated on basal-prandial insulin therapy. A total of 62 patients with type 2 diabetes on mealtime rapid-acting insulin analogue and bedtime NPH were randomized to either continuation of bedtime NPH (n=31) or morning glargine (n=31) for 6 months while continuing the aspart/lispro at each meal. The two groups were matched for age, sex, diabetes duration, BMI, HbA(1C), endogenous insulin secretion, and proportion of numbers using aspart/lispro and using oral hypoglycemic agents. The dose of insulin glargine was increased by 2-4 units to meet the target fasting blood glucose, whereas the dose of NPH was principally unchanged as a control group. Mean HbA(1C) at baseline was similar between patients with glargine and NPH (7.2% versus 6.9%). The percentage of glargine dose increased significantly (31% at baseline to 48% at 6 months) without any significant changes in total insulin dose. Mean HbA(1C) at 3 months was 6.6% with glargine and 7.0% with NPH (P<0.0001, adjusted mean change between-treatment difference 0.6% [95% CI 0.3-0.9]), and the values at 6 months were 6.6% and 6.9%, respectively (P=0.007). Frequency of hypoglycemia did not differ between the groups. Increasing the dose of glargine without changing the total daily insulin dose resulted in significantly better glycemic control in type 2 diabetic patients on basal-prandial insulin therapy. Conversion from bedtime NPH to morning glargine appears efficacious with no increase in frequency of hypoglycemia.", "Patients with type 2 diabetes are often treated with oral antidiabetic agents plus a basal insulin.\n To investigate the efficacy and safety of glimepiride combined with either morning or bedtime insulin glargine or bedtime neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes.\n Open-label, randomized, controlled trial.\n 111 centers in 13 European countries.\n 695 patients with type 2 diabetes who were previously treated with oral antidiabetic agents.\n Randomization to treatment with morning insulin glargine, bedtime NPH insulin, or bedtime insulin glargine for 24 weeks in addition to 3 mg of glimepiride. The insulin dose was titrated by using a predefined regimen to achieve fasting blood glucose levels of 5.56 mmol/L or lower (< or =100 mg/dL).\n Hemoglobin A(1c) values, blood glucose levels, insulin dose, and body weight.\n Hemoglobin A(1c) levels improved by -1.24% (two-sided 90% CI, -1.10% to -1.38%) with morning insulin glargine, by -0.96% (CI, -0.81% to -1.10%) with bedtime insulin glargine, and by -0.84% (CI, -0.69% to -0.98%) with bedtime NPH insulin. Hemoglobin A(1c) improvement was more pronounced with morning insulin glargine than with NPH insulin (0.40% [CI, 0.23% to 0.58%]; P = 0.001) or bedtime insulin glargine (0.28% [CI, 0.11% to 0.46%]; P = 0.008). Baseline to end-point fasting blood glucose levels improved similarly in all three groups. Nocturnal hypoglycemia was less frequent with morning (39 of 236 patients [17%]) and bedtime insulin glargine (52 of 227 patients [23%]) than with bedtime NPH insulin (89 of 232 patients [38%]) (P < 0.001).\n The risk for nocturnal hypoglycemia was lower with glimepiride in combination with morning and bedtime insulin glargine than with glimepiride in combination with bedtime NPH insulin in patients with type 2 diabetes. Morning insulin glargine provided better glycemic control than did bedtime insulin glargine or bedtime NPH insulin.", "Type 2 diabetes (T2DM) patients often fail to achieve adequate glycemic control with oral antidiabetic drugs (OADs). Insulin has been shown to improve glycemic control in these patients but with increased risk of hypoglycemia. This study compared the efficacy and safety of insulin glargine and NPH insulin, both in combination with a once-daily fixed dose of glimepiride, in terms of glycemic control and incidence of hypoglycemia.\n In this open-label, 24-week randomized trial in ten Latin American countries, T2DM patients poorly controlled on OADs (HbA1c > or = 7.5 and < or = 10.5%) received glimepiride plus insulin glargine (n = 231) or NPH insulin (n = 250) using a forced titration algorithm. The primary endpoint was the equivalence of 24-week mean changes in HbA1c.\n Insulin glargine and NPH insulin achieved similar HbA1c reductions (adjusted mean difference -0.047; 90% CI -0.232, 0.138; per-protocol analysis). Confirmed nocturnal hypoglycemia was significantly lower with insulin glargine vs. NPH insulin (16.9 vs. 30.0%; p <0.01; safety analysis). Patients receiving insulin glargine were significantly more likely to achieve HbA1c levels < 7.0% without hypoglycemia (27 vs. 17%; p = 0.014; per-protocol analysis). There was a more pronounced treatment satisfaction improvement with insulin glargine vs. NPH insulin (p <0.02; full analysis). The proportion of patients who lost time from work or normal activities due to diabetes was lower with insulin glargine vs. NPH (1.8 vs. 3.3%; full analysis).\n In patients with T2DM, inadequately controlled on OADs, once-daily insulin glargine plus glimepiride is effective in improving metabolic control with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin.", "In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia.\n In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups.\n During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01).\n Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.", "The aim of this study was to compare the efficacy and safety of a basal-bolus insulin regimen comprising either insulin detemir or neural protamine hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 2 diabetes.\n This was a 26-week, multinational, open-label, parallel group trial with 505 patients with type 2 diabetes (mean age, 60.4 +/- 8.6 years; mean BMI, 30.4 +/- 5.3 kg/m(2); mean HbA(1c), 7.9 +/- 1.3%). Patients, randomized 2:1 to insulin detemir or NPH insulin, received basal insulin either once or twice daily according to their pretrial insulin treatment and insulin aspart at mealtimes.\n After 26 weeks of treatment, significant reductions in HbA(1c) were observed for insulin detemir (0.2%-points, p = 0.004) and NPH insulin (0.4%-points; p = 0.0001); HbA(1c) levels were comparable at study end (insulin detemir, 7.6%; NPH insulin, 7.5%). The number of basal insulin injections administered per day had no effect on HbA(1c) levels (p = 0.50). Nine-point self-measured blood glucose (SMBG) profiles were similar for the two treatment groups (p = 0.58), as were reductions in fasting plasma glucose (FPG) (insulin detemir, 0.5 mmol/l; NPH insulin, 0.6 mmol/l). At study end, FPG concentrations were similar for the two treatment groups (p = 0.66). By contrast, within-subject day-to-day variation in fasting SMBG was significantly lower with insulin detemir (p = 0.021). Moreover, patients receiving insulin detemir gained significantly less body weight than those who were administered NPH insulin (1.0 and 1.8 kg, respectively, p = 0.017). The frequency of adverse events and the risk of hypoglycaemia were comparable for the two treatment groups.\n Patients with type 2 diabetes, treated for 26 weeks with insulin detemir plus insulin aspart at mealtimes, experienced comparable glycaemic control but significantly lower within-subject variability and less weight gain compared to patients treated with NPH insulin and insulin aspart. Insulin detemir was well tolerated and had a similar safety profile to NPH insulin." ]

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[ "Effect and placebo effect of acupressure (P6) on nausea and vomiting after outpatient gynaecological surgery.", "Effectiveness of an antihistamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial.", "Reminiscence interviews as stress management interventions for older patients undergoing surgery.", "A multiple-component treatment approach to smoking reduction.", "THE EFFECT OF IMIPRAMINE ON ENURESIS.", "A controlled study to assess the clinical efficacy of totally self-administered systematic desensitization.", "The hypotensive effect of a single daily dose of labetalol: a preliminary study.", "Electroacupuncture analgesia for colonoscopy. a prospective, randomized, placebo-controlled study.", "Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia.", "Placebo effect and adaptation to noninvasive monitoring of BP.", "Demonstration by placebo response in asthma by means of exercise testing.", "Topical treatment of venous microangiopathy in patients with venous ulceration with Essaven gel--a placebo-controlled, randomized study.", "Acupuncture for the management of primary dysmenorrhea.", "[Venous leg ulcers: no improvement of wound healing with 685-nm low level laser therapy. Randomised, placebo-controlled, double-blind study].", "Insertion of intradermal needles into painful points provides analgesia for intractable abdominal scar pain.", "Potentiation of placebo analgesia by proglumide.", "Specific and nonspecific factors in the effectiveness of a behavioral approach to the treatment of marital discord.", "Control of postoperative pain by transcutaneous electrical nerve stimulation after thoracic operations.", "A randomized, placebo-controlled trial of exercise therapy in patients with acute low back pain.", "Comparison of topical anaesthesia methods for venous cannulation in adults.", "A randomized controlled trial of fentanyl for abortion pain.", "Does gum chewing ameliorate postoperative ileus? Results of a prospective, randomized, placebo-controlled trial.", "Increasing Latino adolescents' adherence to treatment for latent tuberculosis infection: a controlled trial.", "Meprobamate and chlorpromazine in psychotherapy. Some effects on anxiety and hostility of outpatients.", "Skin temperature biofeedback for Raynaud's disease: a double-blind study.", "A placebo controlled double blind trial to evaluate the effectiveness of pulsed short wave therapy for osteoarthritic hip and knee pain.", "Oral antioxidant therapy for marginal dry eye.", "Relaxation training and attention placebo in the treatment of severe insomnia.", "CONTROLLED STUDY OF PSYCHIATRIC OUTPATIENT TREATMENT.", "Randomized study of vaginal chlorhexidine disinfection during labor to prevent vertical transmission of group B streptococci.", "Zolpidem reduces postoperative pain, fatigue, and narcotic consumption following knee arthroscopy: a prospective randomized placebo-controlled double-blinded study.", "A large randomized placebo controlled study of auricular acupuncture for alcohol dependence.", "P6 acupressure may relieve nausea and vomiting after gynecological surgery: an effectiveness study in 410 women.", "The impact of acupuncture and craniosacral therapy interventions on clinical outcomes in adults with asthma.", "Local application of sustained-release delivery system of chlorhexidine in Down's syndrome population.", "Paradoxical intention and insomnia: an experimental investigation.", "A controlled study of minimal-contact thermal biofeedback treatment in children with migraine.", "Treatment effectiveness of hypnosis and behaviour therapy in smoking cessation: a methodological refinement.", "Repeated measurements of non-invasive ambulatory blood pressure: distinction between reproducibility and the proper effect of placebo.", "Acute pain in a clinical setting: effects of cognitive-behavioural skills training.", "Social functioning in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment.", "A randomized controlled trial of transurethral microwave thermotherapy.", "The effect of high and low frequency electroacupuncture in pain after lower abdominal surgery.", "Cognitive-behavior therapy with adult patients with epilepsy: a controlled outcome study.", "Training children to cope with dental treatment.", "EMDR for panic disorder with agoraphobia: comparison with waiting list and credible attention-placebo control conditions.", "Withdrawal of perphenazine in chronic schizophrenia.", "Efficacy of maintenance use of anticholinergic agents.", "Is transcutaneous electrical nerve stimulation an effective analgesia during colonoscopy?", "Cognitive behavioral psychotherapy for depression following stroke: a randomized controlled trial.", "Effect of acupressure on nausea and vomiting during pregnancy. A randomized, placebo-controlled, pilot study.", "Cognitive-behavioral and patient education interventions in cardiac catheterization procedures: the Palo Alto Medical Psychology Project.", "Use of transcutaneous electrical nerve stimulation for postoperative pain.", "A behavioral treatment program as a therapy in the control of primary hypertension.", "Osteopathic manipulative treatment for chronic low back pain: a randomized controlled trial.", "Acupressure for chemotherapy-induced nausea and vomiting: a randomized clinical trial.", "Role playing and incentives in the modification of the social interaction of chronic psychiatric patients.", "[Can acupuncture prevent cystitis in women?].", "Treatment of chronic schizophrenia with promazine hydrochloride.", "Methylphenidate and attributions in boys with attention-deficit hyperactivity disorder.", "Single-needle acupuncture alleviates gag reflex during transesophageal echocardiography: a blinded, randomized, controlled pilot trial.", "Management of depression in rheumatoid arthritis: a combined pharmacologic and cognitive-behavioral approach.", "The efficacy and safety of 50 mg penicillin G potassium troches for recurrent aphthous ulcers.", "TENS for children's procedural pain.", "Effects of multiple sessions of true and placebo heart rate biofeedback training on the heart rates and anxiety levels of anxious patients during and following treatment.", "A clinical evaluation of depressives found in a rural survey in India.", "Effects of a remedial program on visual-motor perception in spina bifida children.", "Anxiety, relaxation and anaesthesia for day-case surgery.", "Iron supplementation for acute blood loss anemia after coronary artery bypass surgery: a randomized, placebo-controlled study.", "Comparison of no medication, placebo, and hyoscyamine for reducing pain during a barium enema.", "Genital herpetic infection in men and women: clinical course and effect of topical application of adenine arabinoside.", "Placebo-controlled evaluation of abbreviated progressive muscle relaxation and of relaxation combined with cognitive therapy in the treatment of tension headache.", "Evaluation of a treatment approach combining nicotine gum with self-guided behavioral treatments for smoking relapse prevention.", "Randomised controlled trial of intensive cognitive behaviour therapy for patients with chronic schizophrenia.", "Influence of hospitalization and placebo therapy on blood pressure and sympathetic function in essential hypertension.", "Physiotherapy-based rehabilitation following disc herniation operation: results of a randomized clinical trial.", "Both EMLA and placebo cream reduced pain during extracorporeal piezoelectric shock wave lithotripsy with the Piezolith 2300.", "Transcutaneous electrical nerve stimulator for procedural pain associated with intravenous needlesticks.", "Acupuncture in patients with chronic low back pain: a randomized controlled trial.", "Stress management training for hypertensives: cognitive and physiological effects.", "The effect of therapeutic touch on behavioral symptoms of persons with dementia.", "Acupuncture in patients with osteoarthritis of the knee: a randomised trial.", "Interaction of personality and treatment conditions associated with success in a smoking control program.", "Acupuncture treatment of chronic low-back pain -- a randomized, blinded, placebo-controlled trial with 9-month follow-up.", "Three-year outcomes for maintenance therapies in recurrent depression.", "[Comparative study of the action of various treatments and placebos on painful gastro-duodenal ulcer crises].", "Home intervention in the treatment of asthma among inner-city children.", "Anti-inflammatory effects of ultrasound therapy: evidence for a major placebo effect.", "Self-help for bulimia nervosa: a randomized controlled trial.", "Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation.", "Evaluation of TENS during screening flexible sigmoidoscopy.", "A controlled comparative investigation of psychological treatments for chronic sleep-onset insomnia.", "Disulfiram implantation: a trial using placebo implants and two types of controls.", "Reduction of postoperative pain and swelling by ultrasound treatment: a placebo effect.", "General practice consultations: is there any point in being positive?", "The effects of reserpine on schizophrenic patients.", "Self-administered aversive stimulation with hallucinating hospitalized schizophrenics.", "Possible thermogenesis with dexfenfluramine.", "A controlled trial of 'Senokot' in faecal soiling treated by behavioural methods.", "Ethyl vinyl chloride vapocoolant spray fails to decrease pain associated with intravenous cannulation in children.", "Acustimulation wrist bands are not effective for the control of chemotherapy-induced nausea in women with breast cancer.", "Rapid initiation of repigmentation in vitiligo with Dead Sea climatotherapy in combination with pseudocatalase (PC-KUS).", "Project LIFE: a partnership to increase physical activity in elders with multiple chronic illnesses.", "Trachea-noise biofeedback in asthma: a comparison of the effect of trachea-noise biofeedback, a bronchodilator, and no treatment on the rate of recovery from exercise- and eucapnic hyperventilation-induced asthma.", "Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial.", "Expectancy, false galvanic skin response feedback, and systematic desensitization in the modification of phobic behavior.", "Initiation of zinc treatment for acute childhood diarrhoea and risk for vomiting or regurgitation: a randomized, double-blind, placebo-controlled trial.", "Efficacy of laser-acupuncture in the prevention of exercise-induced asthma.", "The treatment of tranquilizer dependence by propranolol.", "Use of a blood glucose monitoring manual to enhance monitoring adherence in adults with diabetes: a randomized controlled trial.", "Effects of pinaverium bromide in the premedication of endoscopic retrograde cholangio-pancreatography and on motor activity of the sphincter of Oddi.", "The use of nicotine chewing gum as an aid to stopping smoking.", "Examination of the effectiveness of various treatment techniques for reducing tension.", "Placebo and naloxone can alter post-surgical pain by separate mechanisms.", "Effects of stress management on clinical outcomes in rheumatoid arthritis.", "Inducing placebo respiratory depressant responses in humans via opioid receptors.", "A self-control behavior therapy program for depression.", "The effect of a cognitive behavioral intervention on oral hygiene.", "Effect of TENS on pain, medications, and pulmonary function following coronary artery bypass graft surgery.", "Does acupuncture improve the orthopedic management of chronic low back pain--a randomized, blinded, controlled trial with 3 months follow up.", "Influence of sensory suggestibility on treatment outcome in headache patients.", "Efficacy of P6 acupressure in the treatment of nausea and vomiting during pregnancy.", "Behavioural versus cognitive social-skills training with intellectually-handicapped adults.", "Acustimulation of the Neiguan point during gastroscopy: its effects on nausea and retching.", "The effect of chiropractic care on jet lag of Finnish junior elite athletes.", "A controlled study of reserpine on chronically disturbed patients.", "Acupressure and fatigue in patients with end-stage renal disease-a randomized controlled trial.", "Acupuncture in patients with tension-type headache: randomised controlled trial.", "Acupressure and quality of sleep in patients with end-stage renal disease--a randomized controlled trial.", "Auricular acupuncture for dental anxiety: a randomized controlled trial.", "Is routinely given conscious sedation of benefit during colonoscopy?", "Evaluation of specific and non-specific effects in homeopathy: feasibility study for a randomised trial.", "Pain evaluation during carbon dioxide laser vaporization for cervical intraepithelial neoplasia: a randomized trial.", "Physiologic observations in a controlled clinical trial of the antiemetic effectiveness of 5, 10, and 15 mg of delta 9-tetrahydrocannabinol in cancer chemotherapy. Ophthalmologic implications.", "Randomized controlled trials on treatment by homeopaths and self-treatment with homeopathic medicines: design and protocol.", "Segmental noxious versus innocuous electrical stimulation for chronic pain relief and the effect of fading sensation during treatment.", "A controlled evaluation of thermal biofeedback and thermal biofeedback combined with cognitive therapy in the treatment of vascular headache.", "Acupuncture for diagnostic fiberoptic bronchoscopy: a prospective, randomized, placebo-controlled study.", "Effect of the intensity of transcutaneous acupoint electrical stimulation on the postoperative analgesic requirement.", "Prevention of breast pain and milk secretion with bromocriptine after second-trimester abortion.", "Cognitive-educational treatment of fibromyalgia: a randomized clinical trial. I. Clinical effects.", "The antitussive effect of placebo treatment on cough associated with acute upper respiratory infection.", "Psychosocial treatment for recurrent genital herpes.", "House dust mite allergen reduction and allergy at 4 yr: follow up of the PIAMA-study.", "Oral transmucosal fentanyl citrate for premedication in adults.", "Evaluation of Simulated Presence: a personalized approach to enhance well-being in persons with Alzheimer's disease.", "Effectiveness of naltrexone in a community treatment program.", "Acustimulation wristbands for the relief of chemotherapy-induced nausea.", "The effects of psychological preparation on pain and recovery after minor gynaecological surgery: a preliminary report.", "Functional electrical stimulation improves motor recovery of the lower extremity and walking ability of subjects with first acute stroke: a randomized placebo-controlled trial.", "Clinical hypnosis in the alleviation of procedure-related pain in pediatric oncology patients.", "Effect of low sodium diet or potassium supplementation on adolescent blood pressure.", "The effects of applied tension on symptoms in French-speaking blood donors: a randomized trial.", "The influence of a placebo, body position and medication on motion sickness.", "Reducing reactions to blood donation with applied muscle tension: a randomized controlled trial.", "The effects of relaxation response training on menopausal symptoms.", "Nicotine replacement to reduce cigarette consumption in smokers who are unwilling to quit: a randomized trial.", "Effects of pill-giving on maintenance of placebo response in patients with chronic mild depression.", "Acupuncture as an adjunct to exercise based physiotherapy for osteoarthritis of the knee: randomised controlled trial.", "Controlled comparison of progressive relaxation, stimulus control, and paradoxical intention therapies for insomnia.", "The Trager approach in the treatment of chronic headache: a pilot study.", "Bright light treatment decreases depression in institutionalized older adults: a placebo-controlled crossover study.", "Effects of chiropractic treatment on blood pressure and anxiety: a randomized, controlled trial.", "Transcutaneous electrical nerve stimulation following appendicectomy: the placebo effect.", "Electroacupuncture for control of myeloablative chemotherapy-induced emesis: A randomized controlled trial.", "Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates.", "Acupuncture and knee osteoarthritis: a three-armed randomized trial.", "Randomized controlled trial of calcaneal taping, sham taping, and plantar fascia stretching for the short-term management of plantar heel pain.", "Chiropractic adjustive manipulation on subjects with acute low back pain: visual analog pain scores and plasma beta-endorphin levels.", "Acupuncture for patients with migraine: a randomized controlled trial.", "Randomised, placebo controlled trial of nebulised furosemide for breathlessness in patients with cancer.", "Prehospital analgesia with acupressure in victims of minor trauma: a prospective, randomized, double-blinded trial.", "Sedation, topical pharyngeal anesthesia and cardiorespiratory safety during gastroscopy.", "The Fasting Hyperglycaemia Study: III. Randomized controlled trial of sulfonylurea therapy in subjects with increased but not diabetic fasting plasma glucose.", "Assessment of efficacy of transcutaneous electrical nerve stimulation for pain management during office-based flexible cystoscopy.", "An investigation of the placebo effect and age-related factors in the report of needle pain from venipuncture in children.", "[Evaluation of 2 homeopathic products on the resumption of transit after digestive surgery. A multicenter controlled trial].", "Efficacy of intranasal midazolam in facilitating suturing of lacerations in preschool children in the emergency department.", "Treatment of hypertension with biofeedback and relaxation techniques.", "Acupuncture and bronchial asthma: a long-term randomized study of the effects of real versus sham acupuncture compared to controls in patients with bronchial asthma.", "Monoamine metabolite and catecholamine measurements in cerebrospinal fluid in determining the quality of the pre-operative night's sleep.", "Static magnetic fields for treatment of fibromyalgia: a randomized controlled trial.", "Prophylactic penicillin: effect on posttreatment symptoms following root canal treatment of asymptomatic periapical pathosis.", "Use of single session hypnosis for smoking cessation.", "Two-week topical treatment with Essaven gel in patients with diabetic microangiopathy--a placebo-controlled, randomized study.", "[Protocol of cervical maturation by acupuncture].", "A dyadic remediation program for care recipients with dementia.", "Changes in cardiovascular risk factors by combined pharmacological and nonpharmacological strategies: the main results of the CELL Study.", "A comparison of progressive relaxation and autogenic training as treatments for insomnia.", "Effect of guar gum on body weight and serum lipids in hypercholesterolemic females.", "Meditation training and essential hypertension: a methodological study.", "Treatment of carpal tunnel syndrome with vitamin B6: a double-blind study.", "Evaluation of postoperative bupivacaine infusion for pain management after anterior cruciate ligament reconstruction.", "Do pelvic floor exercises really improve orgasmic potential?", "Preoperative administration of prostaglandin to avoid dilatation-induced damage in first-trimester pregnancy terminations." ]

