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[ "17565633" ]

[ "Mesalazine with or without cholestyramine in the treatment of microscopic colitis: randomized controlled trial." ]

[ "Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory diseases of the colon with a benign and sometimes relapsing course. Frequency among patients with chronic diarrhea and normal looking colonoscopy is around 10-15%. To date, treatment of CC and LC is not well defined. Data about these conditions are mostly derived from retrospective studies. The aim of the present study was to evaluate the response to treatment and the clinical course of CC and LC in a large group of patients prospectively diagnosed.\n A total of 819 patients underwent a colonoscopy because of chronic watery diarrhea and among them we found 41 patients with LC and 23 with CC. These patients were later randomized and assigned to treatment with mesalazine or mesalazine + cholestyramine for 6 months. Fifty-four patients (84.37%) had resolved diarrhea in less than 2 weeks. After 6 months a colonoscopy with biopsies was repeated. Clinical and histological remission was achieved in 85.36% of patients with LC and in 91.3% with CC, with a better result in patients with CC treated with mesalazine + cholestyramine. During a mean period of 44.9 months, 13% of patients relapsed; four with LC and three with CC. They were retreated for another 6 months. At the end of this period one patient with CC was still symptomatic and persistence of CC was confirmed at histology.\n Treatment with mesalazine seems to be an effective therapeutic option for LC to date, while mesalazine + cholestyramine seems to be more useful in the treatment of CC." ]

[ "15321935", "9215056", "12842680", "11408134", "15722306", "10221191", "15134107" ]

[ "Randomized double-blind clinical trial comparing topical and sub-Tenon's anaesthesia in routine cataract surgery.", "Topical anaesthesia with oxybuprocaine versus sub-Tenon's infiltration with 2% lignocaine for small incision cataract surgery.", "Patient comfort during clear corneal phacoemulsification with sub-Tenon's local anesthesia.", "Topical versus sub-Tenon's anesthesia without sedation in cataract surgery.", "Randomised controlled trial of sub-Tenon's block versus topical anaesthesia for cataract surgery: a comparison of patient satisfaction.", "[Comparative study between topical anesthesia and sub-Tenon's capsule anesthesia for cataract surgery].", "Lidocaine-assisted xylocaine jelly anesthesia versus one quadrant sub-Tenon infiltration for self-sealing sclerocorneal incision routine phacoemulsification." ]

[ "Several local anaesthetic techniques are available for cataract surgery. Recently, topical anaesthesia has gained in popularity. A randomized trial was designed to compare patient discomfort and intraoperative complications following routine cataract surgery under topical or sub-Tenon's anaesthesia.\n A randomized double-blinded placebo-controlled clinical trial of 210 patients assigned to either a sub-Tenon's group (sub-Tenon's anaesthesia with placebo topical balanced salt solution, n=140) or a topical anaesthesia group (topical anaesthesia with placebo sub-Tenon's injection of balanced salt solution, n=70) was carried out. All patients underwent phacoemulsification with intraocular lens implantation. Patients in the sub-Tenon's group received a single injection (3 ml) of a combination of lidocaine 2% (2 ml) and bupivacaine 0.75% (1 ml), and four doses of topical placebo (balanced salt solution). Patients in the topical anaesthesia group received four doses of topical proxymethocaine 0.5% and a placebo sub-Tenon's injection (3 ml) of balanced salt solution. No intracameral injection of local anaesthetic was given. A 10-point visual analogue pain scale was used preoperatively and for postoperative pain assessment immediately after the operation and 30 min postoperatively. The intraoperative complications in the two groups were recorded.\n The mean pain score immediately after surgery was 2.42 (sd 2.2) in the sub-Tenon's group and 3.44 (2.3) in the topical anaesthesia group (P=0.0043). The mean pain score 30 min after surgery was 1.24 (1.7) in the sub-Tenon's group and 2.25 (2.2) in the topical anaesthesia group (P=0.0009).\n Patients undergoing cataract surgery under topical anaesthesia experience more postoperative discomfort than patients receiving sub-Tenon's anaesthesia. Surgery-related complications were similar in both groups.", "To determine whether topical anaesthesia in small incision self-sealing phacoemulsification cataract surgery provides comparable anaesthesia to sub-Tenon's infiltration.\n Thirty five patients undergoing small incision self-sealing phacoemulsification cataract surgery were allocated randomly to receive topical anaesthesia with 0.4% oxybuprocaine or sub-Tenon's infiltration with 2% lignocaine. Pain experienced during the operation was assessed by asking the patient to score on a visual analogue graphic pain score chart.\n The median pain score for the topical group (3) was significantly higher than that of the sub-Tenon's group (0) (p = 0.004).\n Sub-Tenon's infiltration is superior to topical anaesthesia in ensuring patient comfort during small incision scleral tunnel self-sealing phacoemulsification cataract surgery.", "To assess patient comfort with and without intravenous (i.v.) cannulation during 1-quadrant sub-Tenon's anesthesia during phacoemulsification.\n Royal Alexandra Hospital, Paisley, Scotland, United Kingdom.\n This prospective masked controlled clinical trial comprised 119 patients having elective clear corneal phacoemulsification. Fifty had sub-Tenon's anesthesia with an i.v. cannula; 23, sub-Tenon's anesthesia without an i.v. cannula; and 46, topical anesthesia of proparacaine 0.5% without an i.v. cannula. No patient received sedation. All patients had clear corneal phacoemulsification with foldable posterior chamber intraocular lens implantation. The patients' subjective pain experience was measured immediately after surgery by a single independent observer using a 10-point visual analog scale.\n The mean patient-reported pain was low in all 3 groups. The mean i.v. cannula-related pain score in the sub-Tenon's group with an i.v. cannula (1.00; range 0 to 8) was higher than the mean general pain score (0.46; range 0 to 5) and worst pain experienced during surgery score (0.64; range 0 to 3). In the topical anesthesia group, 8 patients (17%) reported greater discomfort directly or indirectly related to the subconjunctival antibiotic injection at the end of surgery.\n Patient-reported pain caused by placing an i.v. cannula in the sub-Tenon's group significantly altered overall patient comfort during the surgical experience. Thus, the routine use of i.v. access during clear corneal phacoemulsification under sub-Tenon's anesthesia should be avoided to improve patient satisfaction.", "To compare pain control using topical anesthesia with that using sub-Tenon's anesthesia for clear corneal phacoemulsification cataract surgery and foldable intraocular lens (IOL) implantation.\n Departments of Ophthalmology, General Hospital Asklepeion Voulas and General Hospital of Athens, University of Athens, Athens, Greece.\n One hundred consecutive patients scheduled for bilateral cataract surgery 1 to 2 months apart were prospectively randomized to receive topical anesthesia (100 eyes) or sub-Tenon's anesthesia (100 eyes). The randomization was stratified so that one half of first-eye surgeries and one half of second-eye surgeries were assigned to each anesthesia group, with each patient receiving each type of anesthesia once. All patients had clear corneal phacoemulsification with foldable IOL implantation. Patients were asked to rate their pain level on a 10-point scale for 4 periods: during the administration of the anesthetic agent, during surgery, immediately after surgery, and 24 hours postoperatively. The surgeon recorded his subjective assessment of ease of surgery and surgical complications using a standardized template.\n Eighty-one percent of patients who received topical anesthesia and 8% of patients who received sub-Tenon's anesthesia reported no pain during delivery of the anesthetic agent. The mean pain score was 0.19 +/- 0.39 (SD) in the topical group and 1.35 +/- 0.63 in the sub-Tenon's group. The difference between groups was statistically significant (P <.001). Seventy-two percent of patients in the topical anesthesia group and 86% in the sub-Tenon's anesthesia group reported no pain or slight discomfort during surgery (mean score 1.13 +/- 1.57 and 0.57 +/- 1.28, respectively) (P <.001). Ninety percent of topical anesthesia patients and 100% of sub-Tenon's anesthesia patients reported no pain or slight discomfort 30 minutes postoperatively (mean score 0.80 +/- 0.93 and 0.12 +/- 036, respectively) (P <.001). All patients in the topical anesthesia group and 77% in the sub-Tenon's group reported no pain 24 hours postoperatively (mean pain 0.00 +/- 0.00 and 0.23 +/- 0.40, respectively) (P <.001). Complications including prolonged akinesia of the globe, chemosis, and conjunctival hemorrhage occurred significantly more frequently in the sub-Tenon's than in the topical group (P <.001).\n Patients having cataract surgery under topical anesthesia had more intraoperative and postoperative discomfort than patients receiving sub-Tenon's anesthesia. However, patients having topical anesthesia reported less pain during its administration and had fewer complications. Both anesthesia methods provided high levels of pain control without additional sedation.", "Sub-Tenon's block (STB) or topical anaesthesia alone (TOP) are popular techniques employed during cataract surgery. TOP is often preferred by healthcare providers because of financial or staffing reasons, despite existing evidence that pain during surgery is better controlled with STB. Pain is not the only consideration that determines patient preference for the anaesthesia technique. The authors decided to investigate the issue of patient satisfaction using the recently developed Iowa Satisfaction with Anesthesia Scale (ISAS).\n In a randomised controlled pilot trial, 28 patients were enrolled to receive either STB with 3 ml of 2% lidocaine and hyaluronidase, or TOP with proxymetacaine 0.5% and amethocaine 1% (Tetracaine) eye drops. Postoperatively patients rated their satisfaction with anaesthesia care by filling in the self administered written questionnaire, the ISAS.\n One patient in the TOP group dropped out of the study because of intolerable pain. Analysis of the questionnaire results with a two sample Wilcoxon rank sum test showed a significant difference in patient satisfaction (p<0.0085). The median satisfaction score was higher in the STB group 2.77 (interquartile range IQR 2.45 to 3), than in the TOP group 2.04 (IQR 1.54 to 2.5).\n In the setting of day case cataract surgery, patients report significantly higher satisfaction scores with STB than with TOP alone.", "We performed a prospective study to compare two techniques of local anesthesia: topical and subtenon anesthesia. Twenty-five patients underwent cataract surgery on both eyes by phakoemulsification and insertion of foldable lenses in the capsular bag. The second eye was operated 24 hours after the first one. We evaluated patient confort, surgeon confort, surgical complications and pupillary diameter evolution during the procedure.\n 64% of patients preferred subtenon anesthesia procedure. Surgeon confort was better with subtenon anesthesia. No surgical complications occurred in either group. The pupillar diameter evolution was different, decreasing for about 25% for topical anesthesia and 15% for subtenon anesthesia.\n Subtenon anesthesia is more comfortable for the patient: deeper anesthesia, reliable, longer lasting; light tolerance is better. It is also more comfortable for the surgeon: better pupillar dilatation during the procedure. Topical anesthesia has inconstant efficiency.", "To compare the effect of xylocaine jelly and intracameral lidocaine with one quadrant instant sub-Tenon infiltration for self-sealing sclerocorneal phacoemulsification.\n One hundred patients were enrolled into a prospective randomized study, receiving either a combination of topical 2% xylocaine jelly and 0.5 ml of intracameral 1% lidocaine or sub-Tenon infiltration with 2 ml of 2% xylocaine on the operating table. All patients underwent a standard divide and conquer phacoemulsification procedure through a superior sclerocorneal frown incision followed by implantation of a polymethylmethacrylate intraocular lens. Intraoperative pain was indicated by the patient by squeezing the bedside nurse's hand, who allocated it to particular stages of surgery on a chart. After surgery, patients assessed the pain experienced using a 10-unit visual analogue scale.\n Pain was indicated on 31 occasions during the operation in the sub-Tenon group (mainly the injection itself) and 67 times in the topical group. The median overall subjective pain score was 3 in the jelly group and 0 in the sub-Tenon. Five eyes (10%) had to be converted to sub-Tenon during the surgery because of intolerable pain.\n Whereas lidocaine supported xylocaine jelly anesthesia provided acceptable analgesia for 90% of patients operated, sub-Tenon anesthesia proved to deliver better intraoperative comfort in all patients receiving sclerocorneal incision cataract surgery." ]

[ "1468241", "348537", "6756454", "7779647", "14662569", "10969225" ]

[ "A comparison of the efficacy of two ear drop preparations ('Audax' and 'Earex') in the softening and removal of impacted ear wax.", "A multicentric clinical trial comparing Otocerol with Cerumol as cerumenolytics.", "Multicentre clinical trial of Exterol as a cerumenolytic.", "Use of solvents to disperse ear wax.", "Randomized clinical trial of docusate, triethanolamine polypeptide, and irrigation in cerumen removal in children.", "Ceruminolytic effects of docusate sodium: a randomized, controlled trial." ]

[ "Thirty-six patients with symptoms of impacted ear wax were recruited to an open, randomized, parallel group study of 'Audax' ear drops and 'Earex' ear drops. Patients had had their symptoms for several weeks and they were assessed on entry for the degree of impaction in each ear. After using the drops, morning and evening for 4 days, they were assessed on the fifth day for degree of impaction, ease of syringing, side-effects or discomfort, and the investigator's and patient's own global impression of efficacy of the ear drops. A trend was seen showing less impaction post-treatment in the 'Audax' group than in the 'Earex' group although the difference did not reach statistical significance. A significant difference was seen in favour of 'Audax' for the frequency and ease of syringing (p < 0.005). No patients in the 'Audax' group reported any side-effect or discomfort although 1 patient using 'Earex' reported slight irritation whilst another found the smell unacceptable. The results of the investigators' and patients' own global impression of efficacy were significantly in favour of 'Audax' ear drops (p < 0.01).", "Fifteen general practitioners conducted a randomized, double-blind comparative trial of two cerumenolytics, namely, Otocerol and Cerumol. A total of 106 patients were entered into the study (fifty-three in each group). Otocerol was shown to be marginally better than Cerumol in all parameters evaluated.", "nan", "nan", "Cerumen obstructing visualization of the tympanic membrane in children is a common and frustrating problem. Docusate sodium, triethanolamine polypeptide, and saline were compared to determine their effectiveness in relieving cerumen obstruction in children.\n A randomized, controlled, double-blind trial was performed on pediatric patients aged 6 months through 5 years with cerumen obstruction. The enrolling physician determined whether the cerumen completely or partially obstructed visualization of the tympanic membrane. One milliliter of docusate sodium, triethanolamine polypeptide, or normal saline as control was placed into the patient's ear canal. If the tympanic membrane was not completely visualized after 15 minutes, the ear was irrigated with 50 mL of tepid water. Irrigation was repeated a second time if needed. The main outcome was the proportion of tympanic membranes that were completely visualized after cerumeno-eblytic agents or control saline, alone or with irrigation if needed.\n Of 92 patients enrolled, 34 received docusate sodium; 30, triethanolamine polypeptide; and 28, saline. Mean +/- SD patient age was 34.7 +/- 18.1 months, and 50 (54%) of the patients were girls. Groups were similar in age, race, sex, ear enrolled, wax consistency, and degree of obstruction. There was no significant difference in the proportion of tympanic membranes completely visualized after treatment with docusate (18/34; 53%), triethanolamine polypeptide (13/30; 43%), or saline (19/28; 68%) (P =.17).\n Application of docusate sodium or triethanolamine polypeptide did not significantly improve the proportion of tympanic membranes that were completely visualized vs application of the saline control.", "Assessment of the tympanic membrane is often impeded by the presence of cerumen. We compared the ceruminolytic effects of triethanolamine polypeptide and docusate sodium in patients with cerumen.\n We conducted a prospective, randomized, controlled, double-blind trial on a convenience sample of cooperative adult and pediatric patients presenting to a university-based emergency department who required removal of cerumen to visualize the tympanic membrane. Structured data collection was performed, and the physician determined whether visualization of the tympanic membrane was partially or totally obscured by cerumen (interobserver agreement, rho=0.79). Patients received intra-aural instillation of 1mL of either docusate sodium or triethanolamine polypeptide in a liquid form. If not completely cleared within 15 minutes, the external ear canal was irrigated with 50 or 100 mL of normal saline solution and additional attempts to visualize the tympanic membrane were made. The main outcome was the proportion of ears in which the tympanic membrane could be totally visualized after ceruminolytic instillation with or without irrigation. This study had 80% power to detect a 40% difference between groups in the proportion of totally visualized tympanic membranes (chi(2) test, alpha=.05).\n Of 50 enrolled patients, 23 received triethanolamine polypeptide and 27 received docusate sodium. Mean patient age was 40 years (range 1 to 81 years); 35% were female. Groups were similar in age, sex, and proportion of completely obscured tympanic membranes at presentation (78%). The ability to completely visualize the tympanic membrane was significantly greater after treatment with docusate sodium versus triethanolamine polypeptide (81% versus 35%; difference in proportions 47%; 95% confidence interval [CI], 22 to 71) particularly in children aged 5 or less (90% versus 0%; difference in proportions 89%; 95% CI 50 to 100).\n Docusate sodium solution is a more effective ceruminolytic than triethanolamine polypeptide, allowing complete or partial visualization of the tympanic membrane in most patients after a single application when followed with irrigation. Use of docusate sodium as a ceruminolytic should be encouraged, particularly in children." ]

[ "15374345" ]

[ "On the efficacy of piracetam in geriatric patients with acute cerebral ischemia: a clinically controlled double-blind study." ]

[ "Using a randomized, double blind group comparison, the efficacy and tolerance of piracetam as an additional therapy of hydroxyethyl starch, venous infusion and low dose heparin treatment, which are the basis of therapy in our hospital, has been studied in patients displaying acute cerebral ischemia. A total of 56 patients were enrolled, of whom 27 were given piracetam and 29 served as a control during a 28-day period. Using single photon emission computer tomography (SPECT) analysis, we observed that in 23 piracetam-treated patients (85.2%) a reduction in the area of brain regions displaying an impaired flow rate occurred (P < 0.001; Fisher's exact two-sided test). Only six of placebo-treated patients (20.7%) showed an improved flow rate. Analysis of the recorded computer tomography map gave an improvement coefficient >2 (flow rate marginally or better improved) for 23 piracetam patients as compared with 5 placebo patients (P < 0.001, Uleman test)." ]

[ "11991447", "20398112", "15963186", "18283231", "15352143", "8121429", "21098343", "15381507", "17656420", "16274368", "20002510", "21834112", "2115755", "12521968", "18845605", "17302660", "15903284", "16813773", "15477703", "12588573", "21649623", "11111630", "10763795", "15066200", "18332052", "21419411", "18083724", "19435759", "15151914", "21507049", "20230348", "15031238", "21045097", "16641143", "12540351", "15213472", "10671804", "21369788", "21453381", "15988879", "17013734", "8301766", "16905764", "19421690", "19221130", "15066066", "18043700", "11527475", "17061151", "12020141", "12568412", "9268276", "21382864", "19282246" ]

[ "Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study.", "Pragmatic, cluster randomized trial of a policy to introduce low-low beds to hospital wards for the prevention of falls and fall injuries.", "Effects of Sun-style Tai Chi exercise on physical fitness and fall prevention in fall-prone older adults.", "A randomized controlled trial of fall prevention by a high-intensity functional exercise program for older people living in residential care facilities.", "A randomized controlled trial of a behavior advisory service for hospitalized older patients with confusion.", "Falls prevention: the efficacy of a bed alarm system in an acute-care setting.", "Patient education to prevent falls among older hospital inpatients: a randomized controlled trial.", "Falls prevention in residential care homes: a randomised controlled trial.", "Does vitamin D stop inpatients falling? A randomised controlled trial.", "Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial.", "An evaluation of an adapted U.S. model of pharmaceutical care to improve psychoactive prescribing for nursing home residents in northern ireland (fleetwood northern ireland study).", "Evaluation of a hospitalist-run acute care for the elderly service.", "The value of assessing falls in an elderly population. A randomized clinical trial.", "Multifactorial intervention after a fall in older people with cognitive impairment and dementia presenting to the accident and emergency department: randomised controlled trial.", "Does a functional activity programme improve function, quality of life, and falls for residents in long term care? Cluster randomised controlled trial.", "A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study.", "Does the addition of a pharmacist transition coordinator improve evidence-based medication management and health outcomes in older adults moving from the hospital to a long-term care facility? Results of a randomized, controlled trial.", "Effects of exercise programs on falls and mobility in frail and pre-frail older adults: A multicenter randomized controlled trial.", "Fall incidence in frail older women after individualized visual feedback-based balance training.", "Effectiveness of a multifaceted intervention on falls in nursing home residents.", "Effect of a pharmacist-led multicomponent intervention focusing on the medication monitoring phase to prevent potential adverse drug events in nursing homes.", "A fall prevention program for elderly individuals. Exercise in long-term care settings.", "Preventing falls on an elderly care rehabilitation ward.", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].", "Cluster randomised trial of a targeted multifactorial intervention to prevent falls among older people in hospital.", "Fewer adverse events as a result of the SAFE or SORRY? programme in hospitals and nursing homes. part i: primary outcome of a cluster randomised trial.", "Educating nursing home staff on fracture prevention: a cluster randomised trial.", "Comparison of a fall risk assessment tool with nurses' judgement alone: a cluster-randomised controlled trial.", "Using targeted risk factor reduction to prevent falls in older in-patients: a randomised controlled trial.", "Evaluating the use of a targeted multiple intervention strategy in reducing patient falls in an acute care hospital: a randomized controlled trial.", "A cluster randomised controlled trial to prevent injury due to falls in a residential aged care population.", "Effectiveness of targeted falls prevention programme in subacute hospital setting: randomised controlled trial.", "Fall prevention in acute care hospitals: a randomized trial.", "Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation.", "Effects of physical training on the physical capacity of frail, demented patients with a history of falling: a randomised controlled trial.", "New intervention program for preventing falls among frail elderly people: the effects of perturbed walking exercise using a bilateral separated treadmill.", "A randomized controlled trial of fall prevention strategies in old peoples' homes.", "Does increased sunlight exposure work as a strategy to improve vitamin D status in the elderly: a cluster randomised controlled trial.", "Short-term, light- to moderate-intensity exercise training improves leg muscle strength in the oldest old: a randomized controlled trial.", "Focus on caregiving. Falls prevention in dementia populations.", "Effects of unipedal standing balance exercise on the prevention of falls and hip fracture among clinically defined high-risk elderly individuals: a randomized controlled trial.", "A randomized trial of physical rehabilitation for very frail nursing home residents.", "Clinical medication review by a pharmacist of elderly people living in care homes--randomised controlled trial.", "Impact of a fall prevention programme in acute hospital settings in Singapore.", "A multifactorial intervention for the prevention of falls in psychogeriatric nursing home patients, a randomised controlled trial (RCT).", "Fall prevention in residential care: a cluster, randomized, controlled trial.", "Multivitamin supplementation improves nutritional status and bone quality in aged care residents.", "A randomized trial of exercise programs among older individuals living in two long-term care facilities: the FallsFREE program.", "A multidisciplinary, multifactorial intervention program reduces postoperative falls and injuries after femoral neck fracture.", "Fall and injury prevention in older people living in residential care facilities. A cluster randomized trial.", "Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.", "A randomized trial of a consultation service to reduce falls in nursing homes.", "Potential of Snoezelen room multisensory stimulation to improve balance in individuals with dementia: a feasibility randomized controlled trial.", "Caring for Aged Dementia Care Resident Study (CADRES) of person-centred care, dementia-care mapping, and usual care in dementia: a cluster-randomised trial." ]

