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[ "11013281", "19127261" ]

[ "Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group.", "A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer." ]

[ "Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation.\n In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain.\n One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087).\n Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.", "Brain metastases represent an important cause of morbidity in patients with lung cancer and are associated with a mean survival of less than 6 months. Thus, new regimens improving the outcome of these patients are urgently needed. On the basis of promising data raised in a phase I/II trial, we initiated an open, randomised, prospective, multicentric phase III trial, comparing whole brain radiation therapy (WBRT; 20 x 2 Gy) alone with WBRT+topotecan (RCT; 0.4 mg m(-2) day(-1) x 20). A total of 320 patients with CNS-metastases due to SCLC or NSCLC were projected. The primary end point was overall survival, whereas second end points were local response and progression-free survival. However, until the cutoff date of study completion (i.e., a study duration of 34 months), only a total of 96 (RCT:47, WBRT:49) patients had been recruited, and so an analysis was performed at that time point. Although the numbers of grade 3/4 non-haematological toxicities (besides alopecia 115 (RCT/WBRT: 55 out of 60) were evenly distributed, the 25 haematological events occurred mainly in the combined treatment arm (24 out of 1). Local response, evaluated 2 weeks after treatment, was assessable in 44 (RCT/WBRT: 23 out of 21) patients, showing CR in eight (3 out of 5), PR in 17 (11 out of 6), SD in 14 (8 out of 6) and PD in five (1 out of 4) patients (all differences n.s.). Neither OAS (RCT/WBRT: median (days)): 87 out of 95, range 3-752/4-433; HR 1.32; 95% CI (0.83; 2.10)) nor PFS (median (days)): 71 out of 66, range, 3-399/4-228; HR 1.28, 95% CI (0.73; 2.43) differed significantly. On the basis of these results and the slow recruitment, a continuation of the study did not seem reasonable. The available data show no significant advantage for concurrent radiochemotherapy for patients with lung cancer; however, the recruited number of patients is too low to exhibit a small advantage of combined treatment." ]

[ "10407930", "19525241", "453340", "16075781", "16558388", "2489863" ]

[ "The effects of preexercise stretching on muscular soreness, tenderness and force loss following heavy eccentric exercise.", "A pragmatic randomised trial of stretching before and after physical activity to prevent injury and soreness.", "Effect of electromyographic feedback and static stretching on artificially induced muscle soreness.", "Effects of immediate post-game recovery procedures on muscle soreness, power and flexiblity levels over the next 48 hours.", "Various treatment techniques on signs and symptoms of delayed onset muscle soreness.", "The effects of static stretching and warm-up on prevention of delayed-onset muscle soreness." ]

[ "The present study sought to investigate the effects of preexercise stretching on delayed onset muscle soreness (DOMS), i.e. soreness, tenderness and loss of muscle force, that usually occurs after strenuous or unaccustomed eccentric exercise. Ten female volunteers performed 10 sets of 10 maximal isokinetic eccentric contractions for knee flexion with both legs after a 5-min ergometer cycling warm-up. Prior to the exercise for one leg, randomly chosen, 4 x 20 s of static stretching for the hamstring muscle group was implemented. Rated soreness, tenderness on algometer pressure and loss of maximal eccentric contractile force was evaluated preexercise and 24, 48 and 96 h postexercise. The exercise bout produced severe DOMS, with parameters peaking and troughing at 48 h postexercise. However, no significant differences were found, regarding any of the parameters, when comparing stretched and nonstretched legs. The present study thus suggests that preexercise static stretching has no preventive effect on the muscular soreness, tenderness and force loss that follows heavy eccentric exercise.", "To determine the effects of stretching before and after physical activity on risks of injury and soreness in a community population.\n Internet-based pragmatic randomised trial conducted between January 2008 and January 2009.\n International.\n A total of 2377 adults who regularly participated in physical activity.\n Participants in the stretch group were asked to perform 30 s static stretches of seven lower limb and trunk muscle groups before and after physical activity for 12 weeks. Participants in the control group were asked not to stretch.\n Participants provided weekly on-line reports of outcomes over 12 weeks. Primary outcomes were any injury to the lower limb or back, and bothersome soreness of the legs, buttocks or back. Injury to muscles, ligaments and tendons was a secondary outcome.\n Stretching did not produce clinically important or statistically significant reductions in all-injury risk (HR=0.97, 95% CI 0.84 to 1.13), but did reduce the risk of experiencing bothersome soreness (mean risk of bothersome soreness in a week was 24.6% in the stretch group and 32.3% in the control group; OR=0.69, 95% CI 0.59 to 0.82). Stretching reduced the risk of injuries to muscles, ligaments and tendons (incidence rate of 0.66 injuries per person-year in the stretch group and 0.88 injuries per person-year in the control group; HR=0.75, 95% CI 0.59 to 0.96).\n Stretching before and after physical activity does not appreciably reduce all-injury risk but probably reduces the risk of some injuries, and does reduce the risk of bothersome soreness.\n anzctr.org.au 12608000044325.", "Thirty-six male subjects aged 18 to 26 years were assigned at random to one of three treatment groups: biofeedback, static stretch, and control. Muscle soreness was produced in all subjects by an 80% maximal eccentric contraction of the biceps brachii. The subjects in the biofeedback group applied auditory electromyographic (EMG) feedback at 6, 25, 30, 49, and 54 hours after the exercise, and the stretch group applied static stretch to the exercised arm at the same time periods. Observations of EMG activity and perceived pain level were made immediately before and after exercise, and at 24, 48, and 72 hours following exercise. When compared with a control group, both auditory biofeedback and static stretching significantly reduced EMG muscle activity but had no significant effect on perceived pain. The EMG activity and perceived pain of the subjects in each treatment group significantly differed across observations.", "This study investigated whether or not immediate post-game recovery procedures could enhance the rate of recovery in Australian football players in the first 48 hr after a game. Control, stretch, pool walking and hot/cold recoveries were trialled. Typical next day recovery training (25 min of pool exercise) was also performed after each game. Muscle soreness ratings and measures of flexibility (sit and reach) and power (6-s cycling sprint and vertical jump) were obtained 45 hr pre-game (Thursdays) (baseline), 15 hr post-game (Sundays, prior to \"next day\" recovery) and 48 hr post-game (Mondays). Performance ratios (Sunday and Monday scores divided respectively by the Thursday score) were used as the primary index of recovery. Muscle soreness was significantly greater (p<0.01) than baseline on both Sunday and Monday in all conditions, but no differences between the three recoveries and control were evident. On Sunday, vertical jump and 6-s work and power scores were only significantly lower than baseline values in control and performance ratios recorded two significant differences (vertical jump: pool walking > control, p<0.01; 6-s power: stretch > control, p<0.01) and moderate to large effect sizes (>0.3). No differences were found between the three experimental recoveries. On Monday no significant differences were recorded in performance between the recoveries and the effect sizes were of lower magnitude. In conclusion, recovery of muscle soreness, flexibility and power at 48 hr post-game was not significantly enhanced by performing an immediate post-game recovery beyond that achieved by performing only next day recovery training.", "Eccentric activities are an important component of physical conditioning and everyday activities. Delayed onset muscle soreness (DOMS) can result from strenuous eccentric tasks and can be a limiting factor in motor performance for several days after exercise. An efficacious method of treatment for DOMS would enhance athletic performance and hasten the return to activities of daily living. The purpose of this study was to identify a treatment method which could assist in the recovery of DOMS. In the selection of treatment methods, emphasis was directed toward treatments that could be rendered independently by an individual, therefore making the treatment valuable to an athletic trainer in team setting. DOMS was induced in 70 untrained volunteers via 15 sets of 15 eccentric contractions of the forearm extensor muscles on a Lido isokinetic dynamometer. All subjects performed a pilot exercise bout for a minimum of 9 weeks before data collection to assure that DOMS would be produced. Data were collected on 15 dependent variables: active and passive wrist flexion and extension, forearm girth, limb volume, visual analogue pain scale, muscle soreness index, isometric strength, concentric and eccentric wrist total work, concentric and eccentric angle of peak torque. Data were collected on six occasions: pre- and post-induced DOMS, 20 minutes after treatment, and 24, 48, and 72 hours after treatment. Subjects were randomly assigned to 1 of 7 groups (6 treatment and 1 control). Treatments included a nonsteroidal anti-inflammatory drug, high velocity concentric muscle contractions on an upper extremity ergometer, ice massage, 10-minute static stretching, topical Amica montana ointment, and sublingual A. montana pellets. A 7 x 6 ANOVA with repeated measures on time was performed on the delta values of each of the 15 dependent variables. Significant main effects (p < .05) were found for all of the dependent variables on time only. There were no significant differences between treatments. Therefore, we conclude that none of the treatments were effective in abating the signs and symptoms of DOMS. In fact, the NSAID and A. montana treatments appeared to impede recovery of muscle function.", "It has been suggested in the lay literature that static stretching and/or warm-up will prevent the occurrence of Delayed-Onset Muscle Soreness (DOMS). The primary purpose of this study was to determine the effects of static stretching and/or warm-up on the level of pain associated with DOMS. Sixty-two healthy male and female volunteers were randomly assigned to four groups: (a) subjects who statically stretched the quadriceps muscle group before a step, (b) subjects who only performed a stepping warm-up, (c) subjects who both stretched and performed a stepping warm-up prior to a step test, and (d) subjects who only performed a step test. The step test (Asmussen, 1956) required subjects to do concentric work with their right leg and eccentric work with their left leg to voluntary exhaustion. Subjects rated their muscle soreness on a ratio scale from zero to six at 24-hour intervals for 5 days following the step test. A 4x2x2 ANOVA with repeated measures on legs and Duncan's New Multiple Range post-hoc test found no difference in peak muscle soreness among the groups doing the step test or for gender (p greater than .05). There was the expected significant difference in peak muscle soreness between eccentrically and concentrically worked legs, with the eccentrically worked leg experiencing greater muscle soreness. We concluded that static stretching and/or warm-up does not prevent DOMS resulting from exhaustive exercise." ]

[ "11821278", "16253504", "2437967", "13977012", "11750964", "3135831", "7197091" ]

[ "Progesterone supplementation during early gestations after IVF or ICSI has no effect on the delivery rates: a randomized controlled trial.", "Dydrogesterone in the reduction of recurrent spontaneous abortion.", "Double-blind controlled trial of progesterone substitution in threatened abortion.", "Double-blind study of effect of 17-hydroxyprogesterone caproate on abortion rate.", "A randomised trial of progesterone prophylaxis after midtrimester amniocentesis.", "Endocrine effects of 17 alpha-hydroxyprogesterone caproate during early pregnancy: a double-blind clinical trial.", "[Is hormonal therapy still justified in imminent abortion? (author's transl)]." ]

[ "The aim was to study whether prolongation of luteal support during early pregnancy influences the delivery rate after IVF.\n Dual centre study including 303 women who achieved pregnancy after IVF or ICSI was used. All were treated with the long protocol using GnRH agonists and given luteal support with 200 mg vaginal progesterone three times daily during 14 days from the day of transfer until the day of a positive HCG test. The study group (n = 150) withdrew vaginal progesterone from the day of positive HCG. The control group (n = 153) continued administration of vaginal progesterone during the next 3 weeks of pregnancy.\n The number of miscarriages prior to and after week 7 of gestation was seven (4.6%) and 15 (10.0%) in the study group and five (3.3%) and 13 (8.5%) in the control group respectively. The number of deliveries was 118 (78.7 %) in the study group and 126 (82.4 %) in the control group. The differences were not significant.\n Prolongation of progesterone supplementation in early pregnancy has no influence on the miscarriage rate, and thus no effect on the delivery rate. Progesterone supplementation can safely be withdrawn at the time of a positive HCG test.", "One hundred and eighty women with a history of recurrent, unexplained spontaneous abortion (mean 3.5 abortions) were randomised to receive oral dydrogesterone (10 mg b.i.d.), intramuscular human chorionic gonadotrophin (hCG; 5000 IU every 4 days) or no additional treatment (controls). Treatment was started as soon as possible after confirmation of pregnancy and continued until the 12th gestational week. All women received standard supportive care. Abortions were significantly (p < or = 0.05) less common in the dydrogesterone group (13.4%) than in the control group (29%); there were no statistically significant differences between the hCG group and the control group. There were no differences between the groups with respect to pregnancy complications or congenital abnormalities. In conclusion, hormonal support with dydrogesterone can increase the chances of a successful pregnancy in women with a history of recurrent spontaneous abortion.", "Between 1983 and 1984 a double-blind randomized study with progesterone substitution in threatened abortion was carried out. Fifty-six patients with vaginal bleeding during the first trimester of pregnancy, the internal cervical os being closed, were referred to the hospital. Twenty-five women (5th and 6th week of gestation) with positive serum concentrations of beta-hCG were admitted to the study without regard to sonogram results. In other 25 women (7th-10th week of pregnancy) and 6 women (greater than or equal to 11th week of pregnancy) fetal heart action and movement could be demonstrated by ultrasound. The patients were prescribed bed rest and vaginal suppositories twice daily, containing either 25 mg progesterone or only polyethylene glycol. The code was not broken until after completion of the study. Serial serum determinations of beta-hCG, estradiol-17 beta (E2), progesterone, and ultrasound were performed. Four patients had to be omitted from final analysis (two tubal pregnancies, one intrauterine infection, one sectio parva). Three of 26 patients progesterone (11%) and five of 26 patients with placebo (19%) had an abortion, which represented no significant difference. Frequency of abortion was increased in women more than 30 years old, in women with previous abortions and after ovulation induction. Progesterone treatment resulted in a significant elevation of serum progesterone concentrations (p less than 0.01), while beta-hCG and E2 were unchanged. The results of this study confirm that pregnancy outcome is favorable in women with bleeding and normal hormone concentrations without hormonal treatment and unfavorable in women with reduced beta-hCG and E2-concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "Midtrimester amniocentesis to investigate fetal karyotype carries a small risk of fetal loss.\n To test the hypothesis that progesterone prophylaxis may reduce this.\n A randomised controlled trial comparing a short prophylactic treatment with progesterone after amniocentesis with untreated controls.\n There were no differences in frequency of miscarriage, preterm delivery or neonatal outcome.\n Prophylactic progesterone treatment after amniocentesis does not improve obstetric outcome.", "The clinical and endocrine effects of progestogen therapy in early pregnancy were investigated using a double-blind randomized trial in 64 patients who had a viable fetus at 6 weeks gestation and had an increased risk of miscarriage. The patients were randomly allocated to receive either 17 alpha-hydroxyprogesterone caproate or a placebo between 7 and 12 weeks gestation. Four fetal ultrasonographic variables and 17 maternal endocrine variables were studied in each woman. Only four maternal serum variables (17 alpha-hydroxyprogesterone, prolactin, thyroxin and thyroxin binding globulin) rose significantly. The serum progesterone levels in the hormone supplemented group were on average 20% higher than in the placebo group but the difference was not statistically significant. However, the relation between the progesterone levels and the fetal outcome was not clear. Therefore it is not advisable to prescribe 17-OHP-C during early pregnancy to prevent a miscarriage.", "In a prospective study, 300 women were treated during 1976 to 1978 alternatingly with hormones or placebo, the comparability of both groups being established in respect of certain influencing factors. No statistically confirmed difference was found in the total success rates of both types of treatment. The age of the pregnant women, and any previous abortions, did not represent any risk factor for imminent abortion. A better success rate was obtained with gestagen therapy, depending on the gestation period. (= 9th week of pregnancy)." ]

[ "9700123", "12566675" ]

[ "A placebo-controlled randomized trial of antithrombin therapy in neonatal respiratory distress syndrome.", "Can the administration of antithrombin III decrease the risk of cerebral hemorrhage in premature infants?" ]

[ "Neonatal respiratory distress syndrome (RDS) is associated with decreased plasma activity of antithrombin (AT) and increased formation of thrombin. We tested whether AT reduces thrombin formation, improves gas exchange, and decreases the duration of mechanical ventilation and supplemental oxygen. One hundred twenty-two infants were randomized to pasteurized AT concentrate or to placebo. Two ml/kg (equivalent to 100 IU AT/kg) were followed by 1 ml/kg (50 IU/kg) every 6 h for 48 h. Outcome measures included plasma AT activity, thrombin-AT (TAT) complex, prothrombin fragment (F1+2), the ratio of arterial to alveolar oxygen pressure [(a/A)PO2], and the ventilator efficiency index (VEI). In the AT group (n = 61), mean (SD) birth weight was 1,198 (301) g, mean (SD) gestational age (GA) was 28.3 (2.0) wk, 54% were male. In the placebo group (n = 61), mean (SD) birth weight was 1,201 (315) g, mean (SD) GA was 28.8 (2. 3) wk, 51% were male. In treated infants, AT activity was raised to means of 1.69 and 2.25 U/ml at 24 and 48 h, respectively. Corresponding means in control infants were 0.37 and 0.44 U/ml (p < 0.0001). F1+2, but not TAT, was significantly reduced by AT (p = 0. 004). VEI and (a/A)PO2 were similar in both groups throughout the first week of life. Median days receiving mechanical ventilation were 7.1 (AT) versus 4.8 (placebo), p = 0.0014. Median days receiving supplemental oxygen were 7.9 (AT) versus 5.5 (placebo), p < 0.0001. There were seven (11.5%) deaths in the AT group and three (4.9%) deaths in the placebo group. We conclude that treatment with AT cannot be recommended in premature infants with RDS.", "This study was carried out to determine whether the administration of antithrombin III decreases the risk of intraventricular hemorrhage in premature infants. In a randomized study, 60 infants born before 30 weeks of gestation were assigned to receive a loading dose of antithrombin III or placebo. There was no significant difference in the incidence of intraventricular hemorrhage between the antithrombin III and the placebo group (27.5 vs. 32%). Partial thromboplastin time, Quick's prothrombin time and platelet count were also not significantly different between the 2 groups. We conclude that the administration of antithrombin III during the first 2 days of life does not decrease incidence of intraventricular hemorrhage. Antithrombin III is a very expensive therapy and its benefits should be carefully investigated before being recommended as valuable therapy.\n Copyright 2003 S. Karger AG, Basel" ]

[ "10868712", "7491551", "14512127", "12665269", "10190915", "10542974", "16735113", "10329812", "8979288", "9828851", "8959118", "16889952", "9230238", "12000495", "18370529", "10414395", "12324672", "8947070", "15805993", "11897984", "15878495", "18475734", "11182010", "7664857", "10836329", "11112113", "11559968", "8290745", "7713201", "9293055", "8222787", "8092438", "8211872", "14694242", "16119035", "9517598", "10325897", "8339809", "9215245", "8215522", "10390394", "11555383" ]

[ "Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients.", "Comparison of fluticasone propionate and beclomethasone dipropionate on direct and indirect measurements of bronchial hyperresponsiveness in patients with stable asthma.", "A randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial of the minimal effective doses of budesonide and fluticasone dry-powder inhalers in adults with mild to moderate asthma.", "The clinical efficacy of fluticasone propionate (Fluvent) compared with beclomethasone dipropionates (Becotide) in patients with mild to moderate brochial asthma at the University College Hospital, Ibadan, Nigeria.", "Efficacy and safety of high-dose inhaled steroids in children with asthma: a comparison of fluticasone propionate with budesonide.", "The effect of high-dose fluticasone propionate and budesonide on lung function and asthma exacerbations in patients with severe asthma.", "A comparison of the relative growth velocities with budesonide and fluticasone propionate in children with asthma.", "A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma.", "Knemometry, urine cortisol excretion, and measures of the insulin-like growth factor axis and collagen turnover in children treated with inhaled glucocorticosteroids.", "Fluticasone propionate 750 micrograms/day versus beclomethasone dipropionate 1500 micrograms/day: comparison of efficacy and adrenal function in paediatric asthma.", "Fluticasone propionate 1 mg daily and beclomethasone dipropionate 2 mg daily: a comparison over 1 yr.", "Potency ratio fluticasone propionate (Flixotide Diskus)/budesonide (Pulmicort Turbuhaler).", "Short-term knemometry and urine cortisol excretion in children treated with fluticasone propionate and budesonide: a dose response study.", "Efficacy and safety of inhaled steroid and cromone treatment in school-age children: a randomized pragmatic pilot study.", "Cost effectiveness of fluticasone and budesonide in patients with moderate asthma.", "Skin bruising, adrenal function and markers of bone metabolism in asthmatics using inhaled beclomethasone and fluticasone.", "Airway and systemic effects of hydrofluoroalkane fluticasone and beclomethasone in patients with asthma.", "Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1).", "Protection by budesonide and fluticasone on allergen-induced airway responses after discontinuation of therapy.", "Significant variability in response to inhaled corticosteroids for persistent asthma.", "Improvement of asthma control with beclomethasone extrafine aerosol compared to fluticasone and budesonide.", "A blinded comparison of fluticasone propionate with budesonide via powder devices in adult patients with moderate-to-severe asthma: a clinical evaluation.", "Comparison of the systemic effects of fluticasone propionate and budesonide given by dry powder inhaler in healthy and asthmatic subjects.", "High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate, 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. International Study Group.", "Systemic effects of inhaled corticosteroids on growth and bone turnover in childhood asthma: a comparison of fluticasone with beclomethasone.", "Therapeutic ratio of inhaled corticosteroids in adult asthma. A dose-range comparison between fluticasone propionate and budesonide, measuring their effect on bronchial hyperresponsiveness and adrenal cortex function.", "A comparison of clinical use of fluticasone propionate and beclomethasone dipropionate in pediatric asthma.", "Evaluation of fluticasone propionate (500 micrograms day-1) administered either as dry powder via a Diskhaler inhaler or pressurized inhaler and compared with beclomethasone dipropionate (1000 micrograms day-1) administered by pressurized inhaler.", "High-dose inhaled steroids in asthmatics: moderate efficacy gain and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Research Council of the Norwegian Thoracic Society.", "Ease of handling and clinical efficacy of fluticasone propionate Accuhaler/Diskus inhaler compared with the Turbohaler inhaler in paediatric patients. UK Study Group.", "A dose-ranging study of fluticasone propionate in adult patients with moderate asthma. International Study Group.", "A comparison of fluticasone propionate 200 micrograms/day with beclomethasone dipropionate 400 micrograms/day in adult asthma.", "Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year. International Study Group.", "Time course of action of two inhaled corticosteroids, fluticasone propionate and budesonide.", "Effects of inhaled corticosteroids on growth in asthmatic children: a comparison of fluticasone propionate with budesonide.", "Safety and efficacy of fluticasone and beclomethasone in moderate to severe asthma. Belgian Multicenter Study Group.", "One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density.", "A comparison of fluticasone propionate, 1 mg daily, with beclomethasone dipropionate, 2 mg daily, in the treatment of severe asthma. International Study Group.", "A randomized, double-blind dose reduction study to compare the minimal effective dose of budesonide Turbuhaler and fluticasone propionate Diskhaler.", "Comparison of the efficacy and safety of inhaled fluticasone propionate 200 micrograms/day with inhaled beclomethasone dipropionate 400 micrograms/day in mild and moderate asthma.", "Systemic effects of inhaled fluticasone propionate and budesonide in adult patients with asthma.", "Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate." ]

[ "This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 microg twice daily given via the Diskus) and budesonide (800 microg twice daily given via the Turbuhaler). Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500-1600 microg day(-1). Sixty patients aged 18-75 years with moderate to severe asthma not fully controlled by treatment with 1500-1600 microg day(-1) budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08.00 to 10.30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period. Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 (95% CI 0.92-1.06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 microg day(-1) via Turbuhaler and fluticasone propionate 1500 microg day(-1) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma.", "Fluticasone propionate is a new inhaled corticosteroid with a 2:1 efficacy ratio compared with beclomethasone dipropionate with regard to lung function and symptom scores, without increased systemic activity. The aim of this study was to investigate whether this was also the case for bronchial hyperresponsiveness, assessed by both a direct (histamine) and an indirect (ultrasonically nebulised distilled water (UNDW)) provocation test.\n Fluticasone propionate, 750 micrograms/day, and beclomethasone dipropionate, 1500 micrograms/day, were compared in a randomised, double blind, crossover study consisting of two six week treatment periods, each preceded by a three week single blind placebo period. Twenty one non-smoking asthmatics (mean forced expiratory volume in one second (FEV1) 74.7% predicted, mean PC20histamine 0.36 mg/ml) completed the study.\n Fluticasone propionate and beclomethasone dipropionate improved FEV1, peak flow rates, asthma symptoms, and bronchial hyperresponsiveness to the same extent. Both fluticasone propionate and beclomethasone dipropionate caused an increase in PC20histamine (mean 2.29 [95% confidence interval 1.45 to 3.13] and 1.95 [1.07 to 2.84] doubling doses, respectively) and in PD20UNDW (1.12 [0.55 to 1.70] and 1.28 [0.88 to 1.70] doubling doses, respectively). Neither treatment changed morning serum cortisol levels, but fluticasone propionate decreased the number of peripheral blood eosinophils less than beclomethasone dipropionate, indicating smaller systemic effects of fluticasone propionate.\n These findings show that fluticasone propionate is as effective as twice the dose of beclomethasone dipropionate on bronchial hyperresponsiveness, assessed by provocation with both histamine and UNDW, without increased systemic activity.", "Inhaled corticosteroids are established first-line anti-inflammatory treatment for asthma. Clinical trials comparing inhaled corticosteroids must take into consideration that because of their excellent effect at low doses, they typically induce a near-maximal response in asthma patients.\n The aim of the present dose-response study was to estimate the minimal effective doses (MEDs) of budesonide and of fluticasone propionate via dry-powder inhaler in adults with mild to moderate asthma.\n This was a randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial performed in adults to compare these 2 inhaled corticosteroids. After a 4- to 6-week run-in period with beclomethasone dipropionate 2000 pg/d, patients fulfilling defined criteria for asthma control were randomly allocated to treatment with budesonide or fluticasone, both administered BID at a total of 800 pg/d. At 5-week intervals, the dose was reduced to 400 and then 200 pg/d (200 and 100 pg BID) if asthma control was maintained according to further defined criteria. The MED was defined as the last dose level before deterioration of asthma control.\n Subjects were 197 asthmatic patients with a mean age of 40.6 years in the budesonide group and 41.5 years in the fluticasone group. In both groups, baseline mean forced expiratory volume in 1 second (FEV(1)) was 79.4% of the predicted normal volume and baseline mean FEV(1) reversibility was 22.3%. The median MED for both groups was 400 microg/d, with no detectable difference in dis-tributions. The budesonide-to-fluticasone ratio for the geometric mean MED was 123% (95% CI, 99-153 [not significant]). No statistically significant differences regarding lung function, symptom scores, or rescue medication usage were found between the treatment groups during the first treatment period. Adverse-event profiles were similar in both groups, and no unexpected adverse events were considered to be caused by the study drugs.\n This effect-controlled study did not detect a statistically significant difference between the MEDs for budesonide and fluticasone via dry-powder inhaler in adults with mild to moderate asthma.", "This open, randomized trial was conducted at the Medical Out patient Department of University College Hospital, Nigeria to compare the clinical efficacy of Beclomethasome dipropionate (Becotide) with Fluticasone propionate (Fluvent) in patients with mild to moderate bronchial asthma. The study was performed as a week screening, 8-weeks open comparative clinical trial involving Fluticasone propionate (Fluvent) at a daily dose of 22 microg and Beclomethasone Dipropionate (Becotide) at a dose of 400 microg daily delivered through pressurized metered-dose inhaler (pMDI). The main objective of this study is to assess the efficacy of Fluvent in patients with mild to moderate asthma compared to Becotide. At the second visit (end of 1 week), 10 patients were given either Becotide of Fluvent but all were maintained on as needed beta2agonist (Salbutamol inhaler) therapy throughout the study. Efficacy was assessed by changes in symptoms, number of times beta2-agonist was used and results of pulmonary function tests (PEFR and FEV1) while safety was assessed by adverse event experiences. The baseline characteristics of the patients randomized into the two drug groups were comparable and of no statistical significance. The changes in the pulmonary function tests as well as the reduction in the asthma symptoms suggest a statistically significant improvement in the asthma status of the patients. However, these changes were more rapid among the patients using Fluvent. Also, there was higher percentage decline in the episodes of asthma symptoms either in the morning, day or night in the Fluvent group than Becotide group. The drugs were well tolerated and no adverse event was noticed on any of the patients. We therefore concluded that Fluvent would be more efficacious than Becotide in the treatment of Asthma.", "To compare the efficacy and adverse effects of inhaled fluticasone propionate (FP), 400 microgram/d, with those of budesonide (BUD), 800 microgram/d, in children with moderate to severe asthma.\n Three hundred thirty-three children, ages 4 to 12 years, receiving inhaled corticosteroids were enrolled in a double-blind, double-dummy, randomized, parallel-group study. After a 2-week run-in phase, 166 children received FP and 167 received BUD for 20 weeks. The primary outcome variable was mean morning peak expiratory flow; the 2 treatments were to be regarded as equivalent if the 90% CI for the treatment difference was within +/- 15 L/min. Pulmonary function, height, and diary cards were assessed at each visit; and morning serum cortisol levels were determined before and after treatment.\n Baseline peak expiratory flow was similar, FP 236 +/- 72 (SD) L/min and BUD 229 +/- 74, increasing after treatment to 277 +/- 41 and 257 +/- 28, a difference between treatments of 12 L/min (90% CI 6-19 L/min; P =.002). Symptom control and use of rescue medication were the same. Cortisol levels after treatment were 199 nmol/L (FP) and 183 nmol/L (BUD) (treatment ratio = 1.09; 90% CI 0.98-1.21; P =.172). Linear growth was less in those receiving BUD (mean difference, 6.2 mm; 95% CI 2.9-9.6; P =.0003).\n FP at half the dose was superior to BUD in improving peak expiratory flow and comparable in controlling symptoms. Growth was reduced with BUD compared with FP, but there was no difference in serum cortisol suppression or hepatic or renal function.", "The purpose of this study was to investigate the comparative efficacy and safety of equal doses of inhaled fluticasone propionate (FP) and inhaled budesonide (BUD) using their respective dry powder inhalers in a population of severe asthmatics requiring high doses of inhaled corticosteroid. This double-blind double-dummy parallel-group study compared the effects of 24 weeks of treatment with FP (2000 micrograms daily via a Diskhaler inhaler; Glaxo Wellcome, Evreux, France) and BUD (2000 micrograms daily via a Turbuhaler inhaler; Astra Pharmaceuticals, Rijswijka, Netherlands) on lung function and asthma exacerbations in 395 patients with asthma. FP was statistically significantly superior to BUD with respect to the percentage of symptom-free days (P = 0.02), the incidence of days free from rescue bronchodilator usage (P = 0.02) and the distribution of change in peak expiratory flow (PEF) expressed as a percentage of the predicted PEF (P = 0.04). During the treatment period FP was statistically significantly superior to BUD for change in forced expiratory volume in 1 sec (FEV1) at 8, 16 and 24 weeks, change in the median daytime symptom score during weeks 5-16, for incidence of symptom-free days and incidence of days free from rescue bronchodilator usage during weeks 17-24. There was no significant difference between FP and BUD with respect to the number of patients experiencing one or more asthma exacerbation (33.8 and 28.4% of patients, respectively). There was, however, evidence that the exacerbations were clinically less severe in patients treated with FP, in that the time to resolution was quicker (11.0 vs. 14.7 days; P = 0.035), mean duration of all exacerbations (for an individual patient) tended to be shorter (18.5 vs. 23.6 days; P = 0.12), the time off work was reduced (4.2 vs. 7.6 days; P = 0.012) and the lowest PEF recorded during the exacerbation was higher (301 vs. 263 l min-1; P = 0.07). There were no clinically relevant differences in the safety (serum cortisol levels, markers of bone turnover, adverse events) of FP and BUD at these microgram equivalent doses. The patients recruited into this study, in retrospect, probably had no need for such high doses of inhaled corticosteroid but, irrespective of this, FP at microgram equivalent doses showed evidence of superior efficacy to BUD with respect to lung function and severity of asthma exacerbations without producing any greater adverse systemic effect.", "There have been no previous large, well-designed direct comparisons of the effects of fluticasone propionate (FP) and budesonide (BUD) on growth in children. This randomised, double-blind study compared the effects on growth of FP and BUD in children aged 6-9 years with persistent asthma. Following a 6-month run-in period (without inhaled corticosteroids), patients with normal growth velocity were randomised to 12 months' treatment with FP 100 micro g bd (n=114) or BUD 200 micro g bd (n=119). Growth velocity was determined by stadiometric height measurement. Lung function, asthma symptoms and use of relief medication were also assessed. Annualised mean growth velocity during run-in was comparable in the two groups (FP: 5.9 cm/yr; BUD: 6.0 cm/yr). During the treatment period, adjusted mean growth velocity was significantly higher in the FP than the BUD group (5.5 cm/yr vs 4.6 cm/yr; P<0.001). Asthma control improved similarly in both treatment groups. Bone mineral density and overnight urinary cortisol:creatinine ratios were similar in the two groups. Drug-related adverse events were reported among 3% of FP-treated children, compared with 2% for BUD. In conclusion, this study demonstrates that FP for childhood asthma has significantly less impact on childhood growth velocity than a therapeutically equivalent dose of BUD.", "Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few.\n We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 micrograms twice daily and 220 micrograms twice daily) with 2 doses of beclomethasone dipropionate (168 micrograms twice daily and 336 micrograms twice daily) in subjects with persistent asthma.\n Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards.\n Fluticasone propionate treatment resulted in significantly (P </=.034) greater improvements in objective pulmonary function parameters than did beclomethasone dipropionate treatment and significantly greater reductions in daily albuterol use (P </=.010) and asthma symptoms (P </=.027). Both low-dose (88 micrograms twice daily) and medium-dose (220 micrograms twice daily) fluticasone propionate significantly increased FEV1 compared with higher doses of beclomethasone dipropionate (P =. 006). Low-dose and medium-dose fluticasone propionate improved FEV1 by 0.31 L (14%) and 0.36 L (15%), respectively, compared with improvements of 0.18 L (8%) and 0.21 L (9%) with low-dose and medium-dose beclomethasone dipropionate. The adverse event profiles were similar for both medications.\n Fluticasone propionate provides greater asthma control at roughly half the dose of beclomethasone dipropionate, with a comparable adverse event profile.", "Correlations between knemometric (lower leg length) growth rates and urine free cortisol excretion, respectively, and serum concentrations of IGF-I, IGF binding protein-3, osteocalcin, carboxy terminal propeptide of type I collagen (PICP), carboxy terminal pryridinoline cross-linked telopeptide of type I procollagen (ICTP), and amino terminal propeptide of type III procollagen (PIIINP) were investigated in 17 asthmatic children aged 7-14 y during treatment with fluticasone propionate, 200 micrograms, and beclomethasone dipropionate, 400 and 800 micrograms/d, taken from dry powder inhalers. The study was a double blind, crossover trial with three active treatment periods and two wash-out periods. All periods were 15 d long. Overnight urine free cortisol/ creatinine x 10(6) did not correlate with knemometric growth rates or any of the serum markers. Significant correlations (Pearson's correlation coefficient, P) between knemometric growth rates and IGF-I (0.41; 0.006), IGFBP-3 (0.35; 0.02), PICP (0.44; 0.003), ICTP (0.35; 0.001), and PIIINP (0.46; 0.002) were found. Compared with fluticasone propionate, 200 micrograms, beclomethasone dipropionate, 400 and 800 micrograms, caused significant suppression of lower leg growth rate (F = 12.41; p = 0.002, and F = 23.30; p = 0.0001, respectively) and of urine free cortisol/creatinine x 10(6) (F = 10.52; p = 0.003, and F = 13.74; p = 0.001). Beclomethasone, 800 micrograms, caused suppression of PICP compared with fluticasone propionate, 200 micrograms (F = 8.31; p = 0.008), and beclomethasone, 400 micrograms (F = 7.53; p = 0.01). Both low (F = 6.82; p = 0.02) and high (F = 23.35; p = 0.0001) doses of beclomethasone were associated with reduced concentrations of ICTP, the high dose being the most suppressive (F = 4.42; p = 0.05). Beclomethasone 400 (F = 9.75; p = 0.004) and 800 micrograms (F = 23.61; p = 0.0001) resulted in reduced levels of PIIINP. Reduced short-term knemometric growth rates in children treated with inhaled glucocorticosteroids reflect suppressive effects on type I and type III collagen turnover.", "Previous studies have suggested a 2:1 efficacy advantage of fluticasone propionate (FP) over beclomethasone dipropionate (BDP) in adults on high dose inhaled steroids and children on low dose inhaled steroids. The lower doses of FP required to provide equivalent efficacy to BDP also appear to have fewer systemic effects as measured by adrenal function.\n The efficacy and safety of FP 750 micrograms/day and BDP 1500 micrograms/day were compared in 30 children with persistent asthma (requiring 1000-2000 micrograms/day of inhaled corticosteroids) in a 12 week randomised double blind crossover study. Medication was delivered by a spacer device in two divided doses. Primary efficacy variables were peak expiratory flows (PEF). Adrenal function was assessed by 24 hour urinary free cortisol levels at eight and 12 weeks and ACTH and low dose synacthen tests (LDST) at 12 weeks. The results were adjusted for sequence and period differences.\n There was no difference in the primary efficacy variables over the two 12 week treatment periods (difference in adjusted means for morning PEF 1.3 l/min (95% CI -6.1 to 8.8), p = 0.112) and symptom scores (cough, tachypnoea, wheeze, shortness of breath; difference in adjusted means of night time scores: -0.06 (95% CI -0.14 to 0.03); p = 0.136). Similar degrees of mild adrenal dysfunction were found during BDP and FP treatment phases. Identical height gain velocities were shown during the corresponding periods.\n FP 750 micrograms/day is as effective as BDP 1500 micrograms/day in children with persistent asthma. At these very high doses we were unable to demonstrate a safety advantage of FP over BDP as assessed by adrenal function. However, measures of adrenal function may have been influenced by concurrent and previous systemic steroid usage, and possibly by effects of disease activity.", "This study was designed primarily to assess the safety and tolerability of fluticasone propionate (FP) 1 mg day-1 by comparison with beclomethasone dipropionate (BDP) 2 mg day-1 over a 12-month study period. Lung function data were also recorded and used to determine whether the potency ratio between the two inhaled corticosteroids observed in previous studies was maintained in the long-term. Two hundred and thirteen patients with an established clinical history of severe chronic asthma and who were currently receiving between 1000 micrograms and 2000 micrograms day-1 of inhaled steroids were randomized to treatment in a ratio of 3:1 for FP:BDP (159 patients FP; 54 patients BDP), both via metered dose inhalers. Both treatments were well tolerated with a similar adverse event profile. No unexpected adverse events were recorded. Most adverse events were related to the patients' asthma, an intercurrent infection or underlying atopy. The incidence of pharmacologically predictable adverse events was equally low in both treatment groups as was the incidence of events suggestive of systemic steroid effect. Mean serum cortisol levels remained within the normal range at all visits for both treatments. At 12 months, however, the mean cortisol levels for the FP group had risen 4% above the baseline value but had dropped 15% below for the BDP group, giving a ratio of FP:BDP of 1.22; P = 0.01; 95% confidence limits (CL) 1.05-1.43. Fluticasone propionate 1 mg day-1 was at least as effective as BDP 2 mg day-1 in improving lung function (PEF, FEV1 and FVC) over this period. Moreover, the difference in FEV1 values at 6 months was significantly greater for the FP group than for the BDP group (P = 0.04; difference = 0.12 1; 95% CL = 0.01, 0.24 1). The difference between treatments in the amount of FEV1 reversibility was also significantly greater for FP at 12 months (difference in treatments = -3%; 95% CL = - 7-0%; P = 0.044). This study supports previous studies and suggests that FP is likely to be of benefit in the long-term treatment of chronic severe asthma.", "In the choice of, or switch between, various inhaled corticosteroids (ICS) it is important to know equipotent doses for clinical treatment effects of the alternatives. Various ICS do have different inherent potency. Further, the ICS are delivered from inhalers that may differ markedly in output characteristics and drug delivery to intrapulmonary airways. Therefore, clinical efficacy comparisons must include drug-inhaler comparisons. We estimated the therapeutic potency ratio of the Flixotide Diskus (fluticasone propionate, FP) and the Pulmicort Turbuhaler (budesonide, BUD) in steroid-naive asthma patients, using a dose-reduction technique (FP 500-0 mcg/day, BUD 800-0 mcg/day). The dose defining end point was loss of asthma control in this paper denoted as exacerbation. In total, 282 patients with proven asthma were enrolled in the study, and 103 in the FP group and 98 in the BUD group completed the study per protocol. In total, 80 patients in the FP-group and 79 in the BUD-group experienced a dose defining exacerbation. The exacerbation frequency increased in a dose-dependent way as the dose was titrated down. From these data the potency difference between the present drug inhaler combinations, Flixotide Diskus and Pulmicort Turbuhaler, was calculated to be between 1.50:1 (95% CI 1.10:1-2.05:1) and 1.75:1 (CI 1.26:1-2.43:1) depending on if patients with insufficient steroid-response were excluded from the calculations or not. In these steroid-naïve patients, the potency difference was evident only at low daily doses, below 200 mcg.", "Few thorough comparisons of the systemic effects of inhaled corticosteroids in children are available. The aim of this study was to compare the effect of budesonide and fluticasone propionate on short-term lower leg growth. Fluticasone propionate, budesonide and placebo were administered for 2 weeks in a randomized, double-blind, double-dummy, cross-over design. Twenty four children aged 6-12 yrs received 200 microg x day(-1) of each drug, or placebo. Another 24 children aged 6-12 years received 400 microg x day(-1) of each drug, or placebo. Dry powder inhalers were used. Lower leg length was measured by knemometry twice a week during all three treatment periods, and 24 h cortisol excretion in the urine was measured at the end of each period. In the low-dose group, lower leg growth rate was the same during treatment with placebo (0.35 mm x week(-1)), fluticasone propionate (0.38 mm x week(-1)) or budesonide (0.26 mm x week(-1)). No significant difference (p=0.39) in lower leg growth rate was found between treatment with 400 microg x day(-1) budesonide (0.30 mm x week(-1)) and 400 microg fluticasone propionate treatment (0.37 mm x week(-1)). Growth rate during treatment with budesonide, 400 microg x day(-1), was significantly lower than during placebo treatment (0.52 mm x week(-1)). Cortisol excretion in the urine during treatment with 200 microg x day(-1) fluticasone propionate was significantly reduced as compared with placebo (p=0.006), but not when compared with 200 microg x day(-1) budesonide (p=0.07). Budesonide 200 microg x day(-1) was not significantly different from placebo. Fluticasone propionate and budesonide, both at 400 microg x day(-1), resulted in a significant reduction in cortisol excretion in the urine as compared with placebo (p=0.001). It is concluded that, dose-for-dose, budesonide Turbuhaler and fluticasone propionate Diskhaler have similar systemic effects.", "In the treatment of asthma, inhaled steroids are more effective than cromolyn, whereas the latter offers extreme safety. The aim of the present pilot study was to evaluate, contemporarily, efficacy and safety aspects of different asthma treatment modalities. In 75 school-age children (mean age 9.5 years; range 5.5-14.7 years), treatment of asthma was started with budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromones (CROM, n = 15). BUD was used at a dose of 800 microg/day during the first 2 months and at 400 microg/day thereafter. The respective FP doses were 500 and 200 microg/day. Efficacy of the treatment was assessed by measuring forced expiratory volume in 1 second (FEV1) and by evaluating the use of bronchodilators. Side-effects of the treatment were evaluated by following growth of the children and by performing low-dose adrenocorticotropin (ACTH) testing. At 4 months FEV1 had improved by a mean of 8.2% in the BUD group and by 5.4% in the FP group (p< 0.01 vs. baseline in both groups; NS between BUD and FP groups). The use of bronchodilators had decreased from five doses/week to one dose/week in the BUD group (p< 0.05), and from three doses/week to one dose/week in the FP group (p< 0.01) (NS between the groups). In the CROM group, the FEV1 value and the use of bronchodilators did not change. The treatment was unsuccessful on the basis of FEV1 decrease and increased bronchodilator use in, respectively, 30 and 15% of the BUD-, 20 and 7% of the FP-, and 50 and 47% of the CROM-treated children. Therefore, to prevent one treatment failure in the CROM group, between three and five children would need to move to treatment with steroids. The treatment had measurable systemic effects on the basis of height standard deviation (SD) score decrease and minor adrenocortical suppression in, respectively, 60 and 30% of the BUD-, 27 and 17% of the FP-, and 20 and 0% of the CROM-treated children. Therefore, to avoid systemic effects in one steroid-treated child, three BUD- and six to 14 FP-treated children would need to move to treatment with CROM. In conclusion, in school-age children asthma should be treated first with inhaled steroids. It is probable that the best combination of efficacy and safety can be achieved by using low steroid doses.", "The objective of this study was to assess the relative cost effectiveness of fluticasone via metered dose inhaler and budesonide via Turbuhaler((R)) in corticosteroid-naive patients with moderate asthma from a third-party payer perspective (German Sickness Funds).\n A retrospective economic assessment of direct medication costs of treatment was performed on data from a prospective, randomised, parallel group, 6-week clinical trial. 457 corticosteroid-naive patients between the ages of 18 and 70 years with moderate asthma were included in the intention-to-treat analysis.\n The fluticasone group had a higher proportion of successfully treated patients (those with a peak expiratory flow rate improvement of >/=10%) [47 vs 42%], a higher average proportion of symptom-free days (40 vs 34%) and lower direct healthcare costs [1997 Deutschmarks (DM)] per day (DM4.23 vs DM5.19) than the budesonide group. Therefore, the daily costs per successfully treated patient (DM9.00 vs DM12.36) and the cost per symptom-free day (DM10.58 vs DM15.26) were both lower with fluticasone than with budesonide. Sensitivity analysis demonstrated that these results were relatively robust over a wide range of plausible assumptions.\n These results showed that from the perspective of a third-party payer, fluticasone was more cost effective than budesonide over the 6-week study period.", "Fluticasone propionate (FP) is generally considered to have twice the efficacy of beclomethasone dipropionate (BDP) on a weight-to-weight basis for the control of asthma, and may have lesser effects on adrenal function. However, the effects of FP and BDP on skin integrity and bone metabolism markers require further examination. Sixty-nine asthmatic subjects were enrolled in a double-blind crossover study in which, after a baseline period, they received BDP or FP (at half the dose of BDP) for two 4-month periods each. A questionnaire on skin bruising, a skin examination, tests of adrenal function and of markers of bone metabolism were performed after 2 months of each period. The number of asthma exacerbations was not significantly different for the two treatment periods (eight for BDP and nine for FP), nor were various indices of asthma control. Whereas the frequency of bruising reported by the questionnaire was not different, there were more bruises on examination for BDP (1.6+/-2.5) than for FP (1.2+/-2.3) (p=0.04). Although baseline serum cortisol was not significantly different for the two drugs, the increase in cortisol after cortrosyn was lower for BDP (357+/-158 micromol x dL(-1)) than for FP (422+/-144 micromol x dL(-1)) (p<0.01). Serum osteocalcin levels were significantly lower in subject on BDP (2.8+/-1.7 microg x mL(-1)) than on FP (3.5+/-1.9 ng x mL(-1)) (p=0.003). Other markers of bone metabolism were not significantly altered. The three major side-effects were loosely, but significantly correlated with the periods on BDP and FP. However, skin bruises, increase in cortisol after Cortrosyn and osteocalcin were not significantly correlated for the period on either BDP or FP. In conclusion, whereas fluticasone propionate used at half the dose of beclomethasone dipropionate has a comparable effect on the control of asthma, fluticasone propionate demonstrated fewer side-effects in terms of skin bruising, adrenal suppression and bone metabolism.", "With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses.\n Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 micro g/day followed by 1000 micro g/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV(1)) of 20% or more (methacholine PD(20)) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC).\n For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD(20) compared with baseline. The improvement was not significantly greater with 1000 micro g/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p<0.05) lower values at 1000 micro g/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)).\n There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 micro g/day. At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.", "The aim of this study was to compare fluticasone propionate (FP) with budesonide (BUD) at a dose of 400 microg x day(-1) in the treatment of children with asthma. Two hundred and twenty nine children with mild-to-moderate asthma, currently receiving 200-400 microg x day(-1) of inhaled corticosteroid, were randomized to receive either 400 microg x day(-1) of FP from the Diskhaler (registered trade mark of the Glaxo Group of Companies) or 400 microg x day(-1) of BUD from the Turbuhaler (registered trade mark of Astra Pharmaceuticals Ltd) for 8 weeks, in a parallel-group, double-blind, double-dummy study. Primary efficacy was assessed by measurement of daily peak expiratory flow (PEF). In addition, pulmonary function tests were performed at each clinic visit and a self-administered patient-centred questionnaire was completed by one parent of each patient at the start and end of study treatment. Mean morning PEF increased following treatment both with FP and BUD, but was significantly higher following treatment with FP during Weeks 1-4 (p=0.015) and Weeks 1-8 (p=0.019). Similar results were found for mean evening PEF and percentage predicted morning and evening PEF. Children receiving FP experienced significantly less disruption in their physical activities (i.e. sports, games) because of their asthma compared to children treated with BUD (p=0.03). Mean cortisol levels increased in both groups, but the increase was significantly higher in the FP group at 4 weeks (p=0.022). Serum and urine markers of bone formation and resorption changed very little and showed no consistent pattern of change. Fluticasone propionate at a dosage of 400 microg x day(-1) from the Diskhaler provided a more rapid and greater improvement in lung function in children with mild-to-moderate asthma than BUD 400 microg day(-1) from the Turbuhaler. Both treatments were well-tolerated, with a similar safety profile.", "Treatment with inhaled steroids is an effective method of reducing bronchoconstriction and airway inflammation after allergen challenge. However, the duration of the protective effects of inhaled steroids after discontinuation of therapy has not been established.\n We sought to evaluate the protective effect of 1 week of inhaled steroid therapy against inhaled allergen challenge 12 hours after discontinuation of therapy.\n In this randomized, double-blind, placebo-controlled crossover trial, 26 asthmatic subjects (>18 years old) not using inhaled steroids were administered 200 microg of budesonide twice daily, 200 microg of fluticasone twice daily, or placebo twice daily for 1 week. Twelve hours after discontinuation of therapy, subjects were administered an inhaled allergen challenge. Each treatment period was separated by a 3-week washout period.\n When compared with placebo (26% +/- 14%), there was a slight but significant protection against the allergen-induced early response after fluticasone treatment (19% +/- 10%, P = .001) but not after budesonide treatment (23% +/- 13%, P = .08). However, when the area under the curve for the early airway response was examined, there was no difference between the 2 drugs in the amount of protection ( P = .62). Partial protection was demonstrated against the late-response allergen-induced sputum eosinophilia with both treatments ( P = .001). By contrast, no protection was observed against allergen-induced airway hyperresponsiveness for either treatment.\n The protective effects of inhaled steroids against allergen-induced early responses, airway eosinophilia, and allergen-induced airway hyperresponsiveness are partially or completely lost as early as 12 hours after discontinuation of therapy.", "A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy.\n The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs.\n A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day.\n Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years).\n Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.", "Qvar Autohaler efficacy on asthma control, assessed with E. Juniper asthma control questionnaire (ACQ), was compared with fluticasone and budesonide. An open randomized study, stratified (2:1) on the intake of long-acting beta2-mimetics (LAbeta2), was performed in patients with moderate to severe poorly controlled asthma (defined by at least one nocturnal discomfort in the last 5 days or a mean of 2 puffs of short-acting beta2-mimetics in the last 7 days or exercise dyspnea) despite treatment with beclomethasone < or = 1000 microg/day (or equivalent). 460 patients received Qvar Autohaler 800 microg/day (n = 149), fluticasone Diskus 1000 microg/day (n = 149) or budesonide Turbuhaler 1600 microg/day (n = 162) during 12 weeks. Asthma control improved in all groups, with no difference between groups. For patients treated with LAbeta2 (n = 286) a significantly greater improvement of the ACQ score was obtained with Qvar Autohaler versus fluticasone (1.0 +/- 1.0 vs. 0.6 +/- 0.9; P = 0.019), but not versus budesonide (0.9 +/- 0.9). Pulmonary function test improvements were similar in the 3 groups. The significant improvement in asthma control in patients receiving LAbeta2 suggests potential advantages for extrafine aerosols as part of anti-inflammatory treatment optimization.", "In Vitro and in vivo data have demonstrated that there are detectable differences between inhaled corticosteroids commonly used to treat asthma. However, controversy still remains as to whether these differences translate into clinical benefits. This 12-week, international, randomized, doubleblind, parallel-group study was undertaken to compare the efficacy and safety of fluticasone propionate (FP) 800 mug daily, administered as a powder via the Diskhaler((R)), and budesonide (BUD) 1600 mug daily, administered using the Turbuhaler((R)), in adult patients with moderate-tosevere asthma. A total of 518 patients participated in the study, 256 of whom received FP and 262 BUD. Assessment of mean morning peak expiratory flow (PEF) over the 12-week treatment period revealed a statistically significant difference in efficacy between FP 800 mug daily and BUD 1600 mug daily in favour of FP (p = 0.003), with an overall improvement of 20.9 l/min with FP compared with 12.4 l/min on BUD. Statistically significant differences in favour of FP were seen over the 12 weeks for mean evening PEF (p = 0.04), diurnal PEF variation (p = 0.03) and percentage predicted PEF (p = 0.003), as well as forced expiratory volume (p = 0.008), forced vital capacity (p = 0.02) and PEF (p = 0.005) measured at clinic visits. The median percentage of symptom-free nights increased over the 12-week study period in both treatment groups, with similar changes seen for the median percentage of days with symptom score < 2, rescue medication use and exacerbations of asthma. The incidence of adverse events was found to be comparable in the two treatment groups. The geometric mean ratios of serum cortisol levels were found to be 1.03 for FP, indicating no mean hypothalamic-pituitary-adrenal axis suppression from baseline, and 0.93 for BUD (p = 0.0002 compared with FP). In summary, FP 800 mug daily showed a greater efficacy/safety ratio in the treatment of moderate-to-severe asthma than BUD 1600 mug daily.", "The potential for long term adverse effects from inhaled corticosteroids relates to their systemic absorption, usually assessed from proxy markers in short term studies. When fluticasone propionate and budesonide have been compared in this way the results have been inconsistent. To determine whether this is because of the subjects studied or the sensitivity of the systemic marker used, we have compared the effects of fluticasone propionate and budesonide in healthy and asthmatic subjects and investigated the effect of treatment on three systemic markers.\n Forty six healthy subjects were randomised to receive inhaled fluticasone propionate 1500 microg/day (via an Accuhaler), budesonide 1600 microg/day (via a Turbuhaler), or placebo; 31 subjects with moderately severe asthma were randomised to receive the same doses of fluticasone propionate or budesonide but not placebo. Systemic effects in healthy and asthmatic subjects were compared after 7 days. Treatment was continued for another 21 days in the subjects with asthma when systemic effects and asthma control were assessed.\n At baseline healthy subjects had higher urinary levels of total cortisol metabolites (TCM) than subjects with asthma. After 7 days of treatment with fluticasone propionate urinary TCM levels in the healthy subjects were significantly lower than in the subjects with asthma (mean difference between groups 1663 microg/day, 95% CI 328 to 2938). This was not the case with budesonide, however, where urinary TCM levels in the healthy subjects remained above those in the asthmatic subjects (mean difference between groups 1210 microg/day, 95% CI -484 to 2904). Urinary TCM levels were considerably more sensitive to the effects of inhaled corticosteroids than morning serum cortisol or osteocalcin concentrations. Only budesonide reduced the serum level of osteocalcin.\n When given by dry powder inhaler for 7 days, fluticasone propionate 1500 microg/day has a greater effect on the hypothalamic-pituitary-adrenal axis in healthy subjects than in subjects with asthma, but this is not the case for budesonide 1600 microg/day. These findings, together with the differences in sensitivity between systemic markers, explain many of the discrepancies in the literature.", "Airway inflammation is now regarded as fundamental in the pathogenesis of asthma and treatment with inhaled corticosteroids has proved effective. There is a need for drugs in this category with higher topical potency but fewer side-effects than those presently available. A double-blind, parallel group study was conducted in 671 patients with severe asthma (already taking between 0.8-2.0 mg of inhaled corticosteroid daily) to compare the safety and efficacy of 6 weeks of treatment with inhaled fluticasone propionate (FP), 1 mg daily, to fluticasone propionate, 2 mg daily, and budesonide (BUD), 1.6 mg daily, delivered via a metered-dose inhaler. Peak expiratory flow (PEF), asthma symptoms, and usage of rescue medication were recorded daily by the patient. At each clinic visit (-2, 0, 3 and 6 weeks) morning serum cortisol levels, bone markers and spirometry were assessed. The changes in mean morning PEF from baseline (weeks 1-6) were: FP 2 mg daily +24 l.min-1; FP 1 mg daily +21 l.min-1; BUD 1.6 mg daily +13 l.min-1. A similar rank order for the three treatments was seen for evening PEF, clinic spirometry, reduction of diurnal PEF variation, symptom scores, and requirement for rescue bronchodilators. The mean serum cortisol levels remained well within the normal range in all three groups. Analysis of the geometric mean cortisol ratio (treatment/baseline ratio after 6 weeks treatment) showed a changed rank order, the values being: FP 1 mg daily 1.04; BUD 1.6 mg daily 0.97; FP 2 mg daily 0.88.(ABSTRACT TRUNCATED AT 250 WORDS)", "Inhaled steroids are frequently used in childhood asthma, but concerns based on limited objective evidence remain, regarding long-term side-effects. In this study the systemic effects of standard doses of inhaled steroids in childhood asthma were assessed, comparing beclomethasone dipropionate (BDP) with fluticasone propionate (FP). The study was prospective, randomized and double-blind. Twenty-three steroid-naive children with moderately severe asthma, aged 5-10 yrs, were allocated either BDP (400 microg x day(-1) or FP (200 microg x day(-1)) using a metered-dose inhaler with a spacer. Asthma control was assessed at regular intervals over 20 months. Fasting morning blood and overnight urine samples were collected for estimation of serum cortisol, serum 1-carboxyterminal telopeptide (ICTP), serum osteocalcin and urine deoxypyridinoline (DPD). Bone mineral density (BMD) was measured at each visit. None of the markers of bone turnover showed any change during the study period. BMD increased at normal rates with age. Serum cortisol significantly decreased on BDP, but not on FP. A significant difference in growth rates was found between the groups, with a slower rate of growth towards the end of the observation period in the BDP group. In conclusion when taken in a relatively modest dose over a period of time, beclomethasone dipropionate had significant effects on the hypothalamic-pituitary-adrenal axis and statural growth in childhood asthma. These systemic effects were not seen with an equipotent dose of fluticasone propionate.", "Inhaled corticosteroids have become the mainstay treatment of bronchial asthma. However, simultaneous evaluations of efficacy and side effects are few. This study aimed to compare the relative effect of fluticasone propionate (FP) and budesonide (BUD) on bronchial responsiveness and endogenous cortisol secretion in adults with asthma. The study was double-blind and included 66 adults with asthma, who were randomized to FP (n = 33) or BUD (n = 33). Prestudy, all participants were clinically stable, using inhaled corticosteroids and hyperresponsive to methacholine. Eligible patients were randomized to three consecutive 2-wk periods with either FP 250 microg twice daily, FP 500 microg twice daily, and FP 1,000 microg twice daily, or BUD 400 microg twice daily, BUD 800 microg twice daily, and BUD 1,600 microg twice daily, delivered by Diskhaler and Turbuhaler, respectively. Before randomization and at the end of each treatment, bronchial methacholine PD(20), 24-h urinary cortisol excretion (24-h UC), plasma cortisol, serum osteocalcin, and blood eosinophils were determined. The relative PD(20) potency between FP and BUD was 2.51 (95% CI, 1.05-5.99; p < 0. 05), while the relative 24-h UC potency was 0.60 (95% CI, 0.44-0.83; p < 0.01). The differential therapeutic ratio (FP/BUD) based on PD(20) potency and 24-h UC was 4.18 (95% CI, 1.16-15.03; p < 0.05). The difference in systemic potency was also seen for plasma cortisol, serum osteocalcin, and blood eosinophils. Therapeutic ratio over a wide dose range, determined by impact on bronchial responsiveness and endogenous corticosteroid production, seems to favor FP.", "Inhaled steroids play a very important role in the prevention and treatment of asthma. Previous studies indicated that fluticasone propionate (FP) had low bioavailability and high local potency. However, the laboratory data in these studies were not obtained among Taiwan population. It is very important that native data should be established. Thus a 12-week research program was designed, involving 77 patients, 51 for FP group and 26 for beclomethasone dipropionate (BD) group. The objects were victims of moderate to severe asthma and their age ranged from 4 to 14 years old. An open, comparative and randomized method was adopted. Except for the 4-week-later daytime symptom score(P = 0.033, BD group was better), no other significant differences were found between the two groups in the symptom score improvement(P > 0.05). All the P-values for the daytime & night-time scores were lower than 0.001, which means obvious improvement after treatment in both groups. P-value for PEF improvement was 0.003 after 4 weeks (BD group was better) and 0.943 after 8 weeks; for FEV1 improvement, it was 0.005 after 4 weeks(BD group was better) and 0.252 after 8 weeks; and for FEV1/FVC improvements, it was 0.067 after 4 weeks and 0.097 after 8 weeks. There was no statistic significance in total eosinophil count (TEC), IgE, eosinophil cationic protein (ECP) serum level changes after 4 or 8 weeks. Adverse effects were all anticipated and no statistic significance showed up, either, between the two groups or in the cortisol levels (P > 0.05). In conclusion, native data indicated that the potency of 100 micrograms of FP was equal to that of 200 micrograms of BD and that few side effects were noted in FP group. It is recommended that this drug be introduced for clinical use.", "Five hundred and eighty-five patients with moderate asthma, currently receiving 400-1000 micrograms day-1 of an inhaled corticosteroid, were treated for 6 weeks in a double-blind, randomized, parallel group study with either 500 micrograms day-1 fluticasone propionate as a dry powder via a Diskhaler inhaler, 500 micrograms day-1 fluticasone propionate via a pressurized inhaler or 1000 micrograms day-1 beclomethasone dipropionate via a pressurized inhaler. For all three treatment groups, mean morning and evening peak expiratory flow rates (PEFRs) increased within 1 week of the start of treatment. There were also improvements in clinic lung function, daytime and night-time asthma symptoms and a reduction in daytime and night-time rescue bronchodilator medication in all three groups. There were no statistically significant differences between the two formulations of fluticasone propionate in any of the efficacy parameters. Fluticasone propionate via the Diskhaler was significantly more effective than beclomethasone dipropionate over the 6 week study period in reducing diurnal variation (mean difference--4 l min-1, 95% CI--8 to 0 l min-1: P = 0.03). Fluticasone propionate via the Diskhaler produced a statistically significant improvement in night-time symptoms when compared to beclomethasone dipropionate whereas, beclomethasone dipropionate 1000 micrograms day-1 was statistically significantly more effective than both formulations of fluticasone propionate in improving daytime symptoms (P < 0.05). However, these statistical differences must be viewed together with the fact that very few patients recorded a score of 2 or more for both daytime or night-time symptoms. There was a similarly low incidence of adverse events with all three treatments with no evidence of hypothalamic pituitary adrenal (HPA)-axis suppression. The results of the 6-week comparative study showed that 500 micrograms day-1 fluticasone propionate whether administered via pressurized inhaler or Diskhaler is as effective and as safe as 1000 micrograms day-1 beclomethasone dipropionate administered via a pressurized inhaler in the treatment of moderate asthma. Over 12 months fluticasone propionate 500 micrograms day-1 via a pressurized inhaler was at least as effective and as well tolerated as beclomethasone dipropionate 1000 micrograms day-1.", "We wanted to evaluate the improvement in efficacy when increasing the daily dose of inhaled steroids and to compare the efficacy, safety, and tolerance of 1.6 mg beclomethasone dipropionate (BDP) with that of 2.0 mg fluticasone propionate (FP). The study was a randomized, double-blind, 3 month, multicentre study. One hundred and thirty four asthmatics currently using inhaled steroids (0.4-1.6 mg BDP or budesonide (BUD)) were stratified according to pretrial daily steroid use. Within each stratum they were randomized to either 1.6 mg BDP or 2.0 mg FP. A significant increase in the primary efficacy variables, i.e. mean morning and evening peak expiratory flow (PEF) (approximately 20 l.min-1) during the treatment period, was found for both treatments. No significant differences between the drugs were revealed for these primary or any other secondary efficacy variables (use of beta 2-agonists, symptom scores, and PEF, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) recorded at the clinical visits). However, significant differences between treatments occurred regarding decrease of serum cortisol and adrenocorticotropic hormone. We conclude that, although both treatments gave statistically significant increases in efficacy parameters when compared with baseline, the increases were so small that they can be regarded as being clinically unimportant. Daily doses of BDP, 1.6 mg, and FP, 2.0 mg, had comparable effects on lung function. A suppression of the hypothalamic pituitary adrenal (HPA) axis was only found with a daily dose of 2 mg FP.", "A total of 323 children aged 4-11 years who were receiving, or had symptoms indicating a clinical requirement for, inhaled corticosteroid at a daily dose of 400 micrograms budesonide (BUD) or beclomethasone dipropionate (BDP), or 200 micrograms fluticasone propionate (FP), were randomised into this multicentre, open-label, parallel group study. Patients received either FP 100 micrograms b.d. administered via the Accuhaler/Diskus inhaler (n = 159) or BUD 200 micrograms b.d. administered via a Turbohaler inhaler (n = 164) for four weeks and recorded daily their morning and evening peak expiratory flow (PEF), asthma symptoms and use of relief medication. Device handling was assessed by a questionnaire, with responses recorded on three- or five-point ordinal scales. The primary efficacy parameter was mean percent predicted morning PEF. The device handling results showed the Accuhaler/Diskus inhaler was rated more favourably than the Turbohaler inhaler in terms of ease of correct inhaler use, ease of telling how many doses were left, ease of knowing whether a dose had been inhaled and overall liking of the device. More patients in the Accuhaler/Diskus group (85%) than in the Turbohaler group (58%) said they would be happy to receive the same device again, while 8% and 25% respectively said they would not be happy to be given it again. In addition, the change from baseline to week 4 of treatment in mean percent predicted morning PEF was greater in the FP Accuhaler/Diskus group, indicating that FP 200 micrograms daily via Accuhaler/Diskus inhaler is at least as clinically effective as BUD 400 micrograms daily via the Turbohaler inhaler.", "In this 4-week, multicenter, double-blind, randomized, parallel group study, the dose-effect relationship of four doses of inhaled fluticasone propionate (50, 100, 200, and 400 micrograms twice daily) was investigated and compared with beclomethasone dipropionate, 200 micrograms twice daily. A total of 672 patients with moderate asthma currently receiving 1,000 micrograms/d or less of an inhaled steroid were recruited. The study demonstrated a significant dose-related improvement in lung function with fluticasone propionate. Linear dose-related increases were observed in morning (increase per doubling dose was 4.3 L/min; 95 percent confidence interval [CI], 1.8, 6.8 L/min; p = 0.001) and evening peak expiratory flow rate (PEFR) (increase per doubling dose was 3.0 L/min; 95 percent CI, 0.5, 5.5 L/min; p = 0.017), clinic lung function (at 4 weeks, increase in percent predicted PEFR per doubling dose = 1.1 percent; 95 percent CI, 0.2, 2.1 percent; p = 0.022; increase in percent predicted FEV1 per doubling dose = 1.1 percent; 95 percent CI, 0.3, 1.9 percent; p = 0.10:increase in percent predicted FVC per doubling dose = 1.3 percent, 95 percent CI, 0.5, 2.1 percent; p = 0.001), and the percentage of symptom-free days over days 1 to 14 of treatment (increase per doubling dose = 1.9, 95 percent CI, 0.0, 3.9; p = 0.048). There was also a dose-related reduction in extra bronchodilator usage (days 1 to 14 p = 0.002; days 15 to 28 p = 0.01). In addition, there was a significant decrease in diurnal variation with increasing doses of fluticasone propionate (decrease per doubling dose = 2.0 L/min, 95 percent CI, 0.4; p = 0.024). The number of asthma exacerbations was also reduced as the dose of fluticasone propionate increased. Fluticasone propionate was well tolerated, adverse events were few, and there was a similar incidence in all groups. Furthermore, there was no evidence of any hypothalamic pituitary adrenal axis suppression. The data from the study were consistent with other clinical studies that have shown fluticasone propionate to be more potent than beclomethasone dipropionate in terms of improvement in lung function. In conclusion, this study provided evidence of a dose-related improvement in asthma control for fluticasone propionate in the dose range 100 to 800 micrograms daily, in patients with moderate asthma.", "A total of 261 patients with symptomatic, mild to moderate asthma were randomized to treatment in this 4-week, double-blind, parallel-group comparison of fluticasone propionate 200 micrograms/d with beclomethasone dipropionate 400 micrograms/d. Improvements from both treatments were seen in diary card data. Morning peak expiratory flow rate (PEFR) improved from 375 to 390 and 371 to 382 l/min with fluticasone propionate and beclomethasone dipropionate, respectively. Symptom scores, percentage of symptom-free days and nights, and use of rescue beta 2-agonist medication also improved, as did clinical lung function. With the exception of percentage of rescue-free days, which was greater for beclomethasone dipropionate, none of the differences between the groups were statistically significant. There was a significant difference between treatments in the number of rescue-free days over days 1-28; however, there was no difference between treatments in the number of rescue-free days over days 1-14, nor was there any difference in the number of inhalations of rescue medication used throughout the study. Very few adverse effects were reported. Although all mean plasma cortisol values were within the normal range, they were significantly different between treatments, rising from 402 to 429 nmol/l with fluticasone propionate, and falling from 435 to 394 nmol/l with beclomethasone dipropionate (P = 0.006). Mean stimulated cortisol levels 30 min after tetracosactin injection were also significantly greater with fluticasone propionate (P = 0.024). In conclusion, fluticasone propionate 200 micrograms/d is as effective as beclomethasone dipropionate 400 micrograms/d with less effect on plasma cortisol levels.", "High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma. Although effective, they may cause systemic side effects. Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses.\n Fluticasone propionate, 1.5 mg per day, was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate. The study was multicentre, double blind and of a parallel design. For the first three months patients attended the clinic every four weeks and completed daily diary cards. For the next nine months they were only seen at three monthly intervals in the clinic.\n During the first three months diary card peak expiratory flow (PEF) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate (difference in morning PEF 15 l/min (95% CI 6 to 25)), and these differences were apparent at the end of the first week. The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8% compared with those receiving beclomethasone dipropionate. No significant differences between the two groups were observed in morning plasma cortisol levels, urinary free cortisol levels, or response to synthetic ACTH stimulation. In addition, both the rates of withdrawal and of adverse events were low, and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate.\n This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate, with no increase in systemic or other side effects.", "It is important to be able to compare the efficacy and systemic effects of inhaled corticosteroids but their slow onset of action makes it difficult to measure the maximum response to a given dose. Submaximal responses could be compared if the time course of action of the inhaled corticosteroids being compared was similar. We have compared the time course of action of fluticasone and budesonide, measuring response as change in the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD20AMP).\n Eighteen subjects with mild asthma, aged 18-65, took part in a three way randomised crossover study. Subjects took fluticasone (1500 microg/day), budesonide (1600 microg/day), and placebo each for 4 weeks with a washout period of at least 2 weeks between treatments; PD20AMP and forced expiratory volume in 1 second (FEV1) were measured during and after treatment. The time taken to achieve 50% of the maximum response (T50%) was compared as a measure of onset of action.\n There was a progressive increase in PD20AMP during the 4 weeks of treatment with both fluticasone and budesonide but not placebo; the increase after 1 and 4 weeks was 2.28 and 4.50 doubling doses (DD) for fluticasone and 2.49 and 3.65 DD for budesonide. T50% was 9.3 days for fluticasone and 7.5 days for budesonide with a median difference between fluticasone and budesonide of 0.1 days (95% CI -1.4 to 2.65). There was a wide range of response to both inhaled corticosteroids but good correlation between the response to fluticasone and budesonide within subjects. FEV1 and morning peak expiratory flow rate (PEFR) increased during the first week of both active treatments and were stable thereafter. There was a small progressive improvement in nocturnal symptoms with both active treatments.\n PD20AMP was a more sensitive marker of response to inhaled corticosteroid therapy than FEV1 and PEFR. The time course of action of fluticasone and budesonide on PD20AMP is similar, suggesting that comparative studies of their efficacy using 1 or 2 week treatment periods are valid. When a new inhaled corticosteroid becomes available, a pilot study comparing its time course of action with that of an established corticosteroid should allow comparative studies to be performed more efficiently.", "In asthmatic children inhaled corticosteroids are widely used. However, there are some concerns about the systemic adverse effects of these drugs, especially in the growing child. We performed this prospective study in order to compare the effects of 400 microg/day of budesonide (BUD) and 250 microg/day of fluticasone propionate (FP) on growth in prepubertal (aged 4-11.5 years), moderate persisting asthmatic children. One hundred patients (51 boys and 49 girls), who were randomized into two groups, were recruited for the study. The first group was treated with BUD, 2X 200 microg/day, and the second group was treated with FP, 2X 125 microg/day, by using a medium-size volume-spacer metered-dose inhaler. Growth in children with asthma who were treated by inhaled corticosteroids was calculated by growth velocity over a 12-month period. Comparisons between treatment groups were calculated by t-test and chi-square test. There were no significant differences between BUD and FP groups for sex, age, first height, and growth velocity. Moderate persisting, prepubertal asthmatic children treated with 250 microg/day of FP appeared to have no different linear growth than those children who received 400 microg/day of BUD.", "There are still some concerns about the safety of high doses of inhaled glucocorticosteroids (ICS). We compared the safety and efficacy of fluticasone propionate (FP) and beclomethasone dipropionate (BDP) in 306 patients with moderate to severe asthma in a double-blind, multicenter, cross-over study of 12 mo duration. During the 1-mo run-in period, bronchodilators were replaced by salmeterol 50 microg twice daily, increasing morning peak expiratory flow rate (PEFR) by 28 L/min (p < 0.001) and FEV1 by 6.2% predicted (p < 0.001). At randomization the current ICS was replaced by 500 microg BDP or 250 microg FP in accordance with previously taken 500 microg BDP or 400 microg budesonide (BUD). No significant differences between the two treatments regarding morning plasma cortisol, urinary excretion of calcium and hydroxyproline, FEV1, and PEFR were observed at any time point during the study. Osteocalcin and bone mineral density (BMD) were improved over baseline in the FP group, resulting in higher serum osteocalcin levels (mean difference 0.28 ng/ml; p < 0.001) and higher BMD in the spine (1.0%; p = 0.05), femoral neck (1.6; p < 0.01), and Ward's triangle (3.6%; p = 0.01) as compared with BDP. We conclude that chronic treatment with FP, at half the dose of BDP, results in a similar antiasthma effect but a more favorable safety profile with respect to bone metabolism and mineral density.", "Inhaled corticosteroids are recognised as the most effective agents in the treatment of asthma. However, concerns have been expressed about the effects of high doses of inhaled corticosteroids on safety in relation to bone resorption and formation. This study measures the effects of two inhaled corticosteroids on bone markers and bone mineral density (BMD) over one year.\n A one year randomised, prospective, open parallel study comparing inhaled fluticasone propionate (FP), 500 micrograms twice daily in 30 patients, and budesonide (BUD), 800 micrograms twice daily in 29 patients, delivered by metered dose inhaler and large volume spacers was performed in adults with moderate to severe asthma. Biochemical markers of bone turnover (osteocalcin, procollagen type 1 C-terminal propeptide (PICP), immunoreactive free deoxypyridinoline (iFDpd), N-terminal crosslinked telopeptides of type I collagen (NTx)), BMD at the spine and femoral neck, and serum cortisol concentrations were measured at baseline and 12 months later.\n There were no significant differences between the inhaled steroids on bone markers of bone resorption and formation or bone mineral density. Bone mineral density of the spine increased slightly in both groups over the 12 month period. Serum osteocalcin levels increased from baseline in both treatment groups (FP 16.9%, p = 0.02; BUD 14.3%, p = 0.04). PICP did not differ significantly from baseline. Both markers of bone resorption (iFDpd, NTx) varied considerably with no significant changes after one year. There was a significant correlation in percentage change from baseline between BMD of the spine and osteocalcin at 12 months (r = 0.4, p = 0.017). Mean serum cortisol levels remained within the normal range in both groups following treatment.\n There was no evidence of a decrease in BMD during 12 months of treatment with high doses of either FP or BUD. The change in spine BMD correlated with the increase in osteocalcin. Studies extending over several years are needed to establish whether these findings persist.", "We wanted to compare the efficacy and safety of fluticasone propionate, a new topically active inhaled corticosteroid, to that of high dose beclomethasone dipropionate, in severe adult asthma. Patients currently receiving between 1.5-2.0 mg.day-1 of an inhaled corticosteroid were treated for six weeks in a double-blind, randomized, parallel group study with 1 mg.day-1 fluticasone propionate (n = 82), or 2 mg.day-1 beclomethasone dipropionate (n = 72). Mean morning peak expiratory flow rates (PEFR) increased from 303 to 321 l.min-1 with fluticasone propionate, and from 294 to 319 l.min-1 with beclomethasone dipropionate. There was an increase in evening PEFR, asthma symptoms improved, and rescue beta 2-agonist use decreased for both treatment groups. None of these differences between treatments were statistically significant. However, diurnal variation was significantly reduced with fluticasone propionate, when compared with beclomethasone dipropionate (difference = 7 l.min-1; p = 0.038). Clinic lung function also improved with both treatments and, apart from % predicted PEFR, which showed no difference after beclomethasone dipropionate but increased from 73 to 78% with fluticasone propionate, there were no differences between treatments. Forced expiratory volume in one second (FEV1) increased with both treatments. The geometric mean plasma cortisol concentration rose after treatment with fluticasone propionate (from 293 to 309 nmol.l-1) and fell after beclomethasone dipropionate (from 256 to 224 nmol.l-1); the difference between treatments was significant. The incidence of adverse events was low in both treatment groups. In conclusion, 1 mg.day-1 fluticasone propionate was as effective as 2 mg.day-1 beclomethasone dipropionate in the control of severe asthma.(ABSTRACT TRUNCATED AT 250 WORDS)", "New inhaled glucocorticosteroids and inhalers are being developed. Their clinical equipotency is difficult to assess and is often discussed.\n This study was carried out to compare the effect of budesonide Turbuhaler and fluticasone propionate (FP) Diskhaler in a dose reduction study in children (ages 5 to 16 years) with asthma.\n Children treated with budesonide administered through a pressurized metered-dose inhaler with a large volume spacer had their budesonide dose gradually reduced to define the minimal effective dose with this delivery system. After this period, 217 children were randomly allocated to treatment with half the dose of either budesonide Turbukaler or FP Diskhaler for 5 weeks in a double-blind trial. If no deterioration in asthma control was seen, the dose was further reduced by 50% at 5-week intervals until deterioration in asthma control was seen. Throughout the study, morning and evening peak expiratory flow, symptoms, and use of rescue beta 2-agonist were recorded in diaries. Lung function tests and a standardized exercise test were performed at the clinic at the end of each treatment period. Urine cortisol excretion (24 hours) was measured before and after the first 5-week treatment period. Standardized criteria for deterioration in asthma control, based on diary card variables and exercise testing, were used to determine the minimal effective dose for each patient; and from this, the number of dose reduction steps was calculated.\n No statistically significant difference was seen in number of dose reduction steps from baseline or in minimal effective dose between the two treatments; mean reduction was 1.59 dose steps for budesonide Turbuhaler and 1.65 dose steps for FP Diskhaler (p = 0.52), and minimal effective dose was 188 micrograms for budesonide Turbuhaler and 180 micrograms for FP Diskhaler. After these dose reductions, the same level of asthma control was observed in the budesonide Turbuhaler and FP Diskhaler groups. Furthermore, no statistically significant differences between the two inhaler-drug combinations were seen in daytime or nighttime symptoms, morning and evening peak expiratory flow, use of rescue beta 2-agonist, lung functions at the clinic, exercise-induced fall in lung function, or 24-hour urinary cortisol excretion during the first 5-week period.\n Microgram for microgram, budesonide Turbuhaler and FP Diskhaler are equally effective in treatment of children with moderate asthma.", "This study was designed to compare the efficacy and safety of a new inhaled corticosteroid, fluticasone propionate at a total daily dose of 200 micrograms, with beclomethasone dipropionate 400 micrograms/day in childhood asthma. A total of 398 asthmatic children (aged 4-19 years) were randomised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler. During the study the patients recorded morning and evening peak expiratory flow rate (PEFR), symptom scores, and use of beta 2 agonist rescue medication. In addition, clinic visit PEFR and forced expiratory volume in one second were measured. Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment. For the purposes of analysis the diary card data were grouped into three periods: week 3 (days 15-21), week 6 (days 36-42), and weeks 1-6 (days 1-42). The results showed no significant difference between treatments on most efficacy parameters. However, there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 (fluticasone propionate 6.1%, beclomethasone dipropionate 3.9%) and at week 6 (fluticasone propionate 8.3%, beclomethasone dipropionate 5. 9%) and % predicted evening PEFR at week 6 (fluticasone propionate 7.3%, beclomethasone dipropionate 4.9% and over weeks 1-6 (fluticasone propionate 5.5%, beclomethasone dipropionate 3.6%. Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 81%) and % days without rescue medication at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 80%) and over weeks 1-6 (fluticasone propionate 80%, beclomethasone dipropionate 73%). Except for a higher incidence of sore throat in the fluticasone propionate group, the two treatments did not differ with regard to safety. There was no evidence of adrenal suppression with either treatment. In conclusion, fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma.", "We assessed the systemic effects of budesonide (BUD) and fluticasone propionate (FP) in 23 patients with asthma, using a double-blind, placebo-controlled, double-dummy, and cross-over design. The following five treatments were given in a randomized order for 1 wk with a washout period in between of 2 wk: (1) placebo; (2) FP, 200 micrograms twice a day, inhaled from a Diskhaler; (3) FP, 1,000 micrograms twice a day, inhaled from a Diskhaler; (4) BUD, 200 micrograms twice a day, inhaled from a Turbuhaler; and (5) BUD, 800 micrograms twice a day, inhaled from a Turbuhaler. The primary variable was the area under the curve of serum cortisol versus time (AUC0-20), derived from serum samples taken every 2 h over a 20-h period following the last evening dose at 10:00 P.M. The lower doses of BUD and FLU did not cause any adrenal suppression. Compared with placebo, however, FP (1, 000 micrograms, twice daily and BUD (800 micrograms, twice daily) decreased the AUC0-20 by 34 and 16%, respectively. Fluticasone (1,000 micrograms, twice daily) was more suppressive than BUD (800 micrograms, twice daily) (p = 0.0006). The FEV1, measured the morning after the last inhalation, was significantly higher after the active treatments, compared with placebo (p < 0.02), but did not differ between all active treatments. We conclude that high doses of BUD and FP (in particular the latter), inhaled via their respective dry powder inhalers for 1 wk, result in a measurable systemic activity in patients with asthma.", "High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD.\n Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life.\n It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group.\n It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects." ]

[ "2041443" ]

[ "Double-blind controlled study of botulinum toxin in adductor spasmodic dysphonia." ]

[ "The treatment of adductor spasmodic dysphonia using botulinum toxin A was conducted in 13 patients as a double-blind, placebo-controlled study. Patients were diagnosed independently by an interdisciplinary team consisting of speech pathologists, an otolaryngologist, and a neurologist. The toxin or saline was injected into each thyroarytenoid muscle under electromyographic and laryngoscopic guidance. Botulinum toxin A markedly reduced perturbation, decreased fundamental frequency range, and improved the spectrographic characteristics of the voice. Fundamental frequency and phonation time remained unchanged. Patients injected with botulinum toxin A noticed significant improvement in their voices in comparison with the placebo-treated group. Excessive breathiness of the voice occurred in two patients, and mild bleeding in one patient in the botulinum toxin A-treated group. Injection with saline resulted in edema of the vocal cord in one patient. Botulinum toxin A proved to be an effective and safe treatment of adductor spasmodic dysphonia." ]

[ "10413387", "10871977", "18626028", "16696748", "20008582", "11443021" ]

[ "Evidence suggesting that a chronic disease self-management program can improve health status while reducing hospitalization: a randomized trial.", "Physician, nurse, and social worker collaboration in primary care for chronically ill seniors.", "Integration of depression and hypertension treatment: a pilot, randomized controlled trial.", "A randomized trial of a multicomponent home intervention to reduce functional difficulties in older adults.", "Randomized controlled trial of anticipatory and preventive multidisciplinary team care: for complex patients in a community-based primary care setting.", "Pharmacist-led medication review in patients over 65: a randomized, controlled trial in primary care." ]

[ "This study evaluated the effectiveness (changes in health behaviors, health status, and health service utilization) of a self-management program for chronic disease designed for use with a heterogeneous group of chronic disease patients. It also explored the differential effectiveness of the intervention for subjects with specific diseases and comorbidities.\n The study was a six-month randomized, controlled trial at community-based sites comparing treatment subjects with wait-list control subjects. Participants were 952 patients 40 years of age or older with a physician-confirmed diagnosis of heart disease, lung disease, stroke, or arthritis. Health behaviors, health status, and health service utilization, as determined by mailed, self-administered questionnaires, were measured.\n Treatment subjects, when compared with control subjects, demonstrated improvements at 6 months in weekly minutes of exercise, frequency of cognitive symptom management, communication with physicians, self-reported health, health distress, fatigue, disability, and social/role activities limitations. They also had fewer hospitalizations and days in the hospital. No differences were found in pain/physical discomfort, shortness of breath, or psychological well-being.\n An intervention designed specifically to meet the needs of a heterogeneous group of chronic disease patients, including those with comorbid conditions, was feasible and beneficial beyond usual care in terms of improved health behaviors and health status. It also resulted in fewer hospitalizations and days of hospitalization.", "To examine the impact of an interdisciplinary, collaborative practice intervention involving a primary care physician, a nurse, and a social worker for community-dwelling seniors with chronic illnesses.\n A concurrent, controlled cohort study of 543 patients in 18 private office practices of primary care physicians was conducted. The intervention group received care from their primary care physician working with a registered nurse and a social worker, while the control group received care as usual from their primary care physician. The outcome measures included changes in number of hospital admissions, readmissions, office visits, emergency department visits, skilled nursing facility admissions, home care visits, and changes in patient self-rated physical, emotional, and social functioning.\n From 1992 (baseline year) to 1993, the two groups did not differ in service use or in self-reported health status. From 1993 to 1994, the hospitalization rate of the control group increased from 0.34 to 0.52, while the rate in the intervention group stayed at baseline (P= .03). The proportion of intervention patients with readmissions decreased from 6% to 4%, while the rate in the control group increased from 4% to 9% (P=.03). In the intervention group, mean office visits to all physicians fell by 1.5 visits compared with a 0.5-visit increase for the control group (P=.003). The patients in the intervention group reported an increase in social activities compared with the control group's decrease (P=.04). With fewer hospital admissions, average per-patient savings for 1994 were estimated at $90, inclusive of the intervention's cost but exclusive of savings from fewer office visits.\n This model of primary care collaborative practice shows potential for reducing utilization and maintaining health status for seniors with chronic illnesses. Future work should explore the specific benefit accruing from physician involvement in the collaborative practice team.", "We wanted to examine whether integrating depression treatment into care for hypertension improved adherence to antidepressant and antihypertensive medications, depression outcomes, and blood pressure control among older primary care patients.\n Older adults prescribed pharmacotherapy for depression and hypertension from physicians at a large primary care practice in West Philadelphia were randomly assigned to an integrated care intervention or usual care. Outcomes were assessed at baseline, 2, 4, and 6 weeks using the Center for Epidemiologic Studies Depression Scale (CES-D) to assess depression, an electronic monitor to measure blood pressure, and the Medication Event Monitoring System to assess adherence.\n In all, 64 participants aged 50 to 80 years participated. Participants in the integrated care intervention had fewer depressive symptoms (CES-D mean scores, intervention 9.9 vs usual care 19.3; P <.01), lower systolic blood pressure (intervention 127.3 mm Hg vs usual care 141.3 mm Hg; P <.01), and lower diastolic blood pressure (intervention 75.8 mm Hg vs usual care 85.0 mm Hg; P <.01) compared with participants in the usual care group at 6 weeks. Compared with the usual care group, the proportion of participants in the intervention group who had 80% or greater adherence to an antidepressant medication (intervention 71.9% vs usual care 31.3%; P <.01) and to an antihypertensive medication (intervention 78.1% vs usual care 31.3%; P <.001) was greater at 6 weeks.\n A pilot, randomized controlled trial integrating depression and hypertension treatment was successful in improving patient outcomes. Integrated interventions may be more feasible and effective in real-world practices, where there are competing demands for limited resources.", "To test the efficacy of a multicomponent intervention to reduce functional difficulties, fear of falling, and home hazards and enhance self-efficacy and adaptive coping in older adults with chronic conditions.\n A prospective, two-group, randomized trial. Participants were randomized to a treatment group or no-treatment group.\n Urban community-living older people.\n Three hundred nineteen community-living adults aged 70 and older who reported difficulty with one or more activities of daily living.\n Occupational and physical therapy sessions involving home modifications and training in their use; instruction in strategies of problem-solving, energy conservation, safe performance, and fall recovery techniques; and balance and muscle strength training.\n Outcome measures included self-rated functional difficulties with ambulation, instrumental activities of daily living, activities of daily living, fear of falling, confidence performing daily tasks, and use of adaptive strategies. Observations of home hazards were also conducted.\n At 6 months, intervention participants had less difficulty than controls with instrumental activities of daily living (P=.04, 95% confidence interval (CI)=-0.28-0.00) and activities of daily living (P=.03, 95% CI=-0.24 to -0.01), with largest reductions in bathing (P=.02, 95% CI=-0.52 to -0.06) and toileting (P=.049, 95% CI=-0.35-0.00). They also had greater self-efficacy (P=.03, 95% CI=0.02-0.27), less fear of falling (P=.001, 95% CI=0.26-0.96), fewer home hazards (P=.05, 95% CI=-3.06-0.00), and greater use of adaptive strategies (P=.009, 95% CI=0.03-0.22). Benefits were sustained at 12 months for most outcomes.\n A multicomponent intervention targeting modifiable environmental and behavioral factors results in life quality improvements in community-dwelling older people who had functional difficulties, with most benefits retained over a year.", "T o examine whether quality of care (QOC) improves when nurse practitioners and pharmacists work with family physicians in community practice and focus their work on patients who are 50 years of age and older and considered to be at risk of experiencing adverse health outcomes.\n Randomized controlled trial.\n A family health network with 8 family physicians, 5 nurses, and 11 administrative personnel serving 10 000 patients in a rural area near Ottawa, Ont.\n Patients 50 years of age and older at risk of experiencing adverse health outcomes (N = 241).\n At-risk patients were randomly assigned to receive usual care from their family physicians or Anticipatory and Preventive Team Care (APTCare) from a collaborative team composed of their physicians, 1 of 3 nurse practitioners, and a pharmacist.\n Quality of care for chronic disease management (CDM) for diabetes, coronary artery disease, congestive heart failure, and chronic obstructive pulmonary disease.\n Controlling for baseline demographic characteristics, the APTCare approach improved CDM QOC by 9.2% (P < .001) compared with traditional care. The APTCare intervention also improved preventive care by 16.5% (P < .001). We did not observe significant differences in other secondary outcome measures (intermediate clinical outcomes, quality of life [Short-Form 36 and health-related quality of life scales], functional status [instrumental activities of daily living scale] and service usage).\n Additional resources in the form of collaborative multidisciplinary care teams with intensive interventions in primary care can improve QOC for CDM in a population of older at-risk patients. The appropriateness of this intervention will depend on its cost-effectiveness. TRIAL REGISTRATION NUMBER NCT00238836 (CONSORT).", "regular medication review has been recommended for those over 75 and those on multiple drug therapy. Pharmacists are a potential source of assistance in reviewing medication. Evidence of the benefits of this process is needed.\n to study the effect of medication review led by a pharmacist on resolution of pharmaceutical care issues, medicine costs, use of health and social services and health-related quality of life.\n randomized, controlled trial.\n general medical practices in the Grampian region of Scotland.\n patients aged at least 65 years, with at least two chronic disease states who were taking at least four prescribed medicines regularly.\n pharmacists reviewed the drug therapy of 332 patients, using information obtained from the practice computer, medical records and patient interviews. In 168 patients, a pharmaceutical care plan was then drawn up and implemented. The 164 control patients continued to receive normal care. All outcome measures were assessed at baseline and after 3 months.\n all patients had at least two pharmaceutical care issues at baseline. Half of these were identified from the prescription record, the rest from notes and patient interview. Of all the issues, 21% were resolved by information found in notes and 8.5% by patient interview. General practitioners agreed with 96% of all care issues documented on the care plans in the intervention group. At the time of follow-up, 70% of the remaining care issues had been resolved in the intervention group, while only 14% had been resolved in the control group. There were no changes in medicine costs or health-related quality of life in either group. There were small increases in contacts with health-care professionals and slightly fewer hospital admissions among the intervention group than the control group.\n pharmacist-led medication review has the capacity to identify and resolve pharmaceutical care issues and may have some impact on the use of other health services." ]

[ "7582281", "7023529", "9759798", "7622762", "2894492", "9626025", "3247516", "2702243", "8757206", "7812574", "1357554", "9589818", "9412549", "1357551", "7952551", "11348933", "8542165", "8977598", "10806139", "7503401", "10319056", "9033441", "8104272", "2782734", "8542164", "10027428", "10335000", "10799426", "11206232", "11956046", "8103655", "9893773", "7910880", "8756801", "3780287", "9394077", "8778601", "7767541" ]

[ "Interaction of inhaled beta 2 agonist and inhaled corticosteroid on airway responsiveness to allergen and methacholine.", "Regular versus symptomatic aerosol bronchodilator treatment of asthma.", "A 3-month comparison of formoterol with terbutaline via turbuhaler. A placebo-controlled study.", "Regular use of inhaled albuterol and the allergen-induced late asthmatic response.", "Rebound increase in bronchial responsiveness after treatment with inhaled terbutaline.", "Effects of treatment with formoterol on bronchoprotection against methacholine.", "Intermittent and continuous salbutamol rotacaps inhalation in asthmatic patients.", "Changes in bronchial reactivity in asthmatic children after treatment with beclomethasone alone or in association with salbutamol.", "The effect of inhaled albuterol in moderate to severe asthma.", "Quality of life in asthma clinical trials: comparison of salmeterol and salbutamol.", "A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma.", "Salmeterol powder compared with albuterol aerosol as maintenance therapy for asthma in adolescent and adult patients.", "Effect of regular inhaled albuterol on allergen-induced late responses and sputum eosinophils in asthmatic subjects.", "Tolerance to the nonbronchodilator effects of inhaled beta 2-agonists in asthma.", "Effect of regular terbutaline and budesonide on bronchial reactivity to allergen challenge.", "A placebo-controlled clinical trial of regular monotherapy with short-acting and long-acting beta(2)-agonists in allergic asthmatic patients.", "Rebound airway obstruction and responsiveness after cessation of terbutaline: effects of budesonide.", "Effect of regular terbutaline on the airway response to inhaled budesonide.", "Effects of terbutaline and budesonide on sputum cells and bronchial hyperresponsiveness in asthma.", "Inhaled formoterol dry powder in the treatment of patients with reversible obstructive airway disease. A 3-month, placebo-controlled comparison of the efficacy and safety of formoterol and salbutamol, followed by a 12-month trial with formoterol.", "Asthma control during long-term treatment with regular inhaled salbutamol and salmeterol.", "Short-term regular beta 2-adrenergic agonists treatment is safe in mild asthmatics taking low doses of inhaled steroids.", "Regular inhaled salbutamol and airway responsiveness to allergen.", "Tachyphylaxis to systemic but not to airway responses during prolonged therapy with high dose inhaled salbutamol in asthmatics.", "The effect of regular inhaled albuterol on exercise-induced bronchoconstriction.", "Comparative efficacy and safety of albuterol sulfate Spiros inhaler and albuterol metered-dose inhaler in asthma.", "Randomised trial of an inhaled beta2 agonist, inhaled corticosteroid and their combination in the treatment of asthma.", "Inhaled salbutamol for wheezy infants: a randomised controlled trial.", "A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler.", "Beta2-agonist tolerance and exercise-induced bronchospasm.", "Asthma control during and after cessation of regular beta 2-agonist treatment.", "Low-dose formoterol Turbuhaler (Oxis) b.i.d., a 3-month placebo-controlled comparison with terbutaline (q.i.d.).", "Regular vs as-needed inhaled salbutamol in asthma control.", "A placebo-controlled, crossover comparison of salmeterol and salbutamol in patients with asthma.", "Long-term regularly inhaled salbutamol.", "A comparison of regular with intermittent bronchodilators in asthma patients on inhaled steroids.", "Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. Asthma Clinical Research Network.", "Regular albuterol, nedocromil sodium, and bronchial inflammation in asthma." ]

[ "Regular treatment with salbutamol increases airway responsiveness to allergen but not to methacholine and produces tolerance to the bronchoprotective effect of salbutamol. The current study addresses the effect of inhaled corticosteroid on these aspects of regular beta 2 agonist use. A group of 13 atopic asthmatic subjects free from all asthma medications and remote from allergen exposure were studied. We used a double-blind, random-order, crossover study to compare four 1-wk treatment periods with > or = 1 wk washout: placebo, salbutamol, 200 micrograms four times per day, budesonide, 400 micrograms four times per day, and the combination of salbutamol and budesonide. We measured the methacholine PC20 and the methacholine dose shift produced acutely by 200 micrograms salbutamol after 7 d and the allergen PC15 after 8 d treatment. Blinded medications were withheld for 8 to 10 h before measurements. The methacholine PC20 was not affected by regular salbutamol but increased significantly (p < 0.014) after both budesonide-containing regimens. Neither the dose shift nor its significant reduction by regularly used beta 2 agonist were influenced by the inhaled corticosteroid. The four allergen PC15 values were significantly different from each other. Compared with placebo, the allergen PC15 was 0.6 doubling doses lower after salbutamol (p = 0.021) and 1.3 doubling doses higher after budesonide (p < 0.001); the allergen PC15 was reduced by 0.53 doubling doses from this new baseline (p = 0.039) when salbutamol and budesonide were used together.(ABSTRACT TRUNCATED AT 250 WORDS)", "Regular treatment with salbutamol or placebo aerosols was compared in a double-blind study in 18 asthma patients. Although symptom scores and respiratory function tests were not significantly different, wheezing attacks requiring additional puffs of a standard salbutamol aerosol were significantly more frequent during the period on placebo when patients were receiving symptomatic treatment only. Thus regular treatment with bronchodilator aerosols provides better control of asthma than symptomatic use alone.", "Oxis Turbuhaler is a new dry powder formulation of long-acting beta2-agonist formoterol. This study compared the efficacy and safety of regular use of the long-acting beta2-agonist formoterol and the short-acting terbutaline for 3 months in patients with asthma.\n After 1-week run-in, 343 patients received either formoterol 12 microg bid (F) (delivered dose of 9 microg), terbutaline 500 microg qid (T) or placebo qid, in a parallel-group, double-blind, randomized manner. They had a mean of 61% of predicted forced expiratory volume in 1 second (FEV1) and a mean reversibility of 26%. Eighty-nine percent used inhaled corticosteroids.\n During run-in mean morning peak expiratory flow (PEF L/min) for F was 366 and 348 for T, and 344 for placebo (P). The F group improved morning PEF significantly compared with P (P = .0022) and T (P = .0001). Changes from run-in were + 18, -1.5, and +5 L/min after F, T, and P, respectively. The F group was statistically significantly better than P and T in increasing evening PEF and in reducing night-time asthma. The F and T statistically significantly reduced the use of rescue medication compared with P. The bronchodilating response to the study drug and to an additional 1.25 mg terbutaline was of the same magnitude before and throughout the study. No statistically significant treatment-by-time interaction was observed (P > .20). There were no adverse effects of clinical relevance.\n Formoterol Turbuhaler, 12 microg bid, was more effective than terbutaline Turbuhaler, 0.5 mg qid, and placebo. Regular use of formoterol or terbutaline did not significantly influence the response to additional inhalation of terbutaline.", "We have recently demonstrated that a 2-week course of inhaled albuterol 200 micrograms four times daily caused a near doubling of the allergen-induced early asthmatic response. We hypothesized that this might extend to the more clinically relevant late asthmatic response.\n We studied 11 patients with atopic asthma who were free from all medications including inhaled beta 2-agonists for more than 4 weeks. We performed a double-blind, random-order, crossover study, comparing the effect of 1-week treatment periods of albuterol 200 micrograms four times daily and placebo 2 puffs four times daily on the early and late asthmatic responses to the same dose of allergen.\n Regular use of albuterol did not influence the baseline forced expiratory volume in 1 second (FEV1) (3.40 vs 3.42 L, p = 0.84) or the baseline methacholine provocative concentration causing a 20% fall in FEV1 (PC20) (geometric mean, 2.4 mg/ml vs 1.9 mg/ml, p = 0.38). However, all aspects of the allergen-induced asthmatic response were increased. After the 1-week albuterol treatment, the early asthmatic response was slightly greater (21.1% vs 17.9% FEV1 fall, p = 0.26), the late response was greater (23.1% vs 13.2% FEV1 fall, p = 0.0027), and the allergen-induced increase in airway responsiveness (change in log methacholine PC20) was greater (0.37 vs 0.20, p = 0.045).\n One week of albuterol treatment (200 micrograms four times daily) increased the late asthmatic response and allergen-induced increase in airway responsiveness. This suggests that the combination of regular use of inhaled beta 2-agonist and allergen exposure may cause more airway inflammation than allergen exposure alone.", "To investigate whether cessation of regular beta-agonist treatment results in an increase in bronchial responsiveness, two double-blind, randomised crossover studies were done. Subjects with mild asthma were investigated to determine the course of change in bronchial responsiveness, measured as the provocative dose (PD20) of histamine that caused a 20% fall in forced expiratory volume in 1 s after short-term and longer term treatment with an inhaled beta-agonist. In the first study in 8 subjects, 500 and 2000 micrograms terbutaline thrice in 1 day protected against histamine-induced bronchoconstriction, and the increase in PD20 compared with placebo remained high throughout the day and overnight. In the second study 8 subjects received placebo or terbutaline 750 micrograms thrice daily for 14 days. The protection afforded by terbutaline against histamine-induced bronchoconstriction on day 14 was less than that on day 1 by 40% in the morning and 82% in the afternoon. On day 15 PD20 was lower after stopping terbutaline than placebo, with a maximum difference of 1.5 (95% CI 0.6-2.5) doubling-doses of histamine 23 h after the end of treatment. Thus treatment with terbutaline for 1 day did not result in any rebound increase in bronchial responsiveness. Treatment for 2 weeks impaired the ability of terbutaline to protect against histamine-induced bronchoconstriction, and was followed by a rebound increase in bronchial responsiveness after cessation of treatment.", "In addition to their bronchodilatory effects, beta(2)-agonists protect against bronchoconstriction, such as that caused by methacholine challenge. However, tachyphylaxis to this beneficial effect develops after chronic use of beta(2)-agonists. We studied whether the frequency or dose of treatment with a long-acting beta(2)-agonist (formoterol) affects the degree of bronchoprotection afforded against methacholine challenge and to compare this with the effects of a short-acting beta(2)-agonist (terbutaline).\n In a randomized, parallel group, double-blind study at two centers, patients with stable asthma of mild to moderate severity who were treated with inhaled corticosteroids were treated with formoterol 6 micrograms twice daily, 24 micrograms twice daily, 12 micrograms once daily; terbutaline 500 micrograms four times daily; or placebo. Treatments were given by dry powder inhaler for a period of 2 weeks. Of the 72 patients who were enrolled, 67 completed the study. Methacholine challenge was performed to calculate the provocative dose that caused a 20% fall in forced expiratory volume in 1 second at baseline (unprotected) after an initial 1-week run-in without beta(2)-agonists, 1 hour after the first dose of study treatment, and again 1 hour after 7 and 14 days of study treatment.\n Each of the four active treatments exhibited significant tachyphylaxis (P < 0.05) to protection against methacholine challenge when comparing first/last dose (as geometric mean protection ratio versus baseline): formoterol 24 micrograms twice daily (9.6-fold/1.6-fold), 12 micrograms once daily (7.1-fold/2.2-fold), 6 micrograms twice daily (6.2-fold/2.3-fold), and terbutaline 500 micrograms four times daily (2.9-fold/2.0-fold). There were no significant differences among treatments after 2 weeks in bronchoprotection against methacholine challenge. For all formoterol regimens, the bronchodilator response 1 hour after inhalation was maintained over the 2-week treatment period. Diurnal control of morning and evening peak flow was significantly better with formoterol 24 micrograms twice daily than with terbutaline.\n Tachyphylaxis to bronchoprotection against methacholine challenge develops after 2 weeks of therapy with formoterol, a long-acting beta(2)-agonist, at all three dosage regimens that were tested. In contrast, the bronchodilator effects of formoterol were maintained during the 2 weeks of treatment.", "We studied 18 asthmatic patients over an 8-week period. Each patient received for 4 weeks continuous and for 4 weeks intermittent salbutamol rotacaps (400 micrograms) using a double-crossover technique. No significant differences were found between the two treatment regimens as judged by daily card scores and daily PEFR (both a.m and p.m.). Lung Function tests performed monthly in the hospital showed no significant differences between two treatments or the development of bronchial beta-adrenoreceptor resistance.", "Airway inflammation is consistently present in patients with severe asthma. The combination of inhaled steroids and bronchodilators may be useful both for treating symptoms and improving the underlying inflammatory condition. We have compared the effect of beclomethasone dipropionate (BDP) combined with salbutamol (S), BDP alone, and placebo, on the severity of bronchial responsiveness in 30 children with allergic asthma during the period of specific allergen exposure. In children treated with BDP alone, PC20-FEV1 methacholine was 0.66 +/- 0.54 at the beginning and 1.91 +/- 2.11 at the end of the study period (p greater than 0.05). In children treated with BDP + S PC20, methacholine was 1.21 +/- 1.43 at the beginning and 4.22 +/- 3.88 at the end of the study (p less than 0.05). The group of children treated with placebo had a PC20-FEV1 methacholine of 0.79 +/- 0.61 at the beginning of the study and 0.80 +/- 0.46 at the end of the study. The results of the present study show that maintenance treatment with inhaled beclomethasone combined with salbutamol may lead to greater improvement in bronchial hyperreactivity than treatment with inhaled beclomethasone dipropionate alone.", "Some recent clinical investigations suggest that regular use of inhaled bronchodilators may lead to deterioration in asthma control.\n The purpose of this study was to evaluate the effect of albuterol dosing schedule on clinical outcome in subjects with moderate to severe stable asthma.\n Seventeen adults were randomized to two 15-week treatment periods in a double-blind crossover design. Throughout the study, subjects were instructed to take two inhalations four times daily from an unlabeled \"test\" canister. In the four times daily and as-needed (QID + PRN) period, this canister contained albuterol; in the as-needed (PRN) period, it contained placebo. A \"rescue\" albuterol canister was available for as-needed use at all times. Inhaler actuations from both the test and rescue canisters were electronically recorded. Outcome measures included prednisone requirements, morning and evening symptoms and peak expiratory flow rates, total and nighttime rescue albuterol use, and asthma-specific quality of life.\n The two treatment periods did not differ in symptoms, nighttime albuterol use, or asthma quality of life. During the QID+PRN period both morning and evening peak expiratory flow rates were significantly higher (p < 0.01 and 0.001, respectively) and total rescue use of albuterol was significantly less (p < 0.05) than the PRN period. Days on prednisone tended to be lower in the regular dosing period (p = 0.08).\n In our sample of patients with moderate to severe asthma, four times daily dosing of albuterol did not lead to deterioration of asthma control.", "Most clinical trials in asthma have focused on outcomes that are primarily of importance to the clinician. Very few have assessed whether patients feel better and can function better in day-to-day activities. The aim of this study was to compare the effects of salmeterol (50 micrograms twice daily), salbutamol (200 micrograms four times a day), and placebo on asthma-specific quality of life and to relate the findings to conventional clinical asthma outcomes. The study was a 12-wk multicenter, double blind, randomized, placebo-controlled crossover trial with each trial medication taken for 4 wk. The subjects were 140 adults with mild to moderate asthma enrolled from 14 respiratory clinics across Canada. Outcome measures were: (1) the Asthma Quality of Life Questionnaire and spirometry at the end of each treatment period; and (2) daily asthma symptoms, morning and evening peak expiratory flow rates (PEFRs), and rescue salbutamol use during the last 14 d of each treatment period. Asthma-specific quality of life, both overall and for the individual domains (activity limitation, symptoms, emotional function, and exposure to environmental stimuli) was better with salmeterol than with placebo (p < 0.0001), and better with salmeterol than with salbutamol (p < 0.001). In both comparisons, differences were not only statistically significant, but most were also clinically important. There were moderate correlations between change in quality of life and change in clinical outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)", "An effective, long-acting bronchodilator could benefit patients with asthma who have symptoms not controlled by antiinflammatory drugs. We compared a new long-acting, inhaled beta 2-adrenoceptor agonist, salmeterol, with a short-acting beta 2-agonist, albuterol, in the treatment of mild-to-moderate asthma.\n We randomly assigned 234 patients (150 male and 84 female patients 12 to 73 years old) to one of three treatment groups: one group received 42 micrograms of salmeterol twice daily, one received 180 micrograms of albuterol four times daily, and one received placebo. Treatment was assigned in a double-blind fashion, and all patients could use supplemental inhaled albuterol as needed during the 12-week treatment period.\n Measurements of the forced expiratory volume in one second, performed hourly for 12 consecutive hours, showed that a single dose of salmeterol produced a greater mean area under the curve than two doses of albuterol taken 6 hours apart (6.3 vs. 4.9 liter.hr, P < 0.05). The difference was significant on day 1 and at week 4 of the study, but not at week 8 or 12. Salmeterol was also more effective than albuterol or placebo (with albuterol taken as needed) in increasing the morning peak expiratory flow rate: salmeterol induced a mean increase of 24 liters per minute over the pretreatment values, as compared with a decrease of 6 liters per minute with albuterol (P < 0.001) and an increase of 1 liter per minute with placebo (P = 0.002). The mean overall symptom score was improved most by salmeterol treatment (P < 0.05), with the number of days with symptoms and of nights with awakenings decreasing by 22 percent and 52 percent, respectively; there were no differences in results between albuterol treatment and placebo administration. We found no evidence of tolerance to the bronchodilating effects of salmeterol, and adverse reactions to all the treatments were infrequent and mild.\n For the management of mild-to-moderate asthma, salmeterol given twice daily is superior to albuterol given either four times daily or as needed.", "Two multicenter, randomized, double-masked, placebo-controlled studies involving 451 adolescent and adult patients with mild-to-moderate asthma compared the efficacy and safety of salmeterol powder 50 micrograms twice daily with albuterol 180 micrograms four times daily or placebo (with albuterol as needed) for 12 weeks. Patients had forced expiratory volume in 1 second (FEV1) of 50% to 80%. Throughout the 12-week treatment period, the mean change from baseline in percentage of predicted FEV1 was significantly greater with salmeterol than with placebo; mean area under the curve for FEV1 was significantly greater with salmeterol than with albuterol or placebo. Significant improvements in morning and evening peak expiratory flow, percentage of nights without awakening, and asthma symptoms were observed with salmeterol. Salmeterol was well tolerated, and no clinically significant changes in electrocardiographic activity were observed.", "Treatment with inhaled beta(2)-agonists immediately before allergen inhalation inhibits allergen-induced early, but not late asthmatic responses (LAR). By contrast, 2 wk treatment with inhaled albuterol increases airway responses to inhaled allergen. We examined the effects of regular albuterol treatment on allergen-induced increases in inflammatory cells in blood and induced sputum. Ten mild, stable allergic asthmatics inhaled albuterol (800 micrograms/day) or placebo for 7 d in a controlled, randomized, double-blind, crossover study. Allergen inhalation was performed 12 h after the final dose. Methacholine airway responsiveness and blood samples were analyzed before and 24 h after, and induced sputum was obtained before, 7 h and 24 h after allergen. Allergen significantly reduced methacholine PC20, increased blood eosinophil numbers, and numbers of sputum neutrophils, EG2 positive and metachromatic cells (p < 0.05), without significant differences between treatments. Albuterol treatment significantly increased the LAR compared to placebo treatment (p = 0.003) and significantly enhanced the number of sputum eosinophils (p = 0.009) and sputum ECP (p = 0.04) at 7 h but not 24 h post-allergen (p > 0.05). We conclude that regular use of inhaled albuterol significantly increases the LAR to inhaled allergen, in association with an increase in the number of sputum eosinophils and the release of ECP, suggesting albuterol increases the late response by increasing eosinophil influx into the airways.", "Tolerance to the direct bronchodilator effects of beta 2-agonists does not appear to occur in asthma. However, it is not known whether this is true for the nonbronchodilator effects of these agents, which protect the airways against bronchoconstrictive stimuli.\n We investigated whether tolerance develops to the protective effect of inhaled terbutaline on airway responsiveness to the bronchoconstrictors methacholine (which acts directly on airway smooth muscle) and AMP (which acts indirectly by stimulating the release of mediators from mast cells) during sustained treatment with terbutaline. In a randomized, double-blind, crossover study, 12 patients with mild asthma each inhaled a single dose of terbutaline (500 micrograms) or placebo before a challenge with a series of doubling doses of inhaled methacholine or AMP, before and after treatment for seven days with 500 micrograms of terbutaline four times daily or placebo.\n Before the seven days of treatment with terbutaline, a single dose of terbutaline reduced airway responsiveness to methacholine by 2.7 doubling doses (95 percent confidence interval, 1.9 to 3.5), but it had an even greater protective effect against AMP, reducing airway responsiveness by 3.8 doubling doses (95 percent confidence interval, 2.7 to 4.9; P less than 0.001). After seven days of treatment with terbutaline, the protective effect of terbutaline against methacholine decreased to 2.2 doubling doses (95 percent confidence interval, 1.3 to 3.0; P = 0.04), and that against AMP decreased even more, to 1.7 doubling doses (95 percent confidence interval, 1.1 to 2.4; P less than 0.001). By contrast, the bronchodilator response to terbutaline was unchanged during seven days of treatment with this agent.\n We observed tolerance to the nonbronchodilator actions of the inhaled beta 2-agonist terbutaline in patients with mild asthma, an effect that may be more pronounced in mast cells than in bronchial smooth muscle. This property of beta-agonists may constitute a drawback to their regular use in patients with asthma.", "There is a transient rebound increase in bronchial reactivity to histamine and methacholine following regular treatment with an inhaled beta 2-agonist. We set out to determine whether the response to allergen was increased after cessation of regular inhaled terbutaline and whether concomitant inhaled budesonide modifies this response. In a double-blind, double-dummy, parallel group design we studied 41 subjects (37 evaluable) with mild asthma who were allergic to Dermatophagoides pteronyssinus, grass pollen, or cat fur. Following a 2 wk run-in period, subjects underwent a fixed three-dose allergen challenge based on their previously determined provocative concentration of allergen producing a 20% fall in FEV1 (PC20) before starting terbutaline 1,000 micrograms or placebo three times daily and budesonide 800 micrograms or placebo twice daily for a period of 2 to 4 wk (mean 18 d). The same three-dose allergen challenge was repeated 33 h after stopping treatment. During treatment evening peak flow values were highest in the terbutaline plus budesonide group. Following regular terbutaline there was no rebound increase in bronchial reactivity to allergen. Following budesonide there was a significantly smaller response to allergen and an increased FEV1 compared with the other three groups, including the budesonide plus terbutaline group. The changes in median (95% CI) allergen PC20 after budesonide, terbutaline, budesonide plus terbutaline, and placebo were 0.79 (0.3, 2.3), 0.11 (-0.4, 0.6), 0.24 (-0.4, 0.5) and -0.47 (-1.5, 0.1) doubling doses (p < 0.01). The respective changes in mean FEV1 were 0.34, -0.16, -0.01, and 0.06 L (p < 0.005). Thus bronchial reactivity to allergen was not increased after regular inhaled terbutaline.(ABSTRACT TRUNCATED AT 250 WORDS)", "Some recent studies suggest that regular beta(2)-agonist use may result in inadequate control of asthma. It has been hypothesized that this occurs particularly in allergic asthmatic patients exposed to relevant allergens. Moreover, it is still unclear whether this occurs during the use of both short-acting and long-acting beta(2)-agonists.\n Asthmatic patients (n = 145) allergic to house dust mite (HDM) were randomly allocated to monotherapy with a short-acting beta(2)-agonist (SA; n = 48), a long-acting beta(2)-agonist (LA; n = 50), or placebo (n = 47), double blind, double dummy. The study covered three periods: (1) a 4-week run-in period, in which no changes took place; followed by (2) cessation of treatment with asthma medication including inhaled corticosteroids, introduction of allergen avoidance measures (active/placebo treatment) to lower HDM exposure in the active group, and an 8-week washout period to adjust patients to these changes; followed by (3) a 12-week study medication period. At the start of the 12-week medication period, and every 4 weeks thereafter, spirometric measurements (FEV(1) and provocative concentration of histamine causing a 20% fall in FEV(1) [PC(20)]) were performed. Peak flow and asthma symptoms were recorded daily. Additionally, at the start and every 6 weeks thereafter, dust samples were collected from mattresses and living room and bedroom floors to assess HDM (der p 1) concentrations. Effects on FEV(1), PC(20), peak flow, and asthma symptoms were analyzed with repeated-measurement analysis and corrected for the exposure to HDM allergens.\n There were no significant differences among the three medication groups after 12 weeks for FEV(1). However, a significant decrease in mean FEV(1) percent predicted (95% confidence interval [CI]) was observed within the SA group: - 6.6 (- 10.4 to - 2.8) (p = 0.0002). A decrease in geometric mean PC(20) (95% CI) of - 1.2 (- 1.96 to - 0.44) doubling concentration was observed within the SA group (p = 0.05). No significant changes in FEV(1) and PC(20) were observed > 12 weeks within the LA group or the placebo group. There were neither changes in peak flow and asthma symptom scores among the three medication groups nor within the groups. Moreover, none of the parameters showed interactive effects with allergen exposure.\n There were no significant differences among the three medication groups for FEV(1) and PC(20). The within-treatment group comparison showed a significant small decline in FEV(1) for the SA group (but not for the LA group), which could indicate that monotherapy with SAs might have negative effects on FEV(1). This was not seen during regular use of LAS: No clear pathophysiologic mechanism can explain these findings at the moment. Relatively high or low exposure to allergens did not alter these findings.", "Regular monotherapy with inhaled beta 2-agonists may lead to a temporary increase of airway obstruction and increase of airway responsiveness after cessation of treatment. We investigated whether anti-inflammatory therapy may affect these rebound phenomena. In a double-blind, placebo-controlled study, we assessed lung function (FEV1) and airway responsiveness (PC20 methacholine [PC20]) during and after cessation of 2 wk of regular treatment with placebo and low-dose (250 micrograms) and high-dose (1,000 micrograms) inhaled terbutaline three times daily. Patients with mild allergic asthma (means [+/- SD] age of 28.2 +/- 6.6 yr, mean FEV1% of 91.9 +/- 14.6%, and geometric mean PC20 of 0.25 mg/ml) were studied. One group (n = 16) was randomized to budesonide treatment, 400 micrograms three times daily; the other group (n = 14) to placebo. PC20 and FEV1 were measured 10, 14, 34, and 82 h after the last terbutaline or placebo inhalation. A different method of statistical analysis was used, in that measurements performed at 10, 14, and 34 h were expressed relative to 82 h values in each period as an area-under-the-curve (AUC) value. FEV1 did not significantly change during placebo and budesonide treatment. Mean PC20 and morning and evening peak expiratory flow were significantly higher during budesonide treatment (p < 0.01). PC20 did not significantly change after cessation of terbutaline treatment in both placebo and budesonide treatment groups. AUC-FEV1 values after cessation of treatment with both doses of terbutaline were significantly different from the 82 h values (p < 0.05). The decrease in FEV1 was significantly greater after the last terbutaline and placebo inhalation in the placebo group compared with the budesonide treatment group (p = 0.02). We conclude that cessation of regular treatment after 2 wk with both low-dose and high-dose inhaled terbutaline does not result in a significant rebound airway responsiveness in patients with mild asthma. However, the results suggest a small rebound bronchoconstriction that does not occur when asthmatic patients are also treated with budesonide.", "The rebound increase in bronchial reactivity and fall in forced expiratory volume in one second (FEV1) following treatment with beta agonists seen in several studies has occurred regardless of concurrent steroid therapy. Little is known about the effect of adding beta agonists to corticosteroids, but in a recent study regular treatment with terbutaline appeared to reduce some of the beneficial effects of budesonide. The effects of budesonide alone and in combination with regular terbutaline treatment on lung function, symptom scores, and bronchial reactivity were therefore examined.\n Sixteen subjects with mild stable asthma inhaled budesonide 800 micrograms twice daily for two periods of 14 days with terbutaline 1000 micrograms three times daily or placebo in a double blind crossover fashion. FEV1 and the dose of histamine or adenosine monophosphate (AMP) causing a 20% fall in FEV1 (PD20) were measured before and 12 hours after the final dose of treatment, and changes from baseline were compared. Seven day mean values for daily morning and evening peak expiratory flow (PEF) values, symptom scores, and rescue medication were compared before and during treatment.\n Morning and evening PEF rose more with budesonide plus terbutaline than with budesonide alone, with a mean difference of 19 l/min occurring in the evening (95% confidence interval (CI) 2 to 36). There was no difference in symptom scores during treatment. Following treatment the mean increase in FEV1 was 150 ml higher with budesonide alone (95% CI-10 to 300). There was no difference between treatments in change in histamine and AMP PD20.\n Evening PEF was greater when budesonide was combined with regular terbutaline. There was no evidence of a difference in bronchial reactivity following the two treatment regimens. The findings of a previous study were not confirmed as the reduction in FEV1 after budesonide and terbutaline was smaller and not statistically significant. Further work is needed to determine whether this disparity in findings in the two studies is due to a type 2 statistical error in this study or a spurious finding in the previous study.", "Previous studies have shown that the regular administration of short acting beta-agonists can be associated with adverse effects on airway caliber and bronchial hyperresponsiveness (BHR) and that this may occur through a proinflammatory mechanism. The aim was to explore possible adverse effects of high-dose beta-agonist therapy and to assess any adverse interaction with corticosteroids. We undertook a randomized, crossover study to investigate the effects of 6 wk of treatment with regular terbutaline (1 mg four times a day), regular budesonide (400 microg twice a day), combined treatment, and placebo in subjects with mild to moderate asthma. Major endpoints were PD(15) saline, PD(20) methacholine, and induced sputum differential cell counts. Thirty-four subjects were randomized and 28 completed the study. PD(15) saline decreased on terbutaline alone compared with placebo treatment and on combined treatment compared with budesonide alone (mean fold decrease of 0.57 [95% CI = 0.36, 0.90] and 0.65 [95% CI = 0.43, 0.97], respectively). PD(20) methacholine was not affected by the use of terbutaline either alone or in combination with budesonide. The percentage of eosinophils in induced sputum increased during terbutaline treatment alone compared with placebo (median 8.3% versus 4.4%, p = 0.049). The addition of terbutaline to budesonide did not affect the percentage of eosinophils compared with budesonide treatment alone. These findings support the hypothesis that short-acting beta-agonists have a permissive effect on airway inflammation and that when used in high dose there may be an unfavorable interaction with inhaled corticosteroids.", "Inhaled formoterol is a potent selective beta 2-agonist with rapid onset and at least 12-h duration of bronchodilation. The aim of the study was to compare the bronchodilating effect of inhaled formoterol dry powder (dp) 12 micrograms b.i.d. with salbutamol dp 400 micrograms q.i.d. and placebo in patients with reversible obstructive airway disease (ROAD). The study design consisted of a closed 12-week double-blind, placebo-controlled, multicenter trial followed by an open noncomparative, multicenter, 12-month follow-up trial, in which the tolerability of formoterol dp was assessed. A total of 304 patients (146 men, 158 women) aged 18-79 years, ill during 0.1-64 years, were randomized. No demographic or baseline differences were found among the different treatment groups. The bronchodilating effect of formoterol, assessed by morning premedication PEFR, was significantly superior to placebo (P < 0.0001) and salbutamol (P < 0.0001). Efficacy was maintained during the open follow-up study with 12 micrograms b.i.d. in most of the patients. A few patients, however, needed 24 micrograms b.i.d. to control their ROAD. Formoterol 12 micrograms b.i.d. significantly reduced morning and evening asthma symptoms and sleep disturbances, and reduced significantly the need for rescue medication. The tolerability of the three treatment groups was comparable. In conclusion, formoterol 12 micrograms dp b.i.d. was significantly superior to both salbutamol 400 micrograms dp q.i.d. and placebo, and reduced asthma symptoms significantly. Overall, formoterol showed a tolerability profile comparable to that of salbutamol, and no tachyphylaxis was observed during 1 year of treatment.", "The adverse effects of long term treatment of asthma with the short acting beta agonist fenoterol have been established in both epidemiological and clinical studies. A study was undertaken to investigate the efficacy and safety of long term treatment with salbutamol and salmeterol in patients with mild to moderate bronchial asthma.\n In a two centre double dummy crossover study 165 patients were randomly assigned to receive salbutamol 400 micrograms q.i.d., salmeterol 50 micrograms b.i.d., or placebo via a Diskhaler. All patients used salbutamol as required for symptom relief. The study comprised a four week run in and three treatment periods of 24 weeks, each of which was followed by a four week washout. Asthma control was assessed by measuring mean morning and evening peak expiratory flow rate (PEFR), a composite daily asthma score, and minor and major exacerbation rates. Washout assessments included methacholine challenge and bronchodilator dose response tests. Analysis was by intention to treat.\n Data from 157 patients were analysed. Relative to placebo, the mean morning PEFR increased by 30 l/min (95% CI 26 to 35) for salmeterol but did not change for salbutamol. Evening PEFR increased by 25 l/min (95% CI 21 to 30) and 21 l/min (95% CI 17 to 26), respectively (p < 0.001). Salmeterol improved the asthma score compared to placebo (p < 0.001), but there was no overall difference with salbutamol. Only daytime symptoms were improved with salbutamol. The minor exacerbation rates were 0.29, 0.88, and 0.97 exacerbations/patient/year for salmeterol, salbutamol and placebo, respectively (p < 0.0001 for salmeterol). The corresponding major exacerbation rates were 0.22, 0.51 and 0.40, respectively (p < 0.03 for salmeterol). For salbutamol the asthma score deteriorated over time (p < 0.01), and the time spent in major exacerbation was significantly longer compared with placebo (12.3 days (95% CI 4.2 to 20.4) versus 8.4 days (95% CI 5.2 to 11.6), p = 0.02). There was no evidence of rebound deterioration in asthma control, lung function, or bronchial hyper-responsiveness following cessation of either active treatment, and no evidence of tolerance to salbutamol or salmeterol.\n Regular treatment with salmeterol is effective in controlling asthma symptoms and reduces minor more than major exacerbation rates. Salbutamol was associated with improved daytime symptoms but subtle deterioration in asthma control occurred over time. Salbutamol should therefore be used only as required.", "Regular treatment with beta 2-adrenergic agonists is controversial in bronchial asthma. To investigate whether beta 2-adrenergic agonists can be used safely if associated with low doses of inhaled steroids, for a short period, without a deterioration of asthma control, we have examined 24 mild asthmatics. In a parallel, double-blind, placebo-controlled study, 1 week of run-in and run-out period framed 3 weeks of treatment. All patients received inhaled beclomethasone dipropionate (BDP 250 micrograms t.i.d.); after 1 week, 12 patients inhaled 400 micrograms of broxaterol and 12 patients received placebo t.i.d. FVC, FEV1, PD20-FEV1 methacholine, morning and evening PEF, and PEF amplitude % mean were measured before, during, and after treatment. No significant changes were noted in patients receiving inhaled broxaterol. There were no differences in symptoms and the use of rescue medication (salbutamol spray). We conclude that short-term regular treatment with beta 2-adrenergic agonists is not associated with a deterioration in asthma control in mild asthmatics inhaling low doses of steroids.", "Regular inhaled beta 2 agonist causes tolerance to the acute protective effect of beta 2 agonist against bronchoconstriction induced by chemical stimuli such as AMP, histamine, and methacholine. We examined a more clinically relevant stimulus, inhaled allergen, in a double-blind, cross-over, random-order trial in 13 mild atopic asthmatics, who had not used beta 2 agonist for at least 4 weeks. We compared regular inhaled salbutamol (200 micrograms four times daily for 2 weeks) with placebo (2 weeks) for effects on bronchodilator response, baseline methacholine, and allergen airway responsiveness, and on the acute protective effect of salbutamol against both stimuli. Baseline forced expiratory volume in 1 s (FEV1), bronchodilator response, and methacholine responsiveness were the same during both treatment periods. After regular salbutamol, the allergen PC20 (provocation concentration producing a 20% FEV1 decrease) fell by 0.91 (SD 0.66) (p = 0.0009) doubling doses, and the protective effects of salbutamol on methacholine and allergen were both significantly reduced (p = 0.026 and 0.025, respectively). Taking into account the reduced baseline allergen PC20, the post-salbutamol allergen PC20 was almost 2 doubling doses (1.94 [1.43], p < 0.01) lower during salbutamol treatment. Thus, 2 weeks of regular inhaled salbutamol increased airway responsiveness to allergen but not to methacholine, and caused tolerance to the protective effect of salbutamol on bronchoconstriction induced by both stimuli. These effects of inhaled beta 2 agonist provide further evidence to support detrimental effects of their regular use.", "High doses of inhaled salbutamol produce substantial improvements in airway response in patients with asthma, and are associated with dose-dependent systemic beta-adrenoceptor responses. The purpose of the present study was to investigate whether tachyphylaxis occurs during prolonged treatment with high dose inhaled salbutamol. Twelve asthmatic patients (FEV1, 81 +/- 4% predicted), requiring only occasional inhaled beta-agonists as their sole therapy, were given a 14-day treatment with high dose inhaled salbutamol (HDS), 4,000 micrograms daily, low dose inhaled salbutamol (LDS), 800 micrograms daily, or placebo (PI) by metered-dose inhaler in a double-blind, randomized crossover design. During the 14-day run-in and during washout periods, inhaled beta-agonists were withheld and ipratropium bromide was substituted for rescue purposes. At the end of each 14-day treatment, a dose-response curve (DRC) was performed, and airway (FEV1, FEF25-75) chronotropic (HR), tremor, and metabolic (K, Glu) responses were measured at each step (from 100 to 4,000 micrograms). Treatment had no significant effect on baseline values. There were dose-dependent increases in FEV1 and FEF25-75 (p less than 0.001), and pretreatment with HDS did not displace the DRC to the right. DRC for HR (p less than 0.001), K (p less than 0.001), and Glu (p less than 0.005) were attenuated after treatment with HDS compared with PI. There were also differences between HDS and LDS for HR (p less than 0.001) and Glu (p less than 0.05) responses. Frequency and severity of subjective adverse effects were also reduced after HDS: tremor (p less than 0.001), palpitations (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "Pretreatment with inhaled beta 2-agonists is often recommended for the prevention of exercise-induced bronchoconstriction. Regular treatment with inhaled beta 2-agonists has been associated with worsened baseline airway caliber and increased airway responsiveness. In this study, we have investigated the effects of regular inhaled albuterol on the severity of exercise-induced bronchoconstriction using a double-blind, placebo-controlled, randomized, crossover design. Ten subjects inhaled either albuterol or placebo (2 x 100 micrograms, four times per day) for 7 d. On the eighth and ninth days of treatment periods, subjects performed 5-min constant work rate cycle ergometry exercise challenges after inhaling 200 micrograms of placebo (eighth day) or albuterol (ninth day). Forced expired volume in 1 s (FEV1) was measured on arrival in the laboratory as well as before and for 1 h after exercise. One week of regular inhaled albuterol compared with placebo resulted in: (1) a lower baseline FEV1 (mean difference, 230 ml) (p = 0.02); (2) a lower minimum postexercises FEV1 without inhaled albuterol pretreatment (mean difference, 390 ml; range, -50 ml to 1,250 ml) (p = 0.01); (3) a lower minimum postexercise FEV1 with inhaled albuterol pretreatment (p < 0.01). The smallest degree of exercise-induced bronchoconstriction occurred after a week of regular placebo and pretreatment with inhaled albuterol immediately before exercise. Inhalation of albuterol four times daily for 1 wk worsens exercise-induced bronchoconstriction; however, it remains extremely effective when used immediately before exercise for preventing bronchoconstriction.", "To compare the long-term efficacy and safety of albuterol administration using a Spiros Inhalation System (Dura Pharmaceuticals; San Diego, CA) dry powder inhaler (DPI) and albuterol (Ventolin; Glaxo Wellcome; Research Triangle Park, NC) administration using a metered-dose inhaler (MDI) in patients with asthma.\n This was a phase III, 12-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 283 adolescent and adult patients with mild to moderate asthma. The patients were randomized into one of three treatment groups: the Spiros group, who were given 108 microg/actuation of albuterol sulfate equivalent to 90 microg of albuterol base; the MDI group, who were given 90 microg/actuation of albuterol; and the placebo group.\n Over the length of the study, the Spiros and MDI groups were comparable in all FEV1 parameters. Both active treatment groups were superior to the placebo group for each FEV1 parameter at all visits. With the exception of differences at treatment week 0 for the maximum percent change in the FEV1, the duration of effect, and the area under the curve at baseline, there were no statistically significant differences between the Spiros and MDI groups for any FEV1 parameters. Using a repeated-measures analysis, the FEV1 parameters at week 0 for the Spiros group were not statistically significantly different from the parameters at weeks 4, 8, and 12. The same analysis effect at week 0 for the MDI group was greater for maximum percent change in the FEV1 from baseline (weeks 4, 8, and 12) and duration of effect. Adverse events and changes in clinical laboratory values, vital signs, ECG results, and physical examinations were reported with similar incidence in each of the three treatment groups.\n Both active treatments were superior to the placebo treatment. The Spiros DPI was well tolerated and was as effective as the albuterol MDI in treating patients with moderate asthma.", "Although many asthmatic patients are treated with a combination of beta2 agonist and corticosteroid inhalers, the clinical effects of combining the drugs are unknown. Studies on the early asthmatic response to allergen suggest that beta2 agonists may reduce the benefit of inhaled corticosteroids. A study of the effects of combining the drugs on asthma control was undertaken.\n Sixty one subjects with mild to moderate asthma were randomised to a double blind crossover comparison of inhaled budesonide (200-400 microg twice daily), terbutaline (500-1000 microg four times daily), combined treatment, and placebo. Each treatment was given for six weeks following a four week washout period. Ipratropium was used for symptom relief. Treatments were ranked from worst (1) to best (4) based on need for oral steroid, mean morning peak flow, nocturnal awakening, ipratropium use, and asthma symptoms. Lung function and bronchial hyperresponsiveness were measured before and after each treatment.\n Evaluable data for all four treatments were obtained from 47 subjects. The mean rank of each treatment was: placebo = 2.05; terbutaline = 2.13; budesonide = 2.48; combined treatment = 3.34. Combined treatment was ranked significantly better than any other treatment (p<0.01). Mean (95% CI) morning and evening peak flows were 14 (5 to 23) and 24 (15 to 34) l/min higher, respectively, during combined treatment than during budesonide, and 27 (17 to 37) and 15 (7 to 23) l/min higher than during terbutaline. Asthma symptoms tended to be least frequent during combined treatment but were not significantly different from budesonide alone. There was no significant difference between combined treatment and budesonide alone for lung function and bronchial hyperresponsiveness.\n In this group of mild to moderate asthmatic subjects the combination of beta2 agonist and corticosteroid gave better asthma control than either treatment alone. There was no evidence that regular beta2 agonist treatment impaired the beneficial effect of inhaled corticosteroid.", "Salbutamol is frequently used as a bronchodilator for infants who wheeze. Many single dose studies have questioned its effectiveness.\n To investigate the response of wheezy infants to salbutamol over an extended time period in order to elucidate either symptomatic relief or a protective effect.\n Eighty infants under 1 year, with persistent or recurrent wheeze and a personal or family history of atopy, were recruited to a randomised, double blind, cross over, placebo controlled trial. Salbutamol (200 microg three times daily) or placebo were administered regularly over two consecutive treatment periods of four weeks via a spacer and mask. Symptoms of wheeze and cough were recorded in a diary. At the end of the study pulmonary function tests were performed before and after salbutamol (400 microg).\n Forty eight infants completed the diary study; 40 infants underwent pulmonary function testing. No difference in mean daily symptom score was observed between the salbutamol and placebo periods. There was no difference in the number of symptom free days. Compliance and forced expiratory flows remained unchanged and resistance increased following salbutamol. There was no relation between the response measured by symptom score or pulmonary function in individual patients.\n In wheezy infants with an atopic background, there was no significant beneficial effect of salbutamol on either clinical symptoms or pulmonary function. Clinical effects could not be predicted from pulmonary function tests. Salbutamol cannot be recommended as the bronchodilator of choice in this age group.", "Formoterol is a beta2-adrenergic agent which, when inhaled, produces rapid and long-lasting bronchodilatation.\n The aim of this study was to compare the efficacy, safety, and tolerability of formoterol powder for inhalation delivered via the Aerolizer device with placebo and with albuterol delivered via metered-dose inhaler in patients with mild to moderate persistent asthma.\n In a multicenter, double-blind, parallel-group study, 541 patients were randomized at 26 trial sites to receive either formoterol, 12 microg twice daily; formoterol, 24 microg twice daily; albuterol, 180 microg four times daily; or a placebo for 12 weeks. The effects of each treatment on lung function, asthma symptoms, and frequency of rescue albuterol use were evaluated. Adverse effects and clinical laboratory parameters were also evaluated.\n The bronchodilatory effects of formoterol were rapid in onset and persisted for 12 hours. Both formoterol doses were more effective than placebo and albuterol for objective measures of lung function. Morning and evening peak expiratory flow rates were more improved with formoterol, and formoterol provided significantly greater improvements in asthma symptom scores compared with both albuterol and placebo. Overall, patients taking formoterol used significantly less rescue medication than did those taking albuterol or placebo. Nocturnal awakenings occurred less often with formoterol than with placebo or albuterol. The therapeutic effects of formoterol were maintained over the entire 12 weeks of treatment. Adverse events were similar for all treatment groups, and clinical laboratory data were unremarkable.\n Rapid-onset, long-acting formoterol, administered via the Aerolizer inhaler, is an effective and safe treatment for patients with mild to moderate persistent asthma.", "The effect of regular inhaled beta-agonist on the treatment of exercise-induced bronchoconstriction was studied. Eight subjects with exercise-induced bronchoconstriction took 1 week each of salbutamol 200 microg qid or placebo in a random-order, double-blind, crossover study. They then withheld this treatment for 8 hours before performing a dry-air, sub-maximal exercise challenge at a work-rate previously shown to induce a 15% fall in forced expiratory volume in 1 second (FEV1). Five minutes after exercise, they inhaled salbutamol 100, 100, and 200 microg at 5-minute intervals. The mean pre-exercise FEV1 was similar on both study days. However, pretreatment for 1 week with salbutamol led to a significantly greater fall in FEV1 after exercise. The FEV1 remained lower than during the placebo arm despite the administration of salbutamol after exercise. This difference persisted 25 minutes after exercise. It is concluded that regular beta-agonist treatment leads to increased exercise-induced bronchoconstriction and a suboptimal bronchodilator response to beta-agonist. The data suggest that previous regular beta-agonist treatment may lead to a failure to respond to emergency bronchodilator treatment during an acute asthma attack and support current opinion that regular short-acting beta-agonist therapy should not be used to treat asthma.", "It has been suggested that regular treatment with high doses of beta 2-agonists might result in poorer control of asthma and increased bronchial responsiveness. We have examined change in FEV1 (delta FEV1), bronchial reactivity, peak expiratory flow (PEF), and symptoms during and after 3 wk of regular treatment with a relatively low dose of albuterol and broxaterol, a new beta 2-agonist. Eleven subjects 18 to 50 yr of age with mild asthma inhaled albuterol (200 micrograms), broxaterol (400 micrograms), or placebo three times a day for 3 wk with a 2- to 4-wk run-in/washout period between treatments. Ipratropium bromide was allowed for symptomatic relief. The PD20 (dose of histamine causing a 20% fall in FEV1) was measured before and 11, 35, and 59 h after cessation of treatment and a bronchodilator dose-response study before and 83 h after cessation of treatment. Change from baseline after albuterol and broxaterol are compared with change after placebo. Diurnal change in PEF (amplitude % mean) increased during treatment with albuterol by 6.5% (95% CI, 1.7-12.3; p < 0.02) mainly because of a fall in morning PEF. Cessation of treatment with both beta 2-agonists was associated with a fall in FEV1 and PD20 compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)", "This study compared the efficacy of a low dose of formoterol Turbuhaler 6 micrograms b.i.d. (F) with that of terbutaline 0.5 mg q.i.d. (T), and placebo (P) from Turbuhaler. After a 2-week run-in, 397 adults with mild to moderate asthma were randomly allocated to one of the treatments for 12 weeks. During run-in, the mean morning peak expiratory flow (PEF) was 360 (F), 368 (T) and 367 1 min-1 (P). F was better than T (P = 0.014) and P (P = 0.0001) in improving morning PEF [mean changes from run-in: 20 (F), 9 (T), and 21 min-1 (P)]. F was statistically significantly more effective than either T or P in reducing asthma symptoms. F gave also statistically significantly higher evening PEF and less use of rescue medication than P. Bronchodilator response to study drugs and additional 1.25 mg terbutaline was similar before and after the 12-week treatment period. There were no adverse effects of clinical relevance. In conclusion, formoterol Turbuhaler, 6 micrograms b.i.d. was more effective in improving PEF and offered better asthma control than either terbutaline Turbuhaler, 0.5 mg q.i.d. or placebo. Regular use of formoterol did not reduce the bronchodilator response to additional terbutaline. There were no clinically relevant adverse effects.", "Recent studies have suggested that regular use of inhaled beta 2 agonists cause loss of asthma control as measured by worsening peak-flow rates, increased asthma symptoms, and more frequent need for supplementary bronchodilators. However, the magnitude of this effect and the reliability of investigator-originated definitions of control is unknown. We studied 341 people with asthma in a four-week, randomised, crossover trial of regular salbutamol (2 puffs--200 micrograms--four times daily) for two weeks and as needed for two weeks. There were no significant differences in morning and evening peak-flow rates between treatments but asthma symptoms and supplementary bronchodilator use were significantly less frequent when salbutamol was given regularly. Asthma episodes occurred 1.39 (1.52) times per day during regular treatment and 2.44 (1.75) times per day during as-needed treatment (p < 0.0001) and 0.50 (0.56) vs 0.65 (0.66) times per night (p < 0.0001). Daytime use of supplementary salbutamol was 1.14 (1.40) vs 2.35 (1.71) puffs per day, (p < 0.0001); night-time use was 0.45 (0.55) vs 0.64 (0.66) puffs per night (p < 0.0001). When control endpoints were compared between treatment periods for each individual by two blinded investigators and control judged by six different sets of criteria, in 70 asthmatics there was no difference in symptom control between periods but in the remainder, control was achieved more often by regular than by as-needed salbutamol (166 vs 69, p < 0.0001). In asthma of moderate severity, regularly administered salbutamol does not produce lower peak flow rates than as-needed salbutamol and is associated with less frequent asthma symptoms.", "We compared the effects of salmeterol (Sm) (50 micrograms twice daily) with that of salbutamol (Sb) (200 micrograms four times daily) and placebo (P) in patients with mild-to-moderate asthma with asthma symptoms and related the effectiveness of these therapies between patients who used concurrent inhaled corticosteroids (ICS) and those who did not. The study was a 12-wk, multicenter, double-blind, placebo-controlled crossover trial with 367 adult asthmatics randomized to each trial medication for 4 wk. Inhaled Sb was provided as rescue medication to all patients throughout the trial. Only 80% of patients, albeit the majority, were receiving maintenance treatment with ICS throughout this trial; this reflects practice current in early 1990. Each study day, patients recorded their morning and evening peak expiratory flows (PEF), assessment of asthma symptoms, and use of rescue medication. Both morning and evening PEF were greater during treatment with Sm than with Sb (mean differences between the treatments of 29.8 and 14.3 L/min, respectively) or P (27.7 and 20.3 L/min, respectively) (p < 0.0001). Sm was also more effective than Sb or P in lowering diurnal variation in PEF and increasing the percentage of symptom-free days and rescue-free days and nights with no sleep disturbance (p < or = 0.0004). Sb was more effective than P in increasing evening PEF and the percentage of symptom-free days (p < 0.05) and rescue-free days (p < 0.0001). The same clinical superiority of Sm compared with Sb and P was observed in those patients using ICS (p < 0.001 for all treatment comparisons), and to a greater extent than in those patients not using ICS (i.e., Sm was more effective than Sb and P in just six of the 20 treatment comparisons; p < 0.05). In conclusion, Sm 50 micrograms twice daily is effective in the management of mild-to-moderate asthma and it further improves asthma control in patients already using ICS.", "Seventeen asthmatic patients were allocated at random to one of two treatment regimens: prophylactic (10 patients), in which salbutamol inhaler was used regularly in a dose of 200 micrograms 4-times daily; or symptomatic (7 patients), in which a placebo inhaler was used regularly as 2 actuations 4-times daily. In both regimens, an 'escape' salbutamol inhaler was given to be used for symptomatic relief if and when needed. The study lasted 12 months, after a run-in period of 1 month to accustom patients to the trial procedure. At the end of the year, 16 patients transferred to the alternative regimen for a further 3 months. Both groups were well matched except that the group starting with the prophylactic regimen had more severe airways obstruction than the symptomatic group. Patients were assessed by daily scores of their asthmatic symptoms, twice daily PEFR measurements and the amount of anti-asthmatic medication used. Acute reversibility tests were performed every month at the clinic visits. Patients treated prophylactically had less seasonal variation in PEFR and generally lower symptom scores despite a lower mean PEFR. There was no evidence to suggest tolerance was developing either by acute reversibility tests or by an escalating use of symptomatic salbutamol or other anti-asthma medication. The prophylactic use of salbutamol seemed to provide a more stable control of asthma, offering potential benefit to patients.", "The aim of this study was to compare the effect of regular versus intermittent (p.r.n.) bronchodilators on bronchial reactivity and asthma control in patients on concomitant inhaled corticosteroids. We studied 12 patients with asthma in a prospective, randomised, single-blind, single-dummy, three-period crossover trial comparing placebo (2 puffs t.d.s.), salbutamol (200 micrograms t.d.s.) and oxitropium bromide (200 micrograms t.d.s.) for 28 days each. Computerised spirometry and bronchial reactivity to histamine were obtained on entry and after each treatment period. Symptom scores, use of rescue bronchodilator and peak expiratory flow rates were recorded daily. There were no significant differences in bronchial hyperreactivity between the salbutamol, oxitropium and placebo treatment periods. There were no significant differences in baseline FEV1, FEF25-75%, symptom scores, use of rescue bronchodilator or morning and evening PEFR between treatment periods. Intermittent beta agonist therapy is as effective as regular therapy in terms of asthma control and bronchial hyperreactivity in patients on concomitant inhaled corticosteroid therapy. Since intermittent therapy achieves similar results with significantly lower beta agonist consumption, the data support current recommendations that beta agonists should be taken on a p.r.n. basis in asthma patients on inhaled steroids.", "Inhaled beta-agonists are the most commonly used treatment for asthma, but data suggest that regularly scheduled use of these agents may have deleterious effect on the control of asthma. We compared the effects of regularly scheduled use of inhaled albuterol with those of albuterol used only as needed in patients with mild chronic, stable asthma.\n In a multicenter, double-blind study, we randomly assigned 255 patients with mild asthma to inhale albuterol either on a regular schedule (126 patients) or only as needed (129 patients). The patients were followed for 16 weeks.\n The primary outcome indicator, peak expiratory air flow measured in the morning, did not change significantly during the treatment period in the scheduled (416 liters per minute after the run-in period and 414 liters per minute after the treatment period) or the as-needed (424 liters per minute at both times) treatment groups (P=0.71). There were no significant differences between the two groups in peak flow variability, forced expiratory volume in one second, the number of puffs of supplemental albuterol needed, asthma symptoms, asthma quality-of-life score, or airway responsiveness to methacholine. The statistically significant differences between the groups in evening peak flow and in the short-term bronchodilator response to inhaled albuterol were small and judged to be clinically unimportant.\n In patients with mild asthma, neither deleterious nor beneficial effects derived from the regular use of inhaled albuterol beyond those derived from use of the drug as needed. Inhaled albuterol should be prescribed for patients with mild asthma on an as-needed basis.", "Adult, nonsmoking patients with mild to moderate asthma were randomized to receive 4 mg nedocromil sodium (n = 13), 200 micrograms albuterol (n = 13), or placebo (n = 12) four times daily for 16 wk in a double-blind, double-dummy protocol. Before and after treatment, patients underwent histamine bronchial provocation, followed by fiberoptic bronchoscopy. Bronchial mucosal biopsy tissue and bronchoalveolar lavage fluid were examined in detail. Daily diary cards were kept by each patient. Compared with baseline, the numbers of total (EG1) and activated (EG2) eosinophils, expressed as cells per square millimeter of bronchial biopsy tissue, decreased after treatment with nedocromil sodium (pretreatment: EG1 = 152.2 +/- 42.5 and EG2 = 143.8 +/- 36.8; post-treatment: EG1 = 115.4 +/- 35.1 and EG2 = 104.9 +/- 31.6) and increased after treatment with albuterol (pretreatment: EG1 = 129.3 +/- 28.0 and EG2 = 127.5 +/- 30.2; post-treatment: EG1 = 238.0 +/- 55.0 and EG2 = 211.4 +/- 50.4). Although the changes between the active treatment groups were significantly different (p < 0.05), no such significant differences were found in eosinophil numbers before and after treatment when comparisons were made between either of the active treatment groups and the placebo group. Although not significant, the changes in concentration of eosinophil cationic protein in bronchoalveolar lavage reflected the changes seen in numbers of activated eosinophils. No treatment differences were detected for mast cell or lymphocyte numbers. There were no statistical differences between treatment groups for clinical findings, with the exception of evening peak flow, which was significantly increased (p < 0.05) in the albuterol group.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "19376585", "20855114", "22537617", "21459215", "17917738", "20980427", "20416952", "22330964", "21529957", "16154196" ]

[ "Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema.", "Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study.", "One-year outcomes of the da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema.", "The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema.", "Intravitreal bevacizumab with or without triamcinolone for refractory diabetic macular edema; a placebo-controlled, randomized clinical trial.", "Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study.", "A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2.", "Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE.", "A phase 2/3, multicenter, randomized, double-masked, 2-year trial of pegaptanib sodium for the treatment of diabetic macular edema.", "A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema." ]

[ "To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment of diabetic macular edema (DME).\n Randomized 3-arm clinical trial.\n A total of 150 eyes of 129 patients with clinically significant DME and no previous treatment.\n The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB (50 eyes); the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT (50 eyes); and the MPC group, patients who underwent focal or modified grid laser (50 eyes). Retreatment was performed at 12-week intervals whenever indicated.\n Change in best-corrected visual acuity (VA) at week 24.\n VA changes among the groups were statistically significant at 6 (P<0.001) and 24 (P = 0.012) weeks. The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks. VA changes +/- standard deviation at 36 weeks were -0.28+/-0.25, -0.04+/-0.33, and +0.01+/-0.27 logarithm of minimum angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively (P = 0.053). Significant central macular thickness (CMT) reduction was observed in all groups only up to 6 weeks; however, CMT changes were not significant among the groups in all visits. Overall, retreatment was required for 27 eyes up to 36 weeks (14 in the IVB group, 10 in the IVB/IVT group, and 3 in the MPC group). In the IVB group, in which a greater VA improvement was observed, only 1 injection was required in 72% of the cases. VA improvement >2 Snellen lines at 36 weeks was detected in 37%, 25%, and 14.8% of patients in the IVB, IVB/IVT, and MPC groups, respectively.\n Intravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation. A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected. No adjunctive effect of IVT was demonstrated.\n The author(s) have no proprietary or commercial interest in any materials discussed in this article.", "To determine the long-term effects of ranibizumab (RBZ) in patients with diabetic macular edema (DME).\n Prospective, randomized, interventional, multicenter clinical trial.\n One hundred twenty-six patients with DME.\n Subjects were randomized 1:1:1 to receive 0.5 mg RBZ at baseline and months 1, 3, and 5 (group 1), focal or grid laser photocoagulation at baseline and month 3 if needed (group 2), or a combination of 0.5 mg RBZ and focal or grid laser at baseline and month 3 (group 3). Starting at month 6, if retreatment criteria were met, all subjects could be treated with RBZ.\n The mean change from baseline in best-corrected visual acuity (BCVA) at month 24.\n After the primary end point at month 6, most patients in all groups were treated only with RBZ, and the mean number of injections was 5.3, 4.4, and 2.9 during the 18-month follow-up period in groups 1, 2, and 3, respectively. For the 33 patients in group 1, 34 patients in group 2, and 34 patients in group 3 who remained in the study through 24 months, the mean improvement in BCVA was 7.4, 0.5, and 3.8 letters at the 6-month primary end point, compared with 7.7, 5.1, and 6.8 letters at month 24, and the percentage of patients who gained 3 lines or more of BCVA was 21, 0, and 6 at month 6, compared with 24, 18, and 26 at month 24. The percentage of patients with 20/40 or better Snellen equivalent at month 24 was 45% in group 1, 44% in group 2, and 35% in group 3. Mean foveal thickness (FTH), defined as center subfield thickness, at month 24 was 340 μm, 286 μm, and 258 μm for groups 1, 2, and 3, respectively, and the percentage of patients with center subfield thickness of 250 μm or less was 36%, 47%, and 68%, respectively.\n Intraocular injections of RBZ provided benefit for patients with DME for at least 2 years, and when combined with focal or grid laser treatments, the amount of residual edema was reduced, as were the frequency of injections needed to control edema.\n Proprietary or commercial disclosure may be found after the references.\n Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To compare different doses and dosing regimens of Vascular Endothelial Growth Factor (VEGF) Trap-Eye with laser photocoagulation in eyes with diabetic macular edema (DME).\n Randomized, double-masked, multicenter, phase 2 clinical trial.\n Diabetic patients (n = 221) with center-involved DME.\n Participants were assigned randomly to 1 of 5 treatment regimens: VEGF Trap-Eye 0.5 mg every 4 weeks (0.5q4); 2 mg every 4 weeks (2q4); 2 mg every 8 weeks after 3 initial monthly doses (2q8); or 2 mg dosing as needed after 3 initial monthly doses (2PRN), or macular laser photocoagulation.\n The change in best-corrected visual acuity (BCVA) at 24 weeks (the primary end point) and at 52 weeks, proportion of eyes that gained 15 letters or more in Early Treatment of Diabetic Retinopathy Study (ETDRS) BCVA, and mean changes in central retinal thickness (CRT) from baseline.\n As previously reported, mean improvements in BCVA in the VEGF Trap-Eye groups at week 24 were 8.6, 11.4, 8.5, and 10.3 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus 2.5 letters for the laser group (P ≤ 0.0085 versus laser). Mean improvements in BCVA in the VEGF Trap-Eye groups at week 52 were 11.0, 13.1, 9.7, and 12.0 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus -1.3 letters for the laser group (P ≤ 0.0001 versus laser). Proportions of eyes with gains in BCVA of 15 or more ETDRS letters at week 52 in the VEGF Trap-Eye groups were 40.9%, 45.5%, 23.8%, and 42.2% versus 11.4% for laser (P = 0.0031, P = 0.0007, P = 0.1608, and P = 0.0016, respectively, versus laser). Mean reductions in CRT in the VEGF Trap-Eye groups at week 52 were -165.4 μm, -227.4 μm, -187.8 μm, and -180.3 μm versus -58.4 μm for laser (P < 0.0001 versus laser). Vascular Endothelial Growth Factor Trap-Eye generally was well tolerated. The most frequent ocular adverse events with VEGF Trap-Eye were conjunctival hemorrhage, eye pain, ocular hyperemia, and increased intraocular pressure, whereas common systemic adverse events included hypertension, nausea, and congestive heart failure.\n Significant gains in BCVA from baseline achieved at week 24 were maintained or improved at week 52 in all VEGF Trap-Eye groups. Vascular Endothelial Growth Factor Trap-Eye warrants further investigation for the treatment of DME.\n Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic macular edema (DME).\n A 12-month, randomized, double-masked, multicenter, laser-controlled phase III study.\n We included 345 patients aged ≥18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME.\n Patients were randomized to ranibizumab + sham laser (n = 116), ranibizumab + laser (n = 118), or sham injections + laser (n = 111). Ranibizumab/sham was given for 3 months then pro re nata (PRN); laser/sham laser was given at baseline then PRN (patients had scheduled monthly visits).\n Mean average change in BCVA from baseline to month 1 through 12 and safety.\n Ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 (+6.1 and +5.9 vs +0.8; both P<0.0001). At month 12, a significantly greater proportion of patients had a BCVA letter score ≥15 and BCVA letter score level >73 (20/40 Snellen equivalent) with ranibizumab (22.6% and 53%, respectively) and ranibizumab + laser (22.9% and 44.9%) versus laser (8.2% and 23.6%). The mean central retinal thickness was significantly reduced from baseline with ranibizumab (-118.7 μm) and ranibizumab + laser (-128.3 μm) versus laser (-61.3 μm; both P<0.001). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved significantly from baseline with ranibizumab alone and combined with laser (P<0.05 for composite score and vision-related subscales) versus laser. Patients received ∼7 (mean) ranibizumab/sham injections over 12 months. No endophthalmitis cases occurred. Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms. Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study.\n Ranibizumab monotherapy and combined with laser provided superior visual acuity gain over standard laser in patients with visual impairment due to DME. Visual acuity gains were associated with significant gains in VFQ-25 scores. At 1 year, no differences were detected between the ranibizumab and ranibizumab + laser arms. Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration.\n Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To evaluate the effect of three intravitreal injections of bevacizumab (IVB) alone or combined with triamcinolone (IVT) in the first injection for treatment of refractory diabetic macular edema (DME).\n In this prospective, placebo-controlled, randomized clinical trial, 115 eyes of 101 patients with refractory DME were included. Subjects were randomly assigned to one of the three study arms: 1) three injections of IVB (1.25 mg/0.05 ml) at 6-week intervals, 2) combined IVB and IVT (1.25 mg/0.05 ml and 2 mg/0.05 ml respectively) followed by two injections of IVB at 6-week intervals, and 3) sham injection (control group). The primary outcome measure was change in central macular thickness (CMT). Secondary outcome measures were change in best-corrected logMAR visual acuity (BCVA ) and incidence of potential adverse events.\n Central macular thickness was reduced significantly in both the IVB and IVB/IVT groups. At week 24, CMT change compared to the baseline was -95.7 microm (95% CI, -172.2 to -19.26) in the IVB group, -92.1 microm (95% CI, -154.4 to -29.7) in the IVB/IVT group, and 34.9 microm (95% CI, 7.9 to 61.9) in the control group. There was a significant difference between the IVB and control groups (P = 0.012) and between the IVB/IVT and control groups (P = 0.022). Improvement of BCVA was initiated at weeks 6 and 12 in the IVB/IVT and IVB groups respectively. In terms of BCVA change compared to the baseline at 24 weeks, the differences between the IVB and control groups (P = 0.01) and also between the IVB/IVT and control groups (P = 0.006) were significant. No significant differences were detected in the changes of CMT and BCVA between the IVB and IVB/IVT groups (P = 0.99). Anterior chamber reaction was noticed in eight (19.5%) and seven (18.9%) eyes respectively in the IVB and IVB/IVT groups the day after injection, and it resolved with no sequel. Elevation of IOP occurred in three eyes (8.1%) in the IVB/IVT group.\n Three consecutive intravitreal injections of bevacizumab had a beneficial effect on refractory DME in terms of CMT reduction and BCVA improvement. Addition of triamcinolone in the first injection seemed to induce earlier visual improvement; however, it did not show any significant additive effect later during follow-up.", "The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.\n This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age>18 years, type 1 or 2 diabetes, central retinal thickness [CRT]≥300 μm, and best corrected visual acuity [BCVA] of 73-39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n=51 each) or sham (n=49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n=151, patients receiving≥1 injection).\n At month 12, mean±SD BCVA improved from baseline by 10.3±9.1 letters with ranibizumab and declined by 1.4±14.2 letters with sham (P<0.0001). Mean CRT reduction was 194.2±135.1 μm with ranibizumab and 48.4±153.4 μm with sham (P<0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P<0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab.\n Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.", "To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant diabetic macular edema (CSME).\n Prospective, randomized, masked, single-center, 2-year, 2-arm clinical trial.\n A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT.\n Subjects were randomized to either ivB (6 weekly; minimum of 3 injections and maximum of 9 injections in the first 12 months) or MLT (4 monthly; minimum of 1 treatment and maximum of 4 treatments in the first 12 months).\n The primary end point was the difference in ETDRS best-corrected visual acuity (BCVA) at 12 months between the bevacizumab and laser arms.\n The baseline mean ETDRS BCVA was 55.7+/-9.7 (range 34-69) in the bevacizumab group and 54.6+/-8.6 (range 36-68) in the laser arm. The mean ETDRS BCVA at 12 months was 61.3+/-10.4 (range 34-79) in the bevacizumab group and 50.0+/-16.6 (range 8-76) in the laser arm (P = 0.0006). Furthermore, the bevacizumab group gained a median of 8 ETDRS letters, whereas the laser group lost a median of 0.5 ETDRS letters (P = 0.0002). The odds of gaining > or =10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group (adjusted odds ratio, 5.1; 95% confidence interval, 1.3-19.7; P = 0.019). At 12 months, central macular thickness decreased from 507+/-145 microm (range 281-900 microm) at baseline to 378+/-134 microm (range 167-699 microm) (P<0.001) in the ivB group, whereas it decreased to a lesser extent in the laser group, from 481+/-121 microm (range 279-844 microm) to 413+/-135 microm (range 170-708 microm) (P = 0.02). The median number of injections was 9 (interquartile range [IQR] 8-9) in the ivB group, and the median number of laser treatments was 3 (IQR 2-4) in the MLT group.\n The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia.\n Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema (DME) patients.\n Two parallel, methodologically identical, phase III, multicenter, double-masked, sham injection-controlled, randomized studies.\n Adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40-20/320 Snellen equivalent) and central subfield thickness ≥275 μm on time-domain optical coherence tomography (OCT).\n Monthly intravitreal ranibizumab (0.5 or 0.3 mg) or sham injections. Macular laser was available per-protocol-specified criteria.\n Proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months.\n In RISE (NCT00473330), 377 patients were randomized (127 to sham, 125 to 0.3 mg, 125 to 0.5 mg). At 24 months, 18.1% of sham patients gained ≥15 letters versus 44.8% of 0.3-mg (P<0.0001; difference vs sham adjusted for randomization stratification factors, 24.3%; 95% confidence interval [CI], 13.8-34.8) and 39.2% of 0.5-mg ranibizumab patients (P<0.001; adjusted difference, 20.9%; 95% CI, 10.7-31.1). In RIDE (NCT00473382), 382 patients were randomized (130 to sham, 125 to 0.3 mg, 127 to 0.5 mg). Significantly more ranibizumab-treated patients gained ≥15 letters: 12.3% of sham patients versus 33.6% of 0.3-mg patients (P<0.0001; adjusted difference, 20.8%; 95% CI, 11.4-30.2) and 45.7% of 0.5-mg ranibizumab patients (P<0.0001; adjusted difference, 33.3%; 95% CI, 23.8-42.8). Significant improvements in macular edema were noted on OCT, and retinopathy was less likely to worsen and more likely to improve in ranibizumab-treated patients. Ranibizumab-treated patients underwent significantly fewer macular laser procedures (mean of 1.8 and 1.6 laser procedures over 24 months in the sham groups vs 0.3-0.8 in ranibizumab groups). Ocular safety was consistent with prior ranibizumab studies; endophthalmitis occurred in 4 ranibizumab patients. The total incidence of deaths from vascular or unknown causes, nonfatal myocardial infarctions, and nonfatal cerebrovascular accidents, which are possible effects from systemic vascular endothelial growth factor inhibition, was 4.9% to 5.5% of sham patients and 2.4% to 8.8% of ranibizumab patients.\n Ranibizumab rapidly and sustainably improved vision, reduced the risk of further vision loss, and improved macular edema in patients with DME, with low rates of ocular and nonocular harm.\n Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To confirm the safety and compare the efficacy of intravitreal pegaptanib sodium 0.3 mg versus sham injections in subjects with diabetic macular edema (DME) involving the center of the macula associated with vision loss not due to ischemia.\n Randomized (1:1), sham-controlled, multicenter, parallel-group trial.\n Subjects with DME.\n Subjects received pegaptanib 0.3 mg or sham injections every 6 weeks in year 1 (total = 9 injections) and could receive focal/grid photocoagulation beginning at week 18. During year 2, subjects received injections as often as every 6 weeks per prespecified criteria.\n The primary efficacy endpoint was the proportion gaining ≥ 10 letters of visual acuity (VA) from baseline to year 1. Safety was monitored throughout.\n In all, 260 (pegaptanib, n = 133; sham, n = 127) and 207 (pegaptanib, n = 107; sham, n = 100) subjects were included in years 1 and 2 intent-to-treat analyses, respectively. A total of 49 of the 133 (36.8%) subjects from the pegaptanib group and 25 of the 127 (19.7%) from the sham group experienced a VA improvement of ≥ 10 letters at week 54 compared with baseline (odds ratio [OR], 2.38; 95% confidence interval, 1.32-4.30; P = 0.0047). For pegaptanib-treated subjects, change in mean VA from baseline by visit was superior (P<0.05) to sham at weeks 6, 24, 30, 36, 42, 54, 78, 84, 90, 96, and 102. At week 102, pegaptanib-treated subjects gained, on average, 6.1 letters versus 1.3 letters for sham (P<0.01). Fewer pegaptanib- than sham-treated subjects received focal/grid laser treatment (week 54, 31/133 [23.3%] vs 53/127 [41.7%], respectively, P = 0.002; week 102, 27/107 [25.2%] vs 45/100 [45.0%], respectively, P = 0.003). The pegaptanib treatment group showed significantly better results on the National Eye Institute-Visual Functioning Questionnaire than sham for subscales important in this population. Pegaptanib was well tolerated; the frequencies of discontinuations, adverse events, treatment-related adverse events, and serious adverse events were comparable in the pegaptanib and sham groups.\n Patients with DME derive clinical benefit from treatment with the selective vascular endothelial growth factor antagonist pegaptanib 0.3 mg. These findings indicate that intravitreal pegaptanib is effective in the treatment of DME and, taken together with prior study data, support a positive safety profile in this population.\n Proprietary or commercial disclosure may be found after the references.\n Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To evaluate the safety and efficacy of pegaptanib sodium injection (pegaptanib) in the treatment of diabetic macular edema (DME).\n Randomized, double-masked, multicenter, dose-ranging, controlled trial.\n Individuals with a best-corrected visual acuity (VA) between 20/50 and 20/320 in the study eye and DME involving the center of the macula for whom the investigator judged photocoagulation could be safely withheld for 16 weeks.\n Intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at study entry, week 6, and week 12 with additional injections and/or focal photocoagulation as needed for another 18 weeks. Final assessments were conducted at week 36.\n Best-corrected VA, central retinal thickness at the center point of the central subfield as assessed by optical coherence tomography measurement, and additional therapy with photocoagulation between weeks 12 and 36.\n One hundred seventy-two patients appeared balanced for baseline demographic and ocular characteristics. Median VA was better at week 36 with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger proportion of those receiving 0.3 mg gained VAs of > or =10 letters (approximately 2 lines) (34% vs. 10%, P = 0.003) and > or =15 letters (18% vs. 7%, P = 0.12). Mean central retinal thickness decreased by 68 microm with 0.3 mg, versus an increase of 4 microm with sham (P = 0.02). Larger proportions of those receiving 0.3 mg had an absolute decrease of both > or =100 microm (42% vs. 16%, P = 0.02) and > or =75 microm (49% vs. 19%, P = 0.008). Photocoagulation was deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25% vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib subjects) and was not associated with severe visual loss.\n In this phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more likely to show reduction in central retinal thickness, and were deemed less likely to need additional therapy with photocoagulation at follow-up." ]

[ "15662490", "12114886", "14764128", "14501737", "14961887", "15821528", "15339761" ]

[ "Impact of duloxetine on quality of life for women with symptoms of urinary incontinence.", "Duloxetine versus placebo in the treatment of stress urinary incontinence.", "Duloxetine vs placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial.", "Duloxetine versus placebo for the treatment of North American women with stress urinary incontinence.", "Duloxetine versus placebo in the treatment of European and Canadian women with stress urinary incontinence.", "A randomized controlled trial of duloxetine alone, pelvic floor muscle training alone, combined treatment and no active treatment in women with stress urinary incontinence.", "Pharmacological treatment of women awaiting surgery for stress urinary incontinence." ]

[ "The objective of this study was to evaluate the effectiveness of duloxetine in improving quality of life among women with stress and mixed urinary incontinence. The study included 451 women with self-reported stress incontinence episodes (>or=1/week) who were randomized to duloxetine (40 mg BID) or placebo in a double-blind, usual care design. Patients and physicians were allowed to titrate, augment, and/or discontinue treatment. Concomitant treatments were permitted. The primary outcome was the Incontinence Quality of Life Questionnaire (I-QOL) score, with assessments at 3, 6, and 9 months. Other measures included the Patient Global Impression of Improvement (PGI-I) and adverse events. The adjusted mean change in I-QOL total score was greater in the duloxetine group than in the placebo group and at a level comparable to that found in previous clinical trials, but the difference between placebo and duloxetine was not statistically significant in the intent-to-treat, last observation carried forward (LOCF) analysis. The difference approached statistical significance in favor of duloxetine at 3 months (p=0.07). PGI-I ratings did not demonstrate significant superiority for duloxetine in LOCF analysis; however, study completers taking duloxetine were significantly more likely to rate themselves as \"better\" (70.2%) than completers taking placebo (50.8%, p<0.05). Women utilized a variety of treatment methods including pelvic floor muscle training, estrogen, anticholinergic medication, weight reduction, and smoking cessation. In this study, while mean I-QOL change scores were numerically higher for the duloxetine group than mean change scores for the placebo group, this difference was not statistically significant. Among women who completed the study on study drug, a significantly greater proportion of duloxetine women versus placebo women rated their condition to be better.", "The purpose of this study was to assess the efficacy and safety of duloxetine, a selective inhibitor of serotonin and norepinephrine reuptake, in the treatment of stress urinary incontinence.\n A double-blind, randomized, placebo-controlled study was conducted in 553 women aged 18 to 65 years with a predominant symptom of stress urinary incontinence. Subjects were randomized to placebo (n = 138 women) or duloxetine at one of three doses (20 mg/d, n = 138 women; 40 mg/d, n = 137 women; or 80 mg/d, n = 140 women). Outcome variables that were assessed after 12 weeks of treatment included incontinence episode frequency recorded in a real-time diary and answers provided to the Patient Global Impression of Improvement scale and the Incontinence Quality of Life questionnaire.\n Duloxetine was associated with significant and dose-dependent decreases in incontinence episode frequency that paralleled improvements that were observed in the Patient Global Impression of Improvement scale and the Incontinence Quality of Life questionnaire. The median incontinence episode frequency decrease with the use of the pooled diary analysis with placebo was 41% compared with 54% for duloxetine 20 mg per day (P =.06), 59% for duloxetine 40 mg per day (P =.002), and 64% for duloxetine 80 mg per day (P <.001). One half of the subjects at the 80 mg per day dose had a > or = 64% reduction in incontinence episode frequency (P <.001 vs placebo); 67% had > or = 50% reduction (P =.001 vs placebo). These improvements were observed despite significant concurrent dose-dependent increases in the average voiding interval in the duloxetine groups compared with the placebo group. Similar statistically significant improvements were demonstrated in a subgroup of 163 subjects who had more severe stress urinary incontinence (> or = 14 incontinence episode frequency per week; 49%-64% reduction in incontinence episode frequency in the duloxetine groups compared with 30% in the placebo group). Discontinuation rates for adverse events were 5% for placebo and 9%, 12%, and 15% for duloxetine 20, 40, and 80 mg per day, respectively (P =.04). Nausea was the most common symptom that led to discontinuation. None of the adverse events that were reported were considered to be clinically severe.\n This trial provides evidence for the efficacy and safety of duloxetine as a pharmacologic agent for the treatment of stress urinary incontinence.", "To further assess, in a phase 3 study, treatment with duloxetine for women with stress urinary incontinence (SUI) in other geographical regions, including Argentina, Australia, Brazil, Finland, Poland, South Africa and Spain, as previous trials in North America and Europe provided evidence for the safety and efficacy of duloxetine as a pharmacological treatment for SUI in women.\n The study included 458 women aged 27-79 years enrolled in a double-blind, placebo-controlled trial. The patients with predominantly SUI were identified using a validated clinical algorithm. They were randomly assigned to receive placebo (231) or duloxetine 40 mg twice daily (227) for 12 weeks. The primary outcome variables included the incontinence episode frequency (IEF) and the Incontinence Quality of Life (I-QOL) questionnaire. Van Elteren's test was used to analyse the percentage changes in IEF where the stratification variable was weekly baseline IEF (IEF < 14 and > or = 14). Analysis of covariance was used to analyse I-QOL scores.\n The mean baseline IEF was 18.4/week; 55% of patients had a baseline IEF of > or = 14. There was a significantly greater median decrease in IEF with duloxetine with placebo (54% vs 40%, P = 0.05), with comparable significant improvements in quality of life (I-QOL score increases of 10.3 vs 6.4, P = 0.007). The improvements with duloxetine were associated with significantly greater increases in voiding intervals than with placebo (20.4 vs 8.5 min, P < 0.001). The placebo response was 10.7% and 12.5% higher than those reported in two European and North American phase 3 trials. This may have been related to more patients being naïve for incontinence management in the current trial. Discontinuation rates for adverse events were 1.7% for placebo and 17.2% for duloxetine (P < 0.001), with nausea being the most common reason for discontinuation (3.1%); it was the most common adverse event with duloxetine, but was mild or moderate in most (81%), did not worsen in any patient and resolved within 7 days in 60% and within 1 month in 86% of continuing patients; 88% of women who experienced nausea while taking duloxetine completed the trial.\n These results show improvements in incontinence and quality of life with duloxetine 40 mg twice daily for 12 weeks that are in keeping with those reported in two other recently completed phase 3 trials in Europe and North America.", "Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, increases rhabdosphincter contractility via the stimulation of pudendal motor neuron alpha-1 adrenergic and 5-hydroxytryptamine-2 receptors. In this first phase 3 study we assessed the efficacy and safety of duloxetine in women with stress urinary incontinence (SUI).\n A total of 683 North American women 22 to 84 years old were enrolled in this double-blind, placebo controlled study. The case definition included a predominant symptom of SUI with a weekly incontinence episode frequency (IEF) of 7 or greater, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequency, a bladder capacity of 400 ml or greater, and a positive cough stress test and stress pad test. After a 2-week placebo lead-in period subjects were randomly assigned to receive placebo (339) or 80 mg duloxetine daily (344) as 40 mg twice daily for 12 weeks. Primary outcome variables included IEF and an incontinence quality of life questionnaire. Van Elteren's test was used to analyze percent changes in IEF with a stratification variable of weekly baseline IEF (less than 14 and 14 or greater). ANCOVA was used to analyze incontinence quality of life scores.\n Mean baseline IEF was 18 weekly and 436 subjects (64%) had a baseline IEF of 14 or greater. There was a significant decrease in IEF with duloxetine compared with placebo (50% vs 27%, p <0.001) with comparably significant improvements in quality of life (11.0 vs 6.8, p <0.001). Of subjects on duloxetine 51% had a 50% to 100% decrease in IEF compared with 34% of those on placebo (p <0.001). These improvements with duloxetine were associated with a significant increases in the voiding interval compared with placebo (20 vs 2 minutes, p <0.001) and they were observed across the spectrum of incontinence severity. The discontinuation rate for adverse events was 4% for placebo and 24% for duloxetine (p <0.001) with nausea the most common reason for discontinuation (6.4%). Nausea, which was also the most common side effect, tended to be mild to moderate and transient, usually resolving after 1 week to 1 month. Of the 78 women who experienced treatment emergent nausea while taking duloxetine 58 (74%) completed the trial.\n These phase 3 data are consistent with phase 2 data and they provide further evidence for the safety and efficacy of duloxetine as a pharmacological agent for the treatment of women with SUI.", "To assess the efficacy and safety of duloxetine in women with stress urinary incontinence.\n Randomised double-blind, placebo-controlled clinical trial.\n Fort-six centres in seven European countries and Canada.\n Four hundred and ninety-four women aged 24-83 years identified as having predominant symptoms of stress urinary incontinence using a clinical algorithm that was 100% predictive of urodynamic stress urinary incontinence in a subgroup of 34 women.\n The case definition included a predominant symptom of stress urinary incontinence with a weekly incontinence episode frequency > or =7, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequencies, a bladder capacity > or =400 mL and both a positive cough stress test and positive stress pad test. Subjects completed two urinary diaries prior to randomisation and three diaries during the active treatment phase of the study, each completed during the week prior to monthly visits. Subjects also completed quality of life questionnaires at each visit. Safety was assessed by the evaluation of treatment-emergent adverse events, discontinuation of treatment because of adverse events, serious adverse events, vital sign measurements, electrocardiograms (ECG) and clinical laboratory tests.\n After a two-week placebo lead-in, women received placebo or duloxetine 40 mg BD for 12 weeks.\n The percentage decrease in incontinence episode frequency and the change in the Incontinence Quality of Life (I-QOL) questionnaire total score were prespecified as co-primary outcome variables in the protocol.\n Incontinence episode frequency decreased significantly with duloxetine compared with placebo (median decrease of 50%vs 29%; P= 0.002) with comparable improvements in the more severely incontinent subgroup (those experiencing at least 14 incontinence episodes per week at baseline; 56%vs 27% decreases; P < 0.001). The primary analysis of I-QOL scores did not reveal a significant difference between treatment groups, due primarily to the carrying forward of low scores from patients who discontinued treatment very early due to duloxetine-associated adverse events. The increase in I-QOL scores was significantly greater for duloxetine than for placebo at each of the three postrandomisation visits after 4, 8, and 12 weeks of treatment. Discontinuation rates for adverse events were higher for duloxetine (22%vs 5%; P < 0.001) with nausea being the most common reason for discontinuation (5.3%). Nausea tended to be mild to moderate, not progressive, and transient.\n The findings support duloxetine as a potential treatment for women with stress urinary incontinence.", "We primarily compared the effectiveness of combined pelvic floor muscle training (PFMT) and duloxetine with imitation PFMT and placebo for 12 weeks in women with stress urinary incontinence (SUI). In addition, we compared the effectiveness of combined treatment with single treatments, single treatments with each other and single treatments with no treatment.\n This blinded, doubly controlled, randomized trial enrolled 201 women 18 to 75 years old with SUI at 17 incontinence centers in the Netherlands, United Kingdom and United States. Women averaged 2 or more incontinence episodes daily and were randomized to 1 of 4 combinations of 80 mg duloxetine daily, placebo, PFMT and imitation PFMT, including combined treatment (in 52), no active treatment (in 47), PFMT only (in 50) and duloxetine only (in 52). The primary efficacy measure was incontinence episode frequency. Other efficacy variables included the number of continence pads used and the Incontinence Quality of Life questionnaire score.\n The intent to treat population incontinence episode frequency analysis demonstrated the superiority of duloxetine with or without PFMT compared with no treatment or with PFMT alone. However, pad and Incontinence Quality of Life analyses suggested greater improvement with combined treatment than single treatment. A completer population analysis demonstrated the efficacy of duloxetine with or without PFMT and suggested combined treatment was more effective than either treatment alone.\n The data support significant efficacy of combined PFMT and duloxetine in the treatment of women with SUI. We hypothesize that complementary modes of action of duloxetine and PFMT may result in an additive effect of combined treatment.", "Duloxetine, a serotonin/norepinephrine reuptake inhibitor, has been effective in the treatment of mild and moderate stress urinary incontinence. The aim of this trial was to assess its efficacy for women with severe stress urinary incontinence.\n One hundred nine women, aged 33-75 years, enrolled into this double-blind, randomized, placebo-controlled study. Subjects had to have a predominant symptom of stress urinary incontinence with an incontinence episode frequency 14 per week or more, pure urodynamic stress urinary incontinence, and continence surgery already scheduled. Women were randomized to placebo (n = 54) or duloxetine 80 mg/d (n = 55) for 4 weeks, escalated to 120 mg/d for 4 weeks. Assessment variables included incontinence episode frequency, continence pad use, the Incontinence Quality of Life (I-QOL) questionnaire, and the Willingness to Consider Surgery rating. A responder was defined as a subject with an incontinence episode frequency reduction of 50% or more.\n There were significant improvements with duloxetine compared with placebo in incontinence episode frequency (-60% versus -27%, P <.001), I-QOL score (+10.6 versus +2.4, P =.003), and pad use (-34.5% versus -4.8%, P =.008). At the conclusion of the 8-week study, 10/49 (20%) duloxetine-treated women were no longer interested in surgery, compared with 0/45 placebo-treated women (P =.001). Duloxetine-treated subjects were significantly more likely to be classified as responders (relative risk 4.68, 95% confidence interval 2.27-9.66). The number of subjects-needed-to-treat to gain an additional incontinence episode frequency responder with duloxetine was 2.02. All duloxetine responses were observed within 2 weeks. Side effects and discontinuations because of side effects were significantly more common with duloxetine.\n The data support duloxetine's efficacy in women with severe stress urinary incontinence and suggest that some women responding to duloxetine may reconsider their willingness to undergo surgery." ]

[ "9443925", "11695068", "7625419", "10550467", "12695269", "8989272", "12374248", "9875874", "7477143", "9738515", "8950879" ]

[ "Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group.", "Comparison of alendronate, calcitonin and calcium treatments in postmenopausal osteoporosis.", "Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling.", "Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Fosamax International Trial Study Group.", "Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial.", "Dose-response relationships for alendronate treatment in osteoporotic elderly women. Alendronate Elderly Osteoporosis Study Centers.", "Tolerability of once-weekly alendronate in patients with osteoporosis: a randomized, double-blind, placebo-controlled study.", "Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.", "Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group.", "Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial.", "Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group." ]