[ "Acupuncture and acupressure have previously been reported to possess antiemetic effect. We wanted to investigate the \"true\" and placebo effect of acupressure in prevention of postoperative nausea and vomiting (PONV).\n Sixty women undergoing outpatient minor gynaecological surgery were entered into a double-blind and randomised study. One group received acupressure with bilateral stimulation of P6 (A), a second group received bilateral placebo stimulation (P) and a third group received no acupressure wrist band and served as a reference group (R). PONV was evaluated as number of patients with complete response (no PONV), nausea only or vomiting. In addition, the need for rescue antiemetic medication and nausea after 24 h was registered.\n Complete response was obtained in 11, 11 and 9 patients in groups, A, P and R, respectively. Nine, 7 and 6 patients had nausea before discharge home, and 1, 1 and 8 patients were nauseated (8 vs 1 patient: P < 0.05) 24 h after operation in A, P and R groups, respectively. When compared to placebo acupressure (2 patients vomited and 5 needed rescue), significantly (P < 0.05) fewer needed rescue antiemetic medication after acupressure at P6 (no vomiting or rescue medication). When compared to the observation group (5 vomited and 4 needed rescue antiemetics), significantly fewer vomited after acupressure (P < 0.05)\n In patients undergoing brief gynaecological surgery, placebo effect of acupressure decreased nausea after 24 h but vomiting and need of rescue antiemetics was reduced only by acupressure with the correct P6 point stimulation.", "We tested the hypothesis that antihistamine-decongestant combinations cause no clinically significant relief of the symptoms of upper respiratory tract infections in young children by randomly assigning 96 children to one of three treatment groups: antihistamine-decongestant, placebo, and no treatment. There were no differences among the three study groups in the proportion of children considered \"better\" overall by the parent 48 hours after the initial assessment (drug, 67%; placebo, 71%; no treatment, 57%; p = 0.53). There were no differences among groups in individual or composite symptom score changes. Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms. In the proportion of parents believing that their child needed medicine, there was no difference between those who consented to participate and those who refused. Parents who wanted medicine at the initial visit reported more improvement at follow-up, regardless of whether the child received drug, placebo, or no treatment. We conclude that there is no clinically significant improvement in symptoms of upper respiratory tract infection, including no significant placebo effect, in young children for whom an antihistamine-decongestant is prescribed.", "A standard reminiscence interview and one that focused on successfully met challenges reduced state anxiety and enhanced coping self-efficacy when measured against both attention-placebo and no-intervention control groups in a sample of 104 elderly male patients facing surgery. Age-peer interviewers did not elicit significantly greater overall reductions in state anxiety or increases in coping self-efficacy scores than younger interviewers (nonpeers), but did produce significantly higher coping self-efficacy scores than nonpeers when administering the challenge reminiscence interview.", "nan", "nan", "nan", "We analyzed the efficacy of a single daily dose of labetalol (300 mg) administered at 9 a.m. in six inpatients suffering from medium-severe hypertension. The study was conducted on 3 consecutive days, during which the patients were on labetalol, placebo, and non-treatment (control) according to a trial design of the Latin square type, balanced for residual effects. The hypotensive effect of labetalol manifests itself between hours 1 and 2 after administration of the drug. The systolic and diastolic blood pressure values always proved lower after labetalol as compared to placebo and non-treatment (control) as well as to the average of the latter two values (placebo + control) divided by 2. No side effects were detected.", "A study was undertaken to compare the effectiveness of acupuncture in reducing patient's discomfort and anxiety during colonoscopy with a standard sedation protocol.\n Thirty patients scheduled to undergo colonoscopy were randomly assigned to receive acupuncture, sham, or no acupuncture. A verbal rating scale was used to measure patient's pain when the endoscope reached four scheduled positions. Midazolam was administered at baseline and again anytime patients complained of \"severe\" pain. The amount of midazolam administered was recorded. A verbal rating scale was used to assess patient's satisfaction with the level of sedation achieved.\n Pain level was lower, although not significantly, in the acupuncture group. Midazolam boluses were required in three patients with acupuncture (30%), eight in the sham group (80%), and nine in the control group (90%) (p = 0.01). Six patients in the acupuncture group (60%) reported optimum acceptance of colonoscopy compared with only one in the sham group (10%) and none in the control group (0%) (p = 0.016). Satisfaction scores, assessed 24-72 h after colonoscopy, were extremely high (median score 90 of 100) in the three groups.\n Acupuncture may decrease the demand for sedative drugs during colonoscopy by reducing discomfort and anxiety of the patient and the well-known adverse effects of pharmacologic sedation.", "Post-herpetic neuralgia (PHN) is a common and often intractable neuropathic pain syndrome predominantly affecting the elderly. Topical local anesthetics have shown promise in both uncontrolled and controlled studies. Thirty-five subjects with established PHN affecting the torso or extremities completed a four-session, random order, double-blind, vehicle-controlled study of the analgesic effects of topically applied 5% lidocaine in the form of a non-woven polyethylene adhesive patch. All subjects had allodynia on examination. Up to 3 patches, covering a maximum of 420 cm2, were applied to cover the area of greatest pain as fully as possible. Lidocaine containing patches were applied in two of the four 12-h-long sessions, in one session vehicle patches were applied, and one session was a no-treatment observation session. Lidocaine containing patches significantly reduced pain intensity at all time points 30 min to 12 h compared to no-treatment observation, and at all time points 4--12 h compared to vehicle patches. Lidocaine patches were superior to both no-treatment observation and vehicle patches in averaged category pain relief scores. The highest blood lidocaine level measured was 0.1 micrograms/ml, indicating minimal systemic absorption of lidocaine. Patch application was without systemic side effect and well tolerated when applied on allodynic skin for 12 h. This study demonstrates that topical 5% lidocaine in patch form is easy to use and relieves post-herpetic neuralgia.", "Three 24 h ambulatory monitorings of BP were performed at two-week intervals in 21 untreated hypertensives (mean age 38 +/- 10 yrs, 13 males and 9 females). After the first baseline monitoring, the patients were randomised, according to a cross-over design, to one of the following sequences: no therapy to placebo or placebo to no therapy. At the end of each period, noninvasive ambulatory monitoring was performed. Mean +/- SE 24 h systolic (SBP) and diastolic (DBP) pressures recorded at the first monitoring were 129.2 +/- 3.5 mmHg and 81.7 +/- 2.3 mmHg respectively. At the second and third monitorings, mean 24 h BP differences versus baseline levels were -2.9 +/- 1.8 and -4.7 +/- 1.7 mmHg for SBP, and -2.0 +/- 1.1 and -2.7 +/- 1.5 mmHg for DBP. Both SBP and DBP differences at repeated monitorings were significant by analysis of variance (P less than 0.05). No significant effects on BP of treatment sequence or of placebo administration were found. Analysis of covariance showed a significant relationship between initial 24 h BP and subsequent mean 24 h BP differences (SBP: beta = -0.260, DBP: beta = -0.124). ANOVA performed on waking and sleeping BP separately showed the observed differences to be significant only during waking hours. Regression analysis showed that the decrease in 24 h BP at repeated monitorings was significantly related to the extent of 'white coat'-induced BP increase only for DBP (P = 0.022). For both 24 h SBP and DBP, however, a negative correlation between the alarm reaction to the presence of the physician and 24 h BP decrease at repeated monitorings was observed. It is concluded that noninvasive ambulatory monitoring is subject to adaptative phenomena but not to placebo effect. Factors influencing the defence reactions to manual measurements and to ambulatory monitoring might be partly different.", "nan", "The involvement of the microcirculation in chronic venous insufficiency (CVI), due to venous hypertension, causes venous hypertensive microangiopathy (VHM) and ulceration. VHM is characterized by enlarged, convoluted capillaries; microvascular thrombosis; obliteration of some capillaries; increase in flux, permeability, and edema and altered microlymphatics. PO2 is decreased and CO2 increased. Capillary exchanges are altered and nutritional alterations eventually lead to venous ulcers. Edema is associated with increased capillary pressure, reduced clearance, and increased exchange surface of capillaries, which become tortuous and glomerular-like. The aim of this randomized, placebo-controlled study was to evaluate local treatment with Essaven gel (EG) in subjects with venous microangiopathy and ulcers. Measurements of laser Doppler flux, PO2, and PCO2 in standardized conditions showed positive changes (a significant decrease of the abnormally increased flux and CO2 while PO2 increased) in the EG treatment group. Changes in the placebo and control group were more limited (changes in the placebo group were mainly associated with skin manipulation when placebo-EG was applied). In conclusion, Essaven gel, in comparison with placebo, acutely improves the microcirculation in VHM even with a single acute application.", "The effectiveness of acupuncture in managing the pain of primary dysmenorrhea was investigated in a randomized and controlled prospective clinical study. Forty-three women were followed for one year in one of four groups: the Real Acupuncture group was given appropriate acupuncture and the Placebo Acupuncture group was given random point acupuncture on a weekly basis for three menstrual cycles; the Standard Control group was followed without medical or acupuncture intervention; the Visitation Control group had monthly nonacupuncture visits with the project physician for three cycles. In the Real Acupuncture group, 10 of 11 (90.9%) women showed improvement; in the Placebo Acupuncture group, 4 of 11 (36.4%); in the Standard Control group, 2 of 11 (18.2%); and in the Visitation Control group 1 of 10 (10%). There was a 41% reduction of analgesic medication used by the women in the Real Acupuncture group after their treatment series, and no change or increased use of medication seen in the other groups.", "Venous leg ulcers (ulcera crurum venosa) are frequently seen in elderly patients. It has been suggested that low level laser irradiation has a biostimulative and wound healing effect; however, this has not yet been clinically verified by controlled studies.\n The difference in size reduction of leg ulcers with and without low level laser or placebo laser treatment was measured in 44 patients randomised into two treatment groups (685-nm low level laser and placebo laser) or a control group which served to quantify the effect of laser application. All patients received standardized wound care.\n The aim of the study was to compare the effectiveness of low level laser irradiation with that of a placebo \"light source\". The size of the ulcers was planimetrically measured at baseline (day 1), at the end of therapy (day 28) and 2 months later (day 90). The difference in wound size was evaluated.\n There were no statistically significant differences in reduction of wound size between the three groups, thus suggesting that low level laser light does not have any stimulatory effect on wound healing in ulcera crurum venosa.", "Conventional treatments are often ineffective for patients having painful abdominal scars. There are painful points in and around scar tissue. We tested the hypothesis that insertion of intradermal needles into these painful points reduces scar pain.\n Patients with abdominal scar pain with painful points that is not relieved by conventional treatments were allocated to a treatment group (n = 23), a sham-treatment group (n = 23), or a control group (n = 24). In the treatment group, intradermal needles were inserted into painful points detected by a pressure threshold meter (pain < or = 2.5 kg/cm(2)). In the sham-treatment group, the same needles were inserted into nonpainful points. The needles were kept in place for 24 hours. This process was repeated 20 times over a 4-week period. Responses were evaluated before and at the end of treatment, and 4 and 26 weeks after the treatment. Continuous and lancinating pain was evaluated on a 10-cm visual analog scale. We measured the area of pain and the pressure required to initiate painful-point pain. All patients took diclofenac as needed and completed a diary of daily diclofenac consumption.\n Patients in the treatment group showed a marked reduction in all pain parameters (>70%). In contrast, analgesia was minimal in the other groups. The decreases in the pain threshold pressure correlated with the decreases in continuous and lancinating pain (r =.57 and r =.63, respectively).\n Our data suggest that insertion of intradermal needles into painful points is a remarkably effective treatment for intractable abdominal scar pain. Analgesia presumably results from inactivation of painful points, through a yet to be elucidated mechanism.", "nan", "nan", "Transcutaneous electrical nerve stimulation (TENS) has been used extensively to control postoperative pain, but its effects are controversial. This is probably due to the different types of operations performed and, therefore, to the varying intensity of postoperative pain. Here we present an extensive study with TENS in 324 patients who underwent different types of thoracic surgical procedures: posterolateral thoracotomy, muscle-sparing thoracotomy, costotomy, sternotomy, and video-assisted thoracoscopy.\n Each patient cohort was randomly subdivided into three treatment groups: TENS, placebo TENS and control. The effectiveness of TENS was assessed by two factors: the time from the beginning of treatment to the request for further analgesia and the total medication intake during the first 12 hours after operation.\n Whereas posterolateral thoracotomy produced severe pain, muscle-sparing thoracotomy, costotomy, and sternotomy caused moderate pain, and video-assisted thoracoscopy caused only mild pain. The TENS treatment was not effective in the posterolateral thoracotomy group, but it was useful as an adjunct to other medications in the muscle-sparing thoracotomy, costotomy, and sternotomy groups. In contrast, representing the only pain control treatment with no adjunct drugs, it was very effective in patients having video-assisted thoracoscopy.\n These findings show that TENS is useful after thoracic surgical procedures only when postoperative pain is mild to moderate; it is uneffective for severe pain.", "To assess the efficacy of exercise therapy for acute low back pain, a randomized, placebo-controlled trial was performed in 40 Dutch general practices. Patients received either exercise instruction with advice for daily life by a physiotherapist; placebo ultrasound therapy by a physiotherapist; or usual care by the general practitioner. All patients received analgesic agents and information on low back pain before randomization. Four hundred seventy-three patients were included. No differences in number of recurrences, functional health status, or medical care usage could be found among the three groups. In the exercise group, duration of recurrences was shorter and patients were less tired during the first 3 months than in the usual care group, but no differences were found between the exercise and placebo groups. It was concluded that exercise therapy for patients with acute low back pain has no advantage over usual care from the general practitioner.", "A prospective, randomized clinical trial was performed in order to assess the efficacy and side-effects of commonly used topical anaesthesia methods in adults receiving peripheral venous cannulation. The study was double-blinded to the degree that the methodologies allowed. One hundred and fifty healthy adults undergoing elective surgery were allocated at random to five groups: EMLA cream, ethyl chloride spray, intracutaneous infiltration with 2% lidocaine, placebo cream and no treatment. Venipuncture was performed with a 18G cannula on the dorsal side of the hand. Puncture pain and pain caused by the topical treatment itself were measured using a visual analogue scale (VAS, range: 0-100 mm). Haemodynamic response, difficulties in performing the puncture and side-effects were recorded. All analgesic techniques were well tolerated. Haemodynamic response and degree of puncture difficulty showed no differences among the groups. Puncture pain (median mrnVAS) following infiltration (1.0) and EMLA (10.0) was significantly lower than no treatment (30.0) or placebo (30.0). The benefit of local infiltration was altered by injection pain (11.5). Spray did not significantly lower puncture pain (26.5) and, in addition, was associated with discomfort (10.5). In adults, EMLA cream significantly reduces puncture pain and represents an acceptable alternate method for topical anaesthesia in venous cannulation. Local lidocaine infiltration is impaired by applicational pain, whereas spraying the puncture site with ethyl chloride has no analgesic benefit.", "Our aim was to find out whether intravenous fentanyl was effective in reducing the pain of first-trimester abortion.\n This randomized controlled trial included 825 women attending a nonhospital abortion facility. Some women chose standard care. Women who did not choose standard care were randomly assigned to receive either 50 to 100 microg of fentanyl, a placebo, or no intervention. With SAS software and a mixed effects analysis of variance model with covariates, we compared mean pain scores of the fentanyl and placebo groups to detect a difference of at least 1 point on an 11-point pain scale.\n The mean pain score of the fentanyl group was 1.0 point less than that of the placebo group (95% confidence interval, 3.7-4.3) and 0.9 point less than that of the observational group (95% confidence interval, 4.7-5.1). This pain reduction was statistically significant, but the women who were studied wanted a 2-point reduction from fentanyl.\n Fentanyl, when compared with the placebo, reduced abortion pain by 1.0 point on an 11-point scale. This reduction was of questionable clinical significance and was less than desired by the women included in the study.", "A preliminary report has been interpreted to suggest that gum chewing reduces duration of postcolectomy ileus.\n We rigorously tested this hypothesis in a prospective, randomized, placebo-controlled study. Patients undergoing open colectomy (n = 66) were randomized to receive 1 of 3 postoperative regimens beginning on postoperative day 1: sips (control, n = 21); sips and accupressure wrist bracelet (placebo, n = 23); and sips and gum chewing (treatment, n = 22). Patients were unaware of which regimen constituted placebo or treatment; end points were assessed by blinded investigators. Power was set a priori at 85% to detect a 0.75-day difference in time to first postoperative passage of flatus between placebo and treatment groups. Groups were compared using the log-rank test.\n Groups were equivalent with respect to demographic and surgical characteristics. Median times to first postoperative passage of flatus were as follows: sips, 67 hours; bracelet and sips, 72 hours; gum and sips, 60 hours (p = 0.384). There were no significant differences in time to passage of first bowel movement, time until patients were ready for discharge, or time until actual discharge among the three groups. Inpatient and 30-day followup demonstrated no difference in frequency or distribution of postoperative complications.\n In contrast to findings of a preliminary study, our clinical trial suggests that gum chewing, although safe, does not reduce duration of postcolectomy ileus.", "We sought to determine the efficacy of coaching Latino adolescents with latent tuberculosis infection to adhere to isoniazid treatment.\n Participants (n = 286) were randomly assigned to adherence coaching, attention control, or usual care groups. Adherence was measured via interviews and validated with urine assays.\n Coaching resulted in significant increases in adherence compared with attention and usual care groups. Bicultural adolescents were more likely to be adherent than those most or least acculturated. Age and risk behavior were negatively related to adherence.\n Coaching can increase Latino adolescents' adherence to treatment for latent tuberculosis infection and should contribute to tuberculosis control for adolescents at high risk of contracting the disease.", "nan", "The lack of control procedures inherent in most of the experiments conducted to assess the effectiveness of skin temperature biofeedback in the treatment of Raynaud's disease renders the results inconclusive. In this study, control groups and a double-blind approach are adopted. Thirty-six patients, carefully screened for a diagnosis of primary Raynaud's disease, were assigned to a skin temperature increase group (N = 12), to an EMG relaxation control group (N = 12), or to a notreatment control group (N = 12). All patients kept records of their symptoms for the duration of the study. Each subject in the two training groups received 20 sessions, the last 2 conducted under cold stress. data analysis according to original group assignment, as well as following regrouping of subjects according to several learning criteria, showed that while all patients reported a marked decrease in the number of vasospastic attacks, no significant differences were found among the three groups on the clinical measures used to assess symptomatic relief. The general improvement reported must therefore be attributed to nonspecific factors.", "The aim of this study was to investigate the effectiveness of pulsed short wave (PSW) in the relief of pain in osteoarthritis of the hip and knee. Ninety-two patients, mean age 63 years, (34 men and 58 women) were randomly allocated to one of three groups: (1) Active PSW, using the dosage found in a pilot study to be non-significantly most effective, (2) Placebo PSW, (3) No treatment control group. Nine sessions of treatment were provided over a 3-week period, each application lasting for 15 min. The machine was modified by the manufacturers so that the therapist was able to administer the treatment and carry out assessments without being aware of the treatment allocation. Outcome measures included sensory and affective pain diary reports averaged over days and weeks, self-reported benefit and the General Health Questionnaire. Analysis of variance with repeated measures over time was used to find out if the active treatment had a specific effect, incremental to the placebo effect. There were no significant differences between the active and placebo groups over time. According to the pain diary reports, both active and placebo groups tended to improve slightly during treatment, but worsened after its withdrawal. Patients who were given the placebo application tended to report more benefit than those who had the active treatment, although this did not quite reach statistical significance (P < 0.06). Patients who were not on a waiting list for surgery did significantly better over time than those who were (P < 0.03). There were no significant differences between the groups over time for the other outcome variables. Any treatment effect on this patient population appears to have been largely placebo-mediated. No evidence was found therefore for the specific effectiveness of PSW for treatment of osteoarthritic hip or knee pain.", "To assess the efficacy of an orally administered antioxidant dietary supplement for managing marginal dry eye.\n A prospective, randomised, placebo controlled trial with cross-over.\n Eye Clinic, Department of Vision Sciences, Glasgow Caledonian University.\n Forty marginal dry eye sufferers composed of 30 females and 10 males (median age 53 y; range 38-69 y).\n Baseline assessments were made of tear volume sufficiency (thread test), tear quality (stability), ocular surface status (conjunctival impression cytology) and dry eye symptoms (questionnaire). Each subject was administered courses of active treatment, placebo and no treatment, in random order for 1 month each and results compared to baseline.\n Tear stability and ocular surface status were significantly improved following active treatment (P<0.05). No changes from baseline were detected following administration of placebo and no treatment (P>0.05). Absolute increase in tear stability correlated with absolute change in goblet cell population density. Tear volume was not improved following any treatment period and dry eye symptom responses were subject to placebo effect.\n Oral antioxidants improved both tear stability and conjunctival health, although it is not yet understood whether increased ocular surface health mediates increased tear stability or vice versa.\n This study was supported by a PhD scholarship funded by the Department of Vision Sciences, Glasgow Caledonian University, Scotland. Antioxidant supplements and placebos were kindly donated by Vitabiotics.", "nan", "nan", "To evaluate the effect of vaginal disinfection with chlorhexidine gel during labor on vertical transmission of group B streptococcus, as a method to prevent vertical transmission and subsequent neonatal early onset group B streptococcal disease.\n A prospective study with randomization of 1020 parturients to one of three groups as soon as labor started. In all parturients, anus, introitus and cervix were cultured semiquantitatively. Two groups were treated double-blindly with 10 ml of either a 0.3% chlorhexidine gel or a placebo gel, applicated around the portio and into the fornices. If labor still continued, a second application was given after 10 h. The third group received no treatment. Ear, pharynx and umbilicus of all newborns were also cultured semiquantitatively.\n Nine hundred and eighty one women were evaluated. The overall incidence of group B streptococcal carriership was 19.4%. Vertical transmission was 52.4% in the chlorhexidine group, 71.4% in the placebo group and 66.7% in the control group (P = 0.069). When testing the transmission rates for the chlorhexidine versus the combined placebo plus control group (69.3%), the difference was 16.9% (P = 0.026).\n Vaginal disinfection with a chlorhexidine gel during labor modestly reduces group B streptococcal vertical transmission. Because the method is cheap, simple and safe, it should be considered for routine use. Our results indicate that it may reduce the incidence of early onset group B streptococcal sepsis by 2-32%.", "Sixty-eight patients undergoing outpatient knee arthroscopy for treatment of meniscal tears or loose bodies were divided into three treatment groups (zolpidem [24 patients], control [24 patients], and placebo [20 patients]). All groups received postoperative hydrocodone and ibuprofen. Patients in the zolpidem group received a single dose of zolpidem tartrate for the first seven postoperative nights. Patients in the placebo group received a gelatin capsule similar in appearance to zolpidem and patients in the control group received only hydrocodone and ibuprofen. Patients in the control group demonstrated significantly worse mean daily postoperative pain and more daily postoperative fatigue on visual analog scales when compared with the zolpidem group (P=.03 and P=.04, respectively). Patients in the placebo group had worse daily postoperative pain and more daily postoperative fatigue when compared to the zolpidem group, although these differences did not reach statistical significance (P=.15, power=0.6; and P=.27, power=0.48, respectively). Patients in the control group consumed significantly higher quantities of hydrocodone/acetaminophen postoperatively (P=.04) than patients in the zolpidem group. Finally, patients in the placebo group consumed higher quantities of hydrocodone/acetaminophen than the zolpidem group although the difference did not reach statistical significance (P=.4; power=0.15). Power was calculated for each insignificant relationship based on observed effect and sample sizes and variances. This study demonstrates that sleep and fatigue may be an important factor in the effective pain management following knee arthroscopy. Future postoperative treatment regimens should address sleep and fatigue to maximize analgesic effects in these patients.", "We report clinical data on the efficacy of acupuncture for alcohol dependence. 503 patients whose primary substance of abuse was alcohol participated in this randomized, single blind, placebo controlled trial. Patients were assigned to either specific acupuncture, nonspecific acupuncture, symptom based acupuncture or convention treatment alone. Alcohol use was assessed, along with depression, anxiety, functional status, and preference for therapy. This article will focus on results pertaining to alcohol use. Significant improvement was shown on nearly all measures. There were few differences associated with treatment assignment and there were no treatment differences on alcohol use measures, although 49% of subjects reported acupuncture reduced their desire for alcohol. The placebo and preference for treatment measures did not materially effect the results. Generally, acupuncture was not found to make a significant contribution over and above that achieved by conventional treatment alone in reduction of alcohol use.\n Copyright 2002 Elsevier Science Inc.", "To investigate the effect of sensory stimulation of the P6 point on postoperative nausea and vomiting (PONV) after gynecological surgery in the everyday clinical setting (effectiveness study).\n Four hundred and ten women undergoing general anesthesia for elective gynecological surgery were included in a prospective, consecutive, randomized, multicentre, placebo-controlled, double-blind clinical trial with a reference group. One group was given bilateral P6 acupressure (n = 135), a second group similar pressure on bilateral non-acupressure points (n = 139), and a third group (n = 136) served as reference group. Nausea (scale 0-6), vomiting, pain, and satisfaction with the treatment were recorded. Primary outcome was complete response, i.e., no nausea, vomiting or rescue medication for 24 hr. Results were analyzed by applying logistic regression with indicators of treatments, type of operation and risk score for PONV as explanatory variables.\n Complete response was more frequent in the P6 acupressure group than in the reference group (P = 0.0194) Conversely, the incidence of PONV was 46% in the reference group, 38% after pressure on a non-acupoint and 33% after P6 acupressure. The decrease from 46% to 33% was statistically significant. When considering vaginal cases separately, the decrease in PONV was from 36% to 20% (P = 0.0168). The corresponding decrease from 59% to 55% in the laparoscopic surgery group was not statistically significant.\n P6 acupressure is a non-invasive method that may have a place as prophylactic antiemetic therapy during gynecological surgery.", "Synergy has been proposed between modalities operating at different levels of action. Acupuncture and craniosacral therapy are two very different modalities for which synergy has been proposed. This study sought to test for such synergy and to determine if complementary therapies would improve pulmonary function and quality of life for people suffering from asthma, as well as reducing anxiety, depression, and medication usage.\n Subjects were randomly assignment to one of five groups: acupuncture, craniosacral therapy, acupuncture and craniosacral, attention control, and waiting list control.\n Subjects received 12 sessions of equal length with pretreatment and posttreatment assessment of pulmonary function, asthma quality of life, depression, and anxiety. Medication use was also assessed.\n Synergy was not demonstrated. When treatment was compared with the control group, statistically treatment was significantly better than the control group in improving asthma quality of life, whereas reducing medication use with pulmonary function test results remained the same. However, the combination of acupuncture and craniosacral treatment was not superior to each therapy alone. In fact, although all active patients received 12 treatment sessions, those who received all treatments from one practitioner had statistically significant reductions in anxiety when compared with those receiving the same number of treatments from multiple practitioners. No effects on depression were found.\n Acupuncture and/or craniosacral therapy are potentially useful adjuncts to the conventional care of adults with asthma, but the combination of the two does not provide additional benefit over each therapy alone.", "The effect of local applications of sustained-release delivery polymer containing chlorhexidine as an adjunct to mechanical plaque removal was studied in institutionalized children with Down's syndrome. Thirty children, ages 8-13, participated in the study. Clinical parameters (P1I, GI, papillary bleeding) were recorded and bacterial samples from selected permanent teeth were collected and processed before and following treatment. Following the registration of clinical findings and collection of plaque, all children had their teeth scaled and polished and were randomized into three treatment groups of ten subjects each: Subjects in group I had their teeth coated with ethyl cellulose containing chlorhexidine; those in group II had their teeth coated with placebo polymer and those in group III received no further treatment. Individual oral hygiene habits were not interfered with. The application of the solutions to the respective groups was done every 3 days for 21 days. Chlorhexidine treatment significantly reduced the PLI, GI total aerobic counts and S. viridans counts compared to no treatment. The placebo group showed similar effects to that of the chlorhexidine-treated group except for the total aerobic counts which were not affected. The results suggest that the use of chlorhexidine in a sustained-release dosage form applied to the tooth surfaces may prove useful in the control of plaque and its sequela in children with Down's syndrome.", "nan", "To evaluate the effectiveness of handwarming biofeedback (HWB) and stress management training in comparison to attention (handcooling, HCB) and wait-list control groups. Thermal biofeedback has been used in many pediatric migraine treatment studies and has demonstrated a consistent therapeutic effect. No published studies to date have compared this treatment modality with credible attention control using biofeedback technology.\n Thirty-six children and adolescents (mean age: 12.8 years), as well as the mothers and fathers of these children enrolled in the study, were randomly assigned to the three groups. Thirty-four children completed treatment. Both treatment groups received four sessions of biofeedback training and a portable biofeedback device for home practice. Ratings of treatment credibility showed that the children rated the two treatments as equally credible. Assessment included anxiety and depression questionnaires for the children and both of their parents.\n Children who had been assigned to the HWB group were more likely to achieve clinical improvement in migraine after treatment than the children in the HCB group. Treatment gains were maintained up to 6 months after treatment. Home practice data reflected a general increase in temperature in the HWB group and a decrease in temperature for the HCB group.\n The results of this study confirm the findings of earlier pediatric migraine biofeedback treatment studies and also provide support for the specific effect of treatments including stress management and HWB. Future studies with larger sample sizes will aid in delineating the appropriateness of HCB as a control treatment.", "Studies in smoking cessation have generally failed to adequately control for active treatment effects and have assumed that measures of smoking behaviour (i.e., estimated smoking rate, self-monitoring and chemical analysis) are equally reliable measures. Sixty smokers were randomly assigned to one of four different smoking cessation treatment groups: hypnosis, focussed smoking, attention placebo and a waiting list control. Subjects were asked to estimate and monitor their own smoking behaviour. Blood samples were also taken for thiocyanate analysis before treatment. Smoking rates were similarly measured directly, at 3 months and 6 months after treatment. The results indicate that the three measures of smoking behaviour were all highly correlated. No significant differences were found between treatments, directly after treatment or at the 3- and 6-month follow-ups. These results suggest that active treatment effects may not be responsible for behavioural change in a smoking cessation program. The implications of these findings are discussed.", "OBJECTIVE: To determine whether non-invasive ambulatory blood pressure is more reproducible and less affected by the placebo treatment than are clinic blood pressure measurements. METHOD: Thirty-four essential hypertensive outpatients were randomly allocated after a 4-week preselection period in two groups in a cross-over study design. One group received placebo for 4 weeks while the other formed the control group (reproducibility), then the treatments were exchanged for another 4 weeks. Clinic and ambulatory blood pressures were measured at three different times for each patient, namely bnefore the random allocation to groups and at the end of each period, using a mercury sphygmomanometer and 24 h non-invasive ambulatory blood pressure monitoring. RESULTS: Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressures (by 3.4+/-13 and 3.6+/-8 mmHg, respectively), but not in 24 h, daytime and night-time blood pressures. Circadian hourly blood pressure and heart rate curves were virtually superimposable. In the 13 placebo responder patients selected on the basis of clinic blood pressure, placebo decreased the clinic blood pressure and also reduced systolic and diastolic ambulatory blood pressures, mainly during the day period (by 5.2+/-6.2 and 4.89+/-7.8 mmHg, respectively). This effect is specific and related to the placebo administration because repetition of the measurements without any treatment showed no significant difference. To characterize at baseline the placebo responder patients, comparison with the non-placebo responders showed lower baseline values of ambulatory systolic blood pressure recorded during 24 h daytime and night-time in the placebo responder group. CONCLUSION: The 24 h ambulatory blood pressure average is not affected by placebo in the present group of patients but that a placebo effect occurs mainly during the daytime in patients who decreased their clinic blood pressure under placebo (placebo responders); the placebo-induced reduction in blood pressure is related to a specific effect of placebo and is independent from any alerting reaction or reproducibility hypothesis. This study clearly indicates the necessity of including placebo and ambulatory blood pressure monitoring in the therapeutic and pharmacological trials of antihypertensive drugs.", "nan", "To test that methylphenidate combined with intensive multimodal psychosocial intervention, which includes social skills training, significantly enhances social functioning in children with attention-deficit/hyperactivity disorder (ADHD) compared with methylphenidate alone and methylphenidate plus nonspecific psychosocial treatment (attention control).\n One hundred three children with ADHD (ages 7-9), free of conduct and learning disorders, who responded to short-term methylphenidate were randomized for 2 years to receive (1) methylphenidate alone, (2) methylphenidate plus multimodal psychosocial treatment that included social skills training, or (3) methylphenidate plus attention control treatment. Assessments included parent, child, and teacher ratings of social function and direct school observations in gym.\n No advantage was found on any measure of social functioning for the combination treatment over methylphenidate alone or methylphenidate plus attention control. Significant improvement occurred across all treatments and continued over 2 years.\n In young children with ADHD, there is no support for clinic-based social skills training as part of a long-term psychosocial intervention to improve social behavior. Significant benefits from methylphenidate were stable over 2 years.\n Copyright 2004 American Academy of Child and Adolescent Psychiatry", "To establish the short term clinical and urodynamic effect of transurethral microwave thermotherapy (TUMT) in men with symptomatic uncomplicated benign prostatic hyperplasia (BPH) using a randomized controlled trial comparing the treatment with both 'placebo-like' and untreated control groups.\n The study comprised 120 symptomatic patients with BPH who were candidates for transurethral resection and TUMT. They were randomized to one of three groups: group 1 underwent a standard TUMT, group 2 underwent a simulated treatment identical to group 1 but with no emission of microwaves and group 3 received no treatment. The treatment of the first two groups was 'double-blind' and the heat experienced by the patients during treatment was simulated in both. Patients were assessed on entry to the study and 6 months after treatment using an identical protocol to measure the American Urological Association (AUA) symptom score, maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), minimum urethral opening pressure (Pmuo) and maximum detrusor pressure (Pdet max).\n In the untreated group there were no clinically or statistically significant changes in the median AUA symptom score, Qmax, PVR, Pmuo and Pdet max. In group 1 the AUA score changed significantly, from 19 to 9.5, but the Qmax, PVR, Pmuo and Pdet max did not. In group 2, the AUA score also changed significantly, from 17.5 to 9.5, but Qmax, PVR, Pmuo and Pdet max did not.\n The untreated control group showed no clinically relevant deterioration or improvement. The standard and simulated TUMT groups showed little clinically relevant improvement in 'objective' variables, while the clinically significant symptom improvement was of a similar magnitude in both groups.", "In the present study, we examined the effects of preoperative electroacupuncture (EA) at classical bilateral acupuncture points (Zusanli, also known as ST-36) on postoperative pain and opioid-related side effects. One hundred healthy consenting women undergoing lower abdominal surgery were randomly assigned to four treatment regimens: Group I (n=25), control; Group II (n=25), sham-EA (needle insertion without electrical stimulation); Group III (n=25), low-EA (2 Hz of electrical stimulation); and Group IV (n=25), high-EA (100 Hz of electrical stimulation). EA groups received needle insertion with or without electrical stimulation 20 min prior to anesthesia. All patients received patient-controlled analgesia (PCA) of morphine postoperation. Postoperative pain was evaluated by recording (1). the time of the first required analgesic, (2). the number of PCA demands, (3). the total amount of morphine required by PCA, and (4) patients' VAS pain score. We found that the time of first analgesic requested was 10, 18, 28, and 28 min in the control, sham-, low-, and high-EA groups, respectively. During the first 24h, the total amount of morphine required was decreased by 21, 43 and 61% in the sham-, low- and high-EA groups, respectively. The incidence of nausea and dizziness during the first 24h after surgery was significantly reduced in both the low-EA and high-EA groups compared with the control and sham-EA groups. We also found that sham-EA exerts a beneficial effect with respect to its pain relieving quality but not the side effect profiles. Our findings demonstrates that preoperative treatment with low-EA and high-EA can reduce postoperative analgesic requirements and associated side effects in patients undergoing lower abdominal surgery.", "The present study evaluated the efficacy of group cognitive-behavior therapy for the alleviation of psychosocial problems and reduction of seizures with adult epileptic patients. Twenty-seven outpatients were randomly assigned to one of three groups: Cognitive-Behavior Therapy, Supportive Counseling (attention-placebo control), and Waiting list (no treatment control). The major outcome measures used were: patient's, neurologist's, and therapist's global ratings of psychological adjustment, patient's target complaints and weekly seizure frequency, patient's and neurologist's ratings of seizure control, the Minnesota Multiphasic Personality Inventory, the Washington Psychosocial Seizure Inventory, and the Beck Depression Inventory. No significant differences were found among the three groups on these measures except for therapist's global ratings of psychological adjustment, on which both the Cognitive-Behavior Therapy and Supportive Counseling groups improved significantly after therapy, but the Waiting List control group did not. Overall, little support was found for the efficacy of group cognitive behavior therapy (eight 2-h weekly sessions) for the reduction of psychosocial difficulties or seizures. Implications of the present findings are discussed, with the need for further controlled outcome research stressed.", "nan", "In a randomized controlled trial, eye movement desensitization and reprocessing (EMDR) for panic disorder with agoraphobia (PDA) was compared with both waiting list and credible attention-placebo control groups. EMDR was significantly better than waiting list for some outcome measures (questionnaire, diary, and interview measures of severity of anxiety, panic disorder, and agoraphobia) but not for others (panic attack frequency and anxious cognitions). However, low power and, for panic frequency, floor effects may account for these negative results. Differences between EMDR and the attention-placebo control condition were not statistically significant on any measure, and, in this case, the effect sizes were generally small (eta2 = .00-.06), suggesting the poor results for EMDR were not due to lack of power. Because there are established effective treatments such as cognitive-behavior therapy for PDA, these data, unless contradicted by future research, indicate EMDR should not be the first-line treatment for this disorder.", "nan", "Twenty-seven long-term psychiatric inpatients maintained on neuroleptics with concomitant antiparkinsonian medication were entered into a study in which anticholinergic medication was gradually withdrawn in a randomized double-blind within-subjects design. The extrapyramidal symptoms of each patient were compared when taking their usual anticholinergic medication, when taking placebo and when taking no antiparkinsonian drug. The relapse rate on no medication was 14%, and if patients relapsed on no medication they also relapsed on placebo. The relapse rate was not significantly different on active medication. Nor were there significant differences in ratings of parkinsonism or dyskinesia. The lack of difference between double-blind and overt withdrawal does not mean that studies that find a much higher relapse rate are necessarily unaffected by nonspecific factors, as significant unblinding may occur in clinical trials.", "To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) as analgesia during colonoscopy.\n In a randomised controlled trial, patients undergoing diagnostic colonoscopy were assigned to one of three groups: standard medication only (midazolam); active TENS plus standard medication; or non-functioning TENS and standard medication. Efficacy of TENS was determined using numerical rating scores for pain and the post-procedural evaluation questionnaire.\n Patients undergoing diagnostic colonoscopy in a teaching hospital.\n There was no statistically significant differences between the three groups. However in the active TENS group there was a greater variation in \"physical discomfort\" and \"psychological distress\", suggesting TENS may be effective in subgroup of patients.", "There is inconclusive evidence of the effectiveness of psychological interventions for depression after stroke. We report the results from a randomized controlled trial of cognitive behavioral therapy (CBT).\n Stroke patients admitted to hospital were invited to complete mood questionnaires 1, 3 and 6 months after stroke. Patients who were depressed were invited to take part in a trial and randomly allocated to receive CBT (n=39), an attention placebo intervention (n= 43), or standard care (n=41). Outcome assessments were undertaken at 3 and 6 months after recruitment, on the Beck Depression Inventory, Wakefield Depression Inventory, Extended Activities of Daily Living scale, London Handicap Scale, and a rating of satisfaction with care.\n There were no significant differences between the groups in patients' mood, independence in instrumental activities of daily living, handicap, or satisfaction with care.\n CBT in the treatment of depression following stroke was found to be ineffective in this study. However, because of the small sample size, method of recruitment, and selection criteria, further randomized trials are required.", "To compare the antiemetic effect of acupressure at the Neiguan point (P6) in a group of healthy women with normal pregnancy and nausea and vomiting during pregnancy (NVP) with a similar group receiving acupressure at a placebo point and another, similar group not receiving any treatment.\n A randomized, placebo-controlled, pilot study involving 60 women.\n It is possible to reduce NVP significantly with acupressure at P6 as compared to acupressure at a placebo point or no treatment at all in healthy women with normal pregnancies. Relief from nausea appeared one day after starting treatment in both the P6 and placebo groups but lasted for only six days in the placebo group. The P6 group, however, experienced significantly less nausea after 14 days as compared to the other two groups.\n This study involved 60 healthy women with normal pregnancy and suffering from NVP. According to the results, in healthy women with normal pregnancy it is possible to reduce NVP significantly at P6 as compared to acupressure at a placebo point and to no treatment.", "nan", "This study examined the effects of transcutaneous electrical nerve stimulation (TENS) on incisional pain caused by the procedure of cleaning and packing an abdominal surgical wound. Seventy-five subjects (mean age 56.9 years) were randomly assigned to one of three intervention groups: TENS, placebo-TENS, or no-treatment control. The appropriate experimental treatment was administered during the routine dressing change which took place two mornings after surgery. Using an 11-point, visual analogue pain scale, subjects described pain experienced during the dressing change. Subjects who received TENS reported a significantly lower level of pain after dressing change than did those subjects who received either placebo-TENS or no-treatment. Drug administration variables did not contribute significantly to level of reported pain.", "In order to assess the effects of a Behavioral Treatment Program in the control of primary hypertension, twenty one unmedicated hypertensives were randomly allocated to three groups: first, a treatment group (BHG) receiving a Behavioral Treatment which included: deep muscle relaxation, peripheral temperature Biofeedback and anxiety management training; second, the placebo attention control group (PHG) and third, a control group of hypertensives too (CHG). Additionally, were compared with seven normotensives subjects (CNG). The post-treatment measures showed a significant reduction (p < 0.001) in systolic and diastolic values only in the (BHG). In a six months follow-up the (BHG) group still showed a significant reduction in the systolic and diastolic BP (p < 0.02; p < 0.01). Moreover individual variations in response to treatment were observed in this group, (BHG).", "A randomized controlled trial was conducted.\n To determine the efficacy of osteopathic manipulative treatment as a complementary treatment for chronic nonspecific low back pain.\n Osteopathic manipulative treatment may be useful for acute or subacute low back pain. However, its role in chronic low back pain is unclear.\n This trial was conducted in a university-based clinic from 2000 through 2001. Of the 199 subjects who responded to recruitment procedures, 91 met the eligibility criteria. They were randomized, with 82 patients completing the 1-month follow-up evaluation, 71 completing the 3-month evaluation, and 66 completing the 6-month evaluation. The subjects were randomized to osteopathic manipulative treatment, sham manipulation, or a no-intervention control group, and they were allowed to continue their usual care for low back pain. The main outcomes included the SF-36 Health Survey, a 10-cm visual analog scale for overall back pain, the Roland-Morris Disability Questionnaire, lost work or school days because of back pain, and satisfaction with back care.\n As compared with the no-intervention control subjects, the patients who received osteopathic manipulative treatment reported greater improvements in back pain, greater satisfaction with back care throughout the trial, better physical functioning and mental health at 1 month, and fewer cotreatments at 6 months. The subjects who received sham manipulation also reported greater improvements in back pain and physical functioning and greater satisfaction than the no-intervention control subjects. There were no significant benefits with osteopathic manipulative treatment, as compared with sham manipulation.\n Osteopathic manipulative treatment and sham manipulation both appear to provide some benefits when used in addition to usual care for the treatment of chronic nonspecific low back pain. It remains unclear whether the benefits of osteopathic manipulative treatment can be attributed to the manipulative techniques themselves or whether they are related to other aspects of osteopathic manipulative treatment, such as range of motion activities or time spent interacting with patients, which may represent placebo effects.", "To compare differences in the chemotherapy-induced nausea and vomiting (CINV) among three groups of women (acupressure, placebo acupressure, and usual care) undergoing chemo-therapy for breast cancer.\n A multicenter, longitudinal, randomized clinical trial throughout one cycle of chemotherapy.\n Ten community clinical oncology programs associated with the M.D. Anderson Cancer Center and nine independent sites located throughout the United States.\n 160 women who were beginning their second or third cycle of chemotherapy for breast cancer treatment and had moderate nausea intensity scores with their previous cycles.\n Subjects were randomized to one of three groups: acupressure to P6 point (active), acupressure to SI3 point (placebo), or usual care only. Subjects in the acupressure group were taught to apply an acupressure wrist device by research assistants who were unaware of the active acupressure point. All subjects completed a daily log for 21 days containing measures of nausea and vomiting and recording methods (including antiemetics and acupressure) used to control these symptoms.\n Acute and delayed nausea and vomiting.\n No significant differences existed in the demographic, disease, or treatment variables among the treatment groups. No significant differences were found in acute nausea or emesis by treatment group. With delayed nausea and vomiting, the acupressure group had a statistically significant reduction in the amount of vomiting and the intensity of nausea over time when compared with the placebo and usual-care groups. No significant differences were found between the placebo and usual-care groups in delayed nausea or vomiting.\n Acupressure at the P6 point is a value-added technique in addition to pharmaceutical management for women undergoing treatment for breast cancer to reduce the amount and intensity of delayed CINV.\n Acupressure is a safe and effective tool for managing delayed CINV and should be offered to women undergoing chemotherapy for breast cancer.", "nan", "67 adult women with a history of recurrent lower urinary tract infection (UTI) were randomized for acupuncture treatment, sham acupuncture, or no treatment. The incidence rate of UTI over the following six months was noted. In the acupuncture group a total of 85% was free of cystitis during the six-month observational period, as compared to 58% in the sham group (p < 0.05), and 36% in the control group (p < 0.01). Compared to the acupuncture group, twice as many incidents of cytitis occurred in the sham group, and three times as many in the control group (p < 0.05). Acupuncture seems a worthwhile alternative in the prevention of frequently recurring cystitis in women.", "nan", "In Experiment 1, 28 attention-deficit hyperactivity disorder (ADHD) boys underwent a double-blind, placebo-controlled medication assessment in a summer day-treatment program. Daily, boys were asked questions to assess their attributions for and evaluations of their behavior. Objective measures showed improved behavior with methylphenidate; however, boys tended to attribute their performance to effort rather than to medication, particularly when medicated. Experiment 2 involved 38 ADHD boys the following summer and replicated the procedures in Experiment 1, with the addition of a no-pill condition and a comparison of attributions for success and failure outcomes. Simply taking a pill (no-pill vs. placebo comparison) did not show significant effects, whereas the results of Experiment 1 were replicated with placebo-methylphenidate comparisons. Across drug conditions a self-enhancing attributional pattern was obtained; the majority of attributions for success were to ability or effort, whereas attributions for failure were to the pill or to counselors.", "To study the effect of single-needle acupuncture in suppressing gag-reflex in transesophageal echocardiography (TEE).\n Prospective, blinded trial. Settings/locations: Patients with ischemic stroke or transient ischemic attack undergoing TEE because of presumed cardioembolic origin in a specialized stroke unit of the Johann Wolfgang Goethe-University, Frankfurt/Main, Germany. Subjects/Study interventions: Forty-one (41) patients were studied. Patients received single-needle acupuncture with a 0.2 x 13 mm disposable acupuncture needle (Suzhou Medical Appliances, China), 10-mm deep either at Chengjiang (midline between lower lip and chin) or superficially at a sham point (tip of the chin) during TEE or no acupuncture for alleviating gag reflex.\n Severity of gagging was rated on a visual-analogue scale.\n The acupuncture group experienced significantly less gagging than the sham group (p = 0.037) or the nonacupuncture group (p = 0.013).\n Acupuncture of CV24 is an easy to apply and effective method to reduce gag reflex during TEE.", "To examine the effectiveness of cognitive-behavioral and pharmacologic treatment of depression in rheumatoid arthritis (RA).\n Subjects (n = 54) with confirmed diagnoses of both major depression and RA were randomly assigned to 1 of 3 groups: 1) cognitive-behavioral/pharmacologic group (CB-PHARM), 2) attention-control/pharmacologic group, or 3) pharmacologic control group. Measures of depression, psychosocial status, health status, pain, and disease activity were collected at baseline, posttreatment (10 weeks), 6-month followup, and 15-month followup. Data were analyzed to compare the treatment effectiveness of the groups; data also were aggregated to examine the effects of antidepressive medication over time. Lastly, a no-treatment control group was defined from a cohort of persons who declined participation.\n Baseline comparisons on demographic and dependent measures revealed a need to assess covariates on age and education; baseline scores on dependent measures also were entered as covariates. Analyses of covariance revealed no statistically significant group differences at postintervention, 6-month followup, or 15-month followup, except higher state and trait anxiety scores for the CB-PHARM group at the 15-month followup. In the longitudinal analyses of the effects of antidepressive medication, significant improvement in psychological status and health status were found at posttreatment, 6-month followup, and 15-month followup, but no significant improvements were shown for pain or disease activity. In addition, the comparison of the aggregated pharmacologic group with a no-treatment group revealed a statistically significant benefit for the 3 groups that received the antidepressive medication.\n In persons with RA, cognitive-behavioral approaches to the management of depression were not found to be additive to antidepressant medication alone, but antidepressant intervention was superior to no treatment.", "To determine both the efficacy and safety of the topical application of 50 mg penicillin G potassium troches (Cankercillin) in the treatment of minor recurrent aphthous stomatitis (RAS).\n The investigation used a phase 2 double-blind, randomized placebo-controlled trial with a no-treatment arm. Subjects with minor aphthous ulcers of duration <48 hours were followed for 1 week. The primary endpoint for efficacy was time (days) to complete ulcer resolution, and the secondary endpoint was time (days) to complete pain relief.\n Thirty-one, 33, and 36 subjects were randomized to the active treatment, placebo, and no-treatment arms, respectively. Baseline findings were heterogeneous across arms. Subjects who received penicillin G treatment had complete ulcer healing and pain relief significantly earlier than those in the placebo and no-treatment arms. No allergic reactions were observed.\n Topical penicillin G, by mechanisms which remain unclear, reduces the time of healing and pain relief of minor aphthous ulcers with minimal safety concerns. Larger phase 3 studies are necessary to confirm these findings.", "A 3 x 6 factorial design with a double blind and placebo control was employed to investigate the effect of TENS treatment on pain produced by venipuncture. The three treatment groups consisted of TENS, placebo-TENS and control. Subjects were blocked into six 2-year age groups (ages: 5-17 years). During the period of the study, 896 children attending the outpatient laboratory of a general hospital were screened and 514 children completed the study. The data which were collected before venipuncture included expected pain and state anxiety. Following venipuncture, pain intensity was measured with a vertical visual analogue scale (VAS) and pain affect was assessed with McGrath's faces scale. Significant main effects for treatment and age groups were obtained. Pain intensity and affect were lowest for the TENS group and highest for the control group. The pain scores were greatest for lower age groups and lowest for higher age groups. The results of this study support the use of TENS for children's pain and the need for interventions for children's procedural pain.", "nan", "Those who were labelled as depressives in a rural survey were randomly divided into a Medicine group (who received antidepressive drug treatment), a Placebo group (who received placebo) and a Natural Process group (who received no treatment). The depth of their depression was assessed by Hamilton's Depressive Rating Scale before the beginning of the trial, on the 14th day and on the 28th day of trial. They were compared with a matched group of healthy controls and again with a matched group of depressives who attended an urban clinic for treatment. The results indicate that the rural depressives who never sought treatment voluntarily were not different from those who sought treatment in clinics, so far as their response to treatment is concerned.", "Most studies dealing with spina bifida children concentrate on medical or physical factors, largely ignoring any psychosocial and educational consequences. The present study assessed the effect of a remedial program on visual-motor perception in spina bifida children. Thirty-six spina bifida boys and girls (mean age 82.87 months) with a myelomeningocele and an associated hydrocephalus were assigned randomly to either a control, attention-placebo, or experimental group. Following the administration of the Frostig Program for the Development of Visual Perception, the experimental group significantly improved on a global index of visual perception and the five subtests of Frostig's Development Test of Visual Perception; at a maintenance test two months later, all treatment gains (except on the visual spatial perception subtest) were still evident. These results are discussed in terms of the provision of remedial education for spina bifida children, and a possible cognitive mechanism mediating the behavioral change in the experimental group.", "It is recognized that pre-operative anxiety can have adverse effects on the course and outcome of surgery and there is a considerable amount of research into the influences of interventions for pre-operative anxiety on a number of post-operative variables. However, little attention has been paid to the potential influences of treatments on intra-operative variables, most notably on the facilitation of anaesthesia. The present study examined the impact of a brief relaxation procedure on anaesthesia in comparison to attention-control and no-treatment control procedures. A sample of 21 patients about to undergo anaesthesia for day-case surgery were randomly assigned to one of the three conditions. It was found that the relaxation treatment significantly reduced pre-operative anxiety as measured by the state scale of the State-Trait Anxiety Inventory (Spielberger, 1983). This reduction was reflected in physiological indicators of anxiety. Both the relaxation group and the attention-control group required significantly less time to induce anaesthesia and less of the anaesthetic agent used to maintain anaesthesia. The relaxation group also scored significantly lower than the no-treatment control group on an anaesthetist's rating of difficulty of maintenance of anaesthesia. Whilst the relaxation treatment appeared to have no advantages over the attention-control procedure in terms of anaesthetic requirements, the latter treatment did not reduce anxiety and showed no benefit over the no-treatment control condition in terms of an anaesthetist's rating of difficulty of maintenance of anaesthesia. In addition, following recovery the relaxation subjects reported more favourable perceptions of their treatment than the attention-control subjects.", "To evaluate the use of oral iron replacement therapy as an effective treatment for acute surgically induced anemia.\n Double-blind, placebo-controlled, randomized clinical trial.\n Perioperative acute care hospital and a surgery clinic for a single cardiothoracic physician group.\n One hundred twenty-eight men and postmenopausal women, 50 years of age or older, admitted for elective coronary artery bypass surgery over a consecutive 8-month period.\n Before surgery: serum iron, serum ferritin, hemoglobin and hematocrit. Six days after surgery: hemoglobin and hematocrit. Mean of 59 days after surgery: serum iron, serum ferritin, hemoglobin and hematocrit.\n Patients were randomized to one of four groups: control group; placebo group; low-dose group, 50 mg elemental iron + 60 mg ascorbic acid in a multi-vitamin daily; and usual-dose group, 200 mg elemental iron daily.\n One hundred twenty-one subjects completed the study: 100 men (82.6%) mean age 64.5 years and 21 women (17.4%), mean age 65.7 years. There were no statistically significant age or gender differences among groups. Statistical analysis revealed, except for side effects, no differences between or among groups for any variable measured during the last two time intervals. The mean hemoglobin and hematocrit of the entire sample at 6 days was 9.5 +/- 1.2 gm/dl and 28% +/- 2.3%, respectively. At a mean of 59 days later these values increased equally for all groups to a mean for the cohort of 13.6 +/- 1 gm/dl for hemoglobin and 40.6% +/- 3 for hematocrit. Serum iron and ferritin were within the normal range. The 200 mg group experienced significantly more side effects (p < 0.01).\n Thus the use of oral iron supplements for the treatment of acute blood loss anemia after uncomplicated coronary artery bypass surgery did not assist in restoring red blood cell mass or help maintain total body iron stores.", "We carried out a prospective, randomized study to evaluate the usefulness of premedication with an oral anticholinergic for relief of pain during and after a barium enema of the colon.\n Patients were randomized into three groups: no medication, placebo, and sublingual 1-hyoscyamine sulfate. The placebo or hyoscyamine tablet was placed under the tongue 15-30 min before the examination. After the procedure the patients were interviewed. An analog scale (0-10) was used to score the level of pain that the patients experienced during the examination. Forty-eight hours after the examination, the patients returned by mail a survey that used the same scale and asked about delayed pain.\n Data from 110 patients were studied. Sixty-nine patients were women, and 41 were men. They ranged from 24 to 82 years old (mean, 55 years). For the no-medication group (n = 36), the mean pain score was 4.1; for the placebo group (n = 34), 3.8; and for the hyoscyamine group (n = 40), 4.2. No statistically significant difference in pain scores was found between any groups (p = .72). Six patients from each group reported minor side effects. The mean scores from the returned surveys (n = 79) were 3.8 for the no-medication group (n = 26) and placebo group (n = 22) and 3.1 for the hyoscyamine group (n = 31). No statistically significant difference was found between any of these groups (p = .48) or between delayed pain responses and initial pain responses (p = .27).\n Although safe, hyoscyamine seems to provide no benefit over no drug or a placebo when used as a pain premedication for patients undergoing a barium enema.", "Sixty-three episodes of genital herpetic infection in 55 men and 45 episodes in 42 women were randomly assigned to topical treatment with 3% adenine arabinoside, topical treatment with placebo ointment, or no therapy. In addition, 10 episodes in women who were not randomly assigned to therapy were evaluated and followed. Clinical evaluation and viral cultures were done on day 3, day 8, and weekly thereafter until the lesions had healed. The natural clinical course of genital herpetic infection was defined in patients given placebo or no therapy. Patients with a history of previous genital herpetic infection had significantly less pain, few lesions, and shorter duration of illness and viral shedding than patients who had no history of previous genital infection with Herpesvirus. An unexpected finding was that 87% of women experiencing their first episode of genital herpetic infection had cervical cultures positive for Herpesvirus hominis, whereas only 4% of women with recurrent herpetic infection had a positive cervical culture. Treatment with 3% adenine arabinoside did not influence the course of either primary or recurrent genital infection with Herpesvirus.", "Sixty-six tension headache patients were randomly assigned to one of four conditions for 8 weeks: (a) progressive muscle relaxation (PMR) alone; (b) PMR plus cognitive therapy (PMR + Cog); (c) pseudomeditation, a credible attention-placebo control; or (d) continued headache monitoring. A comparison of overall headache activity (headache index), derived from a daily headache diary, for 4 weeks before treatment to 4 weeks after treatment, revealed that active treatment (PMR and PMR + Cog) was superior to either control condition. Moreover, level of headache medication consumption decreased significantly for the active treatment groups. Although headache-index comparisons of the two active treatments showed no advantage for adding cognitive therapy to PMR, a measure of clinically significant change showed a trend for PMR + Cog to be superior to PMR alone.", "1,218 smokers able to quit smoking for 48 hr were randomly assigned to one of 12 cells in a 4 x 3 fully crossed factorial experiment. A pharmacologic factor contained four levels: nicotine polacrilex (gum) delivered ad lib or on a fixed regimen, placebo gum, and no gum. A self-guided behavioral treatment factor contained three levels: self-selected relapse prevention modules, randomly administered modules, and no modules. Those receiving nicotine gum were more likely to be abstinent at the 2- and 6-month follow-ups. The fixed regimen accounted for most of the effect for gum. There was no effect for the relapse prevention module factor. Men and women showed a differential treatment response. Men who received nicotine gum were more likely to be abstinent at each follow-up (2, 6, and 12 months). No treatment was significantly better among women. We conclude that research on different gum chewing regimens is warranted and that further examination of possible gender differences in response to replacement therapy is needed.", "To investigate whether intensive cognitive behaviour therapy results in significant improvement in positive psychotic symptoms in patients with chronic schizophrenia.\n Patients with chronic schizophrenia were randomly allocated, stratified according to severity of symptoms and sex, to intensive cognitive behaviour therapy and routine care, supportive counselling and routine care, and routine care alone.\n Adjunct treatments were carried out in outpatient clinics or in the patient's home.\n 87 patients with persistent positive symptoms who complied with medication; 72 completed treatment.\n Assessments of positive psychotic symptoms before treatment and 3 months after treatment. Number of patients who showed a 50% or more improvement in symptoms. Exacerbation of symptoms and rates of readmission to hospital.\n Significant improvements were found in the severity (F=5.42, df =2,86; P=0.006) and number (F=4.99, df=2,86; P=0.009) of positive symptoms in those treated with cognitive behaviour therapy. The supportive counselling group showed a non-significant improvement. Significantly more patients treated with cognitive behaviour therapy showed an improvement of 50% or more in their symptoms (chi2=5.18, df=1; P=0.02). Logistic regression indicated that receipt of cognitive behaviour therapy results in almost eight times greater odds (odds ratio 7.88) of showing this improvement. The group receiving routine care alone also experienced more exacerbations and days spent in hospital.\n Cognitive behaviour therapy is a potentially useful adjunct treatment in the management of patients with chronic schizophrenia.", "The decline in blood pressure (BP) in essential hypertensives following hospitalization may result from: 1) regression toward the mean; 2) reduction of anxiety as patients habituate to a new environment; 3) the placebo effect of medication; and 4) an independent effect of hospitalization itself. A randomized crossover study of 12 essential hypertensives demonstrated a fall in supine blood pressure from 165.0/97.9 +/- 2.3/1.1 mm Hg to 154.3/89.6 +/- 2.7/1.1 mm Hg (p less than 0.005) due to hospitalization. A similar reduction in BP from 164.9/99.5 +/- 8.4/4.1 mm Hg to 151.9/93.4 +/- 4.5/1.9 mm Hg (p less than 0.005) resulted from regression toward the mean and habituation during the study period. Urinary catecholamines fell from 68.7 +/- 5.0 to 55.1 +/- 4.3 micrograms/g creatinine/24 hours (p less than 0.05) due to hospitalization and from 56.1 +/- 5.4 to 49.7 +/- 4.3 micrograms/g creatinine/24 hours (p less than 0.05) with time. Although placebo therapy tended to reduce BP, it failed to do so significantly. When expressed as a percentage of the individual's overall mean, urinary catecholamine excretion fell from 110.5% +/- 3.7% to 89.5% +/- 3.7% (p less than 0.001) during hospitalization and from 105.8% +/- 3.9% to 94.2% +/- 3.9% (p less than 0.05) during the outpatient period. Blood pressure and sympathetic activity rapidly returned to prehospitalization values on discharge. These factors may confound the analysis of drug effects on BP and sympathetic activity in essential hypertensives following admission to hospital.", "Three-group, randomized, single blinded, controlled trial.\n To test the effectiveness of physiotherapy-based rehabilitation starting 1 week after lumbar disc surgery. In addition, we tried to estimate the contribution of specific effects to the observed outcome (efficacy).\n Physiotherapy-based rehabilitation is usually recommended for patients following lumbar disc surgery. Few and conflicting data exist for the relative effectiveness of this intervention.\n A total of 120 patients following first-time, uncomplicated lumbar disc surgery were randomly assigned to \"comprehensive\" physiotherapy, \"sham\" neck massage, or no therapy. Before enrollment, all subjects completed a minimal physiotherapeutic intervention. Physiotherapy was administered by experienced physiotherapists and consisted of 20 sessions per patient over 12 weeks. Masseurs administered \"sham massage\" to the neck. The amount of treatment time was equal to that of physiotherapy. The main outcome measure was the Low Back Pain Rating Score (LBPRS) at 6 and 12 weeks, and 1.5 years after randomization. Secondary parameters were patients' overall satisfaction with treatment outcome and socioeconomic and psychologic measures.\n At the end of therapy (12 weeks), the LBPRS revealed a significantly better improvement in the physiotherapy group than in the untreated group. LBPRS outcome, however, did not significantly differ between physiotherapy and \"sham\" therapy. There was a tendency toward significance between the sham therapy and no therapy. Within the 1.5-year follow-up, LBP rating scales remained significantly improved compared with baseline, but there were no significant outcome differences. No statistically significant between-group differences were found for the secondary outcome parameters.\n As compared with no therapy, physiotherapy following first-time disc herniation operation is effective in the short-term. Because of the limited benefits of physiotherapy relative to \"sham\" therapy, it is open to question whether this treatment acts primarily physiologically in patients following first-time lumbar disc surgery, but psychological factors may contribute substantially to the benefits observed.", "The objectives were to determine whether a eutectic mixture of local anesthetic (EMLA) or placebo cream reduces pain during extracorporeal piezoelectric shock wave lithotripsy (EPSWL), and to determine which of the components of the application (i.e., the occlusive dressing, the cream, or the local anesthetic) contributes to analgesia.\n A randomized, double blind, crossover study (part 1) was performed in 12 patients who were scheduled for EPSWL procedures on an ambulatory basis who received the first treatment without any intervention and who had verbal pain scores of 70 or more (on a 0-to- 100 scale). For the next two treatments at 2-week intervals, patients were randomly assigned to receive either 10 g EMLA or 10 g placebo cream and then crossed over to receive the other. The cream and occlusive dressing were left in place and immersed in water throughout the procedure. Verbal numeric pain score was assessed at 5 min after receiving the maximal tolerable intensity of shock wave and at the end of the procedure. The study continued (part 2) in 202 ambulatory patients; 125 men and 77 women, American Society of Anesthesiologists physical status I and II, subjected to EPSWL were randomly allocated into five groups who received (1) nothing on the skin (control), (2) plastic occlusive dressing, (3) placebo cream and plastic occlusive dressing, (4) EMLA cream and plastic occlusive dressing, (5) EMLA cream and plastic occlusive dressing for 60 min to achieve cutaneous anesthesia, which was removed before EPSWL. Pain score was evaluated 10 min into the procedure and at the end of the procedure.\n Both parts of the study showed that patients who received either EMLA or placebo cream with dressing throughout the procedure experienced less pain and tolerated higher energy levels compared with the control. Patients who received only pre-EPSWL cutaneous anesthesia of EMLA and who received only the occlusive dressing did not have a reduction in pain score.\n EMLA and placebo creams under occlusive dressing reduced pain during EPSWL. The presence of the cream itself as a coupling medium contributed to analgesia. This may be a useful, simple, safe, and economical adjuvant technique to reduce pain during immersion EPSWL.", "Venipuncture continues to be considered a painful and unpleasant experience for those receiving medical treatment. A prospective study investigating whether the application of a transcutaneous electrical nerve stimulator (TENS) decreases the complaints of pain and unpleasantness with i.v. needle insertion was conducted using a group of 71 subjects who were double-blinded and randomized to one of three groups: TENS, placebo-TENS, and control. This article gives an overview of this research and describes its findings.", "Acupuncture is widely used by patients with low back pain, although its effectiveness is unclear. We investigated the efficacy of acupuncture compared with minimal acupuncture and with no acupuncture in patients with chronic low back pain.\n Patients were randomized to treatment with acupuncture, minimal acupuncture (superficial needling at nonacupuncture points), or a waiting list control. Acupuncture and minimal acupuncture were administered by specialized acupuncture physicians in 30 outpatient centers, and consisted of 12 sessions per patient over 8 weeks. Patients completed standardized questionnaires at baseline and at 8, 26, and 52 weeks after randomization. The primary outcome variable was the change in low back pain intensity from baseline to the end of week 8, as determined on a visual analog scale (range, 0-100 mm).\n A total of 298 patients (67.8% female; mean +/- SD age, 59 +/- 9 years) were included. Between baseline and week 8, pain intensity decreased by a mean +/- SD of 28.7 +/- 30.3 mm in the acupuncture group, 23.6 +/- 31.0 mm in the minimal acupuncture group, and 6.9 +/- 22.0 mm in the waiting list group. The difference for the acupuncture vs minimal acupuncture group was 5.1 mm (95% confidence interval, -3.7 to 13.9 mm; P = .26), and the difference for the acupuncture vs waiting list group was 21.7 mm (95% confidence interval, 13.9-30.0 mm; P<.001). Also, at 26 (P=.96) and 52 (P=.61) weeks, pain did not differ significantly between the acupuncture and the minimal acupuncture groups.\n Acupuncture was more effective in improving pain than no acupuncture treatment in patients with chronic low back pain, whereas there were no significant differences between acupuncture and minimal acupuncture.", "The contribution of training procedures designed to alter individuals' psychological responses to stressful life stimuli to the reduction of blood-pressure levels of hypertensives was evaluated. The treatment consisted of a set of coping skill-building experiences. Forty-one black males, mildly to moderately hypertensive and under medical supervision in an outpatient cardiovascular unit of a veterans' hospital, participated. Subjects were randomly assigned to one of three groups: Cognitive Self-Management Training (CSM), Attention Placebo Control, and Current Clinic Conditions Control. The dependent measures were the State Anxiety Scale, Trait Anxiety Scale, Coping Strategic Inventory, systolic blood pressure, and diastolic blood pressure. Subjects in the CSM group reported significant increases in the use of cognitive coping strategies in their lives and demonstrated significant decreases in measured levels of state anxiety and systolic blood pressure. Promising reductions of diastolic blood pressure ratings were obtained as well.", "Approximately 80% of nursing home residents who suffer from Alzheimer's disease and related dementia develop behavioral symptoms of dementia. Given the deleterious side effects of pharmacologic therapy in this population there is an urgent need for clinical trials of nonpharmacologic interventions.\n To examine the effect of therapeutic touch on the frequency and intensity of behavioral symptoms of dementia.\n A randomized, double-blind, three-group experimental study: experimental (therapeutic touch), placebo (placebo therapeutic touch), and control (usual care). Fifty-seven residents, aged 67 to 93 years, exhibiting behavioral symptoms of dementia, were randomized to one of the three groups within each of three Special Care Units within three Long-Term Care facilities in a western Canadian province. Behavioral observation was completed every 20 minutes from 8:00AM to 6:00PM for three days pre-intervention and for three days post-intervention by trained observers who were blind to group assignment. The intervention consisted of therapeutic touch given twice daily for 5-7 minutes for three days between 10:00AM and 11:30PM and between 3:00PM and 4:30PM (N = 57). The main outcome variable was overall behavioral symptoms of dementia, consisting of six categories of behaviors: manual manipulation (restlessness), escape restraints, searching and wandering, tapping and banging, pacing and walking, and vocalization.\n Analysis of variance (ANOVA) (F = 3.331, P = .033) and the Kruskal-Wallis test (chi2 = 6.661, P = .036) indicated a significant difference in overall behavioral symptoms of dementia, manual manipulation and vocalization when the experimental group was compared to the placebo and control groups. The experimental (significant) was more effective in decreasing behavioral symptoms of dementia than usual care, while the placebo group indicated a decreasing trend in behavioral symptoms of dementia compared to usual care.\n Therapeutic touch offers a nonpharmacological, clinically relevant modality that could be used to decrease behavioral symptoms of dementia, specifically manual manipulation (restlessness) and vocalization, two prevalent behaviors.", "Acupuncture is widely used by patients with chronic pain although there is little evidence of its effectiveness. We investigated the efficacy of acupuncture compared with minimal acupuncture and with no acupuncture in patients with osteoarthritis of the knee.\n Patients with chronic osteoarthritis of the knee (Kellgren grade < or =2) were randomly assigned to acupuncture (n=150), minimal acupuncture (superficial needling at non-acupuncture points; n=76), or a waiting list control (n=74). Specialised physicians, in 28 outpatient centres, administered acupuncture and minimal acupuncture in 12 sessions over 8 weeks. Patients completed standard questionnaires at baseline and after 8 weeks, 26 weeks, and 52 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index at the end of week 8 (adjusted for baseline score). All main analyses were by intention to treat.\n 294 patients were enrolled from March 6, 2002, to January 17, 2003; eight patients were lost to follow-up after randomisation, but were included in the final analysis. The mean baseline-adjusted WOMAC index at week 8 was 26.9 (SE 1.4) in the acupuncture group, 35.8 (1.9) in the minimal acupuncture group, and 49.6 (2.0) in the waiting list group (treatment difference acupuncture vs minimal acupuncture -8.8, [95% CI -13.5 to -4.2], p=0.0002; acupuncture vs waiting list -22.7 [-27.5 to -17.9], p<0.0001). After 52 weeks the difference between the acupuncture and minimal acupuncture groups was no longer significant (p=0.08).\n After 8 weeks of treatment, pain and joint function are improved more with acupuncture than with minimal acupuncture or no acupuncture in patients with osteoarthritis of the knee. However, this benefit decreases over time.", "nan", "There is some evidence for the efficacy of acupuncture in chronic low-back pain (LBP), but it remains unclear whether acupuncture is superior to placebo. In a randomized, blinded, placebo-controlled trial, we evaluated the effect of traditional acupuncture in chronic LBP. A total of 131 consecutive out-patients of the Department of Orthopaedics, University Goettingen, Germany, (age=48.1 years, 58.5% female, duration of pain: 9.6 years) with non-radiating LBP for at least 6 months and a normal neurological examination were randomized to one of three groups over 12 weeks. Each group received active physiotherapy over 12 weeks. The control group (n=46) received no further treatment, the acupuncture group (n=40) received 20 sessions of traditional acupuncture and the sham-acupuncture group (n=45) 20 sessions of minimal acupuncture. Changes from baseline to the end of treatment and to 9-month follow-up were assessed in pain intensity and in pain disability, and secondary in psychological distress and in spine flexion, compared by intervention groups. Acupuncture was superior to the control condition (physiotherapy) regarding pain intensity (P=0.000), pain disability (P=0.000), and psychological distress (P=0.020) at the end of treatment. Compared to sham-acupuncture, acupuncture reduced psychological distress (P=0.040) only. At 9-month follow-up, the superiority of acupuncture compared to the control condition became less and acupuncture was not different to sham-acupuncture. We found a significant improvement by traditional acupuncture in chronic LBP compared to routine care (physiotherapy) but not compared to sham-acupuncture. The trial demonstrated a placebo effect of traditional acupuncture in chronic LBP.", "We conducted a randomized 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy. A five-cell design was used to determine whether a maintenance form of interpersonal psychotherapy alone or in combination with medication could play a significant role in the prevention of recurrence. A second question was whether maintaining antidepressant medication at the dosage used to treat the acute episode rather than decreasing to a \"maintenance\" dosage would provide prophylaxis superior to that observed in earlier trials in which a maintenance dosage strategy was employed. Survival analysis demonstrated a highly significant prophylactic effect for active imipramine hydrochloride maintained at an average dose of 200 mg and a modest prophylactic effect for monthly interpersonal psychotherapy. We conclude that active imipramine hydrochloride maintained at an average dose of 200 mg is an effective means of preventing recurrence and that monthly interpersonal psychotherapy serves to lengthen the time between episodes in patients not receiving active medication.", "nan", "In Atlanta, as in other major urban areas of the United States, asthma is a leading cause of school absenteeism, emergency department use, and hospitalization. Recent guidelines for asthma management recommend reducing exposure to relevant allergens, but neither the feasibility nor the efficacy of this form of treatment has been established for children living in poverty.\n We sought to investigate allergen avoidance as a treatment for asthma among inner-city children.\n One hundred four children with asthma living in the city of Atlanta were enrolled into a controlled trial of avoidance without being skin tested. The children were randomized to an active avoidance group, a placebo avoidance group, and a second control group for which no house visits occurred until the end of the first year. Avoidance included bed and pillow covers, hot washing of bedding, and cockroach bait. Eighty-five children completed the study, and the outcome was measured as unscheduled clinic visits, emergency department visits, and hospitalization for asthma, as well as changes in mite and cockroach allergen levels.\n There was a significant decrease in acute visits for asthma among children whose homes were visited (P < .001). However, there was no significant difference between the active and placebo homes either in the effect on asthma visits or in allergen concentrations. When the children with mite allergy were considered separately, there was a significant correlation between decreased mite allergen and change in acute visits (P < .01). The avoidance measures for cockroach allergen appeared to be ineffective, and the changes observed did not correlate with changes in visits.\n Applying allergen avoidance as a treatment for asthma among children living in poverty is difficult because of multiple sensitivities and problems applying the protocols in this environment. The current results demonstrate that home visiting positively influences the management of asthma among families living in poverty. Furthermore, the results for children with mite allergy strongly suggest that decreasing relevant allergen exposure should be an objective of treatment in this population.", "The value of therapeutic ultrasound (US) for reducing inflammation was tested in a double-blind controlled study in 150 patients following surgical removal of impacted lower third molars. Facial swelling, trismus, pain and serum C-reactive protein (CRP) were significantly reduced in the US-treated groups and in a placebo group ('mock' US) compared with an untreated control group. The majority of the anti-inflammatory activity was attributable to the placebo effect, and the highest intensity of US (1.5 W.cm-2) was consistently less beneficial than the lower intensities (0.1 and 0.5 W.cm-2) and the mock US.", "The authors examined the effectiveness of unguided self-help as a first step in the treatment of bulimia nervosa.\n A total of 85 women with bulimia nervosa who were on a waiting list for treatment at a hospital-based clinic participated. The patients were randomly assigned to receive one of two self-help manuals or to a waiting list control condition for 8 weeks. One of the self-help manuals addressed the specific symptoms of bulimia nervosa (cognitive behavior self-help), while the other focused on self-assertion skills (nonspecific self-help).\n Twenty patients (23.5%) dropped out of the study. The data were analyzed with intention-to-treat analysis. Although the group-by-time interaction for binge eating and purging was not statistically significant, simple effects showed that there was a significant reduction in symptom frequency in both self-help conditions at posttreatment but not in the waiting list condition. There were no statistically significant changes in levels of dietary restraint, eating concerns, concerns about shape and weight, or general psychopathology. A greater proportion of patients in the cognitive behavior self-help (53.6%) and nonspecific self-help (50.0%) conditions reported at least a 50% reduction in binge eating or purging at posttreatment, compared with the waiting list condition (31.0%). A lower baseline knowledge about eating disorders, more problems with intimacy, and higher compulsivity scores predicted a better response.\n The findings suggest that a subgroup of patients with bulimia nervosa may benefit from unguided self-help as a first step in their treatment. Cognitive behavior self-help and nonspecific self-help had equivalent effects.", "Conventional dentoalveolar osseous reconstruction often involves the use of grafting materials with or without barrier membranes. The purpose of this study was to evaluate the efficacy of bone induction for the placement of dental implants by two concentrations of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on a bioabsorbable collagen sponge (ACS) compared to placebo (ACS alone) and no treatment in a human buccal wall defect model following tooth extraction.\n Eighty patients requiring local alveolar ridge augmentation for buccal wall defects (> or =50% buccal bone loss of the extraction socket) of the maxillary teeth (bicuspids forward) immediately following tooth extraction were enrolled. Two sequential cohorts of 40 patients each were randomized in a double-masked manner to receive 0.75 mg/ml or 1.50 mg/ml rhBMP-2/ACS, placebo (ACS alone), or no treatment in a 2:1:1 ratio. Efficacy was assessed by evaluating the amount of bone induction, the adequacy of the alveolar bone volume to support an endosseous dental implant, and the need for a secondary augmentation.\n Assessment of the alveolar bone indicated that patients treated with 1.50 mg/ml rhBMP-2/ACS had significantly greater bone augmentation compared to controls (P < or =0.05). The adequacy of bone for the placement of a dental implant was approximately twice as great in the rhBMP-2/ACS groups compared to no treatment or placebo. In addition, bone density and histology revealed no differences between newly induced and native bone.\n The data from this randomized, masked, placebo-controlled multicenter clinical study demonstrated that the novel combination of rhBMP-2 and a commonly utilized collagen sponge had a striking effect on de novo osseous formation for the placement of dental implants.", "The expectation of pain is a statistically significant factor negatively affecting patient compliance with current screening flexible sigmoidoscopy recommendations. Numerous pain reduction modalities have been studied with limited success. Transcutaneous electrical nerve stimulation (TENS) has been used to treat pain of various origins. The purpose of this pilot study was to determine the efficacy of TENS in reducing discomfort experienced during screening flexible sigmoidoscopy.A double-blind study was conducted in which 90 subjects were randomized to receive TENS, sham TENS, or control (standard care). The same pulse frequency and intensity were used for all subjects in the TENS group. Subjects completed preprocedural and postprocedural questionnaires, and the endoscopist completed a postprocedural questionnaire. A slight, but statistically insignificant (p =.526) reduction in the mean pain score reported by the TENS group was noted when compared with the sham TENS and control groups (2.00, 2.27, and 2.23 respectively). In light of the fact that only one pulse frequency and intensity of the TENS intervention were used in this study, further study with this safe and cost-effective modality is warranted.", "A sample of physician-referred chronic insomniacs was randomly allocated to either progressive relaxation, stimulus control, paradoxical intention, placebo or no treatment conditions. Treatment process and outcome were investigated in terms of mean and standard deviation (night to night variability) measures of sleep pattern and sleep quality. Only active treatments were associated with significant improvement, but the nature of treatment gains varied. In particular, stimulus control improved sleep pattern, whereas relaxation affected perception of sleep quality. All improvements were maintained at 17 month follow-up. Results are discussed with reference to previous research and guidelines are given for clinical practice.", "Both disulfiram and placebo implant patients abstained longer and had more intense disulfiram-ethanol reactions than did two control groups.", "Ultrasound (US) therapy is used to reduce pain and inflammation and to accelerate healing after soft tissue injury. However, there is little objective evidence of its effectiveness and the mechanisms which may cause these effects are unknown. In a placebo-controlled double-blind clinical trial we examined the contribution of placebo and massage effects in ultrasound therapy following bilateral surgical extraction of lower third molars. Four to 6 h after surgery the patients (25 per group) received either no therapy, US (0.1 W/cm2), 'mock' US with massage, 'mock' US without massage, or 'self-massage' with a dummy applicator. Facial swelling, trismus, serum C-reactive protein, serum cortisol, pain and anxiety were measured 24 h postoperatively. The results showed that the beneficial analgesic and anti-inflammatory effects of US therapy were placebo-mediated, with maximum effect in the placebo ('mock' US) group without circular massaging with the applicator). Self-massage by the patient produced no significant effect. This placebo action was independent of changes in serum cortisol or patient anxiety state. US therapy can significantly reduce postoperative morbidity, but by placebo-mediated mechanisms which are unrelated to the US itself.", "A group of 200 patients who presented in general practice with symptoms but no abnormal physical signs and in whom no definite diagnosis was made were randomly selected for one of four consultations: a consultation conducted in a \"positive manner,\" with and without treatment, and a consultation conducted in a \"non-positive manner,\" called a negative consultation, with and without treatment. Two weeks after consultation there was a significant difference in patient satisfaction between the positive and negative groups but not between the treated and untreated groups. Similarly, 64% of those receiving a positive consultation got better, compared with 39% of those who received a negative consultation (p = 0.001) and 53% of those treated got better compared with 50% of those not treated (p = 0.5).", "nan", "nan", "Fifty obese patients with a body mass index greater than 25 kg/m2 were randomized into 3 groups: control (C = 19), placebo (P = 18) and dexfenfluramine (D = 18). A behavioral modification program which included eating habits, exercise, attitudes, social relationships and six steps to lifetime weight control was taught every week. All patients strictly followed the food manual and recorded their behavior, physical activity and food intake every day through 12 weeks. Placebo and dexfenfluramine 30 mg/day were given in a double blind placebo controlled study. The results showed that all 3 groups had significant decreases in rest times and increased activity times (p < 0.05) and significant reductions of the average total daily energy, carbohydrate and fat intake (p < 0.05). They all lost weight. Mean +/- SEM cumulative weight loss was 8.3 +/- 0.7 kg in group D, 3.3 +/- 1 kg, in group P and 2.9 +/- 0.7 kg, in group C. The mean additional weight loss of 5 kg, and 5.4 kg seen with dexfenfluramine being highly significant (p < 0.001) from group P and C most likely due to increased thermogenesis. Significant (p < 0.05) and gradual reduction of biceps, triceps skinfold and per cent body fat were constantly observed only in the dexfenfluramine group. There were no significant differences among the 3 groups regarding blood pressure, heart rate, hematologic, lipids and biochemical profiles.", "A double-blind randomly controlled trial of one particular laxative, Senokot, used in moderate dosage, was carried out on a group of 40 children with severe and persistent soiling and often with a history of faecal retention. Significant improvement occurred following three months of outpatient treatment using a behavioural approach and either Senokot, placebo or no medication. However, there was no evidence either during the trial or subsequently when Senokot was employed to supplement behavioural treatment in every child who continued with therapy that this laxative contributed in any way to relieving the problem in this group of cases.", "The purpose of the study was to determine the effect of ethyl vinyl chloride vapocoolant spray on pain reported by children undergoing intravenous cannulation. A randomized, double-blinded, placebo-controlled trial was conducted on eligible children between the ages of 9 and 18 years seen in a pediatric emergency department and requiring intravenous cannulation. Informed consent was obtained, and children were randomized to receive ethyl vinyl chloride spray, isopropyl alcohol spray, or no spray (control group). Patient demographics and information pertaining to each intravenous cannulation were recorded. Children indicated the degree of pain associated with intravenous cannulation on a 100-mm visual analog scale (VAS) compared to a baseline pain score of \"zero.\" Statistical analysis was performed by using Stata version 7. One hundred twenty-seven subjects were enrolled: 37 received ethyl vinyl chloride vapocoolant spray, 48 received isopropyl alcohol spray (placebo), and 42 received no pretreatment. Mean VAS scores for pain experienced during cannulation were 34, 33, and 31 mL for each group, respectively. Ethyl vinyl chloride vapocoolant spray failed to measurably reduce pain associated with intravenous cannulation when compared to those pretreated with isopropyl alcohol spray or receiving no intervention.", "This experiment examined the efficacy of an acustimulation wrist band for the relief of chemotherapy-induced nausea using a randomized three-arm clinical trial (active acustimulation, sham acustimulation, and no acustimulation) in 96 women with breast cancer who experienced nausea at their first chemotherapy treatment. Five outcomes related to wrist band efficacy (acute nausea, delayed nausea, vomiting, QOL, and total amount of antiemetic medication used) were examined. The five outcomes were examined separately using analysis of covariance controlling for age and severity of past nausea. There were no significant differences in any of these study measures among the three treatment conditions (P>0.1 for all). Study results do not support the hypothesis that acustimulation bands are efficacious as an adjunct to pharmacological antiemetics for control of chemotherapy-related nausea in female breast cancer patients.", "Low catalase levels and cellular vacuolation in the epidermis of patients with vitiligo support major oxidative stress in this compartment. There is now in vivo evidence for increased epidermal hydrogen peroxide (H(2)O(2)) accumulation in this patient group by utilizing noninvasive Fourier Transform Raman spectroscopy (FT Raman). Epidermal H(2)O(2) can be removed with a topical application of narrow band UVB activated pseudocatalase cream (PC-KUS). (Mn/EDTA-bicarbonate complex, patent No. EPO 58471 1 A), yielding initiation of repigmentation. Dead Sea climatotherapy is another successful treatment modality for vitiligo, but the mode of action has escaped definition so far.\n Epidermal hydrogen peroxide (H(2)O(2)) was assessed in vivo before and after 21 days treatment at the Dead Sea using noninvasive Fourier-Transform Raman spectroscopy. The effectiveness of repigmentation was followed in 59 patients with vitiligo by comparing Dead Sea climatotherapy alone with the combination of Dead Sea climatotherapy/pseudocatalase cream (PC-KUS) as well as Dead Sea climatotherapy/placebo cream. Clinical repigmentation was documented by standardized black/white photography using non-UV coated bulbs as flashlight and by color photography.\n This study on 59 patients who had vitiligo for an average time of 17 years (range 3-53 years) confirmed in vivo H(2)O(2) accumulation in mM concentrations in the epidermis of untreated patients. Furthermore, we demonstrated a pseudocatalase activity after 15 min of Dead Sea bathing, but the decrease of epidermal H(2)O(2) levels was significantly less compared to narrowband UVB activated pseudocatalase cream (PC-KUS). Initiation of repigmentation was already observed between day 10 and day 16 after a combination of Dead Sea climatotherapy/pseudocatalase cream compared to conventional pseudocatalase monotherapy (8-14 weeks) and Dead Sea climatotherapy alone (5-6 weeks).\n The results of this study show a significantly faster initiation of repigmentation in vitiligo after a combination of short-term climatotherapy (21 days) at the Dead Sea in combination with a pseudocatalase cream (PC-KUS) compared to either conventional climatotherapy at the Dead Sea alone or with placebo cream in combination with climatotherapy. This combined therapy is significantly faster in repigmentation than narrowband UVB activated pseudocatalase cream (PC-KUS) treatment alone. The results of this study support the necessity of epidermal H2O2 removal as well as the influence of solar UV-light in the successful treatment of vitiligo.", "The authors describe a medical center-based randomized trial aimed at determining the feasibility and effectiveness of partnering patients and primary-care providers with an exercise health counselor. Study participants included 165 veterans age 70 years and older. The primary end point was change in physical activity at 3 and 6 months comparing patients receiving high-intensity physical activity counseling, attention control counseling, and usual care after receiving standardized clinic-based counseling. We noted a significant Group x Time interaction (p = .041) for physical activity frequency and a similar effect for caloric expenditure (p = .054). Participants receiving high-intensity counseling and usual care increased physical activity over the short term, but those with usual care returned to baseline by the end of the study. The intervention was well received by practitioners and patients. We conclude that partnering primary-care providers with specialized exercise counselors for age- and health-appropriate physical activity counseling is effective.", "We review some of the evidence that supports the existence of psychosomatic triggers to bronchospasm in asthmatics, and hypothesize that it may also be possible to consciously reverse bronchospasm using trachea-noise biofeedback. We precipitated significant levels of bronchospasm in 16 asthmatics using exercise or eucapnic-hyperventilation challenges on five occasions, and administered four different treatments and a no-treatment control. The treatments were trachea-noise biofeedback (TNBF), wrong-information TNBF, an inhaled adrenergic bronchodilator, and a placebo inhaler, all given double blind. Half of the subjects had 3 training days in the use of the TNBF device before study. Our results show that TNBF, in the trained subjects only, is associated with a detectable, but not statistically significant, increase in the rate of recovery from bronchospasm over that found with no treatment. We conclude that, although asthmatics seem to have a strong ability to consciously induce bronchospasm, conscious reversal of a full asthma attack using TNBF is limited. Despite contrary conclusions by other investigators, we believe that this study demonstrated little TNBF-assisted recovery from bronchospasm. We suggest that this is because its effect may be inhibited by humoral mechanisms that sustain the attack, but we believe further work is required to support this.", "To determine whether a home based exercise programme can improve outcomes in patients with knee pain.\n Pragmatic, factorial randomised controlled trial of two years' duration.\n Two general practices in Nottingham.\n 786 men and women aged >/=45 years with self reported knee pain. Interventions: Participants were randomised to four groups to receive exercise therapy, monthly telephone contact, exercise therapy plus telephone contact, or no intervention. Patients in the no intervention and combined exercise and telephone groups were randomised to receive or not receive a placebo health food tablet.\n Primary outcome was self reported score for knee pain on the Western Ontario and McMaster universities (WOMAC) osteoarthritis index at two years. Secondary outcomes included knee specific physical function and stiffness (scored on WOMAC index), general physical function (scored on SF-36 questionnaire), psychological outlook (scored on hospital anxiety and depression scale), and isometric muscle strength.\n 600 (76.3%) participants completed the study. At 24 months, highly significant reductions in knee pain were apparent for the pooled exercise groups compared with the non-exercise groups (mean difference -0.82, 95% confidence interval -1.3 to -0.3). Similar improvements were observed at 6, 12, and 18 months. Regular telephone contact alone did not reduce pain. The reduction in pain was greater the closer patients adhered to the exercise plan.\n A simple home based exercise programme can significantly reduce knee pain. The lack of improvement in patients who received only telephone contact suggests that improvements are not just due to psychosocial effects because of contact with the therapist.", "nan", "The childhood diarrhoea-management guidelines of the World Health Organization/United Nations Children's Fund (WHO/UNICEF) now include zinc treatment, 20 mg per day for 10 days. To determine if a dispersible zinc sulphate tablet formulation is associated with increased risk of vomiting or regurgitation following the initial, first treatment dose, a double-blind, placebo-controlled randomized clinical trial was carried out in the Dhaka hospital of ICDDR,B: Centre for Health and Population Research (n=800) and in an adjacent NGO outpatient clinic (n=800). Children were randomized to one of three groups: no treatment, placebo, or zinc sulphate tablet (20 mg). They were then observed for 60 minutes, and all vomiting or regurgitation episodes were recorded. When compared with placebo, zinc treatment resulted in an attributable risk increase of 14% for vomiting and 5.2% for regurgitation. The median time to vomiting among those receiving zinc was 9.6 minutes and was limited to one episode in 91.2% of the cases. Overall, the proportion of 60-minute post-treatment vomiting attributable to zinc, placebo, and the illness episode was estimated to be 40%, 26%, and 34% respectively. The dispersible zinc sulphate tablet formulation at a dose of 20 mg is associated with increased risks of vomiting and regurgitation. Both are transient side-effects.", "Many asthmatic patients are reluctant to follow the medication schedule prescribed for them and turn to alternative treatment methods. The results of this study indicate that one such method, laser acupuncture, does not prevent exercise-induced asthma.", "Forty four subjects were treated for benzodiazepine dependence. The withdrawal programme lasted for 10 weeks and included regular group support sessions. Patients were also treated with either propranolol, placebo or \"no pill\" under double blind conditions. Twenty three patients complied with the full treatment regimen and completed the trial. The outcome of treatment was moderately successful, with 8 out of the 23 patients stopping their tranquilizers and a further 11 achieving a reduction of 50% or more of their original benzodiazepine dose. Tranquilizer dependence is a difficult condition to treat, but preliminary results suggest that propranolol is helpful in reducing the symptoms of benzodiazepine withdrawal.", "Frequent blood glucose (BG) monitoring is a critical component of diabetes management, yet many barriers exist to consistent monitoring.\n In this randomized controlled trial, we sought to determine if an educational manual, the Blood Sugar Monitoring Owner's Manual (BGMOM), could increase adherence to BG monitoring by helping patients form realistic expectations and responses to BG monitoring results. The 199 participants were recruited from a multidisciplinary diabetes clinic and had high-risk diabetes (hemoglobin A(1C) >or=8.0%); 35% had type 1 diabetes mellitus. Participants were randomized to 1 of 3 groups: BGMOM intervention (BGM+), attention control (BG meter only [MT]), or standard care (SC). The BGM+ and MT groups received BG meters and meter education; the BGM+ group also received BGMOM booklets. The SC group received usual care. Data gathered during 6 months of follow-up included BG monitoring frequency and hemoglobin A(1C) measurement.\n Monitoring frequency increased significantly in the BGM+ group (1.9 +/- 1.3 to 2.8 +/- 1.5 times daily, P<.001) but only slightly in the MT group (1.7 +/- 1.3 to 2.0 +/- 1.3 times daily). The BGM+ group experienced the greatest improvement in hemoglobin A(1C) level (BGM+: -0.13 +/- 1.28; MT: -0.04 +/- 1.31; SC: 0.04 +/- 1.10). Further, a higher percentage of those in the BGM+ group (61%) improved their glycemic control compared with the other groups (44%; P = .05). Finally, the BGM+ group displayed the most knowledge about the definition of hemoglobin A(1C) (P = .04) and reported the least amount of negative affect about out-of-range BG monitoring results (P = .03).\n As an adjunct to standard diabetes education and support, a manual such as the BGMOM can help optimize BG monitoring and glycemic control.", "A double-blind study was carried out in 18 patients with biliary and pancreatic disease to assess the use of pinaverium bromide in premedication for endoscopic retrograde cholangio-pancreatography and its effects on motor activity of the sphincter of Oddi. Patients were divided at random into three groups. One group received 100 mg pinaverium bromide twice daily for 3 days before and then 100 mg 1 hour before the examination, the second group received placebo, and the third had no medication. All patients received 10 to 20 mg diazepam intravenously 10 minutes before endoscopy. Assessments were made of the transit time of various endoscopic phases and patients' tolerance of the procedure. The effects of treatment on the sphincter of Oddi were estimated by means of endoscopic manometry. The results showed that pinaverium bromide allowed transit time reduction in endoscopic procedure, a greater tolerance on the part of the patient and marked reduction in the amplitude and duration of the phasic activity of the sphincter.", "Two hundred and ten subjects entered a trial to test the use of a chewing gum containing nicotine as an aid to stopping smoking. They were divided into three groups: nicotine chewing gum, placebo chewing gum, and control. The trial was double blind between the two chewing gum groups. After 1 month the percentage of confirmed non-smokers in the nicotine gum group was 34%, in placebo chewing gum group 37% and the control group 24%. By 6 months most of the non-smokers had relapsed, but the nicotine gum group (23%) was more successful than the placebo (5% or the control group (14%).", "The effectiveness of various tension-reducing techniques was investigated. Sixty-three subjects were randomly assigned to four treatment groups (EMG feedback, finger temperature feedback, EMG plus finger temperature feedback, autogenic training), a placebo control group, and a waiting-list control group. Physiological as well as a variety of cognitive measures were used to monitor changes in tension. The results showed no significant difference in effectiveness between the six groups. On virtually all cognitive measures there were significant decreases in tension, but not on the physiological measures. The decreases in tension on the cognitive measures were interpreted to be the results of non-specific (placebo) effects. These non-specific effects were not short-term, but did persist for at least three months after completion of treatment.", "The discovery of an endogenous opioid-mediated analgesic system has led to the search for its physiological roles and how it might be activated in natural conditions. Environmental and surgical stress and certain forms of transcutaneous electrical stimulation or acupuncture appear to activate this system. Several studies also suggest that this opioid system mediates placebo analgesia. Placebo reduces post-surgical pain in comparison with no treatment, and this analgesia is apparently reversed by the opioid antagonist, naloxone. However, these studies did not indicate whether naloxone and placebo exert their effects by common or by separate mechanisms. By administering hidden infusions of naloxone (in subjects unaware that the medication was being given) separate from the administration of a placebo, we were able to assess the effects of these two treatments independently. We report here evidence that placebo analgesia can occur after blockade of opioid mechanisms by naloxone and that naloxone can produce hyperalgesia independent of the placebo effect. The combined action of these effects is sufficient to explain the reversal of placebo analgesia by naloxone.", "To examine the effects of stress-management training on clinical outcomes in persons with rheumatoid arthritis (RA).\n Patients with RA (n = 141) were randomly assigned to 1 of 3 groups: a stress management group, an attention control group, or a standard care control group. The stress management and the attention control groups received a 10-week intervention followed by an additional 15-month maintenance phase.\n The stress management group showed statistically significant improvements on measures of helplessness, self-efficacy, coping, pain, and health status. Selected beneficial effects were still detectable at the 15-month followup evaluation.\n The data indicated that stress management interventions are capable of producing important clinical benefits for persons with RA.", "Several lines of evidence indicate that placebos produce analgesia through the activation of endogenous opioid systems. Recently, we showed that placebos may also produce respiratory depressant responses, a typical side-effect of narcotics, when a subject had a prior experience of respiratory depression in the course of narcotic treatment. In the present study, we report that the placebo respiratory depression can be induced after repeated administrations of the partial opioid agonist buprenorphine. The placebo respiratory depressant effect that resulted from the buprenorphine conditioning was completely blocked by a dose of 10 mg of naloxone, indicating that it was mediated by endogenous opioids. These findings show that placebos act, via the activation of opioid receptors, not only on pain mechanisms but on the respiratory centres as well, thus mimicking a typical side-effect of narcotics. In addition, the experimental procedure we used did not produce any expectation of respiratory depression and, similarly, the subjects did not notice any sign of respiratory discomfort. Thus, the placebo respiratory depression elicited in the present study cannot be explained on the basis of cognitive or motivational mechanisms. Rather, it appears to be a sequence effect due to learning, thus suggesting a conditioning mechanism mediated by endogenous opioids.", "nan", "Several medical areas that require patient compliance have successfully used psychological interventions emphasizing cognitive behavioral components. However, there are no published reports on the effect of cognitive behavioral interventions on oral hygiene in adults using an experimental design. For this study, 100 male veterans age 21-65 years were randomly assigned to 4 groups (cognitive behavioral, education, attention control, and control); to compare the effectiveness of these interventions on oral hygiene, a 5-week pre-test-post-test design was utilized. The dependent variables were self-report of brushing and flossing behavior and dental plaque levels utilizing the plaque index. After the interventions, there was only one significant difference between the control and the experimental groups for brushing frequency. There were no significant differences among the experimental groups for this intervention. The self-report of flossing frequency significantly increased in all 3 treatment groups, but there were no significant differences between these groups. In addition, plaque levels decreased significantly in all 3 experimental groups. Plaque levels in the cognitive behavioral group were significantly lower than those of the educational group. It was not possible to determine whether the greater plaque reduction in the cognitive-behavioral group could be attributed to the nature of the intervention or to the extra time spent with patients in the cognitive behavioral group.", "The efficacy of transcutaneous electrical nerve stimulation (TENS) as an adjunct to narcotic medications for the management of postoperative pain was assessed in a prospective, randomized, controlled study of patients following coronary artery bypass graft (CABG) surgery with the right or left internal thoracic artery (ITA). Forty-five male patients (mean age, 57 +/- 6 years) were randomly assigned to (1) TENS, (2) placebo TENS, or (3) control treatments (n = 15 each), following extubation and during the 24- to 72-h postoperative period. Two-way analysis of variance tests indicated no significant differences among treatment groups for (1) pain with cough, (2) narcotic medication intake, (3) FVC, (4) FEV1, and (5) PEFR (p > 0.05). However, pain at rest reported by the TENS group was significantly lower than that reported by the control group (treatment main effect; p < 0.04), although no significant differences were observed between the TENS and placebo or between the placebo and control groups (p > 0.05). All six criterion measures were characterized by significant changes over time for the entire group (n = 45; time main effect; p < 0.01), as follows: pain and medication intake were similar on days 1 and 2, but were significantly less on day 3, and pulmonary functions were significantly lower than preoperatively on day 1, decreased further on day 2, and despite an improvement on day 3, remained significantly lower than preoperative values (p < 0.01). This study suggests that the addition of TENS, applied continuously during the immediate postoperative period following CABG with ITA, may not be advantageous in pain management or the prevention of pulmonary dysfunction.", "This prospective, randomised controlled trial, with three parallel groups, patient and observer blinded for verum and sham acupuncture and a follow up of 3 months raises the question: \"Does a combination of acupuncture and conservative orthopedic treatment improve conservative orthopedic treatment in chronic low back pain (LBP). 186 in-patients of a LBP rehabilitation center with a history of LBP >or=6 weeks, VAS >or=50mm, and no pending compensation claims, were selected; for the three random group 4 weeks of treatment was applied. 174 patients met the protocol criteria and reported after treatment, 124 reported after 3 months follow up. Patients were assorted 4 strata: chronic LBP, <or=0.5 years, 0.5-2 years, 2-5 years, >or=5 years. Analysis was by intention to treat. Group 1 (Verum+COT) received 12 treatments of verum acupuncture and conservative orthopedic treatment (COT). Group 2 (Sham+COT) received 12 treatments of non-specific needling and COT. Group 3 (nil+COT) received COT alone. Verum- and Sham acupuncture were blinded against patient and examiner. The primary endpoints were pain reduction >or=50% on VAS 3 months after the end of the treatment protocol. Secondary endpoints were pain reduction >or=50% on VAS and treatment efficacy on a four-point box scale directly after the end of the treatment protocol and treatment efficacy after 3 months. In the whole sample a pain relief of >or=50% on VAS was reported directly after the end of treatment protocol: Verum+COT 65% (95%CI 51-77%), Sham+COT 34% (95%ci 22-49%), nil+COT 43% (95%ci 29-58%) - results are significant for Verum+COT over Sham+COT (P<or=0.02). The results after 3 months are: Verum+COT 77% (95%ci 62-88%), Sham+COT 29% (95%ci 16-46%), nil+Cot 14% (95%ci 4-30%) - effects are significant for Verum+COT over Sham+COT (P<or=0.001) and for Verum+COT over nil+COT (P<0.001). No difference was found in the mobility of the patients nor in the intake of NSAID diclofenac. Our conclusion is that acupuncture can be an important supplement of conservative orthopedic treatment in the management of chronic LBP.", "In 45 headache patients the relationship between sensory suggestibility and three measures of treatment effect--ratings on (1) intensity of headaches; (2) efficacy of drugs, and (3) physician's competence--was investigated in a double-blind long-term crossover study. Subjects scoring high on sensory suggestibility clearly showed more relief of headaches upon the analgesic as well as upon the placebo. The physician's competence was rated higher by high-suggestible patients, whereas ratings on drug efficacy were low in all patients. The seemingly controversial behavior of high-suggestible patients was interpreted as a call for continuation of the physician's efforts in spite of the relief the patients already achieved.", "Our purpose was to investigate the efficacy of P6 acupressure in reducing or relieving symptoms of nausea with or without vomiting and retching during pregnancy.\n Symptomatic pregnant volunteers (n=161) participated in a 7-day community-based clinical trial. All participants were assigned to one of three groups (i.e., P6 acupressure, placebo [acupressure bands inappropriately placed], or control) on the basis of a process of blocked randomization. Data were analyzed by error bar charts and analysis of variance of difference scores.\n Of 161 women, 149 (92.5%) completed the protocol. Irrespective of group assignment, participants reported significant decreases in nausea (p<0.0009) and vomiting or retching (p<0.0009). However, there was no differential treatment effect as a result of acupressure.\n There was no apparent medical benefit from the use of P6 acupressure. Our findings differ from other recently published studies that did not include a control group.", "nan", "Gastroscopic procedure causes nausea and retching in many patients. Recently, alternative methods have been employed in an effort to reduce these symptoms. The Neiguan point (P6) is an acupuncture point that has been used for approximately 3,000 years to overcome gastric symptoms including nausea and retching. The aim of this study was to investigate the effects of the stimulation of the P6 acupoint on swallowing, nausea and retching during the gastroscopic procedure.\n Three hundred and twenty-seven patients who visited the gastroenterology unit for dyspeptic complaints were included in the study. A portable transcutaneous electrical nerve stimulation device (Reliefband; Maven Lab, Yuba City, CA) was used for acustimulation. The device was attached 15 minutes before the endoscopic procedure and no sedation was applied. The device was turned on in 78 patients (Group 1). The device was attached but not turned on in another 79 patients (Group 2). In Group 3, the device was attached to the Sham point (n: 79). In Group 4 the procedure was performed with no attachments (n: 77). Fourteen patients dropped out of the study because esophagogastroduodenoscopy could not be completed due to patient intolerance or to obstruction in the upper gastrointestinal tract. After the procedure, each patient's opinion about the severity of nausea and retching was measured on a visual analogue scale. Distress in swallowing and the impression of the endoscopist during the procedure were scored from 1 to 4. Patients were queried regarding their willingness to undergo re-endoscopy.\n Groups were compared regarding their distress in swallowing the endoscope, nausea and retching, the impression of the endoscopist during the procedure and their acceptance of re-endoscopy. Groups 1, 2, 3 and 4 were compared using the chi-square test, and no significant difference was observed between the groups (p>0.05).\n Acustimulation of the Neiguan (P6) acupoint does not relieve patients of the nausea observed during gastroscopy, and its application does not facilitate the procedure.", "To determine the effect of chiropractic care on jet lag in Finnish junior elite athletes.\n Fifteen Finnish junior elite athletes.\n Through use of a table of random numbers, each athlete was assigned by sex to one of 3 groups: chiropractic adjustment, sham adjustment, or control. As needed, the chiropractic adjustment group athletes (n = 5) were adjusted on a daily basis by licensed chiropractors using a toggle/recoil procedure. The sham adjustment group athletes (n = 5) received sham adjustments on a daily basis by licensed chiropractors. The control group athletes (n = 5) were not adjusted or sham-adjusted but participated in all test protocols. Sleep, jet lag, chiropractic, and mood data (the last acquired through use of the Profile of Mood States) were collected on a daily basis for 18 consecutive days.\n Repeated-measures analyses of variance (3 x 2) of total mood disturbance scores and heart rate variables indicated that there were no significant (.05 level) between-group differences. Sleep data were analyzed through use of a 3 x 2, repeated-measures multivariate analysis of variance. Pillai's trace indicated that there were no between-group differences. Self-assessment of jet lag by participants after traveling to Georgia and after returning to Finland showed no between-group differences.\n It was concluded that chiropractic care did not reduce the effects of jet lag.", "nan", "The purpose of the study is to investigate the effectiveness of acupressure on fatigue in patients with end-stage renal-disease (ESRD). The study was a randomized control trial; qualified patients were randomly assigned into acupressure group, sham group or control group. A total of 106 participants were included in the study. The measures included the revised Piper Fatigue Scale (PFS), VAS of Fatigue, the Pittsburgh Sleep Quality Index and the Beck Depression Inventory. Data of fatigue measures were collected at pretreatment and a week following treatment. Sleep quality and depression were collected during post-test only. The statistical methods included the descriptive statistics, one-way ANOVA, ANCOVA, and repeated-measures ANOVA. ANCOVA that adjusted for differences in baseline fatigue scores (PFS), post-test of depression and sleep quality, result was significant, F(2,100)=3.99, p=0.02. Post-hoc tests revealed that patients in the acupressure group were significantly having lower scores of fatigue than patients in the control group. ANCOVA results also significant for VAS of Fatigue among groups, F(2,100)=5.63, p=0.003. Comparisons indicated that there were significant differences between the acupressure group and the control group (p=0.01) and between the sham group and control group (p=0.003). Predialysis fatigue was assessed routinely by using a rating of 0-10. Repeated-measures ANOVA results demonstrate the group main effect was significant in the perceived fatigue (F(2,88)=19.46, p<0.001). Follow-up tests indicated there were significant differences between the acupressure group and the control group (p<0.001) and between the sham group and control group (p<0.001). The study provided an alternative method for health care providers to managing ESRD patients with fatigue.", "To investigate the effectiveness of acupuncture compared with minimal acupuncture and with no acupuncture in patients with tension-type headache.\n Three armed randomised controlled multicentre trial.\n 28 outpatient centres in Germany.\n 270 patients (74% women, mean age 43 (SD 13) years) with episodic or chronic tension-type headache.\n Acupuncture, minimal acupuncture (superficial needling at non-acupuncture points), or waiting list control. Acupuncture and minimal acupuncture were administered by specialised physicians and consisted of 12 sessions per patient over eight weeks.\n Difference in numbers of days with headache between the four weeks before randomisation and weeks 9-12 after randomisation, as recorded by participants in headache diaries.\n The number of days with headache decreased by 7.2 (SD 6.5) days in the acupuncture group compared with 6.6 (SD 6.0) days in the minimal acupuncture group and 1.5 (SD 3.7) days in the waiting list group (difference: acupuncture v minimal acupuncture, 0.6 days, 95% confidence interval -1.5 to 2.6 days, P = 0.58; acupuncture v waiting list, 5.7 days, 3.9 to 7.5 days, P < 0.001). The proportion of responders (at least 50% reduction in days with headache) was 46% in the acupuncture group, 35% in the minimal acupuncture group, and 4% in the waiting list group.\n The acupuncture intervention investigated in this trial was more effective than no treatment but not significantly more effective than minimal acupuncture for the treatment of tension-type headache.\n ISRCTN9737659.", "The purpose of the study is to test the effectiveness of acupressure on sleep quality of end-stage renal disease patients. The study was a randomized controlled trial; qualified patients in the dialysis centers of four major hospitals were randomly assigned into an acupressure group, a sham acupressure group, and a control group. A total of 98 participants were included in the study. The main outcomes measured were the Pittsburgh sleep quality index (PSQI) and the sleep log. Data were collected at pretreatment and following treatment. Primary statistical analysis was by means of Analysis of Covariance, the Kruskal-Wallis Test and repeated measure ANOVA. The results indicated that PSQI scores of the acupressure group have a significantly greater improvement (p < 0.01) than the control group. However, there were no differences between the acupressure group and the sham group or the sham group and the control group (p > 0.05). Subscales of PSQI were further analyzed. Results demonstrated significant differences between the acupressure group and the control group in subjective sleep quality (p = 0.009), sleep duration (p = 0.004), habitual sleep efficiency (p = 0.001), and sleep sufficiency (p = 0.004). Significant differences in the subscale of subjective sleep quality (p = 0.003) between the sham acupressure group and the control group were also observed. Sleep log data showed that the acupressure group significantly decreased awake time and improved quality of sleep over time more than the control group (p < 0.01). The improvement could be seen as soon as the acupoints massage was implemented, and it was maintained through the post intervention.\n Copyright 2002 Elsevier Science Ltd.", "Auricular acupuncture can be an effective treatment for acute anxiety, but there is a lack of direct comparisons of acupuncture to proven standard drug treatments. In this study we compared the efficacy of auricular acupuncture with intranasal midazolam, placebo acupuncture, and no treatment for reducing dental anxiety. Patients having dental extractions (n = 67) were randomized to (i) auricular acupuncture, (ii) placebo acupuncture, and (iii) intranasal midazolam and compared with a no treatment group. Anxiety was assessed before the interventions, at 30 min, and after the dental extraction. Physiological variables were assessed continuously. With the no treatment group as control, the auricular acupuncture group, and the midazolam group were significantly less anxious at 30 min as compared with patients in the placebo acupuncture group (Spielberger Stait-Trait Anxiety Inventory X1, P = 0.012 and <0.001, respectively). In addition, patient compliance assessed by the dentist was significantly improved if auricular acupuncture or application of intranasal midazolam had been performed (P = 0.032 and 0.049, respectively). In conclusion, both, auricular acupuncture and intranasal midazolam were similarly effective for the treatment of dental anxiety.", "Sedative drugs are generally given to patients undergoing colonoscopy. However, the benefit of routinely administered conscious sedation for colonoscopy has not been studied in adequately controlled trials.\n We randomly assigned 180 patients scheduled for diagnostic colonoscopy into 3 groups: (1) sedation with intravenous midazolam (midazolam group); (2) sedation with intravenous saline (placebo group); and (3) no intravenous cannula (control group). The endoscopist assessed the procedure immediately after the examination. The patients completed a questionnaire before leaving the endoscopy unit. Another questionnaire was sent to the patients 2 weeks after the examination. Answers were mainly given on a 100 mm visual analog scale.\n Shortly after the procedure, the patients in the midazolam group rated the examination less difficult than those in the placebo group (30 vs. 40 mm; p < 0.05; visual analog scale, 0 to 100 mm: 0 = not at all, 100 = extremely). However, no significant difference was found between midazolam and control groups (30 vs. 36 mm, respectively). Otherwise, there were no differences between the three groups with respect to the patients' or endoscopists' assessments or the examination time.\n Routinely administered sedation does not markedly increase patient tolerance or make colonoscopy technically easier.", "To determine the feasibility, in terms of acceptability to patients, physicians and other staff; data return and statistical power of a study to elucidate the relative contributions of specific and non-specific effects in homeopathic treatment of dermatitis.\n Randomised, controlled 4-arm trial, 2 arms double-blind.\n Outpatient clinic, Royal London Homoeopathic Hospital.\n Seventy-five adult patients with dermatitis.\n Patients were randomly allocated to: 'fast track' open verum homeopathy, 'fast track' double-blind verum homeopathy, 'fast track' double-blind placebo homeopathy or waiting list control.\n One hundred millimeter visual analogue scale of overall symptom severity; 10 point digital scores of sleep, itching, skin condition; weekly 5-point Likert scale of topical steroid use; Dermatology Life Quality Index at entry and completion.\n Recruitment was below target, but the study was acceptable to staff and feasible. Blinded patients were more likely to withdraw (P=0.021, chi2 test). After correction for baseline differences and multiple comparisons, no outcome measure showed statistically significant between group differences. Blindness appeared to have a negative effect, but this was confounded by differential withdrawal.\n A definitive trial of this design is unlikely to discriminate the relative contributions of the non-specific and specific effects to the outcome of homeopathic treatment of dermatitis, because of patient preference issues.", "63 pts affected by CIN of various degrees were randomly divided into 3 groups in order to evaluate the pain experienced during laser vaporization of the lesion. All pts were premenopausal and ages ranged between 19 and 39 years. 21 pts received Naproxene Sodium (550 mg) 30 minutes before surgery; 21 pts received placebo and 21 pts received no drug. Laser vaporization was performed with a Coherent System 451 CO2 laser with a power setting of 28 W/cm2 and a spot size of 1.8 mm. The severity of pain was assessed by means of a Visual Analogue Scale. The mean VAS value was 19 for the group treated with Naproxene Sodium; the mean VAS value was 20 for the placebo group and 23 for the group which received no pre-operative drug. Analysis of data from the 3 groups showed no statistically significant difference. Analgesia or anaesthesia before laser surgery for CIN is not a necessity.", "One hundred twenty patients about to receive their first treatment with potentially nauseant cancer chemotherapy were randomized to one of six antiemetic treatments: (1) no treatment; (2) placebo; (3) prochlorperazine (PCPZ), 10 mg; (4) delta 9-tetrahydrocannabinol (THC), 5 mg; (5) THC, 10 mg; (6) THC, 15 mg. Four doses of each medication were given orally at 4-hour intervals starting 2 hours before chemotherapy. A study nurse was responsible for both objective (nurse) and subjective (patient) symptom questionnaires. Serum levels were obtained at intervals for cross-reacting cannabinoids. Physiologic measurements including intraocular pressure (IOP), blood pressure, and pulmonary function were also recorded. In summary, the patients were remarkably free of adverse physiologic effects. All intraocular pressures before and after treatment were within the normal range, although a surprising statistically significant increase in IOP occurred in the group receiving 5 mg THC.", "BACKGROUND AND OBJECTIVE: This study investigates (1) whether treatment by homeopaths is more efficacious than self-selected conventional health care and (2) whether self-treatment with self-selected homeopathic medicines is more efficacious than placebo in preventing childhood upper respiratory tract infections (URTIs). DESIGN: A four-arm randomized controlled trial involving two independent investigations, one open and pragmatic (evaluating the effect of treatment by homeopaths including homeopathic medicines) and one double-blinded (evaluating the effect of self-treatment with homeopathic medicine). PATIENTS: The planned sample size is 420 children below the age of 10, recruited by a postal invitation to all children diagnosed with URTIs when attending a casualty department in Trondheim, Norway. INTERVENTIONS: The children are randomly assigned to receive either (1) self-selected homeopathic medicine or placebo (270 patients), (2) treatment by one of four different homeopaths who could prescribe any homeopathic medicine (75 patients), or (3) waiting list control using self-selected conventional health care (75 patients). MAIN OUTCOME MEASURE: Total URTI symptom scores from patients' diary over 12 weeks. PLAN: The results of these two studies (available at the end of 2004) have the potential to provide information about the efficacy of treatment by homeopaths independently from the efficacy of homeopathic medicines in children with URTIs.", "It is not clear whether segmental innocuous stimulation has a stronger analgesic effect than segmental noxious stimulation for chronic pain and whether the fading of current sensation during treatment interferes with the analgesic effect, as suggested by the gate control theory. Electrical stimulation (by way of Interferential Current) applied at the pain area (segmental) was administered to 4 groups of patients with osteoarthritis (OA) knee pain. Two groups were administered with noxious stimulation (30% above pain threshold) and two with innocuous stimulation (30% below pain threshold). In each group half of the patients received a fixed current intensity while the other half raised the intensity continuously during treatment whenever fading of sensation was perceived. Group 5 and 6 received sham stimulation and no treatment, respectively. The outcome measures were: chronic pain intensity, morning stiffness, range of motion (ROM), pain threshold and % pain reduction. Both noxious and innocuous stimulation significantly decreased chronic pain (P<0.001) and morning stiffness (P<0.01) and significantly increased pain threshold (P<0.001) and ROM (P<0.001) compared with the control groups. Nevertheless, noxious stimulation decreased pain intensity (P<0.05) and increased pain threshold (P<0.001) significantly more than innocuous stimulation. No differences in treatment outcomes were found between adjusted and unadjusted stimulation. (a) Interferential current is very effective for chronic OA knee pain, (b) segmental noxious stimulation produces a stronger analgesic effect than segmental innocuous stimulation, (c) the fading of sensation during treatment, does not decrease the analgesic effect. Possible mechanisms explaining the findings are discussed.", "One-hundred-sixteen patients suffering from vascular headache (migraine or combined migraine and tension) were, after 4 weeks of pretreatment baseline headache monitoring, randomly assigned to one of four conditions: (a) thermal biofeedback with adjunctive relaxation training (TBF); (b) TBF plus cognitive therapy; (c) pseudomediation as an ostensible attention-placebo control; or (d) headache monitoring. The first three groups received 16 individual sessions over 8 weeks, while the fourth group continued to monitor headaches. All groups then monitored headaches for a 4-week posttreatment baseline. Analyses revealed that all treated groups improved significantly more than the headache monitoring group with no significant differences among the three treated groups. On a measure of clinically significant improvement, the two TBF groups had slightly higher (51%) degree of improvement than the meditation group (37.5%). It is argued that the attention-placebo control became an active relaxation condition.", "Patients usually fear fiberoptic bronchoscopy (FBS) and they report a low level of satisfaction after this examination. We evaluated the efficacy of acupuncture in decreasing patient anxiety before diagnostic FBS and in improving tolerance to the examination. In a prospective double-blind study, we enrolled 48 patients scheduled to undergo diagnostic FBS. Patients were randomly assigned to one of three groups. Group A (16 patients): standard FBS, with airway topic anesthesia; Group B (16 patients): standard FBS, with airway topic anesthesia and acupuncture treatment; Group C (16 patients): standard FBS, with airway topic anesthesia and sham acupuncture. EKG, non-invasive arterial pressure, and pulse oximetry were monitored on a routine basis. We evaluated patient anxiety before and after acupuncture and, at the end of FBS, the discomfort suffered during the examination by a 100-mm Visual Analog Scale (VAS). Patient satisfaction in Group A was 50% worse than in Group B (p = 0.04). We observed a strong, even if not statistically significant, tendency toward a lower pre-FBS anxiety in Group B. Patients in group C had values very close to those recorded in group A. We observed no adverse event and no differences in cardio-respiratory parameters in these three groups; in particular, we did not observe a respiratory depression in Group B. Acupuncture seems an effective resource for a Thoracic Endoscopic Room to improve patient tolerance to FBS.", "Given the inherent side effects associated with both opioid and nonopioid analgesic drugs, a nonpharmacologic therapy that could decrease the need for analgesic medication would be valuable. We designed a sham-controlled study to assess the effect of the intensity of transcutaneous acupoint electrical stimulation (TAES) on postoperative patient-controlled analgesia (PCA) requirement for hydromorphone (HM), the incidence of opioid-related side effects, and the recovery profile after lower abdominal surgery. One hundred one healthy consenting women undergoing lower abdominal procedures with a standardized general anesthetic technique were randomly assigned to one of four postoperative analgesic treatment regimens: Group I (n = 26) PCA only; Group II (n = 25), PCA + sham-TAES (no electrical stimulation); Group III (n = 25), PCA + low-TAES (4-5 mA of electrical stimulation); Group IV (n = 25), PCA + high-TAES (9-12 mA of electrical stimulation). The PCA device was programmed to deliver HM, 0.2-0.4 mg intravenously boluses \"on demand,\" with a minimum lockout interval of 10 min. The TAES skin electrodes were placed at the Hegu acupoint on the nondominant hand and on both sides of the surgical incision. The TAES frequency was set in the dense-and-disperse mode, alternating at 2 Hz and 100 Hz every 3 s, with stimulation of the hand and incision alternated every 6 s. The patients in Groups II-IV were instructed to use TAES every 2 h for 30 min while awake. After discontinuation of PCA, oral pain medications were administered on demand. The postoperative PCA-HM requirement, pain scores, opioid-related side effects, and requirements for antiemetic and antipruritic medication were recorded. High-TAES decreased the HM requirement by 65% and reduced the duration of PCA therapy, as well as the incidence of nausea, dizziness, and pruritus. Low-TAES produced a 34% decrease in the HM requirement compared with only 23% in the \"sham\" TAES group. We conclude that high-TAES produced a significant decrease in the PCA opioid requirement and opioid-related side effects after low intraabdominal surgery.", "Within 24 hours after abortion, 62 patients with a mean gestational age of 19 weeks, who had either induced (n = 50) or spontaneous (n = 12) abortions were randomly allocated to three groups: Group 1, bromocriptine 2.5 mg twice daily for 2 weeks; Group 2, placebo tablets 1 tablet twice daily for 2 weeks; Group 3, no treatment. Fifty-two patients completed the study (bromocriptine n = 18, placebo n = 18 and no treatment n = 16). Placebo had no apparent influence on breast symptoms. In both the placebo group and the untreated group, breast pain and milk secretion peaked on days 3 to 7, and milk secretion often continued for 3 weeks. Only 3/34 (9%) of untreated and placebo treated patients were free of breast symptoms. Compared with placebo, bromocriptine caused a significant reduction in the objective assessment score of breast tenderness (p less than 0.05) and milk secretion (p less than 0.01), in serum prolactin (PRL) (p less than 0.001) and in the subjective assessment score of breast pain (p less than 0.01) and milk secretion (p less than 0.01). Alleviation of breast pain and prevention of milk secretion appears to be indicated after second-trimester abortion, and treatment with bromocriptine is efficacious.", "This randomized controlled clinical trial evaluates the effectiveness of outpatient group cognitive/educational treatment for patients with the fibromyalgia (FM) syndrome. We hypothesized that the combination of group education with cognitive treatment aimed at developing pain coping skills would be more effective than group education alone.\n 131 patients with FM were randomly assigned to 3 conditions: an experimental condition, which was the combined cognitive/educational intervention (ECO); an attention control condition consisting of group education plus group discussion (EDI); and a waiting list control (WLC). For the treatment conditions ECO and EDI, assessments were made 2 weeks before treatment, at start of treatment, at post-treatment, and at 6 and 12 mo followup. WLC patients received only 3 assessments.\n There were no pretreatment differences between the groups, or between dropouts and patients who remained in the study. At post-treatment, and compared with the WLC, the ECO patients improved in knowledge about FM (p = 0.007) and pain coping (p < 0.001). EDI patients improved on pain coping (p = 0.005) and pain control (p = 0.002). EDI patients reported significantly less fear than ECO patients (p = 0.005). There were no other differential effects between ECO and EDI at post-treatment or 6 mo or 12 mo followup. Based on the reliability of change index for clinical significance, the relative short term success rates are 6.4 and 18.4% for ECO and EDI, respectively.\n The surplus value of a highly structured, 12 session group cognitive treatment added to group education cannot be supported by our study. In EDI, fear reduction might have enhanced pain coping and pain control, while poor compliance, the difficulty of homework assignments, and lack of individual support may have limited the effectiveness of ECO.", "The objective of this study was to determine the effects of a placebo treatment on cough in patients with cough associated with acute upper respiratory tract infection (URTI).\n Patients with dry or slightly productive cough associated with a history of URTI were recruited. Cough frequency (CF) over 15 minutes was recorded by means of a microphone connected to a pen recorder. Cough suppression time (CST) was recorded when patients were instructed by means of a red light to try not to cough. Patients received either a single dose of vitamin E (placebo treatment) or no treatment. CF and CST were recorded before and 15 minutes after treatment.\n Twenty-seven patients were randomized to placebo treatment and 27 to the no-treatment group (mean age 22.6 years). The median difference between post- and pretreatment CF was -3 in the no-treatment group and -18 in the placebo group (p = .0003). There was a significant increase in CST in the placebo group compared with no treatment (p = .027).\n The results demonstrate that placebo treatment has significant antitussive activity. This placebo effect may be related to generation of central neurotransmitters such as endogenous opioids.", "nan", "Exposure to high allergen levels in early life is a risk factor for the development of allergy. We previously reported limited effects of mite allergen impermeable mattress covers in the prevention and incidence of asthma and mite allergy (PIAMA) cohort at the age of 1 and 2 yr. We now present the results of follow-up at 4 yr objectives. To examine the effects of early reduction of house dust mite (HDM) allergen exposure by means of mattress covers on the incidence of allergy and asthma symptoms in the PIAMA birth cohort at the age of 4 yr. High-risk children (allergic mother) were prenatally recruited and randomly allocated to three groups; receiving mite allergen impermeable mattress covers (n = 416), placebo covers (n = 394) or no intervention (n = 472). At 4 yr of age, atopy was assessed by questionnaire; specific Immunoglobulin E (IgE) to inhalant and food allergens was measured in serum. Dust samples collected from the children's mattresses were analysed for mite allergens. Dermatophagoides farinae1 allergen (Der f 1) levels in dust were reduced in the active group. However, Dermatophagoides pteronissinus 1 (Der p 1) levels, sensitization and atopic symptoms were similar in all groups. We found no effect of mite allergen impermeable mattress covers on sensitization and atopy at 4 yr. Moreover, the allergen reducing effects of the covers had disappeared for one of the two mite allergens that were measured.", "This study was designed to assess the efficacy of oral transmucosal fentanyl citrate (OTFC) for premedication in an adult population and to determine its effects on anxiety, sedation, gastric volume, and gastric fluid acidity. The fentanyl citrate is incorporated in a lozenge mounted on a handle (oralet). The effects of OTFC, placebo oralet, and no premedication were compared in a prospective, double-blind study on 90 adult ASA physical status I and II patients undergoing same-day admission surgery. Patients were randomly assigned to one of three groups: OTFC group (n = 30), placebo group (n = 30), and control group (n = 30). Arterial blood pressure, heart rate, respiratory frequency, and oxygen saturation determined by pulse oximetry were recorded before any premedication was given, and then every 10 min until the patient was taken to the operating room. Baseline anxiety and sedation levels were assessed to ensure group similarity immediately before premedication was given and at the more anxiety-provoking phase upon entering the operating room. Anxiety levels were rated using the Spielberger State-Trait Anxiety Inventory short form and sedation levels were assessed with the Ramsay scale. Side effects, as reported by the patients, were also recorded. Gastric contents were aspirated via an orogastric tube after induction of anesthesia and were measured for volume and pH. No significant differences were found among the three groups in mean arterial pressure, heart rate, or respiratory frequency. Initial oxygen saturation levels in all groups decreased after 30 min but not less than 96% except for one patient in the OTFC group, who decreased to 88%. On entering the operating room, the OTFC group demonstrated significantly higher levels of anxiolysis than the control group, but no significant differences were seen between the OTFC and the placebo groups or the placebo and control groups. Mean gastric volumes (OTFC, 29 mL; placebo, 26 mL; control, 24 mL) and pH (OTFC, 2.0; placebo, 1.8; control, 2.1) were similar in all groups. There were no significant differences among the groups in levels of sedation achieved. Mild dizziness or light-headedness was the most commonly reported side effect in 23% of the OTFC group. In the OTFC group, 71.4% like the premedicant effect as compared to 46.4% of the placebo group. Most of the groups found the oralet method of premedicant delivery very acceptable. This study demonstrates that the OTFC oralet is an effective anxiolytic in adults. It has minimal side effects and is prepared in an acceptable format. There was no measurable increase in gastric contents or acidity in the oralet groups, compared to those patients who were given nothing by mouth.", "To evaluate the efficacy of Simulated Presence, a personalized approach to enhance well-being among nursing home residents with Alzheimer's disease and related dementia's (ADRD).\n Latin-Square, double blinded, 3-factor design with restrictive randomization of three treatments (the study intervention, a placebo audio tape of a person reading the newspaper, and usual care). The three factors were treatment, time, and facility type.\n Nine nursing homes in Eastern Massachusetts and Southern New Hampshire.\n Fifty-four subjects with documented ADRD who were aged 50 years or older, medically stable, had resided in their current nursing home for at least 3 months, and who had no planned discharge. All subjects had a history of agitated or withdrawn behaviors.\n The purpose of Simulated Presence is to provide a personalized intervention for persons with moderate to severe cognitive impairment. Through a unique testing process, some of the best loved memories of the ADRD person's lifetime are identified and then those memories are introduced to the patient in the format of a telephone conversation using a continuous play audio tape system. The intervention may be used for extended periods of time because each repetition is viewed as a fresh, live telephone call as a result of the short-term memory deficit of the person with ADRD.\n Direct observations of outcomes included using a newly developed scale, the Scale for the Observation of Agitation in Persons with Dementia, an agitation visual analog scale, the Positive Affect Rating Scale (mood and \"interest\"), a withdrawal visual analog scale, and facial diagrams of mood. Reported measures included daily staff observation logs of responses to interventions offered, and weekly staff surveys using the short-form Cohen-Mansfield Agitation Inventory and the Multidimensional Observation Scale for Elderly Subjects (mood and \"interest\"). Severity of dementia was assessed by the Mini-Mental State Exam, the Test for Severe Impairment, the Bedford Alzheimer's Nursing Scale, and the ADL Self-Performance Scale.\n Chi-square analysis of direct observations, using facial diagrams, revealed that Simulated Presence was equivalent to usual care (P = .141) and superior to placebo for producing a happy facial expression (P = .001). A positive effect was also documented in nursing staff observation logs using Analysis of Variance techniques (ANOVA) for subjects during Simulated Presence phases compared with the placebo phases (P < .001) and usual care phases (P < .001). According to ANOVA analyses of \"interest\" from weekly surveys, Simulated Presence was superior to both usual care (P = .001) and placebo (P = .008). We were unable to find evidence of significant differences (P < .05) among interventions for other direct observations and weekly reports of overall agitation or mood aspects of withdrawal. Subjects accepted the intervention most of the time, except for five subjects who refused it more than 50% of the time.\n This study provided evidence that Simulated Presence can be effective in enhancing well-being and decreasing problem behaviors in the nursing home setting as a substitute for or complement to usual care.", "In several large, well-designed, randomized, double-blind studies, the opiate antagonist naltrexone demonstrated efficacy in the treatment of alcohol dependence. Specifically, when combined with certain psychosocial therapies, naltrexone reduces the number of drinking days, heavy drinking, and time to relapse to alcohol use in alcohol-dependent individuals. Whether this efficacy can be generalized to individuals who have alcohol use disorders and present for treatment at front-line community treatment programs has not been well established.\n A total of 145 patients who presented for treatment at a rural community substance abuse treatment center were randomized to receive naltrexone 50 mg daily plus usual program treatment (n = 54), placebo plus usual treatment (n = 43), or usual treatment alone (n = 48) for 12 week. A total of 133 participants had at least one follow-up visit. Primary outcome measures included percent days drinking, average drinks per drinking day, average drinks per day, heavy drinking days (four or more for women and six or more for men), and time to first heavy drinking day. Secondary measures included changes in serum biological markers (alkaline phosphatase, alanine transaminase, aspartate transaminase, and gamma-glutamyltransferase), craving, and psychosocial functioning.\n In the intention-to-treat analysis, there were no between-group differences for any of the primary drinking outcomes at 12 weeks. In post hoc exploratory analyses, the entire sample of participants was divided into two new groups: (1) people who drank during the 2 weeks before the start of medication (entry drinkers) and (2) people who did not drink during this interval (entry abstainers). Entry abstainers were at an advantage at study entry in that they were significantly more likely to have an inpatient hospitalization immediately before entry into outpatient treatment. Mixed-model analysis of variance revealed a main effect for entry group at the 12-week treatment endpoint on the primary outcome measures of percent days drinking, average drinks per drinking day, average drinks per day, heavy drinking days, and time to first heavy drinking day. Participants in any of the randomized groups who were entry abstainers had significantly better improvement on all of the primary outcome measures. The abstainer groups that were randomized to placebo and usual treatment had significantly better outcomes than the entry drinkers in those perspective groups. However, for the naltrexone-treated group, entry drinkers and entry abstainers had similar improvement in drinking-related outcomes.\n These data suggest that naltrexone may offer particular benefit to patients who continue to drink during the early stages of the trial as compared with those who have achieved abstinence before treatment entry.", "Substantial evidence suggests that acupuncture-point stimulation may be effective in controlling side effects of chemotherapy.\n To examine the efficacy of an acustimulation wristband for the relief of chemotherapy-induced nausea.\n Randomized clinical trial using a 3-level crossover design.\n Three outpatient oncology clinics in the northeastern United States.\n Twenty-five women and 2 men who experienced moderate or more severe nausea following their first chemotherapy treatment.\n We compared active acustimulation of the Pericardium 6 (PC-6) point on the ventral surface of the wrist with sham acustimulation (a corresponding point on the posterior surface of the wrist). A control group received no acustimulation.\n Severity of nausea and quantity of antiemetic medication used.\n No statistically significant differences in average severity of nausea were observed between the 3 interventions. However, the data showed a difference close to statistical significance in the severity of delayed nausea reported during active acustimulation compared to no acustimulation (P <.06). In addition, patients took fewer antinausea pills during the active-acustimulation cycle of this experiment compared to the no-acustimulation phase (P < .05).\n Findings on the efficacy of an acustimulation band for the control of chemotherapy-induced nausea are positive but not conclusive. These findings provide ample justification for further study of acustimulation in clinical oncology.", "Investigated the effects of psychologically preparing patients for minor gynaecological surgery. A total of 59 women who were undergoing elective laparoscopy were assigned randomly to three experimental conditions: Preparation, in which an informative preoperative interview was conducted; placebo, in which a reassuring preoperative interview was held; and control, in which no contact was made prior to surgery. The women were assessed postoperatively in terms of pain, anxiety and attitudes and required to complete a follow-up questionnaire that followed a 3-week interval, which assessed subjective report of recovery rate. The results showed similar levels of pain report for all groups, although significantly fewer prepared patients requested postoperative analgesia. No differences in pain reports emerged at follow-up, although there was a tread for prepared patients to report a more rapid return to full health. The results are considered in the context of explanatory models that have been proposed to account for the effects of psychological preparation.", "The effectiveness of functional electrical stimulation (FES) has been investigated in chronic hemiplegia. The present study examines whether FES, given during acute stroke, was more effective in promoting motor recovery of the lower extremity and walking ability than standard rehabilitation alone.\n Forty-six subjects, 70.9+/-8.0 years old and 9.2+/-4.1 days after stroke, were assigned randomly to 1 of 3 groups receiving standard rehabilitation with FES or placebo stimulation or alone (control). FES was applied 30 minutes and placebo stimulation 60 minutes, 5 days per week for 3 weeks. Outcome measurements included composite spasticity score, maximum isometric voluntary contraction of ankle dorsi-flexors and planter-flexors, and walking ability. They were recorded before treatment, weekly during the 3-week treatment, and at week 8 after stroke.\n No significant differences were found in the baseline measurements. After 3 weeks of treatment, there was a significant reduction in the percentage of composite spasticity score, and a significant improvement in the ankle dorsiflexion torque, accompanied by an increase in agonist electromyogram and a reduction in electromyogram cocontraction ratio in the FES group, when compared with the other 2 groups (P<0.05). All subjects in the FES group were able to walk after treatment, and 84.6% of them returned home, in comparison with the placebo (53.3%) and control (46.2%, P<0.05) groups.\n Fifteen sessions of FES, applied to subjects with acute stroke plus standard rehabilitation, improved their motor and walking ability to the degree that more subjects were able to return to home.", "This prospective controlled trial investigated the efficacy of a manual-based clinical hypnosis intervention in alleviating pain in 80 pediatric cancer patients (6-16 years of age) undergoing regular lumbar punctures. Patients were randomly assigned to 1 of 4 groups: direct hypnosis with standard medical treatment, indirect hypnosis with standard medical treatment, attention control with standard medical treatment, and standard medical treatment alone. Patients in the hypnosis groups reported less pain and anxiety and were rated as demonstrating less behavioral distress than those in the control groups. Direct and indirect suggestions were equally effective, and the level of hypnotizability was significantly associated with treatment benefit in the hypnosis groups. Therapeutic benefit degraded when patients were switched to self-hypnosis. The study indicates that hypnosis is effective in preparing pediatric oncology patients for lumbar puncture, but the presence of the therapist may be critical.", "The roots of essential hypertension extend back into the first two decades of life, suggesting that effective intervention during those years may lead to a reduction in the incidence of adult hypertension. Decreasing the dietary sodium/potassium ratio offers a potentially effective approach to blood pressure reduction. This study tested the feasibility of 3-year sodium reduction or potassium supplementation in adolescents and the effect of these interventions on the rate of rise of blood pressure during adolescence. After 19,452 5th to 8th grade students were screened, 210 from the upper 15 percentiles of blood pressure distribution (105 boys, 105 girls) were randomly assigned to one of three groups: low sodium diet (70 mmol sodium intake per day), potassium chloride supplementation (normal diet plus 1 mmol/kg potassium chloride per day), or placebo (normal diet plus placebo capsule). Capsules for the potassium chloride and placebo groups were administered in a double blind protocol. Blood pressure was measured every 3 months for 3 years. The effect of the intervention was determined by comparing the rate of rise (slope) of blood pressure among the groups using a random-coefficient growth curve model. The boys groups and the girls placebo group had similar positive blood pressure slopes that were significantly different from zero. The girls low sodium group had a slightly negative slope (significantly lower than the slope of the girls placebo group), and the girls potassium group had a slightly positive slope. Both of these slopes were not significantly different from zero and were significantly lower than the slopes of the respective boys groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "Blood-donation-related symptoms such as dizziness and weakness discourage people from participating in this important health-related activity. Four hundred sixty-seven young adult, French-speaking blood donors were randomly assigned to (a) a condition in which they learned a possible preventive technique called applied tension and were asked to practice it from the time they got on the donation chair until they were just about to get up, (b) a placebo condition in which they learned applied tension and were asked to practice it from the time they got on the chair until the insertion of the donation needle, or (c) a no-treatment control condition. Donors assigned to the treatment condition reported significantly fewer blood-donation-related symptoms than did donors assigned to the other conditions and rated their likelihood of returning to give blood again as greater than did those in the no treatment condition. Among donors whose chairs were not reclined, participants in the treatment condition had significantly smaller heart rate reactions to blood donation than did those in the other conditions.\n 2006 APA, all rights reserved", "nan", "Unpleasant blood donation-related symptoms may discourage otherwise healthy, altruistic individuals from becoming repeat donors. This study examined a behavioral technique called applied muscle tension (AMT) that might reduce reactions.\n A total of 605 donors at mobile clinics were assigned to either an AMT treatment condition, a no-treatment control condition, or a placebo control condition. AMT involves repeated tensing of major muscles and was taught using an instructional video. Participants in the placebo control group watched the same video but were told to practice the technique only from the time they got on the donation chair until insertion of the needle, without being told that reactions are unlikely during this period.\n There were no differences between men assigned to the three conditions. Women donors assigned to the AMT condition reported significantly fewer donation-related symptoms, required less chair reclining for reactions, and were more likely to produce a full unit of blood than women in both the no-treatment and placebo control conditions. Women in the AMT condition also said they would be more likely to recommend it to a friend who was going to give blood, but there were no significant effects of AMT on the rated probability of giving blood again or blood pressure change.\n Although it was not universally effective and the mechanisms of its effects are unclear, AMT is a simple behavioral technique that may be useful in reducing reactions to blood donation.", "The specific aim of this study was to investigate the efficacy of elicitation of the relaxation response for the treatment of menopausal hot flashes and concurrent psychological symptoms. The volunteer sample consisted of 33 women, between the ages of 44 and 66 years, who were in general good health, with a minimum of 6 months without a menstrual period, experiencing at least five hot flashes per 24-h, and not using hormone replacement therapy. The setting was an outpatient clinic in a tertiary care teaching hospital. The interventions used were relaxation response training and an attention-control group and a daily symptom diary measuring both the frequency and intensity of hot flashes, the Spielberger State-Trait Anxiety Inventory (STAI), and the Profile of Mood Scale (POMS) were the measures used. This was a randomized, controlled, prospective study. Subjects were randomly assigned to one of three groups (relaxation response, reading, or control) for the 10-week study. The first 3 weeks of baseline measurement of frequency and intensity of hot flash symptoms, and the preintervention psychological scores were compared with the final 3 weeks measurement of frequency and intensity and the postintervention psychological scores for symptomatic improvement. The relaxation response group demonstrated significant reductions in hot flash intensity (p < 0.05), tension-anxiety (p < 0.05) and depression (p < 0.05). The reading group demonstrated significant reductions in trait-anxiety (p < 0.05) and confusion-bewilderment (p < 0.05). There were no significant changes for the control group. Daily elicitation of the relaxation response leads to significant reductions in hot flash intensity and the concurrent psychological symptoms of tension-anxiety and depression.", "The objective of this study was to assess whether nicotine replacement therapy, administered in a real-life situation, could reduce cigarette consumption in smokers who were not prepared to quit smoking. Daily smokers of more than 20 cigarettes per day who had no intention to quit smoking in the next 6 months were recruited from the general population and randomly assigned to either a 6-month treatment of nicotine (choice among a 15-mg nicotine patch, a 4-mg nicotine gum, a 10-mg nicotine inhaler, or a combination of these, N = 265), matching placebo products (N = 269), or no intervention (N = 389). Products were sent to participants by mail. Education was limited to a booklet. Of 923 participants, 879 (95%) were followed up after 6 months. Mean baseline consumption was 30 cigarettes per day in all groups. At 6 months, cigarette consumption decreased by a median of 10 cigarettes per day in the nicotine group, 7.5 in the placebo group, and 2.5 among controls ( < 0.04 for all pair-wise comparisons). Smoking cessation rates were low (2%-4%) and did not differ significantly between groups. Quit attempts were less frequent among controls (21%) than among the nicotine (28%, = 0.04) and placebo (27%, = 0.08) subjects. In conclusion, nicotine replacement therapy helped smokers reduce their cigarette consumption and maintain this reduction over 6 months, but a large part of this reduction was attributable to a placebo effect. Nicotine treatment for smoking reduction had no detectable impact on smoking cessation.", "Fifty outpatients with mild, chronic, mood-reactive depression whose mood improved markedly after a 10-day single-blind placebo trial were randomly assigned in a double-blind design either to have their placebo medication discontinued or to have it maintained for an additional 6 weeks. Half of the patients in each condition relapsed within 6 weeks, indicating that pill-taking itself does not influence maintenance of placebo response. Placebo response was more likely to be maintained in patients who were currently married. At the end of 3 months, the overall relapse rate was 58%. The authors raise questions about the utility of the initial 10-day placebo washout in antidepressant clinical trials, and they discuss limits on the generalizability of their findings.", "To investigate the benefit of adding acupuncture to a course of advice and exercise delivered by physiotherapists for pain reduction in patients with osteoarthritis of the knee.\n Multicentre, randomised controlled trial.\n 37 physiotherapy centres accepting primary care patients referred from general practitioners in the Midlands, United Kingdom.\n 352 adults aged 50 or more with a clinical diagnosis of knee osteoarthritis.\n Advice and exercise (n=116), advice and exercise plus true acupuncture (n=117), and advice and exercise plus non-penetrating acupuncture (n=119).\n The primary outcome was change in scores on the Western Ontario and McMaster Universities osteoarthritis index pain subscale at six months. Secondary outcomes included function, pain intensity, and unpleasantness of pain at two weeks, six weeks, six months, and 12 months.\n Follow-up rate at six months was 94%. The mean (SD) baseline pain score was 9.2 (3.8). At six months mean reductions in pain were 2.28 (3.8) for advice and exercise, 2.32 (3.6) for advice and exercise plus true acupuncture, and 2.53 (4.2) for advice and exercise plus non-penetrating acupuncture. Mean differences in change scores between advice and exercise alone and each acupuncture group were 0.08 (95% confidence interval -1.0 to 0.9) for advice and exercise plus true acupuncture and 0.25 (-0.8 to 1.3) for advice and exercise plus non-penetrating acupuncture. Similar non-significant differences were seen at other follow-up points. Compared with advice and exercise alone there were small, statistically significant improvements in pain intensity and unpleasantness at two and six weeks for true acupuncture and at all follow-up points for non-penetrating acupuncture.\n The addition of acupuncture to a course of advice and exercise for osteoarthritis of the knee delivered by physiotherapists provided no additional improvement in pain scores. Small benefits in pain intensity and unpleasantness were observed in both acupuncture groups, making it unlikely that this was due to acupuncture needling effects.\n Current Controlled Trials ISRCTN88597683 [controlled-trials.com] .", "nan", "Although the traditional treatment of headache has been pharmacological, there have been many attempts to treat headaches with other methods with mixed levels of success.\n To obtain preliminary data on the efficacy of the Trager approach in the treatment of chronic headache.\n Small-scale randomized controlled clinical trial.\n University-based clinic.\n Thirty-three volunteers with a self-reported history of chronic headache with at least one headache per week for at least 6 months.\n Medication only control group, medication and attention control group, and medication and Trager treatment group.\n Self-reported frequency, duration, and intensity of headache, medication usage and headache quality of life (HQOL) obtained at baseline and after a 6-week treatment period.\n Analyses of variance demonstrated significant improvement in HQOL for the Trager and attention control groups, and reduction in medication usage for the Trager group (P < 0.05). Within-group analyses revealed that participants randomized to Trager demonstrated a significant decrease in the frequency of headaches (P = 0.045), improvement in HQOL (P = 0.045), and a 44% decrease in medication usage (P = 0.03). Participants randomized to the attention control group demonstrated a significant improvement in HQOL (P = 0.035) and a 19% decrease in medication usage (P = 0.15). Participants randomized to the no-treatment control group revealed a significant increase in headache duration (P = 0.025) and intensity (P = 0.025), and a declination in HQOL (P = 0.035).\n The Trager approach decreased headache frequency and medication usage. Trager and physician attention improved HQOL. A larger, multi-site study is recommended.", "An important parallel exists between patients with seasonal affective disorder and institutionalized older adults. Many older patients, as a result of global physical decline and immobility, are confined to their rooms, experiencing little natural sunlight. Thus, institutionalized older adults are at risk for chronic light deprivation. Testing the hypothesis that chronic light deprivation might be responsible, at least in part, for some depression among institutionalized older adults, the aim of this study was to investigate the efficacy of morning bright light treatment on depression among older adults residing in a long-term care facility.\n In a placebo controlled, crossover design, participants (N = 10, six women and four men; M age = 83.8) received each of the following: (i) 1 week (5 days) of 10,000 lux (therapeutic dose); (ii) 1 week (5 days) of 300 lux (placebo); or 1 week of no treatment (control). Each week of light treatment was 5 consecutive days, 30 minutes daily, with a wash-out period consisting of 1 week between conditions.\n Geriatric Depression Scale (GDS) scores at baseline during all treatment conditions were positively correlated (r = .81, p < .01) with months of institutionalization, where participants with higher GDS scores experienced more time institutionalized. Scores on the GDS remained unchanged during the placebo and control conditions, but depression scores decreased significantly during the 10,000 lux treatment (pretest GDS M = 15 vs posttest GDS M = 11, p < .01). After the 10,000 lux treatment, 50% of the participants no longer scored in the depressed range. Improvement during the 10,000 lux condition was positively correlated (r = .62, p < .05) to baseline GDS scores, where participants with higher GDS scores experienced greater improvement following the 10,000 lux treatment.\n The results of the present study suggest that bright light treatment may be effective among institutionalized older adults, providing nonpharmacological intervention in the treatment of depression. Furthermore, the length of institutionalization may play an important role in determining the efficacy of bright light treatment for older adults in the nursing-home setting.", "This study examined the effects of chiropractic adjustments of the thoracic spine (T1-T5) on blood pressure and state anxiety in 21 patients with elevated blood pressure. Subjects were randomly assigned to one of three treatment conditions: active treatment, placebo treatment, or no treatment control. The adjustments were performed by a mechanical chiropractic adjusting device. Dependent measures obtained pre- and post-treatment included systolic and diastolic blood pressure, and state anxiety. Results indicated that systolic and diastolic blood pressure decreased significantly in the active treatment condition, whereas no significant changes occurred in the placebo and control conditions. State anxiety significantly decreased in the active and control conditions. Results provide support for the hypothesis that blood pressure is reduced following chiropractic treatment. Further study is needed to examine the long-term effects of chiropractic treatment on blood pressure.", "A controlled trial was undertaken to compare the efficacy of transcutaneous electrical nerve stimulation (TENS) with standard intramuscular opiate analgesia in the management of postoperative pain following appendicectomy. Consecutive patients undergoing emergency appendicectomy were randomised into control, sham TENS and active TENS groups. There was a significant decrease in pain severity and analgesic intake in both active and sham TENS groups when compared with the control group (P less than 0.01). No difference was demonstrated in pain severity between active and sham TENS groups but the active TENS group required slightly less analgesia. These results suggest that the major benefit of TENS in the postappendicectomy patient is due to its 'placebo effect' and its use in this situation cannot be recommended.", "High-dose chemotherapy poses considerable challenges to emesis management. Although prior studies suggest that acupuncture may reduce nausea and emesis, it is unclear whether such benefit comes from the nonspecific effects of attention and clinician-patient interaction.\n To compare the effectiveness of electroacupuncture vs minimal needling and mock electrical stimulation or antiemetic medications alone in controlling emesis among patients undergoing a highly emetogenic chemotherapy regimen.\n Three-arm, parallel-group, randomized controlled trial conducted from March 1996 to December 1997, with a 5-day study period and a 9-day follow-up.\n Oncology center at a university medical center.\n One hundred four women (mean age, 46 years) with high-risk breast cancer.\n Patients were randomly assigned to receive low-frequency electroacupuncture at classic antiemetic acupuncture points once daily for 5 days (n = 37); minimal needling at control points with mock electrostimulation on the same schedule (n = 33); or no adjunct needling (n = 34). All patients received concurrent triple antiemetic pharmacotherapy and high-dose chemotherapy (cyclophosphamide, cisplatin, and carmustine).\n Total number of emesis episodes occurring during the 5-day study period and the proportion of emesis-free days, compared among the 3 groups.\n The number of emesis episodes occurring during the 5 days was lower for patients receiving electroacupuncture compared with those receiving minimal needling or pharmacotherapy alone (median number of episodes, 5, 10, and 15, respectively; P<.001). The electroacupuncture group had fewer episodes of emesis than the minimal needling group (P<.001), whereas the minimal needling group had fewer episodes of emesis than the antiemetic pharmacotherapy alone group (P =.01). The differences among groups were not significant during the 9-day follow-up period (P =.18).\n In this study of patients with breast cancer receiving high-dose chemotherapy, adjunct electroacupuncture was more effective in controlling emesis than minimal needling or antiemetic pharmacotherapy alone, although the observed effect had limited duration. JAMA. 2000;284:2755-2761.", "To assess and compare the analgesic effects of orally administered glucose and sucrose and pacifiers. To determine the synergistic analgesic effect of sucrose and pacifiers.\n Randomised prospective study with validated behavioural acute pain rating scale.\n Maternity ward.\n 150 term newborns undergoing venepuncture randomly assigned to one of six treatment groups: no treatment; placebo (2 ml sterile water); 2 ml 30% glucose; 2 ml 30% sucrose; a pacifier; and 2 ml 30% sucrose followed by a pacifier.\n Median (interquartile) pain scores during venepuncture were 7 (5-10) for no treatment; 7 (6-10) for placebo (sterile water); 5 (3-7) for 30% glucose; 5 (2-8) for 30% sucrose; 2 (1-4) for pacifier; and 1 (1-2) for 30% sucrose plus pacifier. Mann-Whitney U test P values for comparisons of 30% glucose, 30% sucrose, pacifier, and 30% sucrose plus pacifier versus placebo (sterile water) were 0.005, 0.01, <0.0001, and <0.0001, respectively. Differences between group median pain scores for these comparisons were 2 (95% confidence interval 1 to 4), 2 (0 to 4), 5 (4 to 7), and 6 (5 to 8), respectively. P values for comparisons of 30% glucose, 30% sucrose, and 30% sucrose plus pacifier versus pacifier were 0.0001, 0.001, and 0.06, respectively. Differences between group medians for these comparisons were 3 (2 to 5), 3 (1 to 5), and 1 (0 to 2), respectively.\n The analgesic effects of concentrated sucrose and glucose and pacifiers are clinically apparent in newborns, pacifiers being more effective than sweet solutions. The association of sucrose and pacifier showed a trend towards lower scores compared with pacifiers alone. These simple and safe interventions should be widely used for minor procedures in neonates.", "Despite the popularity of acupuncture, evidence of its efficacy for reducing pain remains equivocal.\n To assess the efficacy and safety of traditional Chinese acupuncture (TCA) compared with sham acupuncture (needling at defined nonacupuncture points) and conservative therapy in patients with chronic pain due to osteoarthritis of the knee.\n Randomized, controlled trial.\n 315 primary care practices staffed by 320 practitioners with at least 2 years' experience in acupuncture.\n 1007 patients who had had chronic pain for at least 6 months due to osteoarthritis of the knee (American College of Rheumatology [ACR] criteria and Kellgren-Lawrence score of 2 or 3). Interventions: Up to 6 physiotherapy sessions and as-needed anti-inflammatory drugs plus 10 sessions of TCA, 10 sessions of sham acupuncture, or 10 physician visits within 6 weeks. Patients could request up to 5 additional sessions or visits if the initial treatment was viewed as being partially successful.\n Success rate, as defined by at least 36% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 26 weeks. Additional end points were WOMAC score and global patient assessment.\n Success rates were 53.1% for TCA, 51.0% for sham acupuncture, and 29.1% for conservative therapy. Acupuncture groups had higher success rates than conservative therapy groups (relative risk for TCA compared with conservative therapy, 1.75 [95% CI, 1.43 to 2.13]; relative risk for sham acupuncture compared with conservative therapy, 1.73 [CI, 1.42 to 2.11]). There was no difference between TCA and sham acupuncture (relative risk, 1.01 [CI, 0.87 to 1.17]).\n There was no blinding between acupuncture and traditional therapy and no monitoring of acupuncture compliance with study protocol. In general, practitioner-patient contacts were less intense in the conservative therapy group than in the TCA and sham acupuncture groups.\n Compared with physiotherapy and as-needed anti-inflammatory drugs, addition of either TCA or sham acupuncture led to greater improvement in WOMAC score at 26 weeks. No statistically significant difference was observed between TCA and sham acupuncture, suggesting that the observed differences could be due to placebo effects, differences in intensity of provider contact, or a physiologic effect of needling regardless of whether it is done according to TCA principles.", "Prospective, experimental, randomized, single-factor, pretest/posttest design.\n To examine the effects of a calcaneal and Achilles-tendon-taping technique, utilizing only 4 pieces of tape and not involving the medial arch, on the symptoms of plantar heel pain.\n Plantar fasciitis is one of the most common causes of heel and foot pain. Physical therapists have applied many techniques in an attempt to relieve the symptoms of plantar heel pain, including various taping methods for which there is little existing evidence.\n Subjects (n=41) were randomly assigned into 4 groups: (1) stretching of the plantar fascia, (2) calcaneal taping, (3) control (no treatment), and (4) sham taping. A visual analog scale (VAS) for pain and a patient-specific functional scale (PSFS) for functional activities were measured pretreatment and after 1 week of treatment (posttreatment).\n A significant difference was found posttreatment among the groups for the VAS (P < .001). Specifically, significant differences were found between stretching and calcaneal taping (mean + SD, 4.6 +/- 0.7 versus 2.7 +/- 1.8; P = .006), stretching and control (mean +/- SD, 4.6 +/- 0.7 versus 6.2 +/- 1.0; P = .026), calcaneal taping and control (mean +/- SD, 2.7 +/- 1.8 versus 6.2 +/- 1.0; P < .001), and calcaneal taping and sham taping (mean +/- SD, 2.7 +/- 1.8 versus 6.0 +/- 0.9; P < .001). No significant difference among groups was found for posttreatment PSFS (P = .078).\n Calcaneal taping was shown to be a more effective tool for the relief of plantar heel pain than stretching, sham taping, or no treatment.", "The purpose of this study was to evaluate pain scores and plasma beta-endorphin levels following a single spinal adjustive manipulation in subjects with acute low back pain. Eighteen subjects were randomly assigned to either a control group, which received no treatment; a sham group, which received only light physical contact (touch); or an experimental group, which received an adjustive manipulation at a specific lumbar segment. Following a standard protocol, all subjects were administered visual analog pain scales and venous blood was drawn 5 min prior to, 5 min after, and 30 min after intervention. Analysis of the pain scores indicated that there was a slight, but significant, reduction of pain in the experimental group, but no similar reduction in the control or sham groups. Furthermore, this reduction of pain in the experimental group was not accompanied any significant change in the plasma beta-endorphin concentration.", "Acupuncture is widely used to prevent migraine attacks, but the available evidence of its benefit is scarce.\n To investigate the effectiveness of acupuncture compared with sham acupuncture and with no acupuncture in patients with migraine.\n Three-group, randomized, controlled trial (April 2002-January 2003) involving 302 patients (88% women), mean (SD) age of 43 (11) years, with migraine headaches, based on International Headache Society criteria. Patients were treated at 18 outpatient centers in Germany.\n Acupuncture, sham acupuncture, or waiting list control. Acupuncture and sham acupuncture were administered by specialized physicians and consisted of 12 sessions per patient over 8 weeks. Patients completed headache diaries from 4 weeks before to 12 weeks after randomization and from week 21 to 24 after randomization.\n Difference in headache days of moderate or severe intensity between the 4 weeks before and weeks 9 to 12 after randomization.\n Between baseline and weeks 9 to 12, the mean (SD) number of days with headache of moderate or severe intensity decreased by 2.2 (2.7) days from a baseline of 5.2 (2.5) days in the acupuncture group compared with a decrease to 2.2 (2.7) days from a baseline of 5.0 (2.4) days in the sham acupuncture group, and by 0.8 (2.0) days from a baseline if 5.4 (3.0) days in the waiting list group. No difference was detected between the acupuncture and the sham acupuncture groups (0.0 days, 95% confidence interval, -0.7 to 0.7 days; P = .96) while there was a difference between the acupuncture group compared with the waiting list group (1.4 days; 95% confidence interval; 0.8-2.1 days; P<.001). The proportion of responders (reduction in headache days by at least 50%) was 51% in the acupuncture group, 53% in the sham acupuncture group, and 15% in the waiting list group.\n Acupuncture was no more effective than sham acupuncture in reducing migraine headaches although both interventions were more effective than a waiting list control.", "Breathlessness is a common and difficult symptom to treat in patients with cancer. Case reports suggest that nebulised furosemide can relieve breathlessness in such patients but few data are available.\n Patients with primary or secondary lung cancer and a Dyspnoea Exertion Scale score of >or=3 were recruited. Following familiarisation, patients received either nebulised furosemide 40 mg or nebulised 0.9% saline under double blind conditions or no treatment, in random order on 3 consecutive days. Patients undertook number reading and arm exercise tests to assess breathlessness and its impact, and were asked to report subjective benefit and any preference between nebulised treatments.\n 15 patients took part. There were no differences between furosemide, saline and no treatment in the outcomes of the number reading test (eg, mean number read per breath was 6.7, 6.4 and 6.7, respectively) or arm exercise test (eg, mean Borg score at maximum equivalent workload was 2.3, 2.5 and 2.7, respectively). No adverse effects were reported, although there was a small fall in forced expiratory volume in 1 s and forced vital capacity following saline. Six patients considered that their breathlessness improved with nebulised treatment, three preferring saline, one furosemide and two reporting they were of equal benefit.\n Our findings do not support a beneficial effect from nebulised furosemide in patients with cancer related breathlessness. Listed on the National Research Register (N0170118249) and the UK Clinical Research Network Portfolio Database (1428).", "Untreated pain during the transportation of patients after minor trauma is a common problem in emergency medicine. Because paramedics usually are not allowed to perform invasive procedures or to give drugs for pain treatment, a noninvasive, nondrug-based method would be helpful. Acupressure is a traditional Chinese treatment for pain that is based on pain relief followed by a short mechanical stimulation of specific points. Consequently, we tested the hypothesis that effective pain therapy is possible by paramedics who are trained in acupressure. In a double-blinded trial we included 60 trauma patients. We randomly assigned them into three groups (\"true points,\" \"sham-points,\" and \"no acupressure\"). An independent observer, blinded to the treatment assignment, recorded vital variables and visual analog scales for pain and anxiety before and after treatment. At the end of transport, we asked for ratings of overall satisfaction. For statistical evaluation, one-way analysis of variance and the Scheffé F test were used. P < 0.05 was considered statistically significant. Morphometric and demographic data and potential confounding factors such as age, sex, pain, anxiety, blood pressure, and heart rate before treatment did not differ among the groups. At the end of transport we found significantly less pain, anxiety, and heart rate and a greater satisfaction in the \"true points\" groups (P < 0.01). Our results show that acupressure is an effective and simple-to-learn treatment of pain in emergency trauma care and leads to an improvement of the quality of care in emergency transport. We suggest that this technique is easy to learn and risk free and may improve paramedic-based rescue systems.\n We tested, in a double-blinded manner, the hypothesis that acupressure could be an effective pain therapy in minor-trauma patients. Our results show that acupressure is an effective and simple-to-learn treatment of pain in emergency medical care and can improve the quality of care.", "In a prospective, double-blind study, we examined the effects of routine sedation and pharyngeal anesthesia on cardiorespiratory parameters during gastroscopy.\n Intravenous sedation and topical pharyngeal anesthesia are used to alleviate the discomfort during upper gastrointestinal endoscopy. Cardiorespiratory changes during gastroscopy are common.\n Two hundred fifty two consecutive outpatients undergoing gastroscopy were assigned into 4 groups: (1) sedation with intravenous midazolam and placebo throat spray (midazolam group), (2) placebo sedation and pharyngeal anesthesia with lidocaine throat spray (lidocaine group), (3) placebo sedation and placebo throat spray (placebo group), and (4) no intravenous cannula nor throat spray (control group). Arterial oxygen saturation (SaO2), systolic and diastolic blood pressure and continuous electrocardiogram were recorded before, during, and after the endoscopic procedure.\n Gastroscopy increased heart rate in all study groups. Premedication with intravenous midazolam or lidocaine spray alleviated this rise (P<0.001, repeated measures analysis of variance) and decreased the incidence of tachycardia. Similarly, sedation with midazolam or topical pharyngeal anesthesia decreased the rise in systolic blood pressure (P<0.001). Midazolam produced lower SaO2 values during gastroscopy compared with lidocaine, placebo or control groups (P<0.001). However, episodes of desaturation (SaO2 </=92) were no more common in the midazolam group than in other groups.\n Premedication with midazolam alleviated the rise in heart rate and systolic blood pressure but induced a statistically significant decrease in arterial oxygen saturation. However, gastroscopy proved to be a safe procedure both with and without sedation.", "Self-referred subjects (N = 227) thought to be at increased risk of developing diabetes who had fasting plasma glucose (FPG) values in the range of 5.5 to 7.7 mmol.L-1 on two consecutive occasions 2 weeks apart were randomized to sulfonylurea therapy (gliclazide, < or = 160 mg.d-1) or to a control group allocated either to double-blind placebo or to no tablets. Subjects were randomly allocated also to reinforced or basic healthy-living advice in a factorial design. A total of 201 subjects have been evaluated for 1 year in three English and two French hospital outpatient centers. Those allocated to sulfonylurea had a significant (P < .001) reduction in median FPG compared with the control group (6.0 mmol.L-1 to 5.6 mmol.L-1, P < .001, v 6.0 mmol.L-1 to 6.0 mmol.L-1, NS). Median hemoglobin A1c (HbA1c) also improved (P < .0002; 5.8% to 5.6%, P < .001, v 5.7% to 5.6%, NS), as did mean beta-cell function (62% to 70%, P < .01, v 62% to 61%, NS). Mean body weight was unchanged in subjects allocated to sulfonylurea (81.7 kg to 82.4 kg, NS), but decreased in the control group (81.6 kg to 80.4 kg, P < .01). More subjects in the sulfonylurea group versus the control group reported one or more minor symptoms of hypoglycemia over 1 year (50% v 24%, P < .0001). Only two subjects reported major hypoglycemic episodes requiring assistance, both of whom were taking sulfonylurea. Insulin sensitivity did not change between groups. Sulfonylurea therapy with gliclazide improved glycemic control and beta-cell function significantly in subjects with increased but not diabetic FPG levels. The study is being extended to determine whether sulfonylurea therapy prevents progression to non-insulin-dependent diabetes mellitus (NIDDM).", "To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) for its effectiveness in eliminating or minimizing discomfort during office-based flexible cystoscopy.\n A total of 148 patients were prospectively randomized into one of three groups: flexible cystoscopy with no analgesics, a placebo TENS, or an activated TENS. The patient data collected included patient parameters, number of previous flexible cystoscopies, visual analog pain scores during and after the procedure, surgeon's difficulty rating of procedure, and International Prostate Symptom Score before and 24 hours after the procedure.\n No statistically significant difference was found among the three groups regarding patient parameters. The visual analog pain scores were similar before and after the procedure. At 30 seconds, the mean visual analog scale score for the control group, placebo group, and TENS study group was 3.73, 3.65, and 3.52, respectively (control versus placebo, control versus active, and placebo versus active: P = 0.97, 0.29, and 0.53, respectively). At 1 and 5 minutes, the corresponding scores were 3.44, 4.37, and 3.50 (P = 0.88, P = 0.99, and P = 0.99) and 0.86, 1.23, and 0.88 (P = 0.97, P = 0.35, and P = 0.56), respectively. The surgeon's mean difficulty rating for the control procedures was 1.08 and for the placebo group was 2.30 (P = 0.02).\n All patients undergoing flexible cystoscopy in the office setting experienced discomfort. The TENS device provided no significant benefit for pain. The trend toward greater pain scores in the control group could be attributed to the greater degree of difficulty.", "To examine the potential role for a placebo cream in reducing reported needle pain severity in children, and the impact of age-related factors on pain self-report, a convenience sample of 117 children scheduled for venipuncture were randomly assigned to one of three treatments: (a) placebo cream with the suggestion that it might help reduce needle pain, (b) placebo cream with no indication as to the cream's purpose, and (c) no cream (control group). In allocation to treatment, children were stratified by age group, (3-7, 8-11, 12-17 years). They rated their needle pain severity (both predicted and reported) using the Faces Pain Scale, and rated their anxiety about the procedure using the Children's Anxiety and Pain Scale. Children in the cream groups were also asked whether they thought the cream had helped. Using video-tapes, an independent observer, blind to the placebo manipulation, rated each child's reaction to the needle. For the two groups receiving cream, 83% of those children told it might help stated that they believed it did, as compared with only 33% of children who received the cream but were told nothing of its purpose. These beliefs, however, were not reflected in self-report ratings of pain which showed no statistically significant treatment effect. Similarly, children who gave higher preprocedural anxiety ratings were no more likely to report less pain as a result of receiving the cream. There was, however, a treatment effect on the observer's ratings: children receiving cream plus suggestion were assigned significantly lower ratings of pain-related behaviour than those children who received the cream alone. While venipuncture was associated with only mild levels of pain, younger children, irrespective of treatment group, did report more pain than older children. Hierarchical regression analysis indicated that 60% of the variance in self-reported pain severity scores could be accounted for by how much the child thought the needle would hurt, how anxious the child was about receiving the needle, gender (higher pain ratings associated with girls), and estimated body surface area (higher pain ratings associated with smaller bodies). We conclude that the efficacy of placebo treatments for needle pain in children may depend on the suggestion of a possible benefit rather than upon treatment application per se.", "The effects of two homeopathic preparations, Opium and Raphanus, given in dilutions of 10(30) (15 HC) and 10(10) (5 HC) respectively, on the resumption of intestinal peristalsis after operations on the digestive tract were evaluated in a controlled, double-blind therapeutic trial involving patients from 12 hospitals. The patients were allocated at random into 4 groups of 150 each: 1 untreated group and 3 groups who received either Opium and Raphanus, or Opium and the placebo of Raphanus or the placebos of the two products. The results were assessed on the time elapsed between closure of the abdominal wall and the first faeces and (accessorily) the first bowel sounds and passing of flatus per rectum. Pre-operative and operative features were similar in all 4 groups. There was no significant difference in the effects of treatment between the groups, even when such predictive factors as type and duration of surgery and age were taken into account. It is concluded that the trial failed to demonstrate any effect of Opium or Raphanus on the resumption of intestinal peristalsis after digestive tract surgery. Nor did it confirm the activity of ultra-molecular dilutions claimed for this type of drugs.", "Sedating children safely and effectively for minor laceration repair is a well-recognized clinical problem. A randomized, double-blind, and controlled study was conducted to evaluate the efficacy of intranasal midazolam for reducing stress during the suturing of lacerations in preschool children. Fifty-nine children with simple lacerations that required suturing were randomly assigned to one of three groups. Group 1 received intranasal midazolam, 0.4 mg/kg, prior to suturing. Group 2 received an equivalent volume of normal saline intranasally prior to suturing as a placebo. Group 3 was the control group and received no intervention prior to suturing. Heart rate, respiratory rate, blood pressure, and pulse oximetry were monitored at 5-minute intervals throughout the procedure. Subjective variables were also measured at 5-minute intervals and included a cry score, a motion score, and a struggle score. Parent satisfaction was measured via a short telephone interview the following day. There were no significant differences in outcome between the placebo group and the control group. Their results were pooled and compared with the results for the midazolam group. The midazolam group showed significant reductions for mean heart rate, maximum heart rate, and maximum systolic blood pressure when compared with the placebo/control group. Scores for two of the three subjective variables, cry and struggle, were significantly reduced for the midazolam group. The papoose board was considered unnecessary in retrospect for more than half of patients in the midazolam group compared with only one fifth of patients in the placebo/control group.(ABSTRACT TRUNCATED AT 250 WORDS)", "The present study describes a 16-week trial of the use of a combination of biofeedback and relaxation techniques for the treatment of hypertension. Twenty-two hypertensive patients were randomly allocated to one of three groups: (1) diastolic blood pressure feedback, electromyographic feedback, and verbal relaxation; (2) sham blood pressure feedback; and (3) no treatment. For the 14 patients completing active treatment during an initial or crossover period, the average changes in blood pressure as measured outside the laboratory were minimal (0/-1 and +1/0 mm Hg, supine and standing, respectively). Average blood pressure reduction in the laboratory was no greater with active than with sham blood pressure feedback (-3/-2 vs. -5/-2 mm Hg). One subject, however, after showing no change in blood pressure during sham feedback, achieved pronounced and prolonged improvement following active treatment. Overall results do not support the usefulness of these techniques as primary therapy in most hypertensives.", "Acupuncture has traditionally been used in China in the treatment of bronchial asthma and is being increasingly applied in Western countries. Although there are many published studies on acupuncture and asthma, few meet the scientific criteria necessary to prove the effectiveness of acupuncture.\n To examine the short- and long-term effects of real versus sham or no acupuncture in patients with bronchial asthma.\n Randomized partially blinded study with three parallel groups.\n Sixty-six (66) patients of both genders (mean age, 39 years) with mild-to-moderate persistent bronchial asthma.\n After 2 weeks of run-in, the patients with asthma were randomized to receive either real (23 patients) or sham acupuncture (23 patients) or no acupuncture (20 patients). Two acupuncture periods (each 4 weeks) within the first 4 months were followed by a 6-month observation.\n Primary outcome was the change of peak expiratory flow (PEF) variability at the end of the two treatment periods. Secondary outcomes were changes in forced expiratory volume in 1 second (FEV1), airway responsiveness, symptoms of asthma, the use of asthma drugs, and patients' well-being. Moreover, the effect of the intervention on eosinophils and eosinophil cationic protein (ECP) in blood and sputum was assessed.\n PEF variability decreased in all groups. In a subgroup of patients whose asthma medication remained fairly unchanged, PEF variability decreased significantly after needling of real as well as sham points at month 4 and 5 compared to controls (p < or = 0.005). However, there was no difference in the decrease of PEF variability between patients who had the blinded treatment with real or sham acupuncture. Most of the other functional and clinical variables did not differ from those obtained in controls. Eosinophils and ECP in blood and sputum decreased in all groups, but the only significant differences were found in blood eosinophil count at 4 months between sham acupuncture and the control group (p < 0.05) and at 10 months between real and sham acupuncture (p < 0.05) suggesting a possible effect on eosinophilic inflammation.\n In view of the fact that the effects after real and sham acupuncture compared to controls who had no needling at all were small, in all likelihood clinically irrelevant, our data do not seem to support the use of acupuncture in the management of pharmacologically well-treated patients with mild-to-moderate persistent asthma.", "Temazepam 20 mg (n = 18), midazolam 15 mg (n = 14), placebo (n = 15) or no medication (n = 20) were given orally as pre-operative hypnotic in healthy patients operated on under spinal analgesia. The quality of the pre-operative night's sleep assessed subjectively was significantly better in patients receiving temazepam (P = < 0.05) and midazolam (P = < 0.05) compared with those receiving no drug. The concentrations of cortisol and monoamine neurotransmitters or their metabolites in cerebrospinal fluid were of no value in monitoring the quality of the pre-operative night's sleep.", "To test effectiveness of static magnetic fields of two different configurations, produced by magnetic sleep pads, as adjunctive therapies in decreasing patient pain perception and improving functional status in individuals with fibromyalgia.\n Randomized, placebo-controlled, 6-month trial conducted from November 1997 through December 1998.\n Adults who met the 1990 American College of Rheumatology criteria for fibromyalgia were recruited through clinical referral and media announcements and evaluated at a university-based clinic.\n Subjects in Functional Pad A group used a pad for 6 months that provided whole-body exposure to a low, uniform static magnetic field of negative polarity. Subjects in the Functional Pad B group used a pad for 6 months that exposed them to a low static magnetic field that varied spatially and in polarity. Subjects in two Sham groups used pads that were identical in appearance and texture to the functional pads but contained inactive magnets; these groups were combined for analysis. Subjects in the Usual Care group continued with their established treatment regimens.\n Primary outcomes were the change scores at 6 months in the following measures: functional status (Fibromyalgia Impact Questionnaire), pain intensity ratings, tender point count, and a tender point pain intensity score.\n There was a significant difference among groups in pain intensity ratings (p = 0.03), with Functional Pad A group showing the greatest reduction from baseline at 6 months. All four groups showed a decline in number of tender points, but differences among the groups were not significant (p = 0.72). The functional pad groups showed the largest decline in total tender point pain intensity, but overall differences were not significant (p = 0.25). Improvement in functional status was greatest in the functional pad groups, but differences among groups were not significant (p = 0.23).\n Although the functional pad groups showed improvements in functional status, pain intensity level, tender point count, and tender point intensity after 6 months of treatment, with the exception of pain intensity level these improvements did not differ significantly from changes in the Sham group or in the Usual Care group.", "It has been reported that administration of prophylactic penicillin may prevent flare-ups or other undesirable posttreatment sequelae following root canal treatment. To test this hypothesis in a prospective study, 80 patients with a diagnosis of pulp necrosis and chronic apical periodontitis were divided into three groups: group A (prophylactic penicillin, AHA recommendation), group B (placebo, same regimen), and group C (no medication). Medications and evaluations were double-blinded. Patients reported their posttreatment events including incidence of flare-ups, incidence and severity of pain/swelling, and occurrence of adverse side effects. Differences in the three groups were determined statistically using chi-square tests. The outcome showed no significant difference (p = 0.68) among the three groups. That is, administration/nonadministration of penicillin prophylactically was unrelated to posttreatment signs and symptoms following canal preparation. Incidence of flare-ups was very low (1 of 80). Occurrence of pain in the mild-moderate levels was fairly high (approximately 70% overall), but was primarily in the mild category. Overall incidence of side effects was also very low (2 of 80). Severe levels of pain/swelling and flare-up incidence were low with no difference between administration or nonadministration of antibiotics. Based on our data, using penicillin (a potentially dangerous drug) prophylactically to control posttreatment symptoms is not recommended in cases of pulp necrosis and asymptomatic periapical pathosis.", "Twenty of sixty volunteers for smoking cessation were assigned to single-session hypnosis, 20 to a placebo control condition, and 20 to a no-treatment control condition. The single-session hypnosis group smoked significantly less cigarettes and were significantly more abstinent than a placebo control group and a no treatment control group at posttest, and 4-week, 12-week, 24-week and 48-week follow-ups.", "The involvement of the microcirculation in diabetic microangiopathy (DM) causes of severe incapacitation and ulceration. DM is characterized by a diffuse increase in flux, reduction in venoarteriolar response, associated with increased permeability resulting in edema and altered function of microlymphatics. In DM, skin PO2 is decreased and CO2 increased. In this condition capillary exchanges are altered and nutritional alterations eventually lead to skin lesions and ulcers. The aim of this randomized, placebo-controlled study was to evaluate the effect of local (foot) treatment with Essaven gel (EG) in 35 subjects with DM and neuropathy and localized, small (< 0.5 cm in maximum diameter) ulcers treated for 2 weeks. Measurements of laser Doppler (LDF) flux, PO2, and PCO2 in standardized conditions showed positive microcirculatory changes (a significant decrease of the abnormally increased flux and CO2 while PO2 increased) in the active EG group. Changes in the control group were not significant. In the placebo group variations were limited (mainly associated with skin manipulation and gel application). In conclusion, local treatment for 2 weeks with standardized application of EG acutely improves the microcirculation in subjects with DM and small ulceration.", "Protocol was carried out on 98 patients who were divided into three groups selected as (one control group, two \"placebo\" group, and three treated with acupuncture). This protocol showed that it was possible to improve cervical maturation if acupuncture sessions were carried out at the beginning of the 9th month. The Bishop scores in the three groups after 10 days interval show that there was a significant progression of 2.61 points in the group treated with acupuncture as against only 0.89 and 1.08 in the placebo and control groups.", "A cognitive remediation intervention was tested for its effect on functional outcomes of older care recipients with the diagnosis of dementia of the Alzheimer's type. The 78 community-dwelling care recipients were assessed on cognitive and behavioral functioning and randomly assigned to one of three conditions. Care recipients were expected to benefit most from active cognitive stimulation training as compared to placebo (passive) activity or wait-list control conditions. Following each weekly instruction session, the intervention was executed in the home by the family caregiver. Care recipients in the experimental group improved in cognitive and behavioral performance with treatment, but returned to former level of functioning by the 9th month. In contrast, the control group declined, while the placebo group remained static on these variables. These findings support the viability of remediation interventions in dementia despite the trajectory of cognitive decline.", "The objectives of the Cost Effectiveness of Lipid Lowering (CELL) study were twofold: (i) to evaluate the effect on overall cardiovascular risk of two types of health care advice (\"usual' and \"intensive') given in primary care, with or without pharmacological medication, with the target being to attain a moderate decrease in cholesterol; (ii) to evaluate the ritual of daily medication on compliance with the health care advice.\n A prospective, double-blind, randomized, controlled trial of 18 months' duration.\n The study was carried out in 32 health centres (out of a total of approximately 850) in Sweden.\n In all, 681 subjects, aged 30-59 years, were randomized. They had at least two cardiovascular risk factors in addition to moderate primary hyperlipidaemia (total cholesterol of at least 6.50 mmol L-1 on three occasions measured by Reflotron triglycerides less than 4.0 mmol L-1 and an LDL:HDL cholesterol ratio of more than 4.0). Most (87%) of the subjects were males; 626 subjects (92%) completed the 18-month follow-up.\n Half the subjects were randomized to 'intensive advice' given in group sessions led by doctors and nurses in primary care. The other half received 'usual advice'. In each of the two advice groups, one-third received an active lipid-lowering drug (pravastatin), one-third placebo, and one-third no drug at all. The tablets were titrated to achieve a 15% reduction in cholesterol.\n Changes in the overall Framingham risk score, and the development of adverse events in each group.\n The change in Framingham risk score was significantly reduced only in subjects taking lipid-lowering medication (together with intensive advice -0.13; 95% CI-0.20, -0.06, and together with usual advice -0.16; 95% CI -0.23, -0.09). The other subjects receiving intensive advice tended to fare better than those on usual advice. Lifestyle was not influenced significantly over the study period. The ritual of daily medication did not affect the outcome.\n As expected, lipid-lowering medication reduced serum cholesterol as well as overall cardiovascular risk in subjects with several risk factors for cardiovascular disease. There was no additive effect of intensive advice to these subjects. However, there was a meagre but significant effect of intensive advice in subjects not receiving active lipid-lowering drugs. One explanation for this difference may be that those on active lipid-lowering medication who had substantial drops in cholesterol might have felt less inclined to change their lifestyle compared with those on other treatment regimens who had less successful drops in cholesterol. There was no benefit from the ritual of taking daily medication.", "nan", "The effect of guar gum (15 g/day) on serum lipids and body weight of middle-aged hypercholesterolemic females was studied in a double-blind controlled trial. No consistent changes were observed in serum cholesterol, triglycerides or HDL cholesterol in patients taking guar gum, placebo or no medication at all. A highly significant decrease in body weight (62.9 +/- 2.1 vs. 60.4 +/- 2.2 kg, p < 0.0005, paired comparison) was seen in subjects receiving guar gum, whereas body weight remained constant in the other two groups. It is concluded that the daily ingestion of 15 g of guar gum results in a permanent weight loss, but does not influence serum lipids in females with hypercholesterolemia.", "Meditation training appears to be a promising psychological approach to the control of hypertension. However, most studies to date have had serious deficiencies. This study attempted to correct many of these deficiencies. Forty-one unmedicated hypertensives referred by general practitioners were randomly allocated to three groups. The treatment group (SRELAX) underwent training procedures based on Transcendental Meditation; a placebo control group (NSRELAX) underwent identical training but withou a mantra. Both procedures were compared with a no-treatment control group. The results showed modest reductions in blood pressure in both SRELAX and NSRELAX groups, compared with the no-treatment controls, with diastolic percentage reductions reaching significance (p < 0.05). There was considerable subject variation in response, with overall a mean decline i diastolic blood presure of 8-10% on 3-month follow-up. Possible indicators to predict the response of subjects are considered and reasons for the similarity in the effectiveness of the SRELAX and NSRELAX conditions are discussed.", "We undertook a randomized, double-blind, placebo-controlled study to investigate the therapeutic effect of vitamin B6 on carpal tunnel syndrome. After ten weeks in the study, ten of 15 patients improved (this included patients given placebo and those given no treatment). Vitamin B6 seems to have no advantage over conservative therapy for carpal tunnel syndrome. This study also suggests that repeat electrodiagnostic testing is no more useful than clinical symptoms in deciding on surgical intervention after unsuccessful conservative therapy.", "Postoperative pain control has received increasing attention by health care providers in the new millennium. In fact, pain was called the \"sixth vital sign\" by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) in 2001. The continued challenge of effective, safe analgesia in the outpatient setting has promoted the use of various devices designed to deliver local anesthetic directly to the surgical site. We endeavored to evaluate the efficacy of one such device currently in use.\n Prospective, randomized, placebo-controlled, double-blinded study.\n In this study, 49 consecutive patients were prospectively enrolled and randomly assigned to 1 of 3 groups after anterior cruciate ligament (ACL) reconstruction. Patients and investigators were blinded to group assignment. Group 1 (control group) received no catheter. Group 2 (placebo group) received an infusion catheter filled with saline. Group 3 (experimental group) received the same catheter filled with 0.25% bupivacaine solution. All patients received an ipsilateral femoral nerve block with 30 mL 0.25% bupivacaine and 20 mL 0.25% bupivacaine intra-articular injection. Patients recorded narcotic consumption and pain levels on visual analogue scales twice a day for 4 days after surgery. The catheters were removed on day 4 and physical therapy performance was recorded. The patients were then asked to continue to record pain ratings and medication consumption for an additional 4 days after catheter removal. All patients underwent bone-patellar tendon-bone ACL reconstruction by the senior author (P.D.F.). Seven patients were excluded from the study for ineffective femoral nerve block or catheter disconnection or occlusion. Narcotic consumption and the maximum, minimum, and median pain ratings were analyzed by analysis of variance.\n Median pain ratings show lower pain levels (P <.03) for both catheter groups versus the control group. No significant differences were found between the catheter groups for the median pain ratings, but lower maximum pain ratings were seen in the bupivacaine group compared with both placebo and no-catheter control subjects. Postoperative narcotic consumption was also lower in both catheter groups versus control subjects (P <.03). Physical therapy data revealed no difference in range of motion on postoperative day 4. More patients were able to perform straight leg raises during the first therapy session in both the saline placebo catheter group (70%) and bupivacaine group (72%) compared with the control group (50%).\n The data suggest some element of placebo benefit at median pain ratings but a protective effect of the bupivacaine at maximum pain levels.", "Women with orgasmic difficulties are commonly taught pubococcygeal (PC) muscle exercises which, practiced regularly, are said to have both specific and nonspecific beneficial effects on sexual enjoyment. The hypothesis tested was that women practicing these exercises over a 12-week period, would be more likely to become orgasmic than women practicing relaxation exercises, or than women in an attention-control group. Forty-six women were allocated to one of three groups, PC exercise, relaxation or control. PC muscle tone was measured and questionnaires about sexual response were completed over a 12-week period with a 6-month follow-up assessment. Results indicated that there was no difference in orgasmic outcome for the three groups during the experimental period. This was taken to imply that PC exercises are not of specific value for women with normal muscle tone. It remains possible that women with poor muscle tone are helped by the exercises and further research is considered necessary in this area.", "A prospective, randomized, controlled study was carried out to investigate the dilating and softening effect on the cervix of prostaglandin F2-alpha gel administered intracervically and of prostaglandin E2 tablets administered orally. A total of 581 patients were included in the study: 149 received 2.5 mg prostaglandin F2-alpha in gel form intracervically, 150 received 1 mg prostaglandin E2 in tablet form orally, 138 were given placebo gel and 144 no medication at all. In the group given prostaglandin F2-alpha gel intracervically, success was achieved in 85.8% of patients and partial success in 8.8%. In the group given prostaglandin E2 tablets orally, the results were successful in 29.4% and partially successful in 40.6%. The incidence of side effects in the group given prostaglandin F2-alpha gel was rather high - 53%. The results show that prostaglandin can bring about a certain softening of the cervix, but side effects cannot be ruled out. Nevertheless, priming of the cervix is to be recommended in young primigravidas." ]