[ "Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people. Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures, as proved by Decalyos I. Decalyos II is a 2-year, multicenter, randomized, double-masked, placebo-controlled confirmatory study. The intention-to-treat population consisted of 583 ambulatory institutionalized women (mean age 85.2 years, SD = 7.1) randomized to the calcium-vitamin D3 fixed combination group (n = 199); the calcium plus vitamin D3 separate combination group (n = 190) and the placebo group (n = 194). Fixed and separate combination groups received the same daily amount of calcium (1200 mg) and vitamin D3 (800 IU), which had similar pharmacodynamic effects. Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent, with levels returning within the normal range after 6 months. In a subgroup of 114 patients, femoral neck bone mineral density (BMD) decreased in the placebo group (mean = -2.36% per year, SD = 4.92), while remaining unchanged in women treated with calcium-vitamin D3 (mean = 0.29% per year, SD = 8.63). The difference between the two groups was 2.65% (95% CI = -0.44, 5.75%) with a trend in favor of the active treatment group. No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis. The relative risk (RR) of HF in the placebo group compared with the active treatment group was 1.69 (95% CI = 0.96, 3.0), which is similar to that found in Decalyos I (RR = 1.7; 95% CI = 1.0, 2.8). Thus, these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women.", "To evaluate the efficacy of a policy to introduce low-low beds for the prevention of falls and fall injuries on wards that had not previously accessed low-low beds.\n This was a pragmatic, matched, cluster randomized trial with wards paired according to rate of falls. Intervention and control wards were observed for a 6-month period after implementation of the low-low beds on the intervention wards. Data from a 6-month period before this were also collected and included in analyses to ensure comparability between intervention and control group wards.\n Public hospitals located in Queensland, Australia.\n Patients of 18 public hospital wards.\n Provision of one low-low bed for every 12 on a hospital ward, with written guidance for identifying patients at greatest risk of falls.\n Falls and fall injuries in the hospital measured using a computerized incident reporting system.\n There were 10,937 admissions to control and intervention wards combined during the pre-intervention period. There was no significant difference in the rate of falls per 1,000 occupied bed days between intervention and control group wards after the introduction of the low-low beds (generalized estimating equation coefficient=0.23, 95% confidence interval=-0.18-0.65, P=.28). The rate of bed falls, falls resulting in injury, and falls resulting in fracture also did not differ between groups. Some difficulties were encountered in intervention group wards in using the low-low beds as directed.\n A policy for the introduction of low-low beds did not appear to reduce falls or falls with injury, although larger studies would be required to determine their effect on fall-related fractures.", "This paper reports a study to determine changes in the physical fitness (knee and ankle muscle strength, balance, flexibility, and mobility), fall avoidance efficacy, and fall episodes of institutionalized older adults after participating in a 12-week Sun-style Tai Chi exercise programme.\n Fall prevention has a high priority in health promotion for older people because a fall is associated with serious morbidity in this population. Regular exercise is effective in fall prevention for older adults because of improvements in strength and balance. Tai Chi exercise is considered to offer great potential for health promotion and rehabilitation, particularly in the maintenance of good mental and physical condition in older people.\n A quasi-experimental design with a non-equivalent control group was used. Data were collected from September 2001 to January 2002. A total of 68 fall-prone older adults with a mean age of 77.8 years participated in the study, and 29 people in the Tai Chi group and 30 controls completed the post-test measures. The Tai Chi exercise programme was provided three times a week for 12 weeks in the experimental group. Data were analysed for group differences using t-tests.\n At post-test, the experimental group showed significantly improved muscle strength in knee and ankle flexors (P < 0.001) and extensors (P < 0.01), and improved flexibility (P < 0.01) and mobility (P < 0.001) compared with the control group. There was no significant group difference in fall episodes, but the relative risk ratio for the Tai Chi exercise group compared with the control group was 0.62. The experimental group reported significantly more confidence in fall avoidance than did the control group.\n The findings reveal that Tai Chi exercise programmes can safely improve physical strength and reduce fall risk for fall-prone older adults in residential care facilities.", "Falls are particularly common among older people living in residential care facilities. The aim of this randomized controlled trial was to evaluate the effectiveness of a high-intensity functional exercise program in reducing falls in residential care facilities.\n Participants comprised 191 older people, 139 women and 52 men, who were dependent in activities of daily living. Their mean+/-SD score on the Mini-Mental State Examination was 17.8+/-5.1 (range 10-30). Participants were randomized to a high-intensity functional exercise program or a control activity, consisting of 29 sessions over 3 months. The fall rate and proportion of participants sustaining a fall were the outcome measures, subsequently analysed using negative binominal analysis and logistic regression analysis, respectively.\n During the 6-month follow-up period, when all participants were compared, no statistically significant differences between groups were found for fall rate (exercise group 3.6 falls per person years [PY], control group 4.6 falls per PY), incidence rate ratio (95% CI) 0.82 (0.49-1.39), p=0.46, or the proportion of participants sustaining a fall (exercise 53%, control 51%), odds ratio (95% CI) 0.95 (0.52-1.74), p=0.86. A subgroup interaction analysis revealed that, among participants who improved their balance during the intervention period, the exercise group had a lower fall rate than the control group (exercise 2.7 falls per PY, control 5.9 falls per PY), incidence rate ratio (95% CI) 0.44 (0.21-0.91), p=0.03.\n In older people living in residential care facilities, a high-intensity functional exercise program may prevent falls among those who improve their balance.", "To determine whether individualized advice on non-pharmacological strategies for hospitalized older patients with confusion and behavioral problems can improve levels of agitation and reduce the use of psychotropic medication.\n Pragmatic randomized controlled trial in two metropolitan teaching hospitals in South Australia. Seventy-one older patients with confusion and a behavioral disturbance were randomly allocated to receive either an assessment and ongoing individualized advice from an extended practice nurse on non-pharmacological strategies or usual care. Usual care included an assessment by a geriatrician.\n Primary outcomes were levels of agitation (Pittsburgh Agitation Scale), appropriateness of psychotropic medication prescribing (Medication Appropriateness Index) and levels of psychotropics administered (chlorpromazine and diazepam dose equivalents). Secondary outcomes were length of stay, discharge destination, number of falls, restraint use and satisfaction from nursing staff and next of kin.\n Levels of agitation were modest at baseline with mean PAS intervention group 3.4 (SD = 0.5) and control group 4.0 (SD = 0.4) and both groups improved over time to 1.7 (SD = 0.4) for the intervention group and 1.8 (SD = 0.3) for the control group on the final day of data collection. Median length of follow-up was nine days. There was no effect of the intervention on levels of agitation, amount and appropriateness of psychotropic medication prescribed and administered, falls, length of stay, discharge destination, restraint use and nursing and next of kin satisfaction.\n A nursing consultation service providing individualized non-pharmacological advice does not improve patient agitation or use of psychotropic medication for older patients with confusion and behavioral problems in an acute hospital.", "The present study examined the clinical efficacy of a bed alarm system in reducing falls from bed on a geriatric evaluation and treatment unit. A nine-month case-controlled study was designed, in which 70 patients (60 women, 10 men; mean age 84 years, range 67-97 years) at increased risk for bed falls were randomly assigned to either an experimental or a control group. Subjects in the experimental group (n = 35) received a bed alarm system and those in the control group (n = 35) did not. Outcome measures included bed falls, performance of the bed alarm system, and staff attitudes toward the use of the system. Although results failed to demonstrate a statistical difference in bed falls between the experimental (n = 1) and control (n = 4) groups (p = 1.00), there was a clinical trend toward reduced falls in the experimental group. The system functioned properly, activating an alarm in all instances when patients were transferring from bed, and with the exception of one case, nurses could respond in a timely fashion to assist patients and prevent bed falls. The system did not produce any adverse effects in patients, nor did the device interfere with the rendering of medical care. The system was well accepted by patients, families, and nurses. These data suggest that bed alarm systems are beneficial in guarding against bed falls and are an acceptable method of preventing falls.", "Falls are a common adverse event during hospitalization of older adults, and few interventions have been shown to prevent them.\n This study was a 3-group randomized trial to evaluate the efficacy of 2 forms of multimedia patient education compared with usual care for the prevention of in-hospital falls. Older hospital patients (n = 1206) admitted to a mixture of acute (orthopedic, respiratory, and medical) and subacute (geriatric and neurorehabilitation) hospital wards at 2 Australian hospitals were recruited between January 2008 and April 2009. The interventions were a multimedia patient education program based on the health-belief model combined with trained health professional follow-up (complete program), multi-media patient education materials alone (materials only), and usual care (control). Falls data were collected by blinded research assistants by reviewing hospital incident reports, hand searching medical records, and conducting weekly patient interviews.\n Rates of falls per 1000 patient-days did not differ significantly between groups (control, 9.27; materials only, 8.61; and complete program, 7.63). However, there was a significant interaction between the intervention and presence of cognitive impairment. Falls were less frequent among cognitively intact patients in the complete program group (4.01 per 1000 patient-days) than among cognitively intact patients in the materials-only group (8.18 per 1000 patient-days) (adjusted hazard ratio, 0.51; 95% confidence interval, 0.28-0.93]) and control group (8.72 per 1000 patient-days) (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.78).\n Multimedia patient education with trained health professional follow-up reduced falls among patients with intact cognitive function admitted to a range of hospital wards. Trial Registration anzctr.org.au Identifier: ACTRN12608000015347.", "to determine the effect of risk factor modification and balance exercise on falls rates in residential care homes.\n cluster randomised controlled trial.\n 196 residents (aged 60 years or over) in 20 residential care homes were enrolled (38% response rate). Homes were randomly allocated to intervention and control arms. A total of 102 residents were consigned to the intervention arm and 94 to the control arm.\n a multifactorial falls prevention programme including 3 months gait and balance training, medication review, podiatry and optometry.\n number of falls/recurrent falls per person, number of medications per person, and change in Tinetti gait and balance measure.\n in the intervention group there was a mean of 2.2 falls per resident per year compared with 4.0 in the control group; this failed to reach statistical significance (P = 0.2) once the intra-cluster correlation (ICC, 0.10) had been accounted for. Several risk factors were reduced in the intervention arm.\n falls risk factor reduction is possible in residents of care homes. A modest reduction in falls rates was demonstrated but this failed to reach statistical significance.", "Vitamin D deficiency is common in older people and may increase risk of falls and fracture. Hospital inpatients are at particular risk of falling. Previous studies suggest that vitamin D improves neuromuscular function and reduces falls.\n To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are inpatients.\n Randomised, double-blind, controlled study. Participants: two hundred and five acute admissions >65 years to a geriatric medical unit.\n Patients were randomised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg, until discharge or death.\n Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days (IQR 14.75-71.00). In a pre-selected sub-group (54/205 participants), median admission vitamin D level = 22.00 nmol/l (IQR 15.00-30.50). This did not significantly increase in the treatment versus control group. Median study drug adherence = 88%, with no significant difference between study groups (Mann-Whitney: P = 0.711). Although there were fewer fallers in the vitamin D cohort, this did not reach statistical significance (vitamin D: calcium = 36:45 fallers; RR 0.82 (CI 0.59-1.16). Neither the mean number of falls (vitamin D: calcium = 1.040:1.155; Mann-Whitney P = 0.435) or time to first fall (Log-rank test P = 0.377) differed between groups.\n In a population of geriatric hospital inpatients, vitamin D did not reduce the number of fallers. Routine supplementation cannot be recommended to reduce falls in this group.", "To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient.\n Randomized, placebo-controlled double-blind, trial of 2 years' duration.\n Multicenter study in 60 hostels (assisted living facilities) and 89 nursing homes across Australia.\n Six hundred twenty-five residents (mean age 83.4) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L.\n Vitamin D supplementation (ergocalciferol, initially 10,000 IU given once weekly and then 1,000 IU daily) or placebo for 2 years. All subjects received 600 mg of elemental calcium daily as calcium carbonate.\n Falls and fractures recorded prospectively in study diaries by care staff.\n The vitamin D and placebo groups had similar baseline characteristics. In intention-to-treat analysis, the incident rate ratio for falling was 0.73 (95% confidence interval (CI)=0.57-0.95). The odds ratio for ever falling was 0.82 (95% CI=0.59-1.12) and for ever fracturing was 0.69 (95% CI=0.40-1.18). An a priori subgroup analysis of subjects who took at least half the prescribed capsules (n=540), demonstrated an incident rate ratio for falls of 0.63 (95% CI=0.48-0.82), an odds ratio (OR) for ever falling of 0.70 (95% CI=0.50-0.99), and an OR for ever fracturing of 0.68 (95% CI=0.38-1.22).\n Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient.", "To test the effect of an adapted U.S. model of pharmaceutical care on prescribing of inappropriate psychoactive (anxiolytic, hypnotic, and antipsychotic) medications and falls in nursing homes for older people in Northern Ireland (NI).\n Cluster randomized controlled trial.\n Nursing homes randomized to intervention (receipt of the adapted model of care; n=11) or control (usual care continued; n=11).\n Residents aged 65 and older who provided informed consent (N=334; 173 intervention, 161 control).\n Specially trained pharmacists visited intervention homes monthly for 12 months and reviewed residents' clinical and prescribing information, applied an algorithm that guided them in assessing the appropriateness of psychoactive medication, and worked with prescribers (general practitioners) to improve the prescribing of these drugs. The control homes received usual care.\n The primary end point was the proportion of residents prescribed one or more inappropriate psychoactive medicine according to standardized protocols; falls were evaluated using routinely collected falls data mandated by the regulatory body for nursing homes in NI.\n The proportion of residents taking inappropriate psychoactive medications at 12 months in the intervention homes (25/128, 19.5%) was much lower than in the control homes (62/124, 50.0%) (odds ratio=0.26, 95% confidence interval=0.14-0.49) after adjustment for clustering within homes. No differences were observed at 12 months in the falls rate between the intervention and control groups.\n Marked reductions in inappropriate psychoactive medication prescribing in residents resulted from pharmacist review of targeted medications, but there was no effect on falls.", "Comprehensive care for frail older inpatients may improve selected outcomes and reduce harm.\n To evaluate a Hospitalist-run Acute Care for the Elderly (Hospitalist-ACE) service.\n Quasi-randomized, controlled trial.\n Urban academic medical center.\n Medical inpatients age ≥70 years.\n Hospitalist-ACE service components: 1) selected hospitalist attendings; 2) daily interdisciplinary rounds; 3) standardized geriatric assessment; 4) clinical focus on mitigating harm and discharge planning; 5) novel inpatient geriatrics curriculum.\n The primary outcome was recognition of abnormal functional status by the primary medical team. Secondary outcomes included: recognition of abnormal cognitive status and delirium by the primary medical team; use of physical restraints and sleep aids; documentation of code status; hospital charges, length of stay, readmission rates, discharge location, and falls.\n One hundred twenty-two Hospitalist-ACE patients were compared to 95 usual care patients. Hospitalist-ACE patients had significantly greater recognition of abnormal functional status (65% vs 32%, P < 0.0001), and abnormal cognitive status (57% vs 36%, P = 0.02), and greater use of \"Do Not Attempt Resuscitation\" orders (39% vs 26%, P = 0.04). There were no differences in use of physical restraints, or sleep aids, falls, or discharge location. Hospitalist-ACE patients and usual care patients had similar mean lengths of stay in days (3.4 ± 2.7 vs 3.1 ± 2.7, P = 0.52), mean charges ($24,617 ± $15,828 vs $21,488 ± $13,407, P = 0.12), and 30-day readmission rates (12% vs 10%, P = 0.50).\n A Hospitalist-ACE service may improve care processes without significantly increasing resource consumption. No impact on key clinical outcomes was observed.\n Copyright © 2011 Society of Hospital Medicine.", "To measure the effects of a specialized postfall assessment intended to detect causes and underlying risk factors for falls, and to recommend preventive and therapeutic interventions.\n Randomized, controlled trial.\n A long-term residential care facility for elderly persons.\n Within 7 days of a fall, 160 ambulatory subjects (mean age, 87 years) were randomly assigned to receive either a comprehensive postfall assessment (intervention group, n = 79) or usual care (control group, n = 81).\n The postfall assessment included a detailed physical examination and environmental assessment by a nurse practitioner; laboratory tests; electrocardiogram; and 24-hour Holter monitoring. Probable cause or causes for the fall, identified risk factors, and therapeutic recommendations were given to the patient's primary physician.\n Through use of the assessment, many remediable problems (for example, weakness, environmental hazards, orthostatic hypotension, drug side effects, gait dysfunction) were detected. At the end of the 2-year follow-up period, the intervention group had 26% fewer hospitalizations (P less than 0.05) and a 52% reduction in hospital days (P less than 0.01) compared with controls. Patients in the intervention group had 9% fewer falls and 17% fewer deaths than controls by 2 years, but these trends were not statistically significant.\n Our study suggests that falls are a marker of underlying disorders easily identifiable by a careful postfall assessment, which in turn can reduce disability and costs.", "To determine the effectiveness of multifactorial intervention after a fall in older patients with cognitive impairment and dementia attending the accident and emergency department.\n Randomised controlled trial.\n 274 cognitively impaired older people (aged 65 or over) presenting to the accident and emergency department after a fall: 130 were randomised to assessment and intervention and 144 were randomised to assessment followed by conventional care (control group).\n Two accident and emergency departments, Newcastle upon Tyne.\n Primary outcome was number of participants who fell in year after intervention. Secondary outcomes were number of falls (corrected for diary returns), time to first fall, injury rates, fall related attendances at accident and emergency department, fall related hospital admissions, and mortality.\n Intention to treat analysis showed no significant difference between intervention and control groups in proportion of patients who fell during 1 year's follow up (74% (96/130) and 80% (115/144), relative risk ratio 0.92, 95% confidence interval 0.81 to 1.05). No significant differences were found between groups for secondary outcome measures.\n Multifactorial intervention was not effective in preventing falls in older people with cognitive impairment and dementia presenting to the accident and emergency department after a fall.", "To assess the effectiveness of an activity programme in improving function, quality of life, and falls in older people in residential care.\n Cluster randomised controlled trial with one year follow-up.\n 41 low level dependency residential care homes in New Zealand.\n 682 people aged 65 years or over.\n 330 residents were offered a goal setting and individualised activities of daily living activity programme by a gerontology nurse, reinforced by usual healthcare assistants; 352 residents received social visits.\n Function (late life function and disability instruments, elderly mobility scale, FICSIT-4 balance test, timed up and go test), quality of life (life satisfaction index, EuroQol), and falls (time to fall over 12 months). Secondary outcomes were depressive symptoms and hospital admissions.\n 473 (70%) participants completed the trial. The programme had no impact overall. However, in contrast to residents with impaired cognition (no differences between intervention and control group), those with normal cognition in the intervention group may have maintained overall function (late life function and disability instrument total function, P=0.024) and lower limb function (late life function and disability instrument basic lower extremity, P=0.015). In residents with cognitive impairment, the likelihood of depression increased in the intervention group. No other outcomes differed between groups.\n A programme of functional rehabilitation had minimal impact for elderly people in residential care with normal cognition but was not beneficial for those with poor cognition. Trial registration Australian Clinical Trials Register ACTRN12605000667617.", "To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents.\n Secondary data analysis of a previously conducted randomized clinical trial.\n Seven hundred twenty-five-bed long-term care facility.\n One hundred twenty-four nursing home residents (average age 89).\n Participants were randomly assigned to receive one of four vitamin D supplement doses (200 IU, 400 IU, 600 IU, or 800 IU) or placebo daily for 5 months.\n Number of fallers and number of falls assessed using facility incident tracking database.\n Over the 5-month study period, the proportion of participants with falls was 44% in the placebo group (11/25), 58% (15/26) in the 200 IU group, 60% (15/25) in the 400 IU group, 60% (15/25) in the 600 IU group, and 20% (5/23) in the 800 IU group. Participants in the 800 IU group had a 72% lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months (rate ratio=0.28; 95% confidence interval=0.11-0.75). No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups.\n Nursing home residents in the highest vitamin D group (800 IU) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses. Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group.", "Poorly executed transfers of older patients from hospitals to long-term care facilities carry the risk of fragmentation of care, poor clinical outcomes, inappropriate use of emergency department services, and hospital readmission.\n This study was conducted to assess the impact of adding a pharmacist transition coordinator on evidence-based medication management and health outcomes in older adults undergoing first-time transfer from a hospital to a long-term care facility.\n This randomized, single-blind, controlled trial enrolled hospitalized older adults awaiting transfer to a long-term residential care facility for the first time. Patients were randomized either to receive the services of the pharmacist transition coordinator (intervention group) or to undergo the usual hospital discharge process (control group). The intervention included medication-management transfer summaries from hospitals, timely coordinated medication reviews by accredited community pharmacists, and case conferences with physicians and pharmacists. The primary outcome was the quality of prescribing, measured using the Medication Appropriateness Index (MAI). Secondary outcomes were emergency department visits, hospital readmissions, adverse drug events, falls, worsening mobility, worsening behaviors, increased confusion, and worsening pain.\n One hundred ten older adults (67 women, 43 men; mean [SD] age, 82.7 [6.4] years) were recruited from 3 metropolitan hospitals and assigned to 85 metropolitan long-term care facilities. Fifty-six patients were randomized to the intervention group and 54 to the control group; 44 patients in each group were evaluable at 8-week follow-up. There were no significant differences in baseline characteristics between treatment groups, with the exception of the number of medications discontinued during hospitalization: a mean of 1.1 more drugs was discontinued in the control group compared with the intervention group (P = 0.011). The majority of patients (35 [62.5%] in the intervention group, 41 [76.0%] in the control group) changed physicians as part of the transition to a long-term care facility. At 8-week follow-up, there was no change in MAI from baseline in the intervention group, whereas it had worsened in the control group (mean [95% CI], 2.5 [1.4-3.7] vs 6.5 [3.9-9.1], respectively; P = 0.007). Patients who received the intervention and were alive at follow-up exhibited a significant protective effect of the intervention against worsening pain (relative risk ratio [95% CI], 0.55 [0.32-0.94]; P = 0.023) and hospital usage (i.e., the combination of emergency department visits and hospital readmissions) (0.38 [0.15-0.99]; P = 0.035), but did not differ from control patients in terms of adverse drug events (1.05 [0.66-1.68]), falls (1.19 [0.71-1.99]), worsening mobility (0.39 [0.13-1.15]), worsening behaviors (0.52 [0.25-1.10]), or increased confusion (0.59 [0.28-1.22]). When data for patients who had died were included, the intervention had no effect on hospital usage in all patients (0.58 [0.28-1.21]).\n Older people transferring from hospital to a long-term care facility are vulnerable to fragmentation of care and adverse events. In this study, use of a pharmacist transition coordinator improved aspects of inappropriate use of medicines across health sectors.", "To determine the effects of moderate intensity group-exercise programs on falls, functional performance, and disability in older adults; and to investigate the influence of frailty on these effects.\n A 20-week, multicenter randomized controlled trial, with 52-week follow-up.\n Fifteen homes for the elderly.\n Two hundred seventy-eight men and women (mean age +/- standard deviation, 85+/-6y).\n Two exercise programs were randomly distributed across 15 homes. The first program, functional walking (FW), consisted of exercises related to daily mobility activities. In the second program, in balance (IB), exercises were inspired by the principles of Tai Chi. Within each home participants were randomly assigned to an intervention or a control group. Participants in the control groups were asked not to change their usual pattern of activities. The intervention groups followed a 20-week exercise program with 1 meeting a week during the first 4 weeks and 2 meetings a week during the remaining weeks.\n Falls, Performance Oriented Mobility Assessment (POMA), physical performance score, and the Groningen Activity Restriction Scale (GARS) (measuring self-reported disability).\n Fall incidence rate was higher in the FW group (3.3 falls/y) compared with the IB (2.4 falls/y) and control (2.5 falls/y) groups, but this difference was not statistically significant. The risk of becoming a faller in the exercise groups increased significantly in the subgroup of participants who were classified as being frail (hazard ratio [HR] = 2.95; 95% confidence interval [CI], 1.64-5.32). For participants who were classified as being pre-frail, the risk of becoming a faller decreased; this effect became significant after 11 weeks of training (HR = .39; 95% CI, .18-.88). Participants in both exercise groups showed a small, but significant improvement in their POMA and physical performance scores. In the FW group, this held true for the GARS score as well. Post hoc analyses revealed that only the pre-frail participants improved their POMA and physical performance scores.\n Fall-preventive moderate intensity group-exercise programs have positive effects on falling and physical performance in pre-frail, but not in frail elderly.", "The knowledge concerning balance training actually lowering fall rates among frail older persons is limited.\n The aim of this study was to examine the effects of a 4-week individualized visual feedback-based balance training on the fall incidence during 1-year follow-up among frail older women living in residential care.\n Twenty-seven older women from 2 residential care homes were randomized into exercise (n = 20) and control (n = 7) groups. Balance measurements were carried out before and after a 4-week training period and falls were monitored by monthly diaries for 1 year. An interview about fear of falling and physical activity was completed before and after the intervention and after the 1-year follow-up.\n A positive effect of balance training on fall incidence was found. A dynamic Poisson regression model showed that during the follow-up the monthly risk of falling was decreased in the exercise group compared to controls (risk ratio 0.398, 95% CI 0.174-0.911, p = 0.029). In addition, the exercise group reported a reduced fear of falling and increased physical activity after a training period but these changes declined during the follow-up period.\n Individualized visual feedback-based balance training was shown to be a promising method for fall prevention among frail older women. High compliance (97.5%) with the training program showed that carefully targeted training programs can be carried out among older people with health limitations.\n Copyright 2004 S. Karger AG, Basel.", "To evaluate the effectiveness of a multifaceted, nonpharmaceutical intervention on incidence of falls and fallers.\n Prospective, cluster-randomized, controlled 12-month trial.\n Six community nursing homes in Germany.\n Long-stay residents (n = 981) aged 60 and older; mean age 85; 79% female.\n Staff and resident education on fall prevention, advice on environmental adaptations, progressive balance and resistance training, and hip protectors.\n Falls, fallers, and fractures.\n The incidence density rate of falls per 1,000 resident years (RY) was 2,558 for the control group (CG) and 1,399 for the intervention group (IG) (relative risk (RR) = 0.55, 95% confidence interval (CI) = 0.41-0.73). Two hundred forty-seven (52.3%) fallers were detected in the CG and 188 (36.9%) in the IG (RR = 0.75, 95% CI = 0.57-0.98). The incidence density rate of frequent fallers (>2/year) was 115 (24.4%) for the CG and 66 (13.0%) for the IG (RR = 0.56, 95% CI = 0.35-0.89). The incidence density rate of hip fractures per 1,000 RY was 39 for the CG and 43 for the IG (RR = 1.11, 95% CI = 0.49-2.51). Other fractures were diagnosed with an incidence density rate of 52 per 1,000 RY for CG and 41 per 1,000 RY for IG (RR = 0.78, 95% CI = 0.57-1.07).\n The incidence density rate of falls and fallers differed considerably between the control and intervention groups. The study was underpowered to demonstrate a significant difference of hip or nonhip fractures. Because of a low fracture rate in both groups, the investigation of fracture rates would have required a larger sample size to detect an effect of the intervention.", "To determine the extent to which the use of a clinical informatics tool that implements prospective monitoring plans reduces the incidence of potential delirium, falls, hospitalizations potentially due to adverse drug events, and mortality.\n Randomized cluster trial.\n Twenty-five nursing homes serviced by two long-term care pharmacies.\n Residents living in nursing homes during 2003 (1,711 in 12 intervention; 1,491 in 13 usual care) and 2004 (1,769 in 12 intervention; 1,552 in 13 usual care).\n The pharmacy automatically generated Geriatric Risk Assessment MedGuide (GRAM) reports and automated monitoring plans for falls and delirium within 24 hours of admission or as part of the normal time frame of federally mandated drug regimen review.\n Incidence of potential delirium, falls, hospitalizations potentially due to adverse drug events, and mortality.\n GRAM triggered monitoring plans for 491 residents. Newly admitted residents in the intervention homes experienced a lower rate of potential delirium onset than those in usual care homes (adjusted hazard ratio (HR)=0.42, 95% confidence interval (CI)=0.35-0.52), overall hospitalization (adjusted HR=0.89, 95% CI=0.72-1.09), and mortality (adjusted HR=0.88, 95% CI=0.66-1.16). In longer stay residents, the effects of the intervention were attenuated, and all estimates included unity.\n Using health information technology in long-term care pharmacies to identify residents who might benefit from the implementation of prospective medication monitoring care plans when complex medication regimens carry potential risks for falls and delirium may reduce adverse effects associated with appropriate medication use.\n © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.", "The purpose of this research was to explore the role of exercise in preventing falls, specifically assessing the effectiveness of an ankle strengthening and walking program to improve balance, ankle strength, walking speed, and falls efficacy and to decrease falls and subjects' fear of falling. Sixteen individuals participated in the study which was conducted at two nursing homes. Subjects were assigned randomly to an intervention or control group. The participants in the intervention group completed a 3-month supervised program of ankle strengthening exercises and walking. Descriptive statistics were used to characterize the sample, and differences in the least square means were used to assess the outcome variables (i.e., balance, ankle strength, walking speed, falls, fear of falling, falls efficacy) before the exercise program, and again at 3 months and 6 months after the program for the intervention and control subjects. Findings for the intervention group from pretest to 3-month posttest were, for the most part, maintained or in the predicted direction, suggesting that regular exercise shows promise for preventing deterioration and improving fall-related outcomes for elderly nursing home residents.", "Comparison of two flooring types--carpet and vinyl--in the bed areas, and two modes of physiotherapy--conventional therapy and additional leg strengthening exercises--in avoiding falls.\n Randomized 2 x 2 controlled trial.\n Elderly care rehabilitation ward in a community hospital.\n Fifty-four consecutive patients referred for rehabilitation.\n The incidence of falls, and the change in strength.\n There were 10 falls on carpet, and only a single fall on vinyl floor covering (relative risk 8.3, 95% confidence interval 0.95-73, p = 0.05). There were four falls in those receiving additional exercise, and seven falls in those receiving only conventional physiotherapy (relative risk 0.21, 95% confidence interval 0.04-1.2, p = 0.12). Fifty-nine per cent of patients were able to complete strength measurements on admission and discharge. In these, handgrip strength improved more in those given additional exercise than conventional physiotherapy (2.1 kg versus -0.3 kg, p < 0.05).\n There is no evidence to support either intervention in preventing falls on a rehabilitation ward, but within this low-powered study, there was a strong trend towards vinyl being superior.", "The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained.", "To determine the efficacy of a targeted multifactorial falls prevention programme in elderly care wards with relatively short lengths of stay.\n Cluster randomised trial.\n 24 elderly care wards in 12 hospitals in Sydney, Australia.\n 3999 patients, mean age 79 years, with a median hospital stay of seven days.\n A nurse and physiotherapist each worked for 25 hours a week for three months in all intervention wards. They provided a targeted multifactorial intervention that included a risk assessment of falls, staff and patient education, drug review, modification of bedside and ward environments, an exercise programme, and alarms for selected patients.\n Falls during hospital stay.\n Intervention and control wards were similar at baseline for previous rates of falls and individual patient characteristics. Overall, 381 falls occurred during the study. No difference was found in fall rates during follow-up between intervention and control wards: respectively, 9.26 falls per 1000 bed days and 9.20 falls per 1000 bed days (P=0.96). The incidence rate ratio adjusted for individual lengths of stay and previous fall rates in the ward was 0.96 (95% confidence interval 0.72 to 1.28).\n A targeted multifactorial falls prevention programme was not effective among older people in hospital wards with relatively short lengths of stay.\n Australian New Zealand Clinical Trials Registry ACTRNO 12605000467639.", "Patient care guidelines are usually implemented one at a time, yet patients are at risk for multiple, often preventable, adverse events simultaneously.\n This study aimed to test the effect of the SAFE or SORRY? programme on the incidence of three adverse events (pressure ulcers, urinary tract infections and falls). This paper describes Part I of the study: the effect on the incidence of adverse events.\n A cluster randomised trial was conducted between September 2006 and November 2008. After a three-month baseline period the intervention was implemented followed by a nine-month follow-up period.\n Ten wards from four hospitals and ten wards from six nursing homes were stratified for institute and ward type and then randomised to intervention or usual care group.\n During baseline and follow-up, patients (≥18 years) with an expected length of stay of at least five days, were asked to participate.\n The SAFE or SORRY? programme consisted of the essential recommendations of guidelines for the three adverse events. A multifaceted implementation strategy was used for the implementation: education, patient involvement and feedback on process and outcome indicators. The usual care group continued care as usual. Data were collected on the incidence of adverse events and a Poisson regression model was used to estimate the rate ratio of the adverse events between the intervention and the usual care group at follow-up.\n At follow-up, 2201 hospital patients with 3358 patient weeks and 392 nursing home patients with 5799 patient weeks were observed. Poisson regression analyses showed a rate ratio for the development of an adverse event in favour of the intervention group of 0.57 (95% CI: 0.34-0.95) and 0.67 (95% CI: 0.48-0.99) for hospital patients and nursing home patients respectively.\n This study showed that implementing multiple guidelines simultaneously is possible, which is promising. Patients in the intervention groups developed 43% and 33% fewer adverse events compared to the usual care groups in hospitals and nursing homes respectively. Even so, more research is necessary to underline these results.\n clinicaltrials.gov, number NCT00365430.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "to assess whether specialist osteoporosis nurses delivering training to care home staff can reduce fractures and improve the prescription of treatments to reduce fractures versus usual care.\n pragmatic cluster randomised controlled trial (RCT) with randomisation at the Primary Care Organisation (PCO) level.\n care homes (residential, nursing and EMI) across England and Wales within PCOs.\n all 300 PCOs in England and Wales were invited to take part. Of these, 58 agreed to participate and gained ethical approval in time to start the study: 29 clusters were randomised to the intervention group and 29 to the control.\n specialist osteoporosis nurses undertaking short training sessions with care home staff emphase the importance of fracture and fall prevention and train staff on how to identify those residents at high risk of fracture. Residents' risk of fracture and falls was reported to general practitioners (GPs) of patients along with treatment recommendations.\n primary outcome measures were total fractures over the past 12 months and total hip fractures over past the 12 months. Secondary outcome measures were total home falls, number of residents sustaining a fall, number of residents prescribed bisphosphonates, number of residents prescribed calcium and vitamin D and number of residents wearing hip protectors. All outcomes were measured at the care home level.\n of the 230 care homes randomised data were collected from 209 of these containing 5,637 residents. There were no differences between the groups in the incidence rate ratios (IRRs) for total fractures (IRR = 0.94 [0.71, 1.26] P = 0.70) or total hip fractures (IRR = 0.86 [0.63, 1.18] P = 0.36). No differences were found between groups for home falls or hip protector use. A significant increase in bisphosphonate prescription was seen in the intervention group over the control group (IRR = 1.50 [1.00, 2.24] P = 0.05). Calcium and vitamin D prescription was significantly increased in the intervention group over the control group (IRR = 1.64 [1.23, 2.18] P<0.01).\n the intervention significantly increased the prescription of bisphosphonates and calcium/vitamin D, but was not associated with a significant effect on the rate of falls or fractures.", "the impact of fall risk assessment tools on clinical endpoints is unknown.\n we compared a standardised fall risk assessment tool alongside nurses' clinical judgement with nurses' judgement alone.\n a 12-month cluster-randomised controlled trial.\n nursing homes in Hamburg (29 per study group).\n 1,125 residents (n = 574 intervention group, IG; n = 551 control group, CG).\n all homes received structured information on fall prevention before randomisation. The IG monthly administered the Downton Index, and the CG did not use a tool. Measurements were number of participants with at least one fall, falls, fall-related injuries and medical attention, fall preventive measures, physical restraints.\n the mean follow-up was 10.8 +/- 2.9 months in both groups: 105 (IG) and 114 (CG) residents died or moved away. There was no difference between the groups concerning the number of residents with at least one fall (IG: 52%, CG: 53%, mean difference -0.7, 95% confidence interval -10.3 to 8.9, P = 0.88) and the number of falls (n = 1,016 and n = 1,014). All other outcomes were also comparable between the IG and CG.\n application of a fall risk assessment tool in nursing homes does not result in the better clinical outcome than reliance on nurses' clinical judgement alone.", "falls and related injuries are known to be a significant problem for older people. There is evidence that identifying and addressing individual risk factors can reduce the incidence of falls in the community but no evidence of the effectiveness of targeted risk factor reduction methods applied to hospital in-patients.\n to test the efficacy of a targeted risk factor reduction core care plan in reducing risk of falling while in hospital.\n a group (ward) randomised trial.\n elderly care wards and associated community units of a district general hospital in the North of England.\n all elderly patients who received care in eight wards and community units during a 12-month study period.\n matched pairs of wards were randomly allocated to intervention or control groups. In the intervention wards, staff used a pre-printed care plan for patients identified as at risk of falling and introduced appropriate remedial measures. Numbers of falls in each group were then compared.\n after introduction of the care plan there was a significant reduction in the relative risk of recorded falls on intervention wards (relative risk 0.79, 95% CI 0.65-0.95) but not on control wards (RR 1.12, 95% CI 0.96-1.31). The difference in change between the intervention wards and control wards was highly significant (RR 0.71, 95% CI 0.55-0.90, P = 0.006). There was no significant reduction in the incidence of falls-related injuries.\n the use of a core care plan targeting risk factor reduction in older hospital in-patients was associated with a reduction in the relative risk of recorded falls.", "This article is a report of a randomized controlled trial to examine the effectiveness of a targeted multiple intervention strategy in reducing the number of patient falls in an acute care hospital.\n Prevention of patient falls remains a challenge that has eluded healthcare institutions. The effectiveness of targeted multiple fall prevention interventions in reducing the incidences of falling has not been established.\n Patients who scored 5 and above on the Hendrich II Fall Risk Model, a fall assessment tool, were recruited in 2006. Patients who were randomized to the intervention group received targeted multiple interventions. Both the research groups received the standard fall prevention interventions from the ward nurses. The rates of fall incidences for both groups were reported with 95% CI, calculated using Wilson method and compared using the Chi-square test. The relative risk was estimated and 95% CI was calculated using the methods described by Armitage and Berry. The times to first fall events were constructed using the Kaplan-Meier method. The hazard ratio was reported at 95% CI and the comparison was made using the log-rank test.\n There were 912 and 910 participants in the control and intervention groups, respectively. The fall incidence rates were 1·5% (95% CI: 0·9-2·6) and 0·4% (95% CI: 0·2-1·1) in the control and intervention groups, respectively. The relative risk estimate of 0·29 (95% CI: 0·1-0·87) favours the intervention group.\n This study showed that targeted multiple interventions were effective in reducing the incidences of falls in patients in the acute care setting.\n © 2011 Blackwell Publishing Ltd.", "To test the effectiveness of using a full-time project nurse to assist residential aged care facilities in using evidence-based approaches to falls injury prevention.\n Cluster randomised controlled trial involving 5391 residents in 88 aged care facilities in the Hunter and Lower Mid North Coast areas of New South Wales. Residents were followed for 545 days or until death or discharge. Data were collected from July 2005 to June 2007.\n Employment of a project nurse to encourage best-practice falls injury prevention strategies during the 17-month intervention period.\n Monthly data about falls, falls injury and falls injury prevention programs; audit of hospitalisation for fractured neck of femur.\n Despite significant increases in the provision of hip protectors and use of vitamin D supplementation in both intervention and control facilities, there was no difference in the number of falls or falls injuries between the intervention and control groups, nor a reduction in falls overall. There was also no difference between the 7-month pre-intervention period and the intervention period in the number of falls or falls injuries. Factors related to residents having an increased risk of falls with fractured neck of femur included being ambulant, having dementia, increasing age, and having a high falls risk assessment score.\n It is difficult to change falls risk among high-risk populations, including people with dementia. The use of important strategies such as hip protectors and vitamin D and calcium supplementation increased during the study, probably with contamination of control facilities. Longer follow-up may be required to measure the impact on falls outcomes of the strategy of using a facilitating nurse.\n Australian New Zealand Clinical Trials Registry ACTRN12605000540617.", "To assess the effectiveness of a targeted, multiple intervention falls prevention programme in reducing falls and injuries related to falls in a subacute hospital.\n Randomised controlled trial of a targeted multiple intervention programme implemented in addition to usual care compared with usual care alone.\n Three subacute wards in a metropolitan hospital specialising in rehabilitation and care of elderly patients.\n 626 men and women aged 38 to 99 years (average 80 years) were recruited from consecutive admissions to subacute hospital wards.\n Falls risk alert card with information brochure, exercise programme, education programme, and hip protectors.\n Incidence rate of falls, injuries related to falls, and proportion of participants who experienced one or more falls during their stay in hospital.\n Participants in the intervention group (n = 310) experienced 30% fewer falls than participants in the control group (n = 316). This difference was significant (Peto log rank test P = 0.045) and was most obvious after 45 days of observation. In the intervention group there was a trend for a reduction in the proportion of participants who experienced falls (relative risk 0.78, 95% confidence interval 0.56 to 1.06) and 28% fewer falls resulted in injury (log rank test P = 0.20).\n A targeted multiple intervention falls prevention programme reduces the incidence of falls in the subacute hospital setting.", "Falls cause injury and death for persons of all ages, but risk of falls increases markedly with age. Hospitalization further increases risk, yet no evidence exists to support short-stay hospital-based fall prevention strategies to reduce patient falls.\n To investigate whether a fall prevention tool kit (FPTK) using health information technology (HIT) decreases patient falls in hospitals.\n Cluster randomized study conducted January 1, 2009, through June 30, 2009, comparing patient fall rates in 4 urban US hospitals in units that received usual care (4 units and 5104 patients) or the intervention (4 units and 5160 patients).\n The FPTK integrated existing communication and workflow patterns into the HIT application. Based on a valid fall risk assessment scale completed by a nurse, the FPTK software tailored fall prevention interventions to address patients' specific determinants of fall risk. The FPTK produced bed posters composed of brief text with an accompanying icon, patient education handouts, and plans of care, all communicating patient-specific alerts to key stakeholders.\n The primary outcome was patient falls per 1000 patient-days adjusted for site and patient care unit. A secondary outcome was fall-related injuries.\n During the 6-month intervention period, the number of patients with falls differed between control (n = 87) and intervention (n = 67) units (P=.02). Site-adjusted fall rates were significantly higher in control units (4.18 [95% confidence interval {CI}, 3.45-5.06] per 1000 patient-days) than in intervention units (3.15 [95% CI, 2.54-3.90] per 1000 patient-days; P = .04). The FPTK was found to be particularly effective with patients aged 65 years or older (adjusted rate difference, 2.08 [95% CI, 0.61-3.56] per 1000 patient-days; P = .003). No significant effect was noted in fall-related injuries.\n The use of a fall prevention tool kit in hospital units compared with usual care significantly reduced rate of falls.\n clinicaltrials.gov Identifier: NCT00675935.", "To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation.\n A randomised controlled trial of cluster design.\n 223 Residential units (mainly identical 30-bedded units), within 118 homes for elderly people throughout Britain, with 3,717 participating residents (76% women, average age 85 years). The units provided mainly or entirely residential care (35% of residents), nursing care (42%) or care for elderly mentally infirm (EMI) residents (23%).\n Participants were randomly allocated by residential unit (cluster design) to a treated group offered ergocalciferol 2.5 mg every 3 months (equivalent to a daily dose of 1,100 IU), or to a control group. Fractures were reported by staff and confirmed in hospital, and routinely collected data on reported falls were obtained.\n After median follow-up of 10 months (interquartile range 7-14 months), 64 (3.6%) of 1,762 vitamin D-treated residents and 51 (2.6%) of 1,955 controls had one or more non-vertebral fractures, and 24 (1.3%) and 20 (1.0%), respectively, had a hip fracture. The proportion reporting at least one fall was 44% in vitamin D-treated and 43% in control residents. The differences between the vitamin D and control groups were not statistically significant. The incidence of all non-vertebral fractures in the care homes (3.2% per year) and of hip fractures (1.1% per year) was low, similar to rates in elderly people in sheltered accommodation, and the pre-treatment serum 25-hydroxy vitamin D concentration was high [median 47 nmol/l, measured in a 1% (n = 18) sample].\n We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation.", "to develop a physical training programme to improve balance in dependent, demented, people with a history of falling, and so decrease falls and increase autonomy.\n the study was undertaken on 20 demented elderly people with a history of falling with an average age of 81.4+/-4.7 years and an average mini mental state score of 16.3+/-6.5. They had all passed 'get up and go', 'chair sit and reach', walking speed and static balance tests. They were assigned to a control group or a training group; the latter were trained with two sessions a week for 16 weeks.\n walking, mobility, flexibility and static balance were significantly improved in the training group (P<0.05), but not in the controls. The trained subjects did not suffer a relapse, while the controls did during the training period.\n the balance of frail, demented, elderly patients with a history of falling can be improved by training.", "To determine the effects of a perturbed walking exercise using a bilateral separated treadmill in physically disabled elderly.\n Participants of the study were 32 long-term care facility residents and outpatients aged 66-98 yrs. Participants were randomly assigned to a usual exercise group or to a treadmill exercise group. Perturbed gait exercise on a treadmill continued for 6 mos. Number of falls and time to first fall during a 6-mo period, balance and gait functions, and reaction time were evaluated before and after intervention.\n The treadmill exercise group showed significant improvement in balance and reaction time when compared with the usual exercise group. Number of falls in the treadmill exercise group was 21% lower than that in the usual exercise group. However, this difference was not significant. No significant differences were seen in time to first fall.\n Gait training with unexpected perturbation seems to have a beneficial impact on physical function in disabled elderly individuals. The results suggest that this program may be used as an exercise intervention to reduce falls in institutional settings.", "Falls are a major cause of morbidity in old age. A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective. This study set out to examine the preventability of falls in older people living in institutional care.\n To evaluate the effectiveness of falls risk factor assessment/modification and seated balance exercise training in reducing falls among elderly people living in residential care.\n 133 residents with a mean age of 84+/- (SD) 6.8 years were allocated at random by home to receive either a 6-month falls risk factor assessment/modification and seated balance exercise training programme (n = 77) or 6 months of reminiscence therapy (n = 56). The risk factors targeted were postural hypotension, polypharmacy, visual acuity, and ambient lighting levels. Falls risk factor assessments and recommendation for modifications were performed at baseline in the intervention group and assessments repeated at 6 months. Functional reach, reaction time, timed up-and- go, grip strength, spinal flexibility, and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a 'blind' observer. Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period.\n Only 90 of 133 (67.7%) residents completed the 6-month intervention period, and 84 (63.2%) completed the 7- to 12-month falls-monitoring follow-up period. Both prevalence of postural hypotension (p = 0.0005) and poor visual acuity (p = 0.04) were reduced in the intervention group. There was no difference between the groups in the number of falls sustained, the risk of falling [odds ratio 0.45 (95% CI 0.19-1.14)], or in the risk of recurrent falling [odds ratio 1.07 (95% CI 0.40-2.97)]. No significant differences were found between the groups with regard to change in other outcome measures.\n The high drop-out rate reduced the power of this study to detect any effect of the interventions used. It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed standing. Further research is required to identify effective fall prevention strategies for elderly people in residential settings.\n Copyright 2000 S. Karger AG, Basel", "Sunlight exposure by improving vitamin D status could be a simple public health strategy in reducing falls among frail elder people. In a randomised controlled trial, adherence to sunlight exposure was low (median adherence, 26%) and no effect of increased UV exposure on falls risk was observed (incidence rate ratio (IRR) 1.06, P = 0.73).\n This study aimed to determine whether increased sunlight exposure was effective to improve vitamin D status and reduce falls in the elderly.\n In a cluster randomised controlled trial (NCT00322166 at ClinicalTrials.gov), 602 residents aged 70 or more (mean age, 86.4 years; 71% female) were recruited from 51 aged care facilities in Northern Sydney, Australia. Participants were randomised by facility to receive either increased sunlight exposure (additional 30-40 min/day in the early morning) with (UV+) or without (UV) calcium supplementation (600 mg/day) or neither (control) for a year. The co-primary endpoints were change in serum 25 hydroxy vitamin D (25OHD) and falls incidence after 12 months.\n Adherence to sunlight exposure was low (median adherence, 26%; IQR, 7%-45%). Serum 25OHD levels were low at baseline (median, 32.9 nmol/L) and increased only slightly depending on the number of sunlight sessions attended over 12 months (P = 0.04). During the study, 327 falls occurred in 111 (54%) subjects in the control group, 326 falls in 111 (58%) subjects in the UV only group and 335 falls in 108 (52%) subjects in the UV+ group. By intention-to-treat analysis, there was no significant effect of increased UV exposure on falls risk (IRR, 1.06; 95% CI, 0.76-1.48; P = 0.73). However, in 66 participants who attended ≥130 sessions per year (adherence, ≥50% of 260 sessions-five per week), falls were significantly reduced (IRR, 0.52; 95% CI, 0.31-0.88; P = 0.01) compared with the control group.\n Increased sunlight exposure did not reduce vitamin D deficiency or falls risk in frail older people. This public health strategy was not effective most likely due to poor adherence to the intervention.", "To assess the effects of an 8-week exercise training program with a special focus on light- to moderate-intensity resistance exercises (30-70% of one repetition maximum, 1RM) and a subsequent 4-week training cessation period (detraining) on muscle strength and functional capacity in participants aged 90 and older.\n Randomized controlled trial performed during March to September 2009.\n Geriatric nursing home.\n Forty nonagenarians (90-97) were randomly assigned to an intervention or control group (16 women and 4 men per group).\n Eight-week muscle strength exercise intervention focused on lower limb strength exercises of light to moderate intensity.\n Primary outcome: 1RM leg press. Secondary outcomes: handgrip strength, 8-m walk test, 4-step stairs test, Timed Up and Go test, and number of falls.\n A significant group by time interaction effect (P=.02) was observed only for the 1RM leg press. In the intervention group, 1RM leg press increased significantly with training by 10.6 kg [95% confidence interval (CI)=4.1-17.1 kg; P=.01]. Except for the mean group number of falls, which were 1.2 falls fewer per participant in the intervention group (95% CI=0.0-3.0; P=.03), no significant training effect on the secondary outcome measures was found.\n Exercise training, even of short duration and light to moderate intensity, can increase muscle strength while decreasing fall risk in nonagenarians.\n © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.", "nan", "The aim of this study was to assess the effectiveness of the unipedal standing balance exercise for 1 min to prevent falls and hip fractures in high-risk elderly individuals with a randomized controlled trial. This control study was designed as a 6-month intervention trial.\n Subjects included 553 clinically defined high-risk adults who were living in residences or in the community. They were randomized to an exercise group and a control group.\n Randomization to the subjects was performed by a table of random numbers. A unipedal standing balance exercise with open eyes was performed by standing on each leg for 1 min three times per day. As a rule, subjects of the exercise group stood on one leg without holding onto any support, but unstable subjects were permitted to hold onto a bar during the exercise time. Falls and hip fractures were reported by nurses, physical therapists, or facility staff with a survey sheet every month. This survey sheet was required every month for both groups.\n Registered subjects were 553 persons ranging in age from 37 to 102 years (average, 81.6 years of age). Twenty-six subjects dropped out. The number of falls and hip fractures for the 6-month period after the trial for 527 of the 553 subjects for whom related data were available were assessed. The exercise group comprised 315 subjects and the control group included 212 subjects. The cumulative number of falls of the exercise group, with 1 multiple faller omitted, was 118, and the control group recorded 121 falls. A significant intergroup difference was observed. However, the cumulative number of hip fractures was only 1 case in both groups. This difference was not statistically significant.\n The unipedal standing balance exercise is effective to prevent falls but was not shown to be statistically significant in the prevention of hip fracture in this study.", "Past studies suggest multidisciplinary interventions that include physical therapy (PT) can improve function of nursing home residents. This trial specifically evaluates effects of PT for frail long-stay nursing home residents.\n Randomized, controlled trial.\n One academic nursing home and eight community nursing homes.\n A total of 194 elderly nursing home residents dependent in at least two activities of daily living residing in the nursing home for at least 3 months.\n Patients were randomized to individually tailored one-on-one PT sessions or friendly visits (FVs) three times a week for 4 months. Physical therapy included range-of-motion, strength, balance, transfer, and mobility exercises.\n Performance-based physical function assessed by the Physical Disability Index; self-perceived health status assessed with the Sickness Impact Profile; observer-reported activities of daily living; and falls.\n Eighty-nine percent and 92% of PT and FV sessions, respectively, were attended; 5% and 9% of subjects dropped out in the PT group and FV group, respectively. Compared with the FV group, the PT group experienced no significant improvements in overall Physical Disability Index, Sickness Impact Profile, or activities of daily living scores. A 15.5% improvement in the mobility subscale of the Physical Disability Index was seen (95% confidence interval [CI], 6.4% to 24.7%); no benefits in range-of-motion, strength, or balance subscales were found. Compared with the FV group, the PT group used assistive devices for bed mobility tasks less often (P = .06) and were less likely to use assistive devices and wheelchairs for locomotion (P < .005). There were 79 falls in the PT group vs 60 falls in the FV group (P = .11). Charge for the 4-month PT program was $1220 per subject (95% CI, $412 to $1832).\n This standardized physical therapy program provided modest mobility benefits for very frail long-stay nursing home residents with physical disability due to multiple comorbid conditions.", "to measure the impact of pharmacist-conducted clinical medication review with elderly care home residents.\n randomised controlled trial of clinical medication review by a pharmacist against usual care.\n sixty-five care homes for the elderly in Leeds, UK. Participants: a total of 661 residents aged 65+ years on one or more medicines. Intervention: clinical medication review by a pharmacist with patient and clinical records. Recommendations to general practitioner for approval and implementation. Control patients received usual general practitioner care.\n primary: number of changes in medication per participant. Secondary: number and cost of repeat medicines per participant; medication review rate; mortality, falls, hospital admissions, general practitioner consultations, Barthel index, Standardised Mini-Mental State Examination (SMMSE).\n the pharmacist reviewed 315/331 (95.2%) patients in 6 months. A total of 62/330 (18.8%) control patients were reviewed by their general practitioner. The mean number of drug changes per patient were 3.1 for intervention and 2.4 for control group (P < 0.0001). There were respectively 0.8 and 1.3 falls per patient (P < 0.0001). There was no significant difference for GP consultations per patient (means 2.9 and 2.8 in 6 months, P = 0.5), hospitalisations (means 0.2 and 0.3, P = 0.11), deaths (51/331 and 48/330, P = 0.81), Barthel score (9.8 and 9.3, P = 0.06), SMMSE score (13.9 and 13.8, P = 0.62), number and cost of drugs per patient (6.7 and 6.9, P = 0.5) (pounds sterling 42.24 and pounds sterling 42.94 per 28 days). A total of 75.6% (565/747) of pharmacist recommendations were accepted by the general practitioner; and 76.6% (433/565) of accepted recommendations were implemented.\n general practitioners do not review most care home patients' medication. A clinical pharmacist can review them and make recommendations that are usually accepted. This leads to substantial change in patients' medication regimens without change in drug costs. There is a reduction in the number of falls. There is no significant change in consultations, hospitalisation, mortality, SMMSE or Barthel scores.", "This study aimed to develop a multifaceted strategy using tailored interventions to implement a fall prevention programme, and to achieve a change in fall prevention practices and a reduction in fall incidence at an acute care hospital in Singapore.\n A comparative study was conducted at two acute care hospitals (intervention and control) in Singapore. Pre-intervention, post-intervention and six-month follow-up knowledge assessments of 641 nursing staff, and audits of fall rates and fall prevention practices were performed to determine the effectiveness of a multifaceted strategy with targeted interventions in supporting the implementation of a fall prevention programme.\n The mean post-knowledge test scores at six months were statistically significantly higher (t[516] is -3.3, p-value is less than 0.01) at the intervention hospital (10.3 +/- 2.3) compared to the scores at the control hospital (9.8 +/- 1.8). Increased compliance with the use of fall risk assessment tools was evident in 99.4 percent and 99.3 percent of all patient records at the control and intervention hospitals, respectively. Following the implementation strategy for a fall prevention programme, there was a non-significant reduction in fall rates from 1.44 to 1.09 per 1,000 patient days at the intervention hospital. No reduction in the fall rate was observed at the control hospital.\n A multifaceted strategy for the implementation of a fall prevention programme was effective in increasing nurses' knowledge and the use of the fall risk assessment, but did not have a statistically significant impact on a reduction in the fall rate. The increase in nurses' knowledge and change in nursing practice were important markers of success in terms of fall prevention at the acute hospitals.", "to evaluate the effectiveness of a multifactorial intervention on incidence of falls in psychogeriatric nursing home patients.\n cluster-randomised controlled 12-month trial.\n psychogeriatric wards in 12 nursing homes in The Netherlands. Participants: psychogeriatric nursing home patients (n = 518). Intervention: a general medical assessment and an additional specific fall risk evaluation tool, applied by a multidisciplinary fall prevention team, resulting in general and individual fall prevention activities. Measurements: falls.\n there were 355 falls in 169.5 patient-years (2.09 falls per patient per year) in the intervention group and 422 falls in 166.3 patient-years (2.54 falls per patient per year) in the control group. Intention-to-treat analysis with adjustment for ward-related and patient-related parameters, and intra-cluster correlation, showed that the intervention group had a significantly lower mean fall incidence rate than the control group (rate ratio = 0.64, 95% CI = 0.43-0.96, P = 0.029). Subgroup analyses showed that fall risk declined further as patients participated longer in the intervention programme.\n the introduction of a structured multifactorial intervention to prevent falls in psychogeriatric nursing home patients significantly reduces the number of falls. This reduction is substantial and of high clinical relevance.", "To establish the effectiveness of a fall-prevention program in reducing falls and injurious falls in older residential care residents.\n Cluster, randomized, controlled trial.\n Fourteen randomly selected residential care homes in Auckland, New Zealand.\n All older residents (n=628, 95% participation rate).\n Residential care staff, using existing resources, implemented systematic individualized fall-risk management for all residents using a fall-risk assessment tool, high-risk logo, and strategies to address identified risks.\n Number of residents sustaining a fall, falls, and injurious-falls incidence rates.\n During 12 months of follow-up, 103 (43%) residents in the control group and 173 (56%) residents in the intervention group fell (P<.018). There was a significantly higher incidence rate of falls in intervention homes than in control homes (incident rate ratio=1.34, 95% confidence interval=1.06-1.72) during the intervention period after adjusting for dependency level (type of home), baseline fall rate, and clustering. There was no difference in the injurious fall incidence rate or incidence of serious injuries.\n This fall-prevention intervention did not reduce falls or injury from falls. Low-intensity intervention may be worse than usual care.", "To assess the effectiveness of a multivitamin (MV) tablet on nutritional status, quantitative heel ultrasound (QUS), mobility, muscle strength and falls. The design comprised two groups matched on mobility levels, randomized to receive a daily MV or placebo (P) tablet for 6 months. The setting was an Australian residential care facility.\n A total of 92 aged care residents. Serum micronutrients, body weight, QUS, rate of falls, hand grip strength, and the timed up and go test were assessed at baseline and 6 months.\n A total of 49 participants consumed a MV and 43, a matched P for 6 months. There was a greater increase in the MV vs P group for serum 25(OH)D (mean difference+/-standard error, 33.4+/-2.6 nmol l(-1)), folate (13.4+/-2.8 nmol l(-1)), and vitamin B12 (178.0+/-40.3 pmol l(-1)) (all P<0.001). Adequate 25(OH)D concentrations (> or =50 nmol l(-1)) were found among 77% of participants in the MV group vs 10% taking P (P<0.001). Adjusting for baseline levels, the increase in QUS was greater in the MV vs P group (3.0+/-2.0 dB MHz(-1) vs -2.9+/-2.1 dB MHz(-1), respectively, P=0.041). There was a trend towards a 63% lower mean number of falls in the MV vs P group (0.3+/-0.1 falls vs 0.8+/-0.3 falls, P=0.078).\n MV supplementation raised serum vitamin B12 and folate concentrations and increased serum 25(OH)D, which was accompanied by an apparent positive effect on bone density. We also found a trend towards a reduction in falls and this could contribute to a reduction in fractures.", "To use two different exercise programs over a 2-year period to reduce falls and their sequelae among residents of two long-term care facilities.\n Randomized, controlled trial.\n The study took place at two long-term care facilities with services ranging from independent living to skilled nursing.\n One hundred and ten participants whose average age was 84 and who were capable of ambulating with or without assistive devices and could follow simple directions.\n Participants were randomized to one of two exercise groups (resistance/endurance plus basic enhanced programming or tai chi plus basic enhanced programming) or to a control group (basic enhanced programming only). Exercise classes were held three times per week throughout the study.\n Participants were evaluated for cognitive and physical functioning at baseline and 6, 12, and 24 months. Falls were determined from incident reports filed by the nursing staffs at the facilities.\n Time to first fall, time to death, number of days hospitalized, and incidence of falls did not differ among the treatment and control groups (P>.05). Among all participants, those who fell had significantly lower baseline Folstein Mini-Mental State Examination and instrumental activities of daily living scores and experienced significantly greater declines in these measures over the 2-year program.\n There were no significant differences in falls among the two exercise groups and the control group. Lack of treatment differences and low adherence rates suggest that residents of long-term care facilities may require individualized exercise interventions that can be adapted to their changing needs.", "This study evaluates whether a postoperative multidisciplinary, intervention program, including systematic assessment and treatment of fall risk factors, active prevention, detection, and treatment of postoperative complications, could reduce inpatient falls and fall-related injuries after a femoral neck fracture.\n A randomized, controlled trial at the orthopedic and geriatric departments at Umeå University Hospital, Sweden, included 199 patients with femoral neck fracture, aged >or=70 years.\n Twelve patients fell 18 times in the intervention group compared with 26 patients suffering 60 falls in the control group. Only one patient with dementia fell in the intervention group compared with 11 in the control group. The crude postoperative fall incidence rate was 6.29/1,000 days in the intervention group vs 16.28/1,000 days in the control group. The incidence rate ratio was 0.38 [95% confidence interval (CI): 0.20 - 0.76, p=0.006] for the total sample and 0.07 (95% CI: 0.01-0.57, p=0.013) among patients with dementia. There were no new fractures in the intervention group but four in the control group.\n A team applying comprehensive geriatric assessment and rehabilitation, including prevention, detection, and treatment of fall risk factors, can successfully prevent inpatient falls and injuries, even in patients with dementia.", "Falls and resulting injuries are particularly common in older people living in residential care facilities, but knowledge about the prevention of falls is limited.\n To investigate whether a multifactorial intervention program would reduce falls and fall-related injuries.\n A cluster randomized, controlled, nonblinded trial.\n 9 residential care facilities located in a northern Swedish city.\n 439 residents 65 years of age or older.\n An 11-week multidisciplinary program that included both general and resident-specific, tailored strategies. The strategies comprised educating staff, modifying the environment, implementing exercise programs, supplying and repairing aids, reviewing drug regimens, providing free hip protectors, having post-fall problem-solving conferences, and guiding staff.\n The primary outcomes were the number of residents sustaining a fall, the number of falls, and the time to occurrence of the first fall. A secondary outcome was the number of injuries resulting from falls.\n During the 34-week follow-up period, 82 residents (44%) in the intervention program sustained a fall compared with 109 residents (56%) in the control group (risk ratio, 0.78 [95% CI, 0.64 to 0.96]). The adjusted odds ratio was 0.49 (CI, 0.37 to 0.65), and the adjusted incidence rate ratio of falls was 0.60 (CI, 0.50 to 0.73). Each of 3 residents in the intervention group and 12 in the control group had 1 femoral fracture (adjusted odds ratio, 0.23 [CI, 0.06 to 0.94]). Clustering was considered in all regression models.\n An interdisciplinary and multifactorial prevention program targeting residents, staff, and the environment may reduce falls and femoral fractures.", "Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D-group, there were significant increases in median serum 25-hydroxyvitamin D (+71%) and 1,25-dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group. In the 12-week treatment period, mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group. After adjustment, Cal+D-treatment accounted for a 49% reduction of falls (95% CI, 14-71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.", "Falls are a major health problem in nursing homes, but no interventions have been shown to prevent falls in nursing home residents.\n To evaluate an intervention program designed to prevent falls and associated injuries in high-risk nursing home residents.\n Randomized controlled trial.\n Seven pairs of middle Tennessee nursing homes with 1 facility in each pair randomly assigned to the intervention. Facilities had 482 (261 control, 221 intervention) residents who qualified for the study because they had high risk of falls and a potential safety problem that could be addressed by the intervention.\n Comprehensive structured individual assessment with specific safety recommendations that targeted suboptimal practices for environmental and personal safety, wheelchair use, psychotropic drug use, and transferring and ambulation. Facility staff were encouraged to implement the individual recommendations and to improve overall facility safety.\n The mean proportion of recurrent fallers and incidence rate of injurious falls in the facility in the year following the intervention.\n The mean proportion of recurrent fallers in intervention facilities (43.8%) was 19.1% (95% confidence interval, 2.4%-35.8%) lower than that in control facilities (54.1%, P=.03). Intervention facilities had a nonsignificant trend toward a lower mean rate of injurious falls (13.7 vs 19.9 per 100 person-years, reduction of 31.2%, P=.22). Subgroup analyses suggested greatest benefits for residents for whom the recommended interventions were carried out or who had 3 or more falls in the preceding year.\n The high rate of falls and related injuries in nursing homes should not be viewed as inevitable, but as outcomes that can be substantially improved through structured safety programs.", "To investigate the influence of multisensory stimulations in a Snoezelen room on the balance of individuals with dementia.\n Randomized controlled trial.\n Canadian long-term care home.\n Twenty-four residents (average age 86 years), in a long-term care home diagnosed with dementia, were assigned randomly to intervention and control groups. Nineteen participants completed the study. Interventions: Nine intervention group participants completed 30-minute Snoezelen room sessions twice a week for six weeks. Sessions were guided by participants' preferences for stimulation. Interactions with tactile, visual and proprioceptive sensations were encouraged. Ten control group participants received an equal amount of volunteer visits.\n The Functional Reach Test, the eyes-open Sharpened Romberg and the Timed Up and Go Test with and without dual task, assessed static and dynamic balance at baseline and after the intervention. Falls frequencies were recorded six weeks before, during and after intervention. A journal was kept of observations in Snoezelen room.\n Split-plot MANOVA analyses revealed no significant effects of unstructured Snoezelen room sessions on participants' balance. There were no multivariate effects of time (F(4,14) = 1.13, P = 0.38) or group (F(4,14) = 0.63, P = 0.65). Group membership did not alter falls frequency. However, observations of participants' interactions with elements of the Snoezelen room, such as imagery-induced head and eye movements, vibrating sensations and kicking activities, captured events that can be used to create specific multisensory balance-enhancing stimulations.\n Although the null hypothesis was not rejected, further investigation of a potential to influence balance in individuals with dementia through Snoezelen room intervention in long-term care homes is warranted.", "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." ]

[ "9191523", "16198768", "8558223", "9552047", "11230488", "18620949", "10856105", "9654256", "18281266", "11331315", "11567700", "11379605", "14665609", "21256809", "7595738", "14746858" ]

[ "Postsurgical adjuvant therapy for melanoma. Evaluation of a 3-year randomized trial with recombinant interferon-alpha after 3 and 5 years of follow-up.", "Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial.", "Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684.", "Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group.", "High-dose interferon alfa-2b does not diminish antibody response to GM2 vaccination in patients with resected melanoma: results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696.", "Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial.", "High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190.", "Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma.", "Adjuvant low-dose interferon {alpha}2a with or without dacarbazine compared with surgery alone: a prospective-randomized phase III DeCOG trial in melanoma patients with regional lymph node metastasis.", "High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801.", "Effect of long-term adjuvant therapy with interferon alpha-2a in patients with regional node metastases from cutaneous melanoma: a randomised trial.", "Adjuvant interferon alpha 2b in high risk melanoma - the Scottish study.", "Adjuvant interferon in high-risk melanoma: the AIM HIGH Study--United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma.", "Two different durations of adjuvant therapy with intermediate-dose interferon alfa-2b in patients with high-risk melanoma (Nordic IFN trial): a randomised phase 3 trial.", "Randomized, surgical adjuvant clinical trial of recombinant interferon alfa-2a in selected patients with malignant melanoma.", "Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis." ]

[ "Early surgical intervention is still the most successful therapy for patients with melanoma. The results obtained with medical therapies are still quite disappointing, with better results observed in soft tissue and lymph node metastasis. There currently is no standardized adjuvant therapy for primary melanoma. On the basis of the activity demonstrated in vitro against melanoma cell lines and the results obtained in many clinical trials in patients with advanced melanoma, the authors chose to study the use of recombinant interferon-alpha (IFN-alpha) as adjuvant therapy for patients with Stage I and Stage II melanoma.\n A randomized multicenter trial based on the use of recombinant IFN-alpha-2b for 3 years at the dose of 3 MU given intramuscularly 3 times a week for a period of 6 months with a 1-month interval between cycles was conducted in Stage I and Stage II melanoma patients (using the American Joint Committee on Cancer classification). The efficacy of this treatment was evaluated calculating the incidence of recurrence after 3 and 5 years.\n Results were collected at the end of the treatment period and after 5 years of follow-up for a smaller number of patients. Statistical evaluation showed a significant difference between treated patients and untreated controls with regard to progression of the disease. In particular, IFN-alpha appears to be more effective in patients with worse prognosis lesions.\n IFN-alpha appears to be effective as adjuvant therapy for high risk melanoma patients and the risk/benefit ratio appears to be very favorable. The authors' next goal is to separate those patients who might benefit from adjuvant therapy from those who are cured after the surgical intervention only.", "Individuals affected by melanoma with thick primary tumours or regional node involvement have a poor outlook, with only 30-50% alive at 5 years. High-dose and low-dose interferon alfa have been assessed for the treatment of these patients, with the former having considerable toxicity and a consistent effect on disease free survival, but not on overall survival, and the latter no consistent effect on either. Our aim was, therefore, to assess the effect of two regimens of interferon of intermediate dose versus observation alone on distant metastasis-free interval (DMFI) and overall survival in such patients.\n We did a randomised controlled trial in 1388 patients who had had a thick primary tumour (thickness > or = 4 mm) resected (stage IIb) or regional lymph node metastases dissected (stage III) and had been assigned to 13-months (n=553) or 25 months (n=556) of treatment with subcutaneous interferon alfa 2b, or observation (n=279). Treatment comprised 4 weeks of 10 million units (MU) of interferon alfa (5 days per week) followed by either 10 MU three times a week for 1 year or 5 MU three times a week for 2 years, to a total dose of 1760 MU. Our primary endpoint was DMFI. Analyses were by intent to treat.\n After a median follow-up of 4.65 years, we had recorded 760 distant metastases and 681 deaths. At 4.5 years, the 25-month interferon group showed a 7.2% increase in rate of DMFI (hazard ratio 0.83, 97.5% CI 0.66-1.03) and a 5.4% improvement in overall survival. The 13-month interferon group showed a 3.2% increase in rate of DMFI at 4.5 years (0.93, 0.75-1.16) and no extension of overall survival. Toxicity was acceptable, with 18% (195 of 1076) of patients going off study because of toxicity or as a result of refusal of treatment because of side-effects.\n Interferon alfa as used in the regimens studied does not improve outcome for patients with stage IIb/III melanomas, and cannot be recommended. With respect to efficacy of the drug, duration of treatment seemed more important than dose, and should be assessed in future trials.", "Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma.\n A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients.\n A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at > or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy.\n IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.", "Patients with primary cutaneous melanoma with a Breslow thickness > or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor.\n In a prospective randomized study, 311 melanoma patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase).\n Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated.\n Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.", "High-dose interferon alfa-2b (IFNalpha2b) is the only established adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a chemically defined vaccine that is one of the best developed of a range of vaccine candidates for melanoma. A single-institution phase III trial conducted at Memorial Hospital served as the impetus for an intergroup adjuvant E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients. To build on the apparent benefit of IFNalpha2b in resectable high-risk American Joint Committee on Cancer (AJCC) stage IIB or III melanoma, this phase II study was designed to evaluate the combination of GMK and IFNalpha2b. The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFNalpha2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies.\n This trial enrolled 107 patients with resectable high- or very high-risk melanoma (AJCC stages IIB, III, and IV).\n The results demonstrate that IFNalpha2b does not significantly inhibit immunoglobulin M or G serologic responses to the vaccine and that the combination of high-dose IFNalpha2b and GMK is well tolerated in this patient population.\n Cox analysis of the results of the combination with IFNalpha2b show improvement in the relapse-free survival of patients with very high-risk melanoma (including those with resectable M1 disease).", "Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability.\n 1256 patients with resected stage III melanoma were randomly assigned to observation (n=629) or pegylated interferon alfa-2b (n=627) 6 mug/kg per week for 8 weeks (induction) then 3 mug/kg per week (maintenance) for an intended duration of 5 years. Randomisation was stratified for microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumour thickness, sex, and centre. Randomisation was done with a minimisation technique. The primary endpoint was recurrence-free survival. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00006249.\n All randomised patients were included in the primary efficacy analysis. 608 patients in the interferon group and 613 patients in the observation group were included in safety analyses. The median length of treatment with pegylated interferon alfa-2b was 12 (IQR 3.8-33.4) months. At 3.8 (3.2-4.2) years median follow-up, 328 recurrence events had occurred in the interferon group compared with 368 in the observation group (hazard ratio 0.82, 95% CI 0.71-0.96; p=0.01); the 4-year rate of recurrence-free survival was 45.6% (SE 2.2) in the interferon group and 38.9% (2.2) in the observation group. There was no difference in overall survival between the groups. Grade 3 adverse events occurred in 246 (40%) patients in the interferon group and 60 (10%) in the observation group; grade 4 adverse events occurred in 32 (5%) patients in the interferon group and 14 (2%) in the observation group. In the interferon group, the most common grade 3 or 4 adverse events were fatigue (97 patients, 16%), hepatotoxicity (66, 11%), and depression (39, 6%). Treatment with pegylated interferon alfa-2b was discontinued because of toxicity in 191 (31%) patients.\n Adjuvant pegylated interferon alfa-2b for stage III melanoma has a significant, sustained effect on recurrence-free survival.", "Pivotal trial E1684 of adjuvant high-dose interferon alfa-2b (IFNalpha2b) therapy in high-risk melanoma patients demonstrated a significant relapse-free and overall survival (RFS and OS) benefit compared with observation (Obs).\n A prospective, randomized, three-arm, intergroup trial evaluated the efficacy of high-dose IFNalpha2b (HDI) for 1 year and low-dose IFNalpha2b (LDI) for 2 years versus Obs in high-risk (stage IIB and III) melanoma with RFS and OS end points.\n A total of 642 patients were enrolled (608 patients eligible), of whom a majority (75%) had nodal metastasis (50% had nodal recurrence). Unlike E1684, E1690 allowed entry of patients with T4 (> 4 mm) deep primary tumors, regardless of nodal dissection, and 25% of the patients entered onto this trial had deep primary tumors (compared with 11% in E1684). At 52 months' median follow-up, HDI demonstrated an RFS benefit exceeding that of LDI compared with Obs. The 5-year estimated RFS rates for the HDI, LDI, and Obs arms were 44%, 40%, and 35%, respectively. The hazards ratio for the intent-to-treat analysis of HDI versus Obs was 1.28 (P(2) =.05); for LDI versus Obs, it was 1.19 (P(2) =.17). By Cox analysis, the impact of HDI on RFS achieved significance (P(2) =.03). The RFS benefit was equivalent for node-negative and node-positive patients. Neither HDI nor LDI has demonstrated an OS benefit compared with Obs at this time. A major improvement in the median OS of patients in the E1690 Obs arm was noted in comparison with E1684 (6 years v 2.8 years). An analysis of salvage therapy for patients who relapsed on E1690 demonstrated that a significantly larger proportion of patients in the Obs arm received IFNalpha-containing salvage therapy compared with the HDI arm; this therapy was unavailable to patients during E1684, and patients with undissected regional nodes were not included in E1684. This study did not specify therapy at recurrence. Analysis of treatments received at recurrence demonstrated significantly more frequent use of IFNalpha2b at relapse from Obs than from HDI, which may have confounded interpretation of the survival benefit of assigned treatments in E1690.\n The results of the intergroup E1690 trial demonstrate an RFS benefit of IFNalpha2b that is dose-dependent and significant for HDI by Cox multivariable analysis.", "Owing to the limited efficacy of therapy on melanoma at the stage of distant metastases, a well-tolerated adjuvant therapy is needed for patients with high-risk primary melanoma. Our hypothesis was that an adjuvant treatment with low doses of interferon alpha could be effective in patients with localised melanoma.\n After resection of a primary cutaneous melanoma thicker than 1.5 mm, patients without clinically detectable node metastases were randomly assigned to receive either 3x10(6) IU interferon alpha-2a, three-times weekly for 18 months, or no treatment. The primary endpoint was the relapse-free interval.\n 499 patients were enrolled, of whom 489 were eligible. When used as part of a sequential procedure, interferon alpha-2a was of significant benefit for relapse-free interval (p=0.038). A long-term analysis, after a median follow-up of 5 years, showed a significant extension of relapse-free interval (p=0.035) and a clear trend towards an increase in overall survival (p=0.059) in interferon alpha-2a-treated patients compared with controls. There were 100 relapses and 59 deaths among the 244 interferon alpha-2a-treated patients compared with 119 relapses and 76 deaths among the 245 controls. The estimated 3-year-relapse rates were 32% in the interferon alpha-2a group and 44% in controls; the 3-year death rates were 15% and 21%, respectively. Only 10% of patients experienced WHO grade 3 or 4 adverse events. Treatment was compatible with normal daily life.\n Adjuvant therapy of high-risk melanoma with low doses of interferon alpha-2a for 18 months is safe and is beneficial when started before clinically detectable node metastases develop.", "More than half of patients with melanoma that has spread to regional lymph nodes develop recurrent disease within the first 3 years after surgery. The aim of the study was to improve disease-free survival (DFS) and overall survival (OS) with interferon (IFN) alpha2a with or without dacarbazine (DTIC) compared with observation alone.\n A total of 444 patients from 42 centers of the German Dermatologic Cooperative Oncology Group who had received a complete lymph node dissection for pathologically proven regional node involvement were randomized to receive either 3 MU s.c. of IFNalpha2a three times a week for 2 years (Arm A) or combined treatment with same doses of IFNalpha2a plus DTIC 850 mg/m(2) every 4-8 weeks for 2 years (Arm B) or to observation alone (Arm C). Treatment was discontinued at first sign of relapse.\n A total of 441 patients were eligible for intention-to-treat analysis. Kaplan-Meier 4-year OS rate of those who had received IFNalpha2a was 59%. For those with surgery alone, survival was 42% (A versus C, P = 0.0045). No improvement of survival was found for the combined treatment Arm B with 45% survival rate (B versus C, P = 0.76). Similarly, DFS rates showed significant benefit for Arm A, and not for Arm B. Multivariate Cox model confirmed that Arm A has an impact on OS (P = 0.005) but not Arm B (P = 0.34).\n 3 MU interferon alpha2a given s.c. three times a week for 2 years significantly improved OS and DFS in patients with melanoma that had spread to the regional lymph nodes. Interestingly, the addition of DTIC reversed the beneficial effect of adjuvant interferon alpha2a therapy.", "Vaccine alternatives to high-dose interferon alfa-2b therapy (HDI), the current standard adjuvant therapy for high-risk melanoma, are of interest because of toxicity associated with HDI. The GM2 ganglioside is a well-defined melanoma antigen, and anti-GM2 antibodies have been associated with improved prognosis. We conducted a prospective, randomized, intergroup trial to evaluate the efficacy of HDI for 1 year versus vaccination with GM2 conjugated to keyhole limpet hemocyanin and administered with QS-21 (GMK) for 96 weeks (weekly x 4 then every 12 weeks x 8).\n Eligible patients had resected stage IIB/III melanoma. Patients were stratified by sex and number of positive nodes. Primary end points were relapse-free survival (RFS) and overall survival (OS).\n Eight hundred eighty patients were randomized (440 per treatment group); 774 patients were eligible for efficacy analysis. The trial was closed after interim analysis indicated inferiority of GMK compared with HDI. For eligible patients, HDI provided a statistically significant RFS benefit (hazard ratio [HR] = 1.47, P = .0015) and OS benefit (HR = 1.52, P = .009) for GMK versus HDI. Similar benefit was observed in the intent-to-treat analysis (RFS HR = 1.49; OS HR = 1.38). HDI was associated with a treatment benefit in all subsets of patients with zero to > or = four positive nodes, but the greatest benefit was observed in the node-negative subset (RFS HR = 2.07; OS HR = 2.71 [eligible population]). Antibody responses to GM2 (ie, titers > or = 1:80) at days 29, 85, 365, and 720 were associated with a trend toward improved RFS and OS (P2 = .068 at day 29).\n This trial demonstrated a significant treatment benefit of HDI versus GMK in terms of RFS and OS in melanoma patients at high risk of recurrence.", "Less than half of patients with melanoma that has spread to local draining regional lymph nodes (stage III melanoma) live with no disease for 5 years or longer after surgery. We aimed to see whether interferon alpha-2a increased survival prospects in these patients.\n 444 patients from 23 centres in the WHO Melanoma Programme had complete lymphadenectomy for pathologically proven regional nodal spread of melanoma and were randomly assigned to receive either 3 MU subcutaneously of recombinant interferon alpha-2a three times a week for 3 years, or to observation alone after surgery. Patients were stratified by centre, nodes with macroscopic or microscopic melanoma, number of affected nodes, and nodal metastatic spread. Treatment was continued for 3 years or until first sign of relapse.\n 424 patients entered the study. 5-year disease-free survival of those who had surgery plus interferon alpha-2a was 27.5% (95% CI 21.7-33.6); for those who received surgery alone, survival was 28.4% (22.5-34.6) (p=0.50). Neither Kaplan-Meier cumulative survival rates, nor multivariate analysis of survival, showed a difference between those who had surgery and interferon alpha-2a (35%, 95% CI 29-42) and those who had surgery alone (37%, 31-44).\n Patients with melanoma that has spread to the local draining regional lymph nodes tolerate well 3 MU of interferon alpha-2a given subcutaneously three times a week for 3 years, but this treatment does not improve either disease-free or overall survival.", "In 1989, the Scottish melanoma group initiated a randomized trial, comparing observation alone with 6 months' therapy with low dose interferon (given subcutaneously 3 MU day-1, twice weekly), for patients with primary melanomas of at least 3 mm Breslow thickness, or with evidence of regional node involvement. The trial was closed in 1993 with only 95 eligible patients randomized. There were no toxic deaths, and no patient failed to complete the treatment for reasons of toxicity. 6 months' treatment with low-dose interferon- resulted in a statistically significant improved disease-free survival for up to 24 months after randomization (P< 0.05). However, at a median follow-up of over 6 years, although there was an apparent improvement in disease-free survival (from 9 to 22 months), and overall survival (from 27 to 39 months), consistent with larger studies powered to detect such differences, these differences were not statistically significant. The data therefore suggest that 6 months of low-dose interferon is active, and confirm the importance of the large randomized studies, such as the UKCCCR AIM-High and EORTC trials, that seek to confirm a possible survival advantage for low or intermediate dose interferon.", "To evaluate low-dose extended duration interferon alfa-2a as adjuvant therapy in patients with thick (> or = 4 mm) primary cutaneous melanoma and/or locoregional metastases.\n In this randomized controlled trial involving 674 patients, the effect of interferon alfa-2a (3 megaunits three times per week for 2 years or until recurrence) on overall survival (OS) and recurrence-free survival (RFS) was compared with that of no further treatment in radically resected stage IIB and stage III cutaneous malignant melanoma.\n The OS and RFS rates at 5 years were 44% (SE, 2.6) and 32% (SE, 2.1), respectively. There was no significant difference in OS or RFS between the interferon-treated and control arms (odds ratio [OR], 0.94; 95% CI, 0.75 to 1.18; P =.6; and OR, 0.91; 95% CI, 0.75 to 1.10; P =.3; respectively). Male sex (P =.003) and regional lymph node involvement (P =.0009), but not age (P =.7), were statistically significant adverse features for OS. Subgroup analysis by disease stage, age, and sex did not show any clear differences between interferon-treated and control groups in either OS or RFS. Interferon-related toxicities were modest: grade 3 (and in only one case, grade 4) fatigue or mood disturbance was seen in 7% and 4% respectively, of patients. However, there were 50 withdrawals (15%) from interferon treatment due to toxicity.\n The results from this study, taken in isolation, do not indicate that extended-duration low-dose interferon is significantly better than observation alone in the initial treatment of completely resected high-risk malignant melanoma.", "Adjuvant high-dose interferon alfa-2b improves relapse-free survival (RFS) in patients with high-risk melanoma, although benefits in overall survival are uncertain. Because of the toxic effects of high-dose regimens, intermediate doses are being explored. We investigated whether adjuvant therapy with intermediate-dose interferon alfa-2b for 1 or 2 years would improve outcomes in patients with stage IIB-IIC or III resected cutaneous melanoma.\n This randomised, open-label, phase 3, parallel-group trial was undertaken between 1996 and 2004. 855 patients were randomly assigned at 35 centres in the Nordic countries by block randomisation to three groups: observation only (group A); 4 weeks of induction (interferon alfa-2b 10 million units flat dose subcutaneously 5 days per week) followed by 12 months of maintenance therapy (interferon alfa-2b 10 million units flat dose subcutaneously 3 days per week; group B); or 1 month of induction and 24 months of maintenance (group C). Neither investigators nor patients were masked to treatment assignment. Patients were stratified for country and tumour stage; patients with stage III disease were further stratified for presence of metastatic lymph nodes at primary diagnosis versus at relapse, palpable versus non-palpable lymph-node metastases, and number of metastatic lymph nodes. The primary endpoint was overall survival in the two interferon alfa-2b groups combined. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01259934.\n 284 patients were assigned to group A, 285 to group B, and 286 to group C; all patients were analysed. The median follow-up time was 72·4 months (IQR 46·9-98·0). We recorded no significant improvement in overall survival in patients given interferon alfa-2b compared with observation: median overall survival was 56·1 months (IQR 22·3 to >120·0) in group A, 72·1 months (25·8 to >120) in group B, and 64·3 months (24·7 to >120) in group C (p=0·600). Hazard ratios (HR) for overall survival were 0·91 (95% CI 0·74-1·10; p=0·642) for groups B and C combined versus observation; 0·91 (0·72-1·14; p=0·652) for group B versus observation; and 0·91 (0·72-1·15; p=0·858) for group C versus observation. Median RFS was 23·2 months (IQR 5·6 to <120) in group A, 37·8 months (10·8 to >120) in group B, and 28·6 months (8·6 to >120) in group C (p=0·034). HRs for RFS were 0·80 (0·67-0·96; p=0·030) for groups B and C combined versus observation, 0·77 (0·63-0·96; p=0·034) for group B versus observation, and 0·83 (0·68-1·03; p=0·178) for group C versus observation. The most common grade 3 and 4 adverse events were fatigue (five in group A [1·8%], 28 in group B [9·8%], and 32 in group C [11·2%]), myalgia (three [1·1%], 15 [5·3%], 14 [4·9%], respectively), and thrombocytopenia (15 [5·3%], 23 [8·1%], eight [2·8%], respectively).\n Adjuvant therapy with intermediate-dose interferon alfa-2b did not significantly improve overall survival. Interferon alfa-2b with 1-year maintenance therapy significantly improved RFS, but we recorded no significant effect for 2-year maintenance therapy. Further research is in progress to define the subgroup of patients who benefit from adjuvant interferon alfa-2b.\n Schering-Plough (now Merck); the Radiumhemmet Research Funds, Stockholm; the Stockholm County Council; and the Swedish Cancer Society.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "We conducted a randomized prospective trial in selected patients with fully resected high-risk stage I and II malignant melanoma.\n Interferon alfa-2a (IFN-alpha 2a) 20 x 10(6) U/m2 was administered three times each week for 12 weeks by the intramuscular route. Both the treatment group (n = 131) and the control group (n = 131) were evenly balanced with regard to relevant prognostic discriminants.\n The median disease-free survival (DFS) time was 2.4 years for the IFN-alpha 2a group and 2.0 years for the observation group (log-rank P = 0.19). The median survival times were 6.6 years for IFN-alpha 2a and 5.0 years for observation (log-rank P = .40). For stage I patients (n = 102), there was no apparent therapeutic advantage from IFN-alpha 2a therapy. The DFS for stage II patients was a median of 10.8 months in the control group versus 17 months in the treatment group. The overall survival time was 4.1 years for the treatment group versus 2.7 years for the control group. The differences in DFS for stage II patient were significant in a Cox model. These results must be interpreted cautiously because of subset analysis. A severe flu-like toxicity occurred in 44% of patients, 13% lost at least 10% of their baseline weight, and 45% experienced a worsening of Eastern Cooperative Oncology Group (ECOG) performance score.\n Our findings indicate trends that suggest a possible benefit for selected patients with high-risk malignant melanoma. The results will require further study in a larger patient population for confirmation.", "Between 1988 and 1996, the European Organisation for Research and Treatment of Cancer Melanoma Group (EORTC-MG) performed a prospective, randomised phase III adjuvant trial to evaluate the efficacy and toxicity of low dose recombinant interferon-alpha 2 b (rIFN-alpha2b) (1 MU) or recombinant interferon gamma (rIFN-gamma), (0.2 mg) both given subcutaneously (s.c.), every other day (qod), for 12 months in comparison with an untreated control group. The German Cancer Society (DKG) added a fourth arm with Iscador M, a popular mistletoe extract. High-risk stage II patients (thickness >3 mm) and stage III patients (positive lymph nodes) without distant metastasis were randomised and followed until their first progression or death. An intention-to-treat analysis was performed. From 1988 to 1996, a total of 830 patients were randomised: 423 in the three-arm EORTC 18871 trial and 407 patients in the four-arm DKG 80-1 trial. The median follow-up was 8.2 years and a total of 537 relapses and 475 deaths were reported. At 8 years, the disease-free interval (DFI) rate was 32.4% and the overall survival (OS) rate was 40.0%. In terms of the DFI, the hazard ratio estimates (95% Confidence Intervals (CI)) were: 1.04 (0.84, 1.30) for the comparison of rIFN-alpha2b versus control, 0.96 (0.77, 1.20) for rIFN-gamma versus control, and 1.32 (0.93, 1.87) for Iscador M versus control. In terms of OS, the corresponding estimates (95% CI) for the 3 treatment comparisons were: for IFN-alpha2b 0.96 (0.76, 1.21), for rIFN-gamma 0.87 (0.69, 1.10) and for Iscador M 1.21 (0.84, 1.75), respectively. The results show no clinical benefit for adjuvant treatment with low dose rIFN-alpha2b or rIFN-gamma or with Iscador M in high-risk melanoma patients." ]