[ "Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear.\n We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age. An additional 435 women who were prepared to receive a combination of estrogen and progestin were randomly assigned to one of the above treatments or open-label estrogen-progestin. The main outcome measure was the change in bone mineral density of the lumbar spine, hip, distal forearm, and total body measured annually for two years by dual-energy x-ray absorptiometry.\n The women who received placebo lost bone mineral density at all measured sites, whereas the women treated with 5 mg of alendronate daily had a mean (+/-SE) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine, 1.9+/-0.1 percent at the hip, and 0.7+/-0.1 percent for the total body (all P<0.001). Women treated with 2.5 mg of alendronate daily had smaller increases in bone mineral density. Alendronate did not increase bone mineral density of the forearm, but it slowed the loss. The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate. Alendronate was well tolerated, with a safety profile similar to that of placebo or estrogen-progestin.\n Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin.", "The present study was planned to assess the safety, tolerability and efficacy on bone mineral density (BMD), pain, quality of life and fracture risk of alendronate, calcitonin and calcium treatments. A total of 151 postmenopausal women with lumbar spine BMD 2 SD or more below the young adult mean were randomly assigned to one of three groups: 51 patients received oral alendronate 10 mg and calcium 1000 mg (alendronate group), 50 patients intranasal salmon calcitonin 100 IU and oral calcium 1000 mg (calcitonin group), and 50 patients oral calcium 1000 mg (calcium group) daily for one year. BMD was assessed by dual energy X-ray absorbtiometry, pain by a visual analogue scale, and quality of life by the Nottingham health profile. Significant increases in BMD at all sites were obtained in the calcitonin and alendronate groups, but not in the calcium group. Pain and quality of life improved significantly in both the calcitonin and alendronate groups, but not in the calcium group. New vertebral fractures were seen in 31.58% of the alendronate, 37.5% of the calcitonin, and 40% of the calcium groups, representing no statistical difference. No serious side-effects were seen in any of the patients during follow-up.", "The effects of the aminobisphosphonate alendronate sodium on bone mass and markers of bone remodeling were investigated.\n In a multicenter, randomized, double-blind, placebo-controlled, 2-year study, 188 postmenopausal women, aged 42 to 75 years, with low bone mineral density (BMD) of the lumbar spine were randomly assigned to 1 of 6 daily treatment groups: placebo for 2 years, alendronate 5 or 10 mg for 2 years, alendronate 20 or 40 mg for 1 year followed by placebo for 1 year, or alendronate 40 mg for 3 months followed by 2.5 mg for 21 months. All subjects were given 500 mg/d of elemental calcium as calcium carbonate.\n At each dose, alendronate produced significant reductions in markers of bone resorption and formation, and significantly increased bone mass at the lumbar spine, hip, and total body, as compared with decreases (significant at lumbar spine) in subjects receiving placebo. In the 10-mg group, mean urinary deoxypyridinoline/creatinine had declined by 47% at 3 months, and mean serum osteocalcin by 53% at 6 months. Mean changes in BMD over 24 months with 10 mg alendronate were +7.21% +/- 0.49% for the lumbar spine, +5.27% +/- 0.70% for total hip, and +2.53% +/- 0.68% for total body (each P < 0.01) compared to changes of -1.35% +/- 0.61%, -1.20% +/- 0.64% and -0.31% +/- 0.44% at these sites, respectively, with placebo treatment. Progressive increases in BMD of both lumbar spine and total hip were observed in the second year of treatment with 10 mg alendronate (both P < 0.05).\n Alendronate, a potent inhibitor of bone resorption, reduces markers of bone remodeling and significantly increases BMD at the lumbar spine, hip, and total body, and is well tolerated at therapeutic doses (5 or 10 mg daily) in the treatment of osteoporosis in postmenopausal women.", "This randomized, double-masked, placebo-controlled trial evaluated the safety, tolerability and effects on bone mineral density (BMD) of alendronate in a large, multinational population of postmenopausal women with low bone mass. At 153 centers in 34 countries, 1908 otherwise healthy, postmenopausal women with lumbar spine BMD 2 standard deviations or more below the premenopausal adult mean were randomly assigned to receive oral alendronate 10 mg (n = 950) or placebo (n = 958) once daily for 1 year. All patients received 500 mg elemental calcium daily. Baseline characteristics of patients in the two treatment groups were similar. At 12 months, mean increases in BMD were significantly (p</=0.001) greater in the alendronate than the placebo group by 4.9% (95% confidence interval 4.6% to 5.2%) at the lumbar spine, 2.4% (2.0% to 2.8%) at the femoral neck, 3.6% (3.2% to 4.1%) at the trochanter and 3.0% (2.6% to 3.4%) for the total hip. The incidence of nonvertebral fractures was significantly lower in the alendronate than the placebo group (19 vs 37 patients with fractures), representing a 47% risk reduction for nonvertebral fracture for alendronate-treated patients (95% confidence interval 10% to 70%; p = 0.021). Incidences of adverse events, including upper gastrointestinal adverse events, were similar in the two groups. Therefore, for postmenopausal women with low bone mass, alendronate is well tolerated and produces significant, progressive increases in BMD at the lumbar spine and hip in addition to significant reduction in the risk of nonvertebral fracture.", "Many women using hormone replacement therapy (HRT) will discontinue HRT and lose its bone-protective effect. Methods to preserve bone density in these women need to be explored. This multicenter, international, randomized, blinded, 12-month study was conducted to assess the effect of alendronate sodium on bone density in women who had recently discontinued HRT.\n The 144 postmenopausal women included in the study were diagnosed as having low bone mineral density (BMD) and had recently discontinued HRT. They were randomized to receive either a daily dose of 10 mg of alendronate sodium or matching placebo. The main outcome measures were spine, hip, and total body BMD; biochemical markers of bone turnover; and tolerability.\n Alendronate treatment was associated with a 2.3% mean increase (95% confidence interval [CI], 1.7%-3.0%) in spine BMD compared with a mean loss of 3.2% (95% CI, - 4.6% to - 1.7%) in patients receiving placebo, for a difference of 5.5% (95% CI, 4.2%-6.8%) between alendronate and placebo. Greater hip and total body BMD preservation was also observed with alendronate use. Bone turnover decreased significantly with alendronate (bone-specific alkaline phosphatase levels decreased by 20% and urinary N-telopeptide/creatinine ratio by 47%), but increased in the placebo group (by 18% and 36%, respectively). Alendronate was well tolerated, with no increase in adverse events compared with placebo.\n A high rate of bone loss was observed in the first 12 to 15 months after discontinuation of HRT in postmenopausal women with low BMD. Treatment with alendronate increased or maintained both spine and hip BMD and prevented the increase in bone resorption seen with withdrawal of HRT in this population.", "Alendronate (ALN) is an aminobisphosphonate employed as an antiresorptive agent in the treatment of osteoporosis. The present study was carried out to determine dose-response relationships, particularly the effects of relatively low doses of ALN, on bone mineral density (BMD), biochemical indexes of bone and mineral metabolism, and bone histology, with particular attention to effects in elderly women. This prospective, randomized, double blind, 2-yr multicenter study compared the effects of placebo with those of 1.0, 2.5, or 5.0 mg ALN daily. All subjects received supplemental calcium (500 mg daily) as the carbonate. We studied 359 women with lumbar spine BMD at least 2.0 SD below the peak young adult mean. Subjects were stratified by age, with 135 aged 60-69 yr and 224 aged 70-85 yr. Histomorphometry was performed on transiliac bone biopsies obtained from 104 subjects after 1 yr and from 83 subjects after 2 yr. This study elucidated the previously uninvestigated lower region of the dose-response curve for ALN in osteoporosis. Over 2 yr, treatment with 1.0, 2.5, or 5.0 mg/day increased lumbar spine BMD, on the average, by 0.65%, 3.54%, and 5.67%, respectively, compared with that in the placebo group (P < 0.001 vs. placebo for the 2.5 and 5 mg groups). Significant dose-related increases were also seen in BMD at appendicular sites and in total body BMD. Dose-dependent reductions in bone turnover to new steady states were indicated by serum and urine biochemical markers as well as by histomorphometry. There was also a dose-related reduction in the proportion of subjects suffering nonvertebral fractures (P < 0.05). Safety profiles were similar for the ALN and placebo groups and for both age strata. Efficacy was similar for both age strata. There was no evidence of impaired mineralization or other histological abnormalities due to ALN treatment. We conclude that treatment with ALN over a period of 2 yr was well tolerated and produced dose-dependent increases in BMD without evidence of a plateau over the dose range of 1.0-5.0 mg daily. One milligram daily did not result in a significant effect on BMD, and 5.0 mg daily produced favorable effects at all sites measured. Other studies have demonstrated somewhat greater effects on 10 mg daily. ALN, was equally effective and well tolerated in osteoporotic women over 70 yr old as in younger women with the same condition.", "To compare the upper gastrointestinal (GI) tract tolerability of once-weekly oral alendronate, 70 mg, and placebo.\n This was a 12-week multicenter, randomized, double-blind, placebo-controlled study. The first patient initiated treatment on June 5, 2000, and the last patient completed treatment on March 1, 2001. The study enrolled 450 postmenopausal women and men with osteoporosis (224 took alendronate, 226 took placebo) who were ambulatory and community dwelling at 48 outpatient study centers in the United States. By design, approximately half of the patients were naive to bisphosphonates. The primary end point was upper GI tract tolerability based on the incidence of any upper GI tract adverse events. Secondary end points included the number of discontinuations due to drug-related upper GI tract adverse events and the change from baseline in bone resorption, assessed by the urinary N-telopeptide-creatinine ratio at 12 weeks. A subgroup analysis of the primary and secondary end points was performed on the patients stratified by prior bisphosphonate use. The safety and tolerability of the weekly alendronate and placebo regimens were captured as clinical and laboratory adverse events.\n A total of 11% of the alendronate patients and 13% of the placebo patients reported an upper GI tract adverse event. Discontinuations due to drug-related upper GI tract adverse events occurred in 3% of alendronate patients and 1% of placebo patients. The differences between the treatment groups for the primary and secondary end points were not significant. For the primary end point, the upper limit of the 95% confidence interval of the difference was well within the prespecified 14% comparability bound (-2.2%; 95% confidence interval, -8.3% to 3.9%). The overall incidence of upper GI tract adverse events was lower in the subgroup of patients with prior bisphosphonate exposure (8%) than in those who were bisphosphonate naive (16%). However, regardless of prior bisphosphonate exposure, the incidence of upper GI tract adverse events was similar between the alendronate and placebo patients. The urinary N-telopeptide-creatinine ratio showed a significant decrease in the alendronate patients (72% of baseline, P<.001) compared with a slight increase in the placebo patients (106% of baseline) at week 12.\n In this 3-month study, the incidence of upper GI tract adverse events in patients treated with once-weekly alendronate, 70 mg, was comparable to that with placebo.", "Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures.\n To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures.\n Randomized, blinded, placebo-controlled trial.\n Eleven community-based clinical research centers.\n Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later).\n All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial.\n Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry.\n Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects.\n In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.", "Postmenopausal osteoporosis is a serious health problem, and additional treatments are needed.\n We studied the effects of oral alendronate, an aminobisphosphonate, on bone mineral density and the incidence of fractures and height loss in 994 women with postmenopausal osteoporosis. The women were treated with placebo or alendronate (5 or 10 mg daily for three years, or 20 mg for two years followed by 5 mg for one year); all the women received 500 mg of calcium daily. Bone mineral density was measured by dual-energy x-ray absorptiometry. The occurrence of new vertebral fractures and the progression of vertebral deformities were determined by an analysis of digitized radiographs, and loss of height was determined by sequential height measurements.\n The women receiving alendronate had significant, progressive increases in bone mineral density at all skeletal sites, whereas those receiving placebo had decreases in bone mineral density. At three years, the mean (+/- SE) differences in bone mineral density between the women receiving 10 mg of alendronate daily and those receiving placebo were 8.8 +/- 0.4 percent in the spine, 5.9 +/- 0.5 percent in the femoral neck, 7.8 +/- 0.6 percent in the trochanter, and 2.5 +/- 0.3 percent in the total body (P < 0.001 for all comparisons). The 5-mg dose was less effective than the 10-mg dose, and the regimen of 20 mg followed by 5 mg was similar in efficacy to the 10-mg dose. Overall, treatment with alendronate was associated with a 48 percent reduction in the proportion of women with new vertebral fractures (3.2 percent, vs. 6.2 percent in the placebo group; P = 0.03), a decreased progression of vertebral deformities (33 percent, vs. 41 percent in the placebo group; P = 0.028), and a reduced loss of height (P = 0.005) and was well tolerated.\n Daily treatment with alendronate progressively increases the bone mass in the spine, hip, and total body and reduces the incidence of vertebral fractures, the progression of vertebral deformities, and height loss in postmenopausal women with osteoporosis.", "Although the antiresorptive agent alendronate has been shown to increase bone mineral density (BMD) at the hip and spine and decrease the incidence of osteoporotic fractures in older women, few data are available regarding early prediction of long-term response to therapy, particularly with regard to increases in hip BMD. Examining short-term changes in biochemical markers incorporates physiologic response with therapeutic compliance and should provide useful prognostic information for patients. The objective of this study was to examine whether early changes in biochemical markers of bone turnover predict long-term changes in hip BMD in elderly women. The study was a double-blind, placebo-controlled, randomized clinical trial which took place in a community-based academic hospital. One hundred and twenty community-dwelling, ambulatory women 65 years of age and older participated in the study. Intervention consisted of alendronate versus placebo for 2.5 years. All patients received appropriate calcium and vitamin D supplementation. The principal outcome measures included BMD of the hip (total hip, femoral neck, trochanter, and intertrochanter), spine (posteroanterior [PA] and lateral), total body, and radius. Biochemical markers of bone resorption included urinary N-telopeptide cross-linked collagen type I and free deoxypyridinoline; markers of bone formation included serum osteocalcin and bone-specific alkaline phosphatase. Long-term alendronate therapy was associated with increased BMD at the total hip (4.0%), femoral neck (3.1%), trochanter (5.5%), intertrochanter (3.8%), PA spine (7.8%), lateral spine (10.6%), total body (2.2%), and one-third distal radius (1.3%) in elderly women (all p < 0.01). In the placebo group, bone density increased 1.9-2.1% at the spine (p < 0.05) and remained stable at all other sites. At 6 months, there were significant decreases in all markers of bone turnover (-10% to -53%, p < 0.01) in women on alendronate. The changes in urinary cross-linked collagen at 6 months correlated with long-term bone density changes at the hip (r = -0.35, p < 0.01), trochanter (r = -0.36, p < 0.01), PA spine (r = -0.41, p < 0.01), and total body (r = -0.34, p < 0.05). At 6 months, patients with the greatest drop in urinary cross-linked collagen (65% or more) demonstrated the greatest gains in total hip, trochanteric, and vertebral bone density (all p < 0.05). A 30% decrease in urinary cross-linked collagen at 6 months predicted a bone density increase of 2.8-4.1% for the hip regions and 5.8-6.9% for the spine views at the 2.5-year time point (p < 0.05). There were no substantive associations between changes in biochemical markers and bone density in the placebo group. Alendronate therapy was associated with significant long-term gains in BMD at all clinically relevant sites, including the hip, in elderly women. Moreover, these improvements were associated with early decreases in biochemical markers of bone turnover. Early dynamic decreases in urinary cross-linked collagen can be used to monitor and predict long-term response to bisphosphonate therapy in elderly women. Future studies are needed to determine if early assessment improves long-term patient compliance or uncovers poor compliance, thereby aiding the physician in maximizing the benefits of therapy.", "Previous studies have shown that alendronate can increase bone mineral density (BMD) and prevent radiographically defined (morphometric) vertebral fractures. The Fracture Intervention Trial aimed to investigate the effect of alendronate on the risk of morphometric as well as clinically evident fractures in postmenopausal women with low bone mass.\n Women aged 55-81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture. Results for women with at least one vertebral fracture at baseline are reported here. 2027 women were randomly assigned placebo (1005) or alendronate (1022) and followed up for 36 months. The dose of alendronate (initially 5 mg daily) was increased (to 10 mg daily) at 24 months, with maintenance of the double blind. Lateral spine radiography was done at baseline and at 24 and 36 months. New vertebral fractures, the primary endpoint, were defined by morphometry as a decrease of 20% (and at least 4 mm) in at least one vertebral height between the baseline and latest follow-up radiograph. Non-spine clinical fractures were confirmed by radiographic reports. New symptomatic vertebral fractures were based on self-report and confirmed by radiography.\n Follow-up radiographs were obtained for 1946 women (98% of surviving participants). 78 (8.0%) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 (15.0%) in the placebo group (relative risk 0.53 [95% Cl 0.41-0.68]). For clinically apparent vertebral fractures, the corresponding numbers were 23 (2.3%) alendronate and 50 (5.0%) placebo (relative hazard 0.45 [0.27-0.72]). The risk of any clinical fracture, the main secondary endpoint, was lower in the alendronate than in the placebo group (139 [13.6%] vs 183 [18.2%]; relative hazard 0.72 [0.58-0.90]). The relative hazards for hip fracture and wrist fracture for alendronate versus placebo were 0.49 (0.23-0.99) and 0.52 (0.31-0.87). There was no significant difference between the groups in numbers of adverse experiences, including upper-gastrointestinal disorders.\n We conclude that among women with low bone mass and existing vertebral fractures, alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebral fractures, as well as other clinical fractures." ]

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[ "Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery.", "A randomized controlled trial comparing an intraoperative goal-directed strategy with routine clinical practice in patients undergoing peripheral arterial surgery.", "Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial.", "Randomised controlled trial investigating the influence of intravenous fluid titration using oesophageal Doppler monitoring during bowel surgery.", "A double-blind randomized controlled clinical trial to assess the effect of Doppler optimized intraoperative fluid management on outcome following radical cystectomy.", "Response of patients with cirrhosis who have undergone partial hepatectomy to treatment aimed at achieving supranormal oxygen delivery and consumption.", "Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial.", "A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients.", "Randomised controlled trial assessing the impact of a nurse delivered, flow monitored protocol for optimisation of circulatory status after cardiac surgery.", "A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients.", "A prospective randomized trial of preoperative \"optimization\" of cardiac function in patients undergoing elective peripheral vascular surgery.", "A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients.", "Early goal-directed therapy in moderate to high-risk cardiac surgery patients.", "Goal-directed intraoperative therapy reduces morbidity and length of hospital stay in high-risk surgical patients.", "Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery.", "Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery.", "Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture: randomised controlled trial.", "Effects of maximizing oxygen delivery on morbidity and mortality in high-risk surgical patients.", "Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery.", "Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery.", "Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients.", "Fluid management for laparoscopic colectomy: a prospective, randomized assessment of goal-directed administration of balanced salt solution or hetastarch coupled with an enhanced recovery program.", "Impact of perioperative haemodynamic monitoring on cardiac morbidity after major vascular surgery in low risk patients. A randomised pilot trial.", "Goal-directed haemodynamic therapy during elective total hip arthroplasty under regional anaesthesia.", "Effectiveness of pulmonary artery catheters in aortic surgery: a randomized trial.", "Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial [ISRCTN38797445].", "Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection.", "Routine pulmonary artery catheterization does not reduce morbidity and mortality of elective vascular surgery: results of a prospective, randomized trial.", "Goal-directed intraoperative therapy based on autocalibrated arterial pressure waveform analysis reduces hospital stay in high-risk surgical patients: a randomized, controlled trial.", "Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures." ]

[ "Intraoperative fluid therapy regimens using oesophageal Doppler monitoring (ODM) to optimize stroke volume (SV) (goal-directed fluid therapy, GDT) have been associated with a reduction in length of stay (LOS) and complication rates after major surgery. We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge (RfD) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients.\n In this double-blinded controlled trial, 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically 'fit' (n=123) or 'unfit' (n=56) on the basis of their performance during a cardiopulmonary exercise test. Within these fitness strata, patients were randomized to receive a standard fluid regimen with or without ODM-guided intraoperative GDT.\n GDT patients received an average of 1360 ml of additional intraoperative colloid. The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls. Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance (median 6.8 vs 4.9 days, P=0.09, and median 8.8 vs 6.7 days, P=0.09, respectively). Fit GDT patients had an increased RfD (median 7.0 vs 4.7 days; P=0.01) and LOS (median 8.8 vs 6.0 days; P=0.01) compared with controls.\n Intraoperative SV optimization conferred no additional benefit over standard fluid therapy. In an aerobically fit subgroup of patients, GDT was associated with detrimental effects on the primary outcome.\n UK NIHR CRN 7285, ISRCTN 14680495. http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=7285.", "We hypothesized that, in vascular surgery patients, the application of a goal-directed strategy based on a pulse contour-derived cardiac index would be associated with a better haemodynamic status than the application of routine perioperative care and that the amount of fluid and/or inotropes required in such a goal-directed therapy depended on the general anaesthetic technique used.\n Patients undergoing peripheral arterial bypass grafting were randomly assigned to three groups. In group 1, haemodynamic management was performed according to routine clinical practice. In the two other groups (groups 2 and 3) a goal-directed therapy was applied aiming to maintain the pulse contour-derived cardiac index above 2.5 l m min. Patients in groups 1 and 2 received sevoflurane-based anaesthesia and patients in group 3 propofol-based anaesthesia. Haemodynamic variables, amount of fluid and administration of inotropes were assessed at different time intervals.\n The amount of fluid administered was not significantly different between the groups. Two patients in group 1, 13 patients in group 2 and 12 patients in group 3 were treated with dobutamine (P < 0.001). None of the patients anaesthetized with sevoflurane (groups 1 and 2) experienced postoperative cardiovascular complications, whereas four patients in the total intravenous group (group 3) experienced major postoperative cardiovascular complications (P = 0.005).\n In the conditions of the present study, the application of a goal-directed therapy aiming to maintain the cardiac index above 2.5 l min m did not result in a higher tissue oxygen delivery than when applying the standard haemodynamic strategy nor did it depend on the anaesthetic technique used.", "The hypothesis that optimizing hemodynamics using pulmonary artery (PA) catheter (preoperative 'tune-up') would improve outcome in patients undergoing limb-salvage arterial surgery was tested. Eighty-nine patients were randomized to preoperative tune-up either in the surgical intensive care unit (SICU) (group 1) or the preinduction room (group 2) or to control (group 3). The tune-up consisted of fluid loading, afterload reduction, and/or inotropic support to achieve predetermined endpoints. Patients with a PA catheter had significantly fewer adverse intraoperative events (p less than 0.05), less postoperative cardiac morbidity (p less than 0.05), and less early graft thrombosis (p less than 0.05) than the control group. The overall study mortality rate was 3.4%, with a mortality rate of 9.5% in the control group and 1.5% in the PA catheter groups. There were no differences in ICU length of stay (LOS), hospital LOS, or total hospital costs, although the percentage of cost from complications was higher in group 3 (p greater than 0.05). In this group of patients, preoperative cardiac assessment and optimization is associated with improved outcome.", "Oesophageal Doppler monitoring allows non-invasive estimation of stroke volume and cardiac output. We studied the impact of Doppler guided fluid optimisation on haemodynamic parameters, peri-operative morbidity and hospital stay in patients undergoing major bowel surgery. Fifty-seven patients were randomly assigned to Doppler (D) or control (C) groups. All patients received intra-operative fluid therapy at the discretion of the non-investigating anaesthetist. In addition, Group D were given fluid challenges (3 ml x kg(-1)) guided by oesophageal Doppler. Group D received significantly more intra-operative colloid than Group C (mean 28 (SD 16) vs. 19.4 (SD 14.7) ml x kg(-1), p = 0.02). Cardiac output increased significantly for Group D whilst that of controls remained unchanged. The mean difference between the groups in final cardiac output was 0.87 l x min(-1) (95% confidence interval 0.31-1.43 l x min(-1), p = 0.003). Five control patients required postoperative critical care admission. Fluid titration using oesophageal Doppler during bowel surgery can improve haemodynamic parameters and may reduce critical care admissions postoperatively.", "Cardiovascular optimization via esophageal Doppler can minimize gastrointestinal hypoperfusion, reducing the risk of multiple organ dysfunction and postoperative complications during major surgery. We assessed the effect of esophageal Doppler guided cardiovascular optimization in patients undergoing radical cystectomy.\n We conducted a prospective, randomized, double-blind controlled trial at a United Kingdom teaching hospital between 2006 and 2009. A total of 66 patients were randomized to a control arm (34) and an intervention arm (32). The control group received standard intraoperative fluids. The intervention group received (additional) Doppler guided fluid. Primary outcomes were markers of gastrointestinal morbidity such as ileus, flatus and bowel opening. Secondary outcomes were postoperative nausea and vomiting, wound infection and operative intravenous fluid volumes (total and hourly).\n There were significant reductions in the control and intervention arms in the incidence of ileus (18 vs 7, p <0.001), flatus (5.36 vs 3.55 days, p <0.01) and bowel opening (9.79 vs 6.53 days, p = 0.02), respectively. Nausea and vomiting were significantly reduced in the study group at 24 and 48 hours postoperatively (11 vs 3, p <0.01 and 13 vs 1, p <0.0001). Wound infection rates were significantly reduced (8 vs 1 superficial, p <0.01 and 10 vs 2 combined, p <0.01). Study patients received significantly higher volumes (ml/kg per minute) of intravenous fluid (0.19 vs 0.23, p <0.01) related to a significantly higher volume (ml/kg) in the first hour of surgery (14.1 vs 21.0, p = 0.0001).\n Cardiovascular optimization using esophageal Doppler significantly improved postoperative markers of gastrointestinal function.\n Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.", "This study was undertaken to evaluate the response to therapy aimed at achieving supranormal cardiac and oxygen transport variables (cardiac index > than 4.5 L/min/m2, oxygen delivery > 600 ml/min/m2, and oxygen consumption > 170 ml/min/m2) in patients with cirrhosis who have undergone partial hepatectomy and to assess the relationship between those parameters and outcome.\n Thirty-four consecutive patients underwent elective hepatectomy for hepatocellular carcinoma. The postoperative outcomes and hemodynamic and oxygen transport values in 16 patients (group S) who maintained supranormal values were compared with those in 18 patients (group N) treated to maintain normal hemodynamic values. Patients in group S received volume expansion and then, if necessary, dobutamine (3 to 15 micrograms/kg/min) to increase cardiac index, oxygen delivery, and oxygen comsumption simultaneously during the first 12 hours.\n The hemodynamic targets were reached by 56% of patients in group S during the first 12 hours and 31% during the next 12 hours. Postoperative blood lactate levels at 12 and 24 hours were lower in group S than in group N, and total bilirubin concentrations, hepatic venous oxygen saturation, and arterial ketone body ratio, useful markers of postoperative liver function, also showed more favorable changes in group S than in group N. Postoperative morbidity and mortality rates were not significantly different in the two groups, but the incidence of hyperbilirubinemia and liver failure was much lower in group S than in group N.\n These results suggest that fluid therapy aimed at achieving a supranormal pattern by 12 hours after hepatectomy improved the systemic oxygen demand-supply dynamics and hepatic hemodynamics, decreasing the incidence of postoperative hyperbilirubinemia and liver failure in patients with liver cirrhosis.", "Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and/or low dose inotropic therapy. The mechanisms underlying this benefit remain uncertain. The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery.\n Randomised, controlled, single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery. For eight hours after surgery, intra-venous fluid therapy was guided by measurements of central venous pressure (CVP group), or stroke volume (SV group). In a third group stroke volume guided fluid therapy was combined with dopexamine (0.5 mcg/kg/min) (SV & DPX group).\n 135 patients were recruited (n = 45 per group). In the SV & DPX group, increased global oxygen delivery was associated with improved sublingual (P < 0.05) and cutaneous microvascular flow (P < 0.005) (sublingual microscopy and laser Doppler flowmetry). Microvascular flow remained constant in the SV group but deteriorated in the CVP group (P < 0.05). Cutaneous tissue oxygen partial pressure (PtO2) (Clark electrode) improved only in the SV & DPX group (P < 0.001). There were no differences in serum inflammatory markers. There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group (CVP group ten patients (22%); pooled SV and SV & DPX groups seven patients (8%); P = 0.03) (post hoc analysis).\n Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery, microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery. These observations may explain improved clinical outcomes associated with this treatment in previous trials.\n ISRCTN 94850719.", "To assess the effect of deliberate perioperative increase in oxygen delivery on mortality and morbidity in patients who are at high risk of both following surgery.\n Prospective, randomized clinical trial.\n A teaching hospital general intensive care unit, London, England.\n A total of 107 surgical patients, who were assessed as high risk from previously identified criteria, were studied during an 18-month period.\n Patients were randomly assigned to a control group (n = 54) that received best standard perioperative care, or to a protocol group (n = 53) that, in addition, had deliberate increase of oxygen delivery index to greater than 600 mL/min per square meter by use of dopexamine hydrochloride infusion.\n Mortality and complications were assessed to 28 days postoperatively.\n Groups were similar with respect to demographics, admission criteria, operation type, and admission hemodynamic variables. Groups were treated similarly to maintain blood pressure, arterial saturation, hemoglobin concentration, and pulmonary artery occlusion pressure; however, once additional treatment with dopexamine hydrochloride had been given, the protocol group had significantly higher oxygen delivery preoperatively (median, 597 vs 399 mL/min per square meter; P < .001) and postoperatively (P < .001). Results indicate a 75% reduction in mortality (5.7% vs 22.2%; P = .015) and a halving of the mean (+/- SEM) number of complications per patient (0.68 [+/- 0.16] vs 1.35 [+/- 0.20]; P = .008) in patients randomized to the protocol group.\n Perioperative increase of oxygen delivery with dopexamine hydrochloride significantly reduces mortality and morbidity in high-risk surgical patients.", "To assess whether a nurse led, flow monitored protocol for optimising circulatory status in patients after cardiac surgery reduces complications and shortens stay in intensive care and hospital.\n Randomised controlled trial.\n Intensive care unit and cardiothoracic unit of a university teaching hospital.\n 174 patients who underwent cardiac surgery between April 2000 and January 2003.\n Patients were allocated to conventional haemodynamic management or to an algorithm guided by oesophageal Doppler flowmetry to maintain a stroke index above 35 ml/m2.\n 26 control patients had postoperative complications (two deaths) compared with 17 (four deaths) protocol patients (P = 0.08). Duration of hospital stay in the protocol group was significantly reduced from a median of nine (interquartile range 7-12) days to seven (7-10) days (P = 0.02). The mean duration of hospital stay was reduced from 13.9 to 11.4 days, a saving in hospital bed days of 18% (95% confidence interval -12% to 47%). Usage of intensive care beds was reduced by 23% (-8% to 59%).\n A nurse delivered protocol for optimising circulatory status in the early postoperative period after cardiac surgery may significantly shorten hospital stay.", "Some observational studies suggest that the use of pulmonary-artery catheters to guide therapy is associated with increased mortality.\n We performed a randomized trial comparing goal-directed therapy guided by a pulmonary-artery catheter with standard care without the use of a pulmonary-artery catheter. The subjects were high-risk patients 60 years of age or older, with American Society of Anesthesiologists (ASA) class III or IV risk, who were scheduled for urgent or elective major surgery, followed by a stay in an intensive care unit. Outcomes were adjudicated by observers who were unaware of the treatment-group assignments. The primary outcome was in-hospital mortality from any cause.\n Of 3803 eligible patients, 1994 (52.4 percent) underwent randomization. The base-line characteristics of the two treatment groups were similar. A total of 77 of 997 patients who underwent surgery without the use of a pulmonary-artery catheter (7.7 percent) died in the hospital, as compared with 78 of 997 patients in whom a pulmonary-artery catheter was used (7.8 percent)--a difference of 0.1 percentage point (95 percent confidence interval, -2.3 to 2.5). There was a higher rate of pulmonary embolism in the catheter group than in the standard-care group (8 events vs. 0 events, P=0.004). The survival rates at 6 months among patients in the standard-care and catheter groups were 88.1 and 87.4 percent, respectively (difference, -0.7 percentage point [95 percent confidence interval, -3.6 to 2.2]; negative survival differences favor standard care); at 12 months, the rates were 83.9 and 83.0 percent, respectively (difference, -0.9 percentage point [95 percent confidence interval, -4.3 to 2.4]). The median hospital stay was 10 days in each group.\n We found no benefit to therapy directed by pulmonary-artery catheter over standard care in elderly, high-risk surgical patients requiring intensive care.\n Copyright 2003 Massachusetts Medical Society", "Previous investigations have suggested that preoperative invasive hemodynamic monitoring with \"optimization\" of cardiovascular function may favorably affect the outcome among patients undergoing peripheral vascular surgery. The purpose of this study was to evaluate the effect of preoperative optimization of hemodynamic parameters on outcome in patients undergoing aortic reconstruction (AR) or limb salvage procedures (LSP) in a randomized, prospective clinical trial.\n All 72 patients who consented to participate in this study were admitted to the intensive care unit at least 12 hours before operation for placement of a pulmonary artery catheter (PAC). Patients who were randomized to the treatment group (n = 32) were \"optimized\" by adjusting their hemoglobin concentration, oxygen saturation (SaO2), cardiac output, or afterload until the mixed venous O2 saturation (SvO2) was at least 65%. The control group (n = 40) underwent placement of a PAC and had oxygen transport parameters measured without any attempt to optimize SvO2.\n There were no significant differences between the treatment and control groups with respect to age, gender, type of operation, initial Acute Physiology and Chronic Health Evaluation (APACHE) II score, SvO2, pulmonary artery occlusion pressure, or cardiac index. All treatment patients achieved an SvO2 of at least 65% before operation. Comparing the treatment and control groups, postoperative cardiovascular complications occurred in 25% versus 27%, intraoperative complications in 28% versus 20%, and death in 9% versus 5%, respectively. None of these differences was statistically significant as a whole or within the subgroups undergoing AR or LSP.\n These data suggest that preoperative optimization of cardiovascular function by using achievement of SvO2 above 65% as the end point does not result in any reduction of intraoperative or perioperative cardiac complications in patients undergoing PVS. Further studies with alternative assessments and manipulation of different cardiopulmonary parameters may yield additional information.", "Organ dysfunction and multiple organ failure are the main causes of prolonged hospital stay after cardiac surgery, which increases resource use and health care costs. Increased levels of oxygen delivery and consumption are associated with improved outcome in different groups of postoperative patients. Cardiac surgical patients are at risk of inadequate perioperative oxygen delivery caused by extracorporeal circulation and limited cardiovascular reserves. The purpose of our study was to test whether increasing oxygen delivery immediately after cardiac surgery would shorten hospital and intensive care unit (ICU) stay. Four hundred three elective cardiac surgical patients were enrolled in the study and randomly assigned to either the control or the protocol group. Goals of the protocol group were to maintain SvO(2) >70% and lactate concentration < or =2.0 mmol/L from admission to the ICU and up to 8 h thereafter. Hemodynamics, oxygen transport data, and organ dysfunctions were recorded. The median hospital stay was shorter in the protocol group (6 vs 7 days, P < 0.05), and patients were discharged faster from the hospital than those in the control group (P < 0.05). Discharge from the ICU was similar between groups (P = 0. 8). Morbidity was less frequent at the time of hospital discharge in the protocol group (1.1% vs 6.1%, P < 0.01). Increasing oxygen delivery to achieve normal SvO(2) values and lactate concentration during the immediate postoperative period after cardiac surgery can shorten the length of hospital stay. Implications: Health care economics has challenged clinicians to reduce costs and improve resource use in cardiac surgery and anesthesia in a patient population increasing in age and in severity of disease. Optimizing cardiovascular function to maintain adequate oxygen delivery during the immediate postoperative period after cardiac surgery can decrease morbidity and reduce length of hospital stay.", "Early goal-directed therapy is a term used to describe the guidance of intravenous fluid and vasopressor/inotropic therapy by using cardiac output or similar parameters in the immediate post-cardiopulmonary bypass in cardiac surgery patients. Early recognition and therapy during this period may result in better outcome. In keeping with this aim in the cardiac surgery patients, we conducted the present study. The study included 30 patients of both sexes, with EuroSCORE >or=3 undergoing coronary artery bypass surgery under cardiopulmonary bypass. The patients were randomly divided into two groups, namely, control and early goal-directed therapy (EGDT) groups. All the subjects received standardized care; arterial pressure was monitored through radial artery, central venous pressure through a triple lumen in the right internal jugular vein, electrocardiogram, oxygen saturation, temperature, urine output per hour and frequent arterial blood gas analysis. In addition, cardiac index monitoring using FloTrac and continuous central venous oxygen saturation using PreSep was used in patients in the EGTD group. Our aim was to maintain the cardiac index at 2.5-4.2 l/min/m2 , stroke volume index 30-65 ml/beat/m2 , systemic vascular resistance index 1500-2500 dynes/s/cm5/m2 , oxygen delivery index 450-600 ml/min/m2 , continuous central venous oximetry more than 70%, stroke volume variation less than 10%; in addition to the control group parameters such as central venous pressure 6-8 mmHg, mean arterial pressure 90-105 mmHg, normal arterial blood gas analysis values, pulse oximetry, hematocrit value above 30% and urine output more than 1 ml/kg/h. The aims were achieved by altering the administration of intravenous fluids and doses of inotropic or vasodilator agents. Three patients were excluded from the study and the data of 27 patients analyzed. The extra volume used (330+/-160 v/s 80+/-80 ml, P=0.043) number of adjustments of inotropic agents (3.4+/-1.5 v/s 0.4+/-0.7, P=0.026) in the EGDT group were significant. The average duration of ventilation (13.8+/-3.2 v/s 20.7+/-7.1 h), days of use of inotropic agents (1.6+/-0.9 v/s 3.8+/-1.6 d), ICU stay (2.6+/-0.9 v/s 4.9+/-1.8 d) and hospital stay (5.6+/-1.2 v/s 8.9+/-2.1 d) were less in the EGDT group, compared to those in the control group. This study is inconclusive with regard to the beneficial aspects of the early goal-directed therapy in cardiac surgery patients, although a few benefits were observed.", "Postoperative organ failures commonly occur after major abdominal surgery, increasing the utilization of resources and costs of care. Tissue hypoxia is a key trigger of organ dysfunction. A therapeutic strategy designed to detect and reverse tissue hypoxia, as diagnosed by an increase of oxygen extraction (O2ER) over a predefined threshold, could decrease the incidence of organ failures. The primary aim of this study was to compare the number of patients with postoperative organ failure and length of hospital stay between those randomized to conventional vs a protocolized strategy designed to maintain O2ER < 27%.\n A prospective, randomized, controlled trial was performed in nine hospitals in Italy. One hundred thirty-five high-risk patients scheduled for major abdominal surgery were randomized in two groups. All patients were managed to achieve standard goals: mean arterial pressure > 80 mm Hg and urinary output > 0.5 mL/kg/h. The patients of the \"protocol group\" (group A) were also managed to keep O2ER < 27%.\n In group A, fewer patients had at least one organ failure (n = 8, 11.8%) than in group B (n = 20, 29.8%) [p < 0.05], and the total number of organ failures was lower in group A than in group B (27 failures vs 9 failures, p < 0.001). Length of hospital stay was significantly lower in the protocol group than in the control group (11.3 +/- 3.8 days vs 13.4 +/- 6.1 days, p < 0.05). Hospital mortality was similar in both groups.\n Early treatment directed to maintain O2ER at < 27% reduces organ failures and hospital stay of high-risk surgical patients. Clinical trials.gov reference No. NCT00254150.", "Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements. Intraoperative gut hypoperfusion during major surgery is associated with increased morbidity and postoperative hospital stay. We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery.\n This single centre, blinded, prospective controlled trial randomized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based (conventional) intraoperative fluid management. The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aiming for a CVP between 12 and 15 mm Hg.\n The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P<0.05. The median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P<0.001. Doppler patients achieved significantly higher cardiac output, stroke volume, and oxygen delivery. Twenty-nine (45.3%) control patients suffered gastrointestinal morbidity compared with nine (14.1%) in the Doppler guided fluid group P<0.001, overall morbidity was also significantly higher in the control group P=0.05.\n Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay. Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity.", "Intraoperative hypovolemia is common and is a potential cause of organ dysfunction, increased postoperative morbidity, length of hospital stay, and death. The objective of this prospective, randomized study was to assess the effect of goal-directed intraoperative fluid administration on length of postoperative hospital stay.\n One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were randomly assigned to a control group (n = 50) that received standard intraoperative care or to a protocol group (n = 50) that, in addition, received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume. Length of postoperative hospital stay and postoperative surgical morbidity were assessed.\n Groups were similar with respect to demographics, surgical procedures, and baseline hemodynamic variables. The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group. Patients in the protocol group had a shorter duration of hospital stay compared with the control group: 5 +/- 3 versus 7 +/- 3 days (mean +/- SD), with a median of 6 versus 7 days, respectively ( = 0.03). These patients also tolerated oral intake of solid food earlier than the control group: 3 +/- 0.5 versus 4.7 +/- 0.5 days (mean +/- SD), with a median of 3 versus 5 days, respectively ( = 0.01).\n Goal-directed intraoperative fluid administration results in earlier return to bowel function, lower incidence of postoperative nausea and vomiting, and decrease in length of postoperative hospital stay.", "To assess whether intraoperative intravascular volume optimisation improves outcome and shortens hospital stay after repair of proximal femoral fracture.\n Prospective, randomised controlled trial comparing conventional intraoperative fluid management with repeated colloid fluid challenges monitored by oesophageal Doppler ultrasonography to maintain maximal stroke volume throughout the operative period.\n Teaching hospital, London.\n 40 patients undergoing repair of proximal femoral fracture under general anaesthesia.\n Patients were randomly assigned to receive either conventional intraoperative fluid management (control patients) or additional repeated colloid fluid challenges with oesophageal Doppler ultrasonography used to maintain maximal stroke volume throughout the operative period (protocol patients).\n Time declared medically fit for hospital discharge, duration of hospital stay (in acute bed; in acute plus long stay bed), mortality, perioperative haemodynamic changes.\n Intraoperative intravascular fluid loading produced significantly greater changes in stroke volume (median 15 ml (95% confidence interval 10 to 21 ml)) and cardiac output (1.2 l/min (0.1 to 2.3 l/min)) than in the conventionally managed group (-5 ml (-10 to 1 ml) and -0.4 l/min (-1.0 to 0.2 l/min)) (P < 0.001 and P < 0.05, respectively). One protocol patient and two control patients died in hospital. In the survivors, postoperative recovery was significantly faster in the protocol patients, with shorter times to being declared medically fit for discharge (median 10 (9 to 15) days v 15 (11 to 40) days, P < 0.05) and a 39% reduction in hospital stay (12 (8 to 13) days v 20 (10 to 61) days, P < 0.05).\n Proximal femoral fracture repair constitutes surgery in a high risk population. Intraoperative intravascular volume loading to optimal stroke volume resulted in a more rapid postoperative recovery and a significantly reduced hospital stay.", "To evaluate the effects of maximizing the oxygen delivery on morbidity and mortality in patients >60 yrs of age and/or with chronic diseases of vital organs who underwent major elective surgery.\n Prospective, randomized, controlled trial.\n A 24-bed general intensive care unit of a teaching hospital.\n Thirty-seven high-risk patients who underwent major surgery.\n The hemodynamic and oxygen transport variables and outcomes in 18 patients (control group) treated to maintain normal values of oxygen delivery were compared with 19 patients (protocol group) treated to maintain \"supranormal\" values. Therapy in both groups consisted of volume expansion and, when necessary, dobutamine to reach target values, during the surgery and 24 hrs postoperatively.\n We interrupted the study because of a significant difference in the 60-day mortality rate. The mortality rate in the control group was significantly higher when compared with the protocol group (9/18 [50%] vs. 3/19 [15.7%], p < .05). The prevalence of clinical and infectious complications was higher in the control group than in the protocol group (67% and 31% respectively; relative risk, 0.47; 95% confidence interval, 0.226-0.991; p < .05) and there was a trend toward more severe organ dysfunction in nonachievers patients (17/24 [71%] vs. 6/13 [46%], relative risk, 0.65; 95% confidence interval, 0.343-1.237; NS).\n Older patients with existing cardiorespiratory illness undergoing major surgery have a reduced morbidity and mortality when dobutamine is used to maximize oxygen transport.", "To test the hypothesis that perioperative plasma volume expansion would preserve gut mucosal perfusion during elective cardiac surgery.\n Prospective randomized open study.\n Teaching hospital.\n Sixty American Society of Anesthesiology grade III patients with a preoperative left ventricular ejection fraction of 50% or greater undergoing elective cardiac surgery.\n Patients were allocated randomly to a control or protocol group. The control group was treated according to standard practices. After induction of general anesthesia, the protocol group received, in addition, 200-mL boluses of a 6% hydroxyethyl starch solution to obtain a maximum stroke volume. This procedure was repeated every 15 minutes until the end of surgery, except when the patient underwent cardiopulmonary bypass.\n Cardiac stroke volume was estimated by an esophageal Doppler system, and gastric mucosal perfusion was measured by tonometric assessment of gastric intramucosal pH in all patients. Patients were followed up postoperatively until discharge from the hospital or death. The incidence of gut mucosal hypoperfusion (gastric intramucosal pH < 7.32) at the end of surgery was reduced in the protocol group (7% vs 56%) (P < .001), as were the number of patients in whom major complications developed (0 vs 6) (P = .01), mean number of days spent in the hospital (6.4 [range, 5 to 9] vs 10.1 [range, 5 to 48]) (P = .011), and mean number of days spent in the intensive care unit (1 [range, 1 to 1] vs 1.7 [range 1 to 11] days) (P = .023).\n Perioperative plasma volume expansion with colloid during cardiac surgery, guided by esophageal Doppler measurement of cardiac stroke volume, reduced the incidence of gut mucosal hypoperfusion. This group of patients also had an improved outcome when compared with controls.", "To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome.\n Randomised controlled trial with double blinding between inotrope groups. Setting: York District Hospital, England.\n 138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions. Interventions: Patients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluid, and either adrenaline or dopexamine to increase oxygen delivery. Inotropic support was continued during surgery and for at least 12 hours afterwards. The third group (control) received routine perioperative care.\n Hospital mortality and morbidity.\n Overall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P=0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%) patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95% confidence interval 2% to 41%) and 28 patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital.\n Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care.", "Survivors of high-risk surgical operations were previously observed to have significantly higher mean CI, DO2, and VO2 than nonsurvivors. The hypothesis was proposed that increased CI and DO2 are circulatory compensations for increased postoperative metabolism. We tested this hypothesis in two series. In series 1, prospectively allocated by services, mortality and morbidity of the control group were significantly greater than those of the protocol group. In series 2, patients who fulfilled previously defined high-risk criteria were preoperatively randomized to one of three monitoring/treatment groups: CVP-control group, PA-control group and PA-protocol group. Postoperative mortalities in the CVP-control and PA-control groups were not statistically significantly different, but PA-protocol group mortality was significantly reduced compared with its control group. The PA-protocol group had reduced complications, duration of hospitalization, duration in ICU, and mechanical ventilation, and reduced costs when the PA catheter was placed preoperatively and used to augment circulatory responses.", "No consensus exists regarding the optimal fluid (crystalloid or colloid) or strategy (liberal, restricted, or goal directed) for fluid management after colectomy. Prior assessments have used normal saline. This is the first assessment of standard, goal-directed perioperative fluid management with either lactated Ringer's or hetastarch/lactated Ringer's, with use of esophageal Doppler for guidance, in laparoscopic colectomy with an enhanced recovery protocol.\n A double-blinded, prospective, randomized, three-armed study with Institutional Review Board approval was used for patients undergoing laparoscopic segmental colectomy assigned to the standard, goal-directed/lactated Ringer's and goal-directed/hetastarch groups. A standard anesthesia and basal fluid administration protocol was used in addition to the goal-directed strategies guided by esophageal Doppler.\n Sixty-four patients undergoing laparoscopic colectomy (22 standard, 21 goal-directed/lactated Ringer's, 21 goal-directed/hetastarch) had similar operative times (standard, 2.3 hours; goal-directed/lactated Ringer's, 2.5 hours; goal-directed/hetastarch, 2.3 hours). The lactated Ringer's group received the greatest amount of total and milliliters per kilogram per hour of operative fluid (standard, 2,850/18; goal-directed/lactated Ringer's, 3,800/23; and goal-directed/hetastarch, 3,300/17; P < 0.05). The hetastarch group had the longest stay (standard, 64.9 hours; goal-directed/lactated Ringer's, 71.8 hours; goal-directed/hetastarch, 75.5 hours; P < 0.05). The standard group received the greatest amount of fluid during hospitalization (standard, 2.5 ml/kg/h; goal-directed/lactated Ringer's, 1.9 ml/kg/h; goal-directed/hetastarch, 2.1 ml/kg/h; P < 0.05). There was one instance of operative mortality in the goal-directed/hetastarch group.\n Goal-directed fluid management with a colloid/balanced salt solution offers no advantage and is more costly. However, goal-directed, individualized intraoperative fluid management with crystalloid should be evaluated further as a component of enhanced recovery protocols following colectomy because of reduced overall fluid administration.", "to evaluate whether perioperative haemodynamic optimisation influences outcome from infrarenal abdominal aortic aneurysm repair.\n a consecutive series of 100 eligible patients were randomised to either haemodynamic optimisation through the use of a pulmonary artery catheter (CI > 3.0 l/min/sqm, PWP > 10 and <18 mmHg, SVR <1450 dyne/sec/cm(-5), DO(2)> 600 ml/min/sqm) or conventional treatment.\n there were no differences in terms of in-hospital mortality, cardiovascular morbidity, postoperative renal failure or duration of hospital stay between the groups.\n in this study perioperative haemodynamic optimisation was not beneficial.\n Copyright 2002 Elsevier Science Ltd.", "Total hip replacement is one of the most commonly performed major orthopaedic operations. Goal-directed therapy (GDT) using haemodynamic monitoring has previously demonstrated outcome benefits in high-risk surgical patients under general anaesthesia. GDT has never been formally assessed during regional anaesthesia.\n Patients undergoing total hip replacement while under regional anaesthesia were randomised to either the control group (CTRL) or the protocol group (GDT). Patients in the GDT group, in addition to standard monitoring, were connected to the FloTrac sensor/Vigileo monitor haemodynamic monitoring system, and a GDT protocol was used to maximise the stroke volume and target the oxygen delivery index to > 600 mL/minute/m2.\n Patients randomised to the GDT group were given a greater volume of intravenous fluids during the intraoperative period (means ± standard deviation (SD): 6,032 ± 1,388 mL vs. 2,635 ± 346 mL; P < 0.0001), and more of the GDT patients received dobutamine (0 of 20 CTRL patients vs. 11 of 20 GDT patients; P < 0.0003). The GDT patients also received more blood transfused during the intraoperative period (means ± SD: 595 ± 316 mL vs. 0 ± 0 mL; P < 0.0001), although the CTRL group received greater volumes of blood replacement postoperatively (CTRL patients 658 ± 68 mL vs. GDT patients 198 ± 292 mL; P < 0.001). Overall blood consumption (intraoperatively and postoperatively) was not different between the two groups. There were an increased number of complications in the CTRL group (20 of 20 CTRL patients (100%) vs. 16 of 20 GDT patients (80%); P = 0.05). These outcomes were predominantly due to a difference in minor complications (20 of 20 CTRL patients (100%) vs. 15 of 20 GDT patients (75%); P = 0.047).\n GDT applied during regional anaesthesia in patients undergoing elective total hip replacement changes intraoperative fluid management and may improve patient outcomes by decreasing postoperative complications. Larger trials are required to confirm our findings.", "To evaluate the routine use of pulmonary artery catheters (PAC) in patients who undergo aortic surgery.\n One hundred twenty patients were randomized to placement of PACs for perioperative monitoring and hemodynamic optimization (tune up) in the intensive care unit on the night before aortic operation, or to intravenous hydration in the ward and perioperative monitoring without PACs. Before randomization, all patients underwent routine adenosine thallium-201 scintigraphy.\n To meet predetermined endpoints, 30 PAC patients (50%) received nitrates, inotropic agents, or both. PAC patients received more fluid in the preoperative period (p < 0.001) and in the first 24 hours after operation (p = 0.002) than control subjects. Eleven PAC patients (18%) and three control subjects (5%) had adverse intraoperative events (p = 0.02). There were 20 adverse postoperative events in 15 PAC patients (25%; nine cardiac, seven pulmonary, four acute tubular necrosis), which was not different compared with 11 postoperative events in 10 control subjects (17%; five cardiac, five pulmonary, one acute tubular necrosis). There were also no differences in duration of mechanical ventilation, intensive care unit stay, or hospital stay between groups. Postoperative cardiac complications were more common among patients who had a history of congestive heart failure (p = 0.02; odds ratio, 3.75; confidence interval, 1.3 to 11) or reperfusion defects on adenosine thallium scintigraphy (p = 0.01; odds ratio, 3.4; confidence interval, 1.2 to 9.4), regardless of group.\n Routine use of PACs for perioperative monitoring with the above protocol during aortic surgery is not beneficial and may be associated with a higher rate of intraoperative complications. Preoperative tune up does not prevent postoperative cardiac, renal, and other complications. Variables such as cardiac risk factors and adenosine thallium scintigraphy may be more important predictors of cardiac events in patients who undergo aortic operations.", "Goal-directed therapy (GDT) has been shown to improve outcome when commenced before surgery. This requires pre-operative admission to the intensive care unit (ICU). In cardiac surgery, GDT has proved effective when commenced after surgery. The aim of this study was to evaluate the effect of post-operative GDT on the incidence of complications and duration of hospital stay in patients undergoing general surgery.\n This was a randomised controlled trial with concealed allocation. High-risk general surgical patients were allocated to post-operative GDT to attain an oxygen delivery index of 600 ml min(-1) m(-2) or to conventional management. Cardiac output was measured by lithium indicator dilution and pulse power analysis. Patients were followed up for 60 days.\n Sixty-two patients were randomised to GDT and 60 patients to control treatment. The GDT group received more intravenous colloid (1,907 SD +/- 878 ml versus 1,204 SD +/- 898 ml; p < 0.0001) and dopexamine (55 patients (89%) versus 1 patient (2%); p < 0.0001). Fewer GDT patients developed complications (27 patients (44%) versus 41 patients (68%); p = 0.003, relative risk 0.63; 95% confidence intervals 0.46 to 0.87). The number of complications per patient was also reduced (0.7 SD +/- 0.9 per patient versus 1.5 SD +/- 1.5 per patient; p = 0.002). The median duration of hospital stay in the GDT group was significantly reduced (11 days (IQR 7 to 15) versus 14 days (IQR 11 to 27); p = 0.001). There was no significant difference in mortality (seven patients (11.3%) versus nine patients (15%); p = 0.59).\n Post-operative GDT is associated with reductions in post-operative complications and duration of hospital stay. The beneficial effects of GDT may be achieved while avoiding the difficulties of pre-operative ICU admission.", "Protocolized fluid administration using oesophageal Doppler monitoring may improve the postoperative outcome in patients undergoing surgery.\n A total of 108 patients undergoing elective colorectal resection were recruited into a double-blind prospective randomized controlled trial. An oesophageal Doppler probe was placed in all patients. The control group received perioperative fluid at the discretion of the anaesthetist, whereas the intervention group received additional colloid boluses based on Doppler assessment. Primary outcome was length of postoperative hospital stay. Secondary outcomes were morbidity, return of gastrointestinal function and cytokine markers of the systemic inflammatory response. Standard preoperative and postoperative management was used in all patients.\n Demographic and surgical details were similar in the two groups. Aortic flow time, stroke volume, cardiac output and cardiac index during the intraoperative period were higher in the intervention group (P<0.050). The intervention group had a reduced postoperative hospital stay (7 versus 9 days in the control group; P=0.005), fewer intermediate or major postoperative complications (2 versus 15 percent; P=0.043) and tolerated diet earlier (2 versus 4 days; P=0.029). There was a reduced rise in perioperative level of the cytokine interleukin 6 in the intervention group (P=0.039).\n A protocol-based fluid optimization programme using intraoperative oesophageal Doppler monitoring leads to a shorter hospital stay and decreased morbidity in patients undergoing elective colorectal resection.\n Copyright (c) 2006 British Journal of Surgery Society Ltd.", "The authors determined whether the preoperative placement of a pulmonary artery catheter (PAC) with optimization of hemodynamics results in outcome improvement after elective vascular surgery.\n The PAC commonly is used not only in patients who are critically ill, but also perioperatively in major elective surgery. Few prospective studies exist documenting its usefulness.\n One hundred four consecutive patients were randomized to have a PAC placed the morning of operation (group I) or to have a PAC placed only if clinically indicated (group II). Group I patients were resuscitated to preestablished endpoints before surgery and kept at these points both intraoperatively and postoperatively. Group II patients received standard care.\n There was one death in each group. An intraoperative or postoperative complication developed in 13 patients in group I versus 7 patients in group II (p = not significant). Group I patients received more fluid than did group II patients (5137 +/- 315 mL vs. 3789 +/- 306 mL; p < 0.003). There was no significant difference in either overall or surgical intensive care unit length of stay. Only one patient in group II required a postoperative PAC.\n Routine PAC use in elective vascular surgery increases the volume of fluid given to patients without demonstrable improvement in morbidity or mortality.", "Several studies have shown that goal-directed hemodynamic and fluid optimization may result in improved outcome. However, the methods used were either invasive or had other limitations. The aim of this study was to perform intraoperative goal-directed therapy with a minimally invasive, easy to use device (FloTrac/Vigileo), and to evaluate possible improvements in patient outcome determined by the duration of hospital stay and the incidence of complications compared to a standard management protocol.\n In this randomized, controlled trial 60 high-risk patients scheduled for major abdominal surgery were included. Patients were allocated into either an enhanced hemodynamic monitoring group using a cardiac index based intraoperative optimization protocol (FloTrac/Vigileo device, GDT-group, n = 30) or a standard management group (Control-group, n = 30), based on standard monitoring data.\n The median duration of hospital stay was significantly reduced in the GDT-group with 15 (12 - 17.75) days versus 19 (14 - 23.5) days (P = 0.006) and fewer patients developed complications than in the Control-group [6 patients (20%) versus 15 patients (50%), P = 0.03]. The total number of complications was reduced in the GDT-group (17 versus 49 complications, P = 0.001).\n In high-risk patients undergoing major abdominal surgery, implementation of an intraoperative goal-directed hemodynamic optimization protocol using the FloTrac/Vigileo device was associated with a reduced length of hospital stay and a lower incidence of complications compared to a standard management protocol.\n Clinical trial registration information: Unique identifier: NCT00549419.", "A prospective, randomized controlled trial comparing conventional intraoperative fluid management with two differing methods of invasive haemodynamic monitoring to optimize intraoperative fluid therapy, in patients undergoing proximal femoral fracture repair under general anaesthesia.\n Ninety patients randomized to three groups; conventional intraoperative fluid management (Gp CON, n=29), and two groups receiving additional repeated colloid fluid challenges guided by central venous pressure (Gp CVP, n=31) or oesophageal Doppler ultrasonography (Gp DOP, n=30). Primary outcome measures were time to medical fitness to discharge, hospital stay and postoperative morbidity.\n The fluid challenge resulted in significantly greater perioperative changes in central venous pressure between Gp CVP and Gp CON (mean 5 (95% confidence interval 3-7) mm Hg) (P<0.0001). Important perioperative changes were also shown in Gp DOP with increases of 49.4 ms (19.7-79.1 ms) in the corrected flow time, 13.5 ml (7.4-19.6 ml) in stroke volume, and 0.9 (0.49-1.39) litre min(-1) in cardiac output. As a result, fewer patients in Gp CVP and Gp DOP experienced severe intraoperative hypotension (Gp CON 28% (8/29), Gp CVP 9% (3/31), Gp DOP 7% (2/30), P=0.048 (chi-squared, 2 degrees of freedom (df). No differences were seen between the three groups when major morbidity and mortality were combined, P=0.24 (chi-squared, 2 df). Postoperative recovery for survivors, as defined by time to be deemed medically fit for discharge, was significantly faster, in comparison with Gp CON, in both the Gp CVP (10 vs 14 (95% confidence interval 8-12 vs 12-17) days, P=0.008 (t-test)), and Gp DOP (8 vs 14 (95% confidence interval 6-12 vs 12-17) days, P=0.023 (t-test). There were no significant differences between groups, for survivors, with respect to acute orthopaedic hospital and total hospital stay.\n Invasive intraoperative haemodynamic monitoring with fluid challenges during repair of femoral fracture under general anaesthetic shortens time to being medically fit for discharge." ]

[ "16511633", "15644657", "15350708", "1524162", "2245613", "10990101", "11398690", "11455735", "12790861", "15333426", "8143475", "9180492" ]

[ "Tracheal suction by closed system without daily change versus open system.", "Ventilator-associated pneumonia using a closed versus an open tracheal suction system.", "Comparison of the effect of closed versus open endotracheal suction systems on the development of ventilator-associated pneumonia.", "[Endotracheal suctioning using a 24-hour continuous system. Can costs and waste products be reduced?].", "Incidence of colonization, nosocomial pneumonia, and mortality in critically ill patients using a Trach Care closed-suction system versus an open-suction system: prospective, randomized study.", "Nosocomial pneumonia in mechanically ventilated patients, a prospective randomised evaluation of the Stericath closed suctioning system.", "Closed system endotracheal suctioning maintains lung volume during volume-controlled mechanical ventilation.", "Effect of different endotracheal suctioning systems on cardiorespiratory parameters of ventilated patients.", "A prospective, randomized study of ventilator-associated pneumonia in patients using a closed vs. open suction system.", "Closed suctioning system reduces cross-contamination between bronchial system and gastric juices.", "Closed versus open endotracheal suctioning: costs and physiologic consequences.", "Microbial colonization of closed-system suction catheters used in liver transplant patients." ]

[ "Tracheal suctioning costs are higher with a closed tracheal suction system (CTSS) than with an open system (OTSS), due to the need for complete daily change as recommended by the manufacturer. However, is it necessary to change the closed system daily?\n To evaluate the tracheal suctioning costs and incidence of ventilator-associated pneumonia (VAP) using closed system without daily change vs OTSS.\n Prospective and randomised study.\n An Intensive Care Unit in a university hospital.\n Patients requiring mechanical ventilation.\n Patients were randomly assigned to CTSS without daily change or OTSS. We used a CTSS that allowed partial or complete change.\n There were no significant differences between both groups of patients (236 with CTSS and 221 with OTSS) in gender, age, diagnosis, APACHE-II score, mortality, number of aspirations per day, percentage of patients who developed VAP (13.9 vs 14.1%) or the number of ventilator-associated pneumonia per 1000 days of mechanical ventilation (14.1 vs 14.6). There were not significant differences in tracheal suctioning costs per patient/day between CTSS vs OTSS (2.3+/-3.7 vs 2.4+/-0.5 Euros; p=0.96); however, when length of mechanical ventilation was lower than 4 days, the cost was higher with CTSS than with OTSS (7.2+/-4.7 vs 1.9+/-0.6 Euros; p<0.001); and when length of mechanical ventilation was higher than 4days, the cost was lower with CTSS than with OTSS (1.6+/-2.8 vs 2.5+/-0.5 Euros; p<0.001).\n CTSS without daily change is the optimal option for patients needing tracheal suction longer than 4 days.", "The aim of this study was to analyze the prevalence of ventilator-associated pneumonia (VAP) using a closed-tracheal suction system vs. an open system.\n Prospective and randomized study, from October 1, 2002, to December 31, 2003.\n A 24-bed medical-surgical intensive care unit in a 650-bed tertiary hospital.\n Patients requiring mechanical ventilation for >24 hrs.\n Patients were randomized into two groups; one group was suctioned with the closed-tracheal suctioning system and another group with the open system.\n Throat swabs were taken at admission and twice a week until discharge to classify pneumonia in endogenous and exogenous.\n A total of 443 patients (210 with closed-tracheal suction system and 233 with the open system) were included. There were no significant differences between groups of patients in age, sex, diagnosis groups, mortality, number of aspirations per day, and Acute Physiology and Chronic Health Evaluation II score. No significant differences were found in either the percentage of patients who developed VAP (20.47% vs. 18.02%) or in the number of VAP cases per 1000 mechanical ventilation-days (17.59 vs. 15.84). There were also no differences in the VAP incidence by mechanical ventilation duration. At the same time, we did not find any differences in the incidence of exogenous VAP. Likewise, there were also no differences in the microorganisms responsible for pneumonia. Patient cost per day for the closed suction was more expensive than the open suction system (11.11 US dollars +/- 2.25 US dollars vs. 2.50 US dollars +/- 1.12 US dollars, p < .001).\n We conclude that in our study, the closed-tracheal suction system did not reduce VAP incidence, even for exogenous pneumonia.", "The aim of this study was to compare the effect of closed versus open endotracheal suction systems on the development of ventilator-associated pneumonia (VAP). A prospective, randomized, controlled trial was performed in a medical intensive care unit (MICU) of a university hospital in patients who received mechanical ventilation for more than 48 h. Patients were randomized to receive endotracheal suction with either closed catheters (closed suction group; N-41) or single-use catheters (open suction group; N=37). Cultures were taken from the ventilator tubing of 42 patients to determine the rate of colonization. There was no difference between the groups in terms of the frequency of development of VAP, mortality in the MICU, length of MICU stay and duration of mechanical ventilation. Thirteen patients in the open suction group and 16 patients in the closed suction group became colonized (P=0.14). The colonization rates by Acinetobacter spp. and Pseudomonas aeruginosa were more frequent in the closed suction group than in the open suction group (P<0.01 and P=0.04, respectively). In conclusion, closed endotracheal suction resulted in increased colonization rates of ventilator tubing with multi drug-resistant micro-organisms but did not increase the development of VAP and MICU outcome compared with open endotracheal suction.", "Suctioning of the airways is often required in critically ill, intubated, or tracheotomised patients. In addition to the primary cost of these disposable materials, expenditures for waste disposal and environmental problems due to plastics should also be considered. In this study, the primary costs and amount of waste products of the closed suction system \"Trach Care\" were compared with a conventional disposable system. Other advantages and disadvantages of a closed suction system are discussed. METHODS. In this prospective, randomised investigation, both the open disposable suction system and the closed Trach Care system were used, in 60 patients (30 in each group) who were intubated for 1 week or more. During the first 7 days, we counted the number of times endotracheal suctioning was performed and measured the time it took. The costs of purchasing the systems, amounts of waste products, and costs of disposal were compared. RESULTS. The frequency of endotracheal suctioning was quite different from patient to patient and varied from 6 to 41 times per day. On average it was necessary 15 times per day per patient in both groups. Using the disposable system, a mean time of 3.5 min was measured in contrast to 2.5 min with the closed system. The costs of purchase were much lower with the disposable system taking into account all materials needed (17.36 DM vs 53.36 DM per day), whereas the weight of litter produced by the closed system was lower (429 g vs 745 g per day), the costs of disposal being accordingly different. During endotracheal suctioning O2 desaturation was not observed with the closed system, whereas in patients with acute respiratory failure O2 saturation fell rapidly from 90% to as far as 70% when a disposable system was used. CONCLUSION. The closed Trach Care suction system is more expensive to acquire, but may reduce the risk of exogenous nosocomial pneumonias as disconnections from the ventilator are minimised. The workload, weight of waste products, and costs of disposal are lower using the Trach Care system. From the physician's viewpoint, the main advantage of the Trach Care system becomes evident in patients with acute respiratory failure and patients with elevated intracranial pressure. In these cases, we now favor the Trach Care system as a matter of principle.", "Eighty-four intubated, mechanically ventilated patients were prospectively evaluated for incidences of colonization and nosocomial pneumonias dependent on whether they received endotracheal suctioning by an \"open\" suction method vs. \"closed\" suction (Trach Care Closed Suction System) method. Results show that closed suctioning is associated with a significant (67% vs. 39% p less than .02) increase in colonization compared with open suctioning. However, difference in the incidence of nosocomial pneumonia was not significantly (26% vs. 29%) different between closed and open suctioning. Differences in severity of illness (Acute Physiology and Chronic Health Evaluation II and Therapeutic Intervention Scoring System), age, sex, presence of NG tubes, use of H2 antagonists or antacids, use of antibiotics, and history of smoking were all nonsignificant. Survival analysis demonstrated that the probability of survival without developing nosocomial pneumonia was greater among closed-suctioning patients vs. open-suctioned patients (p less than .03). This study shows that suctioning performed via the Trach Care closed-suction system increases the incidence of colonization but not the incidence of nosocomial pneumonia, and may actually decrease mortality when compared with open-suction systems.", "To compare the ventilator-associated pneumonia (VAP) incidence rates in mechanically ventilated patients according to the type of endotracheal suctioning (closed versus open).\n The Neurosurgery Intensive Care Unit of the Grenoble University Hospital, France.\n A prospective randomised study performed after a 6-month period of nursing personnel training.\n One hundred four consecutive patients needing mechanical ventilation for more than 48 h were randomised into two groups. To be eligible, patients had to have no active infection or respiratory affection in their passes. In the Stericath group (S+, n = 54), patients were not disconnected from the ventilator during suctioning. The others were routinely managed (S-, n = 50). In both groups patterns of frequency and duration of suctioning were performed according to a standardised protocol.\n The non-adjusted incidence rate of VAP was lower for S+ than for S- (7.32 versus 15.89 per 1000 patient-days, p = 0.07). Multivariate analysis performed using the Cox model showed an adjusted risk of VAP 3.5 times higher in S- (95% CI: 11.00-12.33). The risk being 4.3 higher in patients receiving gastric acid secretion inhibitors (1.08-16.82). In non-censored cases (n = 76) length of ICU stay increased by an average of 16.8 days when VAP was present (p = 0.0008). No adverse effect due to Stericath use was noted and volume of tracheal aspirate was similar between groups (p = 0.178).\n The use of Stericath reduced the incidence rate of VAP without demonstrating any adverse effect.", "A closed suction system (CS) maintains connection with the mechanical ventilator during tracheal suctioning and is claimed to limit loss in lung volume and oxygenation. We compared changes in lung volume, oxygenation, airway pressure and hemodynamics during endotracheal suctioning performed with CS and with an open suction system (OS).\n Prospective, randomized study.\n Intensive care unit in a university hospital.\n We enrolled ten patients, volume-controlled (VC) ventilated with a Siemens Servo 900 ventilator (PaO2/FIO2 192 +/- 70, PEEP 10.7 +/- 3.9 cmH2O).\n We performed four consecutive tracheal suction maneuvers, two with CS and two with OS, at 20-min intervals. During the suction maneuvers continuous suction was applied for 20 s.\n We measured end-expiratory lung volume changes (delta VL), tidal volume (VTrt), respiratory rate (RR) and minute volume (VErt) by respiratory inductive plethysmography; arterial oxygen saturation (SpO2), airway pressure and arterial pressure (PA). Loss in lung volume during OS (delta VL 1.2 +/- 0.7 l) was significantly higher than during CS (delta VL 0.14 +/- 0.1 l). During OS we observed a marked drop in SpO2, while during CS the change was only minor. During CS ventilation was not interrupted and we observed an immediate increase in RR (due to the activation of the ventilator's trigger), while VTrt decreased, VErt was maintained.\n Avoiding suction-related lung volume loss can be helpful in patients with an increased tendency to alveolar collapse; CS allows suctioning while avoiding dramatic drops in lung volumes and seems to be safe during the VC ventilation setting that we used.", "We conducted this prospective randomised cross-over study to evaluate the effect of closed system (CS) versus open system (OS) endotracheal suctioning on heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), oxygen saturation (SpO2) and electrocardiogram (ECG) rhythm of patients on mechanical ventilation.\n Fourteen adult patients were randomly allocated to receive either CS or OS suctioning in the first instance. For the subsequent suctioning, they were crossed over to the alternate suctioning system. The various cardiorespiratory parameters were recorded at BL1 (baseline 1), S1 (first suction pass), BL2 (baseline 2, i.e. immediately post first suction pass), S2 (second suction pass), T2 (2 minutes post suction) and T5 (5 minutes post suction).\n Compared to CS, OS suctioning was found to result in higher HR at S1 (P < or = 0.05) and S2 (P < or = 0.05); higher MAP at BL2 (P < or = 0.05); lower SpO2 at BL2 (P < or = 0.01) and S2 (P < or = 0.01). There was no significant difference in RR between the two suctioning systems. OS suctioning was also noted to result in a significantly higher incidence of arrhythmia (P < = or 0.05).\n Our study shows that OS suctioning results in more adverse changes in cardiorespiratory parameters compared to CS suctioning.", "The objective of this study was to verify the incidence of nosocomial pneumonia in intubated and extended mechanically ventilated patients having endotracheal suctioning by an open vs. closed suction method aiming to decrease nosocomial pneumonia. Twenty-four (51.1%) patients received open-tracheal suction and 23 (48.9%) received closed-tracheal suction. The inclusion criteria were: surgical and medical patients older than 13 years, undergoing mechanical ventilation for more than 48 hours. Additional data were gathered using the Acute Physiology and Chronic Health Evaluation II, and details on smoking, alcoholism, diabetes mellitus, renal failure, previous lung disease, and previous use of antibiotics, steroids, H2 antagonists and antacids. Among the 24 patients having open-tracheal suction, 11 developed nosocomial pneumonia while of the 23 patients undergoing closed-tracheal suction, seven developed infection (P = 0.278). Risk factors for nosocomial pneumonia were not significantly different between the two groups. In the final logistical regression model the following variables remained: groups (open and closed) [odds ratio (OR) = 0.014; confidence interval (CI) = 0.001-0.416; P = 0.014] and use of prior antibiotics (OR = 2.297; CI = 1.244-4.242; P = 0.008). Use of a closed suction system did not decrease the incidence of nosocomial pneumonia when compared with the open system. The exogenous risk factors were the most important for acquiring this infection.", "In this prospective, randomized study, we evaluated whether a closed suctioning (CS) system (TrachCare) influences crossover contamination between bronchial system and gastric juices when compared with an open suctioning system (OS). The secondary aims were an analysis of the frequency of ventilator-associated pneumonia (VAP) and an analysis of alteration in gas exchange. Antibiograms were performed from tracheal secretions and gastric juice aspirates on Days 1 and 3 of intubation in 24 patients in a medical intensive care unit. Five cross-contaminations were observed in the OS group on Day 3 versus Day 1; the 5 strains shared common genotypes as determined by random amplification of polymorphic DNA. No cross-contaminations were seen in the CS group (P = 0.037). VAP occurred in 5 patients of the OS group but in none of the CS group patients (P = 0.037). Spao(2) decreased significantly in the OS group compared with presuctioning values--the opposite of the CS group. Whereas presuctioning values were comparable between groups, postsuctioning Spao(2) was significantly higher in the CS group. CS significantly reduced cross-contamination between bronchial system and gastric juices and reduced the incidence of VAP when compared with OS. Hypoxic phases can be reduced by the help of CS.", "To examine the physiologic consequences and costs associated with two methods of endotracheal suctioning: closed vs. open.\n A prospective, randomized, controlled study.\n An eight-bed trauma intensive care unit (ICU) in a 460-bed level I trauma center.\n The study included 35 trauma/general surgery patients (16 in the open suction group, 19 in the closed suction group) who were treated with a total of 276 suctioning procedures (127 open, 149 closed).\n Physiologic data collected after hyperoxygenation, immediately after suctioning, and 30 secs after suctioning, were compared with baseline values. Open endotracheal suctioning resulted in significant increases in mean arterial pressure throughout the suctioning procedure. Both methods resulted in increased mean heart rates. However, 30 secs after the procedure, the open-suction method was associated with a significantly higher mean heart rate than was the closed method. Closed suctioning was associated with significantly fewer dysrhythmias. Arterial oxygen saturation and systemic venous oxygen saturation decreased with open suctioning. In contrast, arterial oxygen saturation and systemic venous oxygen saturation increased with the closed suction method. There was no difference between the two methods in the occurrence of nosocomial pneumonia. Open endotracheal suctioning cost $1.88 more per patient per day and required more nursing time.\n The closed suction method resulted in significantly fewer physiologic disturbances. Closed suctioning appears to be an effective and cost-efficient method of endotracheal suctioning that is associated with fewer suction-induced complications.", "The microbial colonization and the associated risk of respiratory infection during the application of a multiple-use closed-system suction catheter (CSSC) and a single-use open-system suction catheter (OSSC) on liver transplant patients was evaluated in this preliminary study. The cost differential for the two systems was also compared. Twenty post-orthotopic liver transplant (OLTx) patients who were mechanically ventilated via an endotracheal (ET) tube were studied. Ten subjects were randomly allocated ET suction by the CSSC and 10 with OSSC. Both groups were similar according to age, sex, clinical severity, presence of a naso-gastric tube, use of H2 antagonists and antibiotics used. Standard protocols were followed to intubate and suction the patients and to change ventilatory equipment. Suctioning performed with the CSSC did not significantly increase the risk of microbial colonization of the respiratory tract. Similarly there was no apparent difference in the incidence of nosocomial pneumonia between the two suction systems, based on the microbiological and clinical data. The mean daily cost of using the CSSC compared to the OSSC was 11.6 times higher. This may be balanced by a reduction in nursing time and reduced risk of spread of infection associated with the CSSC." ]

[ "16801628", "9469327", "18250350", "12867108" ]

[ "Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853--a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group.", "Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17.", "Absolute risk reductions for local recurrence after postoperative radiotherapy after sector resection for ductal carcinoma in situ of the breast.", "Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial." ]

[ "The European Organisation for Research and Treatment of Cancer conducted a randomized trial investigating the role of radiotherapy (RT) after local excision (LE) of ductal carcinoma-in-situ (DCIS) of the breast. We analyzed the efficacy of RT with 10 years follow-up on both the overall risk of local recurrence (LR) and related to clinical, histologic, and treatment factors.\n After complete LE, women with DCIS were randomly assigned to no further treatment or RT (50 Gy). One thousand ten women with mostly (71%) mammographically detected DCIS were included. The median follow-up was 10.5 years.\n The 10-year LR-free rate was 74% in the group treated with LE alone compared with 85% in the women treated by LE plus RT (log-rank P < .0001; hazard ratio [HR] = 0.53). The risk of DCIS and invasive LR was reduced by 48% (P = .0011) and 42% (P = .0065) respectively. Both groups had similar low risks of metastases and death. At multivariate analysis, factors significantly associated with an increased LR risk were young age (< or = 40 years; HR = 1.89), symptomatic detection (HR = 1.55), intermediately or poorly differentiated DCIS (as opposed to well-differentiated DCIS; HR = 1.85 and HR = 1.61 respectively), cribriform or solid growth pattern (as opposed to clinging/micropapillary subtypes; HR = 2.39 and HR = 2.25 respectively), doubtful margins (HR = 1.84), and treatment by LE alone (HR = 1.82). The effect of RT was homogeneous across all assessed risk factors.\n With long-term follow-up, RT after LE for DCIS continued to reduce the risk of LR, with a 47% reduction at 10 years. All patient subgroups benefited from RT.", "In 1993, findings from a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial to evaluate the worth of radiation therapy after lumpectomy concluded that the combination was more beneficial than lumpectomy alone for localized intraductal carcinoma-in-situ (DCIS). This report extends those findings.\n Women (N = 818) with localized DCIS were randomly assigned to lumpectomy or lumpectomy plus radiation (50 Gy). Tissue was removed so that resected specimen margins were histologically tumor-free. Mean follow-up time was 90 months (range, 67 to 130). Size and method of tumor detection were determined by central clinical, mammographic, and pathologic assessment. Life-table estimates of event-free survival and survival, average annual rates of occurrence for specific events, relative risks for event-specific end points, and cumulative probability of specific events comprising event-free survival are presented.\n The benefit of lumpectomy plus radiation was virtually unchanged between 5 and 8 years of follow-up and was due to a reduction in invasive and noninvasive ipsilateral breast tumors (IBTs). Incidence of locoregional and distant events remained similar in both treatment groups; deaths were only infrequently related to breast cancer. Incidence of noninvasive IBT was reduced from 13.4% to 8.2% (P = .007), and of invasive IBT, from 13.4% to 3.9% (P < .0001). All cohorts benefited from radiation regardless of clinical or mammographic tumor characteristics.\n Through 8 years of follow-up, our findings continue to indicate that lumpectomy plus radiation is more beneficial than lumpectomy alone for women with localized, mammographically detected DCIS. When evaluated according to the mammographic characteristics of their DCIS, all groups benefited from radiation.", "Evaluate the effects of radiotherapy after sector resection for ductal carcinoma in situ of the breast (DCIS) in patient groups as defined by age, size of the lesion, focality, completeness of excision and mode of detection.\n A total of 1,067 women in Sweden were randomly assigned to either postoperative radiotherapy (RT) or control from 1987 to 1999, and 1,046 were followed for a mean of 8 years. The main outcome was new ipsilateral breast cancer events and distant metastasis-free survival analyzed according to intention to treat.\n There were 64 ipsilateral events in the RT arm and 141 in the control group corresponding to a risk reduction of 16.0 percentage points at 10 years (95% CI, 10.3% to 21.6%) and a relative risk of 0.40 (95% CI, 0.30 to 0.54). There was no statistically significant difference in distant metastasis-free survival. There was an effect modification by age, yielding a low effect of RT in women younger than 50, but substantial protection in women older than 60 years. The age effect was not confounded by focality, lesion size, completeness of excision, or detection mode. There was no group as defined by our stratification variables that had a low risk without radiotherapy.\n Our results indicate that younger women have a low protective effect of conventional RT after sector resection. Older women benefit substantially. We caution that the age effect was seen in a subgroup analysis. Further search with conventional clinical variables for a low risk group that does not need RT does not seem fruitful.", "As a consequence of mammographic breast screening programmes, ductal carcinoma in situ is diagnosed with increasing frequency. Mastectomy for localised ductal carcinoma in situ is thought to be an over-treatment by many physicians, but there is much controversy as to whether complete local excision alone is sufficient. We aimed to assess the effectiveness of adjuvant radiotherapy and tamoxifen.\n We used a 2x2 factorial design in a randomised controlled trial. Between May, 1990, and August, 1998, 1701 patients recruited from screening programmes were randomised to both treatments in combination or singly, or to none, or to either one (eg, radiotherapy) with an elective decision to give or to withhold the other (ie, in this case tamoxifen). Patients had complete surgical excision of the lesion confirmed by specimen radiography and histology. Patients have been followed up at least once a year. Median follow-up was 52.6 (range 2.4-118.3) months. Our primary endpoint was the incidence of ipsilateral invasive disease.\n Ipsilateral invasive disease was not reduced by tamoxifen but recurrence of overall ductal carcinoma in situ was decreased (hazard ratio 0.68 [0.49-0.96]; p=0.03). Radiotherapy reduced the incidence of ipsilateral invasive disease (0.45 [0.24-0.85]; p=0.01) and ipsilateral ductal carcinoma in situ (0.36 [0.19-0.66]; p=0.0004), but there was no effect on the occurrence of contralateral disease. There was no evidence of interaction between radiotherapy and tamoxifen.\n Radiotherapy can be recommended for patients with ductal carcinoma in situ treated by complete local excision; however, there is little evidence for the use of tamoxifen in these women." ]

[ "9154538", "10768519", "8258205", "3545844", "9181384" ]

[ "Equivalent efficacy and reduced occurrence of diarrhea from a new formulation of amoxicillin/clavulanate potassium (Augmentin) for treatment of acute otitis media in children.", "Efficacy and safety of amoxycillin/clavulanate (Augmentin) twice daily versus three times daily in the treatment of acute otitis media in children. The Augmentin 454 Study Group.", "Is treatment of acute otitis media with once-a-day amoxicillin feasible? Results of a pilot study.", "Amoxicillin twice daily in the treatment of acute otitis media in infants and children.", "Efficacy of twice-daily dosing of amoxycillin/clavulanate in acute otitis media in children." ]

[ "To compare the safety and efficacy, in treating acute otitis media (AOM) in children, of a new formulation of amoxicillin/clavulanate potassium (Augmentin) oral suspension providing 45/6.4 mg/kg/day and administered twice daily (bid) for 5 and 10 days, respectively, with the safety and efficacy of the original formulation providing 40/10 mg/kg/day and administered three times daily (tid) for 10 days.\n Eight hundred sixty-eight children ages 2 months to 12 years with AOM were randomly assigned to one of the three treatment groups. Stringent criteria were used for the diagnosis of AOM and for determinations of \"cure\" and \"improvement.\" Subjects were reexamined on Days 12 to 14 and 32 to 38.\n Among subjects whose treatment and follow-up conformed fully to protocol, the proportion of treatment successes (clinically cured or improved) on Days 12 to 14 was 78.8% (149 of 189) in the tid 10-day group, 86.5% (154 of 178) in the bid 10-day group and 71.1% (140 of 197) in the bid 5-day group. Corresponding values on Days 32 to 38 were 64.2% (95 of 148) in the tid 10-day group, 63.1% (94 of 149) in the bid 10-day group and 57.8% (93 of 161) in the bid 5-day group. None of the differences between the tid 10-day regimen and either of the 2 bid regimens were statistically significant, but the bid 10-day regimen was significantly more effective than the bid 5-day regimen in younger subjects. In the study population as a whole, results were similar to those in per protocol subjects. Overall the incidence of protocol-defined diarrhea was 26.7% (74 of 277) in the tid 10-day group, compared with 9.6% (27 of 280) in the bid 10-day group (P < 0.0001) and 8.7% (25 of 286) in the bid 5-day group (P < 0.0001).\n In comparison with the original formulation of Augmentin administered tid for 10 days in the treatment of AOM in children, the new formulation administered bid for 10 days provides at least equivalent efficacy and causes substantially less diarrhea. Administration for 5 days appears not to provide equivalent efficacy, but the difference appears limited to younger children and the margin of difference is small.", "This multicenter, randomized, single-blind study compared the efficacy and safety of a new, twice-daily formulation of amoxycillin/clavulanate (Augmenting) with the standard three-times-daily formulation. Children with a clinical diagnosis of acute otitis media, aged between 2 months and 12 years, received either amoxycillin/clavulanate 45/6.4 mg/kg/day twice-daily (b.d.) (range 38.3/5.5-76.2/10.9 mg/kg/day) or amoxycillin/clavulanate 40/10 mg/kg/day three-times-daily (t.d.s.) (range 25/6.25-56/14 mg/kg/day) for 7 or 10 days. Patients were evaluated during therapy (Days 3-5), at the end of therapy (Days 7-12) and at follow-up (Days 38-42). At the end of therapy, for the intent-to-treat and per-protocol populations, respectively, clinical success (cure) was achieved by approximately 94% of patients in both treatment groups. A successful bacteriological response at the end of therapy (Visit 3) was documented in 7/9 patients (77.8%) in the twice-daily group and in 11/13 patients (84.6%) in the three-times-daily group. At follow-up (Visit 4), 93.3% of patients in the twice-daily group and 87.9% in the three-times-daily group continued to have a clinically successful response. Both treatment regimens were well tolerated, with most adverse events being of a mild-moderate and transient nature. The most common treatment-related adverse event was diarrhea, occurring in 7.2% of patients in the twice-daily group and in 10.7% of the three-times-daily group. In total, 173 patients (82.8%) in the twice-daily group and 151 patients (73.3%) in the three-times-daily group were compliant with medication. In conclusion, this study confirms that b.d. amoxycillin/clavulanate is an effective treatment for pediatric acute otitis media and demonstrates that the b.d. and t.d.s. formulations of amoxycillin/clavulanate produce equivalent efficacy. Furthermore, there was a trend towards a higher level of compliance and a lower incidence of drug-related adverse events in the twice-daily compared with the three-times-daily treatment group.", "We report a study of the feasibility of once-a-day amoxicillin to treat acute otitis media (AOM). Seventy-seven children between ages 7 months and 12 years with AOM participated in a double-blind, placebo-controlled trial. Subjects received amoxicillin 40 mg/kg/day for 10 days. They were similar in age, sex, history of ear infections, and presenting symptoms. Group I received one total dose of amoxicillin and two doses of placebo daily. Group II received three divided doses of amoxicillin daily. Parents kept a daily diary of symptoms related to the child's illness and possible medication side effects. Ten children were lost to follow-up. In the remaining 67, pneumatic otoscopy and tympanometry after 10 to 14 days revealed that AOM had resolved in 82% of group I and 68% of group II. Groups showed no significant differences in persistence of middle ear effusion; 39% in group I and 24% in group II still had fluid. Diaries showed no significant differences between groups in medication side effects. Thus, reduced-frequency dosing for AOM seems feasible and more realistic than current regimens.", "A total of 110 children with acute otitis media were assigned randomly to treatment with 60 mg/kg per day amoxicillin in a twice-daily (group A) or a thrice-daily (group B) regimen for 10 days. Patients were scheduled for follow-up examinations at mid-treatment, 5 days after the end of therapy and 30, 60, 90 days after starting therapy. At 15 days 6 out of 55 patients (10.9%) treated with amoxicillin twice daily were considered treatment failures compared to 4 children (7.2%) in the thrice daily group. Rates of cure, recurrent otitis media and persistent middle ear effusion were comparable in the two groups of patients at later time intervals. By 90 days the total cure rate was 42.3% (22/52) in children treated twice daily and 41.5% (22/53) in those who had received amoxicillin thrice daily. At the same time persistence of bilateral and unilateral effusion was noted in 12/52 (23.1%) and 8/52 (15.3%) children in group A and in 16/53 (30.1%) and in 10/53 (18.9%) in group B respectively. No significant difference was noted in the two treatment regimens with regard to adverse side effects. Because reduction in division of the amoxicillin dose caused no significant difference in the efficacy of antibiotic treatment of acute otitis media in infants and children, we think that this simplified scheme of therapy can routinely be used in clinical practice and thus improve compliance to antibiotic administration.", "Children with acute otitis media (AOM), aged 2-12 years, were randomised to 10 days treatment with amoxycillin/clavulanate (A/C) 70/10 mg/kg/day given b.i.d. (231 patients) or to A/C 60/15 mg/kg/day given t.i.d. (232 patients). Clinical success rates at end of therapy (10-17 days) were 91.8% for the b.i.d. group and 90.5% for the t.i.d. group and at follow-up (28-42 days) were 80.1% for the b.i.d. group and 77.6% for the t.i.d. group, indicating that the b.i.d. regimen was as effective as the t.i.d. regimen. There was no statistically significant difference in incidence of adverse experiences between the two groups. The overall incidence of protocol defined diarrhoea assessed from diary booklets was low, with a lower incidence in the b.i.d. group (6.7%) than in the t.i.d. group (10.3%). Significantly more patients in the b.i.d. group (83.1%) than in the t.i.d. group (72.8%) had at least 80% compliance over a 7-10 day treatment period. A/C given twice or three-times daily was highly effective in the treatment of AOM in children. The two regimens showed equivalent clinical efficacy, both were well tolerated, and there was evidence of improved compliance with the b.i.d. regimen." ]

[ "1913123", "11797982", "10496712", "2107563" ]

[ "Randomized trial of intra-arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra-arterial streptokinase in peripheral arterial thrombolysis.", "Recombinant tissue plasminogen activator versus urokinase for local thrombolysis of femoropopliteal occlusions: a prospective, randomized multicenter trial.", "Prourokinase versus urokinase for recanalization of peripheral occlusions, safety and efficacy: the PURPOSE trial.", "Recombinant tissue-type plasminogen activator versus urokinase in peripheral arterial and graft occlusions: a randomized trial." ]

[ "Sixty patients were recruited into a randomized parallel group comparison of three thrombolytic regimens for acute or subacute peripheral arterial thrombosis. There were no significant differences in age, duration of history, length of occlusion or presence of neurosensory deficit between the groups. Initially successful lysis was significantly greater with intra-arterial (IA) recombinant tissue plasminogen activator (rt-PA) than with either streptokinase (Sk) (P less than 0.04) or intravenous (IV) rt-PA (P less than 0.01). The duration of therapy varied from a median of 35 h with IA rt-PA to 40 h with Sk (P greater than 0.5). The median (confidence interval) increase in ankle:brachial pressure index following IA rt-PA of 0.57 (0.33-0.82) was significantly higher than for either Sk of 0.24 (0-0.57) or for IV rt-PA of 0.18 (0-0.41). Limb salvage at 30 days was achieved in 80, 60 and 45 per cent respectively for IA rt-PA, Sk and IV rt-PA. Haemorrhagic complications occurred in six patients following Sk and in 13 following IV rt-PA; only one minor haemorrhage occurred following a catheter perforation in a patient who received IA rt-PA (P less than 0.05). IA rt-PA provides a more effective, safer fibrinolytic regimen than conventional therapy with Sk. IV rt-PA has not been as successful and carries a significantly higher risk of haemorrhagic complications.", "To report the outcome of a prospective, randomized, open multicenter trial comparing (1) the effects of local thrombolysis with recombinant tissue plasminogen activator (rtPA) or urokinase (UK) and (2) 2 administration techniques.\n Two hundred thirty-four patients with thromboembolic occlusions in 223 native femoral or popliteal arteries (95%) and 11 bypass grafts (5%) were randomized to rtPA (n = 124) or UK (n = 110) administered either through an endhole catheter (Hess technique) in 81 patients or a microporous balloon catheter (Schneider technique) in 153 patients. When lysis was incomplete, additional catheter interventions were applied to achieve patency. Results were analyzed by fluoroscopy during intervention and by angiography evaluated by independent experts blinded to the methods applied.\n The only significant difference between rtPA and UK was found at the end of lysis using the Hess technique. Complete reperfusion (TIMI grade 3) was produced in 60% of patients by rtPA versus 37% by UK (p = 0.045). By both techniques TIMI grade 3 was achieved in 62% with rtPA and in 50% with UK (p = 0.18). Independent of delivery technique, thrombolytic agent, or additional catheter interventions, TIMI grade 3 was achieved in 81% and angiographic patency in 88%. Primary patency at 6 months was 66%, which was increased by secondary interventions to 75%. Major amputations were performed in 6%, all in patients with initial Fontaine stage III/IV ischemia.\n With local thrombolysis alone, rtPA appears to be more effective than UK; however, additional catheter interventions further improved patency, abolishing the difference between the lytic agents.", "The intraarterial administration of thrombolytic agents is associated with clinical benefits in patients with acute peripheral arterial occlusion, and urokinase has been the agent that has become the standard of care in the United States. Recombinant prourokinase (r-ProUK) offers potential as a novel agent with improved fibrin specificity and, as such, may offer advantages as an attractive alternative to urokinase.\n A randomized, double-blind, parallel, phase II, prospective multicenter trial was undertaken to compare three doses of intra-arterial, catheter-directed r-ProUK (2 mg, 4 mg, or 8 mg/hr for 8 hrs, then 0.5 mg/hr) versus one dose of tissue-culture urokinase (4,000 IU/min for 4 hrs, then 2,000 IU/min) for the treatment of acute lower extremity arterial occlusion of 14 days' duration or less (n = 241). The primary endpoint was complete (>95%) lysis of the occluding thrombus after 8 hours of infusion.\n Increased clot lysis at 8 hours, decreased fibrinogen concentration, and an increased rate of hemorrhagic events were observed as the r-ProUK dose was increased from 2 mg/hr to 8 mg/hr. Similarly, a decreased duration of study drug infusion was seen, decreasing from 16.7 +/- 0.90 hours in the 2 mg/hr group to 12.7 +/- 0.97 hours in the 8 mg/hr group. The results for the urokinase group decreased to a level between those observed for the 2 mg and 8 mg r-ProUK group with respect to clot lysis at 8 hours, fibrinogen decrement, and bleeding complications, approximating those observed in the 4 mg/hr r-ProUK group. These results were achieved with a relatively low rate of major bleeding events and no episodes of intracranial hemorrhage.\n The 8 mg/hr dose of r-ProUK was associated with an increased rate of thrombolysis relative to the other treatment groups, associated with a slightly increased frequency of bleeding complications and decrements in fibrinogen concentration. Conversely, the 2 mg/hr r-ProUK dose was associated with a slightly slower rate of thrombolysis, but bleeding complications and fibrinogenolysis were diminished. r-ProUK is a novel thrombolytic agent with a dose-related safety and efficacy profile. As such, it offers potential as a useful tool in the treatment of peripheral vascular occlusion.", "A randomized prospective trial was undertaken to compare intraarterial administration of recombinant human tissue-type plasminogen activator (rt-PA) with urokinase (UK) in 32 patients with peripheral arterial or bypass graft occlusions. Sixteen patients were randomized to receive rt-PA and 16 to receive UK. The rt-PA dose was administered as a 10-mg bolus into the thrombus, followed by 5 mg/h for up to 24 hours. The UK dose was administered as a 60,000 IU bolus into the thrombus, followed by 240,000 IU/h for 2 hours, 120,000 IU/h for 2 hours, and 60,000 IU/h for up to 20 hours. Serial arteriograms were obtained at baseline and at 4, 8 or 16, and 24 hours. The endpoint was defined as 95% of greater clot lysis. The cumulative numbers of patients with successful thrombolysis (rt-PA vs UK) were four vs none at 4 hours, seven vs one at 8 hours, seven vs three at 16 hours, and eight vs six at 24 hours. Lysis occurred more rapidly in the rt-PA group (P = .04). Major bleeding complications occurred in five rt-PA patients and two UK patients (P = .39). At 24 hours, fibrinogen levels were significantly lower in the rt-PA group than in the UK group (P = .01). There was no apparent difference in 30-day clinical success." ]

[ "16047154", "16296913" ]

[ "Homeopathic treatment of children with attention deficit hyperactivity disorder: a randomised, double blind, placebo controlled crossover trial.", "Homeopathy for attention-deficit/hyperactivity disorder: a pilot randomized-controlled trial." ]

[ "An increasing number of parents turn to homeopathy for treatment of their hyperactive child. Two publications, a randomised, partially blinded trial and a clinical observation study, conclude that homeopathy has positive effects in patients with attention deficit hyperactivity disorder (ADHD). The aim of this study was to obtain scientific evidence of the effectiveness of homeopathy in ADHD. A total of 83 children aged 6-16 years, with ADHD diagnosed using the Diagnostic and Statistical Manual of Mental Disorders-IV criteria, were recruited. Prior to the randomised, double blind, placebo controlled crossover study, they were treated with individually prescribed homeopathic medications. 62 patients, who achieved an improvement of 50% in the Conners' Global Index (CGI), participated in the trial. Thirteen patients did not fulfill this eligibility criterion (CGI). The responders were split into two groups and received either verum for 6 weeks followed by placebo for 6 weeks (arm A), or vice-versa (arm B). At the beginning of the trial and after each crossover period, parents reported the CGI and patients underwent neuropsychological testing. The CGI rating was evaluated again at the end of each crossover period and twice in long-term follow-up. At entry to the crossover trial, cognitive performance such as visual global perception, impulsivity and divided attention, had improved significantly under open label treatment (P<0.0001). During the crossover trial, CGI parent-ratings were significantly lower under verum (average 1.67 points) than under placebo (P =0.0479). Long-term CGI improvement reached 12 points (63%, P <0.0001).\n The trial suggests scientific evidence of the effectiveness of homeopathy in the treatment of attention deficit hyperactivity disorder, particularly in the areas of behavioural and cognitive functions.", "The aim of this study was to carry out a preliminary trial evaluating the effectiveness of homeopathy in the treatment of attention-deficit/hyperactivity disorder (ADHD).\n This work was a randomized, double-blind, placebo-controlled trial.\n This study was conducted in a private homeopathic clinic in the Seattle metropolitan area.\n Subjects included children 6-12 years of age meeting Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria for ADHD.\n Forty-three subjects were randomized to receive a homeopathic consultation and either an individualized homeopathic remedy or placebo. Patients were seen by homeopathic physicians every 6 weeks for 18 weeks.\n Outcome measures included the Conner's Global Index-Parent, Conner's Global Index- Teacher, Conner's Parent Rating Scale-Brief, Continuous Performance Test, and the Clinical Global Impression Scale. Results: There were no statistically significant differences between homeopathic remedy and placebo groups on the primary or secondary outcome variables. However, there were statistically and clinically significant improvements in both groups on many of the outcome measures.\n This pilot study provides no evidence to support a therapeutic effect of individually selected homeopathic remedies in children with ADHD. A therapeutic effect of the homeopathic encounter is suggested and warrants further evaluation. Future studies should be carried out over a longer period of time and should include a control group that does not receive the homeopathic consultation. Comparison to conventional stimulant medication for ADHD also should be considered." ]

[ "3134343", "3069879", "10910801", "1550466", "8120155", "7620754", "1882999", "11386493", "6342421", "11195257", "3282482", "8124322", "2405806", "2221164", "6381556", "2671058" ]

[ "Treatment of bulimia with bupropion: a multicenter controlled trial.", "A trial of isocarboxazid in the treatment of bulimia nervosa.", "Fluoxetine for bulimia nervosa following poor response to psychotherapy.", "Fluoxetine in the treatment of bulimia nervosa. A multicenter, placebo-controlled, double-blind trial. Fluoxetine Bulimia Nervosa Collaborative Study Group.", "Is there a role for selective monoamine oxidase inhibitor therapy in bulimia nervosa? A placebo-controlled trial of brofaromine.", "Long-term fluoxetine treatment of bulimia nervosa. Fluoxetine Bulimia Nervosa Research Group.", "Long-term outcome of antidepressant treatment for bulimia nervosa.", "The relative efficacy of fluoxetine and manual-based self-help in the treatment of outpatients with bulimia nervosa.", "Bulimia treated with imipramine: a placebo-controlled, double-blind study.", "Efficacy and tolerability of moclobemide in bulimia nervosa: a placebo-controlled trial.", "Phenelzine vs placebo in 50 patients with bulimia.", "A double-blind placebo-controlled comparison of phenelzine and imipramine in the treatment of bulimia in atypical depressives.", "A comparison study of antidepressants and structured intensive group psychotherapy in the treatment of bulimia nervosa.", "Successful treatment of nonpurging bulimia nervosa with desipramine: a double-blind, placebo-controlled study.", "A placebo-controlled, double-blind trial of amitriptyline in bulimia.", "A placebo-controlled study of trazodone in bulimia nervosa." ]

[ "In a placebo-controlled, double-blind study of the unique antidepressant agent bupropion in the treatment of nondepressed subjects with bulimia (bupropion group, N = 55; placebo group, N = 26), we found the drug significantly superior to placebo in reducing episodes of binge eating and purging. In general, side effects with bupropion were minimal. However, four subjects experienced grand mal seizures during treatment with bupropion, a frequency of seizures far higher than observed in previous studies with this drug. Pending a satisfactory explanation for the occurrence of these seizures, we recommend that bupropion not be administered alone to bulimic patients.", "Eighteen women completed a double-blind, placebo-controlled crossover study designed to investigate the effects of isocarboxazid in the treatment of bulimia nervosa. There was a significant reduction in binge eating and vomiting during isocarboxazid treatment. Response was not influenced by either the presence or absence of current major depression or personality disorder. There were no serious adverse effects from this monoamine oxidase inhibitor therapy, although over 50% of patients elected to discontinue isocarboxazid 1 year after the study.", "This was an investigation of whether treatment with fluoxetine is useful for individuals with bulimia nervosa who do not respond to psychotherapy or relapse afterward.\n Twenty-two patients with bulimia nervosa who had not responded to, or had relapsed following, a course of cognitive behavior therapy or interpersonal psychotherapy were randomly assigned to receive placebo (N=9) or fluoxetine (60 mg/day, N=13) for 8 weeks.\n The median frequency of binge eating in the previous 28 days declined from 22 to four episodes in the fluoxetine group but increased from 15 to 18 episodes in the placebo group. Similarly, purging frequency in the previous 28 days declined from 30 to six episodes in the fluoxetine group but increased from 15 to 38 episodes in the placebo group.\n Fluoxetine may be a useful intervention for patients with bulimia nervosa who have not responded adequately to psychological treatment.", "Bulimia nervosa represents a serious public health problem in the United States. We performed an 8-week, double-blind trial comparing fluoxetine hydrochloride (60 and 20 mg/d) with placebo in 387 bulimic women treated on an outpatient basis. Fluoxetine at 60 mg/d proved superior to placebo in decreasing the frequency of weekly binge-eating and vomiting episodes at end point. Fluoxetine at 20 mg/d produced an effect between that of the 60-mg/d dosage and that of placebo. Depression, carbohydrate craving, and pathologic eating attitudes and behaviors also improved significantly with fluoxetine, with the higher dosage again showing a more robust effect than the lower dosage. Several adverse events (ie, insomnia, nausea, asthenia, and tremor) occurred significantly more frequently with fluoxetine (60 or 20 mg/d) than with placebo. However, there was no statistically significant difference among treatment groups in the proportion of patients discontinuing the study because of adverse events.", "Pharmacologic and cognitive behavioral therapies have been advocated in the treatment of bulimia nervosa (BN). Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A was selected for a double-blind, placebo-controlled evaluation because of previous demonstrated monoamine oxidase inhibitor efficacy in BN and because of its safer adverse reaction profile. Thirty-six female patients who met DSM-III-R criteria for BN were randomly assigned to the drug group (N = 19) or to the placebo group (N = 17) for an 8-week outpatient trial. Brofaromine produced a significant effect in decreasing episodes of vomiting throughout the trial, although comparable reductions in episodes of binge eating were found in both groups. Also, there were no advantages of drug over placebo on improvements in attitudinal measures and shape or on self-report ratings of depression and anxiety. However, a significant proportion of the subjects on brofaromine lost weight when compared with the placebo group. Methodologic issues including subjective assessment measures, placebo response rates, and the elucidation of responder subgroups are discussed.", "A large collaborative 8-week study has shown fluoxetine to be effective and safe in treating patients with bulimia nervosa. The present study evaluated fluoxetine over 16 weeks.\n Fifteen US out-patient psychiatry clinics conducted a double-blind parallel study in men and women with DSM-III-R bulimia nervosa (483 patients entered, 398 randomised [3:1 ratio, fluoxetine 60 mg/day or placebo], 225 completed). Outcome measures included change in vomiting and binge-eating episodes per week. Eating Disorder Inventory, Clinical Global Impressions and Patient's Global Impression.\n Compared with placebo, fluoxetine treatment resulted in significantly greater reductions in vomiting (F[1,360] = 14.73, P < 0.0001) and binge-eating (F[1,360] = 14.39, P = 0.0002) episodes per week at endpoint and improvement in other outcome measures. Adverse event, vital sign and laboratory analyses indicated that fluoxetine was safe.\n Fluoxetine appeared to be safe and effective in patients with bulimia nervosa for up to 16 weeks.", "The purpose of this study was 1) to replicate previous work indicating that antidepressant medication is superior to placebo in the treatment of bulimia nervosa and 2) to assess the long-term efficacy of this form of treatment.\n Eighty patients entered a three-phase treatment protocol. An 8-week double-blind initiation phase was used to compare the effects of desipramine and placebo. Patients who responded satisfactorily to desipramine entered a 16-week maintenance phase. Patients who remained well were then randomly assigned to either desipramine or placebo for 6 additional months (discontinuation phase). The primary outcome measure was binge frequency, which was assessed weekly by self-report diaries.\n In the initiation phase the superiority of desipramine over placebo in reducing binge frequency was demonstrated. Patients treated with desipramine had a mean reduction in binge frequency of 47% at termination, whereas patients taking placebo experienced a mean increase of 7%. Less than half of the patients treated with desipramine met the criteria for entering the maintenance phase, and 29% of the patients entering that phase relapsed in the following 4 months. There were not enough patients in the discontinuation phase to permit clear conclusions about the need for continued antidepressant medication after 6 months of treatment.\n The study documents a beneficial effect of desipramine in the treatment of bulimia nervosa when compared to placebo. However, limited improvement and considerable relapse with continued treatment suggest serious limitations to the long-term efficacy of a single antidepressant trial in treating bulimia nervosa.", "A randomized, placebo-controlled study was conducted examining the singular and combined effects of fluoxetine and a self-help manual on suppressing bulimic behaviors in women with bulimia nervosa. A total of 91 adult women with bulimia nervosa were randomly assigned to one of four conditions: placebo only, fluoxetine only, placebo and a self-help manual, or fluoxetine and a self-help manual. Subjects were treated for 16 weeks. Primary outcome measures included self-reports of bulimic behaviors. Fluoxetine and a self-help manual were found to be effective in reducing the frequency of vomiting episodes and in improving the response rates for vomiting and binge-eating episodes. Furthermore, both factors were shown to be acting additively on the primary and secondary efficacy measures in this study. Results are discussed in relation to previous research and the implications for treatment of bulimia nervosa.", "Bulimia, the syndrome of compulsive binge eating, is a common and often severe disorder frequently resistant to known therapies. Recent evidence suggesting a link between bulimia and affective disorder prompted the authors to perform a double-blind study of imipramine versus placebo with 22 chronically bulimic women. Imipramine was associated with a significantly reduced frequency of binge eating and with improvement on several other measures of eating behavior. On 1- to 8-month follow-up, 18 of the 20 treated subjects (90%) had responded to imipramine or a subsequent antidepressant. This finding augments the growing evidence that bulimia may be related to affective disorder.", "A 6-week double-blind placebo-controlled trial was carried out to examine the efficacy and tolerability of moclobemide, a monoamine oxidase type A selective and reversible inhibitor, in the treatment of bulimia nervosa. Patients were admitted to the study even if they were unable to adhere to a tyramine-free diet. Fifty-two normal-weight women (age range 18-40 years) suffering from bulimia nervosa (DSM-IV criteria) completed the trial. Particular emphasis was placed on evaluating the incidence of hypertension and other side-effects in chronically treated patients. At the usual antidepressant dose of 600 mg, moclobemide was not significantly superior to placebo in the reducing the weekly number of binge eating episodes or in improving several measures of eating attitudes and behaviour (BITE, EDI, TFEQ) in normal-weight bulimia nervosa. The dropout rate was relatively low (29%), and the side-effects were limited and equally distributed between the two treatment groups. No patient experienced a hypertensive crisis during the study and no serious side-effect was detected. The study indicates that moclobemide 600 mg pro die is not efficacious in bulimia nervosa, but it can be safely administered, even to young subjects, at a very high risk of consuming large amounts of tyramine-rich foods without dietary restrictions.", "To examine the efficacy of the monoamine oxidase inhibitor phenelzine sulfate in the treatment of bulimia, a double-blind, placebo-controlled trial was conducted. In 50 women who completed the trial, phenelzine was significantly superior to placebo in the reduction of binge frequency (64% vs 5%), in the fraction of patients who had ceased bingeing at the end of the trial (35% vs 4%), and in several measures of psychological state. The superiority of phenelzine over placebo was not confined to a depressed subgroup of patients. Although no patient experienced a hypertensive crisis during the study, other side effects of phenelzine were problematic and limit the usefulness of phenelzine in this population.", "Although antidepressants have been found to be superior to placebo in 12 of 14 studies, the relationship between improvement in the depressive diathesis and bulimia is unclear. In this study, the efficacy of placebo, imipramine, and phenelzine is examined in patients comorbid for atypical depression and bulimia. Greater improvement was observed for both depressive and bulimic symptoms with phenelzine than with either imipramine or placebo. Consistent with its poor antidepressant effects in atypical depression, imipramine seemed to have minimal efficacy for the bulimic symptoms of atypical depressives. These data suggest that the presence of bulimia does not alter the treatment response of atypically depressed patients. Furthermore, the data may suggest a link between depression and bulimia in atypical depressives. Demonstrating a statistical difference with a small sample suggests the effect size is robust, however conclusions are limited by a small sample size.", "Previous research on the treatment of outpatients with bulimia nervosa has focused on two treatment strategies: (1) drug therapy, primarily using tricyclic antidepressants, and (2) psychotherapy, often employing behavioral and cognitive behavioral techniques. We report here the short-term treatment outcome of a 12-week comparison trial of bulimic outpatients who were randomly assigned to one of four treatment cells: (1) imipramine hydrochloride treatment, (2) placebo treatment, (3) imipramine treatment combined with intensive group psychotherapy, and (4) placebo treatment combined with intensive group psychotherapy. All three active treatment cells resulted in significant reductions in target-eating behaviors and in a significant improvement in mood relative to placebo treatment. However, the results also suggested that the amount of improvement obtained with the intensive group psychotherapy component was superior to that obtained with antidepressant treatment alone. The addition of antidepressant treatment to the intensive group psychotherapy component did not significantly improve outcome over intensive group psychotherapy combined with placebo treatment in terms of eating behavior, but did result in more improvement in the symptoms of depression and anxiety.", "Twenty-three women with nonpurging bulimia underwent a 12-week, double-blind, placebo-controlled trial of desipramine hydrochloride. Repeated standardized rating scales, mood assessments, and self-reports of dietary habits were used to measure changes in binge frequency and cognitive processes associated with food intake. The women who received desipramine reduced their frequency of binge eating by 63%, but women receiving placebo increased their frequency of binge eating by 16%. Twelve weeks after initiating treatment, 60% of the treatment group but only 15% of the placebo group abstained from binge eating. The women who received desipramine showed significantly more dietary restraint and reported significantly less hunger, suggesting that desipramine acts to suppress appetite. These preliminary findings suggest that the therapeutic effects of desipramine established in the treatment of purging bulimia nervosa extend to patients with nonpurging bulimia.", "Bulimia is an eating disorder characterized by a pattern of episodic binge-eating. Patients with this eating disorder frequently demonstrate depressive symptoms when seen for evaluation. A familial association between bulimia and affective disorders has also been suggested. The authors report a placebo-controlled, double-blind trial of amitriptyline hydrochloride in a series of 32 female outpatients who satisfied DSM-III criteria for bulimia. The results of this study indicated that amitriptyline hydrochloride at a dosage of 150 mg at bedtime had significant antidepressant activity in this group of patients. Patients in both the placebo and active drug group also received a minimal behavioral treatment program in addition to drug therapy. Both groups demonstrated considerable improvement in eating behavior. The magnitude of this improvement was dramatic and not anticipated. The drug was well tolerated and was not associated with weight gain or increased carbohydrate craving.", "Forty-two women who met the new narrower criteria for bulimia nervosa of DSM-III-R completed a placebo-controlled double-blind study with trazodone. The drug proved significantly superior to placebo, both in measures of frequency of binge eating and vomiting and in the patients' subjective assessments of improvement. Trazodone produced few adverse effects." ]

[ "16094017", "15947626", "19375091", "15201783", "18499184", "17763227", "19389019" ]

[ "Using the circumstances of symptom experience to assess the severity of urgency in the overactive bladder.", "Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study.", "Outcome of a randomized, double-blind, placebo controlled trial of botulinum A toxin for refractory overactive bladder.", "Intravesical resiniferatoxin versus botulinum-A toxin injections for neurogenic detrusor overactivity: a prospective randomized study.", "Refractory idiopathic urge urinary incontinence and botulinum A injection.", "Efficacy and impact of botulinum toxin A on quality of life in patients with neurogenic detrusor overactivity: a randomised, placebo-controlled, double-blind study.", "Improvement in quality of life after botulinum toxin-A injections for idiopathic detrusor overactivity: results from a randomized double-blind placebo-controlled trial." ]

[ "We identified a method for quantifying the symptoms of the overactive bladder that addresses the assessment of urgency.\n An observational study of a cohort was used. Data were collected prospectively from 5,423 consultations on 1,797 patients (158 males and 1,639 females) being assessed and treated for the overactive bladder. The study was conducted during 5 years. The reported frequencies and incontinence episodes were recorded. Using ranked ordinal scales (none, mild, moderate, severe) the symptoms of urgency and urge incontinence associated with waking and rising, hearing running water, arriving home (\"latchkey\"), cold weather and when feeling tired or worried were noted. The experiences of urgency and urge incontinence, without reference to the circumstances in which they were experienced were similarly assessed and if on treatment, they were asked to grade their overall response.\n Reported urinary frequency and incontinence episodes were strongly associated with patient grading of response to treatment. Therefore, the symptoms assessed on the scale of none, mild, moderate and severe were compared with disease severity by using reported frequency and incontinence episodes. The description of the symptoms with reference to the situations in which they were experienced showed clear associations with frequency and incontinence, falling along a progressive scale. An overall pattern could be detected in that at points on the scale of none, mild, moderate and severe, the least frequency and incontinence tended to be associated with waking, rising and latchkey symptoms. Next followed symptoms precipitated by running water and cold weather. Aggravation by fatigue or worry was associated with the greatest disease severity (ANOVA F = 8.9, p <0.001). This scale covered a wide range from frequencies of 7 to 15 times daily and incontinence episodes through 0 to 4 times daily.\n Qualifying the experience of urgency and urge incontinence, according to the circumstances in which these symptoms are experienced, seems to offer a promising new method for assessing the severity of urgency and urge incontinence.", "We determined the safety and efficacy of each of 2 doses of botulinum toxin type A (BTX-A) (200 or 300 U BOTOX) injected into the detrusor for urinary incontinence caused by neurogenic detrusor overactivity of predominantly spinal cord origin.\n A total of 59 patients with urinary incontinence caused by neurogenic detrusor overactivity (due to spinal cord injury in 53 and multiple sclerosis in 6) requiring clean intermittent self-catheterization were randomized to receive a single dose into the detrusor of BTX-A (200 U or 300 U) or placebo. Changes in daily frequency of urinary incontinence episodes were monitored via a patient bladder diary during 24 weeks. Key urodynamic assessments (maximum cystometric capacity, reflex detrusor volume and maximum detrusor pressure during bladder contraction) were used to provide objective measures of the treatment effect on bladder function. The impact of treatment on quality of life was assessed using the Incontinence Quality of Life questionnaire.\n There were significant posttreatment decreases in incontinence episodes from baseline in the 2 BTX-A groups (p </=0.05) but not in the placebo group. In addition, more patients who received BTX-A reported no incontinence episodes during at least 1 posttreatment evaluation period. Positive treatment effects were also reflected by significant improvements in bladder function in the BTX-A groups, as assessed by urodynamics and in patient quality of life. Benefits were observed from the first evaluation at week 2 to the end of the 24-week study. No safety concerns were raised.\n Intramuscular injections of BTX-A into the detrusor can provide rapid, well tolerated, clinically significant decreases in the signs and symptoms of urinary incontinence caused by neurogenic detrusor overactivity during a 24-week study period.", "We determined the effectiveness of cystoscopic administration of botulinum-A toxin compared to placebo for the treatment of urinary incontinence in subjects with idiopathic overactive bladder.\n Subjects were recruited from the Division of Urogynecology at the University of Rochester. Inclusion criteria were overactive bladder refractory to anticholinergic medications, multiple daily incontinence episodes and a 24-hour pad weight of 100 gm or greater. Subjects with low leak point pressures, increased post-void residual volume or neurological etiologies were excluded from study. Subjects were randomized to placebo or to 1 of 2 doses of botulinum-A toxin. The detrusor was injected at 8 to 10 sites above the trigone. Evaluations were performed at baseline, and at 3 and 6 weeks after injection, and included bladder diaries, pad weights, quality of life questionnaires and urodynamic studies.\n A total of 22 subjects participated in stage 1 of this 2-stage study. We report on the outcomes of stage 1 of this study. Because stage 2 is still ongoing and investigators remain blind to the doses of botulinum-A toxin, the 2 botulinum-A toxin groups were combined for this report. There were no differences in mean baseline measurements between the 2 groups. Statistically significant improvements in daily incontinence episodes, pads changed per day and quality of life questionnaires were seen in the botulinum-A toxin group with no changes in the placebo group. No change in nocturia, daily voiding frequency, peak flow or detrusor pressure was seen in either group. Of 15 subjects 4 (26%) receiving botulinum-A toxin had a post-void residual volume of 200 cc or greater and 1 subject required intermittent catheterization. Four subjects experienced a urinary tract infection, 2 (13%) in the botulinum-A toxin group and 2 (28%) in the placebo group (not significant).\n Botulinum-A toxin can significantly reduce urge urinary incontinence due to overactive bladder at 6 weeks. However, there is a risk of urinary retention requiring self-catheterization.", "We investigated the effectiveness and safety of intravesical resiniferatoxin (Sigma Chemical Co., St. Louis, Missouri) and botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients with neurogenic detrusor overactivity unresponsive to conventional anticholinergic therapy.\n A total of 25 patients were randomly assigned to receive intravesically 0.6 microM resiniferatoxin in 50 ml of 0.9% NaCl or injections into the detrusor muscle of 300 units botulinum A-toxin diluted in 30 ml 0.9% NaCl. Clinical evaluation and urodynamics were performed at baseline, and at 6, 12 and 18 months after treatment.\n In both arms there was a significant decrease in catheterization and incontinent episodes, and a significant increase in first detrusor contraction and maximum bladder capacity at 6, 12 and 18-month followup. There were no local side effects with either treatment. Botulinum-A toxin induced a significant decrease in the frequency of daily incontinence episodes (p <0.05), a significant increase in first uninhibited detrusor contraction (p <0.01) in maximum bladder capacity (p <0.01), and a significant decrease in maximum pressure of uninhibited detrusor contractions (p <0.01) compared to resiniferatoxin at 6, 12 and 18-month followup.\n In spinal cord injured patients with refractory neurogenic detrusor overactivity, intravesical resiniferatoxin and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with decreases in detrusor overactivity and restoration of urinary continence in a large proportion of patients. Botulinum-A toxin injections provided superior clinical and urodynamic benefits compared to those of intravesical resiniferatoxin.", "We compared 200 U intradetrusor botulinum toxin A vs placebo in women with refractory idiopathic urge incontinence.\n This institutional review board approved, multicenter registered trial randomized women with refractory urge incontinence, detrusor overactivity incontinence and 6 or greater urge incontinence episodes in 3 days to botulinum toxin A or placebo at a 2:1 ratio. Refractory was defined as inadequate symptom control after 2 or more attempts at pharmacotherapy and 1 or more other first line therapies for detrusor overactivity incontinence. The primary outcome measure was time to failure, as evidenced by a Patient Global Impression of Improvement score of 4 or greater at least 2 months after injection, or changes in treatment (initiation or increase) at any time after injection. Safety data, including increased post-void residual volume, defined as more than 200 ml irrespective of symptoms, was obtained at specified time points.\n Approximately 60% of the women who received botulinum toxin A had a clinical response based on the Patient Global Impression of Improvement. The median duration of their responses was 373 days, significantly longer than the 62 days or less for placebo (p <0.0001). In the botulinum toxin A group increased post-void residual urine (12 of 28 women or 43%) and urinary tract infection in those with increased post-void residual urine (9 of 12 or 75%) exceeded expected ranges. Further injections were stopped after 43 patients were randomized, including 28 to botulinum toxin A and 15 to placebo.\n Local injection of 200 U botulinum toxin A was an effective and durable treatment for refractory overactive bladder. However, a transient post-void residual urine increase was experienced in 43% of patients. Botulinum toxin A for idiopathic overactive bladder is still under investigation.", "To evaluate the effect of a single injection of 500 U of botulinum toxin A (BTX-A; Dysport) on use of oral rescue medication, bladder compliance, continence and quality of life in a randomized, placebo-controlled, double-blind study in patients with incontinence due to neurogenic detrusor overactivity. As this group of patients often have severe symptoms, oral tolterodine was allowed as rescue medication and the amount of tolterodine consumed was our primary endpoint.\n A total of 31 patients with urinary leakage due to spinal cord injury, myelomeningocele, trauma at birth, multiple sclerosis and myelitis of another cause were randomized to intravesical injections of either 500 U of BTX-A or placebo. Intake of tolterodine and episodes of urinary leakage were registered. Cystometry was performed after 6, 12 and 26 weeks and quality of life was assessed.\n Patients in the BTX-A group had a significantly lower intake of tolterodine throughout the study compared to those in the placebo group (p=0.003). Cystometric capacity was significantly higher at 6 (p<0.001) and 12 weeks (p=0.026) and maximum detrusor pressure and frequency of urinary leakage were significantly (p<0.01) lower during follow-up in the BTX-A group compared to the placebo group. In addition, many quality-of-life parameters were significantly improved in the BTX-A group compared to the placebo group.\n Intravesical injection of 500 U of BTX-A in patients with neurogenic detrusor instability was shown to be an effective treatment which reduced use of oral medication, high detrusor pressure and frequency of urinary leakage during the overall study period of 26 weeks. Quality of life was also significantly improved.", "OBJECTIVE To determine whether botulinum toxin-A (BTX-A) treatment has an effect on the quality of life (QoL) of patients with overactive bladder (OAB) refractory to anticholinergics. PATIENTS AND METHODS This was a single centre, randomized, double-blind, placebo-controlled trial. Participants were men and women with idiopathic detrusor overactivity (IDO). Participants were randomised to receive either 200 U of BTX-A (Botox(R), Allergan Inc., Irvine, CA, USA; n = 16) or placebo (n = 18) via a trigone-sparing flexible cystoscopic technique. QoL was assessed using the King's Health Questionnaire (KHQ) at baseline and at 4 and 12 weeks, after injection. At 12 weeks patients were 'unblinded' and a further open-label follow-up in the BTX-A group occurred at 24 weeks. The changes in the subdomains of the KHQ were assessed over the study period. RESULTS Overall QoL was significantly improved in the BTX-A treated patients compared with placebo in the blinded part of the study. When analysing the KHQ subdomains, 'Incontinence Impact', 'Emotions', 'Physical Limitations', 'Social Limitations' and 'Severity Measures' were significantly improved in those that received BTX-A compared with placebo. The 'Symptom Severity' domain was also significantly improved at 4 weeks but not at 12 weeks. At 12 weeks 'Role Limitations' also became statistically significant in favour of BTX-A. The open-label extension study suggested these benefits last for at least 24 weeks. CONCLUSIONS BTX-A bladder injections at 200 U appear to improve QoL in patients with OAB symptoms and IDO refractory to anticholinergics for at least 24 weeks. As well as the improvement seen in clinical parameters with this form of therapy, perhaps of more importance to the patient, is the improvement in QoL." ]

[ "9009045", "8936754", "7751487", "10565503", "11926939" ]

[ "Body dysmorphic disorder: a preliminary evaluation of treatment and maintenance using exposure with response prevention.", "Body dysmorphic disorder: a cognitive behavioural model and pilot randomised controlled trial.", "Cognitive-behavioral body image therapy for body dysmorphic disorder.", "Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective efficacy of a serotonin reuptake inhibitor in imagined ugliness.", "A randomized placebo-controlled trial of fluoxetine in body dysmorphic disorder." ]

[ "In recent investigations, body dysmorphic disorder (BDD) has been shown to share common etiological and symptom presentation to obsessive-compulsive disorder (OCD). When treating BDD, there have been some investigations suggesting that exposure with response prevention is effective in alleviating symptoms. Ten patients diagnosed with BDD participated in a study examining the effects of treatment and maintenance using exposure with response prevention. They received a standard behavior therapy protocol which consisted of exposure in vivo and in imagery, with response prevention. Symptom severity, depression, anxiety, and avoidance were assessed weekly during treatment. Following treatment, a 6-month maintenance program was instituted for five patients, with the other five serving as controls. Patients in the maintenance program were assessed bi-weekly with all measures and a 6-month follow-up was conducted. Patients improved for measures of avoidance, BDD symptoms, depression and anxiety when using exposure with response prevention. Although all patients remained symptom free at follow-up, those in the maintenance program continued to improve. Based on these results, BDD appears to be amenable to exposure with response prevention treatment. Additional treatment gains can be obtained when structured maintenance programs are implemented.", "A cognitive behavioural model of body image is presented with specific reference to body dysmorphic disorder (BDD). We make specific hypotheses from the model for testing BDD patients in comparison with: (i) patients with \"real\" disfigurements who seek cosmetic surgery; (ii) subjects with \"real\" disfigurements who are emotionally well adjusted; and (iii) healthy controls without any defect. There have been no randomised controlled trials of treatment for BDD and therefore the model has clear implications for the development of cognitive behavioural therapy. This was evaluated in a pilot controlled trial. Nineteen patients were randomly allocated to either cognitive behaviour therapy or a waiting list control group over 12 weeks. There were no significant pre-post differences on any of the measures in the waiting list group. There were significant changes in the treated group on specific measures of BDD and depressed mood. Cognitive behaviour therapy should be further evaluated in a larger controlled trial in comparison with another psychological treatment such as interpersonal therapy and pharmacotherapy.", "Body dysmorphic disorder (BDD) is a distressing body image disorder that involves excessive preoccupation with physical appearance in a normal appearing person. Prior case reports of behavior therapy were encouraging, but no controlled evaluation of behavior therapy or any other type of treatment had been conducted. In the present study, 54 BDD subjects were randomly assigned to cognitive behavior therapy or no treatment. Patients were treated in small groups for eight 2-hour sessions. Therapy involved modification of intrusive thoughts of body dissatisfaction and overvalued beliefs about physical appearance, exposure to avoided body image situations, and elimination of body checking. Body dysmorphic disorder symptoms were significantly decreased in therapy subjects and the disorder was eliminated in 82% of cases at posttreatment and 77% at follow-up. Overall psychological symptoms and self-esteem also improved in therapy subjects.", "Body dysmorphic disorder (preoccupation with an imagined or slight defect in appearance) is a common and disabling disorder associated with high rates of delusional symptoms and suicide attempts. Although preliminary studies suggest that serotonin reuptake inhibitors may be effective for body dysmorphic disorder, to date no controlled treatment studies have been published.\n Forty patients were enrolled and 29 were randomized into a 16-week, double-blind, crossover-design study of clomipramine, a potent serotonin reuptake inhibitor, and active control desipramine, a selective norepinephrine reuptake inhibitor. Outcome measures included specific ratings of body dysmorphic disorder severity, delusionality, and functional impairment.\n Clomipramine was superior to desipramine in the acute treatment of body dysmorphic disorder symptoms as measured by assessment of patients' obsessive preoccupation with perceived body defects, repetitive behaviors in response to this preoccupation, and global ratings of symptom severity. Treatment efficacy was independent of the presence or severity of comorbid diagnoses of obsessive-compulsive disorder, depression, or social phobia. Likewise, clomipramine was equally effective regardless of whether the patients had insight or held their dysmorphic misperception with delusional intensity. Clomipramine was also superior to desipramine in improving functional disability.\n Clomipramine is more effective than desipramine in the treatment of body dysmorphic disorder and is effective even among those patients who are delusional.", "Research on the pharmacotherapy of body dysmorphic disorder (BDD), a common and often disabling disorder, is limited. Available data suggest that this disorder may respond to serotonin reuptake inhibitors. However, no placebo-controlled treatment studies of BDD have been published.\n Seventy-four patients with DSM-IV BDD or its delusional variant were enrolled and 67 were randomized into a placebo-controlled parallel-group study to evaluate the efficacy and safety of fluoxetine hydrochloride. After 1 week of single-blind placebo treatment, patients were randomized to receive 12 weeks of double-blind treatment with fluoxetine or placebo. Outcome measures included the Yale-Brown Obsessive Compulsive Scale Modified for Body Dysmorphic Disorder (BDD-YBOCS) (the primary outcome measure), the Clinical Global Impressions Scale, the Brown Assessment of Beliefs Scale, and other measures.\n Results of the BDD-YBOCS indicated that fluoxetine was significantly more effective than placebo for BDD beginning at week 8 and continuing at weeks 10 and 12 (F(1,64) = 16.5; P<.001). The response rate was 18 (53%) of 34 to fluoxetine and 6 (18%) of 33 to the placebo (chi(2)(1) = 8.8; P=.003). The BDD symptoms of delusional patients were as likely as those of nondelusional patients to respond to fluoxetine, and no delusional patients responded to the placebo. In the sample as a whole, treatment response was independent of the duration and severity of BDD and the presence of major depression, obsessive-compulsive disorder, or a personality disorder. Fluoxetine was generally well tolerated.\n Fluoxetine is safe and more effective than placebo in delusional and nondelusional patients with BDD." ]

[ "10941887", "14722400", "12973134", "10870148", "8130395", "11413440", "12131732", "14560188", "10101819", "8367786", "9431617", "8235847", "7608225", "11224865", "14685830", "24005193", "12461393", "9431616", "11725230", "10404578", "15346999", "12955608", "10828926", "2071615", "12902951", "2218718", "14749191" ]

[ "Prospective comparison of the effect of direct current electrical stimulation and pulsed electromagnetic fields on instrumented posterolateral lumbar arthrodesis.", "A prospective, randomized controlled clinical trial of anterior lumbar interbody fusion using a titanium cylindrical threaded fusion device.", "Randomized clinical trial of lumbar instrumented fusion and cognitive intervention and exercises in patients with chronic low back pain and disc degeneration.", "Surgery versus conservative management in adult isthmic spondylolisthesis--a prospective randomized study: part 1.", "The role of fusion and instrumentation in the treatment of degenerative spondylolisthesis with spinal stenosis.", "A prospective randomized comparison of 270 degrees fusions to 360 degrees fusions (circumferential fusions).", "Combined magnetic fields accelerate and increase spine fusion: a double-blind, randomized, placebo controlled study.", "ProDisc artificial total lumbar disc replacement: introduction and early results from the United States clinical trial.", "A randomized prospective study of posterolateral lumbar fusion. Outcomes with and without pedicle screw instrumentation.", "A prospective, randomized study of lumbar fusion. Preliminary results.", "1997 Volvo Award winner in clinical studies. The effect of pedicle screw instrumentation on functional outcome and fusion rates in posterolateral lumbar spinal fusion: a prospective, randomized clinical study.", "The use of primary internal fixation in spondylolisthesis.", "Degenerative lumbar spinal stenosis. Decompression with and without arthrodesis.", "Randomized controlled trial of percutaneous intradiscal radiofrequency thermocoagulation for chronic discogenic back pain: lack of effect from a 90-second 70 C lesion.", "A prospective randomized multi-center study for the treatment of lumbar spinal stenosis with the X STOP interspinous implant: 1-year results.", "Cancer risk after use of recombinant bone morphogenetic protein-2 for spinal arthrodesis.", "Circumferential lumbar spinal fusion with Brantigan cage versus posterolateral fusion with titanium Cotrel-Dubousset instrumentation: a prospective, randomized clinical study of 146 patients.", "1997 Volvo Award winner in clinical studies. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective, randomized study comparing decompressive laminectomy and arthrodesis with and without spinal instrumentation.", "2001 Volvo Award Winner in Clinical Studies: Lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish Lumbar Spine Study Group.", "A double-blind study of capacitively coupled electrical stimulation as an adjunct to lumbar spinal fusions.", "Neurological complications of lumbar artificial disc replacement and comparison of clinical results with those related to lumbar arthrodesis in the literature: results of a multicenter, prospective, randomized investigational device exemption study of Charité intervertebral disc. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004.", "Outcome of the Graf ligamentoplasty procedure compared with anterior lumbar interbody fusion with the Hartshill horseshoe cage.", "Lumbar spinal stenosis: conservative or surgical management?: A prospective 10-year study.", "Degenerative lumbar spondylolisthesis with spinal stenosis. A prospective study comparing decompression with decompression and intertransverse process arthrodesis.", "Lumbar spine arthroplasty: early results using the ProDisc II: a prospective randomized trial of arthroplasty versus fusion.", "A randomized double-blind prospective study of the efficacy of pulsed electromagnetic fields for interbody lumbar fusions.", "A randomized, placebo-controlled trial of intradiscal electrothermal therapy for the treatment of discogenic low back pain." ]

[ "The purpose of this prospective study was to compare the effect of adjunctive direct current (DC) electrical stimulation and pulsed electromagnetic field therapy (PEMF) on augmentation of instrumented lumbar fusion. Sixty-one patients undergoing lumbar spine fusion were enrolled in the study and randomized to one of three treatment protocols: 1) adjunctive PEMF group (n = 22) fitted with Spinal-Stim model 8212(AME) within 30 days of surgery; 2) DC group (n = 17) had a SpF-2T stimulator(EBI) implanted at the time of surgery; or 3) control group (n = 22). The fusion mass bone mineral density (BMD) assessment was performed on 3-month and 1-year radiographs for each patient. Lateral flexion-extension and anteroposterior radiographs were evaluated at 1 year to determine the presence of fusion. Clinical outcome patient analyses were performed at 1 year. At 1-year follow-up, radiographic fusion and fusion mass bone density were not significantly different among the groups. In the nonstimulated group, there were 43% excellent, 43% good, and 14% fair results. In the PEMF group, there were 35% excellent, 50% good, 10% fair, and 5% poor results. In the DC group, there were 32% excellent, 37% good, and 31% fair results. The results of the current study suggest that electrical stimulation does not significantly enhance fusion rate in instrumented lumbar arthrodesis, although we observed a statistically insignificant trend toward increased fusion mass BMD in the electrically stimulated groups. The significance of increased BMD remains unknown.", "A prospective, randomized, controlled clinical trial comparing a cylindrical threaded titanium cage to a femoral ring allograft control for anterior lumbar interbody fusion.\n To compare these two implants with regard to arthrodesis. Secondary outcome measures included pain relief, neurological status, and general health status.\n Anterior lumbar interbody fusion is a well-accepted procedure using trapezoidal femoral ring allografts or cylindrical titanium cages. Clinical and biomechanical studies evaluating these two distinct constructs are numerous; however, no prospective, randomized study comparing them has been done.\n A multicenter trial of 140 patients: 78 were randomized to the cylindrical threaded titanium cage device treatment arm and 62 patients randomized into the control group. All had autogenous iliac crest bone graft packed into the device. All patients had a single-level stand-alone anterior lumbar interbody fusion at either the L4-L5 or L5-S1 interspace for symptomatic degenerative disc disease. Radiographic fusion data were collected as well as multiple types of outcome data, including pain/disability scores, neurologic status, and overall health.\n At 12 months, 97% of the cylindrical threaded titanium cage device group and 40% of the control group demonstrated radiographic fusion. At 24 months, 97% of the cylindrical threaded titanium cage group and 52% of the control group showed radiographic fusion. These fusion rate differences are statistically significant (P < 0.001). The Oswestry and neurologic scores were not significantly different between groups.\n This is the first prospective, randomized, multicenter clinical trial that compares fusion cage results to control data.\n Cylindrical threaded titanium cages have a higher fusion rate, comparable improvements in clinical outcome (Oswestry, Low Back Pain Questionnaire, SF-36), and fewer secondary supplemental fixation procedures compared to the femoral ring allograft control.", "Single blind randomized study.\n To compare the effectiveness of lumbar instrumented fusion with cognitive intervention and exercises in patients with chronic low back pain and disc degeneration.\n To the authors' best knowledge, only one randomized study has evaluated the effectiveness of lumbar fusion. The Swedish Lumbar Spine Study reported that lumbar fusion was better than continuing physiotherapy and care by the family physician.\n Sixty-four patients aged 25-60 years with low back pain lasting longer than 1 year and evidence of disc degeneration at L4-L5 and/or L5-S1 at radiographic examination were randomized to either lumbar fusion with posterior transpedicular screws and postoperative physiotherapy, or cognitive intervention and exercises. The cognitive intervention consisted of a lecture to give the patient an understanding that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it. This was reinforced by three daily physical exercise sessions for 3 weeks. The main outcome measure was the Oswestry Disability Index.\n At the 1-year follow-up visit, 97% of the patients, including 6 patients who had either not attended treatment or changed groups, were examined. The Oswestry Disability Index was significantly reduced from 41 to 26 after surgery, compared with 42 to 30 after cognitive intervention and exercises. The mean difference between groups was 2.3 (-6.7 to 11.4) (P = 0.33). Improvements inback pain, use of analgesics, emotional distress, life satisfaction, and return to work were not different. Fear-avoidance beliefs and fingertip-floor distance were reduced more after nonoperative treatment, and lower limb pain was reduced more after surgery. The success rate according to an independent observer was 70% after surgery and 76% after cognitive intervention and exercises. The early complication rate in the surgical group was 18%.\n The main outcome measure showed equal improvement in patients with chronic low back pain and disc degeneration randomized to cognitive intervention and exercises, or lumbar fusion.", "A prospective randomized study was performed.\n To determine whether posterolateral fusion in patients with adult isthmic spondylolisthesis results in an improved outcome compared with an exercise program.\n In spondylolisthesis, satisfactory results have been reported with both surgical and conservative management. The evidence for treatment efficacy, however, is weak because prospective randomized studies are lacking.\n In this study, 111 patients were randomly allocated to an exercise program (n = 34) or posterolateral fusion with or without transpedicular fixation (n = 77). The inclusion criteria were lumbar isthmic spondylolisthesis of any grade, at least 1 year of low back pain or sciatica, and a severely restricted functional ability in individuals 18 to 55 years of age. Pain and functional disability were quantified before treatment and at 1- and 2-year follow-up assessments by visual analog scales (VAS).\n The 2-year follow-up rate was 93%. The functional outcome, as assessed by the Disability Rating Index and the pain reduction, was better in the surgically treated group than in the exercise group at both the 1- and 2-year follow-up assessments (P < 0.01). In the longitudinal analysis, the mean Disability Rating Index and pain improved in the surgical group (P < 0.0001). In the exercise group, the Disability Rating Index did not change at all, whereas the pain decreased slightly (P < 0.02).\n Surgical management of adult isthmic spondylolisthesis improves function and relieves pain more efficiently than an exercise program.", "Between February 1985 and March 1990 44 patients with degenerative spondylolisthesis underwent primary surgery for spinal stenosis (in all cases the decompression preserved the facets bilaterally without discectomy) and were studied prospectively. Forty-three patients have been followed for > or = 2 years and are the basis of this study. There were three treatment groups: group I, no fusion (nine patients); group II, transverse process fusion with autogenous iliac bone graft without instrumentation (11 initial patients, with one lost to follow-up for a total of 10); and group III, transverse process fusion with autogenous iliac crest bone graft and instrumentation (24 patients, 18 with one-level pedicle fixation and six with two-level fixation). A higher proportion of group III subjects had a successful fusion compared with group II (p = 0.002). There was significantly more spondylolisthesis progression in groups I and II than in group III (p = 0.001). A higher proportion of \"spondylolisthesis unchanged subjects\" reported they were helped by the surgery than those whose spondylolisthesis progressed postoperatively (p < 0.01).", "Prospective randomized comparison of anterior lumbar interbody fusion (ALIF) plus transpedicular instrumentation plus posterolateral fusion (PLF) (360 degrees fusion) to ALIF plus transpedicular instrumentation without PLF (270 degrees fusion).\n To compare the clinical outcomes, costs, and utilization of health resources of 360 degrees versus 270 degrees fusions.\n The 360 degrees fusion is effective, but its costs and utilization of health resources are high. The PLF often resorbs and may not be necessary.\n Before and after surgery pain was measured by the Numerical Rating Scale (NRS), and function was measured by the Oswestry Low Back Disability Index (OSI). Costs were calculated by billing records. Operating times, blood loss, and hospital stays were measured at the time of hospital discharge.\n There were 48 patients: 21 women and 27 men. Mean age was 42 years. Follow-up averaged 35 months (range 24-45 months). In both 360 degrees and 270 degrees fusions, there were significant improvements in NRS and OSI, and the percentage of solid ALIF was high. Only 14% of PLF appeared solid bilaterally and 18% appeared solid on one side only. There were no significant differences in changes in NRS, changes in OSI, or percentage solid ALIF between the 360 degrees and 270 degrees fusions. However, the 270 degrees fusion group had significantly less blood loss, shorter operative times, shorter hospital stays, and lower professional fees, and although hospital charges were lower, this difference was not significant.\n Both the 360 degrees and 270 degrees fusions significantly reduce pain and improve function, and there are no significant clinical differences between them. However, there were shorter operating times, less blood loss, lower costs, and less utilization of health care resources associated with the 270 degrees fusions.", "The clinical study conducted was a prospective, randomized, double-blind, placebo-controlled trial.\n The purpose of this study was to evaluate the effect of combined magnetic fields on the healing of primary noninstrumented posterolateral lumbar spine fusion.\n Combined magnetic fields, a new type of biophysical stimulus, have been shown to act by stimulating endogenous production of growth factors that regulate the healing process. This is the first placebo-controlled study to assess the effect of an electromagnetic stimulus on primary noninstrumented posterolateral lumbar spine fusion surgery as well as the first evaluation of combined magnetic fields as an adjunctive stimulus to lumbar spine fusion.\n This multicenter investigational study was conducted at 10 clinical sites under an Investigational Device Exemption from the United States Food and Drug Administration. Eligible patients had one-level or two-level fusions (between L3 and S1) without instrumentation, either with autograft alone or in combination with allograft. The combined magnetic field device used a single posterior coil, centered over the fusion site, with one 30-minute treatment per day for 9 months. Randomization was stratified by site and number of levels fused. Evaluation was performed 3, 6, and 9 months after surgery and 3 months after the end of treatment. The primary endpoint was assessment of fusion at 9 months, based on radiographic evaluation by a blinded panel consisting of the treating physician, a musculoskeletal radiologist, and a spine surgeon.\n Of 243 enrolled patients, 201 were available for evaluation. Among all patients with active devices, 64% healed at 9 months compared with 43% of patients with placebo devices: a significant difference (P = 0.003 by Fisher's exact test). Stratification by gender showed fusion in 67% of women with active devices, compared with 35% of those with placebo devices (P = 0.001 by Fisher's exact test). By contrast, there was not a statistically significant effect of the active device in this male study population. In the overall population of 201 patients, repeated measures analyses of fusion outcomes (by generalized estimating equations) showed a main effect of treatment, favoring the active treatment (P = 0.030). In a model with main effect and a time by treatment interaction, the latter was significant (P = 0.024), indicating acceleration of healing. Performed in the full sample of 243 patients, results of the intent-to-treat analysis were qualitatively the same as in the evaluable sample of 201 patients.\n This investigational study demonstrates that combined magnetic field treatment of 30 min/d increases the probability of successful spine fusion, and statistical analysis using the generalized estimating equations model suggests an acceleration of the healing process. This is the first randomized clinical trial of noninstrumented primary posterolateral lumbar spine fusion, with evaluation by a blinded, unbiased panel. This is the first double-blind study performed to date assessing noninstrumented fusion outcome with extremely critical radiographic criteria. The lower overall fusion rates in this study are attributed to the high-risk patient group with an average age of 57 years, the use of noninstrumented technique with posterolateral fusion only, and the reliance on extremely critical radiographic and clinical criteria and blinded panel for fusion assessment without surgical confirmation.\n In conclusion, the adjunctive use of the combined magnetic field device was statistically beneficial in the overall patient population, as has been shown in previous studies of adjunctive bone growth stimulation for spine fusion. For the first time, stratification of fusion success data by gender demonstrated that the female study population responded positively to the adjunctive combined magnetic field treatment, with no statistically significant effect observed in the male study population. Adjunctive use of the combined magnetic field device significantly increased the 9-month success of radiographic spinal fusion and showed an acceleration of the healing process.", "Multicenter prospective randomized study of artificial disc replacement (ProDisc) versus circumferential fusion (standard of care) for one- and two-level degenerative disc disease. This is an interim analysis on patients seen at the Spine Institute Saint John's Health Center, Santa Monica, California.\n To evaluate early pain and functional outcomes of patients treated with disc replacement or fusion and to assess the capacity of this intervertebral disc replacement for preserving motion in the lumbar spine.\n Disc replacement is intended to reduce pain via removal of the diseased disc while restoring physiologic motion and height at the affected level. The long-term physiologic advantage of disc replacement to fusion is that preservation of motion may prevent additional degeneration at adjacent levels.\n Patients meeting inclusion criteria were consented for study. Randomization was performed using a 2 to 1 ratio of disc replacement procedure to a fusion procedure. Patients rated their pain on the Visual Analogue Scale and completed the Oswestry Disability Index questionnaire. Radiographs were taken. Assessments were made before surgery and after surgery at 6 weeks, 3 months, 6 months, and 1 year (ongoing). Changes from preoperative pain, disability, or motion were separately evaluated as a function of treatment using repeated measures mixed design analysis of variance.\n This analysis includes data up to 6 months from the first 53 randomized patients. There were 35 patients who underwent disc replacements, and 18 patients had fusion procedures. Disc replacement patients had a significant reduction in pain and disability at earlier evaluations. By 6 months, the relative improvement on both the Visual Analogue Scale and Oswestry (both, P < 0.05) were similar for disc replacement and fusion patients. Greater motion was found at L4-L5 for disc replacement patients (P < 0.05) than fusion patients. A similar trend was noted at L5-S1 (P was not significant).\n Disc replacement patients reported significantly less pain (Visual Analogue Scale) and disability (Oswestry) in the early period following surgery compared to fusion patients. This difference disappeared by 6 months. When compared to fusion, the disc replacement allowed preservation of motion at L4-L5 with a similar trend at L5-S1.", "A prospective evaluation of the clinical and radiographic outcomes of 71 patients who underwent lumbar fusion, with or without transpedicular instrumentation. The patients completed a questionnaire that determined pain relief, medication use, return to work, and overall satisfaction with surgery.\n To explore the effect, if any, of instrumentation on the outcome of lumbar fusion surgery, according to reports of the patients, and whether there is a correlation between the radiographic determination of a solid fusion and the same patient-reported outcome.\n The literature on this topic reports pseudarthrosis rates from 0% to 57% and good to excellent results from 56% to 95%. These studies provide no clear-cut recommendations concerning the effect of added lumbar instrumentation on patient-reported outcome in a prospective manner using concurrent control subjects.\n The patients were randomized to groups with and without instrumentation after deciding to undergo a lumbar fusion and consenting to enter the study. Radiographs were obtained and questionnaires filled out at 6 weeks, 6 months, 1 year, and 2 years after surgery.\n There was no statistical difference in patient-reported outcome between the two groups. There was a slight nonsignificant trend toward increased radiographic fusion rate in the group with instrumentation that did not correlate with an increased patient-reported improvement rate.\n These results do not provide data that indicate a benefit in outcome from added instrumentation in elective lumbar fusions.", "One hundred, twenty-four patients undergoing lumbar or lumbosacral fusion for degenerative conditions were entered into a prospective study. The patients were randomly assigned to one of three treatment groups. Group I underwent posterolateral fusion using autogenous bone graft. Group II had autogenous posterolateral fusions supplemented by a semi-rigid pedicle screw/plate fixation system (Luque II; Danek Medical, Memphis, Tennessee). Group III patients underwent posterolateral autogenous fusion with a rigid pedicle screw/rod fixation system (Texas Scottish Rite Hospital [TSRH]-Danek Medical, Memphis, Tennessee). All the patients were operated on by the same surgeon, identical bone grafting technique was used in all, and all were treated in an identical fashion postoperatively. Fusion status was determined from the anteroposterior, oblique, and flexion-extension radiographs obtained at 1 year. Clinical results were rated as excellent if the patients were pain-free and had returned to work; good if the patients had mild backache requiring non-narcotic analgesics and had returned to work; fair if continuing back pain prevented a return to work; or poor if the pain was worse than that which the patient experienced preoperatively or the patient required revision surgery. Nine patients who were originally assigned to Group II or Group III were placed in Group I intraoperatively. This change was due to the identification of severe osteopenia and the determination that pedicle screw purchase was poor. One patient was lost to follow-up. Thus, 51 patients were in Group I, 35 in Group II, and 37 in Group III. Follow-up ranged from 9 to 28 months, averaging 16 months.(ABSTRACT TRUNCATED AT 250 WORDS)", "A prospective randomized clinical study.\n To evaluate supplementary pedicle screw fixation (Cotrel-Dubousset) in posterolateral lumbar spinal fusion.\n The rationale behind lumbar fusion is to eliminate pathologic motion to relieve pain. To improve fusion rates and to allow reduction, a rigid transpedicular screw fixation may be beneficial, but the positive effect of this may be counter-balanced by an increase in complications.\n The inclusion criteria were severe, chronic low back pain from spondylolisthesis Grades 1 and 2 or from primary or secondary degenerative segmental instability. One hundred thirty patients were randomly allocated to receive no instrumentation (n = 66) or Cotrel-Dubousset instrumentation (n = 64) in posterolateral lumbar fusion. Variables were registered at the time of surgery and at 1 and 2 years after surgery.\n Follow-up was achieved in 97.7% of the patients. Fusion rates deduced from plain radiographs were not significantly different between instrumented and noninstrumented groups. The functional outcome assessed by the Dallas Pain Questionnaire improved significantly in both groups, and there were no significant differences in results between the two groups, except for significantly better (P < 0.06) functional outcome in relation to daily activities in the instrumented group when neural decompression had been performed. The global patients' satisfaction was 82% in the instrumented group versus 74% in the noninstrumented group (not significant). Fixation of instrumentation increased operation time, blood loss, and early reoperation rate significantly. Patients experienced only a few minor postoperative complications; none were major. Two infections appeared in the Cotrel-Dubousset group. Significant symptoms from misplacement of pedicle screws were seen in 4.8% of the instrumented patients.\n Lumbar posterolateral fusion with pedicle screw fixation increases the operation time, blood loss, and reoperation rate, and leads to a significant risk of nerve injury. The functional outcome improves significantly with high patient satisfaction, with or without instrumentation. No significant differences were observed between the two groups in functional outcome and fusion rate. The only gain in functional outcome from instrumentation was found in the daily activity category in patients with supplementary neural decompression. The results of this study do not justify the general use of pedicle screw fixation alone as an adjunct to posterolateral lumbar fusion.", "A prospective randomized study was designed to examine differences in the primary fusion rate between two surgically treated groups of patients with spondylolisthesis. Twenty-seven patients underwent L5 laminectomy (Gill procedure) and L5 nerve root decompression. Fourteen patients (group I) underwent in-situ posterolateral fusion, thirteen patients (group II) received internal stabilization with the Steffee plate and screw system. All patients were followed for a minimum of two years. Ten of fourteen (72%) patients treated with non-instrumented fusion went on to union. Ten of thirteen (78%) patients treated with internal fixation achieved union. No statistically significant increase in the primary fusion rate occurred with addition of internal fixation compared to non-instrumented posterolateral grafting alone.", "We prospectively evaluated the results of decompression of the spine, with and without arthrodesis, for the treatment of lumbar spinal stenosis without instability in forty-five patients (twenty-one men and twenty-four women) who had been managed between November 1989 and November 1990. The average age at the time of the operation was sixty-seven years (range, forty-eight to eighty-seven years). The patients were randomly assigned to one of three treatment groups (fifteen patients in each group) according to when they were admitted to the hospital. Group I was treated with decompression with laminotomy and medial facetectomy; Group II, with decompression and arthrodesis of the most stenotic segment; and Group III, with decompression and arthrodesis of all of the decompressed vertebral segments. All of the operations were performed by the same surgeon. The average duration of follow-up was twenty-eight months (range, twenty-four to thirty-two months). All three groups had a significant improvement in the distance that the patients were able to walk at the time of the latest follow-up examination compared with before the operation (p < 0.001 for Group I, p < 0.002 for Group II, and p < 0.005 for Group III). With the numbers available, there were no significant differences in the results among the three groups with regard to the relief of pain (p = 0.25 for Group I compared with Group II, p = 0.36 for Group II compared with Group III, and p = 0.92 for Group I compared with Group III).(ABSTRACT TRUNCATED AT 250 WORDS)", "A prospective double-blind randomized trial in 28 patients.\n To assess the clinical effect of percutaneous intradiscal radiofrequency thermocoagulation for reducing pain, functional disability, and physical impairment in patients with chronic discogenic low back pain.\n Chronic discogenic low back pain is a challenging problem in western countries. A treatment option is radiofrequency heating of the affected disc. Its clinical efficacy has never been formally tested in a controlled trial.\n Twenty-eight patients with a history of at least 1 year of chronic low back pain were selected on the basis of a diagnostic anesthetization of the lower intervertebral discs. Only patients with one putative painful level were selected and randomly assigned to one of two treatment groups. Each patient in the radiofrequency treatment group (n = 13) received a 90-second 70 C lesion of the intervertebral disc. Patients in the control group (n = 15) underwent the same procedure, but without use of radiofrequency current. Both the treating physician and the patients were blinded to the group assignment. Before treatment, physical impairment, rating of pain, the degree of disability, and quality of life were assessed by a blinded investigator.\n Eight weeks after treatment, there was one success in the radiofrequency group (n = 13) and two in the control group (n = 15). The adjusted and unadjusted odds ratio was 0.5 and 1.1, respectively (not significant). Also, visual analog scores for pain, global perceived effect, and the Oswestry disability scale showed no differences between the two groups.\n Percutaneous intradiscal radiofrequency thermocoagulation (90 seconds, 70 C) is not effective in reducing chronic discogenic low back pain.", "Patients suffering from neurogenic intermittent claudication secondary to lumbar spinal stenosis have historically been limited to a choice between a decompressive laminectomy with or without fusion or a regimen of non-operative therapies. The X STOP Interspinous Process Distraction System (St. Francis Medical Technologies, Concord, Calif.), a new interspinous implant for patients whose symptoms are exacerbated in extension and relieved in flexion, has been available in Europe since June 2002. This study reports the results from a prospective, randomized trial of the X STOP conducted at nine centers in the U.S. Two hundred patients were enrolled in the study and 191 were treated; 100 received the X STOP and 91 received non-operative therapy (NON OP) as a control. The Zurich Claudication Questionnaire (ZCQ) was the primary outcomes measurement. Validated for lumbar spinal stenosis patients, the ZCQ measures physical function, symptom severity, and patient satisfaction. Patients completed the ZCQ upon enrollment and at follow-up periods of 6 weeks, 6 months, and 1 year. Using the ZCQ criteria, at 6 weeks the success rate was 52% for X STOP patients and 10% for NON OP patients. At 6 months, the success rates were 52 and 9%, respectively, and at 1 year, 59 and 12%. The results of this prospective study indicate that the X STOP offers a significant improvement over non-operative therapies at 1 year with a success rate comparable to published reports for decompressive laminectomy, but with considerably lower morbidity.", "Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a growth factor known to have in vitro effects on the growth and invasiveness of cancer. It has been approved by the U.S. Food and Drug Administration in limited doses for single-level anterior spinal arthrodesis, but it is commonly used off-label and at high doses. The effect of rhBMP-2 on the risk of cancer has been a concern. We sought to evaluate the risk of new cancers in patients receiving high-dose rhBMP-2.\n We used publicly available data from a pivotal, multicenter, randomized controlled trial of patients with degenerative lumbar spine conditions who underwent a single-level instrumented posterolateral arthrodesis with either high-dose rhBMP-2 in a compression-resistant matrix (CRM) (rhBMP-2/CRM; n = 239) or autogenous bone graft (control group; n = 224). We compared the risks of new cancers in the rhBMP-2/CRM and control groups at two and five years after surgery.\n At two years, with 86% follow-up, there were fifteen new cancer events in eleven patients in the rhBMP-2/CRM group compared with two new cancer events in two patients in the control group treated with autogenous bone graft. The incidence rate of new cancer events per 100 person-years was 3.37 (95% confidence interval [CI], 1.89 to 5.56) in the rhBMP-2/CRM group at two years compared with 0.50 (95% CI, 0.06 to 1.80) in the control group. The incidence rate ratio was 6.75 (95% CI, 1.57 to 60.83; p = 0.0026) at two years. Calculated in terms of the number of patients with one or more cancer events two years after the surgery, the incidence rate per 100 person-years was 2.54 (95% CI, 1.27 to 4.54) in the rhBMP-2/CRM group compared with 0.50 (95% CI, 0.06 to 1.82) in the control group at two years; the incidence rate ratio was 5.04 (95% CI, 1.10 to 46.82; p = 0.0194). At five years, there was a 37% loss of follow-up, but a significantly greater incidence of cancer events was still observed in the rhBMP-2/CRM group.\n A high dose of 40 mg of rhBMP-2/CRM in lumbar spinal arthrodesis was associated with an increased risk of new cancer.\n Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.", "A prospective randomized clinical study with a 2-year follow-up period was conducted.\n To analyze the effects of circumferential fusion using ALIF radiolucent carbon fiber cages and titanium posterior instrumentation on functional outcome, fusion rate, complications, and lumbar lordosis.\n Circumferential fusion has become a common procedure in lumbar spine fusion, both as a primary and salvage procedure. However, the claimed advantages of ALIF plus PLF over conventional PLF lack scientific documentation.\n From April 1996 through November 1999, a total of 148 patients with severe chronic low back pain were randomly selected for either posterolateral lumbar fusion with titanium CD-Horizon (posterolateral group) or circumferential fusion with a ALIF Brantigan cage plus posterior instrumentation. The Dallas Pain Questionnaire (DPQ), the Low Back Pain Rating Scale (LBPR), and a questionnaire concerning work status assessed their outcomes.\n Both groups showed highly significant improvement in all four categories of life quality (DPQ) as well as in the back pain and leg pain index (LBPR), as compared with preoperative status. There was a clear tendency toward better overall functional outcome for patients with the circumferential procedure ( < 0.08), and this patient group also showed significantly less leg pain at the 1-year follow-up evaluation ( < 0.03) and less peak back pain at 2 years ( < 0.04). Sagittal lordosis was restored and maintained in the circumferential group ( < 0.01). The circumferential fusion patients showed a higher posterolateral fusion rate (92%) than the posterolateral group (80%)( < 0.04). The repeat operation rate including implant removal was significantly lower in the circumferential group (7%) ( < 0.009) than in the posterolateral group (22%).\n Circumferential lumbar fusion restored lordosis, provided a higher union rate with significantly fewer repeat operations, showed a tendency toward better functional outcome, and resulted in less peak back pain and leg pain than instrumented posterolateral fusion. The clinical perspective of the current study implies a recommendation to favor circumferential fusion as a definitive surgical procedure in complex lumbar pathology involving major instability, flatback, and previous disc surgery in younger patients, as compared with posterolateral fusion with pedicle screws alone.", "This prospective study analyzed the influence of transpedicular instrumented on the operative treatment of patients with degenerative spondylolisthesis and spinal stenosis.\n To determine whether the addition of transpedicular instrumented improves the clinical outcome and fusion rate of patients undergoing posterolateral fusion after decompression for spinal stenosis with concomitant degenerative spondylolisthesis.\n Decompression is often necessary in the treatment of symptomatic patients who have degenerative spondylolisthesis and spinal stenosis. Results of recent studies demonstrated that outcomes are significantly improved if posterolateral arthrodesis is performed at the listhesed level. A meta-analysis of the literature concluded that adjunctive spinal instrumentation for this procedure can enhance the fusion rate, although the effect on clinical outcome remains uncertain.\n Seventy-six patients who had symptomatic spinal stenosis associated with degenerative lumbar spondylolisthesis were prospectively studied. All patients underwent posterior decompression with concomitant posterolateral intertransverse process arthrodesis. The patients were randomized to a segmental transpedicular instrumented or noninstrumented group.\n Sixty-seven patients were available for a 2-year follow-up. Clinical outcome was excellent or good in 76% of the patients in whom instrumentation was placed and in 85% of those in whom no instrumentation was placed (P = 0.45). Successful arthrodesis occurred in 82% of the instrumented cases versus 45% of the noninstrumented cases (P = 0.0015). Overall, successful fusion did not influence patient outcome (P = 0.435).\n In patients undergoing single-level posterolateral fusion for degenerative spondylolisthesis with spinal stenosis, the use of pedicle screws may lead to a higher fusion rate, but clinical outcome shows no improvement in pain in the back and lower limbs.", "A randomized controlled multicenter study with a 2-year follow-up by an independent observer.\n To determine whether fusion of the lower lumbar spine could reduce pain and diminish disability more effectively when compared with nonsurgical treatment in patients with severe chronic low back pain (CLBP).\n The reported results after fusion surgery on patients with CLBP vary considerably, and the evidence of treatment efficacy is weak in the absence of randomized controlled studies.\n A total of 294 patients referred to 19 spinal centers from 1992 through 1998 were randomized blindly into four treatment groups. Patients aged 25-65 years with CLBP for at least 2 years and with radiologic evidence of disc degeneration at L4-L5, L5-S1, or both were eligible to participate in the study. The surgical group (n=222) included three different fusion techniques, not analyzed separately in this study. Patients in the nonsurgical group (n=72) were treated with different kinds of physical therapy. The surgical group comprised 49.5% men, and the mean age was 43 years. The corresponding figures for the nonsurgical group were 48.6% and 44 years. The patients had suffered from low back pain for a mean of 7.8 and 8.5 years and been on sick leave due to back pain for a mean of 3.2 and 2.9 years, respectively. The Visual Analogue Scale (VAS) was used to measure pain. The Oswestry Low Back Pain Questionnaire, the Million Score and the General Function Score (GFS) were used to measure disability. The Zung Depression Scale was used to measure depressive symptoms. The overall result was assessed by the patient and by an independent observer. Records from the Swedish Social Insurance were used to evaluate work disability. Patients who changed groups were included in the analyses of significance according to the intention-to-treat principle.\n At the 2-year follow-up 289 of 294 (98%) patients, including 25 who had changed groups, were examined. Back pain was reduced in the surgical group by 33% (64 to 43), compared with 7% (63 to 58) in the nonsurgical group (P=0.0002). Pain improved most during the first 6 months and then gradually deteriorated. Disability according to Oswestry was reduced by 25% (47 to 36) compared with 6% (48 to 46) among nonsurgical patients (P=0.015), according to Million by 28% (64 to 46) compared with 8% (66 to 60) (P=0.004), and accordingtoGFS by 31% (49 to 34) compared with 4% (48 to 46) (P=0.005). The depressive symptoms, according to Zung, were reduced by 20% (39 to 31) in the surgical group compared with 7% (39 to 36) in the nonsurgical group (P=0.123). In the surgical group 63% (122/195) rated themselves as \"much better\" or \"better\" compared with 29% (18/62) in the nonsurgical group (P<0.0001). The \"net back to work rate\" was significantly in favor of surgical treatment, or 36% vs. 13% (P=0.002). The early complication rate in the surgical group was 17%.\n Lumbar fusion in a well-informed and selected group of patients with severe CLBP can diminish pain and decrease disability more efficiently than commonly used nonsurgical treatment.", "A randomized double-blind prospective comparison with a placebo control. This report of the results is the first in an ongoing study.\n To evaluate the effect of noninvasive capacitively coupled electrical stimulation on the success rate of lumbar spine fusion surgery, and to compare active with placebo stimulators as adjuncts to contemporary fusion techniques.\n Previous studies have established the effectiveness of direct current and electromagnetic field stimulation as adjuncts for some forms of spinal fusion. None of the previous placebo-controlled studies on external bone stimulation included posterolateral fusion techniques, and most were conducted with prior generations of internal fixation hardware.\n The investigation was conducted by 28 U.S. surgeons. Patients with a primary diagnosis of degenerative disc disease with or without other degenerative changes were selected. The study protocol defined success as a clinical outcome rated as excellent or good and a fusion documented as solid by both the investigator and the blinded independent radiologist. Disagreements on radiographic success were resolved by a second blinded independent reviewer.\n For the 179 patients who completed treatment and evaluation, the overall protocol success rate (both clinical and radiographic results rated as successes) was 84.7% for the active patients and 64.9% for the placebo patients. This difference is highly significant according to the Yates corrected chi-square test (P = 0.0043). Best improvements in patient outcomes (20% or greater success rate) occurred when active stimulation was used in conjunction with posterolateral fusion (P = 0.006) and when internal fixation also was incorporated (P = 0.013).\n This study was consistent in that active stimulation improved results for each stratification, although some strata had insufficient numbers of patients for the results to have statistical significance. Improved success rates when capacitively coupled stimulation is added to internal fixation are hypothesized to result from overcoming the biochemical effects of stress shielding.\n Capacitively coupled stimulation is an effective adjunct to primary spine fusion, especially for patients with posterolateral fusion and those with internal fixation.", "Arthrodesis is the gold standard for surgical treatment of lumbar degenerative disc disease (DDD). Solid fusion, however, can cause stress and increased motion in the segments adjacent to the fused level. This may initiate and/or accelerate the adjacent-segment disease process. Artificial discs are designed to restore and maintain normal motion of the lumbar intervertebral segment. Restoring and maintaining normal motion of the segment reduces stresses and loads on adjacent level segments. A US Food and Drug Administration Investigational Device Exemptions multicentered study of the Charité artificial disc was completed. The control group consisted of individuals who underwent anterior lumbar interbody fusion involving BAK cages and iliac crest bone graft. This is the first report of Class I data in which a lumbar artificial disc is compared with lumbar fusion.\n Of 304 individuals enrolled in the study, 205 were randomized to the Charité disc-treated group and 99 to the BAK fusion-treated (control) group. Neurological status was equivalent between the two groups at 6, 12, and 24 months postoperatively. The number of patients with major, minor, or other neurological complications was equivalent. There was a greater incidence of both major and minor complications in the BAK fusion group at 0 to 42 days postoperatively. Compared with data reported in the lumbar fusion literature, the Charité disc-treated patients had equivalent or better mean changes in visual analog scale and Oswestry Disability Index scores.\n The Charité artificial disc is safe and effective for the treatment of single-level lumbar DDD, resulting in no higher incidence of neurological complications compared with BAK-assisted fusion and leading to equivalent or better outcomes compared with those obtained in the control group and those reported in the lumbar fusion literature.", "The objective of our study was to assess the efficacy of Graf ligamentoplasty in comparison with rigid fixation and fusion with the Hartshill horseshoe cage for similar severity of disc degeneration. Although studies have been done on the Graf ligamentoplasty procedure and the Hartshill horseshoe cage, their efficacy has never been compared in any study. This study was done to decide whether retaining mobility and stabilizing the spine is best or stiffening the lumbar segment by fusion is preferable. Between 1995 and 1997, a prospective randomized study was performed comparing Graf ligament stabilization and anterior lumbar interbody fusion. Twenty-eight patients had single-level Graf ligaments inserted and 27 patients had single-level anterior lumbar interbody fusion (ALIF) with a Hartshill horseshoe cage and tricortical iliac crest autograft. The two groups were similar in age, sex, symptoms, severity of the disc degeneration, and duration of follow-up. The chi-square test and t-test were used to evaluate the outcome. At a minimum follow-up of 2.1 years, we found that 93% of patients who had undergone Graf ligamentoplasty had a satisfactory outcome (rated \"excellent\" or \"better\") compared to 77.8% of patients who had been treated with ALIF with Hartshill horseshoe cage stabilization and fusion, when measured on the Oswestry Disability Index ( P<0.05). Retaining mobility in the lumbar segments gives better results after stabilisation with Graf ligaments than rigid fixation and fusion with the Hartshill horseshoe cage in the short term. We will be watching this cohort of patients over the next few years.", "A cohort of 100 patients with symptomatic lumbar spinal stenosis, characterized in a previous article, were given surgical or conservative treatment and followed for 10 years.\n To identify the short- and long-term results after surgical and conservative treatment, and to determine whether clinical or radiologic predictors for the treatment result can be defined.\n Surgical decompression has been considered the rational treatment. However, clinical experience indicates that many patients do well with conservative treatment.\n In this study, 19 patients with severe symptoms were selected for surgical treatment and 50 patients with moderate symptoms for conservative treatment, whereas 31 patients were randomized between the conservative (n = 18) and surgical (n = 13) treatment groups. Pain was decisive for the choice of treatment group. All patients were observed for 10 years by clinical evaluation and questionnaires. The results, evaluated by patient and physician, were rated as excellent, fair, unchanged, or worse.\n After a period of 3 months, relief of pain had occurred in most patients. Some had relief earlier, whereas for others it took 1 year. After a period of 4 years, excellent or fair results were found in half of the patients selected for conservative treatment, and in four fifths of the patients selected for surgery. Patients with an unsatisfactory result from conservative treatment were offered delayed surgery after 3 to 27 months (median, 3.5 months). The treatment result of delayed surgery was essentially similar to that of the initial group. The treatment result for the patients randomized for surgical treatment was considerably better than for the patients randomized for conservative treatment. Clinically significant deterioration of symptoms during the final 6 years of the follow-up period was not observed. Patients with multilevel afflictions, surgically treated or not, did not have a poorer outcome than those with single-level afflictions. Clinical or radiologic predictors for the final outcome were not found. There were no dropouts, except for 14 deaths.\n The outcome was most favorable for surgical treatment. However, an initial conservative approach seems advisable for many patients because those with an unsatisfactory result can be treated surgically later with a good outcome.", "Fifty patients who had spinal stenosis associated with degenerative lumbar spondylolisthesis were prospectively studied clinically and radiographically to determine if concomitant intertransverse-process arthrodesis provided better results than decompressive laminectomy alone. There were thirty-six women and fourteen men. The mean age of the twenty-five patients who had had an arthrodesis was 63.5 years and that of the twenty-five patients who had not had an arthrodesis, sixty-five years. The level of the operation was between the fourth and fifth lumbar vertebrae in forty-one patients and between the third and fourth lumbar vertebrae in nine patients. The patients were followed for a mean of three years (range, 2.4 to four years). In the patients who had had a concomitant arthrodesis, the results were significantly better with respect to relief of pain in the back and lower limbs.", "This study represents the first 39 patients with at least 6-month follow-up enrolled in a prospective randomized Food and Drug Administration study evaluating the safety and efficacy of the ProDisc II versus the control, a 360 degrees lumbar spinal fusion. Data were collected preoperatively and at 6 weeks, 3 months, and 6 months postoperatively. Visual Analog Scale (VAS), Oswestry Low Back Pain Disability Questionnaire (ODQ), and patient satisfaction rates were evaluated at these intervals, as well as range of motion, return to work, and recreational and ambulatory status. There were 28 ProDisc patients and 11 who underwent fusion. Six patients had two-level surgery. Estimated blood loss (ProDisc = 69 mL versus fusion = 175 mL) and operative time (ProDisc = 75 minutes versus fusion = 219 minutes) were significantly different (P < 0.01). Hospital stays were shorter (ProDisc = 2.1 days versus fusion = 3.5 days [P < 0.01]) for ProDisc patients. There was a significantly greater reduction in the ODQ scores at 3 months in the ProDisc group compared with the fusion group (P < 0.05). No difference was noted in VAS. A trend was identified at 6 months in patient satisfaction rates favoring ProDisc versus fusion (P = 0.08), and motion was significantly improved in ProDisc patients compared with the fusion group (P = 0.02). Ambulatory status as well as recreational activity improved faster in the ProDisc group. The data suggest that total disc arthroplasty may be an attractive option as opposed to lumbar fusion for the surgical treatment of disabling mechanical low back pain secondary to lumbar disc disease.", "A randomized double-blind prospective study of pulsed electromagnetic fields for lumbar interbody fusions was performed on 195 subjects. There were 98 subjects in the active group and 97 subjects in the placebo group. A brace containing equipment to induce an electromagnetic field was applied to patients undergoing interbody fusion in the active group, and a sham brace was used in the control group. In the active group there was a 92% success rate, while the control group had a 65% success rate (P greater than 0.005). The effectiveness of bone graft stimulation with the device is thus established.", "Intradiscal electrothermal therapy (IDET) is a treatment for discogenic low back pain the efficacy of which has not been rigorously tested.\n To compare the efficacy of IDET with that of a placebo treatment.\n Randomized, placebo-controlled, prospective trial.\n Patients were recruited by referral and the media. No inducements were provided to any patient in order to have them participate. Of 1,360 individuals who were prepared to submit to randomization, 260 were found potentially eligible after clinical examination and 64 became eligible after discography. All had discogenic low back pain lasting longer than 6 months, with no comorbidity. Thirty-seven were allocated to IDET and 27 to sham treatment. Both groups were satisfactorily matched for demographic and clinical features.\n IDET was performed using a standard protocol, in which the posterior annulus of the painful disc was heated to 90 C. Sham therapy consisted of introducing a needle onto the disc and exposing the patient to the same visual and auditory environment as for a real procedure. Thirty-two (85%) of the patients randomized to the IDET group and 24 (89%) of those assigned to the sham group complied fully with the protocol of the study, and complete follow-up data are available for all of these patients.\n The principal outcome measures were pain and disability, assessed using a visual analog scale for pain, the Short Form (SF)-36, and the Oswestry disability scale.\n Patients in both groups exhibited improvements, but mean improvements in pain, disability and depression were significantly greater in the group treated with IDET. More patients deteriorated when subjected to sham treatment, whereas a greater proportion showed improvements in pain when treated with IDET. The number needed to treat, to achieve 75% relief of pain, was five. Whereas approximately 40% of the patients achieved greater than 50% relief of their pain, approximately 50% of the patients experienced no appreciable benefit.\n Nonspecific factors associated with the procedure account for a proportion of the apparent efficacy of IDET, but its efficacy cannot be attributed wholly to a placebo effect. The results of this trial cannot be generalized to patients who do not fit the strict inclusion criteria of this study, but IDET appears to provide worthwhile relief in a small proportion of strictly defined patients undergoing this treatment for intractable low back pain." ]

[ "17710657", "19813275", "11990304" ]

[ "Toxicity prevention with amifostine in pediatric osteosarcoma patients treated with cisplatin and doxorubicin.", "Amifostine does not prevent platinum-induced hearing loss associated with the treatment of children with hepatoblastoma: a report of the Intergroup Hepatoblastoma Study P9645 as a part of the Children's Oncology Group.", "Use of amifostine in the therapy of osteosarcoma in children and adolescents." ]

[ "Amifostine has emerged as a pancytoprotectant shown protection against nephrotoxicity, neurotoxicity and ototoxicity in preclinical studies.\n We designed a prospective comparative randomized trial to evaluate the cytoprotective effects of amifostine in patients with osteosarcoma receiving cisplatin and doxorrubicin. Patients were evaluated for renal, hearing and cardiac toxicity.\n We included 28 patients, mean age was 11.6 years, five had metastatic disease. Fifteen patients received amifostine and 13 did not. 20% of patients receiving amifostine developed renal toxicity compared to 30% in the control group (p = 0.318). Grade 1 and 2 audiologic toxicity was present in 100% of the experimental group against 85% of the controls (p = 0.501). Grade 1 cardiac toxicity was present in 2 patients in the control group (p = 0.175). There were no statistical significant differences between the two groups for chemotherapy-related toxicity. Response to chemotherapy was significantly better in the amifostine group.\n amifostine did not reduce the ototoxicity and nephrotoxicity of our treatment regime. It was not well tolerated due to emesis. It is a selective cytoprotectant without reducing the effect of chemotherapy.", "The current study was conducted to determine whether amifostine is effective in reducing the toxicities associated with the administration of platinum-containing regimens in children with hepatoblastoma (HB).\n Patients were enrolled on P9645 beginning in March of 1999. Patients who had stage I/II disease received treatment with 4 cycles of combined cisplatin, 5-fluorouracil, and vincristine (C5V) with or without amifostine. Patients who had stage III/IV disease were randomized to receive treatment with 6 cycles of either C5V with or without amifostine or carboplatin alternating with cisplatin (CC) with or without amifostine. Patients who were randomized to receive amifostine were given a dose of 740 mg/m2 intravenously over 15 minutes before each administration of a platinum agent.\n Eighty-two patients were considered in a special interim analysis of the incidence of toxicity. The disease outcome for patients who received amifostine was similar to the outcome for patients who did not receive amifostine (P=.22). The incidence of significant hearing loss (>40 dB) was similar for patients who did or did not receive amifostine (38% [14 of 37 patients] vs 38% [17 of 45 patients], respectively; P=.68). There were no differences in the incidence of renal or bone marrow toxicities evaluated. Patients who received amifostine had a higher incidence of hypocalcemia (5% vs 0.5%; P=.00006).\n Amifostine in the doses and schedule used in this study failed to significantly reduce the incidence of platinum-induced toxicities in patients with HB.\n Copyright (c) 2009 American Cancer Society.", "Amifostine protects normal tissue from the cytotoxic damage induced by radiation and chemotherapy. In this study, 39 consecutive newly diagnosed children with osteosarcoma were assessed; 20 received amifostine and 19 did not. The chemotherapy regimen included an induction phase of three cycles of cisplatin (100 mg/m2), carboplatin (500 mg/m2), and doxorubicin (60 mg/m2), followed by surgery. Alternating cycles of cisplatin/ifosfamide (9 mg/m2), ifosfamide/doxorubicin, carboplatin/doxorubicin, and ifosfamide/carboplatin were administered every 3 weeks to complete 26 weeks of treatment. Amifostine was administered 15 minutes before the infusions of cisplatin and carboplatin in a total of 193 infusions. Side effects during infusions and renal, hearing, and bone marrow toxicities were evaluated and compared between the two groups. Hypotension was observed in 28 (14.5%) infusions. No patient required discontinuation of therapy. Fewer than two episodes of vomiting occurred in 130 (71%) infusions and two to five episodes occurred in 51 (28%) infusions, and no patient had grade 4 toxicity. There was no difference between the two groups regarding renal toxicity (creatinine clearance). Neutropenia and leukopenia were significantly less frequent in the amifostine group. No difference was observed in platelet and hearing toxicities. Amifostine was well tolerated in doses of 740 mg/m2 in children and adolescents, and myelotoxicity was less severe in the amifostine group. This was a pilot study for further evaluation in a larger randomized trial." ]

[ "2689036", "16306470", "10489659", "9879787", "15960563" ]

[ "[Treatment of pathological laughing with amitriptyline].", "Fluoxetine treatment in poststroke depression, emotional incontinence, and anger proneness: a double-blind, placebo-controlled study.", "Sertraline in stroke-associated lability of mood.", "Fluoxetine as a treatment for post-stroke emotionalism.", "Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression." ]

[ "We investigated the efficacy of amitriptyline in seven patients with pathological laughing caused by cerebrovascular diseases. In a double-blind placebo-controlled cross-over trial comparing amitriptyline with placebo, 5 of these 7 patients were judged to have shown improvement with amitriptyline, and 1 patient improved with placebo. This difference was statistically significant. No significant side effect of amitriptyline was observed. There was no significant change between amitriptyline and placebo in both self-rating depression scale and minimental state test score. These results suggested that amitriptyline was useful in treating pathological laughing.", "The efficacy and safety of the selective serotonin reuptake inhibitor fluoxetine have rarely been studied in the treatment of poststroke emotional disturbances.\n Stroke patients (152) who had poststroke depression (PSD), emotional incontinence (PSEI), or anger proneness (PSAP) were studied. PSD was evaluated by Beck Depression Inventory and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, PSEI by Kim's criteria, and PSAP was assessed by Spielberger Trait Anger Scale. Subjects were randomly given either fluoxetine 20 mg/day (n=76) or placebo (n=76) for 3 months. Follow-up evaluations were done 1, 3, and 6 months after the beginning of the treatment. The primary outcome measurement was the scores of emotional disturbances at each follow-up assessment. The secondary outcome measurements were the percentage changes of the scores and the subjective responses of the patients.\n Although patients in the fluoxetine group more often dropped out because of adverse effects, fluoxetine administration was generally safe. Fluoxetine significantly improved PSEI and PSAP, whereas no definitive improvement of PSD was found. Improvement of PSAP was noted even at 3 months after the discontinuation of the treatment.\n Fluoxetine is efficacious in the treatment of PSEI and PSAP. Its effect on PSD is not solidly confirmed.", "To assess whether a selective serotonin reuptake inhibitor is effective in the treatment of stroke-associated lability of mood.\n Twenty-eight non-depressed patients suffering from post-stroke lability of mood took part in an 8-week double-blind randomized placebo-controlled trial of a selective serotonin reuptake inhibitor (50 mg sertraline per day).\n There were statistically significant improvements in a global rating of emotionalism and a specific benefit on tearfulness. The results are discussed in the light of proposed serontonergic mechanisms for emotional lability following stroke.\n 50 mg of sertraline per day may be an effective and well-tolerated treatment for stroke-associated lability of mood in the absence of depression. This is supportive evidence for the serontonergic hypothesis of lability of mood following stroke.", "The effectiveness of fluoxetine compared to placebo in the treatment of post-stroke emotionalism was investigated in 20 patients using a double-blind protocol. A total of 19 patients completed the study, as one subject in the treatment group had to be withdrawn. The subjects receiving fluoxetine showed a statistically and clinically significant improvement in their emotionalism compared to the placebo group, which was apparent in the majority of subjects from the third day of treatment.", "Poststroke depression is a frequent condition and important to treat. The aim of this trial was to study the efficacy and tolerability of sertraline.\n In 4 Swedish stroke centers, 123 patients (aged 70.7 +/- 9.9 years) were enrolled during the period September 1998 to January 2001 in a randomized, double-blind, placebo-controlled 26-week trial, at a mean of 128 +/- 97 days (range, 3-375 days) after stroke, if they fulfilled DSM-IV criteria of major depressive episode (N = 76) or minor depressive disorder (N = 47). The primary efficacy variable was a change in depression assessed by the Montgomery-Asberg Depression Rating Scale. The Emotional Distress Scale (EDS) was administered and the occurrence of emotionalism and quality of life (QoL) were assessed, as well as neurologic recovery. Efficacy analyses were intention-to-treat, short-term (week 6) and long-term (week 26).\n Of the 123 patients, 62 were treated with sertraline (50-100 mg/day) and 61 with placebo. Both groups improved substantially, with no differences between the treatments, either for major depressive episode or minor depressive disorder, or for short- or long-term antidepressant effect and neurologic outcome. EDS revealed a better outcome with sertraline at week 6 (p < .05). At week 26, the improvement in QoL was better in sertraline patients (p < .05) and there was a trend for emotionalism (p = .07). No serious side effects were seen.\n Poststroke depression as measured by a conventional depression rating scale improved over time irrespective of treatment. Positive effects specific to sertraline were identified in emotional distress, emotionalism, and QoL. The study indicates that poststroke emotional reactions comprise depression and other domains susceptible to pharmacologic therapy." ]

[ "10462251", "11920300", "10699342", "10775784" ]

[ "Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant.", "A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea.", "Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers.", "Safety and immunogenicity of a three-component blood-stage malaria vaccine in adults living in an endemic area of Papua New Guinea." ]