[ "47848" ]

[ "Outpatient vs hospital methadone detoxification: an experimental comparison." ]

[ "This study compares the effectiveness and cost of hospital narcotic detoxificationand outpatient narcotic detoxification using methadone. Forty heroin addicts seeking narcotic withdrawal were randomly assigned to treatment groups. Methadone treatment was planned for no longer than 10 days while psychiatric supportive services were made available to continue as needed. The results suggest little benefit from either treatment approach and there was no significant differences between the treatments. Only a few patients achieved a drug-free state, and of those who did, all but one had returned to use of narcotics within 2 months. The data indicate that detoxification using methadone is a palliative procedure. The cost of outpatient detoxification can be accomplished for approximately one-tenth the cost of inhospital treatment without significantlyaltering the effectiveness of treatment." ]

[ "8577017", "10850938", "8838831", "3117982", "10578025", "8768018", "3093915", "10579275", "8083910", "6406649", "2511499" ]

[ "Early nutrition support modifies immune function in patients sustaining severe head injury.", "Early versus delayed feeding with an immune-enhancing diet in patients with severe head injuries.", "Enteral versus parenteral nutrition: effects on gastrointestinal function and metabolism.", "The effect of nutritional support on outcome from severe head injury.", "Nutritional assessment in head injured patients through the study of rapid turnover visceral proteins.", "[Total enteral nutrition versus mixed enteral and parenteral nutrition in patients at an intensive care unit].", "Nutritional support and neurotrauma: a critical review of early nutrition in forty-five acute head injury patients.", "Prospective, randomized, controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury.", "Enteral versus parenteral nutrition after severe closed head injury.", "The favorable effect of early parenteral feeding on survival in head-injured patients.", "The benefits of early jejunal hyperalimentation in the head-injured patient." ]

[ "Immunosuppression after severe head injury has been characterized by a depressed CD4 (T-helper/inducer)-CD8 (T-suppressor/cytotoxic) ratio and decreased T-lymphocyte responsiveness. Some investigators propose that this immunocompromized state is the result of an injury-associated hypermetabolic response and inadequate nutrient delivery during the immediate postinjury recovery phase. Previous observations from our institution demonstrated a preserved CD4-CD8 ratio in severe closed-head injury (CHI) patients receiving early parenteral nutrition (PN). It was unclear whether early PN or other aspects of patient care eliminated the characteristic depression in cellular immunity. The purpose of this study was to further investigate the effect of early PN on the immune function of CHI patients.\n Nine patients sustaining severe CHI were prospectively randomized to either early PN (n = 4) at day 1 or delayed PN (n = 5) at day 5. Total nutrient administration was delivered at 2 g of protein/kg per day and 40 nonprotein kcal/kg per day for at least the first 14 days of hospitalization. Analysis for T-lymphocyte expression of CD4 and CD8 cell surface antigens and interleukin-6 was performed on days 1, 3, 7, and 14 of hospitalization. T-lymphocyte activation in response to stimulation by concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogens (PWM) was also assessed on these days.\n Significant increases in total CD4 cell counts (2048 +/- 194 to 2809 +/- 129 vs 1728 +/- 347 to 1825 +/- 563, p < .05) and CD4% (42.6 +/- 4.4% to 56.2 +/- 2.6% vs 36.6 +/- 6.6% to 36.6 +/- 11.3%, p < .05) were observed at day 14 in patients receiving early vs delayed PN. An improved lymphocyte response from baseline to day 14 after Con A stimulation was demonstrated in the early PN group (3850 +/- 1596 to 16144 +/- 5024 cpm, p < .05). A significant rise in the CD4-CD8 ratio over baseline to day 14 was also noted in the early PN group (1.43 +/- 0.17 to 2.38 +/- 0.54, p < .05).\n The early aggressive nutrition support of CHI patients appears to modify immunologic function by increasing CD4 cells, CD4-CD8 ratios, and T-lymphocyte responsiveness to Con A.", "Although early enteral feeding clearly reduces septic morbidity after blunt and penetrating trauma, data for head-injured patients are conflicting. This study examines the effects of early vs delayed enteral feedings on outcome in patients with severe closed-head injuries with a Glasgow Coma Scale (GCS) score greater than 3 and less than 11.\n Thirty patients were prospectively randomized to receive an immune-enhancing diet (Impact with fiber) early (initiated < 72 hours after trauma) delivered via an endoscopically placed nasoenteric tube (Stay-Put) or late (administered after gastric ileus resolved). This formula was continued for 14 days or until the patient tolerated oral feeding. Goal rate of nutrition was 21 nonprotein cal/kg/d and 0.3 g N/kg/d.\n Two patients in the early group were excluded due to inability to place the tube, and one patient in the late group died before 72 hours. Five of the remaining 27 died, 1 in the early group and 4 in the late group. There were no significant differences between the groups in length of stay, intensive care unit (ICU) days, significant infection, or GCS score. However, major infection correlated inversely with admission GCS score (R = -0.6, p < .003). Time to reach a GCS score of 14 was significantly longer in patients with significant infections compared with those without (p < .02).\n No difference in length of stay or infectious complications is shown in patients with severe closed-head injury when they are given early vs delayed feeding using an immune-enhancing formula. Severity of the head injury is closely associated with significant infection.", "The effects of total parenteral nutrition (TPN) versus enteral nutrition (TEN) were studied in 34 patients following major neurosurgery. Measurements were made of resting energy expenditure (REE), urea production rate (UPR), visceral proteins, parameters of liver and pancreas function, as well as gastrointestinal absorption. To predict nutritional status, nutritional index (NI) was calculated. UPR revealed no significant differences between the groups. After 12 days of TEN, however, synthesis of visceral proteins increased significantly. In addition, NI improved after TEN (p < 0.05), whereas it remained unchanged after TPN. Thrombocyte and lymphocyte counts rose predominately during enteral nutrition. Only in the TEN group was REE increased by 18% and Glasgow Coma Scale (GCS) enhanced from Day 6 on. Exogenous insulin demand was enhanced in the parenterally fed group, and bilirubin (p < 0.05), amylase (p < 0.05), and lipase (p < 0.01) rose significantly, as did gamma-glutamyl-transferase (p < 0.0005) and alkaline phosphatase (p < 0.0005). After 12 d of TPN, vitamin A absorption was significantly attenuated, indicating reduced fat absorption compared to TEN. Carbohydrate absorption did not show significant changes between the groups. Only during TPN did mean values of xylose absorption remain below the normal range. Therefore, enteral nutrition following neurosurgical procedures is associated with an accelerated normalization of nutritional status and an improved substrate tolerance. TEN opposes early postoperative absorption disturbances of the small intestine.", "Fifty-one brain-injured patients with peak 24-hour admission Glasgow Coma Scale (GCS) scores of 4 to 10 were prospectively randomly assigned to receive total parenteral (TPN) or enteral (EN) nutrition. Patients were studied from hospital admission to 18 days postinjury. Outcome was assessed by the Glasgow Outcome Scale at 3 months, 6 months, and 1 year postinjury. The TPN group received a significantly higher cumulative mean intake of protein than the EN group (mean +/- standard error of the mean: 1.35 +/- 0.12 vs. 0.91 +/- 0.9 gm/kg/day; p = 0.004). Mean cumulative caloric balance was also significantly higher in the TPN than in the EN group (75.6% +/- 5.13% vs. 59% +/- 4.26%; p = 0.02). Nitrogen balance was significantly more negative in the EN group during the 1st week postinjury (p = 0.002). The incidence of pneumonia, urinary tract infections, septic shock, and infections was not significantly different between groups. Classic nutritional assessment parameters such as anergy screens, total lymphocyte counts, and albumin levels were not significantly different between groups. The 11 patients in the EN group who did not tolerate tube feedings for 1 week postinjury had a significantly higher incidence of septic shock (p = 0.008). The change over time in GCS scores between groups was significantly different, with the TPN group showing a mean four-point increase in GCS score compared with a three-point increase in the EN group (p = 0.02). At 3 months the TPN group had a significantly higher percentage of favorable outcomes (43.5% vs. 17.9%, respectively; p = 0.05). At 6 months, 43.5% of the TPN group had a favorable outcome while 32.1% of the EN group had a favorable outcome (p = 0.29). By 1 year, 47.8% of the TPN group and 32.1% of the EN group had a favorable outcome (p = 0.20). In conclusion, more calories and protein usually can be administered to acute brain injury patients via the TPN route than by EN feedings via nasogastric or nasoduodenal routes. Traditional parameters for nutritional assessment are not useful in studying the efficacy of nutritional support during the first 2 weeks after head injury. Neurological recovery from head injury occurs more rapidly in patients with better early nutritional support.", "Nutritional monitoring of rapid turnover visceral protein is important in the recognition of malnutrition in patients admitted to the Intensive Care Unit (ICU). We studied prealbumin and retinol-binding protein in patients who received three different kinds of artificial nutrition in order to evaluate the appropriateness of artificial nutrition.\n 45 consecutive head injury patients received enteral (Group A), parenteral (Group B) or both enteral and parenteral nutrition (Group C) at random. We considered these parameters: prealbumin, retinol binding protein and nitrogen balance before (T1), after 3 (T2), 7 (T3) and 11 (T4) days after the beginning of study. Statistical analysis was performed with Kruskal-Wallis test and Bonferroni's t -test.\n Plasma prealbumin and Retinol binding protein (RBP) showed an increasing of basal values during the study period in all groups (< 0.0001) and more significantly in group A (Enteral nutrition P < 0. 001 vs Total parenteral nutrition (TPN) and Enteral P< 0.01 vs Enteral and parenteral nutrition).\n Data obtained in the present study indicate that a laboratory is essential for monitoring nutritional assessment and for checking the appropriateness of nutritional therapy. We found prealbumin to be the most sensitive measure and found it to be the test of choice for early assessment and intervention.\n Copyright 1999 Harcourt Publishers Ltd.", "To compare metabolic, nutritional and epidemiological data in two groups of patients, one receiving total enteral nutrition, via nasoenteric tube, and one receiving both enteral and parenteral nutrition.\n A prospective, randomized study.\n A general ICU, with both medical and surgical patients, in a big regional University and National Health Service hospital.\n 24 patients requiring Intensive Care after major surgery or because suffering from severe head injury or major neurological impairment.\n All patients initially received total parenteral nutrition: after 4 days 12 patients were \"weaned\" to total enteral nutrition and 12 stayed on mixed parenteral and enteral nutrition. LABORATORY INVESTIGATIONS AND OBSERVATIONAL DATA: Blood levels of albumin, prealbumin, transferrin, ALT, AST, bilirubin, blood urea, blood glucose, total linfocite count, and nutritional and epidemiological data such as nitrogen balance, calorie intake, diarrhea incidence, blood and sputum cultures and radiologic evidence of pneumonia are analysed.\n At T1, NET patients were able to reduce their nitrogen losses (0.27.1 g/kg +/-0.12 vs 0.35 +/- 0.13 at TO; p < 0.05) and improve nitrogen balance (-9 +/- 7 vs -2 +/- 6 at T0; p < 0.05); they also had a better total linfocite count (2034 +/- 304 vs. 1413 +/- 360 of the MISTA group; p < 0.05), and a lower incidence of pneumonia as documented by sputum cultures and radiograms.\n Patients fed with both parenteral and enteral nutrition did no better than those on total enteral nutrition as far as nutritional and metabolic indices were concerned; they also seemed more prone to infections than those on total enteral nutrition, indicating that mixed nutrition may result in more stable feeding, but this does not seem to have any beneficial nutritional, immunological and metabolic effect.", "Forty-five acute head trauma patients were randomized into a neurotrauma nutritional study to compare the efficacy of two forms of standard nutritional supplementation; namely total parenteral nutrition (TPN) versus enteral nutrition (NG). Forty patients were male, 5 were female, with a median age of 28 years. The mean admitting Glasgow coma scale score was 5.8. Patients were given high calorie and nitrogen feedings for the 14 days of the study period in an attempt to achieve positive calorie and nitrogen balance. TPN patients had significantly higher mean daily nitrogen intakes (P less than 0.01) and mean daily nitrogen losses (P less than 0.001) than the NG fed patients; however, no significant differences were discovered with respect to maintenance of serum albumin levels, weight loss, the incidence of infection, nitrogen balance, and final outcome. The exaggerated nitrogen excretion experienced by patients fed large nitrogen loads illustrates a problem in achieving nitrogen equilibrium in acute head injured patients.", "To determine the effect of early enhanced enteral nutrition (EN) on clinical outcome of head-injured patients.\n Prospective, randomized, controlled trial.\n Tertiary neurosurgical and trauma center.\n Eighty-two patients suffering head injury and requiring mechanical ventilation.\n Patients were randomized to receive standard EN (gradually increased from 15 mL/hr up to estimated energy and nitrogen requirements) or enhanced EN (started at a feeding rate that met estimated energy and nitrogen requirements) from day 1. Good neurologic outcome (Glasgow Outcome Scale score of 4 or 5) was determined at 3 and 6 months after injury, and the incidence of infective and total complications was determined during the hospital stay up to 6 months.\n Disease severity assessed by best preintubation Glasgow Coma Scale score, pupillary responses, Injury Severity Score, Acute Physiology and Chronic Health Evaluation II score, computed tomographic scan categorization, and age was similar in both groups. Intervention patients had a higher percentage of energy (p = .0008) and nitrogen (p<.0001) requirements met by EN in the first week after injury. Neurologic outcome at 6 months was similar between groups, but there was a tendency for more intervention patients to have a good neurologic outcome at 3 months than control patients (61% vs. 39%, p = .08). Fewer intervention patients had an infective complication (61% vs. 85%, p = .02) or more than one total complication (37% vs. 61%, p = .046) compared with control patients. Enhanced EN was associated with a reduction in the ratio of serum concentration of C-reactive protein to albumin up to day 6 after injury (p = .004).\n Enhanced EN appears to accelerate neurologic recovery and reduces both the incidence of major complications and postinjury inflammatory responses.", "We measured energy expenditure (MREE) and nitrogen excretion (UUN) in patients with severe head injury randomized to early parenteral (TPN, n = 21) or jejunal (ENT, n = 27) feeding with identical formulations. The MREE rose to 2400 +/- 531 kcal/day in both groups and remained at 135% +/- 26% to 146% +/- 42% of predicted energy expenditure over 4 weeks. Nitrogen excretion peaked the second week at 33.4 +/- 10 (TPN) and 31.2 +/- 7.5 (ENT) g N/day. Both routes were equally effective at meeting nutritional goals (1.2 x MREE, 2.5 g protein/kg/day intake, stabilized albumin and transferrin levels). Infections were equally frequent: 1.86 episodes/TPN patient versus 1.89 episodes/ENT patient. While patient charges were much greater for TPN, the hospital costs were similar for TPN and ENT support regimens. These findings show that patients with head injuries are hypermetabolic for weeks, that only 27% are capable of spontaneously eating nutritional requirements by discharge, and that either TPN or ENT support is equally effective when prescribed according to individual measurements of MREE and nitrogen excretion.", "This prospective randomized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients. Thirty-eight head-injured patients were randomly assigned to receive total parenteral nutrition (TPN) or standard enteral nutrition (SEN). Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization. Survival and functional recovery were monitored in survivors for 1 year. Of the 38 patients, 18 were randomized to the SEN group and 20 to the TPN group. Demographically, the two groups of patients were similar on admission. There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale (p = 0.52). The outcome for the two groups was quite different, with eight of the 18 SEN patients dying within 18 days of injury, whereas no patient in the TPN group died within this period (p less than 0.0001). The basis for the improved survival in the TPN patients appears to be improved nutrition. The TPN patients had a more positive nitrogen balance (p less than 0.06), and a higher serum albumin level and total lymphocyte count. More adequate nutritional status may have improved the patients' immunocompetence, resulting in decreased susceptibility to sepsis. The data from this study strongly support the favorable effect of early TPN on survival from head injury.", "To determine the efficacy of early jejunal hyperalimentation as nutritional support in the head-injured patient, 32 head-injured patients with Glasgow Coma Scale scores less than 10 were studied for the first 7 days after injury. The experimental (E) group had nasojejunal feeding tubes placed fluoroscopically. Within 36 hours of injury, they received nutritional support equal to their measured resting energy expenditure. The control (C) group was fed gastrically when bowel sounds returned. There were no significant differences (P greater than 0.05) in age, Glasgow Coma Scale score, type of neurological injury, or associated injuries between the two groups. The mean resting energy expenditure, serum albumin, glucose, lymphocyte count, body weight, and total nitrogen loss were nearly identical for both groups. With the jejunal feedings, daily caloric (E = 2102 kcal versus C = 1100 kcal) and nitrogen intake (E = 11.1 g versus C = 5.6 g) and daily nitrogen balance (E = -4.3 g versus C = -11.8 g) improved. The incidence of bacterial infections (E = 3 versus C = 14) and days of intensive care unit hospitalization (E = 6 versus C = 10) were significantly reduced (P less than .05). Head-injured patients will tolerate early jejunal hyperalimentation despite the presence of a clinically silent abdomen, and the cost and complications of total parenteral nutrition are avoided. The increased caloric and nitrogen intake and improved nitrogen retention markedly reduced infections and days of stay in the intensive care unit." ]

[ "19081791", "16527165", "12032876", "14668455", "10894281", "10983647", "10983646", "16420253", "12447010" ]