[ "16750450", "16215338", "10743822", "16266356", "16215331", "16729276", "15943961", "1280802", "11997197", "2293142" ]

[ "A 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase III trial comparing the efficacy of oxymorphone extended release and placebo in adults with pain associated with osteoarthritis of the hip or knee.", "Treatment of persistent pain associated with osteoarthritis with controlled-release oxycodone tablets in a randomized controlled clinical trial.", "Double blind randomized placebo control trial of controlled release codeine in the treatment of osteoarthritis of the hip or knee.", "Oxymorphone extended-release tablets relieve moderate to severe pain and improve physical function in osteoarthritis: results of a randomized, double-blind, placebo- and active-controlled phase III trial.", "Impact of controlled-release oxycodone on efficacy beliefs and coping efforts among osteoarthritis patients with moderate to severe pain.", "Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial.", "Adding ultralow-dose naltrexone to oxycodone enhances and prolongs analgesia: a randomized, controlled trial of Oxytrex.", "Ibuprofen plus codeine, ibuprofen, and placebo in a single- and multidose cross-over comparison for coxarthrosis pain.", "Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial.", "Codeine plus paracetamol versus paracetamol in longer-term treatment of chronic pain due to osteoarthritis of the hip. A randomised, double-blind, multi-centre study." ]

[ "Oxymorphone extended release (ER) is a tablet formulation of the mu-opioid agonist oxymorphone designed to achieve a low peak-to-trough fluctuation in plasma concentrations over a 12-hour dosing period.\n This study compared the analgesic efficacy, dose response, and tolerability of 3 doses of oxymorphone ER given every 12 hours with those of placebo in patients with pain related to osteoarthritis (OA) of the hip or knee.\n This was a 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, Phase III trial. Patients with OA of the hip or knee who were receiving an opioid medication for chronic, moderate to severe pain or who were judged by the investigator to have received suboptimal analgesia with nonopioid analgesics entered a 2- to 7-day washout of analgesic medication. When pain in the index joint was >40 mm on a 100-mm visual analog scale (VAS), patients were randomized to receive 1 of 4 regimens: oxymorphone ER 10 mg q12h during weeks 1 and 2; oxymorphone ER 20 mg q12h in week 1 and 40 mg q12h in week 2; oxymorphone ER 20 mg q12h in week 1 and 50 mg q12h in week 2; or placebo q12h during weeks 1 and 2. The primary end point was the change in VAS score for arthritis pain intensity. Other assessments included the Western Ontario and McMaster Universities (WOMAC) OA Index subscales for pain, stiffness, and physical function and the composite index; the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) physical health component summary (PCS) score; the Chronic Pain Sleep Inventory (CPSI) score; vital signs; clinical laboratory parameters; and adverse events (AEs). AEs were recorded at each clinic visit.\n Three hundred seventy patients were randomized to treatment (95 oxymorphone ER 10 mg, 93 oxymorphone ER 40 mg, 91 oxymorphone ER 50 mg, and 91 placebo), and 198 completed the study. Least squares mean changes from baseline in the VAS arthritis pain intensity score were -21, -28, -29, and -17 mm in the oxymorphone ER 10, 40, and 50 mg and placebo groups, respectively (P = 0.002, modified Tukey linear trend test). Oxymorphone ER 40 and 50 mg produced significant improvements from baseline compared with placebo in the WOMAC subscale scores for pain (least squares mean change: -85.1, -108.0, and -42.5, respectively; P < or = 0.025 for 40 mg, P < or = 0.001 for 50 mg), stiffness (-40.5, -48.1, and -17.0; both, P < or = 0.001), and physical function (-256.8, -310.8, and -116.5; P < or = 0.01 and P < or = 0.001, respectively); the SF-36 PCS score (4.6, 3.6, and -0.1; P < 0.001); and the CPSI score (-21.2, -22.2, and -10.7; P < 0.05). The 10-mg dose also was associated with significant improvements compared with placebo in the WOMAC pain (-83.6; P < or = 0.025) and physical function subscales (-232.9; P < or = 0.025) and the SF-36 PCS score (3.9; P < 0.001). The most frequently reported AEs (> or =5% of patients) in the oxymorphone ER groups were nausea (39.4%), vomiting (23.7%), dizziness (22.6%), constipation (22.2%), somnolence (17.6%), pruritus (16.5%), and headache (15.0%). The majority of AEs with oxymorphone ER were mild or moderate in intensity. Three serious AEs (urinary retention, central nervous system depression, and pancreatitis) were considered possibly or probably related to study medication.\n In these patients with chronic, moderate to severe pain related to OA of the hip or knee, oxymorphone ER administered twice daily for 2 weeks produced dose-related reductions in arthritis pain intensity and improvements in physical function.", "This study, lasting up to 90 days, was undertaken in patients with osteoarthritis with persistent moderate to severe pain uncontrolled by standard therapy (nonsteroidal anti-inflammatory drugs, acetaminophen, and/or short-acting opioids) to evaluate functional outcomes, as well as efficacy and safety, of controlled-release oxycodone versus placebo.\n One hundred seven patients received either controlled-release oxycodone or placebo every 12 hours in this double blind, randomized, placebo-controlled, parallel-group study. Stable previous regimens of acetaminophen or nonsteroidal anti-inflammatory agents were allowed to continue. Primary efficacy variables included Brief Pain Inventory average pain intensity scores at completion of initial titration, Western Ontario and McMaster Universities Osteoarthritis Index scores at days 30 and 60, and the percentage of patients discontinuing due to inadequate pain control.\n Controlled-release oxycodone was significantly superior to placebo in decreasing average pain intensity and in reducing pain-induced interference with general activity, walking ability (except at day 30), and normal work, as well as mood, sleep, relations with people (at days 60 and 90), and enjoyment in life. Daily functioning, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index, was also significantly improved in the controlled-release oxycodone group. In the placebo group, a significantly greater percentage of patients discontinued due to inadequate pain control. Adverse events were consistent with opioid adverse events, and no safety concerns were noted.\n Treatment with controlled-release oxycodone of patients with osteoarthritis with persistent moderate to severe pain uncontrolled by standard therapy resulted in significant pain control and improvements in physical functioning.", "Pain is the cardinal feature of osteoarthritis (OA), and with advancing disease there is loss of function and increasing pain even at times of joint rest. Few studies have evaluated the role of opioid analgesics in treating the pain of OA.\n This randomized, double blind, parallel group study compared the efficacy and safety of a 12 hourly controlled release codeine formulation (Codeine Contin) with placebo in patients with chronic pain due to OA of the hips and/or knees. The 4 week treatment period, following an analgesic washout phase of 2-7 days, included weekly clinic evaluations, at which the dose was escalated as appropriate, and daily patient diary completion. Pain (daily), stiffness, and physical function (weekly) were assessed using the multidimensional, self-administered WOMAC (visual analog scale version) questionnaire.\n Sixty-six eligible patients completed the study. The mean initial and final daily doses of controlled release codeine were 50 mg every 12 h at baseline and 159 mg every 12 h at the final assessment. All variables in the efficacy analysis indicated superiority of controlled release codeine over placebo. The WOMAC pain scale showed an improvement of 44.8% over baseline in the controlled release codeine group compared with 12.3% taking placebo (p = 0.0004). For the WOMAC stiffness and physical function scales the improvements over baseline on controlled release codeine were 47.7% and 49.3%, respectively compared with 17.0% and 17.0%, respectively, with placebo (p = 0.003; p = 0.0007). Controlled release codeine was also significantly better than placebo on measures of sleep quality and requirement for supplemental acetaminophen.\n Single entity controlled release codeine is an effective treatment for pain due to OA of the hip or knee.", "To compare oxymorphone extended release (ER) and placebo on indices of pain, function, and safety in patients with chronic osteoarthritis (OA) pain.\n In this multicenter, double-blind, placebo- and active-controlled, parallel-group, dose-ranging study, patients were randomized to oxymorphone ER 20 mg (N = 121), oxymorphone ER 40 mg (N = 121), oxycodone controlled release 20 mg (N = 125), or placebo (N = 124) every 12 hours. The primary efficacy end point was change in arthritis pain intensity (visual analog scale, 0-100) from baseline to week 3 for the oxymorphone ER 40 mg group versus placebo.\n The primary end point was achieved: the week 3 oxymorphone ER least squares mean difference (LSMD) from placebo was -9.0 (95% confidence interval [CI]: -16.2 to -1.8; P = 0.015). Secondary efficacy analysis showed similar improvements at week 4 (LSMD from placebo, -10.3 [95% CI: -17.7 to -2.8]; P = 0.007) and with oxymorphone ER 20 mg at week 3 (LSMD from placebo, -7.7 [95% CI: -15.0 to -0.4]; P = 0.039) and week 4 (LSMD from placebo, -7.5 [95% CI: -15.0 to 0.0]; P = 0.050). Weeks 3 and 4 pain intensity decreased by approximately 30-40%. Oxymorphone ER 20 and 40 mg improved from baseline on the Western Ontario and McMaster Universities Osteoarthritis Composite Index and pain and physical function subscales at week 4. Adverse events in all opioid groups included mild to moderate nausea, constipation, and somnolence.\n In this short-term study, oxymorphone ER was superior to placebo for relieving pain and improving function in patients with moderate to severe chronic OA pain, and is an alternative to other sustained-release opioids.", "This study examines the impact of controlled-release oxycodone (OxyContin) on cognitive-behavioral indicators of efficacy beliefs and coping efforts in patients with osteoarthritis who experience persistent pain.\n This was a double-blind, placebo-controlled study of 104 male and female patients with osteoarthritis who experienced moderate to severe pain. Pain assessment, arthritis helplessness, and coping efforts were assessed before and after for treatment and placebo control groups.\n Examination of differences between treatment and control groups after 2 weeks revealed significant reductions in reported pain, improvements in coping efficacy, and reductions in helplessness and passive coping in response to controlled-release oxycodone treatment compared to placebo. Changes in pain partially mediated the effects on coping in subsequent assessments.\n The findings indicate that controlled-release oxyco- done treatment accounted for improvements in coping with pain beyond that of placebo controls. This medication may be most beneficial to osteoarthritis patients when incorporated as part of a multidisciplinary approach to pain management.", "Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate-to-severe OA pain, in a placebo-controlled study.\n The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate-to-severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1-week pretreatment run-in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).\n Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores -20 in the TDF group versus -14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group.\n TDF can reduce pain and improve function in patients with knee or hip OA.", "Oxytrex is a novel drug that combines oxycodone with ultralow-dose naltrexone, an opioid antagonist. Ultralow-dose opioid antagonists have been demonstrated to enhance and prolong opiate analgesia and alleviate opioid tolerance and withdrawal in rodents. This 3-week, Phase II clinical trial assessed safety and analgesic efficacy of Oxytrex in patients with moderate to severe pain from osteoarthritis. Patients with a pain score > or =5 received placebo, oxycodone 4 times a day (qid), Oxytrex qid, or Oxytrex twice a day (bid). All active treatment groups received the same total daily dose and dose escalation of oxycodone starting at 10 and ending at 40 mg/day. Importantly, the Oxytrex bid group received a lower daily dose of naltrexone than Oxytrex qid (0.002 vs 0.004 mg/day). Oxytrex bid produced a 39% reduction in pain intensity, which was significantly greater than that of placebo (P < .001), oxycodone qid (P = .006), and Oxytrex qid (P = .003). Oxytrex bid was also superior to placebo in quality of analgesia (P = .002), duration of pain control each day (P = .05), patients' global assessments (P = .04), and the Western Ontario and MacMaster Universities Osteoarthritis Index total score (P = .03). The incidence of side effects was comparable between active treatments. In this Phase II dose-ranging study, Oxytrex bid demonstrated greater pain relief with a more convenient dosing schedule compared to oxycodone qid.\n Preclinical data have shown ultralow-dose opioid antagonists to enhance and prolong opioid analgesia while reducing analgesic tolerance and physical dependence. Recent molecular pharmacology data show a mechanism of action to be the prevention of aberrant G protein coupling by opioid receptors that underlies opioid tolerance and dependence.", "The analgesic efficacy of 200 mg ibuprofen plus 30 mg codeine, 200 mg ibuprofen and placebo was investigated in a new analgesic evaluation model using single- and repeated-dose administration. The study was a double-blind randomized cross-over investigation in 26 coxarthrosis patients with persistent pain. After a washout period of at least 2 days with paracetamol available as rescue analgesic, each of the 3 treatments was administered in a total of 6 doses during 24 h. The hourly pain intensity was recorded on a 100-mm visual analogue scale (VAS) for 8 h after the 1st and the 6th dose. The pretreatment VAS score was 31-37 mm. After the 1st dose the 8-h mean pain intensity values were 25, 27, and 26 mm after ibuprofen plus codeine, ibuprofen, and placebo, respectively. Following another 5 doses every 4 h the corresponding values were 10, 17 and 29 mm. Repeated administration of both active drugs reduced the pain intensity significantly. The analgesic efficacy of ibuprofen plus codeine was significantly superior to that of ibuprofen which was, in turn, superior to that of placebo. In conclusion, analgesic efficacy was better differentiated after repeated-dose than after single-dose administration. The present study design was able to differentiate between 200 mg ibuprofen plus 30 mg codeine and 200 mg ibuprofen alone in a relatively small number of patients.", "A randomized, 4-week, double-blind trial followed by an open-label extension trial assessed the efficacy and safety of a once-daily, extended-release morphine formulation (Avinza (previously referred to as Morphelan)) in 295 patients with chronic, moderate-to-severe osteoarthritis pain who had failed to obtain adequate pain relief with NSAIDs and acetaminophen. Participants received one of four treatments: Avinza 30 mg once daily (QAM or QPM), MS Contin(R) 15 mg twice daily, or placebo twice daily. Patients (n =181) received Avinza QAM or QPM during the 26-week open-label extension trial and could increase their dose to optimize pain control. Avinza and MS Contin reduced pain and improved several sleep measures versus placebo. Analgesic efficacy was comparable between Avinza and MS Contin; however, Avinza QAM demonstrated greater improvements in overall quality of sleep. The most common adverse events were constipation and nausea. The majority of AEs occurred at a similar incidence among the active treatment groups.", "This randomized, double-blind, multi-centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip. A total of 158 outclinic patients entered the study. Eighty-three patients (mean age 66 years) were treated with codeine 60 mg plus paracetamol 1 g 3 times daily, and 75 patients (mean age 67 years) with paracetamol 1 g 3 times daily. Ibuprofen 400 mg was prescribed as rescue medication. Due to an unexpected high rate of adverse drug reactions, the study was closed before the planned 400 patients had entered. Over weeks 1-4, 87%, 64%, 61% and 52% of patients in the codeine plus paracetamol group, and 38%, 31%, 22% and 29% of patients in the paracetamol group had one or more adverse drug reactions. Significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks. Nausea, dizziness, vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group. During the first week of treatment, 30 patients (36%) in the codeine plus paracetamol group and 9 (12%) in the paracetamol group dropped out. As evaluated from patients completing the first week of treatment, the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group. Moreover, during the first week the paracetamol group received rescue medicine significantly more frequently. In conclusion, when evaluated after 7 days of treatment, the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint. However, several adverse drug reactions, mainly of the gastrointestinal tract, and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine cannot be recommended for longer-term treatment of chronic pain in elderly patients." ]

[ "11488791", "10392481", "11668312", "19563951", "19640922" ]

[ "Randomized double-blind controlled trial of roxithromycin for prevention of abdominal aortic aneurysm expansion.", "Impaired results of a randomised double blinded clinical trial of propranolol versus placebo on the expansion rate of small abdominal aortic aneurysms.", "Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study.", "The effect of azithromycin and Chlamydophilia pneumonia infection on expansion of small abdominal aortic aneurysms--a prospective randomized double-blind trial.", "Intermittent roxithromycin for preventing progression of small abdominal aortic aneurysms: long-term results of a small clinical trial." ]

[ "Macrolide treatment has been reported to lower the risk of recurrent ischaemic heart disease. The influence of macrolides on the expansion rate of abdominal aortic aneurysms (AAAs) remains unknown. The aim was to investigate the effect of roxithromycin on the expansion rate of small AAAs.\n A total of 92 subjects with a small AAA were recruited from two populations. One population consisted of 6339 men aged 65-73 years who were offered a hospital-based mass screening programme for AAA. From this population 66 subjects were recruited. The remaining 26 men were recruited from among 49 subjects diagnosed at interval screening for an initial aortic diameter between 25 and 29 mm. Subjects were randomized to receive either oral roxithromycin 300 mg once daily for 28 days or matching placebo, and followed for a mean of 1.5 years.\n During the first year the mean annual expansion rate of AAAs was reduced by 44 [corrected] per cent in the intervention group (1.56 mm per year), compared with 2.80 mm per year following placebo (P = 0.02). During the second year the difference was only 5 per cent [corrected]. Multiple linear regression analysis showed that roxithromycin treatment and initial AAA size were significantly related to AAA expansion when adjusted for smoking, diastolic blood pressure and immunoglobulin A level of 20 or more [corrected]. Logistic regression analysis confirmed a significant difference in expansion rates above 2 mm annually between the intervention and placebo groups: odds ratio = 0.09 (95 per cent confidence interval 0.01-0.83) [corrected].\n In comparison to placebo, roxithromycin 300 mg daily for 4 weeks reduced the expansion rate of AAAs.", "To study the propranolol treatment of small abdominal aortic aneurysms (AAA) concerning intention to treat, side effects, and inhibition of expansion.\n \n Two-year lasting prospective randomised double-blinded intervention trial.\n Hospital-based mass screening for AAA with annual ambulatory control of small AAA.\n Of 122 screening-diagnosed small AAA, 51 (42%) were excluded because of contraindications or present beta-blockage, and 17 refused participation. Thus, 54 (44.3%) were included.\n Participants were randomised to 40 mg propranolol twice a day or placebo.\n The same observed was used to follow-up AAA-expansion, side effects, quality of life (QL), branchial and ankle blood pressure (ABI), and pulmonary function (FEV1 and FVC).\n Sixty percent in the propranolol group, and 25% in the placebo group dropped out, mainly caused by dyspnoea in the propranolol group (RR=1.74, 95% C.I.: 1.06-2.86). Five (16.7%) died in the propranolol group, while 1 (4.2%) died in the placebo group (RR=1.6 (1.02-2.51)). Furthermore, decreased pulmonary function, ABI, and QL was noticed in the propranolol group. Consequently, the trial was stopped after two years. Ninety-five percent of the measurements of the AAA were measured within 2 mm variation. If expansion was defined as above 2 mm annually, the relative risk of expansion in the placebo group was 1.17 (0.74-1.85), and 2.44 (0.88-6.77) among the non-drop-outs.\n Only 22% of small screenings-diagnosed AAA were treatable with propranolol for two years. Consequently, only large scale studies are capable of showing potential minor inhibition of expansion by propranolol. However, whether such treatment ever becomes ethically acceptable is debatable.", "Eradication of Chlamydia pneumoniae infection and inhibition of elastolytic matrix metalloproteinases with doxycycline have been suggested to reduce the growth rates of small abdominal aortic aneurysms (AAA). We designed a study to investigate the efficacy of doxycycline in reducing the expansion of small AAAs.\n This was a prospective, double-blind, randomized, placebo-controlled study that was set in a university referral hospital. The study group consisted of 32 of 34 initially eligible patients who had an AAA diameter perpendicular to the aortic axis of 30 mm or more in size or a ratio of infrarenal to suprarenal aortic diameter of 1.2 or more and a diameter less than 55 mm. Patients were randomly assigned to receive either doxycycline (150 mg daily) or placebo during a 3-month period and underwent ultrasound surveillance during an 18-month period. Outcome measures included aneurysm expansion rates, the number of patients who had AAA rupture or repair, C pneumoniae antibody titers, and serum concentrations of C-reactive protein.\n The aneurysm expansion rate in the doxycycline group was significantly lower than that in the placebo group during the 6- to 12-month (P = .01) and the 12- to 18-month periods (P =.01). Five patients (41%) in the placebo group and 1 patient (7%) in the doxycycline group had an overall expansion of the aneurysm of 5 mm or more during the 18-month follow-up. Among the placebo group patients, a higher expansion rate was observed in those with enhanced C pneumoniae immunoglobulin G antibody titers (> 128) than in those with lower titers (P = .03). Doxycycline treatment had no clear effect on antibody titers. However, at 6-month follow-up, C-reactive protein levels in the doxycycline group were significantly lower than the baseline levels (P = .01).\n The results of this small pilot study suggest that doxycycline may favorably alter the outcome of patients with small AAA. However, because of the small size of this randomized study and of the potentially confounding effect of pretreatment risk factors, doxycycline-based treatment cannot be justified only on the ground of the current results. Because of the high prevalence of this disorder and its clinical, social, and economic relevance, a multicenter study should be performed to further investigate whether there is any place for medical treatment of small AAAs.", "The aim of the study was to evaluate the effect of azithromycin on the expansion rate of small abdominal aortic aneurysms (AAAs), and to determine whether or not a correlation exists between serological markers for Chlamydophilia pneumonia (Cpn) infection and AAA expansion.\n Nine vascular centers were included and 259 patients were invited to participate. Ten patients declined and 2 patients had chronic kidney failure, leaving a total of 247 patients. Inclusion criteria were: AAA 35-49 mm and age <80 years. Patients were randomized to receive either azithromycin (Azithromax, Pfizer Inc, New York, NY) 600 mg once daily for 3 days and then 600 mg once weekly for 15 weeks, or placebo in identical tablets. The ultrasound scans were performed in a standardized way within a month before inclusion and every 6 months for a minimum follow-up time of 18 months. Cpn serology was analyzed in blood samples taken at inclusion and 6 months later. Serum was analyzed for Cpn IgA and IgG antibodies by microimmunofluorescence (MIF). Computed tomography (CT) scans were done in 66 patients at inclusion and at 1 year for volume calculations.\n Thirty-four patients were excluded, ie, could not be followed for 18 months, 20 in the placebo group and 16 in the active treatment group. A total of 211 patients had at least two measurements and all were analyzed in an intention-to-treat analysis. Detectable IgA against Cpn was found in 115 patients and detectable IgG against Cpn in 160 patients. No statistically significant differences were found between the groups regarding median expansion rate measured by ultrasound scan (0.22 cm/year, interquartile range [IQR]: 0.09 to 0.34 in the placebo group vs 0.22, IQR: 0.12 to 0.36 in the treatment group, P = .85). Volume calculation did not change that outcome (10.4 cm(3)/year in the placebo group vs 15.9 cm(3)/year in the treatment group, P = .61). No correlation was found between serological markers for Cpn infection and the expansion rate. Patients taking statins in combination with acetylsalicylic acid (ASA) had significantly reduced expansion rate compared to patients who did not take statins or ASA, 0.14 cm/year vs 0.27 cm/year, P < .001.\n Azithromycin did not have any effect on AAA expansion. No correlation was found between serological markers for Cpn and AAA expansion, indicating no clinical relevance for Cpn testing in AAA surveillance. However, a significant reduction in AAA expansion rate was found in patients treated with a combination of ASA and statins.", "Antibodies against Chlamydia pneumoniae are associated with an increased rate of expansion of small abdominal aortic aneurysms (AAAs). Short-term follow-up trials have shown a transient reduction AAA growth rate, in macrolide treated compared with placebo. Therefore we analysed the influence of intermittent, long-term roxithromycin treatment on AAA expansion and referral for surgery.\n Eighty-four patients with small AAAs were randomized to either an annual 4 weeks' treatment with roxithromycin or placebo, and followed prospectively.\n Intermittent, long-term Roxithromycin-treatment reduced mean annual growth rate by 36% compared with placebo after adjustment for potential confounders. Long-term roxithromycin-treated patients had a 29% lower risk of being referred for surgical evaluation, increasing to 57% after adjusting for potential confounders.\n Annual 4 week treatment with 300 mg roxithromycin daily may reduce the progression of small AAAs, and later need for surgical repair. However, more robust studies are needed for confirmation." ]

[ "8731625", "9161945", "2647038", "3918683", "3339500", "2112187", "2007956", "4022702" ]

[ "Effects of immediate modified feeding on infantile gastroenteritis.", "A multicentre study on behalf of the European Society of Paediatric Gastroenterology and Nutrition Working Group on Acute Diarrhoea. Early feeding in childhood gastroenteritis.", "Acute gastroenteritis in well nourished infants: comparison of four feeding regimens.", "Effect on clinical outcome of breast feeding during acute diarrhoea.", "Effect of continued oral feeding on clinical and nutritional outcomes of acute diarrhea in children.", "A comparison of rice-based oral rehydration solution and \"early feeding\" for the treatment of acute diarrhea in infants.", "Oral rehydration therapy: a global perspective.", "Role of soy-based, lactose-free formula during treatment of acute diarrhea." ]

[ "Standard treatment of infants who are dehydrated as a result of acute gastroenteritis is to administer oral rehydration therapy (ORT). Traditionally, food has been withdrawn for 24-48 h, but there is no conclusive evidence that this is of any real benefit to the patient. Immediate modified feeding, in which an infant on ORT is not starved but administered a limited diet, may have benefits in the treatment of gastroenteritis, especially in children who are nutritionally compromised before they develop the illness.\n A pilot study was carried out to investigate the effects of giving infants suffering from acute gastroenteritis a limited modified diet in conjunction with ORT.\n Infants recruited into the study by their general practitioner or by a research doctor in the hospital casualty unit of Bristol Children's Hospital were randomly allocated to receive ORT with or without immediate modified feeding. The duration of diarrhoea, weight change, and incidence of vomiting and lactose intolerance were measured in both treatment groups, and the results were compared.\n Of the infants studied, 27 received ORT and immediate modified feeding, and 32 ORT alone. The duration of diarrhoea, and incidence of vomiting or lactose intolerance were no greater in the group receiving immediate modified feeding. Patients who received ORT and immediate modified feeding appeared to gain more weight than the infants who were starved for 24-48 h, but this difference was not statistically significant.\n Immediate modified feeding is safe and effective, and may have nutritional advantages over traditional ORT with starvation. A similar but multicentre study using unmodified diet, i.e. child's normal diet, is being carried out by a working group of The European Society of Paediatrics, Gastroenterology and Nutrition (ESPGAN).", "nan", "Two hundred well hydrated babies of 6 weeks to 12 months of age who had been fed on formula feeds and who were admitted with acute gastroenteritis were randomly allocated to receive either a standard return to full milk feeds, or immediate full strength feeds with one of three milk formulas, HN25, SMA Gold Cap, or Formula S. There were significant differences in weight change among the four treatment groups at two and five days, with initial weight loss recorded only for the group of babies who were receiving the graded return to full feeding. There was no difference in the duration of diarrhoea after admission, nor in the time to discharge. Eighteen babies were classified as failures of treatment. None had long term complications. Well hydrated infants with acute gastroenteritis may resume full milk feeding immediately.", "The effects of oral rehydration fluid alone and of oral rehydration fluid plus breast feeding on the course and outcome of acute diarrhoea were assessed in two groups of 26 children aged under 2 years. Children who continued to be breast fed during treatment with oral rehydration solutions passed significantly fewer diarrhoeal stools. They also passed, on average, a smaller volume of diarrhoeal stools and recovered from diarrhoea sooner after the start of treatment. Their requirement for oral rehydration fluid was significantly reduced. Breast feeding exerts a beneficial effect on the course and outcome of acute diarrhoea by reducing the number and volume of diarrhoeal stools.", "One hundred twenty-eight nonmalnourished male patients between 3 and 36 months of age were randomly assigned to receive one of four lactose-free dietary treatments to determine the effect of dietary therapy on the severity and nutritional outcome of diarrheal illness. Group 1 received a formula diet composed of casein, sucrose, dextrin with maltose (Dextri-Maltose), and vegetable oil to provide 110 kcal/kg body weight/d (CSO-110). Group 2 received CSO to provide 55 kcal/kg/d (CSO-55) for 2 days and then CSO-110. Group 3 received only oral glucose-electrolyte solution (GES) for 2 days, CSO-55 for the next 2 days, and then CSO-110. Group 4 received the same diets as Group 3 except that only intravenous GES was used for the first 2 days. The GES maintenance solutions provided 24 to 30 kcal/kg/d. Therapeutic success rates were similar among dietary groups, ranging from 90% to 97%. Fecal excretion was initially lower in group 4 (P less than 0.05) but was similar initially among groups treated orally and among all four groups beginning on day 3. Net apparent absorption of nitrogen, fat, carbohydrate, and total energy; retention of nitrogen; and increments in body weight, arm circumference, and skin-fold thickness were positively related to the amounts of dietary energy consumed. Thus continued oral feeding with the CSO diets during the early phase of therapy yielded improved nutritional results.", "To compare the use of rice-based oral rehydration solution (R-ORS), with the introduction of food immediately after rehydration (\"early feeding\"), using standard glucose-based oral rehydration solution (G-ORS) in the management of acute diarrhea, we conducted a four-cell randomized, controlled trial among 200 hospitalized Egyptian infants between 3 and 18 months of age. During the rehydration phase (first 4 hours), three groups were given G-ORS and a fourth group was given R-ORS. During the subsequent maintenance phase, the control group was given a soy-based, lactose-free formula (G-ORS + SF), a second group (G-ORS + RF) was given a rice-based formula, and a third group (G-ORS + rice) was given boiled rice. The fourth group (R-ORS + SF) continued to receive R-ORS for the first 24 hours of the maintenance period, followed by a soy-based lactose-free formula. During the first and second 24 hours of the maintenance period, infants in the three treatment groups had a lower mean stool output in comparison with the control group (p = 0.006 and 0.03, respectively). The mean total stool output in the R-ORS + SF group was significantly lower than in the control group (p = 0.02). There were no statistically significant differences among the four groups in the mean duration of diarrhea. We conclude that (1) infants who were given R-ORS had reduced total stool output (by 35%) compared with the control group and (2) feeding of boiled rice or a rice-based formula immediately after rehydration therapy was as efficacious as treatment with R-ORS alone for 24 hours, followed by feeding with a soy-based, lactose-free formula.", "nan", "A controlled study was conducted comparing the standard method of treating hospitalized infants with acute diarrhea (limited starvation) with the initiation of \"early feeding\" using a soy-based, lactose-free formula in infants of an American Indian tribe 12 months of age or younger. Forty-three patients, randomly assigned to group A, were given a soy-based, lactose-free formula four hours after hospitalization, and 44 patients, randomly assigned to group B, received standard therapy (food was withheld for the first 48 hours of hospitalization). After the first 48 hours, the same soy-based, lactose-free formula was given to the group B patients. Fluid intake and output of stool, urine, and vomitus were measured until the diarrhea resolved. Overall, group A patients showed less mean stool output (121 +/- 129 (SD) mL/kg) than group B patients (299 +/- 319 mL/kg) (P less than .001). Furthermore, the duration of illness was significantly shorter in group A patients (54 +/- 28 hours v 93 +/- 56 hours) (P less than .001). It was concluded that soy-based, lactose-free formulas can be safely used during the acute phase of diarrheal illness in infants and that their use shortens the duration of illness and decreases stool output in comparison with standard therapy." ]

[ "9167811", "15605935", "10694106", "15319103", "4065773", "11689747", "1299491", "2285093", "3056045", "4434039", "11676730" ]

[ "The effect of a pneumatic leg brace on return to play in athletes with tibial stress fractures.", "The use of a pneumatic leg brace in soldiers with tibial stress fractures--a randomized clinical trial.", "A randomized trial of preexercise stretching for prevention of lower-limb injury.", "A prospective study of the effect of foot orthoses composition and fabrication on comfort and the incidence of overuse injuries.", "A prospective study of the effect of a shock-absorbing orthotic device on the incidence of stress fractures in military recruits.", "Relationship between footwear comfort of shoe inserts and anthropometric and sensory factors.", "Does calcium supplementation prevent bone stress injuries? A clinical trial.", "Prevention of common overuse injuries by the use of shock absorbing insoles. A prospective study.", "Prevention of lower extremity stress fractures: a controlled trial of a shock absorbent insole.", "A prospective study on the management of shin splints.", "Effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on injury risk in Army recruits." ]

[ "A total of 18 competitive and recreational athletes were enrolled in a randomized, prospective study looking at the effect of pneumatic leg braces on the time to return to full activity after a tibial stress fracture. All patients had positive bone scans and 15 had positive radiographic findings by Week 12. There were two treatment groups. The traditional treatment group was treated with rest and, after 3 pain-free days, a gradual return to activity. The pneumatic leg brace (Aircast) group had the brace applied to the affected leg and then followed the same return to activity guidelines. The guidelines consisted of a detailed functional progression that allowed pain-free return to play. The brace group was able to resume light activity in 7 days (median) and the traditional group began light activity in 21 days (median). The brace group returned to full, unrestricted activity in 21 +/- 2 days, and the traditional group required 77 +/- 7 days to resume full activity. The Aircast pneumatic brace is effective in allowing athletes with tibial stress fractures to return to full, unrestricted, pain-free activity significantly sooner than traditional treatment.", "Single blind randomized controlled replication study.\n Evaluate the effect of a pneumatic leg brace on return-to-activity and pain in soldiers with tibial stress fractures.\n Thirty-one subjects diagnosed with tibial stress fractures were randomly assigned to either a brace or control group. Dependent variables included time to pain-free single-leg hopping, visual analog pain scale, and time to a pain-free 1-mile run. Twenty subjects (10 brace, 10 control) completed a detailed functional progression culminating in a 1-mile run.\n There was no difference between groups for time to pain-free hop (p > 0.86; power = 0.43) and time to pain-free 1-mile run (p > 0.24; power = 0.92). Subjects in both groups experienced statistically significant improvements in pain measurements (p < 0.002), but no difference was found between groups (p > 0.93).\n The current study demonstrated no added benefit of Aircast leg braces in the treatment of tibial stress fractures in the military training environment.", "This study investigated the effect of muscle stretching during warm-up on the risk of exercise-related injury.\n 1538 male army recruits were randomly allocated to stretch or control groups. During the ensuing 12 wk of training, both groups performed active warm-up exercises before physical training sessions. In addition, the stretch group performed one 20-s static stretch under supervision for each of six major leg muscle groups during every warm-up. The control group did not stretch.\n 333 lower-limb injuries were recorded during the training period, including 214 soft-tissue injuries. There were 158 injuries in the stretch group and 175 in the control group. There was no significant effect of preexercise stretching on all-injuries risk (hazard ratio [HR] = 0.95, 95% CI 0.77-1.18), soft-tissue injury risk (HR = 0.83, 95% CI 0.63-1.09), or bone injury risk (HR = 1.22, 95% CI 0.86-1.76). Fitness (20-m progressive shuttle run test score), age, and enlistment date all significantly predicted injury risk (P < 0.01 for each), but height, weight, and body mass index did not.\n A typical muscle stretching protocol performed during preexercise warm-ups does not produce clinically meaningful reductions in risk of exercise-related injury in army recruits. Fitness may be an important, modifiable risk factor.", "Foot orthoses are widely prescribed both to treat existing pathological conditions and to prevent overuse injuries, but little is known about the effect of their material composition and fabrication technique on patient comfort and the incidence of overuse injuries.\n The acceptance rates and comfort scores of soft custom, soft prefabricated, semirigid biomechanical, and semirigid prefabricated orthoses and their effect on the incidence of stress fractures, ankle sprains, and foot problems were studied in a prospective, randomized, single-blinded clinical trial among 874 infantry recruits during basic training.\n A statistically significantly lower number of recruits given soft prefabricated orthoses (53%) finished basic training in their assigned devices than in the soft custom group (72%), in the semirigid biomechanical group (75%), and in the semirigid prefabricated group (82%) (p = .003). For recruits who finished training in their assigned orthoses, the soft custom (3.54) and soft prefabricated (3.43) orthoses had significantly higher comfort scores than the semirigid biomechanical (3.23) and prefabricated (3.17) orthoses, (p = .0001). There was no statistically significant difference in the incidence of stress fractures, ankle sprains, or foot problems between recruits using the different types of orthoses.\n These findings suggest that if a foot orthosis is being dispensed as prophylaxis for overuse injuries in an active, healthy population, there is little justification for prescribing semirigid biomechanical orthoses. Their cost is high compared to other types of orthoses, without an advantage in comfort or a reduction in stress fractures, ankle sprains, and foot problems.", "In a prospective study of stress fractures the hypothesis that a shock-absorbing orthotic device worn within military boots could lessen the incidence of stress fractures was tested. The incidence of metatarsal, tibial, and femoral stress fractures was lower in the orthotic group, but only the latter difference was statistically significant. The time of onset and the location of stress fractures between orthotic and nonorthotic users did not differ. These findings suggest that the incidence of femoral stress fractures, which are the most dangerous type of stress fracture because of their high risk of developing into displaced fractures, can be reduced by an orthotic device.", "The purposes of this study were (a) to determine lower extremity anthropometric and sensory factors that are related to differences in comfort perception of shoe inserts with varying shape and material and (b) to investigate whether shoe inserts that improve comfort decrease injury frequency in a military population.\n 206 military personnel volunteered for this study. The shoe inserts varied in arch and heel cup shape, hardness, and elasticity in the heel and forefoot regions. A no insert condition was included as the control condition. Measured subject characteristics included foot shape, foot and leg alignment, and tactile and vibration sensitivity of the plantar surface of the foot. Footwear comfort was assessed using a visual analog scale. Injury frequency was evaluated with a questionnaire. The statistical analyses included Student's t-tests for repeated measures, ANOVA (within subjects), MANOVA (within insert combinations), and chi-square tests.\n The average comfort ratings for all shoe inserts were significantly higher than the average comfort rating for the control condition. The incidence of stress fractures and pain at different locations was reduced by 1.5-13.4% for the insert compared with the control group. Foot arch height, foot and leg alignment, and foot sensitivity were significantly related to differences in comfort ratings for the hard/soft, the viscous/elastic, and the high arch/low arch insert combinations.\n Shoe inserts of different shape and material that are comfortable are able to decrease injury frequency. The results of this study showed that subject specific characteristics influence comfort perception of shoe inserts.", "This study investigated the effect of calcium supplementation in preventing bone stress injuries. Healthy male military recruits (N = 1,398) served as subjects, of which 247 were randomly allocated to an experimental group (E) while 1,151 served as a control group (C). For 9 weeks both groups wore the same footwear and had the same physical training program. The baseline dietary intake of calcium in 50 randomly selected subjects of each group was assessed using a 24-hr dietary record. The E group received a daily calcium supplement while the C group did not. Injuries were monitored in all subjects by a panel of doctors who followed specific diagnostic criteria. The mean weekly injury incidence for all overuse injuries, but specifically tibial stress syndrome and stress fractures, was similar in both groups. Mean baseline daily dietary calcium intake was above 800 mg in both subgroups. This study demonstrated that large-scale calcium supplementation (500 mg/day) beyond usual dietary intake did not influence the risk of developing bone stress injuries during a 9-wk physical training program in these young military recruits.", "Sedentary individuals, particularly new military recruits, who start a physical training program have a substantial risk of developing an overuse injury of the lower limb. In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training. The experimental group consisted of 237 randomly selected new recruits, while 1151 recruits were the control group. Insoles were given to the experimental group and compliance was monitored. A panel of doctors documented and classified all injuries occurring during the 9 week period. A total of 54 (22.8%) and 237 (31.9%) injuries were reported in the experimental and control groups, respectively. In both groups, the majority of injuries were overuse (experimental group, 90.7%; control group, 86.4%). The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower (P less than 0.05) in the experimental group. The mean incidence of stress fractures was lower in the experimental group but not significantly so (0.05 less than P less than 0.1). This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles.", "A prospective controlled trial was carried out to determine the usefulness of a viscoelastic polymer insole in prevention of stress fractures and stress reactions of the lower extremities. The subjects were 3,025 US Marine recruits who were followed for 12 weeks of training at Parris Island, South Carolina. Polymer and standard mesh insoles were systematically distributed in boots that were issued to members of odd and even numbered platoons. The most important finding was that an elastic polymer insole with good shock absorbency properties did not prevent stress reactions of bone during a 12-week period of vigorous physical training. To control for the confounding effects of running in running shoes, which occurred for about one and one-half hours per week for the first five weeks, we also examined the association of age of shoes and cost of shoes with injury incidence. A slight trend of increasing stress injuries by increasing age of shoes was observed. However, this trend did not account for the similarity of rates in the two insole groups. In addition, we observed a strong trend of decreasing stress injury rate by history of increasing physical activity, as well as a higher stress injury rate in White compared to Black recruits. The results of the trial were not altered after controlling for these factors. This prospective study confirms previous clinical reports of the association of stress fractures with physical activity history. The clinical application of a shock absorbing insole as a preventive for lower extremity stress reactions is not supported in these uniformly trained recruits. The findings are relevant to civilian populations.", "nan", "This study investigated effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on relative risk of selected injuries in 1093 male Army recruits undertaking 12 weeks of intensive training. Prior to training, ankle dorsiflexion range was measured and recruits were allocated to stretch and control groups using a quasi-random procedure. The stretch group stretched calf muscles under supervision prior to all intense exercise. The control group stretched upper limb muscles instead. Forty-eight injuries were recorded. Survival analysis indicated that ankle dorsiflexion range was a strong predictor of injury (p = 0.03). Definitive evidence of an effect of stretching on injury risk was not found (p = 0.76), but the sample size may have been insufficient to detect such an effect." ]

[ "4584169", "1094544", "6380725", "3529834", "7114310", "4605436" ]

[ "Comparison of thioridazine and diazepam in the control of nonpsychotic symptoms associated with senility: double-blind study.", "Alleviating agitation, apprehension, and related symptoms in geriatric patients: A double-blind comparison of a phenothiazine and a benzodiazepien.", "Multicenter study comparing thioridazine with diazepam and placebo in elderly, nonpsychotic patients with emotional and behavioral disorders.", "A comparison of chlormethiazole and thioridazine in agitated confusional states of the elderly.", "Efficacy of antipsychotic medications in behaviorally disturbed dementia patients.", "Video methodology for research in psychopathology and psychopharmacology: Rationale and application." ]

[ "nan", "A four-week, double-blind study compared the effectiveness of thioridazine and diazepam in 40 geriatric patients with various symptoms of senility. Patients' progress was evaluated with the Hamilton Anxiety Rating Scale, a Modified Nurses' Observation Scale for Inpatient Evaluation (NOSIE), a global rating of degree of illness, and a global rating of degree of overall change. The data indicate that thioridazine was superior to diazepam inrelieving troublesome symptoms of senility.", "Thioridazine was compared with placebo or diazepam or both in 610 elderly, nonpsychotic inpatients in geriatric wards of state hospitals or nursing homes. All patients manifested disruptive and difficult-to-manage behavior that interfered with adjustment to their environment and with proper care and treatment of their medical and emotional problems. Target symptoms such as agitation, anxiety, tension, apprehension, depressed mood, and sleep disturbances showed consistently marked improvement throughout the four-week study, as measured by the modified Hamilton Anxiety Scale, the modified Nurses' Observation Scale for Inpatient Evaluation (NOSIE), and global ratings. Significantly greater improvement on all measures was achieved with thioridazine than with placebo. In addition, greater improvement in the majority of symptoms assessed by the Hamilton Anxiety Scale and NOSIE were seen in patients who received thioridazine than in those given diazepam.", "Chlormethiazole and thioridazine were found to be equally effective in the management of the agitational component of agitated confusional states in the elderly. Confusion and nocturnal awakening were found to be controlled more effectively with chlormethiazole than with thioridazine. Chlormethiazole treatment also resulted in significant reductions in physical disability as assessed by the Clifton Behaviour Rating Scale. A greater incidence of adverse effects was associated with thioridazine treatment.", "This study compared the therapeutic efficacy of thioridazine, loxapine, and a placebo in the treatment of behavioral disturbances in nursing home patients with dementia. Antipsychotic medications were effective for the specific behavioral problems of anxiety, excitement, emotional lability, and uncooperativeness. Subjects with the most severe symptoms at baseline assessment derived the greatest benefit from treatment. Sedation, extrapyramidal symptoms, and decreased blood pressure were common side effects among patients treated with the antipsychotic drugs. The authors conclude that antipsychotic medication has a definite but limited therapeutic role in the treatment of behavioral disturbances in nursing home patients with dementia.", "nan" ]

[ "1588426", "11835741", "782888", "4432786", "19852540" ]

[ "Results of a prospective randomized trial for treatment of severely brain-injured patients with hyperbaric oxygen.", "Glasgow Coma Scale, brain electric activity mapping and Glasgow Outcome Scale after hyperbaric oxygen treatment of severe brain injury.", "Hyperbaric oxygenation for severe head injuries. Preliminary results of a controlled study.", "[Improved reversibility of the traumatic midbrain syndrome using hyperbaric oxygen].", "A prospective, randomized clinical trial to compare the effect of hyperbaric to normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen toxicity in severe traumatic brain injury." ]

[ "The authors enrolled 168 patients with closed-head trauma into a prospective trial to evaluate the effect of hyperbaric oxygen in the treatment of brain injury. Patients were included if they had a total Glasgow Coma Scale (GCS) score of 9 or less for at least 6 hours. After the GCS score was established and consent obtained, the patient was randomly assigned, stratified by GCS score and age, to either a treatment or a control group. Hyperbaric oxygen was administered to the treatment group in a monoplace chamber every 8 hours for 1 hour at 1.5 atm absolute; this treatment course continued for 2 weeks or until the patient was either brain dead or awake. An average of 21 treatments per patient was given. Outcome was assessed by blinded independent examiners. The entire group of 168 patients was followed for 12 months, with two patients lost to follow-up study. The mortality rate was 17% for the 84 hyperbaric oxygen-treated patients and 32% for the 82 control patients (chi-squared test, 1 df, p = 0.037). Among the 80 patients with an initial GCS score of 4, 5, or 6, the mortality rate was 17% for the hyperbaric oxygen-treated group and 42% for the controls (chi-squared test, 1 df, p = 0.04). Analysis of the 87 patients with peak intracranial pressures (ICP) greater than 20 mm Hg revealed a 21% mortality rate for the hyperbaric oxygen-treated patients, as opposed to 48% for the control group (chi-squared test, 1 df, p = 0.02). Myringotomy to reduce pain during hyperbaric oxygen treatment helped to reduce ICP. Analysis of the outcome of survivors reveals that hyperbaric oxygen treatment did not increase the number of patients in the favorable outcome categories (good recovery and moderate disability). The possibility that a different hyperbaric oxygen treatment paradigm or the addition of other agents, such as a 21-aminosteroid, may improve quality of survival is being explored.", "To study the effect of hyperbaric oxy gen (HBO) treatment of severe brain injury.\n Fifty-five patients were divided into a treatment group (n=35 receiving HBO therapy) and a control group (n=20 receiving dehydrating, cortical steroid and antibiotic therapy) to observe the alteration of clinic GCS (Glasgow Coma Scale), brain electric activity mapping (BEAM), prognosis and GOS (Glasgow Outcome Scale) before a nd after hyperbaric oxygen treatment.\n In the treatment group GCS, BEAM and GOS were improved obviously after 3 courses of treatment, GCS increased from 5.1 to 14.6 (P<0.01-0.001),the BEAM abnormal rate reduced from 94.3% to 38% (P<0.01-0.001), the GOS good-mild disability rate was 83.7%, and the middle-severe disability rate was 26.3% compared with the control group. There was a statistic significant difference between the two groups (P<0.01-0.001).\n Hyperbaric oxygen treatment could improve obviously GCS, BEAM and GOS of severe brain injury patients, and effectively reduce the mortality and morbidity. It is an effective method to treat severe brain injury.", "60 patients were included in a prospective study to evaluate the effectiveness of hyperbaric oxygenation (OHP) as a treatment of head injury coma. They were assigned to nine subgroups according to age, level of consciousness and eventual neurosurgical procedure, and then selected randomly for OHP or standard therapy. OHP was administered in one or several series of daily exposure at 2.5 ATA. However, the OHP therapy protocol was to be interrupted in 11 cases developing pulmonary, hyperoxic, or infectious complications. Overall mortality and mean duration of coma in survivors were not different in both groups, indicating that OHP was either ineffective or too intermittently applicated. Analysis of results in subgroups revealed that, in one subgroup (18 patients), the rate of recovered consciousness at 1 month was significantly higher when OHP was used. These patients were under 30 and had a brain stem contusion without supratentorial mass lesion. The view is defended that, besides its toxic action on the normal nervous tissue, OHP can counteract edema and ischemia in the zones of brain injuries.", "nan", "Oxygen delivered in supraphysiological amounts is currently under investigation as a therapy for severe traumatic brain injury (TBI). Hyperoxia can be delivered to the brain under normobaric as well as hyperbaric conditions. In this study the authors directly compare hyperbaric oxygen (HBO2) and normobaric hyperoxia (NBH) treatment effects.\n Sixty-nine patients who had sustained severe TBIs (mean Glasgow Coma Scale Score 5.8) were prospectively randomized to 1 of 3 groups within 24 hours of injury: 1) HBO2, 60 minutes of HBO(2) at 1.5 ATA; 2) NBH, 3 hours of 100% fraction of inspired oxygen at 1 ATA; and 3) control, standard care. Treatments occurred once every 24 hours for 3 consecutive days. Brain tissue PO(2), microdialysis, and intracranial pressure were continuously monitored. Cerebral blood flow (CBF), arteriovenous differences in oxygen, cerebral metabolic rate of oxygen (CMRO2), CSF lactate and F2-isoprostane concentrations, and bronchial alveolar lavage (BAL) fluid interleukin (IL)-8 and IL-6 assays were obtained pretreatment and 1 and 6 hours posttreatment. Mixed-effects linear modeling was used to statistically test differences among the treatment arms as well as changes from pretreatment to posttreatment.\n In comparison with values in the control group, the brain tissue PO2 levels were significantly increased during treatment in both the HBO2 (mean +/- SEM, 223 +/- 29 mm Hg) and NBH (86 +/- 12 mm Hg) groups (p < 0.0001) and following HBO2 until the next treatment session (p = 0.003). Hyperbaric O2 significantly increased CBF and CMRO2 for 6 hours (p < or = 0.01). Cerebrospinal fluid lactate concentrations decreased posttreatment in both the HBO2 and NBH groups (p < 0.05). The dialysate lactate levels in patients who had received HBO2 decreased for 5 hours posttreatment (p = 0.017). Microdialysis lactate/pyruvate (L/P) ratios were significantly decreased posttreatment in both HBO2 and NBH groups (p < 0.05). Cerebral blood flow, CMRO2, microdialysate lactate, and the L/P ratio had significantly greater improvement when a brain tissue PO2 > or = 200 mm Hg was achieved during treatment (p < 0.01). Intracranial pressure was significantly lower after HBO2 until the next treatment session (p < 0.001) in comparison with levels in the control group. The treatment effect persisted over all 3 days. No increase was seen in the CSF F2-isoprostane levels, microdialysate glycerol, and BAL inflammatory markers, which were used to monitor potential O2 toxicity.\n Hyperbaric O2 has a more robust posttreatment effect than NBH on oxidative cerebral metabolism related to its ability to produce a brain tissue PO2 > or = 200 mm Hg. However, it appears that O2 treatment for severe TBI is not an all or nothing phenomenon but represents a graduated effect. No signs of pulmonary or cerebral O2 toxicity were present." ]