[ "Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.", "The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic types.", "A placebo controlled, randomised, double blind trial was conducted in human volunteers to test a mixture of three recombinant Plasmodium falciparum blood stage antigens for its ability to reduce the initial growth rates of parasites. The vaccine contained recombinant MSP2 (3D7 allele), a portion of MSP1 (190LCS.T3) and part of the RESA antigen (C terminal 771 amino acids) in the Montanide ISA 720 adjuvant (SEPPIC). Twelve volunteers received two doses of the vaccine, 6 weeks apart. The five participants in the placebo group received an equivalent volume of the adjuvant emulsion using the same schedule. Antibody responses were low, as has been reported in earlier studies with this combination, while T cell responses were stronger. All the volunteers were challenged with approximately 140 ring infected red cells of the 3D7 cloned line, 4 weeks after the second dose. Parasitaemia was determined once daily from day 4 using a sensitive and quantitative PCR assay. All the volunteers were infected and were treated on day 8, before any developed symptoms. There was no significant difference in initial parasite growth rates between the verum and placebo groups, nor was there any significant correlation between parasite growth rates and any of the measured immunological responses. These results suggest that the formulation tested in this trial did not generate immune responses that were strong enough to reduce parasite growth in naive volunteers.", "A Phase I safety and immunogenicity study with a three-component blood-stage malaria vaccine was conducted in adult male subjects living in an endemic area of Papua New Guinea. The preparations were recombinant proteins which corresponded to parts of the two merozoite surface proteins of Plasmodium falciparum (MSP1 and 2), and of the ring-infected erythrocyte surface antigen (RESA). The three proteins were emulsified with the adjuvant Montanide ISA720. Ten subjects were injected twice (four weeks apart) with the vaccine formulation and two with the adjuvant alone. Mild pain at the site of injection was reported by about half of the subjects but no systemic reaction related to the formulation occurred. There was a sharp rise in geometric mean stimulation index after the second dose compared to baseline for MSP1 and RESA, while the rise was small for MSP2. Geometric mean antibody titres increased for MSP1 during the study, whereas they hardly changed for MSP2 and RESA. The vaccine formulation was safe when used in an already immune population. The vaccine induced good cellular responses, especially for MSP1 and RESA. Boosting of humoral responses was weak, probably because of high baseline antibody levels." ]

[ "3536525", "9221383", "8952557", "9266880", "3979476", "2443762", "9596311", "6336983", "9387969", "8652243", "10894097", "1710483", "11029359", "7972977", "9489119", "9554669", "2481558", "6190551", "8398325", "7692617", "1720370", "9692129", "7865226", "8957368", "2430825" ]

[ "A comparison of intracavitary talc and tetracycline for the control of pleural effusions secondary to breast cancer.", "[Pleurodesis in malignant pleural effusion: bleomycin vs. mitoxantrone].", "Treatment of malignant pleural effusions with a combination of bleomycin and tetracycline. A comparison of bleomycin or tetracycline alone versus a combination of bleomycin and tetracycline.", "Prospective randomized trial of talc slurry vs bleomycin in pleurodesis for symptomatic malignant pleural effusions.", "Treatment of malignant pleural effusions with intrapleural Corynebacterium parvum or tetracycline.", "Intracavitary bleomycin and tetracycline in the management of malignant pleural effusions: a randomized study.", "Sclerotherapy for malignant pleural effusions: a prospective randomized trial of bleomycin vs doxycycline with small-bore catheter drainage.", "Intrapleural tetracycline in malignant pleural effusions. A randomized study.", "Pleurodesis in malignant pleural effusions: a randomized study of tetracycline versus bleomycin.", "Effects of intrapleural mitoxantrone and mepacrine on malignant pleural effusion--a randomised study.", "A comparative study of pleurodesis using talc slurry and bleomycin in the management of malignant pleural effusions.", "Intrapleural palliative treatment of malignant pleural effusions with mitoxantrone versus placebo (pleural tube alone).", "Prospective randomized comparison of thoracoscopic talc poudrage under local anesthesia versus bleomycin instillation for pleurodesis in malignant pleural effusions.", "Tetracycline compared with mechlorethamine in the treatment of malignant pleural effusions. A randomized trial.", "A prospective, randomised study comparing the efficacy of talc slurry and bleomycin in the treatment of malignant pleural effusions.", "Intracavitary bleomycin vs interferon in the management of malignant pleural effusions.", "Comparison of intracavitary bleomycin and talc for control of pleural effusions secondary to carcinoma of the breast.", "Control of pleural effusions in patients with breast cancer. A randomized trial.", "A randomised prospective trial of surgical against medical tetracycline pleurodesis in the management of malignant pleural effusions secondary to breast cancer.", "Chemical pleurodesis in malignant pleural effusions: a randomised prospective study of mepacrine versus bleomycin.", "Intrapleural therapy for malignant pleural effusions. A randomized comparison of bleomycin and tetracycline.", "Treatment of malignant pleural effusion: pleurodesis using a small percutaneous catheter. A prospective randomized study.", "Pleurodesis with doxycycline or Corynebacterium parvum in malignant pleural effusion.", "Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion.", "Corynebacterium parvum in malignant pleural effusion. A randomized prospective study." ]

[ "Forty-one patients with malignant pleural effusions secondary to breast cancer were randomly allocated to treatment with either intracavitary talc or intracavitary tetracycline. Of 33 evaluable patients, radiological control was achieved in 11/12 (92%) of the talc group compared with 10/21 (48%) of the tetracycline group (P = 0.022). Intracavitary talc provides effective palliation of metastatic pleural effusions secondary to breast cancer.", "In a controlled clinical trial we investigated 102 patients with malignant pleural effusion due to breast cancer, lung cancer, ovarian cancer and other tumors to compare the therapeutic effect and adverse events of pleurodesis with bleomycin (BMC) or mitoxantrone (MIT) via chest tube. Finally 96 patients had been treated according to the protocol. Age, gender, Broca index, performance score or distribution of primary tumors were not statistically different between the BMC (n = 49) or MIT group (n = 47). We found no differences between intention-to-treat and according-to-protocol groups as well. 30 days after BMC pleurodesis we found remissions of the effusion in 91% of patients (complete remission [CR] 51%, partial remission [PR] 40%), after 90 days in 83% (40% CR, 43% PR). 30 days after MIT instillation we found remission in 73% of patients (35% CR, 38% PR), after 90 days in 61% (29% CR, 32% PR) (30 and 90 days: p < 0.05). Adverse events were not different between BMC and MIT group. BMC is a safe and effective sclerosing agent for pleurodesis via chest tube.", "Treatment of patients with malignant pleural effusions is mostly palliative. Tetracycline and bleomycin are the two most commonly used agents for the treatment of pleurodesis. In this study, the authors used a combination of the two drugs for this particular purpose.\n Sixty patients with massive malignant pleural effusions were divided in 3 equal groups in a simple randomized manner. Tetracycline (20 mg/kg [maximum of 2 g] in 50 mL of normal saline) was administered through a chest tube in Group 1. Group 2 received bleomycin (1 U/kg [maximum of 60 U] in 50 mL of normal saline). Group 3 received the above 2 preparations (tetracycline, 20 mg/kg [maximum of 2 g] in 40 mL of normal saline and bleomycin, 1 U/kg [maximum of 60 U] in 30 mL of normal saline) instilled one after the other, while the chest tube was clamped for 5 minutes in the interim. Follow-up examinations were performed at 7 days, 30 days, 60 days, 90 days, and 6 months.\n There was no significant difference in the complete response rate of the 3 groups during the first 4 months. At the end of the study, Group 3 had a significantly higher complete response rate (70%) compared with Groups 1 and 2 (35% and 25%, respectively) (P = 0.02).\n The response to use of a combination of bleomycin and tetracycline for the treatment of patients with pleurodesis is superior to that achieved by either of these agents used alone.", "Symptomatic malignant pleural effusions are common sequelae in patients with certain malignancies. Pleurodesis via bedside thoracostomy is the current treatment option most commonly used. To our knowledge, this is the first prospective randomized trial to examine which agent, bleomycin or talc slurry, is superior in terms of effectiveness, safety, and cost.\n Between July 1992 and March 1995, 35 patients presenting to our medical center with symptomatic malignant pleural effusions were prospectively randomized to undergo chemical pleurodesis with either bleomycin or talc slurry via bedside thoracostomy. The conditions of patients were assessed and graded before and after treatment concerning pain, dyspnea, and chest radiographs.\n Twenty-nine patients who underwent 33 treatments (14 with bleomycin and 19 with talc) were available for follow-up. Follow-up ranged from 2 weeks to 8 months (mean, 1.7 months). Both groups demonstrated notable improvement in both pain and dyspnea following treatment, but there were no statistically significant differences between groups in the amount of improvement (two-tailed Student's t test). Permanent control of effusions, defined objectively on chest radiograph, was achieved with 11 bleomycin treatments (79%) and 17 talc treatments (90%) (p=0.388). The procedures were well tolerated and no significant adverse effects were observed. Talc is a much less costly agent than bleomycin ($12.36 cost to our medical center per treatment for talc vs $955.83 for bleomycin).\n Given the similar efficacy and significant cost advantage, we conclude that talc is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions.", "Thirty two patients with malignant pleural effusion were randomly allocated to treatment with intrapleural Corynebacterium parvum or tetracycline hydrochloride in an attempt to prevent symptomatic recurrence of pleural fluid. Success in preventing recurrence of fluid at one month, using up to 2 doses of each drug, was 14 of 16 cases for Corynebacterium parvum, 5 of 9 for tetracycline given via an intercostal needle, and 6 of 7 for tetracycline given through an intercostal tube. These difference were not statistically significant. Corynebacterium parvum was significantly more likely to produce pyrexia equal or greater than 38 degrees C (P less than 0.001) and pain requiring analgesia (P less than 0.05) than tetracycline hydrochloride. Corynebacterium parvum is a useful agent for the management of malignant pleural effusion, but is associated with more side effects than tetracycline.", "Both bleomycin and tetracycline have been suggested as the sclerosing agent of choice in the management of malignant pleural effusions. To determine if one drug is superior to the other in this role, patients with malignant pleural effusions were randomly assigned to receive either bleomycin or tetracycline in the previously evacuated pleural space through a thoracostomy tube. Following instillation of the assigned agent, the tube was clamped for 8 hours and then reattached to suction. When the chest tube drainage had slowed to less than 40 ml in a 24-hour period or if 7 days had passed, the tube was removed. Pleural sclerosis was attempted 42 times in 34 patients. No statistically significant differences were found between the two treatment groups when prevention of effusion reaccumulation and time to removal of the chest tube (efficiency) were compared. Side effects including pleural pain and fever, occurred with both agents, but were manageable. Since one drug was not clearly superior to the other, and bleomycin is more costly, we suggest that tetracycline rather than bleomycin be used when pleural sclerosis is needed to manage malignant pleural effusions.", "Malignant pleural effusions are a common problem for patients with metastatic disease. Most patients are treated with tube thoracostomy and sclerotherapy, although there remains no standard approach. The purpose of this study was to compare the efficacy of bleomycin with doxycycline sclerotherapy for the treatment of malignant pleural effusions using small-bore catheters.\n All patients with a symptomatic malignant pleural effusion referred for chest tube drainage and sclerotherapy over a 2-year period were considered eligible. Using image guidance, a 14F self-retaining catheter was inserted into the pleural space and connected to continuous wall suction. When drainage fell below 200 mL/d, patients were randomized to 60 U of bleomycin or 500 mg of doxycycline sclerotherapy. Response at 30 days was determined.\n One hundred six patients were enrolled in the study. Fifteen men (29%) and 37 women (71%) with a mean age of 57 years received bleomycin sclerotherapy. Twenty-one of the 29 patients (72%) alive and evaluable at 30 days had successful sclerotherapy. Twenty-three men (43%) and 31 women (57%) with a mean age of 61 years received doxycycline sclerotherapy. Twenty-three of the 29 patients (79%) alive and evaluable at 30 days had successful sclerotherapy. There was no significant difference in response rates between doxycycline and bleomycin (p=0.760).\n These data continue to support a role for small-bore chest drainage and sclerotherapy, although there was no significant difference in 30-day response rates between doxycycline and bleomycin.", "Intrapleural instillation of tetracycline (TCN) has been shown to be effective in preventing the recurrence of malignant pleural effusions. Although the precise mechanism of action is unknown, it has been postulated that the pH of the TCN solution may be an important factor. Thirty patients with malignant pleural effusions were randomized in a double-blind trial to receive intrapleural administration of either 500 mg of tetracycline in solution (pH = 2.8) or a solution of similar pH and appearance. All patients had chest tube drainage of their effusion. There were 24/30 patients evaluable. There were 9/13 patients in the TCN group and 1/9 patients in the control group who had no reaccumulation of fluid (P less than 0.05). These results would suggest that the efficacy of TCN as a sclerosing agent is not related to its acidic pH and that intrapleural TCN is more effective than chest tube drainage alone for control of malignant effusions.", "Malignant pleural effusions are commonly managed with tube thoracostomy drainage followed by chemical pleurodesis. Both tetracycline and bleomycin have been shown to be effective for intrapleural instillation, although neither agent has definitively proved advantages over the other. The aim of the present study was to compare these two agents in terms of response rate and toxicity profile. A prospective, randomized trial was carried out in a single centre. Between May 1993 and January 1996, 62 evaluable patients with proved malignant pleural effusion were allocated to receive either intrapleural tetracycline (1.5 g) or bleomycin (60 mg) after the same drainage procedure. Demographic, clinical and fluid parameter data were comparable in both groups. Response was evaluated at 1, 3 and 6 months after pleurodesis. Mean survival and time to relapse did not differ between the two groups. No statistically significant differences were found in terms of efficacy at each evaluation time. Overall, 16 (52%) and 20 (64%) patients had a recurrence of pleural effusion during follow-up in the tetracycline and bleomycin arms, respectively. Fever was most common in bleomycin-treated patients (p=0.024) while pain was most frequent in the tetracycline arm (nonsignificant). Since no study agent was superior to the other in this trial, we suggest that economic costs, drug availability and medical skill should be considered in the choice of a sclerosing agent.", "30 patients with malignant pleuritis were randomised to be treated, either with intrapleural instillation of mepacrine chloride or with mitoxantrone. The patients were evaluated with chest X-ray and a symptom questionnaire during a follow-up period of 12 weeks. Mitoxantrone levels in the pleural space and plasma were measured at different time points in some of the patients. High concentrations of mitoxantrone were found in the pleural fluid while the plasma concentrations were low, giving a plasma/intracavity ratio generally of less than 1:60. The chest X-rays showed excellent results for both treatment modalities. However, the patients treated with mepacrine chloride experienced greater discomfort with fever and pain, and those treated with mitoxantrone reported significantly less dyspnoea and less asthenia after 4 weeks. We conclude that both treatments are equally effective in preventing the recurrence of malignant effusion. However, mitoxantrone seems to have further advantages when it comes to improving the quality of life.", "Differing success rates of various pleurodesis agents have been reported in the management of malignant pleural effusions. A randomized clinical trial was conducted to compare the efficacy of two commonly used agents, talc and bleomycin, for the pleurodesis of malignant pleural effusions.\n Inclusion in the study required proof of a malignant pleural effusion by fluid cytology or pleural biopsy. Exclusion criteria included trapped lung, loculated effusions, recurrent effusions and life expectancy < 1 month. Five grams of talc or 1 unit per kilogram bodyweight of bleomycin mixed in 150 mL of normal saline was administered via tube thoracostomy after complete drainage of the pleural effusion in each patient. Treatment success was defined as the absence of recurrent pleural effusion on the chest radiograph 1 month after pleurodesis.\n Treatment success was achieved in 16 out of 18 patients (89%) in the talc slurry group versus 14 out of 20 patients (70%) in the bleomycin group (P=0.168). Fever and pain were the only side-effects of pleurodesis in both groups.\n These results indicate that talc slurry is as effective as bleomycin in preventing early recurrence of malignant pleural effusions. Pleurodesis with talc instead of bleomycin can result in significant cost savings.", "From 11/87 until 7/90 103 patients entered a prospective randomized trial on the treatment of malignant pleural effusions (MPE) with intrapleural mitoxantrone versus placebo (pleural tube alone with instillation of isotonic NaCl). Our data suggest no statistically significant difference between the two arms with respect to response and response duration. There is no influence on survival time. The toxicity is moderate, with only fever occurring more often in the mitoxantrone arm. We recommend performance of pleurodesis in patients with MPE first by sufficient drainage with a tube of 16-20 char. Only in instances of failure it is necessary to add sclerosing agents such as tetracycline, etc.", "Induction of pleurodesis offers benefit for patients with metastatic tumors and symptomatic malignant pleural effusions, but the best method for achieving this is still unknown. In this prospective, randomized comparison of two well-established pleurodesis procedures, 36 patients with malignant pleural effusions, expanded lungs after drainage, and expected survival of > 1 mo received either bleomycin instillation (60E) via a small-bore thoracostomy tube or thoracoscopic talc poudrage (5 g) under local anesthesia. Efficacy, safety, and cost could be evaluated for 32 treatments (17 bleomycin, 15 talc) in 31 patients. Recurrence rates of effusion with bleomycin and talc poudrage after 30 d were 41% and 13% (p = 0.12), respectively, those after 90 d were 59% and 13%, respectively (p = 0.01), and those after 180 d were 65% and 13% (p = 0.005), respectively. Neither procedure showed any major adverse effect, and both were equally well tolerated. Cost estimation favored thoracoscopic talc poudrage, both for the initial hospitalization and with regard to recurrences. In conclusion, thoracoscopic talc pleurodesis under local anesthesia is superior to bleomycin instillation for pleurodesis in cases of malignant pleural effusion.", "Pleural sclerosis after tube thoracostomy was performed in 40 patients with malignant pleural effusions. The patients were randomly allocated to intrapleural therapy with tetracycline or mechlorethamine. Follow up was obtained on each patient to determine if a symptomatic effusion recurred. The response was classified as a complete or partial response and failure. (Complete response: complete lack of reaccumulation of pleural fluid for at least 60 days. Partial response: small pleural effusion asymptomatic not requiring further treatment for at least 60 days. Failure: all other cases). Tetracycline produced complete or partial control of the effusion in 16 of 20 trials for a duration of 6.1 +/- 4.1 months (range 2-14 months). Mechlorethamine produced control of the effusion in 12 of 20 trials for a duration of 4.4 +/- 1 months (range 2-8 months). These findings indicate that intracavitary tetracycline is a more effective treatment than intracavitary mechlorethamine for the control of neoplastic pleural effusion.", "In comparative studies with other agents, insufflated talc has been shown to be the most effective agent in achieving chemical pleurodesis in patients with malignant pleural effusions. The objective of this study is to compare the efficacy of talc administered as slurry (5 g in 50 mL saline) via tube thoracostomy with that of bleomycin (1 mg/kg in 50 mL saline) (which is the most effective agent other than talc). In a randomised, prospective comparative study, twenty-six consecutive patients with proven malignant pleural effusions (recurrent after at least two pleuroscenteses) in whom no pleurodesis attempt had yet been made, and who were symptomatic, had a Karnovski index < or = 50, and an expected survival of one year or less, were included. Therapeutic failure was defined as recurrent pleural fluid > or = 50% of initial volume or requiring pleurocentesis. Recurrence rates (25% vs 21.4%, NS), fever (25% vs 35.7%, NS), pain (0% both groups) and survival (3.75 +/- 3 vs 5.82 +/- 7.15 months, NS) did not differ between bleomycin or talc treated patients. There were no major complications (e.g., empyema) or side-effects. In conclusion, talc slurry and bleomycin are equally effective in achieving chemical pleurodesis via thoracostomy in patients with malignant pleural effusions, and the safety profile of both agents is similar. Since talc is substantially less expensive than bleomycin, talc slurry probably represents the agent of choice for chemical tube thoracostomy pleurodesis.", "nan", "In a prospective randomized study, patients with pleural effusions secondary to breast carcinoma were randomly allocated to be treated by pleurodesis using either intracavitary talc or bleomycin. For 25 assessable treatments in 22 patients, recurrence of effusion was observed in 5 of 15 (33 per cent) of the bleomycin group compared with none in the talc group. It is concluded that talc is superior to bleomycin in controlling pleural effusions secondary to breast carcinoma, but bleomycin may have a role in patients unfit for general anaesthesia or with extensive disease elsewhere.", "In a controlled randomized trial, 46 patients with pleural effusions secondary to breast cancer were treated at first diagnosis with either intracavitary mustine or talc, to determine which agent produced the more effective pleurodesis. Of the 37 evaluable patients, control of the effusion was achieved in 9/17 (56%) of those treated with mustine and 18/20 (90%) of the talc group (P less than 0.025). This suggests that early treatment with intracavitary talc can effectively palliate this complication of breast cancer.", "Malignant pleural effusion is a frequent complication of metastatic breast cancer leading to a significant degree of morbidity. Drainage of the effusion by thoracocentesis and pleurodesis with tetracycline as the sclerosing agent is an established means of symptomatic relief in these patients. To determine whether the efficacy of tetracycline pleurodesis is improved by surgical rather than medical drainage and instillation of sclerosant, 34 patients were prospectively randomised to a trial comparing the two treatment modalities, of whom 29 were evaluable for response. The total failure rate of primary pleurodesis was 13.4%, the rate of recurrence of effusion within the first month was 24%, and only 1 patient (3.4%) required repeat aspiration in that time period. There was no significant difference in the rate of recurrence or reaspiration of effusion between the two treatment groups. Although the overall survival time from treatment of effusion is significantly longer in the surgical treatment group than in the medical treatment group (P = 0.03), this is likely to be due to factors other than the method of treating the effusion. We conclude that surgical tetracycline pleurodesis has no advantage over medical tetracycline pleurodesis.", "The treatment of recurrent pleural effusion in advanced malignant disease should be efficient and with tolerable side effects. Since 1983 intrathoracic instillation of the anti-malaria drug mepacrine has been used to achieve pleurodesis. The cytotoxic drug bleomycin has been claimed to be equally effective and with fewer side effects. The present study was designed to compare these two agents.\n Forty patients with carcinoma and pleural effusions refractory to repeated pleural aspirations over the previous 12 weeks were randomised to receive treatment with intrathoracic instillation of mepacrine or bleomycin. Fluid volumes before and after pleurodesis, drainage time, and side effects were registered and analysed, and the response to treatment was evaluated by clinical examination and chest radiography.\n The amount of fluid produced after treatment in the patients receiving mepacrine was lower than in those receiving bleomycin, and the duration of chest drainage was shorter. After 30 days 16 of 20 in the mepacrine group responded to treatment and 10 of 20 in the bleomycin group. Most patients died during the three months observation period. Moderate side effects occurred equally in both groups.\n Chemical pleurodesis can reduce or stop pleural effusion in many patients, and in this study mepacrine appeared to be more efficient than bleomycin. A prospective study with a larger number of patients is now warranted.", "Between December 1985 and August 1988, there were 115 patients at 13 centers who were entered on a randomized comparison of tetracycline and bleomycin for treatment of malignant pleural effusions. Fifteen patients were not treated, primarily due to rapid progression of systemic cancer. Fifteen patients entered on a high-dose regimen of bleomycin (120 units) were excluded from this analysis (following early closure of that arm), leaving 85 patients randomized to low-dose bleomycin (60 units; 44 patients) or tetracycline (1 g; 41 patients). Patients were required to have a cytologically positive pleural effusion, good performance status (0, 1, or 2), lung reexpansion following tube thoracostomy with drainage rates of 100 ml/24 or less, no prior intrapleural therapy, no prior systemic bleomycin therapy, no chest irradiation, and no recent (four weeks) change in systemic therapy. A total of 11 patients (five with bleomycin and six with tetracycline) were not evaluable due to technical problems with tube drainage (one), loss to follow-up (two), sudden death due to pulmonary embolus (one), and rapid progression of systemic disease (seven). There were no clinically significant differences in demographic factors, primary site, performance status, or presence of metastases other than pleural effusion. Overall survival did not differ between the two groups. Median time to recurrence or progression of the effusion was 32 days for tetracycline-treated patients and at least 46 days for bleomycin-treated patients (p = 0.037). The recurrence rate within 30 days of instillation was 36 percent (10/28) with bleomycin and 67 percent (18/27) with tetracycline (p = 0.023) (not all patients were restudied in the first 30 days). By 90 days the corresponding recurrence rates were 30 percent (11/37) for bleomycin and 53 percent (19/36) for tetracycline (p = 0.047). Toxicity was similar between groups.", "The aim of this prospective, randomized study was to investigate the possibility of performing pleurodesis using a small percutaneous catheter (Cystofix catheter, CH10, 65 cm) inserted at bedside in patients with recurrent malignant pleural effusion and to compare this catheter with a conventional large bore chest tube (CH24) placed in connection with diagnostic thoracoscopy. After drainage pleurodesis was performed with tetracycline as sclerosing agent. Of 18 evaluable consecutive patients (mean age 67.8 years) nine were randomized for pleurodesis with the small and nine for the large catheter. In the former group, the majority (seven of nine) did not find insertion of the catheter more unpleasant than thoracentesis. In the latter group only a few (two of nine) found insertion comparable with thoracentesis (P < 0.05). All patients found the presence of the large catheter very or somewhat unpleasant (two and seven patients), whereas this was only the case for a few (no and two patients) treated with the small catheter (P < 0.05). In the former group three patients required new thoracentesis, whereas this was only the case for two patients in the latter group (P > 0.05). No complications were seen. We conclude that pleurodesis in patients with recurrent malignant pleural effusion can be performed with a small percutaneous catheter (Cystofix) with an effect similar to that obtained with a large-bore chest tube and with less discomfort for the patient.", "Pleurodesis with doxycycline (100 mg and 600 mg) and Corynebacterium parvum (1 mg and 7 mg) were compared in 41 patients with malignant effusion. To evaluate the mechanisms, pleural fluid pH, leukocytes, granulocytes, interleukin-6 (IL-6) and serum IL-6, as well as C-reactive protein (CRP) were measured before and on 2 consecutive days after treatment. Corynebacterium parvum produced a greater acute-phase response measured with fever, serum CRP and IL-6 than doxycycline. However, no change in pleural fluid IL-6 was demonstrated. Among the 35 assessed patients, 26 had objective response, similar in all four treatment groups. Side-effects were more common with Corynebacterium parvum. Based on this preliminary study we conclude that doxycycline, even in low doses, is a highly effective and well tolerated agent for palliative treatment of malignant pleural effusion. As the responses were similar despite different inflammatory reactions, the two agents probably induce pleural obliteration through different mechanisms.", "Talc has been generally accepted to be the most effective sclerosant for chemical pleurodesis, although the optimal route of administration remains unclear.\n We designed a prospective, randomized study to compare video-assisted thoracoscopic talc insufflation with bedside talc slurry in the treatment of malignant pleural effusion. From September 1993 to November 1995, 57 patients were recruited and randomized to either video-assisted thoracoscopic talc insufflation under general anesthesia (n = 28) or talc slurry by the bedside (n = 29). Patients with poor general condition (Karnofsky score less than 30%), poor pulmonary function (forced expiratory volume in 1 second less than 0.5 L), or trapped lungs were excluded from this study. Five grams of purified talc was used for either video-assisted thoracoscopic talc insufflation or talc slurry.\n There was no statistically significant difference between the two groups of patients with respect to age, sex ratio, chest drainage duration, postprocedural hospital stay, parenteral narcotics requirement, complications, or procedure failure (ie, recurrence).\n Video-assisted thoracoscopic talc insufflation has not been shown to be a superior approach compared with talc slurry in our study. Because the former demands more resources, we advocate that talc slurry should be considered as the procedure of choice in the treatment of symptomatic malignant pleural effusion in patients who do not have trapped lungs.", "In a randomized trial, pleurodesis was attempted with Corynebacterium parvum in one group and bleomycin in another. Patients with malignant pleural effusion which required repeated drainage were treated with instillation of one of these agents after complete drainage of the pleural effusion. There were 32 patients who could be evaluated. Sixty-five per cent of the patients treated with C. parvum had no recurrence after one treatment and another 29% after two treatments. In the bleomycin group, two patients needed only one treatment while the remainder - 13 out of 15 patients - needed further drainage treatments even after two instillations of the drug. The difference was highly significant (p less than 0.001)." ]

[ "12742329", "3154218", "9763048", "17346475", "16880298" ]

[ "Aggressive or expectant management of labour: a randomised clinical trial.", "[Trial of labor. A comparative study between Friedman's partogram and the conventional descriptive partogram].", "Partogram action line study: a randomised trial.", "A randomized controlled trial of a bedside partogram in the active management of primiparous labour.", "Effect of different partogram action lines on birth outcomes: a randomized controlled trial." ]

[ "To compare labour outcomes using aggressive or expectant management protocols.\n Randomised trial.\n Pretoria Academic Complex, South Africa. It serves an indigent urban population.\n Healthy nulliparous women in active labour, at term, with a health singleton pregnancy and cephalic presentation.\n The women were randomised to either aggressive (n = 344) or expectant (n = 350) management protocols. Aggressive management entailed using a single line partogram, a vaginal examination every two hours and use of an oxytocin infusion if the line was crossed. Expectant management entailed using a two line partogram, with the alert line and a parallel action line four hours to the right, with a vaginal examination every four hours. If the action line was reached, oxytocin was started. The women were reassessed every two hours thereafter. Analgesia was prescribed on request.\n Mode of birth, use of oxytocin and analgesia and neonatal outcome.\n The groups were similar with respect to maternal age, cervical dilation at trial entry, number crossing the alert line and birthweight of the infants. Significantly fewer women managed aggressively had caesarean sections (16.0%) than those managed expectantly (23.4%) (relative risk [RR] 0.68, 95% confidence intervals [CI] 0.50, 0.93). Significantly more oxytocin was used in the aggressive management group, but there was no difference with respect to the use of analgesia or episiotomy or in neonatal outcome with respect to the Apgar score at 1 or 10 minutes. There were three perinatal deaths. One woman was found to have an intrauterine death before trial entry and the other two were in the aggressive management group but did not receive oxytocin. Compliance by staff was poor in the aggressive management group.\n Aggressive management of labour reduces the caesarean section rate in nulliparous women but requires more intensive nursing.", "nan", "To assess the effect of three different partograms on caesarean section and maternal satisfaction.\n Prospective randomised clinical trial.\n Regional teaching hospital in North West of England.\n Nine hundred and twenty-eight primigravid women with uncomplicated pregnancies who presented in spontaneous labour at term.\n The women were randomised to have their progress of labour recorded on a partogram with an action line 2, 3 or 4 hours to the right of the alert line. If the progress reached the action line, a diagnosis of prolonged labour was made. Prolonged labour was managed according to the standard ward protocol.\n Primary: Caesarean section rate and maternal satisfaction; secondary: need for augmentation, duration of labour, analgesia, cord blood gas analysis, postpartum haemorrhage, number of vaginal examinations, Apgar score and admission to special care baby unit.\n Caesarean section rate was lowest when labour was managed using a partogram with a 4-hour action line. The difference between the 3- and 4-hour partograms was statistically significant (OR 1 8, 95% CI 1.1-3.2), but the difference between 2 and 4 hours was not (OR 1.4, 95% CI 0.8-2.4). The women in the 2-hour arm were more satisfied with their labour when compared to the women in the 3-hour (P < 00001) and 4-hour (P <00001) arm.\n Our data suggest that women prefer active management of labour. It is possible that partograms which favour earlier intervention are associated with higher caesarean section rate. As the evidence on which to base the choice of partograms remains inconclusive further research is required.", "The partogram is a pictorial representation of the progress of labour, used in an effort to enhance early recognition of dystocia and help avoid Caesarean section (CS). The objective of this study was to evaluate the effect of partogram use on the CS and obstetric intervention rates.\n We conducted a randomized controlled trial of use of the partogram in 1932 primiparous women with uncomplicated pregnancies at term. Patients were randomly assigned to one of two groups: the standard group, who had the progress of labour charted in written notes, or the partogram group, whose progress in labour was recorded using a bedside graphical partogram as well as in written notes. Outcomes were stratified according to whether labour was spontaneous or induced and whether membranes were initially intact or ruptured. The primary outcome was the rate of CS; secondary outcome measures were rates of obstetric intervention for dystocia.\n There was no significant difference between the groups in rates of CS (partogram 24%, standard notes 25%), rates of other interventions, amniotomy, oxytocin use, or the mean cervical dilatation in labour.\n In this study, the use of a partogram without a mandatory management of labour protocol had no effect on rates of CS or other intrapartum interventions in healthy primiparous women at term.", "The World Health Organization recommends partograms with a 4-hour action line, denoting the timing of intervention for prolonged labor; others recommend earlier intervention. We assessed the effect of different action line positioning on birth outcomes.\n A randomized trial of primigravid women with uncomplicated pregnancies, in spontaneous labor at term, was conducted in the northwest of England. Women were assigned to have their labors recorded on a partogram with an action line 2 or 4 hours to the right of the alert line. If progress crossed the action line, diagnosis of prolonged labor was made and managed according to standard protocol. Primary outcomes were rate of cesarean delivery and maternal satisfaction.\n A total of 3,000 women were randomly assigned to groups; 2,975 (99.2%) were available for analysis. Questionnaires were completed by 1,929 (65%) women. There were no differences in cesarean delivery rate (136/1,490 compared with 135/1,485; relative risk [RR] 1, 95% confidence interval [CI] 0.80-1.26) or women dissatisfied with labor experience (72/962 compared with 81/967; RR 0.89, 95% CI 0.66-1.21). More women assigned to the 2-hour arm had labors that crossed the action line (854/1,490 compared with 673/1,485; RR 1.27, 95% CI 1.18-1.37); received more intervention (772/1,490 compared with 624/1,485; RR 1.23, 95% CI 1.14-1.33); and, if admitted to the midwife-led unit, were transferred for consultant-led care (366/674 compared with 285/666; RR 1.26, 95% CI 1.13-1.42).\n In this birth setting, for primigravid women selecting low intervention care, the 2-hour partogram increases the need for intervention without improving maternal or neonatal outcomes, compared with the 4-hour partogram, advocated by the World Health Organization.\n Current Controlled Trials, http://www.controlled-trials.com/isrctn/trial/|/0/78346801.html, ISRCTN78346801." ]

[ "11780880", "9167520", "11431238" ]

[ "Right versus left prefrontal transcranial magnetic stimulation for obsessive-compulsive disorder: a preliminary investigation.", "Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study.", "Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a double-blind, placebo-controlled study." ]

[ "There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful for the treatment of obsessive-compulsive disorder (OCD), but no definitive study has been published, and the effect of laterality of stimulation is uncertain.\n Subjects (N = 12) with resistant OCD were allocated randomly to either right or left prefrontal rTMS daily for 2 weeks and were assessed by an independent rater at 1 and 2 weeks and 1 month later.\n Subjects had an overall significant improvement in the obsessions (p < .01), compulsions (p < .01), and total (p < .01) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 2 weeks and at 1-month follow-up. This improvement was significant for obsessions (p < .05) and tended to significance for total Y-BOCS scores (p = .06) after correction for changes in depression scores on the Montgomery-Asberg Depression Rating Scale. There was no significant difference between right- and left-sided rTMS on any of the parameters examined. Two subjects (33%) in each group showed a clinically significant improvement that persisted at I month but with relapse later in I subject.\n A proportion (about one quarter) of patients with resistant OCD appear to respond to rTMS to either prefrontal lobe, although in the absence of a sham treatment group in this study, we cannot rule out the possibility of this being a placebo response. This treatment warrants further investigation to better establish its efficacy and examine the best parameters for response.", "Prefrontal mechanisms are implicated in obsessive-compulsive disorder. The authors investigated whether prefrontal repetitive transcranial magnetic stimulation influenced obsessive-compulsive disorder symptoms.\n Twelve patients with obsessive-compulsive disorder were given repetitive transcranial magnetic stimulation (80% motor threshold, 20 Hz/2 seconds per minute for 20 minutes) to a right lateral prefrontal, a left lateral prefrontal, and a midoccipital (control) site on separate days, randomized. The patients' symptoms and mood were rated for 8 hours afterward.\n Compulsive urges decreased significantly for 8 hours after right lateral prefrontal repetitive transcranial magnetic stimulation, but there were nonsignificant increases in compulsive urges after repetitive transcranial magnetic stimulation of the midoccipital site. A shorter-lasting (30 minutes), modest, and nonsignificant reduction in compulsive urges occurred after left lateral prefrontal repetitive transcranial magnetic stimulation. Mood improved during and 30 minutes after right lateral prefrontal stimulation.\n These preliminary results suggest that right prefrontal repetitive transcranial magnetic stimulation might affect prefrontal mechanisms involved in obsessive-compulsive disorder.", "The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex for patients with obsessive-compulsive disorder (OCD) was studied under double-blind, placebo-controlled conditions.\n Patients were randomly assigned to 18 sessions of real (N=10) or sham (N=8) rTMS. Treatments lasted 20 minutes, and the frequency was 1 Hz for both conditions, but the intensity was 110% of motor threshold for real rTMS and 20% for the sham condition.\n No significant changes in OCD were detected in either group after treatment. Two patients who received real rTMS, with checking compulsions, and one receiving sham treatment, with sexual/religious obsessions, were considered responders.\n Low-frequency rTMS of the right prefrontal cortex failed to produce significant improvement of OCD and was not significantly different from sham treatment. Further studies are indicated to assess the efficacy of rTMS in OCD and to clarify the optimal stimulation characteristics." ]

[ "3901421", "3890279", "3067105" ]

[ "Double-blind controlled trial of the therapeutic effects of prostacyclin in patients with completed ischaemic stroke.", "Double-blind controlled trial of prostacyclin in cerebral infarction.", "[Use of prostacyclin in patients with ischemic stroke. A double-blind method II]." ]

[ "In a pilot study, 26 patients with acute completed strokes (48 hours to 5 days after cerebral infarction) were randomly assigned to the prostacyclin (PGI2) or placebo groups. PGI2 sodium salt (Epoprostenol, Wellcome Research Laboratories and Upjohn Company) or its solvent (glycine buffer) were infused into the subclavian vein for six-hour periods in five courses separated by six-hour intervals. Prostacyclin was administered at a rate of 2.5-5.0 ng/kg/min. A significant alleviation of neurological deficits occurred 6 and 54 hours after the treatment in patients receiving prostacyclin. This improvement lost its statistical significance at the end of a two-week observation period. It is concluded that further modified controlled studies are required to evaluate the therapeutic usefulness of PGI2 in the treatment of patients with cerebral ischaemia.", "Thirty-two patients with acute cerebral infarction received either prostacyclin or placebo intermittently for 65 hours. Pulse and blood pressure were not altered by prostacyclin. After infusion there was no change in infarct volume or cerebral blood flow in either group. After normalisation for starting values, age and site of cerebral infarction there was a greater than 10% improvement in speech in the prostacyclin group, but minimal changes in neurological score or disability status. Age is related to neurological score at 14 days after stroke by decreasing improvement by 6.8% for each additional 10 years. This study has not been able to demonstrate that prostacyclin is effective in the treatment of ischaemic stroke, but due to the sample size the chance of proving this statistically (the power) was small. Similarly any conclusion that prostacyclin is not effective may be wrong because of the Type II error probability being high.", "Thirty patients with acute ischaemic stroke were allocated randomly into a group treated with prostacyclin and a group receiving placebo. The treatment was started 24 to 72 hours after the onset of stroke. Prostacyclin sodium (Wellcome, U.K. or Chinoin, HPR) or its solvent (glycine buffer) were administered intravenously once daily during 2 weeks in 6-hour infusions. Prostacyclin was infused at rates of 2.5-5.0 ng/kg/min. Statistically significant improvement appeared from the second day on in the prostacyclin group, and only from the eighth day on in the placebo group. However, the final improvement was not statistically different between these groups." ]

[ "2866493", "10676820", "9220214", "9363044", "2898792", "10901839", "7714222", "9600581", "8666569", "2874128", "2649317", "1978371", "1798836", "10485635", "9241006", "10732655", "2870640", "6130066" ]

[ "Comparison of buspirone and diazepam in generalized anxiety disorder.", "Efficacy and safety of lesopitron in outpatients with generalized anxiety disorder.", "Efficacy and safety of two dosing regimens of buspirone in the treatment of outpatients with persistent anxiety.", "Abecarnil for the treatment of generalized anxiety disorder: a placebo-controlled comparison of two dosage ranges of abecarnil and buspirone.", "Clinical profile of gepirone, a nonbenzodiazepine anxiolytic.", "[Efficacy and withdrawal of clobazam, lorazepam and buspirone in the treatment of anxiety disorders].", "Assessment of the efficacy of buspirone in patients affected by generalized anxiety disorder, shifting to buspirone from prior treatment with lorazepam: a placebo-controlled, double-blind study.", "Buspirone and lorazepam in the treatment of generalized anxiety disorder in outpatients.", "Efficacy of buspirone in generalized anxiety disorder with coexisting mild depressive symptoms.", "Low-sedation potential of buspirone compared with alprazolam and lorazepam in the treatment of anxious patients: a double-blind study.", "A pooled, double-blind comparison of the effects of buspirone, diazepam and placebo in women with chronic anxiety.", "Efficacy and safety of a putative anxiolytic agent: ipsapirone.", "Alprazolam versus buspirone in the treatment of outpatients with generalized anxiety disorder.", "Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder.", "Gepirone and diazepam in generalized anxiety disorder: a placebo-controlled trial.", "Prior benzodiazepine use and buspirone response in the treatment of generalized anxiety disorder.", "Double-blind comparison of buspirone and clorazepate in anxious outpatients.", "A double-blind comparison of buspirone and diazepam in outpatients with generalized anxiety disorder." ]

[ "A total of 66 outpatients meeting Diagnostic and Statistical Manual (DSM-III) criteria for generalized anxiety disorder began treatment in a randomized double-blind study that compared the efficacy and safety of buspirone and diazepam. Thirty-nine outpatients completed the 4-week trial. Both drugs were administered in a 1:1 dosage ratio; the daily prescribed dose did not exceed 40 mg. The mean daily dose of buspirone prescribed throughout the study was significantly higher than that of diazepam. Diazepam had a significantly earlier onset of efficacy than buspirone, although both drugs were equivalent after 4 weeks of treatment. Adverse reactions were more frequent in the diazepam group. Total scores from the Hamilton anxiety scale and physician's global ratings show that diazepam was significantly superior to buspirone during the initial 2 weeks of treatment. These findings are further corroborated by the results of patients' self-rated scales.", "To compare the relative efficacy and safety of lesopitron 4-80 mg/d versus lorazepam 2-4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder (GAD).\n Six-week, randomized, double-blind, parallel, placebo and lorazepam-controlled, Phase II, single-center, outpatient study.\n Outpatient clinic.\n One hundred sixty-one patients with GAD were randomized in the main study; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup.\n After a one-week placebo lead-in, patients were randomized to receive placebo, lesopitron, or lorazepam twice daily for six weeks, followed by a one-week taper period. Efficacy was assessed using the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions scale. Safety was assessed through physical examinations, monitoring of vital signs, 12-lead electrocardiograms, laboratory analyses, and adverse event monitoring.\n An overall mean improvement in the HAM-A total score between baseline and end point for all three treatment groups was seen, with mean changes of 3.4 (95% CI 2.0 to 4.8), 6.1 (95% CI 4.1 to 8.1), and 6.1 (95% CI 4.6 to 7.6) for the placebo, lesopitron, and lorazepam groups, respectively (omnibus p = 0.044, uncorrected). Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted. Future trials could be stratified on the basis of referral status (symptomatic volunteer vs. clinical patient with preexisting illness) or previous exposure to anxiolytics, and use a fixed-dose rather than flexible-fixed-dose design.\n The subgroup analysis represents a comparison of treatment outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history. Although the overall study analysis was equivocal, for the approximately 40% of patients with recurrent anxiety disorder, beneficial effects for both lesopitron and lorazepam are suggested.", "This randomized, double-masked, comparative study evaluated the efficacy and safety of buspirone 30 mg/d, administered twice a day (BID) or three times a day (TID), in patients with generalized anxiety disorder (GAD), commonly called persistent anxiety. Patients who participated had GAD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders. Third Edition, Revised, modified to include patients for whom the symptom duration was at least 4 weeks and scored > or = 18 on the Hamilton Rating Scale for Anxiety (HAM-A). After a 7-day placebo lead-in phase, patients who continued to qualify were randomized to receive buspirone, titrated from 15 mg/d (5 mg TID) to 30 mg/d, as either a BID or TID regimen, for 8 weeks. Of the 137 patients who began the study, 120 patients were included in the data evaluation. Both buspirone BID and TID treatment groups demonstrated significant reductions in mean HAM-A total scores and improvement on Clinical Global Impression measures, with no significant differences detected between the two treatment groups for either measure at any time point. The overall incidence of adverse events was similar for both treatment groups, except for a significantly greater incidence of amblyopia in patients receiving buspirone 15 mg BID. In summary, there was no appreciable difference in efficacy or safety between buspirone 15 mg BID or 10 mg TID in patients with persistent anxiety.", "The development of effective and well-tolerated anxiolytic agents is an area of critical clinical importance. Abecarnil, a beta carboline, is a partial benzodiazepine-receptor agonist that has demonstrated promise as an anxiolytic agent. In this study, we examine the efficacy, safety, and discontinuation-related effects of abecarnil, buspirone, and placebo in the acute and long-term treatment of patients who have generalized anxiety disorder.\n This is a double-blind, placebo-controlled study of two dosages of abecarnil and buspirone. In total, 464 patients were randomized. After a placebo run-in week, patients entered a 6-week double-blind treatment period, followed by an optional 18-week maintenance period for treatment responders. After abrupt discontinuation of the acute or maintenance treatment, patients entered a 3-week placebo-substitution follow-up period. Treatment response was assessed with the Hamilton Rating Scale for Anxiety and the Clinical Global Impressions (CGI) Scale.\n Compared with placebo, abecarnil showed significant anxiolytic activity early in the treatment period, particularly in the high-dosage group, though these differences did not maintain statistical significance at the end of the trial. Buspirone was associated with a slower onset of action and better symptom relief than placebo after 6 weeks of therapy. Withdrawal symptoms emerged in patients who abruptly discontinued abecarnil (particularly at the higher dosage) only in those receiving a longer duration of treatment.\n The results of this study need to be understood in the context of a high placebo-response rate, which hampers the ability to demonstrate significant drug-placebo differences. This study suggests that abecarnil may be an effective anxiolytic agent; further attention is warranted to assess its spectrum of clinical effectiveness.", "nan", "This multicentre study was conducted to evaluate the efficacy and consequences of progressive or abrupt withdrawal of clobazam in the treatment of Generalized Anxiety Disorder in a double blind study in comparison to lorazepam and buspirone. 128 outpatients suffering from Generalized Anxiety Disorder according to DMS III criteria were included in the study and treated for three weeks. They were randomly divided into 4 groups: group 1: 32 patients receiving clobazam, abruptly withdrawn and replaced by a placebo; group 2: 29 patients receiving clobazam with progressive withdrawal over 3 weeks, clobazam being replaced by a placebo; group 3: 33 patients receiving lorazepam with progressive withdrawal over 3 weeks, lorazepam being replaced by a placebo; group 4: 34 patients receiving buspirone, abruptly withdrawn and replaced by a placebo. The dosages were increased progressively during the first week of treatment. At the end of this time, the patients received either 30 mg clobazam or 30 mg buspirone or 3 mg lorazepam daily. After the first week, the Hamilton Anxiety Rating Scale (HARS) showed a significant improvement in clobazam and lorazepam groups but not in buspirone group. All the drugs were equally effective after three weeks of treatment. The anti-anxiety activity persisted after withdrawal of the studied drug in the 4 groups, without any signs of rebound anxiety or withdrawal syndrome. No clinically relevant differences were found between the 4 groups regarding safety. The side-effects reported were mainly drowsiness in clobazam and lorazepam groups, nausea and headache in buspirone group. In conclusion, clobazam like lorazepam improved anxiety more quickly than buspirone; after 3 weeks of therapy, efficacy was comparable with the 3 drugs and persisted after treatment discontinuation.", "Forty-four patients with DSM-III-R generalized anxiety disorder participated in this double-blind, randomized study. Patients were on a benzodiazepine before the study and were stabilized on 3 to 5 mg/day lorazepam for 5 weeks (weeks 0 to 5). Thereafter, they were randomized to 15 mg/day buspirone or placebo for the following 6 weeks (weeks 6 to 11). During the first 2 weeks of double-blind, randomized treatment (weeks 6 to 7), lorazepam was tapered off. During weeks 12 to 13, patients received single-blind placebo. Assessment included the Hamilton Rating Scale for Anxiety, the State-Trait Anxiety Inventory, the Zung and Eddy Self-Rating Scale of Anxiety Symptoms, the Hamilton Rating Scale for Depression, and the Rome Depression Inventory, completed at weeks 0, 5, 6, 7, 8, 9, 11, and 13. Side effects were assessed through the Dosage Treatment Emergent Symptoms at the same times. The benzodiazepine-withdrawal syndrome was evaluated through a 27-symptom checklist (Clinical-Rated Benzodiazepine Withdrawal Symptom Schedule) at weeks 0, 5, 6, 7, 11, and 13. The results showed that buspirone was more effective than placebo and comparable to lorazepam. Buspirone-treated patients showed no rebound anxiety or benzodiazepine-withdrawal syndrome compared with placebo. Buspirone caused fewer side effects than lorazepam and was not different from placebo in this respect. Finally, buspirone maintained its anxiolytic effect for at least 2 weeks after the discontinuation of treatment.", "In this double-blind, placebo-controlled 10-week trial, the anxiolytic properties of the nonbenzodiazepine buspirone were compared with the benzodiazepine lorazepam and placebo in 125 outpatients with generalized anxiety disorder according to DSM-III. After a 3- to 7-day wash-out period, patients were allocated at random to receive orally 3 x 5 mg buspirone (n=58), 3 x 1 mg lorazepam (n=57), or placebo (n=10) over a 4-week period. The study also comprised a 2-week taper period and a 4-week placebo-control period to assess the stability of clinical improvement. The patient's clinical state was estimated on entry and at weekly intervals by general practitioners using the Hamilton Rating Scale for Anxiety (HAM-A) and Clinical Global Impression (CGI) assessment and by a self-rating scale (State Trait Anxiety Inventory X2=STAI-X2). Lorazepam treatment resulted in descriptively, but not significantly, greater improvement on the Hamilton Rating Scale for Anxiety during the whole treatment (week 0-4) and taper period (week 5, 6) than did buspirone. After treatment with active drugs had been discontinued, the 4-week placebo control period showed buspirone-treated patients to display a stability of clinical improvement, while the symptoms of lorazepam-treated patients worsened at week 7-10. Both buspirone and lorazepam were more efficacious in reducing anxiety symptoms than placebo during the treatment and taper period; however, in contrast to the active drugs (buspirone, lorazepam), patients of the placebo group showed further clinical improvement during the control period, especially in the HAM-A score, so differences between placebo and active drugs became smaller at the end of the study.", "This study was designed to evaluate the anxiolytic efficacy of buspirone in patients with a diagnosis of generalized anxiety disorder (GAD) with coexisting mild depressive symptoms.\n Patients who participated in this multicenter study scored >/= 18 on the Hamilton Rating Scale for Anxiety (HAM-A) and between 12 and 17 on the Hamilton Rating Scale for Depression (HAM-D). Following a 7- to 10-day placebo lead-in phase, patients who continued to qualify were randomly assigned to receive either buspirone titrated from 15 to 45 mg/day (N = 80) or placebo (N = 82) for the next 6 weeks. 121 patients completed 6 weeks of treatment. The primary efficacy measure was the HAM-A, taken weekly during the study.\n Buspirone-treated patients averaged a 12.4-point reduction from their baseline total HAM-A score of 24.9, while their counterparts on placebo averaged a 9.5-point reduction from their mean baseline total HAM-A score of 25.6. This 2.9-point difference in HAM-A reductions between treatment groups was significantly different (p < .03). Buspirone patients decreased their HAM-D scores by an average 5.7 points from their mean baseline total HAM-D score of 15.8, while placebo patients decreased their HAM-D scores by an average 3.5 points from their mean baseline score of 16.3 (p < .05). Overall, the incidence of adverse events was similar for both treatment groups, but buspirone-treated patients reported significantly more nausea, dizziness, somnolence, and sweating than placebo patients.\n Buspirone is superior to placebo in improving anxiety and depressive symptoms in GAD patients who have coexisting depressive symptoms.", "Buspirone was compared to alprazolam and lorazepam in the treatment of generalized anxiety disorder in a 4-week, double-blind study of 60 patients. All three medications were effective and similar in producing significant reductions in anxiety as assessed by standardized anxiety rating scales and by global evaluations of patients by physicians. There were significant differences in drowsiness, lethargy, and/or fatigue: fewer patients in the buspirone group than in the alprazolam group (16% vs. 60%, respectively; p less than .01) or the lorazepam group (16% vs. 65%, respectively; p less than .0003) experienced these undesirable side effects. This demonstration of similar effectiveness and superior safety would favor buspirone in the treatment of generalized anxiety disorder.", "Pooled data were analyzed for 367 female patients enrolled in a double-blind, placebo-controlled, multi-centre trial comparing buspirone, a non-benzodiazepine anxiolytic, and diazepam in the treatment of generalized anxiety disorder. After a 4 to 7-day wash-out period, patients were allocated at random to receive one or other of the trial medications or placebo over a 4-week period. Mean daily dosages were 24.5 mg for buspirone and 20.8 mg for diazepam (range 10 mg to 60 mg for both drugs). Patients were assessed on entry and at weekly intervals using the Hamilton Anxiety Rating Scale, and at the end of treatment both patients and physicians gave an overall opinion of response to treatment. Details of adverse events were also recorded. The results showed that both buspirone and diazepam were approximately equal in efficacy and superior to placebo. Menstruation and the occurrence of premenstrual tension did not alter the anxiolytic activity of either drug. Patients taking diazepam had significantly more adverse effects, i.e. drowsiness, weakness, fatigue, inco-ordination and depression, than did those in the buspirone group. In a separate commentary, the anxiety disorder and the data from the study are reviewed to place them in the overall perspective of gynaecological care.", "Ipsapirone is an azopirone derivative that selectively interacts with serotonin-1A (5-HT1A) receptors and fails to affect other neurotransmitter receptors. In this study, ipsapirone at 15 mg or 30 mg was compared with diazepam at 15 mg and placebo in a double-blind, random assignment study design in patients with generalized anxiety disorder (GAD). During 4 weeks of treatment, both active drugs were therapeutically superior to placebo, without significant drug vs. drug therapeutic differences. The side-effect profile of ipsapirone at 15 mg was favorable compared to diazepam, but at 30 mg ipsapirone produced significant gastrointestinal disturbances.", "The efficacy and safety of alprazolam and buspirone for treating generalized anxiety disorder (GAD) were compared in a 6-week, double-blind, randomized, placebo-controlled study of 94 outpatients. Mean daily doses at the end of the study were 1.9 mg alprazolam and 18.7 mg buspirone. As judged by the Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Physician's Global Improvement Scale, and other efficacy scales, alprazolam and buspirone were similar in efficacy, but more effective than placebo, for treating anxiety and depression symptoms in these patients. Clinically important differences were noted between drugs in the onset of effect, with alprazolam producing rapid and sustained improvement within the first week of treatment and buspirone producing more gradual, continuous improvement throughout the study. Significantly more buspirone-treated than alprazolam-treated patients failed to complete the study, primarily because of side effects or inefficacy. No clinically important differences were noted between alprazolam and buspirone in side effects, vital signs, or laboratory test results. Alprazolam-treated patients most frequently reported central nervous system-related side effects (drowsiness and sedation), while buspirone-treated patients most frequently reported gastrointestinal system-related side effects (appetite disturbances and abdominal complaints).", "The objective of this randomized, double-blind study was to compare the efficacy and safety of venlafaxine extended release (XR) and buspirone in outpatients with generalized anxiety disorder (GAD) but without concomitant major depressive disorder.\n Male and female outpatients at least 18 years old who met the DSM-IV criteria for GAD and had scores of 18 or higher on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with either venlafaxine XR (75 or 150 mg/day), buspirone (30 mg/day in 3 divided doses), or placebo for 8 weeks. The primary efficacy variables were changes in anxiety as determined by final on-therapy HAM-A total and psychic anxiety scores and Clinical Global Impressions scale (CGI) scores. Other key efficacy variables were HAM-A anxious mood and tension scores and the anxiety subscale scores of the patient-rated Hospital Anxiety and Depression scale (HAD).\n The efficacy analysis included 365 patients and the safety analysis, 405. At week 8, adjusted mean HAM-A psychic anxiety, anxious mood, and tension scores were significantly lower for venlafaxine XR-treated patients than for placebo-treated patients. On the HAD anxiety subscale, venlafaxine XR, 75 or 150 mg/day, was significantly more efficacious than placebo at all time points except weeks 1 (both dosages) and 2 (150-mg/day dosage only) and significantly more efficacious than buspirone at all time points except week 1. On the CGI-Improvement scale, scores for venlafaxine XR (both dosages) and buspirone were numerically superior to those for placebo at all time points, and statistical significance was observed at weeks 3, 4, 6, and 8 for venlafaxine XR and at weeks 6 and 8 for buspirone. The adverse events were not essentially different between treatment groups.\n Venlafaxine XR is an effective, safe, and well-tolerated once-daily anxiolytic agent in patients with GAD without comorbid major depressive disorder. This agent was significantly superior to buspirone on the HAD anxiety subscale. Buspirone demonstrated statistical significance versus placebo on a measure of anxiolytic response.", "This randomized, double-blind clinical trial involving 198 generalized anxiety disorder (GAD) patients was conducted to more clearly define gepirone's role for the treatment of anxiety in daily dosages of 10 to 45 mg compared with diazepam and placebo. A secondary goal was to test for possible discontinuation symptoms after abrupt discontinuation of therapy. After a 1-week washout period, patients were treated for 8 weeks and then abruptly shifted under single-blind conditions for 2 weeks on placebo. The highest attrition rate occurred with patients on gepirone (58%) and the lowest on diazepam (34%). Medication intake for week 4 was 19.5 +/- 12.5 mg/day diazepam and 19.0 +/- 11.5 mg/day gepirone and was similar at week 8. The major adverse events were light-headedness, nausea, and insomnia for gepirone and drowsiness and fatigue for diazepam. Clinical improvement data showed gepirone's anxiolytic response to be delayed, being significant from placebo beginning at week 6, whereas diazepam caused significantly more relief than placebo from week 1 onward. Taper results showed that only diazepam, but not gepirone, caused a temporary worsening of anxiety symptoms or rebound.", "An earlier preliminary report suggested that prior treatment with benzodiazepines might predict a reduced response to buspirone in patients diagnosed with generalized anxiety disorder (GAD). To confirm or refute this hypothesis, the present data analysis was conducted.\n One large data set (N = 735) of GAD patients (DSM-III) treated with buspirone, a benzodiazepine, and a placebo was analyzed by dividing all patients into 3 prior benzodiazepine (BZ) treatment groups: no prior BZ treatment, recent (< 1 month) BZ treatment, and remote (> or = 1 month) BZ treatment. Using an intent-to-treat last-observation-carried-forward (LOCF) data set, acute 4-week treatment response was assessed in terms of clinical improvement, attrition, and adverse events as a function of these 3 prior benzodiazepine treatment groups.\n Patient attrition was significantly higher (p < .05) in the recent BZ treatment group than in the remote and no prior BZ treatment groups with lack of efficacy given as the primary reason by patients receiving buspirone but not benzodiazepine or placebo. In the buspirone group, adverse events occurred more frequently in the recent BZ treatment group than in the remote BZ treatment and no prior BZ treatment groups. Finally, clinical improvement with buspirone was similar to benzodiazepine improvement in the no prior BZ treatment and remote BZ treatment groups, but less than benzodiazepine improvement in the recent BZ treatment group, leading to the smallest buspirone/placebo differences in improvement in the recent BZ treatment group.\n These data suggest that the initiation of buspirone therapy in GAD patients who have only recently terminated benzodiazepine treatment should be undertaken cautiously and combined with appropriate patient education.", "Buspirone, a new nonbenzodiazepine anxiolytic agent, was compared with clorazepate in a double-blind, multicenter trial conducted with 336 outpatients who had moderate to severe anxiety. The two treatments were equally effective for relief of symptoms, including anxiety with associated depression. Although both agents were generally well tolerated, the profile of side effects was dissimilar. Drowsiness and depression occurred significantly (p less than 0.055) more frequently with clorazepate, whereas nausea and headache occurred significantly (p less than 0.055) more frequently with buspirone. Clorazepate-treated patients were significantly (p less than 0.055) more likely to have had an adverse experience that was considered drug related or that interfered with the therapeutic effect. In this study, buspirone was shown to be an effective antianxiety agent, causing significantly less sedation than clorazepate.", "The safety and antianxiety and antidepressive effects of buspirone (average 16.5 mg/day) were compared in a double-blind trial with those of diazepam (15 mg/day). The two drugs were nearly equivalent in relieving symptoms of both anxiety and depression in 100 patients. Scores on the impaired cognition factor of the SCL-56 and confusion factor of the POMS showed significantly greater improvement with buspirone than with diazepam. Side effects, such as sedation and drowsiness, were significantly more frequent and severe with diazepam. Buspirone may be particularly indicated for anxious patients with associated depression." ]

[ "1958942", "11230031", "3318754", "10742877", "16864523", "17262816", "3690108", "10596247" ]

[ "A controlled study of the effect of therapies aimed at adolescent and family psychopathology in anorexia nervosa.", "Psychological therapies for adults with anorexia nervosa: randomised controlled trial of out-patient treatments.", "An evaluation of family therapy in anorexia nervosa and bulimia nervosa.", "Comparison of family therapy and family group psychoeducation in adolescents with anorexia nervosa.", "A randomized controlled study of cognitive behavior therapy and behavioral family therapy for anorexia nervosa patients.", "Anorexia nervosa in Asian-American adolescents: do they differ from their non-Asian peers.", "Brief psychotherapy in the treatment of anorexia nervosa. Outcome at one year.", "A controlled comparison of family versus individual therapy for adolescents with anorexia nervosa." ]

[ "Ninety patients with severe anorexia nervosa fulfilling DSM-III-R criteria were assessed in depth in terms of their family developmental psychopathology and then randomly allocated to either one of three treatment groups or to no treatment. In three treatment regimes, a behavioural approach to diet and weight gain was coupled with individual and family psychotherapy directed at the adolescent maturational problems. All three treatment regimes were highly significantly effective at one year in terms of weight gain, return of menstruation, and aspects of social and sexual adjustment. Body weights above those at pubertal onset were achieved for the group mean maximum and one-year follow-up weights for all three treatment groups but not the control group.", "Currently, without systematic evidence, psychotherapy for anorexia nervosa in adults draws on psychodynamic, cognitive and systemic theories.\n To assess effectiveness of specific psychotherapies in out-patient management of adult patients with anorexia nervosa.\n Eighty-four patients were randomised to four treatments: three specific psychotherapies - (a) a year of focal psychoanalytic psychotherapy; (b) 7 months of cognitive-analytic therapy (CAT); (c) family therapy for 1 year - and (d) low contact, 'routine' treatment for 1 year (control).\n At 1 year, there was symptomatic improvement in the whole group of patients. This improvement was modest, several patients being significantly undernourished at follow-up. Psychoanalytic psychotherapy and family therapy were significantly superior to the control treatment; CAT tended to show benefits.\n Psychoanalytic and family therapy are of specific value in the out-patient treatment of adult patients with anorexia.", "A controlled trial comparing family therapy with individual supportive therapy in anorexia nervosa and bulimia nervosa was undertaken. Eighty patients (57 with anorexia nervosa; 23 with bulimia nervosa) were first admitted to a specialized unit to restore their weight to normal. Before discharge, they were randomly allocated to family therapy or the control treatment (individual supportive therapy). After one year of psychological treatment, they were reassessed, using body weight, menstrual function, and ratings on the Morgan and Russell scales. Family therapy was found to be more effective than individual therapy in patients whose illness was not chronic and had begun before the age of 19 years. A more tentative finding was the greater value of individual supportive therapy in older patients. To our knowledge, this is the first controlled trial of family therapy in anorexia nervosa and clarifies the specific indications for this treatment.", "To compare the effects of 4 months of 2 family-oriented treatments, family therapy and family psychoeducation, on female adolescents with newly diagnosed restrictive eating disorders.\n Twenty-five female adolescents requiring hospitalization were randomized into either family therapy or family group psychoeducation. Outcome measures included medical (body weight) and psychosocial (specific and nonspecific eating disorder psychopathology) variables at baseline and after 4 months of treatments every 2 weeks.\n A significant time effect was found in both treatment groups for the restoration of body weight (percentage of ideal body weight, P < 0.00001). The group averages ranged from 75% to 77% ideal body weight before treatment to 91% to 96% after it. A time effect was also seen on the Family Assessment Measure (P < 0.018), in that the patients of both groups acknowledged more family psychopathology at the end of treatment. No significant group differences were found on any of the self-report measures of specific and nonspecific eating disorder pathology.\n Weight restoration was achieved following the 4-month period of treatment in both the family therapy and family psychoeducation groups, but no significant change was reported in psychological functioning by either adolescents or parents. Family group psychoeducation, the less expensive form of treatment, is an equally effective method of providing family-oriented treatment to newly diagnosed, medically compromised anorexia nervosa patients and their families.", "Very few studies have examined the role of cognitive behavior therapy (CBT) in the outpatient treatment of anorexia nervosa. This study used a randomized, controlled design to evaluate a 12-month, manual based program of CBT, with behavioral family therapy as the comparison group. Twenty-five adolescents and young adults with anorexia nervosa, currently living with their families, were recruited into the study with both treatment groups receiving 21-25 sessions of therapy. Outcome measures included nutritional status, eating behaviors, mood, self-esteem, and family communication. Sixty percent of the total sample and 72% of treatment completers had \"good\" outcome (defined as maintaining weight within 10% of average body weight and regular menstrual cycles) at post-treatment and at six months follow-up. No significant differences between treatment groups were found and the majority of patients did not reach symptomatic recovery. While limited by the small sample size, the findings compliment and extend previous research.", "This study reports on the clinical characteristics and phenomenology of anorexia nervosa (AN) in Asian-American adolescents, and compares them with a non-Asian sample.\n Data were obtained from a family therapy trial for adolescents with AN. Demographic details were collected and participants assessed on a series of structured interviews. Data from Asian participants were compared with that from non-Asians.\n Asians scored lower on all the Eating Disorder Examination (EDE) subscales, significantly on the restraint subscale (1.48 vs. 2.80, p = 0.016) and weight concerns subscale (1.35 vs. 2.30, p = 0.026). They also scored higher on the Family Environment Scale achievement orientation subscale (6.50 vs. 4.81, p = 0.011).\n Asians are demographically similar to their non-Asian peers but tend to come from higher-income families who were more achievement oriented. EDE scores suggest Asians tend to report fewer symptoms. The apparent lack of fat-phobia among Asians could be related to this overall under-reporting of symptoms.", "Thirty out-patients with severe anorexia nervosa were randomly allocated to either 12 sessions of dietary advice or 12 sessions of combined individual and family psychotherapy. At one-year follow-up both groups showed significant overall improvement, and the dietary advice group showed significant weight gain. A similar mean weight gain for the psychotherapy patients did not reach statistical significance, but this group made significant improvements in sexual and social adjustment.", "To compare the effectiveness of behavioral family systems therapy (BFST) with that of ego-oriented individual therapy (EOIT) as treatments for adolescents with anorexia nervosa.\n Thirty-seven adolescents meeting DSM-III-R criteria for anorexia nervosa were randomly assigned to receive BFST or EOIT, in addition to a common medical and dietary regimen. In BFST, the family was seen conjointly, the parents were placed in control of the adolescent's eating, distorted beliefs were targeted through cognitive restructuring, and strategic/behavioral interventions were used to change family interactions. In EOIT, the adolescent was seen individually, with an emphasis on building ego strength and uncovering the dynamics blocking eating; parents were seen collaterally. Measures administered before, after, and at 1-year follow-up tapped body mass index, menstruation, eating attitudes, ego functioning, depression, and family interactions.\n BFST produced greater weight gain and higher rates of resumption of menstruation than EOIT. Both treatments produced comparably large improvements in eating attitudes, depression, and eating-related family conflict, but very few changes occurred on ego functioning.\n BFST and EOIT proved to be effective treatments for adolescents with anorexia nervosa, but BFST produced a faster return to health." ]

[ "19652568", "20023338", "16306834", "17077731", "11154543", "20535041", "19411450", "20495932" ]

[ "The use of screw at the fracture level in the treatment of thoracolumbar burst fractures.", "Long segment instrumentation of thoracolumbar burst fracture: fusion versus nonfusion.", "Posterior fixation of thoracolumbar burst fracture: short-segment pedicle fixation versus long-segment instrumentation.", "Is fusion necessary for surgically treated burst fractures of the thoracolumbar and lumbar spine?: a prospective, randomized study.", "Short-segment pedicle instrumentation of thoracolumbar burst fractures: does transpedicular intracorporeal grafting prevent early failure?", "Transpedicular fixation in management of thoracolumbar burst fractures: monosegmental fixation versus short-segment instrumentation.", "Posterior short-segment fixation with or without fusion for thoracolumbar burst fractures. a five to seven-year prospective randomized study.", "Inclusion of the fracture level in short segment fixation of thoracolumbar fractures." ]

[ "In this prospective randomized study, the results of treating unstable thoracolumbar burst fractures by pedicle instrumentation with and without fracture level screw combination were given.\n Our aim was to evaluate the efficacy of fracture level screw combination in achieving and maintaining correction in the treatment of unstable thoracolumbar burst fractures.\n Most authors reported that intraoperative correction of sagittal deformity is important for the maintenance of fracture reduction and is one of the most consistent predictor of satisfactory functional outcome.\n Seventy-two patients with unstable thoracolumbar burst fractures were randomized into 4 groups with equal number of patients. In group 1, patients were treated by segmental posterior instrumentation with 2 levels above and 2 levels below the fracture level fixation, in group 2 they were treated as in group 1 with fracture level screw incorporation. In group 3, patients were treated by short-segment posterior instrumentation with 1 level above and 1 level below, in group 4 they were treated by short-segment posterior instrumentation with fracture level screw incorporation. Clinical and radiologic parameters were evaluated before surgery, after surgery, and at follow-up.\n The average follow-up was 50 months. Fracture level screw combination provided better intraoperative correction and maintenance in the treatment of unstable thoracolumbar burst fractures, which was more prevalent in short-segment fixation group.\n Reinforcement with fracture level screw combination can help to provide better kyphosis correction and offers immediate spinal stability in patients with thoracolumbar burst fracture.", "The treatment of thoracolumbar burst fracture is a controversial issue. Although spinal fusion has been a touchstone of spinal fixation, nonfusion technique have become raising its popularity recently. Some studies suggested that nonfusion had several advantages over fusion. The aim of this prospective study was to compare long segment posterior instrumentation with fusion versus long-segment posterior instrumentation without fusion.\n For this purpose, 42 consecutive patients were assigned to two groups. Group 1 included 21 patients treated by long segment instrumentation with fusion (WF), whereas Group 2 included 21 patients treated by long segment instrumentation without fusion (WOF). Long segment instrumentation was hook fixation (claw hooks attached to second upper vertebra and infralaminar hooks attached to first upper vertebra) above and pedicle fixation (pedicle screws attached to first and second lower vertebrae) below the fractured vertebra.\n Measurements of local kyphosis, sagittal index and anterior vertebral height compression showed that both group had similar outcome at final follow-up. Moreover, there was no difference between the two groups according to low back outcome score. Also, implant failure rate (4.7%) was quite low in both groups. However, WF group had prolonged operative time, increased blood loss and donor site morbidity.\n Radiological and clinical parameters demonstrated that spinal fusion is not necessary in long segment posterior instrumentation for the management of thoracolumbar burst fractures.", "The treatment of thoracolumbar burst fracture is a controversial issue. Short-segment (SS) pedicle fixation has become a popular treatment option. However, there are several studies regarding the high rate of failure. The aim of this prospective study was to compare SS versus long-segment (LS) instrumentation.\n For this purpose, 18 consecutive patients were assigned to two groups. Group 1 included nine patients treated by SS pedicle fixation, whereas group 2 included nine patients treated by LS instrumentation. SS instrumentation was pedicle fixation one level above and below the fractured vertebra. LS instrumentation was hook fixation (claw hooks attached to second upper vertebra and infralaminar hooks attached to first upper vertebra) above and pedicle fixation (pedicle screws attached to first and second lower vertebrae) below the fractured vertebra.\n As a result, measurements of local kyphosis, sagittal index, and anterior vertebral height compression showed that the LS group had a better outcome at final follow-up (P < 0.05). Also, the SS group had a 55% failure rate, whereas the LS group had prolonged operative time and increased blood loss. However, there was no difference between the two groups according to Low Back Outcome Score.\n In conclusion, radiographic parameters demonstrated that LS instrumentation is a more effective management of thoracolumbar burst fractures. Nevertheless, clinical outcome was the same between the two groups. However, our conclusions were based on posterior-only surgery. Anterior column support would negate the need for LS fixation. Also, SS would have been more successful if two above and two below pedicle screws were used.", "A prospective clinical trial was conducted.\n To compare the results of fusion versus nonfusion for surgically treated burst fractures of the thoracolumbar and lumbar spine.\n The operative results of surgically treated burst fractures with short segmental fixation have been well documented. There is no report comparing the results of fusion and nonfusion.\n Fifty-eight patients were included in this study, with the inclusion criteria as follows: neurologically intact spine with a kyphotic angle > or = 20 degrees, decreased vertebral body height > or = 50% or a canal compromise > or = 50%, incomplete neurologic deficit with a canal compromise 50%, complete neurologic deficit, and multilevel spinal injury or multiple traumas. All patients were randomly assigned to fusion or nonfusion groups, and operative treatment with posterior reduction and instrumentation was carried out. Posterior fusion with autogenous bone graft was performed for the fusion group (n = 30), and no fusion procedure was done for the nonfusion group (n = 28). The average follow-up period was 41 months (range, 24-71 months).\n The average loss of kyphotic angle was not statistically significant between these 2 groups. The radiographic parameters were statistically significantly better in the nonfusion group, including angular change in the flexion-extension lateral view (4.8 degrees vs. 1.0 degrees), lost correction of decreased vertebral body height (3.6% vs. 8.3%), intraoperative estimated blood loss (303 mL vs. 572 mL), and operative time (162 minutes vs. 224 minutes). The scores on the low back outcome scale were not statistically significant for these 2 groups.\n The short-term results of short segmental fixation without fusion for surgically treated burst fractures of the thoracolumbar spine were satisfactory. The advantages of instrumentation without fusion are the elimination of donor site complications, saving more motion segments, and reducing blood loss and operative time.", "A prospective, randomized study comparing two treatment methods for thoracolumbar burst fractures: short-segment instrumentation with transpedicular grafting and the same procedure without transpedicular grafting.\n To evaluate the efficacy of transpedicular grafting in preventing failure of short-segment fixation for the treatment of thoracolumbar burst fractures.\n Short-segment pedicle instrumentation for thoracolumbar burst fractures is known to fail early because of the absence of anterior support. Additional transpedicular grafting has been offered as an alternative to prevent this failure. However, there is controversy about the results of transpedicular grafting.\n Twenty patients with thoracolumbar burst fractures were included in the study. The inclusion criterion was the presence of fractures through the T11-L3 vertebrae without neurologic compromise. The patients were randomized by a simple method into two groups. Group 1 patients were treated using short-segment instrumentation with transpedicular grafting (TPG) (n = 10), and Group 2 patients were treated by short-segment fixation alone (NTPG) (n = 10). Clinical (Likert's questionnaire) and radiologic (sagittal index, percentage of anterior body height compression, and local kyphosis) outcomes were analyzed.\n The two groups were similar in age, follow-up period, and severity of the deformity and fracture. The postoperative and follow-up sagittal index, percentage of anterior body height compression, and average correction loss in local kyphosis in both groups were not significantly different. The failure rate, defined as an increase of 10 degrees or more in local kyphosis and/or screw breakage, was also not significantly different (TPG = 50%, NTPG = 40%, P = 0.99).\n Short-segment transpedicular instrumentation of thoracolumbar burst fractures is associated with a high rate of failure that cannot be decreased by additional transpedicular intracorporeal grafting.", "A prospective clinical trial was conducted.\n To compare the clinical and radiologic late results of monosegmental transpedicular fixation versus short-segment pedicle instrumentation (SSPI) in management of thoracolumbar burst fractures and evaluate the efficacy of monosegmental transpedicular fixation.\n SSPI (1 level above and 1 below the fracture level) are accepted by many surgeons as an accepted technique for the treatment of thoracolumbar burst fractures. To preserve more motion segments, some authors have advocated monosegmental pedicle instrumentation (MSPI). The recent developments showed that MSPI yielded good clinical results; however, there were no report about comparison of clinical outcome between monosegmental and biosegmental transpedicular fixation in management of thoracolumbar burst fractures.\n Eighty-five patients with thoracolumbar burst fractures fulfilling the inclusion criteria were included in the study. The patients were randomized by a simple method into 2 groups. Group 1 were treated with monosegmental transpedicular fixation (n = 47), and group 2 were treated with biosegmental transpedicular fixation (n = 38). Clinical (Low Back Outcome Score and Oswestry Disability Index) and radiologic (load-sharing classification index, sagittal index, and percentage of anterior body height compression) outcomes were analyzed.\n The 2 groups were similar in age, follow-up period, and severity of the deformity and fracture. The postoperative and follow-up sagittal index, local kyphosis, percentage of anterior body height compression, and average correction loss in local kyphosis in both groups were not significantly different. The failure rate between the 2 surgical approaches was also not significantly different (group 1 = 6.38% and group 2 = 5.26%). Oswestry Disability Index improved in both groups by >25 points in a similar amount (P = 0.23). The average follow-up Low Back Outcome Score was 74.9 and 60.2 for group 1 and group 2, respectively (P = 0.033).\n In conclusion, radiologic parameters demonstrated that both MSPI and SSPI are the effective and reliable operative techniques for selected thoracolumbar burst fractures. MSPI shortened the operative time and decreased the amount of blood loss significantly and, thus, offered better clinical results. Nevertheless, long-term studies are supposed to be performed to support the outcomes.", "The impact of fusion as a supplement to short-segment instrumentation for the treatment of thoracolumbar burst fractures is unclear. We conducted a controlled clinical trial to define the effect of fusion on lumbar spine and patient-related functional outcomes.\n From 2000 to 2002, seventy-three consecutive patients with a single-level Denis type-B burst fracture involving the thoracolumbar spine and a load-sharing score of <or=6 were managed with posterior pedicle screw instrumentation. The patients were randomly assigned to treatment with posterolateral fusion (fusion group, n = 37) or without posterolateral fusion (nonfusion group, n = 36). The patients were followed for at least five years after surgery and were assessed with regard to clinical and radiographic outcomes. Clinical outcomes were evaluated with use of the Frankel scale, the motor score of the American Spinal Injury Association, a visual analog scale, and the Short Form-36 (SF-36) questionnaire. Radiographic outcomes were assessed on the basis of the local kyphosis angle and loss of kyphosis correction.\n No significant difference in radiographic or clinical outcomes was noted between the patients managed with the two techniques. Both operative time and blood loss were significantly less in the nonfusion group compared with the fusion group (p < 0.05). Twenty-five of the thirty-seven patients in the fusion group still had some degree of donor-site pain at the time of the latest examination.\n Posterolateral bone-grafting is not necessary when a Denis type-B thoracolumbar burst fracture associated with a load-sharing score of <or=6 is treated with short-segment pedicle screw fixation.", "Short segment posterior fixation is the preferred method for stabilizing thoracolumbar fractures. In case of significant disruption of the anterior column, the simple short segment construct does not ensure adequate stability. In this study, we tried to evaluate the effect of inclusion of the fractured vertebra in short segment fixation of thoracolumbar fractures. In a prospective randomized study, eighty patients with thoracolumbar fractures treated just with posterior pedicular fixation were randomized into two groups receiving either the one level above and one level below excluding the fracture level (bridging group), or including the fracture level (including group). Different clinical and radiological parameters were recorded and followed. A sum of 80 patients (42 patients in group 1 and 38 patients in group 2) were enrolled in the study. The patients in both the groups showed similar clinical outcome. There was a high rate of instrumentation failure in the \"bridging\" group. The \"bridging\" group showed a mean worsening (29%) in kyphosis, whereas the \"including\" group improved significantly by a mean of 6%. The significant effect of the \"including\" technique on the reduction of kyphotic deformity was most prominent in type C fractures. In conclusion, inclusion of the fracture level into the construct offers a better kyphosis correction, in addition to fewer instrument failures, without additional complications, and with a comparable-if not better-clinical and functional outcome. We recommend insertion of screws into pedicles of the fractured thoracolumbar vertebra when considering a short segment posterior fixation, especially in Magerl type C fractures." ]

[ "7616988", "7908356", "1346337", "7913326", "8100611", "7912097", "1970466", "1831059", "7616989" ]

[ "A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter. AIDS Clinical Trials Group.", "Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Concorde Coordinating Committee.", "A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. Results of the Veterans Affairs Cooperative Study.", "Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017)", "Zidovudine in persons with asymptomatic HIV infection and CD4+ cell counts greater than 400 per cubic millimeter. The European-Australian Collaborative Group.", "Randomized double-blind, placebo-controlled trial of twice-daily zidovudine in asymptomatic haemophiliacs infected with the human immunodeficiency virus type 1. European-Australian Haemophilia Collaborative Study Group.", "The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. The AIDS Clinical Trials Group.", "Placebo-controlled trial to evaluate zidovudine in treatment of human immunodeficiency virus infection in asymptomatic patients with hemophilia. NHF-ACTG 036 Study Group.", "A controlled trial of zidovudine in primary human immunodeficiency virus infection." ]

[ "The clinical benefits of zidovudine remain unproved in patients with asymptomatic human immunodeficiency virus (HIV) infection when CD4 cell counts exceed 500 per cubic millimeter. We compared zidovudine therapy given immediately with deferred therapy in such subjects.\n Beginning in 1987, subjects with asymptomatic HIV infection and 500 or more CD4 cells per cubic millimeter were randomly assigned to receive placebo or zidovudine (either 500 or 1500 mg per day, starting immediately). In 1989, the study was modified so that open-label treatment with 500 mg of zidovudine per day (deferred therapy) was offered when CD4 cell counts fell below 500 per cubic millimeter. The study end points included overall survival, survival free of the acquired immunodeficiency syndrome (AIDS), toxic effects, and changes in CD4 cell counts.\n There were 1637 subjects who could be evaluated: 547 in the deferred-therapy group, 549 in the group receiving 500 mg of zidovudine immediately, and 541 in the 1500-mg group. The subjects were followed for up to 6.5 years (group medians, 4.8, 4.8, and 4.9, respectively). There was no significant difference in AIDS-free survival in the deferred-therapy group as compared with the low-dose or high-dose groups (81 cases of progression to AIDS or death vs. 81 and 74, respectively; P = 0.95 and P = 0.13) or in overall survival (51 deaths vs. 47 and 46; P = 0.25 and P = 0.16). The decline in CD4 cells was slower in both immediate-therapy groups than in the deferred-therapy group (P < 0.001 for both). Adverse effects were uncommon, and before the study modification their incidence was similar among the treatment groups, but severe anemia and granulocytopenia were more frequent in the 1500-mg group than in the deferred-therapy group (P < 0.001).\n In asymptomatic, HIV-infected adults with 500 or more CD4 cells per cubic millimeter, treatment with zidovudine slows the decline in the CD4 cell count but does not significantly prolong either AIDS-free or overall survival. These results do not encourage the routine use of zidovudine monotherapy in this population.", "Concorde is a double-blind randomised comparison of two policies of zidovudine treatment in symptom-free individuals infected with human immunodeficiency virus (HIV): (a) immediate zidovudine from the time of randomisation (Imm); and (b) deferred zidovudine (Def) until the onset of AIDS-related complex (ARC) or AIDS (CDC group IV disease) or the development of persistently low CD4 cell counts if the clinician judged that treatment was indicated. Between October, 1988, and October, 1991, 1749 HIV-infected individuals from centres in the UK, Ireland, and France were randomly allocated to zidovudine 250 mg four times daily (877 Imm) or matching placebo (872 Def). Follow-up was to death or Dec 31, 1992 (total 5419 person-years; median 3.3 years) and only 7% of the 1749 had not had a full clinical assessment after July 1, 1992. Of those allocated to the Def group, 418 started zidovudine at some time during the trial, 174 (42%) of them at or after they were judged by the clinician to have developed ARC or AIDS (nearly all confirmed subsequently) and most of the remainder on the basis of low CD4 cell counts. Those in the Imm group spent 81% of the time before ARC or AIDS on zidovudine compared with only 16% for those in the Def group. Despite the large difference in the amount of zidovudine between the two groups and the fact that the number of clinical endpoints (AIDS and death) in Concorde (347) outnumbers the total of those in all other published trials in symptom-free and early symptomatic infection, there was no statistically significant difference in clinical outcome between the two therapeutic policies. The 3-year estimated survival probabilities were 92% (95% CI 90-94%) in Imm and 94% (92-95%) in Def (log-rank p = 0.13), with no significant differences overall or in subgroup analyses by CD4 cell count at baseline. Similarly, there was no significant difference in progression of HIV disease: 3-year progression rates to AIDS or death were 18% in both groups, and to ARC, AIDS, or death were 29% (Imm) and 32% (Def) (p = 0.18), although there was an indication of an early but transient clinical benefit in favour of Imm in progression to ARC, AIDS, or death. However, there was a clear difference in changes in CD4 cell count over time in the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)", "Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established.\n We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed.\n During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash.\n In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.", "To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS.\n Randomized, double-blind placebo-controlled trial.\n Multicentre study in five European countries and Australia.\n Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects with HIV p24 antigenaemia (> 10 pg/ml).\n Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250 mg four times daily dose regimen for the first 4 weeks.\n The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed.\n Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rank P = 0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a trend in a delay in progression to CDC stage IV disease was observed (P = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P = 0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed.\n Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.", "Zidovudine therapy is of benefit in the treatment of symptomatic and asymptomatic human immunodeficiency virus (HIV) infection in persons with CD4+ cell counts of less than 500 per cubic millimeter. The efficacy, safety, and duration of benefit of zidovudine in those with 500 or more CD4+ cells per cubic millimeter are uncertain.\n In a double-blind, placebo-controlled trial, 993 patients with asymptomatic HIV infection and CD4+ cell counts above 400 per cubic millimeter were randomly assigned to receive zidovudine (500 mg twice daily) or placebo for three years. The primary end point was progression of disease, as defined by the development of Centers for Disease Control and Prevention (CDC) group IV disease (including recurrent oral candidiasis, hairy leukoplakia, or progressive diarrhea) or two CD4+ cell counts below 350 per cubic millimeter. This outcome measure was changed from the original end point of the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex to reflect changes in recommendations for management. The study was terminated after the first interim analysis.\n Disease progression was significantly less frequent in the zidovudine group (relative risk, 0.56; 95 percent confidence interval, 0.43 to 0.75; P < 0.001 by the log-rank test). The probability of disease progression at two years was 0.19 with zidovudine, as compared with 0.34 with placebo (95 percent confidence interval for the difference, -0.21 to -0.08). Progression to CDC group IV disease was reduced by half in the zidovudine recipients (relative risk, 0.49; P = 0.049) and decline in CD4+ cell counts to below 350 per cubic millimeter was reduced by 40 percent (relative risk, 0.60; P < 0.001). The inclusion of early HIV disease events (oral candidiasis, oral hairy leukoplakia, and herpes zoster) as end points confirmed the effects of zidovudine on the progression of clinical disease (relative risk, 0.55; 95 percent confidence interval, 0.37 to 0.84; P = 0.004). The median duration of treatment was 94 weeks. Severe hematologic or clinical side effects were rare.\n Treatment with zidovudine benefits HIV-infected persons with CD4+ cell counts above 400 per cubic millimeter. Despite the use of doses larger than those now generally prescribed, zidovudine was well tolerated for up to three years by most of our patients.", "In this double-blind, placebo-controlled trial of HIV-infected asymptomatic haemophiliacs, the efficacy of 2-year zidovudine therapy (1000 mg daily in two divided doses) in preventing progress of HIV infection was prospectively evaluated. Drug tolerance was also studied. 143 haemophiliacs from five European countries and Australia with p24 antigenaemia and/or CD4 cell counts of 0.1-0.4 x 10(9)/l were enrolled. The main measures of outcome were progression to AIDS, CDC group IV disease, symptomatic HIV-related disease, and a decrease in CD4+ T-lymphocyte count to fewer than 0.2 x 10(9)/l. There were no significant treatment differences in the proportion of patients progressing to AIDS, CDC group IV or symptomatic disease. Analysis of time to CD4+ counts less than 0.2 x 10(9)/l showed a non-significant trend in favour of zidovudine. Haemoglobin concentrations were less than 8 g/dl in 4% of zidovudine recipients; neutropenia was less than 0.75 x 10(9) cells/l in 5% of zidovudine recipients; alanine aminotransferase levels were greater than 10 times the upper normal limit in 3% of zidovudine recipients, but also in 4% of placebo recipients. Hence there was a very low prevalence of side-effects in haemophiliacs, despite the use of a higher zidovudine dosage than is currently widely used.", "To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection.\n A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts.\n Multicenter trial at AIDS Clinical Trial units.\n Seven hundred eleven subjects with mildly symptomatic HIV infection.\n Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months.\n Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively.\n Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.", "One hundred ninety-three asymptomatic patients with hereditary coagulation disorders and human immunodeficiency virus (HIV) infection were studied in a controlled trial of zidovudine (ZDV) versus a placebo (with an average of 9.7 months on study). Pretreatment characteristics were well balanced between the placebo and drug-treated groups, including CD4 distributions, types of clotting disorders, transaminase abnormalities, and use of various hemostatic agents. At the time of analysis, 161 patients either were still receiving treatment or had previously reached an endpoint of disease progression while receiving treatment. Twenty-five patients withdrew voluntarily. The toxic effects noted included granulocytopenia and anemia, especially in older patients, and subjective symptoms of asthenia, malaise, and nausea, consistent with the known consequences of treatment with 300 mg ZDV five times daily. There was a trend toward more diagnoses of acquired immunodeficiency syndrome (AIDS), advanced or early AIDS-related complex (ARC), single ARC symptoms, or death in placebo recipients as compared with those receiving ZDV (22 v 13). Because older patients with hemophilia have more rapid disease progression, the same efficacy analysis was performed in the 89 patients aged more than 30 years who were receiving treatment. In this subgroup, there was a similar trend (11 v 6). With regard to the most advanced problems of the infection among the older patients, there were five patients who were newly diagnosed with AIDS or died in the placebo group versus none in the ZDV group (P = .02) among the older patients. The pretreatment distribution of CD4 counts for the placebo and ZDV groups were similar, but patients aged more than 30 years had significantly (P less than .049) fewer CD4 cells than patients aged less than 30 years. A beneficial ZDV effect is also supported by a trend toward higher CD4 counts (a 48-cell increase in the ZDV group at 24 weeks as compared with a four-cell increase in the placebo group) and a significant (P = .03) difference in weight gain in the ZDV patients aged more than 30 years (8 pounds) as compared with the older placebo patients (aged more than 30 years) (2 pounds) at week 24. The findings in the asymptomatic hemophilic patients aged more than 30 years support a useful effect of ZDV, which is similar to observations in the larger study of its use in asymptomatic, nonhemophilic patients.", "It is possible that antiretroviral treatment given early during primary infection with the human immunodeficiency virus (HIV) may reduce acute symptoms, help preserve immune function, and improve the long-term prognosis.\n To assess the effect of early antiviral treatment, we conducted a multicenter, double-blind, placebo-controlled trial in which 77 patients with primary HIV infection were randomly assigned to receive either zidovudine (250 mg twice daily; n = 39) or placebo (n = 38) for six months.\n The mean time from the onset of symptoms until enrollment in the study was 25.1 days. Among the 43 patients who were still symptomatic at the time of enrollment, there was no appreciable difference in the mean (+/- SE) duration of the retroviral syndrome between the zidovudine group (15.0 +/- 4.1 days) and the placebo group (15.8 +/- 3.6 days). During a mean follow-up period of 15 months, minor opportunistic infections developed in eight patients: oral candidiasis in four, herpes zoster in two, and oral hairy leukoplakia in two. Disease progression was significantly less frequent in the zidovudine group (one opportunistic infection) than in the placebo group (seven opportunistic infections; P = 0.009 by the log-rank test). After adjustment for the base-line CD4 cell count, the patients treated with zidovudine had an average gain of 8.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, -1.4 to 19.1) during the first six months of the study, whereas those receiving placebo had an average loss of 12.0 CD4 cells per cubic millimeter per month (95 percent confidence interval, 5.2 to 18.7), for a between-group difference of 20.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, 8.5 to 33.2; P = 0.001).\n Antiretroviral therapy administered during primary HIV infection may improve the subsequent clinical course and increase the CD4 cell count." ]

[ "2429687", "10202747", "16579924", "4926628", "2677866", "6384851", "1341890", "18532969", "10645858", "6372362" ]

[ "A randomized trial of Citanest with Octapressin for relief of pain associated with laser vaporization of the cervix.", "Using amino-cerv after cervical LEEP.", "A trial that compares Monsel's paste with ball electrode for hemostasis after loop electrosurgical excision procedure.", "Vasopressin injection in cervical conization. A double-blind study.", "Hemostasis and cold knife cone biopsy: a prospective randomized trial comparing a suture versus non-suture technique.", "Use of an antifibrinolytic agent (tranexamic acid) and lateral sutures with laser conization of the cervix.", "Does application of Monsel's solution after loop diathermy excision of the transformation zone reduce post operative discharge? Results of a prospective randomised controlled trial.", "Haemostasis after cold-knife conisation: a randomised prospective trial comparing cerclage suture versus electro-cauterization.", "A comparison of the side effects of prilocaine with felypressin and lignocaine with adrenaline in large loop excision of the transformation zone of the cervix: results of a randomised trial.", "The hemostatic effect of tranexamic acid in conisatio colli uteri." ]

[ "Fifty women undergoing laser vaporization of the cervix for cervical intraepithelial neoplasia were randomly allocated to one of two groups. In one group the patients received no anaesthesia, in the other the ectocervix was infiltrated with 2 ml of Citanest with Octapressin (prilocaine 3% with 0.03 i.u./ml. of felypressin) immediately before the procedure. The pain experienced by each group was assessed immediately after treatment by visual analogue and verbal rating scales. The pain experienced by those women receiving local anaesthesia was significantly reduced as assessed by the visual analogue scale (P = 0.011) and this reduction was not quite significant by the verbal rating scale (P = 0.06). The Citanest group had less troublesome bleeding but the difference in bleeding between the two groups was not significant.", "To evaluate the ability of Amino-Cerv to promote healing of the cervix following loop electrical excision procedure (LEEP) of the cervix for cervical intraepithelial neoplasia.\n A randomized study was conducted on 48 women in a private office setting. Patients were divided into two groups, to use or not use Amino-Cerv intravaginally for two weeks after the procedure. Statistical analysis of the findings were performed using the chi 2 test.\n Twenty of 24 (83%) of women using Amino-Cerv had completely healed tissue at four weeks, whereas 12 of 24 (50%) in the untreated group had healed tissue at four weeks. Findings were not statistically significant at two weeks but were statistically significant (P < .005, power = .55) at four weeks after the procedure.\n Amino-Cerv after LEEP of the cervix promotes healing.", "The purpose of this study was to compare Monsel's paste with fulguration with ball electrode for hemostasis after loop electrosurgical excision procedure.\n One hundred healthy women were assigned randomly by computer-generated random numbers to ball electrode or thickened Monsel's paste for hemostasis after loop electrosurgical excision procedure. Patients rated pain during hemostasis using a visual analog scale. At 2 weeks, postprocedural vaginal discharge was rated on a Likert scale. Pathology was reviewed for dysplasia grade and margin status. Recurrent dysplasia on repeat Papanicolaou tests was noted.\n Six patients (2 Monsel's and 4 fulguration) required an alternate method of hemostasis. Patient demographics, postprocedural discharge, and recurrent dysplasia were comparable between the 2 groups. Visual analog scale scores and hemostasis time were significantly higher in the fulguration group. Estimated blood loss, although higher in the fulguration group, was not significant between groups.\n Monsel's paste and fulguration with ball electrode appear be equally effective as hemostatic agents after loop electrosurgical excision procedure.", "nan", "Two methods of obtaining hemostasis after cold knife cone biopsy were compared in a prospective randomized trial involving 200 patients. One method relied primarily on hemostatic sutures, and the other involved the use of a styptic solution (Monsel's solution) and vaginal pack, thus avoiding the use of sutures altogether. The short- and long-term morbidity in these two groups were compared and 12-month follow-up was completed. The use of sutures did not reduce the incidence of primary hemorrhage. Secondary hemorrhage was twice as frequent in the suture group, although this trend did not quite reach statistical significance. During long-term follow-up, significantly more patients in the suture group developed menstrual symptoms, cervical stenosis, and unsatisfactory colposcopy, requiring further operative intervention as a result.", "One hundred forty patients who underwent laser conization and 220 patients who underwent laser miniconizations were prospectively randomized into two study groups. One treatment group was given antifibrinolytic therapy in the form of tranexamic acid (Cyklokapron, KabiVitrum, Sweden) intraoperatively and for 14 days postoperatively. The other group did not receive antifibrinolytic therapy. In the group of 68 patients with laser conizations who were given antifibrinolytic therapy, no postoperative hemorrhages occurred, whereas there were eight such hemorrhages in 72 conizations (11%) in the untreated patients. This difference is statistically significant (P = .004, Fisher exact test for two proportions). Also, for laser miniconization, the frequency of postoperative hemorrhage was almost halved, from 9.1% in 110 patients not receiving antifibrinolytic therapy to 5.5% in the 110 treated patients. The use of lateral cervical sutures did not reduce the frequency of postoperative hemorrhage at laser conization in the present study.", "nan", "The purpose of this study was to compare two different techniques of obtaining haemostasis after cold-knife conisation.\n Seventy-eight women who required conisation for treatment of cervical intraepithelial neoplasia were prospectively enrolled in a randomised clinical trial to receive either cerclage with cold-knife conisation or cautery with cold-knife conisation. Outcome measures evaluated include estimated blood loss, operative time, early late haemorrhage and dysmenorrhoea. The short- and long-term morbidity was compared, and a six-month follow up was completed.\n The procedure-related complication rate was 16.7% in the cautery group, compared with 7.0% in the suture group (P < 0.05). The cerclage group had significantly shorter operative time and intraoperative blood loss than the cautery group (P < 0.05). Postoperative bleeding and dysmenorrhoea were observed in eight (10.2%), and 14 cases (17.9%), in cerclage and cautery group, respectively. Three cases (3.8%) had postoperative infections and were cured with oral antibiotics.\n These results suggest that cerclage suturing technique provided excellent haemostasis and restoration of normal cervical anatomy. Cerclage suture of the cone bed is superior to only cauterization as a method of achieving haemostasis, with significantly less blood loss and shorter operative time.", "To test the hypothesis that prilocaine with felypressin causes fewer side effects than lignocaine with adrenaline when performing large loop excision of the transformation zone of the cervix.\n Randomised trial.\n Colposcopy clinic in a large district general hospital.\n Two hundred consecutive women undergoing large loop excision of the transformation zone of the cervix.\n Two different local anaesthetic combinations (prilocaine with felypressin and lignocaine with adrenaline) were compared in women undergoing large loop excision of the transformation zone. Prospective collection of clinical and treatment data was undertaken with scoring using an ordinal scale of pain experienced by the women during the procedure. Peri-operative blood loss and any side effects were also recorded.\n Side effects associated with the local anaesthetic agents.\n Lignocaine with adrenaline resulted in less blood loss (P = 0.006) but was more likely to cause side effects, such as feeling faint (P = 0.017) and shaking (P < 0.001).\n Prilocaine with felypressin causes fewer side effects than lignocaine with adrenaline and is therefore the preferred local anaesthetic combination for large loop excision of the transformation zone.", "To evaluate the inhibitory effect of tranexamic acid (AMCA) on increased fibrinolyctical activity in connection with conisatio colli uteri we have carried out a randomized, double-blind study with patients operated upon partly with an open method of operation (80 patients) and partly with modified Sturmdorff sutures (150 patients). In connection with the open method the frequency of late bleeding decreased from 17.5% to 2.5%, which is significant. The corresponding decrease in connection with the other method was from 10.7% to 4.1%. This material was not sufficiently large to verify significance. The side effects of the prophylactic treatment with AMCA were few. The study indicates that AMCA affords good protection against late bleeding in conisatio colli uteri." ]

[ "11805614", "2041549" ]

[ "The Sygen multicenter acute spinal cord injury study.", "Recovery of motor function after spinal-cord injury--a randomized, placebo-controlled trial with GM-1 ganglioside." ]

[ "Randomized, double-blind, sequential, multicenter clinical trial of two doses of Sygen versus placebo.\n To determine efficacy and safety of Sygen in acute spinal cord injury.\n An earlier, single-center trial in 28 patients showed an improvement (50.0% vs. 7.1%, P = 0.034) in marked recovery with Sygen.\n Standard clinical trial techniques.\n The prospectively planned analysis at the prespecified endpoint time for all patients was negative. There was a significant effect in all patients in the primary outcome variable (the percentage of marked recovery) at week 8, the end of the dosing period. There was a significant effect in all patients in the time at which marked recovery is first achieved. Restricted to severity Group B, which has small sample size, the primary efficacy analysis showed a trend but did not reach significance. There is a large, consistent and, at some time points, significant effect in the primary outcome variable in the nonoperated patients through week 26. The American Spinal Injury Association motor, light touch, and pinprick scores showed a consistent trend in favor of Sygen, as also did bowel function, bladder function, sacral sensation, and anal contraction. The less severely injured patients appeared to have a greater beneficial drug effect. Evidence against an effect of Sygen was minimal and scattered.\n Although not proven in the primary efficacy analysis of this trial, Sygen appears to be beneficial in patients with severe spinal cord injury.", "Spinal-cord injury is devastating; until recently, there was no medical treatment to improve recovery of the initial neurologic deficit. Studies in animals have shown that monosialotetrahexosylganglioside (GM-1) ganglioside enhances the functional recovery of damaged neurons.\n A prospective, randomized, placebo-controlled, double-blind trial of GM-1 ganglioside was conducted in patients with spinal-cord injuries. Of 37 patients entered into the study, 34 (23 with cervical injuries and 11 with thoracic injuries) completed the test-drug protocol (100 mg of GM-1 sodium salt or placebo intravenously per day for 18 to 32 doses, with the first dose taken within 72 hours of the injury) and a one-year follow-up period. Neurologic recovery was assessed with the Frankel scale (comprising five categories) and the American Spinal Injury Association (ASIA) motor score (a scale of scores from 0 to 100, derived from strength tests of 20 specific muscles, each scored from 0 to 5).\n There was a significant difference between groups in the distribution of improvement of Frankel grades from base line to the one-year follow-up (improvement of 0, 1, 2, and 3 grades in 13, 4, 1, and 0 patients, respectively, in the placebo group and 8, 1, 6, and 1 patients, respectively, in the GM-1 group; P = 0.034 by the Cochran-Mantel-Haenszel chi-square test). The GM-1-treated patients also had a significantly greater mean improvement in ASIA motor score from base line to the one-year follow-up than the placebo-treated patients (36.9 vs. 21.6 points; P = 0.047 by analysis of covariance with the base-line ASIA motor score as the covariate). An analysis of individual muscle recoveries revealed that the increased recovery in the GM-1 group was attributable to initially paralyzed muscles that regained useful motor strength rather than to strengthening of paretic muscles.\n This small study provides evidence that GM-1 enhances the recovery of neurologic function after one year. A larger study must be conducted, however, before GM-1 is considered efficacious and safe in treating spinal-cord injury." ]

[ "7712392", "3598162", "3301614", "3295020", "3053887", "3319453", "8325041", "7239110", "4922276", "4587191", "4894464", "11007104", "4594755", "12480560", "14049", "3315932", "9397979", "2654285", "2656134", "7016484", "354373", "16481971", "1805974" ]

[ "Treatment of porto-systemic encephalopathy with lactitol verus lactulose: a randomized controlled study.", "Lactitol versus lactulose in the treatment of acute portal systemic encephalopathy (PSE). A controlled trial.", "Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a double-blind, randomized clinical trial.", "Lactitol versus lactulose in the treatment of chronic hepatic encephalopathy. A double-blind, randomised, cross-over study.", "Lactitol vs. lactulose in the treatment of chronic recurrent portal-systemic encephalopathy.", "Lactitol, a second-generation disaccharide for treatment of chronic portal-systemic encephalopathy. A double-blind, crossover, randomized clinical trial.", "Double-blind, double-dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy.", "Lactose enemas plus placebo tablets vs. neomycin tablets plus starch enemas in acute portal systemic encephalopathy. A double-blind randomized controlled study.", "A controlled clinical trial of lactulose in hepatic encephalopathy.", "Comparison of results of long-term treatment of chronic hepatic encephalopathy with lactulose and sorbitol.", "Lactulose in the treatment of chronic portal-systemic encephalopathy. A double-blind clinical trial.", "Efficacy of lactulose in cirrhotic patients with subclinical hepatic encephalopathy.", "[Double blind study of lactulose in 8 patients with chronic hepatic encephalopathy after portocaval shunt].", "Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial.", "Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial.", "Lactitol vs. lactulose in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double-blind, randomized trial.", "Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy.", "Lactitol and lactulose for the treatment of subclinical hepatic encephalopathy in cirrhotic patients. A randomised, cross-over study.", "Lactitol in prevention of recurrent episodes of hepatic encephalopathy in cirrhotic patients with portal-systemic shunt.", "Comparison between neomycin and lactulose in 173 patients with hepatic encephalopathy: a randomized clinical study.", "Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy. A controlled, double-blind clinical trial.", "Cyclic treatment of chronic hepatic encephalopathy with rifaximin. Results of a double-blind clinical study.", "[A clinical comparative study of crystalline pure lactulose and powder pure lactitol in portasystemic encephalopathy of cirrhotic patients]." ]

[ "Lactitol (beta-galactosido-sorbitol), a novel disaccharide analogue of lactulose, has been suggested as an alternative to lactulose in the treatment of portosystemic encephalopathy (PSE) in Western country. In order to assess its therapeutic effect and adverse reaction in PSE in the Chinese, we conducted this study.\n Forty-one patients with PSE were enrolled in this study. Patients were randomly divided into 2 groups to receive lactitol (n = 21) or lactulose (n = 20) for 5 days. The doses of both drugs were adjusted to keep daily bowel movement of 2 to 3 times. The PSE index (mental state, EEG, asterixis, number connection test [NCT], and ammonia) was evaluated in each patient before and after treatment. Daily doses of lactitol and lactulose, stool frequency, and side effect were recorded.\n The mean dose of lactitol used was 66.3 +/- 36.4 gm and that of lactulose was 56.9 +/- 32.1 ml of lactulose. The majority of patients (37/41) gained clear consciousness after 5 days' treatment. In the lactitol group, blood ammonia, EEG, NCT, asterixis, mental status and PSE index before treatment were 208 +/- 62 micrograms/ml, 2.9 +/- 0.8, 4.0 +/- 0.0, 2.7 +/- 1.5, 2.9 +/- 0.7 and 77.1 +/- 10.5, respectively. All parameters decreased significantly after 5 days' treatment (119 +/- 50 micrograms/ml, 1.1 +/- 1.0, 2.9 +/- 1.2, 1.7 +/- 1.1, 0.7 +/- 0.7, and 34.4 +/- 16.0, p < 0.05). The lactulose group had the similar results. However, the improvement of PSE index after therapy in the lactitol group was significantly higher than that in the lactulose group (42.7 +/- 19.3 vs 31.1 +/- 13.7, p < 0.05). In addition, more patients in the lactitol group than in the lactulose group (67% vs 20%, p = 0.003) favored the taste of their assigned drugs. No patient who received lactitol experienced any side effects; however, six patients treated with lactulose complained of meteorism and flatulence, and four complained of nausea.\n Both lactitol and lactulose are effective in the treatment of PSE, though the effect of lactitol seems slightly superior to that of lactulose in our study. Lactitol is more acceptable to our patients due to better palatability and less side effects. Lactitol is another good alternative in the treatment of PSE.", "Preliminary data suggest that lactitol (beta-galactoside-sorbitol), a new synthetic non-absorbable disaccharide, has beneficial effects on chronic portal systemic encephalopathy. To compare the efficacy of lactitol vs. lactulose in the treatment of acute portal systemic encephalopathy (PSE), 40 cirrhotic patients with an acute episode of PSE were randomly allocated to one of two groups: group A (20 patients) received lactulose (30 ml/6 h) and group B (20 patients) lactitol (12 g/6 h). These doses were adjusted daily to obtain two bowel movements per day. The duration of treatment was 5 days. Age, sex, hepatic and renal function, precipitating factors and level of PSE measured by clinical examination, EEG and number connection test were similar in the two groups. A complete clinical resolution of PSE occurred in 11 patients in each group. In 5 patients of the lactulose group and in 6 of the lactitol group there was a moderate improvement of PSE during the study. Finally, 4 patients in the lactulose group and 3 in the lactitol group did not respond to treatment. No side effects attributable to therapy were observed in either group. These results indicate that lactitol is as effective as lactulose in the management of patients with cirrhosis and acute PSE.", "A double-blind, controlled trial to study the efficacy of acidifying enemas of lactitol, a new galactoside-sorbitol disaccharide, and lactose vs. nonacidifying tap-water enemas was performed in 45 episodes of acute portal-systemic encephalopathy. At the time of randomization, all patients had encephalopathy of at least Grade 2+ severity, delay in the performance of number connection tests and hyperammonemia. A sequential analysis was performed which revealed after the inclusion of the first 20 patients, a significant failure of the nonacidifying enemas as compared to the lactitol enemas (p less than 0.004). The tap-water enema group was, therefore, suspended but the rest of the study continued after rerandomization for lactose and lactitol groups. A favorable response to treatment was obtained in 19 (86%) of the patients receiving lactitol enemas and in 14 (78%) of those receiving lactose enemas. A similar significant improvement in portal-systemic encephalopathy parameters and index was observed after both treatments. Both types of acidifying enemas induced a significant pH decrease in stool (p less than 0.05). These data suggest that acidifying agents like lactose and lactitol are effective and superior to tap-water enemas for the treatment of acute nitrogenous portal-systemic encephalopathy.", "Lactitol is a disaccharide analogue of lactulose which is available as a pure crystalline powder. The efficacy of lactitol in the treatment of chronic hepatic encephalopathy was assessed in 9 cirrhotic patients in a randomised, double-blind, cross-over comparison with lactulose. The sugars were dispensed in solutions, identical in taste and appearance and with similar physico-chemical properties, which contained either 66.7 g/100 ml of lactitol or 66.7 ml (44.5 g)/100 ml of lactulose syrup. Patients were treated for periods of 3 months with each sugar, during which time they were monitored frequently by use of a number of clinical, psychometric and laboratory variables. The sugar solutions were dispensed in an initial dose of 0.75 ml/kg which was adjusted, as necessary, in order to produce two semi-soft stools per day. An adequate catharsis was achieved with a mean (+/- 1 SD) equivalent daily dose of 31.9 +/- 11.2 g of lactitol or 32.9 +/- 16.7 ml (21.9 +/- 11.1 g) of lactulose syrup. Both sugars were equally as effective in the treatment of this condition, even though events likely to cause decompensation arose in 5 patients during treatment with lactitol but in only 1 during treatment with lactulose. Side effects appeared to be more frequent during treatment with lactulose, despite the fact that the parent sugar was diluted in the trial solution; thus 5 patients experienced excessive flatulence and 8 experienced diarrhoea on lactulose compared with only 2 and 4 on lactitol, respectively. In all cases the excessive flatulence occurred independently of sugar dosage whereas the development of diarrhoea was dose-related.(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare the efficacy and patient acceptability of lactitol vs. lactulose in chronic recurrent portal-systemic encephalopathy (PSE), 25 cirrhotic patients with a history of repeated episodes of hepatic encephalopathy who required chronic administration of lactulose were included in a controlled cross-over clinical trial in which patients received, at random, lactitol (at an initial dosage of 10 g/6 h) or lactulose (15 ml/6 h, 66% w/v, containing 10 g of lactulose) during a 3 month period and then crossed-over to the alternative treatment for the following 3 months. Doses were adjusted to obtain two bowel movements per day. During the study period the daily protein intake was 40-60 g. Clinical and analytical data (including ammonia levels) were obtained, an EEG and the number connection test were performed and the PSE index was determined before treatment and monthly until the end of the treatment. No significant differences were found between the effects of lactitol and lactulose on the neurological and biological parameters, suggesting that the two treatments could be considered as equally effective. Lactitol was significantly better tolerated than lactulose (P = 0.02), the taste of which was assessed as being too sweet and provoking nausea. In conclusion, lactitol is a good alternative to lactulose for patients with chronic recurrent PSE, especially in those who do not tolerate the excessive sweetness of lactulose.", "A double-blind crossover trial was performed to test the therapeutic usefulness and safety of lactitol, a beta-galactoside sorbitol, against lactose in 18 patients with chronic portal-systemic encephalopathy (PSE). The study included four periods: two for washout and two for lactitol and lactose administration. During washout periods, which lasted two weeks each, patients were stabilized with neomycin plus milk of magnesia. Lactitol and lactose were administered during four weeks each. Ten patients were randomly assigned to receive lactose (group A) and eight patients to receive lactitol (group B) first. PSE parameters, ie, mental state, number connection test performance, asterixis and blood ammonia levels were assessed fortnightly. Electroencephalographic tracings and stool pHs were evaluated at the end of each study period. After the first administration of lactose and lactitol, no statistically significant differences in PSE parameters were found. At the same stage, a significant stool acidification (P less than 0.05) was detected. It is concluded that lactitol seems to be safe and efficacious in treating patients with chronic PSE.", "Fifty-eight patients, 30 males and 28 females, aged between 42 and 60 years (mean age 57 years) suffering from cirrhosis of the liver with signs and symptoms of portosystemic encephalopathy were studied. The double-blind study was performed according to a double-dummy experimental design, comparing the antibiotic rifaximin, administered at a dose of 1200 mg/day, with lactulose, administered at a dose of 30 g/day, both for 15 days. At the end of the treatment with the two drugs, there was a significant improvement in the main symptoms of portosystemic encephalopathy (mental state, asterixis, 'A' cancellation test, Reitan test). The improvement, which was also confirmed by a reduction in the overall score attributed to the degree of portosystemic encephalopathy was undoubtedly correlated with the reduction in the levels of serum ammonia concentrations, recorded after only 3 days of treatment. Tolerability of the treatment with rifaximin was decidedly higher with respect to lactulose. The greater rapidity of action and the lack of side-effects with rifaximin recommend the use of this intestinal antibiotic in patients with medium to severe portosystemic encephalopathy.", "A randomized, double-blind comparison of lactose enemas plus placebo tablets vs. starch enemas plus neomycin tablets was performed on 18 patients with acute portal systemic encephalopathy. Ten patients received starch enemas (10%; 1000 ml t.i.d.) plus neomycin tablets and 8 patients received lactose enemas (20%; 1000 ml t.i.d.) plus placebo tablets. A significant mental state improvement was demonstrated in the group of patients treated with starch enemas-neomycin tablets (p less than 0.05) and in the group of patients treated with lactose enemas-placebo tablets (p less than 0.025). Both treatments significantly improved the frequency of asterixis, ammonia blood levels, and electroencephalograms. In addition, patients treated with lactose enemas showed significant improvement in number-connection test times (p less than 0.02), and their stools showed a more acid pH (p less than 0.05). No side effects were evident with either treatment. Lactose enemas are a safe and effective treatment for acute portal systemic encephalopathy.", "nan", "nan", "nan", "To investigate the role of lactulose in the treatment of cirrhotic patients with subclinical hepatic encephalopathy (SHE), 40 cirrhotic patients, 33 males and 7 females, were included in the study. The diagnosis of SHE was made by quantitative psychometric tests including the number connection test (NCT), figure connection test (FCT) parts A and B, and two performance subtests of Wechsler adult intelligence scale, ie, picture completion (PC) and block design (BD) tests. SHE was diagnosed in 26 (65%) of 40 patients. Of these 26 patients, 14 patients were randomized to treatment group (lactulose 30-60 ml/day for three months, SHE-L) and 12 patients to no treatment group (no lactulose, SHE-NL). Psychometric tests were repeated in all patients in both groups and in six patients with no SHE (group NSHE, N = 14) after three months. The mean scores and number of the abnormal psychometric tests at entry were significantly higher in patients in groups SHE-L and SHE-NL than in patients in group NSHE; however, there was no significant difference between SHE-L and SHE-NL. The mean number of the abnormal psychometric tests decreased in patients in group SHE-L after three months of treatment with lactulose (2.9 +/- 0.9 vs 0.8 +/- 1.2; P = 0.004); however, there was no change in patients in group SHE-NL after three months (3.7 +/- 1.5 vs 3.5 +/- 1.3; P = NS). While SHE improved in 8 of 10 patients in group SHE-L, none of the patients in group SHE-NL improved after three months of follow-up (P < 0.001). Two patients in group SHE-NL also developed overt encephalopathy during the study period. We conclude that lactulose treatment in cirrhotic patients with SHE is effective.", "nan", "The efficacy and safety of rifaximin in comparison with lactitol in the treatment of acute hepatic encephalopathy was assessed in a prospective randomized, double-blind, double-dummy, controlled trial.\n A total of 103 patients with grade I-III acute hepatic encephalopathy were randomized to receive rifaximin (50 patients, 1200 mg/day) or lactitol (53 patients, 60 g/day) for 5-10 days. Changes in the portal-systemic encephalopathy (PSE) index on entry and at the end of the study were used to evaluate the efficacy of the two therapies.\n Both groups were comparable before treatment with regard to demographic data and characteristics of the hepatic encephalopathy episode. The global efficacy of both therapies was similar: 81.6% in the rifaximin group and 80.4% in the lactitol group showed improvement or total regression of the episode. A significantly better evolution of the PSE index was observed in the rifaximin group, due to a greater effect of rifaximin in two components of the index: EEG abnormalities and ammonia levels. No serious adverse events related to either treatment were found during the study.\n Rifaximin may be considered a useful and safe alternative therapy to lactitol in the treatment of acute hepatic encephalopathy in cirrhosis.", "A randomized double blind clinical comparison of neomycin and lactulose was performed in 33 cirrhotic patients with chronic portal-systemic encephalopathy (PSE) at seven cooperating hospitals. In order to maintain double blindness, sorbitol syrup was used as a control solution along with neomycin and was compared with lactulose syrup and placebo tablets in a double drug protocol. Twenty-nine patients were studied in a crossover investigation in which each received both therapeutic regimens preceded and followed by control periods. Four additional patients received one or the other agent, but did not receive both. Serial, semiquantitative assessments were made in all patients of mental status, asterixis, and the trailmaking test (TMT) and electroencephalograms (EEG) and arterial ammonia levels. Both neomycin-sorbitol and lactulose were effective in the majority of patients (83 and 90%, respectively). Each of these parameters (mental state, asterixis, TMT, EEG, and NH3) was improved significantly by neomycin-sorbitol and lactulose. The post-treatment levels for each of these measures were similar in the neomycin and lactulose-treated groups. Mean stool pH was reduced by neomycinsorbitol to 6.1 and by lactulose to 5.5. This difference was highly significant statistically. Bowel activity was similar in the two groups. Both drugs were free of toxicity. These investigations demonstrate that both lactulose and neomycin-sorbitol are effective in the treatment of chronic portal-systemic encephalopathy.", "Lactitol (beta-galactosido-sorbitol) is a nonabsorbable disaccharide available as a powder which, in open comparison, is as effective as lactulose in the treatment of chronic hepatic encephalopathy, but is better tolerated. Twenty-five cirrhotic patients experiencing 28 episodes of acute hepatic encephalopathy were randomized blindly to treatment with either lactitol (n = 15) or lactulose (n = 13). The sugars were dispensed in solutions identical in appearance, taste and pH and of similar osmolarity, which contained either 66.7 gm per 100 ml lactitol or 66.7 ml (44.5 gm) per 100 ml lactulose syrup. The initial dose of 0.75 ml per kg was adjusted to produce two semisoft stools per day. Patients were assessed every 12 hr for 5 days. There were no significant differences in sex ratio, age, body weight, clinical status, duration and extent of coma, etiology of liver disease or of hepatic encephalopathy between the two groups of patients on entry to the trial. An adequate catharsis was obtained with an equivalent mean (+/- 1 S.D.) daily dose of 26 +/- 5 gm lactitol or 31 +/- 7 ml (21 +/- 5 gm) lactulose syrup. During the trial, significant improvements occurred in clinical status and psychometric performance and in the electroencephalogram mean cycle frequencies in the majority of patients in both groups. At the end of the trial, 67% of the patients in the lactitol group and 69% of the lactulose group were clinically normal. However, patients treated with lactitol responded significantly more quickly than patients treated with lactulose.(ABSTRACT TRUNCATED AT 250 WORDS)", "Seventy-five cirrhotic patients with hyperammonemia in the past or at the time of the study were randomly divided into two groups (treated with lactulose or nontreated) in 14 hospitals in Japan. Thirty-six cirrhotic patients were diagnosed as having subclinical hepatic encephalopathy (SHE), and 39 were diagnosed as non-SHE. SHE was diagnosed when the results of all three of the quantitative psychometric tests used (number connection test, and symbol digit and block design tests of the Wechsler adult intelligence scale [revised]) were abnormal as compared with age-matched normal values. The mean number of abnormal psychometric test results and the prevalence of SHE were used for a quantitative evaluation of the efficacy of the lactulose treatment. Twenty-two of the SHE patients were treated with lactulose (45 mL/d) for 8 weeks, and the other 14 SHE patients did not receive lactulose. In the SHE patients administered lactulose, the results of the quantitative psychometric evaluation were significantly improved at 4 and 8 weeks after the beginning of the lactulose administration. The SHE had disappeared in 10 (50%) of the 20 treated patients at week 8, but it persisted in 11 (85%) of the untreated 13 patients. We concluded that lactulose treatment in cirrhotic patients with SHE is effective with respect to psychometric tests.", "Fourteen patients with cirrhosis and subclinical hepatic encephalopathy were randomised to treatment with lactitol or lactulose for a 2-month period during which they were monitored clinically, by electroencephalography and by manually administered and computer-based psychometric testing. Following a washout period of 4-6 weeks patients were crossed-over to treatment with the alternative sugar for a similar period of monitoring. None of the patients showed evidence of overt hepatic encephalopathy and only one showed slowing of the electroencephalogram mean cycle frequency at the onset of the trial. However, significant impairment was observed in the group as a whole in the performance of all three manually administered psychometric tests and in four of the ten computer-based test variables. No changes were observed in clinical status or in electroencephalogram mean cycle frequency during treatment with either lactitol or lactulose. However, psychometric performance improved consistently, and to the same degree, during treatment with both sugars. Patients required a mean of 26 g (range 8-36) of lactitol and 25 ml (10-60) of lactulose to achieve two semi-soft stools per day. The majority of patients complained of flatulence during treatment with both sugars but this tended to resolve with continued treatment. Diarrhoea developed in a small number of patients during both treatment periods but this was invariably dose-related. Patients were equally divided in their preference for the two sugars. Patients with subclinical hepatic encephalopathy benefit from treatment with lactitol and lactulose in terms of their psychometric performance. The feasibility and benefits of long-term treatment for this condition need to be elucidated.", "Recurrent episodes of hepatic encephalopathy (HE) frequently occur in surgically shunted cirrhotic patients. The prevention of these episodes is based mainly on the long-term use of lactulose. Recently, lactitol, a nonabsorbable disaccharide similar to lactulose, has been proposed as an alternative in the management of HE. It has the advantage of being better tolerated and producing a more predictable catharsis. The effects of the two agents were compared in a controlled randomized study lasting six months involving 31 cirrhotic patients with portal-systemic shunt, of whom 40% experienced HE. The PSE index (mental state, EEG, asterixis, Raitan test, and ammonia) was assessed in each patient on entry to the study and every three months during treatment. Episodes of HE, side effects, and the patients' comments on efficacy, tolerability, and palatability were recorded. The dose required to induce two bowel movements per day was 48 +/- 25 ml of lactulose syrup and 36 +/- 7 g of lactitol. During the study, the number of patients who had an episode of HE and the PSE index was similar in both groups. The patients judged lactitol better from the point of view of palatability. Meteorism and flatulence, experienced by patients treated with lactulose, was not reported by the lactitol group. We concluded that lactitol is as effective as lactulose in the long-term prevention of episodes of HE in cirrhotics with portal-systemic shunt and may be better tolerated.", "A randomized study was performed in order to compare the course of hepatic encephalopathy in patients treated with neomycin plus magnesium sulfate or with lactulose. Admission criteria were: morphological diagnosis of cirrhosis and absence of comorbidity, of contraindications to drugs, or of previous treatments which could influence the outcome. The treatment groups were similar in terms of clinical characteristics, fatalities, recovery rate from grade 1 encephalopathy, and disappearance rate of neuropsychiatric signs. Transitions from severe to grade 1 or 0 encephalopathy showed a 0.17 (NS) difference in favor of neomycin. Early therapy and evidence of precipitating factors showed a favorable prognostic significance. Ascites, hyperbilirubinemia, poor nutritional state, and hypoprothrombinemia showed bad prognostic significance. This is the first large-scale investigation on hepatic encephalopathy. It demonstrated a similar effectiveness of the two drugs in grade 1 encephalopathy and provides a basis for drug selection in the current management of the syndrome.", "In a double-blind, randomized study the efficacy of lactulose was compared with neomycin-sorbitol in 45 episodes of acute nitrogenous portal-systemic encephalopathy (PSE) induced by dietary protein, azotemia, or gastrointestinal hemorrhage. All patients had underlying cirrhosis, and at the time of randomization had encephalopathy of at least grade 2 severity and arterial ammonia concentrations greater than 150 microgram/100 ml. Two thirds of the patients in each group returned to normal mental status and more than 80% in each group showed at least one grade improvement in mental state. In addition, there was equivalent improvement in asterixis, in the performance of the Number Connection Test, in the electroencephalographic pattern, and in arterial ammonia concentration. The principal difference between the two groups was a greater reduction in stool pH after lactulose therapy than after neomycin-sorbitol therapy. One patient randomized to neomycin-sorbitol had to be withdrawn from the study because of persistent vomiting related to the administration of the medication. Otherwise there were no complications attributable to therapy in either group. These data suggest that neomycin-sorbitol and lactulose are equally effective in the treatment of acute nitrogenous portal-systemic encephalopathy.", "Chronic hepatic encephalopathy (HE) represents a frequent and serious complication of chronic liver disease. Aim of the study is to comparatively evaluate the effect of rifaximin, lactitol and their combination in treating chronic HE.\n Forty out-patients (29 males, 11 females, mean age: 59 years, range 40-70), with viral liver cirrhosis and chronic HE (1st-2nd degree) were studied. HE was assessed by considering: mental state, asterixis, number connection test (NCT), arterial blood ammonia levels. Patients were randomly assigned to the following treatments: rifaximin (plus sorbitol as placebo) (group R); lactitol (group L); rifaximin plus lactitol (group RL). All treatments were continued for 15 days for 3 cycles, intervalled by 15 days of washout.\n The 3 treatments reduced HE, but with different efficacy: patients of group R and RL significantly (p<0.05) documented a faster improvement in HE degree, a higher percentage of patients which normalized mental state and NCT, a faster improvement of asterixis and a longer persistence of normal ammonia levels than patients of group L.\n Rifaximin in combination with lactitol or sorbitol represents an effective and safe treatment of chronic HE.", "The efficacy and the tolerability of the new crystalline pure lactulose formulation (Laevolac Cristalli) vs lactitol is evaluated in 40 patients suffering from liver cirrhosis and treated for the associated encephalopathy (PSE). Both disaccharides proved to be effective in the maintenance therapy of PSE. With respect to the previous formulation of lactulose, the crystalline one has a significantly lower incidence of side-effects. Pure crystalline lactulose, showing a similar efficacy and rise of side-effects, proved to be better accepted by the subjects of this study." ]

[ "10464834", "15813663", "15562142", "10065682", "2217684", "10934074", "9163637", "16476120" ]

[ "Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa.", "The disease-modifying effects of twice-weekly oral azithromycin in patients with bronchiectasis.", "Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa.", "A pilot study of low-dose erythromycin in bronchiectasis.", "Double-blind randomized study of prolonged higher-dose oral amoxycillin in purulent bronchiectasis.", "Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis.", "Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study.", "Effects of claritromycin on inflammatory parameters and clinical conditions in children with bronchiectasis." ]

[ "The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.", "Bronchiectasis is a chronic pulmonary process characterized by recurrent respiratory infections leading to destruction of airways secondary to inflammation. We investigated whether the addition of 6-months' twice-weekly azithromycin to the existing treatment regimen in patients with pulmonary bronchiectasis decreased the number of exacerbations and improved pulmonary function compared with a similar period of time without concurrent azithromycin.\n Thirty patients with high-resolution computed tomography scan-confirmed bronchiectasis were to be recruited. In random order, patients received usual medications for 6 months, and usual medications plus oral azithromycin 500mg twice weekly for 6 months. Patients receiving azithromycin first had a 1-month washout period prior to entering the second phase. Patients recorded weekly peak flow (PF) measurements. Pulmonary function tests (PFTs), 24-hour sputum volume, and needs for intervention with medication or ancillary support were collected at baseline and every 3 months. Exacerbation incidence and sputum volume measurements were compared from baseline to the end of each study phase.\n Twelve patients were enrolled; 11 were included in the analysis. Owing to randomization, most patients received the azithromycin first, which was fairly well tolerated. PFTs did not change significantly during either study phase and PFs appeared to remain stable during azithromycin therapy and throughout the subsequent control phase. Azithromycin significantly decreased the incidence of exacerbations compared with usual medications (5 vs 16; p = 0.019). Mean 24-hour sputum volume significantly decreased (15% [p = 0.005]) during the active treatment phase, and remained decreased during the control phase (p = 0.028). Subjectively, patients reported increased energy and quality of life while receiving treatment with azithromycin.\n The addition of twice-weekly azithromycin significantly decreased the incidence of exacerbation and 24-hour sputum volume and may have stabilized the PFTs and PFs in this 11-patient pilot study. The results of this study justify further investigation of adding azithromycin to the treatment regimens of patients with bronchiectasis for its disease-modifying effects.", "Non-cystic fibrosis (CF) patients with bronchiectasis usually develop chronic bronchial infection with Pseudomonas aeruginosa (PA) that is related to worsening lung function and increased morbidity and mortality.\n To determine whether direct aerosol delivery of tobramycin to the lower airways may control infection and produce only low systemic toxicity.\n A double-blind, placebo-controlled crossover trial involving 30 patients was conducted to determine the clinical effectiveness and safety of 6-month tobramycin inhalation therapy. Patients received 300 mg of aerosolized tobramycin or placebo twice daily in 2 cycles, each for 6 months, with a one-month washout period. The number of exacerbations, number of hospital admissions, number of hospital admission days, antibiotic use, pulmonary function, quality of life, tobramycin toxicity, density of PA in sputum, emergence of bacterial resistance, and emergence of other opportunistic bacteria were recorded.\n The number of admissions and days of admission (mean +/- SD) during the tobramycin period (0.15 +/- 0.37 and 2.05 +/- 5.03) were lower than those during the placebo period (0.75 +/-1.16 and 12.65 +/- 21.8) (p < 0.047). A decrease in PA density in sputum was associated with tobramycin administration in the analysis of the first 6-month cycle (p = 0.038). No significant differences were observed in the number of exacerbations, antibiotic use, pulmonary function, and quality of life. The emergence of bacterial resistance and other bacteria did not differ between the 2 periods of study. Inhaled tobramycin was associated with bronchospasm in 3 patients, but not with detectable ototoxicity or nephrotoxicity.\n Aerosol administration of high-dose tobramycin in non-CF bronchiectatic patients for endobronchial infection with PA appears to be safe and decreases the risk of hospitalization and PA density in sputum. Nevertheless, pulmonary function and quality of life are not improved, and the risk of bronchospasm is appreciable.", "Patients with bronchiectasis suffer from sputum production, recurrent exacerbations, and progressive airway destruction. Erythromycin is effective in diffuse panbronchiolitis, another suppurative airway disorder, although its efficacy is unknown in idiopathic bronchiectasis. A double-blind placebo-controlled study was therefore conducted to evaluate the effects of 8-week administration of low dose erythromycin (500 mg b.i.d.) in steady-state idiopathic bronchiectasis. Patients in the erythromycin group (n=11, 8 female, mean age 50+/-15 yrs), but not the placebo group (n=10, 8 female, mean age 59+/-16 yrs) had significantly improved forced expiratory volume in one second, forced vital capacity and 24-h sputum volume after 8 weeks (p<0.05). There was no parallel improvement in sputum pathogens, leukocytes, interleukin (IL)-1alpha and IL-8, tumour necrosis factor-alpha, or leukotriene B4. The results of this pilot study show that low-dose erythromycin improves lung function and sputum volume in bronchiectasis. Further studies are indicated to evaluate the efficacy of long-term erythromycin therapy in bronchiectasis.", "Thirty-eight patients with bronchiectasis and daily expectoration of purulent sputum despite conventional antibiotic courses were randomly allocated to receive a sachet of amoxycillin (3 g) or matched placebo twice daily for 32 weeks in a double-blind study. Nine patients (four amoxycillin, five placebo) were withdrawn from the study treatment; the response of the two patients (both on amoxycillin) withdrawn within the first six weeks was not assessed. The pretreatment characteristics of the two groups were similar. Independent assessment of overall response based on patients' diary cards showed that a higher proportion improved in the amoxycillin group (11 of 17) than in the placebo group (four of 19; p = 0.02). Patients in the amoxycillin group spent significantly less time confined to bed and away from work during treatment. The frequency of exacerbations during the study treatment phase was similar in the two groups but they were less severe than before study treatment in the amoxycillin group. There was a greater reduction in purulent sputum volume between exacerbations during the study treatment in the amoxycillin group to 20 per cent of pretreatment volume than in the placebo group (88 per cent of pretreatment volume, p = 0.008), although the concentrations of Haemophilus spp. in sputum between exacerbations was similar in the two groups. Adverse effects experienced were minor except in one patient (amoxycillin) withdrawn after developing a rash and in six patients (three amoxycillin, three placebo) who had diarrhoea lasting more than one week necessitating withdrawal of two patients (one amoxycillin, one placebo) from study treatment. Sputum and stool cultures collected regularly during the study showed no important changes in the bacterial flora in either group. Prolonged higher-dose antibiotic therapy in these patients with severe purulent bronchiectasis significantly reduced the host (patient) inflammatory response to colonizing microorganisms and reduced morbidity.", "We conducted a placebo-controlled, double-blind, randomized study to evaluate the microbiological efficacy and safety of inhaled tobramycin for treatment of patients with bronchiectasis and Pseudomonas aeruginosa. Patients were randomly assigned to receive either tobramycin solution for inhalation (TSI) (n = 37) or placebo (n = 37), which was self-administered twice daily for 4 wk and followed by 2-wk off-drug. At Week 4, the TSI group had a mean decrease in P. aeruginosa density of 4.54 log(10) colony-forming units (cfu)/g sputum compared with no change in the placebo group (p < 0.01). At Week 6, P. aeruginosa was eradicated in 35% of TSI patients but was detected in all placebo patients. Investigators indicated that 62% of TSI patients showed an improved medical condition compared with 38% of placebo patients (odds ratio = 2.7, 95% confidence interval [CI] 1.1 to 6.9). Tobramycin-resistant P. aeruginosa strains developed in 11% of TSI patients and 3% of placebo patients (p = 0.36). The mean percent change in FEV(1) percent predicted from Week 0 to Week 4 was similar for the TSI and placebo groups (p = 0.41). More TSI-treated patients than placebo patients reported increased cough, dyspnea, wheezing, and noncardiac chest pain, but the symptoms did not limit therapy. Additional study is warranted to further evaluate TSI in bronchiectasis patients.", "Increased airway responsiveness (AR) is frequently associated with bronchiectasis. Roxithromycin is a new semisynthetic macrolide antibiotic that also has anti-inflammatory activities. This study was designed to see whether roxithromycin could favourably alter the degree of AR in patients with bronchiectasis and increased AR. Twenty five children with bronchiectasis, who had an increased AR (defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) <25 mg x mL(-1) evaluated by the dosimeter method), were randomized, double-blind into two parallel groups. Thirteen of the children were treated with roxithromycin (4 mg x kg(-1) b.i.d.) for 12 weeks and 12 received placebo. FEV1, sputum purulence and leucocyte scores were assessed every 3 weeks. To estimate AR, high-dose methacholine challenge tests were performed before and after treatment. On the dose-response curve to methacholine, PD20 and maximal response (two indices of AR) were measured. Changes in FEV1 were not observed during the course of the study in both groups. A significant improvement in sputum features was noted after 6 weeks of treatment in the roxithromycin group. After 12 weeks of roxithromycin therapy, the geometric mean (range of 1 SD) of provocative cumulative dose producing a 20% fall in FEV1 (PD20) increased significantly (p<0.01) to 169.2 (83.2-344.2) breath units (BU) (1 BU denotes one inhalation of 1 mg x mL(-1) methacholine) and the mean+/-SD of maximal response decreased significantly (p<0.01) to 32.5+/-6.8%, as compared with the initial values (PD20 87.1 (47.3-160.4) BU; maximal response 40.9+/-7.4%). No significant changes in either parameter were observed in the placebo group. Our results indicate that roxithromycin may decrease the degree of airway responsiveness in patients with bronchiectasis and increased airway responsiveness. Further study is necessary to determine the mechanism by which roxithromycin reduces airway responsiveness in bronchiectasis and its clinical impact.", "The effects of the macrolides cannot be ascribed to their antibacterial action alone. Their immunoregulatory and anti-inflammatory functions are significant too. They are frequently used in the treatment of diffuse panbronchiolitis and cystic fibrosis (CF).\n To evaluate the effects of a macrolide antibiotic [clarithromycin (CAM)] on the process of inflammation [by measuring IL-8, TNF-alpha, IL-10 levels and cell profiles in bronchoalveolar lavage (BAL) fluid], pulmonary function and sputum production in children with steady-state bronchiectasis, secondary to causes other than CF or primary immunodeficiencies.\n Seventeen patients randomized to the treatment group received CAM and supportive therapies for 3 months and 17 patients in the control group were given supportive therapies only.\n Compared with the control group, the treatment group showed a significant decrease in IL-8 levels, total cell count, neutrophil ratios in BAL fluid and daily sputum production at the end of the third month. There was also a significant increase in the treatment group's BAL fluid macrophage ratios. The differences in pulmonary function test parameters were not significant.\n Use of CAM in children with steady-state bronchiectasis results in laboratory improvement by reducing the inflammatory processes in the lungs. No corresponding clinical improvement could be shown but although this is possible with long-term use, trial validation is necessary." ]

[ "11926786", "12354470", "12760589" ]

[ "Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension.", "Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial.", "The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension." ]

[ "Inhalation of the stable prostacyclin analogue iloprost is being studied for treatment of pulmonary hypertension. The selective phosphodiesterase-5 inhibitor sildenafil has been reported to cause pulmonary vasodilatation.\n To evaluate the safety and effectiveness of oral sildenafil, alone and in combination with inhaled iloprost, for treatment of pulmonary hypertension.\n Randomized, controlled, open-label trial.\n Intensive care unit.\n 30 patients with severe pulmonary arterial hypertension (n = 16), chronic thromboembolic pulmonary hypertension (n = 13), or pulmonary hypertension due to aplasia of the left pulmonary artery (n = 1), all classified as New York Heart Association class III or IV.\n All patients received inhaled nitric oxide and aerosolized iloprost (inhaled dose, 2.8 microg). They were then randomly assigned to receive 12.5 mg of oral sildenafil, 50 mg of sildenafil, 12.5 mg of sildenafil plus inhaled iloprost, or 50 mg of sildenafil plus inhaled iloprost.\n Systemic and pulmonary arterial pressure, pulmonary arterial occlusion pressure, cardiac output, central venous pressure, peripheral arterial oxygen saturation, and arterial and mixed venous blood gases were measured during right-heart catheterization by using a Swan-Ganz catheter.\n In rank order of pulmonary vasodilatory potency (maximum reduction of pulmonary vascular resistance and increase in cardiac index), 50 mg of sildenafil plus iloprost was most effective, followed by 12.5 mg of sildenafil plus iloprost. Iloprost alone and 50 mg of sildenafil were almost equally effective but were less potent than the combination regimens, and the least potent treatments were 12.5 mg of sildenafil and nitric oxide. In patients who received 50 mg of sildenafil plus iloprost, the maximum change in pulmonary vasodilatory potency was -44.2% (95% CI, -49.5% to -38.8%), compared with -14.1% (CI, -19.1% to -9.2%) in response to nitric oxide. With administration of 50 mg of sildenafil plus iloprost, the area under the curve for reduction in pulmonary vasodilatory resistance surpassed that of administration of 50 mg of sildenafil alone and iloprost alone combined, the vasodilatory effect lasted longer than 3 hours, and systemic arterial pressure and arterial oxygenation were maintained. No serious adverse events occurred.\n Although limited by the small sample and lack of long-term observations, the study shows that oral sildenafil is a potent pulmonary vasodilator that acts synergistically with inhaled iloprost to cause strong pulmonary vasodilatation in both severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.", "Lung fibrosis can be complicated by pulmonary hypertension, limiting exercise tolerance and life expectancy. Furthermore, vasodilators might cause deterioration in gas exchange. Our aim was to compare acute effects of sildenafil, nitric oxide, and epoprostenol in individuals with pulmonary hypertension secondary to lung fibrosis.\n We did a randomised controlled, open-label trial, in 16 individuals admitted to our hospital with pulmonary hypertension secondary to lung fibrosis. After inhalation of nitric oxide (10-20 ppm), we assigned patients to either maximum tolerated dose of intravenous epoprostenol (mean 8.0 ng/kg per min; n=8) or oral sildenafil (50 mg; n=8). Our primary objective was to assess pulmonary vasodilative potency (decrease in pulmonary vascular resistance index) of sildenafil by comparison with inhaled nitric oxide and infused epoprostenol. Analyses were by intention to treat.\n Pulmonary vascular resistance index was reduced by nitric oxide (-21.9%, 95% CI -14.1 to -36.2), epoprostenol (-36.9%, -24.4 to -59.6), and sildenafil (-32.5%, -10.2 to -54.1). However, ratio of pulmonary to systemic vascular resistance decreased only in individuals who received nitric oxide and sildenafil. Baseline measurement of multiple-inert-gas elimination showed right-to-left shunt flow (4.8%, 0.0-28.2) and little perfusion of low ventilation(V)/perfusion(Q) areas (0.1%, 0.0-13.0). Prostacyclin increased V/Q mismatch (shunt 16.8%, 10.8-35.9; low V/Q 3.8%, 0.0-13.0) and decreased arterial oxygenation. By contrast, nitric oxide (4.5%, 0.0-18.0; 0.0%, 0.0-17.3) and sildenafil (3.3%, 0.0-11.3; 0.0%, 0.0-12.4) maintained V/Q matching, with raised arterial partial pressure of oxygen (14.3 mm Hg, -1.7 to 31.3) noted for sildenafil. We recorded no adverse events.\n Sildenafil causes preferential pulmonary vasodilation and improves gas exchange in patients with severe lung fibrosis and secondary pulmonary hypertension.", "Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous infusion of prostacyclin has proved effective. However, it carries the risk of serious complications arising from the complex delivery system. Prostacyclin analogs, endothelin antagonists, and the phosphodiesterase-5 inhibitor sildenafil are emerging promising therapies. This study was aimed at evaluating the utility of oral sildenafil in patients with pulmonary hypertension of varied etiology, poorly controlled on conventional treatment.\n Ten consecutive patients with pulmonary hypertension, either primary or related to previous left-to-right shunts, thromboembolism, or interstitial lung disease, poorly controlled on conventional therapy such as warfarin, calcium antagonists, digitalis, and diuretics, were included. A thorough clinical, laboratory, and comprehensive echo Doppler evaluation was performed before enrollment in the trial to establish the diagnosis and obtain baseline data. Subjects received sildenafil 25 mg 8 hourly, or a matching placebo for two weeks each, in a randomized, double-blind, crossover design. A run-in period of two weeks was permitted between the two therapies during which patients continued to receive the conventional therapy without any vasodilator. At the end of each therapy period, the patients were evaluated for symptoms, New York Heart Association class, distance covered during the 6 min walk test, rating of modified Borg dyspnea score, and systolic pulmonary artery pressure using echo Doppler. The differences in the above variables at the end of sildenafil and placebo therapies were compared. Nine patients completed the study protocol. Sildenafil, compared to placebo, was associated with improved exercise tolerance as determined by the 6 min walk test (266.67+/-131.45 m v. 170+/-105 m; p<0.005), decrease in modified Borg dyspnea score (3.56+/-1.01 v. 5.11+/-1.45; p<0.01), decrease in Doppler-estimated pulmonary artery systolic pressures (55.33+/-16.52 mmHg v. 75.33+/-19.75 mmHg; p<0.005), improvement in New York Heart Association class (2 patients), and improvement in symptoms. Sildenafil was well tolerated with no untoward effects; further, no significant changes in heart rate or blood pressure occurred during the study period.\n Sildenafil improves exercise capacity and symptoms, and decreases pulmonary artery pressures in patients with primary or secondary pulmonary hypertension of varied etiology." ]

[ "8990428", "2764059", "1748256", "14749658" ]

[ "Effects of a partially home-based exercise program for women with gestational diabetes.", "Randomized trial of diet versus diet plus cardiovascular conditioning on glucose levels in gestational diabetes.", "Exercise in gestational diabetes. An optional therapeutic approach?", "Resistance exercise decreases the need for insulin in overweight women with gestational diabetes mellitus." ]

[ "To examine the effectiveness of a partially home-based, moderate-intensity aerobic exercise program for women with gestational diabetes.\n This was a randomized experimental design. Thirty-three women with gestational diabetes were randomly assigned to the exercise or the no-exercise group. Subjects underwent hemoglobin A1C assay and submaximal cycle ergometer fitness tests at baseline and at study conclusion. Subjects kept diaries of home fasting and 2-hour postprandial blood glucose determinations. Exercise subjects were asked to exercise for 30 minutes three to four times weekly at 70% of estimated maximal heart rate for the weeks of study participation. Two exercise sessions weekly were supervised by the investigator, and two were unsupervised at home. Control-group subjects were asked to maintain their current activity level.\n Daily fasting and postprandial blood glucose levels, hemoglobin A1C, incidence of exogenous insulin therapy, and incidence of newborn hypoglycemia were not different between the groups. There was a training effect in the exercise group (P = .005) but not in the control group (P = .25). A significant decline in daily grams of carbohydrate consumed was observed in the control group (P = .03), but not in the exercise group (P = .97). No complications were found in the subjects who exercised.\n A partially home-based exercise program did not reduce blood glucose levels, but did result in a modest increase in cardiorespiratory fitness. The intervention appeared safe.", "We studied the impact of a training program on glucose tolerance in gestational diabetes mellitus. Women with gestational diabetes mellitus (N = 19) were randomized into either group I, a 6-week diet alone group (24 to 30 kcal/kg/24 hours; 20% protein, 40% carbohydrate, 40% fat), or group II, which followed the same diet plus exercise (20 minutes three times a week for 6 weeks). An arm ergometer was used to maintain heart rate in the training range. Glycemic response was monitored by glycosylated hemoglobin, a 50 gm oral glucose challenge with a fasting and 1-hour plasma glucose, and blood glucose self-monitoring, fasting and 1 hour after meals. Week 1 glycemic parameters were the same for both groups. Week 6 data (mean +/- SD) were as follows: group I glycosylated hemoglobin, 4.7% + 0.2% versus group II, 4.2% +/- 0.2%; p less than 0.001. The group I glucose challenge fasting value was 87.6 +/- 6.2 versus 70.1 +/- 6.6 mg/dl, p less than 0.001 for group II. The group I 1-hour plasma glucose challenge result was 187.5 +/- 12.9 mg/dl versus 105.9 +/- 18.9 mg/dl for group II, p less than 0.001. The glycemic levels diverged between the groups at week 4. We conclude that arm ergometer training is feasible in women with gestational diabetes mellitus and results in lower glycosylated hemoglobin, fasting, and 1-hour plasma glucose concentrations than diet alone. Arm ergometer training may provide a useful treatment option for women with gestational diabetes mellitus and may obviate insulin treatment.", "Forty-one patients with gestational diabetes requiring insulin were enrolled in a randomized study to investigate the efficacy of an exercise program in normalizing glucose tolerance. Seventeen of 21 patients completed the exercise program while maintaining normoglycemia and obviating insulin therapy. Maternal and neonatal complications did not differ between the study and control groups. The type of program described appears to be safe and can serve as a model for exercise prescription for pregnant diabetic women to attain improved glucose tolerance.", "This study examines the effects of circuit-type resistance training on the need for insulin in women with gestational diabetes mellitus.\n Thirty-two patients with gestational diabetes mellitus were randomly assigned either to a group that was treated with diet alone or to a group that was treated with diet plus resistance exercise.\n The number of women whose condition required insulin therapy was the same, regardless of treatment. However, a subgroup analysis that examined only overweight women (prepregnant body mass index, >25 kg/m(2)) showed a lower incidence of insulin use in the diet-plus-exercise group (P<.05). Women in the diet-plus-exercise group were prescribed less insulin (P<.05) and showed a longer delay from diagnosis to the initiation of insulin therapy (P<.05), compared with the diet-alone group.\n Resistance exercise training may help to avoid insulin therapy for overweight women with gestational diabetes mellitus." ]

[ "17626040" ]

[ "Mycophenolate mofetil as adjunctive therapy for MMN patients: a randomized, controlled trial." ]

[ "Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterized by slowly progressive asymmetrical limb weakness. Treatment with immunoglobulins (IVIg) leads to improvement of muscle strength. Anecdotal evidence suggests that immunosuppressive drugs as adjunctive therapy may be beneficial. Mycophenolate mofetil (MMF) is a potent and safe immunosuppressant. Safety and efficacy of MMF as adjunctive therapy for MMN patients receiving IVIg maintenance treatment were evaluated in a randomized controlled trial. MMN patients responding to IVIg treatment were eligible for randomization. Muscle strength and functional status were assessed at monthly intervals for 1 year. Three months after the start of MMF or placebo treatment, IVIg doses were reduced stepwise, until a deterioration of functioning or decline in muscle strength could be observed. An IVIg dose reduction of 50% during adjunctive treatment was defined as a primary endpoint. Secondary outcome measures were improvement in muscle strength and functional status after 3 months and reduction of anti GM1-IgM titres after 12 months of MMF treatment. Twenty-eight patients were randomized. One patient allocated to MMF reached the primary endpoint of 50% IVIg dose reduction. After 12 months IVIg reduction did not differ significantly between the two treatment groups. Patients did not experience drug toxicity and none of the patients showed significant disease progression after 12 months. Muscle strength and functional scores after 3 months and anti GM1-IgM titres after 12 months did not change. Adjunctive treatment of MMN patients with MMF at a dose of 1 g twice daily is safe but does not alter disease course or allow significant reduction of IVIg doses." ]

[ "6696222", "2919775", "1781524", "8874561", "1897347", "8494137", "1581266", "2649123", "3293643", "4016522", "3233467", "10702452", "1599061", "1592646", "6704272", "8688256", "2922985", "2099750", "3755875", "3901375", "3564873" ]

[ "Postoperative analgesia for Caesarean section using epidural methadone.", "Epidural analgesia with bupivacaine reduces postoperative paralytic ileus after hysterectomy.", "Gastric emptying following caesarean section and the effect of epidural fentanyl.", "Myoelectric activity in the stomach and duodenum after epidural administration of morphine or bupivacaine.", "Continuous epidural infusion of bupivacaine and morphine for postoperative analgesia after hysterectomy.", "Epidural tramadol for postoperative pain relief.", "Postoperative epidural morphine, but not epidural bupivacaine, delays gastric emptying on the first day after cholecystectomy.", "Continuous thoracic extradural 0.5% bupivacaine with or without morphine: effect on quality of blockade, lung function and the surgical stress response.", "Postoperative analgesia by continuous extradural infusion of bupivacaine and diamorphine.", "Postoperative pain and pulmonary complications: comparison of three analgesic regimens.", "Effect of continuous postoperative epidural analgesia on intestinal motility.", "What concentration of sufentanil should be combined with ropivacaine 0.2% wt/vol for postoperative patient-controlled epidural analgesia?", "Thoracic epidural infusion for postoperative pain relief following abdominal aortic surgery: bupivacaine, fentanyl or a mixture of both?", "[Effect of continuous postoperative analgesia with peridural bupivacaine on intestinal motility following colorectal resection].", "Effects of the extradural administration of morphine, or bupivacaine, on the endocrine response to upper abdominal surgery.", "Patient-controlled extradural analgesia with bupivacaine, fentanyl, or a mixture of both, after Caesarean section.", "Effects of epidural bupivacaine and epidural morphine on bowel function and pain after hysterectomy.", "Epidural analgesia in colonic surgery: results of a randomized prospective study.", "Failure of epidural anesthesia to prevent postoperative paralytic ileus.", "Continuous epidural infusion for analgesia after major abdominal operations: a randomized, prospective, double-blind study.", "The effect of bupivacaine and morphine on pain and bowel function after colonic surgery." ]

[ "A prospective randomised double blind study was carried out to compare the use of epidural methadone, morphine and bupivacaine for pain relief after Caesarean section. The results indicate that methadone is the most effective agent with few side effects. Subsequently this method was used routinely for postoperative analgesia in all patients undergoing Caesarean section. A retrospective study of 178 patients having this method of analgesia was carried out and indicated that epidural methadone is an effective and safe method of postoperative pain relief.", "This study was undertaken to compare the effects of postoperative bupivacaine epidural analgesia with those of intermittent injections of ketobemidone (a synthetic opioid) on postoperative bowel motility in patients who had had hysterectomies. The epidural group (N = 20) received continuous epidural anesthesia with bupivacaine postoperatively for 26-30 hours and the control group (N = 20) received intermittent injections of ketobemidone for postoperative pain relief. Postoperative bowel movements and propulsive colonic motility were estimated from the first passage of flatus and feces and by following radiopaque markers by serial abdominal radiographs. In the epidural group, the times for first passing of flatus (31 +/- 22 hours; mean +/- SD) and feces (70 +/- 44 hours) were significantly shorter than in the control group (flatus 58 +/- 14 hours and feces 103 +/- 26 hours). The average position of the markers was significantly more distally in the epidural group immediately after operation and the markers continued to move forward during the first postoperative day. In the control group, the markers did not move during this period. The results demonstrate that postoperative bowel peristalsis returned earlier in the patients given epidural analgesia with bupivacaine for pain relief than in patients given a narcotic.", "The rate of absorption of paracetamol following oral administration was used as an indirect measure of the rate of gastric emptying. This was to determine the effect on gastric motility of the addition of fentanyl to a solution of local anaesthetic given into the epidural space to provide pain relief following Caesarean section. Thirty subjects were randomly allocated to receive either bupivacaine plus fentanyl or bupivacaine alone. The area under the curve of the graph of plasma paracetamol concentration versus time was calculated for each subject at 45 and 90 minutes after administration of the epidural injection, and this value was used as an index of the rate of gastric emptying. This study demonstrated that gastric emptying may be normal immediately following Caesarean section under epidural anaesthesia, but that if fentanyl is added to the epidural solution, gastric emptying is significantly slower in the first 45 minutes following surgery (p less than 0.05).", "Gastric emptying is delayed in patients receiving postoperative pain relief with epidural morphine compared to patients receiving epidural bupivacaine. The electrophysiological basis for this effect is unknown. The aim of this study was to compare the effects of epidural morphine with epidural bupivacaine on gastroduodenal myoelectric activity (EMG) in patients after surgery.\n Fourteen patients with epidural analgesia who underwent open cholecystectomy were randomly assigned to receive either epidural morphine (EM) or epidural bupivacaine (EB) for postoperative pain relief. During surgery EMG electrodes were placed in the subserosa in the antrum and duodenum and the EMG registration started 3.5 hours after the end of surgery. Gastric emptying measured with the acetaminophen test was studied in the morning the day after surgery.\n The spike activity in the antrum was significantly lower 160-340 minutes after the administration of morphine in the EM-group compared to the activity in the EB-group (P < 0.04). The incidence of regular slow wave rhythm in the antrum was significantly lower 160-520 minutes after the administration of morphine in the EM-group compared to the EB-group (P < 0.03). Duodenal Phase III activity measured with EMG was significantly more frequent during 160-520 minutes after the morphine administration in the EM-group compared to the EB-group (P < 0.02). The acetaminophen absorption was significantly delayed in the epidural morphine group compared to the epidural bupivacaine group.\n Gastroduodenal electromyographic activity was significantly changed during epidural morphine compared to epidural bupivacaine. The delayed gastric emptying during epidural morphine may be explained by decreased and uncoordinated contractile activity in the antrum, shown by decreased spike activity and irregular slow wave rhythm. The increased pressure activity in the duodenum, shown by increased Phase III activity, may also impair gastric emptying.", "The analgesic efficacy and side-effects of combined epidural infusion of bupivacaine and morphine, in comparison with these drugs alone, for postoperative analgesia after hysterectomy (60 patients) were evaluated. Before general anaesthesia, all patients had an epidural catheter placed (Th11-12) and 20 ml of 0.5%, bupivacaine was injected. In random order, epidural infusion was continued for 24 h with either 0.25% bupivacaine 4 ml.h-1 (BUPI-group), a bolus of 2 mg of morphine followed by morphine 0.2 mg.h-1 (MO-group), or a combination of the two drugs (COMB-group). A urinary bladder catheter was kept for 24 h. Supplementary postoperative pain medications were i.m. morphine 0.1 mg.kg-1 or rectal indomethacin 50 mg, on request. Immediately after awakening from general anaesthesia and transfer to the recovery room, 18/20 of the BUPI-group patients, 17/20 of the MO-group patients and 19/20 of the COMB-group patients were pain-free. In the postoperative evening and the first postoperative morning, the corresponding figures were 7/20 and 10/20 in the BUPI-group, 15/20 and 15/20 in the MO-group, and 18/20 and 15/20 in the COMB-group (postop, evening; P less than 0.01 BUPI vs. others). The number of patients requiring supplementary analgesics (morphine and indomethacin during the first 24 h was greatest in the BUPI-group P less than 0.01). The number of patients who vomited during the 24-h period was 3 in the BUPI-group, 9 in the MO-group and 5 in the COMB-group.(ABSTRACT TRUNCATED AT 250 WORDS)", "The efficacy of epidurally administered tramadol hydrochloride, a weak centrally acting analgesic, was studied for the relief of postoperative pain. Sixty patients undergoing abdominal surgery were randomly allocated to three treatment groups to be given the following agents by the epidural route: group 1 tramadol 50 mg; group 2 tramadol 100 mg; group 3 10 ml of bupivacaine 0.25%. The drugs were administered at the patients' request with each patient being allowed four doses in the first 24 h following surgery. Blood pressure, pulse rate, respiratory rate, arterial blood gas analyses, pain scores, the interval between doses and the occurrence of any side effects were recorded. Pain scores (assessed using a visual analogue scale) were significantly less (p < 0.05) at 3, 12, and 24 h in patients receiving tramadol 100 mg than in those receiving tramadol 50 mg or bupivacaine. The mean interval between doses for groups 1, 2 and 3 was 7.40 h, 9.36 h and 5.98 h respectively. The mean interval in group 2 was significantly longer than in group 3 (p < 0.05). The incidence of nausea and vomiting in group 2 was significantly higher than in group 3 (p < 0.05).", "Gastric emptying is delayed during the first days after abdominal surgery. Studies with volunteers have shown that epidural morphine delays gastric emptying but epidural analgesia with bupivacaine does not. The aim of this study was to evaluate whether these differences in healthy volunteers are also found after cholecystectomy when epidural morphine or epidural bupivacaine is used for postoperative pain relief.\n Eighteen healthy patients were randomly allocated into two groups. Nine patients received postoperative analgesia with epidural morphine and nine with thoracic epidural bupivacaine. Acetaminophen absorption was used as an indirect measure of the rate of gastric emptying, measured 22 hours after surgery and again 4 weeks later, so that each patient served as their own control. During epidural morphine, serum acetaminophen concentrations were lower, and the area under the concentration time curve from 0 to 60 minutes (AUC60) was smaller (p less than 0.02), the maximum serum acetaminophen concentration (Cmax) was lower (p less than 0.05), and the time taken to reach the maximum concentration (Tmax) was longer (p less than 0.01) compared to epidural bupivacaine. There were no statistically significant differences in AUC60, Cmax, and Tmax between the two groups during the control study.\n Postoperative gastric emptying was significantly delayed after epidural analgesia with morphine compared to thoracic epidural bupivacaine. Compared to the control situation, epidural bupivacaine did not influence gastric emptying.", "Twenty-two patients undergoing upper abdominal surgery were entered into a randomized, double-blind study to receive extradural (T7-T8) 0.5% bupivacaine 9 ml followed by 25 mg h-1 with or without additional extradural morphine (bolus 4 mg plus 0.5 mg h-1), for 16 h after operation. Addition of morphine was associated with total alleviation of pain, and a stable level of sensory analgesia, but not with changes in blood glucose and cortisol concentrations or postoperative impairment of lung function (PEFR, FEV1, FVC). Two patients were withdrawn because of hypotension or respiratory depression.", "Three solutions administered by continuous extradural infusion for postoperative analgesia were compared in a randomized, double-blind manner. All patients underwent major abdominal gynaecological surgery and received 0.125% bupivacaine in 0.9% saline, diamorphine in 0.9% saline (0.5 mg in 15 ml) or diamorphine mixed with 0.125% bupivacaine (0.5 mg in 15 ml), at a rate of 15 ml h-1. The bupivacaine-diamorphine mixture provided significantly superior analgesia compared with either bupivacaine or diamorphine alone. No major side effects were encountered.", "In a prospective study, patients undergoing cholecystectomy were randomly allocated to receive (a) intermittent intramuscular morphine (n = 25), (b) continuous intravenous morphine infusion (n = 25) or (c) epidural bupivacaine (n = 25) for postoperative pain relief. Morphine by intravenous infusion provided comparable pain relief to intermittent intramuscular morphine; there was no significant difference in the incidence of postoperative pulmonary complications. Patients receiving epidural bupivacaine for 12 h had better analgesia than patients receiving morphine (P less than 0.001). Arterial oxygen tensions were also significantly higher in the epidural group for the first three postoperative days (P less than 0.05). Epidural analgesia was associated with a significant reduction in the incidence of pulmonary complications (P less than 0.01) and chest infection (P less than 0.05).", "The effect of postoperative epidural bupivacaine on intestinal motility was studied by measuring the transit time of barium contrast through the intestines in 16 patients after resection of the left colon and/or rectum. Fourteen patients served as controls and received postoperative injections of pentazocine. Mean transit time through the intestinal tract was 35 h in the epidural group and 150 h in the control group, a difference that is significant at the 0.1 per cent level. The average time before passage of flatus and faeces was different between the two groups at the 0.1 per cent level. We conclude that postoperative epidural bupivacaine constitutes an effective means of analgesia after colorectal surgery and is associated with a short duration of intestinal paralysis.", "In this randomized double-blinded study, we sought to determine an optimal dose-combination of sufentanil with ropivacaine 0.2% wt/vol as postoperative epidural analgesics. One hundred twenty patients undergoing major abdominal surgery under general and thoracic epidural anesthesia (T9-11) were assigned to groups receiving patient-controlled epidural analgesia with ropivacaine 0.2% wt/vol (R), ropivacaine 0.2% wt/vol + sufentanil 0.5 microg/mL (R+S0.5), 0. 75 microg/mL (R+S0.75), 1.0 microg/mL (R+S1). A visual analog score of less than 40 was considered effective, and all side effects were recorded. In randomized subgroups (10 patients per group), plasma pharmacokinetic data were obtained for both epidural drugs. Four patients in Group R and two in Group R+S0.5 were excluded because of inadequate analgesia. The drug infusion rates (range of means: 5.4-5. 9 mL/h) were similar in all patients. Analgesia was superior for sufentanil 0.75 microg/mL with no further enhancement by the larger sufentanil concentration of 1 microg/mL. Sufentanil plasma levels were within the range of the minimal effective concentrations (highest in R+S1), and there was no covariation between plasma levels and pain relief. Free ropivacaine plasma concentrations remained stable for 96 h. No severe side effects were detected, although pruritus correlated with an increasing dose of sufentanil. We conclude that the combination of ropivacaine 0.2% wt/vol and 0.75 microg/mL sufentanil provided the best analgesia with the fewest side effects of the three combinations tested.\n Sufentanil is added to epidural infusions of ropivacaine 0.2% wt/vol to improve the effectiveness of postoperative pain management. Regarding the risk of side effects, however, it is still unclear what concentration of sufentanil should be added to the local anesthetic. For postoperative thoracic epidural analgesia after major abdominal surgery, the combination of ropivacaine 0.2% wt/vol and 0.75 microg/mL sufentanil resulted in an appropriate cost:benefit ratio between good analgesia and side effects.", "Thirty patients who had undergone elective abdominal aortic surgery were studied in a prospective, randomised double-blind comparison of thoracic epidural 0.2% bupivacaine alone, thoracic epidural fentanyl alone and thoracic epidural 0.2% bupivacaine combined with fentanyl. Pain relief, pulmonary function, cardiovascular stability and side effects were assessed. Pain relief was excellent in the combined bupivacaine-fentanyl series, being significantly better than the other groups (p less than 0.05) during the entire study period and was not accompanied by hypotension. Forced expiratory parameters were reduced in all groups throughout the study to 50-60% of the pre-operative values, but there were no significant differences between groups. The incidence of side effects attributable to either epidural bupivacaine or fentanyl was low. This study supports the increasing use of epidural infusion analgesia for postoperative pain management after abdominal surgery.", "In a prospective randomized trial the effects of continuous peridural analgesia on gastrointestinal motility and the postoperative course was studied in 48 consecutive patients with elective colorectal resections. 24 patients had peridural analgesia (PDA) with bupivacaine while 24 patients received intravenous analgesia (IVA) with pentazocine. With PDA the first passage of flatus and faeces was significantly accelerated. PDA was not associated with an increased rate of anastomotic breakdown and there were no respiratory complications in the PDA group.", "The endocrine response, and the relief of pain, following the extradural administration of morphine or a local anaesthetic agent bupivacaine (0.5%) were studied for 24h after abdominal surgery and compared with a control group given conventional i.v. morphine after operation. Samples were taken before and at 2, 4, 6, 12 and 24 h after skin incision. Pain relief in both extradural groups was significantly better when compared with the control group. In all three groups, the plasma concentration of cortisol was increased immediately after surgery. Thereafter, significantly lower values were seen in the extradural groups. Plasma adrenaline concentration was lower immediately after surgery only in the group given the extradural local anaesthetic. Plasma noradrenaline concentration remained unchanged after extradural local anaesthesia while an intermediate increase occurred after extradural morphine. Plasma noradrenaline concentration was significantly greater in the controls compared with both extradural groups. Our results indicate that extradural analgesia with a local anaesthetic drug can suppress the increases in the plasma concentrations of the catecholamines and cortisol after surgery. In contrast to extradural local anaesthetic extradural morphine cannot suppress the endocrine response immediately after surgery. However, later in the postoperative period, extradural morphine can suppress the endocrine response, thus indicating that postoperative pain is a factor involved in the stress response following surgery.", "In this randomized, double-blind study of 60 patients, we have assessed the analgesic efficacy of extradural bupivacaine and extradural fentanyl, either alone or in combination, after Caesarean section. Patients received 0.1% bupivacaine (group B), fentanyl 4 micrograms ml-1 (group F) or 0.05% bupivacaine combined with fentanyl 2 micrograms ml-1 (group BF) by patient-controlled extradural analgesia (PCEA). Adding fentanyl to bupivacaine reduced the dose of bupivacaine by up to 68%, improved analgesia at rest and decreased PCEA use. Motor and sensory block were decreased, but there was more pruritus. Overall patient satisfaction was increased. Adding bupivacaine to fentanyl reduced the dose of fentanyl by up to 57% without altering pain scores or PCEA use. Sensory block increased but pruritus did not decrease. Bupivacaine 0.05% produced clinically significant leg weakness in three patients. Overall patient satisfaction was not altered. There was a significant additive analgesic effect between 0.05% bupivacaine and fentanyl but no clinical benefit was demonstrated from using the combination compared with fentanyl alone for this group of postoperative patients.", "A comparison was made of the effects of continuous epidural analgesia with bupivacaine and intermittent epidural morphine on bowel function after abdominal hysterectomy. The duration of postoperative ileus was assessed as the time from the end of operation to the first postoperative passage of flatus and feces. Twenty-two patients were randomly allocated to two equal groups. An \"epidural morphine\" group received general anesthesia and epidural morphine for postoperative pain relief, and an \"epidural bupivacaine\" group was given combined general anesthesia and epidural anesthesia with 0.5% bupivacaine intraoperatively and epidural analgesia with 0.25% bupivacaine postoperatively. Epidural morphine or bupivacaine was given for 42 h postoperatively. Pain intensity (visual analog scale) was low in both groups, but lower (P less than 0.05) in the epidural bupivacaine group. The time to first passage of flatus was 22 +/- 16 h in the epidural bupivacaine group and 56 +/- 22 h in the epidural morphine group (P less than 0.001). The time to first postoperative passage of feces was shorter (P less than 0.05) in the former than in the latter 57 +/- 44 h vs 92 +/- 22 h). The patients of the epidural bupivacaine group started intake of oral fluids earlier (P less than 0.01) and to a greater extent (P less than 0.05) than those in the epidural morphine group. It is concluded that the duration of postoperative ileus after hysterectomy is shorter when epidural bupivacaine is given for postoperative pain relief than when this is achieved by epidural morphine.", "Colonic surgery patients were studied to measure: the influence of continuous thoracic epidural analgesia (TEA) on a postoperative pain score, the time till onset of defaecation, blood loss, postoperative temperature elevations, rate of bacterial contamination of wounds and urine, and general surgical complications. Group I patients (n = 57) received general anaesthesia and TEA for the operation, followed by continuous TEA (0.25 per cent bupivacaine) for 72 h. Group II patients (n = 59) received general anaesthesia for the operation, followed by systemic analgesia on request. Significant beneficial effects of TEA in group I were demonstrated by lower pain scores in the first 24 h after surgery and earlier defaecation. However, there were fewer temperature elevations in group II. There was no significant difference between the groups in terms of positive bacteriological cultures, blood loss, need for postoperative mechanical ventilation and complications. However, there was a trend toward a higher rate of rectal anastomotic breakdown, increased blood replacement and intensive care therapy, and longer hospitalization in group I. These results do not suggest any significant beneficial therapeutic effect of continuous TEA in colonic surgery compared with a conventional systemic analgesic regimen. In selected patients (i.e. those with severe pain or those prone to develop postoperative ileus) continuous TEA may be beneficial.", "This study used radiopaque markers and serial abdominal radiographs to assess the effect of epidural anesthesia on postoperative colonic ileus. Epidural anesthesia did not result in significantly faster return of propulsive motility in the colon after surgery as compared with control (P greater than 0.05). In addition, no significant difference was seen between the groups in colonic transit time and time for the first passage of gas and feces. The level of inhibition of sympathetic efferent nerves to the abdominal cavity was assessed by repeated measurements of blood glucose levels during the first postoperative day. Blood glucose levels were found to be significantly lower in the epidural group, demonstrating an inhibition of efferent sympathetic nerves below the level of T-5. Results show lack of effect of continuous epidural anesthesia in the prevention of postoperative paralytic ileus and suggest that mechanisms other than spinal reflexes play a major part in the development and maintenance of intestinal paralysis.", "We performed a prospective, randomized, double-blind study of continuous epidural analgesia for 72 hours after major abdominal procedures. Patients were randomly assigned to one of five treatment groups: epidural morphine, epidural bupivacaine, a combination of morphine and bupivacaine, epidural saline solution, and no epidural catheter. All patients received supplemental morphine sulfate or meperidine hydrochloride, intramuscularly or intravenously, as needed. Epidural infusion was begun at 2 to 4 ml/hr, depending on age and height, with two increments of 1 ml/hr allowed if pain relief was insufficient. All pain management decisions were made by nurses, who also monitored epidural function. Performance was measured four ways: pain as measured at regular intervals in the 72-hour period with a visual analog, pain as measured after 72 hours with the McGill Pain Questionnaire, amount of supplemental narcotics needed, and recovery of respiratory function and ambulation as percent of preoperative levels. The group that received the combination of morphine and bupivacaine did best on all measures; in most instances the difference between the results seen with the combination regimen and those seen with saline solution or no catheter were significant at the 0.05 level. With the exception of pruritus, complications were evenly distributed among all treatment groups, including noncatheterized controls. We conclude that epidural analgesia with the combination of morphine and bupivacaine is safe, is easily managed, and gives pain relief superior to that provided by traditional, systemic administration of narcotics.", "Sixty patients scheduled for colonic surgery were randomly allocated to four groups according to postoperative pain medication: I. Control group, the patients received oxycodone intramuscularly (0.15 mg kg-1) on request. II. Epidural bupivacaine (0.25%) continuously administered by infusion pump, 4-6 ml h-1, for 48 h. III. Epidural morphine, 2-6 mg, at the end of operation and repeated on the first and second postoperative mornings. IV. Epidural morphine, 2-6 mg per die, administered for 48 h continuously by infusion pump. All patients received a balanced anaesthesia with enflurane, fentanyl and vecuronium. Postoperatively, intramuscular oxycodone was given on request. There were no significant differences between the groups in changes in peak flow, spirometry and blood-gas analyses postoperatively. Pain intensity (visual analogue scale) was lower in Groups II and III at 3 h and in Group IV at 24 h compared to the control Group I. All the epidurally treated groups needed less additional analgesics than the control Group I. Postoperatively bowel movements occurred on the second day in Group II (bupivacaine) as compared to the fourth day in all other groups (P less than 0.05)." ]

[ "10064664", "20002013", "15181294", "15574620", "22664861" ]

[ "Randomized trial of \"slow\" versus \"fast\" feed advancements on the incidence of necrotizing enterocolitis in very low birth weight infants.", "Slow versus rapid enteral feeding advancement in preterm newborn infants 1000-1499 g: a randomized controlled trial.", "Slow versus fast enteral feed advancement in very low birth weight infants: a randomized control trial.", "Randomized, controlled trial of slow versus rapid feeding volume advancement in preterm infants.", "Randomized controlled trial of slow vs rapid enteral feeding advancements on the clinical outcomes of preterm infants with birth weight 750-1250 g." ]

[ "To determine whether the rate of feed advancement affects the incidence of necrotizing enterocolitis (NEC).\n Prospective randomized controlled trial involving 185 formula-fed infants with birth weight 501 to 1500 g and gestational age </=34 weeks. Infants were randomized into 2 groups: \"slow\" (n = 98), who received 15 cc/kg/d increments (a 10-day schedule to full feeds) and \"fast\" (n = 87), who received 35 cc/kg/d increments (a 5-day schedule to full feeds) of Similac Special Care 20 cal/oz. Feeds were increased only if well tolerated as defined by a protocol.\n The incidence of NEC (Bell stage >/=II) was similar in both groups (slow 13% and fast 9%, P =.5). The incidence of perforation (Bell stage III) was also similar in both groups (slow 4% and fast 2%, P =.8). Feeds were started at a comparable postnatal age in both groups (median age: slow 5 days and fast 4 days, P =.9). Although the neonates in the fast group attained full enteral intake earlier (median days [25th and 75th percentiles]: slow 15 [12, 21] and fast 11 [8, 15], P <.001) and regained their birth weight earlier (slow 15 [11, 20] and fast 12 [8, 15], P <.05), their ages at discharge were not statistically different (slow 47 [31, 67] and fast 43 [29, 62], P =.3)\n A greater than twofold difference in the rate of feed advancement from 15 cc/kg/d to 35 cc/kg/d did not affect the incidence of NEC >/= stage II. Factors other than feed advancement appear to be more important in the pathogenesis or progression of NEC.", "To evaluate whether preterm neonates weighing 1000-1499 g at birth receiving rapid enteral feeding advancement at 30 mL/kg/day attain full feedings (180 mL/kg/day) earlier than those receiving slow enteral feeding advancement at 20 mL/kg/day without increase in the incidence of feeding intolerance or necrotizing enterocolitis.\n A total of 100 stable intramural neonates weighing between 1000 and 1499 g and gestational age less than 34 weeks were randomly allocated to enteral feeding (expressed human milk or formula) advancement of 20 mL/kg/day (n = 50) or 30 mL/kg/day (n = 50). RESULTs: Neonates in the rapid feeding advancement group achieved full volume feedings before the slow advancement group (median 7 days vs. 9 days) (p < 0.001), had significantly fewer days of intravenous fluids (median 2 days vs. 3.4 days) (p < 0.001), shorter length of stay in hospital (median 9.5 days vs. 11 days) (p = 0.003) and regained birth weight earlier (median 16 days vs. 22 days) (p < 0.001). There were no statistical differences in the proportion of infants with apnea, feed interruption or feed intolerance.\n Rapid enteral feeding advancements of 30 mL/kg/day are well tolerated by stable preterm neonates weighing 1000-1499 g.", "To evaluate the tolerance of rapid advancement of enteral feeds in VLBW babies.\n Tertiary teaching hospital.\n Randomized controlled trial.\n All stable neonates with birth weight less than 1250 grams were included in the study. The primary outcome variable was the time taken to achieve full enteral feeds (defined as 180 ml/kg/day). The secondary outcome variables were incidence of Necrotizing enterocolitis (NNEC) and incidence of apnea. At 48 hours, the infants were randomized into the slow advancement group (enteral feeds advanced by increments of 15 ml/kg/day) or fast advancement group (enteral feeds advanced by increments of 30 ml/kg/day). The monitoring during feeding included daily weight record, two hourly abdominal girth charting, gastric aspirates, apnea, time taken to reach full enteral feedings and for NNEC.\n There were 53 infants who were enrolled for the study (27 in the fast advancement group and 26 in the slow advancement group). In the fast advancement group, 20 percent completed the trial; whereas 14 (53.8 percent;) in the slow advancement group completed the study. The two groups were comparable for birth weights, gestational age, sex, intrauterine growth status, Apgar and CRIB scores. The infants in the fast group reached full enteral intake of 180 ml/kg/day significantly earlier (10 +/- 1.8 days) than in the slow group (14.8 +/- 1.5 days). The two groups were comparable for episodes of feed intolerance, apnea, NNEC. Infants in the fast group regained birth weight significantly earlier (median 18 days) than in the slow advancement group (median 23 days).\n Stable VLBW neonates can tolerate rapid advancements of enteral feeding without increased risk of adverse effects.", "To determine whether infants who are fed initially and advanced at 30 mL/kg per day (intervention) take fewer days to get to full feedings than those who are fed initially and advanced at 20 mL/kg per day (control), without increasing their incidence of feeding complications and necrotizing enterocolitis (NEC). We also examined whether these infants regain birth weight earlier, have fewer days of intravenous fluids, and a have shorter hospital stay.\n A randomized, controlled, single-center trial was conducted in a Neonatal Intensive Care Unit of a community-based county hospital in Houston, Texas. Infants between 1000 and 2000 g at birth, gestational age < or =35 weeks, and weight appropriate for gestational age were allocated randomly to feedings of expressed human milk or Enfamil formula starting and advanced at either 30 mL/kg per day or 20 mL/kg per day. Infants remained in the study until discharge or development of stage > or =IIA NEC.\n A total of 155 infants were enrolled: 72 infants in the intervention group and 83 in the control group. Infants in the intervention group achieved full-volume feedings sooner (7 vs 10 days, median), regained birth weight faster (11 vs 13 days, median), and had fewer days of intravenous fluids (6 vs 8 days, median). Three infants in the intervention group and 2 control infants developed NEC for an overall incidence of 3.2% (relative risk: 1.73; 95% confidence interval: 0.30-10.06).\n Among infants between 1000 and 2000 g at birth, starting and advancing feedings at 30 mL/kg per day seems to be a safe practice and results in fewer days to reach full-volume feedings than using 20 mL/kg per day. This intervention also leads to faster weight gain and fewer days of intravenous fluids.", "To evaluate the effect of slow vs rapid rates of advancement of enteral feed volumes on the clinical outcomes in preterm infants with 750-1250 g birth weight.\n A total of 92 stable neonates 750-1250 g and gestational age <32 weeks were randomly allocated to enteral feeding advancement of 20 mL/kg/d (n = 46) or 30 mL/kg/d (n = 46). The primary outcome was days to reach full enteral feeding, defined as 180 mL/kg/d. Secondary outcomes included rates of necrotizing enterocolitis (NEC) and culture-proven sepsis, days of parenteral nutrition (PN), length of hospital stay, and growth end points.\n Neonates in the rapid-feeding advancement group achieved full enteral volume of feedings earlier than the slower advancement group. They received significantly fewer days of PN, exhibited a shorter time to regain birth weight, and had a shorter duration of hospital stay. The incidence of NEC and the number of episodes of feeding intolerance were not significantly different between the groups, whereas the incidence of culture-proven late-onset sepsis was significantly less in infants receiving a rapid feeding advancement. Excluding infants who were small for gestational age at birth, the incidence of extrauterine growth restriction was significantly reduced in the rapid-advancement group at 28 days and at hospital discharge.\n Rapid enteral feeding advancements in 750-1250 g birth weight infants reduce the time to reach full enteral feeding and the use of PN administration. Rapid-advancement enteral feed also decreases extrauterine growth restriction with improved short-term outcomes for these high-risk infants." ]

[ "15774786", "16226397" ]

[ "Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: updated results of a prospective randomized trial.", "A phase III randomized study on the sequencing of radiotherapy and chemotherapy in the conservative management of early-stage breast cancer." ]

[ "The optimal integration of chemotherapy with radiation (RT) for patients with early-stage breast cancer remains uncertain. We present the long-term results of a prospective randomized trial to address this question.\n Two hundred forty-four patients were randomly assigned after conservative breast surgery to receive 12 weeks of cyclophosphamide, doxorubicin, methotrexate, fluorouracil, and prednisone (CAMFP) before RT (CT-first) or after RT (RT-first). Median follow-up for surviving patients was 135 months.\n There were no significant differences between the CT-first and RT-first arms in time to any event, distant metastasis, or death. Sites of first failure were also not significantly different.\n Among breast cancer patients treated with conservative surgery, there is no advantage to giving RT before adjuvant chemotherapy. However, this study does not have enough statistical power to rule out a clinically important survival benefit for either sequence.", "To compare two different timings of radiation treatment in patients with breast cancer who underwent conservative surgery and were candidates to receive adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy.\n A total of 206 patients who had quadrantectomy and axillary dissection for breast cancer and were planned to receive adjuvant CMF chemotherapy were randomized to concurrent or sequential radiotherapy. Radiotherapy was delivered only to the whole breast through tangential fields to a dose of 50 Gy in 20 fractions over 4 weeks, followed by an electron boost of 10-15 Gy in 4-6 fractions to the tumor bed.\n No differences in 5-year breast recurrence-free, metastasis-free, disease-free, and overall survival were observed in the two treatment groups. All patients completed the planned radiotherapy. No evidence of an increased risk of toxicity was observed between the two arms. No difference in radiotherapy and in the chemotherapy dose intensity was observed in the two groups.\n In patients with negative surgical margins receiving adjuvant chemotherapy, radiotherapy can be delayed to up to 7 months. Concurrent administration of CMF chemotherapy and radiotherapy is safe and might be reserved for patients at high risk of local recurrence, such as those with positive surgical margins or larger tumor diameters." ]

[ "17575560", "12915605", "12085247", "11879860", "12849025", "22041948", "20628395", "21825268", "21075644", "17893379", "8260242", "16242900", "18541641" ]