[ "Three generic nevirapine-based antiretroviral treatments in Chinese HIV/AIDS patients: multicentric observation cohort.", "[Clinical trial comparing efficacy and safety of four highly active antiretroviral therapy (HAART) in antiretroviral-naive treatment with advanced HIV infection].", "Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 Infection: the OzCombo 2 study.", "Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection.", "A randomised, open-label comparison of three highly active antiretroviral therapy regimens including two nucleoside analogues and indinavir for previously untreated HIV-1 infection: the OzCombo1 study.", "A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: selection of thymidine analog regimen therapy (START II).", "A comparison of stavudine plus lamivudine versus zidovudine plus lamivudine in combination with indinavir in antiretroviral naive individuals with HIV infection: selection of thymidine analog regimen therapy (START I).", "A prospective, 96-week study of the impact of Trizivir, Combivir/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naive patients: effect of sex and ethnicity.", "Antiviral activity of enteric-coated didanosine, stavudine, and nelfinavir versus zidovudine plus lamivudine and nelfinavir." ]

[ "The purpose of this study was to evaluate the efficacy and safety of three nevirapine-based antiretroviral treatments for adult antiretroviral-naïve Chinese patients with HIV-1 infection.\n This was a prospective, multicenter study. 198 antiretroviral-naïve HIV-1 positive subjects with CD4 lymphocyte counts between 100/ul and 350/ul and plasma HIV-1 RNA levels more than 500 copies/ml were randomized to start three NVP-based antiretroviral treatments: group A, NVP+AZT+ddI; group B, NVP+3TC+d4T; group C, NVP+AZT+3TC. Viral responses, immunologic responses, adverse events and drug resistance were monitored at baseline and the end of week 4, 12, 24, 36, 52. Viralogical response and immunological response were also compared in different strata of baseline CD4 T lymphocyte counts and plasma HIV-1 RNA concentrations. At baseline, the plasma HIV-1 RNA was 4.44+/-0.68, 4.52+/-0.71 and 4.41+/-0.63 lg copies/ml in group A, B and C respectively (p = 0.628). At the end of the study, the plasma viral load reached 2.54+/-1.11, 1.89+/-0.46 and 1.92+/-0.58 lg copies/ml in group A, B and C respectively (p<0.001). At week 52, suppression of plasma HIV-1 RNA to less than 50 copies/ml was achieved in more patients in group B and C than in group A (68.2%, 69% vs. 39.7%; p<0.001). In planned subgroup analyses, the decrease of viral response rate was seen in group A when CD4 cell count >200/ul (subgroup H). But in subgroup L, viral response rate of three groups has no significant statistic difference. There were no statistically significant differences among three groups in immunological response within any of the CD4 or pVL strata. 3 out of 193 patients with available genotype at baseline showed primary drug resistant. Of 26 patients with virologic failure, 17 patients showed secondary drug resistant, 16 subjects in group A and 1 subject in group B. Logistic regression analysis indicated that presence of hepatotoxicity was associated with HCV-Ab positive (OR = 2.096, 95%CI: 1.106-3.973, P = 0.023) and higher CD4 baseline (CD4 count >250/ul) (OR = 2.096, 95%CI: 1.07-4.107, P = 0.031).\n Our findings strongly support the use of 3TC+d4T and 3TC+AZT as the nucleoside analogue combination in NVP-based antiretroviral therapy. The regimen of AZT+ddI+NVP produced poor virological response especially in the stratum of CD4 count more than 200/ul. More patients showed secondary drug resistant in this arm too. Patients with HCV-Ab+ and CD4 count >250/ul appear to have significantly high risk of hepatoxicity.\n ClinicalTrials.gov NCT00618176.", "Comparison of efficacy and safety of four highly active antiretroviral therapy regimens (HAART) including two nucleoside analogues (NA) and a protease inhibitor (PI) in HIV positive patients with advanced infection and antiretroviral naive.\n Multicenter, randomized and open labeled clinical trial in ten community hospitals of Castilla-La Mancha and Madrid. Regimen 1 contains zidovudine (AZT), lamivudine (3TC) and indinavir (IDV) regimen 2 includes AZT, 3TC and ritonavir (RTV), regimen 3 was didanosine (DDI), estavudine (D4T) and IDV, and regimen 4 included DDI, D4T and RTV. Decrease in viral load of HIV (VC) has been assessed as primary endpoint and as secondary one, the increase of the numbers of CD4 lymphocytes, percentage of disease progression, adverse reactions and adherence. Measurements were made at baseline visit and at 6, 12, 24, 36 and 48 weeks.\n A total of 98 patients with a mean baseline CD4 count of 122 x 10(6)/l (range of 5-340) and a baseline viral load of 5.1 log copies/ml were included. At 48 weeks, a mean increase of the CD4 and decrease of the viral load without significant difference between the 4 regimens (103 cells/2.62 log in regimen 1; 169 cells/2.86 log in regimen 2; 171 cells/2.56 log in regimen 3 and 141 cells/1.71 log in regimen 4) were observed in the analysis of the patients in treatment. Treatment was discontinued due to adverse reactions: 24% in regimen 1, 48% in regimen 2, 26% in regimen 3 and 32% in regimen 4, without significant difference. Analyzing by PI groups, 41% of the patients with RTV and 25% of those with IDV discontinued treatment due to adverse effects. There was withdrawal from treatment due to disease progression in 7% of the RTV patients and in 9% of IDV patients.\n In the HIV positive patients with advanced infection, efficacy between the four regimens of HAART is similar, but there is a tendency to require more withdrawal due to adverse effects in the RTV group than in those of IDV, the two used as single PI.", "To assess and compare the efficacy and safety of three triple combination antiretroviral therapies in HIV-1-infected treatment-naive patients.\n Seventy treatment-naive HIV-infected adults with CD4+ T-cell counts >50/microL were randomized to receive either zidovudine + lamivudine + nevirapine (AZT + 3TC + NVP), stavudine + didanosine + nevirapine (d4T+ddI+NVP), or stavudine + lamivudine + nevirapine (d4T+3TC+NVP) for 52 weeks. Patient assessments were conducted monthly and included measurement of plasma HIV RNA levels and CD4+ T-cell counts and evaluations for drug toxicity.\n The mean time-weighted reductions in plasma HIV RNA in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 1.29, 2.13, and 1.78 log(10) copies/mL, respectively (p =.389). The proportions of patients with HIV RNA <50 copies/mL in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 73%, 68%, and 80%, respectively (p =.71). The mean time-weighted increases in CD4+ T-cell counts in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 139, 113, and 174 cells/microL, respectively (p =.30). Three patients ceased assigned treatment due to rash (one from each treatment arm), and 5 of the 45 patients on d4T (3 from the d4T+3TC+NVP arm and 2 from the d4T+ddI+NVP arm) ceased assigned treatment due to neuropathy.\n All three-drug combinations were equally effective at suppressing viral load and increasing CD4+ T-cell counts. No significant differences were detected between the treatment groups in virological or immunological response or cessation of study drugs due to adverse events, although it is possible that the study was underpowered to detect differences. NVP was safe and efficacious in this setting, and efficacy was not influenced by nucleoside reverse transcriptase inhibitor backbone.", "The optimal sequencing of antiretroviral regimens for the treatment of infection with human immunodeficiency virus type 1 (HIV-1) is unknown. We compared several different antiretroviral treatment strategies.\n This multicenter, randomized, partially double-blind trial used a factorial design to compare pairs of sequential three-drug regimens, starting with a regimen including zidovudine and lamivudine or a regimen including didanosine and stavudine in combination with either nelfinavir or efavirenz. The primary end point was the length of time to the failure of the second three-drug regimen.\n A total of 620 subjects who had not previously received antiretroviral therapy were followed for a median of 2.3 years. Starting with a three-drug regimen containing efavirenz combined with zidovudine and lamivudine (but not efavirenz combined with didanosine and stavudine) appeared to delay the failure of the second regimen, as compared with starting with a regimen containing nelfinavir (hazard ratio for failure of the second regimen, 0.71; 95 percent confidence interval, 0.48 to 1.06), as well as to delay the second virologic failure (hazard ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09), and significantly delayed the failure of the first regimen (hazard ratio, 0.39) and the first virologic failure (hazard ratio, 0.34). Starting with zidovudine and lamivudine combined with efavirenz (but not zidovudine and lamivudine combined with nelfinavir) appeared to delay the failure of the second regimen, as compared with starting with didanosine and stavudine (hazard ratio, 0.68), and significantly delayed both the first and the second virologic failures (hazard ratio for the first virologic failure, 0.39; hazard ratio for the second virologic failure, 0.47), as well as the failure of the first regimen (hazard ratio, 0.35). The initial use of zidovudine, lamivudine, and efavirenz resulted in a shorter time to viral suppression.\n The efficacy of antiretroviral drugs depends on how they are combined. The combination of zidovudine, lamivudine, and efavirenz is superior to the other antiretroviral regimens used as initial therapy in this study.\n Copyright 2003 Massachusetts Medical Society", "Highly active antiretroviral therapy (HAART) including two nucleoside analogues and a potent protease inhibitor is standard of care initial therapy for HIV-infected adults. The best-tolerated and most potent initial HAART regimen is unknown and was investigated in this study.\n One hundred and nine HIV-infected adults with no prior antiretroviral therapy, and CD4 lymphocyte counts < 500 x 10(6) cells/l or plasma HIV RNA > 30,000 copies/ml were randomized to zidovudine-lamivudine-indinavir (ZDV-3TC-IDV), stavudine-lamivudine-indinavir (d4T-3TC-IDV) or stavudine-didanosine-indinavir (d4T-ddI-IDV) for 52 weeks. The primary endpoints were plasma HIV RNA and drug-related adverse events. Other assessments were overall safety, adherence and adverse events, CD4 lymphocyte counts, cutaneous delayed type hypersensitivity (DTH) responses and quality of life (Euroqol).\n Only 58% patients had HIV RNA < 50 copies/ml plasma at 12 months, with no significant difference between the three regimes (P = 0.34). Drug-related adverse events sufficiently severe to warrant drug discontinuation were less common (P = 0.06) in patients receiving d4T-3TC-IDV (18%) than in those receiving ZDV-3TC-IDV (34%) or d4T-ddI-IDV (41%). The percentages of patients who remained on their assigned therapy with plasma HIV RNA < 50 copies/ml at 52 weeks were 60% with d4T-3TC-IDV, 53% with ZDV-3TC-IDV and 35% with d4T-ddI-IDV. Virological failure at 52 weeks was more likely in those whose adherence was estimated to be < 100% in the first 4 weeks of therapy (P = 0.02), but not in those who developed grade 3 or 4 drug-related adverse events. At 52 weeks, the mean CD4 lymphocyte count increase was 200 x 10(6) cells/l with only 7% of patients having counts lower than at baseline; DTH responses improved but remained clinically impaired in most patients. Quality of life improved significantly in all groups.\n Initial HAART regimens including IDV failed to suppress plasma HIV RNA to < 50 copies/ml in > 40% patients after only 12 months of therapy although there was significant overall improvement immunologically and in quality of life. The type of dual nucleoside combination used was less important in predicting virological failure than was imperfect adherence early in therapy. Consideration should be given to modifying a HAART regimen relatively early in non-adherent patients.", "Comparison of stavudine (d4T), didanosine (ddI) and indinavir (IDV) with zidovudine (ZDV), lamivudine (3TC) and IDV in HIV-1 infected patients.\n Randomized, open-label.\n Fourteen HIV Clinical Research Centers.\n Two-hundred and five patients with less than 4 weeks antiretroviral treatment, naive to 3TC and protease inhibitors and with CD4 cell counts > or = 200 x 10(6)/l and plasma HIV-1 RNA levels > or = 10,000 copies/ml.\n Stavudine 40 mg and ddI 200 mg twice daily plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h or 300 mg twice daily, 3TC 150 mg twice daily plus IDV.\n The proportion of patients with plasma HIV-1 RNA levels < 500 copies/ml and < or = 50 copies/ml and changes in CD4 cell counts were compared.\n In an analysis of the primary endpoint, 61% of patients on d4T + ddI + IDV and 45% of patients on ZDV + 3TC + IDV had all HIV-1 RNA values obtained between weeks 40 and 48 < 500 copies/ml [95% confidence interval (CI) for the difference between proportions, 1.7-30.3%; P = 0.038]. In an intent-to-treat analysis, the percentage of all patients randomized with all HIV-1 RNA levels < 500 copies/ml between 40 and 48 weeks were 53% for the d4T + ddI + IDV arm and 41% for the ZDV + 3TC + IDV arm (95% CI, -1.4% to 25.7%; P = 0.068). At 48 weeks 41% and 35% were < or = 50 copies/ml for the stavudine- and ZDV-containing arms respectively (P > 0.2). The median time-weighted average increases in CD4 cells count over 48 weeks were 150 x 10(6)/l cells for the d4T arm and 106 x 10(6)/l cells for the ZDV arm (P= 0.001). The occurrence of serious adverse events was not significantly different between arms.\n The combination of stavudine, ddl and IDV resulted in potent antiretroviral effects over a 48-week period, comparable or superior to zidovudine, 3TC and IDV supporting the use of stavudine, ddI and a protease inhibitor as an initial antiretroviral treatment.", "No clinical trial results directly comparing two nucleoside analog pairs in a drug regimen for HIV that includes a protease inhibitor are available.\n To compare the safety and efficacy of stavudine (d4T) + lamivudine (3TC) with zidovudine (ZDV) + 3TC, each in combination with indinavir (IDV).\n Randomized, open-label, multi-center.\n Fifteen HIV clinical research centers.\n Two-hundred and four antiretroviral-naive HIV-1-infected-patients with CD4 cell counts > or = 200 x 10(6)/l and HIV-1 RNA > or = 10,000 copies/ml (bDNA assay), modified to 5000 copies/ml.\n d4T 40 mg twice a day, 3TC 150 mg twice a day plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h (modified to 300 mg every 12 h) plus 3TC and IDV.\n Primary endpoint: plasma HIV-1 RNA < 500 copies/ml. Additional endpoints: HIV-1 RNA < or = 50 copies/ml; change from baseline in HIV-1 RNA and CD4 cell counts; safety and adverse events.\n For HIV-1 RNA, 62% of patients on d4T + 3TC + IDV and 54% of patients on ZDV + 3TC + IDV had < 500 copies/ml HIV RNA at weeks 40 through 48 [90% confidence interval, -0.204 to 0.036; P= 0.213], with 49% and 47% respectively achieving < or = 50 copies/ml at 48 weeks (90% CI, -0.134 to 0.096; P = 0.834). Median change in CD4 cell counts at 48 weeks was +227 x 10(6)/l and +198 x 10(6)/l for the d4T- and ZDV-containing arms, respectively. The median time-weighted average change from baseline in CD4 cell counts was significantly greater at 48 weeks in the d4T-containing arm (142 x 10(6)/l versus 110 x 10(6)/l; P = 0.033). Serious adverse events were not significantly different between treatment arms, but there were significant differences for frequency of adverse events of all severity with increased nausea and vomiting in the ZDV-containing arm, and increased diarrhea and rash in the d4T-containing arm.\n These results support the choice of d4T + 3TC as a nucleoside analog pair in combination with a protease inhibitor in an initial HIV treatment regimen.", "To compare the lipid and metabolic effects, efficacy, and safety of twice-daily regimens of Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg triple nucleoside tablet; TZV), Combivir (lamivudine 150 mg/zidovudine 300 mg combination tablet; COM)+nelfinavir (NFV), and stavudine (d4 T)+lamivudine (3TC)+NFV.\n An international, phase 4, open-label, parallel-group, 34-centre study was conducted in 254 non-diabetic, antiretroviral-naive, HIV-infected out-patients with an HIV-1 RNA level of >1000 HIV-1 RNA copies/mL and < or =200,000 copies/mL and a CD4 cell count of >50 cells/microL.\n Patients were randomized 1 : 1 : 1 to TZV twice daily (n = 85), COM/NFV 1250 mg twice daily (n = 88), or d4T 40 mg+3TC 150 mg+NFV 1250 mg twice daily (n = 81) for 96 weeks. Treatments were compared using analysis of covariance (ANCOVA) with regard to changes from baseline in fasting lipids in the total population and in sex and ethnic subgroups. The proportions of patients achieving HIV-1 RNA <50 and <400 copies/mL were compared using a 95% confidence interval (CI) on the difference between proportions.\n The study population was diverse (50% female, 40% black and 37% Hispanic). Mean baseline low-density lipoprotein (LDL) cholesterol was 99 mg/dL, HIV-1 RNA was 4.43 log10 copies/mL and CD4 cell count was 355 cells/microL. At week 96, fasting LDL cholesterol changed minimally in the TZV group [least square mean (LSM) change from baseline, -8 mg/dL], but increased with d4T/3TC/NFV and COM/NFV (+29 and +19 mg/dL, respectively; P < 0.001 versus TZV). Week 96 LDL-cholesterol levels were significantly lower in the TZV group than in the other two treatment groups in women and men and lower than in the d4T/3TC/NFV group in Hispanic and black patients. In black patients, the week-96 LSM change from baseline in LDL cholesterol was significantly less with TZV than with d4T/3TC/NFV (+1 vs+39 mg/dL; P = 0.003). Total cholesterol >200 mg/dL occurred in a smaller proportion of patients receiving TZV (30%) compared with COM/NFV (50%) or d4T/3TC/NFV (60%; P = 0.005 vs TZV). High-density lipoprotein (HDL) cholesterol did not change markedly with any treatment. Although triglycerides increased, they changed least in women and Hispanic patients receiving TZV. Virological and CD4 responses to the treatments were similar in the total population and in the subgroups. Diarrhoea was reported more often in the NFV arms and nausea in the ZDV arms.\n Over 96 weeks, TZV twice daily has significantly less effect on LDL cholesterol than COM/NFV or d4T/3TC/NFV twice daily, especially in women and black patients, and is associated with similar virological and CD4 responses.", "To assess and compare the activity and safety of capsules containing enteric-coated beadlets of didanosine given once daily with stavudine and nelfinavir with that of a standard reference triple drug regimen of zidovudine plus lamivudine and nelfinavir.\n Multinational, 49-site, prospective, open-label, randomized, two-arm comparison study.\n HIV-infected subjects with limited or no previous antiretroviral therapy who had plasma HIV RNA levels of >or=2000 copies/mL and CD4 cell counts of >or=200/mm3 (511 were randomized to treatment groups, and 352 completed the study).\n Triple antiretroviral therapy for 48 weeks: didanosine EC (400 mg once daily), stavudine (40 mg twice daily), and nelfinavir (750 mg three times daily) or a twice-daily coformulation of zidovudine (300 mg) plus lamivudine (150 mg) and nelfinavir (750 mg three times daily).\n Proportion of subjects with HIV RNA levels of <400 copies/mL at week 48 based on an \"intent-to-treat, missing = treatment failure\" analysis.\n The two treatment groups were similar in the proportion of treatment responders (i.e., HIV RNA level of <400 copies/mL), with 54% of subjects in the didanosine EC and zidovudine plus lamivudine treatment groups responding at week 48. Results of other analyses supported those of the primary analysis. The two study regimens were associated with similar numbers of adverse events.\n The antiviral efficacy of a triple combination regimen containing once-daily didanosine EC is similar to that of a reference triple combination regimen." ]

[ "15701188", "18312984", "11285961", "16925377", "16333546", "15249406", "10593458", "12165821", "10036122", "9918607", "10347293", "10556449", "20485147", "11000355", "15760500", "15772469" ]

[ "Effect of humidified and heated CO2 during gynecologic laparoscopic surgery on analgesic requirements and postoperative pain.", "The effect of heated humidified carbon dioxide on postoperative pain, core temperature, and recovery times in patients having laparoscopic surgery: a randomized controlled trial.", "A randomized controlled trial assessing the effect of heated carbon dioxide for insufflation on pain and recovery after laparoscopic fundoplication.", "Prospective randomized trial of heated humidified versus cold dry carbon dioxide insufflation during laparoscopic gastric bypass.", "Heating and humidifying of carbon dioxide during pneumoperitoneum is not indicated: a prospective randomized trial.", "Double-blind, prospective, randomized study of warmed, humidified carbon dioxide insufflation vs standard carbon dioxide for patients undergoing laparoscopic cholecystectomy.", "Warming of insufflation gas during laparoscopic hysterectomy: effect on body temperature and the autonomic nervous system.", "Effect of heated and humidified carbon dioxide gas on core temperature and postoperative pain: a randomized trial.", "Reduction of laparoscopic-induced hypothermia, postoperative pain and recovery room length of stay by pre-conditioning gas with the Insuflow device: a prospective randomized controlled multi-center study.", "A randomized controlled trial assessing the benefit of humidified insufflation gas during laparoscopic surgery.", "Comparison of immunologic and physiologic effects of CO2 pneumoperitoneum at room and body temperatures.", "Effect of CO(2) gas warming on pain after laparoscopic surgery: a randomized double-blind controlled trial.", "Warming and humidification of insufflation carbon dioxide in laparoscopic colonic surgery: a double-blinded randomized controlled trial.", "The clinical impact of warmed insufflation carbon dioxide gas for laparoscopic cholecystectomy.", "Beneficial effects of humidified, warmed carbon dioxide insufflation during laparoscopic bariatric surgery: a randomized clinical trial.", "Heated and humidified insufflation during laparoscopic gastric bypass surgery: effect on temperature, postoperative pain, and recovery outcomes." ]

[ "To determine the effect of humidified and heated CO(2) for pneumoperitoneum during laparoscopic surgery on analgesic requirements, postoperative pain, and patient satisfaction.\n Prospective, randomized, double-blind, controlled study (Canadian Task Force classification I).\n University hospital.\n Ninety consecutive women scheduled for gynecologic laparoscopic surgery.\n Operative laparoscopic management of adnexa surgery or adhesiolysis.\n Thirty consecutive patients were randomized into each study group. Group I received humidified, heated gas; group II dry, heated gas; and group III (control group) standard dry, cold gas. No significant difference in intraoperative and postoperative analgesic requirements or postoperative pain score between group I and group II was found. There was even a tendency (not significant) toward less pain and higher postoperative satisfaction in patients in the control group. Therefore, the evaluation was stopped after 53 patients.\n The use of humidified, heated gas did not reduce postoperative pain or intraoperative analgesic requirements and is thus not preferable to standard dry, cold gas in gynecologic laparoscopic surgery.", "To determine whether use of heated humidified carbon dioxide as insufflation gas during gynecologic laparoscopy reduced postoperative pain and hypothermia.\n A randomized controlled trial (Canadian Task Force classification 1).\n A tertiary referral hospital.\n Sixty women scheduled for gynecologic laparoscopy between 30 and 90 minutes' duration.\n Operative laparoscopic management of endometriosis, adhesions, or adnexal pathology.\n Sixty patients were randomized into either receiving heated humidified carbon dioxide (study group) or standard cold dry gas (control group). Intraoperative and postoperative core temperature, total analgesic use, postoperative nausea, and recovery room time were recorded. Postoperative pain intensity was assessed using visual analog scale. Statistical analysis was performed using software. No significant difference was revealed between groups with regard to postoperative pain, analgesic requirements, recovery room time, or postoperative nausea. The control group had less postoperative hypothermia, suggesting that external warming blankets may be more effective than heated humidified gas at maintaining intraoperative normothermia.\n The use of heated humidified carbon dioxide insufflation for short-duration gynecologic laparoscopy up to 90 minutes' duration was not associated with any significant benefit with regard to postoperative pain, hypothermia, or time of recovery room stay.", "Insufflation with heated gas for laparoscopy may reduce postoperative pain. This study assessed the effect of heated gas on outcome after fundoplication.\n A blinded, randomized trial compared the effect of heated or standard carbon dioxide (CO2) on core temperature, postoperative pain, analgesic requirement, and postoperative recovery. Pain scores were assessed with a 100 mm visual analog scale (VAS). Recovery was assessed with a patient diary and clinical follow-up assessment at 8 days and 1 month postoperatively.\n For this study, 40 patients were randomized to heated CO2 (n = 19) and standard CO2 (control) (n = 21) groups. The heated CO2 group increased core body temperature from 35.9 degrees to 36.1 degrees C, (p = 0.008), whereas the control group maintained core temperature at 35.8 degrees C. The control group had lower analgesic requirements and pain scores, significant at 12 h (VAS: 20 vs 36 mm; p = 0.04). There was no difference between the groups in terms of late recovery. The heated CO2 group showed a significant correlation between operative duration and requirement for postoperative morphine (p = 0.01).\n Heated gas provides no benefit for patients and may be associated with increased early pain. The elevation of core body temperature observed with heated CO2 is of little clinical significance.", "The replacement of cold dry carbon dioxide with heated humidified gas for insufflation during complex laparoscopic procedures has been reported to decrease hypothermia and peritoneal cell desiccation, with a resultant decrease in postoperative pain and narcotic use and a shortened recovery, but may prevent the paralysis of the peritoneal polymorphonuclear cell cytokine cascade and add to the cost of the procedure. We report our outcomes comparing carbon dioxide insufflation with different characteristics during laparoscopic gastric bypass.\n Fifty consecutive patients were randomized to undergo laparoscopic gastric bypass with either cold-dry or heated-humidified carbon dioxide insufflation. Statistical analysis of variance between groups was determined by Levine's t test with the Greenhouse-Geisser correction, at a significance level of P <.05.\n The two groups were similar for preoperative gender, age, weight, body mass index, and baseline C-reactive protein. The intraoperative room and patient core temperature, liters of insufflation used, lens cleanings, operating time, recovery room time, and narcotics used were not significantly different. The postoperative subjective analog shoulder pain score was significantly less (P = .025) for the heated-humidified group at 18 hours, but not at 6, 12, 24, or 48 hours. The abdominal pain scores and overall narcotic use, postoperative C-reactive protein, and length of stay were not significantly different between the two groups.\n Heated-humidified insufflation resulted in a transient reduction in subjective shoulder pain at 18 hours postoperatively, but no reduction in abdominal pain or narcotics used. We were unable to verify any clinically significant difference between the two groups comparing heated-humidified and cold-dry insufflation after laparoscopic gastric bypass.", "Carbon dioxide (CO2) pneumoperitoneum usually is created by a compressed gas source. This exposes the patient to cool dry gas delivered at room temperature (21 degrees C) with 0% relative humidity. Various delivery methods are available for humidifying and heating CO2 gas. This study was designed to determine the effects of heating and humidifying gas for the intraabdominal environment.\n For this study, 44 patients undergoing laparoscopic Roux-en-Y gastric bypass were randomly assigned to one of four arms in a prospective, randomized, single-blinded fashion: raw CO2 (group 1), heated CO2 (group 2), humidified CO2 (group 3), and heated and humidified CO2 (group 4). A commercially available CO2 heater-humidifier was used. Core temperatures, intraabdominal humidity, perioperative data, and postoperative outcomes were monitored. Peritoneal biopsies were taken in each group at the beginning and end of the case. Biopsies were subjected staining protocols designed to identify structural damage and macrophage activity. Postoperative narcotic use, pain scale scores, recovery room time, and length of hospital stay were recorded. One-way analysis of variance (ANOVA) and the nonparametric Kruskal-Wallis test were used to compare the groups.\n Demographics, volume of CO2 used, intraabdominal humidity, bladder temperatures, lens fogging, and operative times were not significantly different between the groups. Core temperatures were stable, and intraabdominal humidity measurements approached 100% for all the patients over the entire procedure. Total narcotic dosage and pain scale scores were not statistically different. Recovery room times and length of hospital stay were similar in all the groups. Only one biopsy in the heated-humidified group showed an increase in macrophage activity.\n The intraabdominal environment in terms of temperature and humidity was similar in all the groups. There was no significant difference in the intraoperative body temperatures or the postoperative variable measured. No histologic changes were identified. Heating or humidifying of CO2 is not justified for patients undergoing laparoscopic bariatric surgery.", "Patients undergoing warmed, humidified carbon dioxide (CO2) insufflation for laparoscopic cholecystectomy will (1) maintain a warmer intraoperative core temperature, (2) have their surgeon experience less fogging of the camera lens, and (3) have less postoperative pain than patients undergoing laparoscopic cholecystectomy with standard CO2 insufflation.\n A double-blind, prospective, randomized study comparing patients undergoing laparoscopic cholecystectomy with standard CO2 insufflation vs those receiving warmed, humidified CO2 (Insuflow Filter Heater Hydrator; Lexion Medical, St Paul, Minn) was performed. Main variables included patient core temperature, postoperative pain, analgesic requirements, and camera lens fogging.\n One hundred one blinded patients (69 women, 32 men) undergoing laparoscopic cholecystectomy were randomized into 2 groups-52 receiving standard CO2 insufflation (group A) and 49 receiving warmed, humidified CO2 (group B). Mean patient intraoperative core temperature change (group A decreased by 0.03 degrees C, group B increased by 0.29 degrees C, P =.01) and mean abdominal pain (Likert scale, 0-10) at 14 days postoperatively (group A, 1.0; group B, 0.3; P =.02) were different. Other variables (camera lens fogging, early postoperative pain, narcotic requirements, recovery room stay, and return to normal activities) between groups were similar.\n While patients undergoing laparoscopic cholecystectomy with warmed, humidified CO2 had several advantages that were statistically significant, no major clinically relevant differences between groups A and B were evident.", "Hypothermia is a known side effect of laparoscopic operations. It may increase the sympathetic activity of the autonomic nervous system (ANS), which can be evaluated noninvasively by heart rate variability (HRV). We tested the hypothesis that warming of the delivered CO2 insufflation gas helps to maintain the normal body temperature.\n Thirty-seven healthy women undergoing laparoscopic hysterectomy were randomized into heated (37 degrees C, n=18) or unheated (24 degrees C, n = 19) gas insufflation groups. Anesthesia was induced with propofol and maintained with sevoflurane in O2-air. Tympanic (ttymp) temperature was recorded before, during and after the operation. Nasopharyngeal (tnaso) temperature was recorded only during operation. Electrocardiograms were recorded and stored to evaluate changes in HRV. The individual changes in HRV were compared after decibel (dB) transformation.\n A median decrease in tympanic temperatures during the operation was 0.7 degrees C in the heated and 0.3 degrees C in the unheated group (P = 0.01 between groups), and in nasopharyngeal 0.3 degrees C and 0.1 degrees C (P = 0.03), respectively. Preanesthetic tympanic values were reached within 90 min after anesthesia. After dB transformation, HRV high frequency power differed between the groups. It was better preserved in the patients receiving unheated gas.\n The heating of insufflation gas does not prevent a decrease in body temperature and is thus unnecessary during laparoscopic hysterectomy.", "Intraoperative hypothermia is a common event during laparoscopic operations. An external warming blanket has been shown to be effective in preventing hypothermia. It has now been proposed that using heated and humidified insufflation gas can prevent hypothermia and decrease postoperative pain. Therefore, we examined the extent of intraoperative hypothermia in patients undergoing laparoscopic Nissen fundoplication using an upper body warming blanket. We also attempted to determine whether using heated and humidified insufflation gas in addition to an external warming blanket would help to maintain intraoperative core temperature or decrease postoperative pain.\n Twenty patients were randomized to receive either standard carbon dioxide (CO2) gas (control, n = 10) or heated and humidified gas (heated and humidified, n = 10). After the induction of anesthesia, an external warming blanket was placed on all patients in both groups. Intraoperative core temperature and intraabdominal temperature were measured at 15-min intervals. Postoperative pain intensity was assessed using a visual analogue pain scale, and the amount of analgesic consumption was recorded. Volume of gas delivered, number of lens-fogging episodes, intraoperative urine output, and hemodynamic data were also recorded.\n There was no significant difference between the two groups in age, length of operation, or volume of CO2 gas delivered. Compared with baseline value, mean core temperature increased by 0.4 degrees C in the heated and humidified group and by 0.3 degrees C in the control group at 1.5 h after surgical incision. Intraabdominal temperature increased by 0.2 degrees C in the heated and humidified group but decreased by 0.5 degrees C in the control group at 1.5 h after abdominal insufflation. There was no significant difference between the two groups in visual analog pain scale (5.4 +/- 1.6 control vs 4.5 +/- 2.8 heated and humidified), morphine consumed (27 +/- 26 mg control vs 32 +/- 19 mg heated and humidified), urine output, lens-fogging episodes, or hemodynamic parameters.\n Heated and humidified gas, when used in addition to an external warming blanket, minimized the reduction of intraabdominal temperature but did not alter core temperature or reduce postoperative pain.", "To assess the efficacy and safety of Insuflow (Georgia BioMedical, Inc.) filter heater hydrator device in reducing the incidence, severity and extent of hypothermia, length of recovery room stay and postoperative pain at the time of laparoscopy.\n Prospective, randomized, blinded, controlled multi-center study. Patients underwent gynecologic procedures via laparoscopy; surgeons, anesthesiologists and recovery room personnel assessed the results.\n Seven North American institutions.\n Seventy-two women for safety evaluation and efficacy studies.\n Intraoperative pre-conditioning of laparoscopic gas with the Insuflow device (treatment) or standard raw gas (control) during laparoscopic surgery and postoperatively.\n Incidence, severity and extent of hypothermia, postoperative pain perception and length of recovery room stay.\n The Insuflow group had significantly less intraoperative hypothermia, reduced length of recovery room stay and reduced postoperative pain. Pre-conditioning of laparoscopic gas by filtering heating and hydrating was well tolerated with no adverse effects. The safety profile of the Insuflow pre-conditioned gas showed significant benefits compared to currently used raw gas.\n Pre-conditioning laparoscopic gas by filtering heating and hydrating with the Insuflow device was significantly more effective than the currently used standard raw gas and was safe in reducing or eliminating laparoscopic-induced hypothermia, shortening recovery room length of stay and reducing postoperative pain.", "We conducted a randomized controlled trial during laparoscopic cholecystectomy to determine the extent of heat preservation and postoperative pain reduction using humidified carbon dioxide (CO2) gas insufflation instead of standard dry insufflation gas.\n Forty consecutive patients were randomized. Twenty patients received humidified CO2, and 20 control patients received standard CO2 insufflation. A sample of 16 patients from each group was evaluated for postoperative pain levels.\n No adverse effects from the humidification of insufflated gas were observed. There was no significant difference in core body temperature between the two groups for this brief operation. Pain, as assessed by the Analogue Pain Score (APS) was significantly less for the group with humidified gas insufflation than for the control group at 6 h postoperatively as well as on the 1st, 2nd, and 3rd postoperative day and at follow-up 10 days after the operation. In the humidified group, the mean time to return to normal activities was significantly less-5.9 days, as compared to 10.9 days in the control group.\n The use of humidified insufflation gas reduces postoperative pain following laparoscopic cholecystectomy, but except for these relatively brief procedures, the heat-preserving effect of humidified gas insufflation is not significant.", "Prolonged and complex laparoscopic procedures expose patients to large volumes of cool insufflation gas. The aim of this study was to compare the effects of a conventional room temperature carbon dioxide (CO2) pneumoperitoneum with those of a body temperature pneumoperitoneum.\n Patients were randomized to undergo laparoscopic cholecystectomy with a CO2 pneumoperitoneum warmed to either body temperature (n = 15) or room temperature (n = 15). The physiologic and immunologic effects of warming the gas were examined by measuring peroperative core and intraperitoneal temperatures, peritoneal fluid cytokine concentrations, and postoperative pain.\n The mean duration of surgery was 32 min in both groups. Core temperature was reduced in the room temperature group (mean, 0.42 degrees C; p < 0.05). No reduction in temperature occurred when the gas was warmed. Greater levels of cytokines were detected in peritoneal fluid from the room temperature insufflation group tumor necrosis factor alpha (TNF-alpha): mean, 10.9 pg/ml vs. 0.42, p < 0.05; interleukin 1 beta (IL-1beta): mean, 44.8 pg/ml vs. 15.5, p < 0.05; and IL-6: mean, 60.4 ng/ml vs. 47.2. There was no difference in postoperative pain scores or analgesia consumption between the two groups.\n The authors conclude that intraoperative cooling can be prevented by warming the insufflation gas, even in short laparoscopic procedures. In addition, warming the insufflation gas leads to a reduced postoperative intraperitoneal cytokine response.", "Previous studies have suggested that gas temperature has an influence on postlaparoscopy pain. This trial therefore was conducted to study the effect of gas warming on pain after upper abdominal laparoscopic surgery.\n Patients who underwent laparoscopic cholecystectomy, fundoplication, or Heller's myotomy were included and randomly allocated to receive either warm or cold gas. Primary end point was shoulder tip pain, and secondary end points were subcostal, trocar wound, and visceral pains, as well as other postoperative events. Criteria of pain assessment were the visual analog scale, verbal rating scale, and amount of analgesics.\n A total of 100 patients were suitable for postoperative evaluation. The groups were well matched. Shoulder tip and subcostal pains were significantly more intense after gas warming (p < 0.05). The three assessment criteria showed the same differences. No difference was observed concerning trocar wound and visceral pains and the other secondary end points. Subdiaphragmatic temperature was not significantly different (34.4 degrees with warming vs. 34 degrees without warming).\n Gas warming does not reduce, and probably increases, postoperative shoulder tip and subcostal pains.", "We aimed to test the hypothesis that warming and humidification of insufflation CO2 would lead to reduced postoperative pain and improved recovery by reducing peritoneal inflammation in laparoscopic colonic surgery.\n Warming and humidification of insufflation gas is thought be beneficial in laparoscopic surgery, but evidence in prolonged laparoscopic procedures is lacking.\n We used a multicenter, double-blinded, randomized controlled design. The Study Group received warmed (37 degrees C), humidified (98% RH) insufflation carbon dioxide, and the Control Group received standard gas (19 degrees C, 0% RH). Anesthesia and analgesia were standardized. Intraoperative oesophageal temperature was measured at 15 minutes intervals. At the conclusion of surgery, the primary surgeon was asked to rate camera fogging on a Likert scale. Postoperative opiate usage was determined using Morphine Equivalent Daily Dose (MEDD), and pain was measured using visual analogue scores. Peritoneal and plasma cytokine concentrations were measured at 20 hours postoperatively. Postoperative recovery was measured using defined discharge and complication criteria, and the Surgical Recovery Score.\n Eighty-two patients were randomized, with 41 in each arm. Groups were well matched at baseline. Intraoperative core temperature was similar in both groups. Median camera fogging score was significantly worse in the Study group (4 vs. 2, P = 0.040). There were marginal differences in pain scores, but no significant differences were detected in MEDD usage, cytokine concentrations, or any recovery parameters measured.\n Warming and humidification of insufflation CO2 does not attenuate the early inflammatory cytokine response, and confers no clinically significant benefit in laparoscopic colonic surgery.", "Reports suggest that the insufflation of cold gas to produce a pneumoperitoneum for laparoscopic surgery can lead to an intraoperative decrease in core body temperature and increased postoperative pain.\n In a randomized controlled trial with 20 patients undergoing laparoscopic cholecystectomy, the effect of insufflation using carbon dioxide gas warmed to 37 degrees C (group W) was compared with insufflation using room-temperature cold (21 degrees C) gas (group C). Intraoperative body core and intra-abdominal temperatures were determined at the beginning and end of surgery. Postoperative pain intensity was evaluated using a visual analog scale and recording the consumption of analgesics.\n There were no significant group-specific differences during the operation, neither in body temperature (group W: 36.1 +/- 0.4 degrees C vs group C: 35.7 +/- 0.6 degrees C) nor in intra-abdominal temperature (group W: 35.9 +/- 0.3 degrees C vs group C: 35.6 +/- 0. 6 degrees C). Postoperatively, the two groups did not differ in pain susceptibility and need of analgesics.\n The use of carbon dioxide gas warmed to body temperature to produce a pneumoperitoneum during short-term laparoscopic surgery has no clinically important effect.", "Recent data has shown that the use of warmed, humidified carbon dioxide (CO2) insufflation during laparoscopic surgery may be associated with better outcomes.\n We performed a randomized, doubleblind, prospective controlled clinical trial of 30 patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP). Patients were randomized into 2 groups. The first group (group 1, n=15) received standard (dry, room temperature) CO2 for insufflation during the surgery, while the second group (group 2, n=15) received warmed (35 degrees C) and humidified (95%) CO2. Patients received postoperative analgesia from morphine delivered via a patient-controlled analgesia (PCA) pump. Pain scores (on a scale of 0 to 10, 0 being no pain and 10 being the worst pain) were measured postoperatively at 3 h, 6 h, 1 day and 2 days. The amount of morphine that was delivered through the PCA was also measured at the same time intervals. Operating-room (OR) time, core temperature, and total hospital length of stay were documented.\n Postoperative pain as documented by pain scores and narcotic usage were not statistically different in the 2 groups. We demonstrated a statistically significant difference (mean+/-SD) in OR time (76+/-16 min vs 101+/-34 min, P=0.02), total hospital length of stay (3.2+/-.4 days vs 4.0+/-.9 days, P=0.01) and end-of-case core temperature (36.2+/-.5 degrees C vs 35.7+/-.6 degrees C, P=0.02) in group 2 compared with group 1.\n The use of warmed, humidified CO2 insufflation in bariatric patients undergoing LRYGBP was not associated with any significant benefit with regards to postoperative pain.", "Controversy exists regarding the efficacy of heated and humidified intraperitoneal gases in maintaining core body temperature. We performed a sham-controlled study to test the hypothesis that active warming and humidification of the insufflation gas reduces intraoperative heat loss and improves recovery outcomes.\n Fifty morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass procedures using a standardized anesthetic technique were randomly assigned to either a control (sham) group receiving room temperature insufflation gases with an inactive Insuflow (Lexion Medical, St. Paul, MN) device, or an active (Insuflow) group receiving warmed and humidified intraperitoneal gases. Esophageal and/or tympanic membrane temperature was measured perioperatively. Postoperative pain was assessed at 15 minute intervals using an 11-point verbal rating scale, with 0 = none to 10 = maximal. In addition, postoperative opioid requirements, incidence of nausea and vomiting, as well as the quality of recovery, were recorded.\n Use of the active Insuflow device was associated with significantly higher mean +/- standard deviation (SD) intraoperative core body temperatures (35.5 +/- 0.5 vs. 35.0 +/- 0.4 degrees C). Postoperative shivering (0 vs. 19%) and the requirement for morphine in the postanesthesia care unit (5 +/- 4 vs. 10 +/- 5 mg) were both significantly lower in the Insuflow vs. control groups. Patients in the Insuflow group also reported a higher quality of recovery 48 hours after surgery (15 vs. 13, P < 0.05).\n The Insuflow device modestly reduced shivering and heat loss, as well as the need for opioid analgesics in the early postoperative period. However, it failed to improve laparoscopic visualization due to fogging, and provided improvement in the quality of recovery only on postoperative day 2." ]

[ "20398112", "8121429" ]

[ "Pragmatic, cluster randomized trial of a policy to introduce low-low beds to hospital wards for the prevention of falls and fall injuries.", "Falls prevention: the efficacy of a bed alarm system in an acute-care setting." ]

[ "To evaluate the efficacy of a policy to introduce low-low beds for the prevention of falls and fall injuries on wards that had not previously accessed low-low beds.\n This was a pragmatic, matched, cluster randomized trial with wards paired according to rate of falls. Intervention and control wards were observed for a 6-month period after implementation of the low-low beds on the intervention wards. Data from a 6-month period before this were also collected and included in analyses to ensure comparability between intervention and control group wards.\n Public hospitals located in Queensland, Australia.\n Patients of 18 public hospital wards.\n Provision of one low-low bed for every 12 on a hospital ward, with written guidance for identifying patients at greatest risk of falls.\n Falls and fall injuries in the hospital measured using a computerized incident reporting system.\n There were 10,937 admissions to control and intervention wards combined during the pre-intervention period. There was no significant difference in the rate of falls per 1,000 occupied bed days between intervention and control group wards after the introduction of the low-low beds (generalized estimating equation coefficient=0.23, 95% confidence interval=-0.18-0.65, P=.28). The rate of bed falls, falls resulting in injury, and falls resulting in fracture also did not differ between groups. Some difficulties were encountered in intervention group wards in using the low-low beds as directed.\n A policy for the introduction of low-low beds did not appear to reduce falls or falls with injury, although larger studies would be required to determine their effect on fall-related fractures.", "The present study examined the clinical efficacy of a bed alarm system in reducing falls from bed on a geriatric evaluation and treatment unit. A nine-month case-controlled study was designed, in which 70 patients (60 women, 10 men; mean age 84 years, range 67-97 years) at increased risk for bed falls were randomly assigned to either an experimental or a control group. Subjects in the experimental group (n = 35) received a bed alarm system and those in the control group (n = 35) did not. Outcome measures included bed falls, performance of the bed alarm system, and staff attitudes toward the use of the system. Although results failed to demonstrate a statistical difference in bed falls between the experimental (n = 1) and control (n = 4) groups (p = 1.00), there was a clinical trend toward reduced falls in the experimental group. The system functioned properly, activating an alarm in all instances when patients were transferring from bed, and with the exception of one case, nurses could respond in a timely fashion to assist patients and prevent bed falls. The system did not produce any adverse effects in patients, nor did the device interfere with the rendering of medical care. The system was well accepted by patients, families, and nurses. These data suggest that bed alarm systems are beneficial in guarding against bed falls and are an acceptable method of preventing falls." ]

[ "8846523", "17728707", "18387160", "1992306", "12381942", "2027271", "11039260", "19001830", "18693591", "18820280", "16736432", "7800211", "7977479", "8390009", "19666658", "19000540", "15195212", "15481851", "12830461", "10383011", "16931217", "12753270", "17200680", "18385391", "9469496", "19158369", "2919600", "18199805", "11812877", "16595583", "18579668", "17805238", "15673691", "9988142", "9002531", "12081584", "18423809", "10196011", "15086935", "15960148", "1866045", "1584317", "11120549", "18826853", "19825330", "17162430", "15809508", "17971314", "19056618", "18193489", "16076379", "1857534" ]

[ "Aluminum hydroxide, calcium carbonate and calcium acetate in chronic intermittent hemodialysis patients.", "Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients.", "Comparison of sevelamer hydrochloride with colestimide, administered alone or in combination with calcium carbonate, in patients on hemodialysis.", "Aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease.", "Metabolic and skeletal effects of low and high doses of calcium acetate in patients with preterminal chronic renal failure.", "Calcium carbonate as a phosphate binder in dialysis patients: evaluation of an enteric-coated preparation and effect of additional aluminium hydroxide on hyperaluminaemia.", "[A comparison of phosphorus-chelating effect of calcium carbonate versus calcium acetate before dialysis].", "Phosphate binder impact on bone remodeling and coronary calcification--results from the BRiC study.", "Comparison of calcium acetate with calcium carbonate as phosphate binder in patients on maintenance haemodialysis.", "Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on peritoneal dialysis.", "Sevelamer worsens metabolic acidosis in hemodialysis patients.", "Calcium acetate versus calcium carbonate as phosphate-binding agents in chronic haemodialysis.", "Calcium acetate versus calcium carbonate for the control of serum phosphorus in hemodialysis patients.", "Calcium acetate versus calcium carbonate as phosphorus binders in patients on chronic haemodialysis: a controlled study.", "A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis.", "Multicenter prospective randomized, double-blind comparative study between lanthanum carbonate and calcium carbonate as phosphate binders in Japanese hemodialysis patients with hyperphosphatemia.", "Efficacy and safety of sevelamer. Comparison with calcium carbonate in the treatment of hyperphosphatemia in hemodialysis patients.", "Efficacy and safety of lanthanum carbonate for reduction of serum phosphorus in patients with chronic renal failure receiving hemodialysis.", "Randomized, double-blind, placebo-controlled, dose-titration, phase III study assessing the efficacy and tolerability of lanthanum carbonate: a new phosphate binder for the treatment of hyperphosphatemia.", "Calcium ketoglutarate versus calcium acetate for treatment of hyperphosphataemia in patients on maintenance haemodialysis: a cross-over study.", "Results of a randomized crossover study comparing once-daily and thrice-daily sevelamer dosing.", "Treatment of hyperphosphatemia with sevelamer hydrochloride in hemodialysis patients: a comparison with calcium acetate.", "Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.", "A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients.", "Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis.", "Iron-magnesium hydroxycarbonate (fermagate): a novel non-calcium-containing phosphate binder for the treatment of hyperphosphatemia in chronic hemodialysis patients.", "Phosphate-binding effects of sucralfate in patients with chronic renal failure.", "Effects of sevelamer hydrochloride and calcium carbonate on renal osteodystrophy in hemodialysis patients.", "An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate.", "Evolution of bone and plasma concentration of lanthanum in dialysis patients before, during 1 year of treatment with lanthanum carbonate and after 2 years of follow-up.", "Higher strength lanthanum carbonate provides serum phosphorus control with a low tablet burden and is preferred by patients and physicians: a multicenter study.", "The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer.", "Effect of MCI-196 (colestilan) as a phosphate binder on hyperphosphataemia in aemodialysis patients: a double-blind, placebo-controlled, short-term trial.", "A randomized trial of sevelamer hydrochloride (RenaGel) with and without supplemental calcium. Strategies for the control of hyperphosphatemia and hyperparathyroidism in hemodialysis patients.", "Poly[allylamine hydrochloride] (RenaGel): a noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure.", "Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients.", "A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study.", "A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients.", "Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study).", "Lanthanum carbonate (Fosrenol) efficacy and tolerability in the treatment of hyperphosphatemic patients with end-stage renal disease.", "The treatment of uraemic hyperphosphataemia with calcium acetate and calcium carbonate: a comparative study.", "Calcium acetate versus calcium carbonate as phosphate binders in hemodialysis patients.", "Calcium acetate versus calcium carbonate in the control of hyperphosphatemia in hemodialysis patients.", "Improvements in renal osteodystrophy in patients treated with lanthanum carbonate for two years.", "Lanthanum carbonate vs. sevelamer hydrochloride for the reduction of serum phosphorus in hemodialysis patients: a crossover study.", "A comparison of sevelamer hydrochloride with calcium acetate on biomarkers of bone turnover in hemodialysis patients.", "Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate.", "Magnesium carbonate is an effective phosphate binder for chronic hemodialysis patients: a pilot study.", "Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial.", "Magnesium carbonate for phosphate control in patients on hemodialysis. A randomized controlled trial.", "Prospective randomized multicenter trial of sevelamer hydrochloride and calcium carbonate for the treatment of hyperphosphatemia in hemodialysis patients in Japan.", "Comparison of calcium carbonate and aluminium hydroxide as phosphate binders on biochemical bone markers, PTH(1-84), and bone mineral content in dialysis patients." ]