[ "9371898", "10209349", "10954953", "20656704", "17339143", "7964913", "1653141", "9596457" ]

[ "Sumatriptan nasal spray for the acute treatment of migraine. Results of two clinical studies.", "Sumatriptan nasal spray: a dose-ranging study in the acute treatment of migraine.", "A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal spray in the acute treatment of migraine.", "Intranasal sumatriptan powder delivered by a novel breath-actuated bi-directional device for the acute treatment of migraine: A randomised, placebo-controlled study.", "Intranasal sumatriptan study with high placebo response in Taiwanese patients with migraine.", "Intranasal sumatriptan for the acute treatment of migraine. International Intranasal Sumatriptan Study Group.", "A placebo-controlled study of intranasal sumatriptan for the acute treatment of migraine. The Finnish Sumatriptan Group and the Cardiovascular Clinical Research Group.", "Multiple-attack efficacy and tolerability of sumatriptan nasal spray in the treatment of migraine." ]

[ "Sumatriptan nasal spray may be particularly useful for patients whose nausea and vomiting preclude them from using oral migraine medication or for patients who prefer not to use an injectable migraine medication. The objective of this study was to evaluate in two clinical studies the efficacy and tolerability of the intranasal form of sumatriptan in the acute treatment of a single migraine attack. International Headache Society-diagnosed adult migraineurs in two randomized, double-blind, parallel-group, multicenter studies (n = 409 and 436) used sumatriptan nasal spray 20 mg, 10 mg, or placebo (2:1:1) for the acute treatment of a single migraine attack at home. Predose and at predetermined postdose intervals, patients recorded headache severity (none, mild, moderate, severe); time to meaningful relief; clinical disability (none, mildly impaired, severely impaired, bed rest required); presence/absence of nausea, photophobia, and phonophobia; and the occurrence of adverse events. Two hours postdose in the two studies, moderate or severe baseline pain was reduced to mild or none in 62 to 63% of patients treated with sumatriptan 20 mg, 43 to 54% of patients treated with sumatriptan 10 mg, and 29 to 35% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies and 10 mg versus placebo for study 1). Onset of relief relative to placebo began as early as 15 minutes postdose (sumatriptan 20 mg, study 2). Clinical disability at 2 hours postdose was reported as mildly impaired or normal in 72 to 74% of patients treated with sumatriptan 20 mg, 56 to 68% of patients treated with sumatriptan 10 mg, and 47 to 58% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies). Similar efficacy rates were observed for nausea, photophobia, and phonophobia. The most common adverse event in the active treatment groups was disturbance of taste (bad, bitter, or unpleasant taste). Aside from this event, the pattern and incidence of adverse events did not differ among treatment groups. From these results we determined that sumatriptan nasal spray is a rapidly effective, well-tolerated migraine treatment. The 20-mg dose was effective in treating the entire migraine symptom complex, and the 10-mg dose was less consistently effective.", "This multicentre, randomized, double-blind, placebo-controlled, parallel group dose-ranging study compared the efficacy and tolerability of four doses of sumatriptan nasal spray (2.5, 5, 10 and 20 mg) with a placebo, in the acute treatment of a single migraine attack. In total, 544 patients received the study medication as a single spray in one nostril, to treat a single migraine attack in the clinic. Efficacy assessments included the measurement of headache severity, clinical disability, and the presence/absence of associated symptoms. The incidence of headache recurrence was also assessed. The three highest doses of sumatriptan (5 mg 49%, 10 mg 46%, 20 mg 64%) were significantly better than the placebo (25%) at providing headache relief (moderate or severe headache improving to mild or none) 120 min after treatment (P </= 0. 01). Also, the 20 mg dose was significantly superior to both the 10 and 5 mg doses at this time point (P < 0.05). The proportion of patients who were headache-free 120 min after treatment, was also higher following 20 mg (42%) rather than following any other sumatriptan dose (14-24%, P < 0.005 20 vs 10 mg) or placebo (11%). Headache recurrence in patients who had responded to initial treatment was reported by 30-41% of patients who received sumatriptan, compared with 33% of patients in the placebo group. Sumatriptan nasal spray was well tolerated, the incidence of adverse events with each dose of sumatriptan being similar to the placebo (20-27 and 23%, respectively). Apart from bad/bitter taste, the events were comparable with those reported following sumatriptan treatment by other routes of administration.\n Copyright 1999 Lippincott Williams & Wilkins", "A multinational, multicentre, randomised, double-blind, double-dummy, crossover study (368 patients treating two attacks) was conducted to compare the efficacy and tolerability of sumatriptan nasal spray (20 mg) with dihydroergotamine (DHE) nasal spray (1 mg plus optional 1 mg). At the primary efficacy time point of 60 minutes after dosing, significantly more patients obtained headache relief (change from moderate or severe to none or mild) after treatment with sumatriptan than with DHE (53% sumatriptan, 41% DHE, p < 0.001). Significantly more patients reported relief of nausea after sumatriptan than after DHE at 60 minutes (64% sumatriptan, 49% DHE, p = 0.006). A significant difference between the two treatments was first observed at 45 minutes with respect to both headache relief (38% sumatriptan, 31% DHE, p = 0.037) and relief of nausea (55% sumatriptan, 40% DHE, p = 0.014). There were no significant differences between the two treatments for other measures of efficacy. Both treatments were well tolerated, with only 10% of patients in each group reporting one or more adverse events. The most frequently reported adverse event after sumatriptan was a bad or bitter taste, which was reported by 5% of patients. After DHE, 4% of patients reported symptoms of the nasal cavity/sinuses and 3% reported nausea and/or vomiting as adverse events. It is concluded that sumatriptan nasal spray is superior to DHE nasal spray in the relief of pain and nausea associated with acute migraine headache.", "Intranasal sumatriptan is an option for the treatment of migraine; however, nasal delivery using conventional spray pumps is suboptimal.\n Adult subjects (n = 117) with migraine were enrolled in a multicentre, randomised, double-blind, parallel group, placebo-controlled study. A single migraine attack was treated in-clinic with sumatriptan 10 mg, sumatriptan 20 mg or placebo administered intranasally by a novel bi-directional powder delivery device when migraine was moderate or severe.\n A greater proportion of subjects who received sumatriptan were pain-free at 120 minutes compared with those who received placebo (10 mg/20 mg sumatriptan vs. placebo = 54%/57% vs. 25%, P < .05). Significant benefits were also observed for pain relief at 120 minutes (84%/80% vs. 44%, P < .001/.01) and as early as 60 minutes (73%/74% vs. 38%, P < .01) and for 48 hours sustained pain-free (P < .05). Treatment-related adverse events were rare, with a metallic taste being the most commonly reported (10%/13%).\n Sumatriptan nasal powder administered using the new device during a migraine attack was effective and well tolerated.", "Triptan's efficacy in the treatment of migraine has never been reported in Taiwanese. A high placebo effect was reported in Japanese. The objective of this study was to evaluate the efficacy of intranasal sumatriptan in the acute treatment of migraine in Taiwanese patients.\n Fifty-eight patients who had experienced migraine for at least 1 year were randomly assigned to 2 groups, self-administered intranasal sumatriptan 20 mg or placebo to treat a single migraine attack of moderate or severe intensity.\n A significant difference in headache relief rates between the 2 groups was observed at 30 minutes postdose (46% vs. 21%, p < 0.05). One hour postdose, 61% of sumatriptan recipients experienced headache relief compared with 43% of placebo recipients (p = 0.181). The difference in relief rates between groups diminished over time, mainly due to a high placebo response (54% at 2 hours postdose).\n Our study suggests that ethnicity might have a role in placebo response, and highlights the importance of a placebo group in acute migraine trials. However, the small sample size in this study should also be taken into consideration.", "Two double-blind, placebo-controlled, randomised, multicentre, multinational, parallel-group studies were carried out to identify the optimum dose of intranasal sumatriptan for the acute treatment of migraine. Study medication was taken as a single dose through one nostril in the first study, and as a divided dose through two nostrils in the second study. Totals of 245 and 210 patients with a history of migraine were recruited into the one- and two-nostril studies, respectively. In both studies, headache severity had significantly improved at 120 min after doses of 10-40 mg sumatriptan compared to placebo (P < 0.05) and the greatest efficacy rates were obtained with 20 mg sumatriptan. With 20 mg sumatriptan 78% and 74% of patients experienced headache relief in one- and two-nostril studies respectively. Sumatriptan was generally well tolerated, the most frequently reported event being taste disturbance. The results of the two studies are similar and indicate that administering sumatriptan as a divided dose via two nostrils confers no significant advantage over single-nostril administration.", "A double-blind, randomized, multicentre, parallel-group study was carried out to compare intranasal sumatriptan with placebo in the treatment of migraine. Seventy-four patients (37 in each treatment group) were recruited into the study. Patients received two insufflations of the same treatment (sumatriptan or placebo) 15 min apart. Sumatriptan (20 mg plus 20 mg) was more effective than placebo at relieving headache, defined as a reduction in severity from moderate (grade 2) or severe (grade 3) to mild (grade 1) or none (grade 0), at 60 and 120 min. At 120 min, 75% of patients in the sumatriptan group reported headache relief, compared with 32% of patients in the placebo group (p less than 0.001); 53% of patients in the sumatriptan group were completely pain-free, compared with 11% in the placebo group. A clinically significant reduction in the incidence of nausea, vomiting and photophobia was observed in the sumatriptan group compared with the placebo group, and sumatriptan was also more effective at reducing the functional disability of the patients. A similar number of patients reported migraine recurrence, within 24 h in both treatment groups. The observed reduction in headache severity, functional disability and nausea following intranasal administration of sumatriptan would appear to obviate the need for a concomitant anti-emetic during a migraine attack. The results support the further development and testing of intranasal sumatriptan.", "Sumatriptan hemisulfate nasal spray may provide a useful therapeutic option for patients with migraine who find injectable medications inconvenient or uncomfortable and for patients whose migraine-associated nausea and vomiting preclude the use of oral medication. This study was the first US trial to evaluate the effects of sumatriptan nasal spray administered for multiple migraine attacks.\n Sumatriptan nasal spray (5, 10, or 20 mg) was administered via a 1-shot nasal applicator into either nostril for up to 3 migraine attacks occurring over 6 months in a randomized, double-blind, parallel-group, placebo-controlled study.\n Fifty-six outpatient clinical centers in the United States.\n A total of 1086 men and women diagnosed with migraine with or without aura per International Headache Society criteria.\n Percentage of patients with headache relief (moderate or severe predose pain reduced to mild or none); percentage of patients with no or mild (vs moderate or severe) clinical disability; percentage of patients with nausea, vomiting, photophobia, or phonophobia; adverse events; clinical laboratory test results.\n Across attacks, headache relief in the 20-, 10-, and 5-mg drug and placebo groups was experienced 120 minutes postdose by 60%, 54%, 44%, and 32% of patients, respectively (P<.05 for each sumatriptan nasal spray group vs placebo, for the 10-mg vs 5-mg drug group, and for the 20-mg vs 5-mg drug group). Two thirds of the 20-mg patients treating 3 attacks experienced relief at 2 hours postdose for at least 2 of 3 attacks. Clinical disability scores at 120 minutes in the 20-, 10-, and 5-mg drug and placebo groups reflected no or mild impairment in 70%, 67%, 57%, and 50% of patients, respectively (P<.05 for the 10- or 20-mg drug group vs placebo group, and for the 20-mg vs 5- mg drug group). Similar efficacy rates were observed for nausea, photophobia, and phonophobia. For all parameters, individual-attack efficacy rates did not differ from across-attack rates. The incidence of adverse events was not dose related. The most frequently reported adverse event in the active treatment groups was taste disturbance (bad, bitter, or unpleasant).\n Sumatriptan hemisulfate nasal spray (5, 10, or 20 mg) is effective and well tolerated in the treatment of multiple migraine attacks. The 20-mg dose was associated with the highest efficacy rates across the greatest number of parameters." ]

[ "10235419", "15033894", "9882082", "11697757", "8799525", "10805057", "11301569", "6392354", "9549654", "3072354", "8222498" ]

[ "Analgesic efficacy of liquid ketoprofen compared to liquid dipyrone and placebo administered orally as drops in postepisiotomy pain.", "Double-blind, randomized, placebo-controlled trial comparing rofecoxib with dexketoprofen trometamol in surgical dentistry.", "Clinical comparison of dexketoprofen trometamol, ketoprofen, and placebo in postoperative dental pain.", "Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain.", "The efficacy of ketoprofen and paracetamol (acetaminophen) in postoperative pain after third molar surgery.", "The efficacy of buffered ketoprofen in postoperative pain after third molar surgery.", "Onset and duration of analgesia for low-dose ketoprofen in the treatment of postoperative dental pain.", "Double-blind parallel comparison of single oral doses of ketoprofen, codeine, and placebo in patients with moderate to severe dental pain.", "Analgesic efficacy and safety of (R)- ketoprofen in postoperative dental pain.", "Double-blind parallel comparison of ketoprofen (Orudis), acetaminophen plus codeine, and placebo in postoperative pain.", "Ketoprofen, acetaminophen plus oxycodone, and acetaminophen in the relief of postoperative pain." ]

[ "The objective of this single-center, single-dose, double-blind randomized parallel group study was to evaluate the analgesic efficacy of a new liquid formulation of ketoprofen at two dose levels (25 mg or 50 mg) compared to a commercially available liquid form of dipyrone 500 mg and placebo with all treatments administered as drops to patients with severe postepisiotomy pain.\n The study was designed with a sample size of 69 patients per treatment for a total of 276 patients. However, due to administrative changes at the site, the study was prematurely terminated; thus only 108 patients (26 to 28 patients per treatment), 18 years or older, with severe postepisiotomy pain were randomized to one of the four treatments. Treatments were assessed over a 6-hour period using standard scales for pain intensity and pain relief and a number of derived variables based on these data. Since the study medications were not identical in appearance, the preparation and administration of the study medication, and the observation of the patient, were carried out by two different individuals to maintain double-blind conditions.\n All active treatments were significantly superior to placebo for several measures of analgesia including 4-hour and 6-hour SPID and TOTPAR scores. The global rating was assessed as \"good\" or \"excellent\" by over 75% of the patients in the active treatment groups compared to 7.4% of the patients in the placebo group. Reduction in pain intensity was very similar for the two-dose levels of ketoprofen and the comparator dipyrone 500 mg.\n Ketoprofen 25 mg or 50 mg, and dipyrone 500 mg seem to be equally suited for use as pain relief medication after minor surgery, as well as episiotomy. This study did not demonstrate a need for more than 25 mg of ketoprofen in postepisiotomy pain. All treatments were well tolerated. No adverse events were reported.", "Rofecoxib, a selective cyclooxygenase-2 inhibitor, and dexketoprofen trometamol, a single isomer non-steroidal anti-inflammatory drug (NSAID), are available for the treatment of acute pain. Both are claimed to have fewer adverse effects than traditional NSAIDs. We have compared them in a clinical setting.\n We performed a double-blind randomized controlled trial involving 120 patients undergoing surgical removal of a single mandibular third molar at the Edinburgh Dental Institute. Those who developed moderate pain within 4 h of the procedure were allocated to one of three groups: rofecoxib 50 mg (Group RO, n=37); dexketoprofen trometamol 25 mg (Group DE, n=42); or placebo (Group PL, n=41). Participants monitored pain intensity and pain relief for 24 h using visual analogue scales (VAS) and verbal rating scales (VRS). The summed, time-weighted pain relief score to 8 h derived from the VRS (TOTPAR 8) was used as the primary outcome variable.\n No significant difference was demonstrated between Groups RO and DE using TOTPAR 8 as the primary outcome variable. Both drugs were significantly different compared with placebo. Rescue analgesia during the trial period was required by only 15 out of 37 subjects in Group RO, but 35 out of 42 subjects in Group DE. The median times to use of rescue medication were 150 (Group PL), 398 (Group DE) and 1440 min (Group RO). Both drugs were well tolerated and adverse events reported were mild to moderate in severity.\n Rofecoxib and dexketoprofen trometamol are effective treatments for acute pain using a dental pain model and are well tolerated. Rofecoxib has a longer duration of action as a single dose and gave adequate analgesia for over half of that study group; patients in the dexketoprofen trometamol group needed more rescue analgesia.", "The efficacy and tolerability of single doses of dexketoprofen trometamol 12.5 mg, 25 mg, and 50 mg and ketoprofen 50 mg were compared in this double-blind, randomized, placebo-controlled study of 210 patients with moderate to severe pain after removal of one mandibular impacted third molar tooth. Pain intensity and pain relief were monitored for 6 h after administration of medication using visual analogue and verbal rating scales. All four active treatments were significantly more effective than placebo (P < 0.001). Dexketoprofen 25 mg and 50 mg produced an analgesic effect within 30 min of administration and their effect persisted for 6 h. Ketoprofen 50 mg produced a level of analgesia similar to those of the higher doses of dexketoprofen trometamol, but it had a slower onset. The 12.5-mg dose of dexketoprofen trometamol was significantly superior to placebo but produced a lower level and shorter duration of analgesia compared to the other active treatments. There were no significant differences between 25 and 50 mg of dexketoprofen trometamol in any measure of analgesic efficacy. No serious adverse events were observed and there were no significant differences in the incidence of adverse events among treatment groups. These results demonstrate that dexketoprofen trometamol 25 mg is at least as effective as the racemic ketoprofen 50 mg in the treatment of postsurgical dental pain. The more rapid onset of action compared to ketoprofen suggests that dexketoprofen trometamol is more appropriate for treatment of acute pain.", "Ibuprofen is a peripherally acting nonsteroidal anti-inflammatory drug indicated fo ranalgesia, antipyresis, and various arthritic conditions. A solubilized 200 mg liquigel formulation of ibuprofen has been shown to have a more rapid rate of absorption compared with ibuprofen 200 mg tablets. Ibuprofen liquigels have a kinetic profile similar to ibuprofen suspension, with both a higher Cmax and an earlier tmax than any solid tablet. The objective of this single-dose, double-blind, triple-dummy, parallel-group study was to assess the time to onset of relief and overall analgesic efficacy of liquigel ibuprofen 400 mg, ketoprofen 25 mg compared with acetaminophen 1000 mg, and placebo in 239 patients with moderate or severe pain following third molar extractions. Treatments were compared over 6 hours using standard scales for pain intensity and relief and stopwatch onset of meaningful relief. All active treatments provided meaningful relief significantly faster compared with placebo. Ibuprofen provided significantly faster relief compared with acetaminophen and ketoprofen. By the end of the study (6 h), onset of meaningful relief was achieved by 36%, 99%, 96%, and 88% of the patients in the placebo, ketoprofen, ibuprofen, and acetaminophen groups, respectively. The median times to onset of relief were > 6 hours for placebo, 25.5 minutes for ketoprofen, 24.2 minutes for ibuprofen, and 29.9 minutes for acetaminophen. In addition, both ibuprofen and ketoprofen showed statistical superiority over acetaminophen at earlier time points on the time-effect curves for pain relief and pain intensity difference. Consistent results were seen with respect to the 6-hour summary efficacy variables: the three active treatments were significantly better than placebo, and ibuprofen was significantly better than both acetaminophen and ketoprofen. Liquigel ibuprofen 400 mg was shown to provide faster relief and superior overall efficacy compared with ketoprofen 25 mg, acetaminophen 1000 mg, and placebo. No serious adverse effects were reported in this single-dose study.", "1. A placebo-controlled, double-blind, randomized trial was carried out to evaluate the efficacy of single doses of racemic ketoprofen 12.5 and 25 mg and paracetamol 500 and 1000 mg in patients with post-operative pain after third molar surgery over a 6 h investigation period. 2. Outcome variables included overall pain scores (AUC(0,360 min), maximum pain relief, pain relief at 1 h after dosage and the number of patients taking escape analgesics. 3. Overall pain scores (AUC(0,360 min) were significantly lower for all active treatments when compared to placebo (P < 0.01). 4. Both ketoprofen treatments and patients treated with paracetamol 1000 mg reported significantly greater pain relief (P < 0.01) and a later time to taking escape analgesics (P < 0.01) than patients medicated with placebo. 5. At 1 h after dosage, pain scores were significantly less (P < 0.01) after both doses of ketoprofen when compared with placebo. 6. Single doses of ketoprofen 12.5 and 25 mg, together with paracetamol 1000 mg are effective analgesics for treating post-operative pain after third molar surgery. These treatments provide up to 4 h of pain relief after this surgical procedure.", "To evaluate in a randomised, double-blind, placebo-controlled trial, the efficacy (time to onset of meaningful pain relief) of single doses of buffered ketoprofen (12.5 mg) and ibuprofen (200 mg) in 180 patients with postoperative pain after third molar surgery.\n 180 adult patients who had undergone third molar surgery under general anaesthesia participated in this study. After dosing, patients recorded their time to meaningful pain relief, pain intensity on both visual analogue scales and verbal rating scales, pain relief and the need for additional analgesia. Pain recordings were made at fixed time points over a 6-h investigation period.\n Buffered ketoprofen (12.5 mg) provided quicker meaningful pain relief than placebo (P = 0.023). For secondary efficacy measures (SPIDS4, SPIDS6, TOTPAR4, TOTPAR6), the buffered ketoprofen was significantly superior to both placebo (P < 0.001) and ibuprofen (200 mg) (P < 0.05). Similarly, the amount of time before taking an escape analgesic was significantly less in the placebo group than both the ibuprofen and buffered ketoprofen groups (P < 0.03).\n Buffered ketoprofen (12.5 mg) provides effective pain control in the early postoperative period after third molar surgery. This ketoprofen preparation was also superior to ibuprofen (200 mg) with respect to both reducing pain intensity and providing an earlier onset of pain relief.", "The objective of this single dose, double-blind study was to determine the relative analgesic efficacy of low-dose ketoprofen (6.25 mg, 12.5 mg, and 25 mg) compared with ibuprofen (200 mg) and placebo in 175 patients with moderate to severe postoperative pain secondary to extraction of impacted third molars. Analgesia was measured during the 6-hour period after administration based on onset of relief, hourly and summary variables, and duration of treatment effect. All active treatments were significantly more effective than placebo for many hourly measures and for the summary measures sum of pain intensity differences (SPID), sum of hourly pain relief values (TOTPAR), time to peak pain relief, and patient global assessment of study medication. The three ketoprofen doses were significantly more effective than placebo beginning at 30 minutes, whereas ibuprofen was significantly better than placebo beginning at 1 hour. A dose-response relationship was observed for ketoprofen, with the two higher doses providing significantly greater analgesia than the lower dose. However, a plateau effect was seen between the 12.5-mg and 25-mg dose levels. A significantly greater proportion of patients treated with each of the active treatments (ranging from 0.83 to 0.88) reported onset of relief compared with placebo (0.20). The distribution functions of onset of relief differed significantly among treatments, with ketoprofen 12.5 mg and 25 mg having a faster onset than ibuprofen 200 mg and ketoprofen 6.25 mg. The duration of effect was generally shorter for ketoprofen than for ibuprofen, and these difference were significant. This study provides evidence that at the dose levels of 12.5 mg and 25 mg, ketoprofen is an effective analgesic in providing relief of postoperative dental pain. Ketoprofen 12.5 mg and 25 mg provide significantly greater relief in the earlier time period, with a faster onset and shorter duration of effect than ibuprofen 200 mg. The two higher doses of ketoprofen provided similar analgesia, and no additional benefit was obtained by increasing the dose of ketoprofen to 25 mg. Therefore, we conclude that ketoprofen 12.5 mg is an appropriate dose for over-the-counter use.", "Ketoprofen, 25, 50, and 100 mg, was compared with 90 mg codeine and placebo for relief of pain due to removal of impacted third molar teeth. Treatment was self-administered as a single oral dose under double-blind conditions in five parallel groups established by a random code in healthy young adults. Based on 129 patient evaluations of pain experience and pain relief, ketoprofen was shown to have a more rapid onset and longer duration of action than codeine. In the derived variables of SPID (Sum of Pain Intensity Differences) and TOPAR (Total Pain Relief), all three doses of ketoprofen, with no dose-related differences among them, were found to provide statistically superior analgesia to codeine and placebo. All five treatments were associated with some adverse reactions.", "This double-blind, randomized, parallel-group study compared the analgesic efficacy and safety of single doses of (R)- ketoprofen 25 mg and 100 mg to that of acetaminophen 1,000 mg and placebo in 177 patients experiencing moderate to severe pain after surgical removal of their impacted third molars. Both (R)- ketoprofen 100 mg and acetaminophen 1,000 mg were significantly (P < 0.05) more efficacious than placebo for all summary analgesic measures. Other than a more rapid analgesic onset (45 minutes versus 60 minutes) for acetaminophen 1,000 mg, (R)- ketoprofen 100 mg and acetaminophen 1,000 mg were statistically equivalent to each other. The 25 mg dose of (R)- ketoprofen appeared to approach the analgesic threshold dose, being numerically but not statistically superior to placebo for all summary measures. There were no serious adverse events observed in this study, with the overall incidence of side effects being somewhat less in the (R)- ketoprofen groups than in the acetaminophen 1,000 mg group. (R)- Ketoprofen possesses analgesic activity and an acceptable side-effect profile in the oral surgery pain model.", "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.", "Ketoprofen (Orudis) is a nonsteroidal anti-inflammatory drug that is currently approved in the United States for the management of mild to moderate pain. The objective of this trial was to determine the effectiveness of orally administered ketoprofen in the management of severe postoperative pain. This randomized, double-blind parallel study compared the efficacy and safety of single doses of 100 mg or 50 mg ketoprofen, the combination of 650 mg acetaminophen plus 10 mg oxycodone hydrochloride, 650 mg acetaminophen, or placebo in 240 patients with severe postoperative pain after cesarean section. Analgesia for the first dose was assessed over an 8-hour period. Multiple doses of 100 mg or 50 mg ketoprofen and the combination at half the dose (325 mg acetaminophen plus 5 mg oxycodone) were also assessed for up to 7 days. The 100 and 50 mg doses of ketoprofen and the combination were statistically superior to acetaminophen and placebo for many analgesic measures. A dose response was observed between the two doses of ketoprofen, with the 100 mg dose providing significantly greater analgesia over the lower dose. Ketoprofen, 100 mg, was at least as effective as the combination and its effects lasted longer, with the exception of hour 1 when the combination was superior. Remedication time for the group receiving 100 mg ketoprofen was significantly longer than for the other treatment groups. Significantly more patients who took repeated doses of the combination (84%) than those who took either dose of ketoprofen (70%) had adverse effects. Ketoprofen at both dose levels was shown to be effective, long-lasting, and well tolerated, and it should be considered as a viable option for the management of moderate to severe postoperative pain." ]

[ "21093066", "11843924", "1889950", "19393409", "15142073" ]

[ "Prospective double blind randomized clinical trial comparing 75% versus 95% silver nitrate cauterization in the management of idiopathic childhood epistaxis.", "A prospective, single-blind, randomized controlled trial of antiseptic cream for recurrent epistaxis in childhood.", "Management of epistaxis in children.", "A double-blind randomized controlled trial of management of recurrent nosebleeds in children.", "A prospective, single-blind, randomized controlled trial of petroleum jelly/Vaseline for recurrent paediatric epistaxis." ]

[ "Primary outcome measure: to evaluate which concentration of silver nitrate cauterization was more efficacious in the management of idiopathic childhood epistaxis. Secondary outcome measures: to evaluate side effects and pain scores of the differing concentrations.\n Prospective double blind randomized clinical trial.\n All children 16 years of age or younger referred by the accident and emergency department or general practitioner, with recurrent idiopathic epistaxis, who met the inclusion criteria entered the trial. Patients were randomized to receive either the 75% or 95% silver nitrate cauterization. Patients were reviewed at two weeks and eight weeks post cauterization. Pain scores, side effects and success of each treatments were recorded at the follow up clinic.\n 101 patients completed the trial. 52 patients were randomized to receive the 95% concentration, and 49 patients were randomized to receive the 75% cauterization. In the 75% concentration group, 98% of patients had total resolution of their symptoms at the eight-week follow up. Mean pain scores in this group was 1 out of 10. In the 95% group, 90% had total resolution of their symptoms at the eight-week follow up. Mean pain scores in this group was 5 out of 10. There was a statistical difference in efficacy and pain scores (0.01 and 0.001).\n We would recommend the use of 75% silver nitrate cauterization in the management of childhood epistaxis, it appears to be more efficacious, has fewer side effects and is better tolerated.\n Copyright © 2010. Published by Elsevier Ireland Ltd.", "Epistaxis is common in children. Trials show antiseptic cream is as effective as cautery, but it is not known whether either is better than no treatment. We wished to know the efficacy of cream in children with recurrent epistaxis. The design was a single-blind, prospective, randomized controlled trial set in the Otolaryngology clinic in a children's hospital. The participants were 103 children referred by their general practitioner for recurrent epistaxis. Excluded were those with suspected tumours, bleeding disorders or allergies to constituents of the cream. Referral letters were randomized to treatment and no treatment groups. Treatment was antiseptic cream to the nose twice daily for 4 weeks, which was prescribed by the general practitioner before clinic attendance. All children were given an appointment for 8 weeks after randomization. The main outcome measures were the proportion of children in each group with no epistaxis in the 4 weeks preceding clinic review. Complete data were available for 88 (85%) of the children. Of the treatment group, 26/47 (55%) had no epistaxis in the 4 weeks before the clinic appointment. Of the controls, 12/41 (29%) had no epistaxis over the 4 weeks. This is a relative risk reduction of 47% for persistent bleeding (95% CI 9-69%) and an absolute risk reduction of 26% (95% CI 12-40%), giving a number needed to treat of 3.8 (95% CI 2.5-8.5). We conclude that antiseptic cream is an effective treatment for recurrent epistaxis in children.", "A randomised clinical trial of antiseptic nasal carrier cream (Naseptin) and silver nitrate cautery in the treatment of epistaxis in children was carried out. Fifty-four percent responded to cautery with silver nitrate and 50% to treatment with Naseptin antiseptic carrier cream. There were 24 patients in each group. No statistically significant difference was observed between the groups when tested with the chi 2 test. We believe that the first line treatment of epistaxis in children should be the use of antiseptic nasal cream.", "To establish whether a treatment regimen of silver nitrate cautery and 4 weeks of antiseptic nasal cream is superior to antiseptic cream treatment alone in the management of pediatric epistaxis.\n Double-blind randomized controlled trial.\n Children with epistaxis and visible anterior septal vessels were invited to participate. Patients were randomized to receive treatment or control. Treatment patients received silver nitrate cautery, followed by antiseptic cream for 4 weeks. Control patients received sham cautery followed by antiseptic cream for 4 weeks.\n A total of 109 patients were randomized and results were available for 93 (85%). Of those receiving cautery, 21 (45.7%) of 46 had no bleeding in the 4 weeks before follow-up. Of those receiving only antiseptic cream 14 (29.8%) of 47 had no bleeding. (chi(2) = 2.49; P = 0.114). More children in the active treatment group had an improvement in their symptoms compared with controls (42 of 46; 91.3%) in the treatment group vs 33 of 47 (70.2%) controls (chi(2) = 6.626; P = 0.01; relative risk reduction = 71 percent, number needed to treat = 4.7).\n When using subjective improvement in symptoms as the outcome measure, silver nitrate cautery with antiseptic cream twice daily for 4 weeks appears to give a small but statistically significant benefit when compared to antiseptic cream alone.", "The aim of the study was to determine if petroleum jelly was an effective treatment for paediatric epistaxis. A single-blind, prospective, randomized controlled trial was undertaken in an otolaryngology outpatient clinic of a paediatric hospital from March 2001 to March 2002. A total of 105 children referred with recurrent epistaxis were randomized into the study, 52 into the treatment arm and 53 into the control arm. Children in the treatment arm applied Vaseline twice a day bilaterally for 4 weeks and were monitored for any bleeds for the next 4 weeks. Children in the control arm were simply given an 8-week appointment and the number of bleeds were monitored for the 4 weeks prior to their appointment. The outcome measure was the proportion of children in each group without nosebleeds in the preceding 4 weeks. Both groups were equally distributed in age, duration of symptoms and duration of each bleed. Fourteen of 51 (27.5%) patients of the treatment arm and 18 of 53 (34%) of the control arm did not bleed in the 4 weeks before review (chi-square test, P = 0.472). It can be concluded that Vaseline alone confers no benefit over simple observation in recurrent childhood epistaxis." ]

[ "14581707", "9325826" ]

[ "Evaluation of two calcium alginate dressings in the management of venous ulcers.", "Use of a fibrous dressing in exuding leg ulcers." ]

[ "Calcium alginate dressings facilitate the management of highly exudating wounds such as venous ulcers. To evaluate and compare the performance of two calcium alginate dressings in the management of venous ulcers, a prospective, randomized, controlled clinical study was conducted among 19 outpatients at two wound clinics in California. Ten patients (53%) were treated with Alginate A and nine patients (47%) with Alginate B. Dressings were changed weekly and patients were followed for a maximum of 6 weeks or until the venous ulcer no longer required the use of an alginate dressing. At each dressing change, the wound was assessed and dressing performance evaluated. Absorbency of exudate, patient comfort during wear, ease of removal, adherence to wound bed, dressing residue following initial irrigation, patient comfort during removal, ease of application, and conformability were assessed. Patients using Alginate A experienced significantly less foul odor (P = 0.02) and less denuded skin (P = 0.04) than Alginate B at follow-up wound assessments. With the exception of conformability, Alginate A was rated significantly better than Alginate B (P less than or equal to 0.05) in all dressing performance assessments. No significant healing differences were observed. As the different performance characteristics of various calcium alginate dressings become more obvious in clinical practice, further study is warranted to determine their optimal effectiveness.", "In a multicentre, prospective, randomised trial of 44 patients with exuding leg ulcers, a new hydrofibre dressing was compared with an alginate dressing in terms of dressing performance, patient comfort, safety and cost-effectiveness. The groups were well matched with regard to sex and age. A statistically significant difference between treatment groups was observed in mean wear time, with a longer wear time of four days observed in the hydrofibre dressing group compared to three days in the alginate group. The hydrofibre dressing group therefore demonstrated a significantly lower frequency of dressing changes required per week. Significantly more patients achieved a seven-day wear time with the hydrofibre dressing than with the alginate dressing. There was no difference with regard to percentage change in ulcer area. Cost-effectiveness was based on the cost of dressings, compression therapy and nursing time to achieve a healed wound. However, because of small patient numbers, it was difficult to make an accurate comparison. This study suggests that the hydrofibre dressing may have clinical benefits that merit further investigation with larger patient numbers." ]

[ "9624473", "8838183", "1727093" ]

[ "Randomized trial of trimethoprim-sulfamethoxazole versus pyrimethamine-sulfadiazine for therapy of toxoplasmic encephalitis in patients with AIDS. Italian Collaborative Study Group.", "Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS.", "Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. The California Collaborative Treatment Group." ]

[ "The aim of the present pilot study was to compare the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis in patients with AIDS. This was a pilot, multicenter, randomized, and prospective study. Patients were randomly assigned to receive TMP (10 mg/kg of body weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half of the original dosage. Seventy-seven patients were enrolled and randomized to the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S. There was no statistically significant difference in clinical efficacy during acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely to achieve a complete radiologic response after acute therapy. Adverse reactions were significantly more frequent in patients treated with P-S, and skin rash was the most common adverse event noted in these patients. In conclusion, the results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.", "This European multicenter study compares the efficacy and tolerance of the combination of pyrimethamine-clindamycin (Pyr-Cm) with the standard therapy pyrimethamine-sulfadiazine (Pyr-Sdz) for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS. Two hundred ninety-nine human immunodeficiency virus-infected patients with TE were randomly assigned to receive 50 mg of pyrimethamine daily combined with either 2,400 mg of clindamycin or 4 g of sulfadiazine for 6 weeks followed by maintenance therapy with 25 mg of pyrimethamine daily with either 1,200 mg of clindamycin or 2 g of sulfadiazine. An intent-to-treat analysis showed that Pyr-Cm was less effective than Pyr-Sdz; the overall risk of progression of TE was 1.84 times higher for patients receiving Pyr-Cm therapy. There was no statistically significant difference in efficacy during acute therapy, although the rate of crossover motivated by a lack of response was higher among Pyr-Cm recipients. The difference in efficacy was evidenced during the maintenance phase of treatment; the relapse rate was twice as high among patients in the Pyr-Cm group (P = .02). The rate of side effects due to both regimens was similar, although the toxic effects of Pyr-Cm led to fewer discontinuations of therapy than did those of Pyr-Sdz (11% vs. 30%, respectively; P = .001). Pyr-Sdz appears to be the most effective treatment of TE. Pyr-Cm is a valuable alternative but is less effective for long-term prevention of relapses.", "To compare pyrimethamine plus clindamycin (PC) to pyrimethamine plus sulfadiazine (PS) as a treatment for toxoplasmic encephalitis (TE) in patients with the acquired immunodeficiency syndrome (AIDS).\n Randomized, unblinded phase II, multicenter trial with provision for crossover for failure or intolerance of the assigned regimen.\n University hospitals.\n Eighty-four patients with presumptive TE were entered. Thirteen were excluded when they were found to have another diagnosis, and 12 were excluded because they did not meet entry criteria. The baseline characteristics in the remaining 26 patients randomized to PC and 33 randomized to PS were comparable.\n Patients were treated for 6 weeks with pyrimethamine and folinic acid plus either sulfadiazine or clindamycin. Clindamycin was given intravenously during the first 3 weeks.\n There was a trend toward greater survival in patients randomized to PS (hazard ratio, 3.25; 95% CI, 0.63 to 16.8; P = 0.13), but most study deaths were not directly related to TE. In contrast, patients randomized to PC appeared more likely to achieve complete clinical (odds ratio, 0.67; CI, 0.2 to 1.97; P greater than 0.2) and radiologic responses (odds ratio, 0.28; CI, 0.08 to 0.96; P = 0.02). Multivariate analysis revealed drug effects to be largely independent of other variables. Similar efficacy of the treatments was also suggested by a hazard analysis of resolution of abnormal mental status, fever, and headache. Skin rash was the most common adverse event in both treatment arms. Because of toxicity, six patients randomized to PC and 11 patients randomized to PS had to switch to the alternate treatment, but only three were unable to complete therapy after crossover.\n The results of several end points of efficacy, taken together, suggest that the relative efficacy of PC approximately equals that of PS. PC appears to be an acceptable alternative in patients unable to tolerate PS." ]

[ "2148702", "15184205", "11926622" ]

[ "Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice.", "Peak flow monitoring for guided self-management in childhood asthma: a randomized controlled trial.", "Symptom monitoring in childhood asthma: a randomized clinical trial comparing peak expiratory flow rate with symptom monitoring." ]

[ "To compare a peak flow self management plan for asthma with a symptoms only plan.\n Randomisation to one of the self management plans and follow up for a year.\n Four partner, rural training practice in Norfolk.\n 115 Patients (46 children and 69 adults) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic.\n The number of doctor consultations, courses of oral steroids, and short term nebulised salbutamol treatments and the number of patients who required doctor consultations, courses of oral steroids, and short term nebulised salbutamol.\n Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups. The results were similar for children and adults. The proportions of patients requiring a doctor consultation fell from 98% (50/51) to 66% (34/51) in the peak flow group and from 97% (62/64) to 53% (34/64) in the symptoms only group and the proportions requiring oral steroids from 73% (34/46) to 47% (21/46) and 52% (31/60) to 12% (7/60). The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group.\n The peak flow meter was not the crucial ingredient in the improved illness of the two groups. Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma. Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care.", "We asked whether the addition of PEF recordings to a symptom-based self-management plan improved outcome in school children with asthma. In an open-randomized, parallel-group, controlled trial, we studied children aged 7-14 years with moderate asthma. After a 4-week run-in, 90 children were randomized to receive either PEF plus symptom-based management or symptom-based management alone for 12 weeks. Thresholds for action based on PEF were 70% of best (for increasing inhaled steroids) and 50% of best (for commencing prednisolone). Children were asked to perform twice-daily spirometry at home (using an electronic recording spirometer that revealed only PEF to the study group alone) and to record a symptom diary. The mean daily symptom score was the main outcome. There were no differences between groups in mean symptom score or in spirometric lung function, PEF, quality of life score, or reported use of health services over 12 weeks. During acute episodes, children responded to changes in symptoms by increasing their inhaled steroids at a mean value of PEF of greater than 70% of best so that overall PEF did not contribute to this important self-management decision. Knowledge of PEF did not enhance self-management even during acute exacerbations.", "Accurate symptom evaluation is a critical component of asthma management. Limited data are available about the accuracy of symptom evaluation by children with asthma and their parents, or the impact of various symptom-monitoring strategies on asthma morbidity outcomes.\n The purpose of this randomized clinical trial was to evaluate the effect of three different intensities of symptom monitoring on asthma morbidity outcomes.\n One hundred sixty-eight children (ages 6 to 19) of diverse racial, geographic, and socioeconomic backgrounds were randomized to 1 of 3 treatment groups (subjective symptom evaluation, symptom-time peak expiratory flow rate (PEFR) monitoring, daily PEFR monitoring) in this longitudinal, clinical trial. Outcome measures included a summary asthma severity score, forced expiratory volume in 1 second, symptom days, and health care utilization.\n Children who used PEFR meters (PFMs) when symptomatic had a lower asthma severity score, fewer symptom days, and less health care utilization than children in the other two treatment groups. Minority and poor children had the greatest amount of improvement using PFMs when symptomatic. Results were much less striking in white families. Thirty percent of families in the PFM treatment groups discontinued use entirely by 1 year postexit, whereas the majority of families who continued use (94%) used them only when symptomatic to inform symptom interpretation and management decisions.\n Not every child with asthma needs a PFM. Children and families facing extra challenges as a result of illness severity, sociodemographic, or health care system characteristics clearly benefited most from PFM use." ]

[ "10325913", "8155929", "8640047", "11488316", "9894371", "10821721", "10926339", "7822661", "8630596", "8627205", "10983616", "1978947", "11739137", "10390389", "9864004", "12475833", "8323451", "10678614", "9564798", "9655717", "11897984", "9576141", "8707781" ]

[ "Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma.", "Systemic activity of inhaled topical steroid in toddlers studied by knemometry.", "Nebulized budesonide for the treatment of moderate to severe asthma in infants and toddlers.", "High or standard initial dose of budesonide to control mild-to-moderate asthma?", "Initial loading (400 micrograms twice daily) versus static (400 micrograms nocte) dose budesonide for asthma management. PLAN Research Group.", "Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma.", "Comparison of high and low dose of the inhaled steroid, budesonide, as an initial treatment in newly detected asthma.", "Budesonide treatment of moderate and severe asthma in children: a dose-response study.", "Eosinophil and neutrophil activity in asthma in a one-year trial with inhaled budesonide. The impact of smoking.", "Fluticasone propionate aerosol: efficacy in patients with mild to moderate asthma. Fluticasone Propionate Asthma Study Group.", "Effectiveness of low doses (50 and 100 microg b.i.d) of beclomethasone dipropionate delivered as a CFC-free extrafine aerosol in adults with mild to moderate asthma. Study Group.", "Use of inhaled corticosteroids in patients with mild asthma.", "One-year treatment with different dosing schedules of fluticasone propionate in childhood asthma. Effects on hyperresponsiveness, lung function, and height.", "The effect of inhaled fluticasone propionate in the treatment of young asthmatic children: a dose comparison study.", "Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids.", "Efficacy and safety of beclomethasone dipropionate extrafine aerosol in childhood asthma: a 12-week, randomized, double-blind, placebo-controlled study.", "[Effects of high doses of beclomethasone dipropionate in bronchial asthma].", "Low- and high-dose fluticasone propionate in asthma; effects during and after treatment.", "Rapid induction of clinical response with a short-term high-dose starting schedule of budesonide nebulizing suspension in young children with recurrent wheezing episodes.", "Starting with a higher dose of inhaled corticosteroids in primary care asthma treatment.", "Significant variability in response to inhaled corticosteroids for persistent asthma.", "Dose-related response to inhaled fluticasone propionate in patients with methacholine-induced bronchial hyperresponsiveness: a double-blind, placebo-controlled study.", "A 12-week dose-ranging study of fluticasone propionate powder in the treatment of asthma." ]