[ "Increasing oncologists' skills in eliciting and responding to emotional cues: evaluation of a communication skills training program.", "How to optimize physicians' communication skills in cancer care: results of a randomized study assessing the usefulness of posttraining consolidation workshops.", "Does training increase the use of more emotionally laden words by nurses when talking with cancer patients? A randomised study.", "Efficacy of a Cancer Research UK communication skills training model for oncologists: a randomised controlled trial.", "Communication between nurses and simulated patients with cancer: evaluation of a communication training programme.", "Enhancing communication between oncologists and patients with a computer-based training program: a randomized trial.", "Is it possible to improve residents breaking bad news skills? A randomised study assessing the efficacy of a communication skills training program.", "Specific training program improves oncologists' palliative care communication skills in a randomized controlled trial.", "Effects of communication skills training and a Question Prompt Sheet to improve communication with older cancer patients: a randomized controlled trial.", "Improving communication between doctors and breast cancer patients.", "The effects of a 24-h psychological training program on attitudes, communication skills and occupational stress in oncology: a randomised study.", "Transfer of communication skills training from workshop to workplace: the impact of clinical supervision.", "Effectiveness of a three-day communication skills course in changing nurses' communication skills with cancer/palliative care patients: a randomised controlled trial." ]

[ "Psychological morbidity in cancer patients is common, but often undetected and untreated. We developed a communication skills training (CST) program targeting this issue, and evaluated its impact on doctor behaviour.\n Thirty of 35 oncologists from six teaching hospitals in six Australian cities, participated. The CST was a 1.5-day intensive face-to-face workshop incorporating presentation of principles, a DVD modelling ideal behaviour and role-play practice, followed by four 1.5 h monthly video-conferences incorporating role-play of doctor-generated scenarios. Doctors were randomized to receive the CST or not. Simulated patient interviews were videotaped and coded at baseline, after CST and 6 months later. Doctors completed questionnaires assessing stress and burnout at the same time points.\n Doctors in the intervention group displayed more creating environment and fewer blocking behaviours at both follow-ups; however, these differences did not reach statistical significance. Intervention doctors valued the training highly, but did not report substantial reductions in stress and burnout.\n This short training programme demonstrated a positive effect on aspects of doctor behaviour. Video-conferencing after a short training course may be an effective strategy for delivering CST.\n (c) 2007 John Wiley & Sons, Ltd", "Although there is wide recognition of the usefulness of improving physicians' communication skills, no studies have yet assessed the efficacy of post-training consolidation workshops. This study aims to assess the efficacy of six 3-hour consolidation workshops conducted after a 2.5-day basic training program.\n Physicians, after attending the basic training program, were randomly assigned to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual patient interviews that were audiotaped at baseline and after consolidation workshops for the consolidation-workshop group, and approximately 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' perceptions of communication skills improvement were assessed using a 14-item questionnaire.\n Sixty-three physicians completed the training program. Communication skills improved significantly more in the consolidation-workshop group compared with the waiting-list group. In simulated interviews, group-by-time repeated measures analysis of variance showed a significant increase in open and open directive questions (P =.014) and utterances alerting patients to reality (P =.049), as well as a significant decrease in premature reassurance (P =.042). In actual patient interviews, results revealed a significant increase in acknowledgements (P =.022) and empathic statements (P =.009), in educated guesses (P =.041), and in negotiations (P =.008). Patients interacting with physicians who benefited from consolidation workshops reported higher scores concerning their physicians' understanding of their disease (P =.004).\n Consolidation workshops further improve a communication skills training program's efficacy and facilitate the transfer of acquired skills to clinical practice.", "The emotional content of health care professionals-cancer patient communication is often considered as poor and has to be improved by an enhancement of health care professionals empathy. One hundred and fifteen oncology nurses participating in a communication skills training workshop were assessed at three different periods. Nurses randomly allocated to a control group arm (waiting list) were assessed a first time and then 3 and 6 months later. Nurses allocated to the training group were assessed before training workshop, just after and 3 months later. Each nurse completed a 20-min clinical and simulated interview. Each interview was analysed by three content analysis systems: two computer-supported content analysis of emotional words, the Harvard Third Psychosocial Dictionary and the Martindale Regressive Imagery Dictionary and an observer rating system of utterances emotional depth level, the Cancer Research Campaign Workshop Evaluation Manual. The results show that in clinical interviews there is an increased use of emotional words by health care professionals right after having been trained (P=0.056): training group subjects use 4.3 (std: 3.7) emotional words per 1000 used before training workshop, and 7.0 (std: 5.8) right after training workshop and 5.9 (std: 4.3) 3 months later compared to control group subjects which use 4.5 (std: 4.8) emotional words at the first assessment point, 4.3 (std: 4.1) at the second and 4.4 (std: 3.3) at the third. The same trend is noticeable for emotional words used by health care professionals in simulated interviews (P=0.000). The emotional words registry used by health care professionals however remains stable over time in clinical interviews (P=0.141) and is enlarged in simulated interviews (P=0.041). This increased use of emotional words by trained health care professionals facilitates cancer patient emotion words expressions compared to untrained health care professionals especially 3 months after training (P=0.005). This study shows that health care professionals empathy may be improved by communication skills training workshop and that this improvement facilitates cancer patients emotions expression.\n Copyright 2002 Cancer Research UK.", "Doctors' communication with patients is commonly hampered by lack of training in this core skill. This study aimed to assess the efficacy of an intensive 3-day training course on communication skills in a randomised controlled trial with a two-by-two factorial design and several outcomes.\n 160 oncologists from 34 UK cancer centres were randomly allocated to four groups: written feedback followed by course; course alone; written feedback alone; and control. At each of two assessment periods, consultations with six to ten consecutive, consenting patients per doctor were videotaped. 2407 patients participated. Outcome measures included objective and subjective ratings made by researchers, doctors, and patients. The primary outcomes were objective improvements after the intervention in key communication skills. Course content included structured feedback, videotape review of consultations, role-play with simulated patients, interactive group demonstrations, and discussion led by a trained facilitator.\n In Poisson regression analysis of counts of communication behaviours, course attendance significantly improved key outcomes. The estimated effect sizes corresponded to higher rates of use of focused questions (difference between course attenders [n=80] and non-attenders [n=80] 34%, p=0.003), focused and open questions (27%, p=0.005), expressions of empathy (69%, p=0.003), and appropriate responses to patients' cues (38%, p=0.026), and a 24% lower rate of use of leading questions (p=0.11). There was little evidence for the effectiveness of written feedback.\n The communication problems of senior doctors working in cancer medicine are not resolved by time and clinical experience. This trial shows that training courses significantly improve key communication skills. More resources should be allocated to address doctors' training needs in this vital area.", "In this paper the effect of a communication training programme on the instrumental and affective communication skills employed by ward nurses during the admittance interview with recently diagnosed cancer patients was investigated. The training focused on teaching nurses skills to discuss and handle patient emotions. For this purpose, 46 nurses participated in 92 videotaped admittance interviews with simulated patients. The study had a randomized pre-test-post-test design. Multi-level analysis was used to measure the effects of the training. The results revealed that the trained nurses significantly increased asking open-ended psychosocial questions, which indicates that they were actively exploring patients' feelings. Furthermore, the patients showed a significant increase in affective communication. In conclusion, the results of this study demonstrate that, although limited, training can induce favourable changes in the communication skills of nurses, and can even affect patient communication. Future studies should focus on the further evaluation of educational programmes to enhance communication skills.", "Quality cancer care requires addressing patients' emotions, which oncologists infrequently do. Multiday courses can teach oncologists skills to handle emotion; however, such workshops are long and costly.\n To test whether a brief, computerized intervention improves oncologist responses to patient expressions of negative emotion.\n Randomized, controlled, parallel-group trial stratified by site, sex, and oncologic specialty. Oncologists were randomly assigned to receive a communication lecture or the lecture plus a tailored CD-ROM. (ClinicalTrials.gov registration number: NCT00276627)\n Oncology clinics at a comprehensive cancer center and Veterans Affairs Medical Center in Durham, North Carolina, and a comprehensive cancer center in Pittsburgh, Pennsylvania.\n 48 medical, gynecologic, and radiation oncologists and 264 patients with advanced cancer.\n Oncologists were randomly assigned in a 1:1 ratio to receive an interactive CD-ROM about responding to patients' negative emotions. The CD-ROM included tailored feedback on the oncologists' own recorded conversations.\n Postintervention audio recordings were used to identify the number of empathic statements and responses to patients' expressions of negative emotion. Surveys evaluated patients' trust in their oncologists and perceptions of their oncologists' communication skills.\n Oncologists in the intervention group used more empathic statements (relative risk, 1.9 [95% CI, 1.1 to 3.3]; P = 0.024) and were more likely to respond to negative emotions empathically (odds ratio, 2.1 [CI, 1.1 to 4.2]; P = 0.028) than control oncologists. Patients of intervention oncologists reported greater trust in their oncologists than did patients of control oncologists (estimated mean difference, 0.1 [CI, 0.0 to 0.2]; P = 0.036). There was no significant difference in perceptions of communication skills.\n Long-term effects were not examined. The findings may not be generalizable outside of academic medical centers.\n A brief computerized intervention improves how oncologists respond to patients' expressions of negative emotions.\n National Cancer Institute.", "This study aims to assess the efficacy of a 40-h training programme designed to teach residents the communication skills needed to break the bad news.\n Residents were randomly assigned to the training programme or to a waiting list. A simulated patient breaking bad news (BBN) consultation was audiotaped at baseline and after training in the training group and 8 months after baseline in the waiting-list group. Transcripts were analysed by tagging the used communication skills with a content analysis software (LaComm) and by tagging the phases of bad news delivery: pre-delivery, delivery and post-delivery. Training effects were tested with generalised estimating equation (GEE) and multivariate analysis of variance (MANOVA).\n The trained residents (n=50) used effective communication skills more often than the untrained residents (n=48): more open questions (relative rate (RR)=5.79; P<0.001), open directive questions (RR=1.71; P=0.003) and empathy (RR=4.50; P=0.017) and less information transmission (RR=0.72; P=0.001). The pre-delivery phase was longer for the trained (1 min 53 s at baseline and 3 min 55 s after training) compared with the untrained residents (2 min 7 s at baseline and 1 min 46 s at second assessment time; P<0.001).\n This study shows the efficacy of training programme designed to improve residents' BBN skills. The way residents break bad news may thus be improved.", "The aim of the study was to demonstrate that COM-ON-p, concise and individualized communication skills training (CST), improves oncologists' communication skills in consultations focusing on the transition to palliative care.\n Forty-one physicians were randomly assigned to a control (CG) or intervention group (IG). At t(0), all physicians held two video-recorded consultations with actor-patient pairs. Afterward, physicians in the IG participated in COM-ON-p. Five weeks after t(0), a second assessment took place (t(1)). COM-ON-p consists of an 11-hour workshop (1.5 days), pre- and postassessment (2 hours), and coaching (0.5 hours). Physicians focused on practicing individual learning goals with actor patients in small groups. To evaluate the training, blinded raters assessed communication behavior of the physicians in video-recorded actor-patient consultations using a specific checklist. Data were analyzed using a mixed model with baseline levels as covariates.\n Participants in the IG improved significantly more than those in the CG in all three sections of the COM-ON-Checklist: skills specific to the transition to palliative care, global communication skills, and involvement of significant others (all P < .01). Differences between the CG and IG on the global items of communication skills and involvement of significant others were also significant (P < .01). Effect sizes were medium to large, with a 0.5-point improvement on average on a five-point rating scale.\n Physicians can be trained to meet better core challenges during the transition to palliative care through developed concise CST. Generalization and transfer into clinical practice must be proven in additional studies.", "A randomized pre- and post-test control group design was conducted in 12 oncology wards to investigate the effectiveness of an intervention, existing of a communication skills training with web-enabled video feedback and a Question Prompt Sheet (QPS), which aimed to improve patient education to older cancer patients (≥65 years). The effects were studied by analyzing questionnaires and video recordings of patient education sessions preceding chemotherapy with 210 different patients. Patients' recall of information was the primary outcome of the study. Recall was checked against the actual communication in the video-recordings. Moreover, communication skills were assessed by observing the extent to which nurses implemented 67 communication aspects, categorized in seven dimensions, using the QUOTE(chemo). Experimental nurses demonstrated a significant intervention effect on communicating realistic expectations. Within-group improvements were measured in the experimental group for tailored communication, affective communication and interpersonal communication. Although the use of a QPS significantly increased question asking, only limited results were found on older patients' recall scores. The overall proportion recall of recommendations showed a marginally significant pre-/post-change in proportion recall in favour of the experimental group and there was a significant pre-/post-change in two out of six sub-categories. The results indicate that nurses' communication skills can be improved by communication skills training. More research is needed to understand the difficult relationship between patient-provider communication and recall of information.\n Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.", "We wanted to assess the effectiveness of intensive education for physicians compared with a traditional session on communicating with breast cancer patients.\n A randomized controlled trial was conducted in practices in London, Hamilton, and Toronto, Canada, with 17 family physicians, 16 surgeons, and 18 oncologists, and with 102 patients of the surgeons and oncologists. Doctors were randomized to 1 of 2 continuing education approaches: a traditional 2-hour version (control group), or a new 6-hour intensive version including exploring the patients' perspectives and reviewing videotapes and receiving feedback (intervention group). Communication behavior of the physicians was measured objectively both before and after the intervention. As well, 4 postintervention patient outcomes were measured, by design only for surgeons and oncologists: patient-centerdness of the visit, satisfaction, psychological distress, and feeling better.\n No significant differences were found on the communication score of the intervention vs the control physicians when controlling for preintervention communication scores. Intervention family physicians, however, had significantly higher communication subscores than control family physicians. Also, patients of the intervention surgeons and oncologists were significantly more satisfied (scores of 82.06 vs 77.78, P = .03) and felt better (88.2% vs 70.6%, P=.02) than patients of the control surgeons and oncologists when controlling for covariates and adjusting for clustering within doctor.\n The continuing medical education intervention was effective in terms of some but not all physician and patient outcomes.", "The usefulness of psychological training programs (P.T.P.) in health care settings devoted to cancer care is beginning to be recognised but their content, form and effectiveness need further investigation. Seventy-two oncology nurses were randomly assigned to a 24-h P.T.P. or to a waiting list period. Attitudes were assessed by a semantic differential questionnaire, occupational stress was assessed by the Nursing Stress Scale and communication skills were assessed by standardised videotaped role-playing exercises. These were used to compare trained (T.S.) and control subjects (C.S.). The results show a significant training effect on attitudes (P = 0.05), especially on those related to self concept (P = 0.004), and on the level of occupational stress related to inadequate preparation (P = 0.02). Limited changes were found regarding post-training communication skills. T.S. were significantly more in control of the interview than C.S. (P = 0.02). The results indicate that 24-h P.T.P. assessed here are effective. The data also demonstrate the need to consolidate the skills acquired by regular post-training sessions.", "Recent studies have recognised that the communication skills learned in the training environment are not always transferred back into the clinical setting. This paper reports a study which investigated the potential of clinical supervision in enhancing the transfer process.\n A randomised controlled trial was conducted involving 61 clinical nurse specialists. All attended a 3-day communication skills training workshop. Twenty-nine were then randomised to 4 weeks of clinical supervision, aimed at facilitating transfer of newly acquired skills into practice. Assessments, using real and simulated patients, were carried out before the course, immediately after the supervision period and 3 months later. Interviews were rated objectively using the Medical Interview Aural Rating Scale (MIARS) to assess nurses' ability to use key skills, respond to patient cues and identify patient concerns.\n Assessments with simulated patients showed that the training programme was extremely effective in changing competence in all three key areas. However, only those who experienced supervision showed any evidence of transfer. Improvements were found in the supervised groups' use of open questions, negotiation and psychological exploration. Whilst neither group facilitated more disclosure of cues or concerns, those in the experimental group responded more effectively to the cues disclosed, reduced their distancing behaviour and increasing their exploration of cues.\n The study has shown that whilst training enhances skills, without intervention, it may have little effect on clinical practice. The potential role of clinical supervision as one way of enhancing the clinical effectiveness of communication skills training programmes has been demonstrated. PRACTISE IMPLICATIONS: This study raises questions about the effectiveness of training programmes which do not incorporate a transfer element, and provides evidence to support the need for clinical supervision for clinical nurse specialist.", "This multi-centre, two-armed parallel-group pragmatic randomised controlled trial (RCT) evaluated the effectiveness of a 3-day communication skills course in changing nurses' communication skills. The primary outcome was the change in the nurses' communication skills score from pre-course to 12 weeks post-course. The main secondary outcome was the change in the nurses' level of confidence in communicating with patients. A total of 172 nurses were randomised to the course or control. The communication skills score for the intervention group increased by 3.4 points post-course but decreased in the control by 0.05 points (between-group difference in change: 3.41, 95% CI: 2.16-4.66, P < 0.001). Confidence scores increased by 18.16 points for the intervention group but decreased 0.7 points in the control (between-group difference in change: 18.86, 95% CI: 13.39-24.34, P < 0.001). This RCT contributes to the evidence base on the effectiveness of communication skills training in cancer and palliative care." ]

[ "20402591", "16177249" ]

[ "A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis.", "Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis." ]

[ "Syphilis remains an important source of morbidity worldwide. Long-acting penicillin is the only therapy currently recommended for syphilis in much of the world. Because of hesitation to use penicillin for fear of anaphylaxis, there is a need for an effective, well-tolerated alternative to penicillin for syphilis therapy.\n This multicenter, randomized clinical trial was conducted in clinics for the treatment of persons with sexually transmitted diseases. We compared serological cure rates for human immunodeficiency virus (HIV)-negative persons with early syphilis treated with azithromycin at a dosage of 2.0 g administered orally as a single dose with cure rates for those treated with benzathine penicillin G at a dosage of 2.4 million units administered intramuscularly.\n A total of 517 participants were enrolled in the trial. In the intention-to-treat analysis, after 6 months of follow-up, serological cure was observed in 180 (77.6%) of 232 azithromycin recipients and 186 (78.5%) of 237 penicillin recipients (1-sided lower bound 95% confidence interval, 7.2%). Nonserious adverse events were more common among azithromycin recipients than they were among penicillin recipients (61.5% vs 46.3%), and such adverse events were accounted for, in large part, by self-limited gastrointestinal complaints.\n In this trial, the efficacy of azithromycin at a dosage of 2.0 g administered orally was equivalent to that of benzathine penicillin G for the treatment of early syphilis in persons without HIV infection.", "Pilot studies suggest that a single, 2-g oral dose of azithromycin may be an alternative to a 2.4-MU intramuscular dose of penicillin G benzathine in the prevention and treatment of syphilis. We evaluated the efficacy of treatment with azithromycin in a developing country.\n A total of 328 subjects, 25 with primary and 303 with high-titer (a titer of at least 1:8 on a rapid plasmin reagin [RPR] test) latent syphilis, were recruited through screening of high-risk populations in Mbeya, Tanzania, and randomly assigned to receive 2 g of azithromycin orally (163 subjects) or 2.4 million units of penicillin G benzathine intramuscularly (165 subjects). The primary outcome was treatment efficacy, with cure defined serologically (a decline in the RPR titer of at least two dilutions by nine months after treatment) and, in primary syphilis, by epithelialization of ulcers within one or two weeks.\n The average age of participants was 27.0 years, 235 (71.6 percent) were female, and 171 (52.1 percent) were seropositive for human immunodeficiency virus. Cure rates were 97.7 percent (95 percent confidence interval, 94.0 to 99.4) in the azithromycin group and 95.0 percent (95 percent confidence interval, 90.6 to 97.8) in the penicillin G benzathine group (95 percent confidence interval for the difference, -1.7 to 7.1 percent), achieving prespecified criteria for equivalence. Cure rates were also similar three and six months after treatment in the two groups and in all subgroups. Cure rates at three months were 59.4 percent (95 percent confidence interval, 51.8 to 67.1) in the azithromycin group and 59.5 percent (95 percent confidence interval, 51.8 to 67.3) in the penicillin G benzathine group and at six months were 85.5 percent (95 percent confidence interval, 79.4 to 90.6) and 81.5 percent (95 percent confidence interval, 74.8 to 87.4), respectively.\n Single-dose oral azithromycin is effective in treating syphilis and may be particularly useful in developing countries in which the use of penicillin G benzathine injections is problematic. However, recent reports of azithromycin-resistant Treponema pallidum in the United States indicate the importance of continued monitoring for resistance.\n Copyright 2005 Massachusetts Medical Society." ]

[ "8307216", "2807841", "6988034", "19259615", "7974754", "2200557", "6988033", "16175532", "15661415", "12791021", "6351265", "15674491", "15449205", "19474689" ]

[ "The comparison of type of incision for transperitoneal abdominal aortic surgery based on postoperative respiratory complications and morbidity.", "Approach to the abdominal aorta: impairment of respiratory function after supraumbilical transverse and midline laparotomy.", "Midline or transverse laparotomy? A random controlled clinical trial. Part II: Influence on postoperative pulmonary complications.", "Incisional hernia after upper abdominal surgery: a randomised controlled trial of midline versus transverse incision.", "Mini-lap cholecystectomy--an attractive alternative to conventional cholecystectomy.", "Choice of incision and pain following gallbladder surgery.", "Midline or transverse laparotomy? A random controlled clinical trial. Part I: Influence on healing.", "Randomized clinical trial of vertical or transverse laparotomy for abdominal aortic aneurysm repair.", "Pfannenstiel versus vertical laparotomy in patients undergoing radical retropubic prostatectomy with spinal anesthesia: results of a prospective, randomized trial.", "Midline or transverse abdominal incision for right-sided colon cancer-a randomized trial.", "Abdominal incisions: transverse vs vertical placement and continuous vs interrupted closure.", "Transverse versus midline incision for upper abdominal surgery.", "Prospective randomized study of two laparotomy incisions for gastrectomy: midline incision versus transverse incision.", "Midline versus transverse incision in major abdominal surgery: a randomized, double-blind equivalence trial (POVATI: ISRCTN60734227)." ]

[ "Equal access to the abdominal aorta can be attained through midline and transverse abdominal incisions. The surgical literature suggests that transverse incisions cause less postoperative pain and morbidity. Fifty patients (10 females and 40 males, mean age 67 years) undergoing abdominal aortic surgery were randomised to a midline (n = 25) or transverse (n = 25) incision. All patients were evaluated preoperatively and postoperatively for seven days. Changes in pulmonary function (FVC and FEV1), time to open and close the incision, analgesia used (morphine mg/kg/h), clinical or X-ray evidence of chest infection, and the duration of ICU stay were recorded. In the transverse group there was a reduction in the incidence of chest complications (20% vs. 28%, p = ns) and these incisions took longer to open (13.9 +/- 4.6 vs. 9.9 +/- 5.1, p < 0.05), but overall there was no significant difference between any other parameter in the two groups. Our results show no statistically significant difference in morbidity or analgesia consumption following transverse or midline abdominal incisions and we conclude that the type of incision used can be left to the surgeon's preference.", "Midline and transverse incision are commonly used in upper abdominal surgery. A comparison of the two procedures with respect to the respiratory function, assessed by spirometry, blood gas analysis, inspiratory and expiratory pressures, and thoraco-abdominal respiratory synchronism, was made in two groups of patients after surgery on the abdominal aorta. 32 patients affected by abdominal aortic obstructive or aneurysmatic disease, candidates for aortoiliac revascularization, were randomized into two groups of 17 (group A) and 15 (group B) patients respectively. Group A underwent midline laparotomy and group B supraumbilical transverse laparotomy. Ventilatory function and blood gas analysis were determined on the day before operation and on the second and eight postoperative day. All patients showed a depressed ventilatory function postoperatively, but the impairment was significantly minor after transverse laparotomy.", "In a series of 579 patients undergoing major laparotomy, the direction of incision (midline or transverse/oblique muscle-cutting) was decided randomly. The severity of postoperative pulmonary complications was expressed by a scoring system which allowed categorization into mild (score 0-3), moderate (score 4-6) and serious (score 7 or more) complications. The important determinants of high scores were found to be male sex, preoperative pulmonary dysfunction, postoperative ventilatory depression, hypovolaemic and septic shock, inhalation of gastric contents and embolism. In no stratum did the direction of incision have any significant effect.", "To determine whether a transverse incision is an alternative to a midline incision in terms of incisional hernia incidence, surgical site infection, postoperative pain, hospital stay and cosmetics in cholecystectomy. Incisional hernias after midline incision are commonly underestimated but probably complicate between 2 and 20% of all abdominal wall closures. The midline incision is the preferred incision for surgery of the upper abdomen despite evidence that alternatives, such as the lateral paramedian and transverse incision, exist and might reduce the rate of incisional hernia. A RCT was preformed in the pre-laparoscopic cholecystectomy era the data of which were never published.\n One hundred and fifty female patients were randomly allocated to cholecystectomy through midline or transverse incision. Early complications, the duration to discharge and the in-hospital use of analgesics was noted. Patients returned to the surgical outpatient clinic for evaluation of the cosmetic results of the scar and to evaluate possible complications such as fistula, wound dehiscence and incisional hernia after a minimum of 12 months follow-up.\n Two percent (1/60) of patients that had undergone the procedure through a transverse incision presented with an incisional hernia as opposed to 14% (9/63) of patients from the midline incision group (P = 0.017). Transverse incisions were found to be significantly shorter than midline incisions and associated with more pleasing appearance. More patients having undergone a midline incision, reported pain on day one, two and three postoperatively than patients from the transverse group. The use of analgesics did not differ between the two groups.\n In light of our results a transverse incision should, if possible, be considered as the preferred incision in acute and elective surgery of the upper abdomen when laparoscopic surgery is not an option.", "A prospective study was conducted to determine the safety and efficacy of cholecystectomy through a 5 cm transverse abdominal incision. 181 consecutive patients who underwent elective cholecystectomy for symptomatic gall stone disease in a single surgical unit at the All India Institute of Medical Sciences, New Delhi between December 1990 to February 1992, were prospectively randomized into 5 cm transverse and midline incision groups. Operative time, blood loss, post-operative stay and complications were compared in the two groups. Ninety seven patients were included in the transverse incision group and 84 patients in the midline group. Cholecystectomy could be safely performed through a 5 cm transverse incision in 84 patients (86.8%) without increase in operative complications, morbidity or mortality. In another 84 patients cholecystectomy was performed through a midline incision. The average operating time and blood loss were comparable in both groups. The average post-operative stay in 5 cm transverse incision group was 2.6 days (range 1-4 days) and in the midline group was 4.0 days (range 3-5 days). There were 7 post-operative complications (all wound infections) in the 5 cm transverse group and 12 post-operative complications (10 wound infections and 2 pneumonitis) in the midline group. However, the difference in wound infection rate was not statistically significant (p > 0.1). In Conclusion, Cholecystectomy can be safely performed through a 5 cm transverse incision.", "A prospective randomized trial compared pain in the first 24 h after gallbladder surgery via an upper midline or a transverse incision. Pain was measured by the patients' self-administered consumption of pethidine, degree of postoperative respiratory impairment and a visual analogue pain scale. The upper midline incision group self-administered significantly more pethidine than the transverse incision group (P less than 0.001), but there was no difference between the groups in respiratory function or visual analogue pain scale results 24 h after operation. Length of hospital stay was not different. An upper midline incision is more painful than a transverse incision in the first 24 h following gallbladder surgery.", "Five hundred and seventy-nine patients undergoing major laparotomy were randomly allocated to have midline or transverse incisions. Transverse incisions took longer to make and caused more bleeding but (in the absence of wound sepsis) no transverse wound burst and there were only 2 incisional hernias. In the midline group, without wound sepsis, there were 2 burst abdomens and 9 incisional hernias. When, however, those patients who suffered wound sepsis were also considered, there were no significant differences between the two groups.", "The objective of this randomized trial was to evaluate the incidence of incisional hernia after transverse or vertical incisions for open aortic aneurysm repair.\n The study group comprised 69 patients who underwent elective aneurysm repair between November 1998 and November 2000 (60 men, nine women; mean age 72.8 (range 56-95) years). Patients were randomized to a transverse (n = 32) or vertical (n = 37) incision for the procedure. Of the 42 patients who were still alive in February 2004, 37 (15 transverse, 22 vertical incisions) attended for review. Laparotomy scars were assessed both clinically and ultrasonographically by the same examiner, to look for incisional hernia.\n Mean follow-up was 4.4 years. A multivariable logistic regression analysis revealed that the type of incision was the only parameter that significantly influenced the rate of incisional hernia: six of 15 patients with a transverse laparotomy versus 20 of 22 with a vertical laparotomy (P = 0.010).\n The incidence of incisional hernia was high after aortic aneurysm repair, but was lower in patients who had a transverse incision.", "To evaluate the impact of a standard vertical laparotomy versus a Pfannenstiel transverse laparotomy on intra-, peri-operative, and 6-month follow-up outcome in patients undergoing radical retropubic prostatectomy with pelvic lymphadenectomy with spinal anesthesia.\n Between January 2003 and June 2003, 69 age-matched consecutive patients with clinically localized prostate cancer underwent radical retropubic prostatectomy with pelvic lymphadenectomy with spinal anesthesia and were randomized into Group 1 (vertical laparotomy: 35 patients) and Group 2 (Pfannenstiel laparotomy: 34 patients). An extensive analysis of the critical intra-, peri-operative, and 6-month follow-up clinical parameters was performed.\n Both the hemodynamics and the biochemical balance were not significantly different between the two groups. Overall blood loss (p = 0.78), autologous (p = 0.88) and homologous (p = 0.36) blood transfusions were similar regardless of the type of laparotomy. Surgical time was not significantly (p = 0.27) different between the two groups. Similarly, the two forms of laparotomy did not differ regarding the length of the surgical incision (p = 0.21), as measured at the end of the procedure. Post-operative oxygen saturation percentage by pulse oximetry, as well as post-op sedation score, were not significantly different (p = 0.06 and p = 0.97, respectively). Waiting time in the post-operative holding area (p = 0.15), and pain score in the post-operative holding area (p = 0.9) as well as on post-operative day 1 (p = 0.1) were not significantly different between the two groups. The rate of first flatus passage and of unassisted ambulation were similar regardless of the type of laparotomy during post-operative day day 1. The two types of incision made it possible to remove a similar (p = 0.34) number of pelvic lymph nodes and were associated to a similar rate of positive surgical margins among pT2 patients. At the 6-month follow-up the occurrence of a pelvic lymphocele and of deep venous thrombosis was similar in the two groups (p = 0.6 and p = 0.16, respectively). Complete urinary continence and spontaneous erectile function recovery was reported in a similar number of patients regardless of the type of surgical incision (p = 0.59 and p = 0.40, respectively).\n These results suggest that a Pfannenstiel transverse suprapubic laparotomy does not result in a significantly different outcome from a standard vertical laparotomy in patients undergoing a radical retropubic prostatectomy with pelvic lymphadenectomy with L2-L3 spinal anesthesia for clinically localized prostate cancer.", "The influence of the type of abdominal incision on post-operative pain and pulmonary function was investigated in patients operated upon for a right-sided cancer of the large bowel.\n Fifty-three patients scheduled for a right hemicolectomy due to a right-sided colon cancer were randomized to a median vertical (M) or a transverse incision (T). Forty patients, 23 with a M and 17 with a T incision, completed the study and could be evaluated. Pain at rest and after physical activity was assessed with a visual analogue scale, and was also measured as reflected in the need for analgesics. Respiratory function was assessed with pre- and post-operative spirometry.\n Pain after activity was significantly less in patients with a T incision. This group also needed less analgesia. Vital capacity (VC) and forced expiratory volume in 1 s (FEV 1.0) were profoundly reduced after surgery in both groups of patients, but improvement of respiratory function was faster in patients with a transverse incision. No problem with access to the operative field was noted.\n We conclude that a transverse incision is preferable to a midline incision and should be used in right hemicolectomy. This abdominal incision reduces effort-induced pain and interferes less with post-operative pulmonary function, and may reduce the risk of pulmonary complications.", "A previous retrospective review of 2,006 emergency laparotomies had suggested that anesthesia and operative times could be reduced by using a continuous stitch closure for all layers of the incision. A prospective, randomized study was then implemented through use of odd/even digits in the last and next-to-last digits in the hospital number. Of 551 patients subjected to laparotomy because of abdominal trauma, no intraperitoneal injury was found in 212. There was no statistically significant difference in time expended or complications (wound or other, including pulmonary) on contrasting transverse (101) with vertical (111) incisions, or on comparing continuous (104) and interrupted (108) closure, with the exception of an average 26 minutes in time saved by a continuous suture (P = .02). Analysis of these same factors in 339 patients with trauma found at laparotomy could document no statistically significant difference. Such data support the use of a running suture for closure of the abdominal wall as a practical method to save anesthesia and operating time without increased risk of developing a wound or other postoperative complication.", "Transverse and midline abdominal incisions are both commonly used for laparotomy to perform surgery on the pancreas and stomach, but comparative data are limited, especially from prospective randomized trials.\n During a predefined 2-year recruitment period, 94 patients undergoing an elective major laparotomy for disorders of the pancreas or stomach were enrolled in this study. The outcome measures were pulmonary function, incisional pain, and wound characteristics.\n The operation groups were equally divided according to the type of incision used. The patients who underwent transverse incision laparotomy had significantly better postoperative pulmonary function and significantly less postoperative incisional pain than those who underwent midline incision laparotomy (P < 0.05), but there were no differences in morbidity and the incidence of wound complications.\n Performing a transverse incision for surgery on the pancreas or stomach results in better postoperative pulmonary function and less incisional pain than a midline incision, without affecting postoperative morbidity.", "We performed a randomized study to evaluate the differences between upper midline incision and transverse incision for gastrectomy.\n Patients undergoing distal gastrectomy or total gastrectomy for gastric cancer were randomly allocated to have either an upper midline incision or a transverse incision. The times taken to open and close the abdominal cavity, the number of doses of postoperative analgesics, and the incidence of postoperative pneumonia, wound infection, and intestinal obstruction were compared between the patients having the two incisions.\n Times for both opening and closing the abdominal cavity were longer with a transverse incision, in both the distal gastrectomy group and total gastrectomy group. In the patients in whom continuous epidural analgesia was used postoperatively, the number of additional doses of analgesics was smaller in the transverse-incision group after distal gastrectomy. The incidence of postoperative pneumonia was lower in the transverse-incision group after distal gastrectomy. The number of patients with postoperative intestinal obstruction was smaller in the transverse-incision group than in the midline-incision group after distal gastrectomy. In contrast to distal gastrectomy, there was no significant difference in the number of doses of postoperative analgesics, incidence of postoperative pneumonia, or incidence of postoperative intestinal obstruction between the two study groups after total gastrectomy.\n A transverse incision for distal gastrectomy may be more beneficial than an upper midline incision in attenuating postoperative wound pain, decreasing the incidence of postoperative pneumonia, and preventing postoperative intestinal obstruction.", "There are 2 main types of access for patients requiring major open, elective abdominal surgery: the midline or the transverse approach. The aim of this study is to compare both approaches by focusing on postoperative pain, complications, and frequency of incisional hernias.\n A recent Cochrane review suggested that transverse incisions may be less painful but incisional hernia rates do not differ.\n Randomized, patient- and observer-blinded, monocentric, equivalence clinical trial. Patients were scheduled for elective primary abdominal incisions. Composite primary end point measured 48 hours after surgery was the total amount of analgesics (piritramide) required in the last 24 hours and pain (Visual Analogue Scale). Secondary end points were early-onset and late complications. This study is registered in the ISRCTN registry and has the ID number ISRCTN60734227.\n Two hundred patients (101 midline and 99 transverse) were randomized. Both incision types resulted in similar amounts of required analgesics (95% confidence interval [-0.38; -0.33] was included in the equivalence level). For the Visual Analogue Scale, both the 95% and 90% CI (0-10) were neither within the equivalence levels nor were their differences significant at the 5% level. No relevant differences between midline and transverse incisions were observed for 30-day mortality (2 vs. 2, P = 0.99), mortality after one year (15 vs. 23, P = 0.15), pulmonary complications (13 vs. 17, P = 0.43), median length of hospital stay (11 vs. 12 days, P = 0.08), median time to tolerance of solid food (12 vs. 14 days, P = 0.30), and incisional hernias after one year (13 vs. 8, P = 0.48). More wound infections occurred in the transverse group (15 vs. 5, P = 0.02).\n The decision about the incision should be driven by surgeon preference with respect to the patient's disease and anatomy." ]

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[ "Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation.", "Initial experiences of women from hereditary breast cancer families after bilateral prophylactic mastectomy: a retrospective study.", "Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.", "Contralateral prophylactic mastectomy. Predictors of significant histologic findings.", "Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers.", "Efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.", "Complications leading to surgery after breast implantation.", "Patient regrets after bilateral prophylactic mastectomy.", "Efficacy of prophylactic mastectomy in women with unilateral breast cancer: a cancer research network project.", "Clinical experience of prophylactic mastectomy followed by immediate breast reconstruction in women at hereditary risk of breast cancer (HB(O)C) or a proven BRCA1 and BRCA2 germ-line mutation.", "Understanding the experience of prophylactic bilateral mastectomy: a qualitative study of ten women.", "The psychosocial impact of bilateral prophylactic mastectomy: prospective study using questionnaires and semistructured interviews.", "Predictors of quality of life in women with a bilateral prophylactic mastectomy.", "Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer.", "Contralateral prophylactic mastectomy improves the outcome of selected patients undergoing mastectomy for breast cancer.", "Prevention in familial breast cancer: counseling and prophylactic mastectomy.", "Clinical follow-up after bilateral risk reducing ('prophylactic') mastectomy: mental health and body image outcomes.", "Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group.", "Long-term psychological impact of carrying a BRCA1/2 mutation and prophylactic surgery: a 5-year follow-up study.", "Subcutaneous mastectomy data: a final statistical analysis of 1500 patients.", "Reoperations after prophylactic mastectomy with or without implant reconstruction.", "One year follow-up of women opting for presymptomatic testing for BRCA1 and BRCA2: emotional impact of the test outcome and decisions on risk management (surveillance or prophylactic surgery).", "Satisfaction after contralateral prophylactic mastectomy: the significance of mastectomy type, reconstructive complications, and body appearance.", "Predictors of and satisfaction with bilateral prophylactic mastectomy.", "Satisfaction with prophylactic mastectomy and breast reconstruction in genetically predisposed women.", "Long-term satisfaction and psychological and social function following bilateral prophylactic mastectomy.", "Psychosocial functioning in women who have undergone bilateral prophylactic mastectomy.", "Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers.", "Contentment with quality of life among breast cancer survivors with and without contralateral prophylactic mastectomy.", "A population-based study of bilateral prophylactic mastectomy efficacy in women at elevated risk for breast cancer in community practices.", "Postmastectomy reconstruction.", "Issues of regret in women with contralateral prophylactic mastectomies.", "Arguments against routine contralateral mastectomy or undirected biopsy for invasive lobular breast cancer.", "Utilisation of prophylactic mastectomy in 10 European centres.", "Complications following bilateral prophylactic mastectomy." ]

[ "Women with a BRCA1 or BRCA2 mutation have a high risk of breast cancer and may choose to undergo prophylactic bilateral total mastectomy. We investigated the efficacy of this procedure in such women.\n We conducted a prospective study of 139 women with a pathogenic BRCA1 or BRCA2 mutation who were enrolled in a breast-cancer surveillance program at the Rotterdam Family Cancer Clinic. At the time of enrollment, none of the women had a history of breast cancer. Seventy-six of these women eventually underwent prophylactic mastectomy, and the other 63 remained under regular surveillance. The effect of mastectomy on the incidence of breast cancer was analyzed by the Cox proportional-hazards method in which mastectomy was modeled as a time-dependent covariate.\n No cases of breast cancer were observed after prophylactic mastectomy after a mean (+/-SE) follow-up of 2.9+/-1.4 years, whereas eight breast cancers developed in women under regular surveillance after a mean follow-up of 3.0+/-1.5 years (P=0.003; hazard ratio, 0; 95 percent confidence interval, 0 to 0.36). The actuarial mean five-year incidence of breast cancer among all women in the surveillance group was 17+/-7 percent. On the basis of an exponential model, the yearly incidence of breast cancer in this group was 2.5 percent. The observed number of breast cancers in the surveillance group was consistent with the expected number (ratio of observed to expected cases, 1.2; 95 percent confidence interval, 0.4 to 3.7; P=0.80).\n In women with a BRCA1 or BRCA2 mutation, prophylactic bilateral total mastectomy reduces the incidence of breast cancer at three years of follow-up.", "Women from families with breast and/or ovarian cancers seek advice and counselling for risk assessment, but they also want information about preventive measures that might reduce their risk of developing these neoplasms.\n This study was undertaken in order to assess 15 women's experience with the decision-making process prior to undergoing prophylactic bilateral mastectomy (PM) and immediate breast reconstruction (IBR). It was also designed to determine the degree of the women's satisfaction with the information delivered by the different caregivers, and whether the women felt that their need for psychosocial support was appropriately met. An additional goal was to learn about the patients> satisfaction with the operations.\n The women found it difficult to translate the genetic information transmitted to them, although they were satisfied by the way it was given. At some stage during the pre-operative and post-operative period nearly all women stated that they lacked psychological support from the different caregivers. No woman regretted her choice to undergo PM and IBR. By far, the most important issue was the actual risk reduction. However, the result exceeded all patients' initial expectations. When performing PM and IBR, a multidisciplinary team approach, including a psychologist, seems mandatory. It will facilitate the overall management of this group of women.\n Copyright 2000 Harcourt Publishers Ltd.", "To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer.\n Patients included 491 women with stage I or stage II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.\n The actuarial risk of contralateral breast cancer was 29.5% at 10 years. Factors that were predictive of a reduced risk were the presence of a BRCA2 mutation (v BRCA1 mutation; hazard ratio [HR], 0.73; 95% CI, 0.47 to 1.15); age 50 years or older at first diagnosis (v <or= 49 years; HR, 0.63; 95% CI, 0.36 to 1.10); use of tamoxifen (HR, 0.59; 95% CI, 0.35 to 1.01); and history of oophorectomy (HR, 0.44; 95% CI, 0.21 to 0.91). The effect of oophorectomy was particularly strong in women first diagnosed prior to age 49 years (HR, 0.24; 95% CI, 0.07 to 0.77). For women who did not have an oophorectomy or take tamoxifen, the 10-year risk of contralateral cancer was 43.4% for BRCA1 carriers and 34.6% for BRCA2 carriers.\n The risk of contralateral breast cancer in women with a BRCA mutation is approximately 40% at 10 years, and is reduced in women who take tamoxifen or who undergo an oophorectomy.", "Women with unilateral breast carcinoma are at increased risk for developing contralateral breast carcinoma (CBC). The authors sought to identify predictors of malignant or moderate to high-risk histologic findings in contralateral prophylactic mastectomy (CPM) specimens, and to determine the efficacy of CPM.\n The authors performed a retrospective review of 239 patients with unilateral early-stage breast carcinoma who underwent CPM. The number of CBCs expected if the contralateral breast had been left intact was calculated based on CBC rates observed in the Surveillance, Epidemiology, and End Results (SEER) database and on life-table analysis by family history.\n In the current study, 11 patients (4.6%) had occult contralateral malignancies (4 invasive carcinomas and 7 ductal carcinomas in situ) and 44 (18.4%) patients had moderate to high-risk pathology (8 lobular carcinoma in situ, 11 atypical lobular hyperplasia, 25 atypical ductal hyperplasia). At 1846 patient-years of follow-up, only 1 patient (0.4%) developed a new CBC compared with 11 expected cancers based on SEER data. One CBC was observed among 140 patients with a family history of breast carcinoma, compared with 16 expected cancers based on life-table analysis adjusted for adjuvant therapy. The determinants of significant findings at CPM were invasive lobular histology, estrogen and progesterone receptor positivity, additional ipsilateral moderate to high-risk pathology, and age > 40 years at cancer diagnosis.\n CPM was associated with a low risk of subsequent development of breast carcinoma. Evaluation of histologic findings in the ipsilateral breast may help to predict the likelihood of significant disease in the contralateral breast and assist in risk stratification.", "The clinical outcome of contralateral prophylactic mastectomy (CPM) in women with a BRCA1 or BRCA2 mutation and a personal history of invasive breast cancer is unknown. We identified a cohort of 148 female BRCA1 or BRCA2 mutation carriers (115 and 33, respectively) who previously were treated for unilateral invasive breast cancer stages I-IIIa. In all, 79 women underwent a CPM, while the other women remained under intensive surveillance. The mean follow-up was 3.5 years and started at the time of CPM or at the date of mutation testing, whichever came last, that is, on average 5 years after diagnosis of the first breast cancer. One woman developed an invasive contralateral primary breast cancer after CPM, whereas six were observed in the surveillance group (P<0.001). Contralateral prophylactic mastectomy reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO). At 5 years follow-up, overall survival was 94% for the CPM group vs 77% for the surveillance group (P=0.03), but this was unexpectedly mostly due to higher mortality related with first breast cancer and ovarian cancer in the surveillance group. After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant. Our data show that CPM markedly reduces the risk of contralateral breast cancer among BRCA1 or BRCA2 mutation carriers with a history of breast cancer. Longer follow-up is needed to study the impact of CPM on contralateral breast cancer-specific survival. The choice for CPM is highly correlated with that for BPO, while only BPO leads to a significant improvement in overall survival so far.", "To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.\n We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy.\n Of the 745 women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%).\n The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.", "Local complications that require additional surgical procedures are an important problem for women with breast implants.\n We studied 749 women who lived in Olmsted County, Minnesota, and received a first breast implant at the Mayo Clinic between 1964 and 1991. We identified complications that occurred after the initial procedure and after any subsequent implantation. A complication was defined as a surgical procedure performed for any of the following reasons: capsular contracture; rupture of the implant; hematoma or bleeding; infection or seroma of the wound; chronic pain; extrusion, leakage, or sweating of the implant; necrosis of the nipple, areola, or flap; malfunction of the filler port of a tissue expander; and wound dehiscence.\n During follow-up (mean, 7.8 years; range, 0 to 25.8), 208 (27.8 percent) of the women underwent 450 additional implant-related surgical procedures. Ninety-one (20.2 percent) were anticipated, staged procedures or were done because the patient requested a size change or aesthetic improvement, and 359 procedures (79.8 percent) had at least one clinical indication (thus constituting a complication). Complications occurred in 178 (23.8 percent) of the 749 women and involved 274 (18.8 percent) of the 1454 breasts with implants and 321 (18.8 percent) of the 1703 implants. The most frequent problem was capsular contraction (272 cases), followed by rupture of the implant (60), hematoma (55), and wound infection (23). The rate of complications was significantly lower (P<0.001) among women with cosmetic implants (6.5 percent at one year, 12 percent at five years) than among women who underwent implantation after mastectomy for breast cancer (21.8 percent at one year, 34 percent at five years) or prophylactic mastectomy (17.3 percent at one year, 30.4 percent at five years).\n Women who have had breast implantation frequently experience local complications during the subsequent five years. Complications were significantly less frequent among patients who received implants for cosmetic reasons than among those who received implants after mastectomy for cancer or for cancer prophylaxis.", "The discovery of a cadre of breast cancer susceptibility genes has resulted in an increase in the number of women seeking information about prophylactic breast surgery, but virtually no large-scale prospective databases exist to assist women considering prophylactic mastectomy.\n The authors constructed a National Prophylactic Mastectomy Registry comprised of a volunteer population of 817 women from 43 states who have undergone prophylactic mastectomy.\n In the registry, 370 women had undergone bilateral prophylactic mastectomy. Twenty-one (5%) women expressed regrets about the procedure. The median follow-up was 14.6 years (mean 14.8 years; range 0.2-51 years). Those with regrets were subsetted into those with major (n = 10) or minor (n = 7) regrets. Regrets were more common in those women with whom discussion about prophylactic mastectomy was initiated by a physician (19/255), compared with patients who initiated the discussion themselves (2/108; P < .05).\n The overall satisfaction rate of 95% reported here may be explained by the voluntary nature of this registry. The most important factor that predicts an unfavorable outcome following bilateral prophylactic mastectomy is a physician-initiated discussion.", "We investigated the efficacy of contralateral prophylactic mastectomy (CPM) in reducing contralateral breast cancer incidence and breast cancer mortality among women who have already been diagnosed with breast cancer.\n This retrospective cohort study comprised approximately 50,000 women who were diagnosed with unilateral breast cancer during 1979 to 1999. Using computerized data confirmed by chart review, we identified 1,072 women (1.9%) who had CPM. We obtained covariate information for these women and for a sample of 317 women who did not undergo CPM.\n The median time from initial breast cancer diagnosis to the end of follow-up was 5.7 years. Contralateral breast cancer developed in 0.5% of women with CPM, metastatic disease developed in 10.5%, and subsequent breast cancer developed in 12.4%; 8.1% died from breast cancer. Contralateral breast cancer developed in 2.7% of women without CPM, and 11.7% died of breast cancer. After adjustment for initial breast cancer characteristics, treatment, and breast cancer risk factors, the hazard ratio (HR) for the occurrence of contralateral breast cancer after CPM was 0.03 (95% CI, 0.006 to 0.13). After adjustment for breast cancer characteristics and treatment, the HRs for the relationship of CPM with death from breast cancer, with death from other causes, and with all-cause mortality were 0.57 (95% CI, 0.45 to 0.72), 0.78 (95% CI, 0.57 to 1.06), and 0.60 (95% CI, 0.50 to 0.72), respectively.\n CPM seems to protect against the development of contralateral breast cancer, and although women who underwent CPM had relatively low all-cause mortality, CPM also was associated with decreased breast cancer mortality.", "Women with a proven BRCA1 or BRCA2 germ-line mutation or with a 50% risk of carrying the mutation, have an increased risk of breast cancer. Regular surveillance, chemoprevention or prophylactic mastectomy (PM) are options to detect breast cancer at an early stage or to reduce the risk. We describe the management of women who have opted for PM, the postoperative complications of PM, especially in combination with immediate breast reconstruction (IBR), and the oncological follow-up.\n The medical records of all women who underwent a PM from December 1993 to December 1999 have been reviewed with respect to management, patient characteristics, complications and oncological follow-up.\n During the study period 112 women with a median age of 38.8 years opted for a PM: 76 were germline mutation carriers. After PM, 79 women without breast or ovarian cancer in their medical history, were free of disease after 2.5 years (median). Before PM, 29 women had been treated for breast cancer, 3.9 years (median) previously; 5 of these women had developed metastatic disease by the last consultation. Before PM, 2 patients had been treated for DCIS and 2 patients for ovarian cancer. Four DCIS were found; none of these women had evidence of disease 4.0 years (median) after PM. In 59 women laparoscopic prophylactic bilateral oophorectomy (PBO) was performed; 36 simultaneously with PM and 23 separately. A total of 103 women (92%) opted for IBR. After PM, the complication rate for IBR was 21%: 11% within 6 weeks and 10% at long-term follow-up (median 3.5) after PM, including the removal of 10 prostheses.\n Women with an increased risk of breast cancer due to a genetic predisposition should be adequately informed about the different treatment options in the setting of a multidisciplinary approach. PM can simultaneously be combined with PBO and IBR. IBR can facilitate the decision to undergo a PM. PM followed by IBR has an acceptable complication rate.", "Prophylactic bilateral mastectomy represents a new and controversial cancer prevention strategy for women at high-risk of familial breast cancer, the psychosocial implications of which are yet to be fully explored. A qualitative methodology was therefore adopted to provide a discovery-orientated study of the perspectives of ten women who had undergone prophylactic mastectomy and the views of eight of their partners. Each participant was interviewed with the aim of exploring the personal experiences of surgery, factors associated with psychological adjustment and the impact on the family. Data were transcribed and systematically analysed using Grounded Theory. Themes emerging from participants' accounts formed seven significant categories that represented women's key experiences: (i) deciding; (ii) telling; (iii) experiencing surgery and recovering; (iv) maintaining womanliness; (v) processing the loss; and (vi) moving on. The importance of the social context in women's experience and difficulties of isolation/eliciting support were also highlighted: (vii) isolation and being supported. A core category of 'Suffering and countering multiple loss' considered central to women's experience, integrated the seven significant categories and provided further conceptualisation of women's experience. Implications for clinical practice are highlighted.", "To investigate the psychosocial impact of bilateral prophylactic mastectomy for women with increased risk of breast cancer and to identify, preoperatively, risk factors for postoperative distress.\n Prospective study using interviews and questionnaire assessments.\n Participants' homes throughout the United Kingdom.\n 143 women with increased risk of developing breast cancer who were offered bilateral prophylactic mastectomy and who accepted or declined the surgery; a further 11 were offered surgery but deferred making a decision.\n Psychological and sexual morbidity.\n Psychological morbidity decreased significantly over time for the 79 women who chose to have surgery (accepters): 58% (41/71) preoperatively v 41% (29/71) 6 months postoperatively (difference in percentages 17%, 95% confidence interval 2% to 32%; P=0.04) and 60% (39/65) preoperatively v 29% (19/65) 18 months postoperatively (31%, 15% to 47%; P<0.001). Psychological morbidity in the 64 women who declined surgery (decliners) did not decrease significantly: 57% (31/54) at baseline v 43% (23/54) at 6 months (14%, 0% to 29%; P=0.08) and 57% (29/52) at baseline v 41% (21/52) at 18 months (16%; -2% to 33%; P=0.11). Greater than normal proneness to anxiety was more common in the decliners than in the accepters: 78% (45/58) v 56% (41/73) (22%, 6% to 38%; P=0.006). Accepters were more likely than decliners to believe it inevitable that they would develop breast cancer (32% (24/74) v 10% (6/58) (difference in percentages 22%, 9% to 35%; P=0.003)), and decliners were more likely to believe that screening could help (92% (55/60) v 74% (55/74) (18%, 5% to 31%; P=0.007)). Level of sexual discomfort and degree of sexual pleasure did not change significantly over time in either of the two groups.\n Bilateral prophylactic mastectomy may provide psychological benefits in women with a high risk of developing breast cancer.", "The purpose of this study was to assess the quality of life in women who had previously undergone a bilateral prophylactic mastectomy and to determine what factors predict quality of life in this population. Women in Ontario who had undergone prophylactic mastectomy between 1991 and 2000 were asked to complete several questionnaires that assessed current psychosocial functioning, including the Quality of Life Index (QLI). The mean score for the QLI was 23.34 (range 9.53-30.00). QLI scores were negatively correlated with cancer-related distress, body image difficulties, and psychological distress. Conversely, QLI scores were positively correlated with social support. Significant predictors of quality of life included psychological distress and one subscale of body image (vulnerability). Vulnerability and psychological distress are important predictors of quality of life in women who have previously undergone bilateral prophylactic mastectomy.", "Options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic mastectomy. The data on the outcomes for surveillance and prophylactic mastectomy are incomplete.\n We conducted a retrospective study of all women with a family history of breast cancer who underwent bilateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. The women were divided into two groups - high risk and moderate risk - on the basis of family history. A control study of the sisters of the high-risk probands and the Gail model were used to predict the number of breast cancers expected in these two groups in the absence of prophylactic mastectomy.\n We identified 639 women with a family history of breast cancer who had undergone bilateral prophylactic mastectomy: 214 at high risk and 425 at moderate risk. The median length of follow-up was 14 years. The median age at prophylactic mastectomy was 42 years. According to the Gall model, 37.4 breast cancers were expected in the moderate-risk group; 4 breast cancers occurred (reduction in risk, 89.5 percent; P<0.001). We compared the numbers of breast cancers among the 214 high-risk probands with the numbers among their 403 sisters who had not undergone prophylactic mastectomy. Of these sisters, 38.7 percent (156) had been given a diagnosis of breast cancer (115 cases were diagnosed before the respective proband's prophylactic mastectomy, 38 were diagnosed afterward, and the time of the diagnosis was unknown in 3 cases). By contrast, breast cancer was diagnosed in 1.4 percent (3 of 214) of the probands. Thus, prophylactic mastectomy was associated with a reduction in the incidence of breast cancer of at least 90 percent.\n In women with a high risk of breast cancer on the basis of family history, prophylactic mastectomy can significantly reduce the incidence of breast cancer.", "Risk factors for contralateral breast cancer (CBC) may indicate a benefit for contralateral prophylactic mastectomy (CPM) at the time of unilateral mastectomy for breast cancer. The purpose of this study is to evaluate the efficacy of CPM in preventing CBC.\n sixty-four patients undergoing CPM and a control group of 182 patients not undergoing CPM and matched for age, stage, surgery, chemotherapy, and hormonal therapy were retrospectively compared for CBC rate, disease-free survival, and overall survival.\n Thirty-six CBCs occurred in the control group. In the CPM group, 3 CBCs were found at the time of prophylactic mastectomy, but none occurred subsequently (P = 0.005). Disease-free survival at 15 years in the CPM group was 55% (95% confidence interval [CI] 38% to 69%) versus 28% (95% CI 19% to 36%) in the control group (P = 0.01). Overall survival at 15 years was 64% (95% CI 45% to 78%) CPM versus 48% (95% CI 39% to 58%) in controls (P = 0.26).\n CPM prevented CBC and significantly prolonged disease-free survival. Future studies will need to address risk assessment and contralateral breast cancer prevention in patients treated for early breast cancer.", "nan", "In Manchester, approximately 120 women at > or = 1:4 lifetime risk of breast cancer have considered preventative surgery since 1992. Women treated within the Manchester protocol receive two genetic counselling sessions, a psychological assessment and a surgical consultation pre-operatively and annual follow-up post-operatively. The vast majority of women have breast reconstruction.\n Since 1996, mental health and body image have been assessed in women attending annual follow-up using self-report questionnaires: the 28-item General Health Questionnaire (GHQ) and 10-item Body Image Scale (BIS). Women with high scores are assessed by clinical interview together with a proportion who have no significant problems.\n Between 1995 and 1999, 76 women completed surgery. Ten were awaiting post-operative review and 60 (91%) attended for follow-up of whom 45 (75%) were interviewed. Questionnaire data were available for 52 (79%) women, mean age 40.8 years (range 27-58). Six women were gene mutation carriers and of these three had had breast cancer. One additional patient was affected but had not been genetically tested. Eight (17%) of 47 women with assessments in the first post-operative year scored in the 'caseness' range on the GHQ: the mean GHQ score was 3.8 (S.D. 6.7), range 0-25. Results were comparable with those for women attending the Family History Clinic for risk assessment. The mean score on the BIS was 5.1 (S.D. 5.5), range 0-25, comparable with scores for women undergoing conservative surgery for breast cancer. Twenty-one percent of women reported no negative change in body image following surgery (i.e. zero questionnaire summary scores) and the majority of changes reported were of minor degree (item scores 0 or 1). The most frequently reported changes were in sexual attractiveness (55%), feeling less physically attractive (53%) and self-consciousness about appearance (53%): a third of women felt less feminine to a minimal degree. These results appeared stable over time. A minority of women had more serious psychological or body image concerns, usually in relation to surgical complications: they received further psychiatric intervention.\n For the majority of women there is no evidence of significant mental health or body image problems in the first 3 years following Bilateral Prophylactic Mastectomy (BPM), but women who have complications warrant additional psychological help. Careful pre-operative preparation and long-term monitoring are advocated in this new field of cancer prevention.", "Data on the efficacy of bilateral prophylactic mastectomy for breast cancer risk reduction in women with BRCA1 and BRCA2 (BRCA1/2) mutations are limited, despite the clinical use of this risk-management strategy. Thus, we estimated the degree of breast cancer risk reduction after surgery in women who carry these mutations.\n Four hundred eighty-three women with disease-associated germline BRCA1/2 mutations were studied for the occurrence of breast cancer. Cases were mutation carriers who underwent bilateral prophylactic mastectomy and who were followed prospectively from the time of their center ascertainment and their surgery, with analyses performed for both follow-up periods. Controls were BRCA1/2 mutation carriers with no history of bilateral prophylactic mastectomy matched to cases on gene, center, and year of birth. Both cases and controls were excluded for previous or concurrent diagnosis of breast cancer. Analyses were adjusted for duration of endogenous ovarian hormone exposure, including age at bilateral prophylactic oophorectomy if applicable.\n Breast cancer was diagnosed in two (1.9%) of 105 women who had bilateral prophylactic mastectomy and in 184 (48.7%) of 378 matched controls who did not have the procedure, with a mean follow-up of 6.4 years. Bilateral prophylactic mastectomy reduced the risk of breast cancer by approximately 95% in women with prior or concurrent bilateral prophylactic oophorectomy and by approximately 90% in women with intact ovaries.\n Bilateral prophylactic mastectomy reduces the risk of breast cancer in women with BRCA1/2 mutations by approximately 90%.", "To explore long-term psychosocial consequences of carrying a BRCA1/2 mutation and to identify possible risk factors for long-term psychological distress.\n Five years after genetic test disclosure, 65 female participants (23 carriers, 42 noncarriers) of our psychological follow-up study completed a questionnaire and 51 participants were interviewed. We assessed general and hereditary cancer-related distress, risk perception, openness to discuss the test result with relatives, body image and sexual functioning.\n Carriers did not differ from noncarriers on several distress measures and both groups showed a significant increase in anxiety and depression from 1 to 5 years follow-up. Carriers having undergone prophylactic surgery (21 of 23 carriers) had a less favorable body image than noncarriers and 70% reported changes in the sexual relationship. A major psychological benefit of prophylactic surgery was a reduction in the fear of developing cancer. Predictors of long-term distress were hereditary cancer-related distress at blood sampling, having young children, and having lost a relative to breast/ovarian cancer. Long-term distress was also associated with less open communication about the test result within the family, changes in relationships with relatives, doubting about the validity of the test result, and higher risk perception.\n Our findings support the emerging consensus that genetic predisposition testing for BRCA1/2 does not pose major mental health risks, but our findings also show that the impact of prophylactic surgery on aspects such as body image and sexuality should not be underestimated, and that some women are at risk for high distress, and as a result, need more attentive care.", "A statistical analysis of 1500 patients who underwent subcutaneous mastectomy is presented. Their data suggest that most patients who were treated by subcutaneous mastectomy had proliferative fibrocystic disease or macrocystic disease, among other high risk factors. The data also suggest that a thoroughly performed subcutaneous mastectomy is an effective means of providing prophylaxis in women who are at high risk for breast cancer. Conclusions were confirmed by many unsolicited comments of patients who underwent the procedure and were grateful to their doctors who performed it.", "The authors characterized the unanticipated reoperations after prophylactic mastectomy, with or without implant reconstruction.\n The surgical cohort was comprised of 1417 women with a family history of breast carcinoma. The women received a prophylactic mastectomy with (bilateral, n = 593; contralateral, n = 506) or without reconstruction (n = 318) at the Mayo Clinic (Rochester, MN) between 1960 and 1993. Reoperations and indications for reoperation were compiled from medical records and a patient survey.\n Three hundred eighteen women received a bilateral (n = 39) or contralateral (n = 279) prophylactic mastectomy without reconstruction. With a median follow-up of 15 years, 18 women (6%) required reoperation. Most of these reoperations occurred within the first year after prophylactic mastectomy. Five hundred ninety-three women had reconstruction with implants following bilateral prophylactic mastectomy. Approximately one-half of the women (52%) required at least 1 unanticipated reoperation during a median follow-up of 14 years. Approximately 39% of all reoperations occurred within 1 year of breast reconstruction and 69% within 5 years. Implant-related issues were the most common cause for reoperation. Some women with breast carcinoma elected to receive contralateral prophylactic mastectomy with therapeutic mastectomy for the affected breast. Five hundred six women received reconstruction with implants. During a median follow-up of 8.8 years, 189 women (37%) required unanticipated reoperation. The most common indication was implant-related issues. The time course of reoperations was similar to that for women in the bilateral group.\n Surgical reoperations were fairly common among women who received prophylactic mastectomy with implant reconstruction. Most of the reoperations were implant related. Reoperations were fairly uncommon after prophylactic mastectomy without reconstruction.\n Copyright 2003 American Cancer Society.", "Genetic testing enables women at risk for hereditary breast and/or ovarian cancer to find out whether they have inherited the gene mutation (BRCA1/BRCA2), and if so, to opt for frequent surveillance and/or prophylactic surgery (bilateral mastectomy and/or oophorectomy). Here, a follow-up is described for 63 healthy women at 50% risk of being a BRCA1/BRCA2 mutation carrier who underwent genetic testing. The course of distress and problems regarding body image and sexuality up to 1 year after disclosure of the test-outcome were described separately for mutation carriers undergoing mastectomy (n = 14), for mutation carriers opting for surveillance (n = 12) and for non-mutation carriers (n = 37). Furthermore, we analyzed whether women opting for prophylactic mastectomy differed from those opting for close surveillance with respect to biographical characteristics, experiences with cancer in relatives and personality. Women opting for prophylactic mastectomy had significantly higher distress levels than mutation carriers who opted for surveillance, and the non-mutation carriers. This difference in levels of distress was highest at pre- and post-test and had almost disappeared at 1-year follow-up. Besides, mutation carriers opting for prophylactic mastectomy were more often in their thirties, more often had young children and had a longer awareness of the genetic nature of cancer in the family than those opting for regular surveillance. Adverse effects were observed in women who underwent prophylactic mastectomy (mostly in combination with immediate breast reconstruction) regarding the perception of how their breast region looked like and felt, the intimate relationship and physical wellbeing whereas women opting for prophylactic mastectomy reported more distress than the other women in the study, their distress levels had significantly decreased 6 months or longer after surgery, possibly due to the significant risk reduction of developing breast cancer. This might explain, why most women who underwent prophylactic mastectomy were satisfied with this decision, despite a perceived negative impact on body image, the intimate relationship and physical wellbeing.", "Contralateral prophylactic mastectomy (CPM) is one option for reducing the risk of a second breast cancer in women with a personal and family history of breast cancer. Few data are available regarding satisfaction, psychological, and social function after CPM. The purpose of this research is to evaluate women's long-term satisfaction with CPM, factors influencing satisfaction, and psychological and social function after CPM.\n This was a descriptive study of all women with a family history of breast cancer, known to be alive, who elected CPM at Mayo Clinic (Rochester, MN) between 1960 and 1993 (n = 621). Ninety-four percent of the women (n = 583) completed a study-specific questionnaire.\n A mean of 10.3 years after the procedure, the majority of women (83%) were satisfied with their CPM. A smaller number were neutral (8%) or dissatisfied (9%). Women who had a subcutaneous mastectomy had more problems with reconstruction, and fewer of these women were satisfied than women with simple mastectomy. Decreased satisfaction with CPM was associated with decreased satisfaction with appearance, complications with reconstruction, reconstruction after CPM, and increased level of stress in life. The majority of women experienced no change or favorable effects in self-esteem (83%), level of stress in life (83%), and emotional stability (88%). Satisfaction with body appearance, feelings of femininity, and sexual relationships were the most adversely affected with 33%, 26%, and 23% of the women responding negatively.\n Although most women are satisfied with CPM, each woman should weigh the benefits alongside the potential adverse effects.", "Women with a first-degree relative with breast cancer are at increased risk of developing this disease. The optimal medical management of these women is unclear, with options including close breast cancer screening, bilateral prophylactic mastectomy, or participation in chemoprevention trials. Among women who undergo prophylactic bilateral mastectomy, very little is known about satisfaction with this surgery. Also, we know very little about variables related to prophylactic mastectomy decision making.\n Participants were women at increased risk of breast cancer due to family history. These women were categorized by self-report as not interested in prophylactic mastectomy (n = 58), interested but deciding against surgery (n = 92), or subsequently having a bilateral prophylactic mastectomy (n = 14). Information on screening practices, risk perception, level of depression, and cancer-related worry was collected. Women completing prophylactic mastectomy reported on their satisfaction with the surgery and breast reconstruction.\n Women selecting surgery reported more breast cancer worry. The group expressing no interest in surgery reported fewer biopsies and lower risk estimates. Women completing surgery were satisfied with their decision, although satisfaction with reconstruction was mixed.\n Factors influencing surgical decision making may include breast-cancer-related worry, biopsy history, and subjective breast cancer risk.", "Prophylactic mastectomy with breast reconstruction is a risk-reducing strategy for women at increased risk of breast cancer. It remains a very radical intervention, and long-term data on satisfaction are insufficiently available. In the present follow-up study, the authors assess satisfaction with prophylactic mastectomy and breast reconstruction and its impact on sexual relationships.\n The authors conducted a retrospective study using a short self-report questionnaire administered to 114 genetically predisposed women who underwent prophylactic mastectomy and breast reconstruction mainly by subpectorally implanted silicone prostheses performed at one institution.\n The median follow-up time between prophylactic mastectomy/breast reconstruction and completion of the questionnaire was 3 years. Sixty percent of all participants were satisfied with the result of prophylactic mastectomy/breast reconstruction. Satisfaction was significantly and negatively correlated with perceived lack of information, experienced complications, ongoing complaints, whether or not the reconstructed breasts feel \"like your own,\" and not choosing this type of breast reconstruction again. Adverse effects in the patient's sexual relationship were strongly correlated with perceived lack of information, discrepant expectations, ongoing complaints and limitations, whether or not the reconstructed breasts feel \"like your own,\" altered feelings of femininity, partner's negative perception on femininity and sexuality, and not choosing this type of breast reconstruction again.\n A majority of women would choose the procedure again, but adverse effects and untoward changes in the perception of the sexual relationship need to be addressed in the counselling of women at high risk, to optimize an informed choice and enable adequate adjustment postoperatively.", "Prophylactic mastectomy is a preventive option for women who wish to reduce their risk of breast cancer. There has been concern about possible negative psychological sequelae following this procedure. However, few data are available regarding long-term satisfaction and psychological and social function following this procedure.\n To evaluate patients' long-term satisfaction and psychological and social function following prophylactic mastectomy.\n Descriptive study of all women known to be alive (n = 609) who had a family history of breast cancer and elected to undergo bilateral prophylactic mastectomy at a large, tertiary US health care clinic between 1960 and 1993, 94% (n = 572) of whom completed a study questionnaire.\n Satisfaction with procedure and effects on psychological and social function, based on responses to the study-specific questionnaire.\n Mean time from prophylactic mastectomy to last follow-up was 14.5 years. Most women (70%) were satisfied with the procedure; 11% were neutral; and 19% were dissatisfied. Among the psychological and social variables, the most striking finding was that 74% reported a diminished level of emotional concern about developing breast cancer. The majority of women reported no change/favorable effects in levels of emotional stability (68%/23%), level of stress (58%/28%), self-esteem (69%/13%), sexual relationships (73%/4%), and feelings of femininity (67%/8%). Forty-eight percent reported no change in their level of satisfaction with body appearance; 16% reported favorable effects. However, 9%, 14%, 18%, 23%, 25%, and 36% reported negative effects in these 6 variables, respectively.\n This study suggests that positive outcomes following prophylactic mastectomy include decreased emotional concern about developing breast cancer and generally favorable psychological and social outcomes. These must be weighed against the irreversibility of the decision, potential problems with implants and reconstructive surgery, and occurrence of adverse psychological and social outcomes in some women. JAMA. 2000;284:319-324", "The purpose of this study was to determine the current psychosocial functioning of women who had previously had a bilateral prophylactic mastectomy. Women in the province of Ontario who had undergone prophylactic mastectomy between 1991 and 2000 were asked to complete questionnaires that assessed psychological distress, sexual activity, overall satisfaction with decision to have a prophylactic mastectomy, and body image. Ninety-seven percent of the women were satisfied with their decision to have a prophylactic mastectomy, but young women (<50 years) were less likely to report satisfaction than older women (p=0.001). Women with a strong family history of breast cancer or a BRCA1 or BRCA2 mutation experienced more cancer-related distress than those with a limited family history. Women who had reconstruction following mastectomy reported higher levels of satisfaction with general body shape and appearance than those without reconstruction. In conclusion, the majority of women were satisfied with their decision to undergo prophylactic mastectomy and were not experiencing abnormal levels of psychological distress, low levels of sexual activity, or difficulties with body image.\n Copyright 2003 John Wiley & Sons, Ltd.", "In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes.\n We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models.\n We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of follow-up (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations predicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5%-100% (95% confidence interval = 41.4% to 100%).\n Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.", "To understand psychosocial outcomes after prophylactic removal of the contralateral breast in women with unilateral breast cancer.\n We mailed surveys to women with contralateral prophylactic mastectomy after breast cancer diagnosis between 1979 and 1999 at six health care delivery systems, and to a smaller random sample of women with breast cancer without the procedure. Measures were modeled on instruments developed to assess contentment with quality of life, body image, sexual satisfaction, breast cancer concern, depression, and health perception. We examined associations between quality of life and the other domains using logistic regression.\n The response rate was 72.6%. Among 519 women who underwent contralateral prophylactic mastectomy, 86.5% were satisfied with their decision; 76.3% reported high contentment with quality of life compared with 75.4% of 61 women who did not undergo the procedure (P = .88). Among all case subjects, less contentment with quality of life was not associated with contralateral prophylactic mastectomy or demographic characteristics, but was associated with poor or fair general health perception (odds ratio [OR], 7.0; 95% CI, 3.4 to 14.1); possible depression (OR, 5.4; 95% CI, 3.1 to 9.2); dissatisfaction with appearance when dressed (OR, 3.5; 95% CI, 2.0 to 6.0); self-consciousness about appearance (OR, 2.0; 95% CI, 1.1 to 3.7); and avoiding thoughts about breast cancer (modest: OR, 2.2; 95% CI, 1.1 to 4.5; highest: OR, 1.7; 95% CI, 0.9 to 3.2).\n Most women undergoing contralateral prophylactic mastectomy report satisfaction with their decision and experience psychosocial outcomes similar to breast cancer survivors without the procedure.", "Findings from several studies suggest that bilateral prophylactic mastectomy reduces breast cancer incidence by 90% or more, but the studies used highly selected patients from referral centers, and the comparison groups were not population based. We studied the efficacy of bilateral prophylactic mastectomy in women with elevated breast cancer risk cared for in community practices.\n We conducted a retrospective case-cohort study of women aged 18 to 80 years with 1 or more breast cancer risk factors (family history of breast cancer, history of atypical hyperplasia, or > or =1 breast biopsies with benign findings). Using computerized data and medical records, we identified 276 women with bilateral prophylactic mastectomy and a stratified random sample of 196 women representing an underlying cohort of 666 800 women with elevated breast cancer risk without prophylactic mastectomy, and then we determined who developed breast cancer.\n Breast cancer developed in 1 woman (0.4%) after bilateral prophylactic mastectomy vs 26 800 women (4.0%) without prophylactic mastectomy. Stratifying by birth year, the hazard ratio for breast cancer occurrence after bilateral prophylactic mastectomy was 0.005 (95% confidence interval, 0.001-0.044). No woman with bilateral prophylactic mastectomy died of breast cancer vs a calculated 0.2% of women without prophylactic mastectomy.\n Bilateral prophylactic mastectomy reduced breast cancer incidence in women at elevated risk for breast cancer cared for in community-based practices. However, the absolute risk of breast cancer incidence and death in women who did not undergo the procedure in these settings was relatively low.", "Reconstructive surgery following mastectomy has had an increased acceptability with improved techniques and prostheses. Plastic reconstructive procedures following prophylactic mastectomy were performed in 104 patients and following mastectomy for cancer in 88 patients. Capsular contractions have not occurred with the use of a subpectoral pocket and detection of recurrent cancer is not hampered by the materials now used.", "Patients with a history of carcinoma of one breast have an estimated risk of 0.5% to 0.75% per year of developing a contralateral breast cancer. This risk prompts many women to consider contralateral prophylactic mastectomy (CPM) as a preventive measure. Virtually nothing is known about patient acceptance following CPM. We have developed a National Prophylactic Mastectomy Registry comprised of a volunteer population of 817 women from 43 states who have undergone prophylactic (unilateral or bilateral) mastectomy.\n Of the 346 women with CPM who responded to national notices, 296 women returned detailed questionnaires. The information obtained included patient demographics, family history, reproductive history, ipsilateral breast cancer staging and treatment, as well as issues involving the CPM.\n At median follow-up of 4.9 years, the respondents were primarily married (79%), white (97%) women who had some level of college education or above (81%). These women cited the following reasons for choosing CPM: (1) physician advice regarding the high risk of developing contralateral breast cancer (30%); (2) fear of developing more breast cancer (14%); (3) desire for cosmetic symmetry (10%); (4) family history (7%); (5) fibrocystic breast disease (4%); (6) a combination of all of these reasons (32%); (7) other (2%); and (8) unknown (1%). Eighteen of the 296 women (6%) expressed regrets regarding their decision to undergo CPM. Unlike women with bilateral prophylactic mastectomies, regrets tended to be less common in the women with whom the discussion of CPM had been initiated by their physician (5%) than in the women who had initiated the discussion themselves (8%) (P = ns). Family history and stage of index lesion had no impact on regret status. The reasons for regret included: (1) poor cosmetic result, either of the CPM or of the reconstruction (39%); (2) diminished sense of sexuality (22%); (3) lack of education regarding alternative surveillance methods or CPM efficacy (22%); and (4) other reasons (17%).\n To minimize the risk of regrets in women contemplating CPM, it is imperative that these women be counseled regarding an estimation of contralateral breast cancer risk, the alternatives to CPM, and the efficacy of CPM. In addition, these women should have realistic expectations of the cosmetic outcomes of surgery and understand the potential impact on their body image.", "Management of the contralateral normal-appearing breast in a patient with ipsilateral invasive lobular carcinoma (ILC) is controversial.\n The case histories of patients with histologically proven ILC who underwent definitive surgery at our institution from 1978 to 1991 were retrospectively reviewed.\n Of the 419 women with ILC, 36 (8.6%) had bilateral cancer, with a cumulative risk of 10% at 10 years. Twenty-five (69%) of these cancers were suspected before operation. From 105 contralateral prophylactic surgical procedures, seven (64%) in-situ and four (36%) invasive cancers were detected. The age at presentation and multifocality of the index cancer were significantly different between patients with unilateral and those with bilateral cancers. No survival difference was noted between patients whose contralateral cancers were suspected clinically and those whose cancers were detected prophylactically. Survival rates between patients with unilateral versus bilateral cancers were also not different. However, patients with contralateral prophylactic surgery had a better prognosis than those with unilateral tumors and no prophylaxis.\n Ten percent of patients with ILC experienced bilateral cancers during a period of 10 years. Survival was not influenced by the development of a second cancer, but it improved with surgical prophylaxis.", "Increasingly women at high risk of breast cancer are opting for prophylactic surgery to reduce their risks. Data from 10 European centres that offer a risk counselling and screening service to women at risk show different approaches to the option of preventive surgery, although most centres adhere to a protocol including at least two risk counselling sessions and a psychological assessment. Thus far the combined centres have data on 174 women who have undergone prophylactic mastectomy with in excess of 400 women years of follow up. Operations were carried out on women with lifetime risks of 25-80%, with an average annual expected incidence rate of 1% per women. No breast cancers have occurred in this cohort. Long term follow up on an extended group of women will be necessary to truly address the risk of subsequent breast cancer and the psychological sequelae.", "Bilateral prophylactic mastectomy significantly decreases breast cancer risk, but complications of the procedure have only been described in single-site studies. We describe the frequency and type of complications in women who underwent bilateral prophylactic mastectomy in a multisite community-based cohort.\n Women aged 18-80 years undergoing bilateral prophylactic mastectomy without a personal history of breast cancer at one of six health plans were eligible. We identified women from automated data sources, then reviewed hospital data, ambulatory notes, and other chart elements to confirm eligibility and obtain all charted information about complications and surgeries performed after prophylactic mastectomy, including reconstructive procedures. Reconstructions were characterized by type (implant vs. tissue graft). Complications were noted for a 1-year period after any surgical procedure.\n We identified 269 women with prophylactic mastectomy who were followed for a mean of 7.4 years. Their mean age was 44.9 years. Nearly 80% undertook reconstruction, most with prosthetic implants. One or more complications occurred in 64%. The most common complications were pain (35% of women), infection (17%), and seroma (17%). Women with no reconstruction had fewer complications (mean of .93) than women who had implant (2.0) or tissue graft (2.4) reconstruction procedures (differences from no reconstruction: 1.07 [95% confidence interval = 0.36 to 1.77] and 1.50 [95% confidence interval = 0.44 to 2.56] respectively). Delay of reconstruction after mastectomy was associated with a borderline-significant higher risk of complications (80.6%) compared to simultaneous reconstruction (64.0%, P = .055).\n We found that almost two-thirds of women undergoing bilateral prophylactic mastectomy had at least one complication following surgery. Further work should be done to minimize and to understand the effect of complications of bilateral prophylactic mastectomy." ]

[ "17353403", "9591958", "8205276" ]

[ "Beta carotene supplementation and age-related maculopathy in a randomized trial of US physicians.", "Six-year supplementation with alpha-tocopherol and beta-carotene and age-related maculopathy.", "Randomized trials of primary prevention of cardiovascular disease in women. An investigator's view." ]

[ "To test whether beta carotene supplementation affects the incidence of age-related maculopathy (ARM) in a large-scale randomized trial.\n Randomized, double-masked, placebo-controlled trial among 22 071 apparently healthy US male physicians aged 40 to 84 years. Participants were randomly assigned to receive beta carotene (50 mg every other day) or placebo. Main Outcome Measure Incident ARM responsible for a reduction in best-corrected visual acuity to 20/30 or worse.\n After 12 years of treatment and follow-up, there were 162 cases of ARM in the beta carotene group vs 170 cases in the placebo group (relative risk [RR], 0.96; 95% confidence interval [CI], 0.78-1.20). The results were similar for the secondary end points of ARM with or without vision loss (275 vs 274 cases; RR, 1.01; 95% CI, 0.86-1.20) and advanced ARM (63 vs 66 cases; RR, 0.97; 95% CI, 0.69-1.37).\n These randomized data relative to 12 years of treatment among a large population of apparently healthy men indicate that beta carotene supplementation has no beneficial or harmful effect on the incidence of ARM. Long-term supplemental use of beta carotene neither decreases nor increases the risk of ARM.", "Animal research and observational studies in man suggest a protective effect of antioxidant vitamins in the development of age-related maculopathy (ARM).\n The ATBC study, a population-based, controlled clinical trial of alpha-tocopherol and beta carotene to prevent lung cancer, took place in Finland between 1984 and 1993. Over 29,000 smoking males aged 50 to 69 years were randomly assigned to alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both of these, or placebo. We performed an end-of-trial ophthalmological examination on a random sample of 941 participants aged 65 years or more from two of the fourteen study areas, to discover if the five to eight-year intervention with alpha-tocopherol and/or beta-carotene had been associated with a difference in ARM prevalence. Age-related maculopathy was assessed using colour photographs of the macula.\n Altogether, 269 cases of ARM were found; there were more cases in the AT group (32%; 75/237), BC group (29%; 68/234), and combined antioxidant group (28%; 73/257) than in the placebo group (25%; 53/213). However, neither substance was significantly associated with the risk of ARM in a logistic regression analysis controlling for possible risk factors.\n No beneficial effect of long-term supplementation with alpha-tocopherol or beta-carotene on the occurrence of ARM was detected among smoking males.", "In recent years, increasing attention has focused on the need for more research to be conducted in women on health issues directly relevant to women. No one would disagree that the need for such studies is both crucial and timely. However, while the need for more research in women is urgent, the planning and conduct of such studies must always be driven by good science. Specifically, investigations in women may have unique and important scientific and logistic problems which must be recognized and addressed. However, if the trials are well designed and conducted, they will provide a sound and reliable body of data upon which to base rational clinical decision making and public health recommendations for women from women. These general issues are discussed in the context of a particular trial, the Women's Health Study, a randomized trial of the risks and benefits of low-dose aspirin, beta-carotene and vitamin E in the primary prevention of cardiovascular disease and cancer among healthy women." ]

[ "10649160" ]

[ "A pilot randomized controlled trial of two regimens of fetal surveillance for small-for-gestational-age fetuses with normal results of umbilical artery doppler velocimetry." ]

[ "This study was undertaken to determine whether the frequency of fetal surveillance could be safely reduced from twice weekly to fortnightly in the case of small-for-gestational-age fetuses with normal results of umbilical artery Doppler velocimetry studies.\n Pregnant women between 24 and 36 weeks' gestation (n = 167) with small-for-gestational-age fetuses and normal results of umbilical artery Doppler velocimetry studies were randomly allocated to undergo twice-weekly or fortnightly fetal surveillance. Statistical analysis was carried out according to intention to treat.\n Eighty-five women were randomly assigned to undergo twice-weekly fetal surveillance and 82 were randomly assigned to undergo fortnightly fetal surveillance. Those randomly assigned to twice-weekly surveillance were delivered 4 days earlier (264 vs 268 days; P =.04) and were more likely to have labor induced (n = 70, 82%, vs n = 54, 66%; P =.02) than those randomly assigned to fortnightly surveillance. Fifty-four babies (23%) were admitted to the neonatal nursery, but there were no differences in neonatal morbidity between the groups.\n Maternal intervention (induction) was more common in the twice-weekly group. No differences in neonatal outcomes were detected. A much larger trial is required to determine the safety and potential benefits of less frequent surveillance of small-for gestational-age fetuses with normal results of umbilical artery Doppler velocimetry studies." ]

[ "18085694", "17050564", "5323069", "19572992" ]

[ "Azithromycin does not improve disease course in hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease: a randomized equivalence trial.", "Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial.", "Antibiotic treatment of epidemic bronchiolitis--a double-blind trial.", "Management of bronchiolitis without antibiotics: a multicentre randomized control trial in Bangladesh." ]

[ "Nearly half of all hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) are treated with (parenteral) antibiotics. The present study was designed to test our hypothesis that the use of antibiotics would not lead to a reduced duration of hospitalization in mild to moderate RSV LRTD.\n Seventy-one patients < or =24 months of age with a virologically confirmed clinical diagnosis of RSV LRTD were randomized to azithromycin 10 mg/kg/day (n = 32) or placebo (n = 39) in a multicenter, randomized, double-blind, placebo-controlled equivalence trial during three RSV seasons (2002-2004 through 2005-2006). Primary endpoint was duration of hospitalization, secondary endpoints included duration of oxygen supplementation and nasogastric tube feeding, course of RSV symptom score, number of PICU referrals and number of patients who received additional antibiotic treatment. Data were analyzed according to the intention-to-treat principle using the Mann-Whitney U-test or chi2 test considering P < 0.05 as statistically significant.\n Included patients were comparable with respect to baseline demographics, clinical characteristics, laboratory and roentgenologic investigations. The mean duration of hospitalization was not significantly different between patients treated with azithromycin or placebo (132.0 +/- 10.8 vs. 139.6 +/- 7.7 hr, P = 0.328). Azithromycin was not associated with a stronger resolution of clinical symptoms represented by the RSV symptom score. Four patients were treated with antibiotics after 72 hr, three of them were assigned to placebo (P = 0.406).\n Infants and young children with RSV LRTD do not benefit from routine treatment with antibiotics (ISRCTN number 86554663).\n Copyright 2007 Wiley-Liss, Inc.", "Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract infection in infancy. To date, there is no effective therapy for RSV bronchiolitis. In order to investigate the efficacy of clarithromycin in the treatment of RSV bronchiolitis, the present authors conducted a randomised, double-blind, placebo-controlled trial comparing clarithromycin with placebo in 21 infants with a diagnosis of RSV bronchiolitis. The infants were randomised to receive clarithromycin or placebo daily for 3 weeks. Levels of interleukin (IL)-4, IL-8, eotaxin, and interferon-gamma were determined in plasma, before and after treatment, using ELISA. Six months after treatment, parents were surveyed as to whether their child had experienced wheezing within the previous 6 months. Treatment with clarithromycin was associated with a statistically significant reduction in the length of hospital stay, the duration of need for supplemental oxygen and the need for beta(2)-agonist treatment. There were significant decreases in plasma IL-4, IL-8 and eotaxin levels after 3 weeks of treatment with clarithromycin. Readmission to the hospital within 6 months after discharge was significantly lower in the clarithromycin group. In conclusion, clarithromycin has statistically significant effects on the clinical and laboratory findings in respiratory syncytial virus bronchiolitis. Therefore, clarithromycin treatment may be helpful in reducing the short-term effects of respiratory syncytial virus bronchiolitis.", "nan", "To ascertain that antibiotics have no role in the management of bronchiolitis.\n Multicentre randomized control trial (RCT).\n Five purposively selected teaching hospitals in Bangladesh.\n Children under 24 months old with bronchiolitis.\n Children were randomized into three groups of therapeutic interventions: parenteral ampicillin (P-Ab), oral erythromycin (O-Ab) and no antibiotic (N-Ab) in adjunct to supportive measures.\n Clinical improvement was assessed using 18 symptoms/signs which were graded on a two-point recovery scale of 'rapid' and 'gradual', indicating improvement within 'four days' and 'beyond four days', respectively.\n Each intervention group consisted of 98 +/- 1 children having comparable clinico-epidemiological characteristics at the baseline. The trial revealed that most chesty features (features appearing to arise from chest, i.e. cough, breathing difficulty, wheeze, chest indrawing, tachypnoea, tachycardia, rhonchi and crepitation) demonstrated a gradual recovery, beyond 4th admission day and, not differing among the three intervention groups (p > 0.23, p < 0.62, p = 0.54, p < 0.27, p = 0.75, p = 0.76, p = 0.81, p > 0.98, respectively). Most non-chesty features (features appearing to arise away from chest, i.e. feeding/sleeping difficulties, social smile, restlessness, inconsolable crying, nasal flaring, fever and hypoxaemia) demonstrated a rapid recovery, within 4 days, remaining comparable among the three intervention groups (p < 0.07, p = 0.65, p = 0.24, p < 0.61, p = 0.22, p = 0.84, p = 0.29 and p = 0.96, respectively). However, nasal symptoms (runny nose and nasal blockage) also showed no difference among groups (p = 0.36 and p = 0.66, respectively). Thus, the dynamics of clinical outcome obviates that children not receiving antibiotics had similar clinical outcome than those who did.\n In hospital settings, managing bronchiolitis with only supportive measures but without antibiotics remains preferable." ]

[ "7618387", "4622149", "8876883", "2675768", "871980", "15197202", "8961989", "6423263", "8433024", "8500374", "7995145", "7530469", "14728936", "6360300", "2752859", "2245382", "12905554", "3521832", "16983741", "7712435" ]

[ "Local recurrence of rectal cancer following preoperative irradiation.", "Preoperative irradiation of rectosigmoid carcinoma including its regional lymph nodes.", "Randomized study on preoperative radiotherapy in rectal carcinoma. Stockholm Colorectal Cancer Study Group.", "[Comparison of surgical therapy and combined irradiation in rectal cancer--first report, effect of irradiation on the tumor. Study Group of Surgical Therapy and Combined Irradiation in Rectal Cancer].", "Preoperative irradiation in operable cancer of the rectum: report of the Toronto trial.", "Improved sphincter preservation in low rectal cancer with high-dose preoperative radiotherapy: the lyon R96-02 randomized trial.", "Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Medical Research Council Rectal Cancer Working Party.", "Final results of a randomized trial on the treatment of rectal cancer with preoperative radiotherapy alone or in combination with 5-fluorouracil, followed by radical surgery. Trial of the European Organization on Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group.", "Combination preoperative radiation and endocavitary hyperthermia for rectal cancer: long-term results of 44 patients.", "Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects.", "Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma. Results of a prospective, randomized trial.", "Long-term results of a randomised trial of short-course low-dose adjuvant pre-operative radiotherapy for rectal cancer: reduction in local treatment failure.", "Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group.", "The evaluation of low dose pre-operative X-ray therapy in the management of operable rectal cancer; results of a randomly controlled trial.", "A comparison of nonoperative vs. preoperative radiotherapy in rectal carcinoma. A 10-year randomized trial.", "Low-dose preoperative radiation postpones recurrences in operable rectal cancer. Results of a randomized multicenter trial in western Norway.", "Long-term results of the Lyons R90-01 randomized trial of preoperative radiotherapy with delayed surgery and its effect on sphincter-saving surgery in rectal cancer.", "Preoperative radiation and surgery for cancer of the rectum. Veterans Administration Surgical Oncology Group Trial II.", "Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer.", "The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study Group." ]

[ "The authors investigated local recurrence of rectal cancer in patients' groups preoperatively irradiated (40-50 Gy) or treated by surgery alone. In advanced disease both treatment groups were administered postoperative chemotherapy, too. Local recurrence was observed in 30.2% in patients treated by surgery alone, while it dropped to 11.65% in the patients' group subjected to radiation therapy prior to surgery (p < 0.05). Impairment of degree of differentiation resulted in an enhanced number of recurrences in both groups, even if they appeared later in irradiated patients.", "nan", "A population based prospective randomized trial on preoperative radiotherapy in operable rectal cancer was conducted in Stockholm, Sweden. Five hundred fifty-seven patients from 12 institutions were included with histologically proven, clinically resectable rectal adenocarcinoma. Patients planned for local excision or previously irradiated to the pelvis were excluded.\n A total of 272 patients were allocated to preoperative irradiation with 25 Gy in five cycles during 5-7 days to the rectum and the pararectal tissues (RT+ group) and 285 patients were allocated to surgery only (RT- group). The median follow-up time was 50 months. No patient was lost to follow-up. Surgery was considered curative in 479 patients (86%).\n Locoregional recurrence occurred in 10% of the patients in the RT+ group versus 21% in the RT- group (p < 0.01). Among the curatively operated patients, distant metastases occurred in 19% in the RT+ group versus 26% in the RT- group (p = 0.02). The overall survival was improved in the irradiated patients (p = 0.02). Postoperative complications were more common after irradiation but were usually mild. The postoperative mortality was low in both groups.\n Preoperative short-term, high-dose radiotherapy as given in this trial reduces the risk of local and distant recurrence and improves survival after curative surgery for rectal carcinoma.", "In order to establish the best protocol for the treatment of rectal cancers, a cooperative study on preoperative radiation therapy was conducted by 44 institutions in eastern Japan. A total of 166 cases that did not receive preoperative chemotherapy were analyzed, and the following conclusions were obtained. A comparison between two groups of patients, one that had received preoperative irradiation and the other that had not, revealed remarkable tumor regression in the former along with reduction of in rectal stenosis, condition of the border of the lesion, bleeding, constriction and central excavation. There were no significant differences between the two groups in terms of lymph node metastasis. Histological examination based on the criteria established by Oboshi and Shimosato showed radiation effects better than grade II b in 32.1% primary tumors and in 33.3% of metastatic lymph nodes within the radiation field. No significant differences in the incidence of side effects or complications were noted between the two groups.", "The authors have studied the value of preoperative radiotherapy in 125 patients with cancer of the rectum. The patients were divided into two groups, control (no irradiation) and experimental (irradiation), and according to Dukes' pathological stage. The crude survival indicated no difference between the two groups, but analysis by stage and group demonstrated that for patients with a Dukes' stage C lesion, 500 rads of cobalt-60 gamma irradiation a few hours before excision of the lesion approximately doubles the probability of survival at 5 years. The prospect of surgical cure is three times higher in cancers arising above the peritoneal reflection than in those arising below it. If the practice of abdominoperineal resection is to continue the authors recommend that preoperative irradiation become a routine procedure.", "The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial. The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures.\n Patients with rectal carcinoma located in the lower rectum, staged T2 or T3, Nx, or M0 with endorectal sonography, and not involving more than two-thirds circumference, were randomly assigned to one of two groups: preoperative external-beam radiotherapy (EBRT; 39 Gy in 13 fractions over 17 days) versus the same EBRT with boost (85 Gy in three fractions) using endocavitary contact x-ray.\n Between 1996 and 2001, 88 patients were enrolled onto the study. A significant improvement was seen in favor of the contact x-ray boost for complete clinical response (24% v 2%) and for a complete or near-complete sterilization of the operative specimen (57% v 34%). A significant increase in sphincter preservation was observed in the boost group (76% v 44%; P =.004). At a median follow-up of 35 months, there was no difference in morbidity, local relapse, and 2-year overall survival.\n A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome.", "Survival rates after surgery for rectal cancer remain at about 40% at 5 years from diagnosis. The aim of this study was to find out whether local recurrence rate could be reduced and survival increased by a moderately high dose of preoperative radiotherapy in patients with locally advanced, but otherwise operable, carcinoma of the rectum.\n We carried out a prospective randomised trial of surgery alone (n = 140) versus surgery preceded by 40 Gy radiotherapy (n = 139) given in 20 fractions of 2 Gy over 4 weeks. The patients, from 20 regional centres throughout the UK, were enrolled between 1981 and 1989, and followed up for a minimum of 5 years or to death.\n 217 patients died, 114 of 140 allocated surgery alone and 103 of 139 allocated preoperative radiotherapy: median survival times were 24 months and 31 months, respectively. The hazard ratio for overall survival was 0.79 (95% CI 0.60-1.04, p = 0.10). At 5 years' follow-up 65 patients allocated surgery alone and 50 who received preoperative radiotherapy had local recurrence (hazard ratio 0.68 [0.47-0.98], p = 0.04); the corresponding numbers of patients with distant recurrence were 67 and 49 (hazard ratio 0.66 [0.46-0.95], p = 0.02). There was a significant benefit of radiotherapy on disease-free survival (hazard ratio 0.76 [0.58-1.0], p = 0.05). There was no increase in postoperative or late complications in the radiotherapy group.\n Our results provide further evidence that preoperative radiotherapy can reduce the rate of local recurrence of rectal cancer in patients with locally advanced disease. However, survival results are still equivocal, and so we must await the results of a meta-analysis of all radiotherapy trials from which precise and definitive results, particularly for survival, may be obtained.", "To improve surgical results of potentially operable rectal cancer, the European Organization on Research and Treatment of Cancer conducted a two-arm randomized clinical trial to compare the efficiency of preoperative administration of radiotherapy, with or without 5-fluorouracil before radical surgery. Two hundred forty-seven eligible patients were admitted from November 1972 through April 1976. The overall survival observed in the group treated with preoperative radiotherapy appears to be better than in the group of patients where preoperative combined modality was administered. Five-year survival is 59% versus 46% with a marginal statistical significance of P = 0.06. Although the combined modality arm had a higher incidence of side effects and postoperative deaths, it had a greater effect than the radiotherapy-alone arm in controlling the disease process, mainly distant metastases to the liver with a result bordering on statistical significance (P = 0.07). The incidence of nonmalignant and intercurrent deaths were higher in the combined modality group, whereas deaths due to malignancy were higher in the radiotherapy-alone group. Observing more stringent selection in disease and patients' criteria, side effects and intercurrent deaths can be effectively reduced with further improvement in adjuvant therapy results.", "Long-term results of 122 patients with advanced rectal cancer who were randomly treated with three different methods from July 1984 to July 1986. Of 122 patients, 44 were treated with endocavitary 915 MHz microwave applicators combined with 10 MeV X-ray or 60CO followed by surgery (group A), 38 with preoperative radiation (group B) and 40 with surgery (group C) as a control group. The temperature on the surface of the applicator touching the middle of the caudad to cephaladic extent of disease was 45-50 degrees C for 45 min twice a week for 6-8 sessions. Radiation dose was 30 Gy or 40 Gy/4 weeks. Of cases with stages 0 and A, 45.5% (20/44) were in group A, 23.7% (9/38) in group B and 12.5% (5/40) in group C (chi 2 test p < 0.05 and p < 0.01, respectively). Five-year survival rate was 66.7% (24/36) in group A, 50% (14/28) in group B and 40.5% (15/37) in group C. Percentage of survival at 5 years was 73.7% (14/19) for 40 Gy plus heat, 57.1% (8/14) for 40 Gy alone, 58.8% (10/17) for 30 Gy plus heat, and 42.9% (6/14) for 30 Gy alone. Data suggest a survival advantage for patients treated with preoperative radiation combined with endocavitary hyperthermia.", "From 1980 to 1985, 471 patients with resectable rectal and rectosigmoid cancer were randomly allocated to receive either preoperative short-term high-dose irradiation (25.5 Gy in one week) for all patients or prolonged postoperative radiotherapy (60 Gy in seven to eight weeks) only for patients with a Dukes B or C lesion. After a minimum follow-up of five years, the local recurrence rate was statistically significantly lower after preoperative than after postoperative radiotherapy (13 percent vs. 22 percent; P = 0.02). No difference in overall survival was noted (P = 0.5). To evaluate possible late side effects on the bowel, urinary bladder, or skin after surgery and additional preoperative or postoperative radiotherapy, all patients included in the randomized trial, together with 58 patients from a preceding pilot study with the same preoperative regimen, were studied in a prolonged follow-up program. The hospital files of all patients were re-examined. Of the patients who were carefully examined, 176 had a survival exceeding five years and 19 had a survival exceeding 10 years. Overall, 7 percent (33/464) either were operated upon or have had a radiologic diagnosis of small bowel obstruction: 14/255 (5 percent) after preoperative irradiation, 14/127 (11 percent) after postoperative irradiation, and 5/82 (6 percent) after surgery alone. The cumulative risk of developing a bowel obstruction was significantly increased after postoperative radiotherapy. Among the 98 patients alive after preoperative irradiation, significant morbidity from the bowel was noted in 11 patients, from the urinary bladder in two, and from the skin in six. In the postoperatively treated group of 34 patients, the bowel, urinary bladder, and skin morbidity were significant in five, two, and five patients, respectively. Corresponding morbidity in 44 nonirradiated patients was seen in five, one, and two patients, respectively. It is concluded that preoperative, short-term, high-dose radiotherapy decreases the local recurrence rate relative to postoperative radiotherapy, with no indications of increased late morbidity after a follow-up of 5 to 10 years.", "A prospective, randomized clinical trial was conducted by the Northwest Rectal Cancer Group to study the effects of preoperative radiotherapy given one week before surgery in locally advanced (tethered or fixed) rectal carcinoma.\n A total of 284 patients were entered into the trial between 1982 and 1986; 141 were allocated to receive surgical treatment alone, and 143 were allocated to receive preoperative radiotherapy. A 10 x 10 x 10 cm volume in the posterior pelvis, centered on the tumor, was irradiated at a dose of 20 Gy, divided into four daily fractions of 5 Gy each.\n No differences were observed in any of the clinicopathologic variables in the two arms of the trial; there were no striking down-staging effects in the irradiated tumors. After a minimum follow-up period of 96 months, the overall and cancer-related mortality rates were similar in both arms of the study (P = 0.21 and P = 0.09, respectively). There was a highly significant reduction in local recurrences in the irradiated group (12.8 percent x-ray therapy vs. 36.5 percent surgery; P = 0.0001). The majority of local recurrences after preoperative radiotherapy occurred inside the radiotherapy field (10 cases; 7 percent), with only six cases (5 percent) outside the field. No significant difference was observed in the rates of distant metastasis between the two treatment groups (P = 0.73).\n Although there is no statistically significant survival benefit in the whole series, there is a survival benefit for the subset of patients considered by the surgeon to have undergone a curative operation. We recommend that this form of adjuvant therapy should be offered to all patients with locally advanced rectal cancer who are to undergo radical surgery.", "A prospective randomised multicentre trial compared pre-operative radiotherapy followed by surgery with surgery alone for rectal cancer < or = 12 cm from the anal verge. Of 468 patients (mean age 67 years, range 31-94, 273 males) who met the entry criteria, 228 were randomised to radiotherapy (3 x 5 Gy over 5 days within 2 days of operation) followed by surgery, and 239 to surgery alone. Randomisation was unknown in 1 patient. Follow-up to death or 5 years was achieved in 454 (97%) patients. 31 (7%) of the 468 patients died within 30 days of operation (radiotherapy and surgery 21 [9%], surgery alone 10 [4%]; P < 0.05). Cardiovascular and thromboembolic complications were more common after radiotherapy and surgery (30, 13%) than after surgery alone (8, 3%; P < 0.005). Of the 280 patients who had curative surgery, 52% of those who had radiotherapy and surgery and 56% of those who had surgery alone survived 5 years (P = 0.88). 395 patients attended outpatients clinics at least once. Local treatment failure was identified during follow-up in 82 patients [31/185 (17%) radiotherapy and surgery; 51/210 (24%) surgery alone; P < 0.05]. It occurred in 33 of the 258 patients who had a curative resection and attended outpatients [radiotherapy and surgery, 11/120 (9%), surgery alone, 22/138 (16%); P = 0.08]. Long-term survival was unaffected, but long-term local recurrence was reduced by the addition of low-dose radiotherapy to surgery. Peri-operative mortality was, however, increased.", "The European Organisation for Research and Treatment of Cancer (EORTC) 22921 four-arm randomised trial questioned the value of preoperative chemoradiation (XRT-CT) versus preoperative radiation (XRT) and the value of additional postoperative chemotherapy (CT) versus none in T3-T4 M0 resectable rectal cancer patients. We report on the preoperative toxicity, treatment compliance and early deaths (all deaths up to 30 days after surgery) of the two treatment modalities in patients who were entered into trial before January 2001. In the XRT Group (group A), patients received 45 Gy, 25 fractions over 5 weeks. In the XRT-CT Group (group B), two 5-day courses of CT were added to the first and fifth weeks of XRT. For each CT course: 5-fluorouracil (5-FU) 350 mg/m2/day and Leucovorin (LV) 20 mg/m2/day were given. 398 and 400 patients started treatment in groups A and B, respectively. Grade 2+acute diarrhoea occurred in 17.3 and 34.3% of patients in groups A and B, respectively (P<0.005). The other side-effects remained unchanged or were only marginally increased. The compliance with RT was 98.5 and 95.5% in groups A and B, respectively. In group B, 78.7 and 71.1% of the patients received 95-105% of the planned CT doses at the first and second courses, respectively. 6 patients died preoperatively, 2 from toxicity in group B. 8 patients (1%) died within the 30 days after surgery in both groups. At the doses recommended in the protocol, the addition of 5-FU-LV to preoperative XRT slightly increased the amount of acute toxicity. However, the compliance with the radiation protocol or the feasibility of surgery did not decrease.", "824 patients with operable rectal carcinoma were randomly allocated to be treated by surgery alone, 2000 rad in 10 daily fractions and 500 rad as a single fraction. No difference has been demonstrated in the actuarial survival rates to 5 years. The local recurrence-free and metastasis-free rates are similar in all groups. There is also no evidence that the pre-operative radiotherapy benefited patients in subgroups by Dukes' stage. The complication rates were also similar in the three treatment groups.", "From 1978 to 1980, 68 patients with rectal cancer were randomly allocated to either preoperative irradiation plus surgery or surgical treatment without any preoperative measures. The primary aim of the trial was to investigate the 5-year survival rate in both groups; a secondary aim was to analyze the local recurrence rate and finally the anatomopathologic tumoral classification after surgery. All patients were followed at least 8 years. The preoperative irradiation group (Group A) was submitted to 4000 cGy for 4 weeks and surgery was performed 1 week after irradiation. All tumors were classified anatomically and pathologically according to Broders' and Dukes' classifications. The results indicated that there is a significant difference in the five-year survival rates in both groups: group A had a corrected survival rate of 80 percent; group B (nonirradiated) had a corrected survival rate of 80 percent; group B (nonirradiated) had a corrected survival rate of 34.4 percent. The local recurrence rate was 2.9 percent in group A and 23.5 percent in group B. Regarding tumor regression, before radiotherapy 64.6 percent of the tumors were Broders' Grades 3 and 4; after radiotherapy these were reduced to 20.5 percent. As to Dukes' classification, 26.4 percent of the tumors were type C in group A and, in group B, 47 percent were considered as Dukes' C.", "A randomized, multicenter clinical trial was conducted in Western Norway to study the effectiveness of preoperative radiation therapy in operable rectal cancer, given at a dosage of 3150 cGy in 18 fractions, 2 to 3 weeks before radical surgery. Three hundred nine patients were entered into the trial between May 1976 and December 1985. After radiation no tumor was seen in 4.5% of the patients. There was no increased morbidity or mortality at surgery. The 5-year survival for evaluable patients was 57.5% in the control group and 56.7% in the radiotherapy group. For patients operated on for cure the 5-year survival was 60.9% and 64.2% in the control group and radiotherapy group, respectively. Radiation significantly delayed both local and distant recurrences in patients in the radiation group who had curative resection from 13.3 months in controls to 27.1 months. The local recurrence rate in the corresponding groups was 21.1% and 13.7%, respectively. We conclude that higher preoperative radiation doses should be used in new trials as a higher dosage may transform the observed positive effects into a survival benefit.", "nan", "In a prospective randomized trial, 361 male patients with histologically proven adenocarcinoma of the rectum, judged preoperatively to require abdominoperineal resection (APR), were treated by surgery alone or were given 3,150 rads of preoperative radiotherapy. Surgical resection was done on 320 patients, 262 having \"curative\" APR. Only moderate symptoms from radiotherapy were noted and postoperative complications and 30-day mortality were similar in both groups. Five-year survival for curative APR was the same in both groups (50% for both treated and control patients). The incidence of positive lymph nodes in the resected specimens was 35% in treated and 41% in controls. In the first preoperative radiotherapy trial conducted by the group, 5-year survival in patients undergoing \"curative\" APR was 47% in treated versus 34% in control groups. Additionally, the difference in positive lymph nodes in the resected specimens was substantially greater in the first trial (26% in treated versus 44% in controls).", "Neoadjuvant chemoradiotherapy does not alter anal sphincter preservation or postoperative complications compared with short-course radiotherapy alone in patients with clinical stage T3 or T4 resectable rectal cancer. The aim of this study was to compare survival, local control and late toxicity in the two treatment groups.\n The study randomized 312 patients to receive either preoperative irradiation (25 Gy in five fractions of 5 Gy) and surgery within 7 days or chemoradiation (50.4 Gy in 28 fractions of 1.8 Gy, bolus 5-fluorouracil and leucovorin) and surgery 4-6 weeks later. The median follow-up of living patients was 48 (range 31-69) months.\n Early radiation toxicity was higher in the chemoradiation group (18.2 versus 3.2 per cent; P < 0.001). The actuarial 4-year overall survival was 67.2 per cent in the short-course group and 66.2 per cent in the chemoradiation group (P = 0.960). Disease-free survival was 58.4 versus 55.6 per cent (P = 0.820), crude incidence of local recurrence was 9.0 versus 14.2 per cent (P = 0.170) and severe late toxicity was 10.1 versus 7.1 per cent (P = 0.360) respectively.\n Neoadjuvant chemoradiation did not increase survival, local control or late toxicity compared with short-course radiotherapy alone.", "From 1980 to 1987, 849 patients with clinically resectable rectal adenocarcinoma were randomized into a controlled clinical trial to evaluate the role of preoperative radiotherapy.\n Patients were given either 25 Gy during 5 to 7 days before surgery or underwent surgery alone.\n At a median follow-up time of 107 months (range, 62-144 months) the incidence of pelvic recurrence among 684 \"curatively\" operated patients was significantly lower among those who also received radiotherapy (P < 0.001) in all Dukes' stages. No significant difference was observed between the treatment groups with regard to frequency of distant metastases or overall survival. The time to local recurrence or distant metastasis and survival was significantly prolonged in the irradiated group. However, the postoperative mortality was 8% in the radiotherapy group compared with 2% in the surgery only group (P = 0.01).\n Preoperative short term radiotherapy reduced the incidence of pelvic recurrences and prolonged survival related to rectal cancer compared with surgery alone. The postoperative morbidity was significantly higher in the irradiated group." ]

[ "14268039", "16536100" ]

[ "VALUE OF SHAVING THE PUDENDAL-PERINEAL AREA IN DELIVERY PREPARATION.", "Randomised controlled trial of perineal shaving versus hair cutting in parturients on admission in labor." ]

[ "nan", "To compare the maternal and neonatal outcomes between perineal shaving and hair cutting in parturients on admission in labor\n Five hundred pregnant women with labor pain and no medical or obstetric complications were selected at random on admission to be assigned into two groups at Rajavithi Hospital from 1st November 2001 to 28th February 2002. Forty two women were excluded because of cesarean section. Two hundred and twenty-seven cases received perineal hair cutting and 231 cases received perineal shaving.\n The gestational age at delivery was statistically significant difference between those receiving perineal hair cutting (39.4 week) comparing with those receiving perineal shaving (39.1 week) (p < 0.05). There was no statistically significant difference in 2 groups for puerperal morbidity, perineal wound infection and dehiscence. There were no neonatal infection and puerperal infection in both groups, where as both accoucheurs and perineorrhaphy operators were more satisfied the perineal shaving group than the cutting group (p < 0.001).\n Perineal shaving or hair cutting on admission in labor had no statistical significant difference effect on the perineal wound infection and dehiscence, neonatal infection, puerperal morbidity and infection." ]

[ "10811511", "15346266", "11487673", "12618680", "16672699", "11200349", "9354709", "17592075" ]

[ "Percutaneous transluminal angioplasty with or without stenting for femoropopliteal occlusions? A randomized controlled study.", "[PTA versus Palmaz stent placement in femoropopliteal artery stenoses: results of a multicenter prospective randomized study (REFSA)].", "Randomized study to compare PTA alone versus PTA with Palmaz stent placement for femoropopliteal lesions.", "Systematic versus selective stent placement after superficial femoral artery balloon angioplasty: a multicenter prospective randomized study.", "Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery.", "PTA versus Palmaz stent placement in femoropopliteal artery obstructions: a multicenter prospective randomized study.", "Balloon angioplasty combined with primary stenting versus balloon angioplasty alone in femoropopliteal obstructions: A comparative randomized study.", "Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST)." ]

[ "To investigate the-one year outcome of PTA and stenting and PTA alone for femoropopliteal occlusions.\n Randomized prospective study\n 32 patients with femoropopliteal occlusions were randomized into two treatment groups: PTA and Strecker-stent (n=15) and PTA alone (n=17). The median age of the patients was 71 years. All patients had chronic limb ischaemia, 66% had tissue loss, 19% had rest pain and 15% had disabling claudication. The median ABPI was 0.45. The occlusion was confined to the superficial femoral artery in 30 cases and to the popliteal artery in 2 cases. The median length of the occlusions was 7.3 cm. Aspirin (ASA), 160 mg daily, was administrated postoperatively but no anticoagulation was used. The follow-up included: clinical examination, measurement of ABPI and control angiography at 12 months or earlier when necessary (20 patients).\n There was no mortality or limb loss as a consequence of the treatment. There were six (16%) immediate major complications in five patients. In the PTA group, one patient had a myocardial infarction and three patients needed arteriography due to bleeding. In the stent group, one patient required arteriography and embolectomy. The one-year mortality was 6% and there were no amputations. Four patients (two in each group) were operated on with a femorodistal bypass. The rate of clinical improvement was 71% after PTA and stent and 60% after PTA alone (p=0.17). An increased ABPI (>0.10) was shown in 50% of the stent group and 61% in the PTA group (p=0.17). Angiographic re-occlusions were seen in 33% and 75% in the stent and PTA groups respectively (p=0.17), while the rate of restenosis was significantly higher in the stent group (50% vs 25%) (p=0.033).\n Stenting following PTA for femoropopliteal occlusions does not significantly improve neither the clinical state nor the clinical/angiographic patency. The results do not justify any routine placement of stent following PTA in the successfully recanalized femoropopliteal arteries. The low rate of acceptance of a follow-up angiography indicates that this kind of study should preferably use duplex scanning instead of angiography for follow-up.", "To evaluate whether stent placement is superior to percutaneous transluminal angioplasty (PTA) in the treatment of chronic symptoms in short femoropopliteal arterial stenoses.\n One hundred twenty-four limbs in 116 patients, who ranged in age from 39 to 87 years (mean age, 67 years), were randomized to PTA (n = 53) versus PTA followed by implantation of long-medium Palmaz-Stents (n = 71). Inclusion criteria were intermittent claudication or chronic critical limb ischemia, short stenosis or occlusion (lesion length < or = 5 cm), and at least one patent run-off vessel at angiography. The follow-up included clinical assessment, measurement of ankle/brachial index (ABI), color duplex ultrasound, and/or angiography at 6, 12 and 24 months. Angiographic follow-up between 12 and 36 months was available in 54 limbs (45 %).\n Initial technical success was achieved in 50 of 53 limbs (94.4 %) in the PTA group versus 70 of 71 limbs (98.6 %) in the stent group. Overall, major complications occurred in 9.5 % (n = 11), with n = 4 in the PTA group compared to n = 7 in the stent group. No difference was found between the groups of treatment: clinical success at 1 and 2 years was 80.5 and 77.1 % in the PTA group versus 78.1 and 71.0 % in the stent group. The cumulative 1-year and 2-year angiographic primary patency rates were 66.1 and 49.1 % in the stent group versus 76.1 and 66.1 % in the PTA group. The secondary 1-year and 2-year angiographic patency rates were 88.5 and 53.3 % in the stent group versus 82.7 % and 76.2 % in the PTA group.\n The primary success rate was slightly higher after stent placement than after PTA. However, the angiographic, clinical and hemodynamic success after 1 and 2 years tends to be slightly better for PTA.", "The purpose of this study was to evaluate whether percutaneous transluminal angioplasty (PTA) combined with Palmaz stent placement provides long-term advantages compared to PTA alone after 34 months of follow-up in the femoropopliteal region.\n Thirty patients randomized to undergo PTA in combination with stent placement and 23 patients randomized to undergo PTA alone were evaluated.\n Mean follow-up (+/-SD) for the PTA group was 33.8 months (+/- 8.7) and for the Palmaz group 29.1 months (+/- 6.2), with a maximum follow-up period of 39 months for both groups. No significant differences in primary or secondary patency rates could be observed at 12 or 39 months. After 39 months, the primary patency rate for PTA alone was 68.4% and the secondary patency rate was 89.5%; the primary patency rate for PTA with stent placement was 62% and the secondary patency rate was 90%.\n The results of this study show that even after a long-term follow up of more than 3 years, PTA with stent placement in the femoropopliteal artery does not produce better results than PTA alone, although it does provide better initial luminal gain after the procedure.", "Outcome with selective or systematic stenting with the Palmaz vascular stent was compared in patients with limb-threatening ischemia or persistent disabling claudication despite medical therapy, with less than 7 cm stenosis or occlusion of the superficial femoral artery.\n This was a multicenter prospective randomized trial with centralized allocation of treatment and independent review of vascular events. The primary end point was presence of more than 50% stenosis at 1-year angiographic follow-up. Secondary end points were survival; occurrence of vascular events in the treated leg; and number of failed procedures, defined as more than 50% stenosis or death at 1 year.\n Two hundred twenty-seven patients were enrolled in the study, 112 in the selective stent group, and 115 in the systematic stent group. Seventeen patients (15%) in the selective stent group received a stent after suboptimal results of percutaneous transluminal angioplasty. Angiograms for 140 patients were available at 1-year follow-up and demonstrated no statistical difference between the two groups; more than 50% stenosis of the dilated site was noted in 21 of 65 patients (32,3%) in the selective stent group and 26 of 75 patients (34.7%) in the systematic stent group (P =.85, Fisher exact test). Survival in the percutaneous transluminal angioplasty and stent groups was, respectively, 92% and 96% at 1 year, 89% and 93% at 2 years, and 82% and 80% at 4 years (P =.40, log-rank test). Survival free of new vascular events in the treated limb was 77% and 65% at 1 year, 70% and 53% at 2 years, and 57% and 44% at 4 years (P =.017, log-rank test). Number of failed procedures at 1 year was 29 of 86 (33%) and 30 of 89 (34%) (P = 0.9).\n Systematic stenting of short stenosis or occlusion of the superficial femoral artery is not justified. Palmaz vascular stent placement should be reserved for use in patients with suboptimal results of balloon angioplasty.", "Because stent implantation for disease of the superficial femoral artery has been associated with high rates of late clinical failure, percutaneous transluminal angioplasty is preferred for endovascular treatment, and stenting is recommended only in the event of suboptimal technical results. We evaluated whether primary implantation of a self-expanding nitinol (nickel-titanium) stent yielded anatomical and clinical benefits superior to those afforded by percutaneous transluminal angioplasty with optional secondary stenting.\n We randomly assigned 104 patients who had severe claudication or chronic limb ischemia due to stenosis or occlusion of the superficial femoral artery to undergo primary stent implantation (51 patients) or angioplasty (53 patients). Restenosis and clinical outcomes were assessed at 6 and 12 months.\n The mean (+/-SD) length of the treated segment was 132+/-71 mm in the stent group and 127+/-55 mm in the angioplasty group. Secondary stenting was performed in 17 of 53 patients (32 percent) in the angioplasty group, in most cases because of a suboptimal result after angioplasty. At 6 months, the rate of restenosis on angiography was 24 percent in the stent group and 43 percent in the angioplasty group (P=0.05); at 12 months the rates on duplex ultrasonography were 37 percent and 63 percent, respectively (P=0.01). Patients in the stent group were able to walk significantly farther on a treadmill at 6 and 12 months than those in the angioplasty group.\n In the intermediate term, treatment of superficial-femoral-artery disease by primary implantation of a self-expanding nitinol stent yielded results that were superior to those with the currently recommended approach of balloon angioplasty with optional secondary stenting. (ClinicalTrials.gov number, NCT00281060.).\n Copyright 2006 Massachusetts Medical Society.", "To evaluate if stent placement is superior to percutaneous transluminal angioplasty (PTA) in the treatment of chronic symptoms in short femoropopliteal arterial lesions.\n One hundred fifty-four limbs in 141 patients who ranged in age from 39 to 87 years (mean age, 67 years) were randomized to PTA (n = 77) versus PTA followed by implantation of Palmaz stents (n = 77). Inclusion criteria were patients with intermittent claudication (n = 108, Society of Vascular Surgery/International Society of Cardiovascular Surgery [SVS-ISCVS] categories 1-3) or chronic critical limb ischemia (n = 46 with either ischemic rest pain [category 4] or minor tissue loss [category 5]), short stenosis or occlusion (lesion length < or = 5 cm), and at least one patent run-off vessel at angiography. Follow-up included clinical assessment, measurement of ankle/ brachial index (ABI), color duplex ultrasound, and/or angiography at 6 or 12 months. Angiographic follow-up between 12 and 36 months was available in 46 limbs (29.9%).\n In the PTA group, initial technical success was achieved in 65 of 77 limbs (84%) versus 76 of 77 (99%) limbs in the stent group (chi2 value = 0.009). Overall, major complications occurred in 3.9% (n = 6); n = 4 in the PTA group compared to n = 2 in the stent group. There was no difference between groups of treatment: hemodynamic/clinical success at 1 and 2 years in the PTA group was 72% and 65% versus 77% and 65% in the stent group (Gehan P value = .26). The cumulative 1- and 2-year angiographic primary patency rates were 63% and 53%, respectively, for both groups. The secondary 1- and 2-year angiographic patency rates were 86% and 74% in the PTA group versus 79% and 73% in the stent group (P = .5).\n After stent placement, the primary success rate was significantly higher than after PTA. However, 1-year angiographic and clinical/hemodynamic success was not improved.", "To evaluate whether balloon angioplasty combined with stenting (ST) of symptomatic femoropopliteal disease would provide better results compared with balloon angioplasty alone (BA).\n Fifty-one patients were randomized between ST (24 patients) and BA (27 patients). Follow-up comprised clinical and hemodynamic assessment and color-flow duplex ultrasound examinations.\n Residual stenosis (> or = 30% diameter reduction) occurred in three BA patients, but not in the ST patients. By life-table analysis the cumulative rate of clinical and hemodynamic success after 1 year with ST was 74% (SE 9%) and for those with BA 85% (SE 7%) (p = 0.25). The primary patency at 1 year assessed by color-flow duplex ultrasound was 62% (SE 9%) for ST-treated patients and 74% (SE 8%) for BA patients (p = 0.22). Occlusion occurred in five ST patients (21%) compared with two BA patients (7%).\n ST does not improve clinical and hemodynamic outcome compared with BA. Moreover, the occlusion rate in ST-treated patients is higher.", "Endoluminal treatment of superficial femoral artery lesions is a matter of controversy. The present study was designed to investigate the impact of nitinol stenting of superficial femoral artery lesions with a maximum length of 10 cm on restenosis and clinical outcomes at 1 year.\n Two hundred forty-four patients (168 men; 66+/-9 years) with a single superficial femoral artery lesion and chronic limb ischemia were randomized to implantation of a single Bard Luminexx 3 stent (123 patients) or stand-alone percutaneous transluminal angioplasty (PTA) (121 patients). Mean lesion length was 45 mm. Technical success (residual stenosis <50% for PTA, <30% for stenting) was achieved in 96 patients assigned to PTA (79%) and 117 patients assigned to stenting (95%); 13 PTA group patients (11%) \"crossed over\" to stenting. At 1 year, the primary end point of ultrasound-assessed binary restenosis was reached in 39 of 101 PTA group patients (38.6%) and 32 of 101 stent group patients (31.7%; absolute treatment difference, -6.9%; 95% CI, -19.7% to 6.2%; P=0.377). Target lesion revascularization rates at 1 year were 18.3% and 14.9%, respectively (absolute treatment difference, -3.3%; 95% CI, -13.0% to 6.4%; P=0.595). No statistically significant difference between treatment groups was observed at 12 months in the improvement by at least 1 Rutherford category of peripheral arterial disease.\n In the present study of patients with short superficial femoral artery lesions, the hypothesized absolute difference of 20% in binary restenosis at 1 year between the implantation of a single Luminexx nitinol stent and stand-alone PTA could not be demonstrated. A smaller difference requiring a larger trial might have been missed." ]

[ "8458457", "7844217" ]

[ "A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate.", "Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles." ]

[ "To determine the relative efficacy of intrauterine insemination (IUI), direct intraperitoneal insemination, and intercourse in cycles stimulated with clomiphene citrate (CC) or human menopausal gonadotropins (hMG).\n A prospective randomized trial with a 2(3) factorial design with eight different treatment alternatives. Only one cycle per couple was performed.\n The Departments of Obstetrics and Gynecology, Central Hospital, Västerås and Akademiska Hospital, Uppsala University, Uppsala, Sweden.\n Of 157 randomized couples with unexplained infertility including 51 cases with minimal or mild endometriosis, 148 were selected for comparison.\n Pregnancy rate (PR).\n Follicular stimulation with hMG gave a higher PR than with CC in the insemination cycles, 19% (10/52) and 4% (2/49), respectively, but the PRs in intercourse cycles were not significantly different for hMG and CC, 13% (3/24) and 17% (4/23), respectively. Insemination cycles and intercourse cycles had a similar overall PR, 12% (12/101) and 13% (7/47), respectively. Furthermore, IUI and direct intraperitoneal insemination did not differ in efficacy.\n Follicular stimulation with hMG is more effective than CC in insemination cycles, but insemination as such seems to have no beneficial effect on the PR in stimulated cycles for treatment of unexplained infertility.", "At present, there is general agreement that ovarian stimulation improves pregnancy rates after intra-uterine insemination (IUI). Also, ovulation induction with gonadotrophins is associated with higher success rates than clomiphene citrate in IUI cycles. However, the drawbacks to the use of gonadotrophin stimulation before IUI include the risks of ovarian hyperstimulation and multiple gestation, and the relative cost of a treatment cycle in a view of the medication costs and the need for increased monitoring by hormone assays and ultrasonographic measurements. In the present prospective randomized trial, the efficacy and safety of ovarian stimulation with clomiphene citrate (50 mg/day for 5 days) and IUI (clomiphene/IUI group) were compared with those of late low-dose pure follicle stimulating hormone (FSH, 75 IU/day from day cycle 7 until the leading follicle reached > 17 mm in diameter) and IUI (FSH/IUI group) in ovulatory women who were infertile because of unexplained infertility (n = 40) or male subfertility (n = 60). The mean length of treatment in the FSH group was 6.4 +/- 2.5 days. Multiple follicular development was seen in 25% of clomiphene-stimulated cycles but only in 8% of those treated with FSH. Pregnancy rate per cycle in clomiphene/IUI and FSH/IUI groups was 4% (4/98) and 13% (12/94) respectively (P = 0.02). All pregnancies obtained were singleton. There were two and one clinical abortions in the clomiphene/IUI (50%) and FSH/IUI (8%) groups respectively. No patient developed ovarian hyperstimulation syndrome. Use of our therapeutic scheme, which proved to be efficacious, safe and economic for ovarian stimulation in IUI cycles, is advocated before the institution of in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT) therapy in infertile patients with patient Fallopian tubes. This late low-dose technique of administering pure FSH is suitable for use in offices without immediate access to oestradiol results." ]

[ "17213237", "19627940", "18084173", "19109447", "12468788", "17204680", "16084808", "19229450", "18467648", "17023237", "19523207" ]

[ "Repetitive locomotor training and physiotherapy improve walking and basic activities of daily living after stroke: a single-blind, randomized multicentre trial (DEutsche GAngtrainerStudie, DEGAS).", "The effectiveness of locomotor therapy using robotic-assisted gait training in subacute stroke patients: a randomized controlled trial.", "Can we improve gait skills in chronic hemiplegics? A randomised control trial with gait trainer.", "Multicenter randomized clinical trial evaluating the effectiveness of the Lokomat in subacute stroke.", "Treadmill training with partial body weight support and an electromechanical gait trainer for restoration of gait in subacute stroke patients: a randomized crossover study.", "Effects of locomotion training with assistance of a robot-driven gait orthosis in hemiparetic patients after stroke: a randomized controlled pilot study.", "The effectiveness of body weight-supported gait training and floor walking in patients with chronic stroke.", "Effects of intensive therapy using gait trainer or floor walking exercises early after stroke.", "Enhanced gait-related improvements after therapist- versus robotic-assisted locomotor training in subjects with chronic stroke: a randomized controlled study.", "Effectiveness of gait training using an electromechanical gait trainer, with and without functional electric stimulation, in subacute stroke: a randomized controlled trial.", "Pilot study of Lokomat versus manual-assisted treadmill training for locomotor recovery post-stroke." ]

[ "To evaluate the effect of repetitive locomotor training on an electromechanical gait trainer plus physiotherapy in subacute stroke patients.\n Randomized controlled trial.\n Four German neurological rehabilitation centres.\n One hundred and fifty-five non-ambulatory patients (first-time stroke <60 days).\n Group A received 20 min locomotor training and 25 min physiotherapy; group B had 45 min physiotherapy every week day for four weeks.\n Primary variables were gait ability (Functional Ambulation Category, 0-5) and the Barthel Index (0-100), blindly assessed at study onset, end, and six months later for follow-up. Responders to the therapy had to become ambulatory (Functional Ambulation Category 4 or 5) or reach a Barthel Index of > or = 75. Secondary variables were walking velocity, endurance, mobility and leg power.\n The intention-to-treat analysis revealed that significantly greater number of patients in group A could walk independently: 41 of 77 versus 17 of 78 in group B (P B < 0.0001) at treatment end. Also, significantly more group A patients had reached a Barthel Index > or = 75: 44 of 77 versus 21 of 78 (P B < 0.0001). At six-month follow-up, the superior gait ability in group A persisted (54 of 77 versus 28 of 78, P B < 0.0001), while the Barthel Index responder rate did not differ. For all secondary variables, group A patients had improved significantly more (P B < 0.0001) during the treatment period, but not during follow-up.\n Intensive locomotor training plus physiotherapy resulted in a significantly better gait ability and daily living competence in subacute stroke patients compared with physiotherapy alone.", "To evaluate the effectiveness of early and prolonged locomotor treatment with the use of a robotic-assisted gait training (RAGT) device (Lokomat; Hocoma Inc., Zurich, Switzerland) on the functional outcomes of patients after subacute stroke.\n A nonblinded prospective, randomized, controlled study.\n Rehabilitation department in tertiary university medical center.\n Sixty-seven patients in the first 3 months after subacute stroke were randomized into 2 groups as follows. Thirty-seven patients were treated with RAGT, and 30 were treated with regular physiotherapy. Inclusion criteria were first stroke, independent ambulation before the stroke, and neurological severity between 6 and 20 according to the National Institutes of Health Stroke Scale (NIHSS).\n RAGT treatment was administered 3 times a week for 30 minutes, combined with regular physiotherapy for 6 weeks. Control patients received the equivalent additional time of regular physiotherapy.\n The primary outcome was the ability to walk independently, as assessed by use of the functional ambulatory capacity scale. The secondary outcomes included the neurological status according to the NIHSS; functional motor assessment (determined by use of the stroke activity scale); and gait parameters, including gait velocity, endurance, and number of climbed stairs.\n In the intention-to-treat analysis, subjects in the RAGT group exhibited greater gains than the control group in their ability to walk independently, as expressed by a greater functional ambulatory capacity score (P < .01), and in their neurological status according to NIHSS (P < .01). Among those who achieved independent walking, nonsignificant differences between groups were noted according to secondary outcome measures of gait parameters except from step climbing.\n This controlled study showed, at the end of a 6-week trial, that locomotor therapy with the use of RAGT combined with regular physiotherapy produced promising effects on functional and motor outcomes in patients after subacute stroke as compared with regular physiotherapy alone.", "Partial body weight support (PBWS) is an accepted treatment for hemiplegic patients. The aim of this study is to compare the efficiency of gait trainer with conventional treatment on the gait management after stroke.\n Forty chronic post-stroke hemiplegics were part of a prospective research. Inclusion criteria were: first ever stroke in a chronic stage with stabilised motor deficits; age >18 and <80 years; cognitive and communication skills to understand the treatment; absence of cardiac, psychological and orthopedic contraindications. Patients were randomised into two groups: the control group (CG) that used the Bobath method in 40 minutes sessions, 5 times a week, for 5 weeks, and the experimental group (EG) that used the gait trainer, for the same period of time and frequency. Assessment tools: Motricity Index (MI); Toulouse Motor Scale (TMS); modified Ashworth Spasticity Scale (mASS); Berg Balance Scale (BBS); Rivermead Mobility Index (RMI); Fugl-Meyer Stroke Scale (F-MSS); Functional Ambulation Category (FAC); Barthel Index (BI); 10 meters, time up and go (TUG), 6 minutes, and step tests. EG and CG did the assessments before treatment (T(0)), right after treatment (T(1)), and on follow-up, 3 months later (T(2)).\n CG and EG were homogenous in all the variables at T(0). CG and EG showed improvement in almost all the assessment scales after treatment, although only some with relevant differences. EG showed statistically relevant improvement on T(1) and on T(2) in several of the assessment tools, whereas CG only showed statistically significant improvement after T(1) and only in some of the assessment tools.\n Both groups of chronic hemiplegic patients improved after either PBWS with gait trainer or Bobath treatment. Only subjects undergoing PBWS with gait trainer maintained functional gain after 3 months.", "To compare the efficacy of robotic-assisted gait training with the Lokomat to conventional gait training in individuals with subacute stroke.\n A total of 63 participants<6 months poststroke with an initial walking speed between 0.1 to 0.6 m/s completed the multicenter, randomized clinical trial. All participants received twenty-four 1-hour sessions of either Lokomat or conventional gait training. Outcome measures were evaluated prior to training, after 12 and 24 sessions, and at a 3-month follow-up exam. Self-selected overground walking speed and distance walked in 6 minutes were the primary outcome measures, whereas secondary outcome measures included balance, mobility and function, cadence and symmetry, level of disability, and quality of life measures.\n Participants who received conventional gait training experienced significantly greater gains in walking speed (P=.002) and distance (P=.03) than those trained on the Lokomat. These differences were maintained at the 3-month follow-up evaluation. Secondary measures were not different between the 2 groups, although a 2-fold greater improvement in cadence was observed in the conventional versus Lokomat group.\n For subacute stroke participants with moderate to severe gait impairments, the diversity of conventional gait training interventions appears to be more effective than robotic-assisted gait training for facilitating returns in walking ability.", "The purpose of this study was to compare treadmill and electromechanical gait trainer therapy in subacute, nonambulatory stroke survivors. The gait trainer was designed to provide nonambulatory subjects the repetitive practice of a gait-like movement without overexerting therapists.\n This was a randomized, controlled study with a crossover design following an A-B-A versus a B-A-B pattern. A consisted of 2 weeks of gait trainer therapy, and B consisted of 2 weeks of treadmill therapy. Thirty nonambulatory hemiparetic patients, 4 to 12 weeks after stroke, were randomly assigned to 1 of the 2 groups receiving locomotor therapy every workday for 15 to 20 minutes for 6 weeks. Weekly gait ability (functional ambulation category [FAC]), gait velocity, and the required physical assistance during both kinds of locomotor therapy were the primary outcome measures, and other motor functions (Rivermead motor assessment score) and ankle spasticity (modified Ashworth score) were the secondary outcome measures. Follow-up occurred 6 months later.\n The groups did not differ at study onset with respect to the clinical characteristics and effector variables. During treatment, the FAC, gait velocity, and Rivermead scores improved in both groups, and ankle spasticity did not change. Median FAC level was 4 (3 to 4) in group A compared with 3 (2 to 3) in group B at the end of treatment (P=0.018), but the difference at 6-month follow up was not significant. The therapeutic effort was less on the gait trainer, with 1 instead of 2 therapists assisting the patient at study onset. All but seven patients preferred the gait trainer.\n The newly developed gait trainer was at least as effective as treadmill therapy with partial body weight support while requiring less input from the therapist. Further studies are warranted.", "The success of gait rehabilitation after stroke depends on active walking exercises. However, the disabling after-effects of stroke often make such exercises impossible at the onset of therapy. To facilitate treadmill training of paraparetic patients, a robot-driven gait orthosis (Lokomat) was developed. We investigated the effects of the Lokomat when used with hemiparetic patients.\n The authors conducted a randomized, controlled pilot study of 30 acute stroke survivors. The treatment group received 30 minutes of robotic training daily and the control group 30 minutes of conventional physiotherapy daily in addition to 30 minutes of conventional physiotherapy for each group. Outcome measures were independence of gait, gait speed, gait parameters, and body tissue composition.\n After 4 weeks of therapy, the walking ability of the Lokomat group and the control group expressed as the functional ambulation classification was significantly improved. The functional ambulation category (median+/- interquartile range) was at baseline 0+/-0 in control and 0+/-1 in the therapy group and increased after therapy to 1+/-3 in both groups significantly (P=0.01). There was no significant difference in gain of these parameters between the groups. The Lokomat group had a significantly longer single stance phase (sec; mean+/-SEM) on the paretic leg when walking on the floor. At baseline, it was 0.19+/-0.17 and after therapy 0.49+/-0.07 (P=0.014). The control group had increased their body weight approximately 1.33+/-1.40 kg (mean+/-SEM; P=0.046), mostly as fat mass, whereas the Lokomat group had lost fat mass approximately -2.9+/-1.0 kg (mean+/-SEM; P=0.016) and increased their muscle mass approximately 3.36+/-1.4 kg (mean+/- SEM; P=0.031).\n This pilot study indicates that Lokomat therapy is a promising intervention for gait rehabilitation. Although there was no difference between groups in gain of functional scores, the Lokomat group showed an advantage of robotic training over conventional physiotherapy in improvement of gait abnormality and body tissue composition.", "To compare body weight-supported exercise on a gait trainer with walking exercise overground.\n Randomized controlled trial.\n Rehabilitation hospital.\n Forty-five ambulatory patients with chronic stroke.\n Patients were randomized to 3 groups: (1) gait trainer exercise with functional electric stimulation (GTstim), (2) gait trainer exercise without stimulation (GT), and (3) walking overground (WALK). All patients practiced gait for 15 sessions during 3 weeks (each session, 20 min), and they received additional physiotherapy 55 minutes daily.\n Ten-meter walk test (10MWT), six-minute walk test (6MWT), lower-limb spasticity and muscle force, postural sway tests, Modified Motor Assessment Scale (MMAS), and FIM instrument scores were recorded before, during, and after the rehabilitation and at 6 months follow-up.\n The mean walking distance using the gait trainer was 6900+/-1200 m in the GTstim group and 6500+/-1700 m in GT group. In the WALK group, the distance was 4800+/-2800 m, which was less than the walking distance obtained in the GTstim group (P=.027). The body-weight support was individually reduced from 30% to 9% of the body weight over the course of the program. In the pooled 45 patients, the 10MWT (P<.001), 6MWT (P<.001), MMAS (P<.001), dynamic balance test time (P<.001), and test trip (P=.005) scores improved; however, no differences were found between the groups.\n Both the body weight-supported training and walking exercise training programs resulted in faster gait after the intensive rehabilitation program. Patients' motor performance remained improved at the follow-up.", "To analyse the effects of gait therapy for patients after acute stroke in a randomized controlled trial.\n Fifty-six patients with a mean of 8 days post-stroke participated in: (i) gait trainer exercise; (ii) walking training over ground; or (iii) conventional treatment. Patients in the gait trainer exercise and walking groups practiced gait for 15 sessions over 3 weeks and received additional physiotherapy. Functional Ambulatory Category and several secondary outcome measures assessing gait and mobility were administered before and after rehabilitation and at 6-month follow-up. Patients also evaluated their own effort.\n Walking ability improved more with intensive walk training compared with conventional treatment; median Functional Ambulatory Category was zero in all patients at the start of the study, but it was 3 in both walk-training groups and 0.5 in the conventional treatment group at the end of the therapy. Median Functional Ambulatory Category was 4 in both walk-training groups and 2.5 in conventional treatment group at 6-month follow-up. Mean accomplished walking distance was not different between the gait trainer exercise and over ground walking groups. Borg scale indicated more effort in over ground walking. Secondary outcomes also indicated improvements.\n Exercise therapy with walking training improved gait function irrespective of the method used, but the time and effort required to achieve the results favour the gait trainer exercise. Early intensive gait training resulted in better walking ability than did conventional treatment.", "Locomotor training (LT) using a treadmill can improve walking ability over conventional rehabilitation in individuals with hemiparesis, although the personnel requirements often necessary to provide LT may limit its application. Robotic devices that provide consistent symmetrical assistance have been developed to facilitate LT, although their effectiveness in improving locomotor ability has not been well established.\n Forty-eight ambulatory chronic stroke survivors stratified by severity of locomotor deficits completed a randomized controlled study on the effects of robotic- versus therapist-assisted LT. Both groups received 12 LT sessions for 30 minutes at similar speeds, with guided symmetrical locomotor assistance using a robotic orthosis versus manual facilitation from a single therapist using an assist-as-needed paradigm. Outcome measures included gait speed and symmetry, and clinical measures of activity and participation.\n Greater improvements in speed and single limb stance time on the impaired leg were observed in subjects who received therapist-assisted LT, with larger speed improvements in those with less severe gait deficits. Perceived rating of the effects of physical limitations on quality of life improved only in subjects with severe gait deficits who received therapist-assisted LT.\n Therapist-assisted LT facilitates greater improvements in walking ability in ambulatory stroke survivors as compared to a similar dosage of robotic-assisted LT.", "To compare the therapeutic effects of conventional gait training (CGT), gait training using an electromechanical gait trainer (EGT), and gait training using an electromechanical gait trainer with functional electric stimulation (EGT-FES) in people with subacute stroke.\n Nonblinded randomized controlled trial.\n Rehabilitation hospital for adults.\n Fifty patients were recruited within 6 weeks after stroke onset; 46 of these completed the 4-week training period.\n Participants were randomly assigned to 1 of 3 gait intervention groups: CGT, EGT, or EGT-FES. The experimental intervention was a 20-minute session per day, 5 days a week (weekdays) for 4 weeks. In addition, all participants received their 40-minute sessions of regular physical therapy every weekday as part of their treatment by the hospital.\n Five-meter walking speed test, Elderly Mobility Scale (EMS), Berg Balance Scale, Functional Ambulatory Category (FAC), Motricity Index leg subscale, FIM instrument score, and Barthel Index.\n The EGT and EGT-FES groups had statistically significantly more improvement than the CGT group in the 5-m walking speed test (CGT vs EGT, P=.011; CGT vs EGT-FES, P=.001), Motricity Index (CGT vs EGT-FES, P=.011), EMS (CGT vs EGT, P=.006; CGT vs EGT-FES, P=.009), and FAC (CGT vs EGT, P=.005; CGT vs EGT-FES, P=.002) after the 4 weeks of training. No statistically significant differences were found between the EGT and EGT-FES groups in all outcome measures.\n In this sample with subacute stroke, participants who trained on the electromechanical gait trainer with body-weight support, with or without FES, had a faster gait, better mobility, and improvement in functional ambulation than participants who underwent conventional gait training. Future studies with assessor blinding and larger sample sizes are warranted.", "While manually-assisted body-weight supported treadmill training (BWSTT) has revealed improved locomotor function in persons with post-stroke hemiparesis, outcomes are inconsistent and it is very labor intensive. Thus an alternate treatment approach is desirable. Objectives of this pilot study were to: 1) compare the efficacy of body-weight supported treadmill training (BWSTT) combined with the Lokomat robotic gait orthosis versus manually-assisted BWSTT for locomotor training post-stroke, and 2) assess effects of fast versus slow treadmill training speed.\n Sixteen volunteers with chronic hemiparetic gait (0.62 +/- 0.30 m/s) post-stroke were randomly allocated to Lokomat (n = 8) or manual-BWSTT (n = 8) 3x/wk for 4 weeks. Groups were also stratified by fast (mean 0.92 +/- 0.15 m/s) or slow (0.58 +/- 0.12 m/s) training speeds. The primary outcomes were self-selected overground walking speed and paretic step length ratio. Secondary outcomes included: fast overground walking speed, 6-minute walk test, and a battery of clinical measures.\n No significant differences in primary outcomes were revealed between Lokomat and manual groups as a result of training. However, within the Lokomat group, self-selected walk speed, paretic step length ratio, and four of the six secondary measures improved (p = 0.04-0.05, effect sizes = 0.19-0.60). Within the manual group, only balance scores improved (p = 0.02, effect size = 0.57). Group differences between fast and slow training groups were not revealed (p > or = 0.28).\n Results suggest that Lokomat training may have advantages over manual-BWSTT following a modest intervention dose in chronic hemiparetic persons and further, that our training speeds produce similar gait improvements. Suggestions for a larger randomized controlled trial with optimal study parameters are provided." ]

[ "6658501", "4937681", "5460838", "5710676", "5641006", "4905774", "1263177", "14668283", "15787886", "2711281", "5476865", "138664", "5653282", "7297938", "14238675", "7364189", "7128394", "4818631", "525266", "16137113", "14297280", "7007454", "563620" ]

[ "A prophylactic supplementation of iron and folate in pregnancy.", "The effect of prescribing folic acid during pregnancy on birth-weight and duration of pregnancy. A double-blind trial.", "Reduction of incidence of prematurity by folic acid supplementation in pregnancy.", "Preventive iron and folic acid therapy in pregnancy.", "Folic acid and vitamin B12 supplementation during pregnancy in a population subsisting on a suboptimal diet.", "The prophylaxis of folate deficiency in pregnancy.", "Folate supplements during pregnancy.", "Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal.", "Folic acid supplements in pregnancy and birth outcome: re-analysis of a large randomised controlled trial and update of Cochrane review.", "[Deficiency of folates in pregnancy: effect of supplementary folic acid].", "Megaloblastic anaemia of pregnancy: a clinical and laboratory study with particular reference to the total and labile serum folate levels.", "A prophylactic trial of iron and folic acid supplements in pregnant Burmese women.", "The prevention of megaloblastic anaemia in pregnancy in Nigeria.", "Influence of routine administration of folic acid and iron during pregnancy.", "IRON DEFICIENCY AND ITS RELATION TO FOLIC-ACID STATUS IN PREGNANCY: RESULTS OF A CLINICAL TRIAL.", "[Substitution of folic acid in pregnancy (author's transl)].", "Maternal folate status, birthweight and gestational age.", "[Folic acid deficiency in pregnant women in Switzerland].", "Folic acid supplement and intrauterine growth.", "Effect of N-3 polyunsaturated fatty acid supplementation in pregnancy: the Nuheal trial.", "EFFECT OF FOLIC ACID AND VITAMIN B12 SUPPLEMENTATION ON TESTS OF FOLATE AND VITAMIN B12 NUTRITION IN PREGNANCY.", "Effects of topical and systemic folic acid supplementation on gingivitis in pregnancy.", "[Folic acid and pregnancy, a real problem?]." ]

[ "The supplementation of iron and folic acid were studied in 567 pregnant women with 18 and 26 weeks of gestation. Sixty mg and 180 mg of iron were given daily to pregnant women of group I and group II respectively while 180 mg of iron and 5 mg folic acid were given to group III. The Hb values increased significantly in group II and III after supplementation for 1 1/2 months, however if supplementation was extended for 3 months, highly significant increase in Hb levels were observed in all these groups. These findings indicated that in supplementation for a shorter period, i.e. 1 1/2 months at least 180 mg of iron was needed, and only 60 mg of iron was sufficient to increase Hb levels for a supplementation of 3 months. Vitamin B12 deficiency was not detected in pregnant women both before and after supplementation with iron and iron plus folate for 3 months. It was suggested therefore that perhaps it was not necessary to supplement vitamin B12 to Thai pregnant women. In this study 15% of pregnant women had low serum folate with normal red cell folate level, and a greater number of women with low serum folate concentrations were observed after supplementation with iron alone for 3 months. However, increased serum folate and red cell folate levels after supplementation with 5 mg folic acid indicated that some pregnant women needed folate supplementation in preventing folic acid deficiency during pregnancy.", "nan", "Folic acid administered to pregnant Bantu, whose diet is low in folate, was associated with a significant reduction in the incidence of prematurity. No such effect could be demonstrated in White patients subsisting on an average Western diet. This suggests that folate deficiency may contribute to the \"pregnancy wastage\" in populations whose dietary folate intake is low, and is a further indication for folic acid supplementation during pregnancy in these groups.", "nan", "nan", "nan", "In a controlled, prospective trial, the effects of giving ferrous sulphate 50 mg daily to 76 pregnant women was compared with giving ferrous sulphate 50 mg daily plus folic acid 0.5 mg daily to 82 women in 12 general practices in South-east England.No differences in obstetric complications were found between the two groups, although the evidence of some of the listed complications may be too rare for detection in a sample of patients of this size.", "We previously reported that maternal micronutrient supplementation in rural Nepal decreased low birth weight by approximately 15%.\n We examined the effect of daily maternal micronutrient supplementation on fetal loss and infant mortality.\n The study was a double-blind, cluster-randomized, controlled trial among 4926 pregnant women and their 4130 infants in rural Nepal. In addition to vitamin A (1000 microg retinol equivalents), the intervention groups received either folic acid (FA; 400 microg), FA + iron (60 mg), FA + iron + zinc (30 mg), or multiple micronutrients (MNs; the foregoing plus 10 microg vitamin D, 10 mg vitamin E, 1.6 mg thiamine, 1.8 mg riboflavin, 2.2 mg vitamin B-6, 2.6 microg vitamin B-12, 100 mg vitamin C, 64 microg vitamin K, 20 mg niacin, 2 mg Cu, and 100 mg Mg). The control group received vitamin A only.\n None of the supplements reduced fetal loss. Compared with control infants, infants whose mothers received FA alone or with iron or iron + zinc had a consistent pattern of 15-20% lower 3-mo mortality; this pattern was not observed with MNs. The effect on mortality was restricted to preterm infants, among whom the relative risks (RRs) were 0.36 (95% CI: 0.18, 0.75) for FA, 0.53 (0.30, 0.92) for FA + iron, 0.77 (0.45, 1.32) for FA + iron + zinc, and 0.70 (0.41, 1.17) for MNs. Among term infants, the RR for mortality was close to 1 for all supplements except MNs (RR: 1.74; 95% CI: 1.00, 3.04).\n Maternal micronutrient supplementation failed to reduce overall fetal loss or early infant mortality. Among preterm infants, FA alone or with iron reduced mortality in the first 3 mo of life. MNs may increase mortality risk among term infants, but this effect needs further evaluation.", "Periconceptual folic acid prevents neural tube defects. The effect of folic acid taken throughout pregnancy is unclear, however. We re-analysed data from a large randomised controlled trial performed between 1966 and 1967 and combined the results with those from trials included in a Cochrane review. A total of 2928 women were randomised: 1977 were allocated to placebo, 466 to folic acid 200 microg/day and 485 to folic acid 5 mg/day. Folic acid supplementation was not associated with any difference in mean birthweight, placental weight or gestational age. When combined with trials in the Cochrane review folic acid at high doses was associated with reduced risk of low birthweight (pooled relative risk 0.73 [95% CI 0.53, 0.99]). We found no conclusive evidence of benefit for folic acid supplementation in pregnant women given from time of booking onwards.", "Higher folate needs are present during pregnancy, which may lead to tissular deficiency in the mother and to depleted newborn folate reserves. The aim of this work was to assess the prevalence of folate deficiency and to establish the rates of serum and red cell folate in two groups of mothers and newborn infants, one receiving only iron and the other iron and folate during pregnancy. The rates of serum and red cell folate found at the end of pregnancy were significantly higher in the group which received folate; however, the percentage of cases with tissular folate deficiency was low in both groups, with no significant difference (3.8% and 1.3%, respectively). These findings, along with the lack of effect of supplemental folate on erythropoiesis, pose some questions on the usefulness of supplemental folate during pregnancy in our country.", "It has been shown that the incidence of megaloblastic anaemia in a group of 463 randomly selected pregnant women receiving iron was 12 times as high as in a control group of 235 pregnant women receiving iron and folic acid. The incidence of all types of anaemia in the women receiving iron alone was more than three times the incidence in those having iron and folic acid. Some women who were not anaemic or who had normoblastic anaemia had serum folate levels in the same range as the women with megaloblastic anaemia, but none of the women with megaloblastic anaemia had high serum folate levels. The labile fraction of the serum folate was no more reliable than the total serum folate as a diagnostic criterion of megaloblastic erythropoiesis in the individual case. The blood group distribution in the women with megaloblastic anaemia was the same as in the general population. Babies born to mothers with megaloblastic anaemia tended to be smaller than the rest, although there was no difference in the placental weights. The significance of these findings is discussed.", "Hemoglobin (Hb) concentration, serum iron level, iron binding capacity and blood folate (Lactobacillus casei) activity were determined in 310 unselected pregnant Burmese women. Hb concentration was less than 11 g/dl in 72% of the women; the serum iron level was less than 50 mug/dl in 33%; serum folate activity was less than 3ng/ml in 13%; and red cell folate activity was less than 100 ng/ml in 17% of the women. Ninety-six of the women in our study were randomly divided into four groups, treated from the 22nd to the 25th week of pregnancy until full term with either ferrous sulfate containing 60 mg elemental iron twice daily, 5 mg folic acid twice daily, a combination of both, or a placebo only. At full term, Hb concentration fell in the groups given placebo or folic acid. On the other hand, in the groups given iron alone or iron plus folic acid there was an increase in Hb of 0.4 and 0.7 g/dl, respectively (intergroup difference not statistically significant). Serum iron and blood folate levels fell in the groups not receiving the appropriate hematinic. In spite of deficient serum and red cell folate levels in 30 and 40%, respectively, of the group on iron alone, the mean Hb concentration increased at full term and none of the women had a Hb concentration lower than 10 g/dl. Blood folate levels were lower in the iron-supplemented group than in the placebo group, indicating that iron deficiency does not aggravate the folate nutritional status.", "nan", "Haematological and folic acid status were assessed in 200 women in the 6th month of pregnancy. Folic acid deficiencies with no or little haematological impairment were found in one third of the cases, and their occurrence increased when the socioeconomic level was low. During the last trimester of pregnancy, the women were given either iron alone or iron and folic acid supplementation. In the mothers, the rise of folate values in serum and red blood cells, in the folic acid-supplemented group, had no obvious haematological consequences, showing that iron therapy alone can, in developed countries, prevent the anaemia in pregnancy. In the infants, there was no difference in the haematological indices, whatever the mothers' treatment had been. However, a significant difference appeared for the gestational age and, therefore, the height and weight. Folic acid supplementation during pregnancy increased its duration by virtually 1 week.", "nan", "nan", "nan", "nan", "The effect of a folic acid supplment on birth weight and placental weight in women delivering in the early summer in Denmark was investigated. Thirty-six women with normal pregnancy and expected delivery in the first half of June were selected consecutively. They were paired two and two, and allotted to two groups, one of which was supplied daily with 5 mg folic acid, and the second with tablets without folic acid, from the 23rd week of pregnancy. A significant correlation was found between erythrocyte folic acid and birth weight. The infants in the folic acid group were 12.7 per cent heavier than those in the control group (p less than 0.01). A similar difference was found with regard to placental weight and the number of placental cells.", "In this placebo controlled, randomised, double blind trial, pregnant women received from the 20th week of gestation onwards either 500 mg docosahexaenoic acid (DHA), 400 mg 5-methyl-tetra-hydro-folate (5-MTHF), or placebo, or a combination of 500 mg DHA and 400 mg 5-MTHF. The dietary supplements were well tolerated; the dropout rates did not differ significantly in the active arms of the study (10% to 19%) from that seen in the placebo group (13%). DHA supplementation resulted in significant enhancement of the contribution of DHA to maternal, placental and venous cord blood lipids.", "nan", "A double-blind study evaluated the effects of systemic and topical folate on gingival inflammation during the fourth and eighth months of pregnancy. Thirty women were randomly divided into three groups. Group A received placebo mouthwash and tablets; Group B; placebo mouthwash and 5 mg folate tablets; Group C: folate mouthwash and placebo tablets. Supplementation lasted for 14 days during months 4 and 8. Subjects took one tablet daily and rinsed twice daily for 1 min with the mouthwash. At the start and finish of each 14-day period, fasting serum and red cell folate levels were estimated and oral status assessed by a plaque index (P1I), a gingival index (GI), and gingival exudate flow meter (GEF). Subjects completed 1-week diet sheets which were analysed for dietary folate. All groups were similar in each parameter at the start. Correlation was demonstrated between GI and P1I, and between GI and GEF. GI tended to increase throughout pregnancy in all groups except Group C, when in the eighth month there was a highly significant improvement (0.001 less than P 0.01) despite no significant change in P1I. Although dietary intake of folate was significantly higher during the eighth month in Group C as compared with Groups A and B, (0.001 less than P less than 0.01), the folate mouthwash produced highly significantly improvement in gingival health in pregnancy.", "The efficacy of prophylactic treatment with ferrous sulfate (80 mg Fe++) and the combination of ferrous sulfate with folic acid (80 mg Fe++ and 350 microgram folic acid) were studied in a double blind trial in the 20th, and again in the 30th and 36th week of pregnancy (29 patients). At the beginning of the treatment (20th week) 29% of the patients showed a pathologically reduced serum folic acid level. Combined therapy has a favorable effect on the folic acid levels in the serum and red blood cells; this was confirmed statistically. At the end of pregnancy, 69% of the patients of the control group (ferrous sulfate) showed a pathologically reduced serum level and 23% a subnormal level in erythrocytes. These results unquestionably justify the prophylactic prescription of folic acid during pregnancy." ]

[ "17359519", "10024707", "17698433", "6942317", "1439060", "6626112", "6709586", "7183202", "7360634", "19885943", "883740", "9085389", "9818805", "10689659", "9209728", "12356614", "3933739" ]

[ "Acupressure for smoking cessation--a pilot study.", "A single-blind, placebo-controlled trial of a simple acupuncture treatment in the cessation of smoking.", "A randomized controlled clinical trial of auricular acupuncture in smoking cessation.", "The efficacy of acupuncture as an aid to stopping smoking.", "A randomised 2 x 2 factorial design to evaluate different smoking cessation methods.", "Smoking cessation with behaviour therapy of acupuncture--a controlled study.", "Acupuncture and group therapy in stopping smoking.", "Acupuncture therapy for the treatment of tobacco smoking addiction.", "[Antismoking acupuncture. Short-term results of a double-blind comparative study].", "A six-week acupoint stimulation intervention for quitting smoking.", "[Tobacco withdrawal. Efficacy of acupuncture in a comparative trial].", "Effects of acupuncture on smoking cessation or reduction for motivated smokers.", "Randomized trial of acupuncture for nicotine withdrawal symptoms.", "Electrical stimulation therapy in the treatment of cigarette smoking.", "Evaluation of cranial electrostimulation therapy on short-term smoking cessation.", "Auricular acupuncture, education, and smoking cessation: a randomized, sham-controlled trial.", "Helping people to stop smoking: randomised comparison of groups being treated with acupuncture and nicotine gum with control group." ]

[ "Tobacco smoking is a serious risk to health: several therapies are available to assist those who wish to stop. Smokers who approach publicly funded stop-smoking clinics in the UK are currently offered nicotine replacement therapy (NRT) or bupropion, and group behaviour therapy, for which there is evidence of effectiveness. Acupuncture and acupressure are also used to help smokers, though a systematic review of the evidence of their effectiveness was inconclusive. The aim of this pilot project was to determine the feasibility of a study to test acupressure as an adjunct to one anti-smoking treatment currently offered, and to inform the design of the study.\n An open randomised controlled pilot study was conducted within the six week group programme offered by the Smoking Advice Service in Plymouth, UK. All participants received the usual treatment with NRT and group behavioural therapy, and were randomised into three groups: group A with two auricular acupressure beads, group B with one bead, and group C with no additional therapy. Participants were taught to press the beads when they experienced cravings. Beads were worn in one ear for four weeks, being replaced as necessary. The main outcome measures assessed in the pilot were success at quitting (expired CO < or = 9 ppm), the dose of NRT used, and the rating of withdrawal symptoms using the Mood and Symptoms Scale.\n From 49 smokers attending four clinics, 24 volunteered to participate, 19 attended at least once after quitting, and seven remained to the final week. Participants who dropped out reported significantly fewer previous quit attempts, but no other significant differences. Participants reported stimulating the beads as expected during the initial days after quitting, but most soon reduced the frequency of stimulation. The discomfort caused by the beads was minor, and there were no significant side effects. There were technical problems with adhesiveness of the dressing. Reporting of NRT consumption was poor, with much missing data, but reporting of ratings of withdrawal symptom scores was nearly complete. However, these showed no significant changes or differences between groups for any week.\n Any effects of acupressure on smoking withdrawal, as an adjunct to the use of NRT and behavioural intervention, are unlikely to be detectable by the methods used here and further preliminary studies are required before the hypothesis can be tested.", "Tobacco smoking is a major cause of preventable disease and premature death. Physicians should play an active role in the control of smoking by encouraging cessation and helping the smoker to choose the most suitable aid to cessation.\n To evaluate a simple, ear acupuncture treatment for the cessation of smoking.\n Randomized, single-blind, placebo-controlled trial of 78 currently smoking volunteers from the general public. Volunteers attended an acupuncture clinic in a general practice setting and were given a single treatment of electroacupuncture using two needles at either an active or a placebo site plus self-retained ear seeds for two weeks. The major outcome measure was biochemically validated total cessation of smoking at six months.\n A total of 12.5% of the active treatment group compared with 0% of the placebo group ceased smoking at six months (P = 0.055, 95% confidence interval -0.033 to 0.323).\n This simple ear electroacupuncture treatment was significantly more effective in helping volunteers to quit smoking than placebo treatment.", "Tobacco smoking is responsible for human diseases of the lung, heart, circulatory system and various kinds of cancers, and is a serious public health problem worldwide. Acupuncture has been promoted as a treatment modality for smoking cessation. However, its efficacy still remains controversial.\n We conducted a prospective, randomized, controlled trial using auricular acupuncture for smoking cessation in 131 adults who wanted to stop smoking. Thirteen subjects withdrew from the study and 118 subjects were included in the final analyses (mean age, 53.7 +/- 16.8 years; 100 males, 18 females). The treatment group (n = 59) received auricular acupuncture in Shen Men, Sympathetic, Mouth and Lung points for 8 weeks. The control group (n = 59) received sham acupuncture in non-smoking-cessation-related auricular acupoints (Knee, Elbow, Shoulder and Eye points). The enrolled subjects were then followed monthly for 6 months after stopping the acupuncture treatment.\n Between both groups before acupuncture treatment, there was no significant difference with regard to gender, mean age, education level, and mean values for the age at which smoking started, smoking duration, daily number of cigarettes smoked and nicotine dependent score. At the end of treatment, cigarette consumption had significantly decreased in both groups, but only the treatment group showed a significant decrease in the nicotine withdrawal symptom score. Smoking cessation rate showed no significant difference between the treatment group (27.1%) and the control group (20.3%) at the end of treatment. There was also no significant difference in the smoking cessation rate between the treatment group (16.6%) and the control group (12.1%) at the end of follow-up. There were no major side effects of auricular acupuncture in both groups.\n Our results showed that auricular acupuncture did not have a better efficacy in smoking cessation compared to sham acupuncture. Combined acupuncture with behavior counseling or with nicotine replacement therapy should be used in further smoking cessation trials to enhance the success rate of smoking cessation.", "The present study examines the usefulness of acupuncture as an aid to stopping smoking. Results from 405 subjects show acupuncture can help between 5 and 15 percent of the population to stop smoking for at least six months. Using chronically implanted press needles, previously reported 'effective' auricular acupuncture points for smoking cessation are shown to be no better than 'placebo' auricular points. Additional electroacupuncture on the hand neither increases the probability of stopping smoking nor enhances the reduction in smoking at three week, three month or six month follow-up periods. It is therefore likely that a large psychological component is attached to acupuncture to stop people smoking.", "A study with a 2 x 2 factorial design was performed to evaluate the effectiveness of acupuncture, of nicotine gum and the effect of the association on smoking cessation. After a one-year follow-up period, the success rates were in the same order of magnitude for nicotine gum (active treatment: 10%, placebo: 8%) group and for acupuncture (active treatment: 8%, placebo: 10%) group.", "nan", "nan", "Acupuncture has been reported as an effective treatment for some addictions. The purpose of this study was to evaluate acupuncture treatment effect on the cigarette smoking habit with a motivated population in a controlled clinical setting. From a volunteer research population, sixteen matched pairs were assembled according to age, sex, and severity of smoking habit. Research subjects were randomly assigned to real or sham acupuncture treatment groups. Self-reported cigarette logs were measured pre-treatment and post-treatment. Analysis of variants confirmed homogeneity of group pre-treatment cigarette consumption. Cigarette consumption significantly decreased in both th e real and sham treatment groups. Treatment group, age, sex, or severity of smoking habit were not significant factors in treatment effects for cessation of smoking. Legitimate crossover treatment for sham research group showed a significant decrease (p less than or equal to 0.05) in cigarette consumption; this change was not statistically different from change in cigarette consumption during placebo treatment. A discussion of acupuncture point selection rationale is made as is an analysis of Tehchi sensations and subjective reports of appetite for cigarettes. Acupuncture did not enhance the cessation of cigarette smoking in this study.", "nan", "This study creates a six-week acupoint stimulation program for quitting smoking by conducting an experimental research design and then evaluating its effects. A total of 59 smokers, 28 +/- 7.6 years of mean age, volunteered to participate and were randomly assigned to the experimental or sham group. The current investigation administered anti-smoking acupoints to the experimental group for six weeks, whereas the sham group used sham acupoints for six weeks. Before and after the six-week intervention, the participants completed questionnaires and offered blood samples. This research collected data of demographic factors, serum cotinine, carbon monoxide exhalation, daily tobacco consumption, and quit smoking rate of participants before and after the six-week intervention. After the intervention, it showed no significant differences in the serum level of cotinine and carbon monoxide exhalation between the two groups. The quit rate in the experimental group was 13.3% and 13.7% in the sham group. However, daily tobacco consumption was 10 cigarettes in the experimental group and 11.21 cigarettes in the sham group. This experimental study used the sham group as the control, resulting in no statistically significant findings. Future studies need more evidence-based research on the exact effect or placebo effect of acupoint stimulation and the appropriate design for sham acupoint, to examine quitting effect using acupoint stimulation in adult smokers.", "nan", "This study was undertaken to examine the effects of acupuncture on smoking reduction and possibly also cessation and to examine whether some acupoints are more effective than others for smoking cessation.\n A total of 46 healthy men and women, 39 +/- 9 years of age (mean +/- SD), who smoked 20 +/- 6 cigarettes per day and had smoked for 23 +/- 8 years, and who wanted to quit smoking, volunteered to participate. The subjects were randomly assigned to two groups. One group was given acupuncture treatment at points previously used for anti-smoking (test group, TG). The other group was given acupuncture treatment at points assumed to have no effect for smoking cessation (control group, CG). Before each treatment and after the last treatment each subject answered questionnaires about his or her smoking habits and attitudes. In addition the concentrations of serum cotinine, serum thiocyanate, serum peroxides, and plasma fibrinogen were measured before the first and after the last acupuncture treatment.\n The daily cigarette consumption fell during the treatment period in both groups, but the reduction was larger for TG than for CG (P < 0.002). Altogether 31% of subjects in TG had quit smoking completely at the end of the treatment, compared with none in CG. For TG the concentrations of cotinine and thiocyanate were reduced significantly after the treatment period (P < 0.001), but no significant reductions were observed for CG. For both groups the taste of tobacco worsened during the treatment period, but the effect was more pronounced for TG than for CG (P < 0.05). The desire to smoke fell significantly in both groups after treatment, and the reduction was larger for TG than for CG (P < 0.001). No significant changes in serum peroxides and plasma fibrinogen concentrations were observed during the treatment period for either group.\n This study suggests that acupuncture may help motivated smokers to reduce their smoking or even quit smoking completely. Different acupoints appear to have different effects for smoking cessation and reduction.", "Acupuncture is frequently used for smoking cessation. Positive results from uncontrolled studies have not been supported by meta-analysis of controlled trials. One possible reason for this is that the optimal acupuncture technique was not applied or that the technique was not repeated sufficiently often.\n A randomized, sham-controlled trial was performed with 2 parallel treatment arms; the participant and the evaluator were unaware of which treatment was received. Seventy-six adults who wanted to stop smoking received either 100-Hz electroacupuncture with needles inserted into the appropriate point in each ear or a sham control procedure over the mastoid bone. Interventions were given on days 1, 3, and 7 of smoking cessation. Nicotine withdrawal symptoms were measured by visual analog scale scores recorded in a daily diary for 14 days; smoking cessation was confirmed objectively.\n There was no significant difference between the mean reduction of withdrawal symptom scores of the 2 groups from day 1 to day 14. Fifteen participants (39%) who received electroacupuncture and 16 participants (42%) who received a sham procedure were abstinent on day 14.\n This form of electroacupuncture is no more effective than placebo in reducing nicotine withdrawal symptoms.", "In this study electrical stimulation therapy (EST) is explored as a possible new treatment for smoking cessation within a randomized controlled trial. The investigation follows reports of several authors that electrical stimulation applied to specific acupuncture points is effective in treating a variety of drug dependencies, including cigarette smoking. Three key features of treatment (electrical stimulation, frequency modulation, and electrode placement), were investigated in a 2 x 2 x 2 factorial design, resulting in eight treatment combinations. Out of 265 smokers recruited into the trial 216 completed the one-week treatment. Outcome was assessed in terms of complete abstinence from smoking and symptomatic relief of withdrawal symptoms. Smokers receiving active electrical stimulation obtained higher abstinence rates than those in the inactive groups although the difference did not achieve statistical significance (all active vs. all placebo groups: lambda 1,1(2) = 0.50, p > 0.10, 95% confidence interval = -8.04 to +17.44%; most effective vs. least effective group: lambda 1,1(2) = 3.11, p = 0.08, CI0.95 = -2.2 to +48.8%). The efficacy of electrical stimulation therapy for smoking is not supported.", "The effects of cranial electrical stimulation (CES) on short-term smoking cessation were evaluated in a double-blind study of cigarette smokers who wished to stop smoking. Subjects were randomly assigned to a CES- (n = 51) or a sham-treated group (n = 50). On 5 consecutive days subjects received CES treatments (30-microA, 2-msec, 10-Hz pulsed signal) or no electrical current (sham). There were no significant differences between groups on daily cigarettes smoked, exhaled carbon monoxide, urinary cotinine levels, treatment retention, smoking urges, or total tobacco withdrawal scores, although subjects in the CES group had less cigarette craving and anxiety during the first 2 experimental days. The ineffectiveness of CES to reduce withdrawal symptoms and facilitate smoking cessation are similar to results of other clinical studies of CES in drug dependence, although positive effects of CES in animal studies have been reported.", "This study examined the effect of acupuncture alone and in combination with education on smoking cessation and cigarette consumption.\n We prospectively studied 141 adults in a quasi-factorial design using acupuncture, sham acupuncture, and education.\n All groups showed significant reductions in smoking and posttreatment cigarette consumption, with the combined acupuncture-education group showing the greatest effect from treatment. The trend continued in follow-up; however, significant differences were not maintained. Greater pack-year history (i.e. the number of years smoking multiplied by baseline number of cigarettes smoked per year, divided by 20 cigarettes per pack) negatively correlated with treatment effect. Trend analysis suggested 20 pack-years as the cutoff point for this correlation.\n Acupuncture and education, alone and in combination, significantly reduce smoking; however, combined they show a significantly greater effect, as seen in subjects with a greater pack-year history.", "nan" ]

[ "16319303", "3578861", "11784964", "11380742", "16181163", "12027195" ]

[ "Donepezil in the prevention and treatment of post-surgical delirium.", "Postoperative confusion after anesthesia in elderly patients with femoral neck fractures.", "[Use of procholinergics in the prevention of postoperative delirium in hip fracture surgery in the elderly. A randomized controlled trial].", "Reducing delirium after hip fracture: a randomized trial.", "Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study.", "A novel approach to the prevention of postoperative delirium in the elderly after gastrointestinal surgery." ]

[ "Delirium is a frequent complication of major surgery in older persons. The authors evaluated the possible benefit of donepezil versus placebo in the prevention and treatment of postoperative delirium in an older population without dementia undergoing elective total joint-replacement surgery.\n A sample of 80 patients participated in this randomized, double-blind, placebo-controlled trial of donepezil. Each participant was evaluated before surgery and then received donepezil or placebo for 14 days before surgery and 14 days afterward. Postoperative delirium was assessed with the Delirium Symptom Interview, Confusion Assessment Method, daily medical record, nurse-observation reviews, and DSM-IV diagnostic criteria for delirium. Subsyndromal delirium was also assessed for each participant.\n Delirium, diagnosed by DSM-IV criteria, was found on at least 1 postoperative day in 18.8% of subjects, but there were no significant differences between the donepezil and placebo groups. When delirium was present, it lasted only 1 day, and there was no difference between the groups. Subsyndromal delirium was found on at least 1 postoperative day for 68.8% of subjects, and, when this occurred, lasted 2 days or less, on average. There was no difference between the groups in the occurrence or duration of subsyndromal delirium. There was no difference between the groups in disposition to home or to another facility.\n This pilot study was unable to demonstrate a benefit for donepezil in preventing or treating delirium in a relatively young and cognitively-intact group of elderly patients undergoing elective orthopedic surgery. Furthermore, postoperative delirium was not a major problem in this population.", "Fifty-seven patients, all over the age of 64, with femoral neck fracture were randomized to receive epidural or halothane anesthesia to see if the anesthetic technique influenced the incidence of postoperative confusion. All patients were lucid on admission. Using the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III) as criteria for confusion, we found that 44% of the patients developed confusion that correlated closely to a history of mental depression (P less than 0.01) and to the use of drugs with anticholinergic effect (P less than 0.005). There was no difference in the incidence of confusion between the two anesthetic groups. In patients given halothane, however, early postoperative hypoxemia was associated with confusion (P less than 0.05). Patients with confusion had significantly more postoperative complications and almost four times longer hospitalization times. It is concluded that anticholinergic medication and a history of mental depression are predominant risk factors for development of postoperative confusion and in this respect are more important than the anesthetic technique.", "40 to 50% of elderly with hip fracture present delirium. The morbimortality increase in patients whose presented delirium.\n To study the use of citicoline (CDP choline) in the prevention of delirium in elderly under hip fracture surgery.\n A randomized control trial. The patients with hip fracture without dementia or an other organic brain illness. The medication were administered 24 hours before and during 4 days after surgery. The doses was 1.2 g/day. The primary outcome measure was percentage of patients with delirium measured with Abbreviated Mental Test (AMT) and Confusion Assessment Method (CAM). The Mini Mental State (MMS) was used before and 4 days after surgery. All treatment comparation was considered statistically significant at p< 0.05 calculating chi square and Wilcoxon test.\n The sample size was 81 patients (46 placebo and 35 citicoline). The mean age was 79.45 for tested group and 79.97 for placebo. There was no statistically significant difference between groups with respect to ASA class of anesthesia. The incidence of delirium was 17.39% in placebo and 11.76% in citicoline group (p= 0.6). CAM and AMT at 1, 2, 3, 4 days post surgery was not significant in placebo and citicoline group (p= 0.8 and p= 0.34).\n In the present study the citicoline did not prevent or reduce the incidence of delirium in hip fracture surgery in elderly.", "Delirium (or acute confusional state) affects 35% to 65% of patients after hip-fracture repair, and has been independently associated with poor functional recovery. We performed a randomized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture.\n Prospective, randomized, blinded.\n Inpatient academic tertiary medical center.\n 126 consenting patients 65 and older (mean age 79 +/- 8 years, 79% women) admitted emergently for surgical repair of hip fracture.\n Detailed assessment through interviews with patients and designated proxies and review of medical records was performed at enrollment to ascertain prefracture status. Subjects were then randomized to proactive geriatrics consultation, which began preoperatively or within 24 hours of surgery, or \"usual care.\" A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol. To ascertain study outcomes, all subjects underwent daily, blinded interviews for the duration of their hospitalization, including the Mini-Mental State Examination (MMSE), the Delirium Symptom Interview (DSI), and the Memorial Delirium Assessment Scale (MDAS). Delirium was diagnosed using the Confusion Assessment Method (CAM) algorithm.\n The 62 patients randomized to geriatrics consultation were not significantly different (P>.1) from the 64 usual-care patients in terms of age, gender, prefracture dementia, comorbidity, type of hip fracture, or type of surgical repair. Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively. A mean of 10 recommendations were made throughout the duration of the hospitalization, with 77% adherence by the orthopedics team. Delirium occurred in 20 /62 (32%) intervention patients, versus 32 / 64 (50%) usual-care patients (P =.04), representing a relative risk of 0.64 (95% confidence interval (CI) = 0.37-0.98) for the consultation group. One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group. There was an even greater reduction in cases of severe delirium, occurring in 7/ 60 (12%) of intervention patients and 18 / 62 (29%) of usual-care patients, with a relative risk of 0.40 (95% CI = 0.18-0.89). Despite this reduction in delirium, length of stay did not significantly differ between intervention and usual-care groups (median +/- interquartile range = 5 +/- 2 days in both groups), likely because protocols and pathways predetermined length of stay. In subgroup analyses, geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living (ADL) functional impairment.\n Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair. Geriatrics consultation reduced delirium by over one-third, and reduced severe delirium by over one-half. Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients.", "To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium.\n Randomized, double-blind, placebo-controlled trial.\n Large medical school-affiliated general hospital in Alkmaar, The Netherlands.\n A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium.\n Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients.\n The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay.\n The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6-1.3); the mean highest DRS-R-98 score+/-standard deviation was 14.4+/-3.4 and 18.4+/-4.3, respectively (mean difference 4.0, 95% CI=2.0-5.8; P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0-8.0; P<.001); and the mean number of days in the hospital was 17.1+/-11.1 and 22.6+/-16.7, respectively (mean difference 5.5 days, 95% CI=1.4-2.3; P<.001). No haloperidol-related side effects were noted.\n Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.", "Postoperative delirium (POD) is known to be one of the most critical complications of major operative procedures in elderly patients. Since disorders of the sleep-wake cycle have been reported to be one of the key factors in POD, we attempted to clarify the effectiveness of improving sleep-wake cycle disorders with medication after surgery to prevent POD, by conducting a prospective randomized study of 42 elderly patients who underwent resection of either gastric or colon cancer through an open laparotomy.\n The delirium-free protocol (DFP) group was given an intramuscular injection of diazepam at 20:00 h each night, as well as a continuous intravenous infusion of flunitrazepam and pethidine administered over 8 h, for the first three nights postoperatively. Two patients were excluded because of failure to complete the DFP.\n The incidence of POD was 7/20 (35.0%) in the non-DFP group and 1/20 (5.0%) in the DFP group, this difference being significant (P = 0.023). Morning lethargy produced by the DFP was observed in 40% of the DFP group; however, no other side effects were seen.\n These findings indicate that DFP treatment is effective for controlling POD in elderly patients after general surgery and does not appear to be associated with severe complications or side effects. To our knowledge, this is the first report proposing artificial control of the sleep-awake rhythm by medication as a means of preventing POD in elderly patients." ]

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[ "Intravenous immunoglobulins in association with antibiotics: a therapeutic trial in septic intensive care unit patients.", "Immunoglobulin therapy in patients with endotoxemia and postoperative sepsis--a prospective randomized study.", "[Intravenous immunoglobulin in the treatment of neonatal septicemia].", "A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group.", "Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial.", "Randomized, placebo-controlled trial of HA-1A, a human monoclonal antibody to endotoxin, in children with meningococcal septic shock. European Pediatric Meningococcal Septic Shock Trial Study Group.", "Treatment of gram-negative septic shock with an immunoglobulin preparation: a prospective, randomized clinical trial.", "INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group.", "The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis: another point of view.", "Observations using antiendotoxin antibody (E5) as adjuvant therapy in humans with suspected, serious, gram-negative sepsis.", "Effects of high-dose of intravenous immunoglobulin and antibiotics on survival for severe sepsis undergoing surgery.", "Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group.", "The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830].", "[Immunoglobulin therapy of postoperative sepsis].", "Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group.", "Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial.", "Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels.", "A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group.", "The use of IgM-enriched intravenous immunoglobulin for the treatment of neonatal sepsis in preterm infants.", "CDP571, a humanized antibody to human tumor necrosis factor-alpha: safety, pharmacokinetics, immune response, and influence of the antibody on cytokine concentrations in patients with septic shock. CPD571 Sepsis Study Group.", "[Effect of adjuvant immunoglobulin therapy on infections in patients in an surgical intensive care unit. Results of a randomized controlled study].", "Multicenter randomized placebo controlled trial of therapy with intravenous immunoglobulin in decreasing mortality due to neonatal sepsis.", "IgM-enriched intravenous immunoglobulin therapy in neonatal sepsis.", "Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose-ranging study.", "Intravenous immune globulin therapy for early-onset sepsis in premature neonates.", "Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group.", "Treatment of septic thrombocytopenia with immune globulin.", "Pepsin-treated human gamma globulin in bacterial infections. A randomized study in patients with septicaemia and pneumonia.", "Anti-lipopolysaccharide immunotherapy in management of septic shock of obstetric and gynaecological origin.", "Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group.", "Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group.", "Multicenter evaluation of a human monoclonal antibody to Enterobacteriaceae common antigen in patients with Gram-negative sepsis.", "E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators.", "Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study.", "IgMA-enriched immunoglobulin in neutropenic patients with sepsis syndrome and septic shock: a randomized, controlled, multiple-center trial." ]