[ "Prevention of secondary hyperparathyroidism in uremia necessitates correction of hyperphosphatemia and hypocalcemia. In order to avoid aluminum toxicity, calcium containing phosphate binders are used increasingly, instead of aluminium hydroxide. Recent studies have shown that calcium acetate has many characteristics of an ideal phosphate binder. It is, for instance, a more readily soluble salt compared with calcium carbonate. This advantage might, however, disappear if calcium carbonate is taken on an empty stomach, a few minutes before meals. We examined the efficacy of three different phosphate binding agents in a randomized prospective study of 53 patients on regular hemodialysis. Bicarbonate dialyses were performed with a dialysate calcium concentration of 1.75 mmol/l. After a three-week wash-out period, patients received either aluminum hydroxide (control group), calcium acetate, or calcium carbonate as their phosphate binder. Patients were instructed to take the calcium salts a few minutes before meals on an empty stomach, and aluminum hydroxide during meals. Serum calcium, phosphate, intact parathormone, and alkaline phosphatase levels were determined every month. Patient compliance was estimated every month by asking the patients which phosphate binder and what daily dose they had used.\n Aluminum hydroxide tended to be the most effective phosphate binder. The mean +/- SEM required daily dose of calcium acetate at 12 months was 5.04 +/- 0.60 g, corresponding to 10.1 +/- 1.20 tablets of 500 mg. Co-medication with aluminum hydroxide, however, was needed (1.29 +/- 0.54 g per day, corresponding to 2.6 +/- 1.08 tablets of 500 mg). The required daily calcium carbonate dose appeared to be 2.71 +/- 0.48 g, corresponding to 5.4 +/- 0.95 capsules of 500 mg, with an adjuvant daily aluminum hydroxide dose of 0.69 +/- 0.27 g, corresponding to 1.4 +/- 0.55 tablets of 500 mg (p = 0.0055). Thus, the mean daily doses of elemental calcium were comparable between the calcium acetate and calcium carbonate-treated patients (1.28 +/- 0.15 g versus 1.09 +/- 0.19 g; n.s.). The incidence of hypercalcemic episodes (albumin-corrected serum calcium levels above 2.80 mmol/l) in the calcium acetate-treated group was 18% versus 31% in the calcium carbonate-treated group (p < 0.005). None of the aluminum hydroxide-treated patients experienced hypercalcemic episodes. Mean serum concentrations of alkaline phosphatase, intact parathormone, and aluminum did not differ between the groups.\n In chronic intermittent hemodialysis patients, per gram administered elemental calcium phosphate binding with either calcium acetate or calcium carbonate is equivalent, provided that calcium carbonate is taken on an empty stomach a few minutes before meals. The number of capsules calcium carbonate, but also the total amount in grams, necessary to keep serum phosphate and intact parathormone levels into an acceptable range then is significantly less. This might improve patient compliance.", "Elevated serum phosphorus and calcium are associated with arterial calcification and mortality in dialysis patients. Unlike calcium-based binders, sevelamer attenuates arterial calcification but it is unknown whether sevelamer affects mortality or morbidity. In a multicenter, randomized, open-label, parallel design trial we compared sevelamer and calcium-based binders on all-cause and cause-specific mortality (cardiovascular, infection, and other) in prevalent hemodialysis patients. A total of 2103 patients were initially randomized to treatment and 1068 patients completed the study. All-cause mortality rates and cause-specific mortality rates were not significantly different. There was a significant age interaction on the treatment effect. Only in patients over 65 years of age was there a significant effect of sevelamer in lowering the mortality rate. There was a suggestion that sevelamer was associated with lower overall, but not cardiovascular-linked, mortality in older patients. We suggest that further research is needed to confirm these findings.", "Since hyperphosphatemia in hemodialysis patients can cause secondary hyperparathyroidism and promotes vascular calcification, serum phosphate (Pi) levels must be controlled by phosphate binders. Although sevelamer and colestimide are known as similar non-calcium, non-aluminum phosphate binders in hemodialysis patients, there are no studies that compare the effects of the two agents as either a monotherapy or in combination with calcium carbonate (CaCO3). We randomly allocated 62 hemodialysis patients with hyperphosphatemia to treatment with sevelamer (3.0 g/day) and colestimide (3.0 g/day). During the study, 35 subjects dropped out, leaving 13 in the sevelamer group and 14 in the colestimide group. After a 2-week CaCO3 washout, all subjects received the monotherapy for 4 weeks and then CaCO3 (3.0 g/day) was added for another 4 weeks. Serum corrected calcium levels tended to decrease in both groups during the washout period and monotherapy, but there was no significant difference between the two groups after the addition of CaCO3. Although the calcium x phosphorus product (Ca x P) in the two groups increased during the washout period, there was no significant change or difference between the two groups during monotherapy. However, the addition of CaCO3 significantly reduced serum Pi at Week 8 compared to that at Week 0 in both groups, and significantly lowered Ca x P only in the sevelamer group, but not in the colestimide group(.) In this short-term study, sevelamer and colestimide similarly ameliorated hyperphosphatemia, but the combination of sevelamer and CaCO3 was more effective than colestimide with CaCO3 in controlling the Ca x P product, and it may improve cardiovascular mortality in hemodialysis patients.", "The control of hyperphosphatemia is a major clinical problem in patients with chronic renal failure receiving regular dialysis treatment. Despite continuing concern about aluminum toxicity, aluminum-containing antacids are still used in many of these patients as phosphate-binding agents. Although maximal acceptable doses of aluminum hydroxide have been recommended, the safety and efficacy of these guidelines have not been evaluated.\n Seventeen children and young adults (mean [+/- SD] age, 14.1 +/- 3.7 years) undergoing regular peritoneal dialysis were randomly assigned to treatment with either aluminum hydroxide (n = 7; maximal dose, 30 mg per kilogram of body weight per day) or calcium carbonate (n = 10; dose range, 2.5 to 12 g per day, according to serum phosphorus levels). Aluminum retention was assessed by serial measurements of plasma aluminum, deferoxamine-infusion tests, and measurements of bone aluminum content during a mean (+/- SD) follow-up of 13 +/- 2 months. The evolution of bone disease was also evaluated.\n Plasma aluminum levels and the increment in plasma aluminum after infusion of deferoxamine increased from base-line values in the patients treated with aluminum hydroxide, and aluminum-related bone disease developed in one patient. Serum phosphorus levels remained higher and serum calcium levels lower in the patients receiving aluminum hydroxide than in those receiving calcium carbonate. The skeletal lesions of secondary hyperparathyroidism improved in 7 of 10 patients receiving calcium carbonate but persisted or progressed in 6 of 7 patients given aluminum hydroxide (P less than 0.025).\n Aluminum hydroxide is less effective than calcium carbonate as a phosphate-binding agent for the control of hyperphosphatemia and is associated with aluminum retention in children and young adults with chronic renal failure who are receiving dialysis therapy.", "Secondary hyperparathyroidism commonly evolves, as the glomerular filtration rate falls. The metabolic and skeletal effects of a possible remedy, calcium acetate, have not been studied in patients with preterminal chronic renal failure.\n Men with a mean creatinine clearance of approximately 30 ml/min took calcium acetate for 24 weeks at doses which provided 507 or 1,521 mg calcium/day with meals. Metabolic determinations were made at intervals of 4-8 weeks, and the bone mineral density (BMD) was measured at the beginning and at the end of the trial.\n The low-dose regimen produced no metabolic or skeletal effect. In subjects prescribed the high-dose regimen, the 24-hour urine phosphorus excretion fell from 0.53 mg/mg creatinine to values ranging from 0.34 to 0.41 mg/mg creatinine. The theoretical phosphorus threshold concentration rose by a maximum of 38.6%, and the serum phosphorus concentration did not change. The mean serum calcium concentration rose by a maximum of 7.2%. The mean fractional changes in parathyroid hormone and 1,25-dihydroxyvitamin D concentrations ranged from -27.0 to -39.6% and from -5.0 to -20.3%, respectively. The BMD increased at L1, L3, and L4.\n Calcium acetate prescribed to deliver 1,521 mg calcium/day with meals reduced parathyroid hormone and 1,25-dihydroxyvitamin D concentrations and increased lumbar BMD in men with preterminal chronic renal failure.\n Copyright 2002 S. Karger AG, Basel", "Calcium carbonate has been successfully used as a phosphate binder in patients with chronic renal failure; however, a high frequency of hypercalcaemia has been reported. To study the effects of calcium carbonate preparations with different dissolution characteristics on the incidence of this side effect, we conducted a double-blind, crossover trial in 21 patients undergoing chronic haemodialysis. Aluminum hydroxide therapy was replaced with calcium carbonate. The subjects then randomly received either an enteric-coated or a gastric-coated preparation. Calcium carbonate (3.1-3.6 g/d) controlled serum phosphate concentrations as effectively as aluminium hydroxide (2.9 g/d). Concurrently, there was a significant rise in mean serum calcium and a fall in serum concentrations of both parathyroid hormone and osteocalcin, the latter suggesting a decrease in bone turnover. Overall, hypercalcaemic episodes developed in 9 patients (43%) and occurred at a considerable frequency (33 episodes per 100 patient-months) during treatment with the gastric-coated formulation. Following conversion to enteric-coated calcium carbonate (3.6 g/d) patients had fewer occurrences of hypercalcaemia (12 episodes per 100 patient-months, P less than 0.05) and, as compared to the gastric-coated preparation, increases in serum calcium greater than 3.00 mmol/l were not observed at all. Hyperaluminaemia was regressive during therapy with calcium carbonate, but addition of small doses of aluminium hydroxide caused a large rise in serum aluminium concentrations after infusion of desferrioxamine, indicating an enhanced rate of absorption or aberrant compartmentalization of aluminium. We conclude that calcium carbonate can control hyperphosphataemia in dialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "The hyperphosphatemia, hypocalcemia and low calcitriol levels are pathogenic factors for secondary hyperparathyroidism in chronic renal failure. The phosphorus control is essential to prevent secondary hyperparathyroidism. There are not comparatives studies to test the efficacy of control of phosphorus binders in predialysis patients.\n To compare the efficacy of calcium carbonate vs calcium acetate as phosphate binder in predialysis patients.\n The present study includes 28 patients with chronic renal failure (mean clearance of creatinine 21 ml/min). Patients were separated into two groups: Group 1: (n = 14) received calcium carbonate 2,500 mg/day (1,000 mg of calcium); Group 2: (n = 14) receives calcium acetate 1,000 mg (254 mg of calcium). Calcium and phosphorus were determined every 4 months; i-PTH, alkaline phosphatase and clearance of creatinine were determined every six months.\n Both groups were comparable regarding age, renal function, calcium, phosphorus, alkaline phosphatase and i-PTH on basal situation and the end of study were not different. The serum calcium increased, not significantly, in the calcium carbonate group (group 1) [from 9.2 to 9.8 mg/dl (p = 0.05)], however it was not modified in the calcium acetate group (group 2). The serum phosphorus decreased significantly (p < 0.05) in both groups, independently of the calcium levels. Alkaline phosphatase and i-PTH not was modified during the study period.\n 1) Both calcium carbonate and calcium acetate are similarly effective as phosphate binder. 2) The carbonate group required four fold greater doses of calcium that acetate group. 3) The calcium acetate has less hypercalcemic effect than calcium carbonate.", "Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients. This is a prospective study that compares the effects of calcium acetate and sevelamer on coronary calcification (CAC) and bone histology.\n 101 hemodialysis patients were randomized for each phosphate binder and submitted to multislice coronary tomographies and bone biopsies at entry and 12 months.\n The 71 patients who concluded the study had similar baseline characteristics. On follow-up, the sevelamer group had higher levels of intact parathyroid hormone (498 +/- 352 vs. 326 +/- 236 pg/ml, p = 0.017), bone alkaline phosphatase (38 +/- 24 vs. 28 +/- 15 U/l, p = 0.03) and deoxypyridinoline (135 +/- 107 vs. 89 +/- 71 nmol/l, p = 0.03) and lower LDL cholesterol (74 +/- 21 vs. 91 +/- 28 mg/dl, p = 0.015). Phosphorus (5.8 +/- 1.0 vs. 6 +/- 1.0 mg/dl, p = 0.47) and calcium (1.27 +/- 0.07 vs. 1.23 +/- 0.08 mmol/l, p = 0.68) levels did not differ between groups. CAC progression (35 vs. 24%, p = 0.94) and bone histological diagnosis at baseline and 12 months were similar in both groups. Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption (eroded surface, ES/BS = 9.0 +/- 5.9 vs. 13.1 +/- 9.5%, p = 0.05), whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate (BFR/BS = 0.015 +/- 0.016 vs. 0.062 +/- 0.078, p = 0.003 for calcium and 0.017 +/- 0.016 vs. 0.071 +/- 0.084 microm(3)/microm(2)/day, p = 0.010 for sevelamer).\n There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups.\n (c) 2008 S. Karger AG, Basel.", "Hyperphosphatemia is common in end-stage renal disease patients. Objective of this study is to compare the hypercalcaemic effect and phosphate binding power of calcium acetate and calcium carbonate in end-stage renal disease patients on maintenance haemodialysis.\n This randomised control trial was conducted in four phases with calcium acetate or calcium carbonate. Sixty-four patients on haemodialysis were randomly divided into 2 groups. After a washout period of 2 weeks, each group was given calcium acetate or calcium carbonate for 2 months. After another washout period the patients were crossed over and again received these drugs for 2 months. Serum Calcium, phosphate, and albumin were analysed on Selectra E auto analyser at completion of each phase of study. Hypercalcaemic effect was defined as serum calcium > 2.54 mmol/l, and phosphate binding power as serum phosphate < 1.61 mmol/l.\n Forty-one patients completed the study. Though lower dose of calcium acetate was used, it resulted in equally good control of hyperphosphatemia as compared with calcium carbonate therapy [1.37 mmol/l (SD 0.33) vs. 1.46 mmol/l (SD 0.34), p = 0.16]. Incidence of hypercalcaemia was higher with calcium carbonate therapy (2.73 +/- 0.67 mmol/l vs. 2.32 +/- 0.28 mmol/l, p < 0.01). Both drugs were well tolerated, but patients more frequently complained of muscle cramps while taking calcium acetate.\n It is concluded that calcium acetate has similar effect on serum phosphate levels as compared to calcium carbonate in patients on maintenance haemodialysis. However, calcium acetate results in lesser frequency of hypercalcaemia as compared to calcium carbonate. Tolerance to both drugs was similar, though patients complained of more muscle cramps while taking calcium acetate.", "Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5. Although phosphate binders are often used in patients on peritoneal dialysis (PD), no large randomized controlled studies evaluating their use solely in this population have previously been reported.\n In this multicentre, open-label study, adult patients on PD with serum phosphorus >5.5 mg/dl were randomized (2:1) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate. Doses were titrated to achieve serum phosphorus of 3.0-5.5 mg/dl. Changes in serum phosphorus, calcium, intact parathyroid hormone (iPTH), lipids and plasma biomarkers were assessed.\n A total of 253 patients were screened, 143 of whom were randomized (sevelamer hydrochloride, n = 97; calcium acetate, n = 46). Treatment groups were well balanced with regard to baseline demographics. Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate (P < 0.001). Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group (P = 0.001) but not in the sevelamer hydrochloride group. Sevelamer hydrochloride was also associated with decreases in total cholesterol, low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase (all P < 0.001 versus baseline). Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients. Hypercalcaemia was experienced by more calcium acetate-treated patients (18 versus 2%; P = 0.001).\n In summary, sevelamer hydrochloride provides a reduction in serum phosphorus compared to that obtained with calcium-based binders in PD patients. The effects of sevelamer hydrochloride appear similar in both PD and haemodialysis populations.", "Sevelamer hydrochloride, a major phosphate binder for patients on maintenance hemodialysis (MHD) is associated with reduced serum bicarbonate concentration due to hydrochloric acid release in the gut and to the binding of short chain fatty acids in the large intestine. Since metabolic acidosis can be deleterious, a study was devised to compare the time course of serum bicarbonate concentration during treatment with sevelamer hydrochloride or calcium carbonate.\n Sixteen well nourished patients on MHD who were in excellent clinical conditions and achieving target levels for blood pressure (BP) and hemoglobin (Hb), while on a protein intake of 1.1g/kg body weight (bw), were enrolled in the study. After a 2-week washout period, the patients were divided into two groups, each consisting of eight patients, and randomized either to 24 weeks of sevelamer followed by 24 weeks of calcium carbonate (group A) or to 24 weeks of calcium carbonate followed by 24 weeks of sevelamer (group B). Protein intake, n-protein catabolic rate (nPCR), serum concentrations of calcium, phosphate, calcium x phosphate (Ca x P) product, bicarbonate, intact parathyroid hormone (iPTH) and albumin were monitored. Time course changes in serum bicarbonate concentrations in relation to short and long dialytic intervals (48 vs. 72 hr) were also investigated.\n Both sevelamer and calcium carbonate effectively controlled serum phosphate and the Ca x P product. During calcium carbonate treatment plasma phosphate concentrations were significantly below those of patients on sevelamer. Plasma bicarbonate concentration fell within target DOQI values during calcium carbonate administration both in group A and in group B, a goal which was not achieved under sevelamer administration. After a long dialytic interval in patients on sevelamer, serum bicarbonate concentration averaged 17.3 +/- 1.1 mEq/L, whereas it averaged 21.1 +/- 0.7 mEq/L in patients on calcium carbonate (p<0.01). Finally, a 24-week sevelamer administration caused a statistically significant (p<0.05) reduction (0.8 g/dL) in serum albumin concentration, without affecting iPTH. Taken together, these results indicate that sevelamer worsens metabolic acidosis, which needs to be corrected.", "Hyperphosphataemia plays a key role in the pathogenesis of renal osteodystrophy, and phosphate-binding agents are required in many chronic dialysis patients. Aluminium hydroxide and calcium carbonate are well-established phosphate binders, but their use is associated with toxicity or poor efficacy. Calcium acetate is known to be a potent phosphate binder, and has recently been used successfully in chronic dialysis patients. In this randomized cross-over trial in 31 chronic haemodialysis patients, equimolar doses of calcium acetate and calcium carbonate were administered for 6 weeks each. Compliance was estimated from tablet counts, and biochemical parameters were measured at the end of each treatment period. Of the 31 patients 23 completed both treatment arms; of the remainder, three withdrew due to adverse symptoms, hypercalcaemia necessitated treatment withdrawal in two, and three died. Non-compliance was significantly higher with acetate (18.3% tablets not taken) than with carbonate (8.7%). Serum phosphate was significantly lower after treatment with acetate (1.51 mmol/l) than with carbonate (1.80), as was the Ca x PO4 product (3.59 vs 4.18 respectively) and PTH (17.8 vs 25.4 pmol/l respectively). Serum calcium was significantly higher after acetate therapy (2.40 vs 2.32 mmol/l). No significant difference was found for sodium, potassium, bicarbonate, urea, creatinine, and haemoglobin. This study confirms that the treatment of hyperphosphataemia is more effective with calcium acetate than with calcium carbonate. For the first time an associated beneficial effect on secondary hyperparathyroidism has also been demonstrated. Patient tolerability of calcium acetate was considerably poorer, probably due in part to tablet formulation and bulkiness, as well as possible direct gastrointestinal effects of the acetate salt.", "Recent in vitro and in vivo studies have shown that calcium acetate (CaAC) is a more effective phosphorus binder than, among other calcium salts, calcium carbonate (CaCO3). More efficient binding allows serum phosphorus to be controlled with a lower dose; moreover, less calcium seems to be absorbed when CaAC is used. These properties could reduce the incidence of hypercalcemia; however, in clinical practice few reports have compared these two calcium salts, and results disagree. We evaluated in a 24-week prospective cross-over study the clinical efficiency of CaCO3 and CaAC in 10 selected chronic hemodialysis patients. Only 7 patients completed the study period. The patients were randomly assigned to start treatment with one of the two calcium salts; after 12 weeks they shifted to the other treatment. Serum analytical tests included weekly control of calcium, phosphorus, and alkaline phosphatase. PTH values (intact molecule) were obtained initially and at the end of every study period. The same good control of the phosphorus level (4.79 +/- 0.6 vs. 4.94 +/- 0.8 mg/dl) was obtained with CaAC (mean doses 4.1 +/- 0.3 g/day) as with CaCO3 (mean doses 4.01 +/- 0.8 g/day). The mean serum calcium levels were similar (10.36 +/- 0.5 vs. 10.20 +/- 0.5 mg/dl). The dose of elemental calcium administered was significantly less with CaAC (957 +/- 83 mg/day) than with CaCO3 (1,590 +/- 317 mg/day). However, the incidence of hypercalcemia (Ca > 11 mg/dl) was similar during the two treatment periods (13% with CaAC vs. 14% with CaCO3). Also the incidence of Ca x P products 765 was comparable (9.5 vs. 11.9%).(ABSTRACT TRUNCATED AT 250 WORDS)", "The first reported double-blind cross-over comparison between the phosphorus binders calcium carbonate and calcium acetate was undertaken in 15 stable patients on chronic maintenance haemodialysis. Detailed registration of diet and analysis of the protein catabolic rate suggested an unchanged phosphorus intake during the study. It was found that predialytic serum phosphate concentration was significantly decreased by 0.11 mmol/l (0.34 mg/dl) (P = 0.021, 95% confidence limits 0.02-0.21 mmol/l; 0.06-0.65 mg/dl) during calcium acetate treatment. The calcium phosphate product was insignificantly decreased during treatment with calcium acetate whereas we could not exclude the possibility that calcium concentration had increased.", "Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphataemia in CKD patients. Sevelamer carbonate formulated as a powder for oral suspension presents a novel, patient-friendly alternative to tablet phosphate binders. This study compared the safety and efficacy of sevelamer carbonate powder with sevelamer hydrochloride tablets in CKD patients on haemodialysis.\n This was a multi-centre, open-label, randomized, crossover design study. Thirty-one haemodialysis patients were randomly assigned to either sevelamer carbonate powder or sevelamer hydrochloride tablets for 4 weeks followed by a crossover to the other regimen for an additional 4 weeks.\n The mean serum phosphorus was 1.6 +/- 0.5 mmol/L (5.0 +/- 1.5 mg/dL) during sevelamer carbonate powder treatment and 1.7 +/- 0.4 mmol/L (5.2 +/- 1.1 mg/dL) during sevelamer hydrochloride tablet treatment. Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus; the geometric least square mean ratio was 0.95 (90% CI 0.87-1.03). No statistically significant or clinically meaningful differences were observed in calcium x phosphorus product and lipid levels between sevelamer carbonate powder and sevelamer hydrochloride tablets. Serum bicarbonate levels increased 2.7 +/- 3.7 mmol/L (2.7 +/- 3.7 mEq/L) during sevelamer carbonate treatment. No statistically significant change in bicarbonate was observed during sevelamer hydrochloride treatment. Sevelamer carbonate powder and sevelamer hydrochloride were well tolerated during this study.\n Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus and well tolerated in CKD patients on haemodialysis. Bicarbonate levels improved only during sevelamer carbonate treatment. Sevelamer carbonate powder should provide a welcomed new option for the treatment of hyperphosphataemia for CKD patients on dialysis.", "The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported, but not from a double-blind, comparator-controlled comparative study.\n The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a randomized, double-blind, comparator-controlled, parallel group, multicenter study. This study is the first study using a randomized, double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders.\n In the double-blind phase, the changes in the serum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups. The differences in the corrected serum calcium level or the calcium x phosphate products between the 2 groups were not statistically significant. However, the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group. The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group.\n Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner. However, lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia.", "Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia. The use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis (sevelamer) disclosed efficacy in the short and long-term studies. However, due to race differences we performed a short-term study on the Saudi hemodialysis patients and compared sevelamer with a standard calcium-based phosphate binder.\n An open-label, randomized, cross-over study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were given either sevelamer or calcium carbonate, and the dosages were titrated to achieve phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Twenty patients from the Dialysis Unit of King Fahd Hospital, Jeddah, Kingdom of Saudi Arabia, were recruited for the study between March 2003 and June 2003.\n There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-3.3 +/-2.2 mg/dL) and calcium carbonate (-3.9 +/-2.8 mg/dL). Fifty-two percent of patients developed serum calcium greater than 2.75 mmol/L (11.0 mg/dL) while receiving calcium carbonate versus 26% of patients receiving sevelamer (p<0.05). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 13% mean decrease in serum cholesterol levels.\n Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium carbonate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients.", "Lanthanum carbonate is a highly effective phosphate binder with significant potential as a treatment for hyperphosphatemia in patients with end-stage renal disease (ESRD). Here, the results of a placebo-controlled, dose-ranging study are presented.\n 196 patients (> or = 18 years) receiving hemodialysis for at least 6 months entered a 1- to 3-week, single-blind, placebo run-in phase. Of these, 145 patients were randomized to a double-blind phase in which they received placebo or lanthanum carbonate in daily lanthanum doses of 225, 675, 1,350 or 2,250 mg for 6 weeks. Serum levels of phosphorus, calcium and parathyroid hormone, and adverse events were monitored throughout the study.\n The intent-to-treat analysis (n = 144) showed significant dose-related reductions in serum phosphorus at lanthanum doses of 675, 1,350 and 2,250 mg. After 6 weeks of treatment, phosphorus levels were significantly lower in the lanthanum groups receiving 1,350 mg/day and 2,250 mg/day, compared with the placebo group (respective changes from randomization: -0.95 +/- 1.39 mg/dl (-0.31 +/- 0.45 mmol/l), -1.13 +/- 2.01 mg/dl (-0.36 +/- 0.65 mmol/l), 0.75 +/- 1.47 mg/dl (0.24 +/- 0.47 mmol/l), p < 0.001). Significant reductions in serum phosphorus, compared with placebo, occurred in the lanthanum 1,350 mg/day group from the second week of treatment and in the 2,250 mg/day group from the first week of treatment. Adverse events were mainly gastrointestinal (e.g. nausea and vomiting). Treatment-related adverse events occurred in 39% of patients treated with lanthanum carbonate and 44% of the placebo group.\n Lanthanum carbonate is an effective and well-tolerated agent for the short-term treatment of hyperphosphatemia in patients with ESRD.", "Lanthanum carbonate is a novel, non-calcium, non-aluminum phosphate binder under evaluation for the treatment of hyperphosphatemia in end-stage renal disease (ESRD) patients receiving either hemodialysis or continuous ambulatory peritoneal dialysis.\n This 16-week study assessed the control of serum phosphorus with lanthanum carbonate, and its effects on serum calcium, calcium x phosphorus product, and parathyroid hormone (PTH). Hemodialysis patients > or =18 years old entered into a 1- to 3-week washout period during which serum phosphorus levels rose to >5.9 mg/dL (1.90 mmol/L). In total, 126 patients were titrated with lanthanum carbonate at doses containing 375, 750, 1,500, 2,250, or 3,000 mg/d elemental lanthanum, given in divided doses with meals over a 6-week period, to achieve serum levels < or =5.9 mg/dL. By the end of dose titration, 11/126 (9%) patients received < or =750 mg/d of lanthanum, 25 (20%) received 1,500 mg/d, 37 (29%) received 2,250 mg/d, and 53 (42%) received 3,000 mg/d. Following titration, patients were randomized to receive either lanthanum carbonate or placebo during a 4-week, double-blind maintenance phase.\n At the study endpoint, the mean difference in serum phosphorus between the lanthanum carbonate and placebo treatment arms was 1.91 mg/dL (0.62 mmol/L) (P < 0.0001). Calcium x phosphorus product (P < 0.0001) and serum PTH levels (P < 0.01) were also significantly lower with lanthanum carbonate versus placebo. The incidence of drug-related adverse events was similar between placebo- and lanthanum carbonate-treated patients.\n Lanthanum carbonate is an effective and well-tolerated agent for the treatment of hyperphosphatemia in patients with ESRD.", "Since dietary restrictions and phosphorus removal by haemodialysis (HD) are not sufficient to control serum phosphate (s-phosphate) levels in dialysis patients the use of oral phosphate binders is mandatory. Calcium ketoglutarate (CaKE) is an analogue of glutamic acid exerting phosphate binding properties. Therefore we compared this substance to calcium acetate (CaAC) in a 24-weeks open cross-over trial in 28 maintenance HD patients. Medications and HD prescriptions were kept unchanged during the trial. Following 2 weeks of withdrawal of phosphate binders, patients were randomly assigned to one of the calcium salts for 12 weeks; after a second withdrawal of 2 weeks, all patients were shifted to the other treatment for another 12 weeks. All patients received equimolar doses of CaKE and CaAC with respect to the amount of prescribed elemental calcium. Treatment with CaAC and CaKE significantly reduced s-phosphate levels after 4 weeks (CaAC 1.95+/-0.6 vs. 2.4+/-0.53 mmol/l, P = 0.004; CaKE 1.95+/-0.4 vs. 2.47+/-0.63 mmol/l, P = 0.0001) reaching a virtually stable plateau over the remaining observation time without significant differences between the groups. The incidence of hypercalcaemia defined as a serum calcium level > or =2.8 mmol/l was significantly higher in CaAC than in CaKE treated patients (n = 8 vs. n = 1, P = 0.03). There were no significant differences in serum intact parathyroid hormone (PTH) bicarbonate, albumin or calcitriol levels between the groups after 12 weeks treatment. We conclude that CaKE is as effective as CaAC for treatment of hyperphosphataemia in chronic HD patients and may be particularly helpful in patients who are prone to develop hypercalcaemia.", "Patients with renal failure require complex regimens of renal replacement therapies and medications, including ingestion of phosphate-binding agents 3 times daily. Previous studies suggested that sevelamer may provide extended phosphate binding and be effective with once-daily dosing, thus simplifying the phosphate-binder regimen.\n Twenty-four patients were enrolled in this study, 21 of whom were randomly assigned to sevelamer administration at their previously prescribed dose, either once daily with the largest meal or thrice daily with meals, with crossover to the other regimen after 4 weeks. Eighteen patients completed both treatment periods. The primary efficacy measure for which the study was powered is comparison of the effect of once-daily versus standard thrice-daily sevelamer dosing on serum phosphorus level control, determined by using equivalence testing. Secondary efficacy measures are the effects of the 2 regimens on serum calcium level corrected for albumin level; calcium x phosphorus product; albumin; intact parathyroid hormone; total, low-density lipoprotein, high-density lipoprotein, and non-high-density lipoprotein cholesterol; and triglyceride levels.\n Once-daily sevelamer was as effective as thrice-daily dosing of sevelamer in controlling serum phosphorus, calcium, calcium x phosphorus product, serum albumin, and serum lipid levels. Bioequivalence was not shown for intact parathyroid hormone, likely because of high variability. Mean serum phosphorus levels were 4.6 +/- 0.3 mg/dL (1.49 +/- 0.10 mmol/L) during thrice-daily dosing and 5.0 +/- 0.3 mg/dL (1.61 +/- 0.10 mmol/L) during once-daily dosing. The average prescribed dose of sevelamer during both treatment regimens was 6.7 +/- 2.4 g. Routine laboratory measures were similar in the 2 groups. Both regimens were well-tolerated.\n Despite concerted patient-directed educational efforts, phosphorus level control in patients with renal failure is suboptimal and contributes to increased mortality risk. Once-daily sevelamer could simplify these regimens and encourage medication compliance, perhaps improving hyperphosphatemia management.", "Sevelamer hydrochloride is a recently approved calcium- and aluminium-free phosphate binder. A randomized study comparing sevelamer and calcium acetate was performed to assess the control of hyperphosphatemia in hemodialysis patients.\n Administration of phosphate binders was discontinued during a two-week washout period. The patients were then randomized to receive sevelamer or calcium acetate. The laboratory tests were performed monthly for 34 weeks.\n There was a statistically significant decrease of serum phosphorus in both sevelamer and calcium acetate treatments. In addition, sevelamer improved the lipid profile.\n This study confirms that sevelamer is effective at lowering serum phosphorus in hemodialysis patients and that it has several striking properties that could be beneficial in atherosclerosis in dialysis patients.", "The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known. We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from randomization. This was a predetermined secondary end point of a randomized clinical trial designed to assess progression of coronary artery calcium (CAC) scores in the two treatment arms. Thirty-four deaths occurred during the follow-up period: 23 in subjects randomized to calcium-containing phosphate binders and 11 in subjects randomized to sevelamer. Baseline CAC score was a significant predictor of mortality after adjustment for age, race, gender, and diabetes with increased mortality proportional to baseline score (P=0.002). Mortality was borderline significantly lower in subjects randomized to sevelamer (5.3/100 patient years, confidence interval (CI) (2.2-8.5) compared to those randomized to calcium-containing binders (10.6/100 patient years, CI 6.3-14.9) (P=0.05). The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment (P=0.016, hazard ratio 3.1, CI 1.23-7.61). In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality. Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders.", "Niacinamide inhibits intestinal sodium/phosphorus transporters and reduces serum phosphorus in open-label studies. A prospective, randomized, double-blind, placebo-controlled crossover trial was performed for assessment of the safety and efficacy of niacinamide.\n Hemodialysis patients with phosphorus levels > or =5.0 mg/dl were randomly assigned to 8 wk of niacinamide or placebo, titrated from 500 to 1500 mg/d. After a 2-wk washout period, patients switched to 8 wk of the alternative therapy. Vitamin D analogs and calcimimetics were held constant; phosphorus binders were not changed unless safety criteria were met.\n Thirty-three patients successfully completed the trial. Serum phosphorus fell significantly from 6.26 to 5.47 mg/dl with niacinamide but not with placebo (5.85 to 5.98 mg/dl). A concurrent fall in calcium-phosphorus product was seen with niacinamide, whereas serum calcium, intact parathyroid hormone, uric acid, platelet, triglyceride, LDL, and total cholesterol levels remained stable in both arms. Serum HDL levels rose with niacinamide (50 to 61 mg/dl but not with placebo. Adverse effects were similar between both groups. Among patients who were > or =80% compliant, results were similar, although the decrease in serum phosphorus with niacinamide was more pronounced (6.45 to 5.28 mg/dl) and the increase in HDL approached significance (49 to 58 mg/dl).\n In hemodialysis patients, niacinamide effectively reduces serum phosphorus when co-administered with binders and results in a potentially advantageous increase in HDL cholesterol. Further study in larger randomized trials and other chronic kidney disease populations is indicated.", "The objective of the study was to evaluate the phosphate-binding efficacy, side effects, and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis. The study design used was a randomized, crossover open trial, and the main outcome measurements were plasma ionized calcium levels, plasma phosphate levels, plasma intact parathyroid hormone (PTH) levels, requirements for supplemental aluminum-aminoacetate therapy, patient tolerance, and cost of therapy. Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months. All had previously tolerated therapy with calcium carbonate. Of the 19 patients included, 10 completed both treatment arms. After 12 weeks of therapy, the mean (+/-SEM) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm (4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL; P = 0.004), whereas the mean plasma phosphate (4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL) and PTH levels (266+/-125 pg/mL v 301+/-148 pg/mL) did not differ significantly between the two treatment arms. Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment, while two patients needed this supplement when treated with calcium carbonate. Five of 17 (29%) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance (anorexia, vomiting, diarrhea, general uneasiness), whereas the remaining 12 patients did not experience any side effects at all. The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms; four of them had received treatment with cimetidine or omeprazol before inclusion into the study. Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate (US$6.00/d v US$0.65/d). Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia. However, care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort. Due to the high cost of the therapy, calcium ketoglutarate should be used only for selected patients.", "This phase II study tested the safety and efficacy of fermagate, a calcium-free iron and magnesium hydroxycarbonate binder, for treating hyperphosphatemia in hemodialysis patients.\n A randomized, double-blind, three-arm, parallel-group study compared two doses of fermagate (1 g three times daily or 2 g three times daily with placebo). Sixty-three patients who had been on a stable hemodialysis regimen for > or =3 mo were randomized to the treatment phase. Study medication was administered three times daily just before meals for 21 d. The primary endpoint was reduction in serum phosphate over this period.\n In the intention-to-treat analysis, mean baseline serum phosphate was 2.16 mmol/L. The fermagate 1- and 2-g three-times-daily treatment arms were associated with statistical reductions in mean serum phosphate to 1.71 and 1.47 mmol/L, respectively. Adverse event (AE) incidence in the 1-g fermagate arm was statistically comparable to the placebo group. The 2-g arm was associated with a statistically higher number of patients reporting AEs than the 1-g arm, particularly gastrointestinal AEs, as well as a higher number of discontinuations, complicating interpretation of this dose's efficacy. Both doses were associated with elevations of prehemodialysis serum magnesium levels.\n The efficacy and tolerability of fermagate were dose dependent. Fermagate showed promising efficacy in the treatment of hyperphosphatemia in chronic hemodialysis patients as compared with placebo in this initial phase II study. The optimal balance between efficacy and tolerability needs to be determined from future dose-titration studies, or fixed-dose comparisons of more doses.", "Sucralfate has been reported to reduce serum phosphate concentration in patients with chronic renal failure. To evaluate whether sucralfate could be used to treat hyperphosphatemia secondary to chronic renal failure and whether this treatment resulted in a reduced exposure to aluminum, an open-label crossover study was designed to determine the efficacy, relative potency, safety, and cost of sucralfate v aluminum hydroxide. Of the 21 hemodialysis patients completing both phases of the crossover study, serum phosphate could be maintained below 4.5 mg/dL (1.45 mmol/L) in 16 with sucralfate and in 14 with aluminum hydroxide. The 16 patients controlled on sucralfate consumed 1,694 +/- 190 mg/d of aluminum to maintain a serum phosphate concentration of 3.91 +/- 0.17 mg/dL (1.27 +/- 0.05 mmol/L) compared with the 14 patients controlled on aluminum hydroxide with an aluminum intake of 2,678 +/- 294 mg/d (P less than 0.025) and a serum phosphate concentration of 3.94 +/- 0.13 mg/dL (1.27 +/- 0.04 mmol/L). Thus sucralfate was an effective, albeit expensive, alternative to aluminum hydroxide for the treatment of hyperphosphatemia associated with chronic renal failure. Although the difference in aluminum intake was significant, use of sucralfate did not result in lower serum aluminum concentrations.", "Disturbances in mineral metabolism play a central role in the development of renal bone disease. In a 54-wk, randomized, open-label study, 119 hemodialysis patients were enrolled to compare the effects of sevelamer hydrochloride and calcium carbonate on bone. Biopsy-proven adynamic bone disease was the most frequent bone abnormality at baseline (59%). Serum phosphorus, calcium, and intact parathyroid hormone were well controlled in both groups, although calcium was consistently lower and intact parathyroid hormone higher among patients who were randomly assigned to sevelamer. Compared with baseline values, there were no changes in mineralization lag time or measures of bone turnover (e.g., activation frequency) after 1 yr in either group. Osteoid thickness significantly increased in both groups, but there was no significant difference between them. Bone formation rate per bone surface, however, significantly increased from baseline only in the sevelamer group (P = 0.019). In addition, of those with abnormal microarchitecture at baseline (i.e., trabecular separation), seven of 10 in the sevelamer group normalized after 1 yr compared with zero of three in the calcium group. In summary, sevelamer resulted in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate, but bone formation increased and trabecular architecture improved with sevelamer. Further studies are required to assess whether these changes affect clinical outcomes, such as rates of fracture.", "Hyperphosphataemia contributes to secondary hyperparathyroidism and renal osteodystrophy in patients with end-stage renal disease (ESRD). Calcium salts are widely employed to bind dietary phosphate (P) but they may promote positive net calcium balance and metastatic calcification. We recently reported that ferric compounds bind intestinal phosphate in studies of normal and azotemic rats.\n To extend this observation, we performed an open-label, random order, crossover comparison study of ferric citrate and calcium carbonate in haemodialysis patients from two teaching hospitals. The study sample consisted of 23 women and 22 men with an average age of 52.5 +/- 11.8 (SD) years and an average weight of 54.5 +/- 10.7 kg. All forms of iron therapy were discontinued. Two weeks before the study, patients were instructed to discontinue all P-binding agents. The patients were randomly assigned to receive either calcium carbonate (3 g/day) or ferric citrate (3 g/day) for 4 weeks followed by a 2 week washout period, and then crossed over to the other P-binding agent for 4 weeks.\n From a baseline concentration of 5.6 +/- 1.5 mg/dl, the serum P increased during the washout period to 7.2 +/- 1.9 mg/dl prior to calcium carbonate treatment, and to 6.7 +/- 1.9 mg/dl prior to ferric citrate treatment. The serum P concentration fell significantly during treatment with both calcium carbonate (7.2 +/- 1.9 to 5.2 +/- 1.5 mg/dl, P<0.0001) and ferric citrate (6.7 +/- 1.9 to 5.7 +/- 1.6 mg/dl, P<0.0001). The results were not influenced by order of treatment. Under the conditions of the study protocol, ferric citrate was less effective than calcium carbonate at lowering the serum phosphate concentration. The serum Ca concentration increased during treatment with calcium carbonate but not ferric citrate. Ferric citrate treatment did not affect the serum concentration of aluminium. Ferric citrate treatment was associated with mild and generally tolerable gastrointestinal symptoms.\n Ferric citrate shows promise as a means of lowering the serum phosphate concentration in haemodialysis patients. Further studies are needed to find the optimal dose.", "Lanthanum carbonate (LC) has been proposed as a new phosphate binder. Presented here are the results from one centre that participated in a multicentre trial to assess the effect of treatment with LC and calcium carbonate (CC) on the evolution of renal osteodystrophy in dialysis patients. Bone biopsies were performed at baseline, after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma.\n Twenty new dialysis patients were randomized to receive LC (median dose 1250 mg) for 1 year (n = 10), followed by 2 years of CC treatment or CC (n = 10) during the whole study period (3 years).\n After 36 weeks of treatment, steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml. Six weeks after cessation of 1 year of treatment, the plasma lanthanum levels declined to a value of 0.17 +/- 0.12 ng/ml (P < 0.05) and after 2 years to 0.09 +/- 0.03 ng/ml. Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point. The mean bone concentration in patients receiving LC increased from 0.05 +/- 0.03 to 2.3 +/- 1.6 microg/g (P < 0.05) after 1 year and slightly decreased at the end of the study to 1.9 +/- 1.6 microg/g (P < 0.05).\n Bone deposition after 1 year of treatment with LC is low (highest concentration: 5.5 microg/g). There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity.", "Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d.\n This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with <or=3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B.\n At the end of week 4, 54% of patients achieved serum phosphorus control at dosages <or=3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication.\n Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden.", "Coronary artery calcification is more prevalent in dialysis patients than in patients without kidney disease and this is associated with high serum phosphorus. In this study, we evaluate the effect of calcium carbonate or sevelamer treatments on the progression of calcification in 90 predialysis patients. Inclusion criteria were stable serum calcium, phosphorus, parathyroid hormone, and a similar baseline total calcium score (TCS). These patients were not treated by phosphate binder, vitamin D, or statin. They were given low-phosphorus diets without or with daily calcium carbonate or sevelamer throughout the study that averaged 2 years. Baseline demographic or clinical characteristics along with biochemical parameters were not different among the three groups. The TCS significantly increased in patients on the low-phosphorus diet alone, to a lesser extent in calcium carbonate-treated patients, and not at all in sevelamer-treated patients. The progression of coronary calcification paralleled that of the calcium score. Our study shows that sevelamer treatment should not be restricted to dialysis patients; however, a larger study should be undertaken to confirm these results.", "MCI-196 (colestilan), an anion exchange resin, is widely used as an anti-hypercholesterolaemic drug in Japan. To evaluate the efficacy and safety of MCI-196 as a phosphate binder, a double-blind, randomized, placebo-controlled prospective trial was conducted in Japanese end-stage renal disease patients with hyperphosphataemia on intermittent haemodialysis treatment.\n Phosphate binders were discontinued during a 2-week washout period. Subsequently, patients whose serum phosphorus levels were > or =6.5 mg/dl, but <10 mg/dl were eligible to enter the treatment protocol. Patients were randomized to either MCI-196 6 g/day or placebo for 2 weeks. The efficacy and safety of MCI-196 were assessed in 33 and 46 patients, respectively.\n Serum phosphorus in the placebo group increased by 0.84+/-0.95 mg/dl (mean+/-SD), while serum phosphorus in the MCI-196 group decreased by 0.55+/-1.23 mg/dl. The difference between the two groups was statistically significant (P = 0.002). A reduction of > or =1 mg/dl in serum phosphorus was observed in 43% in the MCI-196 group and 0% of patients in the placebo group (P = 0.0122). Calcium-phosphorus (Ca x P) product, intact parathyroid hormone (iPTH) and low-density lipoprotein (LDL)-cholesterol in the MCI-196 group also decreased significantly compared with the placebo group, while serum calcium was unchanged. Adverse reactions were observed in 51.7% of the MCI-196 group and 29.4% of the placebo group (P = 0.2186). The most frequent adverse reactions in the MCI-196 group were gastrointestinal symptoms and signs, including constipation.\n The present findings suggest that the short-term administration of MCI-196 is effective in decreasing serum phosphorus in haemodialysis patients. Its long-term efficacy needs to be evaluated.", "We have previously shown sevelamer hydrochloride (RenaGel) to be an effective and well-tolerated treatment for hyperphosphatemia in hemodialysis patients.\n We performed a randomized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium, using the serum phosphorus concentration and intact parathyroid hormone (PTH) as the principal outcomes of interest. Calcium (900 mg elemental) was provided as a once-nightly dose on an empty stomach. 71 patients were randomized and included in the intent-to-treat population; 55 completed the 16-week study period (2 weeks washout, 12 weeks treatment, 2 weeks washout). 49% of subjects were taking vitamin D metabolites.\n Serum phosphorus and PTH rose significantly when patients stopped their phosphate binders during both washout periods. RenaGel and RenaGel with calcium were equally effective at reducing serum phosphorus (mean change -2.4 mg/dL vs. -2.3 mg/dL). RenaGel with calcium was associated with a small increase in serum calcium (mean change 0.3 mg/dL vs. 0.0 mg/dL in RenaGel group, P = 0.09) that was not statistically significant. During the treatment phase, the reduction in PTH tended to be greater in the RenaGel with calcium group (median change -67.0 vs. -22.5 pg/mL in RenaGel group, P = 0.07). Non-users of vitamin D metabolites treated with RenaGel with calcium experienced a significant decrease in PTH (median change -114.5 vs. -22 pg/mL in RenaGel group, P = 0.006). Adverse events were seen with equal frequency in both groups, being generally mild in intensity, and rarely attributable to the drugs.\n We conclude that RenaGel and RenaGel with calcium are similarly effective in the treatment of ESRD-related hyperphosphatemia. Provision of supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism.", "Dietary phosphate restriction and the oral administration of calcium and aluminum salts have been the principal means of controlling hyperphosphatemia in individuals with end-stage renal disease over the past decade. Although relatively well-tolerated, a large fraction of patients treated with calcium develop hypercalcemia, particularly when administered concurrently with calcitriol, despite a lowering of the dialysate calcium concentration. We evaluated the efficacy of cross-linked poly[allylamine hydrochloride] (RenaGel; Geltex Pharmaceuticals, Waltham, MA), a nonabsorbable calcium- and aluminum-free phosphate binder, in a randomized, placebo-controlled, double-blind trial of 36 maintenance hemodialysis patients followed over an 8-week period. RenaGel was found to be as effective as calcium carbonate or acetate as a phosphate binder. The reduction in serum phosphorus was significantly greater after 2 weeks of treatment with RenaGel (6.6 +/- 2.1 mg/dL to 5.4 +/- 1.5 mg/dL) compared with placebo (7.0 +/- 2.1 mg/dL to 7.2 +/- 2.4 mg/dL; P = 0.037). There was no significant change in serum calcium concentration in either treatment group. The total serum cholesterol and low-density lipoprotein cholesterol fraction were significantly reduced in RenaGel-treated patients compared with placebo-treated patients (P = 0.013 and P = 0.003, respectively) without a concomitant reduction in high-density lipoprotein cholesterol (P = 0.93). There was no difference among recipients of RenaGel and placebo in terms of adverse events. RenaGel is a safe and effective alternative to oral calcium for the management of hyperphosphatemia in end-stage renal disease.", "Cardiovascular disease is frequent and severe in patients with end-stage renal disease. Disorders of mineral metabolism may contribute by promoting cardiovascular calcification.\n We conducted a randomized clinical trial comparing sevelamer, a non-absorbed polymer, with calcium-based phosphate binders in 200 hemodialysis patients. Study outcomes included the targeted concentrations of serum phosphorus, calcium, and intact parathyroid hormone (PTH), and calcification of the coronary arteries and thoracic aorta using a calcification score derived from electron beam tomography.\n Sevelamer and calcium provided equivalent control of serum phosphorus (end-of-study values 5.1 +/- 1.2 and 5.1 +/- 1.4 mg/dL, respectively, P = 0.33). Serum calcium concentration was significantly higher in the calcium-treated group (P = 0.002), and hypercalcemia was more common (16% vs. 5% with sevelamer, P = 0.04). More subjects in the calcium group had end-of-study intact PTH below the target of 150 to 300 pg/mL (57% vs. 30%, P = 0.001). At study completion, the median absolute calcium score in the coronary arteries and aorta increased significantly in the calcium treated subjects but not in the sevelamer-treated subjects (coronary arteries 36.6 vs. 0, P = 0.03 and aorta 75.1 vs. 0, P = 0.01, respectively). The median percent change in coronary artery (25% vs. 6%, P = 0.02) and aortic (28% vs. 5%, P = 0.02) calcium score also was significantly greater with calcium than with sevelamer.\n Compared with calcium-based phosphate binders, sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients.", "Previous clinical trials showed that progression of coronary artery calcification (CAC) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders. Because sevelamer decreases low-density lipoprotein cholesterol (LDL-C) levels, we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients.\n Randomized, controlled, open-label, noninferiority trial with an upper bound for the noninferiority margin of 1.8.\n 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL, LDL-C levels greater than 80 mg/dL, and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography.\n 103 patients were randomly assigned to calcium acetate, and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups.\n The primary end point was change in CAC score assessed by means of electron-beam computed tomography.\n After 12 months, mean serum LDL-C levels decreased to 68.8 +/- 22.0 mg/dL in the calcium-acetate group and 62.4 +/- 23.0 mg/dL in the sevelamer group (P = 0.3). Geometric mean increases in CAC scores were 35% in the calcium-acetate group and 39% in the sevelamer group, with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 (95% confidence interval, 0.851 to 1.161).\n Treatment assignment was not blinded. The 1.8 a priori margin is large, CAC is a surrogate outcome, duration of treatment was short, and dropout rate was high.\n With intensive lowering of LDL-C levels for 1 year, hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC.", "Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time. This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a standard calcium-based phosphate binder. An open-label, randomized, crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were administered either sevelamer or calcium acetate, and the dosages were titrated upward to achieve improved phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Eighty-four patients from eight centers participated in the study. There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-2.0 +/- 2.3 mg/dL) and calcium acetate (-2.1 +/- 1.9 mg/dL). Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate, versus 5% of patients receiving sevelamer (P < 0.01). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 24% mean decrease in serum low-density lipoprotein cholesterol levels. Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium acetate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients.", "Hyperphosphatemia underlies development of hyperparathyroidism, osteodystrophy, extraosseous calcification, and is associated with increased mortality in hemodialysis patients.\n To determine whether calcium acetate or sevelamer hydrochloride best achieves recently recommended treatment goals of phosphorus </=5.5 mg/dL and Ca x P product </=55 mg(2)/dL(2), we conducted an 8-week randomized, double-blind study in 100 hemodialysis patients.\n Comparisons of time-averaged concentrations (weeks 1 to 8) demonstrated that calcium acetate recipients had lower serum phosphorus (1.08 mg/dL difference, P= 0.0006), higher serum calcium (0.63 mg/dL difference, P < 0.0001), and lower Ca x P (6.1 mg(2)/dL(2) difference, P= 0.022) than sevelamer recipients. At each week, calcium acetate recipients were 20% to 24% more likely to attain goal phosphorus [odds ratio (OR) 2.37, 95% CI 1.28-4.37, P= 0.0058], and 15% to 20% more likely to attain goal Ca x P (OR 2.16, 95% CI 1.20-3.86, P= 0.0097). Transient hypercalcemia occurred in 8 of 48 (16.7%) calcium acetate recipients, all of whom received concomitant intravenous vitamin D. By regression analysis hypercalcemia was more likely with calcium acetate (OR 6.1, 95% CI 2.8-13.3, P < 0.0001). Week 8 intact PTH levels were not significantly different. Serum bicarbonate levels were significantly lower with sevelamer hydrochloride treatment (P < 0.0001).\n Calcium acetate controls serum phosphorus and calcium-phosphate product more effectively than sevelamer hydrochloride. Cost-benefit analysis indicates that in the absence of hypercalcemia, calcium acetate should remain the treatment of choice for hyperphosphatemia in hemodialysis patients.", "High serum phosphorus levels are a common problem in patients receiving long-term dialysis treatment. Lanthanum carbonate (Fosrenol) is a new non-aluminum, non-calcium phosphate binder developed for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). We report data from a recent trial, which, for the first time, assessed the efficacy and tolerability of lanthanum carbonate treatment, compared with placebo, in Chinese patients with ESRD.\n Following a one- to three-week washout phase and a four-week, open-label lanthanum carbonate dose-titration phase, male and female hemodialysis patients were randomized (1:1) to receive either lanthanum carbonate or placebo for four weeks. The primary efficacy parameter of the study was the control of serum phosphorus levels (< or =1.8 mmol/l [< or = 5.6 mg/dl]). Secondary endpoints included the profile of serum phosphorus during titration and parathyroid hormone, calcium, and calcium x phosphorus (Ca x P) product levels. The safety and tolerability of lanthanum carbonate were assessed by monitoring adverse events throughout the study.\n Mean serum phosphorus level at the end of washout was 2.5 +/- 0.5 mmol/l (7.7 +/- 1.5 mg/dl; n=73), and there was no evidence of a difference in levels between the treatment groups pre-randomization. At the end of the study, lanthanum carbonate-treated patients had significantly lower phosphorus levels (1.6 +/- 0.5 mmol/l [5.1 +/- 1.5 mg/dl]; n=30) than those receiving placebo (2.3 +/- 0.4 mmol/l [7.2 +/- 1.3 mg/dl]; n=31; p < 0.001). In addition, a significantly higher proportion of patients receiving lanthanum carbonate had controlled serum phosphorus levels (60%) compared with the placebo group (10%; p < 0.001). Ca x P product levels were also significantly lower in the lanthanum carbonate group at the end of randomized treatment (p < 0.001). Lanthanum carbonate was well tolerated; only one serious adverse event was reported, which was unrelated to treatment.\n Lanthanum carbonate was shown to be an effective and well-tolerated phosphate binder for the treatment of hyperphosphatemia in Chinese patients with ESRD. This finding supports the results of previous US and European studies, which have also shown that lanthanum carbonate treatment effectively controls serum phosphorus levels.", "A comparative study of long-term haemodialysis patients investigated the effects of calcium acetate and calcium carbonate on concentrations of serum phosphate, calcium, and parathyroid hormone. It was demonstrated that both substances led to a significant decrease in phosphate and serum parathyroid hormone. Administration of calcium acetate reduced the serum phosphate concentration in 7 weeks from an initial value of 2.08 +/- 0.53 mmol/l to 1.51 +/- 0.39 mmol/l (P less than 0.01). Following a 1-week wash-out period, calcium carbonate reduced the serum phosphate concentration in the same patients from 1.99 +/- 0.62 mmol/l to 1.34 +/- 0.40 mmol/l (P less than 0.01). Of particular significance, however, is the fact that in relation to daily elementary calcium intake, calcium acetate was a considerably more effective binder of intestinal phosphate than calcium carbonate. During administration of calcium acetate only 1.02 g of elementary calcium were required daily in order to reduce the serum phosphate concentration. The same patients, however, required 1.88 g of elementary calcium during calcium carbonate therapy. Complementary studies investigated the influence of an accompanying calcitriol medication. In this instance, too, calcium acetate was shown to be more effective; although the patients developed hypercalcaemia with calcium acetate, this happened more often with calcium carbonate. In summary it can be said that daily calcium loading of the uraemic organism under calcium acetate therapy is reduced by nearly half as compared to calcium carbonate therapy, and that this can be achieved with the same effective decrease of the serum phosphate concentration.", "We conducted a randomized unblinded parallel clinical trial to compare the effectiveness, side effects and tolerance between calcium acetate (CA) and calcium carbonate (CC) in 80 stable chronic hemodialysis patients selected on the basis of their acceptable control of serum phosphorus (P) levels with aluminum hydroxide (AH). All patients were dialyzed against the same calcium dialyzate (1.62 mmol/l). The serum analytical tests included: calcium corrected to total protein, P, PTH (intact molecule) and bicarbonate. The study was divided into the following periods: P0: baseline measurements; P1: washout (withdrawal of AH for 15 days); P2: random allocation to CA and CC treatment at doses equivalent to 75 mEq of elemental calcium, stratified according to previous doses of AH (2 months); P3: adjustment of doses until control P (2 months). CA was poorly tolerated in 7 patients and CC in 2 (NS). The changes in serum P levels between P0 and P2 periods were lower in the CA group (1.73 +/- 0.25 vs. 1.80 +/- 0.50 mmol/l; p = 0.26) than in the CC group (1.77 +/- 0.35 vs. 1.93 +/- 0.48 mmol/l; p = 0.03, paired t test). Serum calcium was hardly modified by CA (2.42 +/- 0.20 vs. 2.47 +/- 0.17 mmol/l; NS) while in the CC group, it rose significantly (2.40 +/- 0.12 vs. 2.55 +/- 0.22 mmol/l; p = 0.0004). There were no differences in the control of PTH or bicarbonate.(ABSTRACT TRUNCATED AT 250 WORDS)", "Hyperphosphatemia has an important role in the development of bone and mineral abnormalities in end-stage renal disease (ESRD).\n To compare the phosphorus binding power and the hypercalcemic effect of calcium acetate and calcium carbonate in hemodialysis patients.\n Crossover, randomized, double-blind study.\n A private hospital dialysis center.\n Fifty-two patients who were undergoing regular hemodialysis three times a week ([Ca++] dialysate = 3.5 mEq/L).\n Half of the patients were started on 5.6 g/day of calcium acetate and, after a 2 week washout period, received 6.2 g/day of calcium carbonate. The other half followed an inverse protocol.\n Clinical interviews were conducted 3 times a week to monitor for side effects. Determinations of serum urea, calcium, phosphorus, hematocrit, Kt/V and blood gas analysis were obtained before and after each treatment.\n Twenty-three patients completed the study. A significant increase in calcium plasma levels was only observed after treatment with calcium carbonate [9.34 mg/dl (SD 0.91) vs. 9.91 mg/dl (SD 0.79), P < 0.01]. The drop in phosphorus levels was substantial and significant for both salts [5.64 mg/dl (SD 1.54) vs. 4.60 mg/dl (SD 1.32), P < 0.01 and 5.89 mg/dl (SD 1.71) vs. 4.56 mg/dl (SD 1.57), P < 0.01, for calcium acetate and calcium carbonate respectively]. The percentage reduction in serum phosphorus (at the end of the study) per milliequivalent of salt administered per day tended to be higher with calcium acetate but statistical significance was not found.\n Calcium acetate can be a good alternative to calcium carbonate in the handling of hyperphosphatemia in ESRD patients. When calcium acetate is used, control of hyperphosphatemia can be achieved with a lower administration of calcium, perhaps with a lower risk of hypercalcemia.", "To investigate the evolution of renal osteodystrophy in patients on maintenance dialysis, treated with lanthanum carbonate (LC) vs. standard phosphate-binder therapy (Stx).\n This was a 2-year, randomized, prospective, open-label study during which patients on dialysis received LC titrated to a maximum of 3,000 mg/day or their previous phosphate binder treatment with the aim to achieve target phosphorus levels of < or = 5.9 mg/dl. Paired bone biopsy samples for histomorphometric analysis were available at baseline and 1 year (LC 32, Stx 33), and at baseline and 2 years (LC 32, Stx 24).\n With similar phosphorus control, Stx was associated with numerically higher serum calcium levels at most visits. Results of osteocalcin and bone-specific alkaline phosphatase in LC patients were higher throughout the study and correlated with parameters of bone formation; however, the differences were not significant. Histological changes in bone turnover and volume were analyzed with respect to normal ranges. There was an improvement in bone turnover in the LC group, which was significant in the 1-year group, and an improvement in bone volume which was significant in the 2-year group. No significant changes in bone turnover or bone volume were observed in the Stx groups. In the 2-year LC group, 1 patient had osteomalacia at baseline and end of therapy, and a mineralization defect developed in 2 other patients. Several possible factors for a mineralization defect were present in these patients, but no single cause could be clearly identified. Histomorphometric parameters of bone, including formation and mineralization, did not correlate with bone lanthanum. No mineralization defect was observed in the Stx groups.\n These findings show that similar phosphorus control with Stx and LC results in higher bone turnover after 1 year and higher bone volume after 2 years with LC.", "The aim of this crossover study was to compare the reduction of serum phosphorus (SP) with fixed doses of the non-calcium-containing phosphate binders lanthanum carbonate (LC) and sevelamer hydrochloride (SH) in hemodialysis patients.\n Following washout (2 - 3 weeks), 182 patients with SP >or= 6.0 mg/dl and calcium >or= 8.4 mg/dl were randomized (1:1) to receive LC (2,250 to 3,000 mg/day) or SH (4,800 to 6,400 mg/day) for 4 weeks. Patients underwent a second washout (2 weeks) and switched to the alternative binder for 4 weeks.\n At the end of treatment, LC had reduced SP by 1.7 +/- 0.1 mg/dl, compared with 1.4 +/- 0.1 mg/dl for SH; the difference was not statistically significant in the primary analysis (LOCF, p = 0.133). However, the reduction with LC was significantly greater than with SH in a prespecified key secondary analysis of patients who completed 4 weeks of treatment with each binder (0.5 mg/dl difference, p = 0.007). The reduction of SP was also greater with LC than SH after 1 week of treatment (p = 0.024).\n Although the primary analysis found no difference between LC and SH in the reduction of SP, a significant difference in favor of LC was observed in patients who completed treatment. The results of this study show interesting trends with respect to onset and duration of action that warrant further investigation in longer-term studies.", "To evaluate the influence of sevelamer hydrochloride and calcium acetate on biomarkers of bone turnover in patients with hyperphosphatemia receiving hemodialysis.\n In this prospective, open-label, randomized, active-controlled study, 70 patients (38 men and 32 women) with hyperphosphatemia (serum phosphorus level >6.0 mg/dL) underwent a two-week washout period and were randomly selected to receive sevelamer hydrochloride (n = 37) or calcium acetate (n = 33) for eight weeks. Changes in serum levels of intact parathyroid hormone (iPTH), alkaline phosphatase (Alk-P), phosphorus, and calcium were measured and compared.\n After eight weeks of treatment, calcium acetate lowered iPTH levels significantly more than sevelamer hydrochloride did (-178.0 vs. -69.0 pg/mL, p = 0.0019). Levels of Alk-P were significantly elevated in patients given sevelamer hydrochloride compared with levels in those given calcium acetate treatment (24.09 vs. 7.45 U/L, p = 0.0014). Changes in serum phosphorus levels did not differ between sevelamer hydrochloride (-1.93 mg/dL) and calcium acetate (-2.5 mg/dL) at the end of the study (p = 0.0514). Changes in the calcium and phosphorous product did not significantly differ between the sevelamer-hydrochloride group (-18.06 mg2/dL2) and the calcium-acetate group (-19.05 mg2/dL2, p = 0.6764). Fifteen patients (45.5%) treated with calcium acetate had hypercalcemia (serum-adjusted calcium level >10.5 mg/dL); the rate was significantly higher than that of patients treated with sevelamer (five [13.5%] of 37, p = 0.0039).\n Treatment with sevelamer hydrochloride had the advantage of maintaining stable iPTH levels and elevating Alk-P levels while lowering serum phosphorus levels and calcium-phosphorous product.", "Hyperphosphatemia is an important clinical consequence of renal failure, and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients. Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines. This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients.\n In this European multicentre study, 800 patients were randomised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate. Serum levels of phosphate, calcium and parathryoid hormone were followed over the following 20 weeks.\n Around 65% of patients in each group achieved phosphate control, but in the calcium carbonate group this was at the expense of significant hypercalcemia (20.2% of patients vs. 0.4%). Consequently, calcium x phosphate product tended to be better controlled in the lanthanum group.\n This 6-month study demonstrates that serum phosphate control with lanthanum carbonate (750-3,000 mg/day) is similar to that seen with calcium carbonate (1,500-9,000 mg/day), but with a significantly reduced incidence of hypercalcemia. Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate.", "This study was designed to evaluate the efficacy of magnesium carbonate as a phosphate binder in hemodialysis patients.\n This study was a prospective, randomized, open-label trial comparing magnesium carbonate/calcium carbonate versus calcium acetate as a sole phosphate binder.\n This study involved outpatient hemodialysis.\n We recruited 30 stable hemodialysis patients without a history of frequent diarrhea.\n After receiving informed consent, we randomized patients 2:1 to magnesium carbonate versus calcium acetate. The dose of each binder was titrated to achieve the Kidney Disease Outcomes Quality Initiative (K/DOQI) phosphate target of <5.5 mg/dL.\n The efficacy-phase serum phosphorus concentration and the percentage of patients meeting K-DOQI targets for phosphorus, along with the daily elemental calcium intake, were the primary outcome measures.\n Magnesium carbonate provided equal control of serum phosphorus (70.6% of the magnebind group and 62.5% of the calcium acetate group had their average serum phosphorus within the K-DOQI target during the efficacy phase), while significantly reducing daily elemental calcium ingestion from phosphate binders (908 +/- 24 vs. 1743 +/- 37 mg/day, P < .0001).\n Magnesium carbonate was generally well-tolerated in this selected patient population, and was effective in controlling serum phosphorus while reducing elemental calcium ingestion.", "Lanthanum carbonate (FOSRENOL, Shire Pharmaceuticals) is an effective noncalcium, nonresin phosphate binder for the control of hyperphosphatemia in chronic kidney disease (CKD) stage 5 patients undergoing dialysis.\n A Phase 2, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of lanthanum carbonate in CKD stage 3 and 4 patients. Of 281 patients screened, 121 were randomized (2:1) to lanthanum carbonate or placebo (80 versus 41). The modified intent-to-treat population included 90 patients (56 versus 34); 71 (43 versus 28) completed the study. After run-in, when any current phosphate binders were discontinued and dietary counseling reinforced, patients with serum phosphorus >4.6 mg/dl received lanthanum carbonate (titrated up to 3000 mg/d) or matching placebo for 8 wk.\n At the end of treatment, 25 (44.6%) versus nine (26.5%) patients had serum phosphorus < or =4.6 mg/dl (difference 18.1%, P = 0.12) in the lanthanum carbonate and placebo groups, respectively. Statistically significant differences were observed between groups in change from baseline to end of treatment for serum phosphorus (P = 0.02), intact parathyroid hormone (P = 0.02), and urinary phosphorus excretion (P = 0.04). The safety profile and tolerability of lanthanum carbonate were similar to that of placebo.\n Because <1% of phosphorus is in the extracellular fluid, serum measurements may not accurately reflect total body burden in patients with CKD stages 3 and 4. However, lanthanum carbonate is an effective phosphate binder in this patient population, with a safety profile and tolerability similar to that of placebo.", "Magnesium salts bind dietary phosphorus, but their use in renal patients is limited due to their potential for causing side effects. The aim of this study was to evaluate the efficacy and safety of magnesium carbonate (MgCO(3)) as a phosphate-binder in hemodialysis patients.\n Forty-six stable hemodialysis patients were randomly allocated to receive either MgCO(3) (n=25) or calcium carbonate (CaCO(3)), (n=21) for 6 months. The concentration of Mg in the dialysate bath was 0.30 mmol/l in the MgCO(3) group and 0.48 mmol/l in the CaCO(3) group.\n Only two of 25 patients (8%) discontinued ingestion of MgCO(3) due to complications: one (4%) because of persistent diarrhea, and the other (4%) because of recurrent hypermagnesemia. In the MgCO(3) and CaCO(3) groups, respectively, time-averaged (months 1-6) serum concentrations were: phosphate (P), 5.47 vs. 5.29 mg/dl, P=ns; Ca, 9.13 vs. 9.60 mg/dl, P<0.001; Ca x P product, 50.35 vs. 50.70 (mg/dl)(2), P=ns; Mg, 2.57 vs. 2.41 mg/dl, P=ns; intact parathyroid hormone (iPTH), 285 vs. 235 pg/ml, P<0.01. At month 6, iPTH levels did not differ between groups: 251 vs. 212 pg/ml, P=ns. At month 6 the percentages of patients with serum levels of phosphate, Ca x P product and iPTH that fell within the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines were similar in both groups, whereas more patients in the MgCO(3) group (17/23; 73.91%) than in the CaCO(3) group (5/20, 25%) had serum Ca levels that fell within these guidelines, with the difference being significant at P<0.01.\n Our study shows that MgCO(3) administered for a period of 6 months is an effective and inexpensive agent to control serum phosphate levels in hemodialysis patients. The administration of MgCO(3) in combination with a low dialysate Mg concentration avoids the risk of severe hypermagnesemia.", "A prospective, randomized open-label trial of sevelamer hydrochloride with or without calcium carbonate (CC) involved 86 hemodialysis patients in Japan. The dosage of CC was fixed at 3.0 g/day for the 12-week study. After the first 4 weeks all subjects were changed from CC to sevelamer 3.0 g/day for another 4 weeks, then allocated randomly to three groups for the final 4 weeks: group A, sevelamer 6.0 g/day; group B, sevelamer 3.0 g/day and CC 3.0 g/day; group C, CC 3.0 g/day. The target serum phosphorous concentration (P)=5.5 mg/dL and the corrected calcium concentration (Ca) was 9.0-10.0 mg/dL. Of the 86 patients, 62 finished the study without a change of dosage and their data were analyzed (group A, N=16; group B, N=26; group C, N=20). At week 8 compared with week 4, the concentration of P increased from 5.7+/-1.4 to 6.4+/-1.7 mg/dL in group A, and decreased significantly in groups B and C, and in group B compared with groups A and C; groups A and C had similar concentrations at week 8. The Ca concentration decreased significantly from 9.7+/-1.0 to 9.1+/-0.7 mg/dL after the change to sevelamer. At week 8 Ca was not significantly changed in group A, whereas a significant increase occurred in groups B and C. Side-effects with sevelamer administration occurred in 34 of the 86 patients and 24 dropped out of the study, with a high frequency in group A (13/29; 44.8%). In conclusion, there was an additive effect of sevelamer for the treatment of hyperphosphatemia with CC. The combination therapy was better tolerated and showed higher patient compliance than CC or sevelamer monotherapy.", "Bone mineral content, estimated by single-photon absorptiometry of the forearm, serum values of intact parathyroid hormone (PTH(1-84], osteocalcin, alkaline phosphatase, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), and aluminium were determined during treatment with calcium carbonate (CaCO3) or aluminium hydroxide (Al(OH)3) in 11 dialysis patients participating in a randomised cross-over study. Each treatment period lasted 6 months. Serum phosphorus was maintained in the range 1.5-2.0 mmol/l. During Al(OH)3 treatment bone mineral content (BMC) decreased by 11% per half-year (mean), but only by 3% per half-year during CaCO3 treatment (P less than 0.05). Comparing the CaCO3 and Al(OH)3 periods the following differences were found: serum calcium increased during CaCO3 treatment, PTH(1-84) decreased (79% of initial values during CaCO3 versus 196% during Al(OH)3, mean area under curve, P less than 0.05), osteocalcin decreased (89% versus 117%, P less than 0.01), alkaline phosphatase decreased (92% versus 116%, P less than 0.05), and aluminium decreased (56% versus 189%, P less than 0.05). 1,25(OH)2D3 remained unchanged in both periods. No increase in soft-tissue calcification was demonstrated on X-ray of the shoulders in any of the periods. Thus, CaCO3 treatment seems to slow down loss of bone mineral content, and using CaCO3 as phosphate binder may have a more beneficial effect on the progression of uraemic bone disease than Al(OH)3 due to the reduction of hyperparathyroidism and bone turnover." ]

[ "9353612", "1783484", "12691335", "313550", "1762810", "1762809", "6600826", "2090821", "6351130", "9431265", "15109505", "8173850", "16897618", "14606740", "353652", "6364997", "9014958", "78556", "17057564", "3912961" ]

[ "Diabetic peripheral neuropathy: amelioration of pain with transcutaneous electrostimulation.", "Transcutaneous electrical nerve stimulation (TNS) for painful osteoarthrosis of the knee.", "Optimal stimulation duration of tens in the management of osteoarthritic knee pain.", "The analgesic effect of transcutaneous electrical nerve stimulation (TNS) in patients with rheumatoid arthritis. A comparative study of different pulse patterns.", "Comparative effectiveness of different stimulation modes in relieving pain. Part II. A double-blind controlled long-term clinical trial.", "Comparative effectiveness of different stimulation modes in relieving pain. Part I. A pilot study.", "Transcutaneous electrical nerve stimulation in rheumatoid arthritis.", "Transcutaneous nerve stimulation in a group of patients with rheumatic disease involving the temporomandibular joint.", "TNS and osteo-arthritic pain. Preliminary study to establish a controlled method of assessing transcutaneous nerve stimulation as a treatment for the pain caused by osteo-arthritis of the knee.", "The immediate effectiveness of electrical nerve stimulation and electrical muscle stimulation on myofascial trigger points.", "Pain reducing effect of three types of transcutaneous electrical nerve stimulation in patients with chronic pain: a randomized crossover trial.", "The comparative analgesic efficacy of transcutaneous electrical nerve stimulation and a non-steroidal anti-inflammatory drug for painful osteoarthritis.", "Outcome of transcutaneous electrical nerve stimulation in chronic pain: short-term results of a double-blind, randomised, placebo-controlled trial.", "A pilot investigation of the hypoalgesic effects of transcutaneous electrical nerve stimulation upon low back pain in people with multiple sclerosis.", "The placebo effect of transcutaneous electrical stimulation.", "Transcutaneous electrical nerve stimulation in osteoarthrosis: a therapeutic alternative?", "Combined neuromuscular electrical stimulation and transcutaneous electrical nerve stimulation for treatment of chronic back pain: a double-blind, repeated measures comparison.", "[Transcutaneous nerve-stimulation for relief of pain in patients with rheumatoid arthritis].", "Efficacy of transcutaneous electrical nerve stimulation (tens) for chronic low-back pain in a multiple sclerosis population: a randomized, placebo-controlled clinical trial.", "Acupuncture and transcutaneous electric nerve stimulation in the treatment of pain associated with chronic pancreatitis. A randomized study." ]

[ "To evaluate the efficacy of transcutaneous electrotherapy for chronic painful peripheral neuropathy in patients with type 2 diabetes.\n Thirty-one patients with symptoms and signs of peripheral neuropathy were randomized to the electrotherapy or sham treatment (control) group. The electrostimulation was given by a portable unit (H-Wave machine) than generated a biphasic, exponentially decaying waveform (pulse width 4 ms, 25-35 V, > or = 2 Hz). Patients treated each of their lower extremities for 30 min daily for 4 weeks at home. Nine patients from the sham-treatment group participated for a second period, during which all of them received the active electrotherapy. Patient's degree of pain and discomfort was graded on a scale of 0 to 5.\n In the sham-treated group (n = 13), the neuropathic symptoms improved in five (38%) patients, and the pain score declined from 2.92 +/- 0.13 to 2.38 +/- 0.26 (P < 0.04), suggesting a procedure-related placebo effect. In the electrotherapy group (n = 18), symptomatic improvement was seen in 15 (83%) cases, 3 of which were completely asymptomatic; the pain score declined from 3.17 +/- 0.12 to 1.44 +/- 0.25 (P < 0.01) and the posttreatment pain scores were considerably lower (P < 0.03), indicating a substantial treatment effect over and above any placebo influence. Patients in the electrotherapy group reported greater reduction in symptoms (52 +/- 7% vs. 27 +/- 10% in control subjects, P < 0.05) on an analog scale. Moreover, the electrotherapy decreased pain scores (from 3.0 +/- 0.62 to 1.56 +/- 0.32, P < 0.02) in nine patients who had received sham treatment earlier.\n A form of transcutaneous electrotherapy ameliorated the pain and discomfort associated with peripheral neuropathy. This novel modality offers a potential non-pharmacological treatment option.", "nan", "This study examined the optimal stimulation duration of transcutaneous electrical nerve stimulation (TENS) for relieving osteoarthritic knee pain and the duration (as measured by half-life) of post-stimulation analgesia.\n Thirty-eight patients received either: (i) 20 minutes (TENS20); (ii) 40 minutes (TENS40); (iii) 60 minutes (TENS60) of TENS; or (iv) 60 minutes of placebo TENS (TENS(PL)) 5 days a week for 2 weeks.\n A visual analogue scale recorded the magnitude and pain relief period for up to 10 hours after stimulation.\n By Day10, a significantly greater cumulative reduction in the visual analogue scale scores was found in the TENS40 (83.40%) and TENS60 (68.37%) groups than in the TENS20 (54.59%) and TENS(PL) (6.14%) groups (p < 0.000), such a group difference was maintained in the 2-week follow-up session (p < 0.000). In terms of the duration of post-stimulation analgesia period, the duration for the TENS40 (256 minutes) and TENS60 (258 minutes) groups was more prolonged than in the other 2 groups (TENS20 = 168 minutes, TENS(PL) = 35 minutes) by Day10 (p < 0.000). However, the TENS40 group produced the longest pain relief period by the follow-up session.\n 40 minutes is the optimal treatment duration of TENS, in terms of both the magnitude (VAS scores) of pain reduction and the duration of post-stimulation analgesia for knee osetoarthritis.", "Transcutaneous electrical nerve stimulation (TNS) was used on 20 patients with severe wrist pain due to rheumatoid arthritis. Three different stimulation frequencies were used: high 70 Hz stimulation (70 TNS), low frequency 3 Hz stimulation (3 TNS) and brief trains of stimuli with an internal frequency of 70 Hz and with a repetition rate of 3 Hz (3-70 TNS). The analgesic effect was evaluated on the patient's own estimate of pain relief and by means of a loading test in which the length of time the patient could hold a weight before and after TNS was used. The loading test and the patients' own estimate of pain relief corresponded well. After 70 TNS, 18 patients could double their loading time. The corresponding figure for 3-70 TNS was 16 patients and for 3 TNS 5 patients. The average duration of pain relief after cessation of stimulation was 18 h for 70 TNS and 15 h for 3-70 TNS, while those who responded to 3 TNS experienced pain relief for only 4 h on average.", "Part I of our earlier pilot study demonstrated that patients preferred modulated stimulation forms - frequency modulation and burst - rather than conventional continuous mode. To assess whether long-term therapeutic effects validate the immediate test results, this trial was performed in 14 patients with 21 pain conditions. Considering the results of the pilot study, the test stimulator was modified and 4 different forms of transcutaneous electrical nerve stimulation were randomly delivered to each patient who was blind to the modes of stimulation for 20 min. A second observer assessed the pain scores using visual analogue scales. The stimulation modes employed were: (1) conventional continuous stimulation (continuous pulses with a constant frequency of 70 Hz), (2) burst stimulation (80 msec long trains of pulses, each train consisting of 8 pulses, with an internal frequency of 90 Hz repeated 1.3 times a second), (3) high-rate frequency modulation, HRFM (continuous pulses changed from 90 Hz to 55 Hz over 90 msec, 1.3 times a second), (4) low-rate frequency modulation, LRFM (continuous pulses changed from 60 Hz to 20 Hz over 90 msec, 1.3 times a second). After the test treatment of 4 sessions in the clinic, depending on the pain scores and duration of pain relief recorded, the most effective stimulation mode was determined for each patient and a portable stimulator preset appropriately for that mode was given to be used at home, under our supervision, for 3 months. Fourteen pain conditions out of 21 (66%) responded well to the therapy; the majority preferred was the HRFM and burst-type stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)", "In this pilot study, to assess the optimal stimulation parameters, 3 different forms of transcutaneous electrical nerve stimulation were performed in 27 patients. Conventional continuous stimulation with a constant frequency of 70 Hz, burst stimulation (90 msec trains of pulses with an internal frequency of 100 Hz repeated at 2 Hz, each train consisting of 10 pulses), and frequency-modulated stimulation (continuous pulses changed from 90 Hz to 55 Hz over 90 msec) were randomly delivered to the patients for half an hour in 3 separate sessions. The patients were blind to the modes of stimulation. This pilot study demonstrated that patients preferred modulated stimulation modes such as frequency modulation and burst rather than conventional constant mode.", "The therapeutic effect of once weekly transcutaneous electrical nerve stimulation in patients with rheumatoid arthritis was compared with placebo in a randomised, double-blind, non-crossover study lasting three weeks. Thirty-two patients with classic or definite rheumatoid arthritis and wrist involvement were evaluated. Transcutaneous electrical nerve stimulation was better than the placebo in relieving pain at rest and while gripping. In addition, grip strength, measured as power and work done, immediately improved following transcutaneous electrical nerve stimulation but returned almost to initial values between assessments. No significant improvement was shown for the placebo group.", "The effect of transcutaneous nerve stimulation (TNS) was evaluated and compared with placebo TNS in 19 patients (17 women, mean age 33 years) with orofacial functional pain and rheumatic disease involving the temporomandibular joint. In two double-blind noncrossover experiments, high frequency TNS (100 Hz) and low frequency TNS (2 Hz) were evaluated by comparison of the patients' functional and rest pain, muscle and joint tenderness, and jaw function. A significant treatment effect was obtained for all treatment methods regarding functional and rest pain and muscle and joint tenderness. None of the parameters except functional pain, which improved significantly more after high frequency TNS than placebo TNS, revealed any difference between the methods. Jaw function, however, revealed a few differences between high frequency TNS and placebo TNS.", "nan", "This study is designed to investigate the immediate effectiveness of electrotherapy on myofascial trigger points of upper trapezius muscle. Sixty patients (25 males and 35 females) who had myofascial trigger points in one side of the upper trapezius muscles were studied. The involved upper trapezius muscles were treated with three different methods according to a random assignment: group A muscles (n = 18) were given placebo treatment (control group); group B muscles (n = 20) were treated with electrical nerve stimulation (ENS) therapy; and group C muscles (n = 22) were given electrical muscle stimulation (EMS) therapy. The effectiveness of treatment was assessed by conducting three measurements on each muscle before and immediately after treatment: subjective pain intensity [(PI) with a visual analog scale], pressure pain threshold [(PT) with algometry], and range of motion [(ROM) with a goniometer] of upper trapezius muscle (lateral bending of cervical spine to the opposite side). When the effectiveness of treatment was compared with that of the placebo group (group A), there was significant improvement in PI and PT in group B (P < 0.01) but not in group C (P > 0.05). The improvement of ROM was significantly more in group C (P < 0.01) as compared with that in group A or group B. When each group was divided into two additional subgroups based on the initial PI, it was found that ENS could reduce PI and increase PT significantly (P < 0.05), but did not significantly (P > 0.05) improve ROM, as compared with the placebo group for both subgroups. EMS could significantly (P < 0.05) improve ROM, but not PT, better than the placebo groups, for either subgroup. It could reduce PI significantly more (P < 0.05) than placebo controls only for the subgroup with mild to moderate pain, but not with severe pain. For pain relief, ENS was significantly better (P < 0.05) than EMS; but for the improvement of ROM, EMS was significantly better (P < 0.05) than ENS. It is concluded that ENS is more effective for immediate relief of myofascial trigger point pain than EMS, and EMS has a better effect on immediate release of muscle tightness than ENS.", "Transcutaneous electrical nerve stimulation (TENS) is a frequently applied therapy in chronic pain although evidence for effectiveness is inconclusive. Several types of TENS, based on different combinations of frequency, pulse duration and intensity, exist. The precise mechanism of action and the relevance of combinations of stimulus parameters are still unclear. To compare the effectiveness of three types of TENS we conducted a randomized, single blinded crossover trial. Patients received two times a 2-week period of daily TENS treatment, separated by a washout period of 2 weeks. In total, 180 chronic pain patients were randomized into three groups. In group 1, high frequency, low intensity TENS (HFT) was compared with high frequency, high intensity TENS (HIT). In groups 2 and 3, HFT and HIT were compared with a control TENS (COT). The order of applying the different modalities of TENS in each group was also randomized. Primary outcome was the patient's overall assessment of effectiveness and pain reduction (VAS). No differences were found in patient's assessment or pain reducing effect between the three groups, indicating no superiority of one type of TENS. In total, 56% continued TENS after the 2-week treatment period. At 6 months, 42% of all patients still used TENS. We concluded that there were no differences in effectiveness for the three types of TENS used in this study. Because no placebo group was included, no definite conclusions on effectiveness of TENS in general in the treatment of chronic pain could be made.", "Thirty-six non-hospitalized subjects with chronic pain from OA of the knee participated in an evaluation of transcutaneous electrical nerve stimulation (TENS) and naproxen, an NSAID. All pre-experiment treatment was withdrawn. Each subject experienced in some order three 3-week treatment phases: NSAID plus placebo TENS; TENS plus placebo drug; and double placebo. A broad range of pain measures was used, including daily diary ratings, and four-times-per-day ratings entered into a small electronic data logger (the PIPER) worn by the subject. A substantial placebo response occurred across all conditions, which may have masked treatment differences. Broad comparisons across subjects, combining the four main measures of pain, found no significant differences among the three experimental treatments. Analysis of diary and PIPER data for individuals suggested that, in a small minority of subjects, the NSAID plus placebo TENS combination may be more effective than double placebo. The PIPER ratings seemed to tap aspects of the pain experience different from those captured by conventional measures, suggesting the value of very frequent pain assessments, such as those entered by a subject into the PIPER, in the study of chronic pain.", "The aim of this study was to test the efficacy of shortterm transcutaneous electrical nerve stimulation (TENS) treatment in chronic pain with respect to pain intensity and patients' satisfaction with treatment results. We therefore performed a randomised controlled trial comparing TENS and sham TENS. Patients, researchers and therapists were blinded for treatment allocation. One hundred and sixty-three patients with chronic pain referred to the Pain Centre entered the study. Conventional TENS and sham TENS were applied in the segments of pain, for a period of ten days. Outcome measures were pain intensity (visual analogue scale) and patients' satisfaction with treatment result (yes or no). The proportions of patients satisfied with treatment result differed significantly for TENS compared to sham TENS (58 and 42.7% respectively, chi(2)=3.8, p=0.05). However, no differences in pain intensity were found for patients treated with TENS or sham TENS. Only for patients satisfied with treatment results pain intensity gradually decrease equally both for TENS and sham TENS with repeated treatment application.", "To investigate the hypoalgesic effects of transcutaneous electrical nerve stimulation (TENS) upon low back pain (LBP) in people with multiple sclerosis (MS).\n A randomized double-blind placebo controlled clinical pilot study.\n Fifteen people with MS were recruited and randomly allocated to one of the following groups under double blind conditions (n = 5 per group): TENS 1 (4 Hz, 200 micros), TENS 2 (110 Hz, 200 micros), placebo TENS.\n Treatment was applied for 45 minutes three times a week for six weeks with a four-week follow-up.\n The following outcome measures were taken at weeks 1, 6, and 10: visual analogue scale (VAS) (for current LBP, right leg pain, left leg pain); Leeds Multiple Sclerosis Quality of Life Questionnaire; Roland Morris Disability Questionnaire; Short Form-36 (SF-36) Version 1; and the McGill Pain Questionnaire (MPQ). VAS for current LBP, right and left leg pain were also taken before and after treatment, and once a week during the follow-up period.\n Analysis showed no statistically significant effects for any of the data. However, both active treatment groups showed a trend of improvement in the majority of the outcome measures.\n Active TENS was more effective than placebo TENS in decreasing VAS scores following each treatment although results were not statistically significant. Further work in this area is warranted and should include a larger number of participants in the form of a randomized controlled clinical trial to determine the efficacy of this modality.", "The placebo effect of transcutaneous electrical stimulation was studied in 93 patients in a double-blind cross-over trial using a genuine stimulator and a placebo machine. Placebo analgesic effect occurred in 32% of trials, as compared with 48% for actual stimulation. The placebo effect of the transcutaneous electrical stimulator is similar to the placebo effect that is noted in other double-blind studies in which medications are used.", "Thirty patients with chronic pain due to osteoarthrosis (OA) of the knee were enrolled in a randomised double-blind cross-over trial of self-administered transcutaneous electrical nerve stimulation (TENS) and placebo TENS. Medication was standardised to paracetamol tablets only. As measured on visual analogue scales for pain relief 46% of patients responded to active therapy and 43% to placebo. The length of pain relief during active therapy was significantly longer than that during placebo. At the end of the trial more patients wanted to continue using active TENS in preference to placebo or their original medication. Although most of the parameters observed favoured active TENS, it was not possible to establish its clear superiority over placebo, because the response rate to placebo TENS was high and sustained for at least 3 weeks. This trial suggests that a longer study is required to establish the role of TENS as a therapeutic agent in the treatment of the pain of chronic arthritis.", "A preliminary examination of NMES and combined NMES/TENS for the management of chronic back pain.\n Double-blind, placebo-controlled, randomized repeated measures.\n Consecutive sample of 24 chronic back pain patients (16 women and 8 men) attending an outpatient pain clinic (mean age 51.67 years, mean pain duration 3.83 years). All treatments were administered at home.\n Subjects self-administered NMES, combined NMES/TENS, TENS, and placebo treatments. Each treatment had a duration of 5 consecutive hours per day over 2 consecutive days, with a 2-day hiatus between treatments to minimize carryover effects.\n Pain reduction was assessed through pretreatment to posttreatment differences on the Present Pain Intensity (PPI) scale, and a visual analogue scale of Pain Intensity (VAS-I). Posttreatment pain relief was assessed using a visual analogue scale of Pain Relief (VAS-R).\n Combined treatment, NMES, and TENS each produced significant pretreatment to posttreatment reductions in pain intensity as measured by both the PPI and VAS-I (p < .05). Combined treatment was superior to placebo on pain reduction (p = .001, p = .016) as well as pain relief (p < .001). Combined treatment was also superior to both TENS and NMES for pain reduction and pain relief (p < .01). NMES and TENS were superior only to placebo for pain relief (p < .001).\n Combined NMES/TENS treatment consistently produced greater pain reduction and pain relief than placebo, TENS, or NMES. NMES alone, although less effective, did produce as much pain relief as TENS. Although preliminary, this pattern of results suggests that combined NMES/TENS may be a valuable adjunct in the management of chronic back pain. Further research investigating the effectiveness of both NMES and combined NMES/TENS seems warranted.", "nan", "This study was designed to investigate the hypoalgesic effects of self-applied transcutaneous electrical nerve stimulation (TENS) on chronic low-back pain (LBP) in a multiple sclerosis (MS) population.\n Ninety participants with probable or definite MS (aged 21 to 78 y) presenting with chronic LBP were recruited and randomized into 3 groups (n=30 per group): (1) low-frequency TENS group (4 Hz, 200 micros); (2) high-frequency TENS group (110 Hz, 200 micros); and (3) placebo TENS. Participants self-applied TENS for 45 minutes, a minimum of twice daily, for 6 weeks. Outcome measures were recorded at weeks 1, 6, 10, and 32. Primary outcome measures included: Visual Analog Scale for average LBP and the McGill Pain Questionnaire. Secondary outcome measures included: Visual Analog Scale for worst and weekly LBP, back and leg spasm; Roland Morris Disability Questionnaire; Barthel Index; Rivermead Mobility Index; Multiple Sclerosis Quality of Life-54 Instrument, and a daily logbook. Data were analyzed blind using parametric and nonparametric tests, as appropriate.\n Results indicated a statistically significant interactive effect between groups for average LBP (P=0.008); 1-way analysis of covariance did not show any significant effects at any time point once a Bonferonni correction was applied (P>0.05). However, clinically important differences were observed in some of the outcome measures in both active treatment groups during the treatment and follow-up periods.\n Although not statistically significant, the observed effects may have implications for the clinical prescription and the use of TENS within this population.", "In 23 patients with pancreatitis, daily pain for at least 3 months, and no abuse of alcohol, the pain-relieving effect of electroacupuncture (13 patients) or transcutaneous electric nerve stimulation (TENS) (16 patients) was studied. In two prospective studies with a cross-over design, active acupuncture was compared with sham acupuncture, and TENS of the segmental points of the pancreas with sham treatment. Neither electroacupuncture nor TENS brought about pain relief that could substitute for or supplement medical treatment." ]

[ "9631159", "1392710" ]

[ "Performance-based physician reimbursement and influenza immunization rates in the elderly. The Primary-Care Physicians of Monroe County.", "Primary and preschool immunisation in Grampian: progress and the 1990 contract." ]

[ "To investigate the effect of performance-based financial incentives on the influenza immunization rate in primary care physicians' offices.\n Randomized controlled trial during the 1991 influenza immunization season.\n Rochester, New York, and surrounding Monroe County during the Medicare Influenza Vaccine Demonstration Project.\n A total of 54 solo or group practices that had participated in the 1990 Medicare Demonstration Project.\n All physicians in participating practices agreed to enumerate their ambulatory patients aged 65 or older who had been seen during the 1990 or 1991 calendar years, and to track the immunization rate on a weekly basis using a specially designed poster from September 1991 to January 1, 1992. Additionally, physicians agreed to be randomized, by practice group, to the control group or to the incentive group, which could receive an additional $.80 per shot or $1.60 per shot if an immunization rate of 70% or 85%, respectively, was attained.\n The main outcome measures are the 1991 immunization rate and the improvement in immunization rate from the 1990 to 1991 influenza seasons for each group practice.\n For practices in the incentive group, the mean immunization rate was 68.6% (SD 16.6%) compared with 62.7% (SD 18.0%) in the control group practices (P = .22). The median practice-specific improvement in immunization rate was +10.3% in the incentive group compared with +3.5% in the control group (P = .03).\n Despite high background immunization rates, this modest financial incentive was responsible for approximately 7% increase in immunization rate among the ambulatory elderly.", "To examine changes in immunisation performance in Grampian region after the introduction of the 1990 contract for general practitioners.\n Retrospective descriptive study using data held on the Grampian immunisation record system's computer.\n All 95 general practices in Grampian region (313 general practitioners).\n All children in the primary immunisation and preschool booster age groups. This formed two groups of children for each of the four calendar quarters of 1990 and first three quarters of 1991 analysed as (a) those aged 2 years on the first day of the relevant quarter and (b) those aged 5 years on the first day of the relevant quarter, with an average population of 6600 and 6400 respectively.\n Percentage immunised by practice.\n For primary immunisation the number of practices achieving immunisation rates of at least 95% increased from 29 (31%) to 76 (81%), and practices achieving 90% rates rose from 69 (73%) to 87 (93%). For preschool boosters, the number of practices achieving at least 95% immunisation rates increased from 22 (23%) to 61 (64%). By the end of September 1991, 76 (80%) practices were achieving at least 90% levels compared with 36 (39%) at the beginning of 1990. Since the beginning of 1989 the proportion of immunisations not given by general practitioners declined from 14% to 2%.\n Primary and preschool immunisation rates for preschool children in Grampian showed a sustained improvement during 1990 and consolidation in 1991. Although overall trends were unchanged, 18 months after the introduction of the 1990 contract only one practice failed to meet lower target levels of 70% for both primary and preschool immunisation. By September 1991 more than three out of four practices had reached levels of at least 95% for primary immunisation." ]

[ "10776870", "12153623", "384941", "1395983", "2025069", "7474005" ]

[ "Further evaluation of colostomy in penetrating colon injury.", "Randomized clinical trial to determine if delay from time of penetrating colonic injury precludes primary repair.", "Management of perforating colon trauma: randomization between primary closure and exteriorization.", "Colorectal trauma: primary repair or anastomosis with intracolonic bypass vs. ostomy.", "Management of penetrating colon injuries. A prospective randomized trial.", "Primary repair of colon injuries: a prospective randomized study." ]

[ "Our objective was to compare, in a randomized prospective format, complication rates associated with primary repair versus fecal diversion in penetrating colon injury. During a 72-month period, 181 patients with penetrating colon injuries were entered in a randomized prospective study at an urban Level I trauma center. After intraoperative identification of colon injuries, patients were randomized to a primary repair or a diversion group. Randomization was independent of previously identified risk factors, including severity of colon injury, presence of hypotension, blood loss, extent of fecal contamination, and time from injury to operation. Five patients initially entered in the study protocol were removed because they died in the immediate postoperative period (< 24 hours). One hundred seventy-six patients were studied, of which 89 were randomized to primary repair and 87 to diversion. The average age in the diversion group was 26.4 years and it was 28.0 years in the primary repair group (P > 0.05). The average Penetrating Abdominal Trauma Index for the diversion group was 22.3, and it was 23.7 for the primary repair group (P > 0.05). There were 18 (21%) septic related complications in the diversion group and 16 (18%) in the primary repair group (P > .05). With respect to risk factors, complication rates were not higher in one study group versus the other. We conclude that, in the civilian population, all penetrating colon injuries should be managed with primary repair.", "There is often a delay of more than 12 h in transferring patients with penetrating colonic injury from outlying hospitals to a regional referral centre. The aim of this prospective study was to determine whether primary suture of a penetrating colonic injury in the presence of delayed presentation, shock, peritoneal contamination or associated injuries leads to increased morbidity and mortality rates.\n Patients with penetrating colonic injuries were randomized to primary closure or colostomy. Patients were compared with regard to interval from injury to operation, associated injuries, duration of operation, postoperative complications and hospital stay.\n Two hundred and forty patients were seen over a 69-month period. The interval from injury to operation ranged from 3 to 56 h, and was similar in the two treatment groups. Postoperative complications were similar in the two groups but there were significant differences in operation time (mean(s.d.) 127.1(45.8) min for primary repair and 142.3(43.0) min for colostomy; P = 0.009) and length of hospital stay (mean (range) 9 (6-56) versus 26 (13-64) days respectively; P < 0.001).\n Delay from time of penetrating colonic injury is not a contraindication to primary repair. :", "During a 44 month trial, 268 patients with wounds of the colon were entered into a prospective, randomized, nonblinded study. Consideration for primary closure demanded that: preoperative shock was never profound, blood loss was less than 20% of estimated normal volume, no more than two intra-abdominal organ systems had been injured, fecal contamination was minimal, operation was begun within eight hours, and wounds of colon and abdominal wall were never so destructive as to require resection. Once such criteria had been satisfied, colon wound management was dictated by last digit in the randomly assigned hospital number; odd indicated primary closure; even, exteriorization of the wound or primary closure with protection by a proximal vent. Results obtained in 139 determinant patients eligible for randomization revealed that primary closure (67 patients) had a lower infection rate of the incision (48% vs S7%, p > 0.05) and a still lower infection rate for the abdomen proper (15% vs 29%, p < 0.05) on comparison to the 72 patients with a randomized colostomy. Morbidity otherwise for the randomized colostomy was tenfold greater than if a primary closure had been performed. Average postoperative stay was six days longer (p < 0.01) if a colostomy had been created, exclusive of subsequent hospitalization for colostomy closure; while the total extra cost for management of the colon wound by colostomy was approximately $2,700.00. Although immediate mortalities were identical, one late death occurred following colostomy closure. These data not only confirm the safety of primary closure for colon wounds in selected cases, but also indicate that such should become the preferred method of treatment whenever specific criteria have been met.", "This prospective, randomized, controlled study was undertaken to compare primary repair or anastomosis with intracolonic bypass vs. ostomy in severe colon and intraperitoneal rectal injury. Patients were randomized at surgery following confirmation of injury. Data collected included demographics, mechanism and location of injury, trauma score (TS), injury severity score (ISS), penetrating abdominal trauma index (PATI), complications, length of hospital stay, and hospital charges. Twenty-two patients were studied: 11 with intracolonic bypass and 11 controls. The experimental and control groups were statistically similar in demographics and mechanism of injury, severity of injury (TS = 13.8 vs. 12.8; ISS = 27.5 vs. 24.2; PATI = 40.5 vs. 35.0), and complication rate. Length of stay (12.2 days vs. 20.7 days) and charges $27,885 vs. $53,599) tended to be greater in controls, and the comparison did not include subsequent colostomy closure. This study supports intracolonic bypass as a safe alternative to ostomy in severe colon and intraperitoneal rectal trauma.", "Fifty-six patients with penetrating colon injuries were entered into a randomized prospective study. Management of the colon injury was not dependent on the number of associated injuries, amount of fecal contamination, shock, or blood requirements. Twenty-eight patients were treated with primary repair or resection and anastomosis and 28 patients were treated by diversion (24 colostomy, 3 ileostomy, 1 jejunostomy). The average Penetrating Abdominal Trauma Index score was 23.9 for the diversion group and 26 for the primary repair group. There were five (17.9%) septic-related complications in the diversion group. This included four intra-abdominal abscesses and one subcutaneous wound infection. There were six (21.4%) septic-related complications in the primary repair group. This included one wound infection, two positive blood cultures, and three intra-abdominal abscesses. There were no episodes of suture line failure in the primary repair/anastomosis group. The authors conclude that, independent of associated risk factors, primary repair or resection and anastomosis should be considered for treatment of all patients in the civilian population with penetrating colon wounds.", "Due to the results of a 6-year experience with civilian penetrating colon injuries at Mount Carmel/Grace Hospital, in Detroit, Michigan, which had favored primary repair of colon injuries, a prospective randomized study was performed. Seventy-one patients with penetrating colon injuries were entered in a prospective randomized study. Forty-three patients were treated with primary repair or resection and anastomosis, and 28 patients were treated with diversion. The average Penetrating Abdominal Trauma Index score was 25.5 for the primary repair and 23.4 for the diversion groups. The majority of injuries as assessed by the Colon Injury Score (CIS) for the primary repair group were grades 2 (58%) and 3 (28%). The diversion group predominantly had grades 2 (64%) and 3 (25%). There was no significant difference between the two groups. There were 8 (19%) patients with colon and noncolon-related complications in the primary repair group, and 10 (36%) patients with colon, noncolon, and colostomy-related complications in the diversion group. In addition, there were 2 (7%) patients with complications following colostomy reversal. Independent risk factors for adverse outcomes were compared and used to calculate the probability for adverse outcomes with respect to the mode of treatment. The probability for adverse outcomes was statistically greater in the diversion group. An analysis was also made within the primary repair group comparing the subgroups of primary repair with, and without, resection of colon. It appears that the primary repair with resection of colon may have fewer complications; however, this conclusion is based on a statistically insufficient sample size. The authors contend that primary repair or resection with anastomosis is the method of choice for treatment of all penetrating colon injuries in the civilian population despite any associated risk factors for adverse outcomes." ]

[ "2646253", "1455880", "1496141", "3043582", "6794167" ]

[ "Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of esophageal carcinoma: report on 206 patients.", "Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer.", "Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial.", "The value of preoperative radiotherapy in esophageal cancer: results of a study by the EORTC.", "Preoperative radiotherapy for carcinoma of the esophagus." ]