[ "It is desirable to prescribe the minimal effective dose of inhaled steroids to control asthma. To ensure that inflammation is suppressed whilst using the lowest possible dose, a sensitive and specific method for assessing airway inflammation is needed.\n The usefulness of exhaled nitric oxide (NO), sputum eosinophils, and methacholine airway responsiveness (PC20) for monitoring airway inflammatory changes following four weeks of treatment with an inhaled corticosteroid (budesonide via Turbohaler) were compared. Mild stable steroid naive asthmatic subjects were randomised into two double blind, placebo controlled studies. The first was a parallel group study involving three groups receiving either 100 micrograms/day budesonide (n = 8), 400 micrograms/day budesonide (n = 7), or a matched placebo (n = 6). The second was a crossover study involving 10 subjects randomised to receive 1600 micrograms budesonide or placebo. The groups were matched with respect to age, PC20, baseline FEV1 (% predicted), exhaled NO, and sputum eosinophilia.\n There were significant improvements in FEV1 following 400 micrograms and 1600 micrograms budesonide (11.3% and 6.5%, respectively, p < 0.05). This was accompanied by significant reductions in eosinophil numbers in induced sputum (0.7 and 0.9 fold, p < 0.05). However, levels of exhaled NO were reduced following each budesonide dose while PC20 was improved only with 1600 micrograms budesonide. These results suggest that exhaled NO and PC20 may not reflect the control of airway inflammation as accurately as the number of eosinophils in sputum. There were dose dependent changes in exhaled NO, sputum eosinophils, and PC20 to inhaled budesonide but a plateau response of exhaled NO was found at a dose of 400 micrograms daily.\n Monitoring the number of eosinophils in induced sputum may be the most accurate guide to establish the minimum dose of inhaled steroids needed to control inflammation. This, however, requires further studies involving a larger number of patients.", "The short-term linear growth rate of the lower leg in toddlers was measured and evaluated in order to study the possible effect of inhaled budesonide on this factor in toddlers with mild recurrent wheezing. The short-term linear growth rate of the lower leg was measured weekly using a hand-held knemometer. Eighteen toddlers aged 13-36 months (mean 27 months) with a history of recurrent wheezing requiring inhaled topical steroids, but without need of regular medication during the months prior to the study, were studied. The children were randomized blindly through three consecutive treatment periods of four weeks with placebo or budesonide in daily doses of 200 micrograms and 800 micrograms administered as a pressurized aerosol inhaled via a spacer with a face mask. Twenty-nine percent (median) of the nominal dose was delivered at the mouth of the children. Three children were withdrawn because of exacerbations and one because of non-compliance. The precision of the measurement procedure was 51 microns/day. The mean growth rate during placebo, low-dose and high-dose steroid treatment was 92 microns/day, 114 microns/day and 46 microns/day respectively. The growth rate during the high-dose treatment was suppressed significantly compared to placebo treatment (95% CI -76 microns/day to -17 microns/day), whereas the growth rate during low-dose steroid treatment was indistinguishable from placebo treatment (95% CI -7 to +52 microns/day). In conclusion, measurement of short-term linear growth rate by knemometry in toddlers is a fast and gentle method with a high level of precision.(ABSTRACT TRUNCATED AT 250 WORDS)", "Maintenance treatment with nebulized budesonide was studied in young children with asthma not controlled without steroids. In a blind parallel-group study for 18 weeks, 102 children, mean age 22 (5- 47) months, were randomized for treatment starting with 0.25 or 1 mg b.i.d. The patients were reviewed every 3 weeks, and if symptom control had been achieved the dose was reduced, otherwise it was kept. The clinical effect was very good with both dose regimens. The median time to 7 consecutive days without any asthma symptoms was about 1 month with both, highlighting the importance of the duration of therapy rather than the benefits of a high starting dose. In 18 of 24 children who attained the placebo stage, symptoms had reappeared at the last visit. Although an overall minimal effective maintenance dose could not be demonstrated, 47% achieved symptom control on 0.25 mg b.i.d., i.e. fulfilled criteria for further dose reduction. No significant side effects were seen. On average, 25% of the nominal dose reached the patients.", "Guidelines on the use of inhaled steroids in asthma advocate that the daily dose should be chosen according to the severity of the disease. However, the question of the optimal starting dose remains to be properly addressed, as does the issue of the adjustment in dose required for a given patient. Whether a high initial dose of budesonide (800 microg b.i.d) was more efficacious than a standard dose (200 microg b.i.d) in controlling mild-to-moderate asthma was investigated, and whether the dose could be decreased, based on peak expiratory flow (PEF), symptom-score, beta2-agonist use in a double-blind, randomized, parallel-group 18-week study. One-hundred and sixty-nine patients (mean age 38 yrs, mean forced expiratory volume in one second 74% predicted) were enrolled. No difference was detected between the two groups in improvement in morning PEF (+61 L x min(-1) in the high-dose group, +60 L x min(-1) in the standard-dose group by 16 weeks). Morning and evening PEF values stabilized before the end of the first 4 weeks. No difference between groups was observed in symptom score, beta2-agonist use, number of exacerbation per interval and the best forced expiratory volume in one second achieved. The proportion of subjects being able to decrease the doses of budesonide was similar in both treatment strategies. It is concluded that both high and standard initial doses are equally effective in controlling symptoms and improving lung function in mild-to-moderate asthma.", "This double-blind study aimed to determine whether superior asthma control is achieved with budesonide (Pulmicort Turbohaler) at a loading dose (LD) (400 micrograms b.d.) for 6 weeks, followed by step down to 400 micrograms nocte for 12 weeks, compared with a static dose (SD) (400 micrograms nocte) for 18 weeks. A total of 682 patients (mean peak expiratory flow rate (PEFR) 413 l/min), who demonstrated > or = 15% reversibility in PEFR, were randomised into the study. After 18 weeks, patients experienced improvements in morning PEFR (+45 l/min, both groups), symptom score (LD -0.57, SD -0.49, on a scale of 0-3), sleep disturbance (LD -1.21 nights/week, SD -1.06 nights/week) and beta 2-agonist use (LD -1.36 puffs/day, SD -1.06 puffs/day), within both groups (each p = 0.0001). At 18 weeks, 82% (LD) and 84% (SD) of patients benefited from no nocturnal wakening in the previous 7 days. Overall, at 18 weeks, asthma control was not significantly different between the groups. After 6 weeks, improvements in morning PEFR (LD +36 l/min, SD +26 l/min) and beta 2-agonist use (LD -1.10 puffs/day, SD -0.94 puffs/day) were greater in the loading dose than in the static dose group (each p < 0.05). The greater improvement in morning PEFR in the loading dose group was significant by day 7 (p < 0.05). While both regimens are equally effective in achieving asthma control at 18 weeks, early clinical advantage is gained with initial loading dose budesonide (400 micrograms b.d.).", "When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 microg bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV(1)) >/=70% predicted; EIB >/=20% fall in FEV(1) from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were re-randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV(1) from baseline) and methacholine challenge using a dosimetric technique (expressed as PD(20)) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV(1) being reduced from 34.1% to 9.9% for 100 microg FP bid, and from 35.9% to 7.6% for 250 microg FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD(20) methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 microg FP bid, 1.6 dose steps; 250 microg FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment.\n Copyright 2000 Wiley-Liss, Inc.", "The importance of early initiation of inhaled steroids even in mild asthma has been documented in several studies. It is not, however, clear whether the treatment should be started with a high or a low dose of the inhaled steroid. We have compared the effects of high and low dose inhaled steroid, budesonide, in patients with newly detected asthma. We studied 101 adult patients with newly detected bronchial asthma who were without inhaled steroid or any regular pharmacological treatment for their asthma. The patients were randomly allocated to two treatment groups: one to receive 800 microg inhaled budesonide per day and the other to receive 200 microg inhaled budesonide per day. The drugs were given with a Turbuhaler dry powder inhaler. During the 3-month treatment period, no significant differences between the treatment groups were noted in morning or evening PEF values, in spirometric parameters, in asthmatic symptoms or in the use of rescue beta2-agonists. The decrease in bronchial hyperresponsiveness was, however, more marked in the high dose budesonide group, reaching a borderline significance (P=0.10 high vs. low dose budesonide). In addition, in serum markers of asthmatic inflammation significant differences were shown between the treatment groups. The decrease in the number of blood eosinophils during the treatment was more marked in the high dose budesonide group (P=0.02; high vs. low dose budesonide). In serum ECP no change was observed in the low dose budesonide group, but a marked decrease in the high-dose budesonide group (P=0.008; high vs. low dose budesonide). The change was even more marked with regard to serum EPX (P=0.005; high vs. low dose budesonide). Our results support the view that the treatment of newly detected asthma should be started with a high dose of inhaled steroid. The low dose may not be enough to suppress asthmatic inflammation despite good clinical primary response.", "The purpose of the study was to evaluate the dose-response relationships of the inhaled corticosteroid budesonide in a double blind crossover study in 19 children with moderate and severe asthma.\n A 2-week placebo treatment period (run-in) was followed by three 4-week treatment periods during which 100, 200, and 400 micrograms of budesonide were given per day in randomized order. Urinary cortisol excretion, lung functions, and protection against exercise-induced asthma were assessed at the end of run-in and each treatment period. Furthermore, morning and evening peak expiratory flow rates, day and night symptoms, and use of rescue beta 2-agonists were recorded throughout the study.\n One hundred micrograms of budesonide per day markedly improved symptoms, morning and evening peak expiratory flow rates, and use of rescue beta 2-agonists (p < 0.01). No further improvement was seen in these parameters with increasing doses of budesonide. In contrast, a significant dose-response effect was found on lung functions measured at the hospital and fall in lung functions after exercise (p < 0.001); 200 micrograms was significantly better than 100 micrograms, and 400 micrograms was significantly better than 200 micrograms. About 53% of the maximum effect against exercise-induced asthma was achieved by the lowest budesonide dose (p < 0.001), and about 83% by the highest dose. No significant differences were seen in urinary cortisol excretion between run-in and the various budesonide doses.\n Low doses of budesonide, which are not associated with any systemic side effects, have a marked antiasthma effect in children. Protection against exercise-induced asthma requires higher doses than achievement of symptom control.", "The object of this investigation was to study the long-term effects of antiasthma treatment on blood markers of inflammation and lung function in adult asthmatic subjects. For this purpose 85 allergic and nonallergic asthmatic subjects were randomized into three groups, which were given high-dose (1,600 micrograms/d) inhaled budesonide, low-dose (400 micrograms/d) inhaled budesonide, and oral theophylline (600 mg/d), respectively, and were followed for 11 mo with testing of lung function and blood sampling for the assay in serum of eosinophil cationic protein (ECP), eosinophil protein x/eosinophil derived neurotoxin (EPX/EDN) as eosinophil markers, and myeloperoxidase (MPO) and lactoferrin (LF) as neutrophil markers. Lung functions (FEV1% predicted, and histamine PC20) and the eosinophil markers ECP and EPX/EDN were improved and reduced, respectively, by budesonide in a dose-dependent and temporally parallel fashion. Theophylline did not alter lung functions but reduced ECP and EPX/EDN after prolonged treatment. The treatment efficacy of budesonide was attributed solely to an effect on nonsmoking asthmatic subjects, since neither lung functions nor eosinophil markers changed in smokers even with high-dose budesonide. MPO but not LF was reduced after several months of treatment in all three groups, but only in nonsmokers. We conclude that ECP and EPX/EDN may be used to monitor antiinflammatory treatment in asthmatic patients, and that smoking asthmatic subjects are resistant to inhaled corticosteroids.", "This double-blind, randomized, parallel-group, placebo-controlled study investigated the efficacy and tolerability of fluticasone propionate aerosol (25, 50, or 100 mg bid for 12 weeks) administered as primary maintenance therapy to patients whose mild to moderate asthma was inadequately controlled by as-needed use of an inhaled beta-agonist.\n At all clinic visits, fluticasone propionate compared with placebo was associated with significant (P<.05) improvement in pulmonary function indexed by forced expiratory volume in 1 second (FEV1) as well as fewer night awakenings and less use of rescue albuterol. Values for patient-measured morning peak expiratory flow rates (PEFR) were significantly (P<.05) higher and the use of rescue albuterol was significantly (P<.05) lower beginning 3 to 5 days after initiation of therapy in the groups treated with fluticasone propionate, compared with the placebo group. Maximal improvement in FEV1 was achieved during the second week of treatment and maintained throughout the course of therapy. Differences among the three fluticasone propionate dosing groups for these efficacy measures were not statistically significant. The incidence of adverse events was similar across groups.\n These data indicate that fluticasone propionate aerosol is an effective and well-tolerated treatment for asthma and significantly improves pulmonary function within days of initiation of treatment in patients whose asthma is inadequately controlled with as-needed beta-agonists.", "The objective of this study was to evaluate the efficacy and safety of low doses (50 and 100 microg b.i.d.) of hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) extrafine aerosol in improving asthma control. Reformulation of BDP in a new chlorofluorocarbon (CFC)-free propellant (HFA) has produced an extrafine aerosol with increased delivery of the drug to the airways of the lung. The study population comprised 270 steroid-naive patients with mild to moderate asthma (mean baseline forced expiratory volume in 1 sec [FEV1] as a percentage of predicted normal of 65%-85%). This was a 6-week, blinded, placebo-controlled, multicenter study. Patients were randomized to receive 50 or 100 microg b.i.d. HFA-BDP or HFA-placebo. Treatment with either 50 or 100 microg b.i.d. HFA-BDP resulted in a significantly greater improvement compared with placebo in FEV1 (mean change from baseline as percentage of predicted normal of 6.7%, 8.6%, and 0.4%, respectively; p < or = 0.01 active treatment groups vs. placebo), with a significant trend toward increasing improvement with increasing doses (p < or = 0.0001). Treatment also resulted in significantly greater mean changes from baseline in morning peak expiratory flow compared with placebo (29.5, 33.8, and 5.0 L/min, respectively; p < or = 0.01 active treatment groups vs. placebo). All other pulmonary function and asthma symptom measures supported these data. The study treatments were well tolerated. These results show that low doses of HFA-BDP extrafine aerosol effectively improve asthma control in adult patients with mild to moderate asthma. However, it is important that inhaled corticosteroid therapy is still given at a dose high enough to control airway inflammation as well as asthma symptoms.", "A double blind, parallel group study was carried out to investigate the effect of inhaled budesonide in a moderate (200 micrograms) and a low (100 micrograms) twice daily dosage compared with the effect of placebo in 103 adults with mild symptomatic asthma. Subjects recorded peak expiratory flow (PEF), asthma symptoms, and beta 2 agonist consumption at home for a period of seven weeks (a one week run in and six weeks' treatment). Morning baseline PEF (around 80% of predicted normal) increased non-significantly to 88% with 200 micrograms budesonide daily and to 90% (p less than 0.05) with 400 micrograms, compared with 81% with placebo. Evening PEF (around 94% of predicted normal) did not change significantly with active or placebo treatment. By comparison with placebo, there was a significant decrease in nocturnal asthma symptoms and beta 2 agonist consumption. The changes during the day were less pronounced and significant only for 400 micrograms budesonide daily. No significant differences between the two active treatments were detected. It is concluded that low doses of inhaled budesonide are effective in patients with mild symptomatic asthma, particularly for night time symptoms and early morning lung function. The early introduction of inhaled corticosteroids for patients with mild asthma and night time symptoms may improve their quality of life during the night and early morning.", "Dose-dependent effects of inhaled corticosteroids have been described. Although it has been advised to start treatment with inhaled corticosteroids with a high dose tapering off subsequently (stepdown approach), no clinical studies have assessed this strategy. We compared two different dosage schedules of inhaled fluticasone propionate (FP) in chronic persistent childhood asthma with respect to efficacy (airways hyperresponsiveness [PD(20)], lung function, exhaled nitric oxide [eNO]) and safety (height). During this double-blind study, children with asthma (aged 6-10 yr) were randomized to receive either FP 200 microg/d (constant dose approach) or to start with 1000 microg/d with two monthly reductions to 500, 200, and 100 microg/d (stepdown approach). PD(20) improved in both approaches during treatment with FP, with a significantly better PD(20) after 2 mo of 1000 microg/d followed by 500 microg/d in the stepdown approach versus 200 microg/d in the constant dose approach. No significant differences in PD(20) or other efficacy parameters were found after 1 yr. Changes in standing height were similar in both treatment approaches. This study showed no superior clinical effect of a stepdown approach compared with a constant dose strategy of FP for 1 yr in children with chronic persistent asthma.", "The response in asthmatic young children to inhaled steroids within the usual pediatric dose range is unknown. We therefore evaluated the dose-related response in young children with moderate asthma to inhaled fluticasone propionate (FP) (delivered via the Babyhaler spacer device) within the pediatric dose range. A total of 237 children (mean age 28 mo, range 12 to 47) with moderate asthmatic symptoms were studied in this multicenter, randomized, double-blind, parallel group, placebo-controlled study of 12 wk treatment following a 4-wk run-in period. The median use of rescue medication was 1 dose in 2 d during the run-in period. FP 50 micrograms twice daily (FP100) and 100 micrograms twice daily (FP200) was compared with placebo inhaled from a pressurized metered-dose inhaler (pMDI) and the Babyhaler spacer device. With FP200 there was a statistically significant improvement from baseline, as compared with the placebo group, in 8 of 10 diary card parameters, including the three symptom domains of wheeze, cough, and breathlessness, and use of rescue medication. FP100 produced a significant reduction in 5 of these 10 parameters, whereas no significant differences were found between the FP200 and FP100. The numbers of patients with at least one exacerbation during treatment with placebo, FP100, and FP200 were 37%, 26%, and 20%, respectively. This difference between placebo and FP200, as well as the dose-related order was significant (p < 0.05). Both FP doses were as well tolerated as placebo over the 12 wk treatment with a similar incidence of adverse effects. Asthmatic symptoms in 1- to 3-yr-old children responded in a significant and dose-related manner to treatment with FP within a pediatric dose range.", "The aim of the present study was to examine the efficacy of low-dose inhaled budesonide (BUD) administered via Turbuhaler once or twice daily on symptoms, lung function and bronchial hyperreactivity in children with mild asthma. One hundred and sixty-three children (mean age 9.9 yrs, 56 females/107 males) with mild asthma (forced expiratory volume in one second (FEV1) 103% of predicted, morning peak expiratory flow (PEF) 87% pred, reversibility in FEV1 3%, fall in FEV1 after exercise 10.4% from pre-exercise value) and not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. After a two-week run-in period, the children received inhaled BUD 100 microg or 200 microg once daily in the morning, 100 microg twice daily or placebo for 12 weeks. Exercise and methacholine challenges were performed before and at the end of treatment. After 12 weeks of therapy, the fall in FEV1 after an exercise test was significantly less in all three BUD groups (43-5.1%) than in the placebo group (8.6%). Bronchial hyperreactivity to methacholine with the provocative dose causing a 20% fall in FEV1 decreased significantly in the BUD 100 microg twice-daily group compared with placebo (ratio at the end of treatment 156%). Changes in baseline lung function (FEV1 and PEF) were less marked than changes in bronchial responsiveness. In conclusion, low doses of inhaled budesonide, given once or twice daily, provided protection against exercise-induced bronchoconstriction in children with mild asthma and near normal lung function.", "Beclomethasone dipropionate (BDP) has been formulated as an extrafine aerosol (hydrofluoroalkane-134a [HFA]-BDP) [QVAR; 3M Pharmaceuticals; St Paul, MN], which gives improved lung deposition compared with chlorofluorocarbon (CFC)-BDP. The clinical efficacy of HFA-BDP has been established in adult asthma at a required dose below that of CFC-BDP, but has not been evaluated in children.\n To examine the efficacy and safety of HFA-BDP in childhood asthma.\n A 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study involving 353 children aged 5 to 12 years with moderate, symptomatic asthma. After a 2-week run-in period, patients were randomized to HFA-BDP, 80 micro g/d (n = 120); HFA-BDP, 160 micro g/d (n = 117); or HFA-placebo (n = 116) administered twice daily.\n Hospital outpatient.\n HFA-BDP, 80 micro g/d and 160 micro g/d, produced a significant, dose-related increase from baseline in FEV(1) percent predicted compared with placebo. At week 12, mean changes from baseline in FEV(1) percent predicted were 9.2% (p < or = 0.01 vs placebo), 10% (p < or = 0.01 vs placebo), and 3.9% for the HFA-BDP 80 micro g/d, HFA-BDP 160 micro g/d, and placebo groups, respectively. There was also a significant decrease in daily beta-agonist use, improvement in peak expiratory flow, and increase [correction] in the percentage of days free from asthma symptoms (p < or = 0.05 for HFA-BDP, 160 micro g/d, vs placebo at weeks 11 to 12). HFA-BDP was well tolerated, with no significant differences in the incidence or nature of adverse events between HFA-BDP and placebo groups. Neither were there significant differences between groups in mean percentage change from baseline in the morning plasma cortisol level at week 12 or in the percentage of patients with morning plasma cortisol levels below the reference range at baseline and week 12. In a subgroup tested, the percentage of patients with an abnormal response to low-dose adrenocorticotropic hormone stimulation at week 12 was low and similar among all groups.\n HFA-BDP, 80 to 160 micro g/d, is effective and safe in childhood asthma.", "To evaluate the clinical efficacy of high dose inhaled steroids, we examined the effects of standard doses (400 micrograms/day) and high doses (800 micrograms/day) of inhaled beclomethasone dipropionate (BDP, Becotide Inhaler), and the dose for regular use (800 micrograms/day) of salbutamol (Salb. Asmidon Air) on pulmonary function, bronchial hyperresponsiveness and asthma attack score. The subjects were 17 out-patients with mild or moderate bronchial asthma who were not receiving any anti-allergics or steroids. The patients were randomly allocated into three groups i.e., Group I: BDP 400 micrograms/day, Group II: BDP 800 micrograms/day and Group III: Salb. 800 micrograms/day. The administration period was 8 weeks. Pulmonary function test were performed and bronchial hyperresponsiveness was examined before and after the 8 weeks of treatment and attack scores were recorded during this period. It was found that inhalations of 400 micrograms/day and 800 micrograms/day BDP improved FEV1.0% value, peak flow, F-V curve, Dmin. and SGrs/Grs cont. Particularly, inhalation of 800 micrograms/day of BDP significantly improved these values and reduced attack scores in the early stages of the 8 week treatment. In contrast, there was a trend for inhalation of Salbutamol to enhance bronchial hyperresponsiveness and not to improve pulmonary function and asthma attack score. In conclusion, 800 micrograms/day of inhaled BDP is considered to be useful in the treatment of mild or moderate bronchial asthma.", "The dose dependency of the effects of inhaled corticosteroids on markers of asthmatic airway inflammation have not been well studied. There is a need to study the dose/response effects on this inflammation. In order to determine the dose/response effects of fluticasone propionate (FP), 24 asthmatic subjects were randomized to low- (100 microg x day(-1)) or high-dose (1,000 microg x day(-1)) FP for six weeks followed by placebo for 3 weeks. During treatment, the median increase in forced expiratory volume in one second (FEV1)was 12% in the high-dose group (p<0.05) and 10% in the low-dose group (p<0.05) (p>0.05 between groups); the median decrease in the percentage of sputum eosinophils was 93% in the high-dose group (p<0.05) and 46% in the low-dose group (p<0.05) (p>0.05 between groups). Symptoms, salbutamol use, morning peak flow, provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophil cationic protein concentration and tryptase activity improved significantly in both groups (p<0.05), but only the improvement in salbutamol use was greater in the high-dose group (p<0.05). During the run-out, the improvements in FEV1 and PC20 were rapidly reversed in both groups, but the improvements in peak flow and tryptase activity persisted; the improvement in sputum eosinophil concentration persisted only in the high-dose group (p<0.05). It was concluded that dose/response effects for FP are not easily demonstrable because low-dose FP is quite effective. For most outcomes, the effects of high- and low-dose FP are relatively short-lived after treatment is stopped. This finding raises questions about the extent to which inhaled corticosteroids are disease-modifying in asthma.", "There are no data currently available on the correct schedule for the initiation of treatment with nebulized suspension of budesonide in children with recurrent wheezing episodes. We compared the efficacy and safety of starting with a high dose followed by a stepwise decrease to a continuous low dose.\n In a double-blind design, 42 children aged 6 months to 3 years were randomly allocated to receive either a high starting dose of 1 mg budesonide twice daily followed by a stepwise decrease of 25% every second day for 1 week (group A) or a low dose of 0.25 mg twice daily for 1 week (group B). Efficacy was assessed with daily symptom scores and the systemic effect of the corticosteroids with the adrenocorticotropic hormone test.\n The two groups were comparable for all parameters evaluated. During the first week of treatment, there was a significant decrease in asthmatic symptomatology only in group A: a 59% decrease for wheezing (p = 0.0001), 39% for diurnal cough (p = 0.036), and 39% for nocturnal cough (p = 0.04). Mean time to clinical response was 3.0 days in group A and 5.7 days in group B (p = 0.02). This early improvement was sustained for the rest of the follow-up period. The high dose starting schedule was not associated with any change in serum cortisol level.\n The administration of nebulized suspension of budesonide at a high starting dose schedule followed by a rapid (1 week) stepwise decrease yields a significant early improvement in asthma symptoms and causes no change in serum cortisol levels.", "New British guidelines on the treatment of asthma (9) advocate starting with a higher dose of inhaled corticosteroids in newly detected asthma patients. We investigated whether initiating inhaled steroid treatment with a higher dose is clinically more effective than a lower dose in steroid naive patients with asthma. The study had a 13-wk randomized, double-blind, parallel design: 1-mo treatment with 400 microg budesonide twice a day, or 100 microg budesonide twice a day by dry powder inhaler, and follow-up treatment period of 2 mo with 200 microg budesonide once daily for all patients. Forty patients started with 400 microg budesonide twice daily, 44 with 100 microg budesonide twice daily. Mean age was 32 yr, baseline FEV1 value 84% predicted, reversibility 9% from baseline, and mean bronchodilator use 1.6 inhalations/d in the run-in period. After 4 wk of treatment with 400 microg and 100 microg budesonide twice daily mean morning peak expiratory flow (PEF) increased 27 L/min (SD 50), and 38 L/ min (SD 53), respectively (p = 0.30); mean symptom score improved from 1.1 to 0.6 and from 1.1 to 0.5. These effects were maintained in the 2 mo follow-up. This study suggests that starting inhaled corticosteroids at a higher dose is not superior to a lower dose in the treatment of newly detected asthma.", "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.", "Dose-response relationships with inhaled corticosteroids in the treatment of asthma have been difficult to establish. A multicenter, double-blind, parallel-group study was conducted to evaluate the clinical efficacy and safety of low doses of inhaled fluticasone propionate (FP) in patients with mild to moderate asthma. Methacholine challenge testing was conducted in addition to measurement of traditional efficacy variables. After a single-blind screening period, 138 patients > or = 12 years of age were randomly assigned to receive placebo, FP 50 microg, or FP 100 microg, twice daily for 8 weeks. The results of methacholine challenge testing averaged over all visits favored FP 200 microg/day over placebo and FP 100 microg/day (p < 0.05); there were no significant differences between placebo and FP 100 microg/day. Mean changes from baseline to endpoint favored each dose of FP over placebo based on forced expiratory volume in 1 sec (FEV1), patient-measured peak expiratory flow (PEF), total symptom scores, and rescue bronchodilator use (p < 0.05); there were no differences in these parameters between the two doses of FP. The addition of methacholine challenge testing allowed definition of a dose-response relationship that was not apparent with traditional efficacy variables.", "Fluticasone propionate (FP) administered via metered-dose inhaler is a potent corticosteroid effective in the treatment of asthma. To evaluate the efficacy and safety of FP powder administered via a breath-activated inhaler (Diskhaler), a multicenter, double-blind, randomized, placebo-controlled, parallel-group study was conducted in adolescent and adult patients (n = 331) with mild-to-moderate asthma previously treated with beta 2-agonist therapy alone. Patients received FP powder 50, 100, or 250 micrograms or placebo twice daily for 12 weeks. FP-treated patients compared with placebo-treated patients had significantly (p < 0.001) greater improvements in morning predose forced expiratory volume in 1 sec (21-22% increase vs. 9%). Improvement in morning peak flow rate were also significantly (p < 0.001) greater with FP than with placebo (8-10% increase vs. 2% increase). There was also a significant overall treatment difference in the frequency of inhaled albuterol use (p < 0.001) and number of nighttime awakenings due to asthma (p = 0.005). There were no statistically significant difference among the FP treatment groups in any outcome measure. Physicians' global assessments also indicated significant (p < 0.001) differences in efficacy, with 67-74% of FP-treated patients rated as having \"effective\" or \"very effective\" treatment compared with 41% of placebo-treated patients. Significant beneficial effects of FP were observed in lung function and diary card parameters after just 1 week of treatment. Adverse events were similar across treatment groups and primarily related to local irritation. Effect on hypothalamic-pituitary-adrenal axis function was minimal. In summary, all three dosages of inhaled FP powder were well tolerated and improved various asthma-related variables. Improvements in pulmonary function, beyond those achieved with beta 2-agonist therapy alone, were maintained for the duration of the 12-week study." ]

[ "9408720", "7853047", "1614465", "12877755", "7266633", "8932970", "10235168", "8413069", "11158556" ]

[ "Cumulating evidence from randomized trials: utilizing sequential monitoring boundaries for cumulative meta-analysis.", "Cumulative meta-analysis of clinical trials builds evidence for exemplary medical care.", "Cumulative meta-analysis of therapeutic trials for myocardial infarction.", "Identifying null meta-analyses that are ripe for updating.", "A survey of clinical trials of antibiotic prophylaxis in colon surgery: evidence against further use of no-treatment controls.", "Uncertainty of the time of first significance in random effects cumulative meta-analysis.", "Recursive cumulative meta-analysis: a diagnostic for the evolution of total randomized evidence from group and individual patient data.", "Preparing and updating systematic reviews of randomized controlled trials of health care.", "Evolution of treatment effects over time: empirical insight from recursive cumulative metaanalyses." ]

[ "We propose the adaptation of classical monitoring boundaries for use in cumulative meta-analysis as guidelines for deciding when accumulating evidence is statistically significant and medically convincing. The interpretation of information from a randomized controlled trial is compared with that from a meta-analysis. The concept of optimal information size for a meta-analysis is developed and used to adapt monitoring boundaries to cumulative meta-analysis.", "Cumulative meta-analysis of clinical trials (a Bayesian interpretation for accumulating evidence) will profoundly affect medical care by summarizing evidence in the assessment of technology innovations. Application of the technique to the randomized control trials (RCTs) of streptokinase treatment of acute myocardial infarction, reduction of peri-operative mortality by antibiotic prophylaxis, and prevention of death from bleeding peptic ulcers has revealed efficacy years before it was suspected by any other means. Arrangement of the trials according to event rate in the controls, effect sizes, quality of the trials or according to covariables of interest has supplied unique information. If carried out prospectively the technique supplies invaluable information regarding indications for another trial, the number of patients necessary to determine the validity of past trends, and the type of patients who might be benefitted. Careful examination in a cumulative manner of the prior trials can reduce the need for future large trials.", "The large volume of published randomized, controlled trials has led to a need for meta-analyses to track therapeutic advances. Performing a new meta-analysis whenever the results of a new trial of a particular therapy are published permits the study of trends in efficacy and makes it possible to determine when a new treatment appears to be significantly effective or deleterious. We describe the use of such a procedure, cumulative meta-analysis, to assess therapeutic trials among patients with myocardial infarction.\n We performed cumulative meta-analyses of clinical trials that evaluated 15 treatments and preventive measures for acute myocardial infarction.\n An example of this method is its application to the use of intravenous streptokinase as thrombolytic therapy for acute infarction. Thirty-three trials evaluating this therapy were performed between 1959 and 1988. We found that a consistent, statistically significant reduction in total mortality (odds ratios, 0.74; 95 percent confidence interval, 0.59 to 0.92) was achieved in 1973, after only eight trials involving 2432 patients had been completed. The results of the 25 subsequent trials, which enrolled an additional 34,542 patients through 1988, had little or no effect on the odds ratio establishing efficacy, but simply narrowed the 95 percent confidence interval. In particular, two very large trials, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial in 1986 (11,712 patients) and the Second International Study of Infarct Survival trial in 1988 (17,187 patients) did not modify the already established evidence of efficacy. We used a similar approach to study the accumulating evidence of efficacy (or lack of efficacy) of 14 other therapies and preventive measures for myocardial infarction.\n Cumulative meta-analysis of therapeutic trials facilitates the determination of clinical efficacy and harm and may be helpful in tracking trials, planning future trials, and making clinical recommendations for therapy.", "As an increasingly large number of meta-analyses are published, quantitative methods are needed to help clinicians and systematic review teams determine when meta-analyses are not up to date.\n We propose new methods for determining when non-significant meta-analytic results might be overturned, based on a prediction of the number of participants required in new studies. To guide decision making, we introduce the \"new participant ratio\", the ratio of the actual number of participants in new studies to the predicted number required to obtain statistical significance. A simulation study was conducted to study the performance of our methods and a real meta-analysis provides further evidence.\n In our three simulation configurations, our diagnostic test for determining whether a meta-analysis is out of date had sensitivity of 55%, 62%, and 49% with corresponding specificity of 85%, 80%, and 90% respectively.\n Simulations suggest that our methods are able to detect out-of-date meta-analyses. These quick and approximate methods show promise for use by systematic review teams to help decide whether to commit the considerable resources required to update a meta-analysis. Further investigation and evaluation of the methods is required before they can be recommended for general use.", "To evaluate the use of antibiotics given prophylactically of colon surgery, we examined 26 trials published from 1965 to 1980 in which patients given various antibiotic regiments were compared with controls given no antibiotic treatment. In 22 (85 per cent of these trials) antibiotics reduced postoperative wound infection (p less than 0.05 in 14). Combining the results of the trials published from 1965 to 1975 reveals a 95 per cent confidence interval from the true difference in infection rates of 14 +/- 6 per cent (36 per cent for control group vs. 22 per cent for treatment group) and the true difference in death rates of 6.7 +/- 4.4 per cent (11.2 per cent for control group vs 4.5 per cent for treatment group). Yet trials employing control groups given no treatment continue to be reported. Since the use of such controls is justified only when no effective alternative therapy exists, we believe that any further trials of antibiotic prophylaxis in colon surgery should employ a previously proved standard. However, steadily increasing efficacy of treatment means that comparisons of new therapies with standard therapies will become prohibitively expensive because of the large number of patients required.", "We propose a process for evaluating quantities of clinical and statistical interest in cumulative meta-analysis. We use Monte Carlo simulation studies to assess the error variance of the time to significance in cumulative meta-analysis. For the specific cumulative meta-analyses that we simulated, the 95% confidence interval of the treatment effect, estimated by the random effects method at the time of earliest significance, appears to be approximately appropriate except when the hypothesized treatment effect is near the null. The Monte Carlo approach that we used can also estimate the power of a cumulative meta-analysis when two treatments differ in efficacy. We illustrate these issues in the context of five cumulative meta-analyses, each comparing two treatments for preventing mortality from myocardial infarction. These simulated meta-analyses demonstrate our main point, which is that the time of first significance, however parameterized, is itself a random variable with error variance.", "Meta-analyses of randomized evidence may include published, unpublished, and updated data in an ongoing estimation process that continuously accommodates more data. Synthesis may be performed either with group data or with meta-analysis of individual patient data (MIPD). Although MIPD with updated data is considered the gold standard of evidence, there is a need for a careful study of the impact different sources of data have on a meta-analysis and of the change in the treatment effect estimates over sequential information steps. Unpublished data and late-appearing data may be different from early-appearing data. Updated information after the end of the main study follow-up may be affected by cross-overs, missing information, and unblinding. The estimated treatment effect may thus depend on the completeness and updating of the available evidence. To address these issues, we present recursive cumulative meta-analysis (RCM) as an extension of cumulative metaanalysis. Recursive cumulative meta-analysis is based on the principle of recalculating the results of a cumulative meta-analysis with each new or updated piece of information and focuses on the evolution of the treatment effect as a more complete and updated picture of the evidence becomes available. An examination of the perturbations of the cumulative treatment effect over sequential information steps may signal the presence of bias or heterogeneity in a meta-analysis. Recursive cumulative meta-analysis may suggest whether there is a true underlying treatment effect to which the meta-analysis is converging and how treatment effects are sequentially altered by new or modified evidence. The method is illustrated with an example from the conduct of an MIPD on acyclovir in human immunodeficiency virus infection. The relative strengths and limitations of both metaanalysis of group data and MIPD are discussed through the RCM perspective.", "People providing health care tend to turn to review articles rather than reports of primary research when seeking information to guide their practices. For this reason, the process of reviewing the results of primary research must respect scientific principles. Reviews must be kept up to date and disseminated in appropriate ways to the people who make decisions about health care, including policy makers, practitioners, and users of the health services. This article describes the methods developed and used in an attempt to address these challenges for care during pregnancy and childbirth.", "Evidence on how much medical interventions work may change over time. It is important to determine what fluctuations in the treatment effect reported by randomized trials and their metaanalyses may be expected and whether extreme fluctuations signal future major changes. We applied recursive cumulative metaanalysis of randomized controlled trials to evaluate the relative change in the pooled treatment effect (odds ratio) over time for 60 interventions in two medical fields (pregnancy/perinatal medicine, n = 45 interventions; myocardial infarction, n = 15 interventions). We evaluated the scatter of relative changes for different numbers of total patients in previous trials. Outlier cases were noted with changes greater than 2.5 standard deviations of the expected. With 500 accumulated patients, the pooled odds ratio may change by 0.6- to 1.7-fold in the immediate future. When 2000 patients have already been randomized, the respective figures are between 0.74- and 1.35-fold for pregnancy/perinatal medicine and between 0.83- and 1.21-fold for myocardial infarction studies. Extreme early fluctuations in the treatment effect were observed in three interventions (magnesium in myocardial infarction, calcium and antiplatelet agents for prevention of preeclampsia), where recent mega-trials have contradicted prior metaanalyses, as well as in four other examples where early large treatment effects were dissipated when more data appeared. Past experience may help quantify the uncertainty surrounding the treatment effects reported in early clinical trials and their metaanalyses. Early wide oscillations in the evolution of the treatment effect for specific interventions may sometimes signal further major changes in the future." ]

[ "8856425", "12724244", "11074869", "12437794", "9099116", "15367052" ]

[ "Counselling of postnatal depression: a controlled study on a population based Swedish sample.", "Controlled trial of the short- and long-term effect of psychological treatment of post-partum depression. I. Impact on maternal mood.", "Efficacy of interpersonal psychotherapy for postpartum depression.", "A brief psycho-educational group intervention for postnatal depression.", "A controlled study of fluoxetine and cognitive-behavioural counselling in the treatment of postnatal depression.", "The use of paroxetine and cognitive-behavioral therapy in postpartum depression and anxiety: a randomized controlled trial." ]

[ "In a two-stage screening procedure using the Edinburgh Postnatal Depression Scale (EPDS) at 8 and 12 weeks postpartum and the Montgomery-Asberg Depression Rating Scale (MADRS) and DSM-III-R at about 13 weeks postpartum, 41 women identified as depressed were randomly allocated to a study and a control group. The women in the study group received 6 weekly, counselling visits by the Child Health Clinic nurse and the control group received routine primary care. Twelve (80%) of 15 women with major depression in the study group were fully recovered after the intervention compared to 4 (25%) of 16 in the control group. Counselling by health nurses is helpful in managing postnatal depression and seems to work well within the Swedish Primary Health Care system.", "Psychological interventions for postnatal depression can be beneficial in the short term but their longer-term impact is unknown.\n To evaluate the long-term effect on maternal mood of three psychological treatments in relation to routine primary care.\n Women with post-partum depression (n=193) were assigned randomly to one of four conditions: routine primary care, non-directive counselling, cognitive-behavioural therapy or psychodynamic therapy. They were assessed immediately after the treatment phase (at 4.5 months) and at 9, 18 and 60 months post-partum.\n Compared with the control, all three treatments had a significant impact at 4.5 months on maternal mood (Edinburgh Postnatal Depression Scale, EPDS). Only psychodynamic therapy produced a rate of reduction in depression (Structured Clinical Interview for DSM-III - R) significantly superior to that of the control. The benefit of treatment was no longer apparent by 9 months post-partum. Treatment did not reduce subsequent episodes of post-partum depression.\n Psychological intervention for post-partum depression improves maternal mood (EPDS) in the short term. However, this benefit is not superior to spontaneous remission in the long term.", "Postpartum depression causes women great suffering and has negative consequences for their social relationships and for the development of their infants. Research is needed to evaluate the efficacy of psychotherapy for postpartum depression.\n A total of 120 postpartum women meeting DSM-IV criteria for major depression were recruited from the community and randomly assigned to 12 weeks of interpersonal psychotherapy (IPT) or to a waiting list condition (WLC) control group. Subjects completed interview and self-report assessments of depressive symptoms and social adjustment every 4 weeks.\n Ninety-nine of the 120 patients completed the protocol. Hamilton Rating Scale for Depression (HRSD) scores of women receiving IPT declined from 19.4 to 8.3, a significantly greater decrease than occurred in the WLC group (19.8 to 16.8). The Beck Depression Inventory (BDI) scores of women who received IPT declined from 23.6 to 10.6 over 12 weeks, a significantly greater decrease than occurred in the WLC group (23.0 to 19.2). A significantly greater proportion of women who received IPT recovered from their depressive episode based on HRSD scores of 6 or lower (37. 5%) and BDI scores of 9 or lower (43.8%) compared with women in the WLC group (13.7% and 13.7%, respectively). Women receiving IPT also had significant improvement on the Postpartum Adjustment Questionnaire and the Social Adjustment Scale-Self-Report relative to women in the WLC group.\n These findings suggest that IPT is an efficacious treatment for postpartum depression. Interpersonal psychotherapy reduced depressive symptoms and improved social adjustment, and represents an alternative to pharmacotherapy, particularly for women who are breastfeeding.", "To evaluate the efficacy of a controlled psycho-educational group (PEG) intervention for postnatal depression, compared with Routine Primary Care (RPC).\n The participants were 45 women scoring above 12 on the Edinburgh Postnatal Depression Scale who were allocated to the study conditions using block randomization procedures. Short- and long-term changes in mood and psychosocial measures were assessed.\n Compared with RPC, the PEG significantly reduced the level of depressive symptoms, but had no impact on psychosocial outcome.\n A brief PEG is an effective form of treatment for women with low post-partum mood.", "To study the effectiveness of fluoxetine and cognitive-behavioural counselling in depressive illness in postnatal women: to compare fluoxetine and placebo, six sessions and one session of counselling, and combinations of drugs and counselling.\n Randomised, controlled treatment trial, double blind in relation to drug treatment, with four treatment cells: fluoxetine or placebo plus one or six sessions of counselling.\n 87 women satisfying criteria for depressive illness 6-8 weeks after childbirth, 61 (70%) of whom completed 12 weeks of treatment.\n Community based study in south Manchester.\n Psychiatric morbidity after 1, 4, and 12 weeks, measured as mean scores and 95% confidence limits on the revised clinical interview schedule, the Edinburgh postnatal depression scale and the Hamilton depression scale.\n Highly significant improvement was seen in all four treatment groups. The improvement in subjects receiving fluoxetine was significantly greater than in those receiving placebo. The improvement after six sessions of counselling was significantly greater than after a single session. Interaction between counselling and fluoxetine was not statistically significant. These differences were evident after one week, and improvement in all groups was complete after four weeks.\n Both fluoxetine and cognitive-behavioural counselling given as a course of therapy are effective treatments for non-psychotic depression in postnatal women. After an initial session of counselling, additional benefit results from either fluoxetine or further counselling but there seems to be no advantage in receiving both. The choice of treatment may therefore be made by the women themselves.", "Approximately 10% to 16% of women experience a major depressive episode after childbirth. A significant proportion of these women also suffer from comorbid anxiety disorders. The purpose of this study was to evaluate whether the addition of cognitive-behavioral therapy (CBT) to standard antidepressant therapy offers additional benefits in the treatment of post-partum depression with comorbid anxiety disorders.\n Thirty-five women referred to a tertiary care hospital outpatient program with a DSM-IV diagnosis of postpartum depression with comorbid anxiety disorder were randomly assigned to 1 of 2 treatment groups-paroxetine-only monotherapy group (N = 16) or paroxetine plus 12 sessions of CBT combination therapy group (N = 19)-for a 12-week trial. Progress was monitored by a psychiatrist blinded to treatment group, using the Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Yale-Brown Obsessive Compulsive Scale, Clinical Global Impressions scale, and Edinburgh Postnatal Depression Scale. Data were analyzed using 2-tailed statistical tests at an alpha level of.05. The study was conducted from April 1, 2002, to June 30, 2003.\n Both treatment groups showed a highly significant improvement (p <.01) in mood and anxiety symptoms. Groups did not differ significantly in week of recovery, dose of paroxetine at remission, or measures of depression, anxiety, and obsessive-compulsive symptoms at outcome.\n Antidepressant monotherapy and combination therapy with antidepressants and CBT were both efficacious in reducing depression and anxiety symptoms. However, in this sample of acutely depressed/anxious postpartum women, there were no additional benefits from combining the 2 treatment modalities. Further research into the efficacy of combination therapy in the treatment of moderate-to-severe depression with comorbid disorders in postpartum women is recommended." ]

[ "12244891", "2947098" ]

[ "[Ginkgo extract in impaired vision--treatment with special extract EGb 761 of impaired vision due to dry senile macular degeneration].", "[Treatment of senile macular degeneration with Ginkgo biloba extract. A preliminary double-blind drug vs. placebo study]." ]

[ "The therapeutic efficacy of Ginkgo special extract Egb 761 was investigated in a controlled, double-blind trial involving 99 patients with impaired vision due to senile, dry macular degeneration. The primary objective target variable was the change in the corrected visual acuity of the more severely impaired eye at baseline, during a six months treatment period with either 240 mg/die (group I = 50 patients) or 60 mg/die (group II = 49 patients) Egb 761. Marked improvement of the study participants' vision was observed in both treatment groups already after four weeks, with more pronounced improvements in group I (acuity increases by 0.13 in group I vs. 0.10 in group II after 24 weeks). The fraction of patients with improvement of visual acuity > or = 0.2 was nearly twice as large in the group treated with 240 mg/die Egb 761 as in patients receiving the lower dosage (p = 0.08). Subjective health impairments, if present, could be improved during treatment as well. The investigator rated a favorable tolerability for both dosages of Egb 761. In conclusion, the results demonstrate the therapeutic efficacy of Egb 761 in patients with senile, dry macular degeneration, with obvious benefits in every-day life.", "Senile macular degeneration is a frequent cause of blindness for which there is no satisfactory medical treatment. A double-blind trial comparing Ginkgo biloba extract with a placebo was conducted in 10 out-patients at the Hôpital Foch. Drug effectiveness was assessed on the results of fundoscopy and of measurements of visual acuity and visual field. In spite of the small population sample, a statistically significant improvement in long distance visual acuity was observed after treatment with Ginkgo biloba extract. The assumed pathogenesis of senile macular degeneration is discussed with emphasis on free oxygenated radicals." ]

[ "6988335", "3142203", "12793557", "5834726", "3549586", "11478556", "3749909", "1154509", "3333985", "9531201", "3969739", "3291121", "3543805" ]

[ "Rupture of the lateral ligaments of the ankle: a controlled clinical trial.", "Comparison of three different treatments for ruptured lateral ankle ligaments.", "Operative and functional treatment of rupture of the lateral ligament of the ankle. A randomised, prospective trial.", "Injuries of the lateral ligament of the ankle. Conservative vs. operative repair.", "A prospective study of the treatment of severe tears of the lateral ligament of the ankle.", "A comparison of surgical and conservative treatment in ankle ligament tears.", "[Therapy of injuries of the exterior ankle joint ligaments. Randomized study of postoperative therapy and early functional treatment tactics].", "[Lesions of the lateral ligament of the ankle joint].", "[Conservative functional treatment of fibular capsule ligament rupture even in the performance athlete?].", "A randomized, prospective study of operative and non-operative treatment of injuries of the fibular collateral ligaments of the ankle.", "[Treatment of lateral ligament rupture of the ankle. Prospective comparison of operative and conservative treatment].", "[Surgical or conservative treatment of recent rupture of the lateral ligament of the upper ankle joint. Randomized clinical study].", "[Therapy of fresh fibular ligament ruptures]." ]

[ "The results of a randomized study comparing three different principles of treatment for rupture of the lateral ligaments of the ankle are presented. A total of 95 patients was treated and followed up for 17 months. In this series, 32 patients were treated with primary suture and plaster-of-Paris, 33 patients with plaster-of-Paris only and 30 patients with strapping. In all, 31 patients (97%) were completely free of symptoms in the operation group, 22 (67%) in the plaster-of-Paris group and 23 (77%) in the strapping group.", "Two hundred consecutive patients with arthrographically verified rupture of one or both of the lateral ankle ligaments were allocated to treatment with either an operation and a walking cast, walking cast alone, or strapping with an inelastic tape - all for 5 weeks. Eighty-seven percent of the patients attended follow-up after 1 year. Only 5 percent in each treatment group were unsatisfied with the result. There were no differences between the treatment groups in ankle stability or symptoms during different activities, regardless of rupture of the anterior talofibular ligament alone or combined with rupture of the calcaneofibular ligament. However, the patients treated with tape had fewer symptoms, fewer complaints when running, and more ankles recovered to the preinjury state. Therefore, in lateral ankle ligament rupture, tape bandages seem preferable.", "Consecutive patients with a confirmed rupture of at least one of the lateral ligaments of the ankle were randomly assigned to receive either operative or functional treatment. They were evaluated at a median of 8 years (6 to 11). In total, 370 patients were included. Follow-up was available for 317 (86%). Fewer patients allocated to operative treatment reported residual pain compared with those who had been allocated to functional treatment (16% versus 25%, RR 0.64, CI 041 to 1.0). Fewer surgically-treated patients reported symptoms of giving way (20% versus 32%, RR 0.62, CI 0.42 to 0.92) and recurrent sprains (22% versus 34%, RR 0.66, CI 0.45 to 0.94). The anterior drawer test was less frequently positive in surgically-treated patients (30% versus 54%, RR 0.54, CI 0.41 to 0.72). The median Povacz score was significantly higher in the operative group (26 versus 22, p < 0.001). Compared with functional treatment, operative treatment gives a better long-term outcome in terms of residual pain, recurrent sprains and stability.", "nan", "A prospective randomized clinical study was undertaken to compare bandaging, plaster cast immobilisation and operative treatment for recent tears of the lateral ligament of the ankle. The follow-up period was two years. Subjectively, only the fear of giving-way showed a clear difference in favour of operative repair. Objective evaluation, including stress radiographs, demonstrated no statistical differences between the three methods of treatment. Although bandaging appeared somewhat less satisfactory with respect to the resulting stability of the ankle, the differences were not statistically significant. The lateral ligament in patients over 40 years of age showed a statistically significant tendency to heal less well than that of younger patients. Severe ankle sprains in patients under 40 years of age should preferably be treated by operation, especially in younger patients and if the person is physically active. Lateral ligament tears in patients over 40 years of age should be treated conservatively and a secondary reconstruction carried out later, if necessary.", "Good results have been reported after both primary repair and conservative management of grade III ankle sprains. This prospective study found no advantage of operative treatment compared to taping; no significant differences were found between the groups with regard to objective or subjective stability, functional scores, or the overall result.", "nan", "nan", "In a prospective randomised study we examined 80 men and women of 18 to 45 years of age and 40 competitive sportsmen and sportswomen with fresh ruptures of the talofibular and calcaneofibular ligaments treated either surgically or conservatively by functional bracing. We controlled the results by anamnesis and by clinical and radiological follow-up. Conservative treatment leads to the same results after 3-8 months as surgical treatment (5 +/- 2 degrees of talar angulation). Functional conservative treatment results in earlier painless weight bearing in comparison to the surgical treatment which was, however, combined with three weeks immobilization directly after surgery. This proves the superiority of the early functional conservative treatment as long as there are no bony capsuloligamentous tears, osseocartilaginous lesions of the joint surface with splintered-off chips or \"flakes\" of cartilage (\"flake fractures\") or reruptures of a chronically unstable ankle joint. The similarly good results achieved in the group of 40 sportsmen and sportswomen by early functional conservative treatment do not justify operation of ruptures of the talofibular and calcaneofibular ligaments.", "One hundred and forty-six adults who had an isolated injury of the fibular collateral ligaments of the ankle were randomized to be managed operatively or non-operatively. Disruption of the ligaments was diagnosed by means of a physical examination and on the basis of stress radiographs of the ankle made with use of a specially designed device to hold the leg. Operative treatment, performed in seventy-three patients, consisted of suture repair of the disrupted ligaments within seventy-two hours after the injury, followed by immobilization of the ankle in a below-the-knee plaster cast for six weeks. Non-operative treatment, used for seventy-three patients, consisted of the use of an ankle orthosis for six weeks. After a minimum of two years of follow-up, we could detect no significant differences, with the numbers available, between the two groups with regard to the functional result or the degree of joint laxity that was evident on stress radiographs. The non-operative group lost a mean of 1.6 weeks from work, and the operative group lost a mean of 7.0 weeks. We concluded that non-operative treatment of an injury of the fibular collateral ligaments of the ankle yields results that are comparable with those of operative repair and is associated with a shorter period of recovery.", "nan", "nan", "In a prospective, random study carried out at the Casualty Clinic of the University Hospital of Hannover from 15 April 1986 to 31 July 1986, 200 patients were randomly selected from four treatment groups, according to treatment: operative-immobilized (group A, n = 52), operative-functional (group B, n = 50), conservative-immobilized (group C, n = 48) and conservative-functional (group D, n = 50). Follow-up examinations were made in 92.5% of patients after 3 months and 64% after 12 months. At the 3-month and 1-year follow-ups, no statistically significant differences were found in the total evaluation (100-point checklist) Moderately significant instability (6 degrees -10 degrees talar tilt and 6-10 mm anterior talar dislocation) in the conservative groups C and D was observed only in the clinical-radiological instability test. This statistically significant difference is, however, only evident in stress tenographically confirmed dual-ligament lesions. No functional physiological differences can be found after 12 months; on average, the period of incapacitation is 3 weeks shorter than with primary functional treatment, but so far there are no long-term results. Until late results are available, we conclude that conservative treatment, even for professional athletes, can be recommended as the procedure most free of risk and most economical; if at all, operative therapy should only be carried out when the instability is very serious." ]

[ "1564153" ]

[ "A therapeutic trial of the use of penicillin V or erythromycin with or without rifampin in the treatment of psoriasis." ]

[ "After the publication of an uncontrolled trial of nine patients with streptococcus-associated psoriasis who appeared to benefit from a course of oral penicillin or erythromycin with the addition of rifampin in the last 5 days, we wished to confirm or refute the validity of this observation.\n Our purpose was to confirm the effectiveness of antibiotics in the treatment of streptococcus-associated psoriasis.\n Twenty patients were placed randomly into two groups. One group was given penicillin or erythromycin for 14 days with a placebo added during the last 5 of the 14 days. The other group received the same medication with the addition of rifampin in the last 5 days.\n Although all the patients studied met the criteria of the reported preliminary study, we were unable to detect any evidence of improvement in their psoriasis.\n There was no apparent benefit for patients with streptococcus-associated psoriasis from a course of oral penicillin or erythromycin with the addition of rifampin in the last 5 days in a 14-day trial." ]

[ "9375333", "12166561", "1729110", "9311492", "16429430", "6426355", "2921681", "2121079", "11208637" ]

[ "Effect of supplemental oxygen on supramaximal exercise performance and recovery in cystic fibrosis.", "The role of supplemental oxygen during submaximal exercise in patients with cystic fibrosis.", "Supplemental oxygen and exercise performance in patients with cystic fibrosis with severe pulmonary disease.", "Nocturnal ventilatory support in patients with cystic fibrosis: comparison with supplemental oxygen.", "Effect of low altitude at the Dead Sea on exercise capacity and cardiopulmonary response to exercise in cystic fibrosis patients with moderate to severe lung disease.", "The effect of oxygen on sleep, blood gases, and ventilation in cystic fibrosis.", "Nocturnal home oxygen in the treatment of hypoxemic cystic fibrosis patients.", "Oxygen supplementation during exercise in cystic fibrosis.", "Low-flow oxygen and bilevel ventilatory support: effects on ventilation during sleep in cystic fibrosis." ]

[ "The effects of supplemental O2 on recovery from supramaximal exercise and subsequent performance remain unknown. If recovery from exercise could be enhanced in individuals with chronic lung disease, subsequent supramaximal exercise performance could also be improved. Recovery from supramaximal exercise and subsequent supramaximal exercise performance were assessed after 10 min of breathing 100% O2 or room air (RA) in 17 cystic fibrosis (CF) patients [25 +/- 10 (SD) yr old, 53% men, forced expired volume in 1 s = 62 +/- 21% predicted] and 17 normal subjects (25 +/- 8 yr old, 59% men, forced expired volume in 1 s = 112 +/- 15% predicted). Supramaximal performance was assessed as the work of sustained bicycling at a load of 130% of the maximum load achieved during a graded maximal exercise. Peak minute ventilation (VE) and heart rate (HR) were lower in CF patients at the end of each supramaximal bout than in controls. In CF patients, single-exponential time decay constants indicated faster recovery of HR (tau HR = 86 +/- 8 and 73 +/- 6 s in RA and O2, respectively, P < 0.01). Similarly, fast and slow time constants of two-exponential equations providing the best fit for ventilatory recovery were improved in CF patients during O2 breathing (tau 1VE = 132.1 +/- 10.5 vs. 82.5 +/- 10.4 s; tau 2VE = 880.3 +/- 300.1 vs. 368.6 +/- 107.1 s, P < 0.01). However, no such improvements occurred in controls. Supramaximal performance after O2 improved in CF patients (109 +/- 6% of the 1st bout after O2 vs. 94 +/- 6% in RA, P < 0.01). O2 supplementation had no effect on subsequent performance in controls (97 +/- 3% in O2 vs. 93 +/- 3% in RA). We conclude that supplemental O2 after a short bout of supramaximal exercise accelerates recovery and preserves subsequent supramaximal performance in patients with CF.", "Repeated bouts of submaximal exercise are an important part of most pulmonary rehabilitation programmes. Patients with moderate-to-severe cystic fibrosis (CF) often demonstrate oxygen desaturation during submaximal exercise, which may limit their ability to participate in these programmes. This study examines whether arterial desaturation contributes to submaximal exercise limitation by testing whether supplemental O2 improves submaximal exercise capacity. Eight patients with CF (mean forced expiratory volume in one second 41% predicted) each underwent two submaximal exercise tests on a bicycle ergometer at 80% of maximal workload. The two tests were identical except for the addition of supplemental O2 (inspiratory O2 fraction 39%) during one of the tests. Exercise duration was significantly longer in the supplemental O2 study versus control (673+/-63 s versus 835+/-99 s). Arterial O2 saturation was also higher in the supplemental O2 study than the control exercise test (96+/-0.3% versus 86+/-1.5%). There was no statistical difference at end exercise between O2 consumption, minute ventilation and heart rate. There was a significant relationship between improvement in exercise capacity and the amount of desaturation during the control exercise test. Results indicate that supplemental oxygen improves submaximal exercise capacity in patients with moderate-to-severe cystic fibrosis. Oxygen therapy may be an important intervention to improve participation and maximise the benefits of pulmonary exercise rehabilitation programmes.", "Patients with cystic fibrosis (CF) and advanced pulmonary disease have pulmonary limitation of exercise, often associated with arterial oxygen desaturation. Improving oxygenation during exercise by providing supplemental oxygen may improve exercise performance in these patients. To test this, we performed graded exercise stress tests in 22 CF patients with severe pulmonary disease (mean PaO2, 64 +/- 2 mm Hg [+/- SE]; PaCO2 46 +/- 2 mm Hg; RV/TLC, 57 +/- 4 percent; FEV1, 38 +/- 4 percent of predicted; FEF25-75%, 13 +/- 2 percent of predicted; median age, 26 years) and compared them to 21 controls (RV/TLC, 27 +/- 4 percent; FEV1, 112 +/- 2 percent of predicted; FEF25-75%, 80 +/- 4 percent of predicted; median age, 29 years). Each subject performed graded exercise stress tests while breathing FIO2 of 0.21 and FIO2 of 0.30. Subjects were blinded to the composition of the inspired gas, and the order of testing was randomized. We found that CF subjects exercised longer, had a higher maximal VO2, higher O2 pulse, and less arterial oxygen desaturation when receiving supplemental O2. Control subjects exercised longer when breathing supplemental O2 but had no significant change in maximal VO2, O2 pulse, or SaO2. Both CF and control subjects had increased end-tidal PCO2 when exercising while breathing supplemental O2. We conclude that CF patients with advanced pulmonary disease have increased exercise tolerance and aerobic capacity when exercising while breathing supplemental O2.", "Progressive deterioration of lung function in cystic fibrosis (CF) patients may lead to significant hypoxaemia and hypercapnia, especially during sleep. The effects of bi-level noninvasive positive pressure nasal mask ventilation (NIPPV) on respiration and sleep were compared to those of low-flow oxygen therapy in six CF patients (mean +/- SD age 22.3 +/- 4.7 yrs, with severe lung disease (forced expiratory volume in one second (FEV1) 29.4 +/- 3.4% predicted). Compared to the control night, NIPPV and oxygen therapy significantly improved overall night-time oxygen saturation during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep stages. However, significant increases in transcutaneous CO2 tension occurred during oxygen therapy, while NIPPV markedly improved alveolar ventilation during all sleep states. Sleep architecture and arousals remained unchanged during NIPPV and oxygen therapy treatment nights. We conclude that noninvasive positive pressure ventilation improves sleep-related hypoxaemia and hypercapnia in severe cystic fibrosis patients without affecting sleep. The long-term compliance and benefits of noninvasive positive pressure ventilation remain unclear.", "Oxygen supplementation may improve exercise tolerance and the physiological response to exercise in cystic fibrosis (CF) patients. Elevated barometric pressure at low altitude is a simple means of increasing the quantity of inspired oxygen. Our objectives were to examine the effect of natural oxygen enrichment (at the Dead Sea, 396 m below sea level) on exercise capacity, and the physiological responses to maximal and submaximal exercise in CF patients. Patients were tested twice: at sea level (barometric pressure, 754 +/- 6 mmHg, mean +/- SD), and at the Dead Sea (barometric pressure, 791 +/- 3 mmHg), in a randomized crossover design. We studied 14 CF patients (6 females, 8 males), aged 15-45 years, with moderate to severe lung disease (mean forced expired volume in 1 sec = 50.0 +/- 11.2% predicted). Tests at each site included resting spirometry, anthropometry, a graded submaximal exercise test, a maximal exercise test on a treadmill, and a 6-min walk test. Tests were performed in identical order at both sites. Tests at the Dead Sea were performed 72 hr after arrival. No differences between sites were observed in lung function at rest. Peak oxygen consumption was significantly improved at the Dead Sea compared with sea level (1.68 +/- 0.73 vs. 1.57 +/- 0.74 l/min, respectively, P = 0.05), along with an improvement in the ventilatory equivalent for oxygen (41.2 +/- 6.3 vs. 46.1 +/- 7.1, respectively, P < 0.05). During submaximal exercise, blood oxygen saturation improved at the Dead Sea compared with sea level at all exercise intensities (P < 0.05). In conclusion, these results suggest that even a brief stay at the Dead Sea area may have physiological benefits for CF patients with moderate to severe lung disease.\n (c) 2006 Wiley-Liss, Inc.", "We determined the effect of nocturnal low-flow oxygen (NLFO) on arterial oxygen saturation (SaO2), transcutaneous PCO2 (TcPCO2), and sleep quality in 10 patients with cystic fibrosis (CF) and severe stable chronic obstructive pulmonary disease (COPD). The patients were studied on 2 nights, 1 with oxygen and 1 with air at 2 L/min. The NLFO had no effect upon sleep quality in our patients. The minimal SaO2 occurred during REM sleep and averaged 79.4%. With NLFO, this improved to 92.7%. The average maximal rise in TcPCO2 was 5.6 mmHg on falling asleep while breathing air; this increased a further 5.1 mmHg with NLFO. Two patients also had obstructive sleep apnea. Their SaO2 improved dramatically with NLFO, with no deterioration of ventilation. In 4 patients, ventilation was measured quantitatively. The only consistent changes during air were an increase in abdominal contribution to tidal volume and a drop in minute ventilation from Stage 3-4 to REM sleep of 26%, almost entirely caused by a drop in breathing frequency. The same changes occurred with NLFO. We conclude that NLFO is effective in alleviating the nocturnal hypoxemia of patients with CF with stable COPD and does not cause clinically important hypercapnia.", "The effect of nocturnal oxygen therapy on mortality and morbidity rates and on progression of disease was tested in a double-blind, randomized trial of 28 subjects with advanced cystic fibrosis. Patients were selected on the basis that their awake arterial oxygen tension was less than 65 mm Hg when they were clinically stable. Oxygen was prescribed in 1 L/min increments to obtain an awake arterial oxygen tension of greater than or equal to 70 mm Hg. Subjects received humidified oxygen or room air from modified concentrators. They were enrolled over a 3-year period and followed for an average (+/- SD) of 26 +/- 9 months. The average number of hours per night of concentrator use was 5.3 +/- 3.2 hours in the air group and 7.0 +/- 1.9 hours in the oxygen group. Over the follow-up period there were four deaths in each group, and oxygen therapy had no significant effect on the frequency of hospitalizations. Progression of disease was ascertained from nutritional status, pulmonary function, blood gas values, exercise ability, and right ventricular ejection fraction response to exercise (as measured by equilibrium-gated radionuclide angiocardiography), and psychologic status was measured by standardized tests of mood, self-esteem, and cognitive function; group comparisons for the first year revealed no significant differences; however, school or work attendance was maintained in the oxygen group but deteriorated in the air group. Clinical signs of cor pulmonale were documented during follow-up in 10 patients in toto, and all lived at least 9 months from the onset of these signs. The lack of association between the onset of these signs and imminent death, or the usefulness of measurements of the maximal oxygen uptake during progressive exercise and the right ventricular ejection fraction response to exercise as prognostic indicators, suggest that death may not be the result of cor pulmonale. We conclude that nocturnal oxygen treatment in patients with cystic fibrosis did not appear to affect mortality rates, the frequency of hospitalizations, or the progression of disease; oxygen use should be instituted only after the development of symptoms related to hypoxemia.", "Fourteen female and 22 male patients with cystic fibrosis (CF), 8 to 29 yr of age, performed two progressive exercise tests to exhaustion on a cycle ergometer, breathing normoxic air (21% O2) for one test, and hyperoxic air (30% O2) for the other test. The order of gas administration was randomized. Minute ventilation (VE), oxygen uptake (VO2), end-tidal CO2 tension (PETCO2), work rate, oxyhemoglobin saturation (SAO2), and heart rate (HR) were measured throughout the tests. The SaO2 of 11 patients at peak exercise was 90% or less (\"Low Sat\" group). The SaO2 of 23 patients remained above 90% throughout the exercise (\"High Sat\" group). Hyperoxic air minimized desaturation during exercise in the Low Sat group to 2 +/- 2% compared to a decrease of 10 +/- 5% with normoxic air. The decrease in saturation was not significant for the High Sat group (1 +/- 1% for both 21% and 30% O2). Peak work rate and VO2 did not differ significantly between normoxic and hyperoxic conditions. However, VE and HR at peak exercise tended to be lower, and PETCO2 was higher during peak exercise with 30% O2 than 21% O2 for both groups. During submaximal exercise, O2 desaturation was diminished and HR was significantly lower with supplemental O2, specifically in the Low Sat group. VE was significantly lower for both groups during submaximal exercise with hyperoxic air. The results suggest that O2 supplementation minimizes O2 desaturation and enables patients with CF to exercise with reduced ventilatory and cardiovascular work.", "We measured ventilation in all sleep stages in patients with cystic fibrosis (CF) and moderate to severe lung disease, and compared the effects of low-flow oxygen (LFO2) and bilevel ventilatory support (BVS) on ventilation and gas exchange during sleep. Thirteen subjects, age 26 +/- 5.9 yr (mean +/- 1 SD), body mass index (BMI) 20 +/- 3 kg/m2, FEV1 32 +/- 11% predicted, underwent three sleep studies breathing, in random order, room air (RA), LFO2, and BVS +/- O2 with recording of oxyhemoglobin saturation (SpO2) (%) and transcutaneous carbon dioxide (TcCO2) (mm Hg). During RA and LFO2 studies, patients wore a nasal mask with a baseline continuous positive airway pressure (CPAP) of 4 to 5 cm H2O. Minute ventilation (V I) was measured using a pneumotachograph in the circuit and was not different between wake and non-rapid eye movement (NREM) sleep on any night. However, V I was reduced on the RA and LFO2 nights from awake to rapid eye movement (REM) (p < 0.01) and from NREM to REM (p < 0.01). On the BVS night there was no significant difference in V I between NREM and REM sleep. Both BVS and LFO2 improved nocturnal SpO2, especially during REM sleep (p < 0.05). The rise in TcCO2 seen with REM sleep with both RA and LFO2 was attenuated with BVS (p < 0.05). We conclude that BVS leads to improvements in alveolar ventilation during sleep in this patient group." ]