[ "The therapeutic use of iv immunoglobulins of the G class in association with antibiotics in patients with severe sepsis is reported. As compared to the randomized control group of patients treated with antibiotics alone, patient survival was only slightly improved (from 25% to 42%; NS); however, the defervescence time was significantly shorter (10 vs. 16 days), and a greater percentage of microbiologically positive cultures became negative (40% vs. 8%; p less than .01). The percentage of days on antibiotic treatment during ICU hospitalization was consequently reduced (38% vs. 95%; p less than .01). The therapeutic use of iv immunoglobulin G is discussed in terms of antibody substitution and modulation of the immune system.", "nan", "Thirty-seven neonates with confirmed septicemia through hemoculture were studied. Of them, 18 were treated with antibiotic and the other 19 were given 500 mg/kg of intravenous immunoglobin with a pH of 4.25 (IGIV). The greater part of the neonates in this study were full-term or near full-term. There were no differences in age, gestational age and weight, nor in mortality, the bacterias found and the clinical manifestations which were seen in both groups. Yet, the hospitalary stay was shorter for those in the group treated with IGIV (13.9 +/- 5.7 days) than in the trial group (24.4 +/- 10.3 days); as well as some clinical manifestations like diarrhea and splenomegalia (P < 0.05). The serum of the neonates from the IGIV group showed a greater capacity of opsonization and inhibition of bacterial growth than those in the trial group (P < 0.001), coinciding with an increase of 300 mg/dL in the serum levels of IgG of the group treated with IGIV from the 3rd day of the study and the C4 and B-Properdine factor serum levels from the 7th day of the study, while in the trial group, there were no changes in these factors (P < 0.001). Even though no differences were seen in the mortality rate due to septicemia, the results suggest a much shorter evolution of the illness in patients treated with IGIV. In addition, the serum of those patients treated with IGIV showed in in vitro studies, a better bacteriostatic activity and a better capacity to opsonize the bacterias isolated in the hemocultures.(ABSTRACT TRUNCATED AT 250 WORDS)", "To evaluate the safety and efficacy of E5, a murine, monoclonal antibody directed against endotoxin, in the treatment of patients with Gram-negative sepsis.\n A multicenter, randomized, double-blind, placebo-controlled trial.\n Fifty-three hospitals across the United States, including university medical centers, Veterans Affairs Medical Centers, and community hospitals.\n 847 patients were randomized into this study. Enrolled patients met criteria for three conditions: a) known or suspected Gram-negative infection; b) clinical evidence of sepsis; and c) signs of end-organ dysfunction. Patients with refractory shock were excluded from the study.\n Two doses of E5 (2 mg/kg/day by intravenous infusion 24 hrs apart), or placebo that was identical in appearance were administered. In addition, all patients received standard supportive therapy and broad-spectrum antibiotics.\n The primary end point was mortality over 30 days. Secondary outcome measures included the resolution and prevention of organ failure in the same two populations. Additionally, the safety of E5 was evaluated. There was no significant improvement in survival over 30 days among patients with Gram-negative sepsis who received E5 compared with those patients who received placebo (n = 530; p = .21). In addition, E5 did not improve survival for patients with Gram-negative sepsis and organ failure (n = 139; p = .3). However, a significantly greater percentage of patients with Gram-negative sepsis experienced resolution of major organ failure if they received E5, compared with those patients who received placebo (n = 139; 48% E5 vs. 25% placebo; p = .005). This result extended to all patients who entered the study with one or more major organ failures, regardless of the etiology of the infection (n = 225; 41% E5 vs. 27% placebo; p = .024). E5 also provided protection against the development of some organ failures, but significant prevention was only observed for adult respiratory distress syndrome (p = .007) and central nervous system dysfunction (p = .050). Hypersensitivity reactions attributable to E5 occurred in 2.6% of patients. An asymptomatic antibody response occurred in 44% of the E5-treated patients and in 12% of the patients who received placebo.\n In this study, E5 did not reduce mortality in nonshock patients with Gram-negative sepsis whether or not those patients also had organ failure. However, E5 did result in greater resolution of organ failure in patients with Gram-negative sepsis. This benefit extended to those patients with suspected Gram-negative etiology. This finding is important because patients with suspected Gram-negative sepsis and organ failure can be identified without waiting for culture results. In addition, E5 resulted in the prevention of adult respiratory distress syndrome and central nervous system organ failure. However, more studies are needed to determine if this result can be extended to organ failure in general. E5 is safe as a treatment for patients with Gram-negative sepsis.", "The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients). The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group. A significant decrease in the sepsis-related organ failure assessment score at days 2 (P=.02) and 3 (P=.04) was noted in the IVIG group. Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P=.03). Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.", "Meningococcal septic shock has a rapid onset and characteristic skin hemorrhages that allow bedside diagnosis. Initial plasma endotoxin levels are high and correlate closely with clinical outcome. In a double-blind, randomized, placebo-controlled trial (planned, n = 270; actual, n = 269), we compared the effectiveness of HA-1A (6 mg/kg of body weight iv; maximum, 100 mg), a human monoclonal antibody to endotoxin, and placebo in reducing the 28-day all-cause mortality rate among children with a presumptive clinical diagnosis of meningococcal septic shock. Treatment groups were well balanced for baseline characteristics and prespecified prognostic variables. In this trial no significant benefit of HA-1A could be demonstrated. The 28-day mortality rates in the intention-to-treat analysis were as follows: placebo, 28%; HA-1A, 18%; reduction in mortality, 33% (P = .11, per Fisher's exact test, two-tailed; odds ratio = 0.59; 95% confidence interval for the difference, 0.31-1.05). All patients tolerated HA-1A well, and no antibodies to HA-1A were detected.", "To evaluate the effectiveness of a polyclonal immunoglobulin (Ig) preparation containing IgG, IgM, and IgA as an adjunctive therapy for septic shock.\n Prospective, randomized clinical trial.\n A clinical immunology ward at the center for internal medicine in a university hospital.\n Fifty-five patients with septic shock were randomly allocated to two groups according to criteria of septic shock.\n One group of patients (n = 27) received a commercially available immunoglobulin preparation (containing high titers of antibodies specific for determinants to bacterial endotoxin) during the first 3 days after inclusion in the study. The other randomized group (n = 28) did not receive any immunoglobulin preparation.\n During the period of less than or equal to 6 wks after the beginning of clinically apparent septic shock, death related to the septic process occurred in one (4%) of 27 patients who received immunoglobulin. By comparison, nine (32%) of 28 control group patients died during this period (p less than .01). Within the first 48 hrs after onset of the clinically apparent septic process, significantly increased activity of circulating endotoxin and simultaneously decreased specific IgG serum titers to lipid A were detected in the group of nonsurvivors.\n Administration of a polyclonal immunoglobulin preparation in the early phase of septic shock was associated with significantly improved survival.", "To determine the safety and efficacy of BAY x 1351, a murine monoclonal antibody to recombinant human tumor necrosis factor (TNF)-alpha, in patients with sepsis.\n An international, multicenter, prospective, placebo-controlled trial in patients with sepsis, stratified into shock/nonshock groups.\n Forty acute clinical care facilities in 14 countries.\n Of the 564 patients enrolled in the study, 553 patients received study drug or placebo.\n Patients received 15 mg/kg or 3 mg/kg of BAY x 1351, or placebo, as a single intravenous infusion.\n The patients were well matched for severity of illness and for risk factors known to influence the outcome of sepsis. There was no difference in 28-day mortality rates between groups (placebo group 66 [39.5%] of 167;3 mg/kg group 57 [31.5%] of 181; 15 mg/kg group 87 [42.4%] of 205). Approximately 9 months after this study had begun, an interim safety examination of NORASEPT, a North American Sepsis Trial using the same monoclonal antibody, indicated that there was no benefit to patients in the nonshock group and further enrollment of these nonshock septic patients into INTERSEPT was stopped. The analysis therefore focused on the 420 patients in shock. The primary efficacy variable was the 28-day, all-cause mortality rate: placebo group 57 (42.9%) of 133; 3-mg/kg group 51 (36.7%) of 139; and 15-mg/kg group 66 (44.6%) of 148 (not significant). Two secondary efficacy variables were identified prospectively: shock reversal and frequency of organ failures. Life-table analysis showed that in patients who survived 28 days, there was a more rapid reversal of shock in both treatment groups compared with placebo (15-mg/kg group vs. placebo group log-rank statistic p = .007, 3-mg/kg group vs. placebo group p = .01). Similarly, in patients surviving 28 days, there was a significant delay in the time to the onset of first organ failure (log rank 15 mg/kg vs. placebo p = .03, 3 mg/kg vs. placebo p = .07), and more patients in the placebo group developed at least one organ failure: 15-mg/kg group 33 (40.2%) of 82; 3-mg/kg group 39 (44.3%) of 88; and placebo group 45 (59.2%) of 76 (15 mg/kg vs. placebo p = .03, 3 mg/kg vs. placebo p = .06). No significant adverse events were associated with the monoclonal antibody treatment.\n INTERSEPT provides additional clinical data implicating TNF-alpha as an integral mediator of septic shock. The study suggested a possible role for anti-TNF antibody as adjunctive therapy, but this possibility requires confirmation by another clinical trial.", "nan", "To evaluate the safety and efficacy of E5 (Xomen-E5), a murine monoclonal immunoglobulin M antibody, in reducing mortality in patients with serious Gram-negative infections. Phase II, single-site study.\n Randomized, double-blind, placebo-controlled study.\n Surgical, neurosurgical and medical ICUs, comprising approximately 30 beds in a multidisciplinary university hospital.\n Patients with clinical evidence of serious infection admitted to the ICU for monitoring of vital signs and for intensive care nursing. Of the 39 patients enrolled in the study, 23 had documented Gram-negative infection.\n Patients suspected of having life-threatening Gram-negative infections received one of two doses of E5 or placebo. Safety and efficacy were assessed by survival on days 3, 7, and 21, appearance of adverse reactions, development of antimurine antibodies, and effects on BP, urine output, WBC count, and temperature.\n Mortality rate from Gram-negative infection 3 days after the last drug (or placebo) infusion was two (22%) of nine deaths in the placebo group compared with 0 of nine for E5 2.5 mg/kg and 0 of five for E5 7.5 mg/kg. At 21 days after therapy, three patients treated with E5 had died. Only one of these three deaths resulted from infection. Eight of 15 E5 patients tested had immunoglobulin G antimurine antibodies by 3 wks after therapy began, but all were asymptomatic.\n E5 was well tolerated and may have the potential to reduce early morbidity and the mortality rate in seriously ill patients with Gram-negative infections. Results from larger phase III studies are needed to confirm these findings.", "The objective of this study was to assess the impact on outcome of adjuvant therapy (high-dose of immunoglobulin [Ig] M-enriched intravenous Ig, IVIG) in intensive care unit (ICU) patients who underwent surgery by abdominal sepsis. This was a prospective, randomized, double-blind, controlled study set in the medical/surgical ICUs of seven teaching hospitals. Patients with severe sepsis and septic shock of intra-abdominal origin admitted to the ICU within 24 h after the onset of symptoms were included in the study. Polyvalent IgM-enriched Ig (Pentaglobin; IVIG group) at a dosage of 7 mL/kg/day for 5 days or an equal amount of 5% human albumin (control group) was randomized. Fifty-six patients were enrolled. The overall mortality rate was 37.5.%. Twenty patients had shock and 36 had severe sepsis (the mortality rate was 55.0% and 25.0%, respectively). In the intent-to-treat analysis, the mortality rate was reduced from 48.1% in patients treated with antibiotic (ATB) plus albumin to 27.5% (P = 0.06) for patients with ATB plus IVIG. The organ failure score (1.0 +/- 0.6 vs. 1.2 +/- 0.9), organ dysfunction score (1.7 +/- 1.1 vs. 1.8 +/- 1.0), and reoperation rate (17.2% vs. 29.6%) were not different between IVIG and control groups, respectively. Eight patients (14.3%) received inappropriate ATB initial therapy (IAT), and seven died (87.5%). IAT was the only variable independently associated with death (odds ratio, 19.4) in a logistic regression model. We conclude that IVIG administration, when used in combination with adequate antibiotics, improved the survival of surgical ICU patients with intra-abdominal sepsis. The initial choice of antibiotic has a dramatic impact on outcome.", "HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia.\n To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol.\n Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected.\n HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.", "In this prospective, randomized controlled study, we aimed to evaluate the effect of IgM-enriched immunoglobulin treatment on progression of organ failure and septic shock in patients with severe sepsis.\n Forty-two patients with severe sepsis were enrolled in the study. Patients in the study group (n = 21) received an intravenous immunoglobulin preparation (Pentaglobin in addition to standard therapy. Pentaglobin therapy was commenced on the day of diagnosis of severe sepsis: 5 ml/kg per day Pentaglobin (38 g/l IgG, 6 g/l IgM, and 6 g/l IgA) was infused over 6 hours and repeated for 3 consecutive days. Patients in the control group (n = 18) received standard sepsis therapy, but no immunoglobulin administration. Blood samples for procalcitonin (PCT) measurements were taken daily for 8 days. Severity of critical illness and development of organ failure were assessed by obtaining daily acute physiological and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores.\n Procalcitonin levels showed a statistically significant decrease in the Pentaglobin group (P < 0.001); however, an improvement in SOFA scores could not be demonstrated. Procalcitonin levels and SOFA scores did not change significantly in the control group. Septic shock incidence (38% versus 57%) and 28-day mortality rate (23.8% versus 33.3%) were found to be similar between the Pentaglobin and control groups. The evaluation of serial APACHE II scores did not demonstrate a difference between Pentaglobin and control groups either.\n Present data could not demonstrate any beneficial effects of polyclonal immunoglobulin preparation Pentaglobin on organ morbidity, septic shock incidence and mortality rate in patients with severe sepsis.", "35 patients with septic postoperative complications entered a prospectively randomized study. The clinical state of these patients was daily determined using the sepsis score described by Elebute and Stoner. Endotoxin and antithrombin III were measured in the plasma using the limulus-amoebocyte-lysat test for endotoxin determination. The septic patients were treated with an immunoglobulin preparation (Pentaglobin) administered by the intravenous route. This preparation is enriched in IgM and IgA. Due to the immunoglobulin therapy the endotoxin titres decreased; simultaneously a reduction of mortality and shortening of time of hospitalization and of mechanical ventilation were observed.", "To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhIL-1ra) in the treatment of sepsis syndrome.\n Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial.\n A total of 893 patients with sepsis syndrome received an intravenous loading dose of rhIL-1ra, 100 mg, or placebo followed by a continuous 72-hour intravenous infusion of rhIL-1ra (1.0 or 2.0 mg/kg per hour) or placebo.\n Twenty-eight-day all-cause mortality.\n There was not a significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication (n = 893; generalized Wilcoxon statistic, P = .22) or among patients with shock at study entry (n = 713; generalized Wilcoxon statistic, P = .23), the two primary efficacy analyses specified a priori for this trial. Results from secondary analyses suggest an increase in survival time with rhIL-1ra treatment among patients with dysfunction of one or more organs (n = 563; linear dose-response, P = .009). Retrospective analysis demonstrated an increase in survival time with rhIL-1ra treatment among patients with a predicted risk of mortality of 24% or greater (n = 580; linear dose-response, P = .005) as well as among patients with both dysfunction of one or more organs and a predicted risk of mortality of 24% or greater (n = 411; linear dose-response, P = .002).\n There was not a statistically significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication or among patients with shock at study entry. Secondary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greater.", "To evaluate the safety, pharmacokinetics, and efficacy of human recombinant interleukin-1 receptor antagonist (IL-1ra) in the treatment of patients with sepsis syndrome.\n Prospective, open-label, placebo-controlled, phase II, multicenter clinical trial using three different doses of human recombinant IL-1ra.\n Twelve academic medical center intensive care units in the United States.\n Ninety-nine patients with sepsis syndrome or septic shock who received standard supportive care and antimicrobial therapy, in addition to infusion with escalating doses of IL-1ra or placebo.\n Patients received an intravenous loading dose of either human recombinant IL-1ra (100 mg) or placebo, followed by a 72-hr intravenous infusion of either one of three doses of IL-1ra (17, 67, or 133 mg/hr) or placebo. All patients were evaluated for 28-day, all-cause mortality.\n A dose-dependent, 28-day survival benefit was associated with IL-1ra treatment (p = .015), as indicated by the following mortality rates: 11 (44%) deaths among 25 placebo patients; eight (32%) deaths among 25 patients receiving IL-1ra 17 mg/hr; six (25%) deaths among 24 patients receiving IL-1ra 67 mg/hr; and four (16%) deaths among 25 patients receiving IL-1ra 133 mg/hr. A dose-related survival benefit was observed with infusion of IL-1ra in patients with septic shock at study entry (n = 65; p = .002) and in patients with Gram-negative infection (n = 45; p = .04). Patients with an increased circulating interleukin-6 (IL-6) concentration of > 100 pg/mL at study entry demonstrated a dose-related survival benefit with IL-1ra treatment (p = .009). In patients with an increased IL-6 concentration at study entry, the magnitude of the decrease in IL-6 concentration 24 hrs after the initiation of therapy was correlated with increasing the IL-1ra treatment dose (p = .052). A significant dose-related reduction in the Acute Physiology and Chronic Health Evaluation (APACHE II) score was achieved by the end of infusion (p = .038). A renal elimination mechanism for IL-1ra was suggested by the positive correlation between IL-1ra plasma clearance and estimated creatinine clearance (p = .001; r2 = .51). Human recombinant IL-1ra was well tolerated.\n This initial evaluation suggests that human recombinant IL-1ra is safe and may provide a dose-related survival advantage to patients with sepsis syndrome. A larger, definitive clinical trial is needed to confirm these findings.", "To evaluate whether administration of afelimomab, an anti-tumor necrosis factor F(ab')2 monoclonal antibody fragment, would reduce 28-day all-cause mortality in patients with severe sepsis and elevated serum levels of IL-6.\n Prospective, randomized, double-blind, placebo-controlled, multiple-center, phase III clinical trial.\n One hundred fifty-seven intensive care units in the United States and Canada.\n Subjects were 2,634 patients with severe sepsis secondary to documented infection, of whom 998 had elevated interleukin-6 levels.\n Patients were stratified into two groups by means of a rapid qualitative interleukin-6 test kit designed to identify patients with serum interleukin-6 levels above (test positive) or below (test negative) approximately 1000 pg/mL. Of the 2,634 patients, 998 were stratified into the test-positive group, 1,636 into the test-negative group. They were then randomly assigned 1:1 to receive afelimomab 1 mg/kg or placebo for 3 days and were followed for 28 days. The a priori population for efficacy analysis was the group of patients with elevated baseline interleukin-6 levels as defined by a positive rapid interleukin-6 test result.\n In the group of patients with elevated interleukin-6 levels, the mortality rate was 243 of 510 (47.6%) in the placebo group and 213 of 488 (43.6%) in the afelimomab group. Using a logistic regression analysis, treatment with afelimomab was associated with an adjusted reduction in the risk of death of 5.8% (p = .041) and a corresponding reduction of relative risk of death of 11.9%. Mortality rates for the placebo and afelimomab groups in the interleukin-6 test negative population were 234 of 819 (28.6%) and 208 of 817 (25.5%), respectively. In the overall population of interleukin-6 test positive and negative patients, the placebo and afelimomab mortality rates were 477 of 1,329 (35.9%)and 421 of 1,305 (32.2%), respectively. Afelimomab resulted in a significant reduction in tumor necrosis factor and interleukin-6 levels and a more rapid improvement in organ failure scores compared with placebo. The safety profile of afelimomab was similar to that of placebo.\n Afelimomab is safe, biologically active, and well tolerated in patients with severe sepsis, reduces 28-day all-cause mortality, and attenuates the severity of organ dysfunction in patients with elevated interleukin-6 levels.", "To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis.\n Double-blind, randomized, placebo-controlled trial.\n Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals.\n Hospitalized adults with signs of gram-negative infection and a systemic septic response.\n Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later.\n Mortality over the 30-day study period, resolution of organ failures, and safety.\n Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified.\n Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated.", "The value of IgM-enriched immunoglobulin therapy in 44 preterm infants with neonatal sepsis was evaluated in a prospective randomized study. All infants received antibiotic therapy and fresh plasma and/or whole blood transfusions. Twenty randomly-chosen infants were allocated to receive 5 ml/kg/d of IgM-enriched immunoglobulin intravenously for three days. Although the mortality rate in preterm infants whose gestational ages were 31-34 weeks in the immunotherapy group was slightly lower than in the control group, the general mortality rate from sepsis in the control group (9/24) and in the immunotherapy group (6/20) showed no statistically significant difference (37.5% vs 30.0%, p < 0.05).", "To determine the safety of a \"humanized\" antibody to human anti-tumor necrosis factor-alpha (TNF-alpha) in patients with septic shock, and to examine the pharmacokinetics, immune response, and influence of the antibody on cytokine concentrations in this patient group.\n Prospective, randomized, placebo-controlled, phase II multicenter clinical trial, with escalating doses of a fully humanized anti-TNF-alpha antibody (CDP571).\n Seven academic intensive care units in Europe.\n Forty-two patients with rapidly evolving septic shock who received CDP571 in addition to standard supportive care.\n Patients received intravenously either placebo or one of four single doses of CDP571: 0.1, 0.3, 1.0, or 3.0 mg/kg.\n The humanized anti-TNF-alpha antibody was well tolerated. The overall all-cause 28-day mortality rate was 62%. Mortality rate was similar in the placebo and treatment groups, except that all six patients who received 0.3 mg/kg of CDP571 died within 7 days. This outcome, which was not dose-related, is consistent with the poorer prognostic characteristics of this group at baseline. The peak CDP571 concentrations and area under the curve increased proportionately with the dose. The low level of the immune response detected had little effect on the ability of circulating CDP571 to bind TNF-alpha and on the pharmacokinetics of the antibody. An abrupt reduction in circulating TNF-alpha concentration was observed 30 mins after CDP571 administration at all active dosage levels. While interleukin-1 beta and interleukin-6 plasma concentrations decreased with time in all dosage groups, these cytokine concentrations decreased more rapidly during the initial 24 hrs in the treatment groups than in the placebo group.\n The humanized anti-TNF-alpha antibody, CDP571, is well tolerated and able to cause a dose-dependent reduction in circulating TNF-alpha concentrations in patients with septic shock. Further studies are needed to determine the efficacy of this antibody to improve the survival rates of critically ill patients with severe sepsis.", "A randomized controlled clinical trial was conducted on the effects of immunoglobulin in therapy for infections in 104 intensive care patients. At the first sign of infection, one group of 50 patients received an i.v. preparation of immunoglobulin (4 X 100 ml) combined with antibiotics. The other 54 control patients received antibiotics alone. The most common infections in these patients were pneumonia, septicemia, peritonitis and wound sepsis. Infections were significantly seldom the cause of death, especially in patients with high-risk surgery who had been treated with immunoglobulin (p less than or equal to 0.05). Likewise ventilation time in the high-risk surgery group averaged only 5.5 days for those receiving immunoglobulin as opposed to 12.7 days in controls (p less than or equal to 0.01). Whereas the control group, in particular patients with pneumonia, remained in intensive care an average of 21.5 days, those receiving immunoglobulin stayed only 14.8 days (p less than or equal to 0.01). In general, patients treated with immunoglobulin recovered more rapidly from infections than did controls (p less than or equal to 0.01).", "To determine whether therapy with intravenous immunoglobulin G (IVIG) would decrease mortality in neonatal sepsis.\n Three tertiary care neonatal intensive care units in the city of Bangalore.\n All neonates admitted to the Neonatal Intensive Care Units with the clinical diagnosis of sepsis and having at least C-reactive protein and one other rapid diagnostic criteria positive were enrolled. Neonates with a birth weight of less than 1000 g and those with any major congenital malformation were excluded. The neonates were randomized to receive 1 g/kg of IVIG on three consecutive days or an equivalent amount of placebo. The rest of the treatment including antibiotics and supportive care was as per the treating physician's decision. The main outcome variable was survival.\n The trial was carried out over a period of 8 months and recruited 58 neonates. Seven neonates who qualified but did not receive either IVIG or placebo were taken into a separate control group, and one baby who received only one dose of IVIG was excluded from the analysis. Twenty-five neonates were enrolled into the IVIG arm and 25 in the placebo arm. The neonates in the therapy and placebo groups were comparable in terms of birth weight (2144+/-675 g vs. 2072+/-682 g), gestation (37.0+/-3.56 vs. 35.8+/-3.52 weeks), sex distribution, duration of stay, and number requiring ventilation. The placebo group had a significantly higher number of babies with positive blood culture. Seven babies in each group died (p>0.05). There was no significant benefit in using IVIG (OR 1.0; 95% CI 0.25-4.07) (p = 0.74).\n In the sample studied therapy with IVIG did not reduce mortality in neonatal sepsis", "Despite the development of newer generation of antibiotics, mortality from neonatal sepsis remains high. In a prospective, randomized study, we investigated the use of IgM-enriched immunoglobulin therapy in neonatal sepsis. Two groups of 30 infants each (matched for gestational age, sex, weight, and other variables) were randomly allocated to receive either antibiotics alone (control group) or antibiotics plus 5 mL/kg/d for four days of IgM-enriched immunoglobulin intravenously (immunotherapy group). Mortality from sepsis in the control group was 20% (6/30), while in the immunotherapy group it was 3.3% (1/30). We conclude that IgM-enriched immunoglobulin therapy in conjunction with antibiotic therapy significantly reduces mortality from neonatal sepsis.", "To investigate the safety, biological effects, and efficacy of the anti-tumor necrosis factor (TNF) antibody fragment, MAK 195F, in a phase II trial in patient with severe sepsis.\n Prospective, randomized, open label, placebo-controlled, dose-ranging, multicenter, multinational clinical trial.\n Sixteen academic medical centers' intensive care units in six European countries.\n One hundred twenty-two patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy.\n Patients received one of three different doses of the anti-TNF antibody (0.1 mg/kg, 0.3 mg/kg, or 1.0 mg/kg) or placebo; the antibody or placebo was given in nine doses at 8-hr intervals over 3 days.\n There were no significant differences in mortality rates among the groups receiving various doses of the anti-TNF antibody or placebo, but patients with baseline serum interleukin (IL)-6 concentrations of > 1000 pg/mL appeared to benefit from MAK 195F in a dose-dependent fashion. Increased circulating IL-6 concentrations, but not TNF concentrations, were found to be important prognostic indicators for mortality for the patients in the placebo and the two lower dosage groups but not in the high dosage group (1 mg/kg). IL-6 concentrations decreased during the first 24 hrs of treatment in all three anti-TNF groups but not in the placebo group. MAK 195F was well tolerated by all patients. Human antimurine antibodies developed in 40% of the patients receiving the antibody.\n There was no increase in survival from sepsis for the patients receiving anti-TNF treatment in the overall study population. Retrospective stratification of patients by IL-6 concentrations suggests beneficial effects of the drug for patients with baseline circulating IL-6 concentrations of > 1000 pg/mL. This hypothesis requires validation in a larger, blinded, prospective study.", "Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection. To determine whether intravenous immune globulin (IVIG) therapy improves survival rates in early-onset sepsis, we prospectively entered 753 neonates (birth weight 500 to 2000 gm, gestation less than or equal to 34 weeks, age less than or equal to 12 hours) into a multicenter, double-blind, controlled trial. Blood culture specimens were obtained and infants randomly assigned to receive 10 ml (per kilogram) intravenously of a selected IVIG (500 mg/kg) or albumin (5 mg/kg) preparation. Maternal and neonatal risk factors were not different between groups. Thirty-one babies (4.2%) had early-onset sepsis; the causative organisms were group B streptococcus (12 babies), Escherichia coli (6), and others (13). Of these 31 neonates, 7 (23%) died. Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment (p less than 0.05). During these 7 days, 5 (30%) of 17 albumin-treated and none of 14 IVIG-treated patients died (p less than 0.05). The survival rate at 56 days of age, however, was not significantly improved. Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody. Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy (0.5%) than in those receiving albumin. The IVIG therapy in neonates with early-onset sepsis, while reducing the early mortality rate, did not significantly affect the overall survival rate. Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens.", "Despite the availability of potent antibiotics and intensive care, mortality rates from septic shock are 40-70%. We assessed the safety and efficacy of murine monoclonal antibody to human tumour necrosis factor alpha (TNF alpha MAb) in the treatment of septic shock.\n In a randomised, multicentre, double-blind, placebo-controlled clinical trial in 105 hospitals in the USA and Canada, we randomly assigned 1879 patients a single infusion of 7.5 mg/kg TNF alpha MAb (n=949) or placebo (0.25% human serum albumin n=930). Our main outcome measurement was the rate of all-cause mortality at 28 days.\n 382 (40.3%) of 948 patients who received TNF alpha MAb and 398 (42.8%) of 930 who received placebo had died at 28 days (95% CI -0.02 to 0.07, p=0.27). We found no association between therapy with TNF alpha MAb and increased rapidity in reversal of initial shock or prevention of subsequent shock. Similarly, baseline plasma interleukin-6 concentrations of more than 1000 pg/mL or detectable circulating TNF concentrations were not associated with improvement in survival after TNF alpha MAb therapy. Coagulopathy but not other organ or system failures, was significantly decreased in the TNF alpha MAb group compared with placebo (day 7, p<0.001; day 28, p=0.005). Serious adverse events were reported in 55.2% of patients given placebo and 54.1% in the TNF alpha MAb group.\n We did not find an improvement in survival after septic shock with TNF alpha MAb. Therapy not solely dependent on TNF alpha blockade may be required to improve survival.", "Thrombocytopenia frequently complicates systemic infection and results from multiple possible mechanisms. We and others have demonstrated that platelet-associated IgG (PAIgG) levels are elevated in the majority of patients with septic thrombocytopenia. Corticosteroids may be undesirable as a treatment for thrombocytopenia for patients with severe infection because of their potential for suppressing the immune response. We hypothesized that septic thrombocytopenia is, in most cases, an immune disorder analogous to idiopathic thrombocytopenic purpura (ITP) which might respond to intravenous gamma-globulin as a treatment for increasing the platelet count in this disorder. Intravenous immune globulin (IVIG), 400 mg/kg daily for 3 days, was administered in a randomized double-blind placebo-controlled trial. Twenty-nine patients who developed thrombocytopenia during a documented, septic episode were studied. Patients with disseminated intravascular coagulation (DIC), hypersplenism, or drugs known to cause thrombocytopenia were excluded. Elevated PAIgG levels were documented in 52% of evaluable patients. Mean platelet counts in the IVIG group rose from 43K at study entry to 178K (411% rise) by Day 9. In the placebo group platelets rose from 51K to 125K (261% rise; P = 0.02). Seventy-seven percent of the IVIG group had a minimum peak rise of 35K, vs 56% of the placebo group. Three patients in the placebo group had a serious bleeding episode, vs one in the IVIG group. The use of IVIG to treat septic thrombocytopenia not associated with DIC leads to a more rapid, more sustained, and greater increase in platelet count than placebo. Its use is recommended in the septic patient who is bleeding or is likely to need invasive or surgical procedures.", "59 patients with suspected or verified septicaemia and 87 patients with suspected or verified bacterial pneumonia were treated with either antibiotics alone or antibiotics combined with a pepsin-treated human gamma globulin (Gamma-Venin). The gamma globulin was given intravenously in repeated doses of 0.15 g/kg body weight. Extensive clinical and laboratory investigations were performed repeatedly in a strictly standardized fashion. Neither the septicaemia group nor the pneumonia group presented significant differences between treated patients and controls for any of the clinical and laboratory variables studied. Hospital stay, duration of fever and symptoms were also unaffected by the gamma globulin treatment. Subdivision of the material according to aetiology provided no additional information. In 9 patients adverse reactions were seen, e.g., shock in 2 individuals.", "Freeze-dried human plasma rich in anti-lipopolysaccharide (anti-LPS) immunoglobulin G was used to treat septic shock (systolic pressure less than or equal to 80 mm Hg, central venous pressure greater than or equal to 6 cm H2O) in obstetric and gynaecological patients. Mortality in conventionally treated patients was 9/19 (47.4%) compared with 1/14 (7.1%) in anti-LPS-treated patients. Anti-LPS caused the mean arterial pressure to rise from 45.1 +/- 7.36 mm Hg to 69.1 +/- 9.07 mm Hg within 75 min of administration. The mean hospital stay of survivors was 28.1 days for controls and 14.2 days for the anti-LPS-treated patients. The development of complications of septic shock was much reduced in the treated group. Anti-LPS thus appears significantly to reduce mortality and morbidity in septicaemia.", "To determine the therapeutic efficacy and safety of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) in the treatment of patients with severe sepsis.\n Prospective, randomized, double-blind, placebo-controlled, multicenter trial with a planned, midstudy, interim analysis.\n Ninety-one academic medical center intensive care units in North America and Europe.\n Patients with severe sepsis or septic shock (n = 696) received standard supportive care and antimicrobial therapy for sepsis, in addition to rhIL-1ra or placebo.\n Patients were randomized to receive either rhIL-1ra (100 mg) or placebo (vehicle) by intravenous bolus, followed by a 72-hr continuous intravenous infusion of either rhIL-1ra (2.0 mg/kg/hr) or placebo.\n The study was terminated after an interim analysis found that it was unlikely that the primary efficacy end points would be met. The 28-day, all-cause mortality rate was 33.1% (116/350) in the rhIL-1ra treatment group, while the mortality rate in the placebo group was 36.4% (126/346), yielding a 9% reduction in mortality rate (p = .36). The patients were well matched at the time of study entry; 52.9% of placebo-treated patients were in shock while 50.9% of rhIL-1ra-treated patients were in shock at the time of study entry (p = .30). The mortality rate did not significantly differ between treatment groups when analyzed on the basis of site of infection, infecting microorganism, presence of bacteremia, shock, organ dysfunction, or predicted risk of mortality at the time of study entry. No excess number of adverse reactions or microbial superinfections were attributable to rhIL-1ra treatment in this study.\n A 72-hr, continuous intravenous infusion of rhIL-1ra failed to demonstrate a statistically significant reduction in mortality when compared with standard therapy in this multicenter clinical trial. If rhIL-1ra treatment has any therapeutic activity in severe sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial.", "To evaluate the efficacy and safety of anti-tumor necrosis factor alpha monoclonal antibody (TNF-alpha MAb) in the treatment of patients with sepsis syndrome.\n Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial.\n A total of 31 hospitals in the United States and Canada.\n There were 994 patients with sepsis syndrome enrolled in this clinical trial, and 971 patients were infused with the study drug.\n Patients were prospectively stratified into shock or nonshock groups and then randomized to receive a single infusion of 15 mg/kg of TNF-alpha MAb, 7.5 mg/kg of TNF-alpha MAb, or placebo. Patients received standard aggressive medical and surgical care during the 28-day postinfusion period.\n Twenty-eight-day all-cause mortality.\n The distribution of variables describing demographics, organ system dysfunction or failure, preinfusion Acute Physiology and Chronic Health Evaluation II score, number of organs failing at baseline, initial sites of infection, infecting microorganisms, antimicrobials used, and initial invasive procedures was similar among patients in the TNF-alpha MAb and placebo treatment arms. Among all infused patients, there was no difference in all-cause mortality in patients who received placebo as compared with those who received TNF-alpha MAb. In septic patients with shock (n = 478), there was a trend toward a reduction in all-cause mortality, which was most evident 3 days after infusion: 25 of 162 patients treated with 15 mg/kg of TNF-alpha MAb died, 22 of 156 patients treated with 7.5 mg/kg of TNF-alpha MAb died, and 44 of 160 patients in the placebo group died (15 mg/kg: 44% reduction vs placebo, P = .01; 7.5 mg/kg: 48.7% reduction vs placebo, P = .004). At day 28, the reduction in mortality for shock patients was not significant for either dose of TNF-alpha MAb relative to placebo (15 mg/kg, 61 deaths among 162 patients [37.7% mortality]; 7.5 mg/kg, 59 deaths among 156 patients [37.8% mortality]; placebo, 73 deaths among 160 patients [45.6% mortality]; P = .20 for 7.5 mg/kg and P = .15 for 15 mg/kg). Serious adverse events were reported in 4.6% of all infused patients. No immediate hypersensitivity allergic reactions due to TNF-alpha MAb were reported. Serum sickness-like reactions were seen in 2.5% of patients receiving TNF-alpha MAb.\n There was no decrease in mortality between placebo and TNF-alpha MAb in all infused patients. In septic shock patients who received TNF-alpha MAb, a significant reduction in mortality was present 3 days after infusion. Although a trend toward reduced mortality continued at 28 days following treatment with TNF-alpha MAb, the difference in mortality among shock patients treated with placebo or TNF-alpha MAb was not significant.", "To evaluate in Gram-negative sepsis patients the human monoclonal immunoglobulin M antibody (MAB-T88) directed at the enterobacterial common antigen which is a specific surface antigen closely linked to lipopolysaccharide and shared by all members of the Enterobacteriaceae family of Gram-negative bacteria.\n Prospective, randomized, double-blinded, placebo-controlled, multicenter trial.\n Thirty-three academic medical centers in the United States.\n Patients were entered with a clinical diagnosis of sepsis, the presence of either shock or multiple organ dysfunction, and presumptive evidence for Gram-negative infection.\n Patients received a single intravenous infusion, over 30 mins, of either 300 mg of MAB-T88 formulated in albumin, or placebo (albumin).\n The primary analysis group was prospectively identified as those patients with documented evidence of an infection with bacteria of the family Enterobacteriaceae at any site. The primary end point was survival within the first 28 days. A total of 826 patients were enrolled with 55% (n = 455) in the primary analysis group. There were no significant differences between the intervention and control primary analysis group study groups for sites of infection, severity of illness, underlying medical conditions, adequacy of antibiotic or surgical treatment, or other baseline variables except for a higher frequency of chronic renal failure in the MAB-T88 group (4.4% vs. 1.3%, p=.051). The average Acute Physiology and Chronic Health Evaluation II scores were 26.8 +/- 8.6 (mean +/- sd) in the MAB-T88-treated group and 26.5 +/- 8.3 in the placebo-treated group (p =.72). There was no significant difference between MAB-T88- and placebo-treated groups during the first 28-day all-cause mortality in the primary analysis group (34.2% vs. 30.8%, p=.44) or in all 826 patients enrolled (37.0% vs. 34.0%, p=.36). On subset analysis, the use of MAB-T88 was not associated with significant mortality trends. More adverse events were seen with the use of MAB-T88 in the bacteremic enterobacterial common antigen group (p <.05).\n Use of the human monoclonal antibody, MAB-T88, did not improve the mortality in patients with presumed Gram-negative sepsis or in those patients with proven enterobacterial common antigen infections. No subset trends were identified that would support further investigation of this agent in sepsis.", "Knowledge and understanding of gram-negative sepsis have grown over the past 20 years, but the ability to treat severe sepsis successfully has not.\n To assess the efficacy and safety of E5 in the treatment of patients with severe gram-negative sepsis.\n A multicenter, double-blind, randomized, placebo-controlled trial conducted at 136 US medical centers from April 1993 to April 1997, designed with 90% power to detect a 25% relative risk reduction, incorporating 2 planned interim analyses.\n Intensive care units at university medical centers, Veterans Affairs medical centers, and community hospitals.\n Adults aged 18 years or older, with signs and symptoms consistent with severe sepsis and documented or probable gram-negative infection.\n Patients were assigned to receive 2 doses of either E5, a murine monoclonal antibody directed against endotoxin (n = 550; 2 mg/kg per day by intravenous infusion 24 hours apart) or placebo (n = 552).\n The primary end point was mortality at day 14; secondary end points were mortality at day 28, adverse event rates, and 14-day and 28-day mortality in the subgroup without shock at presentation.\n The trial was stopped after the second interim analysis. A total of 1090 patients received study medication and 915 had gram-negative infection confirmed by culture. There were no statistically significant differences in mortality between the E5 and placebo groups at either day 14 (29.7% vs 31.1%; P = .67) or day 28 (38.5% vs 40.3%; P = .56). Patients presenting without shock had a slightly lower mortality when treated with E5 but the difference was not significant (28.9% vs 33.0% for the E5 and placebo groups, respectively, at day 28; P = .32). There was a similar profile of adverse event rates between E5 and placebo.\n Despite adequate sample size and high enrollment of patients with confirmed gram-negative sepsis, E5 did not improve short-term survival. Current study rationale and designs should be carefully reviewed before further large-scale studies of patients with sepsis are conducted.", "Intravenous immunoglobulin as an adjunctive treatment in sepsis was regarded as promising by a Cochrane meta-analysis of smaller trials. In this phase III multicenter trial, we assessed whether intravenous immunoglobulin G (ivIgG) reduced 28-day mortality and improved morbidity in patients with score-defined severe sepsis.\n Randomized, double-blind, placebo-controlled, multicenter trial.\n Twenty-three medical and surgical intensive care units in university centers and large teaching hospitals.\n Patients (n = 653) with score-defined sepsis (sepsis score 12-27) and score-defined sepsis-induced severity of disease (Acute Physiology and Chronic Health Evaluation II score 20-35).\n Patients were assigned to receive either placebo or ivIgG (day 0, 0.6 g/kg body weight; day 1, 0.3 g/kg body weight).\n The prospectively defined primary end point was death from any cause after 28 days. Prospectively defined secondary end points were 7-day all-cause mortality, short-term change in morbidity, and pulmonary function at day 4. Six hundred fifty-three patients from 23 active centers formed the intention-to-treat group, 624 patients the per-protocol group (placebo group, n = 303; ivIgG group, n = 321). The 28-day mortality rate was 37.3% in the placebo group and 39.3% in the ivIgG group and thus not significantly different (p = .6695). Seven-day mortality was not reduced, and 4-day pulmonary function was not improved. Drug-related adverse events were rare in both groups. Exploratory findings revealed a 3-day shortening of mechanical ventilation in the surviving patients and no effect of ivIgG on plasma levels of interleukin-6 and tumor necrosis factor receptors I and II.\n In patients with score-defined severe sepsis, ivIgG with a total dose of 0.9 g/kg body weight does not reduce mortality.", "To evaluate the effect of intravenous IgMA-enriched immunoglobulin (ivIGMA) therapy on mortality in neutropenic patients with hematologic malignancies and sepsis syndrome or septic shock.\n Multiple-center, prospective randomized, controlled study.\n Six university hospitals in Germany.\n Patients were 211 neutropenic patients with sepsis syndrome or septic shock after chemotherapy for severe hematologic disorders between 1992 and 1999.\n Patients received 1300 mL of ivIGMA (7.8 g IgM, 7.8 g IgA, and 49.4 g IgG) infused intravenously within a period of 72 hrs or human albumin according to the same schedule as ivIGMA.\n All-cause mortality at 28 days, sepsis-related mortality at 28 days, all-cause mortality at 60 days, mortality from septic shock, and mortality from microbiologically proven Gram-negative sepsis and septic shock were recorded. Immunoglobulin had no benefit over human albumin. The 28-day mortality rate was 26.2% and 28.2% in the ivIGMA and control patients, respectively (difference, 2.0% [95% confidence interval, -10.2 to 14.2 percentage points]). Likewise, the 60-day mortality rate did not differ between both arms (29.6% vs. 34.7% in the ivIGMA and control patients, respectively). Mortality rates in patients with sepsis syndrome (17.1% vs. 16.7%) and septic shock (51.9% vs. 54.8%) were also found to be similar between both groups.\n Intravenous ivIGMA had no beneficial effects in neutropenic patients with hematologic malignancies and sepsis syndrome and septic shock." ]

[ "6728584", "18927148", "9397127", "9544598", "12390903", "4710458", "16200556" ]

[ "Does pediatric home care make a difference for children with chronic illness? Findings from the Pediatric Ambulatory Care Treatment Study.", "Home oxygen for children with acute bronchiolitis.", "Stress-point intervention for parents of repeatedly hospitalized children with chronic conditions.", "An economic evaluation of home care for children with newly diagnosed diabetes: results from a randomized controlled trial.", "Randomised controlled trial comparing an acute paediatric hospital at home scheme with conventional hospital care.", "Delivery of care to hemophilic children: home care versus hospitalization.", "Hospital and home chemotherapy for children with leukemia: a randomized cross-over study." ]

[ "The ongoing care needed by children with chronic physical illness is a topic of national concern. The Pediatric Ambulatory Care Treatment Study ( PACTS ) is a classic pretest-posttest randomized experiment designed to evaluate a Pediatric Home Care (PHC) program in which an interdisciplinary team provides comprehensive primary health care, support, coordination, patient advocacy, and education to chronically ill children and their families. Home interviews were conducted by an independent research team with the 219 families at enrollment, 6 months, and 1 year; 80% completed all three interviews. Analyses indicate that pediatric home care is effective in improving the satisfaction of the family with care, in improving the child's psychological adjustment, and in lessening the psychiatric symptoms of the mother. The functional status of the children was equally well maintained in both groups, and there was no significant difference in the impact of the illness on the family between the two groups. There are indications that there may be a dose-related effect with respect to the child's psychological adjustment with those in the program for the longest period of time showing the greatest benefit. Such a home care program can be an effective intervention for minimizing the social and psychological consequences of chronic illness.", "A prospective randomised controlled pilot study was performed comparing home oxygen therapy with traditional inpatient hospitalisation for children with acute bronchiolitis. Children aged 3-24 months with acute bronchiolitis, still requiring oxygen supplementation 24 h after admission to hospital, were randomly assigned to receive oxygen supplementation at home with support from \"hospital in the home\" (HiTH) or to continue oxygen supplementation in hospital. 44 children (26 male, mean age 9.2 months) were recruited (HiTH n = 22) between 1 August and 30 November 2007. Only one child from each group was readmitted to hospital and there were no serious complications. Children in the HiTH group spent almost 2 days less in a hospital bed than those managed as traditional inpatients: HiTH 55.2 h (interquartile range (IQR) 40.3-88.9) versus in hospital 96.9 h (IQR 71.2-147.2) p = 0.001. Home oxygen therapy appears to be a feasible alternative to traditional hospital oxygen therapy in selected children with acute bronchiolitis.", "Little is known about how to assist children with chronic conditions and their families cope with repeated hospitalizations. A two-group, pretest-posttest study was done to determine whether a community-based, stress-point nursing intervention for parents could decrease distress and improve child and family functioning. Fifty participants were randomly assigned to intervention or usual care control groups. The intervention focused on specific, parent-verified child and family issues. Three months after hospitalization, intervention parents had better coping and family functioning than those in the usual care group. Intervention parents' anxiety was initially higher and then lower. There were no child behavior differences between the groups after hospitalization. Intervention children had no developmental regression at 2 weeks and better developmental gains 3 months after discharge than the usual care children. Stress-point intervention for families and their children with chronic conditions improved family coping and functioning, and eliminated hospitalization-induced developmental regression.", "This study was undertaken to determine the health and cost effects of using home care to treat newly diagnosed Type I diabetic children rather than traditional inpatient hospital care. There had been no well-designed evaluations of home care for such children, and very few for children with other health conditions.\n Sixty-three children seen at the Montreal Children's Hospital were randomly assigned at diagnosis to home care or traditional inpatient care. The children in the former group were discharged once their metabolic condition stabilized; insulin adjustments and teaching were done in their homes by a trained nurse. The children in the latter group remained hospitalized for insulin adjustments and teaching. All were followed for 24 months. The cost effects were estimated using hospital and parental data.\n Social costs were only $48 higher with home care. It had little effect on social costs, because the increased costs of health care services with home care ($768) were largely offset by parental cost savings ($720). Home care improved the children's metabolic outcomes without adversely affecting their psychosocial outcomes.\n Using home care to reduce hospital stays for children with newly diagnosed Type I diabetes improved the children's health outcomes without significantly increasing social costs.", "To assess the clinical effectiveness of a paediatric hospital at home service compared to conventional hospital care.\n A total of 399 children suffering from breathing difficulty (n = 202), diarrhoea and vomiting (n = 125), or fever (n = 72) were randomised to Hospital at Home or in-patient paediatric care. Main outcome measures were: comparative clinical effectiveness as measured by readmission rate within three months (used as a proxy for parental coping with illness); and length of stay/care and comparative satisfaction of both patients and carers.\n Clinical effectiveness of both services was not significantly different. Length of care was one day longer in the Hospital at Home group; however, most parents and children preferred home care.\n Hospital at Home is a clinically acceptable form of care for these groups of acute paediatric illness. Readmission rates within three months failed to show any advantage in terms of parental coping. Parents and patients expressed a strong preference for hospital at home.", "nan", "The study objective was to compare a hospital-based and a home-based chemotherapy program for children with acute lymphoblastic leukemia (ALL) in relation to Quality of Life (QOL), safety, caregiver burden, and costs.\n A randomized cross-over trial (RCT) design with repeated measures was conducted with 23 children with ALL who attended the oncology outpatient clinic of a metropolitan university affiliated tertiary level pediatric hospital and who also received home visits from a community health services care provider in central Canada.\n During the home-treatment phase, children were more capable of maintaining their usual routines than when receiving hospital chemotherapy (Wilcoxon statistic = 80, P = 0.023), but they appeared to experience greater emotional distress (Wilcoxon sign rank statistic S = 66, P = 0.043) according to parental report. Treatment location had no effect on caregiver burden and adverse effects. No significant differences between groups existed with respect to societal costs of care. As the child's age increased, QOL improved relative to younger children (t(20) = -2.37, P = 0.02), the time burden related to child care tasks was reduced (t(21) = -3.56, P = 0.002), caregiver effort/difficulty in physical and behavioral support decreased (t(21) = -2.09, P = 0.049) and the odds of experiencing one or more adverse events decreased (OR = 0.79, CI = (0.63-1.00), chi(1) (2) = 4.01, P = 0.045).\n With few differences noted between groups, these results indicate preliminary support for administrating some or all of a child's chemotherapy at home. Home chemotherapy was associated with specific improvements and decrements in parent reported QOL. No effects were seen on burden of care, adverse events, or cost. Overall, young age adversely affected QOL, burden of care, and adverse events. These data provide important information to families and caregivers as they consider home or hospital-based therapy in childhood ALL." ]

[ "8797480" ]

[ "Double-blind comparison of cabergoline and bromocriptine in Parkinson's disease patients with motor fluctuations." ]

[ "In the present study we compared the efficacy and safety of the new dopamine agonist cabergoline (CBG) with bromocriptine (BCR) in Parkinson's disease (PD). CBG has a very long half-life and can be administered as a single daily dose. Forty-four PD patients with uncontrolled motor fluctuations participated in the study. Patients were randomly and blindly assigned to equivalent doses of either CBG or BCR in addition to preexisting levodopa. Dosage was titrated to optimal, using up to 6 mg of CBG or 40 mg of BCR daily. CBG was given as a single morning dose whereas BCR was administered tid. Sixteen patients were followed for 1 year and 16 additional patients for 6 months. The mean follow-up duration was 9 +/- 5 months. The main effect of both drugs was observed on motor UPDRS scores, rigidity, bradykinesia items, and the percentage of awake hours spent during \"on\" and \"off\". In general, the effect of CBG was similar to that of BCR. The percentage of awake hours spent during \"on\" was higher with CBG as compared with BCR. Adverse events included dyskinesias, orthostatism, confusion, edema, and paresthesias in limbs. These effects were seen at similar frequencies with both drugs. The study shows that CBG given as a single morning dose is at least as efficacious as BCR given tid. CBG is a promising dopamine agonist for the treatment of motor fluctuations in PD." ]

[ "321508", "3301493", "10945510", "11881837", "2044398", "3212603", "7454926" ]

[ "A memory assessment technique for use in geriatric psychopharmacology: drug efficacy trial with naftidrofuryl.", "[Efficacy and tolerance of long-term naftidrofuryl treatment of patients with senile dementia. Controlled study versus placebo].", "Efficacy of naftidrofuryl in patients with vascular or mixed dementia: results of a multicenter, double-blind trial.", "Naftidrofuryl in the treatment of vascular dementia.", "Efficacy of naftidrofuryl in patients with moderate senile dementia.", "[Naftidrofuryl in patients with multi-infarct dementia and Alzheimer's disease].", "A cognitive impairment scale applicable to verbal samples and its possible use in clinical trials in patients with dementia [proceedings]." ]

[ "This study was conducted to compare an automated test of paced stimulus material (Sperling's Perceptual Trace, SPT) with several other standard memory scales. Sixty patients with mild senile organic brain syndrome were divided into two groups of 30; one group was treated for 90 days with 300 mg daily of naftidrofuryl (Praxilene), and the other group received placebo. The patients were tested before treatment and at 30, 60 and 90 days after the beginning of treatment. The data indicated that the SPT indirectly assesses short-term memory, is resistant to practice effects, and is drug-sensitive. It is suggested that the SPT might become the test of choice in the indirect assessment of short-term memory in the elderly.", "nan", "Dementia is a cerebral disorder resulting in a progressive deterioration of intellectual function that compromises the patient's ability to function. The diagnostic criteria for dementia are primarily clinical and are based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Hachinski score and computed tomography of the brain help distinguish between degenerative and vascular dementias.\n This study examined the efficacy of naftidrofuryl in patients with vascular or mixed dementia.\n This multicenter, randomized, double-blind study compared naftidrofuryl 600 mg/d with placebo for 1 year in patients with vascular or mixed dementia. A preliminary 2-month washout period allowed selection of patients who were compliant with treatment. The end point was change in the scores on the Alzheimer Disease Assessment Scale cognitive subscale and the Mini-Mental State Examination.\n Eighty-four patients were assessable on an intent-to-treat basis, and 74 were assessable for the per-protocol analysis (on-treatment). Statistically significant improvements in cognitive and global function were observed in patients receiving naftidrofuryl. Naftidrofuryl was well tolerated, and produced no clinically significant abnormalities in laboratory test results.\n The results of this study suggest that naftidrofuryl is effective and well tolerated in treating the symptoms of vascular and mixed dementia.", "The design of this study was based on the European guidelines for the treatment of Alzheimer's disease. After a placebo run-in period of 4 weeks, patients with a diagnosis of vascular dementia (VaD) were randomised to receive either 400 mg naftidrofuryl/day, 600 mg naftidrofuryl/day or placebo for 6 months. The patients were assessed using the ADAS-cog, the SCAG, the NOSGER and the CGI item 2 scale. The primary analysis was undertaken on the ITT population. At the end of the study, significantly more patients in the treatment groups showed no deterioration on both ADAS-cog and SCAG scales compared with placebo (400 mg p = 0.005, 600mg p = 0.015). There were also significant differences between the active and placebo groups for the individual scales. This study has demonstrated that treatment with naftidrofuryl can slow the rate of deterioration of patients with vascular dementia.", "In a controlled double-blind study, 78 patients with moderate senile dementia were randomly assigned to 3-months' treatment with 200 mg naftidrofuryl twice daily in slow-release form or with placebo. The patients were selected on the basis of the EACG (Echelle d'Appréciation Clinique en Gériatrie), which was also used as main criterion for confirmatory analysis of the efficacy of naftidrofuryl. A further main criterion was the SGRS (Stockton Geriatric Rating Scale). Secondary criteria examined were visual memory as tested in the Benton test, verbal memory as tested in the Rey test and numerical memory as tested in the digit-span test. The patients' concentration was tested in the Zazzo test. The tests were performed before the patients were admitted to the study and after 1 and 3-months' treatment. Confirmatory analysis of the primary criteria showed a significant treatment difference in favour of naftidrofuryl in the form of improvement in the global symptoms of senile dementia both in the EACG and in the SGRS, the scores in the naftidrofuryl group improving by 15% compared with only 5% in the placebo group. This was paralleled by a significant improvement in visual and verbal memory in the naftidrofuryl group in comparison with placebo. The naftidrofuryl patients also showed a greater improvement in concentration than the placebo group. One patient in the naftidrofuryl group suffered briefly from gastro-intestinal symptoms. There were no changes in routine laboratory parameters studied.", "nan", "nan" ]

[ "10197825", "11082469", "11126185", "9121622", "10624541", "10360138", "9396958", "10686268", "10622338", "11955470", "10067953", "11313095", "15123391", "11561046" ]

[ "Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: a double-blind controlled study.", "A controlled trial of daily left prefrontal cortex TMS for treating depression.", "Substitution of rapid transcranial magnetic stimulation treatments for electroconvulsive therapy treatments in a course of electroconvulsive therapy.", "Transcranial magnetic stimulation: a novel antidepressive strategy?", "Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism.", "Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression.", "Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebo-controlled crossover trial.", "A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression.", "Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS.", "Three and six-month outcome following courses of either ECT or rTMS in a population of severely depressed individuals--preliminary report.", "Repetitive transcranial magnetic stimulation in the treatment of medication-resistant depression: preliminary data.", "Modest adjunctive benefit with transcranial magnetic stimulation in medication-resistant depression.", "Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients.", "Prefrontal repetitive transcranial magnetic stimulation as add on treatment in depression." ]

[ "Transcranial magnetic stimulation (TMS), a noninvasive technique for stimulation of the brain, has recently been suggested to be effective for the treatment of major depression. We conducted a double-blind, placebo-controlled study to assess the efficacy of slow repetitive TMS (rTMS) in patients with major depression.\n Seventy patients with major depression (53 women, 17 men; mean age, 58.7 years; SD, 17.2 years) were randomly assigned to receive rTMS or sham rTMS in a double-blind design. Treatment was administered in 10 daily sessions during a 2-week period. Severity of depression was blindly assessed before, during, and after completion of the treatment protocol.\n All patients completed the first week of treatment and 67 completed the entire protocol. Patients who received rTMS had a significantly greater improvement in depression scores compared with those who received sham treatment. At the end of 2 weeks, 17 of 35 patients in the rTMS group, but only 8 of 32 in the sham-treated group, had an improvement of greater than 50% in their depression ratings.\n This controlled study provides evidence for the short-term efficacy of slow rTMS in patients with recurrent major depression. Additional studies will be necessary to assess the efficacy of rTMS as compared with electroconvulsive therapy as well as the long-term outcome of this treatment in major depression and possibly other psychiatric disorders.", "Transcranial magnetic stimulation (TMS) is a new technology for noninvasively stimulating the brain. Several studies have suggested that daily stimulation of the left prefrontal cortex with TMS for 2 weeks has probable antidepressant effects. We conducted a parallel-design, double-masked, sham-controlled study to address whether 2 weeks of daily TMS over the left prefrontal cortex has antidepressant activity greater than sham.\n Thirty medication-free adult outpatients with nonpsychotic, major depressive (n = 21) or bipolar (n = 9) (depressed phase) disorder who were in a current major depression (Hamilton Rating Scale for Depression [HRSD] 21-item score of >18) were treated each weekday for 2 weeks. Subjects were randomly assigned to receive either daily active (20 subjects) or sham (10 subjects) stimulation. Additionally, the 20 active subjects were equally divided between slower (5 Hz) and faster (20 Hz) frequency treatment. Antidepressant response was defined as greater than a 50% improvement in the baseline HRSD.\n Active TMS resulted in significantly more responders (9/20) than did sham (0/10) (chi(2) = 6.42, p <.01). The number of responders did not differ significantly between the two active cells (3/10 faster and 6/10 slower). Expressed as a percent change from baseline, active TMS subjects had significantly greater improvement on the Beck Depression Inventory as well as the Hamilton Anxiety Rating Scale than did those who received sham.\n Daily left prefrontal TMS for 2 weeks significantly reduced depression symptoms greater than did sham. The two forms of active TMS treatment did not differ significantly.", "Our aim was to determine whether rTMS treatments could be substituted for ECT treatments in a course of ECT, 1) without loss of antidepressant effect, and 2) without increase in subjective side-effects. We used a randomized, single-blind, controlled study. Two streams were conducted. Stream 1 received non-dominant unilateral (UL) ECT only, treatments being given 3 times per week for 2 weeks. Stream 2 received a combination of treatments: one UL ECT on Day 1 and rTMS on the following 4 days, all repeated once, after a 2-day respite. Twenty-two patients were recruited and 11 were allocated to each stream. There was no evidence that the antidepressant effect of the ECT only stream was superior to that of the ECT plus rTMS stream. There was no increase in subjective side-effects in the ECT plus rTMS stream. On the contrary, this stream was accompanied by less side effects than the ECT only stream in this study. In conclusion, we have determined that it is possible to substitute rTMS treatments for ECT treatments in a course of ECT without loss of antidepressant effect or an increase in subjective side-effects, using the described parameters. It is possible that the combination of ECT plus rTMS will provide a means of avoiding some of the subjective side-effects encountered with the conventional course of ECT. Further studies are indicated.", "Transcranial magnetic stimulation (TMS) is a well-established diagnostic probe in neurological practice. The increasing knowledge of biological mechanisms in electroconvulsive therapy presents a clear case for studying the applicability of TMS as a therapeutic tool in psychiatry. Based on the results of our pilot study showing a possible antidepressive effect of TMS, we conducted a controlled clinical trial on patients affected by major depression (DSM-III-R). Group 1 (n = 12) underwent TMS as add-on therapy to standard antidepressive medication, while group 2 (n = 12) was treated only with antidepressive medication. Already after the third add-on TMS session, a statistically significantly greater remission of depressive symptoms occurred in the patients of group 1 (p = 0.003). This statistically significant difference between the groups became even more marked on the last day of the study (p = 0.001, Wilcoxon). The results and further implications of TMS in psychiatric disorders are discussed.", "Recent studies suggest that both high frequency (10-20 Hz) and low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) have an antidepressant effect in some individuals. Electrophysiologic data indicate that high frequency rTMS enhances neuronal firing efficacy and that low frequency rTMS has the opposite effect.\n We investigated the antidepressant effects of 10 daily left prefrontal 1 Hz versus 20 Hz rTMS with the hypothesis that within a given subject, antidepressant response would differ by frequency and vary as a function of baseline cerebral glucose metabolism. After baseline PET scans utilizing [18F]-Fluorodeoxyglucose, thirteen subjects participated in a randomized crossover trial of 2 weeks of 20 Hz paired with 2 weeks 1 Hz or placebo rTMS.\n We found a negative correlation between degree of antidepressant response after 1 Hz compared to 20 Hz rTMS (r = -0.797, p < .004). Additionally, better response to 20 Hz was associated with the degree of baseline hypometabolism, whereas response to 1 Hz rTMS tended to be associated with baseline hypermetabolism.\n These preliminary results suggest that antidepressant response to rTMS might vary as a function of stimulation frequency and may depend on pretreatment cerebral metabolism. Further studies combining rTMS and functional neuroimaging are needed.", "The efficacy and safety of left prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, controlled study.\n Eighteen medication-resistant depressed subjects were randomly assigned to 2 weeks of real or sham rTMS, then permitted up to 4 weeks of real rTMS. Effects on mood, neuropsychological function, EEG, and hearing were assessed.\n The groups receiving real and sham rTMS improved in mood significantly over the 2-week double-blind period, but there was no significant difference between groups.\n Repetitive transcranial magnetic stimulation did not provide significantly greater improvement than did sham treatment. A 4-week course of rTMS, as administered in this study, was safe.", "Preliminary studies have indicated that daily left prefrontal repetitive transcranial magnetic stimulation might have antidepressant activity. The authors sought to confirm this finding by using a double-blind crossover design.\n Twelve depressed adults received in random order 2 weeks of active treatment (repetitive transcranial magnetic stimulation, 20 Hz at 80% motor threshold) and 2 weeks of sham treatment.\n Changes from the relevant phase baseline in scores on the 21-item Hamilton depression scale showed that repetitive transcranial magnetic stimulation significantly improved mood over sham treatment. During the active-treatment phase, Hamilton depression scale scores decreased 5 points, while during sham treatment the scores increased or worsened by 3 points. No adverse effects were noted.\n These placebo-controlled results suggest that daily left prefrontal repetitive transcranial magnetic stimulation has antidepressant activity when administered at these parameters. Further controlled studies are indicated to explore optimal stimulation characteristics and location, potential clinical applications, and possible mechanisms of action.", "Multiple groups have reported on the use of repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant major depression. The purpose of this study is to assess the efficacy of rTMS in unmedicated, treatment-resistant patients who meet criteria for major depression.\n Depressed subjects, who had failed to respond to a median of four treatment trials, were assigned in a randomized double-blind manner to receive either active (n = 10; 20 2-sec trains of 20 Hz stimulation with 58-sec intervals; delivered at 80% motor threshold with the figure-of-eight coil positioned over the left dorsolateral prefrontal cortex) or sham (n = 10; similar conditions with the coil elevated and angled 45 degrees tangentially to the scalp) rTMS. These sequences were applied during 10 consecutive weekdays. Continuous electroencephalogram sampling and daily motor threshold determinations were also obtained.\n The group mean 25-item Hamilton Depression Rating Scale (HDRS) score was 37.2 (+/- 2.0 SEM) points. Adjusted mean decreases in HDRS scores were 14.0 (+/- 3.7) and 0.2 (+/- 4.1) points for the active and control groups, respectively (p <.05). One of 10 subjects receiving active treatment demonstrated a robust response (i.e., HDRS decreased from 47 to 7 points); three other patients demonstrated 40-45% decreases in HDRS scores. No patients receiving sham treatment demonstrated partial or full responses.\n A 2-week course of active rTMS resulted in statistically significant but clinically modest reductions of depressive symptoms, as compared to sham rTMS in a population characterized by treatment resistance.", "In previous studies, fast repetitive transcranial magnetic stimulation (rTMS) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS. However, it is not clear whether fast rTMS is superior to slow rTMS (frequency < or = 1 Hz) which is safe at therapeutically promising higher intensities. The aim of this double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. In conclusion, this study further supported the safety of rTMS but does not show any clinically meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression.", "Recent studies have strengthened the claim that repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depression. The longitudinal outcome of TMS-treated patients, however, has not been described. We report on the 3- and 6-month outcomes of a group of patients treated with either electroconvulsive therapy (ECT) (n = 20) or (rTMS) (n = 21).\n Patients diagnosed with major depressive disorder with or without psychotic features referred for ECT were randomly assigned to receive either ECT or rTMS. Forty-one patients who responded to either treatment constituted the sample. Patients were followed on a monthly basis and outcomes were determined with the Hamilton Rating Scale for Depression-17 items (HRSD) and the Global Assessment of Functioning (GAF) scales. Medications were routinely prescribed.\n There were no differences in the 6-month relapse rate between the groups. Overall, 20% of the patients relapsed (four from the ECT group and four from the rTMS group). Patients reported equally low and not significantly different scores in the HRSD (ECT group 8.4 +/- 5.6 and TMS group 7.9 +/- 7.1) and the GAF (ECT group 72.8 +/- 12 and TMS group 77.8 +/- 17.1) at the 6-month follow up.\n Patients treated with rTMS do as well as those treated with ECT at the 3- and 6-month follow-up points. These data suggest that the clinical gains obtained with rTMS last at least as long as those obtained with ECT.", "nan", "Controverted results have been obtained using high frequency transcranial magnetic stimulation (HF-rTMS) as an antidepressant treatment.\n Forty patients suffering from drug-resistant major depression received ten sessions of HF-rTMS at 90% of the motor threshold on the left prefrontal cortex or sham stimulation, added to their pharmacological treatment, in a randomized double-blind design. In a second open phase, patients still fulfilling criteria of inclusion received ten additional sessions of HF-rTMS at 90 or 110%.\n Real, but not sham HF-rTMS, was associated with a significant decrease in the Hamilton Depression Rating Scale, but only twelve patients decreased more than 50%. Conclusions: Left prefrontal HF-rTMS was effectively associated with antidepressant treatment, although the size effect was small.\n Shortage of the sample and control difficulties of the placebo effect.\n Questionable in more than half of the patients studied.", "Repetitive transcranial magnetic stimulation (rTMS) is a recent putative treatment for affective disorders. Several studies have demonstrated antidepressant effects of rTMS in younger patients; we aimed to assess its effect in older outpatients with treatment-resistant major depression. Twenty-four outpatients (mean age=62 years, S.D.=12) with major depression were randomized for sham or real stimulation and received 10 daily rTMS sessions (20 Hz, 2-s trains, 28-s intertrain intervals, 100% of motor threshold) in addition to the antidepressant medication. For sham stimulation, the coil was tilted 90 degrees. Depression severity was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, items from the NIMH self-rated symptom scale, and a visual analog depression scale. Mini-Mental Status Examination performance, memory, and executive and attentional functions were measured to control for cognitive side effects. Depression ratings revealed significant antidepressant effects within 2 weeks in both sham and real stimulation groups; however, there were no between-group differences. Treatment with rTMS was safe; adverse events were rare and not more prevalent in either group, and cognitive assessment did not show any deterioration. We were unable to demonstrate any additional antidepressant effects of real stimulation in elderly patients with treatment-resistant major depression. Therapeutic effects of rTMS in this clinically challenging patient group remain to be demonstrated.", "A growing number of studies report antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The hypothesis that high frequency (20 Hz) rTMS (HF-rTMS) may speed up and strengthen the therapeutic response to sertraline in MD was tested. Twenty eight patients who had not yet received medication for the present depressive episode (n=12) or had failed a single trial of an antidepressant medication (n=16) were started on sertraline and randomised to receive either real of sham HF-rTMS. HF-rTMS was applied to the left dorsolateral prefrontal area in daily sessions (30 trains of 2 s, 20-40 s intertrain interval, at 90% motor threshold) on 10 consecutive working days. The results suggest that in this patient population, HF-rTMS does not add efficacy over the use of standard antidepressant medication." ]

[ "15705367", "15588464", "15665010", "15589853", "15576390", "16580376", "16172149", "16377062", "14989794", "11464575" ]

[ "Evaluation of two doses of recombinant luteinizing hormone supplementation in an unselected group of women undergoing follicular stimulation for in vitro fertilization.", "Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction.", "Recombinant luteinizing hormone supplementation to recombinant follicle-stimulating hormone induced ovarian hyperstimulation in the GnRH-antagonist multiple-dose protocol.", "Exogenous luteinizing hormone in controlled ovarian hyperstimulation for assisted reproduction techniques.", "Recombinant human LH supplementation versus recombinant human FSH (rFSH) step-up protocol during controlled ovarian stimulation in normogonadotrophic women with initial inadequate ovarian response to rFSH. A multicentre, prospective, randomized controlled trial.", "Effects of recombinant human luteinizing hormone supplementation on ovarian stimulation and the implantation rate in down-regulated women of advanced reproductive age.", "The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study.", "Recombinant gonadotrophins associated with GnRH antagonist (cetrorelix) in ovarian stimulation for ICSI: comparison of r-FSH alone and in combination with r-LH.", "Randomized trial to compare the effect of recombinant human FSH (follitropin alfa) with or without recombinant human LH in women undergoing assisted reproduction treatment.", "The effect of exogenous luteinizing hormone (LH) on oocyte viability: evidence from a comparative study using recombinant human follicle-stimulating hormone (FSH) alone or in combination with recombinant LH for ovarian stimulation in pituitary-suppressed women undergoing assisted reproduction." ]

[ "To evaluate the efficacy of two doses of recombinant (r)LH, 75 IU (recommended) or 37.5 IU, for follicular stimulation and outcomes in a randomized cohort of IVF patients.\n Randomized, prospective analysis.\n Private hospital incorporating an established IVF center.\n Women undergoing IVF who had a body mass index >18 or <35 and no abnormal karyotype, anovulation, oligomenorrhea, or any known endocrinopathy/illness.\n Pituitary desensitization was achieved with triptorelin (0.1 mg SC), and gonadotropin stimulation was performed with either rFSH alone (group A) or in combination with rLH in one of two doses: 37.5 IU (group B) or 75 IU (group C), daily.\n A range of endocrinologic, embryologic, clinical, and outcome parameters were evaluated.\n With rLH supplementation there was a significant increase in the incidence of implantation (9% for rFSH only [group A] vs. 11% and 16% with 37.5 IU rLH and 75.0 IU rLH [groups B and C], respectively) and clinical pregnancy (19% vs. 23% and 31%) (P<.01 and P<.04, respectively), whereas there was no difference in the multiple pregnancy rates. There was a significant (P<.001) increase in the total units of rFSH used in proportion to the amount of rLH supplementation (2,645 U vs. 3,475 U and 3,681 U) and in the level of peripheral E(2) on the day of hCG administration (1,049 pg/mL vs. 1,640 pg/mL and 1,226 pg/mL) (P<.001). There was no significant between difference in mean age, numbers of oocytes recovered, basal and downregulation hormone levels, or the incidence of fertilization in the absence or presence of rLH supplementation, but a higher incidence of grade 1 to 2 embryos was observed when rLH was supplemented.\n After pituitary desensitization, there was an increase in the incidence of implantation, clinical pregnancy, and delivery rates in patients stimulated with rFSH supplemented with rLH.", "An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection.", "Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant (rec) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment. The present study prospectively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol.\n 127 infertile patients with an indication for IVF or ICSI were recruited and randomized (using sealed envelopes) to receive a starting dose of either 150 IU recFSH (follitropin alpha) or 150 IU recFSH plus 75 IU recLH (lutropin alpha) for ovarian hyperstimulation. GnRH-antagonist (Cetrorelix) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG (chorion gonadotropin alpha). Gonadotropin dose adjustments were allowed from stimulation day 6 onwards, HCG was administered as soon as three follicles > or =18 mm were present. The primary outcome parameter was treatment duration until administration of HCG.\n Exogenous LH did not shorten the time necessary to reach ovulation induction criteria. Serum estradiol (E(2)) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group (1924.7 +/- 1256.4 vs 1488.3 +/- 824.0 pg/ml, P < 0.03), and 2.1 +/- 1.4 vs 1.4 +/- 1.5 IU/l, P < 0.01, respectively).\n Except for higher E(2) and LH levels on the day of HCG administration, no positive trend in favour of additional LH was found as defined by treatment outcome parameters.", "To investigate the role of exogenous LH in controlled ovarian hyperstimulation for assisted reproductive technologies.\n Prospective randomized study.\n SISMER fertility unit.\n Women showing a hyporesponsiveness to FSH under GnRH agonist down-regulation were randomized into three groups: group A (n = 54) received an increased dosage of FSH; group B (n = 54) was administered recombinant LH in addition to the increased dose of FSH; group C (n = 22) was given additional FSH and LH using hMG as a combined drug. Fifty-four age-matched women with no need to increase the FSH dose were included as a control group (D).\n None.\n Implantation and live birth rate per started cycles.\n In group B, the pregnancy and implantation rates were statistically higher when compared with groups A and C and did not differ from the control group for normal response. The live birth rate was similar in groups B and D but was half as high in groups A and C.\n Hyporesponsiveness to FSH could be related to iatrogenic LH deficiency that, in turn, could affect oocyte competence. Addition of a small amount of recombinant LH is able to rescue oocyte competence to produce viable embryos.", "In approximately 12-14% of young normogonadotrophic women treated with a depot GnRH agonist long protocol, the initial ovarian response to recombinant human FSH (rFSH) can be suboptimal. We have tested the hypothesis that these women may benefit from recombinant human LH (rLH) supplementation in a multicentre, prospective, randomized trial compared with patients treated with an rFSH step-up protocol.\n A total of 260 young normogonadotrophic women undergoing controlled ovarian stimulation with a GnRH agonist long protocol for IVF/ICSI were enrolled. The starting dose of rFSH was 225 IU. One hundred and thirty patients with serum estradiol levels <180 pg/ml and with at least six follicles with a mean diameter >5 mm but none >10 mm on both day 5 and day 8 of stimulation were randomly allocated to two groups. From the eighth day of stimulation, women in group A (n=65) received 150 IU of rLH in addition to rFSH, while those in group B (n=65) had an increase of 150 IU in the daily dose of rFSH (step-up protocol). One hundred and thirty normally responding women continued monotherapy with rFSH and served as a further control population (group C).\n The mean number of cumulus-oocyte complexes retrieved in group A (9.0+/-4.3) was significantly higher (P<0.01) compared with group B (rFSH 6.1+/-2.6) but significantly lower compared with group C (10.49+/-3.7, P<0.05). Implantation and pregnancy rates were significantly lower (P<0.05) in the rFSH step-up group (10.5 and 29.3% respectively) when compared with normal responders (18.1 and 47.3% respectively).\n rLH supplementation is more effective than increasing the dose of rFSH in terms of ovarian outcome in patients with an initial inadequate ovarian response to rFSH alone.", "To evaluate the effects of recombinant human luteinizing hormone (rhLH) supplementation on ovarian stimulation and implantation rate in down-regulated women of advanced reproductive age.\n Prospective randomized study.\n University teaching hospital.\n A total of 120 consecutive normogonadotropic infertile women > or = 35 years old undergoing their first cycle of IVF or intracytoplasmic sperm injection (ICSI) treatment.\n Ovarian stimulation in a long agonist protocol with a combination of recombinant human follicle-stimulating hormone (rhFSH) and rhLH (group 1, n = 60) starting on day 6 of FSH stimulation until hCG at a daily fixed dose of 150 IU of rhLH, or with rhFSH alone (group 2, n = 60).\n Ovarian stimulation characteristics, ovum retrieval, and IVF/ICSI outcome.\n The mean number of intermediate (10-14 mm) and large (> 14- < 18 mm) but not leading (> or = 18 mm) follicles was significantly lower in group 1 on the day of hCG injection. The oocyte yield and maturity as well as the number of oocytes fertilized were significantly higher in group 2 than in group 1. However, the number of patients having embryo transfer (n = 55 in both treatment groups), the number and quality of embryos replaced, the implantation rate (20.6% vs. 21.7%) and clinical pregnancy rates per embryo transfer (44% vs. 45%) were similar in groups 1 and 2.\n The rhLH supplementation does not increase ovarian response and implantation rates in patients of older reproductive age stimulated with rhFSH under pituitary suppression for assisted reproductive technologies (ARTs).", "The effect of recombinant human LH (r-hLH; lutropin alfa) in women undergoing controlled ovarian stimulation with recombinant human FSH (r-hFSH) prior to IVF was investigated.\n After down-regulation with the GnRH agonist, buserelin, 114 normo-ovulatory women (aged 18-37 years) received r-hFSH alone until the lead follicle reached a diameter of 14 mm. Patients were then randomized in a double-blind fashion to receive r-hFSH in addition to r-hLH, 75 IU s.c., or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF. The primary end-point was the number of metaphase II oocytes.\n There were no significant differences between treatment groups for the primary end-point. Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone (P = 0.0001), but there were no significant differences between the groups in dose and duration of r-hFSH treatment required, oocyte maturation, fertilization rate, pregnancy rate and live birth rate.\n In this patient population, the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points.", "The objective was to verify the outcome of intracytoplasmic sperm injection (ICSI) with ovulation induction performed with GnRH antagonists, comparing the use of recombinant follicle-stimulating hormone (r-FSH) alone and in combination with recombinant luteinizing hormone (r-LH) in a prospective and randomized trial.\n Forty male-factor infertile normo-ovulatory patients undergoing ovarian stimulation for ICSI took part in the study. After initiating ovarian stimulation with only r-FSH, all patients were treated with GnRH antagonist (cetrorelix). When beginning cetrorelix administration, the patients were randomized into two groups: in group I, 20 patients continued to receive r-FSH alone and in group II, 20 patients received combined r-FSH and r-LH. The number of metaphase II oocytes, estradiol concentration at the time of hCG administration, fertilization rate, grade 1 embryo rate, pregnancy rate per cycle, and implantation rate were measured. Results are expressed as mean+/-S.D.\n In group I, the women's age was 32.3+/-2.30 years, and FSH concentration was 7.8+/-1.7 IU/ml. In group II, the women's age was 32.2+/-2.46 years and FSH concentration was 7.5+/-1.7 IU/ml. The number of oocytes retrieved was 9.6+/-2.9 and the number of metaphase II oocytes was 6.7+/-2.2 in group I. In group II the number of retrieved oocytes were 9.9+/-2.6 and the number of metaphase II oocytes 6.9+/-2.1 (p>0.05). Estradiol concentration at the time of hCG was 4.6+/-1.8 nm/l in group I and 6.7+/-2.0 nm/l in group II (p<0.01). Fertilization rate was 73.0% in group I versus 78.2% in group II. In group I, we obtained 53.9% of grade 1 embryos versus 54.4% in group II (p>0.05). Pregnancy and implantation rates in group I were 30.0 and 16.7%, respectively and in group II 35.0 and 20.4%, respectively (p>0.05).\n The use of recombinant LH in addition to recombinant FSH may prevent a decrease in estradiol after GnRH antagonist administration, but does not influence positively the outcome of oocyte number, maturation, embryo quality, fertilization rate, pregnancy rate per cycle, and implantation rate.", "Women undergoing intracytoplasmic sperm injection (ICSI) for male factor infertility were randomly assigned to receive ovarian stimulation in a long agonist protocol with a combination of recombinant human FSH (r-hFSH; Gonal-F) and recombinant human LH (r-hLH; Luveris) (n = 212) starting on day 6 of FSH stimulation until human chorionic gonadotrophin (HCG) at a daily fixed dose of 150 IU r-hLH, or with r-hFSH alone (n = 219). There was no significant difference in the number of metaphase II oocytes retrieved (10.3 versus 10.4) in patients treated with r-hFSH and r-hLH versus r-hFSH alone; however, more embryos were transferred in the LH-supplemented group (2.9 versus 2.8, P = 0.037). Overall, the implantation rates were 22.9 versus 27.0% in patients treated with r-hFSH and r-hLH versus with r-hFSH alone respectively (NS). The respective numbers of MII oocytes retrieved in patients <35 or >or=35 years were 11 versus 8.3 (P = 0.010) for patients treated with r-hFSH alone, and 10.7 versus 9.3 (NS) for those given supplemental r-hLH (150 IU) from day 6. Implantation rates in patients <35 years treated with r-hFSH were higher (30.7%) than those receiving r-hFSH and r-hLH, (23.5%) (P = 0.068). In patients >or=35 years, the implantation rates were 21.7% for those patients supplemented with 150 IU r-hLH from day 6 of stimulation versus 15.7% when treated with FSH alone (NS). Younger patients therefore do not seem to benefit from an LH-supplemented ovarian stimulation protocol, but women >or=35 years undergoing assisted reproduction may benefit from using r-hLH in addition to r-hFSH.", "The purpose of this prospective, randomized study was to compare ovarian response and oocyte and embryo yields in women undergoing ovulation induction for IVF/ICSI using recombinant human FSH (rhFSH) alone or in combination with recombinant human LH (rhLH).\n Patients were randomized to receive rhFSH alone (group F; n = 13) or rhFSH + rhLH (group L; n = 15). rhFSH was administered according to a step-down protocol; patients assigned to group L received rhLH at a fixed dose of 75 IU (1 ampoule) throughout the treatment period.\n The total dose of rhFSH, number of growing follicles, and serum concentrations of estradiol (E2) on the day of hCG administration were similar in both treatment groups. However, the percentage of metaphase II oocytes and fertilization rate were significantly higher in group F than in group L. The lower fertilization rates associated with rhLH were also seen in a subgroup of patients from group L who had undergone a previous ART cycle stimulated with FSH only and thus acted as their own controls. However, when in vitro fertilization (IVF) and intracytoplasmic sperm injection cycles were considered separately, differences in fertilization rates were statistically significant only for oocytes treated by conventional IVF.\n This study shows that the addition of recombinant LH to recombinant FSH in pituitary-suppressed women undergoing ART does not improve the ovarian response and even may have a negative impact on oocyte maturation and fertilization." ]

[ "10325288", "9627289" ]

[ "Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell'Endometriosi.", "Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility. The Canadian Collaborative Group on Endometriosis." ]

[ "In order to analyse the efficacy of resection/ablation of minimal/mild endometriotic lesions for improving fertility, we conducted a randomized clinical trial. Eligible patients were women aged </=36 years who were trying to conceive and had a laparoscopically confirmed diagnosis of minimal/mild endometriosis (stage I or II of the revised American Fertility Society classification) and otherwise unexplained infertility for >/=2 years. Eligible women were randomly assigned to resection or ablation of visible endometriosis (54 patients) or diagnostic laparoscopy only (47 patients). After laparoscopy women tried to conceive spontaneously for 1 year (follow-up period). A total of five women withdrew from the study: three for personal reasons, and two were lost to follow-up. Considering 51 women in the resection/ablation and 45 in the no-treatment group who ended the follow-up period, 12 (24%) in the resection/ablation group and 13 (29%) in the no treatment group conceived; the difference was not significant. Two spontaneous abortions were observed in the resection/ablation group and three in the no-treatment one. Thus the 1 year birth rate was 10 out of 51 women (19.6%) in the resection/ablation group and 10 out of 45 women (22.2%) in the no-treatment group. In conclusion, the results of this study do not support the hypothesis that ablation of endometriotic lesions markedly improves fertility rates.", "To assess whether infertile women with minimal or mild endometriosis have lower fecundity than women with unexplained infertility.\n Prospective cohort study.\n Twenty-three infertility clinics across Canada.\n Three hundred thirty-one infertile women aged 20-39 years.\n Diagnostic laparoscopy for infertility. Infertile women with minimal or mild endometriosis (n = 168) were compared with women with unexplained infertility (n = 263). Both groups were managed expectantly. The women were followed up for 36 weeks after the laparoscopy or, for those who became pregnant, for up to 20 weeks of the pregnancy.\n Fecundity refers to the probability of becoming pregnant in the first 36 weeks after laparoscopy and carrying the pregnancy for > or = 20 weeks. The fecundity rate is the number of pregnancies per 100 person-months.\n Fecundity was 18.2% in infertile women with minimal or mild endometriosis and 23.7% in women without endometriosis (log-rank test). The fecundity rate was 2.52 per 100 person-months in women with endometriosis and 3.48 per 100 person-months in women with unexplained infertility. The crude and adjusted fecundity rate ratios were 0.72 and 0.83 (95% confidence interval = 0.53-1.32), respectively.\n The fecundity of infertile women with minimal or mild endometriosis is not significantly lower than that of women with unexplained infertility." ]

[ "11501505", "10826418", "15570204", "16175324", "11318122", "16633002", "11742165", "7814986", "15297221" ]

[ "The usefulness of restorative laparoscopic-assisted total colectomy for ulcerative colitis.", "Laparoscopic restorative proctocolectomy: case-matched comparative study with open restorative proctocolectomy.", "Hand-assisted laparoscopic versus open restorative proctocolectomy with ileal pouch anal anastomosis: a randomized trial.", "Laparoscopic-assisted vs. open ileal pouch-anal anastomosis: functional outcome in a case-matched series.", "Laparascope-assisted versus conventional restorative proctocolectomy with rectal mucosectomy.", "Safety, feasibility, and short-term outcomes of laparoscopic ileal-pouch-anal anastomosis: a single institutional case-matched experience.", "Functional outcome, quality of life, body image, and cosmesis in patients after laparoscopic-assisted and conventional restorative proctocolectomy: a comparative study.", "Does laparoscopic-assisted ileal pouch anal anastomosis reduce the length of hospitalization?", "[Two stage videoassisted restorative proctocolectomy. Early experience of 12 cases]." ]

[ "The aim of this study was to evaluate the effectiveness of laparoscopic-assisted total colectomy with ileal J-pouch anal anastomosis in comparison with that of conventional open total colectomy in patients with ulcerative colitis. From 1990 until 1999, 11 patients underwent open total colectomy, while 21 patients had laparoscopic-assisted total colectomy. Patients characteristics, perioperative course, and recovery were compared. Differences between the groups were tested using Student's t-test for independent groups and chi-square tests when appropriate. Nasogastric tube could be removed after POD 1.1 vs. 4.8 (p < 0.05), the mean time to passage of stool was 1.7 (range, 1 to 3) vs. 5.4 (range, 3 to 7) days (p < 0.05), and in the laparoscopic group watery stool was soon made solid after POD 24.3 vs. 87.3 (p < 0.01). There were no significant differences in the mean operating time and mean estimated operating blood loss between two groups. Postoperative morbidity did not differ significantly between the patients treated conventionally (45.5%) and laparoscopically (33.3%). The findings of this study indicate that laparoscopic-assisted total colectomy improved cosmetic results and to be a safe and effective treatment for the elective surgery of ulcerative colitis.", "A laparoscopic approach to restorative proctocolectomy is new and has not been compared recently with the traditional open procedure. By using prospectively gathered data, laparoscopic and open restorative proctocolectomy procedures in mucosal ulcerative colitis and familial adenomatous polyposis patients were compared by using a case-matched design.\n Forty patients, composing 20 consecutive laparoscopic cases (13 mucosal ulcerative colitis, 7 familial adenomatous polyposis), were matched for age, gender, and body mass index with 20 open cases (13 mucosal ulcerative colitis, 7 familial adenomatous polyposis) performed during the same time period. Mucosal ulcerative colitis patients were also matched for severity of disease by using hemoglobin and albumin levels, whole blood count, and steroid dependency. A loop ileostomy was made in 12 of 13 laparoscopic mucosal ulcerative colitis patients, all open mucosal ulcerative colitis patients, and no familial adenomatous polyposis patients.\n The median age was 25 (range, 9-61) years. There were no intraoperative complications in either group and no conversions in the laparoscopic group. The operative times (median, range) were significantly longer in laparoscopic cases (330, 180-480 minutes) vs. open cases (230, 180-300 minutes), P < 0.001. Bowel function returned more quickly in laparoscopic cases (2, 1-8 days) vs. open cases (4, 1-13 days), P = 0.03; and the length of stay was shorter in laparoscopic cases (7, 4-14 days) vs. open cases (8, 6-17 days), P = 0.02. For diverted patients, the median length of stay was reduced by two days in laparoscopic cases (6, 4-14 days) vs. open cases (8, 6-17 days), P = 0.01. Complications occurred in 4 of 20 laparoscopic patients (3 obstruction/ileus and 1 pelvic abscess) and 5 of 20 open patients (2 obstruction and ileus, 1 each anastomotic leak and abscess, peptic ulceration, and episode of dehydration).\n Return of intestinal function and length of stay are reduced in the laparoscopic group compared with open group. A laparoscopic approach to restorative proctocolectomy has the potential of becoming an appealing alternative to conventional restorative proctocolectomy surgery.", "The aim of the study was to evaluate postoperative recovery after hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis in a randomized controlled trial.\n Sixty patients were randomized for hand-assisted laparoscopic (n = 30) or open surgery (n = 30). Primary outcome parameter was postoperative recovery in the 3 months after surgery, measured by quality of life questionnaires (SF-36 and GIQLI). Secondary parameters were postoperative morphine requirement and surgical parameters, viz. operating time, morbidity, hospital stay, and costs.\n There was no difference between the 2 procedures in quality of life assessment in the 3 months after surgery. There was a significant decline in quality of life on all scales of the SF-36 (P < 0.001) and total GIQLI score (P < 0.001) in the first 2 weeks in both groups (no significant difference between the groups). Quality of life returned to baseline levels after 4 weeks. Operating times were longer in the laparoscopic group compared with the open group (210 and 133 minutes, respectively; P < 0.001). No significant differences were found in morphine requirement. Neither morbidity nor postoperative hospital stay differed between the laparoscopic and open group (20% versus 17%, in 10 versus 11 days, respectively). Median overall costs were 16.728 for the hand-assisted laparoscopic procedure and 13.406 for the open procedure (P = 0.095).\n Recovery measured using quality of life questionnaires is comparable for hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis. The laparoscopic approach is as safe, but more costly than the open procedure.", "Functional outcomes in laparoscopic-assisted ileal pouch-anal anastomosis have been incompletely studied. More than one-year follow-up has rarely been reported in these patients. This study was designed to assess operative, functional, and quality of life outcomes in patients with ulcerative colitis or familial adenomatous polyposis a minimum of one year after.\n Thirty-three laparoscopic-assisted ileal pouch-anal anastomosis and 33 open ileal pouch-anal anastomosis patients, with a median of 13 months and minimum of 12 months follow-up, were identified from a prospective, laparoscopic database. Functional outcome was prospectively assessed by using a standardized survey. These cohorts were matched by individual patient for year of surgery, age, gender, body mass index, and indication.\n Median age was 27 years (open) and 28 years (laparoscopic). There were 27 females and 6 males in each group. All operations occurred between 1999 and 2001. Median body mass index was 22.3 (open) and 21.7 (laparoscopic) groups. There were no significant differences in diagnosis, use of diversion, and anastomotic technique. Postoperative morbidity occurred in 6 percent of the laparoscopic cases and 12 percent of the open cases. Functional outcome after a minimum of one year revealed equivalent median day and median nocturnal number of stools of six to seven and one to two respectively. Consistency of stool, medication usage, and continence were no different between groups. Daytime and nocturnal incontinence was similar. Quality of life in regard to social, home life, family, travel, sports, recreation, and sex life were equivalent.\n The function and quality of life outcomes for patients undergoing laparoscopic-assisted ileal pouch-anal anastomosis seem to be equivalent to our open experience. Laparoscopic-assisted ileal pouch-anal anastomosis offers selected patients a safe, feasible, and durable alternative.", "To assess the advantages of a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis compared with conventional procedures, we retrospectively analyzed the results of the two procedures as follows: Eleven patients including five patients with familial adenomatous polyposis (FAP) and six with ulcerative colitis (UC) underwent a laparoscope-assisted proctocolectomy and hand-sewn ileal J-pouch anal anastomosis at our department from June 1997 to November 1999. This laparoscope-assisted colectomy (LAC) group was then compared with a group of 13 patients who had undergone conventional ileal pouch anal anastomosis using a standard laparotomy from 1986 to 1997. The median operative time of the LAC group was 8h 23min, which was 81 min longer than that of the standard colectomy (SC) group. The number of days during which eating was prohibited were similar in the two groups but the median postoperative hospital stay was significantly shorter in the LAC group (24.1 days). In the LAC group, the small incisions showed better cosmetic results and there was also a remarkable reduction in the degree of postoperative pain. In conclusion, a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis can be employed widely in patients with FAP and also in selected patients with UC.", "To compare safety and short-term outcomes of 100 laparoscopic ileal pouch-anal anastomosis (IPAA) versus 200 conventional open IPAA patients.\n Outcomes of laparoscopic IPAA (LAP-IPAA) have been incompletely characterized. Previous reports are characterized by small numbers of patients and rarely include case-matched or randomized trial methodology. This report describes 100 LAP-IPAA patients case matched to 200 open IPAA patients.\n Between 1998 and 2004, 100 consecutive LAP-IPAA patients (75 laparoscopic assisted, 25 hand assisted) were identified and case matched to 200 open IPAA control patients by age, operation, gender, date of operation, and body mass index. Operative and postoperative outcomes at 90 days were compared.\n A total of 300 patients (180 female) with a median age of 32 years (range, 17-66 years), and a median body mass index of 23 kg/m (range, 16-34 kg/m) underwent IPAA (100 LAP-IPAA, 200 open IPAA). Diagnosis (chronic ulcerative colitis 97%, familial adenomatous polyposis 3%) and previous operative history were equivalent between groups. One intraoperative complication occurred in each group. Overall, the laparoscopic conversion rate was 6%. Median operative time was longer for the LAP-IPAA group (333 minutes versus 230 minutes, P < 0.0001). LAP-IPAA patients had shorter median time to regular diet (3 versus 5 days), time to ileostomy output (2 versus 3 days), length of stay (4 versus 7 days), and decreased IV narcotic use (all P < 0.05. Postoperative morbidity was equivalent (LAP-IPAA = 33%, open IPAA = 37%), mortality was nil, and readmission rates were equal (LAP-IPAA = 21%, open IPAA = 22%). Reoperation was required in 3% of LAP-IPAA and 6.5% of open IPAA patients (P < 0.2) during the first 3 months.\n LAP-IPAA is equivalent to open IPAA in terms of safety and feasibility. In addition, LAP-IPAA provides significant improvements in short-term recovery outcomes.", "The aim of this study was to assess the functional outcome and the quality of life of laparoscopic-assisted ileal pouch-anal anastomosis compared with conventional ileal pouch-anal anastomosis. Further, body image and cosmesis were evaluated in both groups.\n Sixteen patients who underwent a laparoscopic-assisted ileal pouch-anal anastomosis between March 1996 and September 1999 were matched with 19 patients who had a conventional ileal pouch-anal anastomosis. Patients were matched for the time period after surgery, distribution of familial adenomatous polyposis/ulcerative colitis, and one/two-stage procedure. Thirty-two patients agreed to fill out a set of questionnaires that assessed functional outcome, quality of life, body image, and cosmesis. Quality of life was measured with the Short Form 36 Health Survey questionnaire and the Gastrointestinal Quality of Life Index. The Body Image Questionnaire was used to measure patients' perceptions of and satisfaction with their own body and their attitude toward their bodily appearance (body image) and the degree of satisfaction of patients with respect to the physical appearance of the scar (cosmesis).\n Patients in the conventional group were older than patients in the laparoscopic-assisted group (mean 39.2 +/- 8.4 vs. 30.6 +/- 7.1 years; P < 0.01). No differences were found in functional outcome and quality of life. Satisfaction with the cosmetic result of the scar was significantly higher in the laparoscopic-assisted group compared with the conventional group. Body image score was higher in the laparoscopic-assisted group when compared with the conventional group, although not significant.\n The functional outcome and quality of life of laparoscopic-assisted ileal pouch-anal anastomosis is not different from conventional ileal pouch-anal anastomosis. In the long-term, better cosmesis is the most important advantage after laparoscopic surgery.", "Previous data have suggested that laparoscopic colon and rectal surgery may shorten the length of hospitalization. These claims have been attributed to a reduction of the length of ileus. The definition of \"ileus\" is variable and in all cases is subjective. In this study it was defined as the length of time until the patient passed flatus or stool without nausea, vomiting or abdominal distention. This prospective study was undertaken to compare the duration of ileus and of hospitalization after laparoscopic-assisted (LAC) and standard laparotomy (SC). After restorative proctocolectomy with an ileal-pouch anal anastomosis (IPAA) in both sets of patients. Twenty-two patients underwent LAC and 20 age, sex, and diagnosis-matched controls underwent SC. Mucosal ulcerative colitis (MUC) was the diagnosis in 16 LAC and in 15 SC patients while polyposis was the diagnosis in 6 LAC and in 5 SC patients. The mean time to resolution of postoperative ileus was 4.2 (4-11) days in the LAC group and 3.3 (2-5) days in the SC group. Hospital discharge was similar in each group occurring at a mean of 8.7 (7-13) days after LAC and 8.9 (6-18) days after SC. Neither the length of time for ileus resolution nor the length of hospitalization were reduced in the LAC group. Laparoscopic-assisted IPAA conferred none of the theoretical advantages associated with other laparoscopic procedures.", "This study reports our early experience in two-stage video assisted restorative proctocolectomy (RPC).\n From May 1999 to May 2003, 12 video assisted RPCs were performed (mucosal ulcerative colitis: n = 11; familial adenomatous polyposis: n = 1). These patients were matched for age, gender, body mass index and indication for surgery, with 12 patients who underwent RPC by laparotomy (open group).\n Median operative time was significantly longer in the video assisted RPC group (400 min; range: 360-490) vs open group (300 min; range: 210-390) (P = 0.003). A conversion in midline laparotomy (under the umbilicus) was necessary in 3/12 patients (25%) in the video assisted RPC group. Return to bowel function and oral intake occurred two days earlier after video assisted RPC (respectively, P = 0.009 and P = 0.0001) but length of stay was not significantly shorter in this group. A complication occurred in 3/12 patients (25%) in both groups, which lead to a reoperation in one patient in the open group (ns).\n Two-stage videoassisted RPC is feasible at the cost of a lengthening of operative time, Nevertheless postoperative results after video assisted RPC are comparable to those obtained after RPC by laparotomy." ]

[ "12410546" ]

[ "Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study." ]

[ "The aim of the present study was to carry out a controlled pilot study on the putative anxiolytic effect of valepotriates. Thirty-six outpatients with generalized anxiety disorder (DSM III-R), after a 2-week wash-out, were randomized to one of the following three treatments for 4 weeks (n = 12 per group): valepotriates (mean daily dose: 81.3 mg), diazepam (mean daily dose: 6.5 mg), or placebo. A parallel, double-blind, flexible-dose, placebo-controlled design was employed. No significant difference was observed among the three groups at baseline or in the change from baseline on the Hamilton anxiety scale (HAM-A) or in the trait part of the state-trait anxiety inventory (STAI-trait). Moreover, the three groups presented a significant reduction in the total HAM-A scores. On the other hand, only the diazepam and valepotriates groups showed a significant reduction in the psychic factor of HAM-A. The diazepam group also presented a significant reduction of the STAI-trait. Although the principal analysis (HAM-A between group comparison) found negative results (probably due to the small sample size in each group), the preliminary data obtained in the present study suggest that the valepotriates may have a potential anxiolytic effect on the psychic symptoms of anxiety. However, since the number of subjects per group was very small, the present results must be viewed as preliminary. Thus, further studies addressing this issue are warranted.\n Copyright 2002 John Wiley & Sons, Ltd." ]

[ "11755552", "11454122", "1641524", "9609266", "11769665", "12766829", "8350884", "10329858", "2181748" ]

[ "Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors.", "Effects of oral estrogen and progestin on the lower urinary tract among female nursing home residents.", "Oestriol in the prophylactic treatment of recurrent urinary tract infections in postmenopausal women.", "Low dose oestrogen prophylaxis for recurrent urinary tract infections in elderly women.", "[Prevention and treatment of recurrent urinary system infection with estrogen cream in postmenopausal women].", "Effectiveness of estriol-containing vaginal pessaries and nitrofurantoin macrocrystal therapy in the prevention of recurrent urinary tract infection in postmenopausal women.", "A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections.", "A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women.", "[Treatment with low-dose vaginal estradiol in post-menopausal women. A double-blind controlled trial]." ]

[ "To assess the effects of hormone therapy on urinary tract infection frequency and to examine potential risk factors.\n We used data from the Heart and Estrogen/Progestin Replacement Study, a randomized, blinded trial of the effects of hormone therapy on coronary heart disease events among 2763 postmenopausal women aged 44-79 with established coronary heart disease. Participants were randomly assigned to 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate or placebo and followed for a mean of 4.1 years. History of physician-diagnosed urinary tract infections and risk factors were assessed by self-report at baseline and each annual visit.\n Urinary tract infection frequency was higher in the group randomized to hormone treatment, although the difference was not statistically significant (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.99, 1.37). Statistically significant risk factors for urinary tract infections in multivariable analysis included: women with diabetes on treatment (insulin OR 1.81, 95% CI 1.40, 2.34), oral medications OR 1.44, 95% CI 1.09, 1.90), poor health (OR 1.34, 95% CI 1.14, 1.57), childbirth (OR 1.38, 95% CI 1.00, 1.90), vaginal itching (OR 1.63, 95% CI 1.07, 2.50), vaginal dryness (OR 1.30, 95% CI 1.04, 1.67), and urge incontinence (OR 1.51, 95% CI 1.30, 1.75). Urinary tract infections in the previous year were strongly associated with a single urinary tract infection (OR 7.00, 95% CI 5.91, 8.29) as well as multiple urinary tract infections (OR 18.51, 95% CI 14.27, 24.02).\n Oral hormone therapy did not reduce frequency of urinary tract infections. Potentially modifiable risk factors in postmenopausal women are different from those in younger women, and include diabetes, vaginal symptoms, and urge incontinence.", "To examine the effects of oral estrogen/progestin on incontinence and related lower urinary tract conditions among female nursing home (NH) residents.\n Randomized placebo-controlled trial.\n Five NHs.\n Thirty-two incontinent female residents of average age 88.\n Subjects were randomized to receive either oral estrogen (0.625 mg) combined with progesterone (2.5 mg) or placebo, daily for 6 months. Measures of incontinence severity, the clinical appearance of the vagina, vaginal and urethral cytology, and urine and vaginal cultures were made at baseline, 3 months, and 6 months. In addition to active drug or placebo, all subjects received regular toileting assistance (prompted voiding) by trained research aides during 3-day data-collection periods to compensate for mobility and cognitive impairments.\n At 3 and 6 months there were no significant differences between the groups in the severity of incontinence, the prevalence of bacteriuria, or the results of vaginal cultures. Several clinical findings associated with atrophic vaginitis improved more in the active than the placebo group and vaginal pH and vaginal and urethral cytology exhibited a partial estrogenic effect.\n Our results must be interpreted with caution because of the size and the select nature of our subject sample. Up to 6 months of oral estrogen had only a partial estrogenic effect on vaginal and urethral epithelium and no clinical effects in this patient population. We believe that future studies of estrogen for urinary incontinence in frail NH residents should utilize a topical preparation and consider targeting urinary tract infection as an additional outcome measure.", "A block randomized, double-blind, group-comparative, placebo-controlled study was conducted to assess the effect of oestriol on recurrent urinary tract infections in postmenopausal women. 40 women, median age 78 years (66-91), 20 in each group, were treated with oestriol three mg p.o. per day or corresponding placebo for four weeks, followed by one mg per day for eight weeks. The main response parameter was the number of urinary tract infections per week in the two treatment periods. Both oestriol and placebo reduced the number of infections per week significantly in both periods, compared with the pretreatment period. There was no difference between oestriol and placebo treatment in the first period. In the second period, however, oestriol treatment was significantly more effective than placebo (p = 0.05). Correspondingly, there was a significant difference between the two groups in the vaginal pH at the end of the study (p less than 0.05). We conclude that oestriol reduces recurrent urinary tract infections in postmenopausal women.", "To assess the efficacy of oral oestriol in the prevention of recurrent urinary tract infections in elderly women.\n Double-blind, randomised, parallel group, placebo controlled trial\n Urogynaecology Unit at King's College Hospital with some women recruited from the geriatric units of St. Pancras Hospital and Dulwich Hospital, London (UK).\n Seventy-two postmenopausal women older than 60 years of age (mean 73.2 years) suffering from recurrent urinary tract infections.\n Oral oestriol (3 mg per day) or placebo for six months. MAIN: outcome measures Urinary tract infection rates.\n The study was difficult to conduct because of its design and the age of the participants. Oral oestriol (3 mg per day) was not shown to be superior to placebo in the prevention of recurrent urinary tract infections, but both oestriol and placebo improved urinary symptoms during the trial.\n The power of the study might have been too low to detect a significant difference between the groups, or oral oestriol (3 mg per day) may have been either the wrong dose or the wrong route of administration for this indication.", "To evaluate the effect and feasibility of using estrogen cream for the prevention and treatment of recurrent urinary tract infection (UTI) in postmenopausal women.\n Forty-five postmenopausal women with a history of recurrent UTI were divided into two groups (group premarin and group antibiotic). Participants were assigned to apply intravaginal premarin cream (group premarin, n = 30) or oral antibiotic (group antibiotic, n = 15) for 3 months respectively. Urine routine test, midstream urine and vaginal cultures, vaginal health score (VHS), vaginal cell maturation value (MV), endometrial thickness and blood estrogen level were obtained before and after the study.\n The incidence of UTI in the group premarin was significantly reduced as compared with that in the group antibiotic (2/27 vs. 12/15, P < 0.001). In the group premarin Lactobacilli reappeared (from 0 to 59.3%) and MV (from 9.2 +/- 6.8 to 74.6 +/- 14.1) and VHS (from 5.2 +/- 0.4 to 13.4 +/- 2.5) were improved after 3 months. There was no significant change in the group antibiotic.\n It seems that intravaginal use of estrogen cream would effectively prevent and reduce the UTI in postmenopausal women.", "We compared the efficacy and safety of estriol-containing vaginal pessary use with those of oral nitrofurantoin macrocrystal (NM) therapy for preventing urinary tract infection (UTI) in postmenopausal women with recurrent UTI. Over a period of 9 months, 86 women received an estriol-containing vaginal pessary (0.5 mg estriol) twice weekly, and 85 women received NM (100 mg) once daily. We recorded 124 episodes of UTI in women who received estriol-releasing pessaries and 48 episodes of UTI in women treated with NM (P=.0003). Twenty-eight women (32.6%) who received estriol had no episodes of UTI versus 41 women (48.2%) in the NM group. There was a significant increase in the number of superficial cells in women who received estriol, whereas in the NM group, no such changes occurred. However, there was no change in the extent of Lactobacillus colonization and in the vaginal pH in women who received estriol. Use of an estriol-containing pessary is less effective than oral NM therapy in the prevention of bacteriuria in postmenopausal women because of its failure to restore the population of lactobacilli and to reduce the vaginal pH in these women.", "Recurrent urinary tract infections are a problem for many postmenopausal women. Estrogen replacement restores atrophic mucosa, lowers vaginal pH, and may prevent urinary tract infections.\n We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a randomized, double-blind, placebo-controlled trial of a topically applied intravaginal estriol cream. Midstream urine cultures were obtained at enrollment, monthly for eight months, and whenever urinary symptoms occurred. Vaginal cultures and pH measurements were obtained at entry and after one and eight months. The women were assigned to receive either estriol (n = 50) or placebo (n = 43), both administered intravaginally; 36 and 24, respectively, completed the eight months of follow-up.\n The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo (0.5 vs. 5.9 episodes per patient-year, P < 0.001). Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection (P < 0.001). Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women (61 percent) but in none of the 24 placebo recipients (P < 0.001). With estriol the mean vaginal pH declined from 5.5 to 3.8 (P < 0.001), whereas there was no significant change with placebo. The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged (from 67 to 63 percent) in the placebo recipients (P < 0.005). Side effects were minor, but caused 10 estriol recipients (28 percent) and 4 placebo recipients (17 percent) to discontinue treatment.\n The intravaginal administration of estriol prevents recurrent urinary tract infection in postmenopausal women, probably by modifying the vaginal flora.", "The primary objective was to detect a difference in time until the first recurrence of urinary tract infection during treatment with an estradiol-releasing silicone vaginal ring (Estring; Pharmacia & Upjohn, Inc, Uppsala, Sweden) compared with no estrogen treatment. The secondary objective was to detect any differences in improvement of urethral and vaginal mucosal atrophy and in the subjective assessment of urogenital symptoms. The study also sought to detect a difference in decrease of vaginal pH to <5.5 and to record adverse events.\n This was a multicenter, randomized, open, parallel-group study with an untreated control group. Postmenopausal women with recurrent symptomatic, bacteriologically confirmed urinary tract infections were randomly assigned to receive either Estring (2 mg estradiol) or no estrogen treatment. One ring was carried vaginally for 12 weeks. The duration of treatment was 36 weeks for the Estring group and either 36 weeks or until the first recurrence for the control group. Both intent-to-treat and per-protocol analyses were performed to evaluate efficacy, whereas the safety analysis was limited to the intent-to-treat group. The primary variable was analyzed by survival analysis with the Kaplan-Meier method for estimating the survival density function. To compare the survival curves for the 2 treatment groups a log-rank test was performed for time until first recurrence.\n A total of 108 women were randomly assigned, 53 to the Estring group and 55 to the control group. The cumulative proportion of women remaining free of urinary tract infection was significantly higher in the Estring group than in the control group (P =.008). After 36 weeks of study the cumulative likelihood of remaining free of disease was approximately 45% in the women with the vaginal ring compared with approximately 20% in the control group. Estring lowered vaginal pH, and the time to first recurrence was effectively prolonged by Estring treatment. Vaginal and, to a lesser extent, urethral mucosal cells were significantly more mature in the Estring group. No unexpected adverse events were found.\n Estring is useful to prolong the time to next recurrence among postmenopausal women with recurrent urinary tract infection and to decrease the number of recurrences per year. The silicone vaginal ring also has a clinically significant ability to alleviate other postmenopausal urogenital symptoms. Estring is safe and well tolerated.", "Twenty-three postmenopausal women with recurrent cystitis were allorted at random to treatment for five months with local oestrogen in the vagina or placebo treatment with the object of assessing the local effect on the vaginal epithelium and on the tendency to recurrent cystitis. The therapeutic group and the placebo group were entirely comparable prior to treatment. In the therapeutic group, the oestrogen index in vaginal scrapings was significantly higher after treatment than in the placebo group (p less than 0.01). The number of positive urine cultures and the patients/satisfaction with treatment wee not significantly different in the two groups." ]

[ "11437864", "19922726", "17305788" ]

[ "Sodium carboxyl-methyl-cellulose dressings in the management of deep ulcerations of diabetic foot.", "Randomised controlled trial of the use of three dressing preparations in the management of chronic ulceration of the foot in diabetes.", "Prospective randomized controlled study of Hydrofiber dressing containing ionic silver or calcium alginate dressings in non-ischaemic diabetic foot ulcers." ]

[ "To test the safety and effectiveness of carboxyl-methyl-cellulose dressing (Aquacel; ConvaTec, UK) in the management of deep diabetic foot ulcers, a group of consecutive out-patients attending the foot clinic of the Department of Metabolic Diseases was studied.\n Patients were selected according to the following inclusion criteria: a foot ulcer deeper than 1 cm for > 3 weeks, good peripheral blood supply (palpable peripheral pulses or ABPI > 0.9). Exclusion criteria were as follows: active infection, as evident from clinical signs (purulent discharge, redness, swelling, tenderness) and confirmed by culture exams, plasma creatinine > 2 mg/dl, recent episodes of ketoacidosis, malignancies, and any therapy or pathology which might interfere with the healing process. Twenty patients were enrolled in the study and having obtained their informed consent, their lesions were surgically debrided with the complete elimination of all necrotic tissue and debris up to the bleeding healthy tissue; then ulcers were staged and measured, and patients were randomly assigned to two different treatment groups. Patients in group A were dressed with saline-moistened gauze, while patients in group B were dressed with Aquacel according to the manufacturer's instructions. All patients in both groups received special post-operative shoes (Podiabetes; Zeno Buratto, Treviso, Italy) and crutches until complete re-epithelialization. Ulcers were all left to heal by secondary intent. After 8 weeks patients were blindly evaluated for: the rate of reduction of lesional volume (RLV), rate of granulation tissue (GT), number of infective complications (IC). Intralesional (ILTC) and perilesional (PLTC) temperatures were also recorded with a thermocouple surface digital thermometer, and the difference between the two values (Delta TC) was calculated. Healing time (HT, days), was then compared between the two groups. Data were compared by analysis of variance (ANOVA), linear regression, Kaplan-Meier survival analysis and Fisher's exact test.\n HT was significantly shorter in Group B than in Group A (P < 0.001). RLV was significantly (P < 0.01) higher in Group B patients compared with Group A, as well as GT (P < 0.05). IC were in 1/10 Group B and in 3/10 Group A (P = 0.582). In addition, both ILTC and Delta TC were higher in Group B compared with Group A ones (P < 0.01).\n Carboxyl-methyl-cellulose dressings were shown to be safe, effective and well tolerated in the management of non-ischaemic, non-infected deep diabetic foot ulcers.", "To determine the comparative effectiveness and cost-effectiveness of three dressing products, N-A, Inadine and Aquacel, for patients with diabetic foot ulcers, as well as the feasibility and consequences of less frequent dressing changes by health-care professionals.\n A multicentre, prospective, observer-blinded, parallel group, randomised controlled trial, with three arms.\n Established expert multidisciplinary clinics for the management of diabetic foot ulcers across the UK.\n Patients over age 18 with type 1 or type 2 diabetes with a chronic (present for at least 6 weeks) full-thickness foot ulcer (on or below the malleoli) not penetrating to tendon, periosteum or bone, and with a cross-sectional area between 25 and 2500 mm(2).\n Participants were randomised 1:1:1 to treatment with one of N-A (a non-adherent, knitted, viscose filament gauze), Inadine (an iodine-impregnated dressing), both traditional dressings, or Aquacel, a newer product.\n The primary outcome measure was the number of ulcers healed in each group at week 24. Secondary measures included time to healing, new ulcerations, major and minor amputations, and episodes of secondary infection.\n A total of 317 patients were randomised. After 88 withdrawals, 229 remained evaluable. A greater proportion of smaller (25-100 mm(2) ulcers healed within the specified time (48.3% versus 37.3%; p = 0.048). There was, however, no difference between the three dressings in terms of percentage healed by 24 weeks, or in the mean time to healing, whether analysed on the basis of intention to treat (Inadine 44.4%, N-A 38.7%, Aquacel 44.7%; not significant) or per protocol (Inadine 55.2%, N-A 59.4%, Aquacel 63.0%; not significant). There was no difference in the quality of healing, as reflected in the incidence of recurrence within 12 weeks. Likewise, there was no difference in the incidence of adverse events, although a greater proportion of those randomised to the non-adherent dressings were withdrawn from the study (34.9% versus 29.1% Aquacel and 19.4% Inadine; p = 0.038). The only statistically significant difference found in the health economic analysis was the cost associated with the provision of dressings (mean cost per patient: N-A 14.85 pounds, Inadine 17.48 pounds, Aquacel 43.60 pounds). The higher cost of Aquacel was not offset by the fewer dressings required. There was no difference in measures of either generic or condition-specific measures of quality of life. However, there was a significant difference in the change in pain associated with dressing changes between the first and second visits, with least pain reported by those receiving non-adherent dressings (p = 0.012). There was no difference in the costs of professional time, and this may relate to the number of dressing changes undertaken by non-professionals. Fifty-one per cent of all participants had at least one dressing change undertaken by themselves or a non-professional carer, although this ranged from 22% to 82% between the different centres.\n As there was no difference in effectiveness, there is no reason why the least costly of the three dressings could not be used more widely across the UK National Health Service, thus generating potentially substantial savings. The option of involving patients and non-professional carers in changing dressings needs to be assessed more formally and could be associated with further significant reductions in health-care costs.\n Current Controlled Trials ISRCTN78366977.", "Diabetic foot ulcers (DFUs) are at risk of infection and impaired healing, placing patients at risk of lower extremity amputation. DFU care requires debridement and dressings. A prospective, multicentre study compared clinical efficacy and safety of AQUACEL Hydrofiber dressings containing ionic silver (AQAg) with those of Algosteril calcium alginate (CA) dressings in managing out-patients with Type 1 or 2 diabetes mellitus and non-ischaemic Wagner Grade 1 or 2 DFUs.\n Patients stratified by antibiotic use on enrolment were randomly assigned to similar protocols including off-loading, AQAg (n = 67) or CA (n = 67) primary dressings and secondary foam dressings for 8 weeks or until healing. Clinical efficacy measures were healing outcomes and primarily healing speed. Adverse events were recorded.\n AQAg and CA groups were comparable at baseline. All ulcer healing outcomes improved in both groups. The mean time to healing was 53 days for AQAg ulcers and 58 days for CA ulcers (P = 0.34). AQAg-treated ulcers reduced in depth nearly twice as much as CA-treated ulcers (0.25 cm vs. 0.13 cm; P = 0.04). There was more overall ulcer improvement and less deterioration in AQAg subjects (P = 0.058), particularly in the subset initially using antibiotics (P = 0.02). Safety profiles of both groups were similar.\n When added to standard care with appropriate off-loading, AQAg silver dressings were associated with favourable clinical outcomes compared with CA dressings, specifically in ulcer depth reduction and in infected ulcers requiring antibiotic treatment. This study reports the first significant clinical effects of a primary wound dressing containing silver on DFU healing." ]

[ "11445103", "1841829", "3288866" ]

[ "Enteral human IgG for prevention of necrotising enterocolitis: a placebo-controlled, randomised trial.", "Prevention of necrotizing enterocolitis in neonates at risk by oral administration of monomeric IgG.", "Prevention of necrotizing enterocolitis in low-birth-weight infants by IgA-IgG feeding." ]

[ "Neonatal necrotising enterocolitis is a serious, commonly fatal disease in premature neonates. Although feeding with expressed breast milk and other good nursery practices are partly protective, preventive measures are needed. Treating neonates enterally with a mixture of human IgA and IgG, prepared from donated blood, has been claimed to protect against necrotising enterocolitis. However, no IgA preparation is available in Australia. Our aim, therefore, was to identify whether or not enteral IgG could prevent the disorder.\n We did a multicentre, double-blind, placebo- controlled trial. We randomly assigned 768 infants to receive human IgG 1200 mg/kg daily, and 761 to receive placebo, for up to 28 days. Treatment began at the same time as enteral feeding. The primary outcome measure was the proportion of infants who developed definite necrotising enterocolitis during the trial, and any deaths that resulted from the disorder in the treatment and placebo groups. Analysis was on an intention-to-treat basis.\n 43 infants developed definite necrotising enterocolitis in the IgG group, ten of whom died. In the placebo group, 41 infants contracted the disorder and six died (p=0.47). 25 infants on IgG and 36 on placebo had suspect necrotising enterocolitis (p=0.14).\n Supplementation of enteral feeds with human IgG does not reduce necrotising enterocolitis.", "Necrotizing enterocolitis (NEC) represents one of the major causes of morbidity in low-birth-weight (LBW) preterm infants. This randomized clinical trial evaluated the efficacy of an oral immunoglobulin preparation (containing monomeric IgG in a concentration of 90%) in reducing the incidence of NEC in infants of LBW for whom maternal breast milk was not available. One hundred and thirty-two formula-fed newborns with a birth weight less than or equal to 1,500 g or a gestational age less than or equal to 34 weeks were randomly studied. Five hundred mg of IgG pro die, subdivided into 5 doses, were given orally to the test group of 65 neonates during the first 2 weeks of life. Although the number of infants included in this group is limited, the results of this study are encouraging: during the first 15 days after birth, none of the subjects developed NEC, while 4 cases were confirmed in the untreated control group. It, therefore, seems possible that oral monomeric IgG administration may prevent the development of NEC in LBW infants.", "In a randomized clinical trial, we evaluated the efficacy of an oral immunoglobulin preparation (73 percent IgA and 26 percent IgG) in reducing the incidence of necrotizing enterocolitis in infants of low birth weight for whom breast milk from their mothers was not available. A total of 434 infants weighing between 800 and 2000 g were eligible for entry in the study. Of these, 255 were withdrawn - 234 during the first week of the study because breast milk from their mothers became available (123 in the treatment group and 111 in the control group), and 21 because of violations of protocol or because breast milk became available after the first week. The duration of follow-up was 28 days. Among the infants for whom breast milk did not become available during the study, there were no cases of necrotizing enterocolitis among the 88 receiving oral IgA-IgG, as compared with six cases among the 91 control infants (P = 0.0143). Of the infants withdrawn from the study, two assigned to the control group had necrotizing enterocolitis. We conclude that the oral administration of IgA-IgG may prevent the development of necrotizing enterocolitis in low-birth-weight infants." ]

[ "10514155", "12603234", "11563806", "7852062", "11802453", "8442622", "16027567", "8291821", "8147544", "15296021", "17568244", "14644967", "8124120", "1571877", "14769679", "16899830", "3592033", "15141368", "2360750", "1414430", "15991780", "10343421", "15681592", "9046892", "2405112", "9093045", "8831651", "16182355", "9579010", "15533536", "9930042", "8947084", "11720060", "12200104", "11786452", "16595098", "11023136", "2556540", "12622686", "16203030", "2194387" ]

[ "Behavioural counselling in general practice for the promotion of healthy behaviour among adults at increased risk of coronary heart disease: randomised trial.", "A controlled trial of an expert system and self-help manual intervention based on the stages of change versus standard self-help materials in smoking cessation.", "Short- and long-term smoking cessation for three levels of intensity of behavioral treatment.", "A comparison of nursing interventions for smoking cessation in adults with cardiovascular health problems.", "[The effect of smoking cessation counseling at health checkup].", "Nurse-assisted counseling for smokers in primary care.", "The effectiveness of a nursing inpatient smoking cessation program in individuals with cardiovascular disease.", "Predictors of smoking cessation after coronary artery bypass graft surgery. Results of a randomized trial with 5-year follow-up.", "A case-management system for coronary risk factor modification after acute myocardial infarction.", "[Efficacy of a smoking relapse prevention program by postdischarge telephone contacts: a randomized trial].", "Improving outcomes after myocardial infarction: a randomized controlled trial evaluating effects of a telephone follow-up intervention.", "Randomised controlled trial of smoking cessation intervention after admission for coronary heart disease.", "Effectiveness of health checks conducted by nurses in primary care: results of the OXCHECK study after one year. Imperial Cancer Research Fund OXCHECK Study Group.", "Evaluation of the \"Time to Quit\" self-help smoking cessation program.", "High rates of sustained smoking cessation in women hospitalized with cardiovascular disease: the Women's Initiative for Nonsmoking (WINS).", "Nurse-conducted smoking cessation in patients with COPD using nicotine sublingual tablets and behavioral support.", "Evaluation of a minimal-contact smoking cessation intervention in an outpatient setting.", "Efficacy of a smoking-cessation intervention for elective-surgical patients.", "Smoking cessation after acute myocardial infarction: effects of a nurse-managed intervention.", "Does nurse counseling or offer of nicotine gum improve the effectiveness of physician smoking-cessation advice?", "A randomised controlled trial to evaluate the efficacy of a nurse-provided intervention for hospitalised smokers.", "Randomized trial of nurse-assisted strategies for smoking cessation in primary care.", "Efficacy of a smoking cessation intervention using the AHCPR guideline tailored for Koreans: a randomized controlled trial.", "Smoking cessation in hospitalized patients. Results of a randomized trial.", "Adding spirometry, carbon monoxide, and pulmonary symptom results to smoking cessation counseling: a randomized trial.", "Influence of coronary nursing management follow up on lifestyle after acute myocardial infarction.", "Coronary risk factor modification in women after coronary artery bypass surgery.", "Home health care nurses as a new channel for smoking cessation treatment: outcomes from project CARES (Community-nurse Assisted Research and Education on Smoking).", "Transdermal nicotine replacement for hospitalized patients: a randomized clinical trial.", "The TEAM project: the effectiveness of smoking cessation intervention with hospital patients.", "Secondary prevention in coronary heart disease: a randomised trial of nurse led clinics in primary care.", "Nurse-conducted smoking cessation with minimal intervention in a lung clinic: a randomized controlled study.", "Randomized controlled trial of two cigarette quit programmes in coronary care patients after acute myocardial infarction.", "A minimal-contact intervention for cardiac inpatients: long-term effects on smoking cessation.", "Brief intervention during hospital admission to help patients to give up smoking after myocardial infarction and bypass surgery: randomised controlled trial.", "[Effectiveness of a programme of intensive tobacco counselling by nursing professionals].", "Intervention study for smoking cessation in diabetic patients: a randomized controlled trial in both clinical and primary care settings.", "Randomized controlled trial of anti-smoking advice by nurses in general practice.", "Pediatric-based smoking cessation intervention for low-income women: a randomized trial.", "Smoking cessation in patients with COPD in daily general practice (SMOCC): six months' results.", "Smoking prevention among people aged 60 and over: a randomized controlled trial." ]

[ "To measure the effect of behaviourally oriented counselling in general practice on healthy behaviour and biological risk factors in patients at increased risk of coronary heart disease.\n Cluster randomised controlled trial.\n 883 men and women selected for the presence of one or more modifiable risk factors: regular cigarette smoking, high serum cholesterol concentration (6.5-9.0 mmol/l), and high body mass index (25-35) combined with low physical activity.\n Brief behavioural counselling, on the basis of the stage of change model, carried out by practice nurses to reduce smoking and dietary fat intake and to increase regular physical activity.\n Questionnaire measures of diet, exercise, and smoking habits, and blood pressure, serum total cholesterol concentration, weight, body mass index, and smoking cessation (with biochemical validation) at 4 and 12 months.\n Favourable differences were recorded in the intervention group for dietary fat intake, regular exercise, and cigarettes smoked per day at 4 and 12 months. Systolic blood pressure was reduced to a greater extent in the intervention group at 4 but not at 12 months. No differences were found between groups in changes in total serum cholesterol concentration, weight, body mass index, diastolic pressure, or smoking cessation.\n Brief behavioural counselling by practice nurses led to improvements in healthy behaviour. More extended counselling to help patients sustain and build on behaviour changes may be required before differences in biological risk factors emerge.", "To examine the population impact and effectiveness of the Pro-Change smoking cessation course based on the Transtheoretical Model (TTM) compared to standard self-help smoking cessation literature.\n Randomized controlled trial.\n Sixty-five West Midlands general practices.\n Randomly sampled patients recorded as smokers by their general practitioners received an invitation letter and 2471 current smokers agreed.\n Responders were randomized to one of four interventions. The control group received standard self-help literature. In the Manual intervention group, participants received the Pro-Change system, a self-help workbook and three questionnaires at 3-monthly intervals, which generated individually tailored feedback. In the Phone intervention group, participants received the Manual intervention plus three telephone calls. In the Nurse intervention group, participants received the Manual intervention plus three visits to the practice nurse.\n Biochemically confirmed point prevalence of being quit and 6-month sustained abstinence, 12 months after study commencement.\n A total of 9.1% of registered current smokers participated, of whom 83.0% were not ready to quit. Less than half of participants returned questionnaires to generate second and third individualized feedback. Telephone calls reached 75% of those scheduled, but few participants visited the nurse. There were small differences between the three Pro-Change arms. The odds ratio (95% confidence intervals) for all Pro-Change arms combined versus the control arm were 1.50 (0.85-2.67) and 1.53 (0.76-3.10), for point prevalence and 6-month abstinence, respectively. This constitutes 2.1% of the TTM group versus 1.4% of the control group achieving confirmed 6-month sustained abstinence.\n There was no statistically significant benefit of the intervention apparent in this trial and the high relapse of quitters means that any population impact is small.", "Efficacy and costs of 3 levels of medical-behavioral treatment intensity in conjunction with nicotine replacement therapy (NRT) were compared in 240 one-pack-a-day smokers: (a) a low-intensity (LI) group that received 8 weeks of NRT (n = 80) and 1 advice and education (A&E) session with a nurse practitioner (NP); (b) a moderate-intensity (MI) group that was provided NRT and 4 A&E sessions with an NP (n = 80); and (c) a high-intensity (HI) group that received treatment combining NRT, 4 A&E sessions, and 12 weeks of individualized cognitive-behavioral therapy (n = 80). Biochemically confirmed abstinence rates at 9, 26, and 52 weeks posttreatment initiation were highest for the HI (45%, 37%, 35%) group, followed by the LI (35%, 30%, and 27%) and MI (27%, 12%, 12%) groups. Group differences approached statistical significance at 9 weeks and were statistically significant at both 26 and 52 weeks. The cost of LI treatment was $308, that of MI was $338, and the HI treatment cost was $582.", "To examine the relative effectiveness of three different presentations of a smoking cessation program on the smoking behavior of adults with cardiovascular health problems.\n A 2 x 2 x 2 x 4 experimental design with stratification by sex, smoking history, and a cardiovascular event, and randomization to Individual, Group, Written, or No Intervention groups.\n Six community hospital classrooms.\n 255 nonhospitalized adults. THEORETIC FRAMEWORK: Interaction Model of Client Health Behavior.\n Study Intake: Professional referral form, demographic questionnaire, smoking habits questionnaire, health history, perceived threat survey, perceived health status. Follow up: smoking cessation and health questionnaire, saliva thiocyanate testing.\n At 12-month follow-up, a nurse-client interaction was more effective than written self-help materials; however, smoking cessation rates were highest in the No Intervention control group, possibly related to having had coronary artery bypass graft surgery. Variables positively related to quitting were being male and married and having a higher income. With baseline factors considered, a quitter was most likely to be male and less than 48 years of age, have a high degree of perceived threat relative to medical diagnosis, and be in the individual intervention group. Only partial support for the study hypotheses was found.", "Smoking cessation counseling is an important element of tobacco control in the workplace, but it is not easy to persuade workers to stop smoking. We performed a controlled intervention trial to evaluate the effectiveness of a new cessation program developed by Nakamura et al., which consisted of one brief individual counseling session and 4 follow-up telephone calls. Two hundred and twenty-eight smokers who visited our center for an annual health checkup were randomly divided into two group: 117 were assigned to the intervention group, and 111 were controls. Smoking status questionnaires were administered to assess the smoking habit of each subject and to evaluate their stages of change toward smoking cessation before the counseling session. Stage-matched cessation counseling was then provided to the intervention group by nurses who had completed training courses for this program. During the counseling session, carbon monoxide in expired air and nicotine metabolites in urine were measured to enhance self-perception of smoking. Only those clients who set a quit date during their counseling sessions received follow-up telephone calls. It was easy to implement this program (15 to 20 minutes long) during a health checkup. No significant differences were observed in the baseline characteristics of the two groups. The cross-sectional smoking cessation rates at 6 months and 1 year of follow-up were 6.2 times higher in the intervention group than in the control group. The continuous smoking cessation rate at 1 year of follow-up was 7.6 times higher in the intervention group than in the control group. In the intervention group, the lower level of nicotine metabolites in urine and higher smoking stage were related to cessation success, but other baseline characteristics were similar in those who quit smoking and those who did not. The effectiveness and easy applicability of this cessation program was proved in the present study. Further examinations in various settings are expected to clarify the effectiveness of this program.", "Physician-delivered advice to stop smoking is effective, but time demands often reduce the number of smokers who receive assistance. We evaluated three nurse-assisted interventions designed to minimize physician burden and increase counseling in primary care settings.\n Randomized controlled trial with a 12-month follow-up.\n Internal medicine and family practice offices in a health maintenance organization.\n Smokers (n = 3161) who were patients of participating physicians or other medical care providers (n = 60).\n Medical care providers delivered a 30-second stop-smoking prompt to 2707 smokers and referred them to an on-site nurse smoking counselor. The nurse randomly provided a two-page pamphlet (advice control) or one of three nurse-assisted interventions: 1) self-quit training; 2) referral to a group cessation program; or 3) a combination of self-quit training and referral. Each nurse-delivered intervention included a 10-minute video, written materials, and a follow-up phone call.\n Physicians delivered brief advice to 86% of identified smokers during the 1-year program. The proportion of participants reporting abstinence after both 3 and 12 months of follow-up nearly doubled (P = 0.01) for the nurse-assisted self-quit (7.1%), group-referral (7.6%), and combination (6.9%) interventions, compared to brief physician advice alone (3.9%) (P < 0.05). Saliva cotinine tests confirmed these effects (P < 0.004), although quit rates were lower (3.4%, 4.7%, 4.3%, and 2.3%, respectively) because roughly one half of quitters chose not to provide a saliva sample and were counted as smokers.\n Involving nurses in counseling smokers reduces physician burden, makes counseling more likely, and significantly increases cessation rates compared with brief physician advice alone.", "Smoking is an important risk factor for cardiovascular disease (CVD), and quitting is highly beneficial. Yet, less than 30% of CVD patients stop smoking. Relapse-prevention strategies seem most effective when initiated during the exacerbation of the disease.\n A nurse-delivered inpatient smoking cessation program based on the Transtheoretical Model with telephone follow-up tailored to levels of readiness to quit smoking was evaluated on smoking abstinence and progress to ulterior stages of change.\n Participants (N = 168) were randomly assigned by cohorts to inpatient counseling with telephone follow-up, inpatient counseling, and usual care. The inpatient intervention consisted of a 1-hr counseling session, and the telephone follow-up included 6 calls during the first 2 months after discharge. The nursing intervention was tailored to the individual's stage of change. End points at 2 and 6 months included actual and continuous smoking cessation rates (biochemical markers) and increased motivation (progress to ulterior stages of change).\n Assuming that surviving patients lost to follow-up were smokers, the 6-month smoking abstinence rate was 41.5% in the inpatient counseling with telephone follow-up group, compared with 30.2% and 20% in the inpatient counseling and usual care groups, respectively (p = .05). Progress to ulterior stages of change was 43.3%, 32.1%, and 18.2%, respectively (p = .02). Stage of change at baseline and intervention predicted smoking status at 6 months.\n This tailored smoking cessation program with telephone follow-up significantly increased smoking cessation at 6 months, and progression to ulterior stages of change. The telephone follow-up was an important adjunct. It is, therefore, recommended to include such comprehensive smoking cessation programs within hospital settings for individuals with CVD.", "To test the efficacy of a smoking cessation program for inpatients recovering from coronary artery bypass graft surgery and to identify predictors of cessation.\n Randomized, controlled clinical trial.\n Postoperative cardiac surgery unit of a large teaching hospital.\n Patients scheduled for coronary artery bypass surgery by participating surgeons between 1 July 1986 and 1 July 1987 who had smoked 1 or more packs of cigarettes in the 6 months before admission. Of 120 eligible patients, 93 enrolled and 87 were discharged alive. All survivors were followed for at least 1 year; 94% were followed for a median of 5.5 years.\n A three-session, nurse-delivered behavior modification program using a videotape and face-to-face counseling was compared to usual care.\n Smoking status was assessed six times in the year after surgery and 5.5 years after surgery. Self-reported nonsmoking was validated by saliva cotinine assay 1 and 5.5 years after surgery.\n No statistically significant differences were found between control (n = 43) and intervention (n = 44) groups at baseline. One and 5.5 years after hospital discharge, validated continuous nonsmoking rates were identical in intervention and control groups (51% at 1 year; 44% at 5.5 years). Multiple logistic regression identified four factors that were independently associated with nonsmoking for 1 year: fewer than 3 previous attempts to quit (odds ratio, 7.4; 95% Cl, 1.9 to 29.1); more than 1 week of preoperative nonsmoking (odds ratio, 10.0; Cl, 2.0 to 50.2); definite intention to quit smoking (odds ratio, 12.0; Cl, 2.6 to 55.1); and no difficulty not smoking in the hospital (odds ratio, 9.6; Cl, 1.8 to 52.2). Nonsmoking for 5.5 years was independently associated with two of these factors: fewer than three previous attempts to quit and intention to quit smoking after surgery. Cessation was not related to demographic factors, daily cigarette consumption, disease severity, hospital course, social support, or beliefs and attitudes.\n Even without specific intervention, nearly one half of smokers quit for 5 years after coronary artery bypass surgery. A short inpatient education program did not increase this rate. Future efforts should target the time after discharge and focus on increasing motivation in patients who have repeatedly failed to quit.", "To evaluate the efficacy of a physician-directed, nurse-managed, home-based case-management system for coronary risk factor modification.\n Randomized clinical trial in which patients received a special intervention (n = 293) or usual medical care (n = 292) during the first year after acute myocardial infarction.\n 5 Kaiser Permanente Medical Centers in the San Francisco Bay area.\n 585 men and women aged 70 years or younger who were hospitalized for acute myocardial infarction.\n In the hospital, specially trained nurses initiated interventions for smoking cessation, exercise training, and diet-drug therapy for hyperlipidemia. Intervention after discharge was implemented primarily by telephone and mail contact with patients in their homes. All medically eligible patients received exercise training; all smokers received the smoking cessation intervention; and all patients received dietary counseling and, if needed, lipid-lowering drug therapy.\n Smoking prevalence and plasma low-density lipoprotein cholesterol (LDL) concentrations were measured 2 months after infarction, and functional capacity was measured 6 months after infarction.\n In the special intervention and usual care groups, the cotinine-confirmed smoking cessation rates were 70% and 53% (P = 0.03), plasma LDL cholesterol levels were 2.77 +/- 0.69 mmol/L and 3.41 +/- 0.90 mmol/L (107 +/- 30 mg/dL and 132 +/- 30 mg/dL) (P = 0.001), and functional capacities were 9.3 +/- 2.4 METS and 8.4 +/- 2.5 METS (P = 0.001), respectively.\n In a large health maintenance organization, a case-management system was considerably more effective than usual medical care for modification of coronary risk factors after myocardial infarction.", "This randomized controlled trial assessed the efficacy of a smoking relapse prevention program featuring 3 postdischarge telephone contacts with subjects who had quit smoking on hospitalization.\n Patients were randomly assigned to public health nurse-mediated behaviorally oriented in-patient counseling focused on relapse prevention (control group, n = 49), or the same inpatient counseling with postdischarge telephone contacts at 7, 21 and 42 days after discharge (intervention group, n = 57). The main outcome measure, smoking cessation rate, was obtained from self-reports at 3, 6 and 12 months after discharge. Smoking cessation at 12 months after discharge was confirmed by urinary nicotine concentration.\n At 3, 6 and 12 months smoking cessation rates were 83%, 63% and 56% for the intervention group, and 76%, 65% and 51% for control group. After adjustment for sex, age, having any complication, number of family members, smoking status on admission, strength of nicotine dependence and self confidence to quit smoking, the odds ratio of cessation among the intervention group were 1.46 (95% confidence interval (CI): 0.48-4.47), 0.82 (95% CI: 0.31-2.17) and 0.99 (95% CI: 0.40-2.45) at 3, 6 and 12 months after discharge, respectively.\n This program had limited efficacy to maintain postdischarge smoking abstinence. We should re-consider the modality of smoking cessation program for relapse prevention among hospitalized patients.", "Providing information is an important part of standard care and treatment for acute myocardial infarction inpatients. Evidence exists indicating that acute myocardial infarction patients experience an information gap in the period immediately after discharge from the hospital. The aim of this study was to assess the short-term effects of a nurse-led telephone follow-up intervention to provide information and support to patients with acute myocardial infarction after their discharge from hospital.\n A prospective randomized, controlled trial with a 6-month follow-up was conducted. A total of 288 patients were allocated to either an intervention group (n=156) or a control group (n=132). The latter received routine post-discharge care. The primary endpoint measured at 3 and 6 months after discharge was the health-related quality of life using the 36-item Short Form Health Survey. Secondary endpoints included smoking and exercise habits.\n In both groups, health-related quality of life improved significantly over time on most subscales. A statistically significant difference in favour of the intervention group was found on the 36-item Short Form Health Survey Physical Health Component Summary Scale (P=0.034) after 6 months. No difference was found between the groups on the Mental Health Component Summary Scale. We found a significant difference with respect to frequency of physical activity in favour of the intervention group after 6 months (P=0.004). More participants in the intervention group than the control group had ceased smoking at the 6-month follow-up (P=0.055).\n A nurse-led systematic telephone follow-up intervention significantly improved the physical dimension of health-related quality of life in patients in the intervention group compared with usual care patients. Participation in this intervention also seemed to promote health behaviour change in patients after acute myocardial infarction.", "To determine whether a nurse led smoking cessation intervention affects smoking cessation rates in patients admitted for coronary heart disease.\n Randomised controlled trial.\n Cardiac ward of a general hospital, Norway.\n 240 smokers aged under 76 years admitted for myocardial infarction, unstable angina, or cardiac bypass surgery. 118 were randomly assigned to the intervention and 122 to usual care (control group).\n The intervention was based on a booklet and focused on fear arousal and prevention of relapses. The intervention was delivered by cardiac nurses without special training. The intervention was initiated in hospital, and the participants were contacted regularly for at least five months.\n Smoking cessation rates at 12 months determined by self report and biochemical verification.\n 12 months after admission to hospital, 57% (n = 57/100) of patients in the intervention group and 37% (n = 44/118) in the control group had quit smoking (absolute risk reduction 20%, 95% confidence interval 6% to 33%). The number needed to treat to get one additional person who would quit was 5 (95% confidence interval, 3 to 16). Assuming all dropouts relapsed at 12 months, the smoking cessation rates were 50% in the intervention group and 37% in the control group (absolute risk reduction 13%, 0% to 26%).\n A smoking cessation programme delivered by cardiac nurses without special training, significantly reduced smoking rates in patients 12 months after admission to hospital for coronary heart disease.", "To assess the effectiveness of health checks by nurses in reducing risk factors for cardiovascular disease in patients from general practice.\n Randomised controlled trial.\n Five urban general practices in Bedfordshire.\n 2136 patients receiving an initial health check in 1989-91 and scheduled to be re-examined one year later in 1990-2 (intervention group); 3988 patients receiving an initial health check in 1990-2 (control group). All patients were aged 35-64 years at recruitment in 1989.\n Serum total cholesterol concentration, blood pressure, body mass index, confirmed smoking cessation.\n Mean serum total cholesterol was 2.3% lower in the intervention group than in the controls (difference 0.14 mmol/l (95% confidence interval 0.08 to 0.20)); the difference was greater in women (3.2%, P < 0.0001) than men (1.0%, P = 0.18). There was no significant difference in smoking prevalence, quit rates, or body mass index. Systolic and diastolic blood pressure were 2.5% and 2.4% lower respectively in the intervention group. The proportion of patients with diastolic blood pressure > or = 100 mm Hg was 2.6% (55/2131) in the intervention group and 3.4% (137/3987) in the controls (difference 0.9% (0.0 to 1.7)); the proportion with total cholesterol concentration > or = 8 mmol/l 4.8% (100/2068) and 7.6% (295/3905) (difference 2.7% (1.5 to 4.0)); and that with body mass index > or = 30 12.4% (264/2125) and 14.0% (559/3984) (difference 1.6% (-0.2 to 3.4)).\n General health checks by nurses are ineffective in helping smokers to stop smoking, but they help patients to modify their diet and total cholesterol concentration. The public health importance of this dietary change depends on whether it is sustained.", "Public health and hospital nurses have widespread contact with smokers; an effective smoking cessation program administered by nurses has tremendous potential. This study evaluated: 1) the effectiveness of the self-help cessation program, \"Time to Quit\"/\"Moi aussi, j'écrase\" (TTQ), provided on a one-to-one basis; and 2) a smoking cessation training program for baccalaureate nursing students. Nursing students recruited 307 smokers who were randomly assigned to receive one of two interventions. Control smokers received a list of community smoking cessation resources and experimental subjects received this list plus TTQ. Smoking self-reports and cotinine levels were obtained at baseline, six weeks and nine months. More smokers receiving TTQ had reduced at six weeks post-intervention, while there were no differences in quit or reduction rates at the nine-month follow-up. Students were positive about learning the techniques and their knowledge scores were significantly higher than those of non-participating students.", "Although men hospitalized with cardiovascular disease (CVD) show high smoking-cessation rates, similar data for women are lacking. We tested the efficacy of smoking-cessation intervention in women hospitalized for CVD.\n In this randomized controlled trial conducted from 1996 to 2001, 277 women diagnosed with CVD (mean age 61+/-10 years) were randomly assigned within 1 of 12 San Francisco Bay Area hospitals to a usual-care group (UG; n=135) or intervention group (IG; n=142). Baseline histories were obtained, and interviews to ascertain self-reported smoking status occurred at 6, 12, 24, and 30 months after hospitalization. The UG received strong physician's advice, a self-help pamphlet, and a list of community resources. The IG received strong physician's advice and a nurse-managed cognitive behavioral relapse-prevention intervention at bedside, with telephone contact at intervals after discharge. The groups were similar demographically and had smoked cigarettes for a median of 38 (IG) or 40 (UG) years. Time to resumption of continuous smoking was assessed by Kaplan-Meier analysis, and risk differences between groups were determined. Time smoke-free was significantly greater for the IG than the UG (P=0.038). Point prevalence for nonsmoking at the interviews was somewhat greater for the IG than the UG (P>0.15 at all times).\n Cognitive behavioral intervention resulted in longer average times to resumption of smoking, but in these 2 groups of older women with limited social and financial resources, long-term success rates were similar. Systematic identification of smokers and even the brief intervention afforded the UG yielded a high smoking-cessation rate over time.", "Few studies have examined the effect of nicotine replacement therapy (NRT) in COPD patients.\n To evaluate the efficacy of nicotine sublingual tablets and two levels of support for smoking cessation in COPD patients.\n Double-blind, multicenter, placebo-controlled smoking cessation trial.\n Pulmonary outpatient clinics.\n Three hundred seventy COPD patients who smoked a mean of 19.6 cigarettes per day (mean, 42.7 pack-years; mean FEV(1), 56% of predicted).\n Nicotine sublingual tablet or placebo for 12 weeks combined with either low support (four visits plus six telephone calls) or high support (seven visits plus five telephone calls) provided by nurses.\n Carbon monoxide-verified abstinence rates and St. George Respiratory Questionnaire (SGRQ) assessed at 6 months and 12 months.\n Two hundred eighty-eight of 370 patients were evaluable for the final study end points. Smoking cessation rates were statistically significantly superior with sublingual nicotine vs placebo for all measures of abstinence: 6-month point prevalence, 23% vs 10%; 12-month point prevalence, 17% vs 10%. There was no significant difference in effect between low vs high behavioral support. The SGRQ score improved significantly in abstainers vs nonabstainers; the changes in mean scores were -10.9 vs - 2.9 for total score, and - 28.6 vs - 2.3 for symptom score, respectively.\n This trial demonstrated the long-term efficacy of NRT for cessation for the general population of COPD smokers, regardless of daily cigarette consumption. Cessation success rates were in the same range as in healthy smokers, and abstinence improved SGRQ scores. NRT should be used to aid cessation in all smokers with COPD, regardless of disease severity and number of cigarettes smoked.", "We examined the ability of a provider-initiated, minimal-contact intervention to modify the smoking behavior of ambulatory clinic patients. Smokers at two outpatient sites were assigned to one of three groups: provider intervention only (PI); provider intervention plus self-help manual (PI/M); and usual care (control) group (C). The physician message emphasized the patient's personal susceptibility, the physician's concern, and the patient's ability to quit (self-efficacy). The nurse consultation concentrated on benefits and barriers associated with stopping, and on strategies for cessation. Telephone interviews were conducted with the 250 participants within a few days of their clinic visit and again at one and six months. Both PI and PI/M proved to be superior to usual care in motivating attempts to quit at both one-month and six-month follow-ups, and logistic regression analyses indicated that participants receiving the self-help manual in addition to the health provider message were between two and three times more likely to quit smoking during the study period than were participants in either of the other study groups.", "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.", "To determine the effect of a nurse-managed intervention for smoking cessation in patients who have had a myocardial infarction.\n Randomized, with a 6-month treatment period and a 6-month follow-up.\n Kaiser Foundation hospitals in Redwood City, Santa Clara, Hayward, and San Jose, California.\n Sequential sample of 173 patients, 70 years of age or younger, who were smoking before hospitalization for acute myocardial infarction. Eighty-six patients were randomly assigned to the intervention and 87 to usual care; 130 patients (75%) completed the study and were available for follow-up.\n Nurse-managed and focused on preventing relapse to smoking, the intervention was initiated in the hospital and maintained thereafter primarily through telephone contact. Patients were given an 18-page manual that emphasized how to identify and cope with high-risk situations for smoking relapse.\n One year after myocardial infarction, the smoking cessation rate, verified biochemically, was 71% in the intervention group compared with 45% in the usual care group, a 26% difference (95% CI, 9.5% to 42.6%). Assuming that all surviving patients lost to follow-up were smoking, the 12-month smoking cessation rate was 61% in the intervention group compared with 32% in the usual care group, a 29% difference (95% CI, 14.5% to 43.5%). Patients who either resumed smoking within 3 weeks after infarction or expressed little intention of stopping in the hospital were unlikely to have stopped by 12 months.\n A nurse-managed smoking cessation intervention largely conducted by telephone, initiated in the hospital, and focused on relapse prevention can significantly reduce smoking rates at 12 months in patients who have had a myocardial infarction.", "Medical advice and use of nicotine gum have recently received increased attention as effective tools to encourage smokers to quit, yet the relative value of nurse vs physician counseling has not been explored in depth. In this study, 425 smokers attending three urban primary care centers in Barcelona were systematically allocated to one of three groups: group A patients received a brief counseling session to quit from their family physician; group B patients were given the same brief counseling along with a free supply of nicotine gum; group C received a brief health-education session from the primary care nurse. Three hundred forty-nine patients (82%) could be reached by telephone at the two-month follow up. By that time, after correcting for the estimated validity of the phone report of smoking status, the proportion declaring themselves to be nonsmokers was 10.9%, 11.1%, and 10.8%, respectively, without significant differences between them. At one-year follow up the proportions were 4.4%, 5.3%, and 6.0%. In the logistic regression analysis, only the expected difficulty of quitting was predictive of one-year abstention, OR = 3.1 (95% CI: 1.3-7.3). The present study shows no difference between physician versus nurse counseling and no improvement in the proportion of quitters with the addition of nicotine gum in the physician-counseled group.", "Does the provision of a nurse-based intervention lead to smoking cessation in hospital patients?\n At tertiary teaching hospital in Newcastle, Australia, 4,779 eligible (aged 18-80, admitted for at least 24 hours, and able to provide informed consent) and consenting (73.4%) in-patients were recruited into a larger cross-sectional survey. 1,422 (29.7%) smokers (in the last 12 months) were randomly assigned to control (n = 711) or intervention group (n = 711). The brief nurse-delivered intervention incorporated: tailored information, assessment of withdrawal, offer of nicotine replacement therapy, booklets, and a discharge letter. Self-reported cessation at 12 months was validated with CO and salivary cotinine.\n There were no significant differences between groups in self-reported abstinence at three or 12 months post intervention, based on an intention to treat analysis. At three months, self-reported abstinence was 27.3% (I) and 27.5% (C); at 12 months was 18.5% (I) and 20.6% (C). There were no differences in validation of self-report between intervention and control groups at 12 months.\n This brief nurse-provided in-patient intervention did not significantly increase the smoking cessation rates compared with the control group at either three or 12-month follow-up.\n A systematic total quality improvement model of accountable outcome-focused treatment, incorporating assertive physician-led pharmacotherapy, routine assessment and recording of nicotine dependence (ICD 10 coding), in- and outpatient services and engagement from multidisciplinary teams of health professionals may be required to improve treatment modalities for this chronic addictive disorder.", "Brief advice to stop smoking from general practitioners (GPs) has been repeatedly shown to increase smoking cessation by a small, but measurable amount. Some studies have suggested that adding more intensive interventions to brief advice may increase its effectiveness, but it is unclear whether this is true in general practice.\n To determine whether brief advice from a doctor together with counselling and follow-up from a trained practice nurse is more effective than brief advice alone in helping people to stop smoking.\n The design was a randomized controlled trial. Four hundred and ninety-seven general practice patients aged older than 18 years and smoking at least one cigarette per day in six general practices in Oxfordshire, Berkshire, and Buckinghamshire were randomized to one of two interventions: brief verbal or written advice from a GP plus extended counselling and follow-up from a trained practice nurse; brief advice from a GP alone. The primary outcome was sustained abstinence from smoking at three and 12 months. A secondary outcome was forward movement in the stages of change cycle.\n The proportion showing sustained abstinence was 3.6% in the extended counselling group, and 4.4% in the brief advice group (difference = -0.8%; 95% confidence interval = -4.3% to 2.6%). Seventy-four (30%) of those randomized to extended counselling actually took up this offer. No significant progression in stages of change was detected between the two groups.\n In unselected general practice patients who smoke, brief advice from a GP combined with intensive intervention and follow-up by a practice nurse is no more effective than brief advice alone.", "This study was undertaken to evaluate a tailored smoking cessation intervention, which is applicable to Korean culture, using the Agency for Health Care Policy and Research (AHCPR) guideline. On-site counselors provided brief nurse-assisted smoking cessation counseling, including follow-up telephone support, to prevent a relapse in 200 randomly assigned smoking patients. These patients were referred by their physicians regardless of their willingness in smoking cessation in the outpatient department at a university hospital. Nicotine replacement therapy was not provided. Another 201 patients served as a control. After 5 months, current smoking cessation was self-reported on the phone and validated later by a portable carbon monoxide analyzer. After 5 months, the participants in the intervention group were no more likely to quit smoking than the control group. A subgroup analysis by age showed that the intervention among 166 younger smokers (aged 49 or less) was significantly more likely to be effective {risk ratio = 5.76 [95% confidence interval (CI) 1.34-24.74]} than it was among 235 older smokers (aged 50 or more) [risk ratio = 1.03 (95% CI 0.53-1.99)]. This study suggests a smoking cessation intervention using the AHCPR guideline tailored for Koreans, is effective for assisting outpatients aged 49 or younger to quit smoking.", "Few research studies have evaluated the effectiveness of smoking interventions in hospitalized patients. This randomized controlled trial compared the efficacy of 2 smoking cessation programs in patients hospitalized in 4 community hospitals in a large health maintenance organization within the San Francisco Bay Area in California.\n Patients were randomly assigned to usual care (n = 990), nurse-mediated, behaviorally oriented inpatient counseling focused on relapse prevention with 1 postdischarge telephone contact (minimal intervention, n = 473), or the same inpatient counseling with 4 postdischarge telephone contacts (intensive intervention, n = 561). The main outcome measure, smoking cessation rate, was corroborated by plasma cotinine determination or family confirmation, 1 year after enrollment.\n At 1 year smoking cessation rates were 27%, 22%, and 20% for intensive intervention, minimal intervention, and usual care groups, respectively (P = .009 for intensive vs usual care). Subgroup analyses by diagnosis revealed that the odds of cessation among patients with cardiovascular disease or other internal medical conditions were greater among those receiving the intensive intervention than among their counterparts receiving usual care (odds ratios, 1.6 and 2.0, respectively).\n A multicomponent smoking cessation program consisting of physician advice; in-hospital, nurse-mediated counseling; and multiple postdischarge telephone contacts was effective in increasing smoking cessation rates among hospitalized smokers. Hospital-wide smoking cessation programs could substantially increase the effectiveness of hospital smoking bans.", "Smokers are often advised to quit in a discussion of future health risks. The authors tested whether adding information about personal effects of smoking would motivate hospital outpatients to stop smoking more than advice about potential hazards would. Ninety smokers in a general screening clinic were randomized to receive education alone or education plus an additional motivational intervention that contained immediate feedback about the smoker's exhaled carbon monoxide (CO) values, spirometry results, and pulmonary symptoms. A self-report of smoking status was obtained one, four, and 12 months after the intervention. In addition, at 12 months, exhaled CO measurements were made. Smokers who received the additional motivational intervention were more than twice as likely to report quitting some time during the 12-month follow-up (40% vs. 16%, p = 0.015). At 12 months, 33% of the intervention group and 10% of the control group smokers tested had achieved CO-validated cessation (p = 0.03). Counting all patients not contacted as continuing to smoke, the percentages were 20% vs. 7% (p = 0.06). These practical feedback methods to motivate cessation deserve testing in other settings.", "To examine the ability of a secondary prevention programme to improve the lifestyle in myocardial infarction patients aged 50-70 years.\n Habitual physical activity, food habits, and smoking habits were assessed from questionnaires at admission to hospital and at the one year follow up. Initially, all patients were invited to join an exercise programme and were informed about cardiovascular risk factors. Four weeks after discharge from the hospital, 87 patients were randomised to follow up at the coronary prevention unit by a special trained nurse (the intervention group), and 81 to follow up by their general practitioners (the usual care group). After randomisation, the intervention group was educated about the effects of smoking cessation, dietary management, and regular physical activity. The intervention group also participated in a physical training programme two to three times weekly for 10-12 weeks.\n 89% of the patients referred to the intervention group improved their food habits compared with 62% of the patients referred to the usual care group (P = 0.008). Furthermore, 50% of the smokers referred to the intervention group stopped smoking compared to 29% in the usual care group (P = 0.09). Changes in physical activity did not differ between the groups.\n This secondary prevention programme based on a nurse rehabilitator was successful in improving food habits in patients with acute myocardial infarction. Initiating the smoking cessation programme during the hospital stay followed by repeated counselling during follow up might have improved the results. The exercise programme had no advantage in supporting physical activity compared to usual care.", "In a trial to evaluate the effectiveness of a nurse-directed intervention designed to help patients decrease dietary intake of fat, quit or decrease smoking, and increase exercise, 138 women who underwent coronary artery bypass surgery were randomized to receive special intervention (SI) or usual care (UC). The SI group received a behavioral program based on self-efficacy theory in the home 2 weeks after discharge with regular follow-up. The UC group received routine medical care. Risk factors and lifestyle behaviors were measured at baseline and 1 year after surgery in 116 (84%) women (SI = 59, UC = 57). The SI group decreased their total fat intake from a mean of 38% of calories at baseline to 35% at 1 year, while the UC group increased it from 36% to 38%. The prevalence of smoking decreased from 24% at baseline to 8% at 1 year in the SI group and from 19% to 14% in the UC group. At follow-up, the quit rate in those smoking at baseline was 64% in the SI group, with no new smokers, and 55% in the UC group, with three new smokers. Both groups reported improvement in exercise, with the proportion of women reporting participation in some form of regular exercise slightly higher in the SI group than in the UC group, 54% and 51%, respectively.", "Clinical guidelines for smoking cessation may not be sufficient for helping some subgroups of smokers quit. Incorporating smoking cessation into home-based medical care can proactively reach high-risk smokers who may not have access to (or spontaneously seek) smoking cessation.\n Home health care nurses (N = 98) were randomly assigned to deliver either Motivational Enhancement (ME; Motivational Interviewing + Carbon Monoxide Feedback) or Standard Care (AHCPR Guidelines for smoking cessation) to their patients. Seventy percent of patients were eligible and willing to participate (N = 273; 54% female, mean age = 57 years, 83% Caucasian, 41% < high school education). The study was conducted in Providence, RI, USA from 1998 to 2003.\n Biochemically verified continuous abstinence rates at the 12-month follow-up were 4.2% (SC) and 8.7% (ME) for intent to treat analyses, and 5.2% (SC) and 11.8% (ME) using all available cases (P > 0.05). ME reported more quit attempts and significantly greater reductions in the number of cigarettes smoked per day at all follow-ups through 12 months of post-treatment (all P values < 0.05).\n Use of an existing public health channel such as home health care to reach smokers who vary in their motivation to quit could have the potential for large public health impact.", "This study was undertaken to assess the safety and efficacy of a treatment involving brief counseling and the nicotine patch among hospital inpatients and to identify variables associated with long-term smoking cessation following hospitalization.\n One hundred eighty-five patients were randomly assigned to one of three smoking cessation interventions: (1) A Minimal Care (MC) condition, consisting of a brief physician-delivered motivational message to stop smoking, (2) a Counseling + Active Nicotine Patch (CAP) condition in which patients received the motivational message, a 6-week supply of nicotine patches, and extended bedside and telephone counseling, and (3) a Counseling + Placebo Patch (CPP) condition identical to the CAP condition except the supplied patches contained no nicotine.\n At 6-month follow-up, abstinence rates for the three treatments were 4.9, 6.5, and 9.7% for the MC, CPP, and CAP treatments, respectively. These differences were not statistically significant. Patients admitted for respiratory disease were more likely to quit than patients with any other diagnosis. The nicotine patch was well tolerated by hospital inpatients.\n The initiation of nicotine patch therapy during hospitalization appears to be safe when used among patients carrying a wide range of diagnoses. Our study provided no evidence of the superiority of nicotine patches versus placebo, but this does not preclude the possibility that future research using larger samples might detect differences between patch groups. Hospital interventions for smoking cessation may be most effective among patients hospitalized for a smoking-related illness such as respiratory disease.", "This study evaluated the effectiveness of three smoking cessation interventions for this population: (1) modified usual care (UC); (2) brief advice (A); and (3) brief advice plus more extended counseling during and after hospitalization (A + C).\n Smokers (2,095) who were in-patients in four hospitals were randomly assigned to condition. Smoking status was ascertained via phone interview 7 days and 12 months post-discharge. At 12 months, reports of abstinence were validated by analysis of saliva cotinine. Intent to treat analyses were performed.\n At 7-day follow-up, 24.2% of participants reported abstinence in the previous 7 days. There were no differences between conditions. At 12-month follow-up, self-reported abstinence was significantly higher in the A + C condition (UC (15.0%) vs. A (15.2%) vs. A + C (19.8%)). There was no significant difference among conditions in cotinine-validated abstinence, however (UC (8.8%) vs. A (10.0%) vs. A + C (9.9%)).\n These interventions for hospital in-patients did not increase abstinence rates. Features of the study that might have contributed to this finding were the inclusiveness of the participation criteria, the fact that pharmacological aids were not provided, and a stage-matching approach that resulted in less intensive counseling for participants unwilling to set a quit date.", "To evaluate whether nurse run clinics in general practice improve secondary prevention in patients with coronary heart disease.\n Randomised controlled trial.\n A random sample of 19 general practices in northeast Scotland.\n 1173 patients (685 men and 488 women) under 80 years with working diagnoses of coronary heart disease, but without terminal illness or dementia and not housebound.\n Nurse run clinics promoted medical and lifestyle aspects of secondary prevention and offered regular follow up.\n Components of secondary prevention assessed at baseline and one year were: aspirin use; blood pressure management; lipid management; physical activity; dietary fat; and smoking status. A cumulative score was generated by counting the number of appropriate components of secondary prevention for each patient.\n There were significant improvements in aspirin management (odds ratio 3.22, 95% confidence interval 2.15 to 4.80), blood pressure management (5.32, 3.01 to 9.41), lipid management (3.19, 2.39 to 4.26), physical activity (1.67, 1.23 to 2.26) and diet (1.47, 1.10 to 1.96). There was no effect on smoking cessation (0.78, 0.47 to 1.28). Of six possible components of secondary prevention, the baseline mean was 3.27. The adjusted mean improvement attributable to intervention was 0.55 of a component (0.44 to 0.67). Improvement was found regardless of practice baseline performance.\n Nurse run clinics proved practical to implement in general practice and effectively increased secondary prevention in coronary heart disease. Most patients gained at least one effective component of secondary prevention and, for them, future cardiovascular events and mortality could be reduced by up to a third.", "This study aimed to evaluate the effect of a motivational, minimal intervention approach to smoking cessation in an open, randomized design conducted by nurses as routine work in a lung clinic. Subjects who smoked less than 10 cigarettes x day(-1), and subjects who smoked > or = 10 cigarettes x day(-1) and who had refused to participate in a smoking cessation trial with nicotine replacement therapy, were randomly allocated to a motivational approach to smoking cessation or to a control group. The motivational approach consisted of a nurse-conducted 5 min consultation concerning reasons to quit smoking, brochures about smoking cessation and advice about how to quit. After 4-6 weeks, subjects in the motivational group received a letter encouraging them to quit smoking. After 1 year, all subjects were contacted by phone and smoking status reported. Subjects claiming to be abstinent attended the clinic for carbon monoxide verification. A total of 507 subjects were enrolled, 254 in the motivational group and 253 in the control group. The mean age of the motivational group was 51 yrs, 50% were males and they smoked a mean of 13 cigarettes x day(-1). The mean age of the control group was 53 yrs, 61% were males and they smoked a mean of 12 cigarettes x day(-1). At the 1 year follow-up, the success rate for point prevalence (no smoking at 1 year and during the preceding month) was 8, 7% in the motivational group versus 3.6% in the control group (p=0.025). The 12 months sustained success rate (no smoking at all during the year) was 3.1 versus 1.2% (p=0.22). The point prevalence for light smokers (<10 cigarettes x day(-1)) was 13.9% in the motivational group versus 6.3% in control group (p=0.12), and for heavy smokers (10 or more cigarettes x day(-1)) 5.2% versus 1.9% (p=0.20). In conclusion, the effect of this nurse-conducted, minimal intervention, motivational approach seems promising as the quit rate at 1 year follow-up had doubled.", "Tobacco cessation after acute myocardial infarction (AMI) substantially improves outcome but how effective individual programmes are needs to be established. To date, few studies have examined this factor.\n To assess the outcome of two smoking cessation programmes after AMI.\n One hundred and ninety-eight current smokers admitted to coronary care with an AMI participated in a randomized controlled study comparing two outpatient tobacco interventions, the Stanford Heart Attack Staying Free (SF) programme and a Usual Care (UC) programme.\n Log-rank analyses revealed that patients in the SF programme were retained longer (P < 0.001) and had higher cotinine validated abstinence rates (P < 0.001) compared with patients in the UC programme. Twelve months after intervention, 39% of the SF programme compared with 2% of the UC programme demonstrated cotinine validated tobacco cessation, representing a significant reduced relapse rate in the SF programme (chi2, P< 0.001).\n The SF smoking cessation programme initiated in hospital can significantly reduce smoking rates at 12 months after myocardial infarction. Although superior to the UC quit programme, Australian outcomes were lower than the American programme originators' published outcomes.", "This study examined the 1-year effects of a minimal-contact smoking cessation intervention for cardiac inpatients.\n The multicenter study included cardiac inpatients who had smoked prior to hospitalization. A pretest-posttest quasi-experimental design was used. Patients' experimental condition depended on the hospital they were assigned to. The design was partially randomized: 4 of the 11 hospitals selected the experimental condition themselves (2 experimental, 2 control), while the remaining 7 hospitals were randomly assigned. The experimental group consisted of patients of 5 hospitals (N = 388). Patients of 6 other hospitals served as the control group (N = 401). The intervention included stop-smoking advice by the cardiologist, brief counseling by the nurse, the provision of self-help materials, and aftercare by the cardiologist.\n Logistic regression analyses controlling for baseline differences and covariates did not show significant intervention effects on point prevalence and continuous abstinence. The study also showed that the outcomes were not significantly related to the way hospitals were assigned to the experimental condition.\n While short-term effects were found, the minimal-contact intervention did not result in significant effects after 12 months, at least if patients lost to follow-up were treated as posttest smokers. Efforts should be made to improve the intervention, especially the aftercare.", "To evaluate a smoking cessation intervention that can be routinely delivered to smokers admitted with cardiac problems.\n Randomised controlled trial of usual care compared with intervention delivered on hospital wards by cardiac rehabilitation nurses.\n Inpatient wards in 17 hospitals in England.\n 540 smokers admitted to hospital after myocardial infarction or for cardiac bypass surgery who expressed interest in stopping smoking.\n Brief verbal advice and standard booklet (usual care). Intervention lasting 20-30 minutes including carbon monoxide reading, special booklet, quiz, contact with other people giving up, declaration of commitment to give up, sticker in patient's notes (intervention group).\n Continuous abstinence at six weeks and 12 months determined by self report and by biochemical validation at these end points. Feasibility of the intervention and delivery of its components.\n After six weeks 151 (59%) and 159 (60%) patients remained abstinent in the control and intervention group, respectively (P=0.84). After 12 months the figures were 102 (41%) and 94 (37%) (P=0.40). Recruitment was slow, and delivery of the intervention was inconsistent, raising concerns about the feasibility of the intervention within routine care. Patients who received the declaration of commitment component were almost twice as likely to remain abstinent than those who did not receive it (P<0.01). Low dependence on tobacco and high motivation to give up were the main independent predictors of positive outcome. Patients who had had bypass surgery were over twice as likely to return to smoking as patients who had had a myocardial infarction.\n Single session interventions delivered within routine care may have insufficient power to influence highly dependent smokers.", "To determine the effectiveness of a systematic intensive tobacco counselling programme conducted by nursing professionals.\n Randomised clinical trial with control.\n Primary care nursing and medical consultations.\n Smokers requesting help in our centre's medical clinics during the recruitment period, up to the sample size required (125). Inclusion criteria were: aged between 18 and 70, people who smoked during the preceding month any number of cigarettes a day, and a score over 7 on the Richmond test.\n The patients recruited were randomised, according to the clinic from which they came, to the group that received brief counselling from the doctor (control group) or to the group that received brief counselling plus nursing follow-up (intervention group). Follow-up visits were programmed in this latter group for up to 3 months after giving up smoking.\n Abstinence at 12 and 24 months.\n The effectiveness of the intervention considered as the rate of abstinence at 12 months was 13.8% (95% CI, 6.5-24.7) in the control group and 6.7% (95% CI, 1.8-16.2) in the intervention group, with no significant differences between the two.\n In smokers seen in primary care, the effectiveness of a programme of intensive tobacco counselling by nursing staff is no more effective than the doctor's brief, one-off counselling. Brief counselling has a better cost-effectiveness relationship than intensive counselling.", "To evaluate the effectiveness of a nurse-managed smoking cessation intervention in diabetic patients.\n This randomized controlled clinical trial involved 280 diabetic smokers (age range 17-84 years) who were randomized either into control (n = 133) or intervention (n = 147) groups at 12 primary care centers and 2 hospitals located in Navarre, Spain. The intervention consisted of a 40-min nurse visit that included counseling, education, and contracting information (a negotiated cessation date). The follow-up consisted of telephone calls, letters, and visits. The control group received the usual care for diabetic smokers. Baseline and 6-month follow-up measurements included smoking status (self-reported cessation was verified by urine cotinine concentrations), mean number of cigarettes smoked per day, and stage of change.\n At the 6-month follow-up, the smoking cessation incidence was 17.0% in the intervention group compared with 2.3% in the usual care group, which was a 14.7% difference (95% CI 8.2-21.3%). Among participants who continued smoking, a significant reduction was evident in the average cigarette consumption at the 6-month follow-up. The mean number of cigarettes per day decreased from 20.0 at baseline to 15.5 at 6 months for the experimental group versus from 19.7 to 18.1 for the control group (P < 0.01).\n A structured intervention managed by a single nurse was shown to be effective in changing the smoking behavior of diabetic patients.", "Practice nurses are playing an increasingly prominent role in preventive care, including the provision of anti-smoking advice during routine health checks. A randomized controlled trial was designed to assess the effectiveness of anti-smoking advice provided by nurses in helping smokers to stop smoking. A total of 14,830 patients aged 16-65 years from 11 general practices completed a brief questionnaire on general health, including smoking status, at surgery attendance. The doctor identified 4330 smokers and randomly allocated 4210 to control or intervention groups. The doctor asked those in the intervention group to make an appointment with the practice nurse for a health check. The attendance rate at the health check was 26%. Smokers were sent follow-up questionnaires at one month and one year, and those who did not respond to two reminders were assumed to have continued to smoke. There was no significant difference in reported cessation between the intervention and control groups at one month or one year. However, there was a significant difference in the proportion of patients who reported giving up within one month and who had not lapsed by one year--0.9% in controls and 3.6% in the intervention group (P less than 0.01). Nevertheless, the effect of the nurse intervention itself may be small as the sustained cessation rate in attenders was only 42.4% higher than in non-attenders. The deception rate in reporting cessation, as measured by urinary cotinine, was of the order of 25%.", "Continued high rates of smoking among socioeconomically disadvantaged women lead to increases in children's health problems associated with exposure to tobacco smoke. The pediatric clinic is a \"teachable setting\" in which to provide advice and assistance to parents who smoke.\n To evaluate a smoking cessation intervention for women.\n Two-arm (usual care vs intervention) randomized trial.\n Pediatric clinics serving an ethnically diverse population of low-income families in the greater Seattle, Wash, area.\n During the clinic visit, women received a motivational message from the child's clinician, a guide to quitting smoking, and a 10-minute motivational interview with a nurse or study interventionist. Women received as many as 3 outreach telephone counseling calls from the clinic nurse or interventionist in the 3 months following the visit.\n Self-identified women smokers (n = 303) whose children received care at participating clinics.\n Self-reported abstinence from smoking 12 months after enrollment in the study, defined as not smoking, even a puff, during the 7 days prior to assessment.\n Response rates at 3 and 12 months were 80% and 81%. At both follow-ups, abstinence rates were twice as great in the intervention group as in the control group (7.7% vs 3.4% and 13.5% vs 6.9%, respectively). The 12-month difference was statistically significant.\n A pediatric clinic smoking cessation intervention has long-term effects in a socioeconomically disadvantaged sample of women smokers. The results encourage implementation of evidence-based clinical guidelines for smoking cessation in pediatric practice.", "Chronic Obstructive Pulmonary Disease (COPD) forms an increasing health problem. Despite smoking cessation improving the prognosis of the disease, many patients persist smoking. The present study presents the results of a smoking cessation counseling protocol in general practice (Smoking Cessation in patients with COPD in general practice (SMOCC)).\n A randomized controlled trial of patients with COPD compared smoking cessation counseling according to an intensified minimal intervention strategy with usual care. In total 43 general practices with 392 patients participated in Nijmegen, The Netherlands, in 2001-2002.\n Significantly more smokers in the experimental group made a quit attempt (44.9% versus 36.5%) and actually quit smoking than in the control group (16.0% versus 8.8%). The motivation to stop smoking at baseline was not associated with smoking cessation.\n The SMOCC strategy doubled the self-reported quit rates and was complied well by the general practitioners. Implementation in general practice is recommended.", "This study aimed to test the hypothesis that people aged 60 and older respond to assistance in stopping smoking. Using a single general practitioner visit backed up by a practice nurse, 14% of the smokers had discontinued the habit 6 months after the intervention period. The intervention group also showed some improvements in a standardized measure of breathlessness." ]

[ "19318534", "21371991", "16046689", "21722952" ]

[ "Txt2stop: a pilot randomised controlled trial of mobile phone-based smoking cessation support.", "A theory-based video messaging mobile phone intervention for smoking cessation: randomized controlled trial.", "Do u smoke after txt? Results of a randomised trial of smoking cessation using mobile phone text messaging.", "Smoking cessation support delivered via mobile phone text messaging (txt2stop): a single-blind, randomised trial." ]

[ "To conduct a pilot randomised controlled trial of mobile phone-based smoking cessation support intervention for the UK population.\n Randomised controlled trial (txt2stop).\n Community.\n 200 participants responding to radio, poster and leaflet-based promotions regarding the trial.\n The response rate for the outcome measures planned for the main trial. Participants' qualitative responses to open-ended questions about the intervention content. Secondary outcomes were the outcomes planned for the main trial including the point prevalence of self-reported smoking at 4 weeks and pooled effect estimate for the short-term results for the STOMP and txt2stop trials.\n The response rate at 4 weeks was 96% and at 6 months was 92%. The results at 4 weeks show a doubling of self-reported quitting relative risk (RR) 2.08 (95% CI 1.11 to 3.89), 26% vs 12%. The pooled effect estimate combining txt2stop and a previous New Zealand trial in the short term is RR 2.18 (95% CI 1.79 to 2.65).\n Mobile phone-based smoking cessation is an innovative means of delivering smoking cessation support, which doubles the self-reported quit rate in the short term. It could represent an important, but as yet largely unused, medium to deliver age-appropriate public health measures. The long-term effect of this mobile phone-based smoking cessation support will be established by a large randomised controlled trial currently in recruitment.", "Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones. This social cognitive theory-based intervention (called \"STUB IT\") used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques.\n The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation.\n A randomized controlled trial was conducted with 6-month follow-up. Participants had to be 16 years of age or over, be current daily smokers, be ready to quit, and have a video message-capable phone. Recruitment targeted younger adults predominantly through radio and online advertising. Registration and data collection were completed online, prompted by text messages. The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date, role model, and timing of messages. Extra messages were available on demand to beat cravings and address lapses. The control group also set a quit date and received a general health video message sent to their phone every 2 weeks.\n The target sample size was not achieved due to difficulty recruiting young adult quitters. Of the 226 randomized participants, 47% (107/226) were female and 24% (54/226) were Maori (indigenous population of New Zealand). Their mean age was 27 years (SD 8.7), and there was a high level of nicotine addiction. Continuous abstinence at 6 months was 26.4% (29/110) in the intervention group and 27.6% (32/116) in the control group (P = .8). Feedback from participants indicated that the support provided by the video role models was important and appreciated.\n This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone. However, there was sufficient positive feedback about the ease of use of this novel intervention, and the support obtained by observing the role model video messages, to warrant further investigation.\n Australian New Zealand Clinical Trials Registry Number: ACTRN12606000476538; http://www.anzctr.org.au/trial_view.aspx?ID=81688 (Archived by WebCite at http://www.webcitation.org/5umMU4sZi).", "To determine the effectiveness of a mobile phone text messaging smoking cessation programme.\n Randomised controlled trial\n New Zealand\n 1705 smokers from throughout New Zealand who wanted to quit, were aged over 15 years, and owned a mobile phone were randomised to an intervention group that received regular, personalised text messages providing smoking cessation advice, support, and distraction, or to a control group. All participants received a free month of text messaging; starting for the intervention group on their quit day to assist with quitting, and starting for the control group at six months to encourage follow up. Follow up data were available for 1624 (95%) at six weeks and 1265 (74%) at six months.\n The main trial outcome was current non-smoking (that is, not smoking in the past week) six weeks after randomisation. Secondary outcomes included current non-smoking at 12 and 26 weeks.\n More participants had quit at six weeks in the intervention compared to the control group: 239 (28%) v 109 (13%), relative risk 2.20 (95% confidence interval 1.79 to 2.70), p < 0.0001. This treatment effect was consistent across subgroups defined by age, sex, income level, or geographic location (p homogeneity > 0.2). The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests. Reported quit rates remained high at six months, but there was some uncertainty about between group differences because of incomplete follow up.\n This programme offers potential for a new way to help young smokers to quit, being affordable, personalised, age appropriate, and not location dependent. Future research should test these findings in different settings, and provide further assessment of long term quit rates.", "Smoking cessation programmes delivered via mobile phone text messaging show increases in self-reported quitting in the short term. We assessed the effect of an automated smoking cessation programme delivered via mobile phone text messaging on continuous abstinence, which was biochemically verified at 6 months.\n In this single-blind, randomised trial, undertaken in the UK, smokers willing to make a quit attempt were randomly allocated, using an independent telephone randomisation system, to a mobile phone text messaging smoking cessation programme (txt2stop), comprising motivational messages and behavioural-change support, or to a control group that received text messages unrelated to quitting. The system automatically generated intervention or control group texts according to the allocation. Outcome assessors were masked to treatment allocation. The primary outcome was self-reported continuous smoking abstinence, biochemically verified at 6 months. All analyses were by intention to treat. This study is registered, number ISRCTN 80978588.\n We assessed 11,914 participants for eligibility. 5800 participants were randomised, of whom 2915 smokers were allocated to the txt2stop intervention and 2885 were allocated to the control group; eight were excluded because they were randomised more than once. Primary outcome data were available for 5524 (95%) participants. Biochemically verified continuous abstinence at 6 months was significantly increased in the txt2stop group (10·7% txt2stop vs 4·9% control, relative risk [RR] 2·20, 95% CI 1·80-2·68; p<0·0001). Similar results were obtained when participants that were lost to follow-up were treated as smokers (268 [9%] of 2911 txt2stop vs 124 [4%] of 2881 control [RR 2·14, 95% CI 1·74-2·63; p<0·0001]), and when they were excluded (268 [10%] of 2735 txt2stop vs 124 [4%] of 2789 control [2·20, 1·79-2·71; p<0·0001]). No significant heterogeneity was shown in any of the prespecified subgroups.\n The txt2stop smoking cessation programme significantly improved smoking cessation rates at 6 months and should be considered for inclusion in smoking cessation services.\n UK Medical Research Council, Primary Care Research Networks.\n Copyright © 2011 Elsevier Ltd. All rights reserved." ]

[ "3944680", "8517902", "375178", "3312553", "9329410", "7472106" ]

[ "Continuous versus intermittent heparin infusion of umbilical artery catheters in the newborn infant.", "Effect of adding heparin in very low concentration to the infusate to prolong the patency of umbilical artery catheters.", "Effect of heparinization of fluids infused through an umbilical artery catheter on catheter patency and frequency of complications.", "Effect of heparin infusates in umbilical arterial catheters on frequency of thrombotic complications.", "Heparin and the risk of intraventricular hemorrhage in premature infants.", "Prevention of umbilical artery catheter clots with heparinized infusates." ]

[ "nan", "A randomized controlled study was done to determine whether the addition of heparin, in very low concentration (0.25 U/ml), to fluids administered through an umbilical artery catheter (UAC) would affect the duration of catheter patency. UAC occlusion occurred in 2 of 15 patients in the heparin group and in 11 of 15 patients in the control group (p = 0.001). Using life-table analysis, the functional life span of UAC was estimated. On day 8, 100% of UACs in heparin group and 9% of UACs in control group were patent (p < 0.05). Coagulation profile remained unaltered after addition of heparin compared with that before the start of the therapy. There was no difference in the incidence of subependymal intraventricular hemorrhage between the two groups. It is concluded that heparin in such low concentration is effective in prolonging duration of UAC patency without causing adverse effects.", "Heparinization of fluids (1 unit/ml) infused through an umbilical artery catheter (UAC) was efficacious in prolonging catheter patency in a double-blind, randomized, controlled clinical study. On the basis of life-table analysis, the half-life of catheter function was seven days in the heparinized group as compared with just over two days in the nonheparinized group (P less than .01). UAC occlusion occurred in 4 of 32 patients in the heparinized and 19 of 30 in the nonheparinized group (chi 2 = 17.6, P less than .01). Blood transfusions, number of arterial blood gases drawn through the UACs, and fluid infusion rates were not related to catheter occlusion. Heparinization of the UAC infusion did not alter the partial thromboplastin time or the incidence of catheter-related thromboembolic phenomena in the extremities. Heparinization of fluids infused through a UAC appears to be useful in the care of critically ill neonates.", "We studied 111 infants requiring an umbilical artery catheter, 59 with heparin and 52 without. Thirty-four thrombi were detected, 16 in the heparin group and 18 in the control group. The numbers of thrombi in the two groups was not significantly different, but the number of clotted or nonfunctioning umbilical artery catheters was greater in the control group (P less than 0.05), as was the incidence of hypertension (P less than 0.05). There were no other significant differences between the two groups. We conclude that the use of low doses of heparin may not change the incidence of umbilical artery catheter-related thrombi, but it does appear to lower the incidence of their sequelae.", "This study was carried out to determine whether the routine use of low-dose heparin in umbilical catheter infusates increases the risk of intraventricular hemorrhage or alters the coagulation profile in premature infants.\n In a randomized, blinded trial, 113 infants born at less than 31 weeks' gestation were assigned to receive, in their umbilical catheter infusate, either 1 unit of heparin per milliliter (n = 55) or no heparin (n = 58). Prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and antithrombin III activity levels were determined at the start and the completion of the study. Cranial ultrasonography was performed during the first week of life.\n There was no difference in the incidence of intraventricular hemorrhage between the heparin and no heparin groups, 35.8% and 31.5%, respectively (p = 0.6). Similarly, no difference was detected in the incidence of severe intraventricular hemorrhage (grades III/IV). Prothrombin time, activated partial thromboplastin time, and fibrinogen levels were not significantly different between the two groups. However, the use of heparin was associated with a lower antithrombin III activity level. Antenatal indomethacin use was associated with a 2.9 increased risk of intraventricular hemorrhage (95% confidence interval, 1.15 to 7.17).\n A low dose of heparin added to umbilical catheter infusates does not increase the incidence or severity of intraventricular hemorrhage or significantly alter the coagulation profile in premature infants.", "49 neonates requiring umbilical artery catheters (UACs) were randomly assigned to receive standard or heparin-containing infusates. 3 of 23 (13%) of the patients receiving heparin had catheters removed because they became functionally occluded compared to 15 of 26 (58%) in the control group (p less than 0.005). 4 of 13 (31%) single injection aortograms obtained in control infants demonstrated thrombi, compared to none of 7 in the heparin group. 1 patient in the heparin group had an aortic clot demonstrated at post-mortum examination. There were neither clinical coagulopathies nor abnormalities of partial thromboplastin time attributable to the administration of heparinized fluids. Heparinization of UAC infusates appears to be a safe method of reducing the risk of catheter occlusion. Heparin effect on large vessel clot risk remains unproven." ]

[ "17244293" ]

[ "Effects of Cash and Counseling on personal care and well-being." ]