[ "From June 1977 to May 1985, a prospective randomized clinical trial on pre-operative radiation for esophageal carcinoma was carried out in 206 patients. Lesions under 8 cm in length and patients younger than 65 years, at least on semi-liquid diet and not contra-indicated for surgery were randomized into a combined group (104 patients) or a surgery alone group (102 patients). Eight MV X ray units were used for the pre-operative radiation using A-P portals to deliver 4,000 cGy to the whole mediastinum and the left gastroepiploic lymphatic chain. Surgery was carried out after 2 to 4 week's rest. The immediate results of the combined group and the surgery alone group were: resection rate 93% and 85%, operative mortality 5% and 6%, intra-thoracic anastomotic leak 0% and 1%, positive pathology at the esophageal stump 0% and 2%, and lymph nodes metastasis 27% and 35% respectively. The 5-year survival rates of the combined group and the surgery alone group were 35% and 30%. We have noticed that those patients with lesions showing radiation reaction of grade III gave a 5-year survival of 50% (12/24). Because intra- and extra-thoracic lymphnode metastasis caused failures (41% and 34% of these two groups), increasing the preoperative tumor dose to 60 Gy or designing post-operative irradiation to cover the bilateral supraclavicular areas was necessary. The whole mediastinum and the left gastroepiploic lymphatics could further improve the results of surgery. Further studies are needed.", "In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival.", "One-hundred-and-seventy-six patients with potentially operable squamous cell carcinoma or adenocarcinoma of the middle or lower thirds of the oesophagus were randomly assigned to preoperative radiotherapy or surgery alone. Patients assigned to the radiotherapy arm received 20 Gy in 10 treatments over 2 weeks, using parallel opposed 4 MV beams. The preoperative radiotherapy was not associated with any significant acute morbidity or any increase in operative complications. The median survival of the overall group of 176 patients was 8 months, and the 5-year survival was 13%. There was no significant difference in the survival of the 90 patients who received preoperative radiotherapy and the 86 who were managed by surgery alone. Proportional hazards analysis identified lymph node involvement, high tumour grade and male sex as significant adverse prognostic features, but the treatment option assigned had no prognostic significance. It was concluded that low dose preoperative radiotherapy offered no advantage over surgery alone.", "nan", "From 21 March to 22 June 1976, 124 patients with squamous cell carcinoma of the esophagus were randomized for inclusion in a prospective trial of preoperative irradiation. Fifteen patients were excluded because of inoperability. Sixty-seven patients were randomly selected to receive 4,000 rads of cobalt radiation for eight days prior to operation; 57 patients were operated upon without receiving radiation therapy. No significant differences were noted between the two groups with regard to age, sex, tumor site, experience of the surgeon, method of approach or surgical technique. Eight esophageal resections were performed upon 47 of the 62 irradiated patients and 33 of the 47 nonirradiated patients. Of the 62 irradiated patients, 14 died during operation, compared with 11 of the 47 nonirradiated patients, the difference between the two groups not being statistically significant. Irradiation was associated with a higher mortality for lesions in the mid third part of the esophagus, 11 of 29 versus four of 19, but again, the difference was not significant. In the irradiated patients, the five year actuarial postoperative survival rate was 9.5 versus 11.5 per cent for the nonirradiated patients. In conclusion, preoperative radiation therapy does not produce a statistically significant short term or long term benefit in the management of squamous cell carcinoma of the esophagus." ]

[ "16202734", "15229013", "8022438", "17000504", "10214835", "16101611", "15207678", "8694046", "19205272", "9397098", "9598952", "12517648", "12789117", "10561618", "11787914", "9642607", "3151520", "15919397", "12798539", "11904609", "16041629", "11598557", "15491575", "11444340", "19241302", "15841929", "17888920", "15884282", "15042010", "14526299", "12388963", "12881083", "18979392" ]

[ "A prospective, randomized comparison of vaginal misoprostol versus intra-amniotic prostaglandins for midtrimester termination of pregnancy.", "Vaginal misoprostol versus concentrated oxytocin and vaginal PGE2 for second-trimester labor induction.", "A comparison of intravaginal misoprostol with prostaglandin E2 for termination of second-trimester pregnancy.", "Misoprostol (alone) in second trimester terminations of pregnancy: as effective as Gemeprost?", "A comparison of two dosing regimens of intravaginal misoprostol for second-trimester pregnancy termination.", "A randomised controlled trial of 6 and 12 hourly administration of vaginal misoprostol for second trimester pregnancy termination.", "Oral misoprostol vs. vaginal misoprostol for termination of pregnancy with intrauterine fetal demise in the second-trimester.", "A comparison of misoprostol with and without laminaria tents for induction of second-trimester abortion.", "Vaginal versus oral misoprostol for second-trimester pregnancy termination: a randomized trial.", "A comparison between two doses of intravaginal misoprostol and gemeprost for induction of second-trimester abortion.", "Second-trimester termination of pregnancy by extra-amniotic prostaglandin F2alpha or endocervical misoprostol. A comparative study.", "A randomized trial of oral and vaginal misoprostol to manage delivery in cases of fetal death.", "A comparative study of vaginal misoprostol and intravenous oxytocin for induction of labour in women with intra uterine fetal death in Mulago Hospital, Uganda.", "Second-trimester uterine evacuation: A comparison of intra-amniotic (15S)-15-methyl-prostaglandin F2alpha and intravaginal misoprostol.", "A randomised trial of oral versus vaginal administration of misoprostol for the purpose of mid-trimester termination of pregnancy.", "Efficacy of intravaginal misoprostol in second-trimester pregnancy termination: a randomized controlled trial.", "[Tocographic pattern induced by misoprostol].", "Second trimester abortion using intravaginal misoprostol.", "A comparison of oral misoprostol with vaginal misoprostol administration in second-trimester pregnancy termination for fetal abnormality.", "The optimization of intravaginal misoprostol dosing schedules in second-trimester pregnancy termination.", "Randomized controlled trial of vaginal misoprostol versus vaginal misoprostol and isosorbide dinitrate for termination of pregnancy at 13-29 weeks.", "[Oxytocin and misoprostol administered intravaginally for termination of pregnancy at 13 to 29 weeks of amenorrhea. A prospective randomized trial].", "Intravaginal misoprostol for pregnancy termination.", "The use of misoprostol for mid-trimester therapeutic termination of pregnancy.", "Sublingual misoprostol 100 microgram versus 200 microgram for second trimester abortion: a randomised trial.", "Randomized comparison of 3 misoprostol protocols for abortion induction at 13-20 weeks of gestation.", "Sublingual compared with oral and vaginal misoprostol for termination of pregnancy with second-trimester fetal demise.", "Comparison of vaginal and oral misoprostol, for the induction of labour in women with intra-uterine foetal death.", "Randomized controlled trial of misoprostol for second-trimester pregnancy termination associated with fetal malformation.", "A randomized comparison of two regimens of misoprostol for second-trimester pregnancy termination.", "A randomized controlled trial comparing two protocols for the use of misoprostol in midtrimester pregnancy termination.", "Second-trimester pregnancy termination: comparison of three different methods.", "Mifepristone and misoprostol versus Dilapan and sulprostone for second trimester termination of pregnancy." ]

[ "The purpose of this study was to compare the efficacy and adverse effects of vaginal misoprostol and intra-amniotic PGF2alpha for midtrimester abortion.\n One hundred thirty-two women between 12 and 24 weeks' gestation, seeking abortion in a tertiary hospital, were randomized to receive vaginal misoprostol (400 microg every 3 hours) or intra-amniotic PGF2alpha (carboprost 1.5 mg). Main outcome measures were induction-to-abortion interval, success rates at 24 and 48 hours, and adverse effects.\n Successful abortion rates at 24 and 48 hours between intra-amniotic PGF2alpha and vaginal misoprostol were not statistically different. However, vaginal misoprostol results in a significantly shorter mean induction-to-abortion interval, compared with intra-amniotic PGF2alpha (misoprostol: 16.2 hours; intra-amniotic PGF2alpha: 20.8 hours; P = .006), particularly among multiparous women (misoprostol: 13.1 hours; intra-amniotic PGF2alpha 18.3 hours; P = .011) and for gestation below 130 days (misoprostol: 14.6 hours; intra-amniotic PGF2alpha: 20.2 hours; P = .015). Fever and shivering were commoner with vaginal misoprostol.\n Vaginal misoprostol should be the regimen of choice for midtrimester abortion, particularly for multiparous women and women in the early second trimester.", "To compare the efficacy, side effects, and complications of high-dose vaginal misoprostol with concentrated intravenous oxytocin plus low-dose vaginal prostaglandin (PGE(2)) for second-trimester labor induction.\n One hundred twenty-six consenting women with maternal or fetal indications for pregnancy termination and no prior cesarean delivery were randomly assigned to receive either vaginal misoprostol 600 microg 1x, 400 microg every 4 hours 5x (misoprostol group, n = 60) or escalating-dose concentrated oxytocin infusions (277-1,667 mU/min) plus vaginal PGE(2) 10 mg every 6 hours 4x (oxytocin group, n = 66). Both groups received concurrent extra-amniotic saline infusion for cervical ripening. Women who failed their assigned regimen received 20 mg of PGE(2) suppositories every 4 hours until delivery. Analysis was by intent to treat.\n Demographic characteristics were similar between study groups. Median induction-to-delivery interval was significantly shorter in the misoprostol group (12 hours) than in the oxytocin group (17 hours; P <.001). There was a higher induction success rate at 24 hours in the misoprostol group (95%) than in the oxytocin group (85%; P =.06), although this difference did not reach statistical significance. The incidence of live birth (25% versus 17%), chorioamnionitis (5% versus 2%), and postpartum hemorrhage greater than 500 mL (3% versus 3%) were similar between the misoprostol and oxytocin groups, respectively. Diarrhea (2% versus 11%; P =.04), nausea/emesis (25% versus 42%; P =.04), and retained placenta requiring curettage (2% versus 15%; P =.008) were significantly less common in the misoprostol group when compared with the oxytocin group, respectively. Isolated intrapartum fever, however, was more frequent in the misoprostol group (67%) than in the oxytocin group (21%; P <.001).\n Compared with concentrated oxytocin plus low-dose vaginal PGE(2), high-dose vaginal misoprostol is associated with significantly shorter induction-to-delivery intervals, fewer side effects, a lower incidence of retained placenta, and comparable incidence of live birth.", "The most widely used medical method of terminating second-trimester pregnancy is the intravaginal administration of prostaglandin E2 (dinoprostone [PGE2]). This treatment is highly effective but is associated with severe gastrointestinal side effects and hyperpyrexia.\n We conducted a prospective, randomized trial comparing the efficacy and safety of misoprostol, a prostaglandin E1 analogue (200 micrograms intravaginally every 12 hours), with the efficacy and safety of PGE2 (20 mg intravaginally every 3 hours). The study population included 55 pregnant women between 12 and 22 weeks' gestation who were undergoing termination of pregnancy for either intrauterine fetal death (37 women) or medical or genetic reasons (18 women).\n The rate of successful abortions within 24 hours was 81 percent (22 of 27 women) with PGE2 and 89 percent (25 of 28 women) with misoprostol (P = 0.47). All the women who received misoprostol had successful abortions within 38 hours. Among those who had an abortion within 24 hours, the mean interval from treatment to abortion was similar in both groups (10.6 hours with PGE2 and 12.0 hours with misoprostol, P = 0.33). The rate of complete abortion, defined as the passage of the fetus and the placenta simultaneously, was 32 percent for PGE2 and 43 percent for misoprostol (P = 0.56). Certain side effects were more frequent in the women receiving PGE2 than in those receiving misoprostol: pyrexia (63 percent vs. 11 percent; P < 0.001), uterine pain (67 percent vs. 57 percent, P = 0.58), vomiting (33 percent vs. 4 percent, P = 0.005), and diarrhea (30 percent vs. 4 percent, P = 0.012). The average cost per treatment was $315.30 for PGE2, as compared with $0.97 for misoprostol.\n Misoprostol is at least as effective as PGE2 for the termination of second-trimester pregnancy involving either a dead or a living fetus, but it is less costly, is easier to administer, and is associated with fewer adverse effects.", "Gemeprost (Cervagem) has been used widely compared with Misoprostol (Cytotec) alone in second trimester pregnancy termination. This prospective randomised trial was to evaluate the efficacy of intravaginal Misoprostol (alone) and Gemeprost in second trimester termination of pregnancy. A total of 54 women with 27 on each arm were involved. A total of 25 patients (92.6%) in the Misoprostol group and 22 patients (81.5%) in the Gemeprost group delivered within 48 h. The Misoprostol group delivered earlier, although average number of tablets required were similar. The side-effects were not significant between the two groups in fact, but there was more pyrexia in the Gemeprost group (p = 0.004). Misoprostol in second trimester termination of pregnancy is clinically as effective and less costly than the standard regimen of Gemeprost.", "To compare the effectiveness of misoprostol administered intravaginally every 6 versus every 12 hours for termination of second-trimester pregnancies.\n One hundred pregnant women at 12-22 weeks' gestation were randomized to receive 200 microg of misoprostol intravaginally either every 6 or every 12 hours for up to 48 hours.\n The incidences of abortion within 48 hours after initial drug administration were 87.2 and 89.2%, the complete abortion rates 43.9 and 33.3%, and the mean abortion intervals 13.8 and 14.0 hours in the 6- and 12-hour groups, respectively. Side effects were similar between groups.\n Misoprostol administered vaginally is effective for terminating second-trimester pregnancies. Shortening the dosing interval from 12 to 6 hours produced no significant benefit.", "To compare the effectiveness of vaginal misoprostol administered 6 or 12 hourly for second trimester pregnancy termination.\n A randomised controlled trial.\n University teaching hospital.\n Two hundred and seventy-nine pregnant women at gestations between 14 and 26 weeks undergoing pregnancy termination.\n Women were randomised to receive 600-microg misoprostol tablets vaginally either every 6 hours or every 12 hours until abortion occurred.\n Induction-abortion interval, success rate within 24 and 48 hours and adverse effects.\n There was no significant difference in the median induction to abortion interval 6 hours (16 hours) and 12 hours (16 hours; P= 0.80). The total dose of misoprostol was higher in the 6-hour group (1800 vs 1200 microg). The cumulative abortion rates within 24 hours were 74% and 67% and within 48 hours 94% and 92%, in the 6- and 12-hour groups, respectively. Fever was more common in the 6-hour group (53%) versus the 12-hour group (31%; P < 0.001). The incidence of nausea, vomiting, diarrhoea, severe bleeding and abdominal pain were similar.\n Misoprostol (600 microg) administered at 12-hour intervals was associated with fewer adverse effects and was as effective as a 6-hour interval.", "nan", "Our purpose was to determine whether intracervical placement of laminaria tents would improve the effectiveness of the prostaglandin analog misoprostol for the elective termination of pregnancies in the second trimester.\n Sixty-eight women between 12 and 22 weeks of gestation with either an intrauterine fetal death (n = 40) or medical or genetic indications for pregnancy termination (n = 30) were randomized to receive 200 micrograms of misoprostol administered vaginally every 12 hours with or without intracervical placement of laminaria concurrently with the first dose of misoprostol.\n The rate of abortion 24 hours after initiation of treatment was 69.7% in the 33 women receiving misoprostol alone and 68.6% in the 35 women treated with misoprostol and laminaria. The abortion rates 48 hours after initiation of treatment were 84.8% and 91.4%, respectively, an insignificant difference. The complete abortion rate was also similar between women receiving misoprostol alone (39.3%) and the group receiving misoprostol and laminaria (37.5%). There were no significant differences in the incidence of fever, vomiting, diarrhea, or pain. The mean interval from initiation of treatment to abortion was also similar, 15.7 hours in those receiving misoprostol alone and 17.4 hours in those treated with misoprostol and laminaria. In both groups women who had live fetuses at the start of the procedure had a higher failure rate of abortion and a longer time interval to abortion than women whose fetus was dead.\n Laminaria tents inserted concurrently with the first dose of misoprostol do not significantly improve the abortifacient effect of vaginal misoprostol in the second trimester of pregnancy.", "The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination. Sixty women in second trimester of gestation with indications for pregnancy termination were randomly assigned in two equal groups to receive either vaginal or oral misoprostol. The dosing regimen was 400 microg as the initial dose followed by 400 microg up to 3 doses (1200 microg) if needed in each group. Efficacy and side effects were compared. The percentage of women who delivered was significantly higher in vaginal group than the oral group (86.7 vs. 43.3 p = 0.0006). No significant differences in complication rates and induction to delivery interval were noted between the two groups. Vaginal administration of misoprostol resulted in a higher success rate for second trimester pregnancy termination, whereas, no significant differences in induction to delivery time and complication rates were noted between vaginal and oral groups.", "To compare the abortifacient efficacies of two intravaginally administered misoprostol doses and gemeprost in termination of second-trimester pregnancy.\n Eighty-one women between 12 and 24 weeks' gestation requesting abortion were randomized to receive intravaginally either 100 micrograms of misoprostol at 6-hour intervals (n = 27), 200 micrograms of misoprostol at 12-hour intervals (n = 26), or 1.0 mg of gemeprost at 3-hour intervals (n = 28). The regimen was continued until abortion, or for 36 hours, with assessment of the rate of complete and incomplete abortions as well as side effects within 48 hours from the start of the treatment.\n The final rates of terminations were 74% in the 100-microgram misoprostol group, 92% in the 200-microgram misoprostol group, and 89% in the gemeprost group. Abortion was complete in 37%, 61%, and 32% in each group, respectively (P = .03, when the 200-microgram misoprostol group was compared with the two other groups). The induction-to-abortion interval was longer (P = .001) in the misoprostol groups (mean 23.1 hours for the 100-microgram and 27.8 hours for the 200-microgram dose) than in the gemeprost group (14.5 hours). There was less pain (P = .01), diarrhea (P = .001), and vomiting (P = .01) in the misoprostol groups than in the gemeprost group. The mean blood loss in the misoprostol groups was lower than in the gemeprost group (P = .001).\n Intravaginal application of 200 micrograms of misoprostol at 12-hour intervals in induction of second-trimester abortion is equally effective to a standard gemeprost regimen. Misoprostol causes fewer side effects and is cheaper and more practical to use.", "To compare the efficacy and side effects of extra-amniotic prostaglandin F2alpha with intracervical misoprostol for midtrimester termination of pregnancy\n Forty women were randomized to receive either intracervical misoprostol or extra-amniotic prostaglandin F2alpha for termination of pregnancy for congenital abnormalities or intrauterine fetal death. Induction-abortion interval and the incidence of side effects were analyzed for both groups.\n All women in the PGF2alpha group; aborted within 28 hours, 16 (80%) of which aborted within 20 hours. Medical termination of pregnancy was complete in 13 cases (65%). In the misoprostol group; all women aborted within 20 hours, 18 (90%) of which aborted within 13 hours. Medical termination of pregnancy was complete in 17 cases (85%). The induction to abortion intervals for the extra-amniotic PGF2alpha and intracervical misoprostol were 16+/-5.9 hours, and 10.3+/-4 hours (mean+/-s.d.) respectively. This was statistically significant (p=0.001). The incidence of prostaglandin-associated pyrexia, vomiting and diarrhea were significantly increased in the PGF2alpha group (p<0.05). Abdominal pain was similar in both groups. There was no post-abortive hemorrhage or infection.\n Misoprostol is an effective, easy to use, safe and cheap drug for termination of second trimester pregnancy. Intracervical administration of misoprostol appears to be effective and well-tolerated with less side effects and no complications. Larger, randomized comparative studies should be carried out to assess its potential advantages.", "To compare the effectiveness and side effects of oral and vaginal misoprostol for the termination of second and third trimester pregnancy with intrauterine fetal death.\n Eighty pregnant women at 16-41 weeks' gestation with intrauterine fetal death were randomized in two groups to receive either 400 micro g of misoprostol orally every 4 hours (n = 40) or 200 micro g of misoprostol vaginally every 12 hours (n = 40) until the termination of pregnancy was completed. The adverse effects, progress, and outcomes of delivery were assessed.\n The groups were similar in age, weight, height, gestational age, parity, and modified Bishop scores before intervention. The mean induction-to-delivery time in the oral group (13.95 [standard deviation (SD) = 5.63] hours) was significantly shorter than the time in the vaginal group (18.87 [SD = 10.38] hours, P =.001). The number of deliveries within 24 hours after the initial drug administration in the oral group (92.5%) was significantly higher than the number in the vaginal group (67.5%, P <.001), and all delivered within 48 hours after the initial drug administration. However, the gastrointestinal side effects in the oral group was significantly higher than in the vaginal group (P =.005).\n Misoprostol (400 micro g given orally every 4 hours) was more effective than misoprostol (200 micro g given vaginally every 12 hours) for the termination of second and third trimester pregnancy with intrauterine fetal death, but with more gastrointestinal side effects.", "Intrauterine fetal death is a major problem in obstetrics particularly in developing countries such as Uganda. Induction of labour in cases of fetal death using the available method of oxytocin is often difficult, expensive and frustrating.\n To compare the effectiveness of vaginal misoprostol and intravenous oxytocin in induction of labour in women with intrauterine fetal death.\n One hundred and twenty mothers were allocated in a randomised controlled way to one of the two induction groups. Oxytocin infusion was titrated based on patient response. The starting dose was 50 mcg (1/4 tablet) in misoprostol group and the dose was doubled every six hours till effective contractions were achieved. The two groups were compared for induction to delivery intervals, costs of the drugs and their safety during induction.\n The success rate within 48 hours of induction was 100% in the misoprostol group and 96.7% in oxytocin group. The mean induction to delivery time was significantly longer in the oxytocin group compared with the misoprostol group (23.3 versus 12.4 hours; p= 0.004). In the gestational age before 28 weeks, the induction to delivery interval in oxytocin group, was more than twice that used in misoprostol. However beyond 28 weeks, there was no significant difference. Women with intact membranes had induction to delivery interval of 27.9 hours in the oxytocin group and 14.7 hours in the misoprostol group (p=0.002). When the membranes were ruptured, the values were 10.5 and 8.5 hours respectively (p=0.6). The induction to delivery time in cases with Bishop's score < 6 was 29.8 hours in the oxytocin group and 15.9 hours in misoprostol group (p=0.001). The corresponding values for Bishop's scores > 6 were 10 and 7.9 hours respectively (p=0.6). The majority of patients in misoprostol group (62%), required less than one tablet for successful induction. Misoprostol was cheaper (0.65 US dollars than oxytocin (7.86 US dollars) Retained placenta occurred in only 3.3% of the patients in the misoprostol group. There were no cases of ruptured uterus in both groups.\n Intravaginal misoprostol is more effective and cheaper than intravenous oxytocin for inducing labour in patients with intrauterine fetal death.", "Our purpose was to compare the efficacy, safety, and adverse effects of intra-amniotically administered (15S)-15-methyl-prostaglandin F(2alpha) and intravaginally administered misoprostol for second-trimester uterine evacuation.\n Fifty-one patients were randomly assigned to receive either a single 2.5-mg intra-amniotic injection of (15S)-15-methyl-prostaglandin F(2)(alpha) (n = 26) or two 200-microg intravaginal doses of misoprostol (n = 25) at 12-hour intervals. The primary outcome measured was evacuation of the uterus within 24 hours.\n The mean time from initiation of termination to uterine evacuation was less in the prostaglandin group than in the misoprostol group (17.5 +/- 8.6 hours vs 22.3 +/- 12.5 hours), but this was not statistically significant (P >.05). The rate of successful fetal evacuation at 24 hours was significantly higher in the prostaglandin group than in the misoprostol group (88% vs 60%, P =.02). The complete-abortion rate and the incidence of adverse effects were similar in both groups.\n The use of an intra-amniotic injection of (15S)-15-methyl-prostaglandin F(2alpha) for midtrimester pregnancy termination is safe and is associated with a greater number of successful uterine evacuations within 24 hours, without an increase in adverse effects, than intravaginal administration of misoprostol.", "A prospective randomised controlled trial was undertaken to compare the efficacy of two routes of administration, oral versus vaginal, of the prostaglandin E1 analogue misoprostol (Cytotec) to effect termination of pregnancy in the mid-trimester. Fifty-five women were recruited into the trial; 26 to receive all doses orally and 29 via the vaginal route. The dosing regimen was 400 microg as the initial dose followed by a second dose of 200 microg two hours later and then four-hourly 200 microg doses until delivery or 32 hours from commencement of treatment. If delivery had not been effected by the last dose of misoprostol, a Syntocinon infusion was started synchronously Misoprostol administered vaginally was significantly more effective than when administered orally as judged by induction-to-delivery interval and also the need or otherwise to augment therapy with a Syntocinon infusion. The average induction-to-delivery interval was 17.5 hours in the vaginal group compared to 33 hours in the oral group (p = 0.0003). The percentages of women who delivered at 24 and 48 hours were 93% and 100% in the vaginal administration group and 19% and 70% in the oral administration group (p < 0.05). No significant differences in complication rates or side effects were noted between the two groups", "A prospective randomized, double-blind, controlled clinical trial to compare the clinical efficacy and side effects of intravaginal misoprostol with the traditional prostaglandin, gemeprost, in second-trimester pregnancy interruption was conducted. A sample size of 100 women was calculated to demonstrate that misoprostol was as effective as gemeprost in achieving delivery within 24 hours (alpha = 0.1, 80% power). Women were recruited with fetal death in utero, severe fetal anomaly, or psychosocial pregnancy termination between 14 and 28 weeks gestation and randomized to receive either 1 mg gemeprost 3 hourly for 5 doses, or 200 mcg misoprostol 6 hourly for 4 doses, intravaginally. The therapeutic regimens were repeated if undelivered by 24 hours. Those undelivered after 48 hours received an extra-amniotic PGF2 alpha infusion. The median gestation at recruitment was identical: gemeprost 19 weeks (IQ 17-22 weeks) vs. misoprostol 19 weeks (IQ 17-21 weeks), P = 0.887. Delivery within 24 hours occurred in 75.1% of women receiving gemeprost and 74.9% receiving misoprostol (P = 1.0). The median time from prostaglandin commencement to delivery was similar: gemeprost 13.7 hours (IQ 9.0-23.5 hours) vs. misoprostol 16.9 hours (IQ 10.3-23.5 hours), P = 0.769. A significant reduction in the incidence of vomiting in women randomized to misoprostol occurred (34% vs. 13.2%, P = 0.017). There was no significant difference in the incidence of maternal fever > 37.5 degrees C, nausea, diarrhea, or placental retention. A 200-fold pharmaceutical cost advantage was observed with the use of misoprostol compared with gemeprost. Intravaginal misoprostol performs as effectively as gemeprost in achieving delivery in the second trimester without increase in adverse effects and displaying a significant cost advantage.", "nan", "nan", "To compare the clinical efficacy and side effects of oral misoprostol with vaginal misoprostol for second-trimester pregnancy termination.\n A randomized clinical trial of medical pregnancy termination between 14 and 26 weeks' gestation was conducted. Three misoprostol regimens were compared: 400 microg vaginally at 6-hour intervals (group 1), 400 microg orally at 3-hour intervals (group 2), and a loading dose of 600 microg vaginally followed by 200 microg orally at 3-hour intervals (group 3). A sample size of 225 women was required for equivalence of the three regimens, with an interim safety analysis planned at 80 women.\n A significant difference between the groups was evident at the interim safety analysis and the study ceased. The subset of 84 women recruited before the study closure is described. There was a significant difference in the median time to achieve delivery among the three groups: group 1, 14.5 hours (95% confidence interval 12.0, 16.9), versus group 2, 25.5 hours (13.5, 23.8), versus group 3, 16.4 hours (interquartile range 14.2-37.3) (P =.042). Within 24 hours of commencement 85.7% of women in group 1, 44.8% in group 2, and 74.1% in group 3 delivered (P =.003). At 48 hours 0% in group 1, 20.7% in group 2, and 3.7% in group 3 were undelivered (P =.011). There was no difference in women's perceptions of the termination process.\n In second-trimester pregnancy termination, a vaginal misoprostol regimen of 400 microg every 6 hours was 1.9 times more likely to result in delivery within 24 hours from commencement than an oral regimen of 400 microg every 3 hours.", "The purpose of this study was to compare the clinical efficacy and side effects of 3 doses of intravaginal misoprostol for second-trimester pregnancy termination.\n This was a prospective randomized, double-blind controlled clinical trial of 150 women who underwent pregnancy termination between 14 and 30 weeks of gestation. Three intravaginal misoprostol regimens were compared: 200 microg misoprostol at 6-hour intervals (group 1), 400 microg misoprostol at 6-hour intervals (group 2), and a loading dose of 600 microg misoprostol followed by 200 microg at 6-hour intervals (group 3).\n There was a significant difference in the median time to achieve delivery among the 3 groups: group 1 (18.2 hours [IQ, 13.3-32.5 hours]) vs group 2 (15.1 hours [IQ, 10.9-23.7 hours]) vs group 3 (13.2 hours [IQ, 11.2-21.7 hours]; P =.035). Fifty-nine percent of the women in group 1, 76% of the women in group 2, and 80% of the women in group 3 delivered within 24 hours (P =.013). There were 7.8% of the women in group 1, 0% of the women in group 2, and 2% of the women in group 3 who were undelivered at 48 hours (P =.02). There was an increase in the incidence of fever in the first 12 hours (P =.038) and in the incidence of vomiting within 3 hours of the initial dose (P =.048) in group 3 compared with the other groups.\n Intravaginal misoprostol 400 microg at 6-hour intervals appears to be the preferred regimen for second-trimester pregnancy termination, with a shorter commencement to delivery interval than the 200 microg regimen and fewer maternal side-effects than the 600 microg loading dose regimen.", "When compared to the use of 12 hourly 200 microg vaginal misoprostol on its own, the addition of a single dose of 5 mg did not significantly increase the abortion or delivery rate in pregnancy termination at 13-29 weeks gestation. All patients were given intravenous syntocinon at 30 mU/min from the first dose of misoprostol onwards.", "To compare the effectiveness of misoprostol administrated intravaginally alone versus misoprostol with oxytocin infusion for termination of pregnancy at 13 to 29 weeks. Subjects and methods. Ninety women at 13-29 weeks requesting pregnancy termination were randomized to receive 200 microgram of misoprotol intravaginally every 12 hours either with oxytocin infusion or alone for up to 48 hours.\n The mean induction to abortion interval was significantly shorter in the misoprostol-oxytocin group than in the misoprostol alone group (22+/-10.8 hours versus 27+/-14.1 hours respectively p<0.05). The 48 hours successful abortion rates were 95% and 90% respectively. Abortion was complete in 79.1% and 62.5% respectively. Side effects were similar between groups.\n Vaginal misoprostol associated with oxytocin infusion is more effective than misoprostol alone in termination of second-trimester pregnancy.", "nan", "Extra-amniotic prostaglandin F2alpha (PG F2alpha) is probably the most widely used medical method for mid-trimester termination of pregnancy. The method is highly effective but is financially costly, particularly for poor countries faced with restricted health budgets. The aim of this study was to establish whether misoprostol administered vaginally is as effective as PG F2alpha. Sixty-one patients were prospectively randomized to receive either misoprostol (n=30) vaginally, or PG F2alpha (n=31) extra-amniotically. The overall success rate was 83.6%. The success rates in the misoprostol and PG F2alpha groups were 83.3% and 83.8% respectively. There was no statistical difference in the groups in relation to side effects. In this carefully selected group of patients, misoprostol was as safe and effective as PG F2alpha in mid-trimester termination of pregnancy. In these days of financial constraints, misoprostol is the preferred method for mid-trimester termination of pregnancy.", "To compare the efficacy of repeated doses of 100 microg vs. 200 microg misoprostol given sublingually for induction of second trimester abortion.\n One hundred and sixty-two women at 15-22 weeks' gestation were randomized to receive every 2 h either 100 microg (group 1; n = 81) or 200 microg (group 2; n = 81) misoprostol sublingually. The primary outcome measure was the abortion rate within 24 h. The secondary outcome measures were the induction-abortion interval, the total misoprostol dose required, and side effects of the regimen.\n There was no significant difference between the two groups with regard to the abortion rates within 12 h (43.2% in group 1 vs. 48.1% in group 2; p = 0.52; relative risk [RR]: 0.81; 95% confidence interval [CI]: 0.4-1.5) and 24 h (92.6% in group 1 vs. 91.4% in group 2; p = 0.77; RR: 1.11; 95% CI: 0.37-3.6). The induction-abortion intervals in the two groups were of similar length (885 minutes in group 1 vs. 912 minutes in group 2; p = 0.72). When the total dose of misoprostol was compared between the two groups, women belonging to group 2 on average had received significantly more misoprostol than those in group 1 (1274 +/- 592 microg [7 +/- 3 doses] vs. 614 +/- 432 microg [6 +/- 4 doses], respectively; p = 0.000).\n Sublingual administration of repeated doses of 100 microg misoprostol for abortion induction appears to be equally effective to that of repeated doses of 200 microg.", "To evaluate the induction-to-abortion time of 3 pharmacokinetic-based protocols at 13-20 weeks of gestation.\n A randomized trial was conducted on 153 patients. The oral group (n = 51) received 100 microg misoprostol orally every 2 hours, the vaginal group (n = 51) received 200 microg misoprostol vaginally every 4 hours, and the sublingual group (n = 51) received 100 microg misoprostol sublingually every 2 hours.\n The mean induction-to-delivery time was shorter in the sublingual group (mean, 651 +/- 507) as compared to the vaginal group (mean, 1,056 +/- 634, p = 0.01). The number of patients who delivered within 12 hours was significantly higher in the sublingual group (n = 39, 78%) as compared to the oral (n = 26, 52%) and vaginal (n = 20, 40%) groups (p < 0.001). The numbers of patients who delivered within 24 hours were comparable in the sublingual (n = 47, 94%) and oral (n = 46, 92%) groups but higher than in the vaginal group (n = 39, 78%; p = 0.02). The total misoprostol dose was 543 +/- 422 microg in the sublingual group, 878 +/- 533 microg in the vaginal group and 741 +/- 413 microg in the oral group (p < 0.001).\n A pharmacokinetic-based application of 100 microg of sublingual misoprostol every 4 hours is more effective for induction of second-trimester abortion as compared to 100 microg oral misoprostol every 2 hours and 200 microg vaginal misoprostol every 4 hours.", "nan", "To compare the efficacy of vaginal and oral misoprostol for the induction of labour in women with intra-uterine foetal death (IUFD).\n A prospective randomised clinical trial, comparing 200 microg oral and 200 microg vaginal misoprostol, six hourly for a maximum of four doses for the induction of labour in women with IUFD.\n Ga-Rankuwa hospital (Department of Obstetrics and Gynaecology), Pretoria, South Africa. It is a tertiary institution serving predominantly black indigenous population.\n The primary outcome measure was the induction to delivery time, and secondary outcome measures were the number of patients requiring augmentation with oxytocin and all complications were noted.\n Twenty women were randomised to the vaginal route and 18 to the oral route. The induction to delivery time was shorter with vaginal misoprostol (13.5 +/- 8.3 hrs) compared to oral misoprostol (21.4 +/- 13.9 hrs; p < 0.05). There was no significant difference in the amount of misoprostol needed to achieve successful induction in the two groups. More women (10/18) who received oral misoprostol required oxytocin augmentation to complete the induction of labour compared with 4/20 women in the vaginal group (p < 0.05; Odds Ratio 2.8; 95% Cl 1.36 - 4.24). There were no cases of failed induction. The systemic side effects (shivering, diarrhoea, vomiting and pyrexia) were more common with oral misoprostol (44.5%) compared to vaginal misoprostol (20%). This difference gives an overall Odds Ratio of 2.2 at 95% Cl of 1.6-2.8(p < 0.05).\n Vaginal misoprostol achieved successful induction of labour in women with IUFD in a shorter time than oral misoprostol with significantly less side effects.", "Our purpose was to compare the effectiveness, women's views of the termination procedure, and success of umbilical cord culture for vaginal and oral misoprostol versus intra-amniotic prostaglandin PGF(2alpha) for second-trimester pregnancy termination (STPT).\n We randomized 217 women, 15 to 24 weeks' gestation, into 3 groups. Oral (OM) and vaginal (VM) misoprostol groups received 400 microg of misoprostol every 4 hours for 24 hours. The intra-amniotic PGF(2alpha) (IAPG) group received 40 mg of PGF(2alpha) followed by oxytocin infusion. Women completed self-administered questionnaires 3 weeks after the termination procedure. Umbilical cord samples were collected at delivery for karyotype analysis. The primary outcome was the time from start of the procedure to placental delivery. Secondary outcomes were maternal complications, women's acceptance of the termination procedure, and success rates of umbilical cord culture.\n The time was longer for the OM group (30.5+/-14.4 hours) compared with the VM group (18.3+/-8.2 hours) and the IAPG group (21.1+/-10.2 hours), P<.001 for both comparisons. Women in the VM group reported being more willing to repeat the termination method in the future and reported fewer side effects than those in the other groups, P<.001. Failure rates for umbilical cord cultures were 9.6%, 17.0%, and 45.6% for the VM, OM, and IAPG groups, respectively.\n Oral misoprostol is less effective than intra-amniotic PGF(2alpha) or vaginal misoprostol for STPT. Women report vaginal misoprostol more acceptable than other methods. Umbilical cord culture failure rate is highest in the IAPG group.", "The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination.\n We performed a randomized clinical trial in patients who were at 14 to 23 weeks of gestation and who were admitted for medical termination of pregnancy. All patients received 800 microg of vaginal misoprostol and were assigned randomly to 400 microg of oral misoprostol or 400 microg of vaginal misoprostol every 8 hours. Efficacy and side effects were compared. The mean induction time of the study group was compared with that of an historic control group that had received 400 microg vaginally every 12 hours.\n Forty-three women were assigned randomly, 22 women to vaginal misoprostol and 21 women to oral misoprostol. Induction time and hospital stay were slightly shorter for the oral group; however, the differences were not significant. Side effects were similar for both groups.\n After an initial 800 microg dose of vaginal misoprostol, a regimen of 400 microg of oral misoprostol every 8 hours is as effective as the same dose of vaginal misoprostol with no additional side effects, which provides a convenient alternative for midtrimester pregnancy termination.", "Our purpose was to compare the efficacy of oral misoprostol with that of vaginal misoprostol for midtrimester termination of pregnancy.\n Women seen for midtrimester pregnancy termination were randomly assigned to receive either misoprostol orally in a dose of 200 microg every hour for 3 hours followed by 400 microg every 4 hours or vaginally in a dose of 400 microg every 4 hours. The protocol was followed for 24 hours, after which time further management was at the discretion of the attending physician. The primary outcome measure was the induction-to-delivery interval. Sample size was calculated a priori. Statistical analysis was performed with the t test for continuous variables and the chi(2) test for categorical variables. P <.05 was considered significant.\n One hundred fourteen women were randomized, with 49 receiving vaginal misoprostol and 65 receiving oral misoprostol. The two groups were comparable with respect to maternal age, parity, indication for pregnancy termination, gestational age, and maternal weight. The mean induction-to-delivery interval was significantly shorter for the vaginal group (19.6 +/- 17.5 hours vs 34.5 +/- 28.2 hours, P <.01). Length of stay was also shorter in the vaginal group (32.3 +/- 17.3 hours vs 50.9 +/- 27.9 hours, P <.01). Significantly more patients in the vaginal group were delivered within 24 hours (85.1% vs 39.5%, P <.01), and more patients in the oral group required changes in the method of induction when they were undelivered after 24 hours (38.2% vs 7%, P <.01). The only complication was an increase in febrile morbidity in the vaginal group (25% vs 6.7%, P =.046). This did not result in an increased use of antibiotics, and all the fevers resolved post partum without further complications.\n Vaginal administration of misoprostol resulted in a shorter induction-to-delivery interval. The shorter length of stay should result in improved patient care.", "The object of this study was to compare intravaginal misoprostol and dinoprostone (prostaglandin E2) for second-trimester pregnancy termination, and to examine the role of the nitric oxide donor, glyceryl trinitrate, as a possible alternative to prostaglandins to induce cervical ripening in second-trimester pregnancy termination. This was a randomised clinical trial. The trial involved pregnant women between 13 and 28 weeks' gestation admitted with clear medical or obstetric indications for pregnancy termination, and was carried out in the department of obstetrics and gynecology, Assiut University Hospital, Egypt. Patients were classified into Group A, where pregnancy termination was induced by vaginal misoprostol 100 micrograms every 4 hours with a maximum dose of 500 micrograms; Group B, where induction was by vaginal dinoprostone 6 mg every 6 hours with a maximum dose of 24 mg; and Group C, where induction involved vaginal glyceryl trinitrate 500 micrograms every 6 hours with a maximum dose of 2.5 mg. Twenty-four hours after the start of induction, the rate of complete abortion in the three groups was 100%, 66.67% and 0%, respectively. The rate of complete abortion was 100% in the nitric oxide (glyceryl trinitrate)-induced group after introducing a complementary procedure. The induction-abortion interval was significantly shorter, the number of doses needed was less and the maximum Bishop score reached was greater with misoprostol than with dinoprostone. A higher rate of side effects occurred with the misoprostol-induced group (74%) compared with the other two groups (46.6% and 0%). Misoprostol is a cheap, effective drug for second-trimester pregnancy termination with short induction abortion intervals but a higher rate of side effects. Prostin E2 is also effective in termination of second-trimester pregnancy but is expensive and may require high doses to be administered. Glyceryl trinitrate is an effective drug for cervical ripening (softening) but it has no role in the stimulation of uterine contractions.", "To compare two methods for second trimester termination of pregnancy: mifepristone and misoprostol versus Dilapan and sulprostone.\n This was a randomized study involving 16 patients with a singleton live fetus with congenital malformations or genetic disorders. Eight patients were treated with 200 mg mifepristone orally followed by 200 microg misoprostol vaginally 3 hourly and eight patients received a sulprostone infusion after cervical dilatation with Dilapan.\n Mifepristone and misoprostol had a mean induction interval of 17.8 hours and sulprostone and Dilapan 20.9 hours. The mean induction interval did not differ significantly. Mean hospital stay was shorter in the patients treated with misoprostol: 2.1 vs. 3.3 days (p = 0.02) with a 95% confidence interval of -2.1 to 0.3.\n Mifepristone and misoprostol did not reduce the induction interval significantly compared to the sulprostone and Dilapan treatment for second trimester pregnancy termination. Hospital admission was significantly shorter in patients treated with mifepristone and misoprostol." ]

[ "15063521", "15821899", "9234872", "15566133", "17053946", "8288661", "10342350", "16075172", "10857066", "18656872" ]

[ "Complex tibial fracture outcomes following treatment with low-intensity pulsed ultrasound.", "The effect of low intensity ultrasound and bioabsorbable self-reinforced poly-L-lactide screw fixation on bone in lateral malleolar fractures.", "Accelerated healing of distal radial fractures with the use of specific, low-intensity ultrasound. A multicenter, prospective, randomized, double-blind, placebo-controlled study.", "The effect of pulsed ultrasound in the treatment of tibial stress fractures.", "The effects of extracorporeal shockwave on acute high-energy long bone fractures of the lower extremity.", "Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound.", "No effect of low-intensity ultrasound on healing time of intramedullary fixed tibial fractures.", "Effect of ultrasound therapy on bone healing of lateral malleolar fractures of the ankle joint fixed with bioabsorbable screws.", "[Does low intensity, pulsed ultrasound speed healing of scaphoid fractures?].", "Low-intensity pulsed ultrasound (LIPUS) in fresh clavicle fractures: a multi-centre double blind randomised controlled trial." ]

[ "A clinical study was conducted to investigate the effect of low-intensity pulsed ultrasound (US) stimulation (LIPUS) on the healing of complex tibial fractures. Thirty complex tibial fractures were randomly assigned to the treatment with LIPUS (n = 16) or by a dummy machine (sham-exposed: n = 14). The fractures were immobilized by either internal or external fixations according to the clinical indications. LIPUS was given 20 min/day for 90 days. Fracture healing was monitored by clinical, radiological, densitometric and biochemical assessments. The LIPUS-treated group showed statistically significantly better healing, as demonstrated by all assessments. Complications were minimal in the LIPUS group. There were two cases of delayed union, with one in each group. There were two cases of infection in the control group. The delayed-union cases were subsequently treated by LIPUS and the infection cases were treated with standard protocol. Fracture healing in these patients was again treated by LIPUS.", "There are no previous reports of low intensity pulsed ultrasound therapy in connection with bioabsorbable fracture fixation. In this randomised, prospective, double-blind and placebo-controlled study, the effects of ultrasound on bone mineral density and bone healing were examined in lateral malleolar fractures fixed with a bioabsorbable self-reinforced poly-L-lactide screw (SR-PLLA).\n Thirty adult patients with SR-PLLA screw-fixed lateral malleolar fracture underwent ultrasound therapy 20 min daily for 6 weeks. Half of the patients were provided randomly with a sham ultrasound device. Bone mineral density and bone healing were assessed by dual-energy X-ray absorptiometry (DXA) and by radiographs.\n Bone mineral density of the fractured lateral malleolus tended to increase slightly during 12 weeks of follow-up. The increase was symmetrical and statistically non-significant between the ultrasound and non-ultrasound group. All the fractures healed uneventfully. The biocompatibility of the bioabsorbable SR-PLLA fixation device and low intensity pulsed ultrasound was good. Despite the slight tendency for more frequent callus formation in the ultrasound group, no statistically significant effect of low intensity pulsed ultrasound on lateral malleolar fracture healing could be observed.\n It was not possible to observe any statistically significant effect of low intensity pulsed ultrasound on lateral malleolar fracture healing in this study. Further studies are needed to examine the role of ultrasound therapy in the healing of fractures treated with bioabsorbable fixation devices.", "A multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to test the efficacy of a specifically programmed, low-intensity, non-thermal, pulsed ultrasound medical device for shortening the time to radiographic healing of dorsally angulated fractures (negative volar angulation) of the distal aspect of the radius that had been treated with manipulation and a cast. Sixty patients (sixty-one fractures) were enrolled in the study within seven days after the fracture. The patients used either an active ultrasound device (thirty fractures) or a placebo device (thirty-one fractures) daily for twenty minutes at home for ten weeks. The two types of devices were identical except that the placebo devices emitted no ultrasound energy. Clinical examination was performed and radiographs were made at one, two, three, four, five, six, eight, ten, twelve, and sixteen weeks after the fracture by each site investigator. The time to union was significantly shorter for the fractures that were treated with ultrasound than it was for those that were treated with the placebo (mean [and standard error], 61 +/- 3 days compared with 98 +/- 5 days; p < 0.0001). Each radiographic stage of healing also was significantly accelerated in the group that was treated with ultrasound as compared with that treated with the placebo. Compared with treatment with the placebo, treatment with ultrasound was associated with a significantly smaller loss of reduction (20 +/- 6 per cent compared with 43 +/- 8 per cent; p < 0.01), as determined by the degree of volar angulation, as well as with a significant decrease in the mean time until the loss of reduction ceased (12 +/- 4 days compared with 25 +/- 4 days; p < 0.04). We concluded that this specific ultrasound signal accelerates the healing of fractures of the distal radial metaphysis and decreases the loss of reduction during fracture-healing.", "Tibial stress fractures commonly occur in athletes and military recruits. This prospective, randomized, double-blind clinical study sought to determine whether pulsed ultrasound reduces tibial stress fracture healing time. Twenty-six midshipmen (43 tibial stress fractures) were randomized to pulsed ultrasound or placebo treatment. Twenty-minute daily treatments continued until patients were asymptomatic with signs of healing on plain radiographs. The groups were not significantly different in demographics, delay from symptom onset to diagnosis, missed treatment days, total number of treatments, or time to return to duty. Pulsed ultrasound did not significantly reduce the healing time for tibial stress fractures.", "High-energy long bone fractures of the lower extremity are at risk of poor fracture healing and high rate of non-union. Extracorporeal shockwave was shown effective to heal non-union of long bone fracture. However, the effect of shockwave on acute fractures is unknown. The purpose of this study was to investigate the effects of shockwave on acute high-energy fractures of the lower extremity.\n Between January and October 2004, 56 patients with 59 acute high-energy fractures were enrolled in this study. Patients were randomly divided into two groups with 28 patients with 28 fractures in the study group and 28 patients with 31 fractures in the control group. Both groups showed similar age, gender, type of fracture and follow-up time. Patients in the study group received open reduction and internal fixation and shockwave treatment immediately after surgery on odd-numbered days of the week, whereas, patients in the control group received open reduction and internal fixation without shockwave treatment on even-numbered days of the week. Postoperative managements were similarly performed in both groups including crutch walking with non-weight bearing on the affected limb until fracture healing shown on radiographs. The evaluation parameters included clinical assessments of pain score and weight bearing status of the affected leg and serial radiographs at 3, 6 and 12 months. The primary end-point is the rate of non-union at 12 months, and the secondary end point is the rate of fracture healing at 3, 6 and 12 months.\n At 12 months, the rate of non-union was 11% for the study group versus 20% for the control group (P < 0.001). Significantly, better rate of fracture healing was noted in the study group than the control group at 3, 6 and 12 months (P < 0.001).\n Extracorporeal shockwave is effective on promoting fracture healing and decreasing the rate of non-union in acute high-energy fractures of the lower extremity.", "Sixty-seven closed or grade-I open fractures of the tibial shaft were examined in a prospective, randomized, double-blind evaluation of use of a new ultrasound stimulating device as an adjunct to conventional treatment with a cast. Thirty-three fractures were treated with the active device and thirty-four, with a placebo control device. At the end of the treatment, there was a statistically significant decrease in the time to clinical healing (86 +/- 5.8 days in the active-treatment group compared with 114 +/- 10.4 days in the control group) (p = 0.01) and also a significant decrease in the time to over-all (clinical and radiographic) healing (96 +/- 4.9 days in the active-treatment group compared with 154 +/- 13.7 days in the control group) (p = 0.0001). The patients' compliance with the use of the device was excellent, and there were no serious complications related to its use. This study confirms earlier animal and clinical studies that demonstrated the efficacy of low-intensity ultrasound stimulation in the acceleration of the normal fracture-repair process.", "To determine whether stimulation with low-intensity ultrasound will reduce the radiologic healing time of fresh tibial shaft fractures fixed with a reamed and statically locked intramedullary rod.\n Prospective, randomized, double blinded, and placebo controlled.\n Thirty-two adult patients were included, fifteen in the active ultrasound group and seventeen in the placebo group. They all used an ultrasound device twenty minutes daily for seventy-five days without knowing whether it was active or inactive. Standardized radiographs were taken every third week until healing and at six and twelve months. All radiographs were assessed blinded and independently by a radiologist and an orthopaedic surgeon. The codes were not broken until all fractures had healed and all radiographs had been evaluated.\n The time until the first visible callus averaged 40+/-3 days for the active group and 37+/-3 days for the placebo (p=0.44). The healing time, defined as radiologic bridging of three cortices, was on average 155+/-22 days (median 113 days) for the active treatment group and 125+/-11 days (median 112 days) for the placebo group (p=0.76) as assessed by the radiologist and 128+/-13 days for the active group and 114+/-9 days for the placebo group (p=0.40) as evaluated by the orthopaedic surgeon.\n We conclude that low-intensity ultrasound treatment did not shorten healing time in fresh tibial fractures treated with a reamed and statically locked intramedullary nail. Our results are not in accordance with previous findings reporting reduced healing time in nonoperatively treated tibial shaft fractures when subjected to ultrasound.", "We investigated the effect of low-intensity ultrasound on bone healing in bioabsorbable self-reinforced poly-L: -lactic acid (SR-PLLA) screw-fixed lateral malleolar fractures. The study design was prospective, randomized, double-blind, and placebo-controlled.\n A total of 22 fractures were fixed with one SR-PLLA screw. All the patients were instructed to use an ultrasound device 20 min daily for 42 days without knowing whether it was active or inactive. Eleven patients had active and eleven sham ultrasound devices. The causes of error during treatment with head module placement and attachment to the convex surface of the lateral distal fibula were minimized by careful targeting and using coupling gel. Radiological fracture healing was assessed by radiographs and multidetector computed tomography (CT) scans in a blinded manner by a radiologist and orthopedic surgeons.\n The overall compliance to the daily ultrasound treatments was good. All wounds healed uneventfully, and no foreign body reactions were observed. No difference was observed between the groups regarding either fracture line visualization or callus formation assessed by plain radiographs. In the CT images at 9 weeks, the share of the endosteal united fracture line compared to the non-united fracture line was slightly higher in the active ultrasound device group than in the sham ultrasound device group, but the difference was not statistically significant.\n The study indicates that the biocompatibility of ultrasound therapy and bioabsorbable SR-PLLA screw fixation is good. There was no obvious effect of low-intensity ultrasound on lateral malleolar fracture healing. However, the relatively small number of patients must be kept in mind when interpreting our results. It is also important to limit any conclusions based on the present study to malleolar fractures fixed with the SR-PLLA screw.", "Since pulsed low-intensity ultrasound (frequency: 1.5 MHz, pulsed by 1 kHz, signal burst width: 200 microseconds, intensity: 30 mW/cm2) has been proven to stimulate fracture healing both clinically and experimentally, our question was whether this therapy also accelerates healing of fresh stable scaphoid fractures. Addressing this question, we did the following prospective randomized clinical trial. Regarding the results of former clinical fresh fracture studies by Heckman and Kristiansen, we postulated that low intensity ultrasound accelerates healing by about 30%. Based on this thesis, we calculated that 30 patients divided into two groups would be necessary to show significant differences between the standard treatment (treated by casting) and an adjunctive ultrasound treatment (treated by casting and additional daily 20 minutes ultrasound treatment) if present. Diagnosis and healing was assessed by CT scans every two weeks. CT's were analyzed by two independent radiologists and one hand surgeon. Furthermore, areas of cancellous bone bridging in correlation to the diameter of the scaphoid was measured in each CT scan. The results showed ultrasounded fractures healing in 43.2 +/- 10.9 days versus 62 +/- 19.2 days in the control group (p < 0.01). Trabecular bridging six weeks after injury showed 81.2% +/- 10.4% healed in the ultrasound-stimulated fractures versus 54.6% +/- 29% in the control (p < 0.05). Our study results confirm those of Heckman and Kristiansen and show a similar acceleration of bone healing. Low intensity ultrasound is successful in accelerating the healing of fresh scaphoid fractures.", "Several randomised trials have been published on the effect of low-intensity pulsed ultrasound (LIPUS) on fracture healing in both distal radius and tibia fractures. Most studies showed a positive effect on time to clinical and radiological healing. We hypothesised that LIPUS has a beneficial effect on the healing of fresh clavicle fractures as well and studied its effect in non-operatively treated shaft fractures.\n We conducted a randomised double blind, placebo-controlled multi-centre trial in 101 adult patients with a non-operatively treated fresh clavicle shaft fracture. Of these patients, 49 used a placebo transducer and 52 patients had an active transducer with ultrasound stimulation (Exogen 2000). Data were analysed on intention to treat basis. Baseline parameters of both groups were not significantly different.\n There were no differences in time to subjective clinical fracture healing, resumption of daily activities, sports or professional work, Visual Analogue pain Scores (VAS) and use of pain medication.\n Our findings did not confirm that LIPUS accelerates clinical healing time of fresh clavicle shaft fractures.\n Level 1 evidence that low-intensity pulsed ultrasound does not accelerate clinical fracture healing in non-operatively treated fresh midshaft clavicle fractures." ]

[ "8092235", "2234715" ]

[ "Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.", "Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial." ]

[ "Our purpose was to determine whether aggressive or expectant management of severe preeclampsia at 28 to 32 weeks is more beneficial to maternal and neonatal outcome.\n Ninety-five eligible patients were randomly assigned to either aggressive (n = 46) or expectant management (n = 49). Aggressive management patients were prepared for delivery, either by cesarean or induction, 48 hours after glucocorticoids were administered. Expectant management patients were managed with bed rest, oral antihypertensives, and intensive antenatal fetal testing.\n At the time of randomization there were no differences between the two groups in mean systolic blood pressure (170 +/- 9.7 vs 172 +/- 9.4 mm Hg), diastolic blood pressure (110 +/- 5.4 vs 112 +/- 4.2 mm Hg), proteinuria (3.0 +/- 2.3 vs 3.6 +/- 2.3 gm per 24 hours), and gestational age (30.4 +/- 1.6 vs 30.7 +/- 1.5 weeks) for the aggressive and expectant management groups. The average latency period in the expectant management group was 15.4 days (range 4 to 36), and this period was not affected by the amount of proteinuria at randomization. There was no eclampsia or perinatal death in either group. The two groups had similar incidences of abruptio placentae (4.1% vs 4.3%) and similar days of postpartum hospital stay. The expectant management group had a significantly higher gestational age at delivery (32.9 +/- 1.5 vs 30.8 +/- 1.7 weeks, p < 0.0001), higher birth weight, lower incidence of admission to the neonatal intensive care unit (76% vs 100%, p = 0.002), lower mean days of hospitalization in the intensive care unit (20.2 +/- 14 vs 36.6 +/- 17.4, p < 0.0001), and lower incidence of neonatal complications.\n Expectant management, with close monitoring of mother and fetus at a perinatal center, reduces neonatal complications and neonatal stay in the newborn intensive care unit.", "Fifty-eight women with severe preeclampsia between 28-34 weeks' gestation qualified for a randomized controlled trial to establish whether elective delivery 48 hours after administration of betamethasone (aggressive-management group) or delivery later as indicated by maternal or fetal condition (expectant-management group) was more beneficial to maternal and fetal outcome. Twenty women who qualified were not randomized because they developed maternal or fetal indications necessitating delivery within 48 hours; these newborns developed most of the complications. Expectant management was not associated with an increase in maternal complications, but it significantly prolonged the gestational age (mean 7.1 days; P less than .05), reduced the number of neonates requiring ventilation (P less than .05), and reduced the number of neonatal complications (P less than .05)." ]

[ "3510286", "290243", "3943336", "3331395", "6338164", "7014790", "15474134", "8525072", "7810251", "6333649" ]

[ "Effect of high-dose dexamethasone on outcome from severe head injury.", "A clinical retrospective and a double-blind study of betamethasone in severe closed brain injuries [proceedings].", "Role of corticosteroids in the development of pneumonia in mechanically ventilated head-trauma victims.", "Effect of dexamethasone on nitrogen metabolism in brain-injured patients.", "Megadose steroids in severe head injury. Results of a prospective double-blind clinical trial.", "Steroids in severe head injury: A prospective randomized clinical trial.", "Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.", "Treatment of patients with severe head injury by triamcinolone: a prospective, controlled multicenter clinical trial of 396 cases.", "\"Ultrahigh\" dexamethasone in acute brain injury. Results from a prospective randomized double-blind multicenter trial (GUDHIS). German Ultrahigh Dexamethasone Head Injury Study Group.", "High dose glucocorticoids in the management of severe head injury." ]

[ "The conflicting evidence concerning the influence of high-dose steroids on intracranial pressure (ICP) and outcome following severe head injury has led to the institution of the prospective double-blind controlled trial reported here. Severely head-injured patients admitted to intensive care during a 3-year period were randomly allocated to a dexamethasone- or placebo-treated group. Adults in the steroid group received dexamethasone, 50 mg intravenously, as a bolus on admission to the neurosurgical unit, then 100 mg on Days 1, 2, and 3, 50 mg on Day 4, and 25 mg on Day 5 on continuous intravenous infusion. Children received proportionate intravenous dosages calculated on a weight basis. Severity of head injury was assessed from admission Glasgow Coma Scale (GCS) scores and the appearance of the admission computerized tomography scan. Intracranial pressure (ICP) was monitored in all patients from the surface subarachnoid space. Outcome at 6 months was assessed using the Glasgow Outcome Scale. Steroid and placebo groups were similar in terms of admission GCS score, intracranial pathology, incidence of associated injuries, and time interval from injury to admission to intensive care. The ICP generally increased during the first 48 hours of intensive therapy; there was no difference in this trend between the steroid and placebo groups. A poorer outcome was observed in patients with elevated ICP who received steroids. No increase in the incidence of pulmonary, gastrointestinal, or other extracranial complications was seen in the steroid group. The 6-month outcome did not differ between the steroid and placebo groups. No advantage of high-dose dexamethasone on ICP trends or clinical outcome in the treatment of severe head injury has emerged from this study.", "nan", "The development of pneumonia was monitored in head-trauma patients requiring mechanical ventilation. Of the 66 patients studied, 15 (23%) developed pneumonia within 14 days after ICU admission. In each case the diagnosis was based on x-ray evidence and at least two of the following: increased white blood cell count, increased fever, and/or increased sputum production with a predominant organism on the sputum stain. Coagulase-positive Staphylococcus aureus was the most common etiologic agent. There was no difference in the occurrence of pneumonia between patients treated with no steroids or with low, moderate, or high steroid doses. Although there was an association between thiopental use and the development of pneumonia, dexamethasone treatment was not a significant risk factor in the development of pneumonia in this patient population.", "A randomized prospective clinical trial was conducted to determine the influence of dexamethasone therapy on nitrogen metabolism in patients with isolated head trauma without any pathologies. One group of 12 patients was not given steroids (groups NS). To the 12 patients of the second group, a dose of 0.36 mg/kg/day of dexamethasone was administered for the first nine days of stay (group S) in hospital. At the beginning of the study, between the two groups, there were no differences in age, sex, Glasgow Coma Scale Score, type of injury. In order to avoid bias, phenytoin, barbiturates and muscle-relaxant drugs were not given and the same caloric and protein intake was prefixed for both groups. The urea excretion, nitrogen output, nitrogen balance and cumulative nitrogen balance were not statistically different in the two groups throughout the period of study. Similar were also weight losses, blood glucose, blood urea nitrogen, albumin and creatinine levels. The outcome, evaluated at 3 months, was also similar. The incidence of sepsis, pulmonary and urinary infections, gastric reflux duration and quantity, was not higher in the steroid group compared with non-steroid treated patients.", "A prospective double-blind clinical trial was performed on 161 patients to determine the effectiveness of high-dose steroid therapy in patients admitted comatose after a non-missile-related head injury. Patients were randomized into a high-dose dexamethasone phosphate group and a placebo group. The initial dose of 100 mg of dexamethasone was administered within 6 hours of the accident. For statistical analysis, a sequential test was chosen, using survival at 1 month as a basic criterion of effectiveness. No significant difference was found in the 1-month survival rate or in the distribution of outcome after 6 months, either within the group as a whole, or in subgroups with varying severity of brain damage on admission. The authors conclude that dexamethasone in high doses has no statistically significant effect on morbidity or mortality in head-injured patients who are comatose on admission.", "This is a prospective randomized study of the efficacy of steroid therapy in patients with severe head injury. One hundred patients were randomized into two equal groups: the steroid group received 5 mg/kg/day of methylprednisolone, and the nonsteroid group received no drug. The groups were similar in their clinical features. All patients received a standardized therapeutic regimen. The patients were also classified as early responders or nonresponders to the overall treatment protocol without regard to steroid administration, on the basis of change in Glasgow Coma Scale score during the first 3 days of admission. There was no statistically significant difference in the outcome of the steroid and nonsteroid group at 6 months. Of the responders who were on steroids, 74% had good outcomes or were disabled, compared with 56% of the responders who did not receive steroids. In the nonresponder group, the patients on steroids were actually associated with a worse outcome than those who did not receive steroids: 75% of the nonresponders who received steroids were dead or vegetative, compared to 56% of those who were not receiving steroids. The data suggest that: 1) the effect of steroids may be different for different patient groups; 2) in order to identify these patients, a sensitive coma scale is needed; and 3) a rational approach to steroid therapy in head-injured patients may be to start all patients on steroids, but to discontinue their use in patients identified as not benefiting from steroid therapy.", "Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment.\n 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797.\n Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05).\n Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.", "The present studies were conducted to test whether the outcome of severe head injury is improved by early administration of the synthetic corticosteroid triamcinolone. In a prospective, double-blind, multicenter clinical trial, 396 patients with severe head injury were randomized to a steroid group (n = 187) receiving 200 mg triamcinolone acetonide (Volon A soluble) i.v. within 4 h after trauma, followed by 3 x 40 mg/day i.v. for 4 days, and 3 x 20 mg/day i.v. for a further 4 days, and a placebo group (n = 209) receiving injections which did not contain any active drug. The placebo group was subjected to the same standard treatment procedures. Clinical features were not different between the groups upon admission to hospital. Subdural hematoma, epidural hematoma, and focal supratentorial contusion were among the most frequent diagnoses. The result of treatment with triamcinolone was assessed at discharge from the hospital and at 1 year after trauma, using the Glasgow Outcome Scale. Differences in favor of steroid treatment could be detected with regard to the patients' condition at discharge (P = 0.0634). More patients with steroids had a good recovery (49.2% vs 40.7%), and fewer died (16.0% vs 21.5%). Differences in outcome were even more pronounced (P < 0.0145) in patients with a focal lesion and a Glasgow Coma Score on admission of < 8 (n = 93). In this group, 34.8% of the patients made a good recovery, as against 21.3% of the placebo group; mortality was also lower in the verum group (19.6% vs 38.3%). The results indicate that a major subgroup of patients with severe head injury benefits from early administration of triamcinolone. Efficacy of the treatment can be expected, in particular, in patients with a focal cerebral lesion and a Glasgow Coma Score of < 8 on admission. Administration of steroids beginning at the scene of an accident would therefore be beneficial in these cases.", "In a prospective randomized double-blind multicenter trial, the efficacy and safety of a 51-hour ultra-high intravenous dexamethasone dosing regimen was investigated in patients with moderate and severe head injury. 300 patients between 15 and 55 years of age were randomized to receive either placebo or dexamethasone: 500 mg intravenous infusion within 3 h after trauma initially, followed by 200 mg after 3 h, thereafter 8 times 200 mg at 6 hourly intervals, resulting in a total administered dose of 2,3 g in 51 hours. Primary end points for assessment of efficacy were: Modified Glasgow Coma Scale (grading 3-16) on Day 5, modified Glasgow Outcome Scale (grading 1-6) 10-14 months after injury, and the time interval until consciousness improved above a level of modified GCS > or = 8. Secondary endpoints were CT results and neurological and laboratory data. The two groups were well matched with respect to important prognostic variables, such as age, severity of trauma, and interval between trauma and application of the drug. 269 patients (89.7%) were available for final examination after 10-14 months. Results were surprisingly favourable in both groups: Lethality in the dexamethasone and placebo group was 14.3 and 15.4%, respectively, and 61.7 and 57.4%, respectively, achieved social and professional rehabilitation after 10-14 months (outcome scale 6). No statistical difference was seen between the dexamethasone and the placebo group in any of the primary end points of efficacy and safety (incidence of upper gastrointestinal bleeding, infection, and thrombosis).(ABSTRACT TRUNCATED AT 250 WORDS)", "Eighty-eight patients with a Glasgow coma score of 8 or less 6 hours after nonpenetrating head trauma were given either high dose methylprednisolone sodium succinate (30 mg/kg q6h X2, then 250 mg q6h X6, then tapering over 8 days), low dose methylprednisolone (1.5 mg/kg q6h X2, then 25 mg q6h X6, then tapering over 8 days), or placebo. Standard care including the removal of traumatic hematomas, assisted ventilation, and intracranial pressure monitoring and control was carried out. Follow-up assessments were performed on all surviving patients at 6 months and were graded according to the Glascow outcome scale. No statistically significant difference in outcome was seen between the low dose group and the placebo group. The high dose group experienced a mortality of 39% as compared to a 52% mortality in the low dose and placebo groups (P less than 0.05). Mortality differences were most marked in patients less than 40 years old, with the high dose group experiencing a mortality of 6% as compared to a 43% mortality for the low dose and placebo groups (P less than 0.05). For patients under 50 years old, the incidence of recovery of speech was 62% compared to 36% in the low dose and placebo groups (P less than 0.5). The increased survival in those treated with high dose corticoids, however, was associated with an increase in the poorer outcome categories." ]

[ "9583331", "9444683", "7573630", "15282836", "9357345", "10587936", "10812314" ]

[ "Drug abuse day treatment: a randomized clinical trial comparing day and residential treatment programs.", "Outcomes of homeless mentally ill chemical abusers in community residences and a therapeutic community.", "The effectiveness of alternative planned durations of residential drug abuse treatment.", "Modified TC for MICA offenders: crime outcomes.", "The effects of planned duration of residential drug abuse treatment on recovery and HIV risk behavior.", "Comparing the impact of standard and abbreviated treatment in a therapeutic community. Findings from the district of Columbia treatment initiative experiment.", "Treatment refusal/attrition among adults randomly assigned to programs at a drug treatment campus: The New Jersey Substance Abuse Treatment Campus, Seacaucus, NJ." ]

[ "Clients entering a therapeutic community (TC)-oriented drug treatment program were randomly assigned to day or residential conditions and interviewed at 2 weeks and 6 months after admission. Outcomes included Addiction Severity Index composite scores and summary scores for the Beck Depression Inventory, Symptom Checklist-90-R, and a social support scale. Only clients who remained in treatment for at least 2 weeks were included. The mean age of the sample (N = 261) was 32.9 (SD = 6.7 years) and the mean education level was 12.1 years (SD = 1.9 years); 30% were women. Comparison of outcome scores at 6 months between groups, while controlling for baseline values, indicated greater improvement for residential clients on social problems and psychiatric symptoms. The groups were similar on the 8 remaining outcomes, including measures of alcohol and drug problems. Overall, the level of improvement among day treatment clients was not significantly different from that of residential clients.", "The feasibility and effectiveness of treating homeless mentally ill chemical abusers in community residences compared with a therapeutic community were evaluated.\n A total of 694 homeless mentally ill chemical abusers were randomly referred to two community residences or a therapeutic community. All programs were enhanced to treat persons with dual diagnoses. Subjects' attrition, substance use, and psychopathology were measured at two, six, and 12 months.\n Forty-two percent of the 694 referred subjects were admitted to their assigned program and showed up for treatment, and 13 percent completed 12 months or more. Clients retained at both types of program showed reductions in substance use and psychopathology, but reductions were greater at the therapeutic community. Compared with subjects in the community residences, those in the therapeutic community were more likely to be drug free, as measured by urine analysis and self-reports, and showed greater improvement in psychiatric symptoms, as measured by the Center for Epidemiological Studies--Depression Scale and the Brief Psychiatric Rating Scale. Their functioning also improved, as measured by the Global Assessment of Functioning scale.\n Homeless mentally ill chemical abusers who are retained in community-based residential programs, especially in therapeutic communities, can be successfully treated.", "Randomized controlled trials were conducted at two residential drug abuse treatment facilities to compare programs that differed in planned duration. One trial compared a 6-month and a 12-month therapeutic community program (n = 184), and the second compared a 3-month and a 6-month relapse prevention program (n = 444). Retention rates over comparable time periods differed minimally by planned treatment duration, and the longer programs had lower completion rates. There was no effect in either trial of planned treatment duration on changes in psychosocial variables between admission and exit or on rates or patterns of drug use at follow-up between 2 and 6 months after exit.", "The study randomly assigned male inmates with co-occurring serious mental illness and chemical abuse (MICA) disorders to either modified therapeutic community (MTC) or mental health (MH) treatment programs. On their release from prison, MICA inmates who completed the prison MTC program could enter the MTC aftercare program. The results, obtained from an intent-to-treat analysis of all study entries, showed that inmates randomized into the MTC group had significantly lower rates of reincarceration compared with those in the MH group. The results also show that differences between the MTC + aftercare and comparison group across a variety of crime outcomes (i.e. any criminal activity, and alcohol or drug related criminal activity) are consistent and significant, and persist after an examination of various threats to validity (e.g. initial motivation, duration of treatment, exposure to risk). This study provides some support for the effectiveness of the prison TC only condition. The findings are encouraging and consonant with other studies of integrated prison and aftercare TC programs for substance abusing non-MICA offenders, although qualified by the possibility that selection bias (i.e. differences in motivation on entry into aftercare) may be operating. Nevertheless, given the available evidence and the need for effective programming for MICA offenders, program and policy makers should strongly consider developing integrated prison and aftercare modified TC programs for MICA offenders.\n Copyright 2004 John Wiley & Sons, Ltd.", "This study assessed the effects of planned duration of residential drug abuse treatment on recovery from drug use and on human immunodeficiency virus (HIV) risk behaviors.\n Two concurrent randomized controlled trials of programs differing in planned duration were conducted: 6-month vs 12-month versions of a traditional therapeutic community program, and 3-month vs 6-month versions of a modified therapeutic community incorporating a relapse prevention and health education program. Outcomes, measured at least 16.5 months after admission, included time from admission to first drug use; severity of drug, alcohol, legal, and employment problems; and risky drug injection and sexual behaviors.\n Among 539 clients (86% of those enrolled), there were no significant effects of planned duration of treatment upon Addiction Severity Index scores or HIV risk behavior. In the relapse prevention program, clients randomized to the 6-month program had a longer time to first drug use than those in the 3-month program (hazard ratio = 0.74; 95% confidence interval = 0.58, 0.93). Employment problems at follow-up were significantly less severe among clients treated in the therapeutic community than among those in the relapse prevention program.\n No overall benefit of extending treatment beyond 6 months was found.", "This study examines the efficacy of providing Enhanced Abbreviated or Standard Inpatient treatment and Outpatient treatment to drug-abusing clients. The experiment randomly assigned 412 clients to two therapeutic community programs, which differed primarily in planned duration. This study addressed limitations of prior research, as it used random assignment of clients to treatment programs, achieved high follow-up rates and used objective measures of drug use and criminal history. Self-reports and objective measures of criminal activity and substance abuse were collected at pre- and posttreatment interviews. Completing the entire 12-month program (inpatient and outpatient) was more important than duration of inpatient program attended. Regardless of program, completers had substantial reductions in posttreatment drug abuse and arrests. A 12-month course of treatment including at least 6 months in a therapeutic community followed by outpatient treatment can produce marked reductions in drug abuse and crime among persons who complete both phases.", "The New Jersey Substance Abuse Treatment Campus was funded to assess the feasibility of establishing a new model for delivering substance abuse treatment services and to serve as a research laboratory for conducting comparative evaluations of those services. The 350-bed campus was designed to improve treatment effectiveness by providing special services needed by underserved populations, and reduce treatment costs by serving large numbers of clients, centralizing services, and sharing facilities. First-time clients who met preliminary eligibility requirements during phone screening were randomly assigned to therapeutic community and chemical dependency programs. We used data collected on 1,573 adults who were ultimately accepted for admission to analyze treatment refusals and attrition during the 25 days after admission. Only 6.4% of the clients refused admission when informed of their treatment assignment. Planned duration of the residential phase of treatment, gender, and language spoken (English/Spanish) interacted with one another and differentially predicted treatment refusal/attrition. These findings may be useful for understanding treatment refusal and attrition in substance abuse treatment programs." ]

[ "12435645", "19887215", "11172245", "9848587", "11641706", "8042491", "16219944", "9934421", "10979525", "18006674", "11182732", "19223205", "12724682", "9784804", "17027405", "8947391", "16219939", "10627426", "17478654", "19962062", "8872929", "15007311", "11796399", "15128189", "19509414", "8198184", "10633889", "18503815", "16943859", "2703509", "18320379" ]

[ "The crank test, the O'Brien test, and routine magnetic resonance imaging scans in the diagnosis of labral tears.", "Reliability and diagnostic accuracy of 5 physical examination tests and combination of tests for subacromial impingement.", "Biceps load test II: A clinical test for SLAP lesions of the shoulder.", "Specificity of the Speed's test: arthroscopic technique for evaluating the biceps tendon at the level of the bicipital groove.", "Transdeltoid palpation (the rent test) in the diagnosis of rotator cuff tears.", "Intraarticular findings in the chronically painful shoulder. A study of 32 posttraumatic cases.", "An evaluation of the provocative tests for superior labral anterior posterior lesions.", "Which is more useful, the \"full can test\" or the \"empty can test,\" in detecting the torn supraspinatus tendon?", "An analysis of the diagnostic accuracy of the Hawkins and Neer subacromial impingement signs.", "The evaluation of various physical examinations for the diagnosis of type II superior labrum anterior and posterior lesion.", "Internal rotation resistance strength test: a new diagnostic test to differentiate intra-articular pathology from outlet (Neer) impingement syndrome in the shoulder.", "External rotation lag sign revisited: accuracy for diagnosis of full thickness supraspinatus tear.", "Clinical testing for tears of the glenoid labrum.", "The active compression test: a new and effective test for diagnosing labral tears and acromioclavicular joint abnormality.", "The bear-hug test: a new and sensitive test for diagnosing a subscapularis tear.", "A prospective evaluation of a new physical examination in predicting glenoid labral tears.", "Are pain location and physical examinations useful in locating a tear site of the rotator cuff?", "Diagnostic values of clinical diagnostic tests in subacromial impingement syndrome.", "The passive compression test: a new clinical test for superior labral tears of the shoulder.", "The passive distraction test: a new diagnostic aid for clinically significant superior labral pathology.", "Lag signs in the diagnosis of rotator cuff rupture.", "Accuracy of the Speed's and Yergason's tests in detecting biceps pathology and SLAP lesions: comparison with arthroscopic findings.", "Painful shoulder: comparison of physical examination and ultrasonographic findings.", "Validity of the supraspinatus test as a single clinical test in diagnosing patients with rotator cuff pathology.", "Clinical utility of traditional and new tests in the diagnosis of biceps tendon injuries and superior labrum anterior and posterior lesions in the shoulder.", "An evaluation of the shoulder relocation test.", "Is supraspinatus pathology as defined by magnetic resonance imaging associated with clinical sign of shoulder impingement?", "The validity of the lag signs in diagnosing full-thickness tears of the rotator cuff: a preliminary investigation.", "Interpreting positive signs of the supraspinatus test in screening for torn rotator cuff.", "Clinical presentation of complete tears of the rotator cuff.", "A new test of resistance in the diagnosis of postero-superior rotator cuff tears." ]