[ "11679990", "15004772", "9089994" ]

[ "Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study.", "Randomized trial comparing pulmonary alterations after conventional with venovenous bypass versus piggyback liver transplantation.", "Piggy-back versus conventional technique in liver transplantation: report of a randomized trial." ]

[ "This study aims to determine whether the use of a temporary portocaval shunt (PCS) improves hemodynamic and metabolic evolution during orthotopic liver transplantation (OLT). Preservation of the vena cava during OLT has gained wide acceptance. However, benefits of adding a temporary PCS to the piggyback technique during the anhepatic phase in patients with cirrhosis have not been shown. Eighty patients with cirrhosis were studied prospectively. They were randomly distributed into two groups: patients with a temporary PCS (n = 40) and those without a PCS (n = 40). In all cases, the piggyback technique was used. Hemodynamic profiles and biochemical data during OLT and clinical evolution after OLT were evaluated. Preoperative data were similar in both groups. Surgical time also was similar (403 +/- 77 v 387 +/- 56 minutes; P = .3). Red blood cell requirements were lower in the PCS group (2.3 +/- 2.5 v 3.3 +/- 2.9 units), although differences were not significant. In the PCS group, 45% of patients did not need red blood cell transfusion, whereas in the other group, only 22% were not administered a transfusion (P = .03). During the anhepatic phase, the decrease in cardiac output was lower in the PCS group (-9.6% v -19%; P = .05), whereas diuresis during the anhepatic phase was greater in the PCS group (3.6 +/- 2.97 v 2.1 +/- 1.38 mL/kg/h; P = .005). There were no differences in liver biochemical parameters during the first 3 postoperative days. Nevertheless, creatinine levels increased significantly during this period only in the no-PCS group. The use of a temporary PCS during OLT improves hemodynamic status, reduces intraoperative transfusion requirements, and preserves renal function during and after OLT.", "During the anhepatic phase of conventional liver transplantation (LT), the inferior vena cava (IVC) is cross-clamped and venovenous bypass (VVB) is usually indicated for diversion of IVC and portal blood flow. VVB can theoretically lead to pulmonary complications due to the contact of the blood with the surfaces of the circuit. In the piggyback method, preservation of the IVC avoids VVB. The aim of this study is to compare pulmonary alterations after conventional with VVB versus piggyback LT. Sixty-seven patients were randomized for conventional VVB (n = 34) or piggyback (n = 33) LT. Pulmonary static compliance (C(st)) and Pa(O2)/F(IO2) ratio were measured pre- and post-LT. Chest X-rays were obtained daily from the 1st to the 5th postoperative day. Pre- and post-LT C(st) were 73.4 +/- 36.0 mL/cm H(2)O and 59.7 +/- 22.0 mL/cm H(2)O in the conventional group and 69.1 +/- 20.0 mL/cm H(2)O and 58.7 +/- 27.1 mL/cmH(2)O in the piggyback group. The difference between the two groups was not significant (P =.702). C(st) significantly decreased after LT (P =.008). The pre- and post-LT Pa(O2)/F(IO2) were 455.6 +/- 126.6 mm Hg and 463.1 +/- 105.9 mm Hg in the conventional group and 468.9 +/- 114.1 mm Hg and 483.3 +/- 119.8 mm Hg in the piggyback group. The difference among the two groups was not significant (P = 0.331). There was no significant difference after LT (P =.382). Upon the radiological evaluation, piggyback group presented a higher frequency of pulmonary infiltrates (80.6% vs. 50.0%; P =.025). In conclusion, piggyback LT recipients have a higher rate of pulmonary infiltrates when compared to those operated upon using the conventional VVB method.", "Liver transplantation with preservation of the recipient vena cava (the \"piggy-back\" technique) has been proposed as an alternative to the traditional method. We performed a randomized study on 39 cirrhotic patients, 20 who underwent the piggy-back technique (group 1) and 19 the traditional method using venovenous bypass (group 2) to evaluate the feasibility and true advantages of the piggy-back technique compared to the traditional method. Two patients were switched to the conventional technique due to the presence of a caudate lobe embracing the vena cava in one patient and a caval lesion in the other. Statistically significant differences between the two groups were only found for the warm ischemia time (48.5 +/- 13 min for piggy-back vs 60 +/- 12 min for the conventional method) and for renal failure (zero cases in group 1 vs four cases in group 2). We therefore believe that liver transplantation with the piggy-back technique can easily be performed in almost all cases, and that only a few, specific situations, such as a very enlarged caudate lobe, do not justify its routine use." ]

[ "2139387", "1413183", "8858269", "3177951", "10844161", "12040966", "12236023", "8737630", "8995348", "7064522", "2698902", "4592458", "7822903", "11748952", "8034203", "7037273", "3053942", "7025500", "7368843", "3544968", "6362258", "7046524", "11081989", "2254672" ]

[ "[Calcium dobesilate in the treatment of primary venous insufficiency of the lower limbs. A controlled clinical study].", "[Effect of 0-(beta-hydroxyethyl)-rutoside (Venoruton) on symptomatic venous insufficiency in the lower limbs].", "Leg oedema protection from a buckwheat herb tea in patients with chronic venous insufficiency: a single-centre, randomised, double-blind, placebo-controlled clinical trial.", "A double-blind trial of calcium dobesilate in chronic venous insufficiency.", "Pycnogenol in chronic venous insufficiency.", "Efficacy and safety of a Butcher's broom preparation (Ruscus aculeatus L. extract) compared to placebo in patients suffering from chronic venous insufficiency.", "The efficacy and safety of a coumarin-/troxerutin-combination (SB-LOT) in patients with chronic venous insufficiency: a double blind placebo-controlled randomised study.", "Investigation of the efficacy of oxerutins compared to placebo in patients with chronic venous insufficiency treated with compression stockings.", "Efficacy of Daflon 500 mg in venous leg ulcer healing: a double-blind, randomized, controlled versus placebo trial in 107 patients.", "[On the therapy of so-called leg pains. Controlled double-blind study of the therapeutic efficacy of Daflon].", "Are the phlebotonic properties shown in clinical pharmacology predictive of a therapeutic benefit in chronic venous insufficiency? Our experience with Daflon 500 mg.", "The effect of hydroxyethylrutosides after acute and chronic oral administration in patients with venous diseases. A double-blind study.", "The effect of hydroxyethylrutosides on capillary filtration in moderate venous hypertension: a double blind study.", "A randomised controlled trial of micronised purified flavonoid fraction vs placebo in patients with chronic venous disease.", "Hydroxyethylrutosides in elderly patients with chronic venous insufficiency: its efficacy and tolerability.", "[Centella asiatica extract in venous disorders of the lower limbs. Comparative clinico-instrumental studies with a placebo].", "Clinical evaluation of a venotropic drug in man. Example of Daflon 500 mg.", "A double-blind trial of O-(beta-hydroxyethyl)-rutoside in patients with chronic venous insufficiency.", "[Clinical, placebo-controlled double-blind study of venoruton in the treatment of chronic venous insufficiency. Importance of the selection of patients].", "Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs.", "General practice treatment of symptoms of venous insufficiency with oxerutins. Results of a 660 patient multicentre study in the UK.", "Double-blind clinical and plethysmographic study of calcium dobesilate in patients with peripheral microvascular disorders.", "PYCNOGENOL in chronic venous insufficiency.", "Doxium 500 in chronic venous insufficiency: a double-blind placebo controlled multicentre study." ]

[ "Fourty patients with lower limb chronic venous insufficiency entered a randomised placebo controlled study with calcium dobesilate for one month. Clinical symptoms and plethysmographic parameters were evaluated before and after therapy in all patients. In the group of patients treated with calcium dobesilate we observed an improvement of clinical and instrumental parameters; no changes were found in the placebo group. We observed good tolerance to the drug and no side effects required withdrawal of treatment.", "Forty-three patients recruited from general practice with symptom-producing chronic venous insufficiency in the lower limbs participated in a randomized double-blind clinical trial with Venoruton (300 mg x 3) or a placebo for 28 days. Twenty-eight patients were treated with Venoruton and 19 with a placebo. None of the patients received other forms of treatment for chronic venous insufficiency. No differences were observed between the two groups as regards changes in symptoms (swelling, pain, heaviness, restlessness, itching and cramps) the subjective assessment of the discomfort in the extremities or the circumference of the limbs. Venoruton does not appear to have any effect on chronic venous insufficiency in the lower limbs.", "The efficacy of a buckwheat herb tea was determined in patients with chronic venous insufficiency (CVI) in a single-centre, randomised, double-blind, placebo-controlled clinical trial.\n Sixty-seven male and female patients (22-74 years) with CVI were randomly divided into two groups after a 2-week run-in period. They received either buckwheat herb tea (Fagopyrum esculentum) or a placebo tea for a period of 3 months. The main outcome measure was the lower leg volume determined by ultrasound. Subjective symptoms were assessed by a clinical symptom score system. The femoral vein diameters were measured by B-scan sonography. In a subgroup of patients capillary permeability was determined by cutaneous fluorescence angiography.\n Although the mean partial leg volume did not change in the treatment group (from 2041 to 2073 ml), it increased in the placebo group by 110 ml (from 1972 to 2082 ml) according to intent to treat. The difference between the groups was significant. The subjective clinical symptoms were significantly reduced in both groups. The mean diameters of the femoral veins were reduced and capillary permeability was improved, but neither change was statistically significant. No drug-related adverse effects were observed.\n CVI is a very placebo-sensitive condition. The treatment with buckwheat herb tea is safe and could have a favourable influence on patients with CVI such that further oedema development is prevented.", "Calcium dobesilate was studied in a double-blind trial in 30 normal subjects and in 30 patients with chronic venous insufficiency (CVI). There were no significant alterations in the normal subjects. In patients with CVI the active drug gave significant improvements (p less than 0.01) in the measured volume of the foot and lower limb, in clinical tenderness (p less than 0.05), and in most of the symptoms (including feelings of heaviness, swelling, tiredness, and aching in the lower extremities). Even though the chronic venous insufficiency had existed for an average of fifteen years, a relatively short course of the drug caused considerable, and significant, improvements in a number of signs and symptoms of the disease.", "Forty patients with chronic venous insufficiency (CVI) and varices of the legs were selected and double-blindly randomly assigned to a treatment with Pycnogenol (French maritime pine bark extract), 100 mg x 3/day or a placebo for 2 months, according to a double-blind experimental design. The effects of the treatment were evaluated by scoring the symptomatology with a semi-quantitative scale, and the venous blood flow by means of a hand-held Doppler ultrasound. The tolerability was evaluated by recording the adverse effects and by means of hematology and blood chemistry parameters, before and at the end of the treatment. Pycnogenol treatment induced a significant reduction in subcutaneous edema as well as heaviness and pain in the legs, on both after 30 and 60 days, the evaluation time periods. Approximately 60% of patients treated with Pycnogenol(R) experienced a complete disappearance of edema (the most rapidly disappearing symptom) and pain at the end of the treatment, while almost all the patients reported a reduction in leg heaviness which disappeared in approximately 33% of patients. These changes were statistically significant. No effect was observed in the placebo-treated subjects. No effect on the venous blood flow was observed in either of the experimental groups.", "Extracts from Butcher's broom rhizome (Ruscus aculeatus) have been widely used in the oral treatment of lower leg edema in patients with chronic venous insufficiency. The aim of the present multi-center, double-blind, randomized, placebo-controlled trial was to confirm the efficacy and safety of a ruscus extract (Fagorutin Ruscus Kapseln) according to the latest scientific standards. 166 women suffering from chronic venous insufficiency (Widmer grade I and II, CEAP (Clinical signs, Etiological classification, Anatomic distribution, Pathophysiology) 3-4) were included. The data of 148 patients (30-89 years, 150-182 cm height, 49-97 kg body weight) with a mean disease duration of 14.6 years in the ruscus extract group and 15.1 years in the placebo group were eligible for the intent-to-treat-analysis. The primary parameter was the area under baseline of the leg volume changes over 12 weeks (AUB0-12). Secondary parameters were the changes in circumference of the lower leg and the ankle, changes in subjective symptoms and quality of life, the overall efficacy and tolerability and safety parameters. The study was carried out according to the guidelines for testing drugs for chronic venous insufficiency. There were significant differences between the treatment groups ruscus and placebo for the AUB0-12 (-827 ml x day), for the change of leg volume after 8 and 12 weeks of treatment (-16.5 ml and -20.5 ml), for changes in ankle and leg circumferences after 8 and 12 weeks of treatment, and for the changes in subjective symptoms, heavy tired legs and sensation of tension (week 12). For the changes in the symptoms heavy lower legs, sensation of tension, and tingling sensation a significant positive correlation with the changes in leg volume was shown. Overall assessment of efficacy was significantly better for ruscus extract compared to placebo. Overall tolerability for both treatments was assessed as good and very good. Of all 48 adverse events occurring in both treatment groups, 22 were reported in the ruscus group, one of them was considered to be related to the study medication (unlikely). Considering the study duration of three months it is concluded, that ruscus extract, in the recommended daily dosage according to the German monograph, is a safe and effective treatment for patients suffering from chronic venous insufficiency.", "The objective was to evaluate the oedema-protective effect of a vasoactive drug (coumarin/troxerutin [SB-LOT]) plus compression stockings in patients suffering from chronic venous insufficiency after decongestion of the legs as recommended by the new guidelines.\n 231 patients were randomly assigned medical compression stockings plus SB-LOT (90 mg coumarin and 540 mg troxerutin per day) or medical compression stockings plus placebo for the first 4 weeks and SB-LOT or placebo for the second 12 weeks of the study. The primary efficacy endpoint was the lower leg volume measured by well-established water plethysmometry.\n 226 patients were evaluated. After ceasing compression stockings, an edema protective effect was detected in the SB-LOT-group but not in the controls. Recurrence of leg volume increase was by 6.5 +/- 12.1 ml and by 36.7 +/- 12.1 ml in the SB-LOT and placebo group, respectively (p = 0.0402). The local complaint score and general aspects of quality of life were also superior for the SB-LOT-group (p = 0.0041). Significant differences were also observed with regard to clinical global impression and therapeutic effect. No serious adverse drug reaction or clinically relevant impairment of laboratory parameters occur.\n This study confirms the oedema-protective effect of SB-LOT in chronic venous insufficiency and provides a treatment option for patients who discontinue compression after a short time.", "The aim of this study was to investigate, if the the combined treatment of compression stockings and drug treatment with oxerutins (O-(beta-hydroxyethyl)-rutosides, Venoruton) provides additional benefit for patients with chronic venous insufficiency (CVI) compared to compression treatment alone. Oxerutins belong to the group of oedema protective agents and possess anti-exudative and membrane protective activity. A total of 133 female patients with CVI grade II participated in this double-blind, randomised, multi-centre, parallel-group study with two treatment groups. The whole study lasted for 19 weeks, and consisted of a one week placebo run-in phase, 12 weeks treatment phase, followed by a 6 weeks treatment-free follow-up period. All patients received a basis compression therapy that consisted of standard compression stockings. In order to standardise initial fitting of stockings in this multi-centre setting, stockings were fitted after one week of standard diuretics starting at baseline and then stockings were worn for the following 11 weeks. Patients were randomised to receive oxerutins (2 x 500 mg daily) or matching placebo. Leg volumes (water displacement) and associated subjective symptoms (visula analogue scale) were measured during a placebo run-in period at enrolment (week - 1) and half a week later (week - 1/2), at baseline week 0), at 4, 8, 12 weeks on treatment, and again after a 3- and 6-weeks treatment-free follow-up. The primary efficacy criterion, the area under the baseline from week 0 to week 18 (AUB0-18) of leg volume changes, as measurement of the global change of leg oedema during the study, resulted in a superior reduction of -5589 ml.d for the combined treatment with oxerutins compared to -2101 ml.d for placebo (p = 0.012). The mean change of leg volume compared to baseline after 12 weeks of treatment was -63.9 ml for stockings and oxerutins, and -32.9 ml for the patients who received stockings and placebo (p < 0.05). Oxerutins showed a prolonged effect in the follow-up phase compared to placebo, with mean AUB values for week 12 to week 18 of -1769 ml.d versus -133 ml.d (p < 0.01). The study demonstrated that the combined therapy of compression stockings and drug treatment with oxerutins is significantly superior in reducing leg oedema resulting from chronic venous insufficiency compared to compression treatment alone.", "The objective of this study was to evaluate the efficacy of Daflon 500 mg (Dios)* in venous ulcers. A multicenter, double-blind, randomized, controlled versus placebo (Plac) trial was conducted, with stratification according to the size of ulcer (< or = 10 cm and > 10 cm). The protocol called for a two-month treatment with Dios (one tablet = 450 mg micronized purified Diosmin) or a placebo, two tablets/day, in addition to compression therapy. Evaluations were performed every fifteen days, from D0 to D60. The primary endpoint, in accordance with Alexander House group requirements were: percentage of patients with complete ulcer healing, ie, comparison between Dios and Plac group at D60, and comparison of survival curves in each group between D0 and D60 (log rank test). Secondary endpoints included ulcer surface area assessed by computerized planimetric measurements, qualitative evaluation of ulcers, and symptoms. The patients were 105 men and women ranging in age from eighteen to eighty-five years, with standard compression stocking, who were undergoing standardized local care of ulcer and had no significant arterial disease (ankle/arm systolic pressure index > 0.8). Fifty-three patients received Dios, and 52 received Plac. The 2 groups were well matched for age (m +/- 1 SD = seventy-one +/- eleven years), gender, ulcer size, and associated disorders. Among patients with ulcer size < or = 10 cm (Dios = 44, Plac = 47) a significantly larger number of patients had a complete ulcer healing at two months in the Dios group (n = 14) in comparison with the Plac group (n = 6) (32% vs 13%, P = 0.028) with a significantly shorter time duration of healing (P = 0.037). No difference was shown for the secondary criteria, except for sensation of heavy legs (P = 0.039) and a less atonic aspect of ulcer (P = 0.030) in favor of Dios. Among the 14 patients with ulcer size > 10 cm (Dios = 9, Plac = 5), subjected to a descriptive analysis only, no ulcer healed. This study showed that a two-month course of Daflon 500 mg at a daily dose of two tablets, in addition to conventional treatment, is of benefit in patients with venous ulcer < or = 10 cm by accelerating complete healing.", "nan", "In 3 controlled clinical trials, double blind versus placebo, the activity of Daflon 500 mg, a new micronised flavonoid fraction, has been evaluated on venous tone using venous plethysmography. A double-blind, randomized cross-over Phase II pharmaco-clinical trial has shown that Daflon 500 mg is statistically more effective than placebo on pathological legs, as well as normal legs. In this study, which included 20 patients suffering from post-thrombotic syndrome, Daflon 500 mg decreased: 1) venous capacity (p less than 0.001); 2) venous distensibility (p less than 0.001); 3) venous outflow time, measured by the two parameters total emptying venous time (p less than 0.001) and T2p (p less than 0.001). These modifications have been observed 2 hours after administration without any significant change in T50 outflow, cardiad index, capillary filtration index, blood pressure, cardiac or respiratory rate. The same acute effect of increasing venous tone has been demonstrated in another pharmacoclinical trial, 1 and 2 hours after ingestion in 3 groups of 10 women suffering from venous insufficiency: group I without varicose, group II during pregnancy and group III with a post-thrombotic syndrome. Finally, in a Phase III clinical trial, in 2 parallel groups of 20 patients each with functional chronic venous insufficiency, Daflon 500 mg has been compared to placebo. It was then demonstrated after 1 and 2 months treatment an improvement in the functional symptoms and edema accompanied by a statistically significant increase of the venous tone. (ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "The aim of this study was to evaluate the effect of hydroxyethylrutosides on capillary filtration in subjects with mild to moderate venous incompetence--superficial varicose veins and/or deep venous disease and ankle oedema--using the vacuum suction chamber (VSC) device applied to the internal perimalleolar region and the wheal vanishing (WV) time. Subjects entered in to the study were randomised to receive either hydroxyethylrutosides (1 g twice daily for 4 weeks) or placebo for four weeks. The two groups entering and completing the study were comparable. Microcirculatory parameters (laser-Doppler resting flux, the venoarteriolar response, transcutaneous PO2 and PCO2) remained constant during the four week study in both groups. The WV time, which was comparable in the two groups at the beginning of the study decreased significantly [from a median 55 min (interquartile 955 min), to a median 45 minutes (interquartile 65-40 min) in the treated group, p < 0.01]. No change was observed in the WV time in the placebo group. Subjective symptoms measured with an analogue scale improved following treatment with hydroxyethylrutosides [foot oedema (p < 0.005), ankle oedema (p < 0.001), and paraesthesia (p < 0.01)]; only night cramps were reported less in patients receiving the placebo (p < 0.05). In conclusion, the WV time can be used to assess the beneficial effect of therapy on capillary filtration in subjects with mild-moderate venous hypertension, even after a short period of treatment, and before other microcirculatory parameters change. Furthermore, the changes observed in WV time correlate well with an improvement in patients symptoms.", "to evaluate the efficacy of a micronised purified flavonoid fraction (MPFF) in the treatment of chronic venous disease (CVD).\n prospective double blind, randomised, control study. PATIENTS and\n one hundred and one patients with symptomatic CVD were randomly allocated to treatment for 60 days with either MPFF (51 patients) or placebo (50 patients) 500 mg twice daily. There were 28 men and 73 women, aged 22-65 years (mean age 48 years). No difference regarding age, gender, clinical class or duration of symptoms was recorded between the treatment and placebo groups. A global score for evaluation of symptoms was used. Patients were investigated with plethysmography (foot-volumetry) and duplex-ultrasonography before and after the treatment period. For statistical comparison Cochran-Mantel-Haenszel test, two-sided Student t-test and covariance analysis were used and p<0.05 was regarded significant.\n improvement of the global score of symptoms was reported by 21 patients in the MPFF group and by 16 in the placebo group (N.S.). For the whole groups, no significant differences were recorded before and after treatment regarding foot-volumetric or ultrasonographic parameters. On the other hand, in patients with edema (20 in the MPFF group, 23 in the placebo group) ultrasonographic reflux time was significantly reduced for those in the treatment group (p=0.03). This finding did not correlate to clinical symptoms.\n in this study, MPFF did not change the symptoms of CVD, except night cramps. A secondary finding was reduced reflux times in patients with oedema, although no ultrasonographic or foot-volumetric parameters changed significantly for the whole group. The role of MPFF in treatment of patients with CVD needs to be further analysed in a large population.\n Copyright 2002 Harcourt Publishers Limited.", "The efficacy and tolerability of O-(beta-hydroxyethyl)-rutosides (HR) in elderly patients (aged over 65 years) with chronic venous insufficiency or varicose veins was studied in a multicentre, double-blind, randomised, placebo-controlled trial. Of the 104 patients entered into the trial, data from 102 were available for analysis of tolerability and from 86 for efficacy. Treatment was for 6 months, with monthly examinations. Three different dosages were used due to slight differences in the registered dosage in various countries: (1) 250 mg 4 times daily (1 g/day), UK, n = 19 patients; (2) 300 mg 3 times daily (900 mg/day), FRG and Belgium, n = 55, and (3) 300 mg 4 times daily (1,200 mg/day), The Netherlands, n = 30. Each centre had its own placebo control group. The HR-treated group (n = 41) showed a significantly greater reduction in the total symptom score, 5.7 +/- 2.4 to 2.3 +/- 1.8, than in the placebo group, 4.4 +/- 3.0 to 3.0 +/- 2.4 (p < 0.01). Of the 5 studied symptoms there was also a significant (p < 0.05) improvement in leg cramps, heavy legs and restless legs. No significant differences between the two groups were seen for aching pains and paraesthesia. A small reduction was also seen in ankle and calf circumferences, which became significant at the end of the trial (p < 0.05). Pitting oedema of the leg (p < 0.01) and eczema of the leg (p < 0.05) also improved significantly greater than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "Chronic venous insufficiency (CVI) of the lower limbs is a complex and fluctuating disease by its pathogenic mechanisms and its clinical symptoms. Although symptoms are subjective, they affect the quality of life and socio-professional activity of many patients. This is why convincing demonstration of therapeutic activity of a venotropic drug should be carried out according to strict methodology. Only randomized double-blind controlled trials versus placebo (no reference drugs being available) could demonstrate the activity on condition that they are set up in a protocol, the statistical design of which, is adapted and defined \"a priori\". Inclusion, non inclusion and judgement criteria must be rigorous, taking into account many exogenous and endogenous factors which could have influence on the severity or the change in CVI and on the comparability of groups at the beginning and at the end of the study. Thus, the main risk factors of CVI (heredity, obesity, obstetrical and gynecological history, estroprogestogen treatment, profession, environment, etc.) and the season when the patient is recruited should be taken into account. With respect to all these restraints on methodology, the venotrotopic activity of a flavonoid Daflon 500 mg (2 tablets daily) was demonstrated in 200 patients (174 women, 26 men) with organic CVI (n = 83) or functional CVI (n = 117) treated for two months in two double-blind randomized trials versus placebo. The venotropic activity of Daflon 500 mg, was shown by a significant reduction of CVI signs and symptoms, whether organic or functional, and a significant improvement in venous hemodynamics according to plethysmographic parameters. Good acceptability was observed after medium and long term trials.", "nan", "nan", "Ninety-four patients suffering from venous insufficiency of the lower limbs participated in a multicenter, double-blind versus placebo study. After randomization, they were allotted for a treatment period of two months to one of three groups: TECA 120 mg/day, TECA 60 mg/day, or placebo. A significant difference (p less than 0.05) in favor of TECA was shown for the symptoms of heaviness in the lower limbs and edema, as well as for the overall evaluation by the patient. The venous distensibility measured by a mercury strain gauge plethysmograph at three occlusion pressures was improved for the TECA groups but aggravated for the placebo group.", "nan", "nan", "The aim of out study was to investigate the efficacy of Pycnogenol - a French maritime pine bark extract - in the treatment of chronic venous insufficiency (CVI). The study consisted of a double-blind phase - in which 20 patients were recruited and randomly treated with placebo or Pycnogenol (100 mg 2 3/day for 2 months) - and an open phase - in which other 20 patients were treated with Pycnogenol at the same dose schedule. In total, 40 patients were enrolled; 30 of them were treated with Pycnogenol and 10 with placebo. Pycnogenol significantly improved the legs' heaviness and subcutaneous edema; the venous pressure was also significantly reduced by the Pycnogenol treatment, thus adding further clinical evidence to its therapeutic efficacy in patients with CVI. Pycnogenol was effective, probably by either stabilizing the collagenous subendothelial basal membrane or scavenging the free radicals, or by a combination of these activities. Clinically, capillary leakage, perivascular inflammation and subcutaneous edema were all reduced. The safety of use of Pycnogenol is demonstrated by the lack of side effects or changes in blood biochemistry and hematologic parameters. Pycnogenol can be therefore recommended both for prevention and treatment of CVI and related veno-capillary disturbances.", "The aim of this double-blind placebo-controlled study was to evaluate the therapeutic efficacy of Doxium in chronic venous insufficiency (CVI). 225 patients were treated randomly for 4 weeks with 1.5 g (3 capsules/day) of Doxium or placebo. The evolution of the leg oedema was determined by measuring calf and ankle circumferences. Pain and discomfort were assessed by visual analogue scale. The results show that at the end of the trial, all the examined parameters (leg oedema, pain, day and night cramps, discomfort, heavy legs, paresthesia and restless legs) were significantly more improved in the Doxium group than in the placebo group: the leg volume was diminished by 3.8% in the Doxium group compared to 1.2% in the placebo (p less than 0.005). The overall assessment by the physicians showed an improvement in 82% of the Doxium-treated patients compared to 42% of the placebo group (p less than 0.0001). The tolerance of the treatment was comparable in both groups." ]

[ "8735578", "7946257", "2167107", "11534537", "7654128" ]

[ "Clomipramine treatment for self-injurious behavior of individuals with mental retardation: a double-blind comparison with placebo.", "Opioid antagonist effects on self-injury in adults with mental retardation: response form and location as determinants of medication effects.", "An orally administered opiate blocker, naltrexone, attenuates self-injurious behavior.", "Sequential analysis of the effects of naltrexone on the environmental mediation of self-injurious behavior.", "Failure of naltrexone hydrochloride to reduce self-injurious and autistic behavior in mentally retarded adults. Double-blind placebo-controlled studies." ]

[ "The efficacy of the serotonin (5-HT) uptake inhibitor clomipramine in the treatment of self-injurious behavior (SIB) was tested in individuals with severe and profound mental retardation. Six of the 8 subjects who completed a double-blind, placebo-controlled crossover trial exhibited a clinically significant improvement (50% or greater reduction from placebo) in the frequency of SIB. Clomipramine treatment was also associated with improvement in SIB intensity, frequency of stereotypy and compulsions, teacher ratings of stereotypy and social withdrawal, and frequency of staff intervention required for problem behaviors. Adverse effects (seizure and tachycardia/agitation) occurred in 2 of the 8 subjects. These results represent the first controlled trial of a 5-HT uptake inhibitor in the treatment of SIB in mental retardation.", "The opioid antagonist naltrexone was administered to 8 adults with severe or profound mental retardation and extensive histories of self-injurious behavior. Five-minute behavioral samples were observed randomly out of every hour from 8 a.m. through 3 p.m., Monday through Friday, for four 2-week phases (baseline, placebo, 50 mg, and 100 mg). During naltrexone administration, there were fewer days with frequent head-banging and self-biting, whereas there were more days on which blows to the head or self-biting were infrequent. Self-injurious participants slept 1.38 hours less per night during baseline, which was unaffected by naltrexone.", "Several recent reports have indicated that opioid blockers are effective in attenuating self-injurious behavior (SIB). In the present study, four patients with SIB were challenged with four fixed doses (0, 25, 50, 100 mg) of naltrexone. In a double-blind procedure, all patients received each dose on a different week as determined by latin square design. Naltrexone was given on Monday and Wednesday of each week, and patients were videotaped daily for 10 minutes in the morning and afternoon. The tapes were scored for incidents of SIB, stereotypy, and activity, with interrater reliability of 0.93. The Conners Teacher Rating Scale was administered by staff in the morning and afternoon each day. The Vineland was completed each week (Thursday). All patients had decreased SIB when treated with naltrexone. Three patients decreased their SIB as dose of naltrexone increased. There were no consistent effects of naltrexone on stereotypy, activity, or performance on the Conners or the Vineland. These results suggest that endogenous opioids are implicated in SIB and that naltrexone is a powerful tool for examination of this treatment-resistant behavior.", "Accumulated evidence shows that biology and the environment can mediate self-injurious behavior (SIB) in persons with mental retardation. Whether pharmacological treatment alters the environmental mediation of self-injury is unclear. Opioid antagonist effects on sequential dependencies for self-injury were studied in the context of experimental single-subject double-blind placebo-controlled designs. Direct observational data were collected for 4 adult subjects in real time on daily rate of SIB and staff interactions. Clinically significant reductions (i.e., > or = 33%) in SIB rate were observed for 3 of the 4 subjects. For all subjects, the magnitude of the sequential dependency between staff behavior and self-injury was significantly greater during treatment with naltrexone than during treatment with a placebo. Results are discussed in relation to behavioral mechanisms of action regulating medication effects for self-injury.", "It is hypothesized that self-injurious behavior (SIB) and symptoms of autism may be due to overactivity in some opioid systems in the brain. We examined the efficacy and safety of naltrexone hydrochloride, an opioid antagonist, in the treatment of SIB and autism in mentally retarded adults.\n Thirty-three mentally retarded adults with autism and/or SIB participated in double-blind, placebo-controlled crossover studies. Active treatment was first a single 100-mg dose of naltrexone hydrochloride. Subsequently, 19 subjects were treated with 50 mg/d and 14 with 150 mg/d of naltrexone hydrochloride for 4 weeks. The outcome was assessed by means of direct observations (n = 11) and on the basis of scores on a list of target behaviors, the Aberrant Behavior Checklist, and the Clinical Global Impression Scale.\n Thirty-two subjects (seven with autism, 16 with autism and SIB, and nine with SIB) completed the trial. Naltrexone treatment failed to have therapeutic effects on SIB and autism. On the contrary, naltrexone increased the incidence of stereotypic behavior on the Aberrant Behavior Checklist, and the care staff evaluated the effect of the 50-mg/d treatment as being significantly worse than that of the placebo treatment as measured by the Clinical Global Impression Scale.\n Our findings suggest that naltrexone has no clinical value for a broad group of mentally retarded subjects with SIB and/or autism." ]

[ "22619027", "21210134", "16835006", "16084880" ]

[ "Efficacy of low-dose hCG in late follicular phase in controlled ovarian stimulation using GnRH agonist protocol.", "The effect of low dose human chorionic gonadotropin on follicular response and oocyte maturation in PCOS patients undergoing IVF cycles: a randomized clinical trial of efficacy and safety.", "Controlled ovarian stimulation with exclusive FSH followed by stimulation with hCG alone, FSH alone or hMG.", "Efficacy of low-dose human chorionic gonadotropin alone to complete controlled ovarian stimulation." ]

[ "Safe, simple and cost-effective protocol is an important goal in ART cycles. The aim of this prospective study was whether administration of low-dose hCG in late follicular phase can be used clinically to replace gonadotropin administration in GnRH long protocol.\n 122 patients who were candidates for ART enrolled the study and randomly divided into two groups. The control group (n = 62) received standard long protocol and gonadotropin administration continued until the day of hCG injection (10,000 IU) for final follicular maturation. The study group (n = 60) received GnRH long protocol and when at least ≥6 follicles with mean diameter ≥12 mm were observed in both ovaries, hMG was displaced by 200 IU per day of hCG until final follicular maturation.\n There were no significant differences in age, basal FSH, infertility duration and infertility etiology between two groups. There were no statistically significant differences between two groups regarding chemical pregnancy, clinical pregnancy, ongoing pregnancy, and abortion per cycle (50, 40, 40, and 20 % in study group vs. 45.2, 35.5, 35.5, and 21.4 % in control group, respectively). Mean dose of used gonadotropins was significantly higher in control group than that in the study group (2,524 ± 893 IU in control group and 1,439 ± 433 IU in study group) (p = 0.000).\n According to our data, we recommend the use of low-dose hCG in GnRH long protocol because of lower doses of used gonadotropins.", "To compare the efficacy of two regimens of low dose human chorionic gonadotropin (hCG) on follicular response and oocyte maturation in women with polycystic ovarian syndrome (PCOS).\n Ninety women with PCOS who underwent assisted reproduction were eligible for this controlled, prospective, randomized study. Our trial was performed at Royan Institute Reproductive Research Center over a 24-month period. Ovarian stimulation in all groups was initiated with recombinant FSH, 150 IU daily. The dose and duration of FSH treatment were adjusted by monitoring follicular development with ultrasound and estradiol levels. Patients were randomized using a block randomization technique which assigned them to three groups: group A (control group) continued r-FSH until oocyte retrieval. In group B, r-FSH was reduced to 75 IU once the lead follicle reached 14 mm in mean diameter and low dose hCG (100 IU/day) was initiated. In group C, r-FSH was discontinued and low dose hCG (200 IU/day) was begun when the lead follicle reached 14 mm in mean diameter. The main outcome measure was follicular response and oocyte maturation.\n As compared to the FSH only group, groups which were given low dose hCG had lower gonadotropin consumption and fewer immature oocytes than the control group. No women in the low dose hCG groups developed severe ovarian hyper-stimulation syndrome. Fertilization, implantation and pregnancy rates were similar in the three groups.\n A combination of FSH and low dose hCG improved oocyte maturity and preserved outcomes with improved safety and lowered cost.", "To assess if low-dose hCG is similar to hMG and to rFSH in the late follicular phase.\n In a prospective randomized controlled trial, 51 patients undergoing controlled ovarian stimulation received ovarian priming with rFSH and then received hCG (200 IU/day) (hCG group, n=17), hMG (225 IU/day) (hMG group, n=17) or rFSH (200 IU/day) (FSH group, n=17) in the late stage of follicular development. Parameters of follicular response and serum estradiol, progesterone and testosterone levels were assessed.\n Pre-ovulatory ovarian follicle occurrence and length of treatment were similar among the three treatment groups. Serum progesterone level on the day of pre-ovulatory hCG was significantly higher in the hCG group than in the hMG or rFSH group. Clinical pregnancy rates were similar for all groups. The total cost of treatment was significantly lower for the hCG group than for the groups supplemented with hMG or rFSH.\n LH in the form of low-dose hCG during the late follicular phase induced the same follicular pattern as hMG and rFSH after ovulation induction. The procedure using hCG produced pregnancy rates similar to those obtained using hMG and rFSH, even though the patients showed higher serum progesterone levels on the hCG day.", "To prove that low-dose hCG alone can be clinically used to replace FSH-containing gonadotropins to complete controlled ovarian hyperstimulation (COH).\n Controlled, prospective, randomized study.\n Academic center.\n Infertile patients who are candidates for assisted reproduction.\n Patients received [1] recombinant FSH or hMG throughout COH (group A); [2] ovarian priming with recombinant FSH/hMG followed by low-dose hCG (200 IU/day) alone (group B).\n Medication consumption; daily serum and follicular fluid (FF) measurements of LH, FSH, hCG, E2, P, T, and androstenedione (A); number and size of follicles; intracytoplasmic sperm injection (ICSI) outcome.\n In group B: [1] duration and dose of recombinant FSH/hMG administration were reduced; [2] preovulatory serum hCG, E2, and T were higher, whereas FSH was lower; [3] FF hCG, E2, T levels, and E2/T, E2/A, and E2/P ratios were higher, whereas A was lower; [4] small but not large preovulatory follicles were reduced; [5] fertilization rates were higher; and [6] serum and FF P levels, and ICSI outcome did not differ.\n Low-dose hCG alone in the late COH stages: [1] reduced recombinant FSH/hMG consumption whereas ICSI outcome was comparable to traditional COH regimens; [2] stimulated follicle growth and maturation independent of FSH administration; [3] was associated with a reduced number of small preovulatory follicles; [4] did not cause premature luteinization; [5] resulted in a more estrogenic intrafollicular environment." ]

[ "19232601", "14672467", "11421517", "15453897", "12865375", "12867764", "17034605", "9339085", "19361800" ]

[ "A new pelvic muscle trainer for the treatment of urinary incontinence.", "Predictors of outcome in the behavioral treatment of urinary incontinence in women.", "Comparative analysis of biofeedback and physical therapy for treatment of urinary stress incontinence in women.", "The effect of home biofeedback training on stress incontinence.", "Effect of behavioral training with or without pelvic floor electrical stimulation on stress incontinence in women: a randomized controlled trial.", "Biofeedback and pelvic floor exercises for the rehabilitation of urinary stress incontinence.", "A randomized controlled trial of the effectiveness of pelvic floor therapies for urodynamic stress and mixed incontinence.", "Behavioral treatment of exercise-induced urinary incontinence among female soldiers.", "The effectiveness of pelvic floor exercises, digital vaginal palpation and interpersonal support on stress urinary incontinence: an experimental study." ]

[ "To describe a new device for home treatment of urinary incontinence (UI) by comparing 3 conservative techniques and monitoring compliance and performance.\n Thirty-two patients with UI were allocated to 1 of 3 intervention groups: pelvic floor muscle exercises (PFME; n=11) alone; PFME combined with biofeedback (n=10); or PFME combined with electrical stimulation (n=11). The outcomes assessed were: changes in quality of life score (QLS), urodynamic and perineometric parameters, episodes of urine loss, subjective assessment of improvement, and actual compliance and performance with treatment.\n Increased pelvic muscle contraction strength (P<0.05), improvement in QLS (P<0.02), and fewer episodes of urine leakage were observed in all 3 groups (P<0.05). Compliance was similar among the groups (P=0.201).\n All 3 techniques were effective for home treatment of UI, with significant control of symptoms and improved quality of life. The device effectively monitored compliance and performance of exercises.", "To identify predictors of outcome of a multicomponent behavioral training program for urge and stress incontinence in women.\n This report is a secondary analysis of data from three prospective, randomized, clinical trials testing behavioral interventions for urinary incontinence. Participants were a volunteer sample of 258 ambulatory, nondemented, community-dwelling women, aged 40-92 years, with stress, urge, or mixed urinary incontinence. Participants received 8 weeks (four visits) of multicomponent behavioral training in each study. The relationship between a number of variables and treatment success were explored by univariate and multivariable logistic regression analyses.\n Successful treatment of predominantly urge incontinence (75% reduction of incontinent episodes as recorded on bladder diary) was associated with not wearing any form of protection for incontinence (P = .045; 95% confidence interval [CI] .282, .987). Achieving total continence (100% reduction) was associated with fewer incontinent episodes at baseline (P < .001; 95% CI .138, .557), previous surgery for incontinence (P = .021; 95% CI 1.169, 6.543), and lower education level (P = .022; 95% CI .175, .871). Successful treatment of predominantly stress incontinence (75% reduction) was related to not having previous evaluation or treatment for incontinence (P = .001; 95% CI .026, .415), and fewer incontinent episodes on baseline bladder diary (P = .026; 95% CI .210, .907). Outcomes were not associated with age, race, type of incontinence, or a number of other variables reflecting medical history, obstetric history, medications, pelvic examination, body mass index, urodynamic parameters, or psychological distress.\n Aside from indicators of severity and previous treatment, there were few associations between baseline clinical variables and outcome of behavioral treatment.", "To compare the effectiveness of an intensive group physical therapy program with individual biofeedback training for female patients with urinary stress incontinence.\n Randomized study of two therapeutic interventions consisting of a specific physical therapy program (PT) or biofeedback training (BF) daily for 4 wk, followed by a 2-mo, unsupervised home exercise program in both groups in an outpatient clinic of a large university hospital. Forty women, referred by gynecologists for nonoperative treatment of genuine stress incontinence of mild-to-moderate severity, were included. Measurements of daytime/nocturnal urinary frequency and subjective improvement of incontinence were the main outcome measures at initial presentation, after completion of the therapy program, and at follow-up after 3 mo. Standardized examinations of digital contraction strength, speculum tests, and manometric measurements were documented as secondary outcome measures.\n In the PT group, the daytime urination frequency decreased 22% after 4 wk of therapy and 19% after 3 mo (P < 0.05) from baseline. The nocturnal urination frequency was reduced by 66% after 4 wk of therapy and 62% after 3 mo (P < 0.001). In the BF group, the daily urination frequency decreased 10% after 4 wk of therapy and 5% after 3 mo (P > 0.05). The nocturnal urination frequency declined 36% after 4 wk of therapy and 66% after 3 months (P < 0.05). Subjective assessment after 3 mo showed that in the PT group, 28% of patients were free of incontinence episodes, 68% reported improved symptoms (incontinence episodes improved by >50%), and 4% were unchanged. In the BF group, 62% were free of incontinence episodes, and 38% were improved. Results of the digital contraction strength assessments, speculum tests, and manometric measurements showed statistically significant improvement in all variables in both groups after 3 months.\n Four weeks of both intensive group physical therapy or individual biofeedback training followed by an unsupervised home exercise program for 2 mo are effective therapies for female urinary stress incontinence and result in a significantly reduced nocturnal urinary frequency and improved subjective outcome. Only group physical therapy resulted in reduced daytime urinary frequency. BF therapy resulted in a better subjective outcome and higher contraction pressures of the pelvic floor muscles.", "To compare the effectiveness of pelvic floor training (PFT) with the aid of a home biofeedback device to PFT alone for urodynamic stress urinary incontinence (SUI) in women after a 1-year follow-up.\n A randomized study comparing two conservative interventions was conducted in an outpatient clinic of a university hospital. Thirty-five consecutive women were randomized to either the PFT with home biofeedback group or the PFT alone group. The intensive training period lasted 12 weeks. After 1 year, 33 women could be evaluated according to the protocol. At the 1-year visit pelvic floor muscle activity was measured and the need for surgical intervention was evaluated. Logistic multivariate analysis was used to predict response to the PFT.\n In the home biofeedback training group 11/16 (68.8%) avoided surgery vs. 10/19 (52.6%) in the PFT alone group. The difference was not statistically significant. In the nonoperated home biofeedback group the increase in pelvic floor muscle activity (p = 0.005 in supine, p = 0.005 in standing) and the decrease in leakage index (p = 0.05) was significant after 12 weeks and pelvic floor activity remained constant. By contrast, in the nonoperated PFT group the increase in pelvic floor muscle activity after 12 weeks predicted a good result for conservative treatment.\n This randomized controlled trial suggests that the home biofeedback method in PFT has a good success rate of 68.8%. The change achieved in leakage index after 12 weeks of training predicted an effective outcome for conservative treatment.", "Pelvic floor electrical stimulation (PFES) has been shown to be effective for stress incontinence. However, its role in a multicomponent behavioral training program has not been defined.\n To determine if PFES increases efficacy of behavioral training for community-dwelling women with stress incontinence.\n Prospective randomized controlled trial conducted from October 1, 1995, through May 1, 2001, at a university-based outpatient continence clinic in the United States.\n Volunteer sample of 200 ambulatory, nondemented, community-dwelling women aged 40 to 78 years with stress or mixed incontinence with stress as the predominant pattern; stratified by race, type of incontinence (stress only vs mixed), and severity (frequency of episodes).\n Patients were randomly assigned to 8 weeks (4 visits) of behavioral training, 8 weeks (4 visits) of the behavioral training plus home PFES, or 8 weeks of self-administered behavioral treatment using a self-help booklet (control condition).\n Primary outcome was percentage reduction in the number of incontinent episodes as documented in bladder diaries. Secondary outcomes were patient satisfaction and changes in quality of life.\n Intention-to-treat analysis showed that incontinence was reduced a mean of 68.6% with behavioral training, 71.9% with behavioral training plus PFES, and 52.5% with the self-help booklet (P =.005). In comparison with the self-help booklet, behavioral training (P =.02) and behavioral training plus PFES (P =.002) were significantly more effective, but they were not significantly different from each other (P =.60). The PFES group had significantly better patient self-perception of outcome (P<.001) and satisfaction with progress (P =.02). Significant improvements were seen across all 3 groups on the Incontinence Impact Questionnaire but with no between-group differences.\n Treatment with PFES did not increase effectiveness of a comprehensive behavioral program for women with stress incontinence. A self-help booklet reduced incontinence and improved quality of life but not as much as the clinic-based programs.", "We investigated the effectiveness of pelvic floor muscle (PFM) exercises or biofeedback for the treatment of urinary stress incontinence (USI). Fifty patients with USI were included in this randomized, controlled, prospective study. Twenty patients were taught PFM exercises via digital palpation and instructed to perform regularly as home program. The second group of 20 patients had PFM exercises via biofeedback three times a week for 2 months. The third group of 10 patients did not have any exercises. The patients were evaluated via pad test, perineometry, digital palpation based PFM strength, incontinence frequency, and visual analog scale based social activity index prior to and 8 weeks after the treatment. The first two groups had significant improvement in USI with respect to the control group (p < 0.001). The rise in PFM strength with perineometry of the biofeedback group was higher than in the digital palpation group after treatment (p < 0.001). PFM exercises are effective for the treatment of USI; the biofeedback method revealed better PFM strength results with respect to digital palpation.\n Copyright 2003 S. Karger AG, Basel", "To assess the efficacy and cost-effectiveness of pelvic floor muscle therapies (PFMT) in women aged > or = 40 years with urodynamic stress incontinence (USI) and mixed UI.\n In a three-arm randomized controlled trial in Leicestershire and Rutland UK, 238 community-dwelling women aged > or = 40 years with USI in whom previous primary behavioural intervention had failed were randomized to receive either intensive PFMT (79), vaginal cone therapy (80) or to continue with primary behavioural intervention (79) for 3 months. The main outcome measure was the frequency of primary UI episodes, and secondary measures were pad-test urine loss, patient perception of problem, assessment of PF function, voiding frequency, and pad usage. Validated scales for urinary dysfunction, and impact on quality of life and satisfaction were collected at an independent interview.\n All three groups had a moderate reduction in UI episodes after intervention but there was no statistically significant difference among the groups. There were marginal improvements in voiding frequency for all groups, with no statistically significant difference among them.\n In women who have already had simple behavioural therapies (including advice on PFM exercises) for urinary dysfunction, the continuation of these behavioural therapies can lead to further improvement. The addition of vaginal cone therapy or intensive PFMT does not seem to contribute to further improvement. The improvement in pelvic floor function was significantly greater in the PFMT arm than in the control arm although this did not translate into changes in urinary symptoms.", "One-third of 450 female soldiers surveyed indicated that they experienced problematic urinary incontinence during exercise and field training activities. The other crucial finding of this survey was probably that 13.3% of the respondents restricted fluids significantly while participating in field exercises. Although only 5.3% of respondents felt that their urine leakage had a significant impact on their regular duties, it is obvious that many more are sufficiently worried about leakage to put themselves at significant risk for dehydration-related injuries. This study tested whether behavioral interventions effective among older people could help younger soldiers. Thirty-nine female soldiers reporting exercise-induced urinary incontinence underwent urodynamic assessments of bladder capacity, urethral closure pressure, and detrusor contraction pressures as well as a symptom questionnaire before and after therapy. They were stratified by diagnosis of physical stress incontinence or mixed urge/stress incontinence and randomized into two groups. Twenty-three participants performed pelvic muscle exercises with urethral biofeedback for 8 weeks, and 16 participants performed pelvic muscle exercises alone. Patient reports as well as the post-treatment examinations indicated that all subjects improved significantly. Only five subjects in the biofeedback/exercise and three in the exercise-only group desired further treatment. All subjects initially diagnosed with detrusor dysfunction had normal readings at the end of the study. Thus, behavioral treatments can be effective against exercise-induced urinary incontinence among most female soldiers.", "The objective of this study is to examine if interpersonal support and digital vaginal palpation (DVP) as part of the pelvic floor muscle exercise (PFME) training is more effective for stress urinary incontinence (SUI) than PFME with a printed handout instruction.\n 108 women who presented to the family medicine outpatient clinic without having urine leakage as a chief complaint were selected. They were randomized to either the group who received interpersonal support and DVP as part of the PFME training (experimental group), or the group who received PFME with a printed handout instruction (control group). The effects were assessed with 1-h pad tests.\n A total of 99 patients (50 experimental, 49 control) completed the study. The patients' mean age was 55.35+/-9.60 years, ranging from 20 to 80 years. All patients without urinary leakage listed as a chief complaint exhibited more or less urine leakage during the 1-h pad test. A significant decrease in the weight of 1-h pad test from baseline was observed in the experimental group (p<0.001) compared to the control group (p=0.514).\n Interpersonal support and DVP as part of the PFME training is more effective than PFME with a printed handout instruction. PFME, performed correctly and consistently, is effective even in patients who have very few symptoms of SUI." ]

[ "12390384", "7997018", "11870500", "7736883" ]

[ "Ranitidine as adjuvant treatment in colorectal cancer.", "Short-course cimetidine and survival with colorectal cancer.", "Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells.", "Cimetidine as an adjuvant treatment in colorectal cancer. A double-blind, randomized pilot study." ]