[ "To examine how a new model of consumer-directed care changes the way that consumers with disabilities meet their personal care needs and, in turn, affects their well-being.\n Eligible Medicaid beneficiaries in Arkansas, Florida, and New Jersey volunteered to participate in the demonstration and were randomly assigned to receive an allowance and direct their own Medicaid supportive services as Cash and Counseling consumers (the treatment group) or to rely on Medicaid services as usual (the control group). The demonstration included elderly and non-elderly adults in all three states and children in Florida.\n Telephone interviews administered 9 months after random assignment.\n Outcomes for the treatment and control group were compared, using regression analysis to control for consumers' baseline characteristics.\n Treatment group members were more likely to receive paid care, had greater satisfaction with their care, and had fewer unmet needs than control group members in nearly every state and age group. However, among the elderly in Florida, Cash and Counseling had little effect on these outcomes because so few treatment group members actually received the allowance. Within each state and age group, consumers were not more susceptible to adverse health outcomes or injuries under Cash and Counseling.\n Cash and Counseling substantially improves the lives of Medicaid beneficiaries of all ages if consumers actually receive the allowance that the program offers." ]

[ "9854760", "10493473", "1830257", "9637578", "16281998", "12764513", "17040926", "3964314", "15883575", "16859871", "15191260", "10413387", "3772925", "17325405", "14639082" ]

[ "A randomized trial of a lay person-led self-management group intervention for back pain patients in primary care.", "Community-based Spanish language arthritis education program: a randomized trial.", "Randomized controlled multicentre evaluation of an education programme for insulin-treated diabetic patients: effects on metabolic control, quality of life, and costs of therapy.", "Pilot randomized trial of education to improve self-management skills of men with symptomatic HIV/AIDS.", "Randomised controlled trial of a lay-led self-management programme for Bangladeshi patients with chronic disease.", "Implementation and quantitative evaluation of chronic disease self-management programme in Shanghai, China: randomized controlled trial.", "Self management of arthritis in primary care: randomised controlled trial.", "Evaluation of arthritis self-management courses led by laypersons and by professionals.", "Chronic disease self-management program for low back pain in the elderly.", "A randomised control trial of a self-management program for people with a chronic illness from Vietnamese, Chinese, Italian and Greek backgrounds.", "Is individual peer support a promising intervention for persons with heart failure?", "Evidence suggesting that a chronic disease self-management program can improve health status while reducing hospitalization: a randomized trial.", "A comparison of lay-taught and professional-taught arthritis self-management courses.", "The effectiveness and cost effectiveness of a national lay-led self care support programme for patients with long-term conditions: a pragmatic randomised controlled trial.", "Hispanic chronic disease self-management: a randomized community-based outcome trial." ]

[ "Randomized, controlled trial.\n To evaluate a four-session self-management group intervention for patients with pain in primary care, led by trained lay persons with back pain. The intervention was designed to reduce patient worries, encourage self-care, and reduce activity limitations.\n Randomized trials of educational interventions suggest that activating interventions may improve back pain outcomes. Expert opinion increasingly regards effective self-management of back pain as important in achieving good outcomes. In this study, an educational intervention designed to activate patients and support effective self-management was evaluated.\n Six to 8 weeks after a primary care visit for back pain, patients were invited to participate in an educational program to improve back pain self-management. Those showing interest by returning a brief questionnaire became eligible for the study. Participants (n = 255) randomly were assigned to either a self-management group intervention or to a usual care control group. The effect of the intervention, relative to usual care, was assessed 3, 6, and 12 months after randomization, controlling for baseline values. The intervention consisted of a four-session group applying problem-solving techniques to back pain self-management, supplemented by educational materials (book and videos) supporting active management of back pain. The groups were led by lay persons trained to implement a fully structured group protocol. The control group received usual care, supplemented by a book on back pain care.\n Participants randomly assigned to the self-management groups reported significantly less worry about back pain and expressed more confidence in self-care. Roland Disability Questionnaire Scores were significantly lower among participants in the self-management groups relative to the usual care controls at 6 months (P = 0.007), and this difference was sustained at 12 months at borderline significance levels (P = 0.09). Among self-management group participants, 48% showed a 50% or greater reduction in Roland Disability Questionnaire Score at 6 months, compared with 33% among the usual care controls.\n Self-management groups led by trained lay persons following a structured protocol were more effective than usual care in reducing worries, producing positive attitudes toward self-care, and reducing activity limitations among patients with back pain in primary care.", "To determine 4-month and 1-year health-related outcomes of a 6-week, lay-led, and community-based arthritis self-management program for Spanish-speaking participants and to determine the role of self-efficacy in predicting health status for this population.\n Three hundred and thirty one subjects were randomized to the program or to a 4-month wait list control group. One hundred ninety eight subjects continued in a 1-year longitudinal study. Data were collected via mailed questionnaires with telephone follow up.\n At 4 months, treatment subjects, compared with controls, demonstrated positive changes in exercise, disability, pain, and self-efficacy (P < 0.05). At 1 year, compared with baseline, treatment subjects demonstrated improvements in exercise, general health, disability, pain, self-efficacy, and depression (P < 0.05). Baseline and 4-month changes in self-efficacy predicted health status at 1 year.\n Spanish-speaking participants of an arthritis self-management program demonstrate short- and long-term benefits (improved health behaviors, health status, and self-efficacy).", "A multicentre controlled randomized education study was performed to evaluate an education programme for insulin-treated diabetic patients. The main objective of the education programme, which took place on an out-patient basis, was to improve the level of self-care of the participants. Fifteen randomly recruited hospitals (558 patients) were equally divided into three groups: two experimental groups who completed the programme under the guidance of a health care professional or a fellow patient, and a control group. Patients in the experimental group were evaluated four times and those in the control group twice, with an intervening period of 6 to 7 months. The effect of the programme on metabolic control, quality of life, and costs of therapy was assessed. No significant effect of education of any one of these variables could be found.(ABSTRACT TRUNCATED AT 250 WORDS)", "To evaluate the acceptability, practicality, and short-term efficacy of a health education program to improve disease self-management in patients with symptomatic HIV/AIDS.\n Randomized controlled trial, baseline and 3-month follow-up questionnaire assessments.\n San Francisco Bay communities.\n Seventy-one men with symptomatic HIV or AIDS were randomly assigned to a seven-session group educational intervention (N=34) or a usual-care control group (N=37).\n Interactive health education groups were used to teach wide-ranging disease self-management skills and information: symptom assessment and management, medication use, physical exercise, relaxation, doctor-patient communication, and nutrition. Each group was led by two trained peer-leaders (one of whom was HIV-positive) recruited from the community.\n The primary outcome of interest was symptom status. Secondary outcomes were self-efficacy and health behaviors. Analysis of covariance was used to compare experimental and control group mean outcomes, adjusting for baseline value differences.\n The symptom severity index (number of symptoms moderate or greater severity) decreased in the experimental, and increased in the control group (-0.9 versus +0.5; p < .03). Pain, fatigue, and psychological symptoms were not significantly different between groups. Self-efficacy for controlling symptoms improved in the experimental, and decreased in the control group (+4 versus -7; p < .02). Changes in stress/relaxation exercises and HIV/AIDS knowledge were not different between groups. A trend was shown toward more frequent physical exercise in the experimental group compared with less in the control group (+1.3 versus -0.5 times/week; p=.06).\n Health education emphasizing self-management skills for HIV/AIDS patients can be implemented and evaluated and was accepted by patients, peer-leaders, and health care providers. Whether this educational program can lead to prolonged improvement in HIV symptoms and behaviors can be adequately addressed only by a larger trial of longer duration.", "Reducing the impact of chronic disease in minority ethnic groups is an important public health challenge. Lay-led education may overcome cultural and language barriers that limit the effectiveness of professionally-led programmes. We report the first randomised trial of a lay-led self-management programme - the Chronic Disease Self-Management Programme (CDSMP) (Expert Patient Programme) - in a south Asian group.\n To determine the effectiveness of a culturally-adapted lay-led self-management programme for Bangladeshi adults with chronic disease.\n Randomised controlled trial.\n Tower Hamlets, east London.\n We recruited Bangladeshi adults with diabetes, cardiovascular disease, respiratory disease or arthritis from general practices and randomised them to the CDSMP or waiting-list control. Self-efficacy (primary outcome), self-management behaviour, communication with clinician, depression scores, and healthcare use were assessed by blinded interviewer-administered questionnaires in Sylheti before randomisation and 4 months later.\n Of the 1363 people invited, 476 (34%) agreed to take part and 92% (439/476) of participants were followed up. The programme improved self-efficacy (difference: 0.67, 95% confidence interval [CI] = 0.08 to 1.25) and self-management behaviour (0.53; 95% CI = 0.01 to 1.06). In the 51% (121/238) of intervention participants attending three or more of the 6-weekly education sessions the programme led to greater improvements in self-efficacy (1.47; 95% CI = 0.50 to 1.82) and self-management behaviour (1.16; 95% CI = 0.50 to 1.82), and reduced HADS depression scores (0.64; 95% CI = 0.07 to 1.22). Communication and healthcare use were not significantly different between groups. The programme cost pound123 (181) per participant.\n A culturally-adapted CDSMP improves self-efficacy and self-care behaviour in Bangladeshi patients with chronic disease. Effects on health status were marginal. Benefits were limited by moderate uptake and attendance.", "To evaluate the effectiveness of the Shanghai Chronic Disease Self-Management Program (CDSMP).\n A randomized controlled trial with six-month follow-up compared patients who received treatment with those who did not receive treatment (waiting-list controls) in five urban communities in Shanghai, China. Participants in the treatment group received education from a lay-led CDSMP course and one copy of a help book immediately; those in the control group received the same education and book six months later.\n In total, 954 volunteer patients with a medical record that confirmed a diagnosis of hypertension, heart disease, chronic lung disease, arthritis, stroke, or diabetes who lived in communities were assigned randomly to treatment (n = 526) and control (n = 428) groups. Overall, 430 (81.7%) and 349 (81.5%) patients in the treatment and control groups completed the six-month study. Patients who received treatment had significant improvements in weekly minutes of aerobic exercise, practice of cognitive symptom management, self-efficacy to manage own symptoms, and self-efficacy to manage own disease in general compared with controls. They also had significant improvements in eight indices of health status and, on average, fewer hospitalizations.\n When implemented in Shanghai, the CDSMP was acceptable culturally to Chinese patients. The programme improved participants' health behaviour, self-efficacy, and health status and reduced the number of hospitalizations six months after the course. The locally based delivery model was integrated into the routine of community government organizations and community health services. Chinese lay leaders taught the CDSMP courses as successfully as professionals.", "To evaluate clinical effectiveness of a self management programme for arthritis in patients in primary care with osteoarthritis.\n Randomised controlled trial.\n 74 general practices in the United Kingdom.\n 812 patients aged 50 and over with osteoarthritis of hips or knees (or both) and pain or disability (or both).\n Participants were randomised to six sessions of self management of arthritis and an education booklet (intervention group) or the education booklet alone (control group).\n Primary outcome was quality of life, as assessed by the short form health survey (SF-36). Several other physical and psychosocial secondary outcomes were assessed. Data were collected at baseline, four months, and 12 months.\n Response rates were 80% and 76% at four and 12 months. The two groups showed significant differences at 12 months on the anxiety subscore of the hospital anxiety and depression scale (mean difference -0.62, 95% confidence interval -1.08 to -0.16), arthritis self efficacy scale for pain (0.98, 0.07 to 1.89), and self efficacy for other aspects of management (1.58, 0.25 to 2.90). Results were similar for intention to treat and per protocol analyses. No significant difference was seen in number of visits to the general practitioner at 12 months.\n The self management of arthritis programme reduced anxiety and improved participants' perceived self efficacy to manage symptoms, but it had no significant effect on pain, physical functioning, or contact with primary care.\n Current Controlled Trials ISRCTN79115352 [controlled-trials.com].", "We compared the relative effectiveness of 2 arthritis patient education interventions. One intervention was modeled after that developed by Lorig, whereas the other had similar content but used health professionals rather than laypersons as instructors. Both interventions resulted in an increase in patients' knowledge of arthritis and in their use of exercise compared with a control group that received no intervention. However, neither intervention was any more effective than nonintervention in lessening patients' pain, improving their functioning, enhancing social support systems, lessening their depression, or improving their health behaviors beyond that of exercise. No differences in outcome measures were found between groups led by professional instructors and those led by lay instructors.", "To evaluate the effectiveness of Stanford's Chronic Disease Self-Management Program (CDSMP) for chronic low back pain (LBP) in older Americans.\n Randomized controlled trial.\n Community-based program offered at 12 locations.\n Community-dwelling seniors (n = 109) aged 60 and older with chronic LBP of mechanical origin.\n Patients were randomly allocated to the CDSMP or to a 6-month, wait-list control group. The program included one 2.5-hour session per week for 6 weeks. Outcomes evaluated at 6 months included 100-point modified Von Korff pain and disability scales; days with pain and disability; SF-36 general health, energy-fatigue, and emotional well-being scales; 2 scales from the Arthritis Self-Efficacy Scale, self-care attitudes/behaviors, and health services utilization.\n For pain at 6 months, the primary outcome, the adjusted mean difference between the program and control, was -1.0 (P = .835). There was a sizable advantage for the program in disability averaged over the course of the entire 6-month study (-9.2, P = .027), but not at the 6-month follow-up (-5.8, P = .278). There was an interaction between intervention and baseline disability days favoring the program for higher baseline values (P = .007). The CDSMP affected emotional well-being (7.6, P = .037) and energy-fatigue (5.1, P = .274). There were no differences for self-efficacy, pain days, and general health.\n There was no advantage for the CDSMP over a wait-list control for improving pain, general health, self-efficacy, and self-care attitudes in older Americans with chronic LBP. A benefit was suggested for emotional well-being, fatigue, functional disability, and days with disability.", "This study investigated the effectiveness of the Chronic Disease Self-management Program (CDSMP) when delivered to for people from Vietnamese, Chinese, Italian and Greek backgrounds living in Victoria, Australia.\n The CDSMP was administered to 320 people with chronic illnesse(es) in selected low income areas in the State of Victoria, Australia. At 6 months, they were compared with randomised wait-list control subjects (n=154) using analyses of covariance.\n Participants in the intervention group had significantly better outcomes on energy, exercise, symptom management, self-efficacy, general health, pain, fatigue and health distress. There were no significant effects for health services utilisation. Interactions across language groups were observed with the Vietnamese and Chinese speaking participants gaining greater benefit.\n Self-management programs can be successfully implemented with culturally and linguistically diverse populations in Australia. Further research is needed to evaluate long-term outcomes; explore effects on service utilisation; and to determine whether the benefits obtained from participating in a self-management program can be maintained.\n Self-management programs should be considered for people from culturally and linguistically diverse backgrounds. Care also needs to be taken in designing recruitment strategies to minimize withdrawal rates and to ensure harder to reach people are given encouragement to participate.", "Peer support has been used effectively in a variety of patient populations, but its effectiveness in improving outcomes in persons with chronic heart failure has not been explored. We trained 9 persons with heart failure to mentor other heart failure patients and tested the effectiveness of this approach in a randomized controlled clinical trial. A low proportion (37%) of the eligible population of hospitalized patients agreed to participate. At the end of the 3-month trial, there was significantly higher heart failure self-care in the intervention group (P < .05). The only difference in social support was a significant decline in perceived support reciprocity in the intervention group (F = 5.94, P = .004). No significant group differences in heart failure readmissions, length of stay, or cost were evident at 90-days, although the heart failure readmission rate was 96% higher in the intervention group when compared to that in the control group. The reasons for low overall enrollment and high readmission rates in the intervention group require further study. Including additional self-care education by a professional, rather than leaving all the education to the mentor, could strengthen the peer support intervention trialed in this study. Small group meetings may be less intrusive and more desirable for this patient population.", "This study evaluated the effectiveness (changes in health behaviors, health status, and health service utilization) of a self-management program for chronic disease designed for use with a heterogeneous group of chronic disease patients. It also explored the differential effectiveness of the intervention for subjects with specific diseases and comorbidities.\n The study was a six-month randomized, controlled trial at community-based sites comparing treatment subjects with wait-list control subjects. Participants were 952 patients 40 years of age or older with a physician-confirmed diagnosis of heart disease, lung disease, stroke, or arthritis. Health behaviors, health status, and health service utilization, as determined by mailed, self-administered questionnaires, were measured.\n Treatment subjects, when compared with control subjects, demonstrated improvements at 6 months in weekly minutes of exercise, frequency of cognitive symptom management, communication with physicians, self-reported health, health distress, fatigue, disability, and social/role activities limitations. They also had fewer hospitalizations and days in the hospital. No differences were found in pain/physical discomfort, shortness of breath, or psychological well-being.\n An intervention designed specifically to meet the needs of a heterogeneous group of chronic disease patients, including those with comorbid conditions, was feasible and beneficial beyond usual care in terms of improved health behaviors and health status. It also resulted in fewer hospitalizations and days of hospitalization.", "One hundred subjects with arthritis were randomized into lay-taught, or professional-taught 12-h arthritis self-management courses, or a control group. Outcomes, knowledge, exercise, relaxation, disability, pain, and number of physician visits were measured aat baseline and 4 months. Professional-taught groups demonstrated greater knowledge gain while lay-taught groups had greater changes in relaxation (p less than .01) and a tendency toward less disability. Although it is impossible to draw definitive conclusions, this study suggests that lay leaders can teach arthritis self-management courses with results similar to those achieved by professionals.", "Supporting patients' self care could have a major effect on the management of long-term conditions, which has led to worldwide interest in effective self care interventions. In England, self care support is being developed through the \"Expert Patients Programme\", which provides lay-led generic courses to improve patients' self care skills. However, the clinical and cost effectiveness of such courses remains unclear.\n Two-arm pragmatic randomised controlled trial design with waiting list control in community settings in England. 629 patients with a wide range of self-defined long-term conditions were studied. The lay-led self care support group involved 6-weekly sessions to teach self care skills. Primary outcomes were self-efficacy, reported energy and routine health services utilisation at 6 months. A cost-effectiveness analysis was also conducted.\n Patients receiving immediate course access reported considerably greater self-efficacy and energy at 6-month follow-up, but reported no statistically significant reductions in routine health services utilisation over the same time period. The cost-effectiveness analysis showed that patients receiving immediate course access reported considerably greater health related quality of life, and a small reduction in costs. If a quality adjusted life year was valued at 20,000 pounds (39,191 dollars; 30,282 Euro), there was a 70% probability that the intervention was cost effective.\n Lay-led self care support groups are effective in improving self-efficacy and energy levels among patients with long-term conditions, and are likely to be cost effective over 6 months at conventional values of a decision-maker's willingness to pay. They may be a useful addition to current services in the management of long-term conditions.", "In light of health disparities and the growing prevalence of chronic disease, there is a need for community-based interventions that improve health behaviors and health status. These interventions should be based on existing theory.\n This study aimed to evaluate the health and utilization outcomes of a 6-week community-based program for Spanish speakers with heart disease, lung disease, or type 2 diabetes.\n The treatment participants in this study (n = 327) took a 6-week peer-led program. At 4 months, they were compared with randomized wait-list control subjects (n = 224) using analyses of covariance. The outcomes for all the treatment participants were assessed at 1 year, as compared with baseline scores (n = 271) using t-tests.\n At 4 months, the participants, as compared with usual-care control subjects, demonstrated improved health status, health behavior, and self-efficacy, as well as fewer emergency room visits (p <.05). At 1 year, the improvements were maintained and remained significantly different from baseline condition.\n This community-based program has the potential to improve the lives of Hispanics with chronic illness while reducing emergency room use." ]

[ "16512804", "15727582", "9042042", "11069570", "16650048", "12548058", "17919141", "16839405", "12589361", "17107398" ]

[ "Prebiotics and synbiotics: two promising approaches for the treatment of atopic dermatitis in children above 2 years.", "Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial.", "Probiotics: a novel approach in the management of food allergy.", "Probiotics in the management of atopic eczema.", "Is the effect of probiotics on atopic dermatitis confined to food sensitized children?", "Probiotic bacteria in the management of atopic disease: underscoring the importance of viability.", "Randomized, placebo-controlled trial of Lactobacillus rhamnosus GG as treatment of atopic dermatitis in infancy.", "No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial.", "Effect of probiotic Lactobacillus strains in children with atopic dermatitis.", "Prospective, randomized controlled trial on Lactobacillus rhamnosus in infants with moderate to severe atopic dermatitis." ]

[ "Appropriate use of prebiotics and optimal combinations of probiotics and prebiotics (synbiotics) could allow significantly better results to be obtained in the treatment of atopic dermatitis (AD).\n To evaluate the efficiency of synbiotics when compared with prebiotics alone (control group) in the treatment of moderate and severe AD in children aged 2 years and over.\n Double-blind prospective randomized study performed on children aged at least 2 years presenting AD with a minimum SCORing Atopic Dermatitis (SCORAD) score of 15. A dose of 1.2 x 10(9) colony-forming units Lactobacillus rhamnosus Lcr35 plus prebiotic preparation or an identically appearing prebiotic preparation alone was given three times a day for 3 months. Patients' diet and usual treatment for AD remained unchanged during the study period. Efficiency was evaluated using the SCORAD score. Use of topical drugs was noted.\n A total of 48 patients were originally enrolled; nine did not complete the study. In synbiotic group, the mean values of the total SCORAD score was 39.1 before treatment vs 20.7 after 3 months of treatment (P < 0.0001). In the prebiotic group, the mean of the total SCORAD score was 39.3 before the treatment vs 24.0 after 3 months (P < 0.0001). After 3 months of treatment, no statistical differences between the two treatment groups with regard to the total SCORAD score were noted (P = 0.535). Neither were there any statistical differences in the total use of ointment between patients receiving prebiotics or synbiotics (P = 0.966) over the study period. Tolerance was excellent in both groups.\n Both synbiotics and prebiotics used alone seem able to significantly improve the manifestations of AD in children aged 2 years and over.", "Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome (AEDS) in food-allergic infants. We aimed to investigate whether probiotic bacteria have any beneficial effect on AEDS.\n Follow-up of severity of AEDS by the Severity Scoring of Atopic Dermatitis (SCORAD) index in 230 infants with suspected cow's milk allergy (CMA) receiving, in a randomized double-blinded manner, concomitant with elimination diet and skin treatment, Lactobacillus GG (LGG), a mixture of four probiotic strains, or placebo for 4 weeks. Four weeks after the treatment, CMA was diagnosed with a double-blind placebo-controlled (DBPC) milk challenge in 120 infants.\n In the whole group, mean SCORAD (at baseline 32.5) decreased by 65%, but with no differences between treatment groups immediately or 4 weeks after the treatment. No treatment differences were observed in infants with CMA either. In IgE-sensitized infants, however, the LGG group showed a greater reduction in SCORAD than did the placebo group, -26.1 vs-19.8 (P=0.036), from baseline to 4 weeks after the treatment. Exclusion of infants who had received antibiotics during the study reinforced the findings in the IgE-sensitized subgroup.\n Treatment with LGG may alleviate AEDS symptoms in IgE-sensitized infants but not in non-IgE-sensitized infants.", "The gastrointestinal microflora is an important constituent of the gut mucosal defense barrier. We have previously shown that a human intestinal floral strain, Lactobacillus GG (ATCC 53103), promotes local antigen-specific immune responses (particularly in the IgA class), prevents permeability defects, and confers controlled antigen absorption.\n The aim of this study was to evaluate the clinical and immunologic effects of cow's milk elimination without (n = 14) and with (n = 13) the addition of Lactobacillus GG (5 x 10(8) colony-forming units/gm formula) in an extensively hydrolyzed whey formula in infants with atopic eczema and cow's milk allergy. The second part of the study involved 10 breast-fed infants who had atopic eczema and cow's milk allergy. In this group Lactobacillus GG was given to nursing mothers.\n The severity of atopic eczema was assessed by clinical scoring. The concentrations of fecal alpha 1- antitrypsin, tumor necrosis factor-alpha, and eosinophil cationic protein were determined as markers of intestinal inflammation before and after dietary intervention.\n The clinical score of atopic dermatitis improved significantly during the 1-month study period in infants treated with the extensively hydrolyzed whey formula fortified with Lactobacillus GG. The concentration of alpha 1-antitrypsin decreased significantly in this group (p = 0.03) but not in the group receiving the whey formula without Lactobacillus GG (p = 0.68). In parallel, the median (lower quartile to upper quartile) concentration of fecal tumor necrosis factor-alpha decreased significantly in this group, from 709 pg/gm (91 to 1131 pg/gm) to 34 pg/gm (19 to 103 pg/gm) (p = 0.003), but not in those receiving the extensively hydrolyzed whey formula only (p = 0.38). The concentration of fecal eosinophil cationic protein remained unaltered during therapy.\n These results suggest that probiotic bacteria may promote endogenous barrier mechanisms in patients with atopic dermatitis and food allergy, and by alleviating intestinal inflammation, may act as a useful tool in the treatment of food allergy.", "Over the last two decades the incidence of allergic diseases has increased in industrialized countries, and consequently new approaches have to be explored.\n The potential of probiotics to control allergic inflammation at an early age was assessed in a randomized double-blind placebo-controlled study.\n A total of 27 infants, mean age 4.6 months, who manifested atopic eczema during exclusive breast-feeding and who have had no exposure to any infant or substitute formula were weaned to probiotic-supplemented, Bifidobacterium lactis Bb-12 or Lactobacillus strain GG (ATCC 53103), extensively hydrolysed whey formulas or to the same formula without probiotics. The extent and severity of atopic eczema, the growth and nutrition of infants, and concentrations of circulating cytokines/chemokines and soluble cell surface adhesion molecules in serum and methyl-histamine and eosinophilic protein X in urine were determined.\n The SCORAD score reflecting the extent and severity of atopic eczema was 16 (7-25) during breast-feeding, median (interquartile range). After 2 months, a significant improvement in skin condition occurred in patients given probiotic-supplemented formulas, as compared to the unsupplemented group; chi(2) = 12.27, P = 0.002. SCORAD decreased in the Bifidobacterium lactis Bb-12 group to 0 (0-3.8), and in the Lactobacillus GG group to 1 (0.1-8.7), vs unsupplemented 13.4 (4.5-18.2), median (interquartile range), in parallel with a reduction in the concentration of soluble CD4 in serum and eosinophilic protein X in urine.\n The results provide the first clinical demonstration of specific probiotic strains modifying the changes related to allergic inflammation. The data further indicate that probiotics may counteract inflammatory responses beyond the intestinal milieu. The combined effects of these probiotic strains will guide infants through the weaning period, when sensitization to newly encountered antigens is initiated. The probiotic approach may thus offer a new direction in the search for future foods for allergy treatment and prevention strategies.", "Probiotics have previously been shown to reduce the severity of atopic dermatitis (AD) in infants and children.\n To examine the effect of two probiotics (Lactobacillus rhamnosus and Bifidobacteria lactis) on established AD in children.\n Atopic children with current dermatitis received 2 x 10(10) colony forming units/g of probiotic (n=29) or placebo (n=30). Both were given daily as a powder mixed with food or water. SCORing Atopic Dermatitis (SCORAD; developed by the European Task Force on Atopic Dermatitis) a measure of the extent and severity of AD, was assessed at baseline, 2 and 12 weeks after starting treatment and 4 weeks after treatment was discontinued.\n SCORAD geometric mean score at baseline was 26.0 (21.9-30.8) in the probiotic group and 35.1 (28.9-42.8) in the placebo group (P=0.02). After adjustment for these between-group baseline differences there was no significant improvement in AD at 12 weeks, SCORAD geometric mean ratio: 0.80 (95% confidence level (CI) 0.62-1.04, P=0.10). Among the food sensitized children, there was an improvement in those treated with probiotics, SCORAD geometric mean ratio: 0.73 (95% CI 0.54-1.00, P=0.047).\n In this study a combination of Lactobacillus rhamnosus and Bifidobacteria lactis improved AD only in food sensitized children.", "The aim of this study was to assess the efficacy of oral supplementation of viable and heat-inactivated probiotic bacteria in the management of atopic disease and to observe their effects on the composition of the gut microbiota.\n The study population included 35 infants with atopic eczema and allergy to cow's milk. At a mean age of 5.5 months, they were assigned in a randomized double-blind manner to receive either extensively hydrolyzed whey formula (placebo group) or the same formula supplemented with viable (viable LGG group) or heat-inactivated Lactobacillus GG (heat-inactivated LGG group), respectively. The changes in symptoms were assessed by the SCORAD method and the presence of some predominant bacterial genera in the feces detected with 16S rRNA-specific probes.\n The treatment with heat-inactivated LGG was associated with adverse gastrointestinal symptoms and diarrhea. Consequently, the recruitment of patients was stopped after the pilot phase. Within the study population, atopic eczema and subjective symptoms were significantly alleviated in all the groups; the SCORAD scores (interquartile range) decreased from 13 (range, 4-29) to 8 (range, 0-29) units in the placebo group, from 19 (range, 4-47) to 5 (range, 0-18) units in the viable LGG group, and from 15 (range, 0-29) to 7 (range, 0-26) units in the heat-inactivated LGG group. The decrease in the SCORAD scores within the viable LGG group tended to be greater than within the placebo group. The treatments did not appear to affect the bacterial numbers within the genera enumerated.\n Supplementation of infant formulas with viable but not heat-inactivated LGG is a potential approach for the management of atopic eczema and cow's milk allergy.", "Some studies have suggested that supplementation of food with lactobacilli may prevent or improve atopic dermatitis in children. This study was designed to investigate the therapeutic effect of Lactobacillus rhamnosus GG (LGG) as a food supplement in infants suffering from atopic dermatitis.\n Infants aged 3-12 months suffering from mild-to-moderate atopic dermatitis (severity scoring of atopic dermatitis or SCORAD index of 15-40) without current antiinflammatory treatment were randomized to receive LGG (5 x 10(9) colony forming units b.i.d.) or placebo as a food supplement for 12 weeks. Severity scoring of atopic dermatitis index and use of hydrocortisone 1% ointment as rescue medication (2 points per application) were recorded at 4, 8, and 12 weeks of treatment and combined as symptom load (SL).\n Fifty-four infants (LGG group, mean +/- SD SCORAD index 24.6 +/- 8.8) and 48 infants (placebo group, SCORAD index 23.6 +/- 7.8) were randomized and completed the treatment period (intention-to-treat analysis). Symptom load generally improved over time at 4 weeks (LGG vs placebo, 23.8 +/- 12.4 vs 20.6 +/- 9.9), 8 weeks (22.5 +/- 14.6 vs 17.9 +/- 13.1), and 12 weeks (19.6 +/- 15.4 vs 15.1 +/- 12.1), without statistically significant group differences. When stratified for age, eczema severity or use of rescue medication, no statistically significant group differences, in improvement, were found. No significant group differences were found for the use of rescue medication (0.8 +/- 45.0 g vs 3.5 +/- 29.8 g), increase in mean logarithmic total serum IgE (0.17 +/- 0.30 kU/l vs 0.26 +/- 0.45 kU/l), and newly developed allergic sensitization against hen's egg or cow's milk (18.8%vs 10.0%).\n This placebo-controlled trial showed no therapeutic effect of LGG against mild-to-moderate atopic dermatitis in infancy.", "Studies have been performed suggesting that administration of probiotics may have therapeutic and/or preventive benefits in the development of sensitization and atopic disease, particularly in infants with atopic dermatitis (AD).\n The purpose of this study was to evaluate the clinical and immunological effects of supplementation of a hydrolysed formula with two probiotic strains of bacteria on symptoms of AD in infancy.\n We conducted a randomized, double-blind, placebo-controlled study. After 4-6 weeks of baseline and double-blind, placebo-controlled challenges for diagnosis of cow's milk allergy (CMA), infants less than 5 months old with AD received a hydrolysed whey-based formula as placebo (n = 17), or supplemented with either Lactobacillus rhamnosus (n = 17) or Lactobacillus GG (n = 16) for 3 months. Before, during and after intervention, the clinical severity of AD was evaluated using SCORing index Atopic Dermatitis (SCORAD). Allergic sensitization was evaluated by measurement of total IgE and a panel of food-specific IgEs as well as skin prick testing for cow's milk. Inflammatory parameters were blood eosinophils, eosinophil protein X in urine, fecal alpha-1-antitrypsin and production of IL-4, IL-5 and IFN-gamma by peripheral blood mononuclear cells after polyclonal stimulation.\n No statistically significant effects of probiotic supplementation on SCORAD, sensitization, inflammatory parameters or cytokine production between groups were found. Only four infants were diagnosed with CMA.\n We found no clinical or immunological effect of the probiotic bacteria used in infants with AD. Our results indicate that oral supplementation with these probiotic bacterial strains will not have a significant impact on the symptoms of infantile AD.", "Recent studies suggest that oral bacteriotherapy with probiotics might be useful in the management of atopic dermatitis (AD).\n The purpose of this investigation was to evaluate the clinical and anti-inflammatory effect of probiotic supplementation in children with AD.\n In a double-blind, placebo-controlled, crossover study, 2 probiotic Lactobacillus strains (lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 122460) were given in combination for 6 weeks to 1- to 13-year-old children with AD. The patients' evaluations were registered after each intervention (ie, better, unchanged, or worse). The clinical severity of the eczema was evaluated by using the scoring atopic dermatitis (SCORAD) score. As inflammatory markers, eosinophil cationic protein in serum and cytokine production by PBMCs were measured.\n After active treatment, 56% of the patients experienced improvement of the eczema, whereas only 15% believed their symptoms had improved after placebo (P =.001). The total SCORAD index, however, did not change significantly. The extent of the eczema decreased during active treatment from a mean of 18.2% to 13.7% (P =.02). The treatment response was more pronounced in allergic patients (at least one positive skin prick test response and elevated IgE levels), and in this group the SCORAD score decreased (P =.02 compared with nonallergic patients). During active treatment, serum eosinophil cationic protein levels decreased (P =.03). No significant changes in the production of the cytokines IL-2, IL-4, IL-10, or IFN-gamma were found.\n A combination of L rhamnosus 19070-2 and L reuteri DSM 122460 was beneficial in the management of AD. The effect was more pronounced in patients with a positive skin prick test response and increased IgE levels.", "A reduction of symptoms of atopic dermatitis (AD) in small infants by the administration of Lactobacillus rhamnosus has been reported in a few studies. One study with older children and adolescents failed to show any effect.\n We conducted a prospective study to reassess the efficacy of orally administered L. rhamnosus strain GG (LGG) in infants with AD.\n In a randomized, double-blind, placebo-controlled study, 54 infants aged 1-55 months with moderate to severe AD were randomized to daily 10 x 10(9) colony-forming units of LGG or to placebo during an 8-week intervention phase. Emollients, class I-II topical corticosteroids and antihistamines were permitted.\n The treatment with LGG was well tolerated. At the end of treatment there were no significant differences between the groups with respect to clinical symptoms (SCORAD, pruritus, sleep loss), the use of topical corticosteroids and antihistamines, immunological parameters, or health-related quality of life of the parents.\n Our results could not confirm LGG as an effective treatment of AD in infancy." ]

[ "1582380", "10731452", "14644967", "8105673", "7994223", "12782900", "6549638", "8831651", "10757101", "9093045", "11786452", "2360750", "8291821", "8147544" ]

[ "Smoking cessation and severity of disease: the Coronary Artery Smoking Intervention Study.", "A randomized controlled trial of smoking cessation counseling after myocardial infarction.", "Randomised controlled trial of smoking cessation intervention after admission for coronary heart disease.", "Secondary prevention after acute myocardial infarction.", "Effects of a health education programme with telephone follow-up during cardiac rehabilitation.", "Stepped care approach to smoking cessation in patients hospitalized for coronary artery disease.", "Limited effects of outpatient teaching and counseling after myocardial infarction: a controlled study.", "Coronary risk factor modification in women after coronary artery bypass surgery.", "[Efficacy of an intervention in smoking cessation in patients with myocardial infarction].", "Influence of coronary nursing management follow up on lifestyle after acute myocardial infarction.", "Brief intervention during hospital admission to help patients to give up smoking after myocardial infarction and bypass surgery: randomised controlled trial.", "Smoking cessation after acute myocardial infarction: effects of a nurse-managed intervention.", "Predictors of smoking cessation after coronary artery bypass graft surgery. Results of a randomized trial with 5-year follow-up.", "A case-management system for coronary risk factor modification after acute myocardial infarction." ]

[ "We tested the effectiveness of an individually delivered behavioral multicomponent smoking intervention (SI) against offering advice only (AO) to 267 patients after coronary arteriography. After 6 months, 51% of AO patients and 62% of SI patients reported abstinence. Validated rates were 34% and 45% for AO and SI patients, respectively. Logistic regression analyses, controlling for severity of illness, stage of change, and self-efficacy, among other variables, showed that, at 6 months, the SI had the most effect for patients with more severe coronary artery disease (CAD) who had been admitted with a myocardial infarction (95% confidence interval = 2.05, 124.85). At 12 months, only severity of disease mediated SI effects (95% confidence interval = 3.10, 58.00). Similar results were seen for cotinine-validated cessation. This study confirms the effectiveness of individually administered SI for more seriously ill patients with CAD and raises questions as to how to better intervene with those individuals with less severe disease.", "Smoking cessation after myocardial infarction (MI) has been associated with a 50% reduction in mortality but in-hospital smoking cessation interventions are rarely part of routine clinical practice.\n One hundred cigarette smokers consecutively admitted during 1996 with MI were assigned to minimal care or to a hospital-based smoking cessation program. Intervention consisted of bedside cessation counseling followed by seven telephone calls over the 6 months following discharge. Primary outcomes were abstinence rates measured at 6 months and 1 year post-discharge.\n At follow-up, 43 and 34% of participants in minimal care and 67 and 55% of participants in intervention were abstinent at 6 and 12 months. respectively (P<0.05). Abstinence rates were calculated assuming that participants lost to attrition were smokers at follow-up. Intervention and self-efficacy were independent predictors of smoking status at follow-up. Low self-efficacy combined with no intervention resulted in a 93% relapse rate by 1 year (P<0.01).\n A hospital-based smoking cessation program consisting of inpatient counseling and telephone follow-up substantially increases smoking abstinence 1 year after discharge in patients post-MI. Patients with low self-efficacy are almost certain to relapse without intervention. Such smoking cessation programs should be part of the management of patients with MI.\n Copyright 2000 American Health Foundation and Academic Press.", "To determine whether a nurse led smoking cessation intervention affects smoking cessation rates in patients admitted for coronary heart disease.\n Randomised controlled trial.\n Cardiac ward of a general hospital, Norway.\n 240 smokers aged under 76 years admitted for myocardial infarction, unstable angina, or cardiac bypass surgery. 118 were randomly assigned to the intervention and 122 to usual care (control group).\n The intervention was based on a booklet and focused on fear arousal and prevention of relapses. The intervention was delivered by cardiac nurses without special training. The intervention was initiated in hospital, and the participants were contacted regularly for at least five months.\n Smoking cessation rates at 12 months determined by self report and biochemical verification.\n 12 months after admission to hospital, 57% (n = 57/100) of patients in the intervention group and 37% (n = 44/118) in the control group had quit smoking (absolute risk reduction 20%, 95% confidence interval 6% to 33%). The number needed to treat to get one additional person who would quit was 5 (95% confidence interval, 3 to 16). Assuming all dropouts relapsed at 12 months, the smoking cessation rates were 50% in the intervention group and 37% in the control group (absolute risk reduction 13%, 0% to 26%).\n A smoking cessation programme delivered by cardiac nurses without special training, significantly reduced smoking rates in patients 12 months after admission to hospital for coronary heart disease.", "The hypothesis that 6 months after acute myocardial infarction, adoption of secondary prevention activities would be higher, quality of life better, and blood cholesterol lower in patients randomly allocated to a mail-out intervention program than in those receiving usual care was tested. Patients were aged < 70 years, admitted to hospitals in and around Newcastle, Australia with a suspected heart attack and discharged alive from the hospital. Cluster randomization, based on the patient's family practitioner, was used to allocate consenting patients to an intervention or usual care group. A low-cost mail-out program was designed to help patients reduce dietary fat, obtain regular exercise by walking and (for smokers only) to quit smoking. Supplementary telephone contact was also used. In addition, a letter was sent to the family doctor regarding the benefit of aspirin and beta blockers for secondary prevention. Of eligible patients, 71% participated, and 79% of the 213 intervention subjects and 87% of the 237 usual care ones returned a 6-month follow-up questionnaire. Self-reported fat intake was significantly lower, an \"emotional\" score obtained from a quality-of-life questionnaire was significantly higher in the intervention than in the usual care group, and \"physical\" and \"social\" scores for quality of life were slightly higher. Blood cholesterol level and other variables were not different between the groups at 6 months. Simple low-cost programs providing support and advice on lifestyle change may be beneficial, particularly in improving patients' perceived quality of life.", "A health education and counselling programme was offered to myocardial infarction patients during and after hospitalization. A randomized pre-test-post-test control group design was used to evaluate the effects of the experimental intervention. During hospitalization the intervention consisted of two individual counselling sessions and two group health education sessions focusing on medication, healthy habits, anxiety and depression. On completion of these sessions, weekly telephone calls were made to patients for a period of six weeks after discharge from hospital. The intervention was offered to 30 myocardial infarction patients and their partners (the experimental group) in addition to standard medical care. Thirty control patients received standard medical care only. Two months after myocardial infarction, patients in the experimental condition reported a significantly greater increase in physical activity, and a significantly greater decrease in unhealthy eating habits. No effects were found regarding smoking cessation, anxiety and depression. Twelve months after discharge from hospital patients in the experimental condition reported a significantly greater decrease in unhealthy eating habits. No effects were found regarding smoking cessation, physical activity, anxiety and depression. In addition, two months after myocardial infarction, it was found that patients whose partners participated in the health education sessions showed a significantly greater decrease in smoking and unhealthy eating habits and a significantly greater increase in physical activity than patients with no partner participating. Twelve months after discharge the only significant result favouring the patients whose partner participated in the health education sessions concerned smoking cessation.", "Smoking cessation is an important goal for smokers with coronary artery disease (CAD) because it reduces cardiac morbidity and mortality. Effective interventions for cigarette smokers with CAD exist, but they often are considered to be intensive and expensive. Stepped-care interventions have been proposed as a promising way to allocate smoking cessation treatments in a cost-effective manner. Stepped care refers to the practice of initiating treatment with low-intensity intervention and then exposing treatment failures to successively more intense interventions.\n To address the efficacy of this approach, 254 cigarette smokers hospitalized with CAD were provided a brief cessation intervention. The participants then were assigned randomly to either a more intensive stepped-care treatment (counseling and nicotine patch therapy) or no additional treatment. Outcomes were point-prevalent abstinence measured 3 months and 1 year after hospital discharge.\n Stepped-care treatment increased smoking cessation rates from 42% to 53% during a 3-month follow-up period (P =.05), but showed little effect at the 1-year follow-up assessment, as evidenced by a cessation rate for the minimal intervention group of 36% versus 39% for the stepped-care group (P =.36).\n A stepped-care approach to smoking cessation increased short-but not long-term point-prevalent abstinence in patients with CAD. For improvement of long-term effectiveness, refinement of the timing and content of stepped-care interventions needs to occur.", "nan", "In a trial to evaluate the effectiveness of a nurse-directed intervention designed to help patients decrease dietary intake of fat, quit or decrease smoking, and increase exercise, 138 women who underwent coronary artery bypass surgery were randomized to receive special intervention (SI) or usual care (UC). The SI group received a behavioral program based on self-efficacy theory in the home 2 weeks after discharge with regular follow-up. The UC group received routine medical care. Risk factors and lifestyle behaviors were measured at baseline and 1 year after surgery in 116 (84%) women (SI = 59, UC = 57). The SI group decreased their total fat intake from a mean of 38% of calories at baseline to 35% at 1 year, while the UC group increased it from 36% to 38%. The prevalence of smoking decreased from 24% at baseline to 8% at 1 year in the SI group and from 19% to 14% in the UC group. At follow-up, the quit rate in those smoking at baseline was 64% in the SI group, with no new smokers, and 55% in the UC group, with three new smokers. Both groups reported improvement in exercise, with the proportion of women reporting participation in some form of regular exercise slightly higher in the SI group than in the UC group, 54% and 51%, respectively.", "The aim of this study was to evaluate the efficacy of an structured intervention based on a medical advice versus to the ordinary anti-tobacco advice in patients with miocardial infarction who are attended in an Intensive Care Unit (ICU).\n 90 patients were randomly selected to receive either the specific intervention (intervention group) or the ordinary advice (control group). The medical advice was given during the ICU hospitalization and during the second, the third and the fourth week. One year later the smoking habit was evaluated.\n After one year 26 patients of the intervention group and 31 patients of the control group had stopped smoking (RR = 0.88 [CI 95% RR] 0.57 to 1.37).\n The percentage of patients who stop smoking after a miocardial infarction is high. The structured medical counselling was not effective to reduce the number of smokers at one year.", "To examine the ability of a secondary prevention programme to improve the lifestyle in myocardial infarction patients aged 50-70 years.\n Habitual physical activity, food habits, and smoking habits were assessed from questionnaires at admission to hospital and at the one year follow up. Initially, all patients were invited to join an exercise programme and were informed about cardiovascular risk factors. Four weeks after discharge from the hospital, 87 patients were randomised to follow up at the coronary prevention unit by a special trained nurse (the intervention group), and 81 to follow up by their general practitioners (the usual care group). After randomisation, the intervention group was educated about the effects of smoking cessation, dietary management, and regular physical activity. The intervention group also participated in a physical training programme two to three times weekly for 10-12 weeks.\n 89% of the patients referred to the intervention group improved their food habits compared with 62% of the patients referred to the usual care group (P = 0.008). Furthermore, 50% of the smokers referred to the intervention group stopped smoking compared to 29% in the usual care group (P = 0.09). Changes in physical activity did not differ between the groups.\n This secondary prevention programme based on a nurse rehabilitator was successful in improving food habits in patients with acute myocardial infarction. Initiating the smoking cessation programme during the hospital stay followed by repeated counselling during follow up might have improved the results. The exercise programme had no advantage in supporting physical activity compared to usual care.", "To evaluate a smoking cessation intervention that can be routinely delivered to smokers admitted with cardiac problems.\n Randomised controlled trial of usual care compared with intervention delivered on hospital wards by cardiac rehabilitation nurses.\n Inpatient wards in 17 hospitals in England.\n 540 smokers admitted to hospital after myocardial infarction or for cardiac bypass surgery who expressed interest in stopping smoking.\n Brief verbal advice and standard booklet (usual care). Intervention lasting 20-30 minutes including carbon monoxide reading, special booklet, quiz, contact with other people giving up, declaration of commitment to give up, sticker in patient's notes (intervention group).\n Continuous abstinence at six weeks and 12 months determined by self report and by biochemical validation at these end points. Feasibility of the intervention and delivery of its components.\n After six weeks 151 (59%) and 159 (60%) patients remained abstinent in the control and intervention group, respectively (P=0.84). After 12 months the figures were 102 (41%) and 94 (37%) (P=0.40). Recruitment was slow, and delivery of the intervention was inconsistent, raising concerns about the feasibility of the intervention within routine care. Patients who received the declaration of commitment component were almost twice as likely to remain abstinent than those who did not receive it (P<0.01). Low dependence on tobacco and high motivation to give up were the main independent predictors of positive outcome. Patients who had had bypass surgery were over twice as likely to return to smoking as patients who had had a myocardial infarction.\n Single session interventions delivered within routine care may have insufficient power to influence highly dependent smokers.", "To determine the effect of a nurse-managed intervention for smoking cessation in patients who have had a myocardial infarction.\n Randomized, with a 6-month treatment period and a 6-month follow-up.\n Kaiser Foundation hospitals in Redwood City, Santa Clara, Hayward, and San Jose, California.\n Sequential sample of 173 patients, 70 years of age or younger, who were smoking before hospitalization for acute myocardial infarction. Eighty-six patients were randomly assigned to the intervention and 87 to usual care; 130 patients (75%) completed the study and were available for follow-up.\n Nurse-managed and focused on preventing relapse to smoking, the intervention was initiated in the hospital and maintained thereafter primarily through telephone contact. Patients were given an 18-page manual that emphasized how to identify and cope with high-risk situations for smoking relapse.\n One year after myocardial infarction, the smoking cessation rate, verified biochemically, was 71% in the intervention group compared with 45% in the usual care group, a 26% difference (95% CI, 9.5% to 42.6%). Assuming that all surviving patients lost to follow-up were smoking, the 12-month smoking cessation rate was 61% in the intervention group compared with 32% in the usual care group, a 29% difference (95% CI, 14.5% to 43.5%). Patients who either resumed smoking within 3 weeks after infarction or expressed little intention of stopping in the hospital were unlikely to have stopped by 12 months.\n A nurse-managed smoking cessation intervention largely conducted by telephone, initiated in the hospital, and focused on relapse prevention can significantly reduce smoking rates at 12 months in patients who have had a myocardial infarction.", "To test the efficacy of a smoking cessation program for inpatients recovering from coronary artery bypass graft surgery and to identify predictors of cessation.\n Randomized, controlled clinical trial.\n Postoperative cardiac surgery unit of a large teaching hospital.\n Patients scheduled for coronary artery bypass surgery by participating surgeons between 1 July 1986 and 1 July 1987 who had smoked 1 or more packs of cigarettes in the 6 months before admission. Of 120 eligible patients, 93 enrolled and 87 were discharged alive. All survivors were followed for at least 1 year; 94% were followed for a median of 5.5 years.\n A three-session, nurse-delivered behavior modification program using a videotape and face-to-face counseling was compared to usual care.\n Smoking status was assessed six times in the year after surgery and 5.5 years after surgery. Self-reported nonsmoking was validated by saliva cotinine assay 1 and 5.5 years after surgery.\n No statistically significant differences were found between control (n = 43) and intervention (n = 44) groups at baseline. One and 5.5 years after hospital discharge, validated continuous nonsmoking rates were identical in intervention and control groups (51% at 1 year; 44% at 5.5 years). Multiple logistic regression identified four factors that were independently associated with nonsmoking for 1 year: fewer than 3 previous attempts to quit (odds ratio, 7.4; 95% Cl, 1.9 to 29.1); more than 1 week of preoperative nonsmoking (odds ratio, 10.0; Cl, 2.0 to 50.2); definite intention to quit smoking (odds ratio, 12.0; Cl, 2.6 to 55.1); and no difficulty not smoking in the hospital (odds ratio, 9.6; Cl, 1.8 to 52.2). Nonsmoking for 5.5 years was independently associated with two of these factors: fewer than three previous attempts to quit and intention to quit smoking after surgery. Cessation was not related to demographic factors, daily cigarette consumption, disease severity, hospital course, social support, or beliefs and attitudes.\n Even without specific intervention, nearly one half of smokers quit for 5 years after coronary artery bypass surgery. A short inpatient education program did not increase this rate. Future efforts should target the time after discharge and focus on increasing motivation in patients who have repeatedly failed to quit.", "To evaluate the efficacy of a physician-directed, nurse-managed, home-based case-management system for coronary risk factor modification.\n Randomized clinical trial in which patients received a special intervention (n = 293) or usual medical care (n = 292) during the first year after acute myocardial infarction.\n 5 Kaiser Permanente Medical Centers in the San Francisco Bay area.\n 585 men and women aged 70 years or younger who were hospitalized for acute myocardial infarction.\n In the hospital, specially trained nurses initiated interventions for smoking cessation, exercise training, and diet-drug therapy for hyperlipidemia. Intervention after discharge was implemented primarily by telephone and mail contact with patients in their homes. All medically eligible patients received exercise training; all smokers received the smoking cessation intervention; and all patients received dietary counseling and, if needed, lipid-lowering drug therapy.\n Smoking prevalence and plasma low-density lipoprotein cholesterol (LDL) concentrations were measured 2 months after infarction, and functional capacity was measured 6 months after infarction.\n In the special intervention and usual care groups, the cotinine-confirmed smoking cessation rates were 70% and 53% (P = 0.03), plasma LDL cholesterol levels were 2.77 +/- 0.69 mmol/L and 3.41 +/- 0.90 mmol/L (107 +/- 30 mg/dL and 132 +/- 30 mg/dL) (P = 0.001), and functional capacities were 9.3 +/- 2.4 METS and 8.4 +/- 2.5 METS (P = 0.001), respectively.\n In a large health maintenance organization, a case-management system was considerably more effective than usual medical care for modification of coronary risk factors after myocardial infarction." ]

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[ "No evidence of an association between MMR vaccine and gait disturbance.", "Timing of routine immunisations and subsequent hay fever risk.", "Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever.", "Combined trivalent and bivalent measles, mumps and rubella virus vaccination. A controlled trial.", "Joint and limb symptoms in children after immunisation with measles, mumps, and rubella vaccine.", "Statistical analysis of MMR vaccine adverse events on aseptic meningitis using the case cross-over design.", "Neurologic disorders after measles-mumps-rubella vaccination.", "Risks of convulsion and aseptic meningitis following measles-mumps-rubella vaccination in the United Kingdom.", "MMR vaccination and pervasive developmental disorders: a case-control study.", "Surveillance of symptoms following MMR vaccine in children.", "An evaluation of measles, mumps and rubella vaccine in a population of Yorkshire infants.", "Frequency of true adverse reactions to measles-mumps-rubella vaccine. A double-blind placebo-controlled trial in twins.", "Trivalent combined measles-mumps-rubella vaccine. Findings in clinical-laboratory studies.", "Comparative efficacy of three mumps vaccines during disease outbreak in Eastern Switzerland: cohort study.", "Clinical and laboratory studies of combined live measles, mumps, and rubella vaccines using the RA 27/3 rubella virus.", "Vaccination history and risk of childhood leukaemia.", "Lack of association between measles-mumps-rubella vaccination and autism in children: a case-control study.", "Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study.", "A new combined trivalent live measles (AIK-C strain), mumps (Hoshino strain), and rubella (Takahashi strain) vaccine. Findings in clinical and laboratory studies.", "Comparative efficacy of Rubini, Jeryl-Lynn and Urabe mumps vaccine in an Asian population.", "A population-based study of measles, mumps, and rubella vaccination and autism.", "Childhood vaccination and type 1 diabetes.", "Clinical and serologic evaluation of measles, mumps, and rubella (HPV-77:DE-5 and RA 27/3) virus vaccines, singly and in combination.", "Evaluation of a trivalent measles, mumps, rubella vaccine in children.", "Thrombocytopenic purpura after measles, mumps and rubella vaccination: a retrospective survey by the French regional pharmacovigilance centres and pasteur-mérieux sérums et vaccins.", "Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association.", "No evidence of an increase of bacterial and viral infections following Measles, Mumps and Rubella vaccine.", "Mumps in a boarding school: description of an outbreak and control measures.", "Vaccination and allergic disease: a birth cohort study.", "No demonstrable association between the Leningrad-Zagreb mumps vaccine strain and aseptic meningitis in a large clinical trial in Egypt.", "The effectiveness of the mumps component of the MMR vaccine: a case control study.", "Outbreak of aseptic meningitis associated with mass vaccination with a urabe-containing measles-mumps-rubella vaccine: implications for immunization programs.", "Immunogenicity and efficacy of one dose measles-mumps-rubella (MMR) vaccine at twelve months of age as compared to monovalent measles vaccination at nine months followed by MMR revaccination at fifteen months of age.", "Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations.", "[Estimation of the efficacy of three strains of mumps vaccines during an epidemic of mumps in the Geneva canton (Switzerland)].", "No effect of MMR withdrawal on the incidence of autism: a total population study.", "No evidence for a new variant of measles-mumps-rubella-induced autism.", "[An epidemic outbreak of mumps. A study of vaccinal efficacy].", "Multiple sclerosis incidence in the era of measles-mumps-rubella mass vaccinations.", "A population-based case-control study on viral infections and vaccinations and subsequent multiple sclerosis risk.", "Outbreak of aseptic meningitis and mumps after mass vaccination with MMR vaccine using the Leningrad-Zagreb mumps strain.", "Illness after measles-mumps-rubella vaccination.", "Effectiveness of Jeryl Lynn-containing vaccine in Spanish children.", "Clinical evaluation of a new measles-mumps-rubella trivalent vaccine.", "Measles transmission and vaccine effectiveness during a large outbreak on a densely populated island: implications for vaccination policy.", "MMR vaccine and idiopathic thrombocytopaenic purpura.", "Risk of serious neurologic disease after immunization of young children in Britain and Ireland.", "Measles-mumps-rubella vaccination and asthma-like disease in early childhood.", "Age at first measles-mumps-rubella vaccination in children with autism and school-matched control subjects: a population-based study in metropolitan atlanta.", "Risk of immune thrombocytopenic purpura after measles-mumps-rubella immunization in children.", "Childhood vaccinations and risk of asthma.", "Association between drug and vaccine use and acute immune thrombocytopenia in childhood: a case-control study in Italy.", "Outbreak of mumps associated with poor vaccine efficacy - Oporto Portugal 1996.", "A randomised single blind trial of a combined mumps measles rubella vaccine to evaluate serological response and reactions in the UK population.", "Mumps vaccine L-Zagreb, prepared in chick fibroblasts. I. Production and field trials.", "Risk of hospitalization because of aseptic meningitis after measles-mumps-rubella vaccination in one- to two-year-old children: an analysis of the Vaccine Safety Datalink (VSD) Project.", "MMR vaccination and febrile seizures: evaluation of susceptible subgroups and long-term prognosis.", "MMR vaccine and Crohn's disease: ecological study of hospital admissions in England, 1991 to 2002.", "MMR-vaccine and regression in autism spectrum disorders: negative results presented from Japan.", "Outbreak of measles in primary school students with high first dose MMR vaccination coverage." ]

[ "MMR vaccine has been reported to cause gait disturbance, and this possible association has been claimed to support the MMR-causes-autism theory.\n To determine whether any association between gait disturbance and MMR vaccination exceeds the age related background rate of gait disturbance, using record linkage and self control case series analyses.\n MMR vaccination records were linked to hospital admission and general practitioner attendance data. An increased rate of gait problems with onset in various intervals in the 60 day period after MMR vaccination was looked for in children aged 12 to <24 months.\n No evidence of an increased rate of hospital admission or general practice consultations for gait disturbance was found in the putative post-vaccination risk periods.\n This study provides no evidence for a causal association between MMR and gait disturbance.", "Suggestions that immunisation influences allergic disease risk, either positively (pertussis) or negatively (BCG) are of concern for vaccination policy.\n To determine whether DTP, MMR, and BCG vaccination in infancy influenced hay fever risk.\n Case-control study of 7098 hay fever cases and controls, within two primary care databases. One control per case was matched for practice, age, and sex. Odds ratios (OR) were derived using conditional logistic regression.\n Compared to those completing in month 5 (base group) (39.3%), DTP unvaccinated children (4.3%) had a similar risk of hay fever (OR = 0.94, 95% CI 0.73 to 1.23). However, those completing after 12 months (4.2%) had a reduced risk (OR = 0.60, 95% CI 0.45 to 0.76) compared to the base group. Compared to those vaccinated in month 14 (base group) (29.5%), MMR unvaccinated children (2.3%) had an OR of 0.79 (95% CI 0.58 to 1.08). Completion of MMR after two years was associated with reduced hay fever risk (OR = 0.62, 95% CI 0.48 to 0.80) compared to the base group. The effects of late immunisation with DTP and MMR were independent. Those vaccinated with BCG by age 2 (2.4%) had an odds ratio of 1.28 (95% CI 0.96 to 1.70). Adjustment for consulting behaviour, social factors, or sibship size did not alter these associations.\n Immunisation against DTP or MMR does not increase the risk of hay fever. The lower confidence limit for BCG vaccination contradicts the hypothesised protective effect. The reduced risk of hay fever among children immunised late may be explained by a third factor causing both postponement and reduced risk such as intercurrent febrile illnesses.", "It has been hypothesized that early-life exposure to vaccinations, infections or antibacterials influence allergic disease development. Concurrent exposure to grass pollens may alter any effect.\n To test the hypothesis that exposure to antibacterials, vaccinations (DTP or MMR) or specific infections during the first grass pollen seasons of life influences the risk of hayfever more than at any other time of the year.\n Nested case-control studies were based on birth cohorts within two large databases of computerized patient records from UK general practices: the General Practice Research Database (GPRD) and Doctors' Independent Network (DIN). Seven thousand ninety-eight hayfever cases, diagnosed after age 2, were matched to controls for practice, age, sex and follow-up of control to case ascertainment date. Conditional logistic regression was used to compare exposure by age 1 (age 2 for MMR) inside vs. outside the grass pollen season (May, June, July). Odds ratios (ORs) were pooled across databases.\n There were no associations in either database between MMR during vs. outside the grass pollen season and later hayfever. Of 23 infections studied, none were statistically significant; although analyses for the less common conditions were limited by low statistical power. The pooled OR for hayfever comparing exposure to antibacterials only in the grass pollen season with only outside it was 1.20 (95% CI 0.98-1.47) and for DTP was 0.84 (95% CI 0.72-0.98).\n Although an interaction between early exposure to microbial agents and concurrent grass pollen exposure on hayfever risk seemed plausible, there was little evidence to support it across a range of analyses. However, the effect of DTP though weak deserves further study.", "nan", "To assess whether the combined measles, mumps, and rubella vaccine increases the incidence of joint and limb symptoms in young children.\n Comparison of six week recalled incidence of symptoms in two groups of children: children who had been immunised at the start of the six weeks, and children eligible for immunisation but who had not received it.\n South Manchester Health Authority.\n 2658 children immunised during July 1989-February 1990 and 2359 not yet immunised. Questionnaires were returned for 1846 immunised children and 1075 not immunised.\n Recalled rate of joint and limb episodes determined by postal questionnaire and later by clinical follow up.\n Compared with non-immunised children the immunised group had an increased incidence of new episodes (relative risk 1.6 (95% confidence interval (1.2 to 2.1)) and first ever episodes, though this was not significant (1.7 (0.3 to 3.5)). The risk of first episodes was increased in girls (3.5 (1.1 to 12.2)) but not in boys (1.0 (0.4 to 2.6)). Similarly, an increased risk was seen in children aged under 5 (12.0 (1.6 to 92.3)) but not in older children (0.7 (0.3 to 1.5)). Most episodes were mild and self limiting, but three immunised children required hospital referral.\n Measles, mumps, and rubella vaccine is associated with an increased risk of episodes of joint and limb symptoms, especially in girls and children under 5. The risk of frank arthritis is substantially less than after wild rubella infection.", "Vaccination is quite effective in reducing the incidence of disease. However, it may cause some adverse events. For example, one of the adverse events of measles-mumps-rubella(MMR) vaccination is the occurrence of aseptic meningitis. Since the vaccination rate is usually quite high, it is not plausible to use popular study designs such as cohort or case-control studies. We considered a case cross-over design to investigate the association between MMR vaccination and aseptic meningitis in Korean children. We used the Cochran-Mantel-Haenszel(CMH) approach, and obtained a Mantel-Haenszel odds ratio estimator as a measure of association. However, the validity of case cross-over design or the CMH approach in vaccine adverse studies has not been fully investigated. In this paper, through Monte Carlo simulation studies, we show the appropriateness of the case cross-over design and the CMH approach. We also discuss alternative approaches such as Poisson regression using offset and a simple uniformity test. In conclusion, the case cross-over design seems useful to investigate the association between vaccination and occurrence of acute adverse events.\n Copyright 2004 John Wiley & Sons, Ltd.", "The possibility of adverse neurologic events has fueled much concern about the safety of measles-mumps-rubella (MMR) vaccinations. The available evidence concerning several of the postulated complications is controversial. The aim of this study was to assess whether an association prevails between MMR vaccination and encephalitis, aseptic meningitis, and autism.\n A retrospective study based on linkage of individual MMR vaccination data with a hospital discharge register was conducted among 535 544 1- to 7-year-old children who were vaccinated between November 1982 and June 1986 in Finland. For encephalitis and aseptic meningitis, the numbers of events observed within a 3-month risk interval after vaccination were compared with the expected numbers estimated on the basis of occurrence of encephalitis and aseptic meningitis during the subsequent 3-month intervals. Changes in the overall number of hospitalizations for autism after vaccination throughout the study period were searched for. In addition, hospitalizations because of inflammatory bowel diseases were checked for the children with autism.\n Of the 535 544 children who were vaccinated, 199 were hospitalized for encephalitis, 161 for aseptic meningitis, and 352 for autistic disorders. In 9 children with encephalitis and 10 with meningitis, the disease developed within 3 months of vaccination, revealing no increased occurrence within this designated risk period. We detected no clustering of hospitalizations for autism after vaccination. None of the autistic children made hospital visits for inflammatory bowel diseases.\n We did not identify any association between MMR vaccination and encephalitis, aseptic meningitis, or autism.", "Measles-mumps-rubella (MMR) vaccines containing the Urabe strain of mumps were withdrawn in the United Kingdom in 1992 following demonstration of an increased risk of aseptic meningitis 15-35 days after vaccination. Following introduction of a replacement MMR vaccine (Priorix; GlaxoSmithKline, London, United Kingdom) in 1998, active surveillance of aseptic meningitis and convulsion was established to evaluate the risk associated with the new vaccine. No laboratory-confirmed cases of mumps meningitis were detected among children aged 12-23 months after administration of 1.6 million doses of Priorix (upper 95% confidence limit of risk: 1:437,000) in England and Wales. The upper 95% confidence limit excluded the risk found for mumps meningitis with Urabe vaccines (1:143,000 doses). No cases of aseptic meningitis were detected among children aged 12-23 months, who had received over 99,000 doses of Priorix (upper 95% confidence limit of risk: 1:27,000), in a regional database of hospital-admitted cases. This compares with an observed risk of 1:12,400 for Urabe vaccines. An elevated relative incidence of convulsion was found in the 6- to 11-day period after receipt of Priorix (relative incidence = 6.26, 95% confidence interval: 3.85, 10.18)-consistent with the known effects of the measles component of MMR vaccine-but not in the 15- to 35-day period (relative incidence = 1.48, 95% confidence interval: 0.88, 2.50) as occurred with Urabe-containing vaccines. This study demonstrates the power of active postmarketing surveillance to identify or exclude events too rare to be detected in prelicensure trials.", "Concern that measles-mumps-rubella (MMR) vaccination might cause autism has led to a fall in vaccine coverage. We investigated whether MMR vaccination is associated with an increased risk of autism or other pervasive developmental disorders.\n We did a matched case-control study using the UK General Practice Research Database. Cases were people born in 1973 or later who had first recorded diagnosis of pervasive developmental disorder while registered with a contributing general practice between 1987 and 2001. Controls were matched on age, sex, and general practice.\n 1294 cases and 4469 controls were included. 1010 cases (78.1%) had MMR vaccination recorded before diagnosis, compared with 3671 controls (82.1%) before the age at which their matched case was diagnosed. After adjustment for age at joining the database, the odds ratio for association between MMR and pervasive developmental disorder was 0.86 (95% CI 0.68-1.09). Findings were similar when restricted to children with a diagnosis of autism, to those vaccinated with MMR before the third birthday, or to the period before media coverage of the hypothesis linking MMR with autism.\n Our findings suggest that MMR vaccination is not associated with an increased risk of pervasive developmental disorders.", "nan", "In October 1988 combined measles, mumps and rubella (MMR) vaccination replaced monocomponent measles as part of the routine childhood vaccination programme in the United Kingdom. Prior to this policy change a study was undertaken in 335 children aged 15 months, to evaluate the clinical reactions and immunogenicity of the new combined MMR vaccine (Trimovax, Immravax, Merieux), in comparison with an established monocomponent measles vaccine (Rouvax, Merieux). Parents were asked to select whether their child should receive MMR vaccine or measles monocomponent; over 95% chose MMR. Children who were given the MMR vaccine had seroconversion rates of 96% for measles, 97% for mumps and 100% for rubella, whilst those who received monocomponent measles vaccine had a seroconversion rate of 100%. The number of side effects reported was similar with both vaccines; all were mild and self-limiting. The results from this study confirm the efficacy and low reactogenicity of MMR vaccine and support its use as part of the routine childhood immunisation programme in the United Kingdom.", "The vast majority of adverse reactions following immunisation of children with live measles-mumps-rubella (MMR) vaccine were shown in a double-blind, placebo-controlled, cross-over study in 581 twin pairs to be only temporally but not causally related to the vaccination. The true frequency of side-effects caused by MMR vaccine, estimated from the discordance rates of individual signs and symptoms between MMR vaccinees and their placebo-injected twins, was between 0.5 and 4.0%. Moreover, respiratory symptoms, nausea, and vomiting were observed more frequently in the placebo-injected group than in the MMR vaccinated group.", "nan", "nan", "nan", "Previous studies on vaccination and childhood leukaemia generated inconsistent results.\n In the Northern California Childhood Leukaemia Study, a case-control study with incident cases and matched birth certificate controls, detailed written vaccination records were collected. A total of 323 cases aged 0-14 years at diagnosis and 409 controls were included in this analysis. All vaccinations were censored on the reference date (date of diagnosis for cases and the corresponding date for matched controls). Conditional logistic regression analysis was conducted, adjusting for potential confounding factors. A primary variable of interest is the number of administrations (doses) of various types of vaccines.\n Vaccinations against diphtheria, pertussis, tetanus, poliomyelitis, measles, mumps, and rubella were not associated with the risk of leukaemia. The odds ratio for each dose of Haemophilus influenzae type b (Hib) vaccine was 0.81 (95% CI 0.68-0.96). Compared with children who received two or fewer doses of Hib vaccine, those who received three or more doses had a significantly reduced risk of childhood leukaemia (odds ratio = 0.55, 95% confidence interval 0.32-0.94). The number of doses of hepatitis B vaccine received was not associated with leukaemia risk.\n Hib vaccination is associated with a reduced risk of childhood leukaemia. Future studies with detailed exposure assessment and large sample sizes are needed to further address the role of vaccinations in the etiology of childhood leukaemia.", "The first objective of the study was to determine whether there is a relationship between the measles-mumps-rubella (MMR) vaccination and autism in children. The second objective was to examine whether the risk of autism differs between use of MMR and the single measles vaccine.\n Case-control study.\n The 96 cases with childhood or atypical autism, aged 2 to 15, were included into the study group. Controls consisted of 192 children individually matched to cases by year of birth, sex, and general practitioners.\n Data on autism diagnosis and vaccination history were from physicians. Data on the other probable autism risk factors were collected from mothers. Logistic conditional regression was used to assess the risk of autism resulting from vaccination. Assessment was made for children vaccinated (1) Before diagnosis of autism, and (2) Before first symptoms of autism onset. Odds ratios were adjusted to mother's age, medication during pregnancy, gestation time, perinatal injury and Apgar score.\n For children vaccinated before diagnosis, autism risk was lower in children vaccinated with MMR than in the nonvaccinated (OR: 0.17, 95% CI: 0.06-0.52) as well as to vaccinated with single measles vaccine (OR: 0.44, 95% CI: 0.22-0.91). The risk for vaccinated versus nonvaccinated (independent of vaccine type) was 0.28 (95% CI: 0.10-0.76). The risk connected with being vaccinated before onset of first symptoms was significantly lower only for MMR versus single vaccine (OR: 0.47, 95% CI: 0.22-0.99).\n The study provides evidence against the association of autism with either MMR or a single measles vaccine.", "Whole-cell pertussis (wP) and measles vaccines are effective in preventing disease but have also been suspected of increasing the risk of encephalopathy or encephalitis. Although many countries now use acellular pertussis vaccines, wP vaccine is still widely used in the developing world. It is therefore important to evaluate whether wP vaccine increases the risk of neurologic disorders.\n A retrospective case-control study was performed at 4 health maintenance organizations. Records from January 1, 1981, through December 31, 1995, were examined to identify children aged 0 to 6 years old hospitalized with encephalopathy or related conditions. The cause of the encephalopathy was categorized as known, unknown or suspected but unconfirmed. Up to 3 controls were matched to each case. Conditional logistic regression was used to analyze the relative risk of encephalopathy after vaccination with diphtheria-tetanus-pertussis (DTP) or measles-mumps-rubella (MMR) vaccines in the 90 days before disease onset as defined by chart review compared with an equivalent period among controls indexed by matching on case onset date.\n Four-hundred fifty-two cases were identified. Cases were no more likely than controls to have received either vaccine during the 90 days before disease onset. When encephalopathies of known etiology were excluded, the odds ratio for case children having received DTP within 7 days before onset of disease was 1.22 (95% confidence interval [CI] = 0.45-3.31, P = 0.693) compared with control children. For MMR in the 90 days before onset of encephalopathy, the odds ratio was 1.23 (95% confidence interval = 0.51-2.98, P = 0.647).\n In this study of more than 2 million children, DTP and MMR vaccines were not associated with an increased risk of encephalopathy after vaccination.", "Trivalent virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was administered to a total of 1369 healthy children, 8 months to 18 years of age. For comparative study, monovalent vaccines of AIK-C strain and Hoshino strain were administered to 147 and 122 initially seronegative children, respectively. The clinical and serological responses following vaccination were analyzed. Among the recipients of the trivalent vaccine, 893 were initially seronegative to all three viruses. Inoculation induced sufficient serological responses: 99.7% for measles and rubella viruses and 96.3% for mumps virus. The incidence of febrile reaction (greater than or equal to 37.5 degrees C axillary temperature) was low, 15.9%, and a temperature of 39.0 degrees C or higher occurred in only 1.3% of the subjects. The seroconversion rate, magnitude of antibody titers, and incidence of clinical reactions following the trivalent vaccination were similar to those occurring after the monovalent measles vaccination.", "The comparative efficacy of the three mumps vaccine strains (Jeryl-Lynn, Urabe and Rubini) was conducted in an Asian population from data arising from an epidemiological investigation of seven institutional outbreaks of mumps in Singapore.\n Demographic information (gender, age, ethnic group), clinical presentation and vaccination history (date and place of mumps vaccination, type of mumps vaccine received) of all children who attended the six childcare centres and one primary school where outbreaks of 20 or more cases of mumps occurred in 1999 were collected. The attack rate of the unvaccinated group and the attack rates of the vaccine groups (for each vaccine strain) were determined and the vaccine efficacy of the three vaccines calculated.\n The vaccine efficacy of the Jeryl-Lynn strain, Urabe strain and Rubini strain mumps vaccine were 80.7, 54.4 and -55.3%, respectively.\n Rubini strain mumps vaccine conferred no protection and has since been deregistered in Singapore.", "It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism.\n We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children's autism status was obtained from the Danish Psychiatric Central Register, which contains information on all diagnoses received by patients in psychiatric hospitals and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark.\n Of the 537,303 children in the cohort (representing 2,129,864 person-years), 440,655 (82.0 percent) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder and 422 with a diagnosis of other autistic-spectrum disorders. After adjustment for potential confounders, the relative risk of autistic disorder in the group of vaccinated children, as compared with the unvaccinated group, was 0.92 (95 percent confidence interval, 0.68 to 1.24), and the relative risk of another autistic-spectrum disorder was 0.83 (95 percent confidence interval, 0.65 to 1.07). There was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder.\n This study provides strong evidence against the hypothesis that MMR vaccination causes autism.\n Copyright 2002 Massachusetts Medical Society", "A link between childhood vaccinations and the development of type 1 diabetes has been proposed.\n We evaluated a cohort comprising all children born in Denmark from January 1, 1990, through December 31, 2000, for whom detailed information on vaccinations and type 1 diabetes was available. Using Poisson regression models, we estimated rate ratios according to vaccination status, including the trend associated with the number of doses, among all children and in a subgroup of children who had siblings with type 1 diabetes. Given recent claims of clustering of cases of diabetes two to four years after vaccination, we also estimated rate ratios during the period after vaccination.\n Type 1 diabetes was diagnosed in 681 children during 4,720,517 person-years of follow-up. The rate ratio for type 1 diabetes among children who received at least one dose of vaccine, as compared with unvaccinated children, was 0.91 (95 percent confidence interval, 0.74 to 1.12) for Haemophilus influenzae type b vaccine; 1.02 (95 percent confidence interval, 0.75 to 1.37) for diphtheria, tetanus, and inactivated poliovirus vaccine; 0.96 (95 percent confidence interval, 0.71 to 1.30) for diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccine; 1.06 (95 percent confidence interval, 0.80 to 1.40) for whole-cell pertussis vaccine; 1.14 (95 percent confidence interval, 0.90 to 1.45) for measles, mumps, and rubella vaccine; and 1.08 (95 percent confidence interval, 0.74 to 1.57) for oral poliovirus vaccine. The development of type 1 diabetes in genetically predisposed children (defined as those who had siblings with type 1 diabetes) was not significantly associated with vaccination. Furthermore, there was no evidence of any clustering of cases two to four years after vaccination with any vaccine.\n These results do not support a causal relation between childhood vaccination and type 1 diabetes.\n Copyright 2004 Massachusetts Medical Society", "A double-blind, placebo-controlled comparison of single component and combination measles, mumps, and rubella (HPV-77:DE-5 and RA 27/3) virus vaccines involving 502 young children was conducted. The rubella antibody response was similar with RA 27/3 rubella and measles-mumps-rubella (RA 27/3) vaccines, but was diminished with the combination vaccine that incorporated HPV-77:DE-5 rubella. There was no evidence of enhanced clinical reactivity with either of the measles-mumps-rubella vaccines.", "nan", "Thrombocytopenic purpura (TP) after vaccination with measles, mumps and rubella has occasionally been reported.\n To evaluate the incidence and characteristics of thrombocytopenic purpura reported in France after measles, mumps or rubella vaccination with monovalent or multivalent vaccines.\n A retrospective epidemiologic survey was conducted. All confirmed cases of TP reported spontaneously either to the French Regional Pharmacovigilance Centres or to the manufacturer (Pasteur-Mérieux Sérums et Vaccins) between 1984 and June 30, 1992, were reviewed.\n Sixty cases of TP in children between 1 and 11 years of age occurred 2 to 45 days after administration of 1 of 7 vaccines. The reported incidence of TP varied from 0.17 and 0.23/100,000 doses of measles or rubella vaccines, respectively, given alone to 0.87/100,000 doses of combined measles-rubella vaccines and 0.95/100,000 doses of the measles-mumps-rubella vaccine. The mean platelet count was 8000 +/- 6000/mm3 and was lower than 10,000/mm3 in 58% of cases. The immediate outcome was favorable in 89.5% of cases.\n According to the clinical course and biologic findings, vaccine-associated TP appears to be similar to that occurring after natural measles or rubella infections and is not distinguishable from acute childhood idiopathic thrombocytopenic purpura not associated with vaccination. Such observations, combined with a clear temporal relationship between measles-mumps-rubella vaccination and the occurrence of TP, make a causal relationship highly plausible. Nevertheless the incidence of these events remains relatively low with a favorable immediate outcome.", "We undertook an epidemiological study to investigate whether measles, mumps, and rubella (MMR) vaccine may be causally associated with autism.\n Children with autism born since 1979 were identified from special needs/disability registers and special schools in eight North Thames health districts, UK. Information from clinical records was linked to immunisation data held on the child health computing system. We looked for evidence of a change in trend in incidence or age at diagnosis associated with the introduction of MMR vaccination to the UK in 1988. Clustering of onsets within defined postvaccination periods was investigated by the case-series method.\n We identified 498 cases of autism (261 of core autism, 166 of atypical autism, and 71 of Asperger's syndrome). In 293 cases the diagnosis could be confirmed by the criteria of the International Classification of Diseases, tenth revision (ICD10: 214 [82%] core autism, 52 [31%] atypical autism, 27 [38%] Asperger's syndrome). There was a steady increase in cases by year of birth with no sudden \"step-up\" or change in the trend line after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no temporal association between onset of autism within 1 or 2 years after vaccination with MMR (relative incidence compared with control period 0.94 [95% CI 0.60-1.47] and 1.09 [0.79-1.52]). Developmental regression was not clustered in the months after vaccination (relative incidence within 2 months and 4 months after MMR vaccination 0.92 [0.38-2.21] and 1.00 [0.52-1.95]). No significant temporal clustering for age at onset of parental concern was seen for cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination. This appeared to be an artifact related to the difficulty of defining precisely the onset of symptoms in this disorder.\n Our analyses do not support a causal association between MMR vaccine and autism. If such an association occurs, it is so rare that it could not be identified in this large regional sample.", "The suggestion that multi-antigen vaccines might overload the immune system has led to calls for single antigen vaccines. In 2003 we showed that rather than an increase there appeared to be a reduced risk of severe bacterial infection in the three months following Measles, Mumps and Rubella vaccine (MMR). The present analysis of illnesses in a general population is based on an additional 10 years of data for bacterial infections and also includes admissions with viral infections. Analyses were carried out using the self-controlled case-series method and separately for bacterial and viral infection cases, using risk periods of 0-30 days, 31-60 days and 61-90 days post MMR vaccine. An analysis was also carried out for those cases which were given MMR and Meningococcal serogroup C (MCC) vaccines concomitantly. A reduced risk was seen in the 0-30-day period for both bacterial infection (relative incidence=0.68, 95% CI 0.54-0.86) and viral infections (relative incidence=0.68, 95% CI 0.49-0.93). There was no increased risk in any period when looking at combined viral or bacterial infections or for individual infections with the single exception of an increased risk in the 31-60 days post vaccination period for herpes infections (relative incidence=1.69, 95% CI 1.06-2.70). For the children given Meningococcal group C vaccines concomitantly no significantly increased risk was seen in either the bacterial (relative incidence=0.54, 95% CI 0.26-1.13) or viral cases (relative incidence=0.46, 95% CI 0.11-1.93). Our study confirms that the MMR vaccine does not increase the risk of invasive bacterial or viral infection in the 90 days after the vaccination and does not support the hypothesis that there is an induced immune deficiency due to overload from multi-antigen vaccines.", "The number of cases of mumps in the UK has increased during 2004-2005. Understanding why some people are more susceptible to mumps infection will help target vaccination and other control measures in the future. This paper describes a mumps outbreak in a boarding school in Scotland (October to November 2004).\n To describe the characteristics of cases in a mumps outbreak; and to conduct a case-control study looking at the effect of previous measles-mumps-rubella (MMR) vaccination.\n Descriptive epidemiology.\n Clinical, laboratory and surveillance data.\n A private school with 600 boarding and day pupils.\n Fifty cases were notified to the public health department as having mumps. Twenty of the cases (40%) were confirmed virologically, all born between 1987-1991. A matched case-control study was conducted to explore the effect of prior MMR vaccination. Compared to no vaccine, MMR protected against mumps (odds ratio = 0.7), two doses offering best protection (odds ratio = 0.5), but the study was not large enough to detect a statistically significant difference.\n Some children and young people in the UK are currently incompletely vaccinated. This outbreak illustrates the potential of a mumps outbreak to disrupt the medical, educational and social life of a school. All children should be vaccinated with two doses of MMR vaccine before school entry. Children and young people born between 1979-1991 should be given the necessary additional dose(s) of MMR vaccine.", "We examined the effect of vaccination for diphtheria; polio; pertussis and tetanus; or measles, mumps, and rubella on the incidence of physician-diagnosed asthma and eczema.\n We used a previously established birth cohort in the West Midlands General Practice research database.\n We found an association between vaccination and the development of allergic disease; however, this association was present only among children with the fewest physician visits and can be explained by this factor.\n Our data suggest that currently recommended routine vaccinations are not a risk factor for asthma or eczema.", "To address the claim that the Leningrad-Zagreb (L-Z) mumps vaccine strain is causally associated with aseptic meningitis, a prospective, post-marketing safety study was conducted with a measles-mumps-rubella vaccine (MMR) (TRESIVAC(R); Serum Institute of India Ltd., Pune, India), which uses the L-Z strain as its mumps component in Egypt. In all, 453 119 children (65 423 children aged 16-24 months and 329 211 children aged 5-7 years) received MMR. The control groups which, as a result of local health regulations, were slightly younger than vaccinees, comprised 12 253 and 46 232 children, respectively. Using questionnaires, the parents recorded solicited local, systemic and neurological adverse events for up to 42 days post-vaccination. All data were analysed externally on an intention-to-treat basis by individuals not participating in the study. Local and/or systemic reactions were reported in a small percentage of participants, with pain, fever and parotitis being the most common signs among vaccinees in both age groups. No case of aseptic meningitis, encephalitis, anaphylaxis or convulsions was observed in any participant. Thus, in this series of more than 450 000 Egyptian children, the L-Z mumps vaccine strain in this vaccine did not cause aseptic meningitis. The vaccine is considerably cheaper than Western competitors and a valid alternative to other MMR vaccines.", "In 1998/1999, an outbreak of mumps occurred among children of a religious community in North East London. A case control study was conducted to assess the effectiveness of the mumps component of the MMR vaccine. One hundred and sixty-one cases of mumps were identified and 192 controls were selected. Fifty-one percent of cases and 77% of controls had a history at least one MMR vaccination. The observed effectiveness of any MMR vaccination adjusted for age, sex and general practice was 69% (95% CI: 41-84%). This is consistent with the results of other observational studies of mumps containing vaccines, but lower than the immunogenicity of mumps vaccines reported by clinical trials. This discrepancy is because observational studies tend to underestimate vaccine effectiveness, and because immunogenicity is not necessarily an accurate biological marker of vaccine effectiveness. Two doses of vaccine were more effective (88% (95% CI: 62-96%)) than a single dose (64% (95% CI: 40-78%)). The current two-dose vaccination programme remains the best method for controlling mumps infection in the community.", "A mass immunization campaign with a Urabe-containing measles-mumps-rubella vaccine was carried out in 1997 in the city of Salvador, northeastern Brazil, with a target population of children aged 1-11 years. There was an outbreak of aseptic meningitis following the mass campaign. Cases of aseptic meningitis were ascertained through data collected from the records of children admitted to the local referral hospital for infectious diseases between March and October of 1997, using previously defined eligibility criteria. Vaccination histories were obtained through home visits or telephone calls. Eighty-seven cases fulfilled the study criteria. Of those, 58 cases were diagnosed after the vaccination campaign. An elevated risk of aseptic meningitis was observed 3 weeks after Brazil's national vaccination day compared with the risk in the prevaccination period (relative risk = 14.3; 95% confidence interval: 7.9, 25.7). This result was confirmed by a case series analysis (relative risk = 30.4; 95% confidence interval: 11.5, 80.8). The estimated risk of aseptic meningitis was 1 in 14,000 doses. This study confirms a link between measles-mumps-rubella vaccination and aseptic meningitis. The authors discuss the implications of this for the organization and planning of mass immunization campaigns.", "measles is a common cause of morbidity and mortality in developing countries. Although the measles-mumps-rubella vaccine (MMR) is currently in use in developed countries, monovalent measles vaccine (MV) is routinely recommended by World Health Organization (WHO) at 9 months of age in Turkey, as in many other developing countries. In this study, 442 Turkish children received MV at 9 months of age and were revaccinated with MMR vaccine at 15 months of age. In the second group 495 children received MMR at 12 months of age with no earlier measles vaccination. Antibodies were measured before the first vaccination and 6 weeks after the MMR. All children had been followed for occurrence of measles infection for 60 months. Two vaccination schedules were compared for immunogenicity and protection rates.\n seroconversion and clinical protection rates were significantly higher in children who received only MMR at 12 months of age than in children revaccinated at 15 months of age. Seroconversion rate for measles was 69.9% in children who received MMR at 12 months of age and 90.3% in children revaccinated at 15 months of age (P=0.0003). While there was no measles case in children who were revaccinated, 12 (2.7%) children in the first group acquired measles during the follow-up period. Vaccination at 12 months of age appeared to be better than the current national standard. The late elimination of maternal antibodies and the inhibitory effect of a weak antibody response after the first dose of vaccine at 9 months may explain the better immunogenicity and efficacy of the MMR vaccine given at 12 months of age.", "The prevalence of pervasive developmental disorders has increased in recent years. Links with the measles component of the measles-mumps-rubella vaccine and the cumulative exposure to thimerosal through other vaccines have been postulated.\n The purpose of this work was to estimate the pervasive developmental disorder prevalence in Montreal, Canada, in cohorts born from 1987 to 1998 and evaluate the relationship of trends in pervasive developmental disorder rates with: (1) changes in cumulative exposure to ethylmercury (thimerosal) occurring through modifications in the immunization schedule of young children and (2) trends in measles-mumps-rubella vaccination use rates and the introduction of a 2-measles-mumps-rubella dosing schedule during the study period.\n We surveyed 27749 children born from 1987 to 1998 attending 55 schools from the largest Anglophone school board. Children with pervasive developmental disorders were identified by a special needs team. The cumulative exposure by age 2 years to thimerosal was calculated for 1987-1998 birth cohorts. Ethylmercury exposure ranged from medium (100-125 microg) from 1987 to 1991 to high (200-225 microg) from 1992 to 1995 to nil from 1996 onwards when thimerosal was entirely discontinued. Measles-mumps-rubella coverage for each birth cohort was estimated through surveys of vaccination rates. The immunization schedule included a measles-mumps-rubella single dose at 12 months of age up to 1995, and a second measles-mumps-rubella dose at 18 months of age was added on after 1996.\n We found 180 children (82.8% males) with a pervasive developmental disorder diagnosis who attended the surveyed schools, yielding a prevalence for pervasive developmental disorder of 64.9 per 10000. The prevalence for specific pervasive developmental disorder subtypes were, for autistic disorder: 21.6 of 10000; for pervasive developmental disorder not otherwise specified: 32.8 of 10000; and for Asperger syndrome: 10.1 of 10000. A statistically significant linear increase in pervasive developmental disorder prevalence was noted during the study period. The prevalence of pervasive developmental disorder in thimerosal-free birth cohorts was significantly higher than that in thimerosal-exposed cohorts (82.7 of 10000 vs 59.5 of 10000). Using logistic regression models of the prevalence data, we found no significant effect of thimerosal exposure used either as a continuous or a categorical variable. Thus, thimerosal exposure was unrelated to the increasing trend in pervasive developmental disorder prevalence. These results were robust when additional analyses were performed to address possible limitations because of the ecological nature of the data and to evaluate potential effects of misclassification on exposure or diagnosis. Measles-mumps-rubella vaccination coverage averaged 93% during the study interval with a statistically significant decreasing trend from 96.1% in the older birth cohorts (1988-89) to approximately 92.4% in younger birth cohorts (1996-1998). Thus, pervasive developmental disorder rates significantly increased when measles-mumps-rubella vaccination uptake rates significantly decreased. In addition, pervasive developmental disorder prevalence increased at the same rate before and after the introduction in 1996 of the second measles-mumps-rubella dose, suggesting no increased risk of pervasive developmental disorder associated with a 2-measles-mumps-rubella dosing schedule before age 2 years. Results held true when additional analyses were performed to test for the potential effects of misclassification on exposure or diagnostic status. Thus, no relationship was found between pervasive developmental disorder rates and 1- or 2-dose measles-mumps-rubella immunization schedule.\n The prevalence of pervasive developmental disorder in Montreal was high, increasing in recent birth cohorts as found in most countries. Factors accounting for the increase include a broadening of diagnostic concepts and criteria, increased awareness and, therefore, better identification of children with pervasive developmental disorders in communities and epidemiologic surveys, and improved access to services. The findings ruled out an association between pervasive developmental disorder and either high levels of ethylmercury exposure comparable with those experienced in the United States in the 1990s or 1- or 2-dose measles-mumps-rubella vaccinations.", "The number of mumps cases reported in Switzerland markedly increased from 1993 to 1995 although vaccination coverage against mumps had risen steadily since the national MMR immunization program was launched in 1987. In 1991, an estimated 80% of children 27 to 36 month-old were immunized against mumps. The purpose of the present study was to assess the hypothesis that the epidemic was the consequence of a low vaccine efficacy of the Rubini strain--a mumps vaccine strain that has been widely used in Switzerland.\n Vaccine efficacy was assessed by measuring secondary attack rates among immunized and nonimmunized children 16 year-old or younger who wre family contacts of cases.\n From February 1993 to April 1996, Geneva pediatricians reported 283 primary cases of mumps and 63 secondary cases. Estimate of vaccine efficacy was equal to 6.3% (95% CI: -45.9; 39.8) for the Rubini strain, as compared to 73.1% (95% CI: 41.8; 87.6) for the Urabe Am 9 strain, and 61.6% (95% CI: 0.0; 85.4) for the Jeryl Lynn strain, two vaccine strains of mumps that had also been used in Geneva.\n Our study supports the hypothesis that the Rubini vaccine strain of mumps does not confer sufficient long-lasting protection against mumps.", "A causal relationship between the measles, mumps, and rubella (MMR) vaccine and occurrence of autism spectrum disorders (ASD) has been claimed, based on an increase in ASD in the USA and the UK after introduction of the MMR vaccine. However, the possibility that this increase is coincidental has not been eliminated. The unique circumstances of a Japanese MMR vaccination program provide an opportunity for comparison of ASD incidence before and after termination of the program.\n This study examined cumulative incidence of ASD up to age seven for children born from 1988 to 1996 in Kohoku Ward (population approximately 300,000), Yokohama, Japan. ASD cases included all cases of pervasive developmental disorders according to ICD-10 guidelines.\n The MMR vaccination rate in the city of Yokohama declined significantly in the birth cohorts of years 1988 through 1992, and not a single vaccination was administered in 1993 or thereafter. In contrast, cumulative incidence of ASD up to age seven increased significantly in the birth cohorts of years 1988 through 1996 and most notably rose dramatically beginning with the birth cohort of 1993.\n The significance of this finding is that MMR vaccination is most unlikely to be a main cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD.", "A link has been postulated between measles-mumps-rubella (MMR) vaccine and a form of autism that is a combination of developmental regression and gastrointestinal symptoms that occur shortly after immunization. This hypothesis has involved 3 separate claims: 1) that there is new phenotype of autism involving regression and gastrointestinal symptoms, 2) that this new variant is responsible for the alleged rise of autism rates, and 3) that this phenotype is associated with biological findings suggestive of the persistence of measles infection. We tested the first of these claims. If this new \"autistic enterocolitis\" syndrome had some validity, then 1 or several of the following 6 predictions should be supported by empirical data: 1) childhood disintegrative disorder has become more frequent, 2) the mean age of first parental concern for autistic children who are exposed to MMR is closer to the mean immunization age than in children who are not exposed to MMR, 3) regression in the development of children with autism has become more common in MMR-vaccinated children, 4) the age of onset for autistic children with regression clusters around the MMR immunization date and is different from that of autistic children without regression, 5) children with regressive autism have distinct symptom and severity profiles, and 6) regressive autism is associated with gastrointestinal symptoms and/or inflammatory bowel disorder.\n Three samples were used. Epidemiologic data on 96 children (95 immunized with MMR at a median age of 13.5 months) who were born between 1992 and 1995 and had a pervasive developmental disorder diagnosis as reported in a recent UK survey (post-MMR sample) were compared with data from 2 previous clinical samples (1 pre-MMR [n = 98] and 1 post-MMR [n = 68]) of autistic patients. All patients were assessed with the standardized Autism Diagnostic Interview (ADI), allowing rigorous comparison of age at first parental concerns and rates of regression across samples. Reliability was excellent on ADI scores, age of parental concern, and developmental regression. Furthermore, data on bowel symptoms and disorders were available in the epidemiologic survey from both pediatric and parental sources, and immunization dates were obtained from computerized records.\n The prevalence of childhood disintegrative disorder was 0.6/10 000 (95% confidence interval: 0.02-3.6/10 000); this very low rate is consistent with previous estimates and is not suggestive of an increased frequency of this form of pervasive developmental disorder in samples of children who are immunized with MMR. There was no difference in the mean age at first parental concern between the 2 samples exposed to MMR (19.3 and 19.2 months) and the pre-MMR sample (19.5 months). Thus, MMR immunization was not associated with a shift toward an earlier age for first parental concerns. Similarly, the rate of developmental regression reported in the post-MMR sample (15.6%) was not different from that in the pre-MMR sample (18.4%); therefore, there was no suggestion that regression in the developmental course of autism had increased in frequency since MMR was introduced. In the epidemiologic sample, the subset of autistic children with regression had no other developmental or clinical characteristics, which would have argued for a specific, etiologically distinct phenotype. Parents of autistic children with developmental regression detected the first symptoms at a very similar age (19.8 months) to those of autistic children without regression (19.3 months). Moreover, the mean intervals from MMR immunization to parental recognition of autistic symptoms were comparable in autistic children with or without regression (248 vs 272 days; not significant). In the epidemiologic sample, gastrointestinal symptoms were reported in 18.8% of children. Constipation was the most common symptom (9.4%), and no inflammatory bowel disorder was reported. Furthermore, there was no association between developmental regression and gastrointestinal symptoms (odds ratio: 0.63; 95% confidence interval: 0.06-3.2; not significant), and only 2.1% of the sample experienced both problems, a rate that did not exceed chance expectations.\n No evidence was found to support a distinct syndrome of MMR-induced autism or of \"autistic enterocolitis.\" These results add to the recent accumulation of large-scale epidemiologic studies that all failed to support an association between MMR and autism at population level. When combined, the current findings do not argue for changes in current immunization programs and recommendations.", "Description of an outbreak of mumps in an urban area. Study of the effectiveness of the mumps component of the triple virus (TV) vaccination.\n Cross sectional descriptive study of the outbreak. The cases were obtained from the Andalusian Register of Infectious Diseases (SVEA in Spanish). The effectiveness of the vaccine was studied through a retrospective cohort design, with the cohorts defined according to their vaccination history.\n Urban area of low social class and income and young population pyramid. The outbreak occurred between March and November 1997. The effectiveness of vaccination at one school was studied. PATIENTS AND OTHER PARTICIPANTS, RESIDENTS IN THE AREA: The source of the population was the 1996 municipal census.\n The declared cases of mumps were taken from the SVEA. The state of vaccination was documented through a review of the school registration records, vaccination cards and the health centre register of names.\n A total of 283 cases of mumps were declared. There were more cases in the 0-10 age group than at older ages. 79% of cases were vaccinated (95% CI, 74.3-73.7). Effectiveness of a dose of the mumps component of the vaccine was low (46%; CI, 0-84), though the effectiveness of a second dose was higher (87%; CI, 27-99).\n The low effectiveness of the mumps component of the TV vaccination was confirmed. It is proposed that the age for the second dose should be brought forward to school-starting age (primary, first year). Ensuring school vaccination is recommended.", "Viral childhood infections may be involved in the multiple sclerosis (MS) pathogenesis. Following national Swedish vaccination programs, measles sharply declined in the 1970s, and measles, mumps, and rubella were virtually eliminated in cohorts born from 1981.\n To examine whether the vaccination induced reduction in these infections influences the MS incidence. In addition, the public health aspect justified an early evaluation of beneficial as well as harmful effects of mass vaccinations.\n From an incidence material of 534 MS patients, born 1959-1990, we selected one unvaccinated cohort and four cohorts, each corresponding to a vaccination program (MS patients = 251).\n With the ability to detect a decrease by 30-35%, and an increase by 37-48% in the MS incidence in the first three cohorts, we found no vaccination related MS incidence changes. The background MS incidence showed a significant gradual age dependent increase.\n While the present follow-up provided limited power in the last cohort, there is no evidence as yet that the radical decline in three viral infections influenced the MS incidence. However, the increasing background MS incidence of unknown cause may have concealed a reduction in MS risk associated with mass vaccinations.", "Viral infections are probably involved in the pathogenesis of multiple sclerosis (MS). A recent cohort study in the Gothenburg population revealed no change in MS incidence associated with the introduction of the Swedish measles, mumps and rubella vaccination programmes. The aim of the present study was to clarify whether these infections or vaccinations, and two other infections, varicella and infectious mononucleosis, influence MS risk. We performed a population-based case-control study in Gothenburg that included 509 MS cases and 2,067 controls, born 1959-1986. Data on infections and vaccinations were obtained from questionnaires and from child health and school health records. We found no significant associations between measles, mumps, rubella or varicella and MS risk. These results were consistent between the two source materials. Infectious mononucleosis was associated with significantly higher MS risk (odds ratio 2.03, 95% CI 1.52-2.73). Overall, there was no significant association between measles-mumps-rubella (MMR) vaccination and MS risk, while those MMR vaccinated before age ten only were at significantly higher MS risk (odds ratio 4.92, 95% CI 1.97-12.20). Those MMR vaccinated both before and after age ten had intermediate MS risk. Infection with measles, mumps, rubella and varicella did not influence MS risk in contrast to infectious mononucleosis which conferred doubled MS risk. The association with 'early' MMR vaccination only was an isolated finding, limited by a small number of subjects and multiple testing. Most likely this was a chance finding. Future studies could investigate it on an a priori basis.", "Data from routine surveillance during two mass immunisation campaigns (MIC) with Measles-mumps-rubella (MMR)vaccine using Leningrad-Zagreb mumps strain in two states in Brazil were analysed to estimate the risk of vaccine-related meningitis and mumps. Increase in the incidence of the two diseases was observed in both states, 3 weeks after the vaccination campaigns. The estimated number of doses applied per one case of vaccine-related meningitis ranged from 6199 (95% CI: 4854-8058) to 19,247 (95% CI: 12,648-29,513) depending on the diagnostic criteria used and state. It was 300 doses (95% CI: 286-317) for each case of mumps. The implications for vaccination policy are discussed.", "To provide accurate information on the common sequelae of measles-mumps-rubella (MMR) vaccination and to compare post-vaccine symptoms in children vaccinated at 13 and 15 months.\n Prospective cluster randomized controlled trial.\n Twenty-two family practices in southwestern Ontario.\n All 376 infants who were due to receive MMR vaccine in the next year, 253 (67.3%) successfully completed the study.\n MMR vaccine administered at 13 months by half of the family physicians and at 15 months by the remaining half.\n Family physician's physical findings in children 7 days and 30 days after vaccine; reported illnesses by mothers in a daily diary in the month before and after vaccination and medical records of visits to family physicians and hospital admissions in the month before and after vaccination.\n Compared with the incidence rates in the corresponding weeks before vaccination, the rates of lymphadenopathy (23.8%) and fever (16.8%) were higher 1 week afterward and the rate of rash (26.9%) was higher 7 to 14 days afterward. Fewer health problems were reported in the third and fourth weeks after vaccination than in the corresponding weeks beforehand. Hospital admissions after vaccination were no more frequent than those before once cause and time of admission were taken into account. The two age groups did not differ in any of the outcomes.\n Mothers should be informed about the possibility of increased physical findings in the weeks after MMR vaccination, especially lymphadenopathy, nasal discharge and rash. Since the occurrence of sequelae does not seem to differ significantly between 13-month-old recipients and 15-month-old recipients, it should not influence the decision of when to administer the vaccine.", "We evaluated the effectiveness of the Jeryl Lynn strain vaccine in a large outbreak of mumps in Navarre, Spain, 2006-2008. Each of the 241 cases of mumps occurring in children over 15 months of age born between 1998 and 2005 was compared with 5 controls individually matched by sex, birth date, district of residence and paediatrician. Vaccination history was obtained blindly from clinical records. Conditional logistic regression was used to obtain the matched odds ratios (ORs), and effectiveness was calculated as 1-OR. Some 70% of cases had received one dose of measles-mumps-rubella vaccine, and 24% had received two doses. Overall vaccine effectiveness was 72% (95% CI, 39-87%). Two doses were more effective (83%; 54-94%) than a single dose (66%; 25-85%). Among vaccinated children, risk was higher in those who had received the first dose after 36 months of age (OR=3.1; 1.2-8.4) and those who had received the second dose 3 or more years before study enrolment (OR=10.2; 1.5-70.7). Early waning of immunity in children after the second dose may contribute to reduced vaccine effectiveness for mumps prevention.", "In a series of clinical studies of a combined measles (Schwarz strain), mumps (Jeryl Lynn strain), and rubella (Cendehill strain) vaccine, 1,481 children received the vaccine or a placebo. The vaccine did not cause any significant reactions. The frequencies of mild, transient fever or rash or both in triple-susceptible vaccinees were similar to those that follow use of Schwarz strain measles vaccine alone. Measles, mumps, and rubella seroconversion rates in triple-susceptible vaccinees ranged from 95% to 100%. Geometric mean antibody titers were as high as those that usually result from use of these same virus strains as monovalent vaccines.", "The Republic of the Marshall Islands (RMI) is a South Pacific nation freely associated with the United States. In 2003, the RMI experienced the largest measles outbreak within the United States or its associated areas for more than a decade, although the reported coverage of 1-dose measles-mumps-rubella (MMR) vaccine was 80%-93%. The outbreak ended only after vaccination of >35,000 persons among a population of 51,000. Of outbreak cases, 41% were reported to have been previously vaccinated. We studied measles attack rates in RMI households to assess vaccine effectiveness and patterns of disease transmission.\n For the household secondary attack rate study, households were selected by convenience sampling of outbreak measles cases. The primary case was defined as the first person with measles in a household. Secondary cases were household members with measles onset 7-18 days after the primary case's rash onset. Vaccine effectiveness analysis was limited to children aged 6 months to 14 years, with vaccination status verified against written records.\n Seventy-two households were included in the study. The median household size was 11 persons, and the median number of persons per room was 5.5. Secondary cases were more likely than primary cases to be infants (46% vs. 13%; P=.03). MMR vaccine effectiveness was 92% (95% confidence interval [CI], 67%-98%) for 1 dose and 95% (95% CI, 82%-98%) for 2 doses.\n Measles vaccine effectiveness was high; thus, diminished effectiveness was not the main cause of the outbreak. In communities with high population density and household crowding, very high population immunity is needed to prevent measles outbreaks and to protect infants below the age of vaccination. This may require excellent implementation of a routine 2-dose measles vaccination strategy.", "To estimate the relationship between idiopathic thrombocytopaenic purpura (ITP) and the measles, mumps and rubella (MMR) vaccination in children; calculating the relative risk estimate for ITP with in 6 weeks after MMR vaccination and the attributable risk of ITP within 6 weeks after MMR vaccination.\n Using the General Practice Research Database we identified children with a first-time diagnosis of ITP from a base population of children aged less than 6 years between January 1988 and December 1999. After describing the characteristics of all the children identified with ITP, we focused on cases aged 13-24 months to perform a population-based, case-control analysis to estimate the relative risk of developing ITP within 6 weeks after MMR vaccination. We also calculated the risk of ITP attributable to the MMR vaccination.\n Sixty-three children with a first time diagnosis of ITP were identified; 23 cases were between 13 and 24 months old. The relative risk estimate for ITP within 6 weeks after MMR vaccination, compared to the combined group of unvaccinated children and children vaccinated with MMR more than 26 weeks previously was 6.3 (95% CI 1.3-30.1). The attributable risk of developing ITP within 6 weeks after MMR vaccination was estimated to be 1 in 25,000 vaccinations (95% confidence interval 21,300, 89,400).\n This study confirms the increased risk of ITP within 6 weeks after MMR vaccination. However, the attributable risk of ITP within 6 weeks after MMR vaccination is low.", "We sought to investigate the risk of serious neurologic disease after immunization in early childhood.\n The results of a 3-year prospective study of children (2-35 months old) in Britain and Ireland with encephalitis and/or severe illness with convulsions and fever were linked to each child's vaccine history. Cases were reported via the British Paediatric Surveillance Unit's network. The self-controlled case-series method was used to investigate associations between immunization and acute potential adverse events. The risk periods investigated were 0 to 3 and 0 to 7 days post-diphtheria, tetanus, whole cell pertussis, Haemophilus influenzae type b or meningococcal C conjugate vaccine and 6 to 11 and 15 to 35 days post-measles, mumps, rubella vaccine.\n A total of 157 disease episodes from 155 children met the analytical case definition. There were 11 cases of herpes simplex encephalitis and 23 cases of primary human herpesvirus 6 and/or 7 infection. There was no evidence of a raised relative incidence of serious neurologic disease in any of the specified risk periods with the exception of a raised relative incidence of 5.68 in the 6-11 days after measles, mumps, rubella vaccine. Based on this relative incidence, between 3 and 6 of the 6 cases in this period were estimated to be attributable to the vaccine with a best estimate of 5. The 6 cases all had fever with convulsions lasting >30 minutes; in all but 1, there was complete recovery by discharge from hospital. Of the 5 patients who recovered, 1 had a concurrent primary human herpesvirus 6 infection and one a primary human herpesvirus 7.\n Six to 11 days after measles, mumps, rubella vaccine there is an increased risk of fever and convulsions lasting >30 minutes. All 6 of the episodes temporally related to immunization met the criteria for complex febrile convulsions. The estimated attributable risk of serious neurological disease was similar to that previously found for measles vaccine.", "The authors evaluated the association between receipt of measles-mumps-rubella (MMR) vaccine and asthma-like disease in early childhood in a Danish nationwide cohort study (N = 871,234). Two outcomes were included: hospitalizations with asthma diagnoses and use of anti-asthma medications (for a subset of the cohort only). Poisson regression was used to estimate rate ratios according to vaccination status. MMR-vaccinated children were less often hospitalized with an asthma diagnosis (rate ratio (RR) = 0.75, 95% confidence interval (CI): 0.73, 0.78) and used fewer courses of anti-asthma medication (RR = 0.92, 95% CI: 0.91, 0.92) than unvaccinated children. This \"protective\" effect of MMR vaccine was more pronounced for hospitalizations with severe asthma diagnoses (status asthmaticus: RR = 0.63, 95% CI: 0.49, 0.82) and use of medication that was highly specific for asthma (long-acting beta2-agonist inhalant: RR = 0.68, 95% CI: 0.63, 0.73). MMR vaccine was not negatively associated with anti-asthma medications often used for wheezing illnesses in early childhood (systemic beta2-agonist: RR = 1.02, 95% CI: 1.01, 1.02). These results are compatible not with an increased risk of asthma following MMR vaccination but rather with the hypothesis that MMR vaccination is associated with a reduced risk of asthma-like disease in young children.", "To compare ages at first measles-mumps-rubella (MMR) vaccination between children with autism and children who did not have autism in the total population and in selected subgroups, including children with regression in development.\n A case-control study was conducted in metropolitan Atlanta. Case children (N = 624) were identified from multiple sources and matched to control children (N = 1824) on age, gender, and school. Vaccination data were abstracted from immunization forms required for school entry. Records of children who were born in Georgia were linked to Georgia birth certificates for information on maternal and birth factors. Conditional logistic regression was used to estimate odds ratios (ORs).\n The overall distribution of ages at MMR vaccination among children with autism was similar to that of matched control children; most case (70.5%) and control children (67.5%) were vaccinated between 12 and 17 months of age. Similar proportions of case and control children had been vaccinated before 18 or before 24 months. No significant associations for either of these age cutoffs were found for specific case subgroups, including those with evidence of developmental regression. More case (93.4%) than control children (90.6%) were vaccinated before 36 months (OR: 1.49; 95% confidence interval: 1.04-2.14 in the total sample; OR: 1.23; 95% confidence interval: 0.64-2.36 in the birth certificate sample). This association was strongest in the 3- to 5-year age group.\n Similar proportions of case and control children were vaccinated by the recommended age or shortly after (ie, before 18 months) and before the age by which atypical development is usually recognized in children with autism (ie, 24 months). Vaccination before 36 months was more common among case children than control children, especially among children 3 to 5 years of age, likely reflecting immunization requirements for enrollment in early intervention programs.", "The measles-mumps-rubella vaccine has been associated with immune thrombocytopenia purpura in 2 small studies.\n By using the Vaccine Safety Datalink, we identified measles-mumps-rubella-vaccinated children aged 1 to 18. A case of immune thrombocytopenia purpura was defined as a patient with a platelet count of < or = 50,000/microL with clinical bleeding and normal red and white blood cell indices. The immune thrombocytopenia purpura incidence rates during exposed (42 days after vaccination) and unexposed time periods were determined. A retrospective cohort of vaccinated children was used to determine incident rate ratios for children aged 1 to 18 years, 12 to 23 months, and 12 to 15 months.\n A total of 1,036,689 children received 1,107,814 measles-mumps-rubella vaccinations; there were 259 confirmed patients with immune thrombocytopenia purpura. Because only 5 exposed cases occurred after age 2, analyses were limited to children aged 12 to 23 months. Exposed patients aged 12 to 23 months had lower median platelet counts than those who were unexposed and had similar median duration of illness (11 vs 10 days). The incident rate ratio was highest for children aged 12 to 15 months at 7.10. The incident rate ratio for boys aged 12 to 15 months was 14.59, and the incident rate ratio for girls in the same age group was 3.22. Seventy-six percent of immune thrombocytopenia purpura cases in children aged 12 to 23 months were attributable to measles-mumps-rubella vaccination. This vaccine causes 1 case of immune thrombocytopenia purpura per every 40,000 doses.\n Measles-mumps-rubella vaccine that is given in the second year of life is associated with an increased risk of immune thrombocytopenia purpura.", "A few previous studies have suggested that childhood vaccines, particularly whole cell pertussis vaccine, may increase the risk of asthma. We evaluated the suggested association between childhood vaccinations and risk of asthma.\n Cohort study involving 167,240 children who were enrolled in 4 large health maintenance organizations during 1991 to 1997, with follow-up from birth until at least 18 months to a maximum of 6 years of age. Vaccinations were ascertained through computerized immunization tracking systems, and onset of asthma was identified through computerized data on medical care encounters and medication dispensings.\n In the study 18,407 children (11.0%) developed asthma, with a median age at onset of 11 months. The relative risks (95% confidence intervals) of asthma were: 0.92 (0.83 to 1.02) for diphtheria, tetanus and whole cell pertussis vaccine; 1.09 (0.9 to 1.23) for oral polio vaccine; 0.97 (0.91 to 1.04) for measles, mumps and rubella (MMR) vaccine; 1.18 (1.02 to 1.36) for Haemophilus influenzae type b (Hib); and 1.20 (1.13 to 1.27) for hepatitis B vaccine. The Hib result was not consistent across health maintenance organizations. In a subanalysis restricted to children who had at least 2 medical care encounters during their first year, the relative risks decreased to 1.07 (0.71 to 1.60) for Hib and 1.09 (0.88 to 1.34) for hepatitis B vaccine.\n There is no association between diphtheria, tetanus and whole cell pertussis vaccine, oral polio vaccine or measles, mumps and rubella vaccine and the risk of asthma. The weak associations for Hib and hepatitis B vaccines seem to be at least partially accounted for by health care utilization or information bias.", "Immune thrombocytopenic purpura (ITP) is an immunomediated disease characterized by a decrease in platelet count and, in its more severe forms, by bleeding symptoms. Many drugs have been implicated in the pathogenesis of drug-induced thrombocytopenia in adults; only limited data on drug-related ITP in children have been published. Our study was set up to evaluate the consistency of the association between drug and vaccine use and ITP in children. This study is part of an Italian multicentre study on adverse drug reactions in children, coordinated by the Italian National Institute of Health, which was started in November 1999 and is ongoing. The study was conducted by enrolling all children aged more than 1 month who were hospitalized through the paediatric emergency department for the following conditions: thrombocytopenia (platelet count <100 x 103/L); acute neurological disorders; non-infectious mucocutaneous diseases and vasculitis; and endoscopically confirmed gastroduodenal lesions and/or clinically defined haematemesis and melaena. Children with chronic pathologies or concomitant diagnoses of cancer or immunodeficiency were not included in our study. During hospital admission, a physician interviewed parents using a structured questionnaire. The main aim of the interview was to collect information on drug exposure in a time period of 3 weeks and vaccine exposure in a period of 6 weeks preceding hospitalization. Using a case-control study design, exposure of children with thrombocytopenia (cases) to drugs and vaccines was compared with similar exposure of children with gastroduodenal lesions and neurological disorders (controls); this allowed us to estimate the odds ratios (ORs) of the occurrence of thrombocytopenia associated with the use of drugs or vaccines. Up to December 2007, the study population included 387 cases of thrombocytopenia and 1924 controls. Despite the low platelet count, ITP was generally a mild disease, without serious bleeding in the majority of cases and associated with a short length of hospital stay. After adjusting for concurrent use of other drugs, use of the antibacterials was associated with a more than 2-fold increase in the risk of developing ITP (OR 2.4; 95% CI 1.8, 3.1). Mucolytics and NSAIDs were associated with an OR of 1.9; 95% CI 1.2, 2.9 and 1.5; 95% CI 1.0, 2.1 respectively, while paracetamol (acetaminophen) was associated with an OR of 1.5; 95% CI 1.2, 2.0. MMR vaccination was associated with an increased risk of developing ITP (OR 2.4; 95% CI 1.2, 4.7). The results of this study provide evidence for an association between ITP and exposure to selected antibacterials, NSAIDs, paracetamol, mucolytics and MMR vaccination.", "Vaccination against mumps in Portugal began in 1987, with the introduction of the combined measles, mumps, and rubella vaccine (MMR) in the national vaccination programme (Programa Nacional de Vacinacao: PNV) for both sexes at 15 months. In November 1990,", "Four hundred and twenty children were randomly assigned to receive either mumps measles rubella (MMR) vaccine (207) or measles vaccine (213) in a single blind study, to investigate the reactogenicity and serology of the MMR vaccine. There was no significant difference between the number of children developing symptoms after MMR vaccination to those developing symptoms after measles vaccination. Both vaccines are associated with a rash, temperature and restlessness five to thirteen days after vaccination. The serological response to measles vaccine was similar in both groups with 92-6% seroconverting with MMR, and 96-8% with measles. Seroconvertion against mumps and rubella with the MMR vaccine was 88% and 96% respectively. This study confirms the safety and efficacy of the MMR vaccine in a UK population.", "Leningrad-L3 Mumps Vaccine virus has been further attenuated by adaptation and passage on SPF chick embryo fibroblast cell cultures. This new mumps strain has been designated L-Zagreb and has been used to prepare mumps vaccines which meet the WHO requirements. Observations during both the field trial period prior to registration and during the later use of the vaccine showed that the few reactions observed were mild and that seroconversion was obtained in 88-98% of vaccines. The morbidity of mumps in Croatia declined more than tenfold after the introduction of the new vaccine. During a mumps epidemic, vaccine efficiency was calculated to be 97-100%.", "To assess the level of increased risk, if any, of hospitalizations for aseptic meningitis after Jeryl-Lynn mumps strain measles-mumps-rubella (MMR) vaccine in the Vaccine Safety Datalink population.\n A possible increased risk of aseptic meningitis 8 to 14 days after receipt of MMR was observed in a preliminary screening analysis of automated data from the Vaccine Safety Datalink (VSD) project Year 2 analysis. To further evaluate this association a retrospective 10-year matched case-control study was undertaken in the four health maintenance organizations (HMOs) in the VSD project. Cases ascertained from a broad scan of the automated data were validated against a standard case definition. Two controls matched on age, sex, HMO and HMO membership were assigned per case.\n The VSD project involves the cooperative collection of automated vaccination and medical outcome data from four large HMOs that currently have 500,000 children younger than 7 years of age under surveillance. Review of automated screening results from the first 2 years of data revealed a possible increased risk of aseptic meningitis 0 to 14 days after MMR with a relative risk of 3.61 (95% confidence interval, 1.0 to 13.1) although the total number of cases was small. Although the automated data had suggested a possible association of aseptic meningitis with MMR containing the Jeryl-Lynn strain of mumps, review of validated hospitalized cases during the observation period did not reveal evidence of an increased risk of aseptic meningitis after MMR containing the Jeryl-Lynn strain of mumps (odds ratio < 1.0 for all analyses).\n Although it is recognized that hospitalized cases represent a minority of the total cases of aseptic meningitis, it is reassuring that in this evaluation no increased risk of aseptic meningitis after MMR vaccine was found.", "The rate of febrile seizures increases following measles, mumps, and rubella (MMR) vaccination but it is unknown whether the rate varies according to personal or family history of seizures, perinatal factors, or socioeconomic status. Furthermore, little is known about the long-term outcome of febrile seizures following vaccination.\n To estimate incidence rate ratios (RRs) and risk differences of febrile seizures following MMR vaccination within subgroups of children and to evaluate the clinical outcome of febrile seizures following vaccination.\n A population-based cohort study of all children born in Denmark between January 1, 1991, and December 31, 1998, who were alive at 3 months; 537,171 children were followed up until December 31, 1999, by using data from the Danish Civil Registration System and 4 other national registries.\n Incidence of first febrile seizure, recurrent febrile seizures, and subsequent epilepsy.\n A total of 439,251 children (82%) received MMR vaccination and 17,986 children developed febrile seizures at least once; 973 of these febrile seizures occurred within 2 weeks of MMR vaccination. The RR of febrile seizures increased during the 2 weeks following MMR vaccination (2.75; 95% confidence interval [CI], 2.55-2.97), and thereafter was close to the observed RR for nonvaccinated children. The RR did not vary significantly in the subgroups of children that had been defined by their family history of seizures, perinatal factors, or socioeconomic status. At 15 to 17 months, the risk difference of febrile seizures within 2 weeks following MMR vaccination was 1.56 per 1000 children overall (95% CI, 1.44-1.68), 3.97 per 1000 (95% CI, 2.90-5.40) for siblings of children with a history of febrile seizures, and 19.47 per 1000 (95% CI, 16.05-23.55) for children with a personal history of febrile seizures. Children with febrile seizures following MMR vaccinations had a slightly increased rate of recurrent febrile seizures (RR, 1.19; 95% CI, 1.01-1.41) but no increased rate of epilepsy (RR, 0.70; 95% CI, 0.33-1.50) compared with children who were nonvaccinated at the time of their first febrile seizure.\n MMR vaccination was associated with a transient increased rate of febrile seizures but the risk difference was small even in high-risk children. The long-term rate of epilepsy was not increased in children who had febrile seizures following vaccination compared with children who had febrile seizures of a different etiology.", "nan", "It has been suggested that the measles, mumps, and rubella vaccine (MMR) is a cause of regressive autism. As MMR was used in Japan only between 1989 and 1993, this time period affords a natural experiment to examine this hypothesis. Data on 904 patients with autism spectrum disorders (ASD) were analyzed. During the period of MMR usage no significant difference was found in the incidence of regression between MMR-vaccinated children and non-vaccinated children. Among the proportion and incidence of regression across the three MMR-program-related periods (before, during and after MMR usage), no significant difference was found between those who had received MMR and those who had not. Moreover, the incidence of regression did not change significantly across the three periods.", "Indigenous cases of measles continue to occur in Singapore despite the implementation of a two-dose mumps, measles and rubella (MMR) vaccination policy in 1998. We investigated a measles outbreak that took place in a primary school from April 17 to May 6, 2004 to identify all cases, evaluate vaccine efficacy (VE) and implement outbreak control measures.\n A case of measles was defined as anyone having generalised rash and fever with or without cough, coryza or conjunctivitis during the outbreak period, and who had either laboratory-confirmed acute measles infection or was epidemiologically linked to a patient with laboratory-confirmed measles infection. Vaccination status was obtained from the studentos health booklet and confirmed with the National Immunisation Registry. Attack rates in unvaccinated (ARU) and vaccinated (ARV) students were calculated and VE was evaluated using the formula: VE (percent) = [(ARU-ARV) / ARU] x 100 percent.\n Nine students, aged between eight and 14 years, from five classes in primary three and primary six, were epidemiologically linked to have measles. None of them had received the second dose of the MMR vaccine. 93 percent of students in the affected classes (n = 184) had prior documented evidence of receiving at least one dose of MMR vaccination, as compared to 96.5 percent for the entire school enrolment (n = 1,309). The attack rate was 1.2 percent in the vaccinated group and 53.8 percent in the unvaccinated group. The VE for the primary dose of MMR in the affected classes was 97.8 percent.\n It is important to achieve a high coverage for the primary dose of MMR vaccine in order to prevent any potential outbreaks prior to receiving the booster dose." ]

[ "15929052" ]

[ "Autologous mesenchymal stem cell transplantation in stroke patients." ]

[ "Mesenchymal stem cell (MSC) transplantation improves recovery from ischemic stroke in animals. We examined the feasibility, efficacy, and safety of cell therapy using culture-expanded autologous MSCs in patients with ischemic stroke. We prospectively and randomly allocated 30 patients with cerebral infarcts within the middle cerebral arterial territory and with severe neurological deficits into one of two treatment groups: the MSC group (n = 5) received intravenous infusion of 1 x 10(8) autologous MSCs, whereas the control group (n = 25) did not receive MSCs. Changes in neurological deficits and improvements in function were compared between the groups for 1 year after symptom onset. Neuroimaging was performed serially in five patients from each group. Outcomes improved in MSC-treated patients compared with the control patients: the Barthel index (p = 0.011, 0.017, and 0.115 at 3, 6, and 12 months, respectively) and modified Rankin score (p = 0.076, 0.171, and 0.286 at 3, 6, and 12 months, respectively) of the MSC group improved consistently during the follow-up period. Serial evaluations showed no adverse cell-related, serological, or imaging-defined effects. In patients with severe cerebral infarcts, the intravenous infusion of autologous MSCs appears to be a feasible and safe therapy that may improve functional recovery." ]

[ "12795572", "9550248", "2136866", "12963672", "1827472", "15555694", "15292629" ]

[ "Family-focused treatment versus individual treatment for bipolar disorder: results of a randomized clinical trial.", "Effects of psychoeducational intervention for married patients with bipolar disorder and their spouses.", "A randomized clinical trial of inpatient family intervention. V. Results for affective disorders.", "A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder.", "Psychoeducation of partners of bipolar-manic patients.", "Does adjunctive family therapy enhance recovery from bipolar I mood episodes?", "Impact of a psychoeducational family intervention on caregivers of stabilized bipolar patients." ]

[ "Recently hospitalized bipolar, manic patients (N = 53) were randomly assigned to a 9-month, manual-based, family-focused psychoeducational therapy (n = 28) or to an individually focused patient treatment (n = 25). All patients received concurrent treatment with mood-stabilizing medications. Structured follow-up assessments were conducted at 3-month intervals for a 1-year period ofactive treatment and a 1-year period of posttreatment follow-up. Compared with patients in individual therapy, those in family-focused treatment were less likely to be rehospitalized during the 2-year study period. Patients in family treatment also experienced fewer mood disorder relapses over the 2 years, although they did not differ from patients in individual treatment in their likelihood of a first relapse. Results suggest that family psychoeducational treatment is a useful adjunct to pharmacotherapy in decreasing the risk of relapse and hospitalization frequently associated with bipolar disorder.", "The relative benefit of adding a structured psychoeducational intervention to standard medication treatment for married patients with bipolar disorder and their spouses was assessed. Patients were randomly assigned to receive either medication management or medication management plus a marital intervention with their spouses for an 11-month period. Patients' symptoms, functioning, and adherence to their medication regimens were measured at study entry and at 11 months. Significant effects favoring the combined treatments were observed for overall patient functioning but not for symptom levels. The marital intervention was associated with improved medication adherence. Combined psychosocial and medication treatment does not affect patients' symptom levels beyond the effects of medication alone, but it does result in significant incremental gains in overall patient functioning.", "This paper reports the results at follow-up of a randomized clinical trial of combining family intervention with drug treatment during hospitalization for patients with affective disorder. The results suggest that female bipolar patients and their families benefited from family intervention, whereas unipolar patients and families did not. Patient outcome was positively correlated with the achievement of the goals of family intervention.", "Bipolar patients are at risk for relapses of their illness even when undergoing optimal pharmacotherapy. This study was performed to determine whether combining family-focused therapy (FFT) with pharmacotherapy during a postepisode interval enhances patients' mood stability during maintenance treatment.\n In a randomized controlled trial, 101 bipolar patients were assigned to FFT and pharmacotherapy or a less intensive crisis management (CM) intervention and pharmacotherapy. Outcome assessments were conducted every 3 to 6 months for 2 years. Participants (mean +/- SD age, 35.6 +/- 10.2 years) were referred from inpatient or outpatient clinics after onset of a manic, mixed, or depressed episode. FFT consisted of 21 sessions of psychoeducation, communication training, and problem-solving skills training. Crisis management consisted of 2 sessions of family education plus crisis intervention sessions as needed. Both protocols lasted 9 months. Patients received pharmacotherapy for 2 study years. Main outcome measures included time to relapse, depressive and manic symptoms, and medication adherence.\n Rates of study completion did not differ across the FFT (22/31, 71%) and CM groups (43/70, 61%). Patients undergoing FFT had fewer relapses (11/31, 35%) and longer survival intervals (mean +/- SD, 73.5 +/- 28.8 weeks) than patients undergoing CM (38/70, 54%; mean +/- SD, 53.2 +/- 39.6 weeks; hazard ratio, 0.38; 95% confidence interval, 0.20-0.75; P =.003; intent to treat). Patients undergoing FFT showed greater reductions in mood disorder symptoms and better medication adherence during the 2 years than patients undergoing CM.\n Combining family psychoeducation with pharmacotherapy enhances the postepisode symptomatic adjustment and drug adherence of bipolar patients.", "The partners of 14 bipolar-manic patients attending psychoeducation sessions were compared with 12 controls. After the sessions and 6 months later they showed more knowledge of the disease, medication and social strategies. Patient compliance did not change over the next year. The risk of this procedure is the initially increased level of anxiety of the patients.", "Family therapy is sometimes used as adjunctive treatment to pharmacotherapy to help patients recover from mood episodes of bipolar I disorder. However, the efficacy of this practice is not known.\n Ninety-two patients meeting criteria for a current bipolar I mood episode were randomly assigned to family therapy plus pharmacotherapy, multifamily psychoeducational group therapy plus pharmacotherapy, or pharmacotherapy alone. Time to recovery was analyzed with survival analysis.\n The proportion of subjects within each treatment group who recovered did not significantly differ, nor did time to recovery.\n The analyses did not include other outcomes such as psychosocial functioning, prophylaxis against recurrences of mood episodes, or compliance with pharmacotherapy.\n Neither adjunctive family therapy nor adjunctive multifamily psychoeducational group therapy significantly improves the rate of recovery from mood episodes of bipolar I disorder, compared to treatment with pharmacotherapy alone.", "Environmental stress has an important role in the course of bipolar disorder. Some findings have shown that family beliefs about the illness could predict family burden, and this burden could influence the outcome of bipolar disorder. To the best of our knowledge, there is scant information about the effects of family intervention on the caregiver's burden in bipolar disorder. The aim of this study was to assess the effects of psychoeducational family intervention on bipolar patients' caregivers, including the assessment of the caregiver's burden.\n 45 medicated euthymic bipolar outpatients were randomized into an experimental and a control group. Relatives of patients from the experimental group received 12 psychoeducational, 90-min sessions about bipolar disorder and coping skills. The caregivers' knowledge of bipolar disorder, the relationship subscales of the Family Environment Scale, and the family burden subscales from an adapted version of the Social Behavior Assessment Schedule were assessed for both caregiver groups before and after the intervention.\n Psycho-educated caregivers significantly improved their knowledge of bipolar disorder and reduced both the subjective burden and the caregiver's belief about the link between the objective burden and the patient. No significant differences were found in the objective burden nor in the family relationship subscales.\n These preliminary results suggest that psychoeducational intervention on caregivers of bipolar patients may improve the caregiver's knowledge of the illness, reduce their distress or subjective burden and alter their beliefs about the link between the disruptions in their life and the patient's illness." ]

[ "224958", "10080557", "4943915", "14153363", "8161288" ]

[ "The effect of fluphenazine upon social and vocational functioning in remitted schizophrenics.", "Comparative effectiveness of fluphenazine decanoate injections every 2 weeks versus every 6 weeks.", "Drug treatment in newly admitted schizophrenic patients.", "THIOPROPERAZINE IN CHRONIC SCHIZOPHRENIA.", "Fluphenazine vs placebo supplementation for prodromal signs of relapse in schizophrenia." ]

[ "Thirty-six remitted schizophrenics who participated in an outpatient study of fluphenazine decanoate or oral fluphenazine vs placebo given for a year were examined for the effect of drug treatment upon social and vocational functioning. Only the period prior to any clinical relapse was evaluated. We found no difference between those on drug or placebo, and conclude that antipsychotic drugs, at least in the context of an aftercare clinic offering a rich spectrum of nonpharmacological services, and when combined with antiparkinson medication, do not interfere with social and vocational functioning.", "Dose reduction strategies for the maintenance treatment of schizophrenia are designed to maintain the benefits of antipsychotic drug therapy while reducing risks. Previous strategies with decanoate preparations have been based on the use of lower doses per injection to achieve dose reduction; these strategies have achieved dose reduction but have resulted in some increase in symptoms. The authors tested a new dose reduction approach: increasing the interval between injections during intramuscular decanoate antipsychotic treatment.\n Fifty outpatients with schizophrenia or schizoaffective disorder were randomly assigned to receive 25 mg of fluphenazine decanoate intramuscularly either every 2 weeks or every 6 weeks for 54 weeks in a double-blind design.\n The two dose regimens did not differ significantly in relapse, symptom, or side effect measures. The every-6-weeks regimen was associated with a significant reduction in total antipsychotic exposure.\n The use of injections every 6 weeks instead of every 2 weeks may increase compliance and improve patients' comfort as well as decrease cumulative antipsychotic exposure, without increasing relapse rates or symptoms.", "nan", "nan", "We studied the effectiveness of treating patients with low doses of fluphenazine decanoate and supplementing them with oral fluphenazine when there was evidence of prodromal symptoms of psychotic exacerbations.\n Eighty schizophrenic patients who were receiving 5 to 10 mg of fluphenazine decanoate every 2 weeks were monitored for prodromal symptoms using an idiosyncratic prodromal rating scale. When patients met our criteria for a prodromal episode, they were randomly assigned to a double-blind comparison of oral fluphenazine hydrochloride (5 mg twice daily) or a placebo for the current and future prodromal episodes. We compared rates of psychotic exacerbations in the two treatment groups.\n Thirty-six patients (45%) met the criteria for a prodrome at some point during the trial and were randomized to drug or placebo. Using survival analysis during the entire 2 years, we did not find a significant difference between fluphenazine and placebo in the likelihood that a prodrome would continue to an exacerbation. Survival analysis beginning at the start of the second year of treatment did indicate a significant reduction in exacerbation risk for patients receiving drug supplementation (P = .032). Similarly, there was no difference between the two groups in the proportion of time at risk spent in exacerbation during the first year, but patients receiving active drug supplementation spent less time in an exacerbated state in the second year (P = .05).\n Our treatment strategy appeared to be effective for some patients, particularly those who were able to remain in the study beyond the first year. Although the occurrence of a prodrome was a fairly good marker that a patient was at high risk of ultimate exacerbation with our low-dose maintenance protocol, prodromes were not highly sensitive indicators of imminent exacerbation." ]

[ "9814400", "2863675", "18177775", "17567657", "9057377", "15572814", "2903386", "12526069", "2194687", "9690406", "2612203", "21829969", "18182412", "17901791", "7667050", "10048679", "9802626", "16816491", "11853793", "9124837", "15569557", "7807627", "15451221", "9476458", "8584362" ]

[ "Effectiveness of intramuscular penicillin versus oral amoxicillin in the early treatment of outpatient pediatric pneumonia.", "Chloramphenicol alone versus chloramphenicol plus penicillin for severe pneumonia in children.", "Ambulatory short-course high-dose oral amoxicillin for treatment of severe pneumonia in children: a randomised equivalency trial.", "Comparison of oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children (PIVOT trial): a multicentre pragmatic randomised controlled equivalence trial.", "Effectiveness of ampicillin and combination of penicillin and chloramphenicol in the treatment of pneumonias: randomized controlled trial.", "Comparison of two antibiotic regimens in the empirical treatment of severe childhood pneumonia.", "Trial of co-trimoxazole versus procaine penicillin with ampicillin in treatment of community-acquired pneumonia in young Gambian children.", "Comparative randomized trial of azithromycin versus erythromycin and amoxicillin for treatment of community-acquired pneumonia in children.", "Randomized trial of sulfamethoxazole + trimethoprim versus procaine penicillin for the outpatient treatment of childhood pneumonia in Zimbabwe.", "Antimicrobial resistance and clinical effectiveness of co-trimoxazole versus amoxycillin for pneumonia among children in Pakistan: randomised controlled trial. Pakistan Co-trimoxazole Study Group.", "An open, comparative evaluation of amoxycillin and amoxycillin plus clavulanic acid ('Augmentin') in the treatment of bacterial pneumonia in children.", "Antibiotic treatment schemes for very severe community-acquired pneumonia in children: a randomized clinical study.", "Chloramphenicol versus ampicillin plus gentamicin for community acquired very severe pneumonia among children aged 2-59 months in low resource settings: multicentre randomised controlled trial (SPEAR study).", "Comparative study of levofloxacin in the treatment of children with community-acquired pneumonia.", "Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric community-acquired pneumonia: comparative efficacy and safety of clarithromycin vs. erythromycin ethylsuccinate.", "Etiology and treatment of community-acquired pneumonia in ambulatory children.", "Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children.", "Penicillin and gentamicin therapy vs amoxicillin/clavulanate in severe hypoxemic pneumonia.", "Chloramphenicol versus benzylpenicillin and gentamicin for the treatment of severe pneumonia in children in Papua New Guinea: a randomised trial.", "Prospective open randomized study comparing efficacies and safeties of a 3-day course of azithromycin and a 10-day course of erythromycin in children with community-acquired acute lower respiratory tract infections.", "Comparative efficacy of amoxicillin, cefuroxime and clarithromycin in the treatment of community -acquired pneumonia in children.", "Trial of co-trimoxazole versus procaine penicillin G and benzathin penicillin + procaine penicillin G in the treatment of childhood pneumonia.", "Oral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: a randomised multicentre equivalency study.", "Benzathine penicillin for unilateral lobar or segmental infiltrates presumptively caused by Streptococcus pneumoniae in children 2-12 years old.", "A randomized trial of chloramphenicol vs. trimethoprim-sulfamethoxazole for the treatment of malnourished children with community-acquired pneumonia." ]

[ "To determine if intramuscular (IM) penicillin is more effective than oral (PO) amoxicillin in the early outpatient treatment of pediatric patients with presumed bacterial pneumonia.\n Prospective, randomized, evaluator-blinded, clinical trial.\n Pediatric emergency department (ED) of an urban children's hospital.\n ED patients with radiographically confirmed pneumonias managed as outpatients. Patients with chronic illnesses, wheezing, allergy to amoxicillin or penicillin, recent antibiotic therapy, or concurrent diagnosis of another febrile illness were excluded.\n Patients received either a two-day supply of PO amoxicillin (50 mg/kg/day divided tid), or an IM injection of procaine penicillin G (PPG) (50,000 units/kg). They had a complete blood count (CBC), blood culture, and nasopharyngeal swab for viral culture done at initial visit. They returned in 24 to 36 hours for reevaluation.\n The main measures were temperature, respiratory rate, and general appearance score; additional measures were accessory muscle use, pulse oximetry, parental report of activity/oral intake.\n One hundred seventy patients were enrolled. There were no significant differences between the two groups at initial or follow-up visits with respect to temperature, respiratory rate, accessory muscle use, pulse oximetry, or parental reports of activity level and oral intake. Only in the general appearance of children less than two years of age did there appear to be a difference (P = 0.03). When subanalysis excluded patients with positive viral studies (n = 17) or chest x-rays \"reread\" by an attending pediatric radiologist as \"no infiltrate\" (n = 29), this difference disappeared (P = 0.10). Three patients in the PO group, and five in the IM group failed by all three main outcome measures (P = 1.00). Four patients in the PO group, and five in the IM group were hospitalized at the follow-up visit (P = 1.00).\n There does not appear to be a significant difference between PO amoxicillin and IM penicillin in the early outpatient treatment of pediatric patients with presumed bacterial pneumonia.", "748 children with severe pneumonia in three hospitals in Papua New Guinea were randomised to receive intramuscular injections of either chloramphenicol alone or chloramphenicol plus penicillin. Sequential analysis showed no difference between the two treatments. 48 (13%) of the 377 children in the chloramphenicol alone group died, and 3 (0.8%) were changed to different treatment. 62 (17%) of the 371 children in the chloramphenicol-plus-penicillin group died, and 6 (1.6%) were changed to different treatment. The difference in failure rates (death or withdrawal for change of treatment) was 4.8% +/- 5.2% (+/- 95% confidence limits). In children with severe pneumonia, treatment with chloramphenicol alone is as effective as treatment with chloramphenicol plus penicillin.", "WHO case management guidelines for severe pneumonia involve referral to hospital for treatment with parenteral antibiotics. If equally as effective as parenteral treatment, home-based oral antibiotic treatment could reduce referral, admission, and treatment costs. Our aim was to determine whether home treatment with high-dose oral amoxicillin and inpatient treatment with parenteral ampicillin were equivalent for the treatment of severe pneumonia in children.\n This randomised, open-label equivalency trial was done at seven study sites in Pakistan. 2037 children aged 3-59 months with severe pneumonia were randomly allocated to either initial hospitalisation and parenteral ampicillin (100 mg/kg per day in four doses) for 48 h, followed by 3 days of oral amoxicillin (80-90 mg/kg per day; n=1012) or to home-based treatment for 5 days with oral amoxicillin (80-90 mg/kg per day in two doses; n=1025). Follow-up assessments were done at 1, 3, 6, and 14 days after enrollment. The primary outcome was treatment failure (clinical deterioration) by day 6. Analyses were done per protocol and by intention to treat. This trial is registered, ISRCTN95821329.\n In the per-protocol population, 36 individuals were excluded from the hospitalised group and 37 from the ambulatory group, mainly because of protocol violations or loss to follow-up. There were 87 (8.6%) treatment failures in the hospitalised group and 77 (7.5%) in the ambulatory group (risk difference 1.1%; 95% CI -1.3 to 3.5) by day 6. Five (0.2%) children died within 14 days of enrollment, one in the ambulatory group and four in the hospitalised group. In each case, treatment failure was declared before death and the antibiotic had been changed. None of the deaths were considered to be associated with treatment allocation; there were no serious adverse events reported in the trial.\n Home treatment with high-dose oral amoxicillin is equivalent to currently recommended hospitalisation and parenteral ampicillin for treatment of severe pneumonia without underlying complications, suggesting that WHO recommendations for treatment of severe pneumonia need to be revised.", "To ascertain whether therapeutic equivalence exists for the treatment of paediatric community acquired pneumonia by the oral and intravenous (IV) routes.\n A multicentre pragmatic randomised controlled non-blinded equivalence trial was undertaken in eight paediatric centres in England (district general and tertiary hospitals). Equivalence was defined as no more than a 20% difference between treatments of the proportion meeting the primary outcome measure at any time. 246 children who required admission to hospital and had fever, respiratory symptoms or signs and radiologically confirmed pneumonia were included in the study. Exclusion criteria were wheeze, oxygen saturations <85% in air, shock requiring >20 ml/kg fluid resuscitation, immunodeficiency, pleural effusion at presentation requiring drainage, chronic lung condition (excluding asthma), penicillin allergy and age <6 months. The patients were randomised to receive oral amoxicillin for 7 days (n = 126) or IV benzyl penicillin (n = 120). Children in the IV group were changed to oral amoxicillin after a median of six IV doses and received 7 days of antibiotics in total. The predefined primary outcome measure was time for the temperature to be <38 degrees C for 24 continuous hours and oxygen requirement to cease. Secondary outcomes were time in hospital, complications, duration of oxygen requirement and time to resolution of illness.\n Oral amoxicillin and IV benzyl penicillin were shown to be equivalent. Median time for temperature to settle was 1.3 days in both groups (p<0.001 for equivalence). Three children in the oral group were changed to IV antibiotics and seven children in the IV group were changed to different IV antibiotics. Median time to complete resolution of symptoms was 9 days in both groups.\n Oral amoxicillin is effective for most children admitted to hospital with pneumonia (all but those with the most severe disease who were excluded from this study). Prior to this study, the British Thoracic Society guidelines on childhood pneumonia could not draw on evidence to address this issue. This will spare children and their families the trauma and pain of cannulation, and children will spend less time in hospital.", "To assess the effectiveness of ampicillin and a combination of benzyl penicillin and chloramphenicol in the treatment of pneumonias.\n Randomized controlled trial.\n Tertiary care hospital.\n Patients 5 months to 4 years old with pneumonias of < 2 weeks duration. Exclusion criteria included acute bronchiolitis, allergy to penicillin, postmeasles pneumonia or prior administration of trial antibiotics in full dose for more than 2 days.\n Patients were randomized to receive either ampicillin (100 mg/kg/day) or combination of benzyl penicillin (100,000 units/kg/day) and chloramphenicol (100 mg/kg/day). The outcome measure was cure rate.\n There were 52 and 49 patients in the ampicillin and the combination groups, respectively. There was no significant difference in the baseline characteristics between groups except, nasal flare and cyanosis which were less in benzyl penicillin plus chloramphenicol group. There was also no difference either in the primary outcome, cure rate or secondary outcomes (days for cure, duration of tachypnea, fever and grunt) in the two.\n Considering the potential toxicity of chloramphenicol and the number of injections and doses to be given for the combination, ampicillin as a single drug could be preferred for the treatment of pneumonias, in this part of the country.", "The diagnosis and the treatment of community-acquired severe pneumonia is still a serious child health problem in developing countries. The aim of this study is to evaluate the effectiveness of two different antibiotic regimens in the empirical treatment of severe childhood pneumonia.\n We enrolled 97 infants (aged 2-24 months) with severe community-acquired pneumonia in a randomized-controlled trial of 10 days of treatment with penicillin G+chloramphenicol (n:46) or ceftriaxone (n:51). We evaluated the effectiveness of treatments with symptoms and some laboratory tests during and at the end of the study.\n The cure rates were similar in both groups and the antibiotic regimens in all patients were found effective (P< 0.001). The number of nurse rounds was much more in penicillin plus chloramphenicol group than ceftriaxone group.\n Both penicillin G plus chloramphenicol and ceftriaxone are effective in the empirical treatment of severe community pneumonia of young children. In spite of more nurse visits for antibiotic treatment, penicillin G+ chloramphenicol combination may be a cheaper alternative to ceftriaxone in the treatment of childhood pneumonia.", "134 Gambian children under 5 years of age with severe pneumonia (as defined by the World Health Organisation classification of acute respiratory infections) were given either oral co-trimoxazole for 5 days, or a single intramuscular dose of fortified procaine penicillin and 5 days of oral ampicillin. At 2 weeks, there was no significant difference in outcome between the two groups. Co-trimoxazole is much less expensive than ampicillin or procaine penicillin, requires only twice-daily administration, and can be given by health-care staff with little training. The results support the use of co-trimoxazole as the antibiotic of first choice in outpatient management of young children with pneumonia in developing countries.", "Our objective was to compare the clinical efficacy of azithromycin vs. erythromycin and amoxicillin in the treatment of presumed bacterial community-acquired pneumonia in ambulatory children, and to evaluate the etiologies of these illnesses. One hundred and ten children, aged 1 month to 14 years, were enrolled between January 1996-January 1999. Children were distributed into two groups according to clinical and radiological patterns: classic or atypical pneumonia. Patients with classic pneumonia were randomly assigned to receive oral amoxicillin 75 mg/kg/day for 7 days, or azithromycin 10 mg/kg/day for 3 days; patients with atypical pneumonia received azithromycin 10 mg/kg/day for 3 days, or erythromycin 50 mg/kg/day for 14 days. Chest X-ray, clinical, and laboratory parameters were obtained on enrollment. Clinic visits were performed on days 3, 7, and 14, and chest X-ray follow-up on days 7 and 14. Microbiological diagnosis of classic pathogens was based on blood and bronchial secretion cultures. The diagnosis of atypical pathogens C. pneumoniae, C. trachomatis, and M. pneumoniae was based on PCR and serologic tests.Forty-seven children met the criteria for classic pneumonia (23 children received azithromycin, and 24 received amoxicillin), and 59 children had atypical pneumonia (33 children were treated with azithromycin, and 26 with erythromycin). Demographic characteristics at enrollment were similar between children with classic pneumonia treated with azithromycin and erythromycin and children treated with azithromycin and erythromycin for atypical pneumonia. However, on day 7, children with classic pneumonia who received azithromycin normalized their chest X-ray more often than those who received amoxicillin (81.0% vs. 60.9%, respectively, P = 0.009). The same was true for children with atypical pneumonia; their chest X-rays had normalized by day 14 (100% in those with azithromycin vs. 81% in those with erythromycin, P = 0.059). Also, children with atypical pneumonia treated with azithromycin had earlier cessation of cough than children treated with erythromycin (3.6 +/- 1.9 vs. 5.5 +/- 3.6 days respectively, P = 0.02). There were only three children with side effects (mild diarrhea, all in the erythromycin group). Etiological agents were identified in 41% of children. In conclusion, azithromycin is an effective therapeutic option for the treatment of community-acquired classic and atypical pneumonia in children.\n Copyright 2003 Wiley-Liss, Inc.", "Reported are the results of a randomized trial of sulfamethoxazole + trimethoprim versus procaine penicillin for the outpatient treatment of pneumonia in 614 children aged 3 months to 12 years at primary health care clinics in Chitungwiza, a large town near Harare, Zimbabwe. Diagnosis and treatment were carried out by nurses, without medical supervision. The presence of lower respiratory tract infection that required antibiotics was diagnosed on the basis of a recent history of a cough and the presence of a respiratory rate of greater than 50 per minute. Patients were followed up by a research nurse with minimal drop-out losses. Referred children were examined and assessed by a doctor at the Chitungwiza General Hospital. Of the study children, 65 (11%) were referred to hospital, but only 8 (1.3%) had pneumonia that required a change in the treatment (5 in the sulfamethoxazole + trimethoprim group and 3 in the procaine penicillin group). There were no significant differences in outcome between the two treatment groups. One child, who had evidence of infection with human immunodeficiency virus (HIV), died. Sulfamethoxazole + trimethoprim and procaine penicillin were highly and equally effective for the outpatient treatment of children who had been clinically diagnosed to have pneumonia by primary health care workers.", "Co-trimoxazole is widely used in treatment of paediatric pneumonia in developing countries, but drug resistance may decrease its effectiveness. We studied the effectiveness of co-trimoxazole compared with that of amoxycillin in pneumonia therapy, and assessed the clinical impact of co-trimoxazole resistance.\n We recruited 595 children, aged 2-59 months, with non-severe or severe pneumonia (WHO criteria) diagnosed in the outpatient wards of two urban Pakistan hospitals. Patients were randomly assigned on a 2:1 basis co-trimoxazole (n=398) or amoxycillin (n=197) in standard WHO doses and dosing schedules, and were monitored in study wards. The primary outcome was inpatient therapy failure (clinical criteria) or clinical evidence of pneumonia at outpatient follow-up examination.\n There were 92 (23%) therapy failures in the co-trimoxazole group and 30 (15%) in the amoxycillin group (p=0.03)-26 (13%) versus 12 (12%) among children with non-severe pneumonia (p=0.856) and 66 (33%) versus 18 (18%) among those with severe pneumonia (p=0.009). For patients with severe pneumonia, age under 1 year (p=0.056) and positive chest radiographs (p=0.005) also predicted therapy failure. There was no significant association between antimicrobial minimum inhibitory concentration and outcome among bacteraemic children treated with co-trimoxazole.\n Co-trimoxazole provided effective therapy in non-severe pneumonia. For severe, life-threatening pneumonia, however, co-trimoxazole is less likely than amoxycillin to be effective.", "One hundred children with clinically diagnosed bacterial pneumonia were assigned at random to receive treatment with either amoxycillin (250 or 500 mg) or amoxycillin (250 or 500 mg) plus clavulanic acid (62.5 or 125 mg) 3-times daily, dosage and duration of treatment being determined by the severity of the condition. There were no clinically significant differences between the two groups on entry and the mean duration of treatment was 6.8 days in both. By Day 3 of treatment, significant differences in improvement in chest pain, dyspnoea, pyrexia and sputum production were noted in favour of amoxycillin/clavulanic acid. The response to treatment was significantly better in the combination group with an excellent or good response recorded in 60% and 30% of patients, compared with 26% and 36% in the amoxycillin group. Only 2 adverse reactions were reported, 1 case each of skin rash and diarrhoea in the combined group. The overall clinical efficacy rate of 93.8% in amoxycillin/clavulanic acid-treated patients was significantly better than the 60.4% clinical success recorded in the amoxycillin group.", "To compare clinical response to initial empiric treatment with oxacillin plus ceftriaxone and amoxicillin plus clavulanic acid in hospitalized children diagnosed with very severe community-acquired pneumonia (CAP).\n A prospective randomized clinical study was conducted among children 2 months to 5 years old with a diagnosis of very severe CAP in the pediatric ward of São Paulo State University Hospital in Botucatu, São Paulo, Brazil, from April 2007 to May 2008. Patients were randomly divided into two groups by type of treatment: an oxacillin/ceftriaxone group (OCG, n = 48) and an amoxicillin/clavulanic acid group (ACG, n = 56). Analyzed outcomes were: time to clinical improvement (fever and tachypnea), time on oxygen therapy, length of stay in hospital, need to widen antimicrobial spectrum, and complications (including pleural effusion).\n The two groups did not differ statistically for age, sex, symptom duration before admission, or previous antibiotic treatment. Time to improve tachypnea was less among ACG patients than OCG patients (4.8 ± 2.2 versus 5.8 ± 2.4 days respectively; P = 0.028), as was length of hospital stay (11.0 ± 6.2 versus 14.4 ± 4.5 days respectively; P = 0.002). There were no statistically significant differences between the two groups for fever improvement time, time on oxygen therapy, need to widen antimicrobial spectrum, or frequency of pleural effusion.\n Both treatment plans are effective in treating very severe CAP in 2-month-to 5-year-old hospitalized children. The only analyzed outcome that favored amoxicillin/clavulanic acid treatment was time required to improve tachypnea.\n ClinicalTrials.gov ID: NCT01166932.", "To evaluate whether five days' treatment with injectable ampicillin plus gentamicin compared with chloramphenicol reduces treatment failure in children aged 2-59 months with community acquired very severe pneumonia in low resource settings.\n Open label randomised controlled trial.\n Inpatient wards within tertiary care hospitals in Bangladesh, Ecuador, India, Mexico, Pakistan, Yemen, and Zambia.\n Children aged 2-59 months with WHO defined very severe pneumonia.\n Chloramphenicol versus a combination of ampicillin plus gentamicin.\n Primary outcome measure was treatment failure at five days. Secondary outcomes were treatment failure defined similarly among all participants evaluated at 48 hours and at 10 and 21 days.\n More children failed treatment with chloramphenicol at day 5 (16% v 11%; relative risk 1.43, 95% confidence interval 1.03 to 1.97) and also by days 10 and 21. Overall, 112 bacterial isolates were obtained from blood and lung aspirates in 110 children (11.5%), with the most common organisms being Staphylococcus aureus (n=47) and Streptococcus pneumoniae (n=22). In subgroup analysis, bacteraemia with any organism increased the risk of treatment failure at 21 days in the chloramphenicol group (2.09, 1.41 to 3.10) but not in the ampicillin plus gentamicin group (1.12, 0.59 to 2.13). Similarly, isolation of S pneumoniae increased the risk of treatment failure at day 21 (4.06, 2.73 to 6.03) and death (5.80, 2.62 to 12.85) in the chloramphenicol group but not in the ampicillin plus gentamicin group. No difference was found in treatment failure for children with S aureus bacteraemia in the two groups, but the power to detect a difference in this subgroup analysis was low. Independent predictors of treatment failure by multivariate analysis were hypoxaemia (oxygen saturation <90%), receiving chloramphenicol, being female, and poor immunisation status.\n Injectable ampicillin plus gentamicin is superior to injectable chloramphenicol for the treatment of community acquired very severe pneumonia in children aged 2-59 months in low resource settings.\n Current Controlled Trials ISRCTN39543942.", "Levofloxacin has established efficacy and safety in the treatment of community-acquired pneumonia (CAP) in adults, and its use as an alternative therapy for children with CAP has been proposed.\n Assess the clinical efficacy and safety of levofloxacin compared with standard of care antibiotic therapy in the treatment of CAP in children aged 6 months to 16 years.\n In an open-label, multicenter, noninferiority trial, children with CAP were randomized 3:1 to receive levofloxacin or comparator antimicrobial therapy (0.5 to <5 years: amoxicillin/clavulanate or ceftriaxone; > or =5 years: clarithromycin or ceftriaxone with clarithromycin or erythromycin lactobinate) for 10 days. The primary outcome was cure rates at the test-of-cure visit (10-17 days after completing treatment) as determined by symptoms, physical examination, and chest radiography.\n Seven hundred and thirty-eight children were enrolled and 539 (405 levofloxacin-treated, 134 comparator-treated) were clinically evaluable at test-of-cure visit. Clinical cure rates were 94.3% (382 of 405) in levofloxacin-treated and 94.0% (126 of 134) in comparator-treated children. Cure rates were also similar for levofloxacin and comparator for each age group (<5 years, 92.2% versus 90.8%; > or =5 years, 96.5% versus 97.1%; respectively) and for children categorized as being at higher risk for severe disease. Mycoplasma pneumoniae was the most frequently identified cause of pneumonia (230 children). Levofloxacin was as well tolerated as comparators, with similar type and incidence of adverse events.\n Levofloxacin was as well tolerated and effective as standard-of-care antibiotics for the treatment of CAP in infants and children.", "We evaluated 260 previously healthy children ages 3 through 12 years who had clinical signs and symptoms of pneumonia, radiographically confirmed. Patients were randomized 1:1 to a 10-day course of either clarithromycin suspension 15 mg/kg/day divided twice a day or erythromycin suspension 40 mg/kg/day divided twice a day or three times a day. Evidence of infection with Chlamydia pneumoniae was detected in 28% (74) of patients: 13% (34) by nasopharyngeal culture and 18% (48) by serology with the microimmunofluorescence assay. Evidence of infection with Mycoplasma pneumoniae was detected in 27% (69) of patients: 20% (53) by nasopharyngeal culture or polymerase chain reaction and 17% (44) by serology with the use of enzyme-linked immunosorbent assay. Serologic confirmation of infection was observed in 23% (8) and 53% (28) of patients with bacteriologically detected C. pneumoniae and M. pneumoniae, respectively. Treatment with clarithromycin vs. erythromycin, respectively, yielded the following outcomes: clinical success 98% (121 of 124) vs. 95% (105 of 110); radiologic success 98% (109 of 111) vs. 94% (92 of 110); and eradication by pathogen, C. pneumoniae 79% (15 of 19) vs. 86% (12 of 14) and M. pneumoniae 100% (9 of 9) vs. 100% (4 of 4). Adverse events were primarily gastrointestinal occurring in almost one-fourth of patients in both groups, and were mild to moderate in severity. Clarithromycin and erythromycin were similarly effective and safe for the treatment of radiographically proved, community-acquired pneumonia in children older than 2 years old.(ABSTRACT TRUNCATED AT 250 WORDS)", "To determine the etiology of community-acquired pneumonia in ambulatory children and to compare responses to treatment with azithromycin, amoxicillin-clavulanate or erythromycin estolate.\n Ambulatory patients with pneumonia were identified at the Children's Medical Center of Dallas, TX. Children age 6 months to 16 years with radiographic and clinical evidence of pneumonia were enrolled and randomized to receive either azithromycin suspension for 5 days or a 10-day course of amoxicillin-clavulanate for those <5 years or erythromycin estolate suspension for those > or = 5 years. Blood culture was obtained in all patients and we obtained nasopharyngeal and pharyngeal swabs for culture and polymerase chain reaction (PCR) testing for Chlamydia pneumoniae and Mycoplasma pneumoniae and nasopharyngeal swabs for viral direct fluorescent antibody and culture. Acute and convalescent serum specimens were tested for antibodies to C. pneumoniae, M. pneumoniae and Streptococcus pneumoniae. Patients were evaluated 10 to 37 days later when repeat specimens for serology, PCR and culture were obtained. For comparative purposes healthy children attending the well-child clinic had nasopharyngeal and pharyngeal swabs obtained for PCR and culture for C. pneumoniae and M. pneumoniae.\n Between February, 1996, and December, 1997, we enrolled 174 patients, 168 of whom fulfilled protocol criteria for evaluation. There were 55% males and 63% were <5 years of age. All blood cultures were sterile and there was no correlation between the white blood cell and differential counts and etiology of pneumonia. Etiologic agents were identified in 73 (43%) of 168 patients. Infection was attributed to M. pneumoniae in 7% (12 of 168), C. pneumoniae in 6% (10 of 168), S. pneumoniae in 27% (35 of 129) and viruses in 20% (31 of 157). None of the swab specimens from 75 healthy control children was positive for C. pneumoniae or M. pneumoniae. Clinical response to therapy was similar for the three antibiotic regimens evaluated, including those with infection attributed to bacterial agents.\n Although a possible microbial etiology was identified in 43% of the evaluable patients, clinical findings and results of blood cultures, chest radiographs and white blood cell and differential counts did not distinguish patients with a defined etiology from those without a known cause for pneumonia. There were no differences in the clinical responses of patients to the antimicrobial regimens studied.", "To compare the safety and efficacy of azithromycin with amoxicillin/clavulanate or erythromycin for the treatment of community-acquired pneumonia, including atypical pneumonia caused by Mycoplasma pneumoniae and Chlamydia pneumoniae.\n Multicenter, parallel group, double blind trial in which patients 6 months to 16 years of age with community-acquired pneumonia were randomized 2:1 to receive either azithromycin for 5 days or conventional therapy for 10 days (amoxicillin/clavulanate if < or =5 years of age or erythromycin estolate if >5 years of age). Patients from 23 geographically diverse sites were evaluated for clinical outcomes and/or adverse events at Days 3 to 5, Days 15 to 19 and 4 to 6 weeks posttherapy. Microbiology (culture or polymerase chain reaction) was done at baseline and Days 15 to 19 for bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serology for C. pneumoniae and M. pneumoniae was done at baseline and 4 to 6 weeks posttherapy.\n Of 456 patients enrolled during 17 consecutive months, 420 were evaluable. Clinical success at Study Days 15 to 19 was 94.6% in the azithromycin group and 96.2% in the comparative treatment group (P = 0.735) and at 4 to 6 weeks posttherapy 90.6 and 87.1%, respectively (P = 0.330). Evidence of infection was identified in 46% of 420 evaluable patients (1.9% bacteria, 29.5% M. pneumoniae and 15% C. pneumoniae). Microbiologic eradication was 81% for C. pneumoniae and 100% for M. pneumoniae in the azithromycin group vs. 100 and 57%, respectively, in the comparator group. Treatment-related adverse events occurred in 11.3% of the azithromycin group and 31% in the comparator group (P < 0.05).\n Azithromycin used once daily for 5 days produced a satisfactory therapeutic outcome similar to those of amoxicillin/clavulanate or erythromycin given three times a day for 10 days for treatment of community-acquired pneumonia. Azithromycin had significantly fewer side effects than comparator drugs.", "To compare the efficacy of sequential injectable crystalline penicillin (C.pen) and gentamicin combination followed by oral amoxicillin with sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe or very severe hypoxemic pneumonia.\n Children aged 2-59 months with WHO-defined severe or very severe pneumonia with hypoxemia (SpO2 < 90%) were included in the study. Patients with fever > 10 days, bacterial meningitis, prior antibiotic therapy > 24 hours, stridor, heart disease and allergy to any of the study drugs were excluded. They were randomly allocated to two groups--Group A and Group B. Group A received C. pen and gentamicin intravenously (IV), followed by oral amoxicillin and group B got amox-clav IV, followed by oral amox-clav. Minimum duration of IV therapy was 3 days and total 7 days. Respiratory rate, oxygen saturation and chest wall indrawing were monitored 6 hourly.\n 71 patients were included. There were two (5.2%) blood cultures positive in group A and three (9%) in group B. Organisms isolated were S. pneumoniae (n=3) and H. influenzae-b (n=2). There was only one treatment failure in each of the groups. One was due to penicillin resistant H. influenzae -b and the other was due to worsening of pneumonia. The mean time taken for normalization of tachypnea, hypoxia, chest wall indrawing and inability to feed was similar (P-N.S). Mean duration of IV therapy in group A was 76+/-25 hrs and group B was 75+/-24 hrs (p>0.1).\n In children of 2-59 months, sequential injectable C. pen and gentamicin combination, followed by oral amoxicillin or sequential IV and oral amox-clav were equally effective for the treatment of severe or very severe hypoxemic community acquired pneumonia.", "Pneumonia is the most frequent cause of child mortality in less-developed countries. We aimed to establish whether the combination of benzylpenicillin and gentamicin or chloramphenicol would be better as first-line treatment in children with severe pneumonia in Papua New Guinea.\n We did an open randomised trial in which we enrolled children aged 1 month to 5 years of age who fulfilled the WHO criteria for very severe pneumonia and who presented to hospitals in two provinces. Children were randomly assigned to receive chloramphenicol (25 mg/kg 6 hourly) or benzylpenicillin (50 mg/kg 6 hourly) plus gentamicin (7.5 mg/kg daily) by intramuscular injection. The primary outcome measure was a good or an adverse outcome.\n 1116 children were enrolled; 559 children were treated with chloramphenicol and 557 with benzylpenicillin and gentamicin. At presentation the median haemoglobin oxygen saturation was 71% (IQR 57-77) for those allocated chloramphenicol and 69% (55-77) for those allocated penicillin and gentamicin. 147 (26%) children treated with chloramphenicol and 123 (22%) treated with penicillin and gentamicin had adverse outcomes (p=0.11). 36 children treated with chloramphenicol and 29 treated with penicillin and gentamicin died. More children treated with chloramphenicol than penicillin and gentamicin represented with severe pneumonia within 1 month of hospital discharge (p=0.03).\n For children with severe pneumonia in less-developed countries the probability of a good outcome is similar if treated with chloramphenicol or with the combination of benzylpenicillin and gentamicin.", "The efficacies and safeties of a 3-day, 3-dose course of azithromycin (10 mg/kg of body weight per day) and a 10-day, 30-dose course of erythromycin (40 mg/kg/day) for the treatment of acute lower respiratory tract infections in children were compared in an open randomized multicenter study. Sixty-eight of 85 evaluable patients (80%) had radiologically proven pneumonia, and 20% had bronchitis. Treatment success defined as cure or major improvement was achieved in 42 of 45 (93%) azithromycin recipients versus 36 of 40 (90%) erythromycin recipients. Adverse events were reported in 12 of 45 and 6 of 40 of the patients treated with azithromycin and erythromycin, respectively, a difference which was not statistically significant. In conclusion, a 3-day course of azithromycin is as effective as a 10-day course of erythromycin in the treatment of community-acquired lower respiratory tract infections in children, with comparable safety and acceptability profiles. This shorter treatment course might have a beneficial effect on compliance, especially in the pediatric age group.", "To compare the clinical response to amoxicillin, cefuroxime and clarithromycin in the treatment of community-acquired pneumonia in children and to see the cost effectiveness of each treatment.\n Randomized clinical control trial.\n Department of Pediatrics, Khyber teaching hospital, Peshawar, from October 2001 to February 2002.\n Patients between 3 to 72 months of age, admitted in the hospital with community acquired pneumonia, were randomly divided into three groups,1,2,3. They were started on amoxicillin, cefuroxime and clarithromycin respectively. The patients were assessed daily. If there was no clinical improvement at 48 hours the antibiotic was changed. ANOVA statistical test was applied to see the clinical response to the treatment in the three groups. Cost effectiveness of the treatment was compared.\n There was no statistical difference in the clinical response at 48 hours of initiating treatment and at discharge (p > 0.01 each). The mean hospital stay in group 1 and 2 was 3.3 days and group 3 was 3.2 days respectively (p > 0.01). Ninety-seven percent patients in group 1 and 3, and 95% patients in group 2 showed clinical improvement. The cost of treatment of community acquired pneumonia for 8 days was Rs 496/-, 730/-, 1018/- for amoxicillin, clarithromycin and cefuroxime respectively.\n Amoxicillin was found the most cost effective followed by clarithromycin and cefuroxime respectively in the treatment of non-severe and severe community-acquired pneumonia.", "This study, which aimed to assess the results of three different regimens in the treatment of pneumonia, was carried out at the Pediatric Outpatient Department of Capa Children's Hospital in Istanbul on 151 patients aged between 4 months and 14 years. The first group (n = 46) received co-trimoxazole orally for 10 days and the second group (n = 63) procaine penicillin G in intramuscularly for 10 days. Benzathin penicillin G combined with procaine penicillin G was given to the third group (n = 42) as a single dose intramuscularly. While the best results were obtained with penicillin procaine G, no statistically significant difference was found between this regimen and co-trimoxazole therapy (chi 2 = 0.305023 P = 0.5). We suggest that co-trimoxazole is easy to administer and cost effective in the ambulatory treatment of pneumonia in children.", "Injectable penicillin is the recommended treatment for WHO-defined severe pneumonia (lower chest indrawing). If oral amoxicillin proves equally effective, it could reduce referral, admission, and treatment costs. We aimed to determine whether oral amoxicillin and parenteral penicillin were equivalent in the treatment of severe pneumonia in children aged 3-59 months.\n This multicentre, randomised, open-label equivalency study was undertaken at tertiary-care centres in eight developing countries in Africa, Asia, and South America. Children aged 3-59 months with severe pneumonia were admitted for 48 h and, if symptoms improved, were discharged with a 5-day course of oral amoxicillin. 1702 children were randomly allocated to receive either oral amoxicillin (n=857) or parenteral penicillin (n=845) for 48 h. Follow-up assessments were done at 5 and 14 days after enrollment. Primary outcome was treatment failure (persistence of lower chest indrawing or new danger signs) at 48 h. Analyses were by intention-to-treat and per protocol.\n Treatment failure was 19% in each group (161 patients, pencillin; 167 amoxillin; risk difference -0.4%; 95% CI -4.2 to 3.3) at 48 h. Infancy (age 3-11 months; odds ratio 2.72, 95% CI 1.95 to 3.79), very fast breathing (1.94, 1.42 to 2.65), and hypoxia (1.95, 1.34 to 2.82) at baseline predicted treatment failure by multivariate analysis.\n Injectable penicillin and oral amoxicillin are equivalent for severe pneumonia treatment in controlled settings. Potential benefits of oral treatment include decreases in (1) risk of needle-borne infections; (2) need for referral or admission; (3) administration costs; and (4) costs to the family.", "A randomized controlled study was carried out to assess the efficacy of a single dose of benzathine penicillin for treating children 2-12 years old with presumed S. pneumoniae pneumonia. One-hundred-and-seventy-six children screened at self-referral pediatric emergency services in Belo Horizonte, Brazil, were randomized to only one injection of benzathine penicillin (n = 93, case-group) or a 7-day procaine penicillin regimen (n = 83, control-group), upon diagnosis of pneumococcal pneumonia based on clinical and radiological characteristics. Follow-up was carried out on the second day after treatment and around the 7th and/or 14th day after treatment allocation. No statistical significant difference was found for sociodemographic, clinical, laboratory or radiographic characteristics among the two groups. Evident or total radiographic clearing was demonstrated for 92.3 and 95.1 per cent of the benzathine penicillin and procaine penicillin groups, respectively (P = 0.54). Benzathine penicillin may be considered an alternative to classic regimens for treating pneumonia due to sensitive strains of S. pneumoniae among children 2-12 years old. Other benefits are its lower cost, better compliance and low rates of adverse reactions.", "Children in developing countries who present with malnutrition often have infections, particularly pneumonia, at the time of presentation. We evaluated the initial antibiotic management of 144 Gambian children who presented for the first time with malnutrition and who had clinical or radiologic evidence of pneumonia. They were enrolled in a double blind trial of trimethoprim-sulfamethoxazole vs. chloramphenicol. Most children in the study underwent detailed investigations of bacterial and viral etiology as part of another study. The study drug was administered for a week along with oral metronidazole, vitamins and standardized nutritional therapy. Treatment failure was defined as the need for change to parenteral antibiotics during treatment, failure to respond to a week of treatment with the study drug or relapse during the following 2 weeks. There were no differences between the treatment groups in the clinical indicators of severity, etiology or radiologic findings. Thirty-three children were excluded from the analysis because of tuberculosis, inappropriate enrollment or inadequate follow-up. Of the 111 children remaining, 32 (16 in each arm of the study) failed treatment. Clinical failure was not related to in vitro antimicrobial resistance in the 20 cases in which invasive bacterial isolates were obtained. Those who failed treatment were more likely to have had lower chest wall indrawing and positive bacterial cultures than those who were successfully treated. In an area with infrequent antimicrobial resistance of common respiratory pathogens, oral chloramphenicol and trimethoprim-sulfamethoxazole were equally effective in the initial management of malnourished children with community-acquired pneumonia." ]

[ "13723875", "13767897", "1708969", "11157692", "14360845" ]

[ "The treatment of acute rheumatic fever.", "Treatment of rheumatic fever and rheumatic carditis. Observations providing a basis for the selection of aspirin or adrenocortical steroids.", "A double-blind placebo-controlled trial of prednisone in active rheumatic carditis.", "Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial.", "Therapeutic agents in rheumatic carditis; comparative effects of acetylsalicylic acid, corticotropin, and cortisone." ]

[ "nan", "nan", "In view of the controversy surrounding the use of corticosteroids in the management of active rheumatic carditis, a prospective double-blind controlled clinical trial comparing prednisone (2 mg/kg/24 h in three divided doses) versus placebo was carried out in 35 children with this disease, using strict clinical criteria to define carditis and excluding cases where the diagnosis was doubtful. The duration of the study, which included long-term follow-up, was 7 years. The results failed to show that prednisone at this dosage and frequency was of any benefit either in the short-term clinical response or in the long-term follow-up with regard to later requirement of valvular surgery (using the 5% level of significance). Other findings were that one-third of cases improved with time, irrespective of treatment, most of them having mild to moderate carditis initially.", "Acute rheumatic fever (ARF) remains the leading cause of acquired heart disease in children worldwide. No therapeutic agent has been shown to alter the clinical outcome of the acute illness. Immunological mechanisms appear to be involved in the pathogenesis of ARF. Intravenous immunoglobulin (IVIG), a proven immunomodulator, may benefit cardiac conditions of an autoimmune nature. We investigated whether IVIG modified the natural history of ARF by reducing the extent and severity of carditis.\n This prospective, double-blind, randomized, placebo-controlled trial evaluated IVIG in patients with a first episode of rheumatic fever, stratifying patients by the presence and severity of carditis before randomization. Patients were randomly allocated to receive 1 g/kg IVIG on days 1 and 2 and 0.4 g/kg on days 14 and 28, or they received a placebo infusion. Clinical, laboratory, and echocardiographic evaluation was performed at 0, 2, 4, 6, 26, and 52 weeks. Fifty-nine patients were treated, of whom 39 had carditis (including 4 subclinical) and/or migratory polyarthritis (n=39). There was no difference between groups in the rate of normalization of the erythrocyte sedimentation rate or acute-phase proteins at the 6-week follow-up. On echocardiography, 59% in the IVIG group and 69% in the placebo group had carditis at baseline. There was no significant difference in the cardiac outcome, including the proportion of valves involved, or in the severity of valvar regurgitation at 1 year. At 1 year, 41% of the IVIG and 50% of the placebo group had carditis.\n IVIG did not alter the natural history of ARF, with no detectable difference in the clinical, laboratory, or echocardiographic parameters of the disease process during the subsequent 12 months.", "nan" ]

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[ "Improving glycaemic control of patients with Type 2 diabetes in a primary care setting: a French application of the Staged Diabetes Management programme.", "Physician management of hypercholesterolemia. A randomized trial of continuing medical education.", "A randomized controlled trial of two strategies to implement active sick leave for patients with low back pain.", "Improving management of obesity in primary care: cluster randomised trial.", "A cluster randomised trial to evaluate a nutrition training programme.", "Effect of a medication management training package for nurses on clinical outcomes for patients with schizophrenia: cluster randomised controlled trial.", "Interactional group discussion: results of a controlled trial using a behavioral intervention to reduce the use of injections in public health facilities.", "Education program for general practitioners on breast and cervical cancer screening: a randomized trial. PRE.SA.GF Collaborative Group.", "Positioning of stroke patients: evaluation of a teaching intervention with nurses.", "Effectiveness of a skin cancer control educational intervention for internal medicine housestaff and attending physicians.", "Randomised controlled trial of a theoretically grounded tailored intervention to diffuse evidence-based public health practice [ISRCTN23257060].", "The effectiveness of continuing medical education in changing the behavior of physicians caring for patients with acute myocardial infarction. A controlled randomized trial.", "An educational programme for peer review groups to improve treatment of chronic heart failure and diabetes mellitus type 2 in general practice.", "Experimental evaluation of the effects of drug information on antibiotic prescribing: a study in outpatient care in an area of Sri lanka.", "The effect of educational intervention on intercultural communication: results of a randomised controlled trial.", "The effects of continuing medical education on family doctor performance in office practice: a randomized control study.", "Training obstetricians and midwives to present screening tests: evaluation of two brief interventions.", "Can evidence change the rate of back surgery? A randomized trial of community-based education.", "The impact of an educational program on improving diabetes knowledge and changing behaviors of nurses in long-term care facilities.", "Cancer: improving early detection and prevention. A community practice randomised trial.", "An intervention to increase patients' trust in their physicians. Stanford Trust Study Physician Group.", "Family Physicians and Exercise Counseling: Can they be influenced to provide more?", "Can small group education and peer review improve care for patients with asthma/chronic obstructive pulmonary disease?", "Effects of an education program for community pharmacists on detecting drug-related problems in elderly patients.", "Continuing medical education using clinical algorithms. A controlled-trial assessment of effect on neonatal care.", "The effects of two continuing medical education programs on communication skills of practicing primary care physicians.", "Identification and management of domestic violence: a randomized trial.", "Improving drug use through continuing education: a randomized controlled trial in Zambia.", "Spirometry in primary care practice: the importance of quality assurance and the impact of spirometry workshops.", "Cluster randomised controlled trial of tailored interventions to improve the management of urinary tract infections in women and sore throat.", "Effects of a clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire Depression Project randomised controlled trial.", "Does a 3-day workshop for family medicine trainees improve preventive care? A randomized control trial.", "A randomized controlled trial assessing the impact of problem-based versus didactic teaching methods in CME.", "Diabetes care from diagnosis: effects of training in patient-centred care on beliefs, attitudes and behaviour of primary care professionals.", "Small group intervention vs formal seminar for improving appropriate drug use.", "Randomized controlled trial of education and feedback for implementation of guidelines for acute low back pain.", "Breast-feeding training for health professionals and resultant institutional changes.", "A pragmatic cluster randomized controlled trial of an educational intervention for GPs in the assessment and management of depression.", "Cluster randomised trial of an active, multifaceted educational intervention based on the WHO Reproductive Health Library to improve obstetric practices.", "Implementation strategies for a Scottish national epilepsy guideline in primary care: results of the Tayside Implementation of Guidelines in Epilepsy Randomized (TIGER) trial.", "Effectiveness of an educational strategy to improve family physicians' detection and management of depression: a randomized controlled trial.", "Pragmatic randomised controlled trial to evaluate guidelines for the management of infertility across the primary care-secondary care interface.", "Methods to encourage the use of antenatal corticosteroid therapy for fetal maturation: a randomized controlled trial.", "Improving the recognition and management of depression: is there a role for physician education?", "Efficacy of a Cancer Research UK communication skills training model for oncologists: a randomised controlled trial.", "One-to-one versus group sessions to improve prescription in primary care: a pragmatic randomized controlled trial.", "A multimethod quality improvement intervention to improve preventive cardiovascular care: a cluster randomized trial.", "Strategies to promote the use of advance directives in a residency outpatient practice.", "Effect of clinician communication skills training on patient satisfaction. A randomized, controlled trial.", "Can residents be trained to counsel patients about quitting smoking? Results from a randomized trial.", "Evaluating an educational intervention to improve the treatment of asthma in four European countries. Drug Education Project Group.", "Impact of IMCI training and language used by provider on quality of counseling provided to parents of sick children in Bougouni District, Mali.", "Staff training and ambulatory tuberculosis treatment outcomes: a cluster randomized controlled trial in South Africa.", "Randomized, controlled trial of prescribing training in a South African province.", "Effects of brief therapy training on practicing psychotherapists and their clients.", "A randomized intervention to improve heart failure outcomes in community-based home health care.", "Effectiveness of a multiple intervention to reduce antibiotic prescribing for respiratory tract symptoms in primary care: randomised controlled trial.", "Improving the health behaviours of elderly people: randomised controlled trial of a general practice education programme.", "Randomised controlled trial of training health visitors to identify and help couples with relationship problems following a birth.", "Multifaceted intervention to improve rheumatologists' management of glucocorticoid-induced osteoporosis: a randomized controlled trial.", "Effect of a practice-based strategy on test ordering performance of primary care physicians: a randomized trial.", "Effectiveness of teaching general practitioners skills in brief cognitive behaviour therapy to treat patients with depression: randomised controlled trial.", "Randomised controlled trial to change the hospital management of unstable angina.", "Physicians' communication with a cancer patient and a relative: a randomized study assessing the efficacy of consolidation workshops.", "A randomized trial to increase smoking intervention by physicians. Doctors Helping Smokers, Round I.", "Intervention among frequent attenders of the out-of-hours service: a stratified cluster randomized controlled trial.", "Feasibility of a national cholesterol guideline in daily practice. A randomized controlled trial in 20 general practices.", "Training pharmacy workers in recognition, management, and prevention of STDs: district-randomized controlled trial.", "Arthritis care in older-adult centers. A controlled study of an education program for public health nurses.", "Improving physicians' interviewing skills and reducing patients' emotional distress. A randomized clinical trial.", "Improving test ordering in primary care: the added value of a small-group quality improvement strategy compared with classic feedback only.", "Improving pediatricians' compliance-enhancing practices. A randomized trial.", "Teaching sigmoidoscopy to primary care physicians: a controlled study of continuing medical education.", "Efficacy of case method learning in general practice for secondary prevention in patients with coronary artery disease: randomised controlled study.", "Effect of training and a structured office practice on physician-delivered nutrition counseling: the Worcester-Area Trial for Counseling in Hyperlipidemia (WATCH)." ]