[ "Tears of the superior labrum of the shoulder, anterior to posterior, are difficult to diagnose clinically.\n We examined whether the crank or O'Brien tests were reliable tools for detecting glenoid labral tears.\n Nonrandomized prospective study.\n Results of diagnostic shoulder arthroscopy were compared with those of the preoperative tests and magnetic resonance imaging for 65 patients who had symptoms of shoulder pain.\n The crank test result was positive in 29 patients (45%), and the O'Brien test was positive in 41 patients (63%). The crank test had a positive predictive value of 41%, was 56% specific, 46% sensitive, and had a negative predictive value of 61%. The O'Brien test had a positive predictive value of 34%, was 31% specific, 54% sensitive, and had a negative predictive value of 50%. Magnetic resonance imaging had a positive predictive value of 63%, was 92% specific, 42% sensitive, and had a negative predictive value of 83%.\n The O'Brien and crank tests were not sensitive clinical indicators for detecting glenoid labral tears and other tears of the anterior and posterior labrum. Results were often falsely positive for patients with other shoulder conditions, including impingement or rotator cuff tears.", "To investigate the reliability and diagnostic accuracy of individual tests and combination of tests for subacromial impingement syndrome (SAIS).\n A prospective, blinded study design.\n Orthopedic surgeon shoulder clinic.\n Patients with shoulder pain (n=55, mean age=40.6y).\n Patients were evaluated with 5 physical examination tests for SAIS: Neer, Hawkins-Kennedy, painful arc, empty can (Jobe), and external rotation resistance tests. Surgical diagnosis was the reference standard.\n Diagnostic accuracy calculated with a receiver operating characteristic (ROC) curve and sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (-LR). A forward stepwise binary logistic regression analysis was used to determine the best test combination for SAIS. An ROC curve analysis was also used to determine the cut point of the number of tests discriminating between the presence and absence of SAIS. Kappa coefficients and percent agreement assessed interrater reliability.\n The ROC analyses revealed a significant area under the curve (AUC) (AUC=.67-.72, P<.05) for all tests, except for the Hawkins-Kennedy. The tests with a +LR greater than or equal to 2.0 were the painful arc (+LR=2.25; 95% CI, 1.33-3.81), empty can (+LR=3.90; 95% CI, 1.5-10.12), and the external rotation resistance tests (+LR=4.39; 95% CI, 1.74-11.07). Tests with -LR less than or equal to 0.50 were the painful arc (-LR=.38; 95% CI, .16-.90), external rotation resistance (-LR=.50; 95% CI, .28-.89), and Neer tests (-LR=.35; 95% CI, .12-.97). The regression analysis had no specific test combinations for confirming or ruling out SAIS. The ROC analysis was significant (AUC=.79, P=.001), with a cut point of 3 positive tests out of 5 tests. Reliability was moderate to substantial agreement (kappa=.45-.67) for the painful arc, empty can, and external rotation resistance tests and fair strength of agreement (kappa=.39-.40) for the Neer and Hawkins-Kennedy tests.\n The single tests of painful arc, external rotation resistance, and Neer are useful screening tests to rule out SAIS. The single tests of painful arc, external rotation resistance, and empty can are helpful to confirm SAIS. The reliability of all tests was acceptable for clinical use. Based on reliability and diagnostic accuracy, the single tests of the painful arc, external rotation resistance, and empty can have the best overall clinical utility. The cut point of 3 or more positive of 5 tests can confirm the diagnosis of SAIS, while less than 3 positive of 5 rules out SAIS.", "The purpose of this report is to describe the biceps load test II for evaluating the superior labral anterior and posterior (SLAP) lesions.\n This is a double-blind study in consecutive data, which includes diagnostic accuracy of a test using sensitivity, specificity, and interexaminer reliability.\n In the supine position, the arm is elevated to 120 degrees and externally rotated to its maximal point, with the elbow in the 90 degrees flexion and the forearm in the supinated position. The patient is asked to flex the elbow while resisting the elbow flexion by the examiner. The test is considered positive if the patient complains of pain during the resisted elbow flexion. The test is negative if pain is not elicited or if the pre-existing pain during the elevation and external rotation of the arm is unchanged or diminished by the resisted elbow flexion. A prospective study was performed in 127 patients to evaluate the diagnostic accuracy for the biceps load test II. Two independent examiners were assigned to perform the new diagnostic test. The results of the tests were confirmed during the arthroscopic examination.\n A positive test result in 38 subjects correlated with a SLAP lesion in 35 patients and an intact biceps-superior labrum in 3 patients. A negative test result in 89 patients correlated with an intact superior labrum complex in 85 patients, whereas 4 patients with a negative test result had a type II SLAP lesion. The biceps load test II had a sensitivity of 89.7%, a specificity of 96.9%, a positive-predictive value of 92.1%, a negative-predictive value of 95.5%, and a kappa coefficient of 0.815. The abduction and external rotation of the shoulder during the test changes the relative direction of the biceps fiber in a position of oblique angle to the posterosuperior labrum. The resisted contraction of the biceps increases the pain generated on the superior labrum that is already peeled off the glenoid margin in the abducted and externally rotated position.\n The biceps load test II is an effective diagnostic test for SLAP lesions.", "A positive Speed's test result is usually thought to suggest inflammation or lesions related to the biceps/labral complex. The specificity, sensitivity, and positive and negative predictive values are determined for the Speed's test. A prospective study design was developed for all patients with shoulder pain who presented between October 1, 1994 and February 28, 1995. The clinical results of the Speed's test were correlated with biceps/labral pathology by direct arthroscopic visualization. A neuroprobe is used to pull the biceps tendon into the articular portion of the glenohumeral joint so as to visualize the biceps tendon at the level of the bicipital groove. Forty-six shoulders in 45 patients, 31 men (average age, 53 years; range, 16 to 76 years) and 14 women (average age, 64 years; range, 30 to 80 years) with 26 dominant and 20 nondominant extremities were operated on during this time interval. The clinical evaluation showed that the speed's test was positive in 40 shoulders. Biceps/labral complex pathology was present in 10 of these patients. A specificity of 13.8%, a sensitivity of 90%, a positive predictive value of 23%, and a negative predictive value of 83% were calculated. Thus, it is concluded that the Speed's test is a nonspecific but sensitive test for macroscopic biceps/labral pathology. This clinical examination is positive with a various number of other pathological shoulder problems.", "The purpose of this study was to assess the diagnostic accuracy of transdeltoid palpation (the rent test) for the diagnosis of full thickness rotator cuff tear. Clinical and arthroscopic findings were documented prospectively for 109 consecutive patients undergoing shoulder arthroscopy by the senior author. A retrospective analysis was then performed on these data to assess the accuracy of transdeltoid palpation in the diagnosis of full thickness rotator cuff tear. Transdeltoid palpation was found to have a sensitivity of 95.7% and specificity of 96.8% for the diagnosis of full thickness rotator cuff tear. The positive and negative predictive values for transdeltoid palpation were 95.7% and 96.8%, respectively. Overall, the diagnostic accuracy of transdeltoid palpation was 96.3%. We conclude that transdeltoid palpation is highly accurate for the clinical diagnosis of full thickness rotator cuff tear.", "32 consecutive patients suffering from chronic shoulder pain for more than 6 months after a single, nondislocating shoulder trauma were examined clinically and by special radiographs, dynamic sonography, MRI and arthroscopy. Typical complaints were pain during loading, especially during over the head activities. Symptoms of a \"dead arm\" and instability were also present. Patients with previous dislocations, traumas or radiographic signs of degenerative shoulder lesions were excluded. The patients had a decreased active range of motion and positive signs of apprehension and impingement, but only 4 had clinical signs of shoulder instability. Diagnostic evaluation identified labral tears, partial and total rotator cuff lesions with subacromial impingement and tendinitis of the biceps tendon. Surgery was performed in 24 patients, using capsulolabral and rotator cuff reconstruction, arthroscopic labral resection and open subacromial decompression. In conclusion, patients with chronic posttraumatic shoulder pain have intraarticular injuries, especially tears of the glenoid labrum. History, clinical findings, radiography and sonography are seldom diagnostic. MRI is valuable, particularly for identification of labral pathology, but arthroscopy appears necessary for a preoperative assessment.", "Although our understanding of superior labral anterior posterior lesions has grown, the physical diagnosis remains imperfect.\n Cohort study (diagnostic); Level of evidence, 2.\n To determine the most effective provocative maneuver with which to diagnose superior labral anterior posterior lesions.\n A series of 132 consecutive patients scheduled to undergo diagnostic shoulder arthroscopy were examined preoperatively over a 6-month period, and the final diagnosis in each case was made arthroscopically. The following assessments were included: active compression (O'Brien), anterior slide, pain provocation, crank, Jobe relocation, Hawkins, Neer, Speed, and Yergason tests.\n The most sensitive diagnostic tools for type II superior labral lesions were the active compression, Hawkins, Speed, Neer, and Jobe relocation tests. When type I and type II lesions were combined, the results were similar. However, none of the sensitive tests were specific for either type I or type II lesions.\n The authors' results contradict the current literature regarding provocative testing for both stable and unstable superior labral lesions. There is no single maneuver that can accurately diagnose superior labral anterior posterior lesions; arthroscopy remains the standard by which to diagnose such lesions.", "The purpose of this study was to determine the clinical usefulness of the full can and empty can tests for determining the presence of a torn supraspinatus tendon. The two tests were performed in 143 shoulders of 136 consecutive patients. In each test, the muscle strength was determined by manual muscle testing, and the presence of pain during the maneuver was recorded. We interpreted the tests as positive when there was 1) pain, 2) muscle weakness, or 3) pain or muscle weakness or both. Shoulders were examined by high-resolution magnetic resonance imaging with 95% accuracy for full-thickness rotator cuff tears. There were 35 shoulders with full-thickness tears of the supraspinatus tendon. The accuracy of the tests was the greatest when muscle weakness was interpreted as indicating a torn supraspinatus tendon in both the full can test (75% accurate) and the empty can test (70% accurate). However, there was no significant difference between the accuracy of the tests when this criterion was used. Pain was observed in 62 shoulders (43%) during the full can test and in 71 shoulders (50%) during the empty can test, but the difference was not statistically significant. Muscle weakness should be interpreted as indicative of supraspinatus tendon tear. Using this indicator, both tests are equivalent in terms of accuracy, but considering pain provocation, the full can test may be more beneficial in the clinical setting.", "The purpose of this study was to assess the diagnostic accuracy of the Neer and Hawkins impingement signs for the diagnosis of subacromial bursitis or rotator cuff pathosis. Eighty-five consecutive patients undergoing shoulder arthroscopy by a single surgeon were documented prospectively for the positive and negative clinical and arthroscopic pathologic findings. The Neer sign was found to have a sensitivity of 75% for the appearance suggestive of subacromial bursitis; this compared with 92% for the Hawkins sign. For rotator cuff tearing, the sensitivity of the Neer sign was 85% and the sensitivity of the Hawkins sign was 88%. Specificity and positive predictive values for the two tests were low, being not much higher than pretest probability. The two tests had a high negative predictive value (96% for bursitis, 90% for rotator cuff tearing) when they were combined. The results are compared with those reported in the literature. We conclude that the Neer and Hawkins signs are sensitive for appearances suggestive of subacromial bursitis and rotator cuff partial or complete tearing with a high negative predictive value. However, they lack specificity in comparison with arthroscopic findings.", "Many types of physical examinations have been used to diagnose superior labrum anterior and posterior lesions; no decisive clinical test is available for confirming the diagnosis.\n A selection from 10 well-established physical tests, alone or in combination, can be used to differentiate lesions with biceps anchor detachment from those with an intact biceps anchor with arthroscopic correlation.\n Case control study (diagnosis); Level of evidence, 3.\n Among 297 patients who underwent shoulder arthroscopy between January 2004 and July 2005, 146 patients were enrolled in the study as a type II superior labrum anterior and posterior lesion group and an age-matched control group. Sensitivity, specificity, and predictive values of each test and all possible combinations of 2 and 3 tests were analyzed. The same procedures were repeated in patients younger than and older than 40 years.\n The sensitivities of the Whipple, O'Brien, apprehension, and compression-rotation tests and the specificities of the Yergason, biceps load II, and Kibler tests were relatively high. No single physical examination was found to be simultaneously highly sensitive and specific for the diagnosis of a type II superior labrum anterior and posterior lesion. When 2 of the 3 relatively sensitive tests (O'Brien, apprehension, or compression-rotation test) were combined with 1 of the 3 relatively specific tests (Speed, Yergason, or biceps load II test), sensitivity and specificity reached approximately 70% and 95%, respectively. Similar trends were noted in the younger and older patient groups and in the isolated type II superior labrum anterior and posterior lesion group.\n The data suggest that some combinations of 2 relatively sensitive clinical tests and 1 relatively specific clinical test increase the diagnostic efficacy of superior labrum anterior and posterior lesions. Requiring 1 of the 3 chosen tests to be positive will result in a sensitivity of about 75%, whereas requiring all 3 to be positive will result in a specificity of about 90%.", "This prospective study introduces a new sign to differentiate between outlet impingement and non-outlet (intra-articular) causes of shoulder pain in patients with positive impingement sign: the internal rotation resistance strength test (IRRST). It was hypothesized that positive test results are predictive of non-outlet impingement, whereas negative test results confirm outlet impingement. A prospective comparison between IRRST and arthroscopic findings of 115 consecutive patients showed the test to be highly accurate in differentiating between these two diagnoses (positive predictive value 88%, negative predictive value 96%, sensitivity 88%, specificity 96%, and accuracy 94.5%). The IRRST, in conjunction with impingement and apprehension signs, adds to our armamentarium of tests that distinguish between subacromial outlet impingement and intra-articular forms of pathology.", "This study reassessed the sensitivity and the specificity of the external rotator lag sign (ERLS) for diagnosis of supraspinatus tears in a large cohort of patients.\n The ERLS was used to assess 401 consecutive patients with 406 painful shoulder conditions. The clinical diagnosis was controlled either arthroscopically or by open surgery.\n For isolated full-thickness supraspinatus tears, the ERLS had a sensitivity of 56% and a specificity of 98%. When the lesion involved the infraspinatus and the teres minor the sensitivity improved substantially. There was a strong correlation between the extension of the tear and the amount of the lag. The lag increased from 7 degrees for an isolated rupture of the supraspinatus tendon to 26 degrees in case of extension to the teres minor.\n The ERLS is highly specific and acceptably sensitive for diagnosis of full-thickness tears, even in case of an isolated lesion of the supraspinatus tendon.\n Level 2; Prospective cohort treatment study.", "With the increasing use of shoulder arthroscopy, diagnosis of glenoid labral lesions has become increasingly common. However, a physical examination maneuver that would allow a definitive clinical diagnosis of a glenoid labral tear, and more specifically a SLAP lesion, has been elusive. This study correlated the results of commonly used examination maneuvers with findings at shoulder arthroscopy. The working hypothesis was that 7 commonly used clinical tests, alone or in logical combinations, would provide diagnoses with reliability greater than the accepted standards for magnetic resonance imaging arthrography; i.e., greater than 95% sensitivity and specificity.\n Consecutive sample, sensitivity-specificity study.\n Sixty shoulders undergoing arthroscopy for a variety of pathologies were examined before surgery. All subjects submitted to the Speed test, an anterior apprehension maneuver, Yergason test, O'Brien test, Jobe relocation test, the crank test, and a test for tenderness of the bicipital groove. The examination results were compared with surgical findings and analyzed for sensitivity and specificity in the diagnosis of SLAP lesions and other glenoid labral tears.\n The results of the O'Brien test (63% sensitive, 73% specific) and Jobe relocation test (44% sensitive, 87% specific) were statistically correlated with presence of a tear in the labrum and the apprehension test approached statistical significance. Performing all 3 tests and accepting a positive result for any of them increased the statistical value, although the sensitivity and specificity were still disappointingly low (72% and 73%, respectively). The other 4 tests were not found to be useful for labral tears, and none of the tests or combinations were statistically valid for specific detection of a SLAP lesion.\n Clinical testing is useful in strengthening a diagnosis of a glenoid labral lesion, but the sensitivity and specificity are relatively low. Thus a decision to proceed with surgery should not be based on clinical examination alone.", "Labral tears and acromioclavicular joint abnormalities were differentiated on physical examination using a new diagnostic test. The standing patient forward flexed the arm to 90 degrees with the elbow in full extension and then adducted the arm 10 degrees to 15 degrees medial to the sagittal plane of the body and internally rotated it so that the thumb pointed downward. The examiner, standing behind the patient, applied a uniform downward force to the arm. With the arm in the same position, the palm was then fully supinated and the maneuver was repeated. The test was considered positive if pain was elicited during the first maneuver, and was reduced or eliminated with the second. Pain localized to the acromioclavicular joint or \"on top\" was diagnostic of acromioclavicular joint abnormality, whereas pain or painful clicking described as \"inside\" the shoulder was considered indicative of labral abnormality. A prospective study was performed on 318 patients to determine the sensitivity, specificity, and positive and negative predictive values of the test. Fifty-three of 56 patients whose preoperative examinations indicated a labral tear had confirmed labral tears that were repaired at surgery. Fifty-five of 62 patients who had pain in the acromioclavicular joint and whose preoperative examinations indicated abnormalities in the joint had positive clinical, operative, or radiographic evidence of acromioclavicular injury. There were no false-negative results in either group.", "It was our intent to devise a new clinical test that would more accurately diagnose subscapularis tears than the current clinical tests. This new test is called the bear-hug test. The purpose of this study was to assess the bear-hug test and compare it with the current tests of subscapularis function (lift-off, belly-press, and Napoleon tests).\n Between January 2004 and March 2004, 68 consecutive patients scheduled for an arthroscopic procedure were evaluated preoperatively; the preoperative clinical examination findings were then correlated with arthroscopic findings. Lift-off, belly-press, Napoleon, and bear-hug tests were included in the examination. Furthermore, for the belly-press and bear-hug tests, the strength was precisely quantified by means of an electronic digital tensiometer (Kern HBC). Diagnostic arthroscopy was the reference that determined the actual pathologic lesions.\n Subscapularis tears occurred with a prevalence rate of 29.4%. Of the subscapularis tears, 40% were not predicted by preoperative assessment by use of all of the tests. The bear-hug test was found to be the most sensitive test (60%) of all of those studied (belly-press test, 40%; Napoleon test, 25%; and lift-off test, 17.6%). In contrast, all 4 tests had a high specificity (lift-off test, 100%; Napoleon test, 97.9%; belly-press test, 97.9%; and bear-hug test, 91.7%). No statistically significant difference was found between the area under the receiver operating characteristic curve of the bear-hug test and that of the belly-press test in diagnosing a torn subscapularis. However, the areas under the receiver operating characteristic curve for both the bear-hug test and the belly-press test were significantly greater than those for the lift-off and Napoleon tests (P < .05). Positive bear-hug and belly-press tests suggest a tear of at least 30% of the subscapularis, whereas a positive Napoleon test indicates that greater than 50% of the subscapularis is torn. Furthermore, a positive lift-off test is not found until at least 75% of the subscapularis is torn.\n The bear-hug test optimizes the chance of detecting a tear of the upper part of the subscapularis tendon. Moreover, because the bear-hug test represents the most sensitive test, it can be considered to be the most likely clinical test to alert the surgeon to a possible subscapularis tear. Performing all of the subscapularis tests is useful in predicting the size of the tear.\n Level I, diagnostic study: testing of previously developed criteria in a series of consecutive patients with arthroscopy used as the criterion standard.", "We studied 62 patients (40 men and 22 women) with an average age of 28 years over a 28-month period who presented with shoulder pain that was refractory to 3 months of conservative management. Patients with a prior glenohumeral dislocation or a rotator cuff tear were excluded. The \"crank\" test was performed with the arm elevated to 160 degrees in the scapular plane of the body, loaded axially along the humerus, and with maximal internal and external rotation. Although similar tests have been described, the crank test is a new examination previously unreported. Half of the patients (31) had a positive crank test. Arthroscopy performed on all 62 patients revealed glenoid labral tears in 32 patients. Two patients who had positive crank tests did not have labral tears but had partial-thickness, articular-side rotator cuff tears. The sensitivity of the crank test was 91%, the specificity was 93%, the positive predictive value was 94%, and the negative predictive value was 90%. With these data, the crank test fulfills the criteria as a single physical examination test that is highly accurate for the preoperative diagnosis of glenoid labral tears. Accordingly, expensive imaging modalities currently used in this patient population may be employed less in the future.", "Pain is the most common symptom of patients with rotator cuff tendinopathy, but little is known about the relationship between the site of pain and the site of cuff pathologic lesions. Also, accuracies of physical examinations used to locate a tear by assessing the muscle strength seem to be affected by the threshold for muscle weakness, but no studies have been reported regarding the efficacies of physical examinations in reference to their threshold.\n Pain location is useful in locating a tear site. Efficacies of physical examinations to evaluate the function of the cuff muscles depend on the threshold for muscle weakness.\n Case series; Level of evidence, 4.\n The authors retrospectively reviewed the clinical charts of 160 shoulders of 149 patients (mean age, 53 years) with either rotator cuff tears (140 shoulders) or cuff tendinitis (20 shoulders). The location of pain was recorded on a standardized form with 6 different areas. The diagnostic accuracies of the following tests were assessed with various thresholds for muscle weakness: supraspinatus test, the external rotation strength test, and the lift-off test.\n Lateral and anterior portions of the shoulder were the most common sites of pain regardless of existence of tear or tear location. The supraspinatus test was most accurate when it was assessed to have positive results with the muscle strength less than manual muscle testing grade 5, whereas the lift-off test was most accurate with a threshold less than grade 3. The external rotation strength test was most accurate with a threshold of less than grade 4+.\n The authors conclude that pain location is not useful in locating the site of a tear, whereas the physical examinations aiming to locate the tear site are clinically useful when assessed to have positive results with appropriate threshold for muscle weakness.", "Subacromial impingement syndrome (SIS) is a frequent cause of shoulder pain. The aim of this study was to investigate the diagnostic values of clinical diagnostic tests, in patients with SIS.\n 72 female, 48 male patients with shoulder pain were included in the study. Five had bilateral shoulder pain, so 125 painful shoulders were evaluated. Details were recorded about the patients' ages and sexes, as well as characteristics of pain and related problems. Detailed physical examination and routine laboratory tests were performed. Conventional radiography and subsequent magnetic resonance imaging of the shoulder region of all patients were performed. Patients were divided into two groups according to the results of subacromial injection test, a reference standard test for SIS. Test positive patients constituted SIS group and test negative patients the non-SIS group. Sensitivity, specificity, accuracy, positive and negative predictive values of some clinical diagnostic tests such as Neer, Hawkins, horizontal adduction, painful arc, drop arm, Yergason and Speed tests for SIS were determined by using 2 x 2 table.\n The most sensitive diagnostic tests were found to be Hawkins test (92.1%), Neer test (88.7%) and horizontal adduction test (82.0%). Tests with highest specificity were drop arm test (97.2%), Yergason test (86.1%) and painful arc test (80.5%) consecutively.\n The highly sensitive tests seem to have low specificity values and the highly specific ones to have low sensitivity values. Although this finding suggests that these diagnostic tests are insufficient for certain diagnosis, it is suggested they play an important part in clinical evaluation.", "Even though there are several physical tests available for superior labrum anterior posterior lesions, there have been very few reports on their accuracy, and none can be regarded as completely predictive for the presence of a superior labrum anterior posterior lesion in the shoulder joint.\n This new clinical test is a useful and accurate technique for detecting superior labral tears in the shoulder joint.\n Cohort study (diagnosis); Level of evidence, 2.\n This test was conducted independently by 2 physicians before any other diagnostic evaluation. In all cases, the glenohumeral joint was investigated first, and the appropriate treatments were performed on the lesion. A protocol was established to evaluate the sensitivity, specificity, and positive and negative predictive values of this new clinical test. The reproducibility of this test was evaluated with a kappa coefficient.\n Sixty-one patients (61 shoulders) were examined with the passive compression test, and all underwent arthroscopic surgery. In 31 patients with a positive passive compression test result, 27 had a superior labrum anterior posterior lesion, and in 30 patients with a negative passive compression test result, 6 had a superior labrum anterior posterior lesion. The sensitivity of the test was 81.8%, and the specificity was 85.7%. The positive predictive value was 87.1%, and the negative predictive value was 80.0%. The kappa coefficient was 0.771 between the 2 independent examiners (P< .01).\n The passive compression test is a useful and accurate technique for predicting superior labral tears of the shoulder joint.", "The purpose of this report is to present a new provocative maneuver, the passive distraction test (PDT), as an examination tool to be used in the evaluation of patients thought to have a SLAP lesion and to compare its accuracy, precision, and reproducibility alone and in conjunction with previously published maneuvers.\n A retrospective analysis of 319 consecutive arthroscopies performed between May 2001 and November 2003 was performed. A total of 65 cases were excluded, 53 because of limitation of elevation to less than 150 degrees or pain in the starting test position and 12 who had previous shoulder procedures performed by the senior author, leaving 254 cases for review. A thorough history was obtained and a thorough physical examination performed with a focus on the involved shoulder including specific provocative maneuvers for the clinical diagnosis of a SLAP lesion. The active compression test, the anterior slide test, and the PDT were used to clinically diagnose a SLAP lesion. The results from the 3 provocative maneuvers were compared with the arthroscopic findings to determine the sensitivity, specificity, negative predictive value (NPV), and positive predictive value of each test alone and in a logical combination.\n Of 254 shoulder arthroscopies, 61 had a clinically significant SLAP lesion, for an incidence of 24%. The sensitivity and specificity for the PDT were 53% and 94%, respectively, with an NPV of 87% and positive predictive value of 72%. In combination, the PDT and the active compression test yielded an NPV of 90.5%.\n The PDT can be used alone or in combination to aid in the clinical evaluation and diagnosis of a SLAP lesion.\n Level IV, retrospective, diagnostic, sensitivity-specificity study.", "We assessed the relative value of lag signs for the evaluation of rotator cuff rupture in a prospective study of 100 consecutive painful shoulders with impingement syndrome, stages 1 to 3. Lag signs were compared with the Jobe and lift-off signs. Three tests were designed to assess the main components of the rotator cuff: the external rotation lag sign (ERLS) for the supraspinatus and the infraspinatus tendons, the drop sign for the infraspinatus, and the internal rotation lag sign (IRLS) for the subscapularis tendon. For assessment of the supraspinatus and infraspinatus the ERLS was less sensitive but more specific than the jobe sign. The drop sign was the least sensitive but was as specific as the ERLS. Partial ruptures of the supraspinatus remained concealed to the ERLS. For assessment of the subscapularis the IRLS was as specific but more sensitive than the lift-off sign. Partial ruptures of the subscapularis tendon could be missed by the lift-off sign but were detected by the IRLS. The magnitude of the lag correlated with the size of the rupture for both the ERLS and the IRLS. Clinical testing for lag signs was efficient, reproducible, and reliable. In patients with little or no restriction of motion it enhanced the accuracy of clinical diagnosis in rotator cuff lesions.", "The purpose of this study was to explore and describe reasons for variation in diagnostic accuracy of clinical tests using Yergason's and Speed's tests in predicting biceps tendon pathology and SLAP lesions. Shoulder arthroscopy was used as the gold standard.\n Prospective blinded study of consecutive patients with a wide spectrum of shoulder conditions.\n One hundred fifty-two subjects (65 women and 87 men) with complaints of shoulder pain were examined. Fifty subjects (16 women and 34 men) ranging in age from 24 to 79 years (mean age, 50 years; SD = 14.36) met the criteria for surgery. The validity of the Yergason's and Speed's tests was evaluated against findings at surgery.\n The surgical findings related to biceps pathology and SLAP lesions were as follows: 2 bicipital tendonitis, both associated with significant rotator cuff pathology; 10 biceps partial tears; and 2 complete ruptures. Fifteen patients had SLAP lesion type I, 12 type II, and 1 type IV. The sensitivity, specificity, and positive and negative predictive values were 43%, 79%, 60%, and 65% for Yergason's test and 32%, 75%, 50%, and 58% for Speed's test, respectively. The likelihood ratios were 1.28 and 0.91 for Speed's test and 2.05 and 0.72 for Yergason's test. These ratios were provided to assist clinicians in calculating the probability of biceps pathology and SLAP lesions for a single patient with a different history-specific prevalence of having the pathology.\n Although Speed's and Yergason's tests are moderately specific, they do not generate a large change in the post-test probability and are unlikely to make a significant change in the pretest diagnosis. Clinicians should understand that clinical examination tests do not perform consistently and have variable predictive values in different patient populations and settings.\n Level I diagnostic study: testing of previously developed criteria in a series of consecutive patients (using surgery as gold standard).", "High frequency ultrasonography is an accurate non-invasive imaging technique for evaluating patients with painful shoulder.\n To compare the clinical diagnosis established by a physical examination with high frequency ultrasonographic findings in patients with painful shoulder.\n Thirty one consecutive patients with a first flare of shoulder pain were prospectively included in the study. All had a physical examination performed by two blinded rheumatologists. Ultrasonographic examination was carried out within one week of the physical examination by a third rheumatologist experienced in this technique who had no knowledge of the clinical findings. Ultrasonography was considered the optimal diagnostic technique.\n Clinical assessment showed low accuracy in the diagnosis of periarticular shoulder lesions.\n Ultrasonography should be used wherever possible to improve diagnosis and treatment of painful shoulder.", "Prospective blinded comparison of clinical examination and surgical findings of consecutive patients seen at a tertiary shoulder center.\n To investigate the validity of the supraspinatus test in diagnosing rotator cuff pathology using arthroscopy or open surgery as reference standards. A positive supraspinatus test was defined as pain for all types of rotator cuff pathology and weakness for full-thickness tears.\n Rotator cuff tenopathy is a very common condition. However, there have been relatively few studies documenting the validity of physical examination for this condition and further investigation of the measurement properties of these tests is warranted.\n One hundred two consecutive subjects were examined. Fifty subjects, ranging in age between 24 and 79 years (mean age, 50 years; SD, 14.4 years) and composed of 16 females and 34 males, underwent surgery.\n The sensitivity of the supraspinatus test was 62%, 41%, and 88% for \"supraspinatus tendonitis or partial thickness tear,\" \"full-thickness tear,\" and \"large to massive tears,\" respectively. The specificity values were 54%, 70%, and 70% for the above conditions, respectively. The negative likelihood ratios varied from 0.17 to 0.84, and the positive likelihood ratios varied from 1.35 to 2.93, depending on the presence of pain or weakness.\n Application of the supraspinatus test in isolation is helpful in diagnosing large or massive rotator cuff tears. The change that this test makes in pretest probability of less extensive rotator cuff pathology is insignificant.", "Clinical tests are a key element in diagnosing shoulder lesions.\n This study examined the clinical utility of traditional and new examination tests, the upper cut for biceps injuries, and the modified dynamic labral shear for superior glenoid labral lesions.\n Cohort study (Diagnosis); Level of evidence, 2.\n A total of 325 consecutive patients who were seen for shoulder pain underwent a standardized clinical testing battery. Six clinical tests that have been previously reported in the literature (Yergason's, Speed's, bear hug, belly press, O'Brien's, and anterior slide) and 2 new examination tests (upper cut and modified dynamic labral shear) were performed. Clinical examination findings were correlated with findings in those who came to surgery (101 patients). Sensitivity, specificity, accuracy, positive/negative predictive value, and positive/negative likelihood ratio were calculated for each test. A binary logistic regression analysis was used to determine which tests produced the most significant findings.\n For biceps disease, the bear hug and upper cut were most sensitive (0.79 and 0.73, respectively), whereas the belly press and Speed's test were most specific (0.85 and 0.81, respectively). The upper cut was most accurate (0.77) and produced the highest positive likelihood ratio (3.38). For labral injury, the modified dynamic labral shear demonstrated sensitivity of 0.72, specificity of 0.98, accuracy of 0.84, and a positive likelihood ratio of 31.57. A binary logistic regression analysis revealed that the combination of the upper cut and Speed's tests were significantly better at detecting biceps lesions (P = .021, R(2) = .400) than other tests, whereas labral lesions were best identified by combination of the modified dynamic labral shear and O'Brien's maneuvers (P = .045, R(2) = .641).\n The new tests are helpful additions to the clinical examination for shoulder injury. The modified dynamic labral shear test demonstrates high scores for clinical utility and exhibits a high likelihood ratio, indicating a significant probability of affecting the clinical decision, which should moderately or significantly improve the diagnostic conclusion and allow the clinician to be more efficient in making an accurate diagnosis.", "The purpose of this study was to evaluate the sensitivity, specificity, negative and positive predictive values, and accuracy of the shoulder relocation test in 100 patients who underwent shoulder surgery. Based on operative data and examination under anesthesia, the diagnoses were grouped into six categories: anterior instability (without cuff disease), posterior instability, rotator cuff disease (without associated anterior instability), acromioclavicular disorder, osteoarthrosis, and instability of the biceps tendon. The test was performed on the day of surgery by placing the arm in a position of 90 degrees of humerothoracic abduction and 90 degrees of external rotation (90 degrees/90 degrees). Patient responses of pain and apprehension (considered separately) were assessed in this position both with and without application of an anterior force to the proximal humerus. The relocation test assessed diminution of pain and apprehension after application of a posteriorly directed force to the proximal humerus relative to the position of 90 degrees/90 degrees alone and to the position of an anterior force being applied to the proximal humerus. Overall, 63 patients reported pain with 90 degrees/90 degrees; 74 reported pain when an anterior force to the proximal humerus was applied: the anterior instability group alone had 46 and 63 reports of pain, respectively; the rotator cuff group alone had 82 and 88 reports of pain, respectively. The only positive responses for apprehension were in the anterior instability group, of which 63% had apprehension with 90 degrees/90 degrees alone and 74 had apprehension when an anterior humeral force was applied.(ABSTRACT TRUNCATED AT 250 WORDS)", "To examine the association between supraspinatus pathology and clinical sign of impingement, 42 workers with and 31 age-matched workers without signs of subacromial impingement had their shoulder examined by magnetic resonance imaging. All subjects were selected from an epidemiologic study evaluating the risk of shoulder impingement syndrome in relation to ergonomic exposure. Physical examination was conducted according to the same protocol and included assessment of shoulder function. Magnetic resonance images were evaluated in a blinded manner with regard to clinical status and age. Twenty-two (55%) subjects in the impingement group and 16 (52%) subjects in the control group had a pathologic supraspinatus tendon (odds ratio 1.13 [95% confidence interval 0.45 to 2.88]). The prevalence of supraspinatus pathology increased from 32% in the youngest to 48% in the middle and 72% in the oldest age group. The results of this study indicate that supraspinatus pathology is related to age rather than to clinical sign of impingement.", "To investigate whether the lag signs were valid tools in diagnosing full-thickness tears of the rotator cuff.\n A same-subject, correlation, double-blinded design was used. The results of the external rotation lag sign, drop sign, and internal rotation lag sign were compared with the criterion standard of diagnostic ultrasound to establish their accuracy.\n A regional orthopedic hospital.\n Consecutive subjects (N=37), 21 women and 16 men, with shoulder pain referred to a consultant orthopedic surgeon specializing in shoulder conditions were recruited for this investigation.\n Not applicable.\n Sensitivity, specificity, and positive and negative likelihood ratios of the lag signs when using ultrasound as the reference test.\n The specificities of the drop sign and internal rotation lag sign were 77% and 84%, respectively, which, together with low positive likelihood ratios 3.2 (95% confidence interval [CI], 1.5-6.7) and 6.2 (95% CI, 1.9-12.0), indicate that a positive result was poor at recognizing the presence of full-thickness tears. The drop sign had a sensitivity of 73% with a negative likelihood ratio of .34 (95% CI, 0.2-0.8), suggesting that a negative test was fair at ruling out the presence of full-thickness tears. The sensitivity of the internal rotation lag sign (100%) supported by the negative likelihood ratio of 0 (95% CI, 0.0-2.5) suggests that a negative test will effectively rule out the presence of full-thickness tears of the subscapularis. A positive external rotation lag sign is the clinical test most likely to indicate that full-thickness tears of the supraspinatus and infraspinatus are present (specificity, 94%). However, the external rotation lag sign did demonstrate a low sensitivity score of 46% and negative likelihood ratio of .57 (95% CI, 0.4-0.9), which means that a negative test will not rule out the presence of full-thickness tears.\n The findings of this investigation suggest that a clinical diagnosis of a full-thickness tear of the rotator cuff cannot be conclusively reached using one or more of the lag signs.", "The purpose of this study was to investigate the validity of the supraspinatus test as a screening test for detecting torn rotator cuff and to determine what its valuable positive signs were. Both the empty-can test and full-can test were performed on 200 shoulders diagnosed by magnetic resonance imaging (MRI)-and in some cases, surgical findings-to have full-thickness or partial-thickness torn rotator cuff s, or no tear in the rotator cuff . During the maneuver, the presence of pain or weakness or both pain and weakness were recorded as positive signs, and the distribution of these signs were analyzed according to the degree of tear. The predictive values were calculated in 2 ways by considering (1) only full-thickness tears as tears and (2) both full- and partial-thickness tears as tears. The 2 tests and the 2 ways of considering partial-thickness tears were compared. Pain and weakness were severity-dependent, and the empty-can test had a higher incidence of pain. The sensitivities of the 2 supraspinatus tests in all positive signs were higher when including partial-thickness tears in the tear group ; however, their specificities were higher when excluding partial-thickness tears. Both pain and weakness were interpretive for the supraspinatus test, and both tests were sensitive to full- and partial- thickness tears and specific for full-thickness tears.", "To determine whether the presence and extent of a tear of the rotator cuff could be predicted on the basis of a patient's history, physical examination, and radiographic findings, detailed data from the histories and physical examinations of 103 patients who were known to have a tear of the rotator cuff were correlated with the radiographic and operative findings on these patients. An age-matched control group of fifty-one patients who had similar symptoms, but whose arthrograms showed normal results, was used to establish a baseline incidence of ten specific radiographic findings in the shoulder. Two discrete groups of patients who had a tear of the rotator cuff were identified. Twenty-eight patients (27 per cent) had a tear of a single tendon; the histories and the physical and radiographic findings in this group were consistent with a symptomatic local mechanical-impingement process in the shoulder. Sixty (80 per cent) of the seventy-five patients in the other group had a history of acute trauma to a shoulder. The patients in this second group were older and were non-athletic, and had not previously had symptoms that were severe enough to need treatment. These patients were subsequently found to have a complete tear of more than one of the tendons of the rotator cuff. Multiple radiographic findings in the shoulder and other coexisting orthopaedic conditions also were more common in these patients. In this group, we believe that acute trauma in a shoulder that had chronic degenerative changes, rather than localized mechanical impingement, caused the tendons to rupture.", "The aim of this study was to assess the diagnostic accuracy of a new clinical test for the diagnosis of subacromial impingement and full thickness postero-superior rotator cuff tears. One hundred and twenty patients who underwent arthroscopic treatment for acromioplasty or cuff repair were previously submitted to a new test of resistance. The test is performed in the standing position with the involved arm in 90 degrees abduction, 20 degrees -30 degrees anteposition and in external rotation (as for full-can test). Thus, the patient was invited to follow the way of a spiral drawn on a drawing sheet for 20 turns; 1 turn = from the centre to the end of the spiral and vice versa (spiral width = 20 cm). The test was considered positive when the patient was not able to conclude it due to strength decrease or to shoulder pain. Sensitivity, specificity, positive and negative predictive values as well as diagnostic accuracy were calculated for our test of resistance. The test resulted scarcely reliable as detector of subacromial impingement and not very reliable as detector of small tear. When the test is positive there is a high probability that a subacromial disease exists; instead, when it is negative there is a high probability that the patient has not a large or massive cuff tear. The resistance test (Gum-Turn test) adds to our armamentarium of physical examination signs in patients with painful shoulder and furnishes further information on possible dimensions of tendinous tear." ]

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[ "Active cycle of breathing techniques in non-invasive ventilation for acute hypercapnic respiratory failure.", "[Influence of an oscillating physiotherapy device (RC-Cornet trade mark) on the regional distribution of the pulmonary aerosol deposition in patients with COPD].", "Effect of physiotherapy on pulmonary function. A laboratory study.", "Influence of oscillating positive expiratory pressure and the forced expiratory technique on sputum cell counts and quantity of induced sputum in patients with asthma or chronic obstructive pulmonary disease.", "Physiotherapy and intermittent positive-pressure ventilation of chronic bronchitis.", "Use of a mucus clearance device enhances the bronchodilator response in patients with stable COPD.", "A preliminary study of the effect of a vibrating pad on bronchial clearance.", "[Course of Severe COPD with and without Physiotherapy with the RC-Cornet(R)].", "Effect of positive expiratory pressure mask physiotherapy (PEP) versus forced expiration technique (FET/PD) on regional lung clearance in chronic bronchitics.", "Physiologic effects of chest percussion and postural drainage in patients with stable chronic bronchitis.", "THE VALUE OF LUNG PHYSIOTHERAPY IN THE TREATMENT OF ACUTE EXACERBATIONS IN CHRONIC BRONCHITIS.", "Effects of postural drainage, exercise, and cough on mucus clearance in chronic bronchitis.", "[Physical therapy in patients with COPD and tracheobronchial instability--comparison of 2 oscillating PEP systems (RC-Cornet, VRP1 Desitin). Results of a randommized prospective study of 90 patients].", "[Physiotherapy in chronic obstructive pulmonary disease: oscillatory breathing with flutter VRP1].", "PEEP-masks in patients with severe obstructive pulmonary disease: a negative report.", "Treatment of chronic bronchitis with terbutaline inhaled from a cone spacer with and without positive expiratory pressure.", "Nebulized terbutaline and positive expiratory pressure in chronic obstructive pulmonary disease.", "Effect of chest wall vibrations on pulmonary function in chronic bronchitis.", "Intrapulmonary percussive ventilation in acute exacerbations of COPD patients with mild respiratory acidosis: a randomized controlled trial [ISRCTN17802078]." ]

[ "We hypothesised that applying the active cycle of breathing techniques (ACBT) in patients with acute hypercapnic respiratory failure undergoing non-invasive ventilation would improve patient outcome. Thirty-four patients were randomised so that 17 patients with acute hypercapnic respiratory failure received the ACBT and non-invasive ventilation (ACBT group), and 17 patients received non-invasive ventilation alone (control group). The primary outcome measure was length of time requiring non-invasive ventilation, and secondary outcome measures were change in acute physiology score, change in arterial blood gas values, total duration of non-invasive ventilation, and length of stay in the intensive care unit. Although not significant, there was a greater decrease in arterial carbon dioxide pressure in the ACBT group compared to the control group (-21.41 mmHg vs -17.45 mmHg, p = 0.27). Total duration of ventilation tended to be shorter in the ACBT group than in the control group (64.9 hours vs 84.1 hours, p = 0.15). Length of time in need of non-invasive ventilation was significantly lower in the ACBT group than in the control group (5.0 days vs 6.7 days, p = 0.03). There was no significant difference in length of stay in the intensive care unit between the two groups (8.0 vs 9.4 days, p = 0.31). The use of ACBT may have positive effects in the treatment of patients with acute hypercapnic respiratory failure, resulting in a shorter length of time requiring non-invasive ventilation.", "The inhalation of ipratropium bromide via a jet nebulizer obtained a significantly higher bronchodilation, if the oscillating physiotherapy device RC-Cornet trade mark was integrated into the exaspiratory limb of the nebulizer. Therefore we investigated the influence of the RC-Cornet trade mark on the central pulmonary radioaerosol deposition as well as the relationship between central and peripheral lung deposition in patients with chronic obstructive lung disease in a controlled study.\n Lung ventilation scintigraphy was performed routinely in 14 pat. with COPD (Nebulizer: PARI VECTOR trade mark, radioaerosol 500 MBq tin-colloid). At first all pat. inhaled a single breath from the nebulizer, afterwards the lungs were scanned with a planar gamma camera. Both groups (biometric and lung function data were identical) then inhaled another 5 breaths. In group A the RC-Cornet trade mark was inserted into the exaspiratory limb, in group B a normal exaspiratory valve. Once more lung scans were collected. Evaluation of the scans by means of a \"region of interest\" technique, dividing the lungs in a central and a peripheral area. Measuring of the radioactivity (impulse) per pixel and determination of the penetration index (PI).\n The following 5 breaths led to a significant increase of the central aerosol deposition (i. e. decrease of PI) in comparison with the measuring after the first breath in both groups (A 0,41 +/- 0,07 to 0,38 +/- 0,08, p = 0,04; B 0,38 +/- 0,08 to 0,34 +/- 0,11, p = 0,02). However, no difference could be recognized between the groups. No significant difference was seen with respect to the impulses per pixel.\n Neither the aerosol deposition in the central region of the lung nor the relation between central and peripheral deposition (PI) differs between the both groups. The effect of the RC-Cornet trade mark mentioned in the introduction seems to be caused by physiotherapeutic induced changes of the mucus transport and not by an enhanced central drug deposition.", "33 patients with acute exacerbations of chronic bronchitis were studied within 4 days of admission to hospital. Physiotherapy produced an acute rise in lung volume and conductance, without altering specific conductance. There was no consistent change in arterial-blood gases.", "To evaluate whether respiratory therapy techniques influence the number of cells within and quantity of induced sputum in patients with asthma or chronic obstructive pulmonary disease (COPD).\n Randomized clinical trial, in which patients with asthma or COPD under intervention (n = 16 and 10, respectively) were compared with control groups (n = 16 and 10). Patients in the asthma/intervention (A/I) and COPD/intervention (C/I) groups were submitted to oscillating positive expiratory pressure maneuvers for 5 min, followed by 10 forced expiratory technique sequences. These patients were also submitted to an induced sputum protocol with inhaled hypertonic saline (3%, 4% or 5%; A/I group) or inhaled isotonic saline (C/I group). The asthma/control (A/C) and COPD/control (C/C) groups were submitted only to the standard induced sputum protocol.\n The final mean weight of the sputum samples was significantly greater in the A/I group than in the A/C group (2,767.25 +/- 998.08 mg vs. 1,689.17 +/- 1,189.96 mg; p = 0.03). The mean/median total cell counts (x10(6)/mL) were higher in the A/I and C/I groups than in the A/C and C/C groups (4.06/0.95 and 0.63/0.39, p = 0.05, vs. 5.08/1.77 and 0.64/0.40, p = 0.02). There were no statistically significant differences among the groups in terms of cell viability.\n The use of respiratory therapy techniques can increase sputum sample weight in asthma patients, as well as increasing total cell counts in patients with asthma or COPD.", "Patients aged over 45 admitted to hospital with exacerbations of chronic bronchitis alone or in association with cor pulmonale, pneumonia, or respiratory failure were placed in one of three groups (men with hypoxia, men without hypoxia, and women). Patients within these groups were then randomly allocated to receive either standard drug treatment alone or standard drug treatment plus intermittent positive-pressure ventilation (IPPV). No significant differences occurred between the controls and patients receiving physiotherapy and IPPV in any group. We conclude that when a patient with chronic bronchitis and respiratory failure is deteriorating emphasis should be on correct diagnosis, fluid electrolyte balance, and nutrition together with oxygen treatment when necessary, rather than on additional physiotherapy.", "To determine whether the use of a mucus clearance device (MCD) [Flutter; Axcan Scandipharm; Birmingham, AL] could improve the bronchodilator response to inhaled ipratropium and salbutamol delivered by a metered-dose inhaler in patients with stable, severe COPD.\n Twenty-three patients with severe COPD were studied. Mean +/- SD age was 71.7 +/- 6.3 years. Mean FEV(1) was 0.74 +/- 0.28 L or 34.5 +/- 12.7% predicted.\n Patients were tested in random order on 2 subsequent days after using an MCD or a sham MCD. A bronchodilator (four puffs; each puff delivering 20 microg of ipratropium bromide and 120 microg of salbutamol sulfate) was administered by metered-dose inhaler with a holding chamber after use of the MCD or sham MCD. Spirometry was performed before and after use of the MCD or sham MCD, and at 30 min, 60 min, and 120 min after the bronchodilator. Six-minute walk distance was tested between 30 min and 60 min; oxygen saturation, pulse, and a dyspnea score were recorded before and after walking.\n Immediately after use of the MCD, but not the sham MCD, there was a statistically significant (p < 0.05) improvement in FEV(1) and FVC (11 +/- 24% vs 1 +/- 7% and 18 +/- 33% vs 6 +/- 18%, respectively). Whether patients were pretreated with the MCD or sham MCD, there was a significant improvement in FEV(1) and FVC compared to baseline with combined bronchodilator therapy. At 120 min, the change in FEV(1) after treatment with the MCD was greater than with the sham MCD (186 +/- 110 mL vs 130 +/- 120 mL; p < 0.05). When comparing the MCD to the sham MCD, 6-min walk distance was greater (174 +/- 92 m vs 162 +/- 86 m; p < 0.05), with less dyspnea before and at the end of walking.\n Patients with severe COPD may demonstrate a significant bronchodilator response to combined ipratropium and salbutamol delivered by metered-dose inhaler. This response may be enhanced and additional functional improvement obtained with the prior use of a bronchial MCD.", "The effect of vibration (41.0 +/- 5.4 Hz; 2 mm amplitude) on the clearance of lung secretions was ascertained in 10 patients with chronic bronchitis who complained of difficulty in raising sputum. Vibration was applied to the back for one hour by an electrically driven pad while the patients reclined on a couch with the trunk at 45 degrees to the vertical. Each patient had randomized control and experimental runs of 5 hours' duration that were identical in all respects except for vibration. The rate of clearance of secretions from the lung was assessed by serial whole lung counts after inhaling monodispersed tracer particles tagged with a gamma-emitting radioisotope (technetium-99m) and by sputum production. The mean rates of clearance and of sputum production were slightly higher during the vibration runs than the control runs but the differences were not significant.", "The efficacy of respiratory physiotherapy by combined-PEP (RC-Cornet(R) in combined-PEP-position) was evaluated in a long-term study with the following set up.\n Randomized prospective clinical trial over 2 years in 50 patients with severe COPD (12 f, 38 m, 63,1 y, FEV 1 41 %, DLCO 51 % of the normal). Patients were without infection and exsmokers at begin of the trial. One group was treated only by drug therapy (theophylline, salmeterol, ipratropiumbromide, systemic steroids 5 mg prednisolone equivalent). The second group received the same drug therapy plus physical therapy with the RC-Cornet(R) (oscillating PEP; in combined PEP-position) 3 times daily at least for 5 minutes or whenever needed. Lung function data were controlled every 3 month during first year and every 4 month in the second year. The compliance was checked by theophylline and cortisol blood levels, inspection of the functionality of the RC-Cornet(R) and by questioning the patient about compliance with the therapy.\n TGV (% of normal) and airway resistance (measured by bodyplethysmography) decreased significantly in contrast to the \"mere\" drug therapy (p < 0.0177, p < 0.0179). VC (% of normal) increased significant p < 0.0179 in the RC-Cornet(R) therapy group. In this group significantly less patients (13/24) needed antibiotics in comparison to the \"mere\" drug group (Chi-Quadrat p < 0.0004). Also the need for hospital care was significantly less in the RC-Cornet(R) group (5/12) in comparison to the drug therapy group (Chi-Quadrat < 0.000765). The length of hospital stay in the two groups was not significantly different: 16.2 +/- 6.3 days in the RC-Cornet(R)-group and 18.3 +/- 4.7 days in the drug therapy-group.\n This study proves the efficacy of respiratory physiotherapy with combined-PEP in addition to drug therapy in the management of COPD-patients.", "On theoretical grounds it is assumed that positive expiratory pressure mask physiotherapy (PEP) as a means of promoting mucus clearance is especially effective in the more distal airways. In a randomized cross-over trial including a control measurement the effect of PEP and of the forced expiration technique combined with postural drainage (FET/PD) on regional lung clearance was evaluated in seven patients with chronic bronchitis and abundant sputum production (mean 32 g.day-1). PEP consisted of positive expiratory pressure mask breathing interspersed with breathing exercises, forced expiration manoeuvres (huffing) and, if necessary, coughing. FET consisted of breathing exercises, huffing and also, if necessary, coughing. FET was combined with PD. Following inhalation of a radio-aerosol regional lung clearance was estimated by means of gamma camera imaging. The results after PEP appeared to be not significantly different from control. The mean clearance in all three lung zones (peripheral, intermediate and inner) was largest after FET/PD as compared with PEP and control. Statistical significance (p less than 0.02) was reached only for clearance in the inner region. It is concluded that PEP has no demonstrable effect on regional lung clearance in these patients.", "The effects of a 30-minute period of chest percussion and postural drainage were compared to a sham treatment (infrared lamp) in 35 patients with stable chronic bronchitis and to a period of directed coughing in 11 of these same patients. There were no differences in subjective responses or arterial blood gas levels following therapy. Spirometric studies showed small improvements over baseline values following either treatment but no difference between active and sham treatments. The volume of sputum expectorated during percussion and drainage was significantly greater than during the infrared warming (5.5 vs 1.4 ml) or during the directed coughing (9.0 vs 3.5 ml). Although chest percussion and postural drainage are effective in augmenting the volume of expectorated sputum, no significant alternations in air flow or gas exchange after two hours were demonstrated.", "nan", "The effects of postural drainage, exercise, and cough on mucus clearance were compared in 8 patients with chronic bronchitis. A bolus of 99mTc albumin aerosol was inhaled at a high inspiratory flow rate to enhance proximal deposition. Retention of deposited aerosol in the lung, as a function of time, was quantified using a gamma camera and subsequent computer analysis. Coughing greatly accelerated total lung (P less than 0.005) and peripheral (P less than 0.005) mucus clearance. Exercise resulted in much smaller changes than did cough, but significantly increased total lung clearance (P less than 0.005). Postural drainage in which coughing was prohibited did not alter clearance. These results have therapeutic implications and stress the importance of controlling cough when evaluating therapeutic interventions by these techniques.", "In a randomized prospective study in 90 patients with COAD and tracheo-bronchial instability 3 groups were formed. Group 1: Therapy as group 3+ Physiotherapy with VRP1 Desitin, Group 2: Therapy as group 3+ Physiotherapy with RC-Cornet, Group 3: Control group: daily 40 mg prednisolon i.v., 2 x theophylline i.v. in relation to serum levels and 3 x inhalation of beta 2+ parasympathicolytic with a compressor inhaler. Therapy group 1 and 2 received the same drug and inhalation therapy as the controls. Controls of lung function before and after physiotherapy and visual analog scales for dyspnoea, cough, sputum and acceptance of the physiotherapy were performed at days 1, 4 and 7. With RC-Cornet the residual volume decreases statistically significant in comparison to VRP1 Desitin. Hyperventilation is also statistically significant smaller in RC-Cornet compared to VRP1 Desitin. The subjective improvement of sputum, dyspnoea and acceptance of the method of physiotherapy was statistically significant better for RC-Cornet. Regarding cough the significance was just failed by p < 0.055. RC-Cornet is a comfortable, effective, small accepted tool for the long term physiotherapy of patients with COAD and tracheobronchial instability.", "Chronic obstructive pulmonary disease (COPD) is characterized by sputum production and cough. It has been shown that mucus hypersecretion predisposes to recurrent bronchial infection and that reduction in airway secretions is associated with clinical improvement. Recently a new pipe-shaped device for chest physiotherapy, the flutter VRP1 (\"VarioRaw:\" Aubonne, Switzerland), was introduced in order to help clear bronchial hypersecretion. We determined the long-term efficacy of daily chest physiotherapy with the VRP1 in COPD and bronchial hypersecretion. 13 men and 7 women with COPD and sputum hypersecretion were studied; 10 were assigned to the physiotherapy group, and 10 to the control group getting sham therapy. After 3 months of physiotherapy, FVC, FEV1 and distance walked in 12 minutes increased in the treated group, but were almost unchanged in the sham-treated group. Arterial blood gases, the maximum voluntary ventilation, and respiratory rate at rest were unchanged in both groups. There was also an overall significant improvement in COPD symptoms in the physiotherapy group compared to baseline (p < 0.05). We conclude that long-term home physiotherapy with the flutter VRP1 is effective in COPD in improving airflow, functional ability and symptoms.", "Positive pressure during expiration by face masks applied by the patient has gained wide acceptance in the treatment of chronic bronchitis, but the efficacy is still unproven. The effect of 6 months of treatment with PEEP-masks (positive end-expiratory pressure) was therefore studied in 47 patients with severe irreversible obstructive pulmonary disease (forced expiratory volume in one second (FEV1) about 1 l), and mucus hypersecretion. Patients were double-blindly randomized to at least 45 min daily treatment with PEEP-masks with either 10 or 0 cm water pressure. After 6 months of treatment, no statistical difference was found between the two groups in change of median values (month 6 - month 0) of FEV1, forced vital capacity (FVC), arterial oxygen tension (PaO2), amount of sputum or dyspnoea. Median values of arterial carbon dioxide tension (PaCO2) decreased significantly (0.03 kPa) in the placebo group. Cough intensity and dyspnoea during walking on staircases improved significantly in the placebo group. No difference among groups was found in number of days bedridden, hospitalized, number of exacerbations or antibiotic consumption. We conclude, that the use of PEEP-masks in these patients is without clinical documentation and cannot be recommended.", "Patients with chronic bronchitis were randomly allocated to 4 weeks treatment with terbutaline 0.5 mg inhaled through a cone spacer with an expiratory resistance creating a positive expiratory pressure (+PEP group) or without (-PEP group). The patients recorded their symptoms in a diary and peak expiratory flow (PEFR) was measured before and after each inhalation. PEFR increased significantly after inhaled terbutaline both with and without PEP. The mean increase in PEFR after terbutaline inhalations was significantly greater (p less than 0.0001) in the +PEP group (24 L/min) compared to the -PEP group (17 L/min). The +PEP group had less sputum and less difficulty with coughing up sputum compared to the -PEP group. This study showed a small but significant enhancement of the bronchodilation and a beneficial effect on symptoms when inhalation of beta-2-agonist was combined with PEP in patients with chronic bronchitis.", "The effect of positive expiratory pressure (PEP) and inhaled terbutaline was evaluated in ten patients with chronic obstructive pulmonary disease in a randomized cross-over study with three 2 weeks periods. In one period 5 mg terbutaline was inhaled 3 times daily from a nebulizer combined with PEP. In a second period 5 mg terbutaline was inhaled similarly but without PEP and in a third period placebo inhalations were combined with PEP. Symptom score and peak expiratory flow (PEF) measured before and after each inhalation was noted in a diary. The treatment with nebulized terbutaline combined with PEP gave the best relief in symptoms. All treatments increased PEF significantly. PEP alone gave the least increase in PEF (25 1/min), and there was no difference between the increase in PEF after terbutaline inhaled with PEP (28 1/min) compared to terbutaline alone (29 1/min).", "Manual chest wall vibration is one physiotherapeutic technique frequently employed in the management of respiratory disease. A clinical study was undertaken to examine the effects of manual chest wall vibrations on pulmonary function and arterial oxygen saturation in patients with chronic bronchitis. Twelve patients participated in a three-day experimental design where the factors of three different days and three different treatments were randomized and balanced. On one day, deep-breathing exercises were given; on another, deep-breathing exercises with vibrations; and on the remaining day, no treatment was given. Lung volumes were measured before and after each maneuver, and arterial oxygen saturation was monitored continuously. There was a significant decrease in the expiratory reserve volume (ERV) immediately following the deep-breathing exercises alone, which remained constant after the 15-minute rest period (p = 0.032). The remaining outcome parameters do not appear to be significantly affected. Chest wall vibrations do not decrease the ERV in patients with chronic bronchitis.", "We hypothesized that the use of intrapulmonary percussive ventilation (IPV), a technique designed to improve mucus clearance, could prove effective in avoiding further deterioration in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) with mild respiratory acidosis.\n The study was performed in a medical intensive care unit of a university hospital. Thirty-three patients with exacerbations of COPD with a respiratory frequency >or= 25/min, a PaCO2 > 45 Torr and 7.35 <or= pH <or= 7.38 were included in the study. Patients were randomly assigned to receive either standard treatment (control group) or standard treatment plus IPV (IPV group). The IPV group underwent two daily sessions of 30 minutes performed by a chest physiotherapist through a full face mask. The therapy was considered successful when both worsening of the exacerbation and a decrease in pH to under 7.35, which would have required non-invasive ventilation, were avoided.\n Thirty minutes of IPV led to a significant decrease in respiratory rate, an increase in PaO2 and a decrease in PaCO2 (p < 0.05). Exacerbation worsened in 6 out of 17 patients in the control group versus 0 out of 16 in the IPV group (p < 0.05). The hospital stay was significantly shorter in the IPV group than in the control group (6.8 +/- 1.0 vs. 7.9 +/- 1.3 days, p < 0.05).\n IPV is a safe technique and may prevent further deterioration in patients with acute exacerbations of COPD with mild respiratory acidosis." ]

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[ "Radiation therapy for superior vena caval syndrome due to lung cancer.", "Application of expandable metallic stents to the venous system.", "[Tactics in treating patients with small cell cancer of the lung with superior vena cava obstruction syndrome].", "Superior vena cava syndrome revisited.", "Vena caval and central venous stenoses: management with Palmaz balloon-expandable intraluminal stents.", "Gianturco-Rösch expandable Z-stents in the treatment of superior vena cava syndrome.", "Case report: migration and shortening of a self-expanding metallic stent complicating the treatment of malignant superior vena cava stenosis.", "[Therapy of venous stenosis using wall stents].", "Superior vena cava obstruction in small cell bronchogenic carcinoma. Clinical parameters and survival.", "Resolution of superior vena cava obstruction in small cell lung cancer patients treated with chemotherapy.", "Superior vena caval obstruction syndrome in small cell lung cancer.", "Placement of venous stents: clinical experience with a self-expanding prosthesis.", "Prognostic value of the superior vena cava syndrome as the presenting sign of small cell anaplastic carcinoma of the lung.", "Self-expandable metallic stent therapy for superior vena cava syndrome: clinical observations.", "Gianturco self-expanding stents: clinical experience in the vena cava and large veins.", "Stent implantation in patients with superior vena cava syndrome.", "Case report: superior vena cava obstruction complicated by central venous thrombosis--treatment with thrombolysis and Gianturco-Z stents.", "Case report: superior vena caval obstruction treated by thrombolysis, mechanical thrombectomy and metallic stents.", "Superior vena cava obstruction in small-cell lung cancer.", "Superior vena cava syndrome.", "Superior vena cava stent placement: results with the Wallstent endoprosthesis.", "Stenting and superior vena caval syndrome.", "[Superior vena cava syndrome in microcytic carcinoma of the lung: incidence, treatment response and prognostic importance].", "Percutaneous management of superior vena cava occlusions.", "Treatment of obstruction of the superior vena cava by combination chemotherapy with and without irradiation in small-cell carcinoma of the bronchus.", "Superior vena cava syndrome due to non--small-cell lung cancer. Resolution with chemotherapy alone.", "[Stent implantation for the palliative therapy of upper inflow obstruction in bronchial carcinoma].", "Treatment of malignant obstruction of the superior vena cava with the self-expanding Wallstent.", "Intravascular stents in the management of superior vena cava syndrome.", "Small cell lung cancer with and without superior vena cava syndrome: a multivariate analysis of prognostic factors in 408 cases.", "Response of superior vena cava syndrome to radiation therapy.", "Expandable Wallstent for the treatment of obstruction of the superior vena cava.", "[Venous angioplasty and Wallstent implantation in emergency treatment of superior vena cava syndrome caused by tumor].", "Clinical outcome of stenting in superior vena cava syndrome associated with malignant tumors. Comparison with conventional treatment.", "[Radiotherapy in locoregional treatment of inoperable non-small cell lung cancer: results from a series of 381 patients].", "Palliative effectiveness of radiation therapy in the treatment of superior vena cava syndrome.", "Combination chemotherapy in the management of superior vena caval obstruction in small-cell anaplastic carcinoma of the lung.", "Superior vena caval obstruction due to small-cell anaplastic lung carcinoma. Response to chemotherapy.", "[Endoprosthetic dilatation of the vena cava eliminates obstruction in superior vena cava syndrome]." ]