[ "Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated.\n Patients scheduled for elective resection of primary tumours were consecutively included in a randomized double-blind placebo-controlled clinical study designed to evaluate the effect of ranitidine on survival. Before skin incision ranitidine 100 mg or placebo was given intravenously twice daily followed by oral ranitidine 150 mg or placebo twice daily for 5 years. Adjuvant cytotoxic or radiation therapy was not given. An observer-blinded interim analysis performed after 40 months showed that there was no effect of ranitidine on overall survival, and the study was discontinued in accordance with the protocol. The patient cohort has been followed continuously without loss of any patient, and a final statistical analysis was performed on an intention-to-treat basis after more than 5 years; this included a subgroup analysis of perioperative blood transfusion and postoperative infectious complications.\n The median observation period of the 740 patients included was 6.8 (range 5.4-7.9) years. A univariate analysis of all 740 patients and of the subgroup of 560 who underwent curative resection showed no significant effect of ranitidine on survival. Furthermore, ranitidine had no survival benefit in curatively resected patients who received a perioperative blood transfusion (n = 358), but it improved the survival of non-transfused patients (n = 202; hazard ratio (HR) 0.6 (95 per cent confidence interval (c.i.) 0.4 to 0.9), P = 0.02) and of non-transfused patients who did not develop postoperative infectious complications (n = 170; HR 0.6 (95 per cent c.i. 0.4 to 0.9), P = 0.01). In multivariate analysis of patients who had a curative resection, including Dukes' stage, age, gender, tumour location, blood transfusion, postoperative infectious complications and treatment, ranitidine still had an independent, beneficial effect on survival (HR 0.6 (95 per cent c.i. 0.4 to 1.0), P = 0.04) within the subgroup of patients who did not receive perioperative blood transfusion and did not develop postoperative infectious complications.\n Ranitidine may prolong the survival of patients who undergo curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications.", "nan", "Cimetidine has been shown to have beneficial effects in colorectal cancer patients. In this study, a total of 64 colorectal cancer patients who received curative operation were examined for the effects of cimetidine treatment on survival and recurrence. The cimetidine group was given 800 mg day(-1) of cimetidine orally together with 200 mg day(-1) of 5-fluorouracil, while the control group received 5-fluorouracil alone. The treatment was initiated 2 weeks after the operation and terminated after 1 year. Robust beneficial effects of cimetidine were noted: the 10-year survival rate of the cimetidine group was 84.6% whereas that of control group was 49.8% (P<0.0001). According to our previous observations that cimetidine blocked the expression of E-selectin on vascular endothelium and inhibited the adhesion of cancer cells to the endothelium, we have further stratified the patients according to the expression levels of sialyl Lewis antigens X (sL(x)) and A (sL(a)). We found that cimetidine treatment was particularly effective in patients whose tumour had higher sL(x) and sL(a) antigen levels. For example, the 10-year cumulative survival rate of the cimetidine group with higher CSLEX staining, recognizing sL(x), of tumours was 95.5%, whereas that of control group was 35.1% (P=0.0001). In contrast, in the group of patients with no or low levels CSLEX staining, cimetidine did not show significant beneficial effect (the 10-year survival rate of the cimetidine group was 70.0% and that of control group was 85.7% (P=n.s.)). These results clearly indicate that cimetidine treatment dramatically improved survival in colorectal cancer patients with tumour cells expressing high levels of sL(x) and sL(a).\n Copyright 2002 The Cancer Research Campaign", "To evaluate the influence of a H2 receptor antagonist (cimetidine) on survival in patients with colorectal carcinoma, a randomized, controlled pilot study was performed in three university hospitals in Copenhagen, Denmark.\n A total of 192 patients, who had undergone a resection or an exploratory operation for adenocarcinoma of the colon or rectum between May 1988 and May 1991, were enrolled in the study. After a median observation time of 40 months, outcome was noted for each patient concerning cancer-specific mortality rate.\n In patients operated with curative intent (n = 148), no difference was found in cancer-specific mortality between the two treatments. However, a tendency toward reduction in mortality rate was found in patients with curatively operated Dukes Stage C carcinoma (P = 0.11, log-rank test; difference, 29 percent; 90 percent confidence interval, 2 to 57 percent) in the cimetidine-treated group. In patients with disseminated disease no total difference was found between the two treatment groups.\n Cimetidine does not seem to reduce mortality in patients with colorectal cancer, but there seems to be a tendency toward a survival benefit in patients undergoing surgery for Dukes Stage C carcinoma. Results seem to justify trials in this patient category to reveal a benefit of H2 receptor antagonists in adjuvant therapy of colorectal carcinoma." ]

[ "11706485", "16707509", "9236651", "12202439", "15760312", "7815886" ]

[ "[Curettage or not after spontaneous abortion?].", "Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial).", "Randomised trial of expectant versus surgical management of spontaneous miscarriage.", "Management of miscarriage: a randomized controlled trial of expectant management versus surgical evacuation.", "A randomised trial of surgical, medical and expectant management of first trimester spontaneous miscarriage.", "Expectant management of first-trimester spontaneous abortion." ]

[ "In most cases of miscarriage, standard procedure has until recently been surgical revision of the uterine cavity.\n 94 women with first trimester miscarriage were randomized to surgical revision (n = 48) or expectation (n = 46) after informed consent. Women with unacceptable pain or bleeding, or uterine contents of more than 20 mm diameter on sonography were not included. The patients were followed up seven to ten days later with gynaecological examination, sonography, and determination of levels of haemoglobin, leukocytes, C-reactive protein and HCG.\n In the revision group there were no operative complications, no cases of infection, and no unscheduled consultations. Mean duration of bleeding was 4.8 days (range 1-11 days). In the observation group there were no cases of infection, surgical revision was carried out in seven patients, and there were six unscheduled consultations. Mean duration of bleeding was 7.3 days (range 2-27 days). The women undergoing surgical revision had less pain and bleeding.\n Women with first trimester miscarriage may safely be observed without surgical revision but may have somewhat more pain and more vaginal bleeding than if revision is carried out.", "To ascertain whether a clinically important difference exists in the incidence of gynaecological infection between surgical management and expectant or medical management of miscarriage.\n Randomised controlled trial comparing medical and expectant management with surgical management of first trimester miscarriage.\n Early pregnancy assessment units of seven hospitals in the United Kingdom.\n Women of less than 13 weeks' gestation, with a diagnosis of early fetal demise or incomplete miscarriage.\n Expectant management (no specific intervention); medical management (vaginal dose of misoprostol preceded, for women with early fetal demise, by oral mifepristone 24-48 hours earlier); surgical management (surgical evacuation).\n Confirmed gynaecological infection at 14 days and eight weeks; need for unplanned admission or surgical intervention.\n 1200 women were recruited: 399 to expectant management, 398 to medical management, and 403 to surgical management. No differences were found in the incidence of confirmed infection within 14 days between the expectant group (3%) and the surgical group (3%) (risk difference 0.2%, 95% confidence interval - 2.2% to 2.7%) or between the medical group (2%) and the surgical group (0.7%, - 1.6% to 3.1%). Compared with the surgical group, the number of unplanned hospital admissions was significantly higher in both the expectant group (risk difference - 41%, - 47% to - 36%) and the medical group (- 10%, - 15% to - 6%). Similarly, when compared with the surgical group, the number of women who had an unplanned surgical curettage was significantly higher in the expectant group (risk difference - 39%, - 44% to - 34%) and the medical group (- 30%, - 35% to - 25%).\n The incidence of gynaecological infection after surgical, expectant, and medical management of first trimester miscarriage is low (2-3%), and no evidence exists of a difference by the method of management. However, significantly more unplanned admissions and unplanned surgical curettage occurred after expectant management and medical management than after surgical management. TRIAL REGISTRATION NATIONAL RESEARCH REGISTER: N0467011677/N0467073587.", "Thirty-five women with retained products of conception after spontaneous miscarriage were randomised to expectant (n = 19) or surgical (n = 16) management, respectively. Women were reviewed at one week, two weeks and six months. There were no significant differences in the number of days of pain, bleeding, sick leave or return to normal periods. Nine of twelve women from the expectant group and six of nine from the surgical group who attempted to conceive did so by six months. All 16 women were satisfied with conservative management. This study provides further reassurance when considering expectant management for spontaneous miscarriage both in the short and medium term.", "In many countries, surgical uterine evacuation is the standard treatment for women with a miscarriage, but expectant management has been advocated as an alternative. The choice between the two options cannot be based on published evidence alone, because randomized clinical trials are scarce while generalizability of findings to patients with a strong preference for either management options is unclear.\n In a randomized controlled trial, the complications and efficacy of either expectant or surgical management for miscarriages were compared, and the results in patients who refused randomization and were managed according to their own preference were studied. In total, 122 patients were randomized and 305 were managed according to their choice.\n No differences were found in the number of emergency curettages and complications between expectant and surgical management. Efficacy at 6 weeks was 30/64 (47%) in women allocated to expectant management, and 55/58 (95%) in women allocated to surgical evacuation. After 7 days, 37% of expectantly managed women had a spontaneous complete miscarriage. After 6 weeks, intention-to-treat analysis including cross-overs showed similar effectiveness (92% versus 100%). Results in the preference groups were comparable with those in the randomized groups.\n In our experience a waiting period of 7 days after diagnosis may prevent 37% of surgical procedures.", "Medical management and expectant care have been considered possible alternatives to surgical evacuation of the uterus for first trimester spontaneous miscarriage in recent years.\n To compare the effectiveness and safety of medical and expectant management with surgical management for first trimester incomplete or inevitable miscarriage.\n Forty women were recruited following diagnosis of incomplete or inevitable miscarriage, and randomised to surgical, medical or expectant care via an off-site, computerised enrollment system. The primary outcome was the effectiveness of medical (vaginal misoprostol) and expectant management relative to surgical evacuation, assessed at 10-14 days and 8 weeks post-recruitment. Infection, pain, bleeding, anxiety, depression, physical and emotional recovery were assessed also. Analysis was by intention-to-treat.\n Effectiveness at 8 weeks was lower for medical (80.0%) and expectant (78.6%) than for surgical management (100.0%). Two women in the medical group had confirmed infections. Bleeding lasted longer in the expectant group than in the surgical group. There were no significant differences in pain, physical recovery, anxiety or depression between the groups. 54.6%, 42.9% and 57.1% of the surgical, medical and expectant groups respectively would opt for the same treatment again.\n Expectant care appears to be sufficiently safe and effective to be offered as an option for women. Medical management might carry a higher risk of infection than surgical or expectant care.", "Approximately 15% of registered pregnancies end in spontaneous abortion, and for 50 years or so dilatation and curettage (D&C) has been the usual management. In a prospective randomised trial we compared the clinical results after either expectant management or D&C, for miscarriages of less than 13 weeks' gestation in which transvaginal ultrasound examination showed intrauterine tissue and/or blood clots with a diameter 15-50 mm. 103 patients were randomised to expectant management and spontaneous resolution of pregnancy occurred within 3 days in 81 cases (79%). 52 patients were randomised to D&C. 3 infections were diagnosed among patients who underwent expectant management (3%); 5 infections and 1 case of postoperative anaemia were observed among patients randomised to D&C (11%). The duration of vaginal bleeding was a mean of 1.3 days longer in the expectant management group (p < 0.02). Convalescence time, time during which patients experienced pain, and packed-cell volume 3 and 14 days after inclusion did not differ significantly between the groups. This study shows that expectant management of selected cases of spontaneous abortion has a similar outcome to D&C." ]

[ "7548461", "8719121", "7877117", "2142697", "11223108", "12203667", "12823078", "1737074", "12011795", "1912117" ]

[ "Clinical and chronobiological effects of light therapy on nonseasonal affective disorders.", "Bright light therapy stabilizes the antidepressant effect of partial sleep deprivation.", "Sleep deprivation and bright light as potential augmenters of antidepressant drug treatment--neurobiological and psychometric assessment of course.", "Sleep deprivation in bright and dim light: antidepressant effects on major depressive disorder.", "Sleep deprivation as a predictor of response to light therapy in major depression.", "Bright light augments antidepressant effects of medication and wake therapy.", "Morning light treatment hastens the antidepressant effect of citalopram: a placebo-controlled trial.", "Controlled trial of bright light for nonseasonal major depressive disorders.", "Bright light therapy and/or imipramine for inpatients with recurrent non-seasonal depression.", "Phototherapy in nonseasonal depression." ]

[ "Light therapy (bright or dim light) was given at different times (morning or evening) to 27 unmedicated patients with nonseasonal depression (according to DSM-III-R criteria) and 16 normal volunteers. Circadian rhythms in body temperature were measured before and after light therapy. Bright light significantly improved clinical symptoms of depression, as measured by the Hamilton Rating Scale for Depression (HRSD), independent of the time of phototherapy. Dim light therapy had no effect on HRSD scores. Circadian rhythms of body temperatures in patients with affective disorder were more sensitive to the entraining effects of bright light than those of normal subjects, but these effects were not related to clinical improvement. Bright light exposure has an antidepressant effect on patients with nonseasonal depression, but the effect is unlikely to be mediated via the same circadian system that regulates body temperature.", "Partial sleep deprivation (PSD) results in a pronounced decrease of depressive symptoms in the majority of patients with major depressive disorder. Generally this acute antidepressant effect is not stable, relapse usually occurs after one night of recovery sleep. We therefore studied whether light therapy, beginning in the morning after PSD, is able to prevent the relapse after sleep deprivation, using a controlled, balanced, parallel design. All patients received an antidepressant medication, which was kept constant before and during the study period. Fourteen of 20 patients (70%) showed a reduction of at least 40% in the Hamilton Depression Rating Scale (HDRS) in the morning after PSD and were classified as PSD responders. Responders as well as nonresponders were randomly assigned to receive either bright light (BL/3000 lux) or dim light (DL/100 lux) therapy during the following 6 days after PSD. In the responder group BL therapy prevented significantly (p = 0.005) the relapse after the next night of sleep and prolonged significantly (p = 0.011) the antidepressant effects of PSD up to 7 days. In contrast, patients in the DL condition relapsed after the recovery night and showed no further improvement of the depressive syndrome after 1 week of DL therapy. PSD nonresponders did not benefit from light treatment. These findings indicate that BL therapy might be efficacious to prevent relapse after PSD.", "The present study was designed to investigate the clinical efficacy of trimipramine with adjunct sleep deprivation (SD) or bright light (BL) and to evaluate psychometric and neurobiological variables that might be of predictive value for treatment response. We used (1) the combined dexamethasone-corticotropin releasing hormone test (DEX-CRH test) to characterize alterations of the hypothalamic-pituitary-adrenal (HPA) system; (2) polysomnography to evaluate sleep disturbances; and (3) a standardized test battery to assess cognitive psychomotor functions after study initiation and after 5 weeks of treatment. The overall response rate (> or = 50% decrease in score on Hamilton Rating Scale for Depression [HRS]) was 55% (N = 42). The response rate in the group with trimipramine monotherapy (N = 14) was 79%, whereas in the groups with adjunct SD (N = 14) and BL (N = 14), respectively, it was only 43%. All three groups showed significant improvement at the end of the third week of treatment. Neither of the adjunct treatments hastened the onset of antidepressant action as measured by HRS. A significantly higher proportion of nonresponders than responders (p < .05) had HPA dysregulation, disturbed rapid eye movement (REM) sleep (REM latency, REM% first third of night) and decreased non-REM sleep (% stage 2). The non-responders showed significantly more corticotropin (ACTH) secretion after CRH stimulation in the DEX-CRH test than the responders and a less rapid normalization of the neuroendocrine dysregulation (cortisol secretion) (p < .01). In addition, REM latency was significantly shorter in the BL group than in the monotherapy group and estimated duration of illness significantly longer in the SD group than in the monotherapy group. REM latency, percentage of REM sleep during the first third of the total sleep period, percentage of non-REM sleep stage 2 and ACTH release after a DEX-CRH challenge predicted response across all three treatment groups. The neurobiological symptoms were unevenly distributed, among the three groups, thus creating heterogeneity in these measures. This heterogeneity may have contributed to the different treatment response rates as defined by psychopathology (HRS). In contrast, the neuropsychological tests and some of the sleep-EEG investigations revealed different response patterns for different groups: The onset of improvement in simple cognitive functions and in sleep continuity was earlier in the adjunct treatment groups. This study underlines the need for a multidimensional approach including use of neurobiological and neuropsychological measures to identify the therapeutic profiles of different treatment strategies and predictors of outcome.", "Twenty-three patients with a major depressive disorder were deprived of a night's sleep twice weekly, one week staying up in the dimly lit living room of the ward (less than 60 lux), and one week in a brightly lit room (greater than 2000 lux). Immediate, but transient beneficial effects of sleep deprivation were observed primarily in eight patients (the 'responders'). The immediate effects did not differ greatly for the two conditions, indicating that exposure to light at night is an implausible explanation for the antidepressant effects of total sleep deprivation. There was some evidence that the bright light condition led to a more prolonged improvement of the responders.", "While the majority of depressed patients benefit from total sleep deprivation (TSD), light therapy is regarded as a first-line treatment only for seasonal affective disorder (SAD). The results of light therapy in nonseasonal major depressive disorder have been non-conclusive. We examined the correlation of TSD response and light therapy response in major depressed patients.\n 40 inpatients with major depressive disorder (seven with seasonal pattern, 33 without seasonal pattern) were deprived of a night's sleep. The TSD responders, as well as the TSD nonresponders, were randomly assigned to receive adjunct light therapy either with bright white light (2500 lux) or dim red light (50 lux) during 2 weeks beginning on the third day after TSD.\n The 20 TSD responders improved significantly better under the light therapy than the 20 TSD nonresponders (according to the Hamilton Depression Rating Scale and the self-rating depression scale Bf-S; v. Zerssen).\n No significant difference could be found between the two light intensities. Since the patients were additionally treated with medication an interaction with the two adjunctive therapies cannot be excluded.\n Our results indicate that a positive TSD response in major depressed patients can be predicative of beneficial outcome of subsequent light therapy.", "Inpatient studies have suggested that bright light therapy can be used to sustain the antidepressant effects of wake therapy (sleep deprivation). In an outpatient trial, a half night of home wake treatment was followed by 1 week of light treatment. All subjects had Major Depressive Disorders according to DSM-IV criteria and were receiving concomitant antidepressant medication. Subjects were randomly assigned to receive either 10,000 lux bright white light for 30 min between 6 and 9 AM or dim red (placebo) light at a comparable time. Seven subjects completed treatment with bright white light and six completed treatment with placebo. On the Hamilton Depression Rating Scale (HDRS17, SIGH-SAD-SR version), the group receiving bright light improved 27% in 1 week (P=0.002). The group receiving placebo did not improve, except for one outlier. The benefit of bright light was significant compared to placebo with removal of the outlier (P<0.025).\n Copyright Wiley-Liss, Inc.", "Selective serotonin reuptake inhibitors are effective in approximately 70% of patients with a major depressive episode, but therapeutic changes usually require 2 weeks of administration to become clinically relevant. Adjunct light therapy has been proposed to hasten the effects of drug treatment. The purpose of the present study was to evaluate the effect of morning light therapy or placebo combined with citalopram in the treatment of patients affected by a major depressive episode without psychotic features.\n Thirty inpatients (DSM-IV major depressive disorder [N = 21] and bipolar disorder [N = 9]) were treated with citalopram, 40 mg, and randomized in a 3:2 manner to receive 30 minutes of 400 lux green light treatment in the morning or placebo (exposure to a deactivated negative ion generator) during the first 2 weeks of drug treatment. Timing of light therapy was individually defined to obtain a 2-hour phase advance to morning light. Outcome was measured with the Hamilton Rating Scale for Depression and the Zung Self-Rating Depression Scale every week, and with a Visual Analogue Scale 3 times a day during the first week.\n All outcome measures showed significantly (p <.05) better mood improvement in light-treated patients, resulting in faster responses to antidepressant treatment.\n The combination of citalopram and light treatment was more effective than citalopram and placebo in the treatment of major depression. With an optimized timing of administration, low-intensity light treatment significantly hastened and potentiated the effect of citalopram, thus providing the clinical psychiatrists with an augmenting strategy that was found effective and devoid of side effects.", "Psychotropic drug-free hospitalized veterans with nonseasonal major depressive disorders or depressed forms of bipolar disorder were treated with light for 1 week. Twenty-five patients were randomly assigned to bright white light treatment (2000-3000 lux), and 26 patients were randomized to dim red light placebo control treatment. Unlike those treated with dim red light, those treated with bright white light showed declines in three measures of depression during treatment. Partial relapse appeared within 2 days. A global depression score showed a statistically significant (p = 0.02) difference favoring bright white light treatment. Two bright-light-treated patients became mildly hypomanic, but side effects were mild. Improvement was not correlated with patient expectations; indeed, patients expected somewhat greater benefit from the placebo. Patients treated in summer responded as well as those treated in winter. Baseline electroencephalogram (EEG) sleep stage data (e.g., rapid eye movement; REM latency) did not predict treatment responses. These 1-week treatment results suggest that bright light might produce benefits for patients with nonseasonal depression. Bright light should not be recommended for routine clinical application before additional assessments with longer treatment durations are done.", "The aim of a double-blind study was to assess the efficacy of bright light therapy and/or imipramine in the treatment of inpatients suffering with recurrent non-seasonal major depressive disorder.\n 34 in-patients with DSM-III-R diagnosis of major depressive disorder, recurrent type, were randomly allocated into 3 treatment groups. After 4-day washout period with baseline assessment they underwent 3 weeks of different types of treatment: a) Group A: bright light therapy (5000 lux from 6-8 a.m.) and imipramine 150 mg/day. b) Group B: bright light therapy (5000 lux from 6-8 a.m.) and imipramine-like placebo. c) Group C: dim red light (500 lux from 6-8 a.m.) and imipramine 150 mg/day. Outcome measures included weekly Hamilton Psychiatric Rating Scale for Depression, Clinical Global Impression Scale, Montgomery and Asberg Psychiatric Rating Scale for Depression and Beck Depression Inventory.\n Patients of all three groups improved significantly. The improvement of the patients of group B treated with bright light therapy plus placebo was superior to the other two groups, but not significantly.\n Bright light therapy can be effective in the treatment of non-seasonal major depressive disorder.", "Previous reports have shown that bright light exposure may benefit patients with seasonal depression. In the present study, the possible therapeutic effect of bright light in nonseasonal major depressive disorder was examined. Forty-two depressed patients not receiving additional antidepressant medication were exposed to bright white light of 2500 lux or dim red light of 50 lux over one week for two hr daily in the morning. The change in depressive symptoms was assessed by rating scales (Hamilton Depression Rating Scale, CGI) and by self-rating scales (Depression Scale, Complaint List, Visual Analogue Scale). Consistent for all ratings, the decrease in depressive symptoms after bright white light was only slight and not different from dim red-light exposure. Contrary to the findings in seasonal affective disorder, phototherapy administered over one week for two hr daily is not effective in nonseasonal major depressive disorder." ]

[ "10723972", "12023699", "9727782", "20416389", "15219299", "16627836", "8701480", "15953743" ]

[ "Magnesium sulfate as a vehicle for nebulized salbutamol in acute asthma.", "A randomized clinical trial of nebulized magnesium sulfate in addition to albuterol in the treatment of acute mild-to-moderate asthma exacerbations in adults.", "Nebulized magnesium sulphate versus nebulized salbutamol in acute bronchial asthma: a clinical trial.", "Usefulness of inhaled magnesium sulfate in the coadjuvant management of severe asthma crisis in an emergency department.", "Comparison of nebulized magnesium sulfate plus albuterol to nebulized albuterol plus saline in children with acute exacerbations of mild to moderate asthma.", "Comparison of nebulised magnesium sulphate and salbutamol combined with salbutamol alone in the treatment of acute bronchial asthma: a randomised study.", "Inhalation therapy with magnesium sulfate and salbutamol sulfate in bronchial asthma.", "A randomized clinical trial of magnesium sulphate as a vehicle for nebulized salbutamol in the treatment of moderate to severe asthma attacks." ]

[ "Magnesium sulfate is thought to be an effective bronchodilator when administered intravenously to patients with acute severe asthma, and it can be safely administered via inhalation to patients with stable asthma. Our goal was to determine if isotonic magnesium sulfate could be used as a vehicle for nebulized salbutamol for patients with acute asthma.\n We enrolled 35 patients with acute asthma in a randomized, double-blind, controlled trial. After measurement of peak expiratory flow, patients received 2.5 mg salbutamol plus either 3 mL normal saline solution (n = 16) or isotonic magnesium sulfate (n = 19) through a jet nebulizer. Peak flow was reassessed 10 and 20 minutes after treatment.\n Peak flow at baseline was similar in the two groups. Ten minutes after baseline, the mean (+/- SD) percentage increase in peak flow was greater in the magnesium sulfate-salbutamol group (61% +/- 45%) than in the normal saline-salbutamol group (31% +/- 28%; difference = 30%; 95% confidence interval [CI] for the difference: 3% to 56%; P = 0.03). At 20 minutes, the percentage increase in peak flow was 57% greater in the magnesium sulfate group (95% CI: 4% to 110%, P = 0.04). There was a significant inverse correlation between baseline peak flow (percent of predicted) and the percentage increase in peak flow at 20 minutes in the magnesium sulfate group (r = -0.82, P <0.0001), but not in the saline group (r = -0.12, P = 0.67).\n In patients with acute asthma, isotonic magnesium sulfate, as a vehicle for nebulized salbutamol, increased the peak flow response to treatment in comparison with salbutamol plus normal saline.", "We sought to compare the efficacy and safety of nebulized magnesium sulfate (MgSO(4)) plus albuterol with that of albuterol alone in adult patients with mild-to-moderate acute asthma exacerbations.\n Patients were randomized to receive nebulized MgSO(4) (384 mg in 6 mL of sterile water) or an equal volume of placebo (normal saline solution) in a double-blind fashion after each dose of nebulized albuterol administered (2.5 mg/3 mL) every 20 minutes for the first hour of the study. Spirometry was performed at baseline and every 20 minutes for 2 hours. Monitoring for safety included vital signs, pulse oximetry, and serum magnesium levels. Improvement in percent predicted forced expiratory volume in 1 second was chosen as a primary efficacy end point.\n Among 74 patients enrolled, 37 were randomized to each of 2 study groups. There were no statistically or clinically significant differences between the 2 study groups in percent predicted forced expiratory volume in 1 second at any point during the trial or overall. There were no significant differences in vital signs, pulse oximetry, or serum magnesium levels at any point during the study.\n The combination of nebulized MgSO(4) and albuterol provides no benefit in addition to that provided by therapy with albuterol in adult patients with mild-to-moderate asthma exacerbations. The efficacy of nebulized MgSO(4) in patients with severe asthma exacerbations remains unknown.", "Intravenous magnesium sulphate (MgSO4) has successfully been used in the treatment of acute asthma. The present study investigated the efficacy of nebulized MgSO4 as a bronchodilator in acute asthma as compared to nebulized salbutamol. This was a randomized, double-blind, controlled clinical trial. Asthmatics aged 12-60 yrs in acute exacerbation, with a peak expiratory flow (PEF) <300 L x min(-1), not having taken bronchodilators and not requiring assisted ventilation were included. Patients were randomized to receive treatment with serial nebulizations of either 3 mL (3.2% solution, 95 mg) MgSO4 solution or 3 mL (2.5 mg) salbutamol solution. All patients were also given 100 mg hydrocortisone i.v., and were monitored continuously for 2 h after which they were given supplemental treatment (if and when needed) and either discharged or admitted. Fischl index, PEF improvements (in % predicted) and admission rates were the outcome variables. Thirty-three patients were studied. Fischl score improvement was comparable and significant in both groups (4.31 to 0.43 in the MgSO4 group and 4.29 to 0.76 in the salbutamol group). The increase in PEF was statistically significant and comparable in both groups (by 35% pred in the MgSO4 and by 42% pred in the salbutamol group). Two patients warranted admission in the salbutamol group and one in the MgSO4 group. Nebulized MgSO4 had a significant bronchodilatory effect in acute asthma. This effect was not significantly different from that of nebulized salbutamol.", "Treatment of severe asthma may be difficult despite the use of several medications including parenteral corticosteroids. Intravenous magnesium sulfate (MgSO(4)) is one ancillary drug for severe crisis; its inhaled use is controversial.\n To evaluate the usefulness of inhaled MgSO(4) compared to placebo in improving lung function, oxygen saturation, and reducing hospital admission as an adjunct to standard treatment in severe asthma crisis.\n We conducted a placebo-controlled, double-blind clinical trial with asthmatic patients >18 years of age with asthmatic crisis and FEV(1)<60% of predicted (%p). All subjects received 125 mg of IV methylprednisolone followed by nebulization with the combination of albuterol (7.5mg) and ipratropium bromide (1.5mg) diluted in 3 ml of isotonic saline solution (as placebo) or 3 ml (333 mg) of MgSO(4). After 90 min, subjects with FEV(1)<60%p or SpO(2)<88% or persistent symptoms were admitted to the emergency department (ED).\n We included 30 patients per group who were similar at baseline. The MgSO(4) group showed higher post-bronchodilator (post-BD) FEV(1)%p (69+/-13 vs. 61+/-12, p<0.014) and SpO(2) (92+/-4 vs. 88+/-5%, p<0.006) than the placebo group. Fewer treated patients were admitted to the ED (5 vs. 13) (p<0.047), with relative risk (RR) of 0.26 (95% CI 0.079-0.870).\n Adding inhaled MgSO(4) treatment to standard therapy in severe asthma crisis improves FEV(1)%p and SpO(2) post-BD and reduces the rate of ED admissions.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "A prospective, randomized, double blinded study was conducted to determine whether a combination of nebulized magnesium sulfate and albuterol as a single dose adds any benefit in management of children with mild to moderate asthma when compared to nebulized albuterol with saline. The difference in FEV1 was significant at 10 and 20 min after a single dose of the combined treatment with magnesium and albuterol when compared with the albuterol and saline group (1.41 L +/- 0.53 vs. 1.13 L +/- 0.34, respectively, p = 0.03). The addition of magnesium to albuterol seems to provide short-term benefits in children with acute exacerbations of mild to moderate asthma.", "To test the hypothesis that combined administration of multiple doses of nebulised salbutamol and magnesium sulphate provides additional benefit compared with salbutamol alone in adult patients with acute asthma.\n Randomised, double blind, prospective study.\n A total of 100 patients presenting to an emergency department with an acute attack of bronchial asthma were randomised to two groups: nebulisation with a combination of salbutamol and magnesium sulphate (group A) and nebulisation with salbutamol only (group B). Both groups received nebulisation thrice at intervals of 20 minutes. Salbutamol and magnesium sulphate were administered in doses of 0.5 mg and 500 mg, respectively, and the solutions were made isotonic to plasma osmolality. Pulse rate, blood pressure, and peak expiratory flow rate (PEFR) were measured at baseline and at 15, 60, 75, and 120 minutes. Serum magnesium levels and blood gases were measured at 0 and 120 minutes in both groups.\n All patients had either acute severe or life threatening asthma. The baseline characteristics were comparable in the two groups. Both groups showed significant rise in PEFR at all time intervals, however, there was no significant difference between the groups in rise in PEFR at any time point. Serum magnesium levels remained within normal limits, and there was no difference in requirement of additional medication during the study or hospital admission rates in both groups. No significant side effects were noted.\n This study suggests that there is no therapeutic benefit of adding magnesium sulphate to salbutamol nebulisation in the treatment of patients with acute severe or life threatening asthma.", "Inhalation therapy with magnesium sulfate and salbutamol sulfate was applied to two groups, each consisting of 20 patients with acute asthma. The effects of inhaled magnesium sulfate and salbutamol sulfate were compared. The evaluation of patients was done using respiratory score, peak expiratory flow rate with a Wright peak flow meter, respiration rate, heart rate and blood pressure. Although magnesium sulfate's bronchodilating effect continued for approximately one hour, treatment of acute asthma using salbutamol sulfate inhalation was found to be more successful and its effect continued for six hours.", "Although it is well known that intravenous administration of MgSO4 as an adjunct to conventional therapy is effective in treating asthma attacks, the effect of nebulized MgSO4 as a vehicle for salbutamol has been less evaluated. The aim of this study was to compare the effects of nebulized salbutamol administrated through either MgSO4 or isotonic saline solution on the 'peak expiratory flow rate' (PEFR), other respiratory and clinical parameters, and hospitalization rate of patients suffering from moderate to severe asthma attacks. Twenty-six patients with asthma attack were enrolled in the study in a randomized single blind fashion. After obtaining initial peak expiratory flow measurements (PEFR) and clinical evaluation, all patients received 1mg/kg corticosteroids and oxygen therapy and then either isotonic MgSO4 (2.5 ml, 6.3%)+salbutamol (2.5 ml) or saline (2.5 ml)+salbutamol (2.5 ml) through a jet nebulizer (group 1 (n=14) vs group 2 (n=12), respectively). The nebulizations were repeated every 20 min for the first hour and every hour for the rest of 4 h. The PEFR measurements and clinical assessment were performed after nebulization at 20th, 60th, 120th, 180th and 240th minutes. Patients were discharged when PEFR reached the target level of 70% of predicted. The baseline PEFRs and clinical parameters were similar between groups 1 and 2 (50.2+/-18.5 vs 44.1+/-13.9, respectively, p>0.05). The mean% increase in PEFR at different measurement levels was similar between the groups. When the treatment response was evaluated within the groups, group 2 showed statistically significant increase in PEFR (% of predicted) 1h earlier than group 1 (60th vs 120th minute, p=0.003 vs p=0.007). The mean duration of achieving target-PEFRs was 105.7+/-72.1 min for group 1 and 118.3+/-96.7 min for group 2 (p>0.05). This study suggested that the additional usage of MgSO4 to nebulized salbutamol has no beneficial effect on the treatment of asthma attacks." ]

[ "2185026", "3889259", "3540835", "2405141", "2117205", "2903480", "3652706", "2057268", "1973717", "2235230", "2882083" ]

[ "A European multicenter randomized controlled trial of single dose surfactant therapy for idiopathic respiratory distress syndrome.", "Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomized prospective clinical trial.", "Randomized controlled trial of exogenous surfactant for the treatment of hyaline membrane disease.", "A controlled trial of human surfactant replacement therapy for severe respiratory distress syndrome in very low birth weight infants.", "A multicenter randomized controlled clinical trial of bovine surfactant for prevention of respiratory distress syndrome.", "Surfactant replacement therapy for severe neonatal respiratory distress syndrome: an international randomized clinical trial. Collaborative European Multicenter Study Group.", "Endotracheal administration of surfactant in very low birth weight infants with respiratory distress syndrome.", "Reduction of neonatal mortality after multiple doses of bovine surfactant in low birth weight neonates with respiratory distress syndrome.", "Exogenous surfactant for treatment of respiratory distress syndrome in premature infants.", "Surfactant replacement therapy with a single postventilatory dose of a reconstituted bovine surfactant in preterm neonates with respiratory distress syndrome: final analysis of a multicenter, double-blind, randomized trial and comparison with similar trials. The Surfactant-TA Study Group.", "Double-blind controlled trial of single-dose treatment with bovine surfactant in severe hyaline membrane disease." ]

[ "We performed a multicenter prospective randomized controlled trial to determine the efficacy and safety of the surfactant preparation, Survanta (Abbott Laboratories, Chicago, USA), for 750-1750 g infants with idiopathic respiratory distress syndrome, (IRDS) receiving assisted ventilation with 40% or more oxygen. One hundred and six eligible infants from the eight participating centers were randomly assigned between March 1986 and June 1987 to receive either surfactant (100 mg phospholipid/kg, 4 ml/kg) or air (4 ml/kg) administered into the trachea within 8 h of birth (median time of treatment 6.2 h, range 3.2-9.1 h). The study was stopped before enrollment was completed at the request of the United States Food and Drug Administration when significant differences were observed in incidence of periventricular-intraventricular hemorrhage (PIH), between the surfactant treated and control infants. Surfactant treated infants had larger average increases in the arterial-alveolar oxygen ratio, (a/A ratio) (P less than 0.0001), and larger average decreases in FiO2 (P less than 0.0001) and mean airway pressure, (MAP) (P less than 0.017) than controls over the 48 h following treatment. The magnitude of the differences between the surfactant and control groups were 0.19 (SE = 0.03) for a/A ratio, -0.28 (SE = 0.04) for FiO2 and -1.7 cm H2O (SE = 0.70) for MAP. The clinical status on days 7 and 28 after treatment was classified using four predefined ordered categories: (1) no respiratory support; (2) supplemental O2 with or without continuous positive airway pressure (CPAP); (3) intermittent mandatory ventilation; and (4) death. There were no statistically significant differences in the status categories on days 7 or 28 between surfactant and control infants.(ABSTRACT TRUNCATED AT 250 WORDS)", "We performed a randomized, prospective clinical trial comparing intratracheal administration of human surfactant with conventional treatment with intermittent mandatory mechanical ventilation alone for treatment of severe respiratory distress syndrome in preterm infants of less than 30 weeks gestation. Twenty-two infants (mean gestational age 27.0 weeks, mean birth weight 987 gm) were given surfactant, and 23 infants (mean gestational age 27.2 week, mean birth weight 1055 gm) received intermittent mandatory ventilation. Infants given surfactant required less FiO2 during the first week, had lower mean airway pressure during the first 48 hours, and had improved ventilatory index and a/A PO2 ratio. Death or the occurrence of bronchopulmonary dysplasia was significantly less among infants given surfactant (P = 0.019). Pneumothorax, pulmonary interstitial emphysema, and need for FiO2 greater than or equal to 0.3 for greater than 30 days was significantly less in the surfactant group. This trial confirms the efficacy of treatment with human surfactant in preterm infants with severe respiratory distress syndrome.", "We conducted a prospective, randomized, unblinded, controlled trial of exogenous bovine surfactant (surfactant TA) in premature infants requiring ventilator support for the treatment of severe hyaline membrane disease. Forty-one low birth weight infants with severe hyaline membrane disease were randomly assigned to saline or surfactant therapy and treated within eight hours of birth. Significant improvements in oxygenation (increased arterial/alveolar PO2) and respiratory support (decreased mean airway pressure) were seen in the group receiving surfactant within four hours after treatment. These improvements were maintained in the surfactant-treated infants, who also had fewer pneumothoraces and fewer number of days in environments of fractional inspiratory oxygen greater than 0.4 mm Hg. No problems were associated with administration of surfactant, and no acute side effects were detected. We conclude that exogenous surfactant, administered early in the course of severe hyaline membrane disease, is an effective therapy that can diminish the amount of respiratory support required during the first 48 hours of life.", "In a randomized, controlled study, human surfactant derived from amniotic fluid was administered within 12 hours of birth to infants with severe respiratory distress syndrome who were born at 24 to 32 weeks of gestation weighing less than or equal to 1500 gm. A second dose of surfactant was given to patients in the treatment group if they met ventilator requirements indicating relapse or lack of response to the initial dose. No significant improvement was observed in mortality rate (9/28 vs 15/31) or incidence of bronchopulmonary dysplasia (5/28 vs 3/31) when surfactant-treated infants were compared with control subjects, although there was a significant reduction in initial respirator and inspired oxygen requirements and the arterial/alveolar oxygen ratio improved. In addition, there was a significant reduction in pulmonary air leak in treated infants (10/28 vs 20/31; p less than 0.05). Retreatment was associated with an attenuated ventilatory response and with a higher mortality rate (7/14) than that of infants who did not require a second dose (2/14; p = 0.05), indicating a more severe form of disease. Multiple discriminant analysis, including eight independent variables, revealed that increasing birth weight, earlier age at surfactant treatment, and female gender were significantly associated with survival. These data suggest that early surfactant treatment may reduce mortality rates in very low birth weight infants with severe respiratory distress syndrome, as well as reduce ventilator requirements and the incidence of pulmonary air leaks.", "Treatment with bovine surfactant (SF-RI 1) was shown to be efficacious in improving pulmonary function and in increasing survival rate without BPD in very premature infants. Surfactant therapy did not affect the risk of major complications of prematurity.", "In a randomized multicenter trial, involving the collaboration of eight European neonatal intensive care units, the efficacy of replacement therapy with a new surfactant preparation (Curosurf) was tested in 146 patients with severe neonatal respiratory distress syndrome. Criteria for entry included birth weight 700 to 2,000 g, age when treated two to 15 hours, and requirement of artificial ventilation with FiO2 greater than or equal to 0.6. The babies were treated with a single large dose of surfactant (200 mg/kg) at a median age of nine hours (range two to 15 hours). Average FiO2 before treatment was the same (0.80) for both surfactant-treated patients and control patients. Babies receiving surfactant showed, within five minutes, a dramatic improvement of oxygenation as reflected by a nearly threefold increase of the PaO2/FiO2 ratio. Six hours after randomization, the PaO2/FiO2 ratio still showed a 98% improvement in surfactant-treated patients compared with controls (P less than .001), and statistically significant differences in favor of the treated babies persisted until 48 hours after randomization, when surviving control infants began to recover. Treatment with surfactant decreased neonatal (less than or equal to 28 days) mortality from 51% to 31% (P less than .05). Compared with control babies, the surfactant-treated group also had a decreased incidence of pulmonary interstitial emphysema (23% v 39%; P less than .05) and pneumothorax (18% v 35%; P less than .05). The percentage of survivors without bronchopulmonary dysplasia in the treated group was more than twice that of the control group (55% v 26%; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)", "This study was designed to evaluate whether the ventilatory maneuvers associated with surfactant replacement would, per se, influence oxygenation in newborn infants with severe respiratory distress syndrome. Eight patients (700 to 1400 g), all requiring mechanical ventilation with fraction of inspired oxygen greater than 0.6, were included in the trial; four were randomized to receive surfactant, and the others served as controls. Porcine surfactant (2 ml/kg; phospholipid concentration, 100 mg/ml) was instilled via a naso-endotracheal tube at end-expiration and dispersed into the lungs during a period of standardized \"sighing\" mediated by the ventilator: two prolonged ventilatory cycles (10 sec each) with an inspiration/expiration ratio of 4:1, followed by a 6-min ventilation with a frequency of 60 breath/min and an inspiration/expiration ratio of 4:1. Control babies received no surfactant but were otherwise subjected to the same ventilatory maneuvers. Surfactant-treated infants showed a rapid increase in transcutaneous oxygen associated with improved lung aeration in chest x-rays; the response was transient in three babies and persistent in one. No improvement was observed in control babies. We conclude that the beneficial effect of surfactant replacement cannot be attributed to the ventilatory maneuvers associated with the instillation procedure.", "To determine if outcomes of low birth weight neonates with respiratory distress syndrome can be improved by the administration of multiple doses of bovine surfactant, we conducted two identical multicenter, controlled trials, and the results were combined for analysis. Seven hundred and ninety-eight neonates weighing 600 to 1750 g at birth who had developed respiratory distress syndrome within 6 hours of birth were assigned randomly to receive either 100 mg of phospholipid/kg of Survanta, a modified bovine surfactant (n = 402), or a sham dosing procedure (n = 396). Neonates whose respiratory distress persisted could be given up to three more doses, with all doses to be given in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Fewer Survanta-treated neonates died of any cause (18.4% vs 27.3%, P = .002), died of respiratory distress syndrome (9.0% vs 20.3%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (51.2% vs 64.6%, P less than .001). Neonates who received Survanta also had greater improvement in their oxygenation and ventilatory status from baseline to 72 hours than did control neonates. Survanta-treated neonates were at lowered risk for developing pulmonary interstitial emphysema (18.6% vs 39.3%, P less than .001) and other pulmonary air leaks (11.5% vs 25.9%, P less than .001). We conclude that multiple doses of Survanta given after diagnosis of respiratory distress syndrome reduce mortality and morbidity.", "A prospective, randomized and controlled trial was conducted to evaluate the efficacy and safety of surfactant in the treatment of respiratory distress syndrome (RDS) in infants. Eighteen premature infants with RDS were studied. Group I consisted of 9 premature infants with a mean birth weight of 1,455 +/- 265.9 g and a mean gestational age of 31.4 +/- 1.3 weeks. Group II consisted of 9 premature infants with a mean birth weight of 1,411 +/- 379.0 g and a mean gestational age of 30.6 +/- 1.7 weeks. Reconstituted bovine surfactant (Surfactant TA, Tokyo Tanabe Co., Japan), 120 mg/kg body weight was suspended in 4 ml normal saline and delivered to the lungs of the patients in group I through an endotracheal tube via a catheter in five divided doses (mean age at this point was 5.7 +/- 4.5 hours). An air placebo (4 ml per kilogram) was given to the patients in group II. The results showed that significant improvement in oxygenation, characterized by (1) an increase in the ratio of arterial to alveolar oxygen tension; (2) a decrease in the fractional inspiratory oxygen concentration; and (3) changes in mean airway pressure and ventilatory index, were noted in the surfactant-treated group. Pneumothorax was found in one surfactant-treated infant and one control infant. Pulmonary interstitial emphysema was found in one control infant. One control infant later developed bronchopulmonary dysplasia. Four (44.4%) of the surfactant-treated infants and four (44.4%) of the control infants had evidence of patient ductus arteriosus. The mean duration from birth to extubation in the surfactant-treated infants was 121.9 +/- 1.9 hours.", "The effects of a single dose of surfactant TA were assessed in premature neonates (birth weight 750 to 1749 g) with respiratory distress syndrome (RDS) in a multicenter, double-blind, randomized clinical trial. Only neonates with surfactant deficiency and without ultrasonographic evidence of intracranial hemorrhage greater than or equal to grade II were enrolled. Fifty-four patients received surfactant (100 mg of phospholipid per kilogram of body weight) and 46 patients received an air placebo within 8 hours of life. Treatment with this surfactant resulted in a significant reduction in the severity of RDS with a concomitant increase in the proportion of neonates with mild disease. The frequency of pulmonary interstitial emphysema and of pneumothorax was significantly lower in treated neonates compared with control neonates (2% vs 26%, P = .0008, and 7% vs 39%, P = .0004, respectively). The frequency of intracranial hemorrhage was significantly lower in the surfactant group compared with the control group (20% vs 54%, P = .0008) and was also reduced for the smallest neonates in the surfactant group (13% vs 73%, P = .00008). When categorized according to severity of intracranial hemorrhage and severity of bronchopulmonary dysplasia, the surfactant group was at a significant advantage (adjusted Cochran-Mantel-Haenszel X2 = 10.72, P less than .001 and X2 = 4.43, P = .036, respectively). The proportion of neonates surviving without intracranial hemorrhage and/or bronchopulmonary dysplasia was 63% in the surfactant group vs 26% in the control group (P = .0004); as for the smallest neonates, it was 58% in the surfactant group vs 4% in the control group (P = .0002). There were no differences between the groups with respect to the frequency of patent ductus arteriosus (46% vs 37%), pulmonary hemorrhage (6% vs 7%), necrotizing enterocolitis (0% vs 2%), sepsis (4% vs 2%), retinopathy of prematurity (13% vs 22%), or death (15% vs 22%). It is concluded that treatment with the single-dose surfactant regimen used in this study reduces the severity of respiratory distress during the 48 hours after treatment and decreases the major pulmonary morbidity and intracranial hemorrhage in premature neonates with RDS. Further studies are needed to determine whether (1) treatment at birth or as soon as after RDS is diagnosed and (2) the use of multiple dose of this surfactant would result in any additional benefits.", "In a double-blind clinical trial the effects of a single dose of reconstituted bovine surfactant ('Surfactant TA') were assessed in 30 premature infants (birthweight 751-1750 g) with severe hyaline membrane disease. 17 infants had a sonicated saline suspension of 100 mg/kg surfactant phospholipid instilled into the trachea at 5.0 (SD 0.7) hours of age and 13 infants received saline by the same route at 4.3 (1.1) hours of age. In the surfactant-treated group there was early improvement in oxygenation and ventilation. Haemodynamically significant patent ductus arteriosus occurred more often in the surfactant group; pneumothorax and pulmonary interstitial emphysema occurred less often. The combined incidence of death and severe bronchopulmonary dysplasia was significantly lower in the surfactant group (3/17) than in the placebo group (9/13)." ]

[ "14759641" ]

[ "Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial." ]

[ "Treatment with acetyl L-carnitine (ALCAR) has been shown to improve fatigue in patients with chronic fatigue syndrome, but there have been no trials on the effect of ALCAR for treating fatigue in multiple sclerosis (MS). To compare the efficacy of ALCAR with that of amantadine, one of the drugs most widely used to treat MS-related fatigue, 36 MS patients presenting fatigue were enrolled in a randomised, double-blind, crossover study. Patients were treated for 3 months with either amantadine (100 mg twice daily) or ALCAR (1 g twice daily). After a 3-month washout period, they crossed over to the alternative treatment for 3 months. Patients were rated at baseline and every 3 months according to the Fatigue Severity Scale (FSS), the primary endpoint of the study. Secondary outcome variables were: Fatigue Impact Scale (FIS), Beck Depression Inventory (BDI) and Social Experience Checklist (SEC). Six patients withdrew from the study because of adverse reactions (five on amantadine and one on ALCAR). Statistical analysis showed significant effects of ALCAR compared with amantadine for the Fatigue Severity Scale (p = 0.039). There were no significant effects for any of the secondary outcome variables. The results of this study show that ALCAR is better tolerated and more effective than amantadine for the treatment of MS-related fatigue." ]

[ "9871816", "8739664", "6208185", "11401657", "1909083", "2530766", "2699556", "9517912", "3549874", "8685201", "1810358", "10628889", "7675961", "9287259", "7046366", "9590668", "2491140", "8275912", "1431010", "2230067" ]

[ "Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice.", "A double-blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients.", "Comparative cardiac effects of maprotiline and doxepin in elderly depressed patients.", "Citalopram versus nortriptyline in late-life depression: a 12-week randomized single-blind study.", "Double-blind comparative multicentre study of fluvoxamine and mianserin in the treatment of major depressive episode in elderly people.", "A double-blind, multicentre study of paroxetine versus clomipramine in depressed elderly patients.", "Fluoxetine versus trazodone in depressed geriatric patients.", "Double-blind study of the efficacy and safety of milnacipran and imipramine in elderly patients with major depressive episode.", "Cognitive and psychomotor effects of different antidepressants in the treatment of old age depression.", "[Major depressive episodes in patients over 70 years of age. Evaluation of the efficiency and acceptability of tianeptine and mianserin].", "A double-blind, randomised comparison of fluvoxamine with dothiepin in the treatment of depression in elderly patients.", "Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double-blind randomised trial.", "Multicenter double blind study of paroxetine and amitriptyline in elderly depressed inpatients.", "A randomised, double-blind, parallel-group comparison of venlafaxine and dothiepin in geriatric patients with major depression.", "Comparative double-blind study on efficacy and side-effects of trazodone, nomifensine, mianserin in elderly patients.", "Buspirone and imipramine for the treatment of major depression in the elderly.", "The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients.", "[Multicenter double-blind study comparing the efficacy and tolerance of paroxetine and clomipramine in reactive depression in the elderly patient].", "Paroxetine in the treatment of elderly depressed patients in general practice: a double-blind comparison with amitriptyline.", "A controlled trial of adinazolam versus desipramine in geriatric depression." ]