[ "To assess the impact of a French adaptation of the Staged Diabetes Management (SDM) programme on glycaemic control of people with Type 2 diabetes in primary care. Secondary endpoints were blood pressure, blood lipids, healthcare costs and quality of life.\n Prospective, randomized controlled study, of 1 years' duration. General practitioners (GPs) were recruited in four separate districts of a French region. They enrolled consecutive patients with Type 2 diabetes. GPs in the intervention group were educated in the SDM programme. GPs in the control group were asked to provide usual care. Healthcare costs were collected by medical departments of the Health Insurance systems. Quality of life was assessed with the Duke Health Profile.\n Three hundred and forty patients enrolled by 57 GPs completed the study, 192 in the intervention group and 148 in the control group. Patients in the intervention group were managed more adequately in accordance with the guidelines (P < 0.05 for nine out of 10 items). HbA(1c) decreased by 0.31% in the intervention group and increased by 0.56% in the control group, resulting in a difference of 0.87% by the end of the study (P = 0.001). Blood pressure and blood lipids did not differ between groups. Occurrence of major complications was low and identical in both groups. Incremental costs during the study in the intervention group were 35 euros per patient per month, and this was not significantly different in comparison with the control group. Quality of life was not affected by the intervention.\n Educating GPs in the French adaptation of the SDM programme improves glycaemic control in a primary care setting, without significantly increasing healthcare costs.", "To determine the effect of continuing medical education (CME) on compliance with the recommendations of the National Cholesterol Education Program Expert Panel on high serum cholesterol levels in adults, we randomly assigned primary physicians in 174 practices to 3 groups, 2 that underwent either standard or intensive CME and a control group. The standard CME group was offered a free 3-hour seminar on high serum cholesterol levels; the intensive CME group was offered in addition follow-up seminars and free office materials. After 18 months, we audited 13,099 medical records from the 140 practices that remained in the study. There were no significant differences (P > .15) in screening for high serum cholesterol or compliance with guidelines between the groups receiving continuing medical education (51% screening; 33% compliance) and the control group (57% screening; 37% compliance). In the prespecified subgroup of patients with hypercholesterolemia, there was a trend toward a modest benefit from the continuing medical education interventions: compliance was 21% in the control group, 23% in the standard CME group, and 27% in the intensive CME group (P = .07 overall). These results emphasize the need for better ways to change behavior in practicing physicians and the importance of studying the implementation of preventive health recommendations.", "Cluster randomized controlled trial.\n To evaluate the effectiveness of two strategies to improve the use of active sick leave (ASL) for patients with low back pain.\n ASL is a public sickness benefit scheme offered to promote early return to modified work for temporarily disabled workers. It was poorly used, and the authors designed two community interventions to strengthen the implementation of ASL based on the results of a study of barriers to use among back pain patients, employers, general practitioners (GPs), and local National Insurance Administration staff.\n Sixty-five municipalities in three counties in Norway, randomly assigned to a passive intervention, a proactive intervention, or a control group. The interventions were targeted at patients on sick leave for low back pain for more than 16 days (n = 6176), their GPs, employers, and local insurance officers. The passive intervention included reminders about ASL on the sick leave form that GPs must complete, a standard agreement to facilitate ASL, targeted information, and a desktop summary for GPs of clinical practice guidelines for low back pain, emphasizing the importance of advice to stay active. The proactive intervention included these elements plus a resource person to facilitate the use of ASL and a continuing education workshop for GPs. The main outcome measure reported here is the proportion of eligible patients that used ASL.\n ASL was used significantly more in the proactive intervention municipalities (17.7%) compared with the passive intervention and control municipalities (11.5%, P = 0.018).\n A passive intervention that addressed identified barriers to the use of ASL did not increase its use. Although modest, a proactive intervention did increase its use. The main impact of the intervention was through direct contact and motivating telephone calls to patients. To the extent that GPs' practice was changed, it was either patient mediated or by patients bypassing their GP.", "To evaluate a training programme intended to improve the management of obesity, delivered to general practice teams.\n Cluster randomised trial.\n Northern and Yorkshire region of England.\n 44 general practices invited consecutively attending obese adults to participate; 843 patients attended for collection of baseline data and were subsequently randomised.\n 4.5 hour training programme promoting an obesity management model.\n Difference in weight between patients in intervention and control groups at 12 months (main outcome measure) and at 3 months and 18 months; change in practitioners' knowledge and behaviour in obesity management consultations.\n Twelve months after training the patients in the intervention group were 1 (95% confidence interval--1.9 to 3.9) kg heavier than controls (P = 0.5). Some evidence indicated that practitioners' knowledge had improved. Some aspects of the management model, including recording weight, target weight, and dietary targets, occurred more frequently in intervention practices after the training, but in absolute terms levels of implementation were low.\n A training package promoting a brief, prescriptive approach to the treatment of obesity through lifestyle modification, intended to be incorporated into routine clinical practice, did not ultimately affect the weight of this motivated and at risk cohort of patients.", "The need for training to equip primary care staff with the knowledge and skills to provide dietary advice to the public has been acknowledged. Little is known about the effectiveness of such training at improving the dietary counselling skills of multidisciplinary practice teams.\n To evaluate the effectiveness of a nutrition training programme, delivered to primary care teams by a dietitian.\n A paired-cluster randomised trial.\n Twelve general practices in Sunderland, in the United Kingdom.\n A nutrition training programme, aimed at improving the quality of dietary consultations, was developed and delivered to six primary care teams by a dietitian. Main outcome measures were patients' recall of seven key consulting behaviours. Data were collected from patients in intervention and control practices, pre- and post-intervention. Change in knowledge and attitude of practitioners was also measured.\n All 12 practices completed the trial. Data were collected from 251 patients pre-intervention and 228 patients post-intervention. Of the seven consulting behaviours targeted in the training, only the proportion of consultations where written information (diet sheets) was provided to patients was significantly higher (13% higher, 95% confidence interval [CI = 4 to 21, P = 0.004) in the intervention practices post-training. Some evidence of improved practitioner knowledge and attitude was detected.\n This evaluation of a nutrition training intervention detected only a limited impact on the behaviour, knowledge, and attitudes of primary care practitioners in dietary consultations.", "Non-compliance attenuates the efficacy of treatments for physical and mental disorders.\n To assess the effectiveness of a medication management training package for community mental health nurses (CMHNs) in improving compliance and clinical outcomes in patients with schizophrenia.\n Pragmatic randomised controlled trial. Sixty CMHNs in geographical clusters were assigned randomly to medication management training or treatment as usual. Each CMHN identified two patients on their case-load who were assessed at baseline and again after 6 months by a research worker. The primary efficacy outcome of interest was psychopathology, measured using the Positive and Negative Syndrome Scale (PANSS).\n Nurses who had received medication management training produced a significantly greater reduction in patients'overall psychopathology compared with treatment as usual at the end of the 6-month study period (change in PANSS total scores: medication management -16.62, treatment as usual 1.17; difference -17.79; 95% CI -24.12 to -11.45; P<0.001).\n Medication management training for CMHNs is effective in improving clinical outcomes in patients with schizophrenia.", "Injections are commonly overused in Indonesia. More than 60% of patients attending public health facilities receive at least one injection, which increases clinical risk and has adverse economic impact. This study assesses the efficacy of an innovative behavioral intervention, the Interactional Group Discussion (IGD), for reducing the overuse of injections. This study was a controlled trial in a single district with 24 public health centers randomized to intervention and control groups. Prescribers in the intervention group were invited to one IGD, each of which consisted of 6 prescribers and 6 patients; a total of 24 IGDs were held in a 4-week period, and all invited prescribers participated. The groups, which lasted 90-120 minutes, were facilitated by a behavioral scientist and a clinician, who also served as a scientific resource person. The hypothesized mechanism of behavior change involved reality testing prescribers' assumptions about patient beliefs, imparting scientific information about injection efficacy, and establishing peer norms about correct behavior. Outcomes were measured by a retrospective prescribing survey covering the periods 3 months before and 3 months after the intervention, with samples of 100 prescriptions per center per month. Rates of injection and average number of drugs per prescription were computed separately for each center, and t-tests were used to compare pre-post changes in outcomes in both groups. Results showed a significant decrease in injection use from 69.5 to 42.3% in the intervention group, compared to a decrease from 75.6 to 67.1% among controls [-18.7.0% intervention vs control, 95% CI = (-31.1%, -6.4%), P < 0.025]. There was also a significant reduction in average number of drugs per prescription [-0.37 drugs prescribed per patient, 95% CI = (-0.04, -0.52), P < 0.05], indicating that injections were not substituted with other drugs. We conclude that the IGD significantly reduces the overuse of injections. It is suggested to try out other behavioral interventions to improve the rational use of drugs.", "This study was aimed at evaluating the effects of an education program for general practitioners on their prescribing behaviour for cervical and breast cancer screening tests, and assessing the feasibility of general practitioners participation in screening programs. All three cytology laboratories and 19 of the 20 radiologists in one administrative region (\"Haute-Savoie\") in France agreed to participate. The 278 general practices in this region were randomly assigned to either the intervention group (a one-day seminar on screening for breast cancer and cervical cancer) or the control group (n for both = 139). The prescriptions of tests for the following year were noted from the laboratories' and radiologists' records. No significant differences were observed between the intervention group and the control group for the number of mammographies prescribed with a mean of 19.3 and 15.2 per practice, respectively. However, significantly more mammographies were prescribed in women aged over 50 by the intervention group (p = 0.038). Inversely, fewer smear tests were prescribed in the intervention group (mean per practice: 40.5 and 46.1, respectively). A significantly higher number of practices in the intervention group did not prescribe any smear tests (p = 0.007). This study suggests that it is possible to influence general practitioners' participation in screening programs, but that the messages should be carefully presented, since negative effects are possible.", "There is agreement, although little evidence, that consistently positioning stroke patients in allegedly reflex-inhibiting positions is therapeutic and will enhance functional recovery. The nursing staff, therefore, needs to know and implement these postures and understand their potential underlying value. We examined nurses' knowledge of and practice in positioning stroke patients before and after a formal teaching intervention.\n In a quasi-experimental study, 38 stroke patients and 59 nursing staff members (44 trained nurses and 15 healthcare assistants) from 6 wards were studied. The wards were randomly allocated to experimental or control status. Patients were assessed on entry into the study by use of a range of measures to establish group equivalence. Nineteen aspects of their position were documented at intervals throughout their stay with a previously developed observational tool. One thousand sets of observations of patient position were made. Using 2 questionnaires, the nurses' knowledge of the terminology used to denote posture and of issues relating to the moving and positioning of stroke patients was assessed before, immediately after, and 3 months after a package of formal teaching was implemented on the experimental wards. Nurse knowledge and patient position were used as the main outcome measures.\n Immediately after teaching, nurses in the experimental group scored significantly higher than those in the control group on the terminology questionnaire (P < 0.05) and the moving and positioning questionnaire (P < 0.001). Three months later, the experimental group scored higher on the latter questionnaire only (P < 0.005). The positioning of patients in the experimental group was improved overall after the teaching (P < 0.0005), and improvements to specific parts of the body were noted.\n It was possible to effect a degree of change in the nurses' knowledge of and practice in the positioning of stroke patients. However, the quality of patient positioning remained variable. More effective ways of improving positioning need to be developed. Only then can the effects of recommended positioning be evaluated.", "To evaluate the effects of a brief educational program on beliefs, knowledge, and behaviors related to skin cancer control among internal medicine housestaff and attending physicians.\n Randomised controlled trial.\n Urban academic general medicine practice.\n Internal medicine housestaff and attending physicians with continuity clinics at the practice site.\n Two 1-hour educational seminars on skin cancer control conducted jointly by a general internist and a dermatologist.\n Self-reported attitudes and beliefs about skin cancer control, ability to identify and make treatment decisions on 18 skin lesions, and knowledge of skin cancer risk factors were measured by a questionnaire before and after the teaching intervention. Exit surveys of patients at moderate to high risk of skin cancer were conducted 1 month before and 1 month after the intervention to measure physician skin cancer control practices reported by patients. Eighty-two physicians completed baseline questionnaires and were enrolled in the study, 46 in the intervention group and 36 in the control group. Twenty-five physicians attended both sessions, 11 attended one, and 10 attended neither. Postintervention, the percentage of physicians feeling adequately trained increased from 35% to 47% in the control group (p = .34) and from 37% to 57% in the intervention group (p = .06). Intervention physicians had an absolute mean improvement in their risk factor identification score of 6.7%, while control physicians' mean score was unchanged (p = .06). Intervention and control physicians had similar increases in their postintervention lesion identification and management scores. Postintervention, the mean proportion of patients per physician stating they were advised to watch their moles increased more among intervention physicians than control physicians (absolute difference of 19% vs -8%, p = .04). Other changes in behavior were not significant.\n Although we observed a few modest intervention effects, overall this brief skin cancer education intervention did not significantly affect primary care physicians' skin cancer control attitudes, beliefs, knowledge, or behaviors. A more intensive intervention with greater participation may be necessary to show a stronger impact on attitudes and knowledge about skin cancer control among primary care physicians.", "Previous studies have shown that Norwegian public health physicians do not systematically and explicitly use scientific evidence in their practice. They work in an environment that does not encourage the integration of this information in decision-making. In this study we investigate whether a theoretically grounded tailored intervention to diffuse evidence-based public health practice increases the physicians' use of research information.\n 148 self-selected public health physicians were randomised to an intervention group (n = 73) and a control group (n = 75). The intervention group received a multifaceted intervention while the control group received a letter declaring that they had access to library services. Baseline assessments before the intervention and post-testing immediately at the end of a 1.5-year intervention period were conducted. The intervention was theoretically based and consisted of a workshop in evidence-based public health, a newsletter, access to a specially designed information service, to relevant databases, and to an electronic discussion list. The main outcome measure was behaviour as measured by the use of research in different documents.\n The intervention did not demonstrate any evidence of effects on the objective behaviour outcomes. We found, however, a statistical significant difference between the two groups for both knowledge scores: Mean difference of 0.4 (95% CI: 0.2-0.6) in the score for knowledge about EBM-resources and mean difference of 0.2 (95% CI: 0.0-0.3) in the score for conceptual knowledge of importance for critical appraisal. There were no statistical significant differences in attitude-, self-efficacy-, decision-to-adopt- or job-satisfaction scales. There were no significant differences in Cochrane library searching after controlling for baseline values and characteristics.\n Though demonstrating effect on knowledge the study failed to provide support for the hypothesis that a theory-based multifaceted intervention targeted at identified barriers will change professional behaviour.", "A randomized controlled trial was done to assess the ability of continuing medical education to change physicians' knowledge and behavior in the care of patients with acute myocardial infarction. Patient care practices on eight objectives were audited 6 months before and after physicians completed a 2-hour educational program. Sixty-three physicians from eight randomly selected communities constituted the experimental group and 40 physicians from four similar communities served as controls. The average score for desired care practices over all objectives increased from 48.5% to 60% (p less than 0.001). Three objectives showed significantly greater gains for physicians in the experimental group. The generalizability of these effects was also studied in two additional educational contexts: a multitopic and a unitopic university-based continuing medical education program. Similar significant changes in behavior resulted in both contexts. Significant overall increases in knowledge occurred and persisted for all groups. Continuing medical education can effect changes in physicians' knowledge and care practices that can persist for at least 6 months.", "Peer review groups are considered helpful for quality improvement in primary care. An interactive educational programme for small peer groups was developed, focusing on the implementation of newly developed treatment guidelines. The aim is to evaluate the effect of the programme on adherence to treatment guidelines in general practice.\n A cluster randomized trial using a balanced incomplete block design was used; one arm received a programme on treatment of chronic heart failure (CHF), the other on hypertension treatment in diabetes mellitus type 2 (T2DM). A random sample of 10 CHF and 10 T2DM patients per GP was drawn, for whom data were extracted from electronic patient records 1 years before and 6 months after the intervention. The outcomes were prescribing of ACE inhibitors, and antihypertensive treatment in T2DM. The effect was analysed separately for both programmes using multilevel regression models.\n All 27 peer review groups in one region in the Netherlands were randomized, of which 16 participated. No significant effects were observed in the CHF group or in the T2DM group. The opportunity for change was limited, as only 53% of the CHF patients and 60% of the T2DM patients had a contact with their GP between the intervention and follow-up measurement.\n The peer review programme was not successful for changing the treatment of chronic patients, although the programme focused on dealing with barriers perceived by the participants. Not all problems perceived can be solved in a peer group discussion.", "The intervention level of epidemiology is useful for studying effects in health systems research. Due to practical and ethical reasons, it is often difficult to apply experimental methods such as classical randomized clinical trials in the field. However with alternative approaches such as 'randomization by group' some of these problems can be overcome. Drug information has since long been considered as an instrument to influence physicians, however evaluation of its effects is a new field of research. In the present study the impact of drug information on prescribing behaviour was evaluated in an outpatient setting in Sri Lanka. The study included 15 state health institutions (45 prescribers) with a common drug formulary. Groups of prescribers were randomized into two interventions; newsletters and newsletters reinforced by a group seminar, and one control group. The target topic was 'rational prescribing of antibiotics'. Some 18,766 randomly selected outpatient drug prescriptions were studied. Antibiotics (and sulphonamides) were prescribed to 33.2% of the patients. An overall trend towards a decrease in proportion of patients prescribed antibiotics in the two intervention groups was seen, although the difference was not significant (p greater than 0.05) compared to the control group. This is similar to the effect of written information on prescribing in other studies. A mean difference of -7.4% in written, -7.3% in written + seminar and -0.4% in the control group was shown. The general antibiotic prescribing pattern did not change in any of the three groups. Penicillin was the most commonly prescribed antibiotic and tetracycline was only rarely prescribed to children. This experiment indicates the feasibility of drug information intervention studies in developing countries.(ABSTRACT TRUNCATED AT 250 WORDS)", "Due to worldwide migration to Western countries, physicians are increasingly encountering patients with different ethnic backgrounds. Communication problems can arise as a result of differences in cultural backgrounds and poor language proficiency.\n To assess the effectiveness of an educational intervention on intercultural communication aimed to decrease inequalities in care provided between Western and non-Western patients.\n A randomised controlled trial with randomisation at the GP level and outcome measurements at the patient level.\n General practice in Rotterdam.\n Thirty-eight Dutch GPs in the Rotterdam region, with at least 25% of inhabitants of non-Western origin, and 2407 visiting patients were invited to participate in the study. A total of 986 consultations were finally included. The GPs were educated about cultural differences and trained in intercultural communication. Patients received a videotaped instruction focusing on how to communicate with their GP in a direct way. The primary outcome measure was mutual understanding and the secondary outcomes were patient's satisfaction and perceived quality of care. The intervention effect was assessed for all patients together, for the 'Western' and 'non-Western' patients, and for patients with different cultural backgrounds separately.\n An intervention effect was seen 6 months after the intervention, as improvement in mutual understanding (and some improvement in perceived quality of care) in consultations with 'non-Western' patients.\n A double intervention on intercultural communication given to both physician and patient decreases the gap in quality of care between 'Western' and 'non-Western' patients.", "A randomized controlled study was conducted to determine if specifically designed continuing medical education in the fields of cardiovascular and cancer medicine could change doctor office behaviour significantly. Thirty-one volunteer family doctors from 25 offices participated. Six (three cardiovascular and three cancer) learning objectives were defined. Two educational formats were selected as the independent variables: (1) group interaction opportunities (face-to-face and teleconference); and (2) concisely written newsletters. Chart measures of doctor performance prior to and 6 and 12 months following education served as the dependent variables. The family doctors receiving education were found to perform the recommended behaviours significantly more than those who did not receive the education (P less than 0.05) at 6 months post-education. This difference was maintained at the 12-month post-educational period for one of the educational programmes offered. A carefully planned programme of continuing medical education will result in favourable changes in the office practice of volunteer doctors. These changes can persist for as long as 12 months. Adherence to several essential learning principles is required.", "The objective of this study was to assess the effects of two brief training interventions to improve obstetricians' and midwives' explanations to patients of a routine prenatal screening test. Health professionals were randomly allocated to one of two intervention groups or a control group. Information-giving about the test and communication skills were assessed at baseline, post-training and 3-month follow-up from audiotaped consultations. Both intervention groups received a 1-h training session involving small group discussions focused around a video. In addition, one group received individual feedback on their baseline and post-training consultations. Twenty-six midwives and nine obstetricians completed the study according to the protocol. Changes between baseline and post-training, and between baseline and follow-up, were computed. Information-giving and communication skills improved significantly in subjects receiving training and feedback on their performance, with the greatest improvements occurring before feedback was given. Those receiving training without feedback significantly improved their communication skills and showed some improvement in information-giving. These results show that modest improvements in communication can be made with relatively brief training. Greater and more sustained improvements may be found if all staff were trained, and trained on a regular basis.", "Timely adoption of clinical practice guidelines is more likely to happen when the guidelines are used in combination with adjuvant educational strategies that address social as well as rational influences.\n To implement the conservative, evidence-based approach to low-back pain recommended in national guidelines, with the anticipated effect of reducing population-based rates of surgery.\n A randomized, controlled trial.\n Ten communities in western Washington State with annual rates of back surgery above the 1990 national average (158 operations per 100,000 adults).\n Spine surgeons, primary care physicians, patients who were surgical candidates, and hospital administrators.\n The five communities randomized to the intervention group received a package of six educational activities tailored to local needs by community planning groups. Surgeon study groups, primary care continuing medical education conferences, administrative consensus processes, videodisc-aided patient decision making, surgical outcomes management, and generalist academic detailing were serially implemented over a 30-month intervention period.\n Quarterly observations of surgical rates.\n After implementation of the intervention, surgery rates declined in the intervention communities but increased slightly in the control communities. The net effect of the intervention is estimated to be a decline of 20.9 operations per 100,000, a relative reduction of 8.9% (P = 0.01).\n We were able to use scientific evidence to engender voluntary change in back pain practice patterns across entire communities.", "Nursing staffs from two long-term care facilities attended a multisession educational program about the care of residents with diabetes (treatment group). A control group consisted of the nursing staffs from two other similar facilities who did not participate in the educational program. Both groups were given a knowledge pretest and posttest. A chart review also was conducted following the educational intervention to determine any changes in the diabetes care provided by the treatment group. Following the educational program, the treatment group had a significant increase in their mean score on the knowledge test compared with the control group. However, a review of the residents' charts revealed no significant increases in specific behaviors related to diabetes care. The findings suggest that, in addition to educational programs, more focused training concerning diabetes care is needed to improve the care of residents with diabetes in long-term care facilities. Implications for diabetes educators are discussed.", "To test the impact of physician education and facilitator assisted office system interventions on cancer early detection and preventive services.\n A randomised trial of two interventions alone and in combination.\n Physicians in 98 ambulatory care practices in the United States.\n The education intervention consisted of a day long physician meeting directed at improving knowledge, attitudes, and skills relevant to cancer prevention and early detection. The office system intervention consisted of assistance from a project facilitator in establishing routines for providing needed services. These routines included division of responsibilities for providing services among physicians and their staff and the use of medical record flow sheets.\n The proportions of patients provided the cancer prevention and early detection services indicated annually according to the US National Cancer Institute.\n Based on cross sectional patient surveys, the office system intervention was associated with an increase in mammography, the recommendation to do breast self examination, clinical breast examination, faecal occult blood testing, advice to quit smoking, and the recommendation to decrease dietary fat. Education was associated only with an increase in mammography. Record review for a patient cohort confirmed cross sectional survey findings regarding the office system for mammography and faecal occult blood testing.\n Community practices assisted by a facilitator in the development and implementation of an office system can substantially improve provision of cancer early detection and preventive services.", "To investigate the effect of a one-day workshop in which physicians were taught trust-building behaviors on their patients' levels of trust and on outcomes of care.\n In 1994, the study recruited 20 community-based family physicians and enrolled 412 consecutive adult patients from those physicians' practices. Ten of the physicians (the intervention group) were randomly assigned to receive a one-day training course in building and maintaining patients' trust. Outcomes were patients' trust in their physicians, patients' and physicians' satisfaction with the office visit, continuity in the patient-physician relationship, patients' adherence to their treatment plans, and the numbers of diagnostic tests and referrals.\n Physicians and patients in the intervention and control groups were similar in demographic and other data. There was no significant difference in any outcome. Although their overall ratings were not statistically significantly different, the patients of physicians in the intervention group reported more positive physician behaviors than did the patients of physicians in the control group.\n The trust-building workshop had no measurable effect on patients' trust or on outcomes hypothesized to be related to trust.", "This trial took 22 volunteer family physicians and randomly exposed some to training intervention and some to no training to study the effect on frequency and quality of exercise prescription to ambulatory adults. During the 6 weeks after training, the trained physicians addressed the issue of exercise with 35.3% of patients. The untrained physicians discussed exercise with only 8.6% of their patients.", "To study the effectiveness of an intensive small group education and peer review programme aimed at implementing national guidelines on asthma/chronic obstructive pulmonary disease (COPD) on care provision by general practitioners (GPs) and on patient outcomes.\n A randomised experimental study with pre-measurement and post-measurement (after one year) in an experimental group and a control group in Dutch general practice.\n Two groups of GPs were formed and randomised. The education and peer review group (17 GPs with 210 patients) had an intervention consisting of an interactive group education and peer review programme (four sessions each lasting two hours). The control group consisted of 17 GPs with 223 patients (no intervention).\n Knowledge, skills, opinion about asthma and COPD care, presence of equipment in practice; actual performance about peakflow measurement, non-pharmacological and pharmacological treatment; asthma symptoms (Dutch Medical Research Council), smoking habits, exacerbation ratio, and disease specific quality of life (QOL-RIQ). Data were collected by a written questionnaire for GPs, by self recording of consultations by GPs, and by a written self administered questionnaire for adult patients with asthma/COPD.\n Data from 34 GP questionnaires, 433 patient questionnaires, and recordings from 934 consultations/visits and 350 repeat prescriptions were available. Compared with the control group there were only significant changes for self estimated skills (+16%, 95% confidence interval 4% to 26%) and presence of peakflow meters in practice (+18%, p < 0.05). No significant changes were found for provided care and patient outcomes compared with the control group. In the subgroup of more severe patients, the group of older patients, and in the group of patients not using anti-inflammatory medication at baseline, no significant changes compared with the control group were seen in patient outcomes.\n Except for two aspects, intensive small group education and peer review in asthma and COPD care do not seem to be effective in changing relevant aspects of the provided care by GPs in accordance with guidelines, nor in changing patients' health status.", "Community pharmacists are in a position to assume increased responsibility for preventing and resolving drug-related problems in ambulatory patients. Such an expanded role is mandated under provisions of the Omnibus Budget Reconciliation Act of 1990. The need for pharmacist oversight of drug therapy may be most acute in elderly patients. This study reports on a program to teach community pharmacists a process of assessing drug therapy of elderly patients and intervening to correct problems. Community pharmacists (N = 102) were assigned to treatment and control conditions. Both groups targeted patients meeting criteria and enrolled them into the study. Treatment group pharmacists, who participated in a training program, also assessed the medication use of enrolled patients to identify and resolve medication-related problems. Patients (N = 762) were telephoned by researchers 1 month after enrollment for an interview. Comparisons between treatment and control group patients were made on reports of pharmacist activities, knowledge of regimens, compliance, and potential drug therapy problems, such as interactions and side effects. Treatment patients were more likely to report that pharmacists provided information and assessed for problems than were control patients. These differences were maintained on 3-month follow-up questionnaires. No differences were found on the odds that patients indicated misunderstanding of regimens, non-compliance, or potential therapeutic problems.", "nan", "To evaluate and compare the effects of two types of continuing medical education (CME) programs on the communication skills of practicing primary care physicians.\n Fifty-three community-based general internists and family practitioners practicing in the Portland, Oregon, metropolitan area and 473 of their patients.\n For the short program (a 4 1/2-hour workshop), 31 physicians were randomized to either the intervention or the control group. In the long program (a 2 1/2-day course), 20 physicians participated with no randomization. A research assistant visited all physicians' offices both one month before and one month after the CME program and audiotaped five sequential visits each time. Data were based on analysis of the content and the affect of the interviews, using the Roter Interactional Analysis Scheme.\n Based on both t-test analysis and analysis of covariance, no effect on communication was evident from the short program. The physicians enrolled in the long program asked more open-ended questions, more frequently asked patients' opinions, and gave more biomedical information than did the physicians in the short program. Patients of the physicians who attended the long program tended to disclose more biomedical and psychosocial information to their physicians. In addition, there was a decrease in negative affect for both patient and physician, and patients tended to demonstrate fewer signs of outward distress during the visit.\n This study demonstrates some potentially important changes in physicians' and patients' communication after a 2 1/2-day CME program. The changes demonstrated in both content and affect may have important influences on both biologic outcome and physician and patient satisfaction.", "Diagnosis of domestic violence (DV) in primary care is low compared to its prevalence. Care for patients is deficient. Over a 1-year period, we tested the effectiveness of an intensive intervention to improve asking about DV, case finding, and management in primary care. The intervention included skill training for providers, environmental orchestration (posters in clinical areas, DV questions on health questionnaires), and measurement and feedback.\n We conducted a group-randomized controlled trial in five primary care clinics of a large health maintenance organization (HMO). Outcomes were assessed at baseline and follow-up by survey, medical record review, and qualitative means.\n Improved provider self-efficacy, decreased fear of offense and safety concerns, and increased perceived asking about DV were documented at 9 months, and also at 21 months (except for perceived asking) after intervention initiation. Documented asking about DV was increased by 14.3% with a 3.9-fold relative increase at 9 months in intervention clinics compared to controls. Case finding increased 1.3-fold (95%, confidence interval 0.67-2.7).\n The intervention improved documented asking about DV in practice up to 9 months later. This was mainly because of the routine use of health questionnaires containing DV questions at physical examination visits and the placement of DV posters in clinical areas. A small increase in case finding also resulted. System changes appear to be a cost-effective method to increase DV asking and identification.", "The objective of this study was to evaluate the impact of three continuing education seminars (within a period of 4 months) on the quality of patient management and rational drug use. The study was designed as a randomized controlled trial. Prescribers in 16 general health centers were allocated to an intervention (eight health centers) or a control (eight health centers) group. A total of 5,685 patient cards was analyzed for quality of case management and rational drug use. In the intervention health centers the average number of drugs per patient decreased from 2.3 to 1.9 (p = 0.005) and the proportion of patients managed with nonpharmacological treatment increased from 1 to 13.2%. Recorded history taking, examination, and diagnosis improved in the intervention health centers. More drugs were correctly chosen in the intervention health centers compared to control health centers (p = 0.03). The proportion of patients prescribed antibiotics decreased and the proportion of patients adequately managed increased in the intervention health centers. Our conclusion is that continuing education in the form of repeated seminars is effective in influencing prescribers and in promoting rational drug use in primary care.", "To determine the quality of spirometry performed in primary care practice and to assess the impact of formal training.\n Randomized, controlled prospective interventional study.\n Primary care practice, Auckland City, New Zealand.\n Thirty randomly selected primary care practices randomized to \"trained\" or \"usual\" groups. One doctor and one practice nurse were nominated to participate from each practice.\n \"Trained\" was defined as participation in an \"initial\" spirometry workshop at week 0 and a \"maintenance of standards\" workshop at week 12. \"Usual\" was defined as no formal training until week 12, when participants they attended the same \"initial\" workshop provided for the trained group. The study duration was 16 weeks. Each practice was provided with a spirometer to be used at their clinical discretion.\n Spirometry data were uploaded weekly and analyzed using American Thoracic Society (ATS) criteria for acceptability and reproducibility. The workshops were assessed objectively with practical and written assessments, confirming a significant training effect. However, analysis of spirometry performed in clinical practice by the trained practitioners revealed three acceptable blows in only 18.9% of patient tests. In comparison, 5.1% of patient tests performed by the usual practitioners had three acceptable blows (p<0.0001). Only 13.5% of patient tests in the trained group and 3.4% in the usual group (p<0.0001) satisfied full acceptability and reproducibility criteria. However, 33.1% and 12.5% of patient tests in the trained and usual groups, respectively (p<0.0001), achieved at least two acceptable blows, the minimum requirement. Nonacceptability was largely ascribable to failure to satisfy end-of-test criteria; a blow of at least 6 s. Visual inspection of the results of these blows as registered on the spirometer for the presence of a plateau on the volume-time curve suggests that < 15% were acceptable.\n Although a significant training effect was demonstrated, the quality of the spirometry performed in clinical practice did not generally satisfy full ATS criteria for acceptability and reproducibility. Further study would be required to determine the clinical impact. However, the ATS guidelines allow for the use of data from unacceptable or nonreproducible maneuvers at the discretion of the interpreter. Since most of the failures were end-of-test related, the FEV1 levels are likely to be valid. Our results serve to emphasize the importance of effective training and quality assurance programs to the provision of successful spirometry in primary care practice.", "To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat.\n Unblinded, cluster randomised pretest-post-test trial.\n 142 general practices in Norway.\n 72 practices received interventions to implement guidelines for urinary tract infection and 70 practices received interventions to implement guidelines for sore throat, serving as controls for each other. 59 practices in the urinary tract infection group and 61 practices in the sore throat group completed the study. Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection.\n Interventions were developed to overcome identified barriers to implementing the guidelines. The main components of the tailored interventions were patient educational material, computer based decision support and reminders, an increase in the fee for telephone consultations, and interactive courses for general practitioners and practice assistants.\n Changes in rates of use of antibiotics, laboratory tests, and telephone consultations. Results: Patients in the sore throat group were 3% less likely to receive antibiotics after the intervention. Women with symptoms of urinary tract infection in the intervention group were 5.1% less likely to have a laboratory test ordered. No significant differences were found between the groups for the other outcomes. Large variation was found across the included practices in the rates of antibiotic prescription, use of laboratory tests and telephone consultations, and in the extent of change for all three outcome measures.\n Passively delivered, complex interventions targeted at identified barriers to change had little effect in changing practice.", "Depression is a major individual and public-health burden throughout the world and is managed mainly in primary care. The most effective strategy to reduce this burden has been believed to be education of primary-care practitioners. We tested this assumption by assessing the effectiveness of an educational programme based on a clinical-practice guideline in improving the recognition and outcome of primary-care depression.\n We carried out a randomised controlled trial in a representative sample of 60 primary-care practices (26% of the total) in an English health district. Education was delivered to practice teams and quality tested by feedback from participants and expert raters. The primary endpoints were recognition of depression, defined by the hospital anxiety and depression (HAD) scale, and clinical improvement. Analysis was by intention to treat.\n The education was well received by participants, 80% of whom thought it would change their management of patients with depression. 21409 patients were screened, of whom 4192 were classified as depressed by the HAD scale. The sensitivity of physicians to depressive symptoms was 39% in the intervention group and 36% in the control group after education (odds ratio 1.2 [95% CI 0.88-1.61]). The outcome of depressed patients as a whole at 6 weeks or 6 months after the assessment did not significantly improve.\n Although well received, this in-practice programme, which was designed to convey the current consensus on best practice for the care of depression, did not deliver improvements in recognition of or recovery from depression.", "To evaluate the impact on clinical behavior of a 3-day workshop designed to increase trainees' rates of smoking cessation counseling and reminders about Pap smears in routine consultations.\n Randomized control trial.\n Accredited teaching practices of the Royal Australian College of General Practitioners' Training Program.\n Thirty-four trainees and 1,500 consecutive adult patients ages 16-65 years.\n Trainees randomly allocated to the experimental group participated in a 3-day interactive workshop on disease prevention during their 13-week family medicine term. Audiotapes of consultations with adults conducted by trainees at the beginning and end of the rotation were analyzed blind to compare assessment of patients' smoking status and, for women, date of last Pap smear. A questionnaire mailed to each patient after the consultation also allowed identification of smokers and women overdue for a smear. Consultations with these patients at risk were analyzed for preventive counseling. Inter- and intrarater reliability was calculated for audiotape analysis.\n Preworkshop rates of questions about smoking were low, occurring in 22% of consultations. While trainees allocated to the experimental workshop were more likely to ask a routine question about smoking at the end of the term than those in the control group (P = 0.01), two-thirds of smokers remained undetected irrespective of trainee group and fewer than one in five were advised to stop smoking. Reminders about Pap smears did not change as a result of training and remained low in fewer than 20% of consultations. kappa values demonstrated high reliability of audiotape analysis.\n This direct measurement of clinical behavior revealed that low levels of preventive care provided by trainees are resistant to skills training without reinforcement in clinical practice. In view of the importance of prevention in routine consultations, we recommend continued evaluation of more intensive educational programs. Those withstanding rigorous evaluation could be considered for implementation in similar training contexts seeking to improve the frequency and quality of disease prevention in primary medical care.", "A Continuing Medical Education short course was designed to examine the effect of presenting topics in three learning formats - traditional lectures, large-group, case discussions or small-group, problem-solving sessions, on knowledge and performance of family physicians. The physicians in the small group session rated the CME short course higher and performed better on one aspect of patient management than the lecture or large group physicians but there were no other differences between groups on knowledge or physician performance.", "In a randomised trial, general practitioners and nurses in 21 practices were trained in patient-centred consulting and use of materials for people with Type 2 diabetes (GPs 0.5 days; nurses 1.5 days; two optional follow-up half-days). Twenty practices formed the comparison group. Professional beliefs, attitudes and behaviour were measured (pre-trial, close-of-course and end-of-trial), supported by patient reports of nurse behaviour (141 trained: 108 comparison patients, 1 year after diagnosis). A total of 49 practice nurses responded (29 trained; 20 comparison). Trained nurses rated relative importance of patient-centred to professional-centred care as greater than comparison nurses. Trained nurses became less keen on the approach during the trial, and perceived time constraints persisted. Patients diagnosed later in the study were less likely to recognise intervention materials. Trained nurses rated delivery of important aspects of care and satisfaction with style of care as lower than comparison nurses, but patients were more positive about delivery of care from trained than comparison nurses. Although nurses rated patient-centred care as important, whether or not they had been trained as part of the trial, the short, generalizable training programme significantly reduced nurse perceptions of their ability to deliver it. Nonetheless, patients reported that important aspects of diabetes care were delivered more if their nurses had been trained in patient-centred consulting. This raises issues concerning measurement scales completed by trained professionals.", "In an attempt to evaluate the efficacy of different methods of interventions to improve the appropriate use of drugs for acute diarrhoea, a controlled study has been carried out in 6 districts in Yogyakarta and Central Java provinces, Indonesia. This study was designed to investigate the impacts of two different methods of educational intervention, i.e. a small group face-to-face intervention and a formal seminar for prescribers, on prescribing practice in acute diarrhoea. The districts were randomly assigned into 3 groups and 15 health centers were selected from each district. Prescribers in Group 1 underwent a small group face-to-face intervention conducted in the respective health center. Those in Group 2 attended a formal seminar conducted at the district level. Prescribers in Group 3 served as the control group. Both interventions were given on a single occasion without follow-up supervision or monitoring. Written information materials on the appropriate management of acute diarrhoea were developed and were provided to all prescribers in the intervention groups. Focus group discussions (FGDs) involving prescribers and consumers in the 6 districts were carried out to identify various underlying motivations of drug use in acute diarrhoea. The findings of the FGDs were used as part of the intervention materials. To evaluate the impacts of these interventions on prescribing practice, a prescribing survey for patients under five years old with acute diarrhoea was carried out in health centers covering 3-month periods before and after the intervention. The results showed that both interventions were equally effective in improving the levels of knowledge of prescribers about the appropriate management of acute diarrhoea. They were also partially effective in improving the appropriate use of drugs, reducing the use of non-rehydration medications. There was a highly significant reduction of antimicrobial usage either after small-group face-to-face intervention (77.4 +/- 2.7% to 60.4 +/- 2.9%; P < 0.001) or formal seminar (82.3 +/- 3.0% to 72.3 +/- 3.6%; P < 0.001), and the former caused significantly (P < 0.001) greater reduction than the latter. There was also a significant (P < 0.01) reduction in the usage of antidiarrhoeals after both interventions, i.e. from 20.3 +/- 3.7% to 12.5 +/- 3.3% (P < 0.01) after face-to-face intervention and from 48.5 +/- 4.1% to 27.0 +/- 4.3% (P < 0.01) after seminar. However, the formal seminar had a significantly (P < 0.01) greater impact than the small group face-to-face intervention. There was also a trend toward increased oral rehydration solution (ORS) usage after both interventions, but this did not achieve the level of statistical significance (P > 0.05). No changes were observed in the control group. Although the small group face-to-face intervention did not appear to offer greater impacts over large seminars in improving the appropriate use of drugs in acute diarrhoea, since the unit cost of training is far less costly than the seminar, it might be feasibly implemented in the existing supervisory structure of the health system.", "The effect of clinical guidelines on resource utilization for complex conditions with substantial barriers to clinician behavior change has not been well studied. We report the impact of a multifaceted guideline implementation intervention on primary care clinician utilization of radiologic and specialty services for the care of acute low back pain.\n Physician groups were randomized to receive guideline education and individual feedback, supporting patient education materials, both, or neither. The impact on guideline adherence and resource utilization was evaluated during the 12-month period before and after implementation.\n Fourteen physician groups with 120 primary care physician and associate practitioners from 2 group model HMO practices.\n Guideline implementation utilized an education/audit/feedback model with local peer opinion leaders. The patient education component included written and videotaped materials on the care of low back pain.\n The clinician intervention was associated with an absolute increase in guideline-consistent behavior of 5.4% in the intervention group versus a decline of 2.7% in the control group (P =.04). The patient education intervention produced no significant change in guideline-consistent behavior, but was poorly adopted. Patient characteristics including duration of pain, prior history of low back pain, and number of visits during the illness episode were strong predictors of service utilization and guideline-consistent behavior.\n Implementation of an education and feedback-supported acute low back pain care guideline for primary care clinicians was associated with an increase in guideline-consistent behavior. Patient education materials did not enhance guideline effectiveness. Implementation barriers could limit the utility of this approach in usual care settings.", "Assessed is a breast-feeding training course that was attended by health professionals at the Santos Lactation Center (SLC), Santos, São Paulo, Brazil, as well as its impact on the implementation of breast-feeding programmes in maternity hospitals. Eight maternity hospitals were studied--four were randomly allocated to the experimental group and sent three health professionals to attend an 18-day course at SLC; the remaining four institutions constituted the control group. The compliance of all eight hospitals with WHO/UNICEF's \"Ten steps for successful breast-feeding\" was determined using scores obtained before and 6 months after the training course. Institutions in the experimental group had an improved score, but those in the control group did not. The SLC training course was efficient since it enabled the participants to promote breast-feeding practices. However, in order to succeed in implementing breast-feeding programmes, health professionals require also to develop skills to apply the knowledge they acquire in the course, as well as to involve the whole maternity unit team in the activities.", "General practitioners (GPs) can be provided with effective training in the skills to manage depression. However, it remains uncertain whether such training achieves health gain for their patients.\n The study aimed to measure the health gain from training GPs in skills for the assessment and management of depression. The study design was a cluster randomized controlled trial. GP participants were assessed for recognition of psychological disorders, attitudes to depression, prescribing patterns and experience of psychiatry and communication skills training. They were then randomized to receive training at baseline or the end of the study. Patients selected by GPs were assessed at baseline, 3 and 12 months. The primary outcome was depression status, measured by HAM-D. Secondary outcomes were psychiatric symptoms (GHQ-12) quality of life (SF-36), satisfaction with consultations, and health service use and costs.\n Thirty-eight GPs were recruited and 36 (95%) completed the study. They selected 318 patients, of whom 189 (59%) were successfully recruited. At 3 months there were no significant differences between intervention and control patients on HAM-D, GHQ-12 or SF-36. At 12 months there was a positive training effect in two domains of the SF-36, but no differences in HAM-D, GHQ-12 or health care costs. Patients reported trained GPs as somewhat better at listening and understanding but not in the other aspects of satisfaction.\n Although training programmes may improve GPs' skills in managing depression, this does not appear to translate into health gain for depressed patients or the health service.", "We conducted a trial to evaluate the effect of an active, multifaceted educational strategy to promote the use of the WHO Reproductive Health Library (RHL) on obstetric practices.\n Cluster randomised trial. The trial was assigned the International Standardised Randomised Controlled Trial Number ISRCTN14055385.\n Twenty-two hospitals in Mexico City and 18 in the Northeast region of Thailand.\n The intervention consisted primarily of three interactive workshops using RHL over a period of 6 months. The focus of the workshops was to provide access to knowledge and enable its use. A computer and support for using both the computer and RHL were provided at each hospital. The control hospitals did not receive any intervention.\n The main outcome measures were changes in ten selected clinical practices as recommended in RHL starting approximately four to six months after the third workshop. Clinical practice data were collected at each hospital from 1000 consecutively delivered women or for a 6-month period whichever was reached sooner.\n The active, multifaceted educational intervention we employed did not affect the ten targeted practices in a consistent and substantive way. Iron/folate supplementation, uterotonic use after birth and breastfeeding on demand were already frequently practiced, and we were unable to measure external cephalic version. Of the remaining six practices, selective, as opposed to routine episiotomy policy increased in the intervention group (difference in adjusted mean rate = 5.3%; 95% CI -0.1 to 10.7%) in Thailand, and there was a trend towards an increased use of antibiotics at caesarean section in Mexico (difference in adjusted mean rate = 19.0%; 95% CI: -8.0 to 46.0%). There were no differences in the use of labour companionship, magnesium sulphate use for eclampsia, corticosteroids for women delivering before 34 weeks and vacuum extraction. RHL awareness (24.8-65.5% in Mexico and 33.9-83.3% in Thailand) and use (4.8-34.9% in Mexico and 15.5-76.4% in Thailand) increased substantially after the intervention in both countries.\n The multifaceted, active strategy to provide health workers with the knowledge and skills to use RHL to improve their practice led to increased access to and use of RHL, however, no consistent or substantive changes in clinical practices were detected within 4-6 months after the third workshop.", "To determine the effectiveness of two dissemination and implementation strategies to implement a national guideline for epilepsy management in primary care settings.\n Three-arm cluster-randomized controlled trial. The participants were general practitioners from 68 practices in Tayside, Scotland, and 1,133 of their patients with self-reported epilepsy treated with antiepileptic medications (AEDs). Practices were randomized blind to a control, intermediate, or intensive intervention. Control: Postal dissemination of a nationally developed clinical guideline. Intermediate intervention: Postal dissemination of the guideline supported by interactive, accredited workshops, and dedicated, structured protocol documents. Intensive intervention: Intermediate intervention plus a nurse specialist who supported and educated practices in the establishment of epilepsy review clinics. The primary outcome was the SF-36 health-related quality-of-life instrument. Secondary measures were a battery of prevalidated epilepsy-specific quality-of-life instruments. These were administered at baseline and after the intervention phase. Process of care was assessed by case-note review on number of review meetings and counseling sessions for epilepsy before and after the interventions.\n None of the intervention groups showed any change in the primary or secondary outcome measures or process-of-care measures.\n None of the intervention strategies led to improvements in patient quality of life or quality of epilepsy care. Further research is needed to discover why the interventions failed, to identify barriers to adoption of guidelines, and to develop strategies that might improve implementation and uptake in the future.", "Depression, a common disorder often treated by family physicians, may be both underdiagnosed and undertreated. The objective of this study was to determine whether the diagnosis and treatment of depression by family physicians could be improved through an educational strategy.\n In this study, conducted between July and December 1997, 42 family physicians in Newfoundland were randomly assigned to an intervention group (3-hour case-based educational session on clinical practice guidelines [CPGs] for depression and access to a psychiatrist for consultation) or to a control group (receipt of CPGs without educational session or access to the psychiatrist). Physicians were asked to keep a log of patients with newly diagnosed depression and to record information on severity of depression, medications and referrals to mental health professionals. Patients were asked to complete the Centre for Epidemiologic Studies Depression (CES-D) scale before treatment and after 6 months of follow-up. The primary outcome measure was the \"gain\" score (difference between first and last CES-D scores).\n During the study period physicians in the intervention group diagnosed 91 new cases of depression (mean 4.1 per physician) and those in the control group diagnosed 56 (mean 2.8 per physician); the difference was not significant. Most patients (91.2% in the intervention group and 89.3% in the control group received a prescription for an antidepressant on their first visit. Similar proportions (46.2% in the intervention group and 37.5% in the control group) took their medication for the full 6 months; however, significantly more patients in the intervention group were taking an antidepressant at the 6-month follow-up (56% v. 39.3%, p = 0.02). The mean number of visits per patient was similar in the 2 groups (7.7 in the intervention group and 7.6 in the control group). Physicians in the intervention group consulted the psychiatrist 9 times. The overall rate of referrals to psychiatrists and other mental health professionals was 10.9%; however, referrals were significantly higher in the intervention group (15.4% v. 3.5%, p = 0.05). After 6 months of follow-up, a significant difference in gain scores was detected between the intervention and control groups for both the patient's self-rated CES-D scores (mean gain score 19.3 v. 15.5 respectively, p = 0.04) and the physicians' ratings of depression severity before treatment and at 6 months (mean gain 1.1 v. 0.7 respectively, p = 0.02).\n The educational strategy had a modest beneficial effect on the outcomes of patients with depression, but there are still concerns regarding the low rates of drug treatment and referral to mental health professionals by family physicians.", "To investigate the effect of clinical guidelines on the management of infertility across the primary care-secondary care interface.\n Cluster randomised controlled trial.\n General practices and NHS hospitals accepting referrals for infertility in the Greater Glasgow Health Board area. Participants: All 221 general practices in Glasgow; 214 completed the trial.\n General practices in the intervention arm received clinical guidelines developed locally. Control practices received them one year later. Dissemination of the guidelines included educational meetings.\n The time from presentation to referral, investigations completed in general practice, the number and content of visits as a hospital outpatient, the time to reach a management plan, and costs for referrals from the two groups.\n Data on 689 referrals were collected. No significant difference was found in referral rates for infertility. Fewer than 1% of couples were referred inappropriately early. Referrals from intervention practices were significantly more likely to have all relevant investigations carried out (odds ratio 1.32, 95% confidence interval 1.00 to 1.75, P=0.025). 70% of measurements of serum progesterone concentrations during the midluteal phase and 34% of semen analyses were repeated at least once in hospital, despite having been recorded as normal when checked in general practice. No difference was found in the proportion of referrals in which a management plan was reached within one year or in the mean duration between first appointment and date of management plan. NHS costs were not significantly affected.\n Dissemination of infertility guidelines by commonly used methods results in a modest increase in referrals having recommended investigations completed in general practice, but there are no detectable differences in outcome for patients or reduction in costs. Clinicians in secondary care tended to fail to respond to changes in referral practice by doctors. Guidelines that aim to improve the referral process need to be disseminated and implemented so as to lead to changes in both primary care and secondary care.", "Antenatal corticosteroids for fetal maturation have been underused, despite evidence for their benefits in cases of preterm birth.\n To evaluate dissemination strategies aimed at increasing appropriate use of this therapy.\n Twenty-seven tertiary care institutions were randomly assigned to either usual dissemination of practice recommendations (n = 14) or usual dissemination plus an active, focused dissemination effort (n = 13).\n Obstetricians and their preterm delivery cases at participating hospitals.\n Recommendations by a National Institutes of Health (NIH) Consensus Conference held in late February-early March 1994 were disseminated in early May 1994. Usual dissemination was publication of the recommendations and endorsement by the American College of Obstetricians and Gynecologists. Active dissemination was a year-long educational effort led by an influential physician and a nurse coordinator at each facility, consisting of grand rounds, a chart reminder system, group discussion of case scenarios, monitoring, and feedback.\n Use or nonuse of antenatal corticosteroids was abstracted from medical records of eligible women delivering at the participating hospitals in the 12 months immediately prior to release of the NIH recommendations (average number of records abstracted, 130) and in the 12 months following their release (average number of records abstracted, 122).\n Active dissemination significantly increased the odds of corticosteroid use after the conference. Use increased from 33.0% of eligible patients receiving corticosteroids to 57.6%, or by 75% over baseline, in usual dissemination hospitals. Use increased from 32.9% to 68.3%, oran 108% increase, in active dissemination hospitals. Gestational age and maternal diagnosis affected use of the therapy in complex ways.\n An active, focused dissemination effort increased the effectiveness of usual dissemination methods when combined with key principles to change physician practices.", "Many patients who visit primary care physicians suffer from depression, but physicians may miss the diagnosis or undertreat these patients. Improving physicians' communication skills pertaining to diagnosing and managing depression may lead to better outcomes.\n We performed a randomized controlled trial involving 49 primary care physicians to determine the effect of the Depression Education Program on their knowledge of depression and their behavior toward depressed patients. After randomization, physicians in the intervention group completed the Depression Education Program, which consists of 2 4-hour interactive workshops that combine lectures, discussion, audiotape review, and role-playing. Between sessions, physicians audiotaped an interview with one of their patients. Two to 6 weeks following the intervention program, physicians completed a knowledge test and received office visits from 2 unannounced people acting as standardized patients with major depression. These \"patients\" completed a checklist and scales. Logistic and linear regression were used to control for sex, specialty, and suspicion that the patient was a standardized patient.\n For both standardized patients, more intervention physicians than control physicians asked about stresses at home, and they also scored higher on the Participatory Decision-Making scale. During the office visits of one of the standardized patients, more intervention physicians asked about at least 5 criteria for major depression (82% and 38%, P = .006), discussed the possibility of depression (96% and 65%, P = .049), scheduled a return visit within 2 weeks (67% and 33%, P = .004), and scored higher than control physicians on the Patient Satisfaction scale (40.3 and 35.5, P = .014).\n The Depression Education Program changed physicians' behavior and may be an important component in the efforts to improve the care of depressed patients.", "Doctors' communication with patients is commonly hampered by lack of training in this core skill. This study aimed to assess the efficacy of an intensive 3-day training course on communication skills in a randomised controlled trial with a two-by-two factorial design and several outcomes.\n 160 oncologists from 34 UK cancer centres were randomly allocated to four groups: written feedback followed by course; course alone; written feedback alone; and control. At each of two assessment periods, consultations with six to ten consecutive, consenting patients per doctor were videotaped. 2407 patients participated. Outcome measures included objective and subjective ratings made by researchers, doctors, and patients. The primary outcomes were objective improvements after the intervention in key communication skills. Course content included structured feedback, videotape review of consultations, role-play with simulated patients, interactive group demonstrations, and discussion led by a trained facilitator.\n In Poisson regression analysis of counts of communication behaviours, course attendance significantly improved key outcomes. The estimated effect sizes corresponded to higher rates of use of focused questions (difference between course attenders [n=80] and non-attenders [n=80] 34%, p=0.003), focused and open questions (27%, p=0.005), expressions of empathy (69%, p=0.003), and appropriate responses to patients' cues (38%, p=0.026), and a 24% lower rate of use of leading questions (p=0.11). There was little evidence for the effectiveness of written feedback.\n The communication problems of senior doctors working in cancer medicine are not resolved by time and clinical experience. This trial shows that training courses significantly improve key communication skills. More resources should be allocated to address doctors' training needs in this vital area.", "The objective of the study was to evaluate the effectiveness of 2 educational strategies aimed at improving prescribing standards in primary care.\n A pragmatic controlled trial was designed; the study population included general and family practitioners in Galicia (northwestern Spain) divided into 3 study groups: a one-to-one education group (n = 98), a by-group education group (n = 92), and a control group (n = 405). The educational intervention included explicit recommendations for selecting nonsteroidal anti-inflammatory drugs (NSAIDs) for inflammation signs. Some of the subjects were given reminders. Mixed-effect linear models were applied to data analysis. Analyses were done by intention-to-treat. The dependent variable is a rate with a numerator that is the number of prescribed units of the NSAIDs recommended during intervention; the denominator is the total number of prescribed units of the NSAID total.\n One-to-one education obtained an average prescribing behavior improvement of 6.5% (P < 0.001) in the 9 months after intervention. In the education group, the average improvement was 2.4% (P < 0.05) for the same period. Statistically significant differences were observed between the group intervention and one-to-one groups. The reminder increased significantly the effectiveness of the one-to-one intervention.\n A single, short educational session to primary care doctors can improve their prescribing standards during long periods of > or = 9 months. Of the 2 strategies followed in the trial, one-to-one education has shown to be the most effective. Results also show that the effectiveness of these interventions increases when presented together with written material.", "Research is needed to validate effective and practical strategies for improving the provision of evidence-based medicine in primary care.\n To determine whether a multimethod quality improvement intervention was more effective than a less intensive intervention for improving adherence to 21 quality indicators for primary and secondary prevention of cardiovascular disease and stroke.\n 2-year randomized, controlled clinical trial with the practice as the unit of randomization.\n 20 community-based family or general internal medicine practices in 14 states. All used the same electronic medical record.\n 44 physicians, 17 midlevel providers, and approximately 200 staff members; data from the electronic medical records of 87,291 patients.\n All practices received copies of practice guidelines and quarterly performance reports. Intervention practices also hosted quarterly site visits to help them adopt quality improvement approaches and participated in 2 network meetings to share \"best practice\" approaches.\n The percentage of indicators at or above predefined targets and the percentage of patients who had achieved each clinical indicator.\n Intervention practices improved 22.4 percentage points (from 11.3% to 33.7%) in the percentage of indicators at or above the target; control practices improved 16.4 percentage points (from 6.3% to 22.7%). The 6.0-percentage point absolute difference between the intervention and control group was not statistically significant (P > 0.2). Patients in intervention practices had greater improvements than those in control practices for diagnoses of hypertension (improvement difference, 15.7 percentage points [95% CI, 5.2 to 26.3 percentage points]) and blood pressure control in patients with hypertension (improvement difference, 8.0 percentage points [CI, 0.0 to 16.0 percentage points]).\n The study involved a small number of practices and lacked a pure control group.\n Primary care practices that use electronic medical records and receive regular performance reports can improve their adherence to clinical practice guidelines for cardiovascular disease and stroke prevention.", "To evaluate patient education and resident education strategies to promote advance directives in the outpatient setting, and to assess barriers to implementation.\n Controlled clinical trial.\n The internal medicine residents' practice of an urban, university medical center.\n Medical residents and 250 patients seen at least twice in the 3 months prior to the study.\n We randomized practice days: one to patient education, one to resident education, and three controls. Resident education consisted of a lecture, a videotape of a model advance directives discussion, and videotaping of an actual discussion by each resident, followed by individual review. Patient education consisted of distributing pamphlets in the waiting room and offering all patients an opportunity to discuss advance directives.\n We interviewed 187 of these patients (response rate 75%) and surveyed 62 residents (response rate 70%). After 18 months, there were no significant differences in the number of advance directives in charts among the three groups. Documented advance directives discussions with patients in the resident education group increased from 3% to 17% (p < .001), more than those in the patient education (5%) or control group (10%, p = .04). Residents in the resident education group were more likely to report discussing advance directives than those in the patient education or control groups (p = .05). Lack of time (95%) and lack of continuity (76%) were the most frequently cited barriers. In multivariate logistic regression, nonwhite race and non-U.S. birth were negatively associated with patient interest in advance directives. Patient race and birthplace were not associated with actual discussions of advance directives.\n Even with intensive efforts to educate outpatients and residents about advance directives, important barriers remain, raising questions about how best to promote advance directives among outpatients.", "Although substantial resources have been invested in communication skills training for clinicians, little research has been done to test the actual effect of such training on patient satisfaction.\n To determine whether clinicians' exposure to a widely used communication skills training program increased patient satisfaction with ambulatory medical care visits.\n Randomized, controlled trial.\n A not-for-profit group-model health maintenance organization in Portland, Oregon.\n 69 primary care physicians, surgeons, medical subspecialists, physician assistants, and nurse practitioners from the Permanente Medical Group of the Northwest.\n \"Thriving in a Busy Practice: Physician-Patient Communication,\" a communication skills training program consisting of two 4-hour interactive workshops. Between workshops, participants audiotaped office visits and studied the audiotapes.\n Change in mean overall score on the Art of Medicine survey (HealthCare Research, Inc., Denver, Colorado), which measures patients' satisfaction with clinicians' communication behaviors, and global visit satisfaction.\n Although participating clinicians' self-reported ratings of their communication skills moderately improved, communication skills training did not improve patient satisfaction scores. The mean score on the Art of Medicine survey improved more in the control group (0.072 [95% CI, -0.010 to 0.154]) than in the intervention group (0.030 [CI, -0.060 to 0.1201).\n \"Thriving in a Busy Practice: Physician-Patient Communication,\" a typical continuing medical education program geared toward developing clinicians' communication skills, is not effective in improving general patient satisfaction. To improve global visit satisfaction, communication skills training programs may need to be longer and more intensive, teach a broader range of skills, and provide ongoing performance feedback.", "To evaluate the effectiveness of two teaching interventions to increase residents' performance of smoking cessation counseling.\n Randomized controlled factorial trial.\n Eleven residency programs, in internal medicine (six), family medicine (three), and pediatrics (two). Programs were located in three university medical centers and four university-affiliated community hospitals.\n 261 residents who saw ambulatory care patients at least one half-day per week, and 937 returning patients aged 17 to 75 years who reported having smoked five or more cigarettes in the preceding seven days. Of the 937, 843 were eligible for follow-up, and 659 (78%) were interviewed by phone at six months.\n Two interventions (tutorial and prompt) and four groups. The tutorial was a two-hour educational program in minimal-contact smoking cessation counseling for residents. The prompt was a chart-based reminder to assist physician counseling. One group of residents received the tutorial; one, the prompt; and one, both. A fourth group received no intervention.\n Six months after the intervention, physician self-reports showed that residents in the tutorial + prompt and tutorial-only groups had used more counseling techniques (1.5-1.9) than had prompt-only or control residents (0.9). Residents in all three intervention groups advised more patients to quit smoking (76-79%) than did control group residents (69%). The tutorial had more effect on counseling practices than did the prompt. Physician confidence, perceived preparedness, and perceived success followed similar patterns. Exit interviews with 937 patients corroborated physician self-reports of counseling practices. Six months later, self-reported and biochemically verified patient quitting rates for residents in the three intervention groups (self-reported: 5.3-8.2%; biochemically verified: 3.4-5.7%) were higher than those for residents in the control group (self-reported: 5.2%; biochemically verified: 1.7%), though the differences were not statistically significant.\n A simple and feasible educational intervention can increase residents' smoking cessation counseling.", "In the international Drug Education Project, a new educational program for peer groups of doctors was developed and tested to improve the treatment of asthma patients in The Netherlands, Norway, Sweden, and Slovakia. Individualized feedback on prescribing and the underlying decision strategy was presented and discussed within the group of doctors, in relation to existing guidelines. In a parallel, randomized controlled design the effect on competence and actual prescribing was tested. Results were related to national guidelines. In general, the program improved the doctors' attitudes as well as some of their prescribing behavior. The proportion of patients treated with inhaled corticosteroids significantly improved in The Netherlands (effect size 1.27), and the proportion of oral corticosteroid use for exacerbation treatment increased both in The Netherlands and in Norway (effect sizes 1.99 and 0.87, respectively). Overall attitudes of Dutch and Norwegian doctors also improved significantly (effect sizes 1.06 and 0.87, respectively), as did both knowledge (effect size 1.06) and attitudes (effect size 1.49) concerning exacerbation treatment in Slovakia. In Sweden no significant improvements could be measured. Conclusively, improvements in asthma treatment are possible with an educational program based on self-learning in small peer groups, although effects in one health care setting may not occur in another health care setting. Possible explaining factors may be different attitudes to and experiences with guidelines as well as with continuing medical education programs, and differences in the opportunities for change, including prevailing trends in prescribing behavior.", "This study evaluates the impact of the Integrated Management Of Childhood Illness (IMCI) training on quality of counseling provided to caregivers about administration of antimalarials to their children. Ten community health centers in southern Mali were randomized to either training or comparison arms of the study, and health providers' consultations with caregivers were observed. Out of a 10-point counseling scale (Cronbach's alpha=0.77), IMCI-trained providers completed an average of 1.47 (95% CI, -0.25, 3.2) more tasks than did providers who had not received IMCI training in a linear regression analysis that accounted for intra-provider correlations. Drug consultations done in both French and the local language, Bambara, had higher scores than those conducted exclusively in Bambara. The effect of providers receiving IMCI training was more pronounced in bilingual consultations, with an average increase of 2.49 (95% CI, 0.76, 4.22) in IMCI, bilingual consultations, and average increase of 0.87 (95% CI, -0.95, 2.69) in IMCI monolingual (Bambara) consultations as compared to non-IMCI-trained providers in monolingual consultations. IMCI training showed a non-significant trend overall in improving drug counseling provided to caregivers, with significant improvements in bilingual consultations. The IMCI program in Mali should consider strategies such as role-playing of counseling in Bambara or other local languages during training to improve patient-provider communication. Similar problems related to counseling by health workers in local languages are likely to be present throughout Africa, and warrant further study.", "To assess whether adding a training intervention for clinic staff to the usual DOTS strategy (the internationally recommended control strategy for tuberculosis (TB)) would affect the outcomes of TB treatment in primary care clinics with treatment success rates below 70%.\n A cluster randomized controlled trial was conducted from July 1996 to July 2000 in nurse-managed ambulatory primary care clinics in Cape Town, South Africa. Clinics with successful TB treatment completion rates of less than 70% and annual adult pulmonary TB loads of more than 40 patients per year were randomly assigned to either the intervention (n = 12) or control (n = 12) groups. All clinics completed follow-up. Treatment outcomes were measured in cohorts of adult, pulmonary TB patients before the intervention (n = 1200) and 9 months following the training (n = 1177). The intervention comprised an 18-hour experiential, participatory in-service training programme for clinic staff delivered by nurse facilitators and focusing on patient centredness, critical reflection on practice, and quality improvement. The main outcome measure was successful treatment, defined as patients who were cured and those who had completed tuberculosis treatment.\n The estimated effect of the intervention was an increase in successful treatment rates of 4.8% (95% confidence interval (CI): -5.5% to 15.2%) and in bacteriological cure rates of 10.4% (CI: -1.2% to 22%). A treatment effect of 10% was envisaged, based on the views of policy-makers on the minimum effect size for large-scale implementation.\n This is the first evidence from a randomized controlled trial on the effects of experiential, participatory training on TB outcomes in primary care facilities in a developing country. Such training did not appear to improve TB outcomes. However, the results were inconclusive and further studies are required.", "Prescribing practices impact greatly on drug use and expenditure. The situation in developing countries is often compounded by a limited health budget. Furthermore, because of role substitution in these countries, prescribers are often not formally trained in rational prescribing. The study described in this paper assesses the effect of a prescribing training intervention for primary health care nurses.\n A generic training-of-trainers course and a 4-day effective prescribing course were presented to 24 provincial trainers. These trainers then conducted effective prescribing workshops for 20 primary health care nurses per workshop. In 1997, 457 prescribers were trained by this method in South Africa's Northern Province. The study investigated the impact of the training on prescribing practices for two target conditions, in a control and a study group of 11 clinics each, 1 month after and 3 months after the intervention.\n Primary health care clinics in the Lowveld Region of the Northern Province of South Africa.\n Prescribing practices for the two conditions examined were significantly improved by the training. Changed behaviour was not only seen in prescribing for upper respiratory tract infections, used as an example condition, but also for diarrhoea and/or vomiting, a common condition in the region, which was not included in the training programme. These results show that prescribers not only retained the knowledge gained, but were also able to apply their new skills to other conditions (transfer effect). The change in the study group was maintained for 3 months after training, while there were no significant improvements in prescribing in the control group.\n The training intervention had a beneficial effect on prescribing practices.", "A ten hour brief therapy training program with format representative of postgraduate training workshops was delivered to practicing psychotherapists at three public clinics. Training procedures and content were specified and provided to program participants in a manual. Clinician volunteers (n = 22) were randomly assigned to Training (n = 12) and Control (n = 10) conditions. Pretraining assessments found no differences between Training and Control group therapists or their clients (n = 176). Relative to clients of Control therapists, Trained therapists' clients received more brief therapy, reported greater treatment satisfaction, had lower client-reported dropout rates, and obtained better therapist ratings of outcome. Possible causes of the training impact and its limitations were discussed.", "This study examines the effects of a home health intervention designed to standardize nursing care, strengthen nurses' support for patient self-management and yield better CHF patient outcomes. Participants were 371 Medicare CHF patients served by 205 nurses randomized to intervention and control groups in a large urban home healthcare agency (HHA). The intervention consisted of an evidence-based nursing protocol, patient self-care guide, and training to improve nurses'teaching and support skills. Outcome measures included home care,physician and emergency department (ED) use, hospital admission, condition-specific quality of life (QoL), satisfaction with home care services and survival at 90 days. The intervention was associated with a marginally significant reduction in the volume of skilled nursing visits (p = .074), and a reduction variation in the typical number of visits provided (p < .05), without a significant increase in physician or ED use or patient mortality. Hypothesized improvement in other outcomes did not occur.", "To assess the effectiveness of a multiple intervention aimed at reducing antibiotic prescription rates for symptoms of the respiratory tract in primary care.\n Randomised controlled trial.\n Twelve peer review groups including 100 general practitioners with their collaborating pharmacists in the region of Utrecht, Netherlands.\n The intervention consisted of group education meetings, with a consensus procedure on indication for and type of antibiotics and with training in communication skills; monitoring and feedback on prescribing behaviour; group education for assistants of general practitioners and pharmacists; and education material for patients. The control group did not receive any of these elements.\n Antibiotic prescription rates for acute symptoms of the respiratory tract and patients' satisfaction.\n 89 general practitioners completed the study (89%). At baseline, prescription rates for antibiotics for respiratory tract symptoms did not differ between intervention and control group (27% v 29%, respectively). After nine months, the prescription rates in the intervention group fell to 23%, whereas the control group's rose to 37% (mean difference in change -12%, 95% confidence interval -18.9% to -4.0%). Multilevel analysis confirmed the results of the unadjusted analysis (intervention effect -10.7%, -20.3% to -1.0%). Patients' satisfaction was high and did not differ in the two groups at baseline or after the intervention.\n A multiple intervention reduced prescribing rates of antibiotics for respiratory tract symptoms while maintaining a high degree of satisfaction among patients. Further research should focus on the sustainability and cost effectiveness of this intervention.", "To establish the effect of an educational intervention for general practitioners on the health behaviours and wellbeing of elderly patients.\n Randomised controlled trial with 1 year follow up.\n Metropolitan general practices in Melbourne, Australia.\n 42 general practitioners and 267 of their patients aged over 65 years.\n Educational and clinical practice audit programme for general practitioners on health promotion for elderly people.\n Patients' physical activity, functional status, self rated health, immunisation status, social contacts, psychological wellbeing, drug usage, and rate of influenza vaccination. Primary efficacy variables were changes in outcome measures over 1 year period.\n Patients in the intervention group had increased (a) walking by an average of 88 minutes per fortnight, (b) frequency of pleasurable activities, and (c) self rated health compared with the control group. No change was seen in drug usage, rate of influenza vaccination, functional status, or psychological wellbeing as a result of the intervention. Extrapolations of the known effect of these changes in behaviour suggest mortality could be reduced by 22% if activity was sustained for 5 years.\n Education of the general practitioners had a positive effect on health outcomes of their elderly patients. General practitioners may have considerable public health impact in promotion of health for elderly patients.", "Stresses imposed by parenthood can provoke or intensify relationship problems between parents. These problems, which are often associated with postnatal depression, can have serious consequences for family well-being but are often not revealed to primary health care personnel.\n To evaluate a means of extending the primary health care team's ability to identify and respond to relationship problems of mothers and their partners in the postnatal period.\n Cluster randomised controlled trial.\n Specially trained health visitors in nine 'intervention' clinics--each matched with a 'control' clinic' in an outer London borough.\n Health visitors in intervention clinics invited mothers attending for the six-to-eight-week developmental check to complete a screening scale for relationship problems, and offered help (supportive listening, advice, or referral) if needed. When visiting the clinic for the 12-week immunizations, mothers from all clinics were asked to complete a follow-up self-report questionnaire. After the completion of the trial, 25 women who had attended the intervention clinics and had been offered support with a relationship problem were interviewed to elicit their views on the acceptability and value of the intervention. All 25 of the health visitors engaged in the intervention were asked to complete a questionnaire on their experience.\n Screening led to striking differences between intervention and control clinics in the percentage of women identified at the six-to-eight-week check as potentially in need of help with a relationship problem (21% versus 5%, P = 0.007) and in the percentage actually offered help (18% versus 3%, P = 0.014). About one-half of the mothers so identified were also identified as having postnatal depression. At the 12-week visit for immunizations, the intervention group was twice as likely (P = 0.006) as the control group to report having discussed relationship problems with the health visitor and 75% more likely (P = 0.046) to report having received help with a problem.\n The intervention offers a useful way of extending the primary health care team's ability to respond to problems that often have serious consequences for family well-being.", "To assess the effectiveness of a multifaceted intervention to improve the management of glucocorticoid-induced osteoporosis (GIOP).\n Of 21 rheumatologists, 11 were randomly assigned to a 3-part intervention consisting of a lecture and discussion regarding optimal management of GIOP, a confidential doctor-specific audit regarding management of GIOP, and a reminder mailing including concise pharmacologic recommendations. The remaining 10 rheumatologists received no special education. Patients with rheumatoid arthritis (RA) taking oral glucocorticoids seen in the 2 months after the intervention were followed for 6 months. Medical records were assessed to determine the proportion undergoing bone mineral density testing or receiving pharmacologic interventions for GIOP during the 6 months before and 6 months after the intervention.\n There were 373 patients with RA taking oral glucocorticoids whose records were assessed. Patients in both arms of the trial were similar with respect to age, sex, menopausal status, glucocorticoid dosage and duration, duration of RA, disease-modifying antirheumatic drug use, and the proportion with comorbid conditions. At baseline, there was no significant difference between the patients with respect to osteoporosis medication use (intervention 32% versus control 34%) or bone densitometry use (intervention 9% versus control 5%). After the intervention and a 6-month followup period, there were no differences in treatment (intervention 33% versus control 38%) or bone densitometry use (intervention 8% versus control 8%). Adjusting for patient and physician characteristics did not significantly change these results.\n A multifaceted intervention for GIOP, including doctor education, practice audit, and treatment suggestions, had no significant benefit on testing or treatment by rheumatologists over a 6-month followup period. Other intervention approaches need to be tested.", "Numbers of diagnostic tests ordered by primary care physicians are growing and many of these tests seem to be unnecessary according to established, evidence-based guidelines. An innovative strategy that focused on clinical problems and associated tests was developed.\n To determine the effects of a multifaceted strategy aimed at improving the performance of primary care physicians' test ordering.\n Multicenter, randomized controlled trial with a balanced, incomplete block design and randomization at group level. Thirteen groups of primary care physicians underwent the strategy for 3 clinical problems (arm A; cardiovascular topics, upper and lower abdominal complaints), while 13 other groups underwent the strategy for 3 other clinical problems (arm B; chronic obstructive pulmonary disease and asthma, general complaints, degenerative joint complaints). Each arm acted as a control for the other.\n Primary care physician groups in 5 regions in the Netherlands with diagnostic centers recruited from May to September 1998.\n Twenty-six primary care physician groups, including 174 primary care physicians.\n During the 6 months of intervention, physicians discussed 3 consecutive, personal feedback reports in 3 small group meetings, related them to 3 evidence-based clinical guidelines, and made plans for change.\n According to existing national, evidence-based guidelines, a decrease in the total numbers of tests ordered per clinical problem, and of some defined inappropriate tests, is considered a quality improvement.\n For clinical problems allocated to arm A, the mean total number of requested tests per 6 months per physician was reduced from baseline to follow-up by 12% among physicians in the arm A intervention, but was unchanged in the arm B control, with a mean reduction of 67 more tests per physician per 6 months in arm A than in arm B (P =.01). For clinical problems allocated to arm B, the mean total number of requested tests per 6 months per physician was reduced from baseline to follow-up by 8% among physicians in the arm B intervention, and by 3% in the arm A control, with a mean reduction of 28 more tests per physician per 6 months in arm B than in arm A (P =.22). Physicians in arm A had a significant reduction in mean total number of inappropriate tests ordered for problems allocated to arm A, whereas the reduction in inappropriate test ordered physicians in arm B for problems allocated to arm B was not statistically significant.\n In this study, a practice-based, multifaceted strategy using guidelines, feedback, and social interaction resulted in modest improvements in test ordering by primary care physicians.", "To assess the effectiveness of teaching general practitioners skills in brief cognitive behaviour therapy.\n Parallel group, cluster randomised, controlled trial of an educational package on cognitive behaviour therapy.\n General practices in north London.\n 84 general practitioner principals and 272 patients attending their practices who scored above the threshold for psychological distress on the hospital anxiety and depression scale. Intervention: A training package of four half days on brief cognitive behaviour therapy. Main outcome measures: Scores on the depression attitude questionnaire (general practitioners) and the Beck depression inventory (patients).\n Doctors' knowledge of depression and attitudes towards its treatment showed no major difference between intervention and control groups after 6 months. The training had no discernible impact on patients' outcomes.\n General practitioners may require more training and support than a basic educational package on brief cognitive behaviour therapy to acquire skills to help patients with depression.", "To examine the benefits of a guideline-based educational program to improve management of unstable angina pectoris (UAP) in hospital patients.\n Randomised controlled trial.\n 37 public hospitals across New South Wales.\n 1,872 patients admitted with a diagnosis of UAP between 1 February and 30 June 1996 (baseline survey), and 1,368 patients with the same diagnosis admitted between 1 July and 31 December 1998 (follow-up survey).\n Educational sessions run by local opinion leaders, presenting guidelines on management of UAP from the National Health and Medical Research Council and feedback on local practice using data from the baseline survey. Sessions were run between March and June 1998.\n Use of evidence-based practice, identified by review of medical records.\n Use of beta-blockers increased in intervention and control hospitals, although the increase was significant only in the former. Use of calcium-channel blockers decreased significantly in both intervention and control hospitals. However, the change in drug use between baseline and follow-up did not differ significantly between intervention and control hospitals.\n Despite some appropriate changes in drug use for UAP management between 1996 and 1998, there was no evidence that a guideline-based educational program was of benefit in changing management. This reaffirms the difficulty of changing doctors' behaviour through practice guidelines. Alternative methods of encouraging evidence-based practice should be considered.", "Although patients with cancer are often accompanied by a relative during medical interviews, to the authors' knowledge little is known regarding the efficacy of communication skills training programs on physicians' communication skills in this context. The objective of the current study was to assess the efficacy of 6 consolidation workshops, 3 hours in length, that were conducted after a 2.5-day basic training program.\n After attending the basic training program, physicians were assigned randomly to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual interviews that were recorded on an audio tape at baseline, after consolidation workshops for the consolidation-workshops group, and 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' and relatives' perceptions of and satisfaction with physicians' communication performance were assessed using a 15-item questionnaire.\n Sixty-two physicians completed the training program. Compared with physicians who participated to the basic training program, when addressing the patient, physicians who were randomized to the consolidation workshops used more open, open directive, and screening questions (P = 0.011 in simulated patient interviews and P = 0.005 in actual patient interviews) and elicited and clarified psychologic concerns more often (P = 0.006 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the relative, physicians who were randomized to the consolidation workshops gave less premature information (P = 0.032 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the patient and the relative simultaneously, physicians who were randomized to the consolidation workshops used more empathy, educated guesses, alerting to reality, confronting, negotiating, and summarizing (P = 0.003 in simulated patient interviews and P = 0.024 in actual patient interviews). Patients, but not relatives, who interacted with physicians in the consolidation-workshops group were more satisfied globally with the interviews (P = 0.022).\n Six 3-hour consolidation workshops resulted in improved communication skills addressed to patients and to relatives. The current results showed that the transfer of skills addressing relatives' concerns remained limited and that consolidation workshops should focus even more systematically on the practice of three-person interviews.", "Sixty-six physicians were randomized to three groups to conduct a 1-month campaign to help their patients stop smoking. The workshop group received free patient education materials and a 6-hour training workshop. The materials group received free patient education materials, and the no-assistance group received nothing. A telephone interview was completed with 89% of the 6767 eligible adult patients seen during the month of the campaign. The brief training program and patient education materials marginally increased the smoking intervention activities of volunteer physicians in private practice. Both workshop and materials physicians asked 54% of their smoking patients to stop; no-assistance physicians asked 40%. One year later, 36% of patients who had not even been asked by their doctors if they smoked reported that they had tried to stop smoking. If the physician had asked the patient if he or she smoked, the probability of a quit attempt was 47%. Patients who had been asked if they smoked were more likely to claim to have stopped (13%) than patients who had not been asked (9%). However, the proportion of patients claiming continued abstinence (range, 12% to 14%) was not related to the group of the physician.", "To investigate whether the number of frequent attenders (FA) contacts with the out-of-hours service can be reduced by deploying a combination of intervention strategies.\n A stratified cluster randomized controlled trial, each cluster containing a general practice and all its listed patients.\n The out-of-hours service in the county of Northern Jutland (490,000 inhabitants), Denmark.\n The following intervention strategies were deployed: predisposition, individual instruction, economic incitement, continuing medical education meetings, feedback/reminder, and patient-mediated intervention.\n An intervention group of 3500 patients and a control group of 4635 patients.\n Absolute and relative fall in the number of contacts with the out-of-hours service per patient after 6 and 12 months.\n Analysed by group, intervention patients saw a more pronounced decline in the number of contacts than controls, except for two outcomes. However, this difference was only significant after 12 months. For women aged 17-66 years with 5-9 contacts during the previous 12 months, the decrease was significantly more pronounced in the intervention group for all outcomes (p=0.004-0.042). However, for the rest of the subgroups the effect varied more, and in several cases it was more distinct in the control group.\n The data collected point towards an effect of intervention on the use of out-of-hours services even if the responses obtained were not uniform and unequivocal. However, one has to consider the problems of multiple comparisons and in conclusion no convincing effect of the intervention was found.", "To evaluate the feasibility and implementation needs of a cholesterol guideline by assessing the effectiveness of simple dissemination as well as extensive implementation of this guideline on actual performance of general practitioners (GPs).\n Randomized controlled trial.\n Thirty-two Dutch GPs in 20 general practices, 3950 patient records.\n Guideline dissemination to all 32 GPs, and a 5-month programme for improvement in the intervention group. This programme was developed after barriers to working according to the guideline had been investigated, and consisted of group education, desktop supportive materials, feedback on performance, and face-to-face instruction on location.\n The outcome parameters were defined as quality of selective case finding and quality of diagnostic procedures, and were measured by chart audit.\n The quality of selective case finding, especially the targeting of cholesterol testing to those with positive cardiovascular risk profiles, did not improve following intervention. Performance of the procedure necessary to diagnose hypercholesterolaemia even deteriorated. The quantity of cholesterol testing increased in both groups, but this was probably explained by the increased availability of desktop cholesterol analysers.\n Neither simple dissemination nor an intensive programme for improvement had measurable impact on actual performance on working according to the cholesterol guideline. Both the validity and the opinion about feasibility of the guideline in daily practice deserve more attention during guideline development.", "To determine the effectiveness of an intervention for pharmacy workers in improving their recognition and management of sexually transmitted disease (STD) syndromes.\n We randomly selected 14 districts (total population nearly 4 million) from the 24 districts of low socioeconomic status in Lima, Peru. We randomly assigned paired districts to receive training and support for management and prevention of STDs or a control intervention about management of diarrhoea. The STD intervention included interactive luncheon seminars on recognition and management of four STD syndromes (urethral discharge, vaginal discharge, genital ulcers, and pelvic inflammatory disease) and STD/HIV prevention counselling; monthly pharmacy visits by \"prevention salespersons\" who distributed materials that included \"STD/HIV prevention packets\" containing information, condoms, and cards given to patients for referral of their sex partners; and workshops for physicians on managing patients with STD syndromes referred from pharmacies. Standardized simulated patients visited pharmacies in intervention and control districts at one, three, and six months after training to assess outcomes.\n Standardized simulated patients reported significantly better recognition and management (appropriate antimicrobial regimens provided for discharge syndromes and referral to specially trained physicians for genital ulcers or pelvic inflammatory disease) by pharmacy workers of all four STD syndromes. They also reported significantly more frequent recommendations for use of condoms and treatment of partners at pharmacies in intervention districts than in control districts (by \"intention-to-train\" analyses, P<0.05 for 47/48 primary outcome comparisons).\n Training was feasible and effectively improved pharmacy workers' practices.", "In this study, we evaluated an inservice training program for public health nurses. The training program concerned arthritis screening and management of the disease in elderly subjects. Twenty-nine nurses were assigned randomly to experimental (training) or control conditions. Evaluation data from 158 interviews with patients showed that screening for arthritis was done twice as frequently by nurses in the experimental group, compared with that done by nurses who were not in the experimental group (P less than 0.01). Recommended management of arthritis was not correspondingly improved. Stronger inservice programs are discussed in light of the need to anticipate seasonal conflicts between arthritis care and preventive care for the elderly, to change habitual practice patterns, and to increase access to arthritis health professionals.", "Despite high prevalence, emotional distress among primary care patients often goes unrecognized during routine medical encounters.\n To explore the effect of communication-skills training on the process and outcome of care associated with patients' emotional distress.\n A randomized, controlled field trial was conducted with 69 primary care physicians and 648 of their patients. Physicians were randomized to a no-training control group or one of two communication-skills training courses designed to help physicians address patients' emotional distress. The two training courses addressed communication through problem-defining skills or emotion-handling skills. All office visits of study physicians were audiotaped until five emotionally distressed and five nondistressed patients were enrolled based on patient response to the General Health Questionnaire. Physicians were also audiotaped interviewing a simulated patient to evaluate clinical proficiency. Telephone monitoring of distressed patients for utilization of medical services and General Health Questionnaire scores was conducted 2 weeks, 3 months, and 6 months after their audiotaped office visits.\n Audiotape analysis of actual and simulated patients showed that trained physicians used significantly more problem-defining and emotion-handling skills than did untrained physicians, without increasing the length of the visit. Trained physicians also reported more psychosocial problems, engaged in more strategies for managing emotional problems with actual patients, and scored higher in clinical proficiency with simulated patients. Patients of trained physicians reported reduction in emotional distress for as long as 6 months.\n Important changes in physicians' communication skills were evident after an 8-hour program. The training improved the process and outcome of care without lengthening the visits.", "We wanted to evaluate the added value of small peer-group quality improvement meetings compared with simple feedback as a strategy to improve test-ordering behavior. Numbers of tests ordered by primary care physicians are increasing, and many of these tests seem to be unnecessary according to established, evidence-based guidelines.\n We enrolled 194 primary care physicians from 27 local primary care practice groups in 5 health care regions (5 diagnostic centers). The study was a cluster randomized trial with randomization at the local physician group level. We evaluated an innovative, multifaceted strategy, combining written comparative feedback, group education on national guidelines, and social influence by peers in quality improvement sessions in small groups. The strategy was aimed at 3 specific clinical topics: cardiovascular issues, upper abdominal complaints, and lower abdominal complaints. The mean number of tests per physician per 6 months at baseline and the physicians' region were used as independent variables, and the mean number of tests per physician per 6 months was the dependent variable.\n The new strategy was executed in 13 primary care groups, whereas 14 groups received feedback only. For all 3 clinical topics, the decrease in mean total number of tests ordered by physicians in the intervention arm was far more substantial (on average 51 fewer tests per physician per half-year) than the decrease in mean number of tests ordered by physicians in the feedback arm (P = .005). Five tests considered to be inappropriate for the clinical problem of upper abdominal complaints decreased in the intervention arm, with physicians in the feedback arm ordering 13 more tests per 6 months (P = .002). Interdoctor variation in test ordering decreased more in the intervention arm.\n Compared with only disseminating comparative feedback reports to primary care physicians, the new strategy of involving peer interaction and social influence improved the physicians' test-ordering behavior. To be effective, feedback needs to be integrated in an interactive, educational environment.", "Previous evaluations of continuing medical education (CME) have yielded conflicting results regarding its effects on physician knowledge, performance, and subsequent patient outcomes. Poor adherence by mothers to prescribed pediatric regimens is a separate, but well-documented, problem. In the present study we assessed the ability of CME to: (1) increase the knowledge of pediatricians about compliance-enhancing strategies; (2) increase the performance of these practices by pediatricians; and (3) improve mothers' compliance with antibiotic regimens for their children's otitis media. Ninety pediatricians were randomly assigned to either a control group or one of two CME interventions: tutorial plus printed materials or mailed printed materials only. Following the interventions, data on compliance and on reported behaviors of pediatricians were gathered from a random sample of mothers (N = 771) whose children were being treated for otitis media. Findings indicated that CME increased physician knowledge and compliance-enhancing practices and resulted in improvement in mothers' adherence to therapy.", "A sigmoidoscopy skills preceptorship was developed for physicians to increase the rate of sigmoidoscopy by physicians in a health maintenance organization. The preceptorship was designed as a randomized, controlled study of continuing medical education. Baseline sigmoidoscopy rates of participating physicians were similar to those of nonparticipants, as were selected demographic and professional characteristics. Physicians randomized to receive sigmoidoscopy training significantly increased their rate of sigmoidoscopy when compared with controls. The proportion of barium enemas accompanied by sigmoidoscopy likewise increased. All physicians who participated improved when compared with nonparticipants. The sigmoidoscopy skills preceptorship appears to be a worthwhile endeavor in continuing medical education.", "To study the efficacy of case method learning, for general practitioners, on patients' lipid concentrations in the secondary prevention of coronary artery disease.\n Prospective controlled trial.\n Södertälje, Stockholm County, Sweden.\n 255 consecutive patients with coronary artery disease.\n Guidelines were mailed to all general practitioners (n=54) and presented at a common lecture. General practitioners who were randomised to the intervention group participated in recurrent case method learning dialogues at their primary healthcare centres during a two year period. A locally well known cardiologist served as a facilitator.\n Concentration of low density lipoprotein cholesterol at baseline and after two years. Analysis according to intention to treat (intervention and control groups (n=88)) was based on group affiliation at baseline.\n Low density lipoprotein cholesterol was reduced by 0.5 mmol/l (95% confidence interval 0.2 to 0.8 mmol/l) (9.3% (2.9% to 15.8%)) from baseline in patients in the intervention group and by 0.5 (0.1 to 0.9) mmol/l compared with controls (P<0.05). No change occurred in the control group (0.0 (-0.2 to 0.2) mmol/l). Low density lipoprotein cholesterol decreased by 0.6 (0.4 to 0.8) mmol/l in a group of patients who received specialist care.\n Case method learning resulted in a lowering of low density lipoprotein cholesterol in the primary care patients with coronary artery disease comparable to that achieved at a specialist clinic. Conventional presentation of practice guidelines had no effect.", "We examined the effectiveness of a training program for physician-delivered nutrition counseling, alone and in combination with a structured office practice environment for nutrition management, on physicians' counseling practices. Forty-five primary care internists and 1,278 of their patients in the top quarter of the cholesterol distribution at a central Massachusetts health maintenance organization (the Fallon Clinic) were enrolled into a randomized controlled trial. Physicians were randomized by site into three conditions: (1) usual care, (2) physician nutrition counseling training, and (3) physician nutrition counseling training plus a structured office practice environment for nutrition management (prompts and the provision of lipid results and counseling algorithms). A randomly selected 325 patients were given a 10-item patient exit interview (PEI) assessing whether the physician provided advice; assessed past changes, barriers, and resources; negotiated specific plans and goals; provided patient materials; referred the patient to a dietitian; and developed plans for follow-up. Condition 3 physicians demonstrated significantly greater implementation of the nutrition counseling sequence than did physicians in either of the other two conditions (P < .0001). Referrals to nutrition services were markedly reduced in condition 2, despite PEI scores no different than those in condition 1. Higher PEI scores for patients seen by physicians in condition 3 were stable for as long as two years beyond training. Primary care internists, when provided with both training in counseling techniques and a supportive office environment, will carry out patient counseling appropriately. Training alone, however, is not sufficient and may be counterproductive. Medical Subject Headings (MeSH): hypercholesterolemia, diet therapy, coronary disease, health behavior, primary health care, medical education, managed care programs." ]

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[ "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.", "Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy.", "Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.", "Effect of blood glucose control on peripheral nerve function in diabetic patients.", "Intensive therapy in adult insulin-dependent diabetes mellitus is associated with improved insulin sensitivity and reserve: a randomized, controlled, prospective study over 5 years in newly diagnosed patients.", "The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group.", "Effect of near normoglycaemia for two years on progression of early diabetic retinopathy, nephropathy, and neuropathy: the Oslo study.", "Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients.", "Autonomic and somatosensory nerve function after 2 years of continuous subcutaneous insulin infusion in type I diabetes.", "Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial.", "The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus.", "Glucose control and vascular complications in veterans with type 2 diabetes.", "Diabetic neuropathy in elderly Type 2 diabetic patients: effects of insulin treatment.", "Determination of the glycemic threshold for the regression or prevention of diabetic microangiopathies, and the insulin injection regimen to establish strict glycemic control in NIDDM.", "The effects of intensive glycemic control on neuropathy in the VA cooperative study on type II diabetes mellitus (VA CSDM).", "Diabetic neuropathy: effects of intensified glycaemic control with multiple insulin injections." ]

[ "Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial.\n 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy.\n Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg).\n Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)", "Thirty patients with insulin-dependent diabetes mellitus (IDDM) who had advanced background retinopathy were randomized to unchanged conventional treatment (UCT) or to continuous subcutaneous insulin infusion (CSII). They were followed prospectively for 2 yr. The mean blood glucose and hemoglobin A1C (HbA1C) were significantly lower in the CSII group than in the UCT group. The mean blood glucose and HbA1C did not change from the first to the second year in either of the treatment groups in spite of less frequent home-monitoring of blood glucose and less frequent outpatient visits during the second year. Four patients in the CSII group and five in the UCT group developed proliferative retinopathy. However, a marginally significant trend was found toward more frequent improvement of retinal morphology in the CSII group (47%) than in the UCT group (13%). Beat-to-beat variation was found to deteriorate significantly with UCT compared with a nonsignificant improvement with CSII therapy. Vibration sense was unchanged in both treatment groups. It is concluded that near-normal blood glucose levels can be maintained with CSII therapy in spite of less frequent home-monitoring of blood glucose and outpatient visits. Furthermore, established background retinopathy may progress to proliferative retinopathy in spite of 2 yr of near-normal blood glucose levels. However, a marginally significant trend toward more frequent improvement of retinal morphology was found among CSII-treated patients compared with conventionally treated patients. Large-scale, prospective, randomized studies are needed to confirm these results.", "Cardiovascular morbidity is a major burden in patients with type 2 diabetes. In the Steno-2 Study, we compared the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.\n The primary end point of this open, parallel trial was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation. Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin.\n The mean age of the patients was 55.1 years, and the mean follow-up was 7.8 years. The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79).\n A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.\n Copyright 2003 Massachusetts Medical Society", "A prospective, stratified, randomized 3-year clinical trial was conducted on the effect of rigorous versus conventional glucose control on peripheral nerve function in 33 insulin-treated diabetic patients with a duration of diabetes of less than 2 years. The goals for conventional glucose control were the mean of fasting and 80-minute postprandial plasma glucose of 150 mg/dl for non-insulin-dependent diabetes and 200 mg/dl for insulin-dependent diabetes. The goal of rigorous glucose control was an approximation of nondiabetic glucose control. No significant difference in glucose control or peripheral nerve function was observed between the rigorously and the conventionally controlled groups. Eight patients in the conventional-control group spontaneously achieved glucose control in the range that was the objective for the rigorous-control group, and five patients in the rigorous-control group never achieved the desired glucose control. In the remaining 20 patients, with similar baseline glucose control and peripheral nerve function characteristics, observed over a median of 2 years, improved blood glucose control (P less than 0.01) was not associated with any significant improvement in peripheral nerve function. Nevertheless, a significant (P less than 0.05) correlation was found between the degree of abnormal nerve function at entry into the study and change in nerve function during the study. If control of hyperglycemia benefits peripheral nerve function of diabetic patients, its demonstration may require a closer approximation of normoglycemia, a larger difference in glucose control between the two study groups, a longer duration of treatment, and the use of patients with more advanced peripheral nerve function abnormalities than those in this study.", "Optimal blood glucose levels and normal insulin sensitivity are aims in the treatment of insulin-dependent diabetes mellitus (IDDM). Insulin sensitivity and insulin reserve are closely interrelated. It is essential to know more about both of these parameters at clinical diagnosis, because their preservation may delay the occurrence of diabetes-related complications. B-cell function is likely to be retained for a longer period in patients with adult onset of the disease compared with children. In this study, intensive insulin treatment was initiated in newly diagnosed adult patients to determine if it preserved endogenous insulin secretion longer than conventional therapy. Forty-nine patients with newly diagnosed diabetes were carefully categorized as having IDDM according to clinical and serological criteria. They were randomized to an intensive (I group) or conventional (C group) insulin therapy and evaluated for 5 years. Every 6 months, a check-up included glucagon-stimulated C-peptide (GSCP), hyperglycemic glucose clamp with arginine bolus, euglycemic-hyperinsulinemic clamp, and screening for microalbuminuria, retinopathy, and neuropathy. At the end of the study, hemoglobin A1c (HbA1c) was 6.3% +/- 1.9% in the I patients and 8.1% +/- 2.1% in the C patients (P < .001). Blood glucose concentrations less than 3.5 mmol/L were more frequent in the I group than in the C group (P < .05). Insulin sensitivity (M/I) and GSCP were higher in intensively treated patients after 5 years (M/I, I group 40 +/- 10 nmol x kg(-1) x min(-1) x pmol/L1 v C group 21 +/- 11, P < .005; GSCP, I group 0.6 +/- 0.2 nmol/L v C group 0.19 +/- 0.11, P < .005). The prevalence of peripheral neuropathy was significantly lower in the I group at the end of the study. In conclusion, intensive therapy is more effective in the preservation of insulin action and reserve. In our patients, no case of severe hypoglycemia was observed, indicating that intensive therapy was safe in these patients.", "Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.\n A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.\n In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.\n Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.", "Forty five insulin dependent diabetics were randomised to treatment with continuous subcutaneous insulin infusion (CSII), multiple insulin injections (five or six daily), or conventional twice daily insulin injections. Near normoglycaemia was obtained with CSII and multiple injections but not with conventional treatment (p less than 0.01). Hypoglycaemic coma was observed less frequently with CSII than with multiple injections and conventional treatment (p less than 0.001), but blood glucose concentrations below 2.5 mmol/l (45 mg/100 ml) were more common. After two years fewer retinal microaneurysms and haemorrhages had developed in the patients given CSII and multiple injections compared with those given conventional treatment, in whom the number had increased significantly (p less than 0.01). Motor nerve conduction velocity deteriorated in the patients given conventional treatment; in those given CSII it was unchanged during the first year but had improved after two years (p less than 0.01). Glomerular hyperfiltration was reduced with CSII, but no change occurred in urine albumin excretion rates. Long term near normoglycaemia may prevent the progression of early stages of late diabetic complications.", "To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, an 8-year prospective study of Japanese patients with type 2 diabetes was performed.\n A total of 110 patients with type 2 diabetes (55 with no retinopathy [the primary prevention cohort] and 55 with simple retinopathy [the secondary intervention cohort]) were randomly assigned to multiple insulin injection therapy (MIT) groups and administered three or more daily insulin injections or assigned to conventional insulin injection therapy (CIT) groups and administered one or two daily intermediate-acting insulin injections. Worsening of microvascular complications was regularly assessed during 8 years. Two or more steps up in the 19 stages of the modified Early Treatment of Diabetic Retinopathy Study classification in retinopathy and one or more stages up among three stages in nephropathy (normoalbuminuria, microalbuminuria, and albuminuria) were defined as worsening of complications.\n In both primary prevention and secondary intervention cohorts, the cumulative percentages of worsening in retinopathy and nephropathy were significantly lower (P < 0.05) in the MIT group than in the CIT group. In neurological tests after 8 years, the MIT group showed significant improvement (P < 0.05) in the median nerve conduction velocities (motor and sensory nerves), whereas the CIT group showed significant deterioration (P < 0.05) in the nerve conduction velocities and vibration threshold. From this study, the glycemic threshold to prevent the onset and progression of diabetic microvascular complications was as follows: HbA1c < 6.5%, fasting blood glucose concentration < 110 mg/dl, and 2-h postprandial blood glucose concentration < 180 mg/dl.\n Intensive glycemic control can delay the onset and progression of the early stages of diabetic microvascular complications in Japanese patients with type 2 diabetes.", "Autonomic and somatosensory nerve function was studied in 24 insulin-dependent diabetic subjects (aged 29 +/- 7 yrs, diabetes duration 8 +/- 4 yr) randomly allocated to either continuous subcutaneous insulin infusion (CSII; n = 12) or unchanged conventional insulin therapy (CIT; n = 12). Measures of glycemic control and somatosensory and autonomic nerve function were comparable in the two groups at the start. Glycemic control was significantly improved in the CSII group throughout study, whereas it remained unchanged in the CIT group. In the CIT group, vibratory perception threshold (VPT) of the great toe and the medial malleolus deteriorated, as did heart rate variation (HRV) at rest, at deep breathing (.05 less than P less than .06), and at standing. In contrast, CSII patients retained their VPT and HRV. Comparison of nerve function alterations during the 2-yr trial showed better preservation in CSII than in CIT patients of VPT in the great toe (0.8 +/- 1.7 vs. -1.4 +/- 1.9 V, P less than .01) and the medial malleolus (1.5 +/- 2.9 vs. -1.4 +/- 1.8 V, P less than .05) and of HRV at rest (10 +/- 24 vs. -13 +/- 22 ms, P less than .05) and at standing (-0.01 +/- 0.13 vs. -0.15 +/- 0.16 ms, P less than .05). We conclude that intensified glycemic control can favorably influence parasympathetic and somatosensory nerve function in insulin-dependent diabetes mellitus.", "Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes.\n ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA(1c) concentrations (>7.5%), and cardiovascular disease (or >or=2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A(1c) [HbA(1c)] of <6.0%) or standard (7.0-7.9%) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291.7 micromol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620.\n 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1.00, 95% CI 0.88-1.14; p=1.00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0.96, 0.89-1.02; p=0.19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0.95, 95% CI 0.85-1.07, p=0.42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0.95, 0.89-1.01, p=0.12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0.05).\n Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia.\n US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "A cause-and-effect relation between blood glucose concentrations and microvascular complications in patients with insulin-dependent diabetes mellitus has not been established.\n We randomly assigned 102 patients with insulin-dependent diabetes mellitus, nonproliferative retinopathy, normal serum creatinine concentrations, and unsatisfactory blood glucose control to intensified insulin treatment (48 patients) or standard insulin treatment (54 patients). We then evaluated them for microvascular complications after 18 months and 3, 5, and 7.5 years.\n Mean (+/- SD) glycosylated hemoglobin values were reduced from 9.5 +/- 1.3 percent to 7.1 +/- 0.7 percent in the group receiving intensified treatment and from 9.4 +/- 1.4 percent to 8.5 +/- 0.7 percent in the group receiving standard treatment (P = 0.001). In 12 of the patients receiving intensified treatment (27 percent of those included in the analysis) and 27 of those receiving standard treatment (52 percent), serious retinopathy requiring photocoagulation developed (P = 0.01). Visual acuity decreased in 6 patients receiving intensified treatment (14 percent) and in 18 receiving standard treatment (35 percent) (P = 0.02). Nephropathy (urinary albumin excretion, > 200 micrograms per minute) developed in one patient in the group receiving intensified treatment, as compared with nine patients in the group receiving standard treatment (P = 0.01). No patient in the intensified-treatment group had nephropathy with subnormal glomerular filtration rates, as compared with six patients in the standard-treatment group (P = 0.02). The conduction velocities of the ulnar, tibial, peroneal, and sural nerves decreased significantly more in the standard-treatment group than in the intensified-treatment group. The odds ratio for serious retinopathy was 0.4 (95 percent confidence interval, 0.2 to 1.0; P = 0.04) in the intensified-treatment group as compared with the standard-treatment group. The corresponding odds ratio for nephropathy was 0.1 (95 percent confidence interval, 0 to 0.8; P = 0.04).\n Long-term intensified insulin treatment, as compared with standard treatment, retards the development of microvascular complications in patients with insulin-dependent diabetes mellitus.", "The effects of intensive glucose control on cardiovascular events in patients with long-standing type 2 diabetes mellitus remain uncertain.\n We randomly assigned 1791 military veterans (mean age, 60.4 years) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. Other cardiovascular risk factors were treated uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and 40% of the patients had already had a cardiovascular event. The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level, as compared with the standard-therapy group. The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene.\n The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group.\n Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications with the exception of progression of albuminuria (P = 0.01) [added]. (ClinicalTrials.gov number, NCT00032487.)\n 2009 Massachusetts Medical Society", "To study the occurrence of diabetic neuropathy and the effect of insulin treatment in elderly Type 2 diabetic patients.\n In 38 patients and 20 controls symptoms and neurophysiological examinations including electroneurography, vibration perception and temperature discrimination thresholds were investigated. Patients were randomized to insulin (n = 18) or sulfonylurea (n = 16) treatment and were re-investigated after 1 year.\n Neuropathy was present in 21/38 patients (56%). It was asymptomatic in 17/38 (45%) and symptomatic in 4/38 (11%). The occurrence of neuropathy was less common in healthy controls, 3/20 (15%) (P < 0.01). Temperature discrimination thresholds was the test that most often revealed pathology. The metabolic control after 1 year was significantly improved in the insulin treated group and unchanged in the sulfonylurea treated group. There were no changes as regards occurrence of neuropathy between or within the two treatment groups after 1 year.\n Diabetic neuropathy is common among elderly Type 2 diabetic patients. It is mostly asymptomatic. Improvement was not seen after 1 year of insulin treatment.", "nan", "To determine whether a difference in HbA(1c) could be safely sustained between a standard therapy (STD) arm and an intensive therapy (INT) arm, while maintaining HbA(1c) levels in both arms within a range acceptable in community practice. The effects of intensive treatment on various parameters were studied in this feasibility trial. We report here the results of 24 months of INT on peripheral and autonomic neuropathy.A prospective trial was conducted in five medical centers in 153 men of 60 +/- 6 years of age who had a known diagnosis of diabetes for 7.8 +/- 4 years. They were randomly assigned to a standard insulin treatment group (one morning injection per day) or to an intensive therapy group designed to attain near-normal glycemia and a clinically significant separation of glycohemoglobin from the standard arm. A four-step plan was used in the intensive therapy group along with daily self-monitoring of glucose: (1) an evening insulin injection, (2) the same injection adding daytime glipizide, (3) two injections of insulin alone, and (4) multiple daily injections. Peripheral neuropathy was diagnosed clinically by a history and physical examination, and by abnormal autonomic neuropathy Valsalva ratio (VR < 1.2) and RR variation (RRV < 10). An average HbA(1c) separation of 2.07% was achieved with INT, having HbA(1c) at or below 7.3% (p = 0. 001 versus STD). Baseline prevalence of peripheral neuropathy was 53% in STD, and 48% in INT. By 24 months, the prevalence increased to 69% in STD (p = 0.005 versus baseline), and to 64% in INT (p = 0. 008 versus baseline, but no different than STD). Though INT did not reverse all elements of peripheral neuropathy, there was a decreased prevalence of cranial neuropathy (p = 0.053 versus STD) and more frequent preservation of touch sensation in the upper extremities (p = 0.03 versus STD) in INT. At baseline, an abnormal Valsalva ratio and/or RR variation was seen in 38% of STD and 31% of INT. By 24 months in STD, the prevalence rose to 55% (p = 0.0067 versus baseline), and in INT, to 48% (p = 0.012 versus baseline and no different from STD). The prevalence of erectile dysfunction increased from 53% at baseline to 73% at 2 years, p = 0.002 in STD, and from 51% to 73% at 2 years (p = 0.003 versus baseline) and no different from STD. There was no change in the frequency of abnormal gastrointestinal or sweating symptoms. Our conclusion was that 2 years of meticulous glycemic control did not decrease overall prevalence of peripheral or autonomic neuropathy. In fact, the prevalence rose equivalently and significantly in both treatment arms. There was some benefit, however, in decreased frequency of cranial neuropathy and better preservation of touch sensation in INT.", "nan" ]

[ "3114710", "2651597" ]

[ "Successful direct extubation of very low birth weight infants from low intermittent mandatory ventilation rate.", "Successful extubation of newborn infants without preextubation trial of continuous positive airway pressure." ]

[ "It is common practice to use endotracheal continuous positive airway pressure for various time periods up to 24 hours before attempting extubation in infants who are mechanically ventilated. A few studies in newborns have indicated that airway resistance is increased through small endotracheal tubes. This increases the work of breathing and the likelihood of subsequent ventilatory failure. In this study, 27 very low birth weight infants who were 1/2 to 28 days old at the time of extubation were randomly divided into two groups. One group of 13 study infants were extubated directly from intermittent mandatory ventilation rates of six to ten per minute, and the other 14 control infants were placed on continuous positive airway pressure through endotracheal tubes for six hours prior to an attempt to extubate. There was no difference between the two groups in gestational age, postnatal age, weight, or severity of lung disease at the time of extubation. All 13 study infants were successfully extubated without significant apnea or respiratory acidosis. Of the 14 control infants, only seven were successfully extubated; six infants had significant apnea and in one infant respiratory acidosis with pH 7.13 and PCO2 65 developed while receiving continuous positive airway pressure (13/13 v 7/14, P less than .005). The seven infants who failed the preextubation trial of continuous positive airway pressure were later extubated from low intermittent mandatory ventilation rates without significant apnea or respiratory acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)", "Sixty newborn infants who had been mechanically ventilated through 3.0- or 3.5-mm endotracheal tubes were studied to examine the necessity of a preextubation trial of continuous positive airway pressure (CPAP). Thirty randomly assigned study infants were directly extubated from intermittent mandatory ventilation rates of six per minute; 30 randomly assigned control infants were extubated after a six-hour trial of continuous positive airway pressure of 3 cm H2O. Changes in respiratory rate, in PCO2, and in PO2/FIO2 were similar. All 30 study infants tolerated direct extubation without significant apnea or respiratory acidosis. Two study and eight control infants developed apnea during six hours after intermittent mandatory ventilation was discontinued (chi 2 = 4.3, P less than .05). Five control and no study infants had apneic episodes greater than or equal to 0.5 per hour (chi 2 = 5.5, P less than .02). The results of this study suggest that newborn infants may tolerate direct extubation from low intermittent mandatory ventilation rates without a preextubation trial of CPAP. A preextubation trial of CPAP appears to be unnecessary and may cause more frequent apnea in newborn infants if used for more than several hours." ]

[ "17828747", "15192618", "10891816", "16291357", "12825213", "11443157", "15181060" ]

[ "Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia.", "Suppression of adrenal function in children with acute lymphoblastic leukemia following induction therapy with corticosteroid and other cytotoxic agents.", "Time course of recovery of adrenal function in children treated for leukemia.", "Clinical impact of corticosteroid-induced adrenal suppression during treatment for acute lymphoblastic leukemia in children: a prospective observational study using the low-dose adrenocorticotropin test.", "Impaired adrenal function after glucocorticoid therapy in children with acute lymphoblastic leukemia.", "Evaluation of the hypothalamic-pituitary-adrenal axis in children with leukemia before and after 6 weeks of high-dose glucocorticoid therapy.", "Early adrenocortical recovery after glucocorticoid therapy in children with leukemia." ]

[ "A 4-week course of high-dose glucocorticoids may cause prolonged adrenal suppression even after a 9-day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high-dose prednisone (PDN) or dexamethasone (DXM).\n Sixty-four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD-ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1-2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period.\n All patients had normal basal cortisol values at diagnosis. Twenty-four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD-ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7-14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression.\n High-dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated.\n (c) 2007 Wiley-Liss, Inc.", "To evaluate adrenal function in children with acute lymphoblastic leukemia (ALL) after induction therapy with corticosteroid and other cytotoxic agents. Study design Children with ALL (N=24) were treated with prednisolone (40 mg/m(2) per day) for 28 days during the induction phase followed by 1 week of oral dexamethasone every 4 weeks. A low-dose (1 microg) adrenocorticotropin (ACTH) test was performed 2 weeks after discontinuation of prednisolone; it was repeated 2 weeks later and then every 4 weeks in patients with adrenal suppression until normal response was achieved.\n Adrenal suppression was found in 46% of patients at 2 weeks after discontinuation of prednisolone; it persisted in 38%, 29%, and 13% of patients through 4 weeks, 8 weeks, and 20 weeks, respectively. Adrenal suppression appeared to last significantly longer in children aged >or=5 years than in children aged <5 years. Four children developed febrile neutropenia; all belonged to the adrenal suppressed group and were unable to mount an adequate adrenal response to the stress.\n About 50% of children with ALL developed adrenal suppression 2 weeks after a 4-week induction therapy with prednisolone. The suppression could persist through 20 weeks and may hinder an adequate adrenal response during acute febrile illness.", "Many protocols for treating children with early B-cell lineage acute lymphoblastic leukemia use 28 consecutive days of high-dose glucocorticoids during induction therapy. We prospectively studied the effects of this therapy on adrenal function.\n Ten children with early B-cell lineage acute lymphoblastic leukemia were evaluated by cosyntropin (corticotropin (1-24)) stimulation testing before initiation of dexamethasone therapy and every 4 weeks thereafter until adrenal function returned to normal.\n All 10 patients had normal adrenal function before dexamethasone treatment and insufficient adrenal responses 24 hours after completing therapy. Each child felt ill for 2 to 4 weeks after completing therapy. Although 7 patients recovered normal adrenal function after 4 weeks, 3 patients did not have normal adrenal function until 8 weeks after discontinuing therapy. Statistically significant differences in both basal and corticotropin-stimulated cortisol levels were noted when comparing tests performed at baseline, 24 hours after completing therapy, and 4 weeks after completing therapy.\n High-dose dexamethasone therapy, a standard treatment for early B-cell acute lymphoblastic leukemia, can cause adrenal insufficiency lasting more than 4 weeks after cessation of treatment. This problem might be avoided by tapering doses of glucocorticoids and providing supplemental glucocorticoids during periods of increased stress.", "To investigate how frequently adrenal function fails to recover after corticosteroid therapy in children with acute lymphoblastic leukemia and to explore the clinical impact of slow adrenal recovery without steroid substitution.\n Low-dose (1 microg) adrenocorticotropic hormone tests were performed before and after steroid courses and during infectious episodes in 24 children. Test results were not available during the study.\n All 13 patients tested before treatment had normal adrenal responses. Adrenal suppression was found in 8 (47%) of 17 patients 5 days after discontinuation of a 5-week induction course of prednisolone and in 1 (20%) of 5 patients 7 days after a 3-week intensification course of dexamethasone, both courses being tapered over 9 days, as well as in all 13 patients tested 2 days after a 1-week prednisolone course. Clinically significant manifestations of adrenal suppression were noted in 3 (12%) patients. Of 204 scheduled tests, 131 were performed.\n High-dose glucocorticoid therapy may cause adrenal suppression lasting more than 1 week in children with acute lymphoblastic leukemia, even after tapering the dose. We suggest steroid replacement during stress episodes within 1 to 2 weeks after discontinuation and thereafter testing adrenal function selectively in accordance with symptoms.", "Glucocorticoids are commonly used in the treatment of childhood acute lymphoblastic leukemia (ALL). The purpose of this study was to assess the incidence of adrenal insufficiency and the time for children with ALL to recover after treatment with the glucorticoids prednisolone or dexamethasone.\n Seventeen children, 2-15 years, with ALL were studied after receiving prednisolone (60 mg/m(2)/day, n = 10) for 5 weeks during remission induction therapy or dexamethasone (10 mg/m(2)/day, n = 7) for 3 weeks during reinduction therapy. Both drugs were tapered over 9 days. The adrenal function was assessed by an ACTH stimulation test within 2 weeks after discontinuing glucocorticoid therapy. In case of adrenal insufficiency, the ACTH test was repeated at 3-5 weeks interval, and patients were put on hydrocortisone substitution therapy.\n Three out of ten patients had a normal adrenal function within the first 2 weeks after prednisolone therapy. Another three patients recovered within 7 weeks, whereas the remaining four patients still showed adrenal insufficiency at the end of follow-up after 2.5-4 months. For dexamethasone, two out of seven patients showed a normal adrenal function within the first 2 weeks. Of the remaining patients, two recovered within 7 weeks, whereas three patients still had a demonstrated adrenal insufficiency at the end of follow-up after 4-8 months.\n Adrenal insufficiency occurs and may persist for several months in children with ALL after treatment with high doses of prednisolone or dexamethasone.\n Copyright 2003 Wiley-Liss, Inc.", "Among the adverse effects arising from chronic high-dose glucocorticoid treatment, adrenal insufficiency secondary to suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a cause for concern. Glucocorticoid-induced adrenal suppression is related to the duration of therapy, type of steroid used and dosage, and schedule of glucocorticoid administration. To evaluate the suppression and recovery time of the HPA axis in children with acute leukemia, we performed the ovine CRH (oCRH) stimulation test in 15 patients, who were given high doses of dexamethasone as part of their induction chemotherapy for 42 days. The oCRH tests were performed before, and 7 and 14 days after, discontinuation of the glucocorticoid. The ACTH levels were not significantly different among the 3 tests. The cortisol levels, however, were significantly (albeit mildly) lower, both basally and after oCRH, 1 and 2 weeks post treatment than before therapy. Six patients had cortisol values that remained suppressed 2 weeks after discontinuation of therapy. One of these patients had manifestations of mild adrenal insufficiency, 6-8 days after discontinuation of therapy, but required no glucocorticoid coverage. We conclude that up to 2 weeks after discontinuation of 6 weeks of high-dose dexamethasone administration, the HPA axis of patients with acute leukemia is mildly suppressed but infrequently associated with clinical manifestations of adrenal insufficiency. This may indicate that major stress, when concurrent with glucocorticoid treatment, may prevent clinically significant adrenal suppression.", "The duration of glucocorticoid-induced inhibition that occurs in the hypothalamic-pituitary-adrenal (HPA) axis after discontinuation of treatment is controversial. The main objective of this prospective study was to evaluate the inhibition of the HPA axis by dexamethasone in children and adolescents with acute lymphoid leukemia. Thirty-five patients (median age of 6.9 yr) were evaluated. A stimulus test with ovine CRH (1 microg/kg) was performed before the introduction of dexamethasone (6 mg/m2.d for 28 d), in the 8th and 28th days of glucocorticoid therapy, and 48 h and 1 month after discontinuation of glucocorticoid therapy. Suppression of the basal secretion as well as the maximum concentration of ACTH occurred during glucocorticoid therapy (P < 0.01). The pituitary function before the introduction of dexamethasone was similar to the one seen 48 h and 1 month after withdrawing it. Suppression of the adrenal function was detected during glucocorticoid therapy, which persisted for 48 h after the steroid was removed from treatment (P < 0.01). One month after ceasing the administration of the glucocorticoid, the adrenal function was similar to that before glucocorticoid therapy. According to these results, a clinical and laboratory follow-up of the HPA axis in the month after the cessation of dexamethasone therapy is suggested to determine glucocorticoid replacement." ]

[ "3276864", "7000998" ]

[ "A randomized, controlled trial of parenteral clindamycin in neonatal necrotizing enterocolitis.", "A randomized, controlled study of oral gentamicin in the treatment of neonatal necrotizing enterocolitis." ]

[ "For an assessment of the efficacy of clindamycin in preventing bowel necrosis (intestinal gangrene or perforation), 42 premature infants with radiographically confirmed necrotizing enterocolitis (NEC) (pneumatosis, intraportal gas, or both) were randomly assigned to receive parenterally either ampicillin and gentamicin (control group, n = 22) or ampicillin, gentamicin, and clindamycin (n = 20), 20 mg/kg/d at 8-hour intervals for 10 to 14 days. Infants who had received antibiotics for greater than 24 hours before randomization and those developing intestinal gangrene or perforation less than 12 hours after randomization were excluded. Intestinal gangrene or perforation developed in four infants in the control group and six in the clindamycin group. Four in each group died of NEC. In the control group, one of 18 survivors developed a late stricture requiring surgical resection, whereas six of 15 survivors in the clindamycin group developed such strictures (P = 0.022). Routine inclusion of clindamycin in medical treatment of NEC does not reduce the frequency of intestinal gangrene or perforation and may be associated with an increase in late stricture formation.", "nan" ]

[ "20194844", "21231927", "20888994", "21321292", "21498674" ]

[ "Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia.", "A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia.", "Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial.", "Chemoimmunotherapy with fludarabine and rituximab produces extended overall survival and progression-free survival in chronic lymphocytic leukemia: long-term follow-up of CALGB study 9712.", "Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia." ]

[ "Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized studies in patients with chronic lymphocytic leukemia (CLL). This trial was designed to compare chemoimmunotherapy with chemotherapy alone in patients with previously treated CLL.\n This international, multicenter, randomized trial compared six cycles of rituximab plus fludarabine and cyclophosphamide (R-FC) with six cycles of fludarabine and cyclophosphamide alone (FC) in patients with previously treated CLL. A total of 552 patients with Binet stage A (1%), B (59%), or C (31%) disease entered the study and were randomly assigned to receive R-FC (n = 276) or FC (n = 276).\n After a median follow-up time of 25 months, rituximab significantly improved progression-free survival in patients with previously treated CLL (hazard ratio = 0.65; P < .001; median, 30.6 months for R-FC v 20.6 months for FC). Event-free survival, response rate, complete response rate, duration of response, and time to new CLL treatment or death were also significantly improved. Although the rates of adverse events, grade 3 or 4 events, and serious adverse events were slightly higher in the R-FC arm, R-FC was generally well tolerated, with no new safety findings and no detrimental effect on quality of life.\n R-FC significantly improved the outcome of patients with previously treated CLL.", "Combination fludarabine (F), cyclophosphamide (C) and rituximab (R) is the standard front-line therapy in chronic lymphocytic leukaemia (CLL), but appropriate treatment of relapsed/refractory CLL is less clear. Combined FC and mitoxantrone (M) has been reported to be effective in a single arm study, and rituximab when added to chemotherapy in CLL is synergistic. A randomized, two-stage, Phase II trial of FCM and FCM-R was conducted in relapsed CLL. The primary endpoint was response rate 2 months after therapy, assessed according to the 2008 International Workshop CLL criteria. In addition, minimal residual disease (MRD) in the marrow was studied 2 months after therapy, with MRD negativity defined as <0·01% CLL cells. Fifty-two patients were entered, 26 in each arm. The overall response rates to FCM and FCM-R were 58% and 65% respectively. Combined complete response (CR) and CR with incomplete marrow recovery [CR(i)] was 15% (95% confidence interval [CI]:4-35%) for FCM and 42% (95%CI:23-63%) for FCM-R, with eight patients achieving MRD negativity (3 FCM; 5 FCM-R). The toxicity of both regimens was acceptable. In conclusion, the addition of rituximab to FCM improves the response rates in relapsed CLL, resulting in more complete remissions and without additional safety concerns. Efficacy and safety should be fully tested in a randomized Phase III trial.\n © 2011 Blackwell Publishing Ltd.", "On the basis of promising results that were reported in several phase 2 trials, we investigated whether the addition of the monoclonal antibody rituximab to first-line chemotherapy with fludarabine and cyclophosphamide would improve the outcome of patients with chronic lymphocytic leukaemia.\n Treatment-naive, physically fit patients (aged 30-81 years) with CD20-positive chronic lymphocytic leukaemia were randomly assigned in a one-to-one ratio to receive six courses of intravenous fludarabine (25 mg/m(2) per day) and cyclophosphamide (250 mg/m(2) per day) for the first 3 days of each 28-day treatment course with or without rituximab (375 mg/m(2) on day 0 of first course, and 500 mg/m(2) on day 1 of second to sixth courses) in 190 centres in 11 countries. Investigators and patients were not masked to the computer-generated treatment assignment. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00281918.\n 408 patients were assigned to fludarabine, cyclophosphamide, and rituximab (chemoimmunotherapy group) and 409 to fludarabine and cyclophosphamide (chemotherapy group); all patients were analysed. At 3 years after randomisation, 65% of patients in the chemoimmunotherapy group were free of progression compared with 45% in the chemotherapy group (hazard ratio 0·56 [95% CI 0·46-0·69], p<0·0001); 87% were alive versus 83%, respectively (0·67 [0·48-0·92]; p=0·01). Chemoimmunotherapy was more frequently associated with grade 3 and 4 neutropenia (136 [34%] of 404 vs 83 [21%] of 396; p<0·0001) and leucocytopenia (97 [24%] vs 48 [12%]; p<0·0001). Other side-effects, including severe infections, were not increased. There were eight (2%) treatment-related deaths in the chemoimmunotherapy group compared with ten (3%) in the chemotherapy group.\n Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab improves progression-free survival and overall survival in patients with chronic lymphocytic leukaemia. Moreover, the results suggest that the choice of a specific first-line treatment changes the natural course of chronic lymphocytic leukaemia.\n F Hoffmann-La Roche.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "The addition of rituximab to fludarabine-based regimens in chronic lymphocytic leukemia (CLL) has been shown to produce high response rates with extended remissions. The long-term follow-up of these regimens with respect to progression, survival, risk of secondary leukemia, and impact of genomic risk factors has been limited.\n We report the long-term follow-up of the chemoimmunotherapy trial CALGB 9712 from the Cancer and Leukemia Group B, for which treatment regimen was previously reported, to examine end points of progression-free survival (PFS), overall survival (OS), impact of genomic features, and risk of therapy-related myeloid neoplasm (t-MN).\n A total of 104 patients were enrolled on this study and now have a median follow-up of 117 months (range, 66 to 131 months). The median OS was 85 months, and 71% of patients were alive at 5 years. The median PFS was 42 months, and 27% were progression free at 5 years. An estimated 13% remained free of progression at almost 10 years of follow-up. Multivariable models of PFS and OS showed that immunoglobulin heavy chain variable region mutational status was significant for both, whereas cytogenetic abnormalities were significant only for OS. No patient developed t-MN before relapse.\n Long-term follow-up of CALGB 9712 demonstrates extended OS and PFS with fludarabine plus rituximab. Patients treated with fludarabine plus rituximab administered concurrently or sequentially have a low risk of t-MN. These long-term data support fludarabine plus rituximab as one acceptable first-line treatment for symptomatic patients with CLL.", "We conducted an international phase 2 trial to evaluate 2 dose levels of ofatumumab, a human CD20 mAb, combined with fludarabine and cyclophosphamide (O-FC) as frontline therapy for chronic lymphocytic leukemia (CLL). Patients with active CLL were randomized to ofatumumab 500 mg (n = 31) or 1000 mg (n = 30) day 1, with fludarabine 25 mg/m(2) and cyclophosphamide 250 mg/m(2) days 2-4, course 1; days 1-3, courses 2-6; every 4 weeks for 6 courses. The first ofatumumab dose was 300 mg for both cohorts. The median age was 56 years; 13% of patients had a 17p deletion; 64% had β2-microglobulin > 3.5 mg/L. Based on the 1996 National Cancer Institute Working Group (NCI-WG) guidelines, the complete response (CR) rate as assessed by an independent review committee was 32% for the 500-mg and 50% for the 1000-mg cohort; the overall response (OR) rate was 77% and 73%, respectively. Based on univariable regression analyses, β2-microglobulin and the number of O-FC courses were significantly correlated (P < .05) with CR and OR rates and progression-free survival (PFS). The most frequent Common Terminology Criteria (CTC) grade 3-4 investigator-reported adverse events were neutropenia (48%), thrombocytopenia (15%), anemia (13%), and infection (8%). O-FC is active and safe in treatment-naive patients with CLL, including high-risk patients. This trial was registered at www.clinicaltrials.gov as NCT00410163." ]

[ "20368196", "10761802", "12745109", "6341720", "18539916", "8833557", "12852722", "1308130", "18701019", "11529585", "7587918", "19092145", "9742976", "18991816", "351218", "15728645", "18256393", "18087561" ]

[ "Glycaemic control and restenosis after percutaneous coronary interventions in patients with diabetes mellitus: a report from the Insulin Diabetes Angioplasty study.", "The role of strict metabolic control by insulin infusion on fibrinolytic profile during an acute coronary event in diabetic patients.", "Effect of intravenous insulin administration on left ventricular performance during non-ST-elevation acute coronary events in patients with diabetes mellitus.", "Effect of blood glucose control on peripheral nerve function in diabetic patients.", "Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.", "Evaluation of a pharmaceutical care model on diabetes management.", "Improvement of glycaemic control in type 2 diabetes: favourable changes in blood pressure, total cholesterol and triglycerides, but not in HDL cholesterol, fibrinogen, Von Willebrand factor and (pro)insulin.", "Glycemic control and complications in type II diabetes. Design of a feasibility trial. VA CS Group (CSDM)", "Effect of short term intensive multitherapy on carotid intima-media thickness in patients with newly diagnosed type 2 diabetes mellitus.", "Effects of improved glycaemic control on endothelial function in patients with type 2 diabetes.", "Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study.", "Glucose control and vascular complications in veterans with type 2 diabetes.", "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.", "[Effect of strict glycemic control on clinical state and course of the disease in patients with chronic heart failure and type II diabetes mellitus. Results of the REMBO \"rational effective multicomponent therapy in the struggle against diabetes mellitus in patients with congestive heart failure\" study].", "Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VII. Mortality and selected nonfatal events with insulin treatment.", "Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity.", "Effect of a multifactorial intervention on mortality in type 2 diabetes.", "[Long-term intensive glycemic and lipid control ameliorates the carotid intima medial thickness in type 2 diabetes mellitus]." ]

[ "We investigated the impact of glucose control on target lesion restenosis after PCI in patients with type 2 diabetes.\n Ninety-three consecutive patients with type 2 diabetes accepted for PCI were randomised to intensified glucose control based on insulin (I-group; n=44) or to continue ongoing glucose-lowering treatment (C-group; n=49).The treatment target was a FBG of 5-7 mmol/L and HbA1c <6.5%. Information on target lesion restenosis after six months was available in 82 patients.\n At baseline HbA1c and FBG did not differ between the I- and C-groups, respectively (HbA1c: 6.5 vs. 6.5%; p=1.0 and FBG: 7.0 vs. 7.3 mmol/L; p=0.3). After six months there was no significant change in HbA1c or FBG in either group (change in HbA1c: -0.2 vs.-0.1%; p=0.3 and in FBG: +0.2 vs. -0.3 mmol/L; p=0.3 in the I- and C-groups, respectively). Target lesion restenosis at six months did not differ, I vs. C = 41 and 44% (p=0.8). Independent predictors for restenosis were previous myocardial infarction (OR 8.0, 95% CI 2.5-25.7; p=<0.001) and FBG at baseline (OR for an increase by 1 mmol/L = 1.4, 95% CI 1.1-1.9; p=0.015).\n Restenosis was predicted by baseline FBG suggesting that it would be of interest to target glucose normalisation in future trials. Intensified insulin treatment did not influence the rate of restenosis indicating that the main focus should be on lowering glucose rather than the tool to normalise glucose.", "Many clinical and laboratory observations give support to the hypothesis that strict metabolic control by insulin infusion during acute coronary events may improve the ischemic damage and prognosis.\n We investigated the impact of intensive insulin treatment on fibrinolytic parameters during an acute ischemic myocardial event (unstable angina or acute myocardial infarction) in patients with type 2 diabetes mellitus.\n The study group consisted of 48 type 2 diabetic patients, of whom 24 were randomized to conventional therapy plus intensive insulin treatment (Group 1) and 24 to conventional therapy only (Group 2). The two groups were comparable according to gender, age, body mass index, waist:hip ratio, duration of diabetes, previous antidiabetic treatment, type of ischemic events, concomitant therapy, and the classic risk factors for coronary disease. Insulin-treated patients were excluded from the study. Plasma levels of fibrinogen, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) were measured on admission and discharge. Fibrinogen (fibr) was measured using the photometric method. PAI-1 and t-PA were measured by enzyme-linked immunosorbent assays.\n T-PA increased in both groups during hospitalization (t-PA(admission) vs. t-PA(discharge): Group 1: 15.42 +/- 4.4 ng x ml(-1) vs. 21.2 +/- 5.74 ng x ml(-1), p = 0.000037; Group 2: 14.47 +/- 6.31 ng x ml(-1) vs. 19.18 +/- 6.88 ng x ml(-1), p = 0.001). On the other hand, fibr and PAI-1 levels increased remarkably in controls (Group 2, fibr(admission) vs. fibr(discharge): 2.98 +/- 1.04 g x l(-1) vs. 3.59 +/- 1.01 g x l(-1), p = 0.002, and PAI-1admission vs. PAI-1 discharge: 30.6 +/- 17.34 ng x ml(-1) vs. 40.62 +/- 23.48 ng x ml(-1), p = 0.003). This finding was not observed in the intensive insulin treatment group (Group 1, fibr(admission) vs. fibr(discharge): 2.87 +/- 0.73 g x l(-1) vs. 2.67 +/- 0.72 g x l(-1), p = 0.101, and PAI-1 admission vs. PAI-1 discharge: 30.75 +/- 15.81 ng x ml(-1) vs. 27.75 +/- 6.43 ng x ml(-1), p = 0.484).\n Intensive insulin treatment during an acute coronary event improves fibrinolytic profile in patients with diabetes mellitus. This is a possible mechanism for the reduced short- and long-term mortality in diabetic patients treated with intensive insulin treatment protocol.", "nan", "A prospective, stratified, randomized 3-year clinical trial was conducted on the effect of rigorous versus conventional glucose control on peripheral nerve function in 33 insulin-treated diabetic patients with a duration of diabetes of less than 2 years. The goals for conventional glucose control were the mean of fasting and 80-minute postprandial plasma glucose of 150 mg/dl for non-insulin-dependent diabetes and 200 mg/dl for insulin-dependent diabetes. The goal of rigorous glucose control was an approximation of nondiabetic glucose control. No significant difference in glucose control or peripheral nerve function was observed between the rigorously and the conventionally controlled groups. Eight patients in the conventional-control group spontaneously achieved glucose control in the range that was the objective for the rigorous-control group, and five patients in the rigorous-control group never achieved the desired glucose control. In the remaining 20 patients, with similar baseline glucose control and peripheral nerve function characteristics, observed over a median of 2 years, improved blood glucose control (P less than 0.01) was not associated with any significant improvement in peripheral nerve function. Nevertheless, a significant (P less than 0.05) correlation was found between the degree of abnormal nerve function at entry into the study and change in nerve function during the study. If control of hyperglycemia benefits peripheral nerve function of diabetic patients, its demonstration may require a closer approximation of normoglycemia, a larger difference in glucose control between the two study groups, a longer duration of treatment, and the use of patients with more advanced peripheral nerve function abnormalities than those in this study.", "In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.\n We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.\n After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001).\n A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)\n 2008 Massachusetts Medical Society", "To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus (NIDDM) in urban African-American patients.\n Eligible patients were randomized to either a pharmacist intervention or control group and followed over a 4-month period. Patients in the intervention group received diabetes education, medication counseling, instructions on dietary regulation, exercise, and home blood glucose monitoring, and evaluation and adjustment of their hypoglycemic regimen. Patients in the control group continued to receive standard medical care provided by their physicians.\n A university-affiliated internal medicine outpatient clinic.\n The study population consisted of urban African American patients with NIDDM currently attending the clinic.\n Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations. Secondary outcome endpoints included blood pressure, serum creatinine, creatinine clearance, microalbumin to creatinine ratio, total cholesterol, triglycerides, high-density lipoprotein, and low density lipoprotein concentrations. Quality-of-life assessments were performed in both groups at baseline and at the end of the study.\n Thirty-nine patients (17 intervention, 22 control) completed the study. The intervention group consisted of 12 women and 5 men with a mean +/- SD age of 59 +/- 12 years, total body weight (TBW) of 93 +/- 22 kg, body mass index (BMI) of 34 +/- 7 kg/m2, and duration of NIDDM 6.8 +/- 6.5 years. The control group consisted of 15 women and 7 men with a mean age of 65 +/- 12 years, TBW of 88 +/- 19 kg, BMI of 33 + 7 kg/m2, and a duration of NIDDM of 6.2 +/- 4.8 y. Significant improvement in glycated hemoglobin (p = 0.003) and fasting plasma glucose (p =0.015) was achieved in the intervention group. No change in glycemia was observed in the control subjects. Statistically significant differences in the final glycated hemoglobin (p = 0.003) and fasting plasma glucose (p = 0.022) concentrations were noted between groups. No significant changes in blood pressure control, lipid profile, renal function parameters, weight, or quality-of-life measures were noted within or between groups.\n Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients.", "Diabetes mellitus causes a substantial increase in cardiovascular risk, which can only partly be reduced by antihyperglycaemic treatment. We were interested in whether improvement in glycaemic control is associated with improvement of other cardiovascular risk factors. Therefore, we studied among type 2 diabetic patients the association between on the one hand changes in glycaemic control and on the other hand within-subject changes of both classic cardiovascular risk factors and less conventional cardiovascular risk indicators that are typically associated with type 2 diabetes (proinsulin, insulin, fibrinogen, von Willebrand factor and the urinary albumin-creatinine ratio).\n The 214 type 2 diabetic patients were randomly assigned to either a strict fasting capillary glucose target level (< 6.5 mmol/l) or a less strict target (< 8.5 mmol/l). Duration of follow-up was two years. Since the interventions did not yield statistically significant differences between the treatment arms, we reanalysed the data focusing on within-subject changes of cardiovascular risk factors and indicators across tertiles of average HbA(1c).\n Individuals in whom HbA(1c) decreased had significant favourable concurrent changes in triglycerides, total cholesterol, blood pressure, and in the albumin-creatinine ratio in those who were normoalbuminuric at baseline. In contrast, these individuals had unfavourable, although not statistically significant, changes in HDL cholesterol, proinsulin, insulin, fibrinogen and von Willebrand factor. In the whole group, fibrinogen increased more than could be expected on the basis of the relationship between fibrinogen and age, namely from 3.5 +/- 0.8 to 3.9 +/- 0.9 g/l (p value < 0.01).\n Our results suggest that improvement in glycaemia in type 2 diabetes is associated with significant favourable changes in triglycerides, total cholesterol, blood pressure and, in normoalbuminuric individuals, albumin-creatinine ratio. In contrast, it is not consistently associated with favourable changes in some cardiovascular risk indicators typically associated with diabetes, which may in part explain why antihyperglycaemic treatment does not clearly lower atherothrombotic disease risk.", "To determine, after 1 yr of follow-up in type II diabetes patients, whether a statistically and clinically significant difference can be achieved in HbA1c between a standard therapy group and an intensively treated group, while maintaining HbA1c levels in both groups within ranges acceptable in regular community practice. Secondary objectives include assessment of patient adherence to protocol, side effects, and accuracy of data collection.\n This is a prospective, randomized, controlled VA CS conducted with 151 patients at five VAMCs. Patients are males, age 40-69 yr, treated at entry with a maximum dose of sulfonylurea or with insulin, exhibiting an HbA1c level > 3 SDs above the normal mean (5.05 + 3 x 0.50 = > 6.55%). Standard control is achieved with insulin and intensive control with a step-up regimen including insulin alone or insulin/glipizide combinations. Education and management of cardiovascular risk factors are handled similarly in both groups. Primary macrovascular end points are nonfatal myocardial infarction, congestive heart failure, stroke, amputation, and cardiovascular death. Primary microvascular end points are appearance and progression of retinopathy, documented by centrally read seven-field-stereo fundus photographs. Other measured indicators include resting and ambulatory ECGs, ventricular function (MUGA scan), serum lipid and apolipoprotein levels, plasma fibrinogen, nonsymptomatic peripheral vasculopathy, neuroautonomic status by heart-beat variation on Valsalva maneuver, and microalbuminuria.\n This study may be the basis for a long-term trial, involving 1400 patients, to assess the long-term effects of metabolic control on macro- and microvascular end points.", "Controlling plasma glucose levels, blood pressure and lipid levels is proven to reduce the risk of vascular complications in patients with type 2 diabetes mellitus. This has prompted intensive multitherapy targeted at several macrovascular risk factors. Carotid intima-media thickness (cIMT) is a reliable measure of early atherosclerosis. We sought to determine whether a 6-month intensive mutiltherapy program resulted in better goal attainment than usual care and its effect on the development of cIMT among patients with newly diagnosed type 2 diabetes mellitus.\n The study randomly assigned 220 patients with newly diagnosed type 2 diabetes mellitus to intensive or traditional therapy groups. The clinical parameters, such as fasting plasma glucose, total cholesterol, triglyceride, blood pressure, body weight and insulin were assessed at the baseline and after the 6-month therapy. cIMT of the patients was also obtained.\n The average levels of fasting plasma glucose, hemoglobin A1c, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the intensive group were significantly lower than those in the control group at the end of 6-month treatment. By 6 months, a higher proportion of patients in the intensive therapy group than in the control group attained goals for fasting plasma glucose (FPG), TC, LDL-C and hemoglobin A1c. With intensive multherapy the level of carotid intima-media thickness in the intensive therapy group was lower than that in the control group ((0.88 +/- 0.26) mm vs (0.96 +/- 0.22) mm, P < 0.01).\n The evidence from this clinical trial demonstrates that intensive glucose, lipid and blood pressure control in patients with newly diagnosed type 2 diabetes is associated with diabetic macrovascular benefits. Intensive multitherapy allows more patients to achieve aims of control and may reduce macrovascular complications and delay disease progression.", "Patients with type 2 diabetes have abnormal endothelial function but it is not certain whether improvements in glycaemic control will improve endothelial function.\n To examine the effects of short-term improved glycaemic control on endothelial function in patients with inadequately regulated type 2 diabetes mellitus.\n Forty-three patients with type 2 diabetes and glycosylated haemoglobin (HbA1c) > 8.9% were randomized to either improved glycaemic control (IC) n = 21 or usual glycaemic control (UC) n = 22 for 20 weeks. Using high-resolution B-mode ultrasound, brachial artery flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN-D) were measured at baseline and 20 weeks later.\n After 20 weeks, HbA1c was significantly lower in IC versus UC (IC 8.02 +/- 0.25% versus UC 10.23 +/- 0.23%, P < 0.0001) but changes in FMD and GTN-D were not different between the groups (FMD at baseline and week 20 IC 5.1 +/- 0.56% versus 4.9 +/- 0.56% and UC 4.2 +/- 0.51% versus 3.1 +/- 0.51%; P = 0.23: GTN-D IC 12.8 +/- 1.34% versus 10.4 +/- 1.32% and UC 13.7 +/- 1.2% versus 12.7 +/- 1.23%; P = 0.39). In the IC group weight increased by 3.2 +/- 0.8 kg after 20 weeks compared to 0.02 +/- 0.70 kg in UC (P = 0.003). Blood pressure and serum lipid concentrations did not change in either group.\n Short-term reduction of HbA1c levels did not appear to affect endothelial function in patients with type 2 diabetes and previously poorly regulated glycaemic control.", "To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, we performed a prospective study of Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with multiple insulin injection treatment. A total of 110 patients with NIDDM was randomly assigned to multiple insulin injection treatment group (MIT group) or to conventional insulin injection treatment group (CIT group). Fifty-five NIDDM patients who showed no retinopathy and urinary albumin excretions < 30 mg/24 h at the baseline were evaluated in the primary-prevention cohort, and the other 55 NIDDM patients who showed simple retinopathy and urinary albumin excretions < 300 mg/24 h were evaluated in the secondary-intervention cohort. The appearance and the progression of retinopathy, nephropathy and neuropathy were evaluated every 6 months over a 6-year period. The worsening of complications in this study was defined as an increase of 2 or more steps in the 19 stages of the modified ETDRS interim scale for retinopathy and an increase of one or more steps in 3 stages (normoalbuminuria, microalbuminuria and albuminuria) for nephropathy. The cumulative percentages of the development and the progression in retinopathy after 6 years were 7.7% for the MIT group and 32.0% for the CIT group in the primary-prevention cohort (P = 0.039), and 19.2% for MIT group and 44.0% for CIT group in the secondary-intervention cohort (P = 0.049). The cumulative percentages of the development and the progression in nephropathy after 6 years were 7.7% for the MIT group and 28.0% for the CIT group in the primary-prevention cohort (P = 0.032), and 11.5% and 32.0%, respectively, for the MIT and CIT groups in the secondary-intervention cohort (P = 0.044). In neurological tests after 6 years, MIT group showed significant improvement in the nerve conduction velocities, while the CIT group showed significant deterioration in the median nerve conduction velocities and vibration threshold. Although both postural hypotension and the coefficient of variation of R-R interval tended to improve in the MIT group, they deteriorated in the CIT group. In conclusion, intensive glycemic control by multiple insulin injection therapy can delay the onset and the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese patients with NIDDM. From this study, the glycemic threshold to prevent the onset and the progression of diabetic microangiopathy is indicated as follows; HbA1c < 6.5%, FBG < 110 mg/dl, and 2-h post-prandial blood glucose concentration < 180 mg/dl.", "The effects of intensive glucose control on cardiovascular events in patients with long-standing type 2 diabetes mellitus remain uncertain.\n We randomly assigned 1791 military veterans (mean age, 60.4 years) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. Other cardiovascular risk factors were treated uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and 40% of the patients had already had a cardiovascular event. The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level, as compared with the standard-therapy group. The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene.\n The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group.\n Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications with the exception of progression of albuminuria (P = 0.01) [added]. (ClinicalTrials.gov number, NCT00032487.)\n 2009 Massachusetts Medical Society", "Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial.\n 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy.\n Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg).\n Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)", "With the aim to investigate influence of glycemic control on clinical state and course of disease, renal function, and neurohormonal profile of patients with chronic heart failure (CHF) and type 2 diabetes mellitus (DM) we studied 81 patients with NYHA functional class (FC) II - III CHF, left ventricular ejection fraction (LVEF) 45% and type 2 DM. As a result of randomization 2 groups were formed - active with achievement of target levels of glycemia (n=41) and usual treatment (n=40). Retrospective analysis in dependence of efficacy of sugar lowering therapy was also conducted. Group 1 (n=18) comprised patients with achieved 1% lowering of glycated hemoglobin (HbA1 ), group 2 (n=26) - patients with bA1c lowering < 1%, group 3 (n=31) - patients with increase of HbA1 . Total duration of the investigation for the first analysis was 12, for the second - 6 months. Control examination was carried out at baseline, after 6 and 12 months of investigation and included assessment of clinico-functional status, glomerular filtration rate, neurohormonal profile (brain natriuretic peptide, noradrenalin, and angiotensin II). The state of carbohydrate metabolism was assessed with the help of determination of the level of HbA1c and oral glucose tolerance test. Absence of dynamics of glycemia in active and nonactive groups, in the active group improvement of clinico-functional status, quality of life, and parameters of remodeling was noted. Complementary retrospective analysis revealed improvement of functional status, renal function, and lowering of RAAS activity at 1% lowering of HbA1 and achievement of its target values. With this it was shown that betterment of functional possibilities ensued at lowering of HbA1c level not less than by 0.8%. Thus necessity and efficacy of strict glycemic control of DM in patients with CHF was proved.", "The University Group Diabetes Program is a long-term prospective clinical trial designed to evaluate the effects of various hypoglycemic agents on vascular complications in patients with asymptomatic adult-onset diabetes. Mortality and blood glucose levels were determined as well as certain nonfatal events for patients assigned to diet alone or to either of two insulin treatment regimens. Lower levels of blood glucose with mean values close to normoglycemia were achieved in the treatment group in which the insulin dosage was adjusted to achieve normoglycemia compared with the levels achieved in patients treated with diet alone or with a fixed dose of insulin. In spite of differences in blood glucose levels among the treatment groups, there were only minor differences in the occurrence of fatal or nonfatal events.", "Patients with diabetes have an unfavourable prognosis after an acute myocardial infarction. In the first DIGAMI study, an insulin-based glucose management improved survival. In DIGAMI 2, three treatment strategies were compared: group 1, acute insulin-glucose infusion followed by insulin-based long-term glucose control; group 2, insulin-glucose infusion followed by standard glucose control; and group 3, routine metabolic management according to local practice.\n DIGAMI 2 recruited 1253 patients (mean age 68 years; 67% males) with type 2 diabetes and suspected acute myocardial infarction randomly assigned to groups 1 (n=474), 2 (n=473), and 3 (n=306). The primary endpoint was all-cause mortality between groups 1 and 2, and a difference was hypothesized as the primary objective. The secondary objective was to compare total mortality between groups 2 and 3, whereas morbidity differences served as tertiary objectives. The median study duration was 2.1 (interquartile range 1.03-3.00) years. At randomization, HbA1c was 7.2, 7.3, and 7.3% in groups 1, 2, and 3, respectively, whereas blood glucose was 12.8, 12.5, and 12.9 mmol/L, respectively. Blood glucose was significantly reduced after 24 h in all groups, more in groups 1 and 2 (9.1 and 9.1 mmol/L) receiving insulin-glucose infusion than in group 3 (10.0 mmol/L). Long-term glucose-lowering treatment differed between groups with multidose insulin (> or =3 doses/day) given to 15 and 13% of patients in groups 2 and 3, respectively compared with 42% in group 1 at hospital discharge. By the end of follow-up, HbA1c did not differ significantly among groups 1-3 ( approximately 6.8%). The corresponding values for fasting blood glucose were 8.0, 8.3, and 8.6 mmol/L. Hence, the target fasting blood glucose for patients in group 1 of 5-7 mmol/L was never reached. The study mortality (groups 1-3 combined) was 18.4%. Mortality between groups 1 (23.4%) and 2 (22.6%; primary endpoint) did not differ significantly (HR 1.03; 95% CI 0.79-1.34; P=0.831), nor did mortality between groups 2 (22.6%) and 3 (19.3%; secondary endpoint) (HR 1.23; CI 0.89-1.69; P=0.203). There were no significant differences in morbidity expressed as non-fatal reinfarctions and strokes among the three groups.\n DIGAMI 2 did not support the fact that an acutely introduced, long-term insulin treatment improves survival in type 2 diabetic patients following myocardial infarction when compared with a conventional management at similar levels of glucose control or that insulin-based treatment lowers the number of non-fatal myocardial reinfarctions and strokes. However, an epidemiological analysis confirms that the glucose level is a strong, independent predictor of long-term mortality in this patient category, underlining that glucose control seems to be an important part of their management.", "Intensified multifactorial intervention - with tight glucose regulation and the use of renin-angiotensin system blockers, aspirin, and lipid-lowering agents - has been shown to reduce the risk of nonfatal cardiovascular disease among patients with type 2 diabetes mellitus and microalbuminuria. We evaluated whether this approach would have an effect on the rates of death from any cause and from cardiovascular causes.\n In the Steno-2 Study, we randomly assigned 160 patients with type 2 diabetes and persistent microalbuminuria to receive either intensive therapy or conventional therapy; the mean treatment period was 7.8 years. Patients were subsequently followed observationally for a mean of 5.5 years, until December 31, 2006. The primary end point at 13.3 years of follow-up was the time to death from any cause.\n Twenty-four patients in the intensive-therapy group died, as compared with 40 in the conventional-therapy group (hazard ratio, 0.54; 95% confidence interval [CI], 0.32 to 0.89; P=0.02). Intensive therapy was associated with a lower risk of death from cardiovascular causes (hazard ratio, 0.43; 95% CI, 0.19 to 0.94; P=0.04) and of cardiovascular events (hazard ratio, 0.41; 95% CI, 0.25 to 0.67; P<0.001). One patient in the intensive-therapy group had progression to end-stage renal disease, as compared with six patients in the conventional-therapy group (P=0.04). Fewer patients in the intensive-therapy group required retinal photocoagulation (relative risk, 0.45; 95% CI, 0.23 to 0.86; P=0.02). Few major side effects were reported.\n In at-risk patients with type 2 diabetes, intensive intervention with multiple drug combinations and behavior modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from cardiovascular causes. (ClinicalTrials.gov number, NCT00320008.)\n Copyright 2008 Massachusetts Medical Society.", "To investigate whether long-term intensive glycemic and lipid control would ameliorate the carotid intima medial thickness (IMT) in patients with type 2 diabetes mellitus (T2DM).\n IMT was evaluated on B-mode ultrasonography in 116 patients with T2DM. Body mass index (BMI), waist-to-hip ratio (WHR), fasting blood glucose (FBG), 2 hour postpradial glucose (2hPG), hemoglobin A(1)c(HbA(1)c), total cholesterol(TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C) were also measured. Of all the patients 89 were divided randomly into group of intensive glycemic and lipid control and group of conventional treatment and underwent 1 year clinical interview.\n (1) IMT in patients with T2DM was significantly correlated with age(r = 0.515,P = 0.000) , SBP (r = 0.208, P = 0.025), TC(r = 0.213,P = 0.022), LDL-C(r = 0.253, P = 0.006) and no correlations were found between IMT and BMI,WHR,FBG, 2hPG ,HbA(1)c, TG and HDL-C. In multivariate regression analysis, age (Beta = 0.527, P = 0.000 )and TC(Beta = 0.243, P = 0.002) were significant independent determinants for IMT. (3) After 1 year the change of IMT in the group of intensive glycemic and lipid control was significantly different compared with the group of conventional treatment [(-0.044+/-0.148)mm vs (0.056+/-0.178), P<0.05]. The change of IMT was not significantly associated with the use of Metformin, Sulphonylurea and Aspirin, but significantly associated with the use of statins. The change of IMT in the group using statins was significantly different compared with that in the group without using statins[(-0.053+/-0.153)mm vs (0.042+/-0.165)mm, P <0.05].\n Carotid IMT appears to be closely related to age and TC in the patients with T2DM. long-term intensive glycemic control and lipid control could ameliorate the IMT in patients with T2DM. The improvement of IMT may be associated with the use of statin drug." ]

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[ "The additive analgesic efficacy of acetaminophen, 1000 mg, and codeine, 60 mg, in dental pain.", "Evaluation of flurbiprofen, acetaminophen, an acetaminophen-codeine combination, and placebo in postoperative oral surgery pain.", "Double-blind comparison of meclofenamate sodium with acetaminophen, acetaminophen with codeine and placebo for relief of postsurgical dental pain.", "Efficacy and quality of ibuprofen and acetaminophen plus codeine analgesia.", "An appraisal of codeine as an analgesic: single-dose analysis.", "The relative efficacy of indoprofen compared with opioid-analgesic combinations.", "Comparative study of flurbiprofen, zomepirac sodium, acetaminophen plus codeine, and acetaminophen for the relief of postsurgical dental pain.", "Analysis of the analgesic efficacy of acetaminophen 1000 mg, codeine phosphate 60 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg in the relief of postoperative pain.", "Double-blind parallel comparison of ketoprofen (Orudis), acetaminophen plus codeine, and placebo in postoperative pain.", "Evaluation of ketorolac, aspirin, and an acetaminophen-codeine combination in postoperative oral surgery pain.", "Analgesic efficacy of rofecoxib compared with codeine/acetaminophen using a model of acute dental pain.", "Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen-codeine combination in postoperative oral surgery pain.", "Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial.", "Efficacy of low dose combination analgesics: acetaminophen/codeine, aspirin/butalbital/caffeine/codeine, and placebo in oral surgery pain.", "Lack of analgesic effect of 50 and 100 mg oral tramadol after orthopaedic surgery: a randomized, double-blind, placebo and standard active drug comparison.", "Evaluation of two opioid-acetaminophen combinations and placebo in postoperative oral surgery pain.", "Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: a randomized, double-blind single-dose study.", "Single-dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions.", "A randomized, double-blind, parallel-group study comparing the analgesic effect of etoricoxib to placebo, naproxen sodium, and acetaminophen with codeine using the dental impaction pain model.", "The analgesic efficacy of flurbiprofen compared to acetaminophen with codeine.", "Additive analgesic effect of codeine and paracetamol can be detected in strong, but not moderate, pain after Caesarean section. Baseline pain-intensity is a determinant of assay-sensitivity in a postoperative analgesic trial.", "Analgesic efficacy of the kappa-receptor agonist, enadoline, in dental surgery pain.", "A 12-hour evaluation of the analgesic efficacy of diflunisal, acetaminophen, and acetaminophen-codeine combination, and placebo in postoperative pain.", "Tramadol/acetaminophen tablets in the treatment of postsurgical orthopedic pain.", "Combination tramadol plus acetaminophen for postsurgical pain.", "Analgesic effect of an aspirin-codeine-butalbital-caffeine combination and an acetaminophen-codeine combination in postoperative oral surgery pain.", "Analgesic efficacy of flurbiprofen in comparison with acetaminophen, acetaminophen plus codeine, and placebo after impacted third molar removal.", "Diflunisal. A new oral analgesic with an unusually long duration of action." ]

[ "In a double-blind, randomized, single-dose trial the analgesic contribution of acetaminophen, 1000 mg, and codeine, 60 mg, was determined. The study was a 2 X 2 factorial experiment in which 120 patients suffering from pain as a result of oral surgery rated their pain intensity and pain relief for up to 5 hours after a single dose of one of: 1000 mg acetaminophen, 60 mg codeine, 1000 mg acetaminophen plus 60 mg codeine, or placebo. The factorial analysis showed that both 1000 mg acetaminophen and 60 mg codeine made a statistically significant (P less than 0.05) contribution to the analgesic effectiveness of the combination on all measures of efficacy (sum of pain intensity differences, largest pain intensity difference, total pain relief, largest pain relief, and time to remedication). The incidence of adverse effects did not appear to differ among the treatments, including placebo.", "Eighty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single, oral dose of flurbiprofen 100 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg with codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of sum of pain intensity differences, peak pain intensity differences, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy. Based on the 12-hour data, acetaminophen alone did not differ significantly from placebo; however, it was superior to placebo for measures of total effect based on the 4-hour data. Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication. All medications had manifested an effect by hour 1; analgesia persisted for 12 hours for flurbiprofen, 6 hours for acetaminophen-codeine, and 3 hours for acetaminophen alone. The frequency of adverse effects was similar for the active medications.", "nan", "Ibuprofen, 400 mg, was compared with 300 mg acetaminophen plus 30 mg of codeine and placebo in 120 post-orthopedic surgery patients with moderate to severe pain. The study was designed as a double-blind, single-dose, parallel-group analgesic efficacy assay. Estimates of analgesia were obtained up to 6 h using categorical and visual analog measures of pain intensity and pain relief. Estimates of selected elements of mood and of sensory and affective components of pain were obtained at 0 and 2 h using contrasting mood word/phrase pairs and a portion of the McGill Pain Questionnaire, respectively. Drugs were distinguishable from placebo in total analgesic effect, and ibuprofen was more effective than acetaminophen plus codeine, especially in terms of duration. While peak effects were comparable, they occurred 1 h later following ibuprofen. Differences among treatments were more discernible using visual analog measures. Side effects were minimal. Ibuprofen provided greater improvement in selected elements of mood than acetaminophen plus codeine at comparable levels of pain relief. While decreases in the sensory component of pain were most highly associated with pain relief provided by ibuprofen, decreases in the affective component were most highly associated with pain relief following acetaminophen plus codeine. These latter results indicate that mood assessment and the discrimination between sensory and affective components of pain could be particularly useful within analgesic drug assays, especially when comparing analgesics of differing pharmacologic class and when comparing the results of such assays in pain syndromes characterized by differing pain quality.", "Codeine, a relatively weak oral narcotic agent, is the most frequently prescribed oral opiate drug. It is also frequently utilized as a control drug in comparative analgesic efficacy studies. These studies are often single dose analysis of pain relief following surgery or childbirth. We conducted a single dose, post-operative analysis of 116 patients who were randomly assigned to receive codeine 60 mg, acetaminophen 600 mg, the combination of codeine and acetaminophen at these doses, or a placebo. Only the combination agent was uniformly superior to placebo. Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis. A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic, in acceptable oral doses, in the single dose setting. Previous reports, however, suggest that the multiple doses of codeine may afford adequate analgesia. Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult.", "This double-blind, parallel-design study used postsurgical dental outpatients as subjects. The patients self-administered a single dose of one of the study medications when they estimated their pain to be of moderate or severe intensity. The study medications were 200 mg of indoprofen, 650 mg of acetaminophen, 650 of acetaminophen with 60 mg of codeine, 650 mg of acetaminophen with 100 mg of d-propoxyphene N, and a placebo. On a report form, data were recorded on baseline pain and then hourly for four hours, intensity of pain, relief of pain, and side effects were reported. Also, an overall evaluation was recorded. Data were analyzed with the use of analysis of variance and Duncan's Multiple Range test. All four active treatments were statistically superior to placebo for sum pain intensity difference, total relief of pain, and overall evaluation parameters. Both opioid-analgesic combinations showed small additive effects over acetaminophen alone, and indoprofen was superior to both combination treatments and acetaminophen alone.", "The relative analgesic efficacy and safety of single oral doses of 50 and 100 mg of flurbiprofen (Ansaid, Upjohn) were compared with 100 mg of zomepirac sodium, 650 mg of acetaminophen plus 60 mg of codeine, 650 mg of acetaminophen alone, and placebo in a randomized, double-blind, parallel-group study. A total of 182 patients entered the study with moderate pain from a third molar extraction and were evaluated for six hours. For many efficacy variables, all active treatments were significantly (p less than or equal to 0.05) more effective than placebo. The two doses of flurbiprofen gave approximately similar results, suggesting a plateau effect above 50 mg. With the exception of relief at one hour, there were no significant differences between zomepirac and either dose of flurbiprofen. However, the mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours. The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine. At the first hour, acetaminophen plus codeine led to significantly better pain relief than did 100 mg of flurbiprofen. After the first hour, flurbiprofen resulted in greater mean scores than acetaminophen alone or acetaminophen plus codeine, and these differences were significant at the fifth and sixth hours. Five patients had adverse reactions while receiving acetaminophen, acetaminophen plus codeine, or placebo. There were no adverse effects with flurbiprofen or zomepirac.", "Patients who experienced pain after surgery were administered a single dose of 1 of 3 treatments: acetaminophen 1000 mg, codeine phosphate 60 mg, or a combination of these. Patients rated their pain intensity on ordinal and visual analog scales just prior to medication and at intervals thereafter for up to 5 hours. They also rated pain relief, pain half gone, and any adverse effects. Sum of pain intensity difference and total pain relief scores were analyzed using Dunnett's procedure. The drug combination was statistically superior to codeine as measured by SPID, TOTPAR, pain half gone, and time to remedication. The combination achieved better mean scores than acetaminophen on all efficacy measures, but was (marginally) statistically superior only in pain half gone. No appreciable differences in adverse effects were noted among the treatments. The difficulty of showing the analgesic efficacy of codeine in a single dose trial is discussed.", "One hundred sixty-one patients with postoperative pain were treated at a single center in a double-blind, randomized, parallel study designed to compare the efficacy and safety of single oral doses of ketoprofen (50 and 150 mg), an acetaminophen (650 mg) plus codeine (60 mg) combination, and placebo. From 1 through 4 hours after administration of the study drugs, the mean summed pain intensity difference (SPID) and time-weighted total pain relief (TOPAR) scores for the three active treatments generally were significantly (P less than 0.05) higher than those for placebo but not significantly different from each other. At the 6-hour evaluation, the ketoprofen groups, but not the acetaminophen-codeine group, had higher (P less than 0.05) mean SPID and TOPAR scores than the placebo group, as a result of a shorter duration of pain relief in the acetaminophen-codeine group. The 6-hour TOPAR scores were significantly (P less than 0.05) higher for both ketoprofen groups than for the acetaminophen-codeine group; the ketoprofen 150 mg group also had significantly (P less than 0.05) higher mean 6-hour SPID and global subjective assessment scores. As a result of a higher frequency of somnolence, there was a significantly (P less than 0.05) greater incidence of central nervous system adverse drug reactions among patients treated with acetaminophen plus codeine than among those treated with 150 mg of ketoprofen. These results indicate that the analgesic efficacy of both 50 and 150 mg doses of ketoprofen equals that of acetaminophen 650 mg plus codeine 60 mg and the duration of the analgesic effect of ketoprofen is significantly longer.", "One-hundred twenty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive oral doses of ketorolac tromethamine 10 mg, aspirin 650 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia. Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia, and significantly superior to acetaminophen-codeine for measures of total effect. The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours. Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery. Differences among the active medications were trivial for the postoperative days 1-6 analyses. The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin.", "To determine analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with acetaminophen/codeine 600/60 mg, we conducted a double-blind, randomized, placebo- and active-comparator-controlled, parallel-group study.\n Patients (N = 390) experiencing moderate or severe pain postextraction of 2 or more third molars, with at least 1 mandibular impaction, were randomized to placebo (n = 30), rofecoxib (n = 180), or codeine/acetaminophen 60/600 mg (n = 180). Time to confirmed perceptible pain relief, and patient evaluations of pain intensity, pain relief, and global assessments were recorded.\n For total pain relief over 6 hours (primary end point), rofecoxib was superior to codeine/acetaminophen (15.5 vs 10.7; P < .001). Rofecoxib was statistically significantly superior to codeine/acetaminophen with respect to TOPAR4, patient global assessment, peak pain relief, and duration of analgesic effect. Median onset of analgesia was similar for both drugs. The codeine/acetaminophen group had more patients with 1 or more adverse events.\n Rofecoxib provided superior analgesic efficacy compared with codeine/acetaminophen with fewer gastrointestinal and nervous system adverse events.", "Two-hundred six outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg, ibuprofen 400 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg; however, these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination. The analgesic effect of each active medication was significant by hour 1 and persisted for 5-6 hours. The data suggest a plateau in ketorolac's analgesic efficacy at the 10-mg level. Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg; ketorolac 20 mg was also superior to acetaminophen-codeine. Differences among active medications were not significant when data for the entire postoperative period (days 0-6) were evaluated. The frequency of adverse effects was similar for the active medications.", "In recent studies of acute pain and primary dysmenorrhea, rofecoxib, a nonsteroidal anti-inflammatory drug that selectively targets the cyclooxygenase-2 enzyme, was found to be similar in efficacy to ibuprofen and naproxen sodium.\n The purpose of this study was to determine the analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with the combination of codeine 60 mg/acetaminophen 600 mg in a model of postsurgical dental pain.\n In this double-blind, placebo- and active comparator-controlled, parallel-group study, patients experiencing moderate or severe pain after the surgical extraction of > or = 2 third molars, at least 1 of which was a mandibular impaction, were randomized to receive placebo, rofecoxib 50 mg, or codeine 60 mg/acetaminophen 600 mg. Patient evaluations of pain intensity, pain relief, and global assessments were recorded throughout the 24-hour period after dosing. The 2-stopwatch method was used to determine time to confirmed perceptible pain relief. The primary end point assessing overall analgesic effect was total pain relief over 6 hours (TOPAR6). Secondary end points were patient global assessment of response to therapy (PGART) at 6 hours, onset of analgesia, peak analgesic effect, and duration of analgesia.\n A total of 393 patients were enrolled; 182 received rofecoxib, 180 received codeine/acetaminophen, and 31 received placebo. The overall analgesic effect of rofecoxib 50 mg was greater than that of codeine 60 mg/acetaminophen 600 mg for TOPAR6 (12.4 vs 7.0; P < 0.001) and PGART at 6 hours (P < 0.001). The onset of analgesic effect was similar for rofecoxib and codeine/acetaminophen. Peak analgesic effect as measured by peak pain relief scores during the first 6 hours was significantly greater in the rofecoxib group compared with the codeine/acetaminophen group (P < 0.001), as was the duration of analgesic effect measured by the time to rescue analgesia (9.6 hours vs 2.3 hours, P < 0.001). Adverse events were reported in 33.0%, 46.1%, and 32.3% of patients treated with rofecoxib, codeine/acetaminophen, and placebo, respectively. The most common adverse events were nausea (6.0%, 25.0%, and 9.7%, respectively) and vomiting (3.8%, 18.3%, and 6.5%, respectively). Significantly more patients in the codeine/acetaminophen group than in the rofecoxib group experienced adverse events overall (P < 0.050) and nausea in particular (P < 0.001).\n In this study of moderate to severe postoperative dental pain, the analgesic efficacy of rofecoxib 50 mg was greater than that of codeine/acetaminophen, with a lower incidence of adverse events and nausea.", "A double-blind, randomized, single-dose study was performed to compare the efficacy and safety of two commonly prescribed combination analgesic products to placebo. The combinations were acetaminophen 300 mg/codeine 30 mg(†), and aspirin 325 mg/butalbital 50 mg/caffeine 40 mg/codeine 30 mg(††). One hundred twenty-three (123) oral surgery outpatients took study medications when their pain became moderate to severe and recorded the levels of pain intensity, pain relief, anxiety and relaxation at 30 minutes and hourly for 6 hours after dosing. Remedication was permitted if study medications did not provide adequate pain relief. Time to remedication, and the number of observations with 50% or better relief, were noted as were any side effects. An overall evaluation was obtained from each patient. Results of the study showed that the aspirin/butalbital/caffeine/codeine combination was significantly more effective than placebo for total pain relief, peak relief and global evaluation. While the acetaminophen/codeine combination was numerically superior to placebo, it achieved statistical significance only for global evaluation. The aspirin/butalbital/caffeine/codeine combination was numerically superior to acetaminophen/codeine for every measure of analgesic efficacy but the differences did not achieve statistical significance. Both active treatment groups experienced significantly less total anxiety than did the placebo group. Only 11 patients reported mild, transient adverse effects; the most common was drowsiness. The adverse effects occurred equally among the three treatment groups. In this study, the aspirin/butalbital/caffeine/codeine combination was significantly superior to placebo and somewhat better than acetaminophen/codeine.", "Tramadol hydrochloride is a synthetic mu-opioid agonist with additional monoaminergic activity. Tramadol's analgesic effect has been equated with that of pethidine, with a more favourable side-effect profile. Tramadol has been the most-selling prescription analgesic in Germany for several years, and it is now available in many other European countries, but still there is a lack of adequately controlled clinical studies of its analgesic properties. The purpose of this study was to compare the analgesic efficacy of 50 and 100 mg oral tramadol with our standard analgesic for postoperative pain treatment, 1000 mg paracetamol + 60 mg codeine, and placebo. A single-dose, parallel group, double-blind design was used. One hundred forty-four patients were enrolled the day after total hip replacement if they had a pain intensity of 60 mm or more on a 0-100 mm visual analogue scale. Treatments were compared on the basis of pain intensity and derived variables (pain intensity difference, and summed pain intensity differences), the need of rescue medication, and a global evaluation. Serum concentrations confirmed rapid and good absorption comparable with that reported in healthy volunteers. The active drug control, paracetamol+codeine, was significantly superior to placebo for all efficacy variable (P = 0.0002-0.004), confirming good assay sensitivity. Paracetamol+codeine was also significantly superior to both 50 mg tramadol (P = 0.002-0.03) and 100 mg tramadol (P = 0.002-0.02). There was no difference between placebo and 50 and 100 mg tramadol for any of the efficacy variables.(ABSTRACT TRUNCATED AT 250 WORDS)", "To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, and placebo in the treatment of pain following oral surgery.\n Randomized, double-blind, single-dose, placebo-controlled, parallel-group study with self-ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6.\n Private, oral surgery practice sites.\n Three hundred twenty-four outpatients with moderate or severe pain after the surgical removal of impacted third molars were selected. One was lost to follow-up and 32 did not need an analgesic; 232 patients had valid efficacy data.\n Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, or placebo when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating; estimates of peak and total analgesia were derived from these subjective reports.\n This study was a valid analgesic assay. Both active treatments were significantly superior to placebo for all measures of analgesic efficacy. The hydrocodone-acetaminophen combination was significantly superior to the codeine-acetaminophen combination for total pain relief and the number of evaluations with 50% relief. Both active treatments manifested an analgesic effect within 30 minutes; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination. Adverse effects were transient, consistent with the pharmacologic profiles of opioids, and none required treatment.\n A slight advantage in analgesic efficacy was demonstrated in this single-dose study for the hydrocodone-acetaminophen combination. Repeat-dose studies, however, should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations.", "In a randomized double-blind study, 120 patients with moderate to strong pain after surgical removal of wisdom teeth were given the following in single oral doses: 100-mg enteric-coated diclofenac tablets; 1 g acetaminophen (INN, paracetamol); 1 g acetaminophen plus 60 mg codeine; 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen; or 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen plus 60 mg codeine. Patients recorded pain intensity and pain relief for 8 hours. Upside assay sensitivity was confirmed because acetaminophen plus codeine was superior to acetaminophen. Diclofenac plus acetaminophen with and without codeine had superior analgesic effect compared with diclofenac, acetaminophen, or acetaminophen plus codeine. Addition of 60 mg codeine increased the degree of side effects. These results support the clinical practice of combining diclofenac with acetaminophen for acute pain. Of clinical importance are superior and prolonged analgesia and fewer side effects after enteric-coated diclofenac tablets plus acetaminophen compared with acetaminophen plus codeine.", "The purpose of this double-blind, randomized study was to compare the efficacy and safety of a single dose of the following medications: 2 tablets of Vicoprofen (ibuprofen 200 mg/hydrocodone 7.5 mg; Knoll Pharmaceutical Co, Mount Olive, NJ), 2 tablets ofp6 acetaminophen with codeine phosphate (acetaminophen 300 mg/codeine 30 mg), and 2 tablets of placebo in the management of moderate to severe postoperative dental pain after surgical extraction of at least one impacted mandibular third molar.\n One hundred twenty-five patients (75 women, 50 men) participated in the study. The time of first perceptible pain relief and meaningful pain relief were measured using a stopwatch technique. Pain intensity and pain relief scores were recorded using standard verbal descriptors at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, and 8 hours after dosing. At the conclusion of the study, patients completed a global evaluation for the effectiveness of the study medication.\n Both active treatments were superior to placebo for all analgesic measures. Pain relief scores were significantly better for Vicoprofen than placebo throughout the study and significantly better than for acetaminophen with codeine from 2 through 8 hours after dosing. The duration of analgesia (time to remedication) was significantly longer for Vicoprofen (median, 5.50 hours) compared with acetaminophen with codeine (median, 3.03 hours) and placebo (median, 1.00 hours). Mean global evaluation for Vicoprofen was significantly better than for placebo and acetaminophen with codeine. Overall, there were no significant differences in the adverse event profile among the 3 treatment groups.\n Vicoprofen was found to be an effective postoperative analgesic medication in the management of acute postoperative dental pain. Its total analgesic effect, duration of analgesia, and global evaluation were superior to acetaminophen with codeine and placebo in this study model.", "To compare the overall analgesic effect, including time to onset, peak and duration of effect for etoricoxib 120 mg, a new COX-2 selective inhibitor, in patients with acute pain to that of placebo. Naproxen sodium 550 mg and acetaminophen/codeine 600/60 mg were the active comparators.\n A total of 201 patients with moderate to severe pain following surgical extraction of > or = 2 third molars, of which at least the mandibular tooth was impacted, were randomly allocated to receive single oral doses of placebo (n = 50), etoricoxib 120 mg (n = 50), naproxen sodium 550 mg (n = 51), or acetaminophen/codeine 600/60 mg (n = 50). The endpoints included total pain relief over 8 hours (TOPAR8, primary end point), sum of pain intensity difference over 8 hours, patient's global evaluation, onset, peak, and duration of analgesia.\n Etoricoxib 120 mg had a significantly greater least squares (LS) mean TOPAR8 score than placebo (20.9 vs 5.4; P < 0.001) and acetaminophen/codeine 600/60 mg (20.9 vs 11.5; P < 0.001), and a similar LS mean TOPAR8 score to naproxen sodium 550 mg (20.9 vs 21.3). All three active treatments had rapid onset of analgesia, median time approximately 30 minutes. The duration of analgesic effect, defined as median time to rescue medication use, was >24 hours for etoricoxib, 20.8 hours for naproxen sodium, 3.6 hours for acetaminophen/codeine, and 1.6 hours for placebo.\n Etoricoxib is a new COX-2 selective inhibitor under development for treatment of osteoarthritis, rheumatoid arthritis, and acute pain. In this study, etoricoxib 120 mg provided rapid and long-lasting pain relief to patients with moderate-to-severe postdental surgery pain. Etoricoxib was generally well tolerated.", "In a single-dose, parallel group, randomized block treatment allocation study, the relative analgesic efficacy of flurbiprofen, a nonsteroidal antiinflammatory drug, was compared to acetaminophen 650 mg with codeine 60 mg, zomepirac sodium 100 mg, and placebo. A total of 226 post-surgical dental patients (146 females and 80 males) participated in the study. Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination. The results of this study support previous work on flurbiprofen.", "A randomized, double-blind, placebo-controlled single oral dose study was done in order to examine whether codeine has an additive analgesic effect to that of paracetamol for moderate and strong postoperative pain after abdominal surgery. The maximum recommended single dose of paracetamol 1000 mg (Paracet) was compared with a combination of a submaximal dose of paracetamol 800 mg plus codeine 60 mg (Paralgin forte) and placebo for pain relief after Caesarean section in 125 patients.\n Visual analogue pain intensity score (VAS 0-100 mm) and categorical pain relief score were recorded for 6 hours after the study drug intake. The main efficacy variables analyzed were: pain intensity difference and summed pain intensity differences during the first 3 and 6 h after study drug intake, total pain relief during the first 3 and 6 h, global evaluation score at the end of the observation period, and time to rescue analgesic.\n Because of protocol violations, 17 patients were excluded from the analysis of effects. Among the 108 patients included in the analysis of analgesic effect, 49 patients had moderate baseline pain (VAS between 40 and 60 mm on a 100 mm scale), and 59 patients had strong baseline pain (VAS more than 60 mm). In patients with strong baseline pain, statistically highly significant differences were documented in efficacy variables between the active drugs and placebo and between the two active drugs. However, in patients with moderate baseline pain, no differences were found between the study drugs in any of the analgesic efficacy variables.\n This study thus confirms that codeine has additive analgesic effect to paracetamol in pain after surgery. Our results show the importance of initial pain intensity in postoperative assessment of analgesic drugs. Assay-sensitivity and test power are increased by selecting patients with sufficiently high initial pain intensity and by comparing groups of patients with identical surgery and similar demographic variables.", "To study the analgesic efficacy of enadoline, a selective agonist of the kappa-opioid receptor, a double-blind, randomized comparison was made of enadoline versus placebo and a combination of acetaminophen-codeine in patients with pain after surgical extraction of impacted molar teeth. An initial study involving a comparison of enadoline, a combination, and placebo failed to show any analgesic effect of enadoline. Therefore, a second study with the same design but using higher doses of enadoline was conducted. Despite continued safety and tolerability even at the higher doses, enadoline could not be shown to be superior to placebo. The acetaminophen-codeine combination was significantly more effective than enadoline or placebo. Enadoline did not show analgesic efficacy in this study. Possible reasons for this lack of efficacy are discussed.", "The analgesic efficacy of single 500 and 1,000 mg doses of diflunisal, a new nonsteroidal antiinflammatory analgesic, was compared in a double-blind study with acetaminophen 600 mg, the combination of acetaminophen 600 mg with codeine 60 mg, and placebo in 132 inpatients with postoperative pain. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medication. Diflunisal 500 and 1,000 mg were significantly superior to placebo for every measure of total and peak analgesia, and a significant analgesic effect persisted for 8 hours. Acetaminophen alone and the acetaminophen-codeine combination were significantly superior to placebo for most measures of analgesia, and their effects were significant for 4 and 5 hours respectively. Differences among the active medications were not statistically significant for measures of total or peak analgesia.", "Tramadol/acetaminophen (APAP) combination tablets were shown effective and safe for postsurgical orthopedic pain in a 6-day, multicenter, randomized, double-blind, active- and placebo-controlled study. Of 305 intent-to-treat (ITT) postsurgical patients, 153 patients undergoing arthroscopy who had at least moderate pain were randomized to receive either tramadol 37.5 mg/APAP 325 mg (mean, 4.3 tablets), or codeine 30 mg/APAP 300 mg (mean, 4.6 tablets), or placebo. Tramadol/APAP was superior to placebo for the following outcome variables: total pain relief (TOTPAR, P = .013), sum of pain intensity differences (SPID, P = .049), sum of total pain relief and sum of pain intensity differences (SPRID, P = .018), and average daily pain relief (P = .031). Similar incidence of adverse events for tramadol/APAP and codeine/APAP was found, except for constipation (0% vs 10.9%) and vomiting (8.2% vs 16.4%).", "This multicenter, randomized, double-blind, active- and placebo-controlled trial evaluated tramadol plus acetaminophen (APAP) for orthopedic (n = 153) and abdominal (n = 152) postsurgical pain.\n Patients with moderate pain or greater were randomized to an initial two tablets of 37.5 mg tramadol plus 325 mg APAP (n = 98), codeine 30 mg plus APAP 300 mg (n = 109), or placebo (n = 98); thereafter, they received 1 to 2 tablets every 4 to 6 hours as needed for pain for 6 days. Outcome measures were pain relief and pain intensity, total pain relief, sum of pain intensity differences, and sum of pain relief and pain intensity differences during 4 hours and the daily averages.\n Tramadol plus APAP was superior to placebo for total pain relief, sum of pain intensity differences, and sum of pain relief and pain intensity differences (P < or =0.015); tramadol plus APAP and codeine plus APAP did not separate (P > or=0.281). For average daily pain relief, average daily pain intensity, and overall medication assessment, tramadol plus APAP was superior to placebo (P < or =0.038); codeine plus APAP did not separate from placebo (P > or =0.125). Discontinuation because of adverse events occurred in 8.2% of tramadol plus APAP, 10.1% of codeine plus APAP, and 3.0% of placebo patients. Except for constipation (4.1% tramadol plus APAP vs 10.1% codeine plus APAP) and vomiting (9.2% vs 14.7%, respectively), adverse events were similar for active treatments.\n Tramadol plus APAP (mean dose 4.4 tablets) was effective and well tolerated for postsurgical pain and showed better tolerability than did codeine plus APAP.", "The efficacy of an aspirin-caffeine-codeine-butalbital combination was compared to an acetaminophen-codeine combination and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self-rating record, patients rated their pain, relief, anxiety and relaxation hourly for up to 6 hours after medicating. Each active medication was significantly superior to placebo for measures of analgesia and relaxation. Although the butalbital-containing combination provided consistently greater analgesia, the differences between active medications were not statistically significant. The acetaminophen-codeine combination significantly reduced anxiety; however, the butalbital containing combination did not. The results of this study suggest that female patients may have greater efficacy than male patients. All adverse effects were transitory and consistent with the known pharmacologic profiles of the study medications or the backup analgesic.", "The analgesic efficacy of 50 and 100 mg flurbiprofen was compared with acetaminophen 650 mg, acetaminophen 650 mg plus codeine 60 mg, and placebo.\n Subjects undergoing the surgical removal of impacted third molars were randomly administered one of the five treatments after the onset of moderate to severe postoperative pain. Pain intensity, pain relief, and side effects were evaluated for 6 hours after drug administration.\n Both doses of flurbiprofen resulted in significant analgesia in comparison with placebo, acetaminophen, and acetaminophen plus codeine as measured by pain intensity difference, pain relief, and global evaluation. The greatest incidence of side effects occurred in the group receiving acetaminophen plus codeine, and the fewest side effects were reported by subjects administered flurbiprofen.\n The results of this study indicate that flurbiprofen is more effective and causes fewer effects than acetaminophen and codeine when used for post-operative dental pain, in ambulatory patients.", "The analgesic efficacy of single 500- and 1,000-mg doses of diflunisal (Dolobid), a new nonsteroidal anti-inflammatory analgesic, was compared in a double-blind study with that of acetaminophen, 600 mg, the combination of acetaminophen, 600 mg, with codeine phosphate, 60 mg, and placebo in 159 oral surgery outpatients. Using a self-rating record, patients rated their pain and its relief hourly for 12 hours after medication. Both doses of diflunisal were significantly more effective than acetaminophen alone and produced peak analgesia comparable to that of the acetaminophen-codeine combination. Diflunisal proved to have an unusually long duration of analgesic action. Acetaminophen and the combination were significantly superior to placebo through hours 2 and 5, respectively; both doses of diflunisal were significantly superior through the end of the 12-hour observation period. None of the active treatments produced more side effects than the placebo." ]

[ "2123759", "3097674", "2891635", "3069269", "1898891", "2113488", "2108981", "2497131", "2110070", "2106449", "8435902", "2567714" ]

[ "Ovarian electrocautery versus human menopausal gonadotrophins and pure follicle stimulating hormone therapy in the treatment of patients with polycystic ovarian disease.", "The additional use of buserelin in HMG-HCG ovulation induction in PCO: a double blind controlled study.", "Initial experiences with subcutaneous pulsatile human menopausal gonadotropin administration: successful induction of ovulation in patients with polycystic ovarian disease.", "LHRH analogues for ovulation induction, with particular reference to polycystic ovary syndrome.", "A comparative, randomized study of low-dose human menopausal gonadotropin and follicle-stimulating hormone in women with polycystic ovarian syndrome.", "The luteal phase in polycystic ovary syndrome during ovulation induction with human menopausal gonadotropin with and without leuprolide acetate.", "Combined luteinizing hormone releasing hormone analogue and exogenous gonadotrophins for the treatment of infertility associated with polycystic ovaries.", "Ovulation induction in polycystic ovarian disease by pure FSH (Metrodin). A comparison between chronic low-dose pulsatile administration and i.m. injections.", "Treatment of clomiphene citrate-resistant polycystic ovarian syndrome with pure follicle-stimulating hormone or human menopausal gonadotropin.", "Comparison of urinary human follicle-stimulating hormone and human menopausal gonadotropin for ovarian stimulation in polycystic ovarian syndrome.", "Efficacy of low dose purified FSH in ovulation induction following pituitary desensitization in polycystic ovarian syndrome.", "Daily or alternate-day FSH therapy in patients with polycystic ovarian disease resistant to clomiphene citrate treatment." ]