[ "nan", "Expandable metallic stents were successfully introduced in 12 patients; 6 with superior vena cava (SVC) obstruction due to tumor invasion or lymph node metastases, 3 with inferior vena cava (IVC) obstruction or stenosis due to lymph node metastases or hepatic tumor, one with common iliac vein (CIV) obstruction due to lymph node metastases, one with idiopathic obstruction of the hepatic IVC and Budd-Chiari syndrome, and one with CIV obstruction following a dialysis shunt. The length of the lesions was between 2 and 15 cm. Multiple (2-7) stents in tandem were inserted percutaneously from a femoral venous approach through a 12 to 16 F (4.0-5.3 mm) Teflon sheath. Postoperatively, all 12 patients became free from symptoms such as SVC syndrome or IVC syndrome. In 11 patients, the symptoms did not recur during the follow-up periods of 1 to 21 months.", "A non-randomized study was carried out to evaluate the immediate and end results of chemo-radiation therapy of 44 cases of small-cell lung cancer aggravated with superior vena cava obstruction syndrome. Both radiation and chemotherapy proved effective in urgent combatting said syndrome. The best results were reliably secured when chemotherapy was supported with radiotherapy at an earlier possible stage. Due to gravity of their condition such case require the therapy as an urgent measure. The treatment proved effective as 40% of patients with localized small-cell lung tumors and the syndrome survived 12 months.", "A clinical review with analysis of prognostic factors, including the impact of the initial management modality, was conducted on 137 patients with superior vena cava syndrome (SVCS) seen at the Veterans General Hospital-Taipei between 1989 and 1993. Malignant diseases account for most of the SVCS in our Chinese patients. Patients received diagnostic intervention for their underlying diseases without obvious complications. Whether or not there is a development of SVCS in lung cancer patients, showed prognostic significance in non-small cell lung cancer (NSCLC) and no significance in small cell lung cancer (SCLC). Those with SVCS as the initial manifestation of malignant disease had a poor prognosis compared to those who developed SVCS later. Survival is best in lymphoma/leukemia patients, followed by malignant thymoma and SCLC, and worst in NSCLC and metastatic cancer. The rapid onset of symptoms from SVCS had a short median survival in lung cancer and significantly compromised survival in SCLC. The overall survival of SCLC with SVCS was not affected, regardless of whether the initial therapy had been radiotherapy or chemotherapy.", "Palmaz balloon-expandable intraluminal stents (BEISs) were used to treat vena caval and adjacent central venous obstructions that failed to respond to conventional balloon angioplasty. An initial series included seven patients: five had superior vena cava (SVC) syndrome due to a malignant neoplasm and/or radiation therapy, one had dialysis access-related stenosis of the subclavian vein, and one had inferior vena cava (IVC) and bilateral common iliac vein obstruction due to abdominopelvic radiation therapy for Hodgkin disease. Treatment produced clinical benefit in all seven patients. Patency was achieved with stents placed across stenoses of the SVC, IVC, and brachiocephalic and subclavian veins. One stent placed in a left common iliac vein was oval and was shown to be occluded on a follow-up computed tomographic scan, suggesting that compression between the right common iliac artery and the spine was responsible. Although caution is recommended in placement at possible compression sites, BEISs can be used to treat obstructions of the vena cava and major central veins.", "Gianturco-Rösch expandable Z-stents were used in 22 patients with superior vena cava syndrome (SVCS). Stents were placed in all patients in the SVC and in 17 patients, also into the innominate veins. Stent placement resulted in complete relief of symptoms in all patients. Twenty-one patients had no SVCS recurrence from 1 to 16 months, to their death, or to the present time. SVCS recurred only in 1 patient 9 months after stent placement due to tumor ingrowth and secondary thrombosis. Based on ours and on other reported experiences, expandable metallic stents are effective devices for treatment of the SVCS which is difficult to manage by other means.", "nan", "To evaluate the patency of Wallstents implanted for the treatment of venous stenoses in patients with benign or malignant disease.\n 22 Wallstents (20 central venous; two peripheral) were implanted during a period of two years in 12 patients (nine men, three women; mean age 57.8 [26-76] years) with malignant venous stenoses (n = 9) or stenosed dialysis shunts (n = 3). Stent diameter ranged from 8-16 mm, length from 32-91 mm. Introduction of the stents were by percutaneous transfemoral catheterisation, in six patients with simultaneous wire placement from a cubital to the femoral vein. The superior vena cava was the involved vessel in six patients (in two each also the subclavian or brachiocephalic veins), in three only the subclavian vein, twice only the inferior vena cava and once the cephalic vein.\n The patency of the stents was checked after 4.7 +/- 3.6 (1-14) months, in seven patients clinically, by digital subtraction phlebography in three, by computed tomography in two. In nine patients there was no evidence of obstruction to flow or flow was normal. Stent occlusion had occurred in three patients, 4, 9 and 14 months after placement. There were no complications. Five patients died after a mean period of 4.8 +/- 3.6 (1-6.5) months from the underlying disease, without symptoms of obstruction to flow.\n Stent placement should be considered early, as it is a well-tolerated and effective palliative procedure for central venous stenoses associated with malignant disease or stenosis of dialysis shunts.", "A clinical pathologic review with analysis of prognostic factors was conducted in 56 patients who were seen at the University of Texas M. D. Anderson Hospital and Tumor Institute between 1969 and 1980 with the syndrome of superior vena cava (SVC) obstruction secondary to small cell bronchogenic carcinoma. Most patients were men (60%), nonambulatory (61%), and had demonstrable extrathoracic disease (70%). The most common symptoms and signs of SVC obstruction were jugular venous distention (100%), swollen face (88%), and dyspnea (50%). Swollen arms (34%) and engorgement of thoracic veins (32%) were also common. Initial treatment consisted of irradiation alone, 17 patients (30%); chemotherapy alone, 32 patients (57%); or both, 7 patients (13%). Patients receiving chemotherapy initially had poor prognoses, as evidenced by the greater proportion of nonambulatory patients (72%) in this group. All but two patients received chemotherapy at some point during their clinical courses. There were 12 (21%) early deaths; 2 (12%) in the radiation arm; 9 (28%) in the chemotherapy arm; and 1 (14%) in the combined modality group. All treatment modalities were rapidly effective in controlling the symptoms associated with SVC obstruction. Within 1 week from onset of treatment, 9 of 14 (64%) evaluable patients responded to irradiation, 23 of 23 (100%) to chemotherapy, and 5 of 6 (83%) to combined modality treatment. The type of initial treatment did not influence survival significantly, although patients who achieved complete clinical remissions survived longer (median, 62 weeks). Death was usually due to disease progression in distant sites. Multivariate analysis indicated that the most important prognosticators of patients' survival were pretreatment performance status, disease-extent score, and age.", "Small cell lung cancer is a highly chemo-sensitive malignancy. As it often presents with a central lesion, superior vena cava obstruction (SVCO) is not an uncommon manifestation. From January 1990 to December 1993, 161 patients with small cell lung carcinoma were seen at our institution. Twenty (12.4%) of these patients presented with symptoms and signs of SVCO. Initial therapy consisted of radiotherapy in 4 patients and chemotherapy in 16 patients. Of those treated with chemotherapy, patient characteristics included 13 males, median age of 62.5 years (range 51 to 78 years), Eastern Co-operative Oncology Group (ECOG) performance status of 3 to 4 in 7 patients; 1 to 2 in 9 patients, and limited stage disease in 8 patients. The median period of follow-up was 5 months. Nine patients received a combination of cisplatin and etoposide (EP), 5 had cyclophosphamide, doxorubicin and vincristine, 1 had cyclophosphamide, etoposide and vincristine and 1 had monotherapy with oral etoposide. Overall response to chemotherapy was 81% (with 31% complete responses). All responders had resolution of SVCO. Only 3 patients did not respond (1 patient defaulted, 1 patient died of neutropenic sepsis at week one and 1 patient had stable disease). Resolution of SVCO was noted within the first 2 weeks after the first cycle; the earliest being 3 days. The only patient given single-agent oral etoposide responded within 10 days after initiation of treatment. Of the 7 patients with poor performance status (ECOG 3 to 4), 3 died from treatment-related complications. Chemotherapy is highly effective as a primary treatment of small cell lung carcinoma despite presentation with SVCO. However, caution is advised in the use of combination chemotherapy for those presenting with poor performance status. Initial therapy with oral etoposide or radiotherapy should be considered as possible alternatives for these patients.", "In a series of 643 patients with small cell lung cancer (SCLC), 55 patients (8.6%) had signs or symptoms of superior vena caval obstruction syndrome (SVCO). Relatively long intervals from the onset of the first symptoms of SVCO to the start of therapy were observed, and invasive diagnostic procedures were safely performed in most patients. The pretreatment characteristics of patients with SVCO were not significantly different from those of patients without signs of the syndrome, and survival was similar in both groups. Patients with SVCO were usually treated first with induction chemotherapy, and prompt resolution of signs and symptoms occurred in the majority. Radiation was effective in controlling SVCO at relapse or after failure of initial chemotherapy. It was concluded that SVCO in patients with SCLC should be treated initially with systemic chemotherapy, as for other presentations of this disease. The current data do not support the commonly held view that SVCO in SCLC should be approached as an oncologic emergency.", "A self-expanding vascular prosthesis was used to treat 20 venous stenoses or occlusions in 13 patients. The lesions were caused by tumor (n = 5), postoperative fibrous scars (n = 2), and chronic hemodialysis fistulas (n = 13). Follow-up ranged between 6 weeks and 53 months (mean follow-up, 14.9 months). Acute occlusion occurred in two stents, one within a tumor stenosis and one in a dialysis shunt after 3 days and 2 days, respectively. Balloon angioplasty, thrombolysis, and aspiration in the first case and balloon angioplasty and thrombolysis in the second case successfully restored patency. Definite occlusion occurred in these two patients after 8 weeks and 5 months, respectively. Ten secondary interventions were performed in three patients with 10 restenoses who had stenotic arm veins in chronic hemodialysis at presentation. Five of seven patients who received treatment for stenoses associated with hemodialysis underwent successful kidney transplantation 5-27 months after placement of vascular stents. Both patients who received treatment for benign strictures had patent stents at follow-up examinations performed at 45 and 53 months, respectively. Four of five stents placed for malignant stenoses were patent at venography (n = 3) or autopsy (n = 1).", "nan", "To study clinical and physiologic aspects of Z-stent therapy for superior vena cava (SVC) syndrome secondary to malignant disease.\n Signs and symptoms of SVC syndrome were classified, graded, and scored in 11 cases. Six patients with caval pressure higher than 22 mm Hg peripheral to the stenosis underwent stent therapy.\n Immediately after Z-stent implantation into the stenotic lesion, the diameter of the constriction increased from 3.3 mm +/- 2.0 (mean +/- standard deviation) to 14.0 mm +/- 3.2, the mean caval pressure peripheral to the stenosis decreased from 26.6 mm Hg +/- 2.5 to 8.9 mm Hg +/- 0.7, and the symptom score decreased from 6.7 +/- 1.8 to 1.3 +/- 1.4. The caval pressure, lesion diameter, and symptom score correlated highly with each other. One complication--transient pulmonary edema attributable to volume overload caused by reperfusion--was observed. Mean survival exceeded 7.1 months.\n Stent placement could be a useful treatment for refractory SVC syndrome.", "Twenty-five patients with stenosis of the vena cava (21) and other large veins (4) have been treated with self-expanding Gianturco metallic stents. Eighteen patients had superior vena cava syndrome. In 17, the stricture was due to malignant superior vena cava compression recurrent after maximum tolerance radiotherapy and/or chemotherapy. In 16 of these patients there was early symptomatic relief. In 1 patient with a benign posttraumatic superior vena cava stricture, the stenosis was not relieved, and occlusion occurred after 1 month. Stenoses associated with dialysis shunts were relieved in 2 other patients. Two malignant and one benign inferior vena cava stenoses were relieved either until death, or in the benign case, for 30 months. One malignant subclavian vein obstruction occluded after 24 h due to stent misplacement and another with extrinsic mediastinal compression remained patent until death, extensive thrombus having been lysed prior to stent placement. The results of this short series suggest that the Gianturco self-expanding stent in the vena cava and large veins is easy and safe to place, and in most cases produces almost immediate palliation of the distressing effects of venous obstruction, often in a preterminal and inoperable patient.", "The purpose of this study was to determine the feasibility of using Wallstent implantation to treat superior vena cava syndrome due to malignant tumors.\n Digital subtraction angiography showed obstruction of the superior vena cava in 13 patients who then underwent transluminal dilatation and Wallstent implantation. The patients were treated with IV heparin and monitored in the emergency department. Thereafter, they were treated with a platelet inhibitor for 4 weeks.\n Because their signs and symptoms improved, patients were able to resume radiation therapy, chemotherapy, or both. One patient died of cardiac arrhythmia 1 day after stent placement. Although eight patients have subsequently died of their bronchial or thyroid gland tumors, superior vena cava syndrome did not recur in any patient.\n Percutaneous implantation of Wallstent endoprostheses provides excellent palliation for superior vena cava syndrome.", "Expandable wire stents can provide effective palliation of superior vena cava obstruction (SVCO). We describe a case of SVCO unresponsive to radiotherapy and chemotherapy, which was complicated by extensive central venous thrombosis. Successful thrombolysis occurred with low-dose streptokinase allowing subsequent stent placement.", "We describe a case of superior vena caval obstruction (SVCO) due to bronchial carcinoma which was complicated by extensive central venous thrombosis. Partial clot lysis was achieved with thrombolytic agents, but therapy had to be discontinued due to bleeding from the gastrointestinal tract and puncture sites. Clot dissolution was completed using the Amplatz Thrombectomy Device, and the subsequent placement of a Gianturco Z-stent resulted in prolonged symptomatic relief.", "To identify prognostic or treatment factors influencing the response of superior vena cava obstruction (SVCO), time to SVCO recurrence, and overall survival of SCLC patients with SVCO at presentation; and to assess the role of retreatment in patients with SVCO at recurrent or persistent disease.\n Between January 1983 and November 1993, 76 consecutive patients who had small-cell lung cancer (SCLC) with SVCO were treated in our institution. Analysis was done according to the disease status at diagnosis of SVCO. The first analysis concerned a group of 50 patients who had SVCO at initial presentation. The second analysis concerned a group who had SVCO as a manifestation of persistent or recurrent disease.\n In the first analysis, 93% had significant improvement in symptoms of SVCO after chemotherapy and 94% after mediastinal radiation. Response is almost universal despite a wide range of radiation fractionation and total dose used. Seventy percent remained SVCO-free before death. Thirty percent developed recurrence of SVCO symptoms 1-16 months (median 8) after the start of initial treatment. Those who received combined chemotherapy and radiation had a longer time to SVCO recurrence (p = 0.018) compared to those who received chemotherapy alone. This effect is mainly seen in limited-stage patients. The presence of SVCO recurrence tends to have an adverse effect on the overall survival (p = 0.077) irrespective of the time when the recurrences occurred (p = 0.296). The median survival of this whole group of 50 patients in the first analysis was 9.5 months, and the 2-year survival was 10%. Stage was strongly predictive of survival (p < 0.001). Sixteen percent (3 of 19) of the patients with limited-stage diseases were long-term survivors (two patients survived 35 months and one survived 70 months). The early mortality from SVCO was 2%. In the second analysis, 85% had previously been treated with chemotherapy alone. The response rate of SVCO in the analysable patients (n = 39) was 77%. There was no significant difference in the response rate of SVCO to treatment comparing patients treated by chemotherapy first or mediastinal radiation first (p = 0.653), but most patients [82% (32 of 39)] received radiation as the initially treatment of SVCO. Ninety-three percent (38 of 41) received mediastinal radiation as a part of their ultimate retreatment regimen, and 68% (28 of 41) received mediastinal radiation as their sole retreatment regimen. Thirty-two percent (13 of 41) received chemotherapy as a part of their ultimate retreatment regimen, and only 7% received chemotherapy alone as their sole retreatment regimen. Eighty-three percent (25 of 30) of those whose SVCO responded remained free of SVCO before death, with a median survival of 3 months after recurrent or persistent disease documented.\n Chemotherapy or mediastinal radiation is very effective as an initial treatment in SCLC patients with SVCO at presentation and at recurrent or persistent disease. There is no obvious need to use big radiation fraction sizes for the first few radiation treatment as was previously believed. In patients with recurrent or persistent SCLC with SVCO, especially in those who previously received chemotherapy only, we have more experience in incorporating mediastinal radiation as a major component of the palliative regimen with highly effective and durable palliation achieved.", "nan", "To assess the clinical success and short-term patency of the Wallstent endoprosthesis in the treatment of superior vena cava (SVC) syndrome.\n Twenty-one 14-mm-diameter endoprostheses were implanted in 15 patients (mean age, 60 years) treated for SVC syndrome due to malignant compression (n = 14) or postirradiation fibrotic stenosis (n = 1) of the SVC.\n Immediate technical success was achieved in all patients. Two early complications occurred: retroperitoneal hemorrhage due to venous iliac tear and early stent thrombosis. In the 14 patients without early stent occlusion, stent placement resulted in complete relief of SVC syndrome; clinical success was 93%. SVC syndrome did not recur from 1 to 14 months, until the patient died (n = 11) or until the end of the study (n = 3). Helical CT showed a patent stent in five patients, respectively, at 3, 6, 8, 10, and 11 months.\n SVC stent placement has good clinical results and a high patency rate at short-term follow-up in patients with SVC syndrome.", "The use of intravascular stents in the management of Superior Vena Caval Obstruction is a relatively recent development. We describe our experience with six patients, aged between 64 and 85 years who developed SVC obstruction secondary to malignant disease and who had one or more intravascular stents inserted. Five of the patients had lung cancer and one metastatic breast carcinoma. Positive histology was available in three cases. A partial or complete clinical response was seen in all patients and two patients developed recurrent symptoms. Stenting appears to provide effective palliation of SVC obstruction symptoms.", "The incidence, response to chemotherapy treatment and prognostic value in the prediction of the Superior Cave vein syndrome (SVCS) surveillance were retrospectively studied in a group of 125 patients presenting microcytic pulmonary carcinoma. We found SVCS in 20 cases (16% of the total group of patients), there were no statistically significant differences between the limited or diseminated stages. All patients were initially treated with polychemotherapy. The efficacy of this treatment to eliminate the symptoms of SVCS could be evaluated in 17 cases while in the other 3 cases that was not possible give the early or toxic death of the patients. Fourteen out of the 17 patients with evaluable SVCS (82%) achieved a complete remission of the syndrome with chemotherapy which parallel with the achievement of a partial or complete response of the primary tumor and its metastasis. The SVCS only reappeared in one case at the moment of tumor recurrence. The remission of symptoms was quickly initiated after treatment and was completed in most cases one week after treatment was started. An statistically significant difference was not observed between the surveillance of patients who presented SVCS at time of diagnosis and those who did not. Given that both groups were balanced with regard to the rest of the prognostic factors (the disease stage, Karnofsky's index, sex, or treatment) the SVCS does not constitute a pejorative prognostic factor in the prediction of surveillance in microcytic pulmonary carcinoma.", "To assess the use of percutaneous endovascular stent insertion in the management of superior vena cava (SVC) occlusion.\n Percutaneous endovascular stent insertion was attempted in 13 patients, age range 20-72 (mean 55.5) years, with symptomatic total occlusion of the SVC. Twelve patients had known malignant disease of the thorax. The other patient (age 20) had chronic SVC obstruction, the cause of which was unknown at the time of the procedure. There was initial angiographic assessment and removal of thrombus by thrombolysis (10 patients) and/or clot aspiration (3 patients). Following successful lysis or aspiration, single or multiple endovascular stents were inserted.\n The inability to cross the lesion with a guidewire prevented stent insertion in 2 patients (15.4%). There was primary success in the remaining 11 patients (84.6%), with associated symptomatic relief. Some recurrence of symptoms occurred in 5 of the 11 patients (45.5%) after a time interval ranging from 14 to 183 days. In all cases of symptomatic recurrence, patency was reestablished with further thrombolysis and/or further stent insertion. All successfully treated patients have since died. All 11 patients remained symptomatically free of SVC occlusion until death, with postprocedure survival ranging from 5 to 243 days.\n The percutaneous management of complete SVC occlusion with thrombolysis and/or clot aspiration followed by stent insertion is safe and effective, giving sustained symptomatic relief.", "In a randomised prospective trial of chemotherapy with and without radiotherapy in small-cell carcinoma of the bronchus, 37 of 366 patients presented with obstruction of the superior vena cava at the time of diagnosis. In the study all patients received four cycles of combination chemotherapy over a period of 12 weeks and, provided there was not progressive disease, then received either radiotherapy to the mediastinum and primary tumour followed by eight further courses of chemotherapy or eight cycles of chemotherapy alone. Of the 37 patients presenting with superior vena caval obstruction, nine had relapsed and treatment was stopped during or after the initial four cycles of chemotherapy. Of the remainder, 15 patients received radiotherapy plus chemotherapy and 13 chemotherapy alone. After four cycles of chemotherapy (12 weeks) 21 of the 37 patients had initial complete relief of symptoms secondary to superior vena caval obstruction, 10 had substantial but partial relief, and six had no relief. Twelve patients developed recurrence of superior vena caval obstruction, of whom six had received radiotherapy and four chemotherapy alone; two relapsed in the initial 12 weeks of the study. The median survival of the patients with superior vena caval obstruction allocated at diagnosis to either treatment arm was identical. The survival of patients with obstruction was similar to that of other patients in the main study. Chemotherapy is an effective treatment for superior vena caval obstruction and there appears to be no additional advantage in giving radiotherapy after 12 weeks of cyclical chemotherapy.", "Three patients with superior vena cava syndrome due to non--small-cell lung cancer were treated with chemotherapy alone. Symptomatic relief began within three days of treatment and substantial resolution of the syndrome occurred in all three patients. One patient had complete remission of tumor and the other two had more than a 50% tumor reduction within the first month of therapy. These are the first case reports indicating that combination chemotherapy may be effective as initial management of the superior vena cava syndrome due to non--small-cell lung cancer.", "To analyse results obtained in the palliative treatment of obstruction of the upper inflow veins by stent implantation in patients with bronchial carcinoma.\n Stents were implanted in 14 patients with upper venous obstruction due to bronchial carcinoma (three women, eleven men: mean age 64 [48-74] years), 4 of the superior vena cava (SVC), 6 of the SVC and brachiocephalic vein, 4 of the SVC and subclavian vein. To prevent thromboembolic phenomena all patients received heparin in therapeutic doses for 1-3 days from the time of stents implantation.\n Treatment was successful (regression of the clinical signs) in 12 of the 14 patients. Six patients died, without recurrence of the clinical signs, an average of 141 (10-420) days after the procedure. Mean survival time of the six patients who remained without symptoms was 3 months (longest interval 9 months). In one patient thrombotic occlusion of the SVC occurred 6 days after stent implantation. However, local thrombolysis successfully re-opened the vessel. Renewed upper vein obstruction occurred in two patients during follow-up. None of the stent filaments fractured and there was no stent dislocation.\n With a success rate of 86% stent implantation proved to be a sparing procedure in the palliative treatment of upper inflow vein obstruction, especially in patients with extensive malignant disease.", "Obstruction of the superior vena cava (SVC) in malignant disease can cause considerable distress to patients. Symptomatic relief can be achieved by the percutaneous implantation of a self-expanding stent (Wallstent) into the stenosis.\n Fourteen patients with obstruction of the SVC were treated with one to three Wallstent endoprostheses. They suffered from advanced bronchogenic carcinoma (n = 12), thyroid carcinoma (n = 1), and breast carcinoma (n = 1). The indication for stent placement was symptomatic obstruction of the SVC and incurable disease. Stenting was performed for symptom relief, and before, during, and after courses of radiotherapy or chemotherapy as needed.\n Twelve patients experienced complete symptomatic relief within two days of stent placement. Two patients did not benefit. Three patients not given anticoagulation developed stent thrombosis between one week and eight months after initial placement, and within one day of endobronchial stent implantation with bronchial laser therapy or balloon dilatation in all three. Patency of the SVC was achieved again by a repeat procedure.\n Stent placement for obstruction of the SVC gives rapid symptomatic relief. Subsequent endobronchial stent implantation with bronchial laser therapy or balloon dilatation could be a risk for caval stent occlusion. Stent thrombosis remains a problem in patients who are not anticoagulated.", "Superior vena cava syndrome can be effectively palliated with the use of intravascular stents. Adjunctive modalities which may be utilized prior to stent placement are thrombolytic therapy and balloon angioplasty. Six patients with an underlying malignancy were treated with these modalities. Complete resolution of symptoms occurred in five patients, and partial resolution occurred in the sixth. Two of the patients who had initial, complete resolution of symptoms had recurrences. One involved rethrombosis of the superior vena cava which occurred twice and required percutaneous thrombectomy, and the second involved restenosis requiring a percutaneous transluminal angioplasty of the SVC just distal to the stent. Both of these patients with second procedures, again, had complete resolution of symptoms. Intravascular stents are a valuable additional treatment of superior vena cava syndrome.", "Patients with small cell lung cancer (SCLC) and superior vena cava syndrome (SVCS) are widely believed to have a grave prognosis. The purpose of this study was to determine the prognosis of patients with SCLC and SVCS as compared to SCLC without SVCS.\n A retrospective analysis of 408 cases of SCLC +/- SVCS was performed. Three- hundred and sixty showed no clinical signs of SVCS and 43 (11%) had SVCS; in 5 patients no adequate information was available about clinical signs of SVCS. All patients were classified as limited disease cases. About 98% received chemotherapy usually as the first treatment followed by radiotherapy. A median total dose of 46 Gy (range 30 to 70 Gy) was given at 2.0 Gy per fraction five times weekly. A prophylactic cranial irradiation was applied if a complete remission was achieved after chemotherapy or after 30 Gy of irradiation. Kaplan-Meier survival curves are shown and comparisons were made by the log-rank and the Gehan/Wilcoxon test. To adjust for prognostic factors, a proportional hazards analysis was done.\n Patients without SVCS had 5-year survival rates ( +/- SE) and a median survival time (MST; 95% confidence intervals) of 11% +/- 2% and 13.7 months (12.7-14.5) in UICC Stage I to III; in Stage III the figures were 9% +/- 2% and 12.6 months (11.2-13.7). In comparison, SCLC with SVCS had 5-year survival rates of 15% +/- 7% and MST of 16.1 months (13.8-20.5). The difference was significant in univariate analysis (Stage II disease: p = 0.008 by the log-rank test). In a multivariate analysis of all patients, Stage (Stage I + II > III; p = 0.0003), SVCS (yes > no; p = 0.005), and Karnofsky performance status ( < or = 70 < 80-100%; p = 0.008) were of significant importance.\n SVCS is a favorable prognostic sign in SCLC. The treatment should be curatively intended.", "The treatment of a superior vena caval obstruction associated with a mediastinal mass is a true radiotherapeutic emergency. The heralding signs and symptoms and the morbidity of the syndrome justify beginning therapy before a pathologic diagnosis is established. In a series of 19 patients with superior vena cava syndrome, there was an excellent response to an initial high-dose course of irradiation, consisting of 400 rads midplane for 3 days, then reduced to conventional daily fractionation. It is concluded that rapid high-dose irradiation in the treatment of a superior vena cava syndrome is safe and effective.", "Palliative treatments for obstruction of the superior vena cava all have disadvantages. The use of a fine braided wire self expanding stent (Wallstent, Schneider (Europe) AG) in patients with malignant and benign causes of superior vena cava obstruction is reported.\n Five patients with obstruction of the superior vena cava were treated with balloon angioplasty of the stricture and the percutaneous insertion of an expandable Wallstent endoprosthesis across the site of the stricture. Four patients had advanced mediastinal malignancy previously treated by radiotherapy and one patient had fibrosing mediastinitis.\n All patients experienced rapid symptomatic relief and, in three cases, complete palliation was achieved during survival times of seven weeks, nine weeks, and 24 weeks, respectively. Two surviving patients (with a recurrent thymoma and fibrosing mediastinitis) were free of symptoms when followed up at eight and nine months respectively.\n Initial experience with the Wallstent endoprosthesis suggests that it is a valuable treatment alternative once conventional therapy has failed and gives rapid relief of symptoms to patients with obstruction of the superior vena cava.", "A 58-year-old man was hospitalized because of threatened asphyxia resulting from massive obstruction to neck vein flow and increased venous markings over the ventral and dorsal thorax. The previous year he had received radiotherapy (total of 55.8 Gy) for squamous cell carcinoma in the right upper lobe of the lung (primary stage T2 N2 M0). The signs of venous congestion had developed over several months.\n Emergency phlebography demonstrated obstruction to superior vena cava (SVC) flow by tumour compression.\n It was possible to pass the SVC obstruction with a hydrophilic guide-wire and then perform a balloon angioplasty, followed later by implantation of two intraluminal expandable stents (\"Wallstent\"). The dyspnoea quickly improved after the successful recanalization. The day after the intervention palliative radiotherapy of the SVC obstruction was begun. But increased venous markings over the thorax recurred, but without dyspnoea, after 4 1/2 months free of signs of venous congestion. Repeat phlebography again demonstrated complete obstruction of the SVC by the tumour. Recanalization by balloon angioplasty was again achieved.\n This case underlines the value of percutaneous balloon angioplasty with stent implantation as supplementary treatment in the late stages of SVC obstruction by tumour.", "We analyzed the clinical outcome of treatment with the expandable metallic stent (EMS) for the superior vena cava (SVC) syndrome associated with malignant tumors, and the results were compared with those of radiotherapy.\n Of 33 patients with the SVC syndrome, 23 were treated by Gianturco EMS placement and 10 were treated by radiotherapy and/or chemotherapy alone. Of the 23 EMS patients, 11 had treatment before EMS placement and 12 had no treatment before EMS placement.\n After stenting, the clinical symptoms disappeared in 78% (18/23) of the patients, i.e. in 50% of the patients with intraluminal tumors, and in 93% of those with extrinsic compression. The clinical symptoms improved in 80% of patients who received radiotherapy. The mean duration of survival was 145 days in patients who underwent stenting, and 146 days in those receiving radiotherapy. However, the survival period differed significantly between patients with intraluminal tumors (44.9 days) and those with extrinsic compression (198.6 days). Between patients with previous treatment and those with no previous treatment, there was no significant difference in response rate or in survival period which were 82% versus 75%, and 127 days versus 162 days, respectively.\n The clinical symptoms showed similar improvement in patients receiving EMS placement or radiotherapy. EMS placement was effective in relieving clinical symptoms in patients who had failed to respond to radiotherapy.", "The prognosis of inoperable non-small cell lung cancer (NSCLC) is poor and thoracic radiation therapy is usually the main step of the therapeutic approach. The results of a retrospective analysis of a series of 381 patients treated from 1977 to 1990 for an inoperable NSCLC are reported.\n Three hundred and twenty two men and 59 women were included into the study. Their mean age was 66 years. A squamous cell carcinoma was observed in 276 cases (72%). A superior vena cava syndrome or a Pancoast's syndrome were present in 21 and 26 patients, respectively. Fifty-two per cent of the patients had a WHO performance status > or = 2. According to the TNM classification, the tumor distribution was as follows: 11 T1, 153 T2, 175 T3, and 42 T4. The mediastinum was involved in 174 patients. All patients were treated by external radiation therapy with a total dose of 60-65 Gy. Classical fractionation of the irradiation dose was done in 217 patients and hypofractionation was used for 164 patients.\n After treatment, improvement of the superior vena and Pancoast's syndromes was observed in 90% of the patients. Radiological complete response was obtained in 177 patients (47%). The 5-year overall survival rate was 6.2%. No significant differences in survival according to the initial tumor size, the mediastinum status or the fractionation scheme were noted. The 5-year survival rate was 13% in patients with a tumor that completely responded to irradiation. Death was mainly due to local failure (231 patients, 69%) and metastatic disease (107 patients, 32%). The radiotherapy tolerance was acceptable.\n Although irradiation provides good palliation and a 10%-survival rate at 3 years, the results relating to radiation therapy were disappointing.", "A study was made of 34 patients concerning the palliation effect of radiation therapy in the treatment of superior vena cava syndrome (SVCS). They were seen between 1986-1993, at the Department of Radiotherapy in Middelheim General Hospital, Belgium, Antwerp. All patients had a syndrome of superior vena cava obstruction secondary to malignancy. The histologic diagnosis delivered an equal distribution of small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). All patients with a SCLC received chemotherapy as initial treatment, but showed no response, relapse or evolution during treatment. Each treatment began with rapid-high dose irradiation, to continue after re-evaluation with rapid high-dose in cases of poor response or with the conventional fractionation of 2 Gy daily in patients showing good relief of symptoms. The initial rapid-high dose schedules depended on the performance status of the patients. Seventy-six percent of the patients with NSCLC showed good relief of their symptoms. It was very unexpected but the majority of NSCLC patients responded more quickly than SCLC patients, within three days after initiating treatment. In SCLC, 94% of the patients responded up until death. The palliation index defined as the ratio of the symptom-free period on the total survival which is 1 in ideal circumstances, was 0.55 in NSCLC and 0.90 in SCLC. In this last group, death was mainly due to disease progression in distant sites.", "Among 225 consecutive patients with small-cell anaplastic bronchogenic carcinoma, 26 (11.5%) had superior vena caval obstruction when the malignancy was diagnosed. Of these 26 patients, a consecutive series of 22 were treated initially with combination chemotherapy (cyclophosphamide, methotrexate and CCNU, in some cases combined with vincristine) alone, and in all these cases resolution of the syndrome was prompt within a median of 7 days. In no case were symptoms increased transiently by the treatment. No difference in response rate was observed between the histologic subtypes of small-cell anaplastic bronchogenic carcinoma according to the WHO classification. Combination chemotherapy alone is an effective treatment of superior vena caval obstruction in patients with small-cell anaplastic bronchogenic carcinoma.", "Among 38 patients with bronchogenic carcinoma, small-cell type, eight patients had superior vena caval obstruction (SVCO) of recent onset. Seven of these patients were initially treated with combination chemotherapy (lomustine, cyclophosphamide, and methotrexate). One patient who had SVCO was treated initially by radiotherapy, with subsequent chemotherapy. In each patient, resolution of the syndrome was prompt, usually was complete by seven days, and was accompanied by objective tumor shrinkage. Symptoms of SVCO were transiently aggravated by the initiation of treatment in only one patient. In one individual treated by chemotherapy alone and in one treated by chemotherapy plus radiotherapy, SVCO recurred after initial control. Chemotherapy is an effective form of management of SVCO caused by small-cell carcinoma of the lung.", "A 62-year-old woman with superior vena cava obstruction (SVCO) secondary to small cell lung cancer was treated with expandable wire stents prior to chemotherapy and irradiation. The treatment resulted in immediate and complete remission of the SVCO symptoms." ]

[ "9728984", "10653329", "8979282", "11114686", "12387988", "11483802", "10755457", "15858956", "8726246", "15817866", "15361309", "20130095", "7769900", "10617701" ]

[ "Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age.", "Erythrocyte fatty acid composition in term infants fed human milk or a formula enriched with a low eicosapentanoic acid fish oil for 4 months.", "Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Ross Pediatric Lipid Study.", "A novel infant formula milk with added long-chain polyunsaturated fatty acids from single-cell sources: a study of growth, satisfaction and health.", "Long-chain polyunsaturated fatty acids and infant formula.", "Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study.", "A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants.", "Long-chain polyunsaturated fatty acids and neurological developmental outcome at 18 months in healthy term infants.", "Visual acuity and fatty acid status of term infants fed human milk and formulas with and without docosahexaenoate and arachidonate from egg yolk lecithin.", "Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo.", "Growth and development of term infants fed with milk with long-chain polyunsaturated fatty acid supplementation.", "The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid.", "Are long-chain polyunsaturated fatty acids essential nutrients in infancy?", "A critical appraisal of the role of dietary long-chain polyunsaturated fatty acids on neural indices of term infants: a randomized, controlled trial." ]

[ "Long-chain polyunsaturated fatty acids (LCPUFA) are important for normal visual and brain development. Although present in human milk, LCPUFA have until recently been absent from artificial formulas, and infants may have limited ability to synthesise LCPUFA. To determine the clinical significance of this relative deficiency of LCPUFA, we undertook a randomised trial of the relation between LCPUFA supplementation and infant cognitive behaviour.\n 44 term infants had been randomised to a formula supplemented with LCPUFA (21) or not supplemented with LCPUFA (23), which they had taken from birth to age 4 months. Infant cognitive behaviour was assessed at 10 months of age by a means-end problem-solving test--the intentional execution of a sequence of steps to achieve a goal. The problem required three intermediate steps to achieve the final goal, uncovering and retrieving a hidden toy.\n Infants who received LCPUFA-supplemented formula had significantly more intentional solutions than infants who received the no-LCPUFA formula (median 2.0 vs 0, p=0.021). Intention scores (median 14.0 vs 11.5 [maximum 18]) were also increased in this group (p=0.035).\n These findings suggest that term infants may benefit from LCPUFA supplementation, and that the effects persist beyond the period of supplementation. Since higher problem-solving scores in infancy are related to higher childhood IQ scores, supplementation with LCPUFA may be important for the development of childhood intelligence.", "When term infants are fed standard formula that does not contain long-chain polyunsaturated fatty acids (LC-PUFA), they still show lower levels of docosahexaenoic acid (DHA) in red blood cell (RBC) phospholipids by several weeks or months postnatally. This study was designed in order to evaluate a potential alternative for supplementing term infant formulas with DHA by adding a high-DHA/low-eicosapentanoic acid fish oil to levels similar to that in human milk (0.3%). A total of 37 term infants were included in the study at 3 days of life. DHA concentrations remained stable between inclusion and 4 months of life at around 8% of the RBC phospholipids in the LC-PUFA enriched formula-fed group whereas it decreased significantly in the standard formula-fed group. In the human milk-fed group, RBC DHA concentrations at 4 months of age were significantly lower than that at birth and were significantly correlated with the duration of breast feeding (r = 0.85; P = 0.0002). A significant decrease of arachidonic acid between inclusion and 4 months of age was observed in the enriched formula-fed group and reached a mean value at 4 months, which was significantly lower than that observed in the human milk or standard formula-fed groups (P<0.0001).\n Supplementing term formulas with a high-docosahexaenoic acid/low-eicosapentanoic acid fish oil up to 4 months of age is efficient in improving docosahexaenoic acid status, however it increases the risk of impaired n-6 fatty acid status.", "The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are present in human milk but not in most infant formulas. In the present study of 134 formula-fed and 63 breast-fed infants, we prospectively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance visual function, or affect growth during the first year. Healthy term infants < 7 d old were randomized to be fed formulas containing linoleic acid (approximately 10% kcal) and alpha-linolenic acid (approximately 1% kcal) plus (1) no added LCP fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%) from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil (DHA formula). A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo. Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in the breast-fed group. Infants fed the AA + DHA formula had levels of both LCP within approximately 10% of the values for infants in the breast-fed group, and infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA levels. There were no differences in growth or in visual function during this 12-mo feeding study.", "To evaluate the growth, feeding and health of babies fed a novel infant formula milk with added long chain polyunsaturated fatty acids (LCPs) produced from single-cell sources, at concentrations similar to those found in mature breast milk.\n Randomized double-blind control trial.\n One-hundred and forty healthy, full-term infants of birth weight 2.5-4.5 kg born at the Maternity Department, East Glamorgan General Hospital, Wales, whose mothers had already decided to bottle feed.\n Subjects were randomized to two groups; one (control group) to receive a standard formula milk and the other to receive the trial milk with added LCPs. Milks were supplied in a double-blind fashion and given for the first 12 weeks of life. Anthropometric measurements were made at recruitment, 3 months, 6 months and 1 y. Feeding diaries were completed at 6 weeks and 3 months, and a parental record was kept of any ill health suffered by the subjects during the first year of life.\n Of 140 infants recruited, 31 did not complete the protocol. Small but statistically significant differences were found only in the subscapular skinfold thickness at 6 weeks and 3 months, that in the trial group being slightly higher, but unlikely to be of any clinical importance. No differences were found in the feeding patterns of the infants in the two groups. Stool patterns were similar, as were the frequencies of illness and allergy.\n This study supports the view that LCPs from single-cell sources do not have detrimental effects on the growth, feeding and general health of infants.", "nan", "To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids, arachidonic acid (AA), and docosahexaenoic acid (DHA) on multiple indices of infant growth and development.\n A double-masked, randomized, parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year (N = 239). Reference groups of breastfed infants (N = 165) weaned to formulas with and without AA+DHA were also studied. Infants in the formula groups were randomized at </=9 days of age to a control formula with no AA or DHA (n = 77) or 1 of 2 otherwise identical formulas containing AA+DHA (AA, 0.46% and DHA, 0.14% of total fatty acids) from either egg-derived triglyceride (egg-DTG [n=80]) or fish oil and fungal oil (fish/fungal [n = 82]) at levels similar to the average in breast milk samples as measured in the reference group. All formulas contained 50% of energy from fat with the essential dietary fatty acids, linoleic acid (20% fatty acids) and alpha-linolenic acid (2% fatty acids). The main study outcomes were AA and DHA levels in plasma and red blood cells, and multiple measures of infant development at multiple ages from birth to 14 months: growth, visual acuity, information processing, general development, language, and temperament.\n AA and DHA levels in plasma and red cells were higher in AA+DHA-supplemented groups than in the control formula group and comparable to those in reference groups. No developmental test results distinguished these groups. Expected differences in family demographics associated with breastfeeding were found, but no advantages to breastfeeding on any of the developmental outcome demonstrated.\n These findings do not support adding AA+DHA to formulas containing 10% energy as linoleic acid and 1% energy as alpha-linolenic acid to enhance growth, visual acuity, information processing, general development, language, or temperament in healthy, term infants during the first 14 months after birth.infant development, breast feeding, infant formula, long-chain polyunsaturated fatty acids, docosahexaenoic acid.", "The effects of dietary docosahexaenoic acid (DHA) supply during infancy on later cognitive development of healthy term infants were evaluated in a randomized clinical trial of infant formula milk supplemented with 0.35% DHA or with 0.36% DHA and 0.72% arachidonic acid (AA), or control formula which provided no DHA or AA. Fifty-six 18-month-old children (26 male, 30 female) who were enrolled in the trial within the first 5 days of life and fed the assigned diet to 17 weeks of age were tested using the Bayley Scales of Infant Development, 2nd edition (BSID-II) (Bayley 1993) at the Retina Foundation of the Southwest, Dallas, TX. These children had also been assessed at 4 months and 12 months of age for blood fatty-acid composition, sweep visual evoked potential (VEP) acuity, and forced-choice preferential looking (FPL) acuity (Birch et al. 1998). Supplementation of infant formula with DHA+AA was associated with a mean increase of 7 points on the Mental Development Index (MDI) of the BSID-II. Both the cognitive and motor subscales of the MDI showed a significant developmental age advantage for DHA- and DHA+AA-supplemented groups over the control group. While a similar trend was found for the language subscale, it did not reach statistical significance. Neither the Psychomotor Development Index nor the Behavior Rating Scale of the BSID-II showed significant differences among diet groups, consistent with a specific advantage of DHA supplementation on mental development. Significant correlations between plasma and RBC-DHA at 4 months of age but not at 12 months of age and MDI at 18 months of age suggest that early dietary supply of DHA was a major dietary determinant of improved performance on the MDI.", "Previously, we found a beneficial effect of 2 mo supplementation of infant formula with long-chain polyunsaturated fatty acids (LC-PUFA) on neurological condition at 3 mo in healthy term infants. The aim of the present follow-up study was to evaluate whether the effect on neurological condition persists until 18 mo.\n A prospective, double-blind, randomized control study was conducted. Three groups were formed: a control (CF; n = 169), an LC-PUFA-supplemented (LF; n = 146) and a breastfed (BF; n = 159) group. Information on potential confounders was collected at enrolment. At the age of 18 mo, neurodevelopmental condition was assessed by the age-specific neurological examination of Hempel and the Bayley scales. The Hempel assessment resulted in a clinical neurological diagnosis, a total optimality score and a score on the fluency of motility. The Bayley scales resulted in mental and psychomotor developmental indices. Attrition at 18 mo was 5.5% and non-selective. Multivariate regression analyses were carried out to evaluate the effect of type of feeding while adjusting for confounders.\n None of the children had developed cerebral palsy and 23 (CF: n = 8; LF: n = 10; BF: n = 5) showed minor neurological dysfunction. The groups did not show statistically significant differences in clinical neurological condition, neurological optimality score, fluency score, and the psychomotor and mental development indices. Multivariate analysis confirmed that there was no effect of type of feeding on neurological condition.\n This study indicates that the beneficial neurodevelopmental effect of 2 mo LC-PUFA supplementation in healthy term infants can not be detected at the age of 18 mo.", "Preterm infants fed formulas with docosahexaenoic acid (DHA, 22:6n-3) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid. In term infants several nonrandomized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity, but the evidence for a cause-and-effect relationship is mixed. In the present study, term infants were randomly assigned to a standard term formula (n = 20) or the same formula with egg yolk lecithin to provide DHA (0.1%) and arachidonic acid (AA, 20:4n-6, 0.43%) (n = 19) at levels reported in milk of American women. A third group of infants was breast fed for > or = 3 mo (n = 19). Grating visual acuity (Teller Acuity Card procedure) and plasma and red blood cell (RBC) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) DHA and AA were determined at corrected ages of 2, 4, 6, 9 (acuity only), and 12 mo past term = 40 wk postmenstrual age (PMA). At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed standard formula. As in preterm infants, the increase was transient. Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants, but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond. Despite normal intrauterine accumulation of DHA and AA, infants fed formula with 2% linolenic acid and 0.1% DHA had better 2-mo visual acuity than infants fed formula with 2% linolenic acid.", "Several studies found a benefit of long-chain polyunsaturated fatty acid (LCP) supplementation for visual or mental development, but others found no benefit. Likely contributors to differences among studies are the amount of LCP supplementation, functional outcomes, and sample size.\n We evaluated LCP supplementation in amounts typical for human milk (based on local and worldwide surveys) in a large cohort of infants by using sweep visual evoked potential (VEP) acuity as the functional outcome.\n The study was a double-masked, randomized, controlled clinical trial in 103 term infants. By age 5 d, infants were randomly assigned to receive either formula with no docosahexaenoic acid (DHA) or arachidonic acid (ARA) or formula supplemented with DHA and ARA as 0.36% and 0.72%, respectively, of total fatty acids. Sweep VEP acuity was the primary outcome. Random dot stereoacuity, blood lipid profile, growth, and tolerance were secondary outcomes.\n VEP acuity in the LCP-supplemented group was significantly better than that in the control group at ages 6, 17, 26, and 52 wk. Stereoacuity in the LCP-supplemented group was significantly better than that in the control group at age 17 wk but not at ages 39 and 52 wk. By ages 17 and 39 wk, the red blood cell DHA concentration in the LCP-supplemented group was more than double and more than triple, respectively, that in the control group. Growth of infants fed LCP-supplemented and control formulas did not differ significantly, and both diets were well tolerated.\n LCP supplementation of term infant formula during the first year of life yields clear differences in visual function and in total red blood cell lipid composition.", "nan", "The range of human milk docosahexaenoic acid (DHA) concentrations worldwide is much broader than the range explored in randomized clinical trials to date.\n The primary objective was to determine the effect of 4 amounts of DHA supplementation on the visual acuity of formula-fed infants at 12 mo of age. Secondary objectives were to evaluate visual acuity maturation, red blood cell fatty acids, tolerance, anthropometric measures, and adverse events.\n This double-masked, randomized trial was conducted at 2 sites (Dallas and Kansas City). Three hundred forty-three healthy, term, formula-fed infants were enrolled at 1-9 d of age and were randomly assigned to be fed 1 of the following 4 infant formulas containing equivalent nutrient amounts, except for long-chain polyunsaturated fatty acids: control (0% DHA), 0.32% DHA, 0.64% DHA, or 0.96% DHA; DHA-supplemented formulas also provided 0.64% arachidonic acid. Visual acuity was measured by visual evoked potentials in 244 infants who completed the 12-mo primary outcome examination.\n Infants fed control formula had significantly poorer visual evoked potential visual acuity at 12 mo of age than did infants who received any of the DHA-supplemented formulas (P < 0.001). There were no significant differences in visual evoked potential visual acuity between the 3 amounts of DHA supplementation for either site at any age tested.\n DHA supplementation of infant formula at 0.32% of total fatty acids improves visual acuity. Higher amounts of DHA supplementation were not associated with additional improvement of visual acuity. This trial was registered at clinicaltrials.gov as NCT00753818.", "We investigated whether the disparity in neural maturation between breastfed and formula-fed term infants could be corrected by the addition of fish oil, a source of docosahexaenoic acid (DHA, 22:6 omega 3), to infant formula. Healthy, term infants were randomised at birth to receive either a supplemented or placebo formula if their mothers had chosen to bottle feed. Breastfed term infants were enrolled as a reference group. Infant erythrocyte fatty acids and anthropometry were assessed on day 5 and at 6, 16, and 30 weeks of age. Visual evoked potential (VEP) acuity was determined at 16 and 30 weeks. VEP acuities of breastfed and supplemented-formula-fed infants were better than those of placebo-formula-fed infants at both 16 and 30 weeks of age (p < 0.001 and p < 0.01). Erythrocyte DHA in breastfed and supplemented-formula-fed infants was maintained near birth levels throughout the 30-week study period but fell in placebo-formula-fed infants (p < 0.001). Erythrocyte DHA was the only fatty acid that consistently correlated with VEP acuity in all infants at both ages tested. A continuous supply of DHA may be required to achieve optimum VEP acuity since infants breastfed for short periods (< 16 weeks) had slower development of VEP than infants receiving a continuous supply of DHA from either breastmilk or supplemented formula. Erythrocyte arachidonic acid (20:4 omega 6) in supplemented-formula-fed infants was reduced below that of infants fed breastmilk or placebo formula at 16 and 30 weeks (p < 0.001), although no adverse effects were noted, with growth of all infants being similar. DHA seems to be an essential nutrient for the optimum neural maturation of term infants as assessed by VEP acuity. Whether supplementation of formula-fed infants with DHA has long-term benefits remains to be elucidated.", "To determine whether dietary long-chain polyunsaturated fatty acids (LCPUFA), such as docosahexaenoic acid (DHA) and arachidonic acid, affect visual evoked potential (VEP) acuity of formula-fed infants, relative to breastfed infants. A secondary objective was to assess the effect of LCPUFA on Bayley's mental developmental index (MDI) and psychomotor developmental index (PDI).\n Formula-fed infants were randomly allocated, in a double-blind manner, to either a placebo (no LCPUFA; n = 21), DHA supplemented (n = 23), or DHA+arachidonic acid supplemented formula (n = 24). Infants were fed their assigned formula from the first week of life until 1 year of age. A parallel reference group of breastfed infants was recruited and followed (n = 46). Infant VEP acuity was assessed at 16 and 34 weeks, and Bayley's MDI and PDI were assessed at 1 and 2 years of age.\n There were no differences among the randomized formula groups for VEP acuity at either 16 or 34 weeks of age. Breastfed infants had better VEP acuity at 34 weeks of age, but not at 16 weeks, compared with all formula-fed infants. Bayley's MDI and PDI were similar in the 3 formula-fed groups at 1 and 2 years. Breastfed infants had higher MDI scores than formula-fed infants at 2 years of age even after adjusting for environmental variables.\n LCPUFA supplementation did not influence VEP acuity development in these well-nourished, formula-fed infants." ]

[ "3551674", "8363066", "8572352" ]

[ "A prospective randomised trial comparing spinal anaesthesia using hyperbaric cinchocaine with general anaesthesia for lower limb vascular surgery.", "Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery. Perioperative Ischemia Randomized Anesthesia Trial Study Group.", "Cardiac outcome after peripheral vascular surgery. Comparison of general and regional anesthesia." ]

[ "One hundred and one patients were randomly allocated to have their peripheral vascular surgery performed under general anaesthesia (51 patients) or spinal anaesthesia (50 patients). Intraoperative haemodynamic changes were markedly different between the two groups with a higher incidence of hypotension in the spinal group (72% vs 31%) and a higher incidence of hypertension in the general anaesthesia group (22% vs 0%). Blood loss was significantly less in the spinal group (560, SD 340, ml vs 792, SD 440, ml). Postoperatively three patients from the general anaesthesia group died from causes unrelated to the anaesthesia, and one had a myocardial infarct. Two patients in the spinal group had myocardial infarcts, both had been treated for bradycardia and hypotension intraoperatively, and one died. There was a significantly higher incidence of postoperative chest infection in the general anaesthesia group (33% vs 16%). There was no significant difference between the groups in the incidence of postoperative confusion, or lower limb amputation rate or need for further surgery prior to hospital discharge.", "Perioperative morbidity may be modifiable in high risk patients by the anesthesiologist's choice of either regional or general anesthesia. This clinical trial compared outcomes between epidural (EA) and general (GA) anesthesia/analgesia regimens in a group of patients at high risk for cardiac and other morbidity who were undergoing similarly stressful surgical procedures.\n One hundred patients scheduled for elective vascular reconstruction of the lower extremities were randomized to receive either EA for surgery followed by epidural analgesia, or GA for surgery followed by intravenous patient-controlled analgesia. Hemodynamic monitoring, blood pressure, and heart rate limits were determined prior to randomization. Management of anesthesia in the immediate postoperative period was standardized. The data collected included continuous electrocardiographic monitoring from the day before surgery through the third postoperative day, serial electrocardiograms, and cardiac enzymes. Cardiac ischemia, myocardial infarction, unstable angina, and cardiac death were identified by a cardiologist blinded to the type of anesthesia received. Other major morbidity was determined at the time of hospital discharge and at 1 and 6 months after surgery.\n Eleven patients who received GA required regrafting or an embolectomy during their hospital stay, compared with two patients who received EA. This association of GA with reoperation remained significant after adjustment for baseline differences. Cardiac outcomes were similar in the two groups with respect to perioperative death (1 EA and 1 GA), death within 6 months (4 EA and 3 GA), nonfatal myocardial infarction within 7 days (2 EA and 2 GA), unstable angina (0 EA and 2 GA), and myocardial ischemia following randomization (17 EA and 23 GA). Rates of major infections in the two groups (1 EA and 2 GA), renal failure (3 EA and 3 GA), and pulmonary complications (3 EA and 7 GA) also were similar.\n Carefully conducted epidural and general anesthesia appear to be associated with comparable rates of cardiac and most other morbidity in patients undergoing lower extremity vascular surgery. However, compared with general anesthesia, epidural anesthesia is associated with a lower incidence of reoperation for inadequate tissue perfusion and, therefore, may be advantageous for this surgical population.", "Despite evidence that regional anesthesia may be associated with fewer perioperative complications than general anesthesia, most studies that have compared cardiac outcome after general or regional anesthesia alone have not shown major differences. This study examines the impact of anesthetic choice on cardiac outcome in patients undergoing peripheral vascular surgery who have a high likelihood of associated coronary artery disease.\n Four hundred twenty-three patients, between 1988 and 1991, were randomly assigned to receive general (n = 138), epidural (n = 149), or spinal anesthesia (n = 136) for femoral to distal artery bypass surgery. All patients were monitored with radial artery and pulmonary artery catheters. Postoperatively, patients were in a monitored setting for 48-72 h and had daily electrocardiograms for 4-5 days and creatine phosphokinase/isoenzymes every 8 h x 3, then daily for 4 days. Cardiac outcomes recorded were myocardial infarction, angina, and congestive heart failure.\n Baseline clinical characteristics were not different between anesthetic groups. Overall, the patient population included 86% who were diabetic, 69% with hypertension, 36% with a history of a prior myocardial infarction, and 41% with a history of smoking. Cardiovascular morbidity and overall mortality were not significantly different between groups when analyzed by either intention to treat or type of anesthesia received. In the intention to treat analysis, incidences of cardiac event or death for general, spinal, and epidural groups were 16.7%, 21.3%, and 15.4%, respectively. The absolute risk difference observed between general and all regional anesthesia groups for cardiac event or death was -1.6% (95% confidence interval -9.2%, 6.1%) This reflected a nonsignificant trend for lower risk of postoperative events with general anesthesia.\n The choice of anesthesia, when delivered as described, does not significantly influence cardiac morbidity and overall mortality in patients undergoing peripheral vascular surgery." ]

[ "11676793", "2205962", "4817683", "16136342", "9571510", "16287669", "10968529", "11374267", "8465450", "11041584" ]

[ "The effect of passive mobilisation following fractures involving the distal radius: a randomised study.", "[The importance of early exercise therapy in the treatment of Colles' fracture. A clinically controlled study].", "Role of physical therapy in recovery of function after Colles' fracture.", "A randomised clinical trial of activity-focussed physiotherapy on patients with distal radius fractures.", "The effect of low frequency, long-wave ultrasound therapy on joint mobility and rehabilitation after wrist fracture.", "Ice and pulsed electromagnetic field to reduce pain and swelling after distal radius fractures.", "Do Colles' fracture patients benefit from routine referral to physiotherapy following cast removal?", "Occupational therapy and Colles' fractures.", "[Effect of pneumatic compression in connection with ergotherapeutic treatment of Colles' fracture. A clinical controlled trial].", "The role of physiotherapy and clinical predictors of outcome after fracture of the distal radius." ]

[ "This study investigated whether passive mobilisation added to the effectiveness of an advice and exercise regimen for patients following distal radial fractures. Thirty-nine patients were randomly allocated to one of two groups. Patients in the first group received advice and exercises; patients in the second group also received a six-week course of passive mobilisation. Range of movement, function and pain were measured pre-treatment, and three and six weeks later. Significant improvements were found over time for all outcome measures. No significant differences were detected between groups for any outcomes except flexion, where the difference was not clinically important. Routine passive mobilisation does not appear to incur additional benefit over an advice and exercise regimen for this patient group.", "Forty patients participated in a study of the importance of early occupational therapy for the prognosis in stable Colles' fractures. Seventeen patients were treated by an occupational therapist 1-3 days after the injury, and the need for appliances and home-care was estimated. Twenty-three patients completed the usual treatment. Five weeks after the injury, we found significantly (p less than 0.05) better function of the hand in the 17 patients with early occupational therapy. This difference in function could not be found after 13 weeks. The rate of complications was the same in the two groups. The results indicate that contact with the occupational therapist shortly after the injury is valuable in patients with stable Colles' fractures.", "nan", "Physiotherapy is considered by some authorities to be an important aspect of management in patients following distal radius fractures. There is evidence of improvement in impairment with physiotherapy; however, there is no evidence to support early return of functional activity. Traditional physiotherapy management has focussed on improving impairment; however, there are no trials with emphasis on skill acquisition via motor re-learning principles.\n Forty-one participants with conservatively managed distal radius fractures were studied in a randomised, single-blinded, prospective trial. Two treatment options were compared: exercise and advice versus activity-focussed physiotherapy with measurement periods of 6 weeks after removal of cast and follow-up at 24 weeks.\n Participants allocated to the exercise and advice group consulted a physiotherapist an average of 0.9 (SD 0.4) times, while the participants allocated to the more intensive activity-focussed group consulted with physiotherapy a mean of 4.4 (SD 2.3) times. At both 6 and 24 weeks there were no significant differences between the groups for change in impairment (as measured by grip strength, range of motion of wrist flexion and extension and pain intensity), activity limitation and participation restriction, as measured by the Patient-Rated Wrist Evaluation (PRWE). Exercise and advice given by a physiotherapist were equally as effective as activity-focussed physiotherapy in recovery both at 6 and 24 weeks.\n The results suggest that after removal of cast from fracture of distal radius, patients may routinely require no more than a single session of advice and exercise provided by a physiotherapist.", "Thirty-eight patients with dorsally-displaced distal fractures were prospectively studied to assess the clinical effects of low frequency ultrasound treatment, started immediately after plaster removal. Nineteen of the patients represented the control group and a double-blind protocol was followed. Assessment took place on the day of plaster removal and 2 and 8 weeks later. There was no significant difference in wrist motion and duration of follow-up between the treated and control patients.", "To examine the relative effectiveness of ice therapy and/or pulsed electromagnetic field in reducing pain and swelling after the immobilization period following a distal radius fracture.\n A total of 83 subjects were randomly allocated to receive 30 minutes of either ice plus pulsed electromagnetic field (group A); ice plus sham pulsed electromagnetic field (group B); pulsed electromagnetic field alone (group C), or sham pulsed electromagnetic field treatment for 5 consecutive days (group D). All subjects received a standard home exercise programme. A visual analogue scale was used for recording pain; volumetric displacement for measuring the swelling of the forearm; and a hand-held goniometer for measuring the range of wrist motions before treatment on days 1, 3 and 5.\n At day 5, a significantly greater cumulative reduction in the visual analogue scores as well as ulnar deviation range of motion was found in group A than the other 3 groups. For volumetric measurement and pronation, participants in group A performed better than subjects in group D but not those in group B.\n The addition of pulsed electromagnetic field to ice therapy produces better overall treatment outcomes than ice alone, or pulsed electromagnetic field alone in pain reduction and range of joint motion in ulnar deviation and flexion for a distal radius fracture after an immobilization period of 6 weeks.", "Colles' fracture patients who received physiotherapy immediately following cast removal were compared with patients who received no active therapy following cast removal in a prospective randomised study. Patients who attended physiotherapy achieved significantly greater increases in wrist extension and grip strength after 6 weeks compared to patients who received no active therapy.", "In this randomized trial, we enrolled 30 patients treated for a distal radius Colles' type fracture. The fractures were reduced if necessary and fixed in a below-elbow plaster cast for 5 weeks. One group consisting of 14 patients received instructions for shoulder; elbow and finger exercise and the other group consisting of 16 patients had occupational therapy. At 5 weeks, 3 and 9 months we measured the functional scores. There were no statistically significant differences between the groups at any time. It seems that for non-surgically treated patients with a distal radius fracture only instructions are necessary.", "We followed forty women with functional deficits in the wrist and hand after sustaining a Colles' fracture. The women participated in occupational therapy three times a week for three weeks. At the initial evaluation, after three weeks, and at a three month evaluation, we measured the following: range of joint movement, grip strength, hand volume (oedema), pain and ADL. There was significant improvement in most of the parameters measured after three weeks of occupational therapy, with a less significant improvement from three weeks to three months. Seventeen of the forty women received twenty minutes of intermittent pneumatic compression before occupational therapy. These patients showed significant improvement in wrist extension, compared with the control group of twenty-three patients. Occupational therapy is recommended for patients showing a functional deficit after Colles' fracture. Intermittent pneumatic compression is recommended as a supplement to occupational therapy.", "The capacity for physiotherapy to improve the outcome after fracture of the distal radius is unproven. We carried out a randomised controlled trial on 96 patients, comparing conventional physiotherapy with a regime of home exercises. The function of the upper limb was assessed at the time of removal of the plaster cast and at three and six months after injury. Factors which may predict poor outcome in these patients were sought. Grip strength and hand function did not significantly differ between the two groups. Flexion and extension of the wrist were the only movements to improve with physiotherapy at six months (p = 0.001). Predictors of poor functional outcome were malunion and impaired function before the fracture. These patients presented with pain, decreased rotation of the forearm and low functional scores at six weeks. Our study has shown that home exercises are adequate rehabilitation after uncomplicated fracture of the distal radius, and routine referral for a course of physiotherapy should be discouraged. The role of physiotherapy in patients at high risk of a poor outcome requires further investigation." ]

[ "17458595", "15166961", "17882491", "16702517", "20859701", "19075173", "12734081", "18688683", "19858704", "18025338", "19382045", "18972167", "20148084", "14515293", "18438208", "22066097", "18789428" ]

[ "Rates and patterns of recurrence for percutaneous radiofrequency ablation and open wedge resection for solitary colorectal liver metastasis.", "Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases.", "Radiofrequency ablation for metachronous liver metastasis from colorectal cancer after curative surgery.", "Solitary colorectal liver metastasis: resection determines outcome.", "Hepatectomy is superior to thermal ablation for patients with a solitary colorectal liver metastasis.", "Colorectal liver metastases: recurrence and survival following hepatic resection, radiofrequency ablation, and combined resection-radiofrequency ablation.", "Feasibility of adjuvant hepatic arterial infusion of chemotherapy after radiofrequency ablation with or without resection in patients with hepatic metastases from colorectal cancer.", "Resection versus laparoscopic radiofrequency thermal ablation of solitary colorectal liver metastasis.", "Radiofrequency ablation as first-line treatment in patients with early colorectal liver metastases amenable to surgery.", "Role of intraoperative thermoablation combined with resection in the treatment of hepatic metastasis from colorectal cancer.", "[Radiofrequency ablation of colorectal liver metastases].", "Radiofrequency ablation vs. resection for hepatic colorectal metastasis: therapeutically equivalent?", "Long-term outcomes following hepatic resection and radiofrequency ablation of colorectal liver metastases.", "Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastases.", "Clinical outcomes of hepatic resection and radiofrequency ablation in patients with solitary colorectal liver metastasis.", "Comparative analysis of radiofrequency ablation and surgical resection for colorectal liver metastases.", "Comparative study of resection and radiofrequency ablation in the treatment of solitary colorectal liver metastases." ]

[ "The purpose of this study was to compare rates and patterns of disease progression following percutaneous, image-guided radiofrequency ablation (RFA) and nonanatomic wedge resection for solitary colorectal liver metastases.\n We identified 30 patients who underwent nonanatomic wedge resection for solitary liver metastases and 22 patients who underwent percutaneous RFA because of prior major hepatectomy (50%), major medical comorbidities (41%), or relative unresectability (9%). Serial imaging studies were retrospectively reviewed for evidence of local tumor progression.\n Patients in the RFA group were more likely to have undergone prior liver resection, to have a disease-free interval greater than 1 year, and to have had an abnormal carcinoembryonic antigen (CEA) level before treatment. Two-year local tumor progression-free survival (PFS) was 88% in the Wedge group and 41% in the RFA group. Two patients in the RFA group underwent re-ablation, and two patients underwent resection to improve the 2-year local tumor disease-free survival to 55%. Approximately 30% of patients in each group presented with distant metastasis as a component of their first recurrence. Median overall survival from the time of resection was 80 months in the Wedge group vs 31 months in the RFA group. However, overall survival from the time of treatment of the colorectal primary was not significantly different between the two groups.\n Local tumor progression is common after percutaneous RFA. Surgical resection remains the gold standard treatment for patients who are candidates for resection. For patients who are poor candidates for resection, RFA may help to manage local disease, but close follow-up and retreatment are necessary to achieve optimal results.", "To examine recurrence and survival rates for patients treated with hepatic resection only, radiofrequency ablation (RFA) plus resection or RFA only for colorectal liver metastases.\n Thermal destruction techniques, particularly RFA, have been rapidly accepted into surgical practice in the last 5 years. Long-term survival data following treatment of colorectal liver metastasis using RFA with or without hepatic resection are lacking.\n Data from 358 consecutive patients with colorectal liver metastases treated for cure with hepatic resection +/- RFA and 70 patients found at laparotomy to have liver-only disease but not to be candidates for potentially curative treatment were compared (1992-2002).\n Of 418 patients treated, 190 (45%) underwent resection only, 101 RFA + resection (24%), 57 RFA only (14%), and 70 laparotomy with biopsy only or arterial infusion pump placement (\"chemotherapy only,\" 17%). RFA was used in operative candidates who could not undergo complete resection of disease. Overall recurrence was most common after RFA (84% vs. 64% RFA + resection vs. 52% resection only, P < 0.001). Liver-only recurrence after RFA was fourfold the rate after resection (44% vs. 11% of patients, P < 0.001), and true local recurrence was most common after RFA (9% of patients vs. 5% RFA + resection vs. 2% resection only, P = 0.02). Overall survival rate was highest after resection (58% at 5 years); 4-year survival after resection, RFA + resection and RFA only were 65%, 36%, and 22%, respectively (P < 0.0001). Survival for \"unresectable\" patients treated with RFA + resection or RFA only was greater than chemotherapy only (P = 0.0017).\n Hepatic resection is the treatment of choice for colorectal liver metastases. RFA alone or in combination with resection for unresectable patients does not provide survival comparable to resection, and provides survival only slightly superior to nonsurgical treatment.", "We compared outcomes of surgery and radiofrequency thermal ablation (RFA) in patients with metachronous liver metastases.\n Between October 1995 and December 2005, 59 patients underwent hepatic resection and 30 underwent RFA for metachronous liver metastases. Patients with extra-hepatic metastases, those who underwent both types of treatment, and those with synchronous hepatic metastasis were excluded.\n The two groups had similar mean age, sex ratio, comorbid medical conditions, primary disease stage, and frequency of solitary metastases. Preoperative mean serum carcinoembryonic antigen (CEA) level was significantly higher in the RFA group (13.4 ng/mL vs. 7.7 ng/mL; p = 0.02). Mean diameter of hepatic metastases was significantly greater in the resection than in the RFA group (3.1 cm vs. 2.0 cm; p = 0.001). Recurrence after treatment of metastasis was observed in 18 of 30 (60.0%) RFA and 33 of 59 (56%) resection patients. Local recurrence at the RFA site was observed in 7 of 30 (23%) patients. Time to recurrence (15 vs. 8 months, p = 0.02) and overall survival (56 vs. 36 months, p = 0.005) were significantly longer in the resection than in the RFA group. In the 69 patients with solitary metastases of diameter </=3 cm, time to recurrence (p = 0.004) and overall survival were significantly greater in the resection group.\n Compared with hepatic resection, RFA for metachronous hepatic metastases from colorectal cancer was associated with higher local recurrence and shorter recurrence-free and overall survival rates, even in patients with solitary, small (</=3 cm) lesions.", "Hepatic resection (HR) and radiofrequency ablation (RFA) have been proposed as equivalent treatments for colorectal liver metastasis.\n Recurrence patterns after HR and RFA for solitary liver metastasis are similar.\n Analysis of a prospective database at a tertiary care center with systematic review of follow-up imaging in all of the patients.\n Patients with solitary liver metastasis as the first site of metastasis treated for cure by HR or RFA were studied (patients received no prior liver-directed therapy). Prognostic factors, recurrence patterns, and survival rates were analyzed.\n Of the 180 patients who were studied, 150 underwent HR and 30 underwent RFA. Radiofrequency ablation was used when resection would leave an inadequate liver remnant (20 patients) or comorbidity precluded safe HR (10 patients). Tumor size and treatment determined recurrence and survival. The local recurrence (LR) rate was markedly lower after HR (5%) than after RFA (37%) (P<.001). Treatment by HR was associated with longer 5-year survival rates than RFA, including LR-free (92% vs 60%, respectively; P<.001), disease-free (50% vs 0%, respectively; P = .001), and overall (71% vs 27%, respectively; P<.001) survival rates. In the subset with tumors 3 cm or larger (n = 79), LR occurred more frequently following RFA (31%) than after HR (3%) (P = .001), with a 5-year LR-free survival rate of 66% after RFA vs 97% after HR (P<.001). Patients with small tumors experienced longer 5-year overall survival rates after HR (72%) as compared with RFA (18%) (P = .006).\n The survival rate following HR of solitary colorectal liver metastasis exceeds 70% at 5 years. Radiofrequency ablation for solitary metastasis is associated with a markedly higher LR rate and shorter recurrence-free and overall survival rates compared with HR, even when small lesions (< or = 3 cm) are considered. Every method should be considered to achieve resection of solitary colorectal liver metastasis, including referral to a specialty center, extended hepatectomy, and chemotherapy.", "Hepatic resection is the mainstay of treatment for solitary colorectal liver metastases (mCRC); however, some patients are not ideal candidates. The aim of this study was to compare outcomes for patients with solitary mCRC who underwent resection or ablation.\n A retrospective review of a hepatobiliary database identified patients with solitary mCRC. Patients who were treated with hepatectomy were compared to patients who underwent thermal ablation.\n The median follow-up time was 25.9 months. Ninety-four patients (67.1%) underwent resection whereas 46 patients (32.8%) underwent ablation. Of the resected patients, most (60%) required a major hepatectomy. Tumor ablation was a significant predictor of overall survival (p = 0.002, OR 3.75, 95% CI 1.696-8.284). Overall, the median disease-free survival was 55.2 months for patients undergoing resection vs. 42.6 months for ablated patients (p = 0.073). Median overall survival was 112.7 months for patients undergoing resection vs. 50.2 months for patients undergoing ablation (p = 0.005).\n Patients with solitary hepatic colorectal cancer metastases should be considered for hepatic resection as this provides superior survival when compared to thermal ablation.", "Although radiofrequency ablation (RFA) is increasingly an accepted option for patients with colorectal liver metastases, patients treated with resection vs RFA may have different tumor biology profiles, which might confound the relationship between choice of liver-directed therapy and outcome.\n Retrospective review of a prospectively collected database.\n Major hepatobiliary center.\n Between January 1, 1999, and August 30, 2006, 258 patients with colorectal liver metastases underwent hepatic resection with or without RFA.\n Evaluation of outcome following resection alone, combined resection-RFA, and RFA alone using 3 statistical methods (paired-match control, Cox proportional hazards multivariate model, and propensity index) to identify and adjust for potential confounding variables.\n The median number of hepatic lesions was 2, and the median size of the largest lesion was 3.0 cm. One hundred ninety-two patients (74.4%) underwent resection alone, 55 patients (21.3%) underwent resection-RFA, and 11 patients (4.3%) underwent RFA alone. Patients who underwent resection-RFA had significantly increased risk of extrahepatic failure at 1 year vs patients who underwent resection alone or RFA alone (P < .05). On matched control and multivariate analyses, patients who underwent RFA with or without resection had significantly worse disease-free and overall survival than patients who underwent resection alone. Propensity score methods revealed that the aggregate distribution of clinical risk factors for resection-RFA was markedly different from that for resection alone. This suggested a lack of comparability to allow for statistical comparisons in the assessment of causal inferences regarding the efficacy of RFA therapy.\n Although results of matched control and multivariate analyses suggested that RFA with or without resection was associated with worse outcome, propensity score methods revealed that the resection-RFA and resection-alone groups were different with regard to baseline tumor and treatment-related factors, making causal inferences about the efficacy of RFA unreliable.", "The safety of combined hepatic artery infusion chemotherapy (HAI) and radiofrequency ablation (RFA) for liver metastases has not been assessed. We conducted a study to determine the feasibility of using HAI after RFA for colorectal cancer (CRC) liver metastases.\n Between 1996 and 2001, patients with hepatic metastases from CRC were enrolled onto a prospective study of RFA plus HAI consisting of continuous-infusion floxuridine and bolus fluorouracil. Surgical complications, treatment-related toxicities, and patient outcomes were recorded.\n Fifty patients were treated with RFA and HAI with or without resection. A median of two lesions per patient, with a median greatest diameter of 2.0 cm, were treated with RFA. Postoperative complications, including 1 death, occurred in 11 of 50 patients. Toxicity from HAI was relatively mild. At 20 months' median follow-up, 32% of patients remained disease free. Ten percent of patients had recurrences at the site of RFA, 30% developed new liver metastases, and 48% developed extrahepatic disease.\n RFA of CRC liver metastases followed by HAI is feasible and is associated with acceptable complication and toxicity rates. The high rate of disease recurrence in our patients indicates that novel combinations of regional and systemic therapies are needed to improve patient outcomes.", "There is scant data in the literature regarding radiofrequency thermal ablation (RFA) versus resection of colorectal liver metastases. The aim of this study is to compare the clinical profile and survival of patients with solitary colorectal liver metastasis undergoing resection versus laparoscopic RFA.\n Between 1996 and 2007, 158 patients underwent RFA (n = 68) and open liver resection (n = 90) of solitary liver metastasis from colorectal cancer. Patients were evaluated in a multidisciplinary fashion and allocated to a treatment type. Data were collected prospectively for the RFA patients and retrospectively for the resection patients.\n Although the groups were matched for age, gender, chemotherapy exposure and tumor size, RFA patients tended to have a higher ASA score and presence of extra-hepatic disease (EHD) at the time of treatment. The main indication for referral to RFA included technical reasons (n = 25), patient comorbidities (n = 24), extra-hepatic disease (n = 10) and patient decision (n = 9). There were no peri-operative mortalities in either group. The complication rate was 2.9% (n = 2) for RFA and 31.1% (n = 28) for resection. The overall Kaplan-Meier median actuarial survival from the date of surgery was 24 months for RFA patients with EHD, 34 months for RFA patients without EHD and 57 months for resection patients (p < 0.0001). The 5-year actual survival was 30% for RFA patients and 40% for resection patients (p = 0.35).\n This study shows that, although patients in both groups had a solitary liver metastasis, other factors including medical comorbidities, technically challenging tumor locations and extra-hepatic disease were different, prompting selection of therapy. With a simultaneous ablation program, higher risk patients have been channeled to RFA, leaving a highly selected group of patients for resection with a very favorable survival. RFA still achieved long-term survival in patients who were otherwise not candidates for resection.", "Aiming at avoidance of futile surgery, we have tested whether radiofrequency ablation (RFA) may be used as first-line treatment in patients with colorectal metastases (CRLM) occurring within the first year after colorectal surgery.\n Surgical resection is the standard treatment in patients with CRLM. Major retrospective analyses have identified the interval between colorectal surgery and the occurrence of CRLM to be of prognostic importance. So far, it is unknown whether survival of the respective patients is hampered if RFA is used as first-line treatment.\n According to a clinical pathway, we have treated patients with CRLM detected within the first year after colorectal surgery preferentially by RFA (n=28). Resection (n=82) was performed in patients who were deemed not amenable to RFA due to number, size, or location of metastatic lesions. The diameter of lesions differed between the groups. All other characteristics of patients and lesions were comparable. Local recurrence and new hepatic lesions were treated with repeated RFA or surgery whenever possible.\n Local recurrence at the site of ablation or resection occurred in 32% and 4% (P<0.001), new metastases apart from the site of previous treatment in 50% and 34% (P=0.179), and systemic recurrence in 32% and 37% (P=0.820) of the patients after RFA and surgery, respectively. Time to progression was significantly shorter in patients primarily treated with RFA (203 vs. 416 days; P=0.017). After primary treatment, 9 RFA patients and 8 surgery patients were amenable to repeated RFA or repeated surgery resulting in identical rates of disease-free patients and identical 3-year overall survival in both treatment groups: 67% and 60%, respectively; P=0.93.\n Despite striking differences in local tumor recurrence and shorter time to progression, survival in patients with early CRLM does not depend on the mode of primary hepatic treatment.", "Thermoablation, either cryosurgical ablation (CSA) or radiofrequency ablation (RFA), combined with resection is effective in the treatment of extensive bilobar colorectal metastasis.\n Retrospective analysis of a prospective hepatobiliary surgical database.\n Tertiary care referral center.\n Consecutive patients with colorectal hepatic metastases selected for surgical treatment.\n All patients underwent hepatic resection combined with CSA or RFA.\n Local recurrence rates at ablation sites, overall survival, disease-free survival, and hepatic disease-free survival.\n Between January 1, 1998, and December 31, 2003, 665 patients with colorectal metastases underwent hepatic resection. Of these, 39 (5.9%) had additional intraoperative thermoablative procedures (19 RFA, 20 CSA). There was 1 (3%) postoperative death not directly associated with the ablation, and the total morbidity rate was 41% (16 of 39). No RFA-related complication occurred; however, 3 patients developed an abscess at cryoablation sites. Actuarial 3-year survival was 47% for the entire group, with a median follow-up of 21.1 months (range, 0.5-71.4 months). The median disease-free survival was 12.3 months (range, 8.4-16.2 months). Overall, the local in situ recurrence rate according to number of ablated tumors was 14% for RFA and 12% for CSA. Tumor size correlated directly with recurrence (P = .02) in RFA-treated lesions.\n Ablation combined with hepatic resection is rarely necessary or applicable. However, in selected patients whose tumors were otherwise unresectable, additional use of ablation allows effective clearance of disease. In these patients with extensive bilobar disease, recurrence rates are high, but long-term survival is encouraging and may be improved with aggressive postoperative chemotherapy.", "Liver resection is the preferred treatment for colorectal liver metastases. About 30 to 40 % of the patients survive for five years after radical resection of liver metastases. In contrast to that, patients who are not fit enough for radical resection of metastases and two are treated by chemotherapy survive only for 18 months on average. The survival of patients with non-resectable liver metastases can be improved by metastases destruction and subsequent chemotherapy. At present, radiofrequency ablation (RFA) is widely used for the destruction of liver tumours.\n In the four-year period (2000-2003), 190 patients with liver metastases of colorectal carcinoma have been operated upon at the 2 (nd) Surgical Department of University Hospital in Olomouc. Radical resection of metastases was carried out in 136 patients (71.5 %), RFA combined with liver resection was performed in 23 patients (12 %) and exclusive RFA of metastases was indicated in 31 patients (16 %). The patients were evaluated for the disease-free survival after one year and the survival rates at 12, 24 and 36 months after operation were determined.\n 12 months after the operation no tumour progression was found in 115 patients (85 %) subjected to radical resection of liver metastases, in 16 patients (52 %) after sole RFA of metastases and in 15 individuals (65 %) who underwent liver metastasis resection combined with RFA of the remaining cancer foci. The survival of patients after 12, 24 and 36 months was 124 / 136 (91 %) 103 / 136 (76 %) and 79 / 136 (58 %) in the group of radical metastasis resection; after sole RFA of the metastases and subsequent chemotherapy, the survival at 12, 24 and 36 months amounted to 27 / 31 (87 %), 19 / 31 (61 %) and 8 / 31 (26 %) of the patients; in the group undergoing metastases resection combined with RFA and adjuvant chemotherapy patient survival at 12, 24 and 36 months was as follows: 19 / 23 (83 %), 13 / 23 (57 %), and 7 / 23 (30 %).\n RFA combined with adjuvant chemotherapy considerably extends the survival of patients with liver metastases of colorectal carcinoma compared to chemotherapy alone. However, no difference in survival was found between our patients subjected to RFA of metastases and adjuvant chemotherapy and those patients undergoing resection of liver metastases combined with RFA of unresectable metastases and subsequent chemotherapy.", "The role of ablation for hepatic colorectal metastases (HCM) continues to evolve as ablation technology changes and systemic chemotherapy improves. Our aim was to evaluate the therapeutic efficacy of radiofrequency ablation (RFA) of HCM compared to surgical resection.\n A retrospective review of our 1,105 patient prospective hepatic database from August 1995 to July 2007 identified 192 patients with only hepatic resection or only ablation for HCM.\n Patients who underwent RFA were similar to resection patients based on a similar Fong score (1.8 vs. 2.1 p = 0.28), presence of extrahepatic disease (15% vs. 9% p = 0.19), mean number of hepatic lesions (2.8 vs. 2.1 p = 0.14), and prior chemotherapy (67% vs. 60% p = 0.33). Median time to recurrence was shorter with ablation than resection (12.2 vs. 31.1 months; p < 0.001). Recurrence at the ablation-resection site was more common with ablation than resection occurring 17% vs. 2% (p < or = 0.001) of the time, respectively. Distant recurrence in the liver was also more common with ablation occurring in 33% of patients vs. 14% for resection (p = 0.002).\n Surgical resection is associated with a lower chance of recurrence and a longer disease-free interval than RFA and should remain the treatment of choice in resectable HCM.", "Recently some have called for randomized controlled trials comparing RFA to hepatic resection, particularly for patients with only a few small metastases. The objectives were to compare local recurrence and survival following RFA and hepatic resection for colorectal liver metastases. This was a retrospective review of open RFA and hepatic resection for colorectal liver metastases between January 1998 and May 2007. All patients who had RFA were considered to have unresectable disease. 58 patients had hepatic resection and 43 had RFA. A 5-year survival after resection was 43% compared to 23% after RFA. For patients with solitary lesions, a 5-year survival was 48% after resection and 15% after RFA. Sixty percent of patients suffered local recurrences after RFA compared to 7% after hepatic resection. RFA is inferior to resection. The results observed in this study support the consensus that RFA cannot be considered an equivalent procedure to hepatic resection.", "Liver resection is the treatment of choice for patients with solitary colorectal liver metastases. In recent years, however, radiofrequency ablation has been used increasingly in the treatment of colorectal liver metastases. In the absence of randomized clinical trials, this study aimed to compare outcome in patients with solitary colorectal liver metastases treated by surgery or by radiofrequency ablation.\n Solitary colorectal liver metastases were treated by radiofrequency destruction in 25 patients. The indications were extrahepatic disease in seven, vessel contiguity in nine and co-morbidity in nine patients. Outcome was compared with that of 20 patients who were treated by liver resection for solitary metastases and had no evidence of extrahepatic disease. Most patients in both groups also received systemic chemotherapy.\n Median survival after liver resection was 41 (range 0-97) months with a 3-year survival rate of 55.4 per cent. There was one postoperative death and morbidity was minimal. Median survival after radiofrequency ablation was 37 (range 9-67) months with a 3-year survival rate of 52.6 per cent.\n Survival after resection and radiofrequency ablation of solitary colorectal liver metastases was comparable. The latter is less invasive and requires either an overnight stay or day-case facilities only.\n Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "The role of the radiofrequency ablation (RFA) in treatment of solitary liver metastasis has not been established yet. Both hepatic resection (HR) and RFA have been used increasingly in the treatment of colorectal liver metastases.\n A systemic review was performed to determine the impact of treatment modality of solitary liver metastasis on recurrence patterns, disease-free survival, and overall survival (OS) rates.\n Solitary liver metastases were treated by HR in 116 patients (75.8%) and 37 patients (24.2%) were treated with RFA. Prognostic factors, recurrence rate, recurrence patterns, and survival rates were analyzed. The cumulative 3-year and 5-year local recurrence free survival rates were markedly higher in the HR group (88.0% and 84.6%) as compared with those in the RFA group [53.3% and 42.6%, respectively (P</=0.001)]. The 5-year OS rate was lower in the RFA group as compared with the HR group without statistical significance (5-year OS, 65.7% in the HR, 48.5% in the RFA group, P=0.227).\n Despite of higher local recurrence rate, RFA may be considered as a therapeutic option for patients who are considered unsuitable for conventional surgical treatment. Randomized prospective controlled trials comparing the therapeutic outcome of RFA and HR are definitely warranted.", "To evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection for the treatment of colorectal liver metastasis (CRLM).\n Between 1996 and 2008, 177 patients underwent RFA, 278 underwent hepatic resection and 27 underwent combination therapy for CRLM. Comparative analysis of clinical outcomes was performed including number of liver metastases, tumor size, and time of CRLM.\n Based on multivariate analysis, overall survival (OS) correlated with the number of liver metastases and the use of combined chemotherapy (P < 0.001, respectively). Disease-free survival (DFS) also correlated with the number of liver metastases (P < 0.001). In the 226 patients with solitary CRLM < 3 cm, OS and DFS rates did not differ between the RFA group and the resection group (P = 0.962 and P = 0.980). In the 70 patients with solitary CRLM ≥ 3 cm, DFS was significantly lower in the RFA group as compared with the resection group (P = 0.015).\n The results indicate that RFA may be a safe alternative treatment for solitary CRLM less than 3 cm, with outcomes equivalent to those achieved with hepatic resection. A randomized controlled study comparing RFA and resection for patients with single small metastasis would help to determine the most efficient treatment modalities for CRLM.", "We compared outcomes in patients with solitary colorectal liver metastases treated by either hepatic resection (HR) or radiofrequency ablation (RFA).\n A retrospective analysis from a prospective database was performed on 67 consecutive patients with solitary colorectal liver metastases treated by either HR or RFA.\n Forty-two patients underwent HR and 25 patients underwent RFA. The 5-year overall and local recurrence-free survival rates after HR (50.1% and 89.7%, respectively) were higher than after RFA (25.5% and 69.7%, respectively) (P = .0263 and .028, respectively). In small tumors less than 3 cm (n = 38), the 5-year survival rates between HR and RFA were similar, including overall (56.1% vs 55.4%, P = .451) and local recurrence-free (95.7% vs 85.6%, P = .304) survival rates. On multivariate analysis, tumor size, metastases treatment, and primary node status were significant prognostic factors.\n HR had better outcomes than RFA for recurrence and survival after treatment of solitary colorectal liver metastases. However, in tumors smaller than 3 cm, RFA can be recommended as an alternative treatment to patients who are not candidates for surgery because the liver metastases is poorly located anatomically, the functional hepatic reserve after a resection would be insufficient, the patient's comorbidity inhibits a major surgery, or extrahepatic metastases are present." ]