[ "Eighty-eight clomiphene citrate-resistant infertile patients with oligomenorrhoea or amenorrhoea attributable to polycystic ovarian disease were divided at random into three groups. Twenty-nine patients were treated with ovarian electrocautery, 30 with human menopausal gonadotrophins (hMG) and 29 with pure follicle stimulating hormone (FSH). Successful ovulation was induced in 71.4, 70.6 and 66.7% of the cycles in the groups respectively. Ten patients conceived after electrocautery and pure FSH therapy while 15 conceived after hMG medication (chi-squared = 1.6464, P = 0.439). The six-cycle cumulative pregnancy rate in the three consecutive groups was 52.1, 55.4, and 38.3%. Four further pregnancies were achieved after treating 10 patients in the electrocautery group with clomiphene citrate (100 mg/day for 5 days) for 25 cycles. The rate of pregnancy wastage in the corresponding groups was 21.4, 53.3 and 40% (chi-squared = 3.127, P = 0.2039). Ovarian electrocautery is equally effective as hMG and pure FSH in the treatment of PCO patients resistant to clomiphene citrate therapy.", "nan", "Human menopausal gonadotropin (hMG) was administered to 10 patients with polycystic ovarian disease (PCOD) who had failed to ovulate in response to clomiphene citrate. Five patients (group 1) were treated with intramuscular hMG injections daily, on an individually adjusted regimen. Five others (group 2) were stimulated with subcutaneous hMG in a pulsatile fashion by means of a portable infusion minipump. The pulse doses ranged between 3.5 and 7.7 IU FSH per pulse at a constant frequency of 90 minutes. Sixteen of 18 treatment cycles were ovulatory, 9 under intramuscular, and 7 under subcutaneous treatment. A total of two patients conceived with singleton pregnancies, one in each treatment group. Neither ovarian hyperstimulation nor complications of injections were noted. The amount of subcutaneous hMG required to achieve ovulation was significantly less (46.5%; P less than .001) than that needed with intramuscular administration. However, there were no differences in the duration of stimulation periods, the lengths of luteal phases, or serum E2 and gonadotropin levels between the groups. In conclusion, pulsatile subcutaneous hMG administration may be an alternative delivery mode for patients with PCOD.", "Infertile women with PCO have been treated with exogenous gonadotrophins (hMG/hCG) for ovulation induction either with or without LHRH-agonist treatment. Those treated without LHRH-agonist-induced LH suppression showed PL in greater than 30% of the cycles and this problem was eliminated by LHRH-agonist therapy. The pregnancy rate (approximately 80% of patients) during the combined therapy was approximately twice that of the group treated with hMG/hCG alone. The suppression of endogenous LH by the LHRH-agonist appeared to have no effect upon the profiles of follicular development in response to hMG, and a high rate of follicle recruitment characterized all PCO treatment cycles irrespective of circulating LH concentrations. These results suggest that LH suppression improves the efficacy of ovulation induction but has no influence on the primary metabolic disturbance in the PCO syndrome.", "Treatment with low-dose follicle-stimulating hormone (FSH) is associated with a high rate of ovulation in anovulatory women with polycystic ovarian syndrome (PCOS), but it is not clear whether the success of treatment is because of the use of pure FSH or the low dose of gonadotropin. We undertook a randomized controlled study to compare the effects of urinary FSH and human menopausal gonadotropin (hMG) using a low-dose regimen in 30 women with PCOS. Each subject received a maximum of three cycles of either FSH or hMG. Ovulation occurred in 75% of subjects and in 77% of cycles induced with FSH and in 94% of women, 85% of cycles of those treated with hMG. A single dominant follicle developed in 70% (FSH) and 65% (hMG) of cycles, respectively. Five singleton pregnancies occurred in each group. This study shows that low-dose FSH and hMG are equally successful in inducing ovulation, suggesting that the success of treatment depends on the low dose of gonadotropin used rather than the presence or absence of luteinizing hormone in the preparation.", "Little data exist on the effects of adjunctive therapy with leuprolide acetate (LA) in the luteal phase of women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with human menopausal gonadotropin (hMG). Additionally, it is not known whether gonadal steroid concentrations in the luteal phase of induced cycles in PCOS are predictive of pregnancy. In this prospective, randomized study comparing cycles using hMG alone (n = 26) with cycles using hMG with LA (n = 33), no differences were noted between treatment groups in progesterone (P), estradiol (E2), and P:E2 ratios on luteal days 3, 6, and 9. When all treatment cycles were pooled, there were no differences in P, E2, or P:E2 ratios, comparing conception and nonconception cycles. We conclude that adjunctive therapy with LA in PCOS patients undergoing ovulation induction with hMG does not alter the luteal phase concentrations of P, E2, and P:E2. Furthermore, no correlation was found between the serum concentrations of these luteal phase steroids and cycle fecundity.", "This study was designed to compare the results of treatment with, firstly, exogenous gonadotrophins, with (57 cycles) and without (65 cycles) pretreatment with a superactive analogue of luteinizing hormone releasing hormone (LHRH) and, secondly, pure follicle stimulating hormone (FSH) (50 cycles) with those of human menopausal gonadotrophin (HMG) (72 cycles) in 46 women with clomiphene-citrate-resistant anovulation associated with polycystic ovaries. Patients randomly allocated to the analogue group received buserelin (Suprefact, Hoechst, UK, Ltd, Hounslow, Middlesex), 800 micrograms/day by nasal insufflation and when hypogonadism was achieved, patients were again randomly allocated for ovarian stimulation with either FSH or HMG. Controls received FSH or HMG alone. Patients pretreated with the analogue had similar pregnancy and ovulation rates, needed larger doses and more days of gonadotrophin therapy and had more ovarian overstimulation than those receiving no pretreatment. The role of superactive LHRH analogues for induction of a single ovulation for in-vivo fertilization is thus uncertain. Pure FSH had no advantages over HMG, the LH content of HMG having no deleterious effect on the ovary.", "A randomized cross-over study was performed to assess the value of pulsatile versus i.m. administration of pure FSH in polycystic ovarian disease. All patients admitted to the study had failed to respond to treatment with clomiphene citrate, while four had also been unsuccessfully treated with i.m. Pergonal. Sixteen cycles with i.m. FSH and 15 cycles with pulsatile s.c. FSH were analysed. The results showed no statistically significant differences in the dosage, the rate of ovulation or pregnancy rate. Hyperstimulation occurred in 30% of both the treatment groups. It is concluded that chronic low-dose pulsatile administration of pure FSH (Metrodin, Serono) has no advantage over chronic low-dose i.m. administration.", "Two hundred ten treatment cycles of follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG) were completed in 49 patients with clomiphene citrate-resistant polycystic ovarian syndrome. The results from 68 cycles of daily intramuscular (IM) FSH and 41 cycles of IM hMG were compared. The ovulation rate, maximum serum estradiol (E2) levels achieved, and pregnancy rate were similar in both groups, but FSH resulted in significantly fewer follicles developing and hyperstimulation. The 68 cycles of daily IM FSH were further compared with the outcome of administering the FSH as an alternate-day IM injection in 70 cycles, and by subcutaneous pulsatile injection in 31 cycles. There were no differences in any of the parameters measured between daily and alternate-day FSH. Pulsatile FSH required a greater total dose over a longer period of time to achieve stimulation. It also produced fewer follicles, a lower maximum serum E2 level, and the lowest incidence of hyperstimulation. Twenty pregnancies resulted, of which 6 aborted in the first trimester; there was 1 set of twins and 13 singleton pregnancies. The cumulative pregnancy rate after 6 treatment cycles was 62%.", "A randomized, double-blind, crossover study was carried out to compare purified urinary follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG) for ovarian stimulation in polycystic ovarian syndrome (PCOS). Twelve patients were stimulated with FSH and hMG in three alternate cycles. FSH, luteinizing hormone (LH), estradiol, dihydroepiandrosterone sulphate, free and total testosterone, delta 5-androstenedione, sex hormone binding globulin, and ovarian volume were monitored during the stimulation. There was no difference between the dose of FSH and hMG necessary to induce preovulatory follicles in the individual patients. The mean increase of ovarian volume during stimulation with FSH and hMG was 120% and 129% respectively (no significant difference). Two patients became pregnant in the first cycle. Two other patients had delayed bleeding and positive serum-human chorionic gonadotropin. No significant difference was found in the endocrine changes during the two different stimulation methods. The LH/FSH ratio was normalized after a few days of treatment regardless of the type of stimulation. The size of the material does not permit a comparison of the efficacy of the two treatment schedules. Our clinical and ultrasonic observations do not support the theory that treatment of infertility in PCOS with FSH is more safe than with hMG.", "We evaluated the efficacy of ovulation induction using purified FSH in either low dose or conventional dosage in patients with polycystic ovarian syndrome. We assessed whether gonadotrophin measurement by radioimmunoassay or immunoradiometric assay is a better indicator of whether pituitary desensitization with a GnRH agonist (Zoladex) has occurred.\n Two different protocols were used. Pituitary desensitization was carried out with a GnRH agonist (Zoladex, ICI Pharmaceuticals UK). The patients were then randomized into one of two treatment groups. Conventional dose protocol: Patients commenced with a daily FSH (Metrodin, Serono Laboratories Ltd, UK) dose of 75 units for at least 7 days. The FSH dose was then increased, if necessary, based on ultrasound scans and plasma oestradiol (E2) levels in 75-unit increments. Low dose protocol: The same protocol was used except that the starting dose of FSH was 37.5 units daily with increments of 37.5 units.\n Low dose protocol (six patients, six cycles). There was a high incidence of multiple follicular development (10.3 +/- 5.6 (+/- SD) follicles, 5.0 +/- 3.8 follicles > 14 mm in diameter). Three cycles resulted in ovulation, one was anovulatory and two patients underwent gamete intrafallopian transfer due to multiple follicular development. Conventional dose protocol (seven patients, eight cycles). Again there was multiple follicular development (10.1 +/- 8.6 follicles, 2.0 +/- 2.3 > 14 mm). Three cycles were ovulatory, one anovulatory, three abandoned due to multiple follicular development and one underwent gamete intrafallopian transfer with the development of severe hyperstimulation necessitating steroid therapy. There was no difference between the two protocols in the number of days of FSH administration (low dose protocol 26 +/- 6.5, conventional dose protocol 23 +/- 8.1 days), the total number of units of FSH given per patient was 2844 +/- 1816 vs 2635 +/- 1726. The peak E2 level (pmol/l) during FSH treatment was 3193 +/- 662 vs 2389 +/- 3099 and the rate of increase in the FSH dose in ampoules of Metrodin per day was 0.058 +/- 0.03 vs 0.057 +/- 0.03. All patients were 'downregulated' (E2 < 70 pmol/l) prior to ovulation induction. However, gonadotrophin levels (IU/l) were 4.3 +/- 1.5 (LH) and 2.8 +/- 1.2 (FSH) by radioimmunoassay and LH was unchanged throughout FSH treatment whereas LH measured by immunoradiometric assay was < 1.0 IU/l prior to ovulation induction and remained so throughout. The mean LH radioimmunoassay to immunoradiometric assay ratio was 6.2 +/- 2.1.\n We conclude that regardless of the starting dose the use of pure FSH in patients with polycystic ovarian syndrome whose LH has been completely down regulated may be associated with multiple follicular development and a poor outcome. LH measured by radioimmunoassay is not a good indicator of whether pituitary densensitization has occurred but LH measured by immunoradiometric assay appears to be. These results strongly suggest that a basic minimum amount of LH is necessary for normal ovulatory development.", "The effectiveness of intramuscular follicle stimulating hormone (FSH) administered as daily or alternate-day injections to patients with polycystic ovarian disease (PCOD) who previously failed to ovulate on clomiphene citrate was compared. The study comprised 20 treatment cycles of daily FSH and 19 of alternate-day FSH in 12 patients. The overall ovulation rate per cycle was 78% and was similar for both groups. Nine out of 12 patients achieved a pregnancy, with twice as many occurring in the alternate-day group. It is concluded that alternate-day FSH therapy is as effective as daily FSH in achieving ovulation and pregnancies in patients with PCOD resistant to treatment with clomiphene citrate." ]

[ "8970662", "8894955", "3534032", "15715034", "7073647", "3432504", "8559866", "389965", "2404539", "6737208" ]

[ "Massage and relaxation therapies' effects on depressed adolescent mothers.", "Controlled trial of a brief cognitive-behavioural intervention in adolescent patients with depressive disorders.", "A comparison of cognitive-behavioral therapy and relaxation training for the treatment of depression in adolescents.", "Massage therapy effects on depressed pregnant women.", "Combined pharmacological and behavioural treatment of depression.", "The antidepressant effect of light in seasonal affective disorder of childhood and adolescence.", "Cognitive behavior therapy, relaxation training, and tricyclic antidepressant medication in the treatment of depression.", "Clinical depression: comparative efficacy of outpatient treatments.", "Treatment of depressed in-patients. Cognitive therapy plus medication, relaxation plus medication, and medication alone.", "Influence of aerobic exercise on depression." ]

[ "Thirty-two depressed adolescent mothers received ten 30-minute sessions of massage therapy or relaxation therapy over a five-week period. Subjects were randomly assigned to each group. Although both groups reported lower anxiety following their first and last therapy sessions, only the massage therapy group showed behavioral and stress hormone changes including a decrease in anxious behavior, pulse, and salivary cortisol levels. A decrease in urine cortisol levels suggested lower stress following the five-week period for the massage therapy group.", "Fifty-three child and adolescent psychiatric patients with depressive disorders were randomly allocated to brief cognitive-behaviour therapy (CBT) or to a control treatment, relaxation training. Forty-eight patients completed the treatment phase of the trial, which comprised 5-8 treatment sessions. Post-treatment assessments showed a clear advantage of CBT over relaxation on measures of both depression and overall outcome. However, there were no significant differences between the treatments on comorbid anxiety and conduct symptoms. At follow-up, the differences between the groups were reduced, partly because of a high relapse rate in the DTP group and partly because subjects in the relaxation group continued to recover.", "nan", "Eighty-four depressed pregnant women were recruited during the second trimester of pregnancy and randomly assigned to a massage therapy group, a progressive muscle relaxation group or a control group that received standard prenatal care alone. These groups were compared to each other and to a non-depressed group at the end of pregnancy. The massage therapy group participants received two 20 min therapy sessions by their significant others each week for 16 weeks of pregnancy, starting during the second trimester. The relaxation group provided themselves with progressive muscle relaxation sessions on the same time schedule. Immediately after the massage therapy sessions on the first and last days of the 16-week period the women reported lower levels of anxiety and depressed mood and less leg and back pain. By the end of the study the massage group had higher dopamine and serotonin levels and lower levels of cortisol and norepinephrine. These changes may have contributed to the reduced fetal activity and the better neonatal outcome for the massage group (i.e. lesser incidence of prematurity and low birthweight), as well as their better performance on the Brazelton Neonatal Behavior Assessment. The data suggest that depressed pregnant women and their offspring can benefit from massage therapy.", "nan", "nan", "Outcomes of seven treatment trials comparing cognitive behavioral therapy to treatment with tricyclic antidepressant medication in major depressive disorder have been quite similar to one another. This led us to question whether treatment outcome in time-limited studies reflected a unique effect of cognitive behavioral therapy. To test the uniqueness hypothesis, relaxation training, a nonpharmacologic, noncognitive treatment, was chosen as a comparison for cognitive behavioral therapy as well as drug therapy. Treatment duration was 16 weeks. The sample of 37 patients treated for major depressive disorder was less depressed than those previously studied. For both cognitive behavioral therapy and relaxation training, outcome of depression was superior to that of tricyclic antidepressant medication by endpoint analysis. The posttreatment scores on the Beck Depression Inventory of 82% of the group receiving cognitive behavioral therapy improved to a Beck Depression Inventory score < or = 9 which was not significantly greater than that for the group receiving relaxation training (73%), so a unique effect was not demonstrated for cognitive behavioral therapy. The outcome for tricyclic antidepressant medication (29% improved to criteria) was significantly worse than that for cognitive behavioral therapy. The patient's pretreatment initial expectancy was not predictive.", "nan", "Thirty in-patients received one of three treatments - medication (nortriptyline) alone (MA), relaxation therapy plus medication (RT&M), or cognitive therapy plus medication (CT&M) (each n = 10) - along with ward milieu. The relaxation and cognitive therapy groups participated in 12 therapy sessions. Symptoms of depression and related cognitive variables were assessed at sessions 1, 6 and 12, and at discharge. All groups improved over the course of the study. CT&M and RT&M groups reported significantly fewer depressive symptoms and negative cognitions at discharge than the MA group. The number of subjects judged depressed at discharge was lower in the CT&M group than in the MA and RT&M groups. It is proposed that a consistent rationale for treatment is a significant facilitating factor in achieving behavioural and cognitive changes in depression.", "Forty-three depressed women were randomly assigned to either (a) an aerobic exercise treatment condition in which they participated in strenuous exercise, (b) a placebo treatment condition in which they practiced relaxation exercises, or (c) a no-treatment condition. Aerobic capacity was assessed before and after the 10-week treatment period. Self-reported depression was assessed before, during, and after the treatment period. The results indicated that subjects in the aerobic exercise condition evidenced reliably greater improvements in aerobic capacity than did the subjects in either of the other conditions (p less than .002 in both cases) and that the subjects in the aerobic exercise condition evidenced reliably greater decreases in depression than did subjects in the placebo condition (p = .05) or subjects in the no-treatment condition (p = .001). These results provide the first controlled evidence concerning the effects of strenuous exercise on depression." ]

[ "1646490", "1545850", "15824291", "8594425", "9280815", "11228276", "15172900", "1325076", "14585937", "9278462", "8391792", "8594426", "15159264", "11177331", "7831649", "1346817" ]

[ "A randomised trial of subcutaneous low molecular weight heparin (CY 216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis. A collaborative European multicentre study.", "Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis.", "A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism.", "A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis.", "Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. The Columbus Investigators.", "Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis.", "Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial.", "Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial.", "Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism.", "A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: Evaluations dans l'Embolie Pulmonaire.", "Subcutaneous low-molecular-weight heparin compared with continuous intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis.", "Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group.", "Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism.", "Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease.", "Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis.", "Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis." ]

[ "The standard treatment of deep vein thrombosis is given by continuous intravenous infusion of unfractionated heparin. This entails hospitalisation, nursing care, immobility and repeated laboratory tests (e.g. activated partial thromboplastin time [APTT], platelet count). In addition approximately 10% of patients suffer major haemorrhages. The potential advantages of a low molecular weight heparin (CY 216) given subcutaneously were explored in a randomised trial with blind quantitative evaluation of venograms. The study included 166 patients and both \"therapeutic efficacy\" and \"intention to-treat\" analyses showed that subcutaneous CY 216 in fixed doses based only on body weight was more effective on the Arnesen and Marder phlebographic scores than continuous i.v. standard heparin with daily dose adjustment according to results of coagulation tests. There was no increase in the risks of pulmonary embolism, haemorrhage or clot extension.", "Low-molecular-weight heparin has a high bioavailability and a prolonged half-life in comparison with conventional unfractionated heparin. Limited data are available for low-molecular-weight heparin as compared with unfractionated heparin for the treatment of deep-vein thrombosis.\n In a multicenter, double-blind clinical trial, we compared fixed-dose subcutaneous low-molecular-weight heparin given once daily with adjusted-dose intravenous heparin given by continuous infusion for the initial treatment of patients with proximal-vein thrombosis, using objective documentation of clinical outcomes.\n Six of 213 patients who received low-molecular-weight heparin (2.8 percent) and 15 of 219 patients who received intravenous heparin (6.9 percent) had new episodes of venous thromboembolism (P = 0.07; 95 percent confidence interval for the difference, 0.02 percent to 8.1 percent). Major bleeding associated with initial therapy occurred in 1 patient receiving low-molecular-weight heparin (0.5 percent) and in 11 patients receiving intravenous heparin (5.0 percent), a reduction in risk of 91 percent (P = 0.006). This apparent protection against major bleeding was lost during long-term therapy. Minor hemorrhagic complications were infrequent. Ten patients receiving low-molecular-weight heparin (4.7 percent) died, as compared with 21 patients receiving intravenous heparin (9.6 percent), a risk reduction of 51 percent (P = 0.049).\n Low-molecular-weight heparin is at least as effective and as safe as classic intravenous heparin therapy under the conditions of this study and more convenient to administer. The simplified therapy provided by low-molecular-weight heparin may allow patients with uncomplicated proximal deep-vein thrombosis to be cared for in an outpatient setting.", "Low-molecular-weight heparins (LMWHs) are now standard therapy for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). No published trials have compared LMWHs, and few studies have examined outpatient therapy for PE. Only tinzaparin sodium has demonstrated superiority to unfractionated heparin in a clinical trial.\n We compared 2 LMWH products, tinzaparin and dalteparin sodium, for the treatment of acute DVT and PE in a randomized, controlled clinical trial of consecutive outpatients presenting to a venous thromboembolism service at 4 tertiary-care hospitals. Patients were treated with subcutaneous tinzaparin sodium, 175 IU/kg every 24 hours, or subcutaneous dalteparin sodium, 200 IU/kg every 24 hours, for at least 5 days. Warfarin sodium therapy was started simultaneously and continued for 90 days. The primary end point was efficacy (recurrence of venous thromboembolism); safety (bleeding) was a composite end point.\n Two hundred fifty-four patients received tinzaparin (39 with PE and 215 with DVT) and 251 received dalteparin (51 with PE and 200 with DVT). Most patients had an active malignancy or idiopathic DVT/PE. The outcome events occurred in 11 (4.4%; 95% confidence interval [CI], 2.2%-7.7%) and 15 patients (5.9%; 95% CI, 3.3%-9.5%) in the dalteparin and tinzaparin groups, respectively, including 9 and 10 recurrences, respectively, and 2 and 5 major hemorrhages, respectively (P = .44). The 95% CI on the difference of -1.5% was -5.3% to 2.4%.\n Tinzaparin and dalteparin are safe and effective for the outpatient treatment of DVT or PE. Our finding of no differences between the LMWHs based on major clinical end points means that practical issues can be the deciding factor on which drug to use.", "Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous standard (unfractionated) heparin. However, the longer plasma half-life, better bioavailability after subcutaneous administration, and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use. We compared these two approaches.\n Patients with acute proximal deep-vein thrombosis were randomly assigned to receive either intravenous standard heparin in the hospital (253 patients) or low-molecular-weight heparin (1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily) administered primarily at home (247 patients). The study design allowed outpatients taking low-molecular-weight heparin to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early. All the patients received warfarin starting on the second day.\n Thirteen of the 247 patients receiving low-molecular-weight heparin (5.3 percent) had recurrent thromboembolism, as compared with 17 of the 253 patients receiving standard heparin (6.7 percent; P=0.57; absolute difference, 1.4 percentage points; 95 percent confidence interval, -3.0 to 5.7). Five patients receiving low-molecular-weight heparin had major bleeding, as compared with three patients receiving standard heparin. After randomization, the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital, as compared with 6.5 days for the standard-heparin group; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all.\n Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home.", "Low-molecular-weight heparin is known to be safe and effective for the initial treatment of patients with proximal deep-vein thrombosis. However, its application to pulmonary embolism or previous episodes of thromboembolism has not been studied.\n We randomly assigned 1021 patients with symptomatic venous thromboembolism to fixed-dose, subcutaneous low-molecular-weight heparin (reviparin sodium) or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy with a coumarin derivative was started concomitantly and continued for 12 weeks. Approximately one third of the patients had associated pulmonary embolism. The outcome events studied over the 12 weeks were symptomatic recurrent venous thromboembolism, major bleeding, and death. We sought to determine whether low-molecular-weight heparin is at least equivalent to unfractionated heparin in patients with venous thromboembolism.\n Twenty-seven of the 510 patients assigned to low-molecular-weight heparin (5.3 percent) had recurrent thromboembolic events, as compared with 25 of the 511 patients assigned to unfractionated heparin (4.9 percent). The difference of 0.4 percentage point indicates that the two therapies have equivalent value according to our predetermined definition of equivalence. Sixteen patients assigned to low-molecular-weight heparin (3.1 percent) and 12 patients assigned to unfractionated heparin (2.3 percent) had episodes of major bleeding (P= 0.63), and the mortality rates in the two groups were 7.1 percent and 7.6 percent, respectively (P=0.89).\n Fixed-dose, subcutaneous low-molecular-weight heparin is as effective and safe as adjusted-dose, intravenous unfractionated heparin for the initial management of venous thromboembolism, regardless of whether the patient has pulmonary embolism or a history of venous thromboembolism.", "Low-molecular-weight heparins are frequently used to treat venous thromboembolism, but optimal dosing regimens and clinical outcomes need further definition.\n In this multicenter, open-label study with blinded adjudication of end points, we randomly assigned patients with acute deep-vein thrombosis to one of three treatment regimens: intravenous administration of unfractionated heparin; subcutaneous administration of a low-molecular-weight heparin, reviparin, twice a day for one week; or subcutaneous administration of reviparin once a day for four weeks. The primary end point was evidence of regression of the thrombus on venography on day 21; secondary end points were recurrent venous thromboembolism, major bleeding within 90 days after enrollment, and death.\n Of the patients receiving unfractionated heparin, 40.2 percent (129 of 321) had thrombus regression, as compared with 53.4 percent (175 of 328) of patients receiving reviparin twice daily and 53.5 percent (167 of 312) of the patients receiving reviparin once daily. With regard to thrombus regression, reviparin administered twice daily was significantly more effective than unfractionated heparin (relative likelihood of thrombus regression, 1.28; 97.5 percent confidence interval, 1.08 to 1.52), as was reviparin administered once daily (relative likelihood, 1.29; 97.5 percent confidence interval, 1.08 to 1.53). Mortality and the frequency of episodes of major bleeding were similar in the three groups.\n In acute deep-vein thrombosis, reviparin regimens are more effective than unfractionated heparin in reducing the size of the thrombus. Reviparin is also more effective than unfractionated heparin for the prevention of recurrent thromboembolism and equally safe.", "The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin).\n To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis.\n Randomized, double-blind study.\n 154 centers worldwide.\n 2205 patients with acute symptomatic deep venous thrombosis.\n Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0 mg in patients weighing >100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0.\n The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes.\n 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% CI, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively.\n Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients.\n Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosis.", "In a prospective multicenter trial, 149 consecutive patients with phlebographically proven proximal and/or distal deep vein thrombosis of the leg were randomly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 (Fraxiparine) in a fixed dose or unfractionated heparin (UFH) in doses adjusted according to the activated partial thromboplastin time. Pre- and post-treatment phlebograms were assessed blindly using the Arnesen's score system in 134 patients available for analysis of the treatment efficacy. The mean phlebographic score after 10 days of treatment was significantly decreased in both groups (p less than 0.001) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant. There was an improvement in 45/68 patients (66%) in the Fraxiparine group and in 32/66 patients (48%) in the UFH group, and an increase in the thrombus size in 10/68 (15%) and 12/66 (18%), respectively. One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group. During a follow-up period of 3 months, two rethromboses had occurred in the UFH group and none in the Fraxiparine group. It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis.", "The standard initial treatment of hemodynamically stable patients with pulmonary embolism is intravenous unfractionated heparin, requiring laboratory monitoring and hospitalization.\n We conducted a randomized, open-label trial involving 2213 patients with acute symptomatic pulmonary embolism to compare the efficacy and safety of the synthetic antithrombotic agent fondaparinux with those of unfractionated heparin and to document noninferiority in terms of efficacy. Patients received either fondaparinux (5.0, 7.5, or 10.0 mg in patients weighing less than 50, 50 to 100, or more than 100 kg, respectively) subcutaneously once daily or a continuous intravenous infusion of unfractionated heparin (ratio of the activated partial-thromboplastin time to a control value, 1.5 to 2.5), both given for at least five days and until the use of vitamin K antagonists resulted in an international normalized ratio above 2.0. The primary efficacy outcome was the three-month incidence of the composite end point of symptomatic, recurrent pulmonary embolism (nonfatal or fatal) and new or recurrent deep-vein thrombosis.\n Forty-two of the 1103 patients randomly assigned to receive fondaparinux (3.8 percent) had recurrent thromboembolic events, as compared with 56 of the 1110 patients randomly assigned to receive unfractionated heparin (5.0 percent), for an absolute difference of -1.2 percent in favor of fondaparinux (95 percent confidence interval, -3.0 to 0.5). Major bleeding occurred in 1.3 percent of the patients treated with fondaparinux and 1.1 percent of those treated with unfractionated heparin. Mortality rates at three months were similar in the two groups. Of the patients in the fondaparinux group, 14.5 percent received the drug in part on an outpatient basis.\n Once-daily, subcutaneous administration of fondaparinux without monitoring is at least as effective and is as safe as adjusted-dose, intravenous administration of unfractionated heparin in the initial treatment of hemodynamically stable patients with pulmonary embolism.\n Copyright 2003 Massachusetts Medical Society", "Low-molecular-weight heparin appears to be at least as effective and safe as standard, unfractionated heparin for the treatment of deep-vein thrombosis, but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism.\n We randomly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin (tinzaparin) given once daily in a fixed dose or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months. We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism, major bleeding, and death.\n In the first eight days of treatment, 9 of 308 patients assigned to receive unfractionated heparin (2.9 percent) reached at least one of the end points, as compared,with 9 of 304 patients assigned to low-molecular-weight heparin (3.0 percent; absolute difference, 0.1 percentage point; 95 percent confidence interval, -2.7 to 2.6). By day 90, 22 patients assigned to unfractionated heparin (7.1 percent) and 18 patients assigned to low-molecular-weight heparin (5.9 percent) had reached at least one end point (P=0.54; absolute difference, 1.2 percentage points; 95 percent confidence interval, -2.7 to 5.1). The risk of major bleeding was similar in the two treatment groups throughout the study.\n Under the conditions of this study, initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism.", "A low-molecular-weight heparin, enoxaparin sodium, has been shown to be effective and safe in preventing deep vein thrombosis both in general surgery and in high-risk orthopedic surgery. We conducted a controlled, randomized trial with enoxaparin in the treatment of established deep vein thrombosis.\n In a multicenter trial, we compared fixed-dose subcutaneous enoxaparin, given twice daily, with adjusted-dose intravenous unfractionated heparin (UFH) given by continuous intravenous infusion for the initial 10 days of treatment of patients with proximal vein thrombosis. The primary efficacy outcome was the change of the size of the thrombus assessed by repeated venograms between day 0 and day 10. The primary analysis of safety was based on the incidence of major bleeding during 10 days of treatment.\n There were 67 patients in each group. Venographic assessment of clot size evolution between day 0 and day 10 showed a statistically significant superiority (P < .002) of enoxaparin over the reference treatment with UFH. Moreover, the incidence of overall recurrent thromboembolic events during 10 days of treatment was significantly higher (P < .002) in the UFH group (seven of 67) than in the enoxaparin group (one of 67). There were no serious bleeding complications in either group.\n Enoxaparin is at least as effective and safe as UFH under the conditions of this study. Moreover, it is more comfortable for patients and less time-consuming for nurses and laboratories. Thus, our study confirmed, with the use of enoxaparin, other observations that low-molecular-weight heparin provides a real therapeutic advance in the treatment of deep vein thrombosis.", "An intravenous course of standard (unfractionated) heparin with the dose adjusted to prolong the activated partial-thromboplastin time to a desired length is the standard initial in-hospital treatment for patients with deep-vein thrombosis, but fixed-dose subcutaneous low-molecular-weight heparin appears to be as effective and safe. Because the latter treatment can be given on an outpatient basis, we compared the two treatments in symptomatic outpatients with proximal-vein thrombosis but no signs of pulmonary embolism.\n We randomly assigned patients to adjusted-dose intravenous standard heparin administered in the hospital (198 patients) or fixed-dose subcutaneous low-molecular-weight heparin administered at home, when feasible (202 patients). We compared the treatments with respect to recurrent venous thromboembolism, major bleeding, quality of life, and costs.\n Seventeen of the 198 patients who received standard heparin (8.6 percent) and 14 of the 202 patients who received low-molecular-weight heparin (6.9 percent) had recurrent thromboembolism (difference, 1.7 percentage points; 95 percent confidence interval, -3.6 to 6.9). Major bleeding occurred in four patients assigned to standard heparin (2.0 percent) and one patient assigned to low-molecular-weight heparin (0.5 percent; difference, 1.5 percentage points; 95 percent confidence interval, -0.7 to 2.7). Quality of life improved in both groups. Physical activity and social functioning were better in the patients assigned to low-molecular-weight heparin. Among the patients in that group, 35 percent were never admitted to the hospital at all, and 40 percent were discharged early. This treatment was associated with a mean reduction in hospital days of 67 percent, ranging from 29 percent to 86 percent in the various study centers.\n In patients with proximal-vein thrombosis, treatment with low-molecular-weight heparin at home is feasible, effective, and safe.", "Few reports have addressed the value of unfractionated heparin (UFH) or low-molecular-weight heparin in treating the full spectrum of patients with venous thromboembolism (VTE), including recurrent VTE and pulmonary embolism.\n In an open, multicenter clinical trial, 720 consecutive patients with acute symptomatic VTE, including 119 noncritically ill patients (16.5%) with pulmonary embolism and 102 (14.2%) with recurrent VTE, were randomly assigned to treatment with subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm (preceded by an intravenous loading dose), or fixed-dose (adjusted only to body weight) subcutaneous nadroparin calcium. Oral anticoagulant therapy was started concomitantly and continued for at least 3 months. We recorded the incidence of major bleeding during the initial heparin treatment and that of recurrent VTE and death during 3 months of follow-up.\n Fifteen (4.2%) of the 360 patients assigned to UFH had recurrent thromboembolic events, as compared with 14 (3.9%) of the 360 patients assigned to nadroparin (absolute difference between rates, 0.3%; 95% confidence interval, -2.5% to 3.1%). Four patients assigned to UFH (1.1%) and 3 patients assigned to nadroparin (0.8%) had episodes of major bleeding (absolute difference between rates, 0.3%; 95% confidence interval, -1.2% to 1.7%). Overall mortality was 3.3% in each group.\n Subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm is as effective and safe as fixed-dose nadroparin for the initial treatment of patients with VTE, including those with pulmonary embolism and recurrent VTE.", "Low-molecular-weight heparins administered subcutaneously once or twice daily have been reported to be as safe and efficacious as intravenous unfractionated heparin in the treatment of acute venous thromboembolic disease.\n To determine whether subcutaneous enoxaparin administered once or twice daily is as effective as continuously infused unfractionated heparin in acute symptomatic venous thromboembolic disease.\n Randomized, controlled, partially blinded equivalence trial.\n 74 hospitals in 16 countries.\n 900 patients with symptomatic lower-extremity deep venous thrombosis, including 287 (32%) with confirmed pulmonary embolism.\n Initial therapy with dose-adjusted intravenous unfractionated heparin compared with subcutaneous enoxaparin at fixed dosages of 1.0 mg/kg of body weight twice daily or 1.5 mg/kg once daily. Long-term oral anticoagulation was started in all patients within 72 hours of randomization.\n Clinical end points assessed during a 3-month follow-up period.\n Equivalent efficacy was seen in the heparin group and both enoxaparin groups. Symptomatic venous thromboembolism recurred in 12 of 290 patients receiving unfractionated heparin (4.1%), 13 of 298 patients receiving once-daily enoxaparin (4.4%), and 9 of 312 patients receiving twice-daily enoxaparin (2.9%). Compared with unfractionated heparin, the treatment difference was 0.2% (95% CI, -3.04% to 3.49%) for once-daily enoxaparin and -1.2% (CI, -4.2% to 1.7%) for twice-daily enoxaparin. Incidence of major hemorrhage did not differ among the three treatment groups. Major hemorrhage occurred in 6 of 290 patients (2.1%) in the unfractionated heparin group, 5 of 298 patients (1.7%) in the once-daily enoxaparin group, and 4 of 312 patients (1.3%) in the twice-daily enoxaparin group.\n Subcutaneous enoxaparin once or twice daily is as effective and safe as dose-adjusted, continuously infused unfractionated heparin in the prevention of recurrent symptomatic venous thromboembolic disease.", "Two hundred and four consecutive patients with venographically confirmed deep vein thrombosis (DVT) were randomised either to a low molecular weight heparin, Fragmin, administered subcutaneously (s.c.) once daily as a fixed dose of 200 IU anti-factor Xa/kg or to continuous intravenous infusion of unfractionated heparin (UFH). The UFH dose was adjusted to maintain the activated partial thromboplastin time between 1.5 and 3.0 times the upper limit of the reference value at each centre. Fragmin or UFH was given for a minimum of 5 days until anticoagulation with warfarin, given from day 1, was established (i.e. an Internation Normalised Ratio, of 2.0-3.0). A second venogram was obtained after Fragmin or UFH treatment. There were no significant differences in the change in mean Marder score before and after treatment between the two treatment groups, irrespective of thrombus localisation. No major bleeding events, symptomatic pulmonary embolism, symptomatic thrombosis progression or death occurred during hospitalisation. Eight documented venous thromboembolic events occurred before the follow-up visit 6 months after randomisation: 5 in patients treated with Fragmin and 3 in those treated with UFH. Six of these events occurred after cessation of warfarin treatment. In conclusion Fragmin given s.c. once daily in a fixed dose adjusted for body weight, is no less effective or safe than a continuous infusion of UFH in the initial treatment of acute DVT.", "In view of the potential of low-molecular-weight heparins (LMWH) to simplify initial therapy and allow outpatient treatment of proximal deep-vein thrombosis, we undertook a randomised comparison of fixed-dose subcutaneous LMWH with adjusted-dose intravenous standard heparin in the initial treatment of this disorder. Our main objectives were to compare the efficacy of these regimens for 6 months of follow-up and to assess the risk of clinically important bleeding. Of 170 consecutive symptomatic patients with venographically proven proximal deep-venous thrombosis, 85 received standard heparin (to achieve an activated partial thromboplastin time of 1.5 to 2.0 times the pretreatment value) and 85 LMWH (adjusted only for body weight) for 10 days. Oral coumarin was started on day 7 and continued for at least 3 months. The frequency of recurrent venous thromboembolism diagnosed objectively did not differ significantly between the standard-heparin and LMWH groups (12 [14%] vs 6 [7%]; difference 7% [95% confidence interval -3% to 15%]; p = 0.13). Clinically important bleeding was infrequent in both groups (3.5% for standard heparin vs 1.1% for LMWH; p greater than 0.2). We conclude that fixed-dose subcutaneous LMWH is at least as effective and safe as intravenous adjusted-dose heparin in the initial treatment of symptomatic proximal-vein thrombosis. Since there is no need for laboratory monitoring with the LMWH regimen, patients with venous thrombosis can be treated at home." ]

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[ "Promoting patient participation and shortening cancer consultations: a randomised trial.", "Evaluation of a patient-centred approach in generalized musculoskeletal chronic pain/fibromyalgia patients in primary care.", "The effects of a shared decision-making intervention in primary care of depression: a cluster-randomized controlled trial.", "A randomized controlled trial of an intervention designed to improve the care given in general practice to Type II diabetic patients: patient outcomes and professional ability to change behaviour.", "Promoting a biopsychosocial orientation in family practice: effect of two teaching programs on the knowledge and attitudes of practising primary care physicians.", "Effectiveness of two preventive interventions for coronary heart disease in primary care.", "Cross-cultural medical education: can patient-centered cultural competency training be effective in non-Western countries?", "Interpersonal skills training: evaluation in an internal medicine residency.", "Factors influencing physicians' detection of cancer patients' and relatives' distress: can a communication skills training program improve physicians' detection?", "A randomized, controlled trial to improve advance care planning among patients undergoing cardiac surgery.", "A randomised controlled trial to assess the effectiveness and cost of a patient orientated self management approach to chronic inflammatory bowel disease.", "The effect of educational intervention on intercultural communication: results of a randomised controlled trial.", "Involving patients in primary care consultations: assessing preferences using discrete choice experiments.", "An intervention to increase patients' trust in their physicians. Stanford Trust Study Physician Group.", "Long-term effects of asthma education for physicians on patient satisfaction and use of health services.", "Effects of training on general practitioners' management of pain in osteoarthritis: a randomized multicenter study.", "Absolute cardiovascular disease risk and shared decision making in primary care: a randomized controlled trial.", "Communication training and antibiotic use in acute respiratory tract infections. A cluster randomised controlled trial in general practice.", "A practical randomized trial to improve diabetes care.", "Effectiveness of a clinical interviewing training program for family practice residents: a randomized controlled trial.", "Eliciting patients' concerns: a randomised controlled trial of different approaches by the doctor.", "Physician and patient communication training in primary care: effects on participation and satisfaction.", "Transfer of communication skills training from workshop to workplace: the impact of clinical supervision.", "Can nurses impact patient outcomes using a patient-centered care model?", "Improving communication skills--a randomized controlled behaviorally oriented intervention study for residents in internal medicine.", "Efficacy of a Cancer Research UK communication skills training model for oncologists: a randomised controlled trial.", "Video information combined with individualized information sessions: Effects upon emotional well-being following coronary artery bypass surgery--A randomized trial.", "Increasing patient knowledge, satisfaction, and involvement: randomized trial of a communication intervention.", "A shared decision-making communication training program for physicians treating fibromyalgia patients: effects of a randomized controlled trial.", "The effectiveness of intensive training for residents in interviewing. A randomized, controlled study.", "Improving communication between doctors and breast cancer patients.", "The effects of two continuing medical education programs on communication skills of practicing primary care physicians.", "Communication skills training in obstetrics and gynaecology: whom should we train? A randomized controlled trial.", "Effective improvement of doctor-patient communication: a randomised controlled trial.", "Randomised controlled trial of patient centred care of diabetes in general practice: impact on current wellbeing and future disease risk. The Diabetes Care From Diagnosis Research Team.", "Introduction of diabetes passports involving both patients and professionals to improve hospital outpatient diabetes care.", "Effectiveness of a three-day communication skills course in changing nurses' communication skills with cancer/palliative care patients: a randomised controlled trial.", "Primary care clinicians treat patients with medically unexplained symptoms: a randomized controlled trial.", "Detecting psychological distress: can general practitioners improve their own performance?", "Improving physicians' interviewing skills and reducing patients' emotional distress. A randomized clinical trial.", "Teaching the medical interview: an intervention study.", "Effects of a physician communication intervention on patient care outcomes.", "Caring for Aged Dementia Care Resident Study (CADRES) of person-centred care, dementia-care mapping, and usual care in dementia: a cluster-randomised trial." ]

[ "Patient participation in medical consultations has been demonstrated to benefit their subsequent psychological well being. Question asking is one way in which patients can be active. We investigated 2 means of promoting cancer patient question asking. One was the provision of a question prompt sheet to patients prior to their initial consultation with their oncologist. The second was the active endorsement and systematic review of the question prompt sheet by their oncologist. 318 patients with heterogeneous cancers, seeing one of 5 medical and 4 radiation oncologists for the first time, were randomised to either receive or not receive a question prompt sheet. Doctors were randomised to either proactively address or passively respond to the question prompt sheet in the subsequent consultation. Anxiety was assessed prior to the consultation. Consultations were audiotaped and content analysed. Anxiety was assessed again immediately following the consultation. Within the next 10 days patients completed questionnaires assessing information needs, anxiety and satisfaction and were given a structured telephone interview assessing information recall. Patients provided with a question prompt sheet asked more questions about prognosis compared with controls and oncologists gave significantly more prognostic information to these patients. Provision of the question prompt sheet prolonged consultations and increased patient anxiety; however, when oncologists specifically addressed the prompt sheet, anxiety levels were significantly reduced, consultation duration was decreased and recall was significantly improved. A patient question prompt sheet, used proactively by the doctor, is a powerful addition to the oncology consultation.\n Copyright 2001 Cancer Research Campaign", "The aim of this paper is to assess whether patient-centred consultations are more effective than the usual style of consultations used by general practitioners with patients suffering from benign chronic musculoskeletal pain and fibromyalgia. It also seeks to evaluate the differential characteristics of these two clinical groups of symptoms. The study was designed as a cluster randomised and simple blind trial. Twenty general practitioners took part and 110 patients were recruited. Compared with patients who received the usual treatment from their family physician, those who received a patient-centred approach showed greater improvement after 1 year in terms of psychological distress (anxiety) and number of tender points, as well as showing positive trends in some important outcomes such as pain intensity. Significantly better results were observed in those patients suffering chronic pain than in those with fibromyalgia, particularly as regards associated symptoms, self-rated pain and physical mobility as measured by the Nottingham health profile.", "Patient-centred depression care approaches should better address barriers of insufficient patient information and involvement in the treatment decision process. Additional research is needed to test the effect of increased patient participation on outcomes. The aim of this study was to assess, if patient participation in decision-making via a shared decision-making intervention leads to improved treatment adherence, satisfaction, and clinical outcome without increasing consultation time.\n Cluster-randomized controlled intervention study based on physician training and patient-centered decision aid compared to usual care in primary care settings in Südbaden region of Germany. Twenty-three primary care physicians treating 405 patients with newly diagnosed depression were enrolled. Patient involvement was measured with the patient perceived involvement in care scale (PICS) and a patient participation scale (MSH-scale). Patient satisfaction was measured by the CSQ-8 questionnaire. Treatment adherence was evaluated by patient and provider self-report. Depression severity and remission outcomes were assessed with the Brief PHQ-D.\n Physician facilitation of patient participation improved significantly and to a greater extent in the intervention compared to the control group. There was no intervention effect for depression severity reduction. Doctor facilitation of patient participation, patient-rated involvement, and physician assessment of adherence improved only in the intervention group. Patient satisfaction at post-intervention was higher in the intervention group compared to the control group. The consultation time did not differ between groups.\n A shared decision-making intervention was better than usual care for improving patient participation in treatment decision-making, and patient satisfaction without increasing consultation time. Additional research is needed to model causal linkages in the decision-making process in regard to outcomes.\n The study results encourage the implementation of patient participation in primary care of depression.", "Our objective was to evaluate the effect of training in a patient-centred intervention for GPs and practice nurses on outcomes for patients with Type II diabetes.\n We carried out a randomized controlled trial within general practices as the basis for randomization and a before-and-after design for measures of patient outcome. A parallel process study examined the use of the method by professionals. The study was carried out in 29 general practices in South Glamorgan who had participated for at least 2 years in a local scheme of audit and CME in relation to Type II diabetes care. The subjects were 252 Type II diabetic patients recruited by 15 experimental and 14 control practices. The main outcome measures were changes in glycosylated haemoglobin, patient satisfaction with care and treatment, functional health status and professional ability to apply the intervention.\n Professionals adopted the innovative method with enthusiasm, but after 2 years only 19% continued to apply the method systematically. The trial was, therefore, unable to demonstrate significant biochemical or functional improvements. This highlights the need to understand the factors associated with professional uptake and subsequent ability to sustain changes in behaviour.\n The efficacy of this behavioural intervention remains unproved, despite its acceptability to professional staff. Detailed and prolonged development and testing of behavioural interventions is an essential first step before embarking on randomized controlled trials which involve complex behavioural changes in professionals or patients.", "The bio-psychosocial (BPS) approach to patient care has gained acceptance in medical education. However, reported teaching programs rarely describe the efficacy of alternative approaches to continuing medical education aimed at promoting a BPS approach. The objective was to describe and evaluate the effect of two teaching programs on learners' BPS knowledge, management intentions, patient-centered attitudes, professional self-esteem, burnout, work related strain and mental workload. The learners were Israeli general practitioners. The first (\"didactic\") program consisted of problem-based reading assignments, lectures and discussions. The second (\"interactive\") program consisted of reading assignments, lectures and discussions, in addition to role-playing exercises, Balint groups and one-to-one counseling by a facilitator. One month before and six months after the teaching interventions, we used structured questionnaires to test for knowledge, management intentions (responses to questions, such as \"what would you tell a patient with ...\") and attitudes. Both programs led to measurable improvement in knowledge, intentions, patient-centered attitudes and self-esteem. The interactive teaching approach improved significantly more the learners' professional self-esteem and intentions than the didactic approach. Self-reported burnout significantly increased after the program. It is concluded that teaching intervention enhanced a BPS orientation and led to changes in knowledge, intentions, self-esteem and attitudes. An interactive method of instruction was more effective in achieving some of these objectives than a didactic one. The observed increase in burnout was unexpected and requires further study and confirmation.", "1. To compare a patient-centred, self-directive intervention with conventional care; 2. To evaluate longitudinal within-group changes of coronary heart disease risk.\n Risk factor changes were evaluated in 110 men with high coronary heart disease risk attending a one year intervention study in general practice. The 22 participating general practice centres were randomly allocated to follow either a patient-centred, self-directive intervention or a conventional approach.\n No significant between-group differences were found in any single risk factor or in the combined risk of coronary heart disease. The improvement of total risk from screening time to conclusion of the study corresponded with changes of relative risks of CHD to 0.64 (95% CI: 0.54-0.77) and 0.65 (0.54-0.77) in the patient-centred, self-directive and the conventional care group respectively (p < 0.0001 in both groups).\n Everyday general practice clinical work seems as efficacious as a specific intervention method based on currently advocated behaviour change principles.", "No evidence addresses the effectiveness of patient-centered cultural competence training in non-Western settings.\n To examine whether a patient-centered cultural competency curriculum improves medical students' skills in eliciting the patients' perspective and exploring illness-related social factors.\n Fifty-seven medical students in Taiwan were randomly assigned to either the control (n = 27) or one of two intervention groups: basic (n = 15) and extensive (n = 15). Both intervention groups received two 2-hour patient-centered cultural competency workshops. In addition, the extensive intervention group received a 2-hour practice session. The control group received no training.\n At the end of the clerkship, all students were evaluated with an objective structured clinical examination (OSCE). Students in the extensive intervention group scored significantly higher than the basic intervention and control groups in eliciting the patient's perspective (F = 18.38, p < 0.001, eta(2) = 0.40). Scores of both intervention groups were significantly higher than the control group in the exploring social factors (F = 6.66, p = 0.003, eta(2) = 0.20).\n Patient-centered cultural competency training can produce improvement in medical students' cross-cultural communication skills in non-Western settings, especially when adequate practice is provided.", "To determine the effectiveness of teaching interpersonal skills in a general internal medicine residency, a program was developed utilizing videotape feedback of house-staff/patient interactions, a modification of Interpersonal Process Recall (IPR). Fifty-one randomly selected house officers at different levels of training were included in a controlled, pretest-posttest study design. The major pre-post measures were three independent ratings of videotapes of actual first-visit interviews between resident and patient. House officers in the experimental group significantly increased the proportion of each interview devoted to psychosocial issues compared with controls, although the interviews remained predominantly medical; increased the use of effective responses; and improved their level of empathy with patients. Personality and attitude measures were found not to correlate with observed interpersonal skills on pretest or posttest videotapes. House officers rated the training program as being interesting, valuable, relevant, and nonthreatening. The data suggest that interpersonal skills can be effectively taught to internal medicine residents utilizing a videotape feedback training program.", "This study aimed to assess the impact on physicians' detection of patients' and relatives' distress of six 3-h consolidation workshops (CW) following a 2.5-day communication skills basic training (BT) program and to investigate factors associated with detection of distress.\n Physicians, after BT, were randomized to CW or to a waiting list. Physicians' detection of patients' and relatives' distress was measured through differences between physicians' ratings of patients' and relatives' distress (VAS) and patients' and relatives' self-reported distress (HADS). Communication skills were analysed according to the CRCWEM.\n Mixed-effects modelling of physicians' detection of patients' distress showed a positive group by time effect in favour of physicians in the CW group. Detection of patients' distress was associated negatively with patients' distress, positively with physicians' concurrent use of psychological assessment and supportive skills, and negatively with general assessment skills. Mixed-effects modelling of physicians' detection of relatives' distress showed no significant group by time effect. Detection of relatives' distress was associated negatively with relatives' distress and with general assessment skills.\n CW following a 2.5-day BT are needed to improve physicians' detection of patients' distress in three-person interviews. Results indicate the need to further improve physicians' detection of relatives' distress.\n (c) 2007 John Wiley & Sons, Ltd", "Although many healthcare providers and researchers consider it necessary to assist patients with end-stage chronic illnesses to plan for the end of life, they tend to avoid discussing end-of-life issues with patients before major surgery. Consequently, surgical patients and their families generally have insufficient knowledge to make plans in case of life-threatening complications.\n The objective of this study was to evaluate short-term effects of Patient-Centered Advance Care Planning (PC-ACP).\n Thirty-two dyads of patients undergoing cardiac surgery and their surrogates were randomly assigned to receive either the PC-ACP intervention (PC-ACP) or usual care.\n Measures studied were patient-surrogate congruence regarding goals for future medical care, patient and surrogate knowledge of advance care planning and anxiety, and patient decisional conflict. Congruence and anxiety were measured before and after the intervention. Decisional conflict and knowledge of advance care planning were measured after the intervention.\n Compared with the control group, PC-ACP significantly improved patient-surrogate congruence (Delta=1.27, P<0.01) and reduced patients' decisional conflict (Delta=-0.77, P<0.05). Anxiety change (pre/post) did not differ between treatment and control groups. No difference in knowledge of advance care planning was found between the 2 groups.\n The PC-ACP can be an effective approach to advance care planning. Its specificity and relevance to patients' actual medical conditions (as exemplified by its plans for potential complications related to cardiac surgery) can lead to greater patient-surrogate congruence without increasing decisional conflict and anxiety.", "We developed a patient centred approach to chronic disease self management by providing information designed to promote patient choice. We then conducted a randomised controlled trial of the approach in inflammatory bowel disease (IBD) to assess whether it could alter clinical outcome and affect health service use.\n A multicentre cluster randomised controlled trial.\n The trial was conducted in the outpatient departments of 19 hospitals with randomisation by treatment centre, 10 control sites, and nine intervention sites. For patients at intervention sites, an individual self management plan was negotiated and written information provided.\n A total of 700 patients with established inflammatory bowel disease were recruited.\n Main outcome measures recorded at one year were: quality of life, health service resource use, and patient satisfaction. Secondary outcomes included measures of enablement-confidence to cope with the condition.\n One year following the intervention, self managing patients had made fewer hospital visits (difference -1.04 (95% confidence interval (CI) -1.43 to -0.65); p<0.001) without increase in the number of primary care visits, and quality of life was maintained without evidence of anxiety about the programme. The two groups were similar with respect to satisfaction with consultations. Immediately after the initial consultation, those who had undergone self management training reported greater confidence in being able to cope with their condition (difference 0.90 (95% CI 0.12-1.68); p<0.03).\n Adoption of this approach for the management of chronic disease such as IBD in the NHS and other managed health care organisations would considerably reduce health provision costs and benefit disease control.", "Due to worldwide migration to Western countries, physicians are increasingly encountering patients with different ethnic backgrounds. Communication problems can arise as a result of differences in cultural backgrounds and poor language proficiency.\n To assess the effectiveness of an educational intervention on intercultural communication aimed to decrease inequalities in care provided between Western and non-Western patients.\n A randomised controlled trial with randomisation at the GP level and outcome measurements at the patient level.\n General practice in Rotterdam.\n Thirty-eight Dutch GPs in the Rotterdam region, with at least 25% of inhabitants of non-Western origin, and 2407 visiting patients were invited to participate in the study. A total of 986 consultations were finally included. The GPs were educated about cultural differences and trained in intercultural communication. Patients received a videotaped instruction focusing on how to communicate with their GP in a direct way. The primary outcome measure was mutual understanding and the secondary outcomes were patient's satisfaction and perceived quality of care. The intervention effect was assessed for all patients together, for the 'Western' and 'non-Western' patients, and for patients with different cultural backgrounds separately.\n An intervention effect was seen 6 months after the intervention, as improvement in mutual understanding (and some improvement in perceived quality of care) in consultations with 'non-Western' patients.\n A double intervention on intercultural communication given to both physician and patient decreases the gap in quality of care between 'Western' and 'non-Western' patients.", "Shared decision making (SDM) involves patients and doctors contributing as partners to treatment decisions. It is not known whether or to what extent SDM contributes to the welfare arising from a consultation, and how important this contribution is relative to other attributes of a consultation.\n To identify patient preferences for SDM relative to other utility bearing attributes of a consultation.\n In parallel with a randomised trial in training GPs in SDM competencies and risk communication skills, a discrete choice experiment exercise was conducted to assess patients' utilities.\n Twenty general practices in South Wales, UK.\n Five hundred and eighty-four responders from 747 patients attending the randomised trial (response rate = 78%). All patients had one of four conditions (atrial fibrillation, menorrhagia, menopausal symptoms or prostatism) and attended a consultation with a doctor in their own practice. Patients were randomised to attend a consultation either with a doctor who had received no training in the study or risk communication training alone or SDM training alone, or both combined.\n Five key utility bearing attributes of a consultation were identified. All significantly influenced patient's choice of preferred consultation style (P<0.001). Larger increases in utility were associated with changes on \"doctor listens\" attribute, followed by easily understood information, a shared treatment decision, more information and longer consultation. Utilities were influenced by whether the doctor had received risk communication training alone or SDM training alone, or both combined, prior to the consultations. The randomised trial itself had identified that the communication processes of these consultations changed significantly, with greater patient involvement in decision making, after the training interventions.\n Shared treatment decisions were valued less than some other attributes of a consultation. However, patient utilities for such involvement appeared responsive to changes in experiences of consultations. This suggests that SDM may gain greater value among patients once they have experienced it.", "To investigate the effect of a one-day workshop in which physicians were taught trust-building behaviors on their patients' levels of trust and on outcomes of care.\n In 1994, the study recruited 20 community-based family physicians and enrolled 412 consecutive adult patients from those physicians' practices. Ten of the physicians (the intervention group) were randomly assigned to receive a one-day training course in building and maintaining patients' trust. Outcomes were patients' trust in their physicians, patients' and physicians' satisfaction with the office visit, continuity in the patient-physician relationship, patients' adherence to their treatment plans, and the numbers of diagnostic tests and referrals.\n Physicians and patients in the intervention and control groups were similar in demographic and other data. There was no significant difference in any outcome. Although their overall ratings were not statistically significantly different, the patients of physicians in the intervention group reported more positive physician behaviors than did the patients of physicians in the control group.\n The trust-building workshop had no measurable effect on patients' trust or on outcomes hypothesized to be related to trust.", "This randomized clinical trial evaluated the long-term impact of an interactive seminar for physicians based on principles of self-regulation on clinician behaviour, children's use of health services for asthma, and parent's views of physician performance. Seventy-four general practice paediatricians, and 637 of their asthma patients aged 1-12 yrs, were randomized to treatment or control. Children and parents were blind to physicians' participation. Data were collected at baseline and follow-up through self-administered surveys (paediatricians), telephone interviews (parents) and medical records. The seminar focused on development of communication and teaching skills and use of therapeutic medical regimens for asthma as outlined in the National Asthma Education and Prevention Program guidelines. Approximately 2 yrs postintervention, treatment group physicians were more likely than control physicians to: use protocols for delivering asthma education (odds ratio (OR) 4.9, p=0.2), write down for patients how to adjust medicines when symptoms change (OR 5.7, p=0.05), and provide more guidelines for modifying therapy (OR 3.8, p=0.06). Parents scored treatment group physicians higher than control physicians on five specific positive communication behaviours. Children seen by treatment group physicians had fewer hospitalizations (p=0.03) and those with higher levels of emergency department (ED) use at baseline had fewer subsequent ED visits (p=0.03). No differences regarding the number of office visits were noted. There were no significant differences found between treatment and control group physicians in the amount of time spent with patients during office visits (26 versus 29 min) or in the number of patients treated with anti-inflammatory medicine. It is concluded that interactive asthma seminars for paediatricians had significant long-term benefits for their asthma care.", "To evaluate the effects of a short interactive training program for general practitioners (GP) on pain management in patients with osteoarthritis (OA).\n A multicenter, parallel-group study. GP were randomized to receive training on relationships and communication, pain evaluation, prescription, and negotiation of a patient contract or to a control group receiving a presentation about obtaining consent in trials. Outcomes were patient assessments of pain and functional ability. We invited 1500 GP to take part in the study. Those who volunteered to receive the training recruited outpatients from May 2001 to April 2002. Patients participating in the evaluation of the effects of the general practitioners' training had lower limb OA and pain on motion [> or = 40 mm on a visual analog scale (VAS)] and had indications for treatment with acetaminophen. The primary endpoint: sum of patient pain relief based on the daily VAS self-evaluation during the 2 weeks of the trial.\n In total, 180 GP (84 trained, 96 nontrained) enrolled 842 patients (414 and 428, respectively). Mean baseline VAS pain was 63 +/- 14 mm. Patients in the trained-GP group had better overall pain relief (316 +/- 290 mm/day vs 265 +/- 243 mm; p < 0.0001), greater improvement in Lequesne and WOMAC scores (p < 0.0001), and better overall perception of treatment (p = 0.002). Acetaminophen use was slightly higher in the trained group; however, the difference in pain relief remained statistically significant (p = 0.0003) after adjustment for this difference.\n This is the first study to demonstrate a positive effect of physician training on patients with a painful condition.", "We wanted to determine the effect of promoting the effective communication of absolute cardiovascular disease (CVD) risk and shared decision making through disseminating a simple decision aid for use in family practice consultations.\n The study was based on a pragmatic, cluster randomized controlled trial (phase III) with continuing medical education (CME) groups of family physicians as the unit of randomization. In the intervention arm, 44 physicians (7 CME groups) consecutively recruited 550 patients in whom cholesterol levels were measured. Forty-seven physicians in the control arm (7 CME groups) similarly included 582 patients. Four hundred sixty patients (83.6%) of the intervention arm and 466 patients (80.1%) of the control arm were seen at follow-up. Physicians attended 2 interactive CME sessions and received a booklet, a paper-based risk calculator, and individual summary sheets for each patient. Control physicians attended 1 CME-session on an alternative topic. Main outcome measures were patient satisfaction and participation after the index consultation, change in CVD risk status, and decisional regret at 6 months' follow-up.\n Intervention patients were significantly more satisfied with process and result (Patient Participation Scale, difference 0.80, P<.001). Decisional regret was significantly lower at follow-up (difference 3.39, P = .02). CVD risk decreased in both groups without a significant difference between study arms.\n A simple transactional decision aid based on calculating absolute individual CVD risk and promoting shared decision making in CVD prevention can be disseminated through CME groups and may lead to higher patient satisfaction and involvement and less decisional regret, without negatively affecting global CVD risk.", "A cluster-randomised controlled trial in general practice\n Physician-patient communication plays a key role in treatment decisions in primary care. We aimed to reduce the antibiotic prescription rate for acute respiratory tract infections using a short training programme in patient-centred communication.\n We conducted a cluster-randomised controlled trial in 45 general practices in Switzerland. Thirty physicians received evidence-based guidelines for the management of acute respiratory tract infections; 15 physicians randomised to the full intervention additionally received training in patient-centred communication. A further 15 physicians, not randomised, served as a control to blind the physicians in the other two groups to the true comparison. The primary outcome was the antibiotic prescription rate reported by pharmacists. Secondary outcomes were patient satisfaction and enablement, re-consultation rates, days with restrictions, and days off work. 1108 adults with acute respiratory infections were screened between January and May 2004. Outcomes were measured in 837 consultations; 624 patients had follow-up interviews at 7 and 14 days.\n The antibiotic prescription rate reported by pharmacists was low in both full and limited intervention groups (13.5% and 15.7% respectively) but only half of the antibiotics were prescribed according to guidelines (53.8% and 53.1%). No significant differences were seen between the two randomised groups in primary and secondary outcomes. In both groups patient satisfaction was high (median score for both 68 out of 70).\n In this trial, patient-centred communication training did not reduce the rate of antibiotic prescriptions below an already unusually low level. Even with this low prescription rate, patient satisfaction with received care was high.", "There is a well-documented gap between diabetes care guidelines and the services received by patients in almost all health care settings. This project reports initial results from a computer-assisted, patient-centered intervention to improve the level of recommended services received by patients from a wide variety of primary care providers.\n Eight hundred eighty-six patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program. Physicians were stratified and randomized to intervention or control conditions and evaluated on 2 primary outcomes: number of recommended laboratory screenings and recommended patient-centered care activities completed. Secondary outcomes were evaluated using the Problem Areas in Diabetes scale and the Patient Health Questionnaire (PHQ)-9 depression scale, and the RE-AIM framework was used to evaluate potential for dissemination.\n The program was well-implemented and significantly improved both number of recommended laboratory assays (3.4 vs 3.1; P <.001) and patient-centered aspects of diabetes care patients received (3.6 vs 3.2; P <.001) compared to those in randomized control practices. Activities that were increased most were foot exams (follow-up rates of 80% vs 52%; P <.003) and nutrition counseling (76% vs 52%; P <.001).\n Patients are very willing to participate in a brief computer-assisted intervention that is effective in enhancing quality of diabetes care. Staff in primary care offices can consistently deliver an intervention of this nature, but most physicians were unwilling to participate in this translation research study.", "This study evaluated the effectiveness of a clinical interviewing training program for third-year family practice trainees and determined which other factors influence residents' training in clinical communication.\n This was a randomized, multicenter, educational trial involving 193 third-year family practice residents from eight centers in Spain. Centers were randomly assigned to two groups, one of which would undertake a communication skills training program and one of which would not. The program was resident centered, based on residents' practice experience, and provided structured feedback. The main outcome measures were residents' consultation behavior with six standardized patient encounters (three before and three after the training) as measured with the GATHA-RES rating scale by an observer blinded to group assignment of the residents.\n The intervention group trainees displayed marginally better communication skills at the start of the study than those in the control group. At the end of the study, trainees who had received the training program did not show better communication skills than those who had not received the training program. Factors related to the training center environment, having a teacher trained in clinical interviewing, younger age, and a longer interview duration correlated with better communication skills.\n The trial program did not appear to improve the global communication skills of trainees. This study highlights the importance of the trainee's teachers, the residency program environment, and earlier exposure to training in planning future programs to improve residents' communication skills.", "Although a 'patient-centred' approach to general practice consultation is widely advocated, there is mixed evidence of its benefits.\n To measure the costs and benefits of using a prompt to elicit patients' concerns when they consult for minor illness.\n An open randomised controlled trial.\n Four training semi-rural general practices in the south- east of the United Kingdom.\n Patients identified during the first part of the consultation as having a self-limiting illness were randomised to a second part of the consultation that was conducted 'as usual' or involved a written prompt to elicit the patient's concerns. After each consultation the doctor noted the diagnosis and the consultation length and the patient self-completed a questionnaire containing measures of satisfaction, enablement and anxiety.\n One hundred and ten patients were studied. Patients in the elicitation group reported a small but significant increase in the 'professional care' score of the consultation satisfaction questionnaire (88.2 versus 80.9, mean difference = 7.3, 95% confidence interval = 2.0 to 12.6) but no other benefits were detected. Consultations in the elicitation group, however, were longer by about a minute.\n Given the pressures on consultation time in general practice there must be questions about the practical value of eliciting patients' concerns if the benefit of doing so is small and the cost large.", "To assess the effects of a communication skills training program for physicians and patients.\n A randomized experiment to improve physician communication skills was assessed 1 and 6 months after a training intervention; patient training to be active participants was assessed after 1 month. Across three primary medical care settings, 156 physicians treating 2,196 patients were randomly assigned to control group or one of three conditions (physician, patient, or both trained).\n Patient satisfaction and perceptions of choice, decision-making, information, and lifestyle counseling; physicians' satisfaction and stress; and global ratings of the communication process.\n The following significant (p < .05) effects emerged: physician training improved patients' satisfaction with information and overall care; increased willingness to recommend the physician; increased physicians' counseling (as reported by patients) about weight loss, exercise, and quitting smoking and alcohol; increased physician satisfaction with physical exam detail; increased independent ratings of physicians' sensitive, connected communication with their patients, and decreased physician satisfaction with interpersonal aspects of professional life. Patient training improved physicians' satisfaction with data collection; if only physician or patient was trained, physician stress increased and physician satisfaction decreased.\n Implications for improving physician-patient relationship outcomes through communication skills training are discussed.\n PsycINFO Database Record (c) 2008 APA, all rights reserved.", "Recent studies have recognised that the communication skills learned in the training environment are not always transferred back into the clinical setting. This paper reports a study which investigated the potential of clinical supervision in enhancing the transfer process.\n A randomised controlled trial was conducted involving 61 clinical nurse specialists. All attended a 3-day communication skills training workshop. Twenty-nine were then randomised to 4 weeks of clinical supervision, aimed at facilitating transfer of newly acquired skills into practice. Assessments, using real and simulated patients, were carried out before the course, immediately after the supervision period and 3 months later. Interviews were rated objectively using the Medical Interview Aural Rating Scale (MIARS) to assess nurses' ability to use key skills, respond to patient cues and identify patient concerns.\n Assessments with simulated patients showed that the training programme was extremely effective in changing competence in all three key areas. However, only those who experienced supervision showed any evidence of transfer. Improvements were found in the supervised groups' use of open questions, negotiation and psychological exploration. Whilst neither group facilitated more disclosure of cues or concerns, those in the experimental group responded more effectively to the cues disclosed, reduced their distancing behaviour and increasing their exploration of cues.\n The study has shown that whilst training enhances skills, without intervention, it may have little effect on clinical practice. The potential role of clinical supervision as one way of enhancing the clinical effectiveness of communication skills training programmes has been demonstrated. PRACTISE IMPLICATIONS: This study raises questions about the effectiveness of training programmes which do not incorporate a transfer element, and provides evidence to support the need for clinical supervision for clinical nurse specialist.", "The aim of this study was to determine if nurses, using patient-centered care (PCC), affect patient satisfaction, perceptions of nursing care, and quality outcomes.\n The Institute of Medicine proposed PCC as 1 of 6 national quality aims, whereas the Centers for Medicare and Medicaid Services highlighted integration of PCC as 1 of 12 actions for quality improvement.\n A total of 116 patients were randomized into an intervention (PCC) or control group. Patients who were to receive PCC were called before admission and cared for by nurses who trained to administer/practice PCC. Control patients received usual care. Both groups completed questionnaires and received postdischarge calls. Length of stay, falls, infections, and adverse events were measured to assess quality of care.\n No significant differences were found between groups for length of stay, infection, falls, postoperative complications, quality of care, satisfaction level, or perceptions of nursing care.\n Patient-centered care did not affect patient's level of satisfaction or quality of care. However, findings yielded clinically relevant results regarding patient/staff responses.", "We investigated whether patient-centered communication skills can be taught to residents in Internal Medicine by using a time-limited behaviorally oriented intervention.\n Residents working at the Department of Internal Medicine were randomly assigned to an intervention group (IG; N = 19) or a control group (CG; N = 23). In addition to 6 hours of standard medical education per week, the IG received specific communication training of 22.5 hours duration within a 6-month period. Initially and 10 months later, participants performed interviews with simulated patients. Interviews were rated by blinded raters who used the Maastricht History and Advice Checklist-Revised.\n Compared with the CG, the IG improved substantially in many specific communication skills. Both groups improved in the \"amount of medical information identified\" and in the ability to \"communicate about feasibility of treatment.\"\n Patient-centered communication skills such as those presented in this intervention study can be taught. The ability to gain medical information and the readiness to communicate about aspects of medical treatment seem to improve with more professional experience; however, they also profit from the intervention.", "Doctors' communication with patients is commonly hampered by lack of training in this core skill. This study aimed to assess the efficacy of an intensive 3-day training course on communication skills in a randomised controlled trial with a two-by-two factorial design and several outcomes.\n 160 oncologists from 34 UK cancer centres were randomly allocated to four groups: written feedback followed by course; course alone; written feedback alone; and control. At each of two assessment periods, consultations with six to ten consecutive, consenting patients per doctor were videotaped. 2407 patients participated. Outcome measures included objective and subjective ratings made by researchers, doctors, and patients. The primary outcomes were objective improvements after the intervention in key communication skills. Course content included structured feedback, videotape review of consultations, role-play with simulated patients, interactive group demonstrations, and discussion led by a trained facilitator.\n In Poisson regression analysis of counts of communication behaviours, course attendance significantly improved key outcomes. The estimated effect sizes corresponded to higher rates of use of focused questions (difference between course attenders [n=80] and non-attenders [n=80] 34%, p=0.003), focused and open questions (27%, p=0.005), expressions of empathy (69%, p=0.003), and appropriate responses to patients' cues (38%, p=0.026), and a 24% lower rate of use of leading questions (p=0.11). There was little evidence for the effectiveness of written feedback.\n The communication problems of senior doctors working in cancer medicine are not resolved by time and clinical experience. This trial shows that training courses significantly improve key communication skills. More resources should be allocated to address doctors' training needs in this vital area.", "To test the efficacy of an information intervention upon emotional recovery following coronary artery bypass surgery.\n Randomized trial. Video information was combined with individualized information sessions carried out by nurses at admission and at discharge from the hospital. The video was shown pre-operatively and again during the session at admission. Patients were helped to express their questions and worries and congruent information and support was provided. Control group patients received standardized information and no video. Recordings were made at baseline, discharge from hospital and during a 2 years follow-up period.\n One hundred and nine patients were randomized to the intervention or the control groups. A MANOVA was used to test of the variance of the outcome variables at each time point. At discharge intervention patients reported less anxiety (p = 0.046) and better subjective health (p = 0.005). They reported better subjective health during the whole follow-up period (0.040 > or = p > or = 0.000), less anxiety up to 1 year (0.042 > or = p > or = 0.004), and less depression from 6 months to 2 years following discharge (0.023 > or = p > or = 0.004).\n The effects of the intervention probably relate to the combined use of the video and patient centered information sessions.\n The intervention can easily be implemented in clinical practice and nurses strongly identified with its principles.", "A brief educational intervention to promote effective communication between physicians, children, and parents during pediatric office visits was designed and tested. A randomized clinical trial involving 141 children (5- to 15-year-olds) tested the effectiveness of the intervention to improve the process and outcome of medical care. The intervention was contained in three brief videotapes (one each for parents, physicians, and patients) and in accompanying written materials. Materials were designed to build skills and motivation for increased child competence and participation during pediatric medical visits. Control subjects saw health education videotapes and received materials comparable in length with those of experimental subjects. Postintervention medical visit process was analyzed using videotapes of visits. Visit outcomes, assessed with standardized instruments and interviews, included children's rapport with physicians, children's anxiety, children's preference for an active health role, children's recall of information, parents' satisfaction with the medical visit, and physician satisfaction. Results indicated that physicians in the intervention group, compared with their counterparts in the control group, more often included children in discussions of medical recommendations (50% vs 29%, t = 2.39, P less than .05); that children in the intervention group, compared with control children, recalled more medication recommendations (77% vs 47%, P less than .01) and reported greater satisfaction and preference for an active health role; and that the intervention and control groups did not differ in parent satisfaction, physician satisfaction, or child anxiety. The results suggest that a brief educational intervention administered during waiting room time can positively impact physician-child rapport and children's preference for an active role in health and their acquisition of medical information.", "Fibromyalgia syndrome (FMS) is a condition of chronic widespread pain that is difficult to control and is associated with strains in physician-patient interaction. Shared decision making (SDM) can be a potential solution to improve interaction. We evaluated the effects of an SDM intervention, including an SDM communication training program for physicians, in a randomized controlled trial with FMS patients. The main objective was to assess whether SDM improves the quality of physician-patient interaction from patients' perspective.\n Patients were randomized to either an SDM group or an information-only group. The SDM group was treated by physicians trained in SDM communication and had access to a computer-based information package; the information-only group received only the information package and was treated by standard physicians. All patients were offered the same evidence-based treatment options for FMS. Patients were assessed with questionnaires on physician-patient interaction (main outcome criteria) and decisional processes. Physicians filled out a questionnaire on interaction difficulties. Assessment took place immediately after the initial consultation.\n Data from 85 FMS patients (44 in the SDM group and 41 in the information-only group) were analyzed. The mean age was 49.9 years (S.D.=10.2), and 91.8% of patients were female. The quality of physician-patient interaction was significantly higher in the SDM group than in the information-only group (P<.001). We found no differences in secondary outcome measures.\n SDM with FMS patients might be a possible means to achieve a positive quality of physician-patient interaction. A specific SDM communication training program teaches physicians to perform SDM and reduces frustration in patients.", "Interviewing and the physician-patient relationship are crucial elements of medical care, but residencies provide little formal instruction in these areas.\n To determine the effects of a training program in interviewing on 1) residents' attitudes toward and skills in interviewing and 2) patients' physical and psychosocial well-being and satisfaction with care.\n Randomized, controlled study.\n Two university-based primary care residencies.\n 63 primary care residents in postgraduate year 1.\n A 1-month, full-time rotation in interviewing and related psychosocial topics.\n Residents and their patients were assessed before and after the 1-month rotation. Questionnaires were used to assess residents' commitment to interviewing and psychosocial medicine, estimate of the importance of such care, and confidence in their ability to provide such care. Knowledge of interviewing and psychosocial medicine was assessed with a multiple-choice test. Audiotaped interviews with real patients and videotaped interviews with simulated patients were rated for specific interviewing behaviors. Patients' anxiety, depression, and social dysfunction; role limitations; somatic symptom status; and levels of satisfaction with medical visits were assessed by questionnaires and telephone interviews.\n Trained residents were superior to untrained residents in knowledge (difference in adjusted post-test mean scores, 15.7% [95% CI, 11% to 20%]); attitudes, such as confidence in psychological sensitivity (difference, 0.61 points on a 7-point scale [CI, 0.32 to 0.91 points]); somatization management (difference, 0.99 points [CI, 0.64 to 1.35 points]); interviewing of real patients (difference, 1.39 points on an 11-point scale [CI, 0.32 to 2.45 points]); and interviewing (data gathering) of simulated patients (difference, 2.67 points [CI, 1.77 to 3.56 points]). Mean differences between the study groups were consistently in the appropriate direction for patient satisfaction and patient well-being, but effect sizes were too small to be considered meaningful.\n An intensive 1-month training rotation in interviewing improved residents' knowledge about, attitudes toward, and skills in interviewing.", "We wanted to assess the effectiveness of intensive education for physicians compared with a traditional session on communicating with breast cancer patients.\n A randomized controlled trial was conducted in practices in London, Hamilton, and Toronto, Canada, with 17 family physicians, 16 surgeons, and 18 oncologists, and with 102 patients of the surgeons and oncologists. Doctors were randomized to 1 of 2 continuing education approaches: a traditional 2-hour version (control group), or a new 6-hour intensive version including exploring the patients' perspectives and reviewing videotapes and receiving feedback (intervention group). Communication behavior of the physicians was measured objectively both before and after the intervention. As well, 4 postintervention patient outcomes were measured, by design only for surgeons and oncologists: patient-centerdness of the visit, satisfaction, psychological distress, and feeling better.\n No significant differences were found on the communication score of the intervention vs the control physicians when controlling for preintervention communication scores. Intervention family physicians, however, had significantly higher communication subscores than control family physicians. Also, patients of the intervention surgeons and oncologists were significantly more satisfied (scores of 82.06 vs 77.78, P = .03) and felt better (88.2% vs 70.6%, P=.02) than patients of the control surgeons and oncologists when controlling for covariates and adjusting for clustering within doctor.\n The continuing medical education intervention was effective in terms of some but not all physician and patient outcomes.", "To evaluate and compare the effects of two types of continuing medical education (CME) programs on the communication skills of practicing primary care physicians.\n Fifty-three community-based general internists and family practitioners practicing in the Portland, Oregon, metropolitan area and 473 of their patients.\n For the short program (a 4 1/2-hour workshop), 31 physicians were randomized to either the intervention or the control group. In the long program (a 2 1/2-day course), 20 physicians participated with no randomization. A research assistant visited all physicians' offices both one month before and one month after the CME program and audiotaped five sequential visits each time. Data were based on analysis of the content and the affect of the interviews, using the Roter Interactional Analysis Scheme.\n Based on both t-test analysis and analysis of covariance, no effect on communication was evident from the short program. The physicians enrolled in the long program asked more open-ended questions, more frequently asked patients' opinions, and gave more biomedical information than did the physicians in the short program. Patients of the physicians who attended the long program tended to disclose more biomedical and psychosocial information to their physicians. In addition, there was a decrease in negative affect for both patient and physician, and patients tended to demonstrate fewer signs of outward distress during the visit.\n This study demonstrates some potentially important changes in physicians' and patients' communication after a 2 1/2-day CME program. The changes demonstrated in both content and affect may have important influences on both biologic outcome and physician and patient satisfaction.", "To determine whether patient-physician communication in obstetrics and gynaecology can be improved by a training program and to investigate if physicians with poorer performance before the training show greater improvement in communication skills scores over the course of the study.\n Intervention study with randomisation in training (n = 16) and control group (n = 16) and patient satisfaction and communication skills of physicians as outcome variables. Physicians' communication skills were assessed by independent raters using a standardised evaluation instrument (adapted version of the MAAS-R) to analyse video recorded interviews before and after the training. Patient satisfaction was assessed with a patient satisfaction questionnaire.\n Using general linear model (GLM) for repeated measures no group x time interaction nor time effects were found for physicians' communication skills. No group x time interaction was found for patients' satisfaction scores; however the significant time effect was mostly attributable to positive changes in patients' rating of the training group. Physicians with poorer performance at the beginning showed greater improvements over the course of the study, especially in the training group.\n In this randomized controlled trial marginal intervention effects for the improvement of communication skills and only partial changes in patient satisfaction scores from pre to post training were shown. However, physicians with poorer performance at the beginning showed greater improvements, suggesting that competence levels were already relatively high at the beginning of the study. Also, formation of communication training groups should be based on specific skill deficits rather than being implemented unspecifically for an entire team of physicians.", "Doctor-patient communication is an essential component of general practice. Improvement of GPs' communication patterns is an important target of training programmes. Available studies have so far failed to provide conclusive evidence of the effectiveness of educational interventions to improve doctor-patient communication.\n To examine the effectiveness of a learner-centred approach that focuses on actual needs, to improve GPs' communication with patients.\n Randomised controlled trial.\n One hundred volunteer GPs in the Netherlands.\n The intervention identified individual GPs' deficiencies in communication skills by observing authentic consultations in their own surgery. This performance assessment was followed by structured activities in small group meetings, aimed at remedying the identified shortcomings. Outcomes were measured using videotaped consultations in the GPs' own surgery before and after the intervention. Communication skills were rated using the MAAS-Global, a validated checklist.\n The scores in the intervention group demonstrated a significant improvement compared with those of the control group (95% confidence interval = 0.04 to 0.75). The effect size was moderate to large (d-value = 0.66). The level of participation significantly contributed to the effectiveness. Largest improvement was found on patient-centred communication skills.\n The approach of structured individual improvement activities based on performance assessment is more effective in improving communication skills than current educational activities.", "To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes.\n Pragmatic parallel group design, with randomisation between practice teams to routine care (comparison group) or routine care plus additional training (intervention group); analysis at one year, allowing for practice effects and stratifiers; self reporting by patients on communication with practitioners, satisfaction with treatment, style of care, and lifestyle.\n 41 practices (21 in intervention group, 20 in comparison group) in a health region in southern England.\n 250/360 patients (aged 30-70 years) diagnosed with type 2 diabetes and completing follow up at one year (142 in intervention group, 108 in comparison group).\n 1.5 days' group training for the doctors and nurses-introducing evidence for and skills of patient centred care and a patient held booklet encouraging questions.\n Quality of life, wellbeing, haemoglobin A1c and lipid concentrations, blood pressure, body mass index (kg/m2).\n Compared with patients in the C group, those in the intervention group reported better communication with the doctors (odds ratio 2.8; 95% confidence interval 1.8 to 4.3) and greater treatment satisfaction (1.6; 1.1 to 2.5) and wellbeing (difference in means (d) 2.8; 0.4 to 5.2). However, their body mass index was significantly higher (d=2.0; 0.3 to 3.8), as were triglyceride concentrations (d=0.4 mmol/l; 0.07 to 0.73 mmol/l), whereas knowledge scores were lower (d=-2.74; -0.23 to -5.25). Differences in lifestyle and glycaemic control were not significant.\n The findings suggest greater attention to the consultation process than to preventive care among trained practitioners; those committed to achieving the benefits of patient centred consulting should not lose the focus on disease management.", "To investigate whether a comprehensive strategy involving both patients and professionals, with the introduction of a diabetes passport as a key component, improves diabetes care.\n The first 150 consecutive patients who visited their internist for a diabetes check up at the internal medicine outpatient departments at each of nine Dutch general hospitals were included in this 1 year clustered, randomised, controlled trial. Health care professionals attended an educational meeting about the use and dissemination of the diabetes passport which is a patient held record. They also received aggregated feedback on baseline data and personal feedback. Educational meetings were also organised for patients. Patient files were used in conjunction with questionnaires to determine adherence rates. Data were analysed using multilevel regression analysis.\n Small but significant changes were found in mean HbA1c levels. In the intervention group, positive health changes for patients were found (-0.3%) when compared to those in the control group (+0.2%). Diastolic blood pressure improved slightly, but no changes were found in systolic blood pressure or cholesterol. Improvements were found with regard to levels of examination of patients' feet and in patient education.\n Efforts to improve professional practice involving both professionals and patients led to small improvements in HbA1c and diastolic blood pressure levels. Further study is needed to establish whether a better structured health care delivery, operating in a more supportive environment can enhance these effects.", "This multi-centre, two-armed parallel-group pragmatic randomised controlled trial (RCT) evaluated the effectiveness of a 3-day communication skills course in changing nurses' communication skills. The primary outcome was the change in the nurses' communication skills score from pre-course to 12 weeks post-course. The main secondary outcome was the change in the nurses' level of confidence in communicating with patients. A total of 172 nurses were randomised to the course or control. The communication skills score for the intervention group increased by 3.4 points post-course but decreased in the control by 0.05 points (between-group difference in change: 3.41, 95% CI: 2.16-4.66, P < 0.001). Confidence scores increased by 18.16 points for the intervention group but decreased 0.7 points in the control (between-group difference in change: 18.86, 95% CI: 13.39-24.34, P < 0.001). This RCT contributes to the evidence base on the effectiveness of communication skills training in cancer and palliative care.", "There is no proven primary care treatment for patients with medically unexplained symptoms (MUS). We hypothesized that a long-term, multidimensional intervention by primary care providers would improve MUS patients' mental health.\n Clinical trial.\n HMO in Lansing, MI.\n Patients from 18 to 65 years old with 2 consecutive years of high utilization were identified as having MUS by a reliable chart rating procedure; 206 subjects were randomized and 200 completed the study.\n From May 2000 to January 2003, 4 primary care clinicians deployed a 12-month intervention consisting of cognitive-behavioral, pharmacological, and other treatment modalities. A behaviorally defined patient-centered method was used by clinicians to facilitate this treatment and the provider-patient relationship.\n The primary endpoint was an improvement from baseline to 12 months of 4 or more points on the Mental Component Summary of the SF-36.\n Two hundred patients averaged 13.6 visits for the year preceding study. The average age was 47.7 years and 79.1% were females. Using intent to treat, 48 treatment and 34 control patients improved (odds ratio [OR]=1.92, 95% confidence interval [CI]: 1.08 to 3.40; P=.02). The relative benefit (relative \"risk\" for improving) was 1.47 (CI: 1.05 to 2.07), and the number needed to treat was 6.4 (95% CI: 0.89 to 11.89). The following baseline measures predicted improvement: severe mental dysfunction (P<.001), severe body pain (P=.039), nonsevere physical dysfunction (P=.003), and at least 16 years of education (P=.022); c-statistic=0.75.\n The first multidimensional intervention by primary care clinicians led to clinically significant improvement in MUS patients.", "Many studies have suggested that general practitioners fail to detect a substantial minority of their patients who are psychologically distressed, and there is concern about the possible sequelae of this. Individual patients may suffer unresolved problems, and there are potential costs to the health service in consequent recurrent consultations, inappropriate referrals or treatment. Educational interventions based on small groups led by facilitators have been shown to alter the consultation behaviours of general practitioners that are known to be related to accurate detection of psychological distress.\n This controlled study aimed to show that, by utilizing a brief self-directed educational intervention focusing on detection of psychological distress, general practitioners can improve their performance significantly. For this purpose, a new educational intervention was designed: the second aim of the study was thus to assess the effectiveness of this specific intervention.\n An educational intervention was designed which focused on skills relevant to detecting psychological distress, using the principles of reflection on general practitioner performance and consultation skill work. It was designed to be used by individual general practitioners without outside support, using a combination of written background material, feedback on performance and analysis of video material. The effectiveness of the intervention was tested by comparing a trial and control cohort of general practitioners, using detection rates as an outcome measure.\n The detection rate of the general practitioners who underwent the intervention improved significantly compared with their performance before intervention and with that of the control group.\n General practitioners can improve their ability to detect psychological distress in their patients utilizing this self-directed educational approach.", "Despite high prevalence, emotional distress among primary care patients often goes unrecognized during routine medical encounters.\n To explore the effect of communication-skills training on the process and outcome of care associated with patients' emotional distress.\n A randomized, controlled field trial was conducted with 69 primary care physicians and 648 of their patients. Physicians were randomized to a no-training control group or one of two communication-skills training courses designed to help physicians address patients' emotional distress. The two training courses addressed communication through problem-defining skills or emotion-handling skills. All office visits of study physicians were audiotaped until five emotionally distressed and five nondistressed patients were enrolled based on patient response to the General Health Questionnaire. Physicians were also audiotaped interviewing a simulated patient to evaluate clinical proficiency. Telephone monitoring of distressed patients for utilization of medical services and General Health Questionnaire scores was conducted 2 weeks, 3 months, and 6 months after their audiotaped office visits.\n Audiotape analysis of actual and simulated patients showed that trained physicians used significantly more problem-defining and emotion-handling skills than did untrained physicians, without increasing the length of the visit. Trained physicians also reported more psychosocial problems, engaged in more strategies for managing emotional problems with actual patients, and scored higher in clinical proficiency with simulated patients. Patients of trained physicians reported reduction in emotional distress for as long as 6 months.\n Important changes in physicians' communication skills were evident after an 8-hour program. The training improved the process and outcome of care without lengthening the visits.", "To study the effects of teaching specific interviewing techniques on verbal behaviors and on health outcomes, internal medicine residents working in a screening clinic were assigned to either an experimental or a control group. The entire clinic visit was audiotaped, transcribed, and coded according to the Verbal Response Mode (VRM) system. Residents in the experimental group were taught interviewing behaviors (patient exposition and physician explanation) that had been found in previous studies to be associated with patient outcomes. Through telephone interviews, patient satisfaction, compliance, and symptom status were determined for all patients. Two hundred and sixty-eight interviews (156 in the experimental group and 112 in the control group) were included in the study. Training did increase patient exposition and physician explanation, but did not affect health outcomes. Residents' attitudes and behaviors during the training are described.", "To determine whether an intervention designed to improve patient-physician communication increases the frequency with which physicians elicit patients' concerns, changes other communication behaviors, and improves health care outcomes.\n Pretest-posttest design with random assignment of physicians to intervention or control groups.\n General medicine clinics of a university-affiliated Veterans Affairs Hospital.\n Forty-two physicians and 348 continuity care patients taking prescription medications for chronic medical conditions.\n Intervention group physicians received 4.5 hours of training on eliciting and responding to patients' concerns and requests, and their patients filled out the Patient Requests for Services Questionnaire prior to a subsequent clinic visit. Control group physicians received 4.5 hours of training in medical decision-making.\n The frequency with which physicians elicited all of a patient's concerns increased in the intervention group as compared with the control group (p = .032). Patients perceptions of the amount of information received from the physician did increase significantly (p < .05), but the actual magnitude of change was small. A measure of patient satisfaction with the physicians was high at baseline and also showed no significant change after the intervention. Likewise, the intervention was not associated with changes in patient compliance with medications or appointments, nor were there any effects on outpatient utilization.\n A low-intensity intervention changed physician behavior but had no effect on patient outcomes such as satisfaction, compliance, or utilization. Interventions may need to focus on physicians and patients to have the greatest effect.", "Evidence for improved outcomes for people with dementia through provision of person-centred care and dementia-care mapping is largely observational. We aimed to do a large, randomised comparison of person-centred care, dementia-care mapping, and usual care.\n In a cluster randomised controlled trial, urban residential sites were randomly assigned to person-centred care, dementia-care mapping, or usual care. Carers received training and support in either intervention or continued usual care. Treatment allocation was masked to assessors. The primary outcome was agitation measured with the Cohen-Mansfield agitation inventory (CMAI). Secondary outcomes included psychiatric symptoms including hallucinations, neuropsychological status, quality of life, falls, and cost of treatment. Outcome measures were assessed before and directly after 4 months of intervention, and at 4 months of follow-up. Hierarchical linear models were used to test treatment and time effects. Analysis was by intention to treat. This trial is registered with the Australia and New Zealand Clinical Trials Registry, number ACTRN12608000084381.\n 15 care sites with 289 residents were randomly assigned. Pairwise contrasts revealed that at follow-up, and relative to usual care, CMAI score was lower in sites providing mapping (mean difference 10.9, 95% CI 0.7-21.1; p=0.04) and person-centred care (13.6, 3.3-23.9; p=0.01). Compared with usual care, fewer falls were recorded in sites that used mapping (0.24, 0.08-0.40; p=0.02) but there were more falls with person-centred care (0.15, 0.02-0.28; p=0.03). There were no other significant effects.\n Person-centred care and dementia-care mapping both seem to reduce agitation in people with dementia in residential care." ]

[ "16039407", "15820815" ]

[ "Prophylactic oophorectomy at elective hysterectomy. Effects on psychological well-being at 1-year follow-up and its correlations to sexuality.", "Perimenopausal androgen decline after oophorectomy does not influence sexuality or psychological well-being." ]

[ "In a prospective study, the 1-year psychological well-being outcome after oophorectomy-hysterectomy, compared to hysterectomy-only and the correlations between the changes in psychological well-being and the changes in sexuality were evaluated.\n Perimenopausal sexually active women (n=362), scheduled for hysterectomy on benign indication, were recruited. Three hundred and twenty-three women (89%) completed the 1-year follow-up; 217 women spared their ovaries and 106 underwent concomitant oophorectomy.\n Psychological well-being was studied by the psychological general well-being index (PGWB) and sexuality by the McCoy's sex questionnaire. The prevalence of climacteric symptoms was reported by the modified Kupperman's index. Hormone-replacement therapy was recorded. Postoperative, all oophorectomized and the hysterectomy-only women with climacteric symptoms were recommended estrogen-replacement therapy.\n The two groups did not differ in PGWB, neither before surgery nor at 1-year follow-up. Postoperative, both groups showed increased well-being regarding depressed mood, general health and total score. Besides, the hysterectomy-only group had increased vitality and the hysterectomy-oophorectomy group showed increased positive well-being and decreased anxiety. Most of the sexual parameters showed positive correlation to the PGWB parameters. The correlations were strong regarding parameters of overall sexual satisfaction, weak, regarding sexual motivation and relationship to partner, while absent regarding coital frequency.\n Concomitant prophylactic oophorectomy, at elective hysterectomy, does not negatively affect psychological well-being in adequately estrogenized perimenopausal women. Indeed, both hysterectomy-only and hysterectomy-oophorectomy have a positive effect on psychological well-being. Most aspects of sexuality are correlated to aspects of psychological well-being.", "To determine whether oophorectomy during the perimenopause, with the associated decline in ovarian androgens, affects sexual function and psychological well-being negatively.\n Prospective, observational study comparing sexuality and psychological well-being in women after hysterectomy only (HYST) vs. hysterectomy and concomitant oophorectomy (HYST+BSO).\n University hospital and district general hospital.\n Three hundred sixty-two perimenopausal women scheduled for elective hysterectomy on benign indication were recruited and 323 (89%) completed the 1-year follow-up (217 in the HYST group and 106 in the HYST+BSO group).\n The patients were evaluated preoperatively and 1 year after surgery. Postoperatively, estrogen replacement therapy was recommended to all women in the HYST+BSO group and to HYST group subjects with climacteric symptoms.\n Sex steroids (T, androstenedione, DHEA-S, and E(2)) and sex hormone-binding globulin (SHBG) were measured. Free androgen index and free E(2) index were calculated. Sexuality (McCoy's Female Sex Questionnaire) and psychological well-being (Psychological General Well-Being Index) were evaluated.\n Preoperatively, no hormonal differences were found between the two groups. At 1-year follow-up, all sex steroid levels and indices were decreased and SHBG was increased in the HYST+BSO group. Ovarian sex steroids were decreased in the HYST group, whereas DHEA-S and SHBG were unaltered. Sexuality was unaltered in the HYST+BSO group, whereas decreased scores were found in 3 of 14 sexual variables in the HYST group. Psychological well-being was improved in both groups. There were no correlations between the observed changes (data 1 year after surgery, compared with preoperative data) in androgen levels and index and the observed changes in any aspect of sexuality or psychological well-being.\n Hormonal changes after oophorectomy in conjunction with perimenopausal hysterectomy do not significantly change postoperative (1-year) sexual or psychological well-being." ]

[ "19583608", "11573637", "14722166", "20951260", "9972747", "11388527", "19117801", "20832550" ]

[ "Thromboelastography-based transfusion algorithm reduces blood product use after elective CABG: a prospective randomized study.", "Reduced haemostatic factor transfusion using heparinase-modified thrombelastography during cardiopulmonary bypass.", "Comparison of structured use of routine laboratory tests or near-patient assessment with clinical judgement in the management of bleeding after cardiac surgery.", "Thromboelastometrically guided transfusion protocol during aortic surgery with circulatory arrest: a prospective, randomized trial.", "Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery.", "Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass.", "Protocol based on thromboelastograph (TEG) out-performs physician preference using laboratory coagulation tests to guide blood replacement during and after cardiac surgery: a pilot study.", "Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial." ]

[ "Bleeding and allogeneic transfusion remain constant problems in cardiac surgical procedures. In this study, we aimed to test the role of a routine thromboelastography (TEG)-based algorithm on bleeding and transfusions in patients undergoing elective coronary artery bypass grafting (CABG).\n Patients (n = 224) undergoing elective CABG with cardiopulmonary bypass were prospectively randomized into two groups according to transfusion strategy: in group 1 (clinician-directed transfusion, n = 110) need for blood transfusion was based on clinician's discretion and standard coagulation tests and in group 2 (TEG algorithm group, n = 114) kaolin-activated (k) TEG-based algorithm-guided perioperative transfusion management. Transfusion, blood loss, and outcome data were recorded.\n There were no differences in consumption of packed cell units, blood loss, re-exploration for bleeding, and early clinical outcome between the groups. Patients in the TEG group had significantly lower median units of fresh frozen plasma and platelets compared with the other group (p = 0.001). The median number of total allogeneic units transfused (packed cells and blood products) was significantly reduced in the TEG group compared with the other group (median 2, range 1-3 units vs. median 3, range 2-4 units, respectively, p = 0.001). The need for tranexamic acid was significantly diminished in the TEG group compared with the other group (10.3% vs. 19%, respectively, p = 0.007).\n Our results show that routine use of a kTEG-guided algorithm reduces the consumption of blood products in patients undergoing elective CABG. Adopting such an algorithm into routine management of these patients may help to improve clinical outcome and reduce the potential risks of transfusion-related complications and total costs after CABG.", "We set out to determine if the heparinase-modified thrombelastogram using anticoagulated blood from patients during cardiac surgery could guide treatment with haemostatic components. In 60 patients a simple algorithm predicted a possible 60-80% decrease in the use of haemostatic components. In a second series, 30 patients were allocated to receive components using this intra-operative algorithm and 30 using clinical criteria and laboratory-based tests. Ten patients in the clinical group received a total of 16 units of fresh frozen plasma and nine platelet concentrates compared with five patients transfused with five units of fresh frozen plasma and one platelet concentrate in the algorithm group. Twelve-hour chest tube losses [algorithm group 470 (295-820) ml, clinically managed group 390 (240-820) ml (median, quartile values)] were not different between groups despite the threefold reduction in the use of haemostatic products, showing that intra-operative monitoring of coagulation in the anticoagulated patient can be used to guide treatment.", "Using algorithms based on point of care coagulation tests can decrease blood loss and blood component transfusion after cardiac surgery. We wished to test the hypothesis that a management algorithm based on near-patient tests would reduce blood loss and blood component use after routine coronary artery surgery with cardiopulmonary bypass when compared with an algorithm based on routine laboratory assays or with clinical judgement.\n Patients (n=102) undergoing elective coronary artery surgery with cardiac bypass were randomized into two groups. In the point of care group, the management algorithm was based on information provided by three devices, the Hepcon, thromboelastography and the PFA-100 platelet function analyser. Management in the laboratory test group depended on rapidly available laboratory clotting tests and transfusion of haemostatic blood components only if specific criteria were met. Blood loss and transfusion was compared between these two groups and with a retrospective case-control group (n=108), in which management of bleeding had been according to the clinician's discretion.\n All three groups had similar median blood losses. The transfusion of packed red blood cells (PRBCs) and blood components was greater in the clinician discretion group (P<0.05) but there was no difference in the transfusion of PRBCs and blood components between the two algorithm-guided groups.\n Following algorithms based on point of care tests or on structured clinical practice with standard laboratory tests does not decrease blood loss, but reduces the transfusion of PRBCs and blood components after routine cardiac surgery, when compared with clinician discretion. Cardiac surgery services should use transfusion guidelines based on laboratory-guided algorithms, and the possible benefits of point of care testing should be tested against this standard.", "Aortic surgical procedures requiring hypothermic circulatory arrest are associated with altered hemostasis and increased bleeding. In a randomized clinical trial, we evaluated effects of thromboelastometrically guided algorithm on transfusion requirements.\n Fifty-six consecutive patients (25 with acute type A dissection) undergoing aortic surgery with hypothermic circulatory arrest were enrolled in a randomized trial during a 6-month period. Patients were randomly allocated to treatment group (n = 27) with thromboelastometrically guided transfusion algorithm or control group (n = 29) with routine transfusion practices (clinical judgment-guided transfusion followed by transfusion according to coagulation test results). Primary end point was cumulative allogeneic blood units (red blood cells, fresh-frozen plasma, and platelets) transfused.\n Transfusion of allogeneic blood was significantly reduced in the thromboelastometry group: median 9.0 units (interquartile range, 2.0-30.0 units) versus. 16.0 units (9.0-23.0 units, P = .02). Most significant decrease was in the use of fresh-frozen plasma (3.0 units, 0-12.0 units, vs 8.0 units, 4.0-18.0 units, P = .005). Postoperative blood loss (890 mL/d, 600-1250 mL/d vs 950 mL/d, 650-1400 mL/d, p = 0.5) and rate of surgical re-exploration (19% vs 24%, P = .7) were similar between groups. Thromboelastometrically guided algorithm significantly decreased need for massive perioperative transfusion (odds ratio, 0.45; 95% confidence interval, 0.2-0.9; P = .03) in multivariable logistic regression analysis.\n Thromboelastometrically guided transfusion is associated with a decreased use of allogeneic blood units and reduced incidence of massive transfusion in patients undergoing aortic surgery with circulatory arrest.\n Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.", "Transfusion therapy after cardiac surgery is empirically guided, partly due to a lack of specific point-of-care hemostasis monitors. In a randomized, blinded, prospective trial, we studied cardiac surgical patients at moderate to high risk of transfusion. Patients were randomly assigned to either a thromboelastography (TEG)-guided transfusion algorithm (n = 53) or routine transfusion therapy (n = 52) for intervention after cardiopulmonary bypass. Coagulation tests, TEG variables, mediastinal tube drainage, and transfusions were compared at multiple time points. There were no demographic or hemostatic test result differences between groups, and all patients were given prophylactic antifibrinolytic therapy. Intraoperative transfusion rates did not differ, but there were significantly fewer postoperative and total transfusions in the TEG group. The proportion of patients receiving fresh-frozen plasma (FFP) was 4 of 53 in the TEG group compared with 16 of 52 in the control group (P < 0.002). Patients receiving platelets were 7 of 53 in the TEG group compared with 15 of 52 in the control group (P < 0.05). Patients in the TEG group also received less volume of FFP (36 +/- 142 vs 217 +/- 463 mL; P < 0.04). Mediastinal tube drainage was not statistically different 6, 12, or 24 h postoperatively. Point-of-care coagulation monitoring using TEG resulted in fewer transfusions in the postoperative period. We conclude that the reduction in transfusions may have been due to improved hemostasis in these patients who had earlier and specific identification of the hemostasis abnormality and thus received more appropriate intraoperative transfusion therapy. These data support the use of TEG in an algorithm to guide transfusion therapy in complex cardiac surgery. Implications: Transfusion of allogeneic blood products is common during complex cardiac surgical procedures. In a prospective, randomized trial, we compared a transfusion algorithm using point-of-care coagulation testing with routine laboratory testing, and found the algorithm to be effective in reducing transfusion requirements.", "Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding.\n The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests.\n Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8% vs. 0%; P = 0.032).\n Use of a coagulation test-based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss.", "Allogenic blood transfusion may affect clinical outcomes negatively. Up to 20% of blood transfusions in the United States are associated with cardiac surgery and so strategies to conserve usage are of importance. This study compares administration according to physician's choice based on laboratory coagulation tests with application of a strict protocol based on the thromboelastograph (TEG).\n Sixty-nine patients presenting for cardiac surgery were randomised to either study or control groups. In the study group a strict protocol was followed covering usage of all blood products according to TEG patterns. In the control group, the physician directed product administration with reference to activated partial thromboplastin time (APTT), international normalised ratio (INR), fibrinogen and platelet count. Bleeding, re-sternotomy, minimum haemoglobin, intubation time, and ICU stay were documented.\n TEG-based management reduced total product usage by 58.8% in the study group but this was not statistically significant. This was associated with a statistically insignificant trend towards better short-term outcomes.\n This pilot study suggests that a strict protocol for blood product replacement based on the TEG might be highly effective in reducing usage without impairing short-term outcome.", "To test in a prospective randomized study the hypothesis that use of thromboelastography (TEG) decreases blood transfusion during major surgery.\n Twenty-eight patients undergoing orthotopic liver transplantation were recruited over 2 years. Patients were randomized into 2 groups: those monitored during surgery using point-of-care TEG analysis, and those monitored using standard laboratory measures of blood coagulation. Specific trigger points for transfusion were established in each group.\n In patients monitored via TEG, significantly less fresh-frozen plasma was used (mean [SD], 12.8 [7.0] units vs 21.5 [12.7] units). There was a trend toward less blood loss in the TEG-monitored patients; however, the difference was not significant. There were no differences in total fluid administration and 3-year survival.\n Thromboelastography-guided transfusion decreases transfusion of fresh- frozen plasma in patients undergoing orthotopic liver transplantation, but does not affect 3-year survival.\n 2010 Elsevier Inc. All rights reserved." ]

[ "16055570", "16458640", "8018648", "3554063", "17303495" ]

[ "Misoprostol compared with laminaria before early second-trimester surgical abortion: a randomized trial.", "Cervical preparation using laminaria with adjunctive buccal misoprostol before second-trimester dilation and evacuation procedures: a randomized clinical trial.", "Randomised trial of hypan versus gemeprost in cervical preparation prior to second trimester termination of pregnancy.", "Lamicel versus laminaria for cervical dilation before early second-trimester abortion: a randomized clinical trial.", "Vaginal vs. sublingual misoprostol with mifepristone for cervical priming in second-trimester abortion by dilation and evacuation: a randomized clinical trial." ]

[ "To compare the efficacy and acceptability of same-day misoprostol and overnight laminaria for cervical ripening before early second-trimester surgical abortion.\n We performed a randomized, double-blinded, controlled trial comparing 400 microg of vaginal misoprostol, given 3-4 hours preoperatively, with overnight laminaria before early second-trimester surgical abortion among women at 13.0-16.0 weeks of gestation (n = 84). The primary outcome was procedure time, and the sample size was based on 95% power to detect a difference of 4.5 minutes between groups. Secondary outcomes included completion of the procedure on the first attempt, procedural difficulty, and patients' pain scores and preferences.\n The average gestational duration was 14 weeks 6 days. Procedures performed after laminaria were significantly faster than those after misoprostol (median 3.4 versus 7.2 minutes, respectively, P = .01). Laminaria patients had significantly greater dilation than misoprostol patients at abortion (mean 43 versus 33 French, P < .001), and more misoprostol patients required additional dilation (85% versus 21%, P < .001). Physicians rated 27% of the misoprostol procedures as moderate-markedly difficult versus 5% of laminaria procedures (P = .01). Differences in efficacy were pronounced among nulliparous patients. There were no significant differences in ability to complete the procedure on the first attempt or patients' intraoperative pain scores. More women in the misoprostol group would choose their assigned method again (93% versus 62%, P < .01), and 82% of all subjects preferred a 1-day procedure.\n Early second-trimester abortions take longer and are technically more challenging after cervical ripening with same-day misoprostol than with overnight laminaria, but patients prefer same-day misoprostol.", "This study was undertaken to determine whether buccal misoprostol improves cervical preparation achieved with laminaria before second-trimester dilation and evacuation procedures.\n A randomized, double blind, placebo-controlled trial of preoperative cervical preparation with overnight laminaria and either buccal placebo or 400 microg buccal misoprostol approximately 90 minutes before second-trimester surgical abortion. Block randomization was used to provide balanced enrollment into 2 separate gestational age study groups: early (13-15(6/7)) and mid (16-20(6/7)) second trimester. Surgeons tested maximal cervical dilation by inserting the largest dilator that could be passed through the cervical os without force. Subject demographics and preprocedure symptoms were tracked.\n Groups were similar in regard to age, gravity, parity, delivery type, and gestational age. Data were analyzed from 125 women in the 13 to 15(6/7) (30 misoprostol, 32 placebo) and 16 to 20(6/7) (31 misoprostol, 32 placebo) gestational age groups. Overall, misoprostol treatment did not improve the initial mean dilation achieved with laminaria alone in either the 13 to 15(6/7) (46.0 fr +/- 5.0; placebo 45.0 fr +/- 6.2, P = .68) or 16 to 20(6/7) (50.9 fr +/- 5.6, placebo 48.9 fr +/- 5.2, P = .16) groups. However, a subanalysis of gestations 19 weeks or more demonstrated significantly greater dilation in the misoprostol group (53.6 fr fr +/- 5.3, placebo 48.5 fr +/- 5.0, P = .01). Subjects receiving misoprostol reported significantly more cramping than those receiving placebo (13-15(6/7) weeks misoprostol 25/30, 83%; placebo 17/32, 53%, P = .02; 16-20(6/7) week misoprostol 25/31, 81%, placebo 16/32, 50%, P = .02).\n Cervical dilation with laminaria is augmented by 400 microg buccal misoprostol in gestations 19 weeks or more, but not in earlier gestations. Misoprostol causes more abdominal cramping.", "nan", "Lamicel is a synthetic osmotic cervical dilator reported to work within two hours. To evaluate its efficacy and side effects, we conducted a double-blind, randomized clinical trial comparing Lamicel with multiple laminaria for cervical dilation in 219 patients before second-trimester abortion. A single Lamicel produced significantly less initial dilation (two-tailed P value = .03) than did multiple laminaria, but the techniques had comparable degrees of difficulty in subsequent dilation to 43 French units (two-tailed P value greater than .05) and rates of achieving dilation of 43 French units with rigid dilators (relative risk 1.0; 95% confidence interval 0.9-1.1). Lamicel removal resulted in a significantly lower rate of bleeding from the os (relative risk 0.3; 95% confidence interval 0.2-0.5). Because of its greater convenience, lower cost per patient, and comparable efficacy, Lamicel appears to be an attractive alternative to multiple laminaria for cervical dilation before abortion at 14-16 menstrual weeks' gestation.", "The study was conducted to assess the effectiveness of mifepristone 200 mg 48 h before administering misoprostol 600 mug, sublingual vs. vaginal route, prior to dilation and evacuation (D&E) in 12- to 20-week pregnancies.\n Randomized clinical trial.\n Clínica Mediterrania Médica, Valencia, Spain.\n Women with 12- to 20-week pregnancies wanting a voluntary abortion between July 9, 2004, and February 9, 2006.\n Nine hundred women were randomized to be included in one of the following four groups: (I) mifepristone 200 mg plus sublingual misoprostol 600 microg before D&E, (II) mifepristone 200 mg plus vaginal misoprostol 600 microg before D&E, (III) sublingual misoprostol 600 microg before D&E and (IV) vaginal misoprostol 600 microg before D&E.\n The degree of cervical dilation achieved before D&E, surgical time necessary to terminate the pregnancy and side effects of misoprostol.\n The average cervical dilation in the mifepristone groups was 12.5+/-2.8 mm (SD) [95% confidence interval (CI), 12.3-12.8] vs. 8.5+/-3.2 mm (SD) (95% CI, 8.2-8.8) in those receiving only misoprostol. Surgical time in the mifepristone sublingual misoprostol group was 11.9+/-4.3 min (SD) vs. 13.0+/-5.3 min (SD) in the sublingual misoprostol group without mifepristone (p=.007); in the mifepristone vaginal misoprostol group, the average surgical time was 12.3+/-5.0 min (SD) vs. 13.0+/-6.2 (SD) in the vaginal misoprostol group without mifepristone (p=.031).\n Administering mifepristone before D&E with misoprostol in second-trimester abortions makes surgery easier and shorter and, to a certain extent, lessens the risk of cervical injuries, especially in D&E in advanced gestational periods." ]

[ "2065405", "3544892", "9425369", "3329780", "10929148", "10717757", "7866044", "11681222", "1812599", "11044276", "3293827", "2190705", "11584755", "3048759", "8698011", "3330414", "6398531", "8673817", "6141423", "8311568", "1496699", "11253274", "1616392", "11672461", "11502317", "8187656" ]

[ "[Comparative efficacy of chloroquine and amodiaquine (25 and 35 mg/kg) in school children infected with P. falciparum (Brazzaville, March 1990)].", "Amodiaquine less effective than chloroquine in the treatment of falciparum malaria in the Philippines.", "In-vivo resistance of Plasmodium falciparum to chloroquine and amodiaquine in south Cameroon and age-related efficacy of the drugs.", "Comparative efficacy of alternative primary therapies for Plasmodium falciparum infections in Malawi.", "In vivo efficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania.", "Amodiaquine remains effective for treating uncomplicated malaria in west and central Africa.", "[Parasitological and clinical response to amodiaquine versus chloroquine in the treatment of Plasmodium falciparum malaria in children in an endemic area].", "[Evaluation of efficacy and tolerance of amodiaquine versus chloroquine in the treatment of uncomplicated malaria outbreak in children of Gabon].", "Falciparum malaria fully cleared by amodiaquine, pyrimethamine-sulfadoxine and pyrimethamine-sulfalene in areas of chloroquine resistance in Dodoma, Tanzania.", "Chemoresistance of Plasmodium falciparum in the urban region of Yaounde, Cameroon. Part 2: Evaluation of the efficacy of amodiaquine and sulfadoxine-pyrimethamine combination in the treatment of uncomplicated Plasmodium falciparum malaria in Yaounde, Cameroon.", "Evaluation of four therapeutic regimens for falciparum malaria in Mozambique, 1986.", "[Uncomplicated malaria attack in an area with high chloroquine resistance. 2. Evaluation of first-choice therapeutic scheme].", "Gametocytaemia in Senegalese children with uncomplicated falciparum malaria treated with chloroquine, amodiaquine or sulfadoxine + pyrimethamine.", "Effectiveness of amodiaquine, sulfadoxine-pyrimethamine, and combinations of these drugs for treating chloroquine-resistant falciparum malaria in Hainan Island, China.", "A randomised controlled trial to assess the relative efficacy of chloroquine, amodiaquine, halofantrine and Fansidar in the treatment of uncomplicated malaria in children.", "[In vivo and in vitro sensitivity to 4-aminoquinolines of Plasmodium falciparum in Madagascar: results of a study conducted on the east coast (July 1985-July 1986)].", "The sensitivity of Plasmodium falciparum to chloroquine and amodiaquine in Ibadan, Nigeria.", "A randomized trial of chloroquine, amodiaquine and pyrimethamine-sulphadoxine in Gambian children with uncomplicated malaria.", "Effectiveness of amodiaquine as treatment for chloroquine-resistant Plasmodium falciparum infections in Kenya.", "Resistance of Plasmodium falciparum to antimalarial drugs in Equatorial Guinea.", "Parasitological, clinical and haematological response of children with Plasmodium falciparum to 4-aminoquinolines and to pyrimethamine-sulfadoxine with quinine in western Kenya.", "[Resistance of Plasmodium falciparum to 3 antimalarials in Turbo (Antioquia, Colombia), 1998].", "Evaluation of the relative efficacy of various antimalarial drugs in Nigerian children under five years of age suffering from acute uncomplicated falciparum malaria.", "Randomized comparison of chloroquine and amodiaquine in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children.", "Amodiaquine, sulfadoxine/pyrimethamine, and combination therapy for treatment of uncomplicated falciparum malaria in Kampala, Uganda: a randomised trial.", "Response of falciparum malaria to chloroquine and three second line antimalarial drugs in a Kenyan coastal school age population." ]

[ "The efficacy of 4 therapeutic schedules was compared in March and April 1990 in Brazzaville school children, aged between 6 and 8 years, with parasitaemia of at least 1,000 trophozoites of Plasmodium falciparum per mm3. It was possible to interpret 125 simplified in vivo tests. The results showed that the activity of amodiaquine is still relatively satisfactory. The activity of chloroquine was slightly lower with the schedule of 25 mg/kg but was good at 35 mg/kg. Although these results were obtained in children who were mostly asymptomatic, they show that the use of amino-4-quinolines is still justified, at least in the initial treatment of uncomplicated malaria in semi-immune congolese subjects.", "Amodiaquine was compared to chloroquine in two groups of Filipino patients with uncomplicated falciparum malaria. Every patient received 25 mg/kg of base orally given over three days. In a hospital study, all eight patients receiving chloroquine cleared their parasitemia by day 6, but six of eight patients receiving amodiaquine failed to clear parasitemia and in four patients there was no response at all (RIII resistance); this difference was significant (P less than 0.01). In a village based study, there was initial clearing of parasitemia in each patient. However, recrudescent infection occurred in all five patients receiving amodiaquine (RI resistance). Five of six falciparum infections were sensitive to chloroquine, while parasitemia reappeared in one patient. In this village, resistance to amodiaquine was significantly more common than resistance to chloroquine (P less than 0.05). To our knowledge, this is the first report of amodiaquine being substantially worse than chloroquine in the treatment of Plasmodium falciparum infection.", "nan", "In Malawi, where high levels of chloroquine resistance were shown using a modified 7-day in vivo test, amodiaquine and pyrimethamine-sulfadoxine were evaluated as alternative initial therapies for Plasmodium falciparum infections in children under 5 years old. Therapy success rates, judged by parasite clearance by day 7 after initiation of therapy, were significantly greater among 39 children treated with amodiaquine at 10 mg/kg (90%), 37 receiving amodiaquine at 25 mg/kg (97%), and 34 receiving pyrimethamine-sulfadoxine (100%) at a dose of 25 mg sulfadoxine/kg, than among those treated with chloroquine at a dose of 25 mg/kg (59%) (P = 0.01). Extension of the follow-up period of those receiving amodiaquine (25 mg/kg) and pyrimethamine-sulfadoxine to 21 d revealed a progressively increasing rate of parasite recrudescence in the amodiaquine group (34%), but no recrudescence in the pyrimethamine-sulfadoxine group. These results suggest that, in Malawi, amodiaquine and pyrimethamine-sulfadoxine are superior to chloroquine in producing prompt clearance of P. falciparum parasites among young children, and that pyrimethamine-sulfadoxine alone is superior to the 4-aminoquinolines in sustaining P. falciparum clearance.", "We conducted two randomized clinical trials to determine the in vivo efficacy of amodiaquine and sulfadoxine/pyrimethamine in treating Plasmodium falciparum malaria. Seventy-five patients under the age of 10 years in Kibwezi, Kenya, and 171 patients in Kigoma, Tanzania, were enrolled for treatment. Due to loss of eight patients in Kibwezi and 37 in Kigoma to follow-up, we used best and worst case scenarios for the parasitological response. The in vivo sensitivity of Plasmodium falciparum to amodiaquine was 75% (no loss to follow-up) in Kibwezi and ranged from 85% in the best to 65% in the worst case scenario in Kigoma. The sensitivity to sulfadoxine/pyrimethamine was 70% to 88% in Kibwezi and 65% to 89% in Kigoma. R1 resistance to amodiaquine was 22% in Kibwezi and varied from 6% in the best to 26% for the worst case scenario in Kigoma. The R1 resistance to sulfadoxine/pyrimethamine was 5% to 23% in Kibwezi and 2% to 26% in Kigoma. R2 resistance was 3% for amodiaquine and 7% for sulfadoxine/pyrimethamine in Kibwezi and 9% in Kigoma for each treatment group. There was no statistically significant difference between treatment groups at either study site, except for a slight difference in R1 resistance in the best case scenario, Kibwezi, in favour of S/P. Although both amodiaquine and sulfadoxine/pyrimethamine resistance seems to be increasing, these antimalarials are still effective in parasite clearance.", "Many countries in Africa are now confronted with the dilemma of shifting drug policies for uncomplicated falciparum malaria from chloroquine, which has become largely ineffective, to a new first-line drug and amodiaquine is one of the possible options. A multicentre, open-label randomized controlled trial of amodiaquine 30 mg/kg vs chloroquine 25 mg/kg over 3 days was performed in Senegal, Cameroon, Gabon, and Burkina Faso between 1996 and 1998 and patients were followed-up for 14 days. Sensitivity of isolates in vitro and whole blood levels of chloroquine and amodiaquine were also measured. The primary efficacy parameter was parasitological clearance on day 14 (parasitological success). The secondary efficacy parameter was absence of signs/symptoms of malaria on day 14 (clinical success). Among the 364 patients randomized and receiving the assigned treatment (chloroquine n = 185, amodiaquine n = 179), 137 and 139, respectively, reached the primary endpoint. Amodiaquine proved significantly more effective than chloroquine. The summary odds ratio (95% CI) was 7.79 (4.54-13.35) for parasitological success, and 6.3 (3.4-11.68) for clinical success. Sensitivity in vitro and chloroquine blood levels were good predictors of chloroquine failure. Amodiaquine remains effective for treating uncomplicated falciparum malaria in areas of West and Central Africa where chloroquine resistance is prevalent. However, measures should be taken to protect the lifespan of amodiaquine where the drug is introduced for use.", "The therapeutic management of malaria in endemic regions is now hampered not only by the limited number of antimalarial agents, but also by the appearance of chemoresistant plasmodial strains and by the sometimes severe adverse effects related to the use of some of these drugs. Between January and July 1993, 100 patients presenting with symptomatic Plasmodium falciparum malaria were randomised to receive amodiaquine or chloroquine at the dose of 30 mg/kg for 3 days. The objective of this study was to compare the efficacy and safety of these two 4-aminoquinolines in the treatment of uncomplicated malaria. The parasite clearance was 4.87 (+/- 0.33) days in the amodiaquine group and 5.55 (+/- 0.31) days in the chloroquine group. All subjects in both groups were afebrile by D7. Cutaneous adverse effects, such as pruritus, were reported with both amodiaquine (3.2%) and chloroquine (6.8%). Amodiaquine was found to be significantly more effective than chloroquine in terms of parasite clearance on D7. The therapeutic failure rate was 0% for amodiaquine versus 16.3% for chloroquine. At a time when chemoresistance of Plasmodium falciparum, especially chloroquine-resistance, has spread to malarial endemic zones, amodiaquine should be very widely indicated in the treatment of simple malaria due to its excellent efficacy and good safety.", "We conducted a prospective study from September 1997 to January 1998 in Libreville (Gabon). Fifty-three (53) children with uncomplicated P. falciparum malaria were included and divided into two groups. The first group (27 patients) was treated with amodiaquine and the second (26 patients) with chloroquine. The efficacy and tolerance of amodiaquine 30 mg/kg base over 3 days (10 mg/kg daily) and chloroquine 25 mg/kg base over 3 days (10 mg/kg day 0, 10 mg/kg day 1, 5 mg/kg day 3) were estimated at days 7 and 14. Clinical examination and parasitaemia were assessed on days 0, 1, 2, 3, 7, 14. Haematological and biochemical parameters were determined on days 0 and 7. Amodiaquine was shown to be more effective than chloroquine in clinical response and ridding patients of parasites: adequate clinical response was significantly higher with amodiaquine than chloroquine [100% (27/27) versus 45% (9/20), p < 0.0005]. Rates for early treatment failure (ETF) and late treatment failure (LTF) were respectively 35% and 12% with chloroquine. The parasitological success rate was significantly higher with amodiaquine than chloroquine on days 7 [93% (25/27) versus 62% (13/21), p < 0.008] and 14 [100% (13/13) versus 44% (4/9), p < 0.01]. The RI resistance type was 7% in the amodiaquine group. The rate of in vivo chloroquino-resistance was 53%, essentially of RII and RIII type. Overall, the two drugs were well tolerated.", "The in vivo response of Plasmodium falciparum to chloroquine, amodiaquine, pyrimethamine-sulfalene (MetakelfinR) and pyrimethamine-sulfadoxine (FansidarR) was assessed in Dodoma in 1988. Asymptomatic schoolchildren with pure P. falciparum infection were given full curative doses of one of the above antimalarials. Daily parasitological follow-ups were made for seven days. Overall successful follow-up cases were 101, 108, 95 and 97 on chloroquine, amodiaquine, MetakelfinR and FansidarR respectively. The overall resistance rate in the area was 28%. Most of the resistant cases were RII type. There was only one case of MetakelfinR resistance. Amodiaquine and FansidarR were fully effective in eliminating asexual parasitaemia from the blood in all the cases during the seven days of follow-up. The results indicate that chloroquine, a commonly used antimalarial in Tanzania, is not as effective as amodiaquine, a less used drug. Although the 'antifols' are still highly effective in Tanzania, their potency could change with continued use. These drugs should, therefore, be protected and used judiciously.", "The spread of chloroquine resistance or its stabilization at a high level calls for a change in the therapeutic strategy, including a possible replacement of chloroquine. We assessed and compared the efficacy of amodiaquine and sulfadoxine-pyrimethamine in Yaoundé. Of 140 adults and children > 5 years enrolled in the study, 59 in the amodiaquine and 58 in the sulfadoxine-pyrimethamine treatment group were followed until day 14. The efficacy of amodiaquine was 100%, whereas 12.1% of the patients treated with sulfadoxine-pyrimethamine responded with an early treatment failure. Side effects in both treatment groups were mild and did not require any specific treatment. We did in vitro drug assays for monodesethylamodiaquine (active metabolite of amodiaquine) and pyrimethamine and measured plasma levels of monodesethylamodiaquine, sulfadoxine, and pyrimethamine. Unlike amodiaquine, the results of the in vitro drug sensitivity test for pyrimethamine were not concordant with the clinical response. A wide inter-individual variation in the plasma drug levels was observed. Unlike chloroquine, the mean plasma concentrations did not vary with age. There was no significant difference in the plasma concentrations of sulfadoxine and pyrimethamine between patients responding with an adequate clinical response and those responding with treatment failure. Amodiaquine has several advantages over sulfadoxine-pyrimethamine combination and may be considered to be an effective drug in an endemic zone with a moderate level of chloroquine resistance.", "A randomized study on the effect of the following four treatment regimens on Plasmodium falciparum parasitaemia was carried out on 200 asymptomatic schoolchildren in Maputo, Mozambique: chloroquine (25 mg/kg body weight), amodiaquine (25 mg/kg), sulfadoxine-pyrimethamine (25 mg/kg and 1.25 mg/kg), or amodiaquine (25 mg/kg) + sulfadoxine-pyrimethamine (25 mg/kg and 1.25 mg/kg) administered on the third day of the study. The results of in vivo tests indicated that 94% of the infections were resistant to chloroquine, 76% to amodiaquine, and 16% to sulfadoxine-pyrimethamine. The cure rate with amodiaquine + sulfadoxine-pyrimethamine was 100%, which was not significantly different from that with sulfadoxine-pyrimethamine alone; the latter regimen was the most rapidly acting of the treatments studied. It is concluded that amodiaquine is not an appropriate substitute for chloroquine, but that the effect of the combination amodiaquine + sulfadoxine-pyrimethamine may be superior to that of sulfadoxine-pyrimethamine alone, although this requires further study.", "The authors evaluate the comparative efficiency of chloroquine and amodiaquine (35 mg/kg during 3 days) for uncomplicated malaria treatment in an area with high chemoresistance level. 236 patients with malaria were examined and treated. 38% of them previously used antimalarials. The increase dosage in comparison with the WHO recommendations (25 mg/kg), lead to no advantages for chloroquine treatment (50% failure), in contrast with amodiaquine (4% failure). Therefore amodiaquine might be preferred in the health field unit for uncomplicated malaria.", "Plasmodium falciparum gametocytaemia was studied in 266 Senegalese children (median 4 years, range 0.5-16) with uncomplicated malaria treated with chloroquine (CQ), amodiaquine (AQ) or sulfadoxine + pyrimethamine (SP). The proportion of resistant infections in vivo to these drugs was 44%, 16% and 7%, respectively. Gametocytes were counted by microscopy in thick smears on days 0, 4, 7 and 14 after treatment. There was a peak of gametocytaemia one week after treatment; on days 0, 7 and 14 the gametocyte prevalences were 35%, 73% and 63%, and the geometric means of gametocyte densities were 1.3, 12.5 and 5.6/microliter of blood. Three factors were found to influence gametocytaemia: treatment, efficacy of treatment, and duration of symptoms before treatment. Gametocyte prevalence and density significantly appeared higher in children treated with SP than with CQ, and higher with CQ than with AQ. Gametocyte prevalence and density were higher in resistant than in sensitive infections. The period between the appearance of the first clinical symptoms and treatment was positively and significantly linked to gametocyte prevalence and density on days 0 and 4. Early treatment with AQ, against sensitive infection, was followed by the lowest gametocytaemia. By contrast, treatment with SP against resistant infection was followed by the highest gametocytaemia. No clear relationship was observed between the density of asexual stages on day 0 and the gametocytaemia at any day between days 0 and 14. The epidemiological significance of post-therapeutic gametocytaemia and its possible role in the spread of resistant parasites are underlined. Solutions are proposed in order to avoid or reduce this gametocytaemia.", "The study was carried out in 1985-86 in Hainan Island where Plasmodium falciparum is resistant to chloroquine. Fifty cases of falciparum malaria were treated with 1800 mg amodiaquine for 3 days: the cure rate was 65.3%, and the mean time to clear fever and asexual parasitaemia was 30.7 and 60.3 hours, respectively; 34.7% of cases showed RI or RII recrudescence, and one patient's temperature did not come down to normal within 7 days.Twenty-one cases were treated with sulfadoxine-pyrimethamine (1500 mg and 75 mg, respectively): 19 were cured, I showed RI and another had an S or RI response; the mean time for fever control was 56.1 hours.Fifty cases were treated with amodiaquine plus sulfadoxine and 49 received amodiaquine plus sulfadoxine-pyrimethamine: the cure rate was 97.9% and 100%, respectively; the mean time for fever clearance was 25.0 and 25.7 hours and for parasite clearance 57.1 and 52.8 hours, respectively. These drug combinations gave much better results for cure and for symptom control than amodiaquine or sulfadoxine-pyrimethamine alone, and may be considered for treatment of chloroquine-resistant falciparum malaria.", "A randomised controlled trial was carried out to determine the relative efficacy of four commonly used antimalarial drugs in children aged three to twelve years presenting with uncomplicated malaria at the Eldoret District Hospital, Kenya. One hundred and eighty eight children were studied between July 1993 and July 1994. There were no significant baseline differences between treatment groups with respect to age, sex, weight, ethnicity, haemoglobin, white blood cell (WBC) counts, parasite counts, previous exposure to malaria and prior treatment. Of the 188 patients, eleven were lost to follow-up while twelve were discontinued from the study due to poor clinical response. Most of the latter (eight out of twelve) were in the chloroquine group. By day seven, there were significant differences (p = 0.004) in parasite clearance between groups. There were no significant statistical differences between the groups (p = 0.12) with regard to the fever clearance time. However, there was a significant statistical difference (p = 0.00003) between the treatment groups in the cure rates. Halofantrine was the most efficacious drug with 82% of the cases cured followed by fansidar(R)(62%), amodiaquine (55%) and chloroquine (29%). RI and RII resistance were observed in all the treatment groups, i.e. halofantrine (18%), fansidar (38%), amodiaquine (45%) and chloroquine (67%) while RIII resistance was only observed in the chloroquine group(3%).", "nan", "An extended in vivo test of the sensitivity of Plasmodium falciparum to antimalarial drugs in Nigerian children showed no evidence of resistance to chloroquine and amodiaquine. However, the results of a small number of in vitro tests suggest a decreased sensitivity of the parasite to chloroquine when compared with the results of earlier studies in the same locality.", "The increasing occurrence of chloroquine-resistant Plasmodium falciparum in sub-Saharan Africa makes it essential to reconsider current recommendations for the treatment of uncomplicated P.falciparum malaria. In an open, randomized trial, we have compared chloroquine (CQ), amodiaquine (AQ), and pyrimethamine-sulphadoxine (PS) in rural Gambian children with uncomplicated P.falciparum malaria. Three hundred children were randomly assigned at the time of consultation (Do) to oral treatment with 25 mg/kg CQ, 25 mg/kg AQ (both given over 3 days), or 1.25/25 mg/kg PS. They were reviewed on day 7 (D7) and day 28 (D28) for symptoms, malaria parasitaemia, and packed cell volume (PCV). Significantly more children treated with PS compared to CQ (17 vs 7%, P = 0.03) or AQ (17 vs 3%, P = 0.001) returned with clinical complaints during the first 3 days after treatment. Five of these patients had a generalized convulsion (1 from the AQ group, 4 from the PS group), of whom 4 developed cerebral malaria. At D7, significantly more patients treated with CQ compared to AQ (25 vs 7%, P = 0.0009) or PS (25 vs 4%, P = 0.0001) were parasitaemic. By D28, the cumulative number of parasitological failures was significantly higher in the CQ group compared to the AQ group (65 vs 35%, P = 0.0001), and significantly higher in the AQ group compared to the PS group (35 vs 14%, P = 0.001). Overall, 91% of parasitological failures observed during the study period were symptomatic and were consequently treated with an alternative antimalarial drug. Over the 28-day study period the mean PCV increased significantly less in the CQ group than in the PS group (1.2 vs 3.8%, P = 0.016) and was lower in the CQ group than in the AQ group (1.2 vs 2.7%, P = 0.12, not significant). These results suggest that PS acts more slowly than 4-aminoquinolines in controlling the clinical features of malaria, and that AQ can be considered as an interim alternative to CQ in the first-line therapy of uncomplicated malaria in African areas of high CQ resistance.", "Studies were conducted in Malindi, Kenya, to assess the response of Plasmodium falciparum to chloroquine and amodiaquine in vivo (by an extended 14-day test) and in vitro (with the Rieckmann micro test). In-vivo resistance was demonstrated in 19 of 69 (28%) infections treated with chloroquine, but in only 2 of 60 (3.3%) of those treated with amodiaquine (p less than 0.001). In-vitro resistance to chloroquine was demonstrated in 15 of 23 (65%) tests. In contrast, 22 of the same 23 isolates were sensitive to amodiaquine in vitro. Effective concentrations by probit analysis for 50% and 99% (EC50 and EC99) inhibition, respectively, were 180.7 and 4319.6 nmol/l for chloroquine and 12.2 and 147.0 nmol/l for amodiaquine. The results suggest that amodiaquine is effective for the treatment of chloroquine-resistant falciparum malaria in Kenya.", "One hundred and sixty-six children from Equatorial Guinea, all under 10 years of age and with acute uncomplicated falciparum malaria, were randomly allocated to four groups and treated with one of the following regimens: chloroquine or amodiaquine (25 mg base/kg body weight over 3 days), quinine (8 mg/kg every 8 h for 3 or 5 days), and sulphadoxine-pyrimethamine (25-1.25 mg/kg, in one dose). The parasite clearance rates up to day 14 were 28% with chloroquine, 74% with amodiaquine, and 95% with quinine or sulphadoxine-pyrimethamine. The times required to clear asexual blood forms of Plasmodium falciparum in sensitive cases were 64, 70, 73 and 65 h, respectively. Although quinine and sulphadoxine-pyrimethamine are equally effective, quinine is recommended for treatment of multidrug-resistant malaria in paediatric patients, essentially because of the risk of serious reactions to sulpha drugs. Health providers are, however, encouraged to keep supplies of sulphadoxine-pyrimethamine as an option and to refer patients quickly, if required.", "Children with Plasmodium falciparum infections in Western Province, Kenya, were studied in 1987 for their parasitological, clinical and haematological response to chloroquine, to amodiaquine and to pyrimethamine-sulfadoxine plus quinine. Ninety-eight children under 5 years of age were treated in 1 of 2 hospitals. Of the 56 patients treated with chloroquine base 25 mg/kg, 91% had resistant infections, with 36% having no significant decrease in parasitaemia (RIII resistance); however, 69% responded clinically within a week. Of the 27 patients treated with amodiaquine base 25 mg/kg, 67% had resistant infections, with 7% RIII resistant; 81% responded clinically. The parasites cleared in all 15 children given pyrimethamine-sulfadoxine plus 3 days of quinine. Only when parasites cleared did patients have improved haemoglobins and haematocrits. This study shows that parasitaemia in children hospitalized in western Kenya responds poorly to 4-aminoquinolines, although the patients improve clinically, at least during the first 7 days. Young children may need to clear parasites to avoid the risk of severe anemia and the need for blood transfusions.", "In 1998 we determined in vivo and in vitro the frequency and the degree of resistance of Plasmodium falciparum to the three antimalarials (chloroquine, amodiaquine, and sulfadoxine/pyrimethamine) most utilized in the municipality of Turbo (in the area of Urabá, Antioquia, Colombia), in a sample representative of the population with malaria. We carried out clinical and parasitological analyses over a 14-day period using the standard test recommended by the World Health Organization. In vivo, P. falciparum showed resistance to chloroquine, amodiaquine, and sulfadoxine/pyrimethamine, with a frequency of 97%, 7%, and 13%, respectively. In vitro, the corresponding figures were 21%, 23%, and 9%, respectively. For chloroquine the level of agreement between the in vivo and in vitro results was 23%.", "A parallel group-randomized comparison of the therapeutic efficacy of chloroquine (CQ), amodiaquine (AM), quinine (QN), sulphadoxine-pyrimethamine (S-P), mefloquine 15 mg kg-1 (M15) and mefloquine 25 mg kg-1 (M25) in acute symptomatic uncomplicated falciparum malaria was carried out in 325 children under the age of five years in Ibadan, southwestern Nigeria, using the 28-day in vivo test. The parasitological cure rate, assessed only up to day 14, was 85% in the CQ group and 100% in the other groups. The mean parasite and fever clearance times were, respectively, 2.64 and 1.20 days in the CQ-sensitive subgroup, 2.32 and 1.13 days in the AM group, 2.27 and 1.17 days in the QN group, 2.23 and 1.76 days in the S-P group, 2.13 and 1.10 days in the M15 group, and 2.07 and 1.09 days in the M25 group. The CQ-treatment failures (seven of 46 patients) were successfully treated with 25 mg kg-1 mefloquine, with parasite and fever clearance times of 1.73 and 1.0 days respectively. The study shows that, in Nigeria, CQ is now less effective than AM, S-P, QN and M in acute falciparum malaria in the group most vulnerable to the infection (the under-five-year-olds).(ABSTRACT TRUNCATED AT 250 WORDS)", "The increasing resistance of Plasmodium falciparum to chloroquine (CQ) has created an urgent need for the evaluation of alternative, effective, safe, cheap, readily available and affordable antimalarial treatments. In the present study, the efficacy of amodiaquine (AQ) in the treatment of acute, symptomatic, uncomplicated, P. falciparum malaria was compared with that of CQ, each drug being given at 10 mg/kg per day for 3 days (days 0, 1 and 2). The 210 subjects (104 given AQ and 106 CQ) were Nigerian children aged 5 months-12 years. Fever-clearance times (FCT), parasite densities on days 1-4 and parasite-clearance times (PCT) were all significantly lower with AQ than with CQ. Mean (S.D.) PCT, for example, were 2.6 (0.8) days with AQ and 3.0 (1.0) days with CQ (P = 0.001). The cure rates obtained on days 14, 21 and 28 - 98.1% v. 79.3% (P =0.000), 97.1% v. 64.2% (P = 0.00001) and 95.2% v. 58.5% (P = 0.0000000) with AQ and CQ, respectively - were all also significantly higher with AQ. All but two of the 20 subjects who were considered CQ-treatment failures by day 14 (i.e. two RIII, two RII and 16 RI) responded to subsequent treatment with AQ, with PCT (but not FCT) significantly shorter than during their initial treatment with CQ. In siblings in whom there was clustering of infections, the cure rates were 100% with AQ (N =12) and 63.6% with CQ (N = 11; P = 0.03). Adverse reactions to CQ and AQ were similar and tolerable: pruritus in 10 and 11 children in the AQ and CQ groups, respectively, and gastro-intestinal disturbances which occurred in three children from each group. Haematological parameters were not adversely affected by either drug. At least in the setting of the present study, AQ appears more effective than CQ, effective against CQ-resistant infections, and well tolerated by children with acute, uncomplicated, P. falciparum malaria. It may therefore be useful as an alternative to CQ in areas of CQ resistance.", "Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance.\n Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/pyrimethamine (25 mg/kg sulfadoxine, and 1.25 mg/kg pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed.\n 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5% vs 13.9%, respectively, risk difference 10.4% [95% CI, 1.6-19.3] p=0.021; parasitological failure in 12.8% vs 26.4%, risk difference 13.6% [1.2-26.0] p=0.041).\n Sulfadoxine/pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.", "Ambulatory rural school children in the Mombasa area with P. falciparum parasitaemia were examined and randomly assigned to treatment with one of three second-line antimalarials--amodiaquine, pyrimethamine/sulphadoxine (P/SD) and pyrimethamine/sulfalene (P/SL). Clinical signs and parasitaemia were followed daily for the first week and on days 14 and 28. WHO Mark II schizont inhibition tests were performed for all the above 3 drugs and chloroquine. The total number of cases was 73. The mean parasite density was 142.1 +/- 207; 102.7 +/- 166; 82.74 +/- 93 parasites per 300 WBC for amodiaquine, P/SD, and P/SL, respectively. In vitro tests showed a chloroquine resistance rate of 60% and no resistance to all of the second line drugs. Also, all children treated successfully cleared their parasitaemia with mean clearance rates of 2.05 +/- 0.57; 1.86 +/- 0.47; 2.05 +/- 0.50 days for amodiaquine, P/SD and P/SL, respectively. Even though, no difference in the effectiveness between the second line drugs used was found, reinfection rates as depicted by day 28 parasitaemia differed--amodiaquine 16%; P/SD 0%; and P/SL4.35%. This difference could be attributed to the difference in the pharmacokinetic properties of the drugs." ]

[ "9925837", "1586185", "11194534", "3105304", "8648531", "16027693", "9310537" ]

[ "Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method.", "Randomised trial of continuous nasogastric, bolus nasogastric, and transpyloric feeding in infants of birth weight under 1400 g.", "Feeding tolerance in preterm infants: randomized trial of bolus and continuous feeding.", "Enteral feeding in very-low-birth-weight infants. A comparison of two nasogastric methods.", "A prospective randomized trial comparing continuous versus intermittent feeding methods in very low birth weight neonates.", "Continuous feeding promotes gastrointestinal tolerance and growth in very low birth weight infants.", "A prospective randomized trial of feeding methods in very low birth weight infants." ]

[ "Data on enteral feeding management of premature infants are limited and often not the subject of randomized clinical trials. Several small studies suggest benefits from the early initiation of feeding, but do not assess the combined effects of time of initiation of feeding, tube-feeding method, and type of milk used. Either singly or in combination, these treatments may affect growth, bone mineralization, biochemical measures of nutritional status, and feeding tolerance, and, ultimately, the duration of hospitalization.\n A total of 171 premature infants, stratified by gestational age (26 to 30 weeks) and diet (human milk or preterm formula) were assigned randomly among four treatment combinations in a balanced two-way design comparing the presence or absence of gastrointestinal (GI) priming for 10 days and continuous infusion versus intermittent bolus tube-feeding.\n The major outcome, time required for infants to attain full oral feeding, was similar among treatments. GI priming was not associated with any measured adverse effect and was associated with better calcium and phosphorus retention, higher serum calcium and alkaline phosphatase activity, and shorter intestinal transit times. The bolus tube-feeding method was associated with significantly less feeding intolerance and greater rate of weight gain than the continuous method. In addition, the greater the quantity of human milk fed, the lower the morbidity.\n Early GI priming with human milk, using the bolus tube-feeding method, may provide the best advantage for the premature infant.", "Forty three infants under 1400 g were fed by a bolus nasogastric, continuous nasogastric, or transpyloric route. There were more complications with transpyloric feeding and no identifiable benefits in the growth rate, oral energy input, or chosen biochemical indices of nutrition. Bolus or continuous nasogastric feeds rather than transpyloric are better routine methods in infants of low birth weight.", "To test the hypothesis that continuous gastric infusion (CGI) is better tolerated than intermittent gastric bolus (IGB) in small very low birth weight (VLBW) infants.\n Two-center, prospective, randomized, unmasked clinical trial.\n 28 VLBW infants (birth weight <1250 g). A strict feeding protocol was followed.\n Patients were randomized to IGB or CGI.\n Time to reach full feeds (160 cc/kg/d)(by design and real), daily weight, caloric intake, residual gastric volume and type of feeding (formula vs. human milk vs. both).\n Five infants failed to complete the study because of death (n = 4) or protocol violation (n = 1). The two groups did not differ by birth weight or gestational age; infants fed via IGB reached full feeds earlier (p = 0.03) and had less delay in reaching full feeds than infants fed via CGI.\n Contrary to our hypothesis, gravity IGB is more effective than CGI in improving feeding tolerance in small VLBW infants.", "Nutritional benefits and feeding-related complications were prospectively compared in 53 preterm very-low-birth-weight infants receiving isoenergetic feeding by either the continuous nasogastric (n = 30) or intermittent nasogastric (n = 23) route. Stepwise regression techniques were used to develop models relating feeding-associated factors. Feeding method significantly affected weight gain in infants 1000 to 1249 g birth weight with continuous nasogastric feeding associated with an additional weight gain of 3.6 to 6.1 g/kg/d. No effects of feeding method on changes in occipitofrontal circumference, triceps skin-fold thickness, bilirubin values, or total protein values were demonstrable. There were few major differences between feeding groups on measures of feeding complications. Continuous nasogastric feeding was fairly well tolerated and resulted in improved weight gain when compared with intermittent nasogastric feeding in preterm infants 1000 to 1249 g birth weight.", "To compare the effects of continuous versus intermittent feedings on physical growth, gastrointestinal tolerance, and macronutrient retention in very low birth weight infants ( < 1500 gm).\n Very low birth weight neonates stratified by birth weight were randomly assigned to either continuous (24-hour) or intermittent (every 3 hours) nasogastric feedings. Feedings with half-strength Similac Special Care formula were initiated between day 2 and 3 and were advanced isoenergetically to goal. Daily weights, volume/caloric intakes, weekly anthropometric and dynamic skin-fold thickness measurements, and data on feeding milestones and clinical complications were collected. Nitrogen, carbohydrate, and fat balance studies were performed on a subset of male subjects.\n Eighty-two neonates with birth weights between 750 and 1500 gm who were born between 27 and 34 weeks of gestation were randomly assigned to continuous (n = 42) and intermittent (n = 40) feeding groups. There were no significant differences in baseline demographics and severity of respiratory distress between groups. There were no significant differences in days to regain birth weight, days to full enteral feedings, days to discharge, and discharge anthropometric measurements between continuously fed and intermittently fed infants, both when evaluated together and according to 250 gm weight intervals. Retention rates of nitrogen, fat, total carbohydrate, and lactose were comparable in the continuously fed (n = 17) and intermittently fed (n = 13) male neonates. Very low birth weight neonates who were fed continuously did not have feeding-related complications.\n Very low birth weight infants achieve similar growth and macronutrient retention rates and have comparable lengths of hospital stay whether they are fed with continuous or intermittent feedings.", "To compare the effects of continuous versus intermittent feeding on gastrointestinal tolerance and growth in very low birth weight (VLBW) infants.\n In a randomized, controlled trial conducted at 3 neonatal units, 70 premature infants with a gestational age 24 to 29 weeks and birth weight < 1200 g were assigned to 1 of 3 feeding methods: continuous nasogastric feeding, intermittent nasogastric feeding, or intermittent orogastric feeding. Feeding was initiated within 30 hours of birth. Daily enteral and parenteral volumes, caloric and protein intakes, growth, enteral intolerance, and clinical complications were recorded. Cox regression analysis was used to determine primary outcome, the time to achieve full enteral feeding.\n The continuously fed infants achieved full enteral feeding significantly faster than the intermittently fed infants (hazard ratio [HR] = 1.86; 95% confidence interval [CI] = 1.07 to 3.22). In stratified analysis according to birth weight, the improvement was even more pronounced in the smallest infants, those with birth weight < or = 850 g (adjusted HR = 4.13; 95% CI = 1.48 to 11.53). Growth rate was significantly faster in the continuously fed infants ( P = .002).\n In VLBW infants, continuous feeding seems to be better than intermittent feeding with regard to gastrointestinal tolerance and growth.", "To test the hypothesis that very low birth weight infants fed by continuous nasogastric gavage (CNG) would achieve full enteral feedings (100 kcal/kg/d) at an earlier postnatal age and have less feeding intolerance (FI) than infants fed by intermittent bolus gavage (IBG).\n Eighty infants were stratified by birth weight (700 to 1000 g and 1001 to 1250 g) and randomized into CNG or IBG feeding groups. CNG infants were comparable with IBG in birth weight, gestational age, sex, race, and day of onset of feeding (5.7 +/- 2.1 days vs 5.6 +/- 2.2 days, respectively). Feedings were given as undiluted Similac Special Care formula (Ross Laboratories, Columbus, OH) via a specific protocol designed for each 50 to 100 g birth weight category. Feedings were advanced isoenergetically by a maximum of 25 mL/kg/d until an endpoint of 100/kcal/kg/d for at least 48 hours was reached. An infant whose feedings were withheld for >12 hours based on predetermined criteria was considered to have an episode of FI.\n Infants in the CNG group reached full enteral feeding at 17.1 +/- 8.9 days compared with 15.5 +/- 5.5 days in the IBG group; these were not statistically different. Secondary outcome variables such as days to regain birth weight (CNG, 12.6 +/- 5 days vs IBG, 12.5 +/- 3.7 days), days to reach discharge weight of 2040 g (CNG, 60 +/- 13.4 days vs IBG, 62 +/- 13.6 days), and number of episodes of FI were not significantly different between feeding methods. FI was primarily associated with birth weight </=1000 g (71%) vs 1001 to 1250 g (38%).\n Feeding methods are associated with similar outcomes when feeding regimens are comparable." ]

[ "3286039", "11704449", "1863725", "1529684", "1622045", "2521029", "1610009", "11698939", "2682243", "1472662", "8937605", "8400098", "8306217", "1903723", "7475139", "8202769", "10408485", "7519132", "1434725", "3517650", "14980901", "1934382", "2405964", "1614196", "2042789", "7674464", "7572006" ]

[ "Does desmopressin acetate reduce blood loss after surgery in patients on cardiopulmonary bypass?", "The effect of tourniquet application, tranexamic acid, and desmopressin on the procoagulant and fibrinolytic systems during total knee replacement.", "Desmopressin acetate is a mild vasodilator that does not reduce blood loss in uncomplicated cardiac surgical procedures.", "Effects of desmopressin on blood loss in hip arthroplasty. Controlled study in 50 patients.", "Haemostatic responses to desmopressin acetate after primary coronary artery bypass surgery.", "Desmopressin acetate following cardiopulmonary bypass: evaluation of coagulation parameters.", "The role of desmopressin acetate in patients undergoing coronary artery bypass surgery. A controlled clinical trial with thromboelastographic risk stratification.", "Desmopressin usage in elective cardiac surgery.", "A trial of desmopressin (1-desamino-8-D-arginine vasopressin) to reduce blood loss in uncomplicated cardiac surgery.", "Repeated dose administration of desmopressin acetate in uncomplicated cardiac surgery: a prospective, blinded, randomized study.", "The role of DDAVP (desmopressin) in orthognathic surgery.", "Influence of desmopressin acetate on homologous blood requirements in cardiac surgical patients pretreated with aspirin.", "Use of desmopressin acetate to reduce blood transfusion requirements during cardiac surgery in patients with acetylsalicylic-acid-induced platelet dysfunction.", "Blood loss and safety with desmopressin or placebo during aorto-iliac graft surgery.", "Aprotinin versus desmopressin for patients undergoing operations with cardiopulmonary bypass. A double-blind placebo-controlled study.", "Desmopressin acetate in cardiac surgery: a double-blind, randomized study.", "Use of point-of-care test in identification of patients who can benefit from desmopressin during cardiac surgery: a randomised controlled trial.", "Randomized study of aprotinin and DDAVP to reduce postoperative bleeding after cardiopulmonary bypass surgery.", "The effect of desmopressin acetate on postoperative hemorrhage in patients receiving aspirin therapy before coronary artery bypass operations.", "Treatment with desmopressin acetate to reduce blood loss after cardiac surgery. A double-blind randomized trial.", "Prophylactic treatment with desmopressin does not reduce postoperative bleeding after coronary surgery in patients treated with aspirin before surgery.", "Hemostatic effects of tranexamic acid and desmopressin during cardiac surgery.", "Desmopressin acetate in uncomplicated coronary artery bypass surgery: a prospective randomized clinical trial.", "Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study.", "Hemodynamic consequences of desmopressin administration after cardiopulmonary bypass.", "Does desmopressin improve hemostasis and reduce blood loss from aortic surgery? A randomized, double-blind study.", "Desmopressin acetate does not reduce blood loss during total hip replacement in patients receiving dextran." ]

[ "It has been suggested that desmopressin acetate (DDAVP) administration reduces blood loss after cardiac surgery. We have investigated the effect of DDAVP administration in a double-blind, randomized, prospective trial including 100 patients placed on cardiopulmonary bypass during surgery. Fifty patients received 0.3 micrograms/kg DDAVP and 50 patients received a placebo administered in a 50 ml saline solution over 15 min when cardiopulmonary bypass had been concluded. Results showed no significant differences either in total blood loss per square meter (458 +/- 206 ml in the DDAVP group vs 536 +/- 304 ml in the placebo group) or in necessity for red cell transfusions (1642 +/- 705 ml in the DDAVP group vs 1574 +/- 645 ml in the placebo group) in the first 72 hr after surgery. Only intraoperative blood loss per square meter was significantly lower (p less than .02) in the DDAVP group (131 +/- 106 ml) as compared with the placebo group (193 +/- 137 ml). The prolongation of bleeding time and the decrease of factor VIII:C and factor VIII:von Willebrand factor 90 min after treatment were significantly lower (p less than .001) in the DDAVP group as compared with the placebo group. We conclude that the administration of DDAVP in patients placed on cardiopulmonary bypass during surgery does not reduce total blood loss and is only effective in reducing intraoperative bleeding.", "To assess the influence of tourniquet inflation-deflation as well as desmopressin and tranexamic acid (TA) administration on prothrombin fragment 1.2, fibrinogen, plasmin antiplasmin complex, and D-dimer concentrations during total knee replacement.\n Randomized, placebo-controlled study.\n Large referral hospital.\n 30 ASA physical status I, II, and III patients undergoing total knee replacement.\n Patients were randomized to one of three treatment groups. Patients received either tranexamic acid, desmopressin, or an equal volume of saline, intravenously.\n Cubital blood was drawn immediately before induction of anesthesia, 1 hour after tourniquet application, and 2 and 15 minutes after tourniquet deflation. Fibrinogen and D-dimer levels were measured using the Clauss Method and latex agglutination, respectively. Plasmin antiplasmin complex and prothrombin fragment 1.2 levels were measured by enzyme-linked immunosorbent assay (ELISA). All assays were performed in duplicate, and intra-assay variability was documented. No statistically significant difference in fibrinogen, D-dimer, plasmin antiplasmin complex, or prothrombin fragment 1.2 levels was demonstrated among the groups. Similarly, within each group there were no statistically significant differences in the variables studied. However, despite the lack of statistical significance, when compared with their levels during tourniquet application, an increase in D-dimer and plasmin antiplasmin complex levels was observed in all three groups at 2 and 15 minutes after tourniquet release. In contrast, no increase in prothrombin fragment 1.2 generation was noted. Significantly more allogeneic blood was transfused in the Control and Desmopressin Groups when compared with the tranexamic acid group (p< 0.02).\n No evidence of tourniquet-induced fibrinolysis or thrombin generation was demonstrated in the systemic circulation. Desmopressin and tranexamic acid had no significant effect on the variables measured.", "Desmopressin acetate (DA) is a synthetic analog of vasopressin that may improve perioperative coagulation in cardiac surgical patients. Twenty-seven adult patients with good left ventricular function and normal preoperative coagulation profiles scheduled to undergo elective cardiac surgery participated in the double-blinded, placebo-controlled study. The 14 patients in the DA group received the drug over 10 minutes (starting 15 minutes after protamine administration). The 13 patients in the placebo group received an equal volume of saline. Preoperative template bleeding time was longer in the placebo group (P = 0.04). Otherwise, there were no statistically significant differences between the groups in demographics, coagulation variables, renal concentrating function, blood loss, or transfusion requirements at any study interval. The only significant hemodynamic differences detected were an increase in cardiac output in the DA group and a corresponding decrease in systemic vascular resistance. Five of 13 patients who received DA required treatment for hypotension, whereas none of 12 patients who received placebo required treatment during the infusion (P = 0.008). The authors conclude that DA causes mild vasodilation, but does not reduce blood loss or transfusion requirements in patients undergoing primary uncomplicated cardiac surgical procedures.", "50 patients undergoing elective total hip replacement under epidural anesthesia and dextran infusion were given two doses of the vasopressin analogue desmopressin 0.3 micrograms/kg BW or placebo in a double-blinded randomized prospective study. Intraoperative blood loss and drainage loss did not differ significantly between groups, but desmopressin reduced the mean total blood loss (calculated from hemoglobin decrease and blood transfusions) by 310 mL (P less than 0.05).", "Previous studies have suggested that the administration of desmopressin (DDAVP) may reduce blood loss after cardiac surgery. The present double-blind, randomized, placebo-controlled trial was performed to determine the effect of DDAVP on haemostasis during and after primary coronary artery bypass surgery. Fifteen patients received an infusion of DDAVP 0.3 microgram/kg and 15 patients received a placebo infusion over 15 min after cardiopulmonary bypass. Following DDAVP administration, the increase in factor VIII:C plasma level was greater than after placebo (the increase at 90 min after treatment 1.10 +/- 0.11 vs. 0.45 +/- 0.09 IU/ml, P less than 0.01). A difference between the treatments tended to occur also in the increase of von Willebrand antigen (0.64 +/- 0.08 vs. 0.23 +/- 0.07 IU/ml, P = 0.0556). A detailed evaluation of various haemostatic parameters showed no significant changes towards hypercoagulability or fibrinolysis. Inspite of the observed potential haemostatic effect of DDAVP, patients treated with DDAVP and placebo had similar postoperative blood losses (950 +/- 185 vs. 1034 +/- 321 ml), similar total haemoglobin losses (45.9 +/- 11.1 vs. 54.7 +/- 25.9 g) and similar red cell transfusion requirements (1.3 (range 0-2) vs. 1.1 (range 0-3) units). The plasma concentrations of factor F VIII:C and von Willebrand factor antigen after cardiopulmonary bypass may explain the failure to achieve a therapeutic effect with DDAVP.", "Desmopressin acetate (DDAVP) has been advocated as efficacious in reducing mediastinal bleeding following cardiopulmonary bypass (CPB), and has been shown to ameliorate platelet dysfunction; however, this has not been evaluated during routine coronary artery bypass grafting (CABG). In the present study, this therapy was evaluated utilizing the thromboelastograph (TEG), a rapid, on-line means of diagnosing a coagulopathy. During elective CABG, 20 patients received either DDAVP, 0.3 microgram/kg, intravenously, following heparin reversal after CPB, or a placebo infusion, in a randomized, double-blind fashion. Hemostasis was monitored with both the TEG and conventional coagulation tests. No significant differences between the two groups were found at induction, postprotamine, post-\"study infusion,\" or 2 hours postoperatively, with the exception of the postoperative PTT (31.1 +/- 3.2 v 36.5 +/- 5.9 seconds for DDAVP v placebo, P = 0.03). Total blood products transfused intraoperatively, and in the first 8, 16, 24, or 48 postoperative hours, were also similar between the groups. No manifestations of hypercoagulability were seen, but hypotension during the infusion was noted in four patients receiving DDAVP, and in none of the controls. It is concluded that the expense and potential complications of DDAVP therapy do not justify its routine use in CABG.", "The role of desmopressin acetate in attenuating blood loss and reducing homologous blood component therapy after cardiopulmonary bypass is unclear. The purpose of this investigation was to identify a subgroup of patients that may benefit from desmopressin acetate therapy. One hundred fifteen patients completed a prospective randomized double-blind, placebo-controlled trial designed to evaluate the effect of desmopressin acetate (0.3 microgram.kg-1) on mediastinal chest tube drainage after elective coronary artery bypass grafting surgery in patients with normal and abnormal platelet-fibrinogen function as diagnosed by the maximal amplitude (MA) on thromboelastographic (TEG) evaluation. The 115 patients evaluated were divided into two groups based on the MA of the post-cardiopulmonary bypass TEG tracing. Group 1 (TEG:MA greater than 50 mm) consisted of 86 patients, of whom 44 received desmopressin and 42 received placebo. Twenty-nine patients had abnormal platelet function (TEG:MA less than 50 mm) and were designated as group 2. In group 2, 13 received desmopressin and 16 placebo. During the first 24 h after cardiopulmonary bypass, the placebo-treated patients in group 2 had significantly greater mediastinal chest tube drainage when compared to placebo patients in group 1 (1,352.6 +/- 773.1 ml vs. 865.3 +/- 384.4 ml, P = 0.002). In addition to increases in blood loss, group 2 placebo patients also were administered an increased number of blood products (P less than 0.05). The desmopressin-treated patients in group 2 neither experienced increased mediastinal chest tube drainage nor received increased amounts of homologous blood products when compared to those in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)", "Desmopressin acetate (DDAVP) has been implicated as a promising agent to reduce blood loss in patients undergoing cardiopulmonary bypass.\n The effects of intraoperative desmopressin were studied in 66 patients undergoing coronary artery bypass grafting, randomized equally into desmopressin and control groups. The desmopressin group received 0.3 microg/kg desmopressin at the end of cardiopulmonary bypass.\n Fibrinogen level of both groups significantly reduced at postoperative 2nd hr, whereas a significant rise was observed at postoperative 24th hr with an intergroup difference favoring the control group (p=0.0307). In the desmopressin group, the activation time of factor VIII shortened during the whole postoperative period being significant (p=0.0127) at postoperative 24th hr. Postoperative von Willebrand factor (vWF) levels of the desmopressin group were significantly higher than the preoperative ones. The control group did not show such important changes in factor VIII and vWF measurements. Platelet aggregation times of both groups prolonged at postoperative 2nd hr. The control group showed significant elevation in ADP induced aggregation time at 2nd hr and significant reductions of platelet activation percentage in response to ADP, epinephrine, collagen and ristocetin at 2nd hr. Postoperative blood loss as well as blood transfusion need did not differ between the two groups.\n Despite the improved platelet functions, desmopressin does not seem to have obvious beneficial effects on postoperative hemostasis in patients without any bleeding disorder and undergoing elective cardiac surgery.", "Previous studies have suggested that desmopressin may reduce the bleeding diathesis that often complicates open-heart surgery. To pursue this question further, we performed a double-blind, randomized, placebo-controlled trial to determine whether the previously reported beneficial effect of desmopressin on hemostasis during complex cardiac surgery was applicable to all elective cardiac surgical procedures involving cardiopulmonary bypass. In 150 consecutive patients, most of whom underwent primary coronary-artery bypass grafting, we compared the effects of intravenous desmopressin (0.3 microgram per kilogram of body weight) with those of saline placebo on postoperative blood loss and the need to replace blood products. The median amount of blood lost within the first 24 hours after operation was similar in the desmopressin and placebo groups (865 vs. 738 ml; P = 0.26). The postoperative use of blood replacement products did not differ significantly between the groups (1025 ml [95 percent confidence interval, 300 to 4140 ml] in the desmopressin group and 860 ml [247 to 5346 ml] in the placebo group). Desmopressin is believed to exert its hemostatic effect by releasing von Willebrand factor. The level of ristocetin cofactor, a functional index of the level of von Willebrand factor, was increased approximately twofold from base line in both treatment groups 90 minutes and 24 hours after the administration of medication. Similarly, the levels of von Willebrand factor multimers increased uniformly in both groups. These findings may be consistent with a normal stress response of von Willebrand factor to major surgery and could explain our failure to detect a therapeutic effect of desmopressin. We conclude that the majority of patients who undergo elective cardiac surgery receive no hemostatic benefit from the use of desmopressin.", "The effects of single or repeated doses of desmopressin on blood loss were examined in uncomplicated cardiac surgery, while assessing the potential for thrombogenic side effects. Seventy patients undergoing elective coronary artery bypass grafting (CABG) were studied. Patients were randomized into three blinded groups: Group I received DDAVP (0.3 micrograms/kg), IV, after cardiopulmonary bypass (CPB) and 12 hours later in the Intensive Care Unit (ICU); Group II, DDAVP (0.3 micrograms/kg), IV, after termination of CPB and saline (placebo) 12 hours later in the ICU; Group III, saline (placebo) IV after CPB and 12 hours later in the ICU. Blood loss and bleeding time decreased for Group I at 24 hours (P < 0.04) when compared to Group III; however, blood product replacement, as well as intraoperative and total blood loss at 36 hours, were not different among treatment and control groups. There were four myocardial infarctions recorded in Group I, two in Group II, and one in Group III. These differences were not found to be statistically significant. It is concluded that in routine CABG the prophylactic use of single or repeat dose DDAVP does not effectively decrease blood loss or blood product replacement.", "Desmopressin (1-deamino-8-D-argininevasopressin, DDAVP) is a synthetic analog of the antidiuretic hormone L-argininevasopressin. DDAVP has been shown to increase the plasma concentration of endothelial factor VIII, thus increasing coagulant activity. There is evidence from controlled clinical trials indicating that DDAVP can reduce blood loss and transfusion requirements for individuals with normal coagulation profiles undergoing various surgical procedures. This study was conducted to evaluate the efficacy of the DDAVP in reduction of blood loss during orthognathic surgery. Twenty patients, 15 females and 5 males, undergoing bimaxillary osteotomy were randomized into two groups of ten. Perioperatively, group 1 patients received 20 micrograms of DDAVP infused over one-half hour. Group II patients did not receive DDAVP. Hypotensive anesthesia (mean arterial pressure < 60 mm Hg) was routinely employed for both groups. On average, the blood loss in group I patients was 144 ml less per patient than group II patients (p < 0.50). Only 2 of 10 patients in group I lost in excess of 750 ml, while 6 to 10 group II patients experienced blood loss greater than 750 ml (p < 0.20). The average postoperative hematocrit for patients in group I dropped by 6.17 of the preoperative mean hematocrit (p < 0.001). The average drop in hematocrits among the group II patients was 11.61 (p < 0.001). When collated, this hematocrit drop of 11.61 for group II and 6.17 for group I (recipients of DDAVP) proved to be significantly different (p < 0.01). It is concluded from this study that patients receiving a standard dose of DDAVP prior to bimaxillary osteotomy would experience reduced intraoperative blood loss, providing that blood pressure is well controlled and fluid replacement is carefully managed. No significant adverse side effects of desmopressin acetate were observed.", "Conflicting results have been reported concerning the effect of the synthetic vasopressin analog desmopressin acetate (DDAVP) on perioperative bleeding and homologous blood requirements in cardiac surgery. Because patients preoperatively treated with platelet-inhibiting drugs are at increased risk of perioperative bleeding, the blood-saving effect of DDAVP was investigated in 40 male patients undergoing primary myocardial revascularization. All patients had taken aspirin within the last 5 days prior to surgery. In a double-blind, randomized trial, the effects of DDAVP (0.3 microgram/kg of body weight) were compared to those of saline placebo on postoperative blood loss and the need to replace blood products. To evaluate the drug's influence on the coagulation and fibrinolytic systems, von Willebrand factor (vWF), the activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI 1), and the split products of cross-linked fibrin (D-dimers) were investigated. The total homologous blood requirement was significantly lower in DDAVP recipients (median 2, range, 0 to 5 U) compared to placebo (median 3.5, range, 0 to 8 U; P < 0.05). Although at all points of measurement (intraoperative and postoperative) transfusion requirement was less in the DDAVP group, hematocrit values of these patients always exceeded those of the placebo group, this difference being significant at the end of the operation. Because no difference in postoperative blood loss was found, the markedly reduced transfusion requirement of the DDAVP-treated patients is explained either by reduced intraoperative bleeding or by a reduced hematocrit of the chest-tube blood.(ABSTRACT TRUNCATED AT 250 WORDS)", "To determine whether desmopressin acetate (DDAVP) has the ability to reduce blood loss in patients with a known bleeding tendency.\n A randomized, double-blind, placebo controlled study.\n A university teaching hospital.\n Men under the age of 70 years who had taken acetylsalicylic acid within 7 days of scheduled coronary artery bypass surgery. Patients with an abnormal hematologic profile or a history of bleeding or who were receiving heparin or undergoing repeat coronary bypass surgery were excluded. Forty-four patients were randomized with restriction in blocks of 10; 20 received DDAVP and 24 received a placebo.\n Blood loss and blood transfusion requirements.\n Patients treated with DDAVP lost significantly (p < 0.01) less blood than those receiving a placebo (1543 mL versus 2376 mL respectively). Nineteen patients had a blood loss of more than 2000 mL; 15 of these were in the placebo group. Significantly (p < 0.02) fewer patients receiving DDAVP required blood transfusion (9 versus 18).\n DDAVP reduces blood loss during cardiac bypass surgery in patients who have taken acetylsalicylic acid within 7 days before operation.", "In a double blind, placebo controlled study in 50 patients undergoing aorto-iliac graft surgery, we studied the effects of desmopressin given prior to surgery on blood loss and blood transfusion requirements. Desmopressin reduced the number of patients with clinically significant bleeding. Blood loss volumes and transfusion requirements were lower in the desmopressin group, but this could not be verified statistically. Even if our study population has a high incidence of generalised arteriosclerotic disease, there were no clinical manifestations of venous thromboembolism, no increase of graft occlusions and no myocardial infarction during the operative or early postoperative period. Desmopressin may be used in patients with excessive peroperative bleeding or a prolonged preoperative bleeding time. In patients where desmopressin is considered to be haemostatically efficacious, it may be used with a maintained margin of safety.", "Aprotinin reduces blood loss in operations done with cardiopulmonary bypass, whereas the use of desmopressin remains controversial. We compared aprotinin, desmopressin, and placebo in a double-blind, randomized trial to evaluate bleeding and transfusion requirements.\n One hundred forty-nine patients (48 received aprotinin, 50 desmopressin, 51 placebo) were included. Blood loss and transfusion requirements were recorded and levels of Factor VIII coagulant activity, von Willebrand's factor, thrombin-antithrombin complexes, and D-dimer were measured. Overall blood loss was 195 +/- 146 ml/m2 in the aprotinin group, 400 +/- 192 ml/m2 in the desmopressin group, and 489 +/- 361 ml/m2 in the placebo group (95% confidence intervals: difference between desmopressin and aprotinin 98 to 312 ml/m2, p < 0.001; difference between placebo and aprotinin 190 to 398 ml/m2, p < 0.001). Twenty-six percent of patients treated with aprotinin, 66% of those treated with desmopressin, and 56% of those treated with placebo were given transfusion (95% confidence intervals: difference between aprotinin versus placebo plus desmopressin 51% to 71%, p < 0.001). Fibrinolytic activation throughout cardiopulmonary bypass was markedly higher with placebo or desmopressin administration. D-dimer level correlated with overall blood loss in patients receiving desmopressin or placebo, but not in those receiving aprotinin.\n Aprotinin administration reduces blood loss and transfusion requirements in cardiopulmonary bypass. This benefit may be explained by a lower activation of fibrinolysis.", "Use of desmopressin acetate (DDAVP) for patients having cardiac surgery is controversial. We did a double-blind, randomized study of 83 patients having cardiac operations at Georgetown University Hospital. The effect of DDAVP on bleeding as compared to placebo was evaluated by blood loss, replacement volume, and laboratory tests. There were no significant differences in baseline and intraoperative data between the DDAVP (n = 40) and placebo (n = 43) groups. Total drainage for the first 24 postoperative hours was 1,214 mL (+/- 78) for the DDAVP group and 1,386 mL (+/- 116) for the placebo group (not significant). There were no significant differences in replacement therapy. In this study, administration of DDAVP did not decrease bleeding.", "Platelet dysfunction is a major cause of excessive microvascular bleeding after cardiac surgery. A new point-of-care test (hemoSTATUS) can identify patients at risk of excessive bleeding. We aimed to find out whether patients who can benefit from desmopressin during cardiac surgery can be identified by this test.\n We enrolled 203 patients scheduled for elective cardiac surgery in a prospective, double-blind, placebo-controlled trial. Patients with abnormal hemoSTATUS clot-ratio results (<60% of maximum in channel 5) after discontinuation of cardiopulmonary bypass were randomly assigned desmopressin (n=50) or placebo (n=51). Patients with normal clot ratios were included in an untreated control group (n=72).\n Intraoperative platelet counts and clot ratios were significantly higher in the untreated control group than in the study-drug groups. In intensive care, clot ratios in patients who received desmopressin were similar to those in the untreated control group, despite significantly lower platelet counts, but were lower in the placebo group than in the other two groups (p=0.0001). Compared with the placebo group, patients who received desmopressin had less blood loss in 24 h (mean 624 [SD 209] vs 1028 mL [682] p=0.0004) and required less transfusion of red blood cells (1.1 [022] vs 2.2 U [0.32] p=0.009), platelets (0.1 [0.04] vs 1.9 U [4.5] p=0.0001), and fresh-frozen plasma (0.1 [0.07] vs 0.75 U [0.21] p=0.0008), and had less total blood-donor exposures (1.56 [0.31] vs 5.2 [0.8] p=0.0001). Placebo patients also had substantially higher blood loss and transfusion requirements than untreated control patients.\n Patients identified with hemoSTATUS as being at increased risk of excessive bleeding after cardiac surgery can benefit from administration of desmopressin. Further studies are, however, needed to confirm these findings as well as to identify the mechanism of action and safety of desmopressin in the clinical setting.", "Patients on cardiopulmonary bypass (CPB) have an increased susceptibility to postoperative bleeding. Previous reports using desmopressin acetate (DDAVP) for the prevention of postoperative bleeding have given contradictory results, whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery. This randomized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB.\n One hundred nine of 122 eligible patients were randomized to four different groups: Group A (n = 28) received aprotinin starting with a bolus of 2 x 10(6) KIU followed by a continuous infusion of 0.5 x 10(6) KIU/h until the end of surgery; group B (n = 25) received of DDAVP 0.3 micrograms/kg i.v. on completion of CPB; group C (n = 28) received two doses of DDAVP, the first as in group B and an additional dose 6 hours after surgery; group D (n = 28) received no treatment. There was a marked reduction of postoperative blood loss either at 12 hours (P < .01) or 72 hours (P < .02) in the aprotinin group compared with all other groups, whereas no significant effect was observed in either of the two DDAVP regimens. A significant reduction in the amount of blood used was observed only in the aprotinin group (P < .01). Of the plasma fibrinolytic components assayed, there was a significant reduction of the fibrin degradation product generation in the aprotinin group (P < .001), whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group. No side effects related to the study drugs were observed in any patient.\n Aprotinin inhibited fibrinolysis; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB. Neither one nor two doses of DDAVP had a beneficial effect. Aprotinin offers a better alternative than DDAVP in the prevention of bleeding after CPB.", "It has been suggested that desmopressin acetate has been effective in reducing hemorrhage after coronary artery bypass grafting in patients receiving aspirin before operation. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine the effectiveness and safety of desmopressin in these patients. Sixty-five patients pretreated with aspirin within 7 days before their scheduled elective coronary artery bypass grafting were randomized to receive desmopressin (0.3 micrograms/kg) or placebo after cessation of bypass and reversal of heparin with protamine. The demographic characteristics and last dose of aspirin were similar in both groups. There was a significant reduction in postoperative blood loss noted between groups for both chest tube blood loss (833 +/- 311 ml for the 1-desamino-8-D-arginine vasopressin [desmopressin] group versus 1176 +/- 674 ml for the placebo group; p = 0.016) and total blood loss (1215 +/- 381 ml for the desmopressin group versus 1637 +/- 761 ml for the placebo group; p = 0.0097). Despite the differences in blood loss between the two groups, the red cell transfusions were not significantly different, but the use of platelets was less in the desmopressin group and almost achieved statistical significance (p = 0.053). Neither was there a difference in the occurrence of thrombotic complications between groups. It appears that desmopressin in this specific subgroup of patients receiving preoperative aspirin is effective as a prophylactic agent for reduction of postsurgical hemorrhage.", "Bleeding after cardiopulmonary bypass remains a cause for concern, requiring reexploration of the chest in approximately 3 percent of patients who have had operations on the heart. We examined the possibility that this problem might be alleviated by desmopressin acetate (DDAVP), which increases the plasma level of von Willebrand factor and improves hemostasis in mild hemophilia and other conditions associated with defective platelet function. In a double-blind, prospective, randomized trial, we studied the effect of intraoperative desmopressin acetate in 70 patients undergoing various cardiac operations requiring cardiopulmonary bypass. Patients undergoing uncomplicated primary coronary-artery bypass grafting were not included. The drug significantly reduced mean operative and early postoperative blood loss (1317 +/- 486 ml in the treated group vs. 2210 +/- 1415 ml in the placebo group); of the 14 patients whose 24-hour blood loss exceeded 2000 ml, 11 had received the placebo. Plasma levels of von Willebrand factor were higher after desmopressin acetate than after placebo. Patients with the most bleeding had relatively low levels of von Willebrand factor before operation, suggesting a role for this factor in the hemorrhagic tendency induced by extracorporeal circulation. There were no untoward side effects of desmopressin acetate. We conclude that the administration of desmopressin acetate can be recommended to reduce blood loss in patients undergoing complex cardiac operations. The beneficial effect of the drug on hemostasis after cardiopulmonary bypass may be related to its effect on von Willebrand factor.", "The synthetic vasopressin analog desmopressin has hemostatic properties and may reduce postoperative bleeding after coronary artery bypass grafting (CABG). A study on the effects of recent aspirin ingestion on platelet function in cardiac surgery showed a greater impairment of platelet function in patients treated with aspirin <2 days before the operation. We evaluated the effects of desmopressin on postoperative bleeding in CABG patients who were treated with aspirin 75 or 160 mg until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel group trial. One-hundred patients were included and divided into two groups. One group received desmopressin 0.3 micro g/kg and the other received placebo (0.9% NaCl) after the neutralization of heparin with protamine sulfate. Postoperative blood loss was recorded for 16 h. The mean (SD) bleeding was 606 (237) mL in the desmopressin group and 601 (301) mL in the placebo group (P = 0.93), representing no significant difference (95% confidence interval, -107 to 117 mL). We conclude that desmopressin does not reduce postoperative bleeding in CABG patients treated with aspirin until the day before surgery.\n Continuation of aspirin until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of desmopressin to these patients after the neutralization of heparin with protamine sulfate does not reduce postoperative bleeding.", "Desmopressin-induced release of tissue plasminogen activator from endothelial cells may explain the absence of its hemostatic effect in patients undergoing cardiac surgery. Prior administration of the antifibrinolytic drug tranexamic acid might unmask such an effect, and combination therapy might thereby improve postoperative hemostasis.\n A double-blinded design randomly allocated 163 adult patients undergoing coronary revascularization, valve replacement, both procedures, or repair of atrial septal defect to four treatment groups: placebo, tranexamic acid given as 10 mg/kg over 30 minutes followed by 1 mg.kg-1.hr-1 for 12 hours initiated before skin incision, desmopressin given as 0.3 micrograms/kg over 20 minutes after protamine infusion, and both drugs. One surgeon performed all operations. Blood loss consisted of mediastinal tube drainage over 12 hours. Follow-up visits sought evidence of myocardial infarction and stroke. Desmopressin decreased neither the 12-hour blood loss nor the amount of homologous red cells transfused. Tranexamic acid alone significantly reduced 12-hour blood loss, by 30% (mean, 318 versus 453 ml; p less than 0.0001), without enhancement by desmopressin. Tranexamic acid also decreased the proportion of patients receiving homologous blood within 12 hours of operation (8% versus 21%, p = 0.024) and within 5 days of operation (22% versus 41%, p = 0.011).\n Desmopressin exerts no hemostatic effect, with or without prior administration of antifibrinolytic drug. Prophylactic tranexamic acid alone appears economical and safe in decreasing blood loss and transfusion requirement after cardiac surgery.", "Bleeding in coronary artery bypass procedures increases morbidity and exposes patients to the risks associated with blood transfusion. Desmopressin acetate (DDAVP), a synthetic vasopressin analogue, may limit bleeding during cardiac surgery. In a prospective randomized trial, the authors evaluated the ability of DDAVP to reduce perioperative bleeding during uncomplicated coronary bypass operations. Sixty-two patients who underwent coronary artery bypass grafting were randomized to receive intraoperatively either a placebo or DDAVP. Both groups were similar with respect to operative characteristics and preoperative hematologic profiles, von Willebrand factor levels increased postoperatively in both placebo (2.77 +/- 1.06 versus 2.17 +/- 1.51 U) and DDAVP groups (2.75 +/- 0.94 versus 1.80 +/- 0.88 U). Only the increase in the DDAVP groups was significant (p less than 0.001). There was no difference in total blood loss between the placebo (1826 +/- 849 ml) and DDAVP groups (1716 +/- 688 ml). Total red cell transfusions were similar in placebo (3.4 +/- 1.3 units of blood) and DDAVP groups (3.6 +/- 0.8 units). These results do not support the intraoperative use of DDAVP to reduce perioperative bleeding in routine coronary artery bypass surgery.", "The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively.", "Desmopressin acetate is used to reduce blood loss after cardiac surgery. However, there have been reports that hypotension can occur with infusion of desmopressin and that postoperative blood loss is not reduced. In this randomized, double-blinded study, we investigated the effects of desmopressin on hemodynamics, coagulation, and postoperative blood loss in patients undergoing primary elective coronary artery bypass grafting (CABG). After reversal of heparin effect, 20 patients received desmopressin 0.3 micrograms.kg-1, infused over 15 min, and 20 patients received a placebo. Desmopressin produced a small but significant decrease in diastolic blood pressure when compared with the placebo (50.8 mmHg vs. 57.6 mmHg for the desmopressin- and placebo-treated groups, respectively; P = 0.0372). A 20% or greater decrease in mean arterial pressure was observed in 7 of 20 patients receiving desmopressin, whereas only one patient in the placebo-treated group experienced a decrease of this magnitude (P = 0.0177). Reductions in arterial pressure were secondary to decreases in systemic vascular resistance (SVR) (mean SVR before and after the drug infusion, 1,006 and 766 dyn.s.cm-5, respectively, for the desmopressin-treated group; and 994 and 1,104 dyn.s.cm-5, respectively, for the placebo-treated group; P = 0.0078).(ABSTRACT TRUNCATED AT 250 WORDS)", "The purpose of this study was to determine the effect of desmopressin acetate (DDAVP) on blood loss, transfusion requirements, and thromboembolic complications in patients undergoing elective aortic operations.\n A randomized, double-blind trial was carried out during a 3-year period with patients receiving 20 micrograms DDAVP or identical-appearing placebo at the time of aortic cross-clamp placement. In addition to major bleeding and thromboembolic end points, bleeding times and platelet counts were monitored serially.\n Forty-three patients were randomized to receive DDAVP, and 48 were assigned to a placebo. An equivalent proportion of patients with aneurysm and patients with occlusive disease was in each group. In spite of mild prolongation in the postoperative bleeding times and moderate thrombocytopenia, DDAVP had no beneficial effect on blood loss or transfusion requirements. Total blood transfusion amount (mean +/- standard deviation) for patients receiving DDAVP was 3.1 +/- 3.0 U compared with 2.7 +/- 3.0 U for those receiving placebo. For all patients the period associated with the greatest blood loss was the time between heparin administration with cross-clamp application and reversal of heparin with protamine sulfate. The incidence of major thromboembolic complications was similar in both groups.\n Thrombocytopenia and mild platelet dysfunction are common after aortic operation, but DDAVP does not improve hemostasis or lessen transfusion requirements. This study does not rule out a beneficial effect of DDAVP in patients who are undergoing more complex aortic operations or who have major hemostatic aberrations.", "The blood loss-reducing effect of desmopressin during dextran therapy was studied in a double-blind fashion in 79 elderly but otherwise healthy patients with preoperative normal bleeding time undergoing total hip replacement for primary coxarthrosis. An infusion of desmopressin (0.3 microgram/kg body weight) or placebo was randomly administered immediately after administration of spinal anaesthesia and six hours later. Haemostasis was evaluated on the basis of vWF: ristocetin cofactor activity, FVIII: C activity, human tissue plasminogen activator (tPA) plasminogen activator inhibitor type (PAI), beta-thromboglobuline (beta TG) and a clot impedance test (Sonoclot). There were no statistically significant differences (P > 0.05) in mean blood loss or transfusion requirements between the placebo and the desmopressin group. There was a significantly increase (P < 0.01) both in vWF: ristocetin cofactor and in FVIII: C activity after both infusions of desmopressin compared with placebo. There was no significant difference in beta TG, tPA, PAI or Sonoclot analysis between the groups. In conclusion, desmopressin did not reduce blood loss in patients undergoing total hip replacement." ]