[ "The enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants (TCAs), and the frequency and type of adverse events, have made the treatment of depression in this group difficult. The selective serotonin reuptake inhibitors (SSRIs) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs. We compared the therapeutic actions and side effects produced by citalopram, the most selective SSRI available, with amitriptyline in a group of elderly patients (aged 65 and older) diagnosed with major depression. In a double-blind, double-dummy, parallel-group, multicenter comparison of citalopram (20 or 40 mg/day) and amitriptyline (50 or 100 mg/day), patients who did not respond to placebo during a 1-week single-blind phase were randomly assigned to receive citalopram or amitriptyline for 8 weeks. Efficacy measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAMD), and Clinical Global Impressions. Both drug treatments produced equivalent time-related declines in severity of depression, so that by 8 weeks slightly more than 50% of the patients in each group experienced marked recovery, defined as MADRS scores < or = 12. Amitriptyline produced a greater overall incidence of adverse events, including a significantly higher (P < 0.001) percentage of patients reporting dry mouth (34% vs. 7%), as well as a significantly higher (P < 0.02) incidence of somnolence. Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group. For only one event (nausea) did the citalopram group report a significantly greater (P = 0.012) incidence (12.8% vs. 4.8%). On the basis of these results, it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly. Because of its low incidence and low magnitude of side effects, citalopram seems especially useful in private practice.", "A total of 115 elderly patients (60-85 years of age) with DSM III diagnosis of major depressive episode were randomly assigned to 6 weeks of treatment with either mirtazapine, 15-45 mg/day, or amitriptyline, 30-90 mg/day. Efficacy was assessed biweekly, using the Hamilton Rating Scale for Depression (HRSD) and Montgomery and Asberg Depression Rating Scale (MADRS) as primary outcome variables. The treatment with both drugs resulted in a similar reduction of total HRDS and MADRS scores, with no statistically significant differences between treatment groups at any assessment point or at endpoint. Statistically significant differences favouring amitriptyline were present according to CGI-Global Improvement Scale at endpoint, HRDS cognitive disturbance factor at weeks 2, 4 and 6 and endpoint and retardation factor at week 6. Adverse events were reported by a similar number of patients in both treatment groups. Additional research is needed to assess further the efficacy and tolerability of mirtazapine among elderly depressed patients.", "In a double-blind study, 49 elderly patients with primary major depression, with or without cardiovascular disease, were treated with maprotiline or doxepin. Holter monitors, 12-lead ECGs, and orthostatic blood pressure measurements were used. Maprotiline was associated with decreased PVCs in patients with a \"high\" baseline rate, while doxepin was associated with increased PVCs in this group. There were no significant differences in orthostatic blood pressure changes between treatment and nontreatment phases or between the two drugs. Small but significant increases in heart rate and prolonged PR interval were noted with both drugs. QRS interval was prolonged by maprotiline but decreased by doxepin. Neither drug produced untoward effects in patients with stable angina or an old myocardial infarction. Maprotiline may have an antiarrhythmic effect which could be beneficial in the treatment of depression with concomitant PVCs. Conversely, doxepin may be more appropriate for depressed patients with heart block or intracardiac conduction delays. Further research is necessary to confirm these suggestions.", "The aim of this single-blind study was to examine the efficacy and tolerability of citalopram compared to nortriptyline in moderate to severe major depressive patients aged 60 years or over. Method: In- and out-patients (N=58) with unipolar major depression were randomized to 12-week flexible dose treatment with nortriptyline or citalopram.\n No significant differences between the number of drop-outs in either group were observed, but the autonomic side-effects were significantly higher for nortriptyline than for citalopram. A significantly higher remission rate to nortriptyline than to citalopram was demonstrated, particularly if severe patients (endogenous or psychotic patients) were assessed.\n The remission rate to a therapeutic plasma level of nortriptyline appears to be higher than the remission rate to a standard dose of citalopram in a group of elderly major depressed patients, especially those with endogenous or psychotic features. On the other hand, citalopram appears to be better tolerated.", "This is a multicentre double-blind study of fluvoxamine versus mianserin in the treatment of major depressive episode in patients over 65 years of age. Fifty-seven patients received either fluvoxamine (100-200 mg daily) or mianserin (40-80 mg daily). There was no statistically significant difference in improvement between the 2 treatment groups as measured by the Montgomery-Asberg Depression Rating Scale. Eleven patients (7 in the fluvoxamine group and 4 in the mianserin group) discontinued treatment because of intolerance. No statistically significant differences were seen in biological parameters with either drug. Both drugs improved the symptoms of depression though the overall response rate was not outstanding. The side effects profile for the fluvoxamine was contrary to previous studies in that frequent nausea and vomiting were not seen.", "nan", "A total of 27 subjects began active treatment in this double-blind study comparing the efficacy and safety of trazodone and fluoxetine in geriatric depressed patients, but only 13 completed 6 weeks on study medication. Both agents were effective according to weekly and endpoint analyses, and there was no evidence of significant effects on blood pressure, pulse, or weight. Separate analysis of patients who had received an adequate trial of medication indicated a trend toward relatively more fluoxetine-treated patients meeting clinical criteria for resolved depression.", "The novel antidepressant agent milnacipran is a dual and equipotent serotonin and noradrenaline reuptake inhibitor. The aim of this double-blind study was to compare the efficacy and safety of milnacipran (50 mg twice daily) with that of imipramine (50 mg twice daily) in elderly patients with major depressive episode. A total of 219 patients were randomly assigned to 8 weeks of double-blind treatment with either milnacipran or imipramine; 72 patients withdrew from the study. At the end of treatment no significant differences were found between milnacipran and imipramine in antidepressant efficacy. A significantly greater number of side-effects, particularly anticholinergic effects, was observed in the imipramine group. Milnacipran may be preferable to imipramine in elderly depressed patients, as it provides the same antidepressant activity as imipramine with a lower incidence of side-effects, and does not impair cognitive ability.", "nan", "The aim of this multicenter study was to compare the efficacy, acceptability and impact on quality of life of tianeptine (T) and mianserine (M) in patients over 70 years of age with major depression.\n Fulfilment of the DSM IIIR criteria for major depression with a total Montgomery and Asberg depression rating scale (MADRS) of at least 25 and a Hamilton anxiety rating scale (HARS) of at least 18 were required for inclusion. The 315 men and women enrolled in the study were given, by double blind assignment, either T: 37.5 mg/day, T: 25 mg/day or M: 30 mg/day. Treatment duration was 6 months in all three groups and follow-up continued for 3 months after withdrawal of tianeptine or mianserine. The main efficacy criterion was the MADRS score evaluated at each of 6 visits at day 15 (D15) and month 1 (M1), M2, M4, M4.5 and M6. The HARS score was another efficacy criterion. Overall assessment of efficacy and acceptability was done at each visit by the patient and the investigator. Both the patient and the physician estimated global effectiveness on a quality of life scale at M1, M3, M6 and M9.\n In the intention-to-treat population (n = 299), the antidepressant efficacy of tianeptine and mianserine was not significantly different, whether assessed as effect on anxiety or on quality of life. Scores however tended to be better in the T: 37.5 mg group. Acceptability was good as shown by the low number of adverse events in all 3 groups, but at D15, the incidence of impaired vigilance or equilibrium was significantly lower in the T: 25 mg group than in the M: 30 mg group, emphasizing the advantage of tianeptine in decreasing the risk of falling. Physician-assessed tolerance and acceptability was significantly different at M3 (p = 0.014) and at M6 (p = 0.028) in favor of T: 37.5 mg, indicating that though increasing dosage does not improve efficacy, there is no risk of poorer acceptability.\n These findings reconfirm the antidepressive efficacy, acceptability and safety of tianeptine. They also confirm the anxiolytic aspect associated with the antidepressive effect of tianeptine without any sedative effect. Tianeptine is particularly well indicated in the treatment of depression in elderly or very elderly subjects.", "The efficacy and tolerability of the selective 5-HT reuptake inhibitor fluvoxamine were compared with the tricyclic dothiepin in 52 elderly (age greater than 64 years) hospital patients in a multi-centre double-blind randomised trial. Patients met DSM-III criteria for 'major depressive episode' and scored greater than 29 on the Montgomery Asberg Depression Rating Scale (MADRS) after a one-week placebo baseline. Active treatment was for six weeks. The dosage of both drugs was 50 mg nocte for three days, 100 mg nocte for the remainder of the first week, thereafter increasing to a maximum of 200 mg/day according to response/tolerance. MADRS scores improved by 63.5% with fluvoxamine and 60.0% with dothiepin; there were no significant differences between treatments at any assessment. Nausea, dizziness, headache, somnolence and constipation in both groups, plus dry mouth and asthenia in the dothiepin group were more frequent than single reports. Two patients in each group discontinued treatment owing to unwanted effects. There were no clinically significant changes in haematological, biochemical or cardiovascular parameters.", "Depression in older people is often unrecognised and untreated or under-treated. Antidepressant treatment may itself exacerbate a pre-existing illness, interact with concomitant medications or produce undesirable cognitive and sedative side effects. Newer antidepressants may offer advantages in terms of a lesser burden of adverse effects.\n The comparative tolerability of the unique selective noradrenaline reuptake inhibitor (selective NRI) reboxetine (4-6 mg/day; n = 176) and that of imipramine (50-100 mg/day; n = 171) was assessed in an elderly ( > 65 years) cohort of depressed or dysthymic patients in an 8-week, double-blind, multicentre trial. Comparative efficacy was also assessed.\n Overall, 68% of patients in the reboxetine group experienced adverse events compared with 71% in the imipramine group. Reboxetine-treated patients were less likely to develop hypotension and related symptoms (7% vs. imipramine 16%) or cardiovascular disorders (12.5% vs. imipramine 21.1%), while those treated with imipramine were less likely to experience insomnia (6.3% vs. 2.9%). Adverse events were more often assessed as related to treatment (43%) and moderate to severe in intensity (73%) with imipramine than with reboxetine (33% and 65%, respectively). Furthermore, there were fewer serious adverse events in the reboxetine-treated group (P = 0.019). The reduction in the Hamilton Rating Scale for Depression (HAM-D) was comparable between the treatment groups in the total population. At the last assessment, the majority of patients in both treatment groups were assessed as normal to borderline or mildly ill using the Clinical Global Impression (CGI) scale. In a subanalysis of the dysthymic patients a modest but significant difference in favour of imipramine was observed for both HAM-D and CGI assessments. This may have been a reflection of a trend towards more severe depressive symptoms at baseline in the reboxetine group.\n Reboxetine is as effective as imipramine in the treatment of depression in elderly patients but is at least as well tolerated with a lower risk of hypotension and related symptoms, fewer serious adverse events, adverse event-related withdrawals and treatment-related adverse events.", "Paroxetine is a phenylpiperidine compound which is a selective serotonin reuptake inhibitor (SSRI). Ninety-one hospitalised patients with a major depression (DSM-III) aged 65 and over from six Austrian and one German center were entered into the study, which compared the efficacy and tolerability of paroxetine versus amitriptyline. After 6 weeks both groups showed similarly good therapeutic results. In the paroxetine group, 64.3% of the patients had a 50% or more reduction of the HAMD total score compared to 58.1% in the amitriptyline group. Side effects were distributed similarly in both groups. Patients in the paroxetine group showed a higher incidence of anxiety and agitation; anticholinergic side effects were registered more often in the amitriptyline group.", "This randomised, double-blind study conducted at nine sites in the UK and the Netherlands compared the safety and antidepressant efficacy of venlafaxine and dothiepin. Ninety-two geriatric patients (aged 64-87 years) with major depression were randomly assigned to receive either venlafaxine or dothiepin for up to 43 days. The dose of venlafaxine or dothiepin was titrated up to a maximum of 150 mg per day for the first 15 days, and thereafter could range from 50 to 150 mg per day. Adjusted mean scores on the MADRS and the HAM-D decreased significantly (p 0.05) for baseline to the end of the study in both groups. A response to therapy was observed in 60% of patients in the venlafaxine group and 53% of patients in the dothiepin group on the MADRS, and in 60% of patients in both groups on the HAM-D. Suicidal ideation scores on the MADRS were significantly (p = 0.042) lower in the venlafaxine group at week 6. Treatment-emergent study events were the primary reasons for withdrawal in only 7% of venlafaxine-treated patients and 8% of dothiepin-treated patients. The results confirm the efficacy and tolerability of venlafaxine for treating major depression in the elderly.", "nan", "The current study was designed to assess the safety and efficacy of imipramine and buspirone in the treatment of major depression in elderly depressed attendees of primary care practices.\n 177 patients aged 65 and over (mean age = 72 years; range, 65-89) who met DSM-III-R criteria of unipolar major depression with a minimum Hamilton Rating Scale for Depression score of 18 were randomly assigned to 8 weeks of double-blind, placebo-controlled treatment with flexible doses of either imipramine or buspirone.\n Moderate to marked global improvement after 8 weeks of treatment (LOCF analysis) occurred in 70% of patients treated with imipramine, 61% of patients treated with buspirone, and 42% of patients treated with placebo (chi2 = 9.1, df = 2, p < .02). Drug treatment was well tolerated, with 77% of imipramine- and 61% of buspirone-treated patients completing 8 weeks of therapy. Imipramine/placebo differences were present from week 2 on, but buspirone/placebo differences occurred only at week 8. The presence of comorbid medical illness or concomitant use of nonpsychiatric prescription medications was not associated with poorer antidepressant response, increased adverse effects, or study attrition.\n Imipramine and to a lesser extent buspirone were found to be effective and well tolerated in the treatment of elderly depressed outpatients.", "Seventy-eight nondemented elderly depressed patients underwent an extensive battery of cognitive tests both before and after seven weeks of treatment with nortriptyline, phenelzine, or placebo. Clinical and cognitive evaluations of the patients were under double-blind conditions. Response to treatment did not appear to significantly affect cognitive capacity; neither did treatment with an active substance as compared to placebo. In addition, the baseline level of cognitive functioning did not appear related to whether a patient responded to treatment. The authors conclude that under optimal conditions neither antidepressant produces measurable changes in the cognitive capacity of nondemented elderly patients.", "This multi-centre, double-blind study, carried out in France, was designed to compare the efficacy and tolerability of paroxetine and clomipramine in elderly patients, aged 60 or above, with reactive depression according to Feighner's criteria. Patients were randomly allocated to treatment with either paroxetine (20 mg o.d.), 41 patients, or clomipramine (increasing from 20 mg o.d. to 20 mg tds), 42 patients, for 5 weeks. Placebo tablets were used to maintain blinding. The degree of depression was determined using the Montgomery-Asberg and the Zung self-rating scales, and also assessed on a visual analogue scale. After 5 weeks of treatment both treatment groups showed a similar degree of improvement on all rating scales. There were no significant differences between the groups. Adverse events occurred in 26 and 28 patients in the paroxetine and clomipramine groups, respectively. In the paroxetine group, many of the events were typical of the gastrointestinal side-effects associated with 5-HT uptake inhibitor therapy. Patients receiving clomipramine experienced events of the type commonly reported with tricyclic antidepressants. There were no significant differences between the groups for either total number of events or for number of patients with specific events. Clinical and laboratory monitoring showed that both drugs were well tolerated.", "A total of 101 patients entered a double-blind, parallel-group study in general practice, comparing the efficacy and tolerability of paroxetine and amitriptyline in elderly depressed patients. All patients received placebo for 1 week followed by active therapy for a total of 6 weeks. Medication was randomly allocated, two-thirds of the patients took paroxetine (20 mg daily) and one-third received amitriptyline (50 mg daily); this dose was increased to 30 mg and 100 mg, respectively, after 1 week. Of the patients who entered the placebo run-in, 90 took active treatment and were evaluable on an intention-to-treat basis (56 paroxetine, 32 amitriptyline). The mean age of the patients was 72 years. Significant reductions in Hamilton Depression Rating Scale (HAMD) from baseline to the end of treatment were seen for both groups (p < 0.01), with no difference between treatments. The HAMD score was reduced by half, or more, for 76% of patients taking paroxetine and 86% taking amitriptyline. Significant improvement was observed in the investigators' Clinical Global Impression (CGI) score for 57% of patients taking paroxetine and 52% on amitriptyline. Improvements after treatment were also observed in the Leeds Sleep Evaluation Questionnaire (LSEQ) scores. Significantly fewer patients taking paroxetine reported adverse events (34% vs 63% taking amitriptyline, p = 0.02). Those taking paroxetine experienced significantly fewer anticholinergic side effects (7% vs 25% taking amitriptyline, p = 0.04). Overall, this study confirmed the effectiveness of paroxetine as an antidepressant drug.(ABSTRACT TRUNCATED AT 250 WORDS)", "Thirty outpatients between the ages of 60 and 85 with DSM-III Major Depression entered an 8 week randomized, double-blind comparison of desipramine and adinazolam mesylate, a triazolobenzodiazepine derivative. Outcome was assessed on several measures including the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Rating Scale, Clinical Global Impressions (CGI), the 35-item Self-Rating Symptom Scale, and Carroll Depression Scale. Patients in both groups demonstrated a highly significant decrease in average HDRS scores (p less than 0.001) over the course of the study. Adinazolam was associated with significantly greater reduction in average HDRS scores by the third day. Repeated measures analysis of variance showed a significantly greater reduction in HDRS scores for adinazolam over the course of the study. The study medications were associated with distinct patterns of adverse reactions. Desipramine more often produced dry mouth, constipation and nervousness, while adinazolam was more likely to cause drowsiness and lightheadedness. Three of these elderly patients, all of whom were taking desipramine reported at least one fall during the study. Adinazolam may be a promising agent in the treatment of depression in the elderly." ]

[ "12522748", "17035445", "68383", "12706704", "15612969", "12924797", "342624", "9367461", "7426351", "15189916", "8106775", "8241913", "7966893", "1530193" ]

[ "Recognizing influenza in older patients with chronic obstructive pulmonary disease who have received influenza vaccine.", "Impact of a winter respiratory virus season on patients with COPD and association with influenza vaccination.", "Longer term effects of live influenza vaccine in patients with chronic pulmonary disease.", "Efficacy trial of live, cold-adapted and inactivated influenza virus vaccines in older adults with chronic obstructive pulmonary disease: a VA cooperative study.", "Adverse effects associated with influenza vaccination in patients with COPD: a randomized controlled study.", "Economic evaluation of influenza vaccination in Thai chronic obstructive pulmonary disease patients.", "Clinical trials of bivalent influenza A/New Jersey/76-A/Victoria/75 vaccines in the elderly.", "Influenza virus vaccination of patients with chronic lung disease.", "A study of live influenza virus vaccine in patients with chronic bronchitis. Report to Medical Research Council's Committee on Influenza and Other Respiratory Virus Vaccines. Advisory Group on pulmonary function tests in relation to live influenza virus vaccines.", "Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study.", "Evaluation of cold-adapted, reassortant influenza B virus vaccines in elderly and chronically ill adults.", "Adverse reactions to influenza vaccine in elderly people: randomised double blind placebo controlled trial.", "The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial.", "Protective efficacy of combined live intranasal and inactivated influenza A virus vaccines in the elderly." ]

[ "A substudy analysis was conducted to determine the clinical characteristics associated with symptomatic, laboratory-documented influenza (LDI) among 2215 veterans with chronic obstructive pulmonary disease who participated in Department of Veterans Affairs Cooperative Study 448 and who received trivalent inactivated influenza virus vaccine with or without intranasal live-attenuated, cold-adapted influenza vaccine. Of 585 evaluable first occurrences of acute respiratory illnesses, 94 (16%) were LDI. Respiratory symptoms of cough, sputum production, and dyspnea occurred in >90% of patients with LDI; 68% had documented or subjective fever, and 81% had myalgias. Stepwise logistic regression identified only fever and myalgia as being statistically associated with LDI. During the influenza outbreak period, the positive predictive value of fever and myalgia was 41%. Clinical criteria were poor predictors of LDI in these older, vaccinated patients with chronic lung disease. Additional studies are warranted to define optimal methods for the diagnosis of influenza among older persons with chronic obstructive pulmonary disease.", "We assessed the effects of an influenza season on patients with COPD. Data from 2,215 veterans in a multicenter, randomized, double-blind influenza vaccine efficacy study were analyzed for changes in spirometric and functional status, comparing patients with laboratory-documented influenza (LDI)-caused illness, non-LDI-caused respiratory illness, or no illness, and for association with influenza vaccination.\n Patients received either IM trivalent inactivated influenza virus vaccine (TIV) plus intranasal trivalent, live attenuated, cold-adapted influenza virus vaccine (TC) or TIV plus intranasal placebo (TP). We performed spirometry, measured the chronic lung disease severity index (CLDSI) score to assess functional status and well-being, and tested for influenza virus infection.\n Worsening in FEV(1), percentage of predicted FEV(1), and CLDSI score (p < 0.001) was associated with acute respiratory illness in 585 illnesses including 94 LDI-caused illnesses. LDI-caused illness was more likely to be associated with worsening in FEV(1) and CLDSI score acutely than non-LDI-caused illness (p < 0.01). Logistic regression showed acute respiratory illness (odds ratio [OR], 1.78; 95% confidence limit [CL], 1.40 to 2.26) to be associated with worsening in CLDSI score, and receipt of TC (OR, 1.39; 95% CL, 1.10 to 1.74) and no illness (OR, 0.70; 95% CL, 0.53 to 0.91 for acute respiratory illness) to be associated with better CLDSI score at the end of the study. Hospitalization was more frequent in patients with acute respiratory illness (p < 0.0001).\n Acute respiratory illness was associated with increased health-care utilization and obstruction to airflow, and worse functional status and well-being. At the end of the study, receipt of TC was associated with improvement and acute respiratory illness was associated with worsening in functional status and well-being.", "WRL 105 strain live influenza vaccine or placebo was given to patients with chronic bronchitis in a double-blind study. The twenty-one vaccinated and twenty-three placebo-treated patients made daily self-assessments of the severity of symptoms of cough, breathlessness, tightness, wheeze, and sputum production in the following 20 weeks. Symptom scores in the first 2 weeks after vaccination or treatment with placebo were used to calculate a baseline range for each patient. Comparison of symptoms in the two groups in the baseline period showed that symptoms were more often reported by vaccinated than by placebo-treated patients but the differences were not statistically significant. One patient who responded serologically to vaccination had a moderately severe influenzal illness starting on the day after vaccination. Comparison of symptom scores during the 18-week surveillance period with baseline values showed that symptoms of breathlessness, tightness, wheeze and cough were significantly more common in vaccinated than in placebo-treated patients and that antibiotic usage was more common in the vaccinated group.", "We assessed whether trivalent live, cold-adapted influenza virus (CAIV-T) vaccine provides added protection when co-administered with trivalent inactivated influenza virus vaccine (TVV) in patients with chronic obstructive pulmonary disease (COPD). Subjects (N=2215) were randomly assigned to receive either TVV intramuscularly (IM) and CAIV-T intranasally (TC), or TVV and placebo (TP). The vaccines were well-tolerated. Efficacy of TC compared to TP was not statistically significant and was 0.16 for any influenza virus strain (95% confidence limit (CL): -0.22, 0.43), 0.26 for A (H3N2) virus (95% CL: -0.17, 0.53), and -0.05 for type B virus (95% CL: -1.13, 0.48). However, there was a possible advantage for TC over TP in reducing respiratory consequences of an influenza season measured by pulmonary function and symptoms at end of study.", "The aim of this study was to assess the frequency and type of adverse reactions following influenza vaccination and its effects on lung function, dyspnoeic symptoms, exercise capacity, and clinical acute respiratory illness (ARI) in patients with COPD, and the relationship of these adverse effects to the degree of airflow obstruction.\n A stratified, randomized, double-blind placebo-controlled study was conducted over an 18-month period at a single university hospital. In total, 125 patients with COPD were randomized to the vaccine group (62 patients who received purified trivalent split-virus vaccine injections) or the placebo group (63 patients). Local and systemic symptoms during the week following the injections were evaluated. Clinical ARI, lung function tests, dyspnoeic symptoms (assessed using a visual analogue scale), and a 6-min walking test were evaluated before and at 1 week and 4 weeks following vaccination.\n The frequency of local adverse reactions was 27% in the vaccine group and 6% in the placebo group (P = 0.002). There was no significant difference in systemic adverse reactions between the vaccine and placebo groups (76% vs. 81%; P= 0.5). No difference was observed in the incidence of ARI between the vaccine and placebo groups during the first week (6.4% vs. 6.3%; P= 1) and the first 4 weeks (24.2% vs. 31.7%; P= 0.5) following vaccination. There was no significant change in lung function, dyspnoeic symptoms, and exercise capacity of the patients in both groups, at 1 week and 4 weeks following vaccination, regardless of the severity of COPD.\n Influenza vaccination is associated with minimal local adverse reactions in patients with COPD. Vaccination does not cause systemic adverse reactions, induce clinical exacerbations or adversely affect lung function, dyspnoeic symptoms and exercise capacity in patients with COPD, regardless of the severity of airflow obstruction.", "To determine the cost-effectiveness and cost-benefit of influenza vaccination in chronic obstructive pulmonary disease (COPD) patients the authors conducted a stratified randomized, double-blind, placebo-controlled trial from June 1997 to November 1998 at a university hospital in Thailand. A total of 125 COPD patients were stratified based on their FEV1 as mild COPD (FEV1 > or = 70% predicted), moderate COPD (FEV1 50-69% predicted) and severe COPD (FEV1 < 50% predicted) and in each severity stratum they were randomized to the vaccine group (received intramuscular injection with purified trivalent split-virus vaccine containing A/Texas/36/91 (H1N1), A/Nanchang 1933/95 (H3N2) and B/Harbin 107/94) or the placebo group (received intramuscular injection with vit B1). Number of episodes of acute respiratory illness (ARI) related to influenza (clinical ARI + a serum hemagglutination inhibition antibody titre of 38 or greater and a four fold titre increase in convalescent serum compared to acute serum) as well as severity of each ARI (outpatient treatment, hospitalization or required mechanical ventilation) and costs of treatment (direct medical costs comprised real drug costs from the hospital dispensary in outpatient cases and real charges in hospitalization cases) were collected and analyzed for the cost-effectiveness and cost-benefit of influenza vaccination. The incidence of influenza-related ARI in the study year was 27 per cent in the placebo group and 6.4 per cent in the vaccine group (relative risk [RR] 0.24, vaccine effectiveness 76%). The incidence was 27.3 per cent, 23.5 per cent and 29.2 per cent in mild, moderate and severe COPD respectively in the placebo group and 4.3 per cent, 12.5 per cent, and 4.3 per cent in the mild, moderate and severe COPD respectively in the vaccine group (RR 0.16, 0.53 and 0.15; vaccine effectiveness 84%, 47%, and 85% respectively). The incremental cost-effectiveness ratios demonstrated that for every 100 patients with mild COPD whom the authors decided to vaccinate, the cost would be 24,840 baht more and would prevent 18.2 outpatients, 4.8 hospitalizations and 0 patient from mechanical ventilation due to ARI related to influenza. Likewise, the authors would have prevented 5.1 outpatients, 5.9 hospitalizations, 5.9 mechanical ventilation and 20.8 outpatients, 3.9 hospitalizations, 8.3 mechanical ventilation for every 100 moderate COPD and every 100 severe COPD patients vaccinated respectively. More than 90 per cent of the costs of treatment of influenza-related ARI were costs of hospitalization and for patients with moderate and severe airflow obstruction, more than 90 per cent of these costs were attributed to the costs of treating the patients who required mechanical ventilation. Predicted cost savings for every 100 mild COPD, 100 moderate COPD and 100 severe COPD patients vaccinated were 125,629 baht, 538,184.3 baht, and 680,647.1 baht respectively. In conclusion: Influenza vaccination is highly effective in the prevention of acute respiratory illness related to influenza virus infection in COPD, regardless of severity of airflow obstruction. Vaccination is more cost-effective in preventing mechanical ventilation episodes and more cost-benefit in patients with more severe airflow obstruction. Influenza vaccination should be recommended to all patients with COPD with the higher priority provided to patients with more severe airflow obstruction.", "This placebo-controlled evaluation in elderly persons of inactivated influenza virus vaccines containing 200 or 400 chicke cell-agglutinating units of both A/New Jersey/76 and A/Victoria/75 antigens revealed mild systemic reactions in 7.8% and moderate reactions in 4.9% of vaccinees. These reactions were more common after administration of whole-virus than subvirion vaccines, more frequent in females than males, and more frequent in persons with low initial titers of antibody to A/New Jersey antigen. Local inflammation occurred in 18.7% of vaccinees (predominantly females) and frequently was seen with systemic reactions, but did not correlate with antibody response. Titers of antibody to A/New Jersey antigen were initially high and 99% of vaccinees had titers of greater than 1:20 after vaccination. Titers of antibody to A/Victoria antigen were initially low, and 56% of vaccinees had titers of greater than 1:20 after vaccination. Fourfold or greater increases in titer occurred in about 50% of vaccinees for each virus, most often concomitantly. Antibody responses to subvirion and whole-virus vaccines were similar, and increased responses with higher doses coincided with increased reactogenicity. Later revaccinations because of low titers of A/Victoria antibody produced negligible antibody responses.", "To evaluate the safety of, and mucosal and systemic immune responses induced by two influenza virus vaccine regimens in subjects with COPD.\n Single-center, blinded, randomized, prospective clinical trial evaluating two vaccine regimens.\n Outpatient clinics of St. Louis Department of Veterans Affairs Medical Center.\n Volunteers (age range, 42 to 88 years) had preexisting COPD with severe obstruction to airflow on average, were male, and were not receiving immunosuppressive medication.\n Twenty-nine volunteers were randomly assigned to receive either bivalent live attenuated influenza A virus vaccine (CAV) or saline solution placebo intranasally. All subjects also received an i.m. injection of trivalent inactivated influenza virus vaccine (TVV) simultaneously.\n Clinical status and pulmonary function measured by spirometry did not change significantly after vaccination. Using hemagglutinins (H1 and H3 HA) which more closely resembled those in CAV, mean levels of anti-HA immunoglobulin A (IgA) antibodies in nasal washings increased significantly after vaccination with CAV and TVV compared to prevaccination, but they did not increase significantly after TVV and intranasal placebo. Mean levels of influenza A virus-stimulated interleukin-2 and -4 produced by peripheral blood mononuclear cells in vitro increased significantly after administration of the combination vaccine regimen and to a lesser extent after TVV and intranasal placebo compared to respective prevaccination levels. The timing of the cytokine response appeared different following CAV and TVV compared to TVV and intranasal placebo.\n Intranasally administered CAV was safe when given with i.m. administered TVV and there may be an immunologic advantage to administration of the combination vaccine regimen compared to TVV with intranasal placebo.", "A multicentre study of the effects of influenza virus RIT 4050 (H3N2) in patients with chronic bronchitis was conducted by members of an MRC Committee. The results showed that RIT 4050 vaccine virus did not cause a deterioration in clinical or physiological status in these patients within the limitation of the relatively reproducible ventilatory tests which were employed. This conclusion applied equally to those who were inoculated and became infected and to those who failed to develop serological evidence of infection. The relatively high proportion of antibody-negative volunteers not infected by the inoculated virus raises doubts concerning the value of this method of immunization for patients at risk during influenza epidemics.", "To determine the effectiveness of influenza vaccination on influenza-related acute respiratory illness (ARI) and overall ARI in patients with COPD, and its relationship to the degree of airflow obstruction.\n Stratified, randomized, double-blind, placebo-controlled trial.\n From June 1997 to November 1998 at a single university hospital. Patients and interventions: One hundred twenty-five patients with COPD were stratified based on their FEV(1) as having mild, moderate, and severe COPD. Within each group, they were randomized to the vaccine group (62 patients who received purified, trivalent, split-virus vaccine) or the placebo group (63 patients).\n The number of episodes and severity of total ARI, classified as outpatient treatment, hospitalization, and requirement of mechanical ventilation; and the number of episodes and severity of influenza-related ARI.\n The incidence of influenza-related ARI was 28.1 per 100 person-years and 6.8 per 100 person-years in the placebo group and vaccine group, respectively (relative risk [RR], 0.24 [p = 0.005]; vaccine effectiveness, 76%). The incidences were 28.2, 23.8, and 31.2 per 100 person-years in the patients with mild, moderate, and severe COPD, respectively, in the placebo group, and 4.5, 13.2, and 4.6 per 100 person-years in the patients with mild, moderate, and severe COPD, respectively, in the vaccine group (RR, 0.16 [p = 0.06]; vaccine effectiveness, 84%; RR, 0.55 [p = 0.5]; vaccine effectiveness, 45%; and RR, 0.15 [p = 0.04]; vaccine effectiveness, 85%, in the patients with mild, moderate, and severe COPD, respectively). Bivariate analysis revealed that the effectiveness of influenza vaccination was not modified by the severity of COPD, comorbid diseases, age, gender, or current smoking status. There was no difference in the incidence or severity of total ARI between the placebo group and the vaccine group.\n Influenza vaccination is highly effective in the prevention of influenza-related ARI regardless of the severity of COPD. Influenza vaccination does not prevent other ARIs unrelated to influenza. The effectiveness of influenza vaccination in the prevention of overall ARI in patients with COPD will depend on how much the proportion of influenza-related ARI contributes to the incidence of total ARI. Influenza vaccination should be recommended to all patients with COPD.", "The safety and immunogenicity of two recent cold-adapted reassortant influenza B viruses were evaluated in persons at high risk for influenza-related morbidity and mortality. Ambulatory adults > 65 years old or with chronic high-risk conditions were randomly assigned to receive parenteral trivalent inactivated influenza vaccine containing either influenza B/Ann Arbor/86 or B/Yamagata/88 hemagglutinin antigens, cold-adapted reassortant influenza B/Ann Arbor/1/86 or B/Yamagata/16/88 viruses (10(7.2) TCID50), or placebo in double-blind fashion. Cold-adapted vaccine viruses were well tolerated, with similar rates of respiratory symptoms in all groups. There were no changes in spirometry or oxygen saturation following vaccination. Immune responses to both types of vaccine were modest, with serum antibody responses occurring significantly more frequently and with higher magnitude in those receiving inactivated than in those receiving cold-adapted vaccine. Cold-adapted, reassortant influenza B vaccines are safe in the elderly and those with chronic illness but are not optimally immunogenic in this group.", "To assess the frequency and type of side effects after influenza vaccination in elderly people.\n Randomised double blind placebo controlled study.\n 15 general practices in the southern Netherlands.\n 1806 patients aged 60 or older, of whom 904 received influenza vaccine and 902 placebo.\n Adverse reactions reported on postal questionnaire completed four weeks after vaccination.\n 210 (23%) patients given vaccine reported one or more adverse reactions compared with 127 (14%) given placebo. The frequency of local adverse reactions were 17.5% in the vaccine group and 7.3% in the placebo group (p < 0.001). There was no difference in systemic adverse reactions (11% v 9.4%; p = 0.34). In general, men reported fewer side effects than women.\n Only local side effects were more common in vaccinated patients and all side effects were mild.", "To determine the efficacy of influenza vaccination in elderly people.\n Randomized double-blind placebo-controlled trial.\n Fifteen family practices in the Netherlands during influenza season 1991-1992.\n A total of 1838 subjects aged 60 years or older, not known as belonging to those high-risk groups in which vaccination was previously given.\n Purified split-virion vaccine containing A/Singapore/6/86(H1N1), A/Beijing/353/89(H3N2), B/Beijing/1/87, and B/Panama/45/90 (n = 927) or intramuscular placebo containing physiological saline solution (n = 911).\n Patients presenting with influenzalike illness up to 5 months after vaccination; self-reported influenza in postal questionnaires 10 weeks and 5 months after vaccination; serological influenza (fourfold increase of antibody titer between 3 weeks and 5 months after vaccination).\n The incidence of serological influenza was 4% in the vaccine group and 9% in the placebo group (relative risk [RR], 0.50; 95% confidence interval [CI], 0.35 to 0.61). The incidences of clinical influenza were 2% and 3%, respectively (RR, 0.53; 95% CI, 0.39 to 0.73). The effect was strongest for the combination of serological and clinical influenza (RR, 0.42; 95% CI, 0.23 to 0.74). The effect was less pronounced for self-reported influenza.\n In the elderly, influenza vaccination may halve the incidence of serological and clinical influenza (in periods of antigenic drift).", "To evaluate the efficacy of adding intranasal live attenuated cold-adapted influenza A vaccine to inactivated influenza vaccine to prevent influenza A in elderly residents of long-term-care institutions.\n Randomized, double-blind, placebo-controlled study conducted over 3 years.\n Three large nursing homes.\n A total of 523 residents of nursing homes (mean age, 84.2 years).\n All participants received trivalent inactivated influenza vaccine parenterally and were randomly assigned to receive either live attenuated influenza A (H3N2) virus vaccine or placebo intranasally.\n Laboratory-documented influenza A was defined as a respiratory illness plus isolation of influenza A virus from nasal secretions, significant serologic response, or both. Participants were considered to have been exposed to influenza A if they resided in an institution in which cases of influenza A were documented. Outbreak-associated illnesses were defined as those occurring between the first and last isolation of influenza virus from within the institution, +/- 3 days.\n Participants who received intranasal vaccine and were subsequently exposed to influenza A had significantly lower rates of laboratory-documented influenza A (9 of 162 vaccine recipients compared with 24 of 169 placebo recipients; vaccine protective efficacy, 60.6%; 95% CI, 18% to 82%), outbreak-associated respiratory illnesses (13 of 162 vaccine recipients compared with 34 of 169 placebo recipients; vaccine protective efficacy, 56.8%; CI 23% to 76%), and outbreak-associated influenza-like illnesses (6 of 162 vaccine recipients compared with 18 of 169 placebo recipients; vaccine protective efficacy, 65.0%; CI 17% to 86%).\n Intranasal immunization with live attenuated influenza A virus vaccine provided additional protection against influenza A when added to parenteral trivalent inactivated influenza vaccine among elderly nursing home residents." ]

[ "20952244", "9989713" ]

[ "Manual or exercise therapy for long-standing adductor-related groin pain: a randomised controlled clinical trial.", "Effectiveness of active physical training as treatment for long-standing adductor-related groin pain in athletes: randomised trial." ]

[ "A multi-modal treatment program (MMT) is more effective than exercise therapy (ET) for the treatment of long-standing adductor-related groin pain.\n Single blinded, prospective, randomised controlled trial.\n Patients: Athletes with pain at the proximal insertion of the adductor muscles on palpation and resisted adduction for at least two months. Interventions: ET: a home-based ET and a structured return to running program with instruction on three occasions from a sports physical therapist. MMT: Heat, Van den Akker manual therapy followed by stretching and a return to running program. Primary outcome: time to return to full sports participation. Secondary outcome measures: objective outcome score and the visual analogue pain score during sports activities. Outcome was assessed at 0, 6, 16 and 24 weeks.\n Athletes who received MMT returned to sports quicker (12.8 weeks, SD 6.0) than athletes in the ET group (17.3 weeks, SD 4.4. p = 0.043). Only 50-55% of athletes in both groups made a full return to sports. There was no difference between the groups in objective outcome (p = 0.72) or VAS during sports (p = 0.12).\n The multi-modal program resulted in a significantly quicker return to sports than ET plus return to running but neither treatment was very effective.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "Groin pain is common among athletes. A major cause of long-standing problems is adductor-related groin pain. The purpose of this randomised clinical trial was to compare an active training programme (AT) with a physiotherapy treatment without active training (PT) in the treatment of adductor-related groin pain in athletes.\n 68 athletes with long-standing (median 40 weeks) adductor-related groin pain--after examination according to a standardised protocol--were randomly assigned to AT or PT. The treatment period was 8-12 weeks. 4 months after the end of treatment a standardised examination was done. The examining physician was unaware of the treatment allocation. The ultimate outcome measure was full return to sports at the same level without groin pain. Analyses were by intention to treat.\n 23 patients in the AT group and four in the PT group returned to sports without groin pain (odds ratio, multiple-logistic-regression analysis, 12.7 [95% CI 3.4-47.2]). The subjective global assessments of the effect of the treatments showed a significant (p=0.006) linear trend towards a better effect in the AT group. A per-protocol analysis did not show appreciably different results.\n AT with a programme aimed at improving strength and coordination of the muscles acting on the pelvis, in particular the adductor muscles, is very effective in the treatment of athletes with long-standing adductor-related groin pain. The potential preventive value of a short programme based upon the principles of AT should be assessed in future, randomised, clinical trials." ]

[ "2899582", "6626903", "2889770", "3324917", "19046051", "2670608" ]

[ "A comparison of the effects of preoperative whole-body bathing with detergent alone and with detergent containing chlorhexidine gluconate on the frequency of wound infections after clean surgery. The European Working Party on Control of Hospital Infections.", "Wound infection following vasectomy.", "A placebo-controlled trial of the effect of two preoperative baths or showers with chlorhexidine detergent on postoperative wound infection rates.", "The effect of washing with chlorhexidine soap on wound infection rate in general surgery. A controlled clinical study.", "Randomized controlled trial of the effectiveness of chlorhexidine showers before elective plastic surgical procedures.", "Do preoperative chlorhexidine baths reduce the risk of infection after vascular reconstruction?" ]

[ "In a prospective, randomized, double-blind, placebo-controlled study involving 27 surgical units in six European countries, the effect of preoperative whole-body bathing on two occasions with a detergent containing chlorhexidine (CHX+) on the incidence of wound infection in elective, clean surgery was compared with two bathings with a detergent without chlorhexidine (CHX-). In the CHX+ group 2.62% of 1413 patients and in the CHX- group 2.36% of 1400 patients subsequently became infected. The infection rate in the CHX+ group was 1.11 times that in the CHX- group with 95% confidence limits ranging between 0.69 and 1.82. Consequently, bathing patients twice preoperatively with chlorhexidine-detergent did not reduce the incidence of infection of clean wounds.", "Ninety-four patients undergoing vasectomy as day cases were studied prospectively. An overall infection rate of 32.9% was recorded and, apart from haematoma formation and the nasal carriage of organisms, no factors were found that increased the risk of infection. A preoperative hibiscrub shower did not affect the infection rate, even though it was responsible for a significant reduction in skin flora. This raises the possibility of infection following vasectomy being secondary, not occurring at the time of surgery.", "The effect of preoperative whole-body washing with chlorhexidine detergent on the incidence of postoperative wound infection was assessed in a placebo-controlled trial of 1989 patients. Patients bathed or showered with chlorhexidine, placebo, or conventional bar soap, on two occasions in the 24 h before operation. The overall infection rate for patients treated with chlorhexidine was 9%, against 12.8% in the bar soap and 11.7% in the placebo groups; in the 'clean' surgery group infections were 7.2% against 10.2% and 10%, respectively. The Staphylococcus aureus infection rate in the 'clean' group was 3% for chlorhexidine against 6% for bar soap.", "Postoperative wound infections in clean surgery were studied to compare the effect of preoperative whole body disinfection with chlorhexidine soap with that of local washing and no washing at all, respectively. The study includes 1530 operations for biliary tract disease, inguinal hernia and breast cancer. The overall infection rate was 3.4%. Among patient who had a preoperative shower with Chlorhexidine the wound infection rate was significantly reduced.", "This randomized controlled trial was designed to assess the effect of preoperative chlorhexidine showers on skin colonization and postoperative infection rates associated with plastic surgical procedures involving the trunk. Chlorhexidine showers were effective in reducing skin colonization with coagulase-negative staphylococci and yeasts, but there was no difference in postoperative infection rates.", "Pathogenic organisms are frequently present on the skin of vascular patients and are a risk factor for postoperative infection. A randomised trial of preoperative antiseptic baths was performed in 64 high risk vascular patients to determine whether two chlorhexidine baths could reduce the incidence of postoperative sepsis. Although pathogenic organisms were isolated preoperatively in 35% of patients, the wound infection rate after chlorhexidine baths (26%) was greater, though not significantly, than after baths with non-medicated soap (11%). An alternative theory that infection arises via lymphatics in the limb was not confirmed when organisms could not be isolated from groin lymph nodes in a group of 35 patients. The case for preoperative antiseptic regimes in vascular surgery remains unproven." ]

[ "20876412" ]

[ "Pregabalin for the treatment of men with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial." ]

[ "Evidence suggests that the urogenital pain of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) may be neuropathic.\n This randomized, double-blind, placebo-controlled trial was conducted across 10 tertiary care centers in North America to determine whether pregabalin, which has been proved effective in other chronic pain syndromes, is effective in reducing CP/CPPS symptoms. In 2006-2007, 324 men with pelvic pain for at least 3 of the previous 6 months were enrolled in this study. Men were randomly assigned to receive pregabalin or placebo in a 2:1 ratio and were treated for 6 weeks. Pregabalin dosage was increased from 150 to 600 mg/d during the first 4 weeks. The primary outcome was a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score. Multiple secondary outcomes were assessed.\n Of 218 men assigned to receive pregabalin, 103 (47.2%) reported at least a 6-point decrease in the NIH-CPSI total score at 6 weeks compared with 35.8% (38 of 106 men) assigned to receive placebo (P = .07, exact Mantel-Haenszel test, adjusting for clinical sites). Compared with the placebo group, men assigned to receive pregabalin experienced reductions in the NIH-CPSI total score and subscores (P < .05), a higher Global Response Assessment response rate (31.2% and 18.9%; P = .02), and improvement in total McGill Pain Questionnaire score (P = .01). Results for the other outcomes did not differ between groups.\n Pregabalin therapy for 6 weeks was not superior to placebo use in the rate of a 6-point decrease (improvement) in the NIH-CPSI total score in men with CP/CPPS.\n clinicaltrials.gov Identifier: NCT00371033." ]

[ "10479834", "8969391", "11575407", "6711845", "7577284", "2006722" ]

[ "[Total intravenous anesthesia in thoracotomy with one-lung ventilation].", "A comparison of the effects of propofol-alfentanil versus isoflurane anesthesia on arterial oxygenation during one-lung ventilation.", "Effects of sevoflurane and propofol on pulmonary shunt fraction during one-lung ventilation for thoracic surgery.", "One-lung anesthesia--a comparison of pulmonary gas exchange during anesthesia with ketamine or enflurane.", "Comparison of the effects of propofol and isoflurane anaesthesia on right ventricular function and shunt fraction during thoracic surgery.", "[A comparison of enflurane and propofol in thoracic surgery]." ]

[ "The aim of this study was to evaluate the benefits of total intravenous anaesthesia (TIVA), with the administration of drugs intravenously and the maintenance of pulmonary ventilation with oxygen enriched air, with respect to inhalatory anaesthesia, in thoracotomies with single lung ventilation.\n The study, devoloped in collaboration between the Service of Anaesthesia and Resuscitation and the Division of Thoracic Surgery of the Hospital of Teramo, was carried out in two groups of patients chosen at random; fifty patients divided into two groups of twenty-five were studied. Pre-medication and induction was similar in both groups; maintenance, however, varied: a total intravenous anaesthesia was given to patients in group A whereas patients in group B received an inhalatory anaesthesia. These parameters were considered: pressure values, heartbeat, PaO2 and PaCO2 levels, SatO2 and EtCO2.\n Both protocols respected anaesthetic guidelines in terms of controlling pressure values, heartbeat and levels of PaCO2 during bipulmonary ventilation. Significantly statistical differences were observed in the oxygenation during one lung ventilation: the mean values of PaO2 being significantly higher in group A.\n On the basis of this experience, it can be conclude that TIVA offers the following advantages: a better oxygenation during one lung ventilation, good recovery of post operative consciousness with no psychomotor disturbances, absence of pollution in the operating theatre.", "To determine whether intravenous propofol-alfentanil anesthesia provides superior arterial oxygenation (Pao2) during one-lung ventilation (OLV) compared with isoflurane inhalation anesthesia.\n A prospective, randomized, cross-over study.\n Tertiary-care university hospital.\n Thirty adults having either thoracoscopic pulmonary surgery or esophageal surgery.\n Patients received either propofol-alfentanil infusion anesthesia or one minimum alveolar concentration (MAC) of isoflurane during the initial period of two-lung ventilation and the first 30 minutes of OLV and then were switched to the other anesthetic for the duration of OLV.\n Arterial blood gases and hemodynamics were recorded during two-lung ventilation and after 20 and 30 minutes of OLV with each anesthetic technique. The mean values (+/- SD) for Pao2 during propofol-alfentanil anesthesia after 20 minutes (222 +/- 100) and 30 minutes (228 +/- 102 mmHg) of one-lung ventilation were not significantly different than after 20 minutes (213 +/- 99) or 30 minutes (214 +/- 96 mmHg) of isoflurane; beta error less than 0.1. Mean heart rate was lower during intravenous (78 +/- 15 min) than inhalation (85 +/- 17 min) anesthesia (rho = 0.03).\n This study does not support the theory that total intravenous anesthesia will decrease the risk of hypoxemia during OLV.", "Forty patients requiring one-lung ventilation (OLV) for thoracic surgery were randomly assigned to receive propofol (4-6 mg kg(-1) h(-1)) or sevoflurane (1 MAC) for maintenance of anaesthesia. Three sets of measurements were taken: (i) after 30 min of two-lung ventilation (TLV), (ii) after 30 min of one-lung ventilation (OLV-1) in the supine position and (iii) during OLV in the lateral position (OLV-2) with the chest open and before surgical manipulation of the lung. There were no differences between groups in patient characteristics or preoperative condition. Increases in shunt fraction during OLV-1 were 17.4% and 17.2% (P=0.94), those during OLV-2 were 18.3% and 16.5% (P=0.59) for the propofol and sevoflurane group, respectively. Cardiac index and other haemodynamic and respiratory variables were similar for the two groups. We conclude that inhibition of hypoxic pulmonary vasoconstriction by sevoflurane may only account for small increases in shunt fraction and that much of the overall shunt fraction during OLV has other causes.", "Twenty-four men undergoing elective pulmonary resection with a period of one-lung ventilation were studied to compare the effects of ketamine-O2 and enflurane-O2 anesthesia on arterial oxygen tension (PaO2) and intrapulmonary shunting (Qs/Qt). No statistically significant differences were demonstrated between ketamine and enflurane in mean peak Qs/Qt, 43% and 42%, respectively, or minimum PaO2 values, 169 torr and 127 torr, respectively. Stroke volume index, left ventricular stroke work index, and cardiac index were, however, significantly greater with ketamine. No emergence hallucinations were observed in either group. These findings suggest that ketamine affords no advantage over enflurane anesthesia in terms of Qs/Qt, and arterial oxygen desaturation during endobronchial anesthesia.", "I.v. anaesthetic agents, including propofol, have not been shown to inhibit hypoxic pulmonary vasoconstriction (HPV). This may encourage the use of propofol in thoracic surgery where one lung ventilation (OLV) is required. We have compared the effects of maintaining anaesthesia with either isoflurane or propofol infusion on right ventricular function and shunt fraction. We studied 10 patients who received isoflurane and 12 who received propofol. When OLV commenced there was a greater reduction in both mean cardiac index (3.2 (SEM 0.2) to 2.4 (0.1) litre min-1 m-2 for propofol, and 3.4 (0.2) to 3.3 (0.4) litre min-1 m-2 for isoflurane) and right ventricular ejection fraction (0.45 (0.03) to 0.37 (0.02) for propofol, and 0.48 (0.02) to 0.42 (0.02) for isoflurane) in patients who received propofol. Furthermore, these reductions were sustained for longer in the propofol group. However, propofol was not associated with a significant increase in shunt fraction during OLV, which increased threefold in patients who received isoflurane.", "Comparisons between propofol and inhalational anesthetics for maintenance of anesthesia are limited. The purpose of our prospective study was to examine differences between enflurane and propofol during pulmonary resections with one-lung ventilation (1LV). METHOD. 28 patients, ASA risk group II-III, gave written informed consent for inclusion in this institutionally approved study. The patients were randomly allocated to one of the following groups: A: propofol 10 mg kg-1 h-1, B: 1 MAC enflurane, for maintenance of anesthesia. In both groups analgesia was achieved by fentanyl and muscle relaxation, by pancuronium. Ventilation via a double-lumen tube was controlled (FiO2 = 1.0, PaCO2 35-40 mmHg). Measurements, including hemodynamics and arterial and mixed venous blood gases, were obtained before induction (I), during two-lung ventilation (2LV) 15 min after induction in the supine position (II) and 20 min after surgical opening of the chest in the lateral decubitus position (III), 20 min after starting 1LV (IV), and after extubation (V). RESULTS. No significant differences between the two groups were found before induction (I), during 2LV (II, III), or after extubation (V). The only significant differences between the two groups were observed during 1LV (IV): the shunt fraction was 33.9 +/- 2.5% in A and 38.5 +/- 2.6% in B (P less than or equal to 0.05). Hypoxic pulmonary vasoconstriction was not inhibited in A, but was inhibited by 21.5% in group B during 1LV. Since no case of hypoxemia occurred in group A during 1LV (range of PaO2: 75.2-417.0 mmHg), but four patients developed hypoxemia in group B (Range of PaO2: 46.6-431.0 mmHg), regimen A might be of value in high-risk patients during thoracic surgery when 1LV is planned." ]

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[ "Does ketamine have preemptive effects in women undergoing abdominal hysterectomy procedures?", "Postoperative analgesia with i.v. patient-controlled morphine: effect of adding ketamine.", "Can ketamine potentiate the analgesic effect of epidural morphine, preincisional or postincisional administration?", "PCA ketamine and morphine after abdominal hysterectomy.", "Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy.", "Effect of the addition of ketamine to morphine in patient-controlled analgesia.", "Small-dose S(+)-ketamine reduces postoperative pain when applied with ropivacaine in epidural anesthesia for total knee arthroplasty.", "Small-dose ketamine enhances morphine-induced analgesia after outpatient surgery.", "Epidural ketamine reduces post-operative epidural PCA consumption of fentanyl/bupivacaine.", "Postoperative pain management with intravenous patient-controlled morphine: comparison of the effect of adding magnesium or ketamine.", "[Lack of pre-emptive analgesic effect of low-dose ketamine in postoperative patients. A prospective, randomised double-blind study].", "Preincisional intravenous low-dose ketamine and local infiltration with ropivacaine reduces postoperative pain after laparoscopic cholecystectomy.", "The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair.", "Mapping of punctuate hyperalgesia around a surgical incision demonstrates that ketamine is a powerful suppressor of central sensitization to pain following surgery.", "Preoperative ketamine improves postoperative analgesia after gynecologic laparoscopic surgery.", "The effects of small-dose ketamine on morphine consumption in surgical intensive care unit patients after major abdominal surgery.", "'Balanced analgesia' in the perioperative period: is there a place for ketamine?", "Intraoperative intravenous ketamine in combination with epidural analgesia: postoperative analgesia after renal surgery.", "Lack of pre-emptive analgesic effect of (R)-ketamine in laparoscopic cholecystectomy.", "Improvement of pain treatment after major abdominal surgery by intravenous S+-ketamine.", "Comparison of postoperative analgesic effects of preemptively used epidural ketamine and neostigmine.", "A randomised, controlled study of peri-operative low dose s(+)-ketamine in combination with postoperative patient-controlled s(+)-ketamine and morphine after radical prostatectomy.", "Analgesic effects and pharmacokinetics of a low dose of ketamine preoperatively administered epidurally or intravenously.", "Adding ketamine in a multimodal patient-controlled epidural regimen reduces postoperative pain and analgesic consumption.", "Perioperative small-dose S(+)-ketamine has no incremental beneficial effects on postoperative pain when standard-practice opioid infusions are used.", "Preemptive analgesia by intravenous low-dose ketamine and epidural morphine in gastrectomy: a randomized double-blind study.", "Comparison of morphine and morphine with ketamine for postoperative analgesia.", "Preoperative epidural ketamine in combination with morphine does not have a clinically relevant intra- and postoperative opioid-sparing effect.", "Evaluation of the safety and efficacy of epidural ketamine combined with morphine for postoperative analgesia after major upper abdominal surgery.", "Effect of i.v. ketamine in combination with epidural bupivacaine or epidural morphine on postoperative pain and wound tenderness after renal surgery.", "Supplementing desflurane-remifentanil anesthesia with small-dose ketamine reduces perioperative opioid analgesic requirements." ]

[ "Ketamine may produce \"preemptive\" analgesia when administered before surgically induced trauma. Therefore, we hypothesized that pre- versus postincisional administration of ketamine would improve pain control after abdominal hysterectomy procedures. Eighty-nine patients were randomly assigned to one of three treatment groups according to a placebo-controlled, double-blinded protocol: Group 1 (placebo) received saline 0.04 mL/kg IV immediately before and after surgery; Group 2 (preincision), received ketamine 0.4 mg/kg IV before skin incision and saline at the end of the operation; and Group 3 (postincision), received saline before skin incision, and ketamine 0.4 mg/kg IV was given after skin closure. The general anesthetic technique was standardized in all three treatment groups. During the first postoperative hour, Group 3 experienced significantly less pain than Groups 1 and 2, as assessed by using both visual analog and verbal rating scales. There were no significant differences between Groups 1 and 2 with respect to pain scores, postoperative opioid analgesic requirements, and incidence of postoperative nausea and vomiting. We conclude that a single dose of ketamine 0.4 mg/kg IV fails to produce preemptive analgesic effects. Implications: Even though ketamine 0.4 mg/kg IV has short-lasting acute analgesic effects, it failed to produce a preemptive effect when given before abdominal hysterectomy procedures.", "We have studied the effect of adding ketamine to i.v. morphine patient-controlled analgesia (PCA) for the treatment of pain after laparotomy. Thirty patients were allocated randomly to receive PCA with saline or ketamine in a double-blind, randomized study. Analgesia was started in the recovery room when visual analogue scale (VAS) scores were > 4. A bolus dose of morphine 3 mg was given to all the patients followed by i.v. PCA. Simultaneously, an infusion of ketamine 2.5 micrograms kg-1 min-1 or saline was started. Pain scores, morphine consumption and side effects were noted for up to 48 h after the start of PCA. VAS scores decreased significantly with time (P = 0.0001) and were similar (P = 0.3083) in both groups. Cumulative morphine consumption at 48 h was significantly lower in the ketamine group (28 mg) than in the control group (54 mg) (P = 0.0003). Nausea was less frequent in the ketamine group (P = 0.03).", "A randomized controlled trial was conducted to determine the effect of adding epidural ketamine to epidural morphine comparing between giving ketamine at preincisional time and postincisional time on postoperative analgesia in patients undergoing gynecological operations. Eighty patients scheduled for gynecological operation under combined epidural-general anesthesia were randomly divided into 4 groups. Group 1 received epidural morphine 3 mg before skin incision. Group 2 received epidural morphine 3 mg after skin incision. Group 3 received epidural morphine 3 mg and ketamine 30 mg before skin incision. Group 4 received epidural morphine 3 mg and ketamine 30 mg after skin incision. Lidocaine 2 per cent with epinephrine 1:200,000 was used as the main anesthetic agent during the operation in all groups. Postoperative analgesics were pethidine 1 mg/kg intramuscularly or paracetamol 1,000 mg oral. The time to the first analgesic requirement and pain during 48 h were recorded. The amount of pethidine and paracetamol required and the time to the first dose of analgesic requirement were not significantly different among the groups. There were no differences in the incidences of pruritus, nausea, vomiting and nightmare. We concluded that adding ketamine to epidural morphine either by preincisional or postincisional administration did not potentiate the analgesic effect of epidural morphine.", "Following a standardized general anaesthetic for total abdominal hysterectomy, patients received either patient controlled analgesia (PCA) with morphine 1 mg/ml (group M, n = 33) or morphine 1 mg/ml plus ketamine 2 mg/ml (group K, n = 37) for 48 hours in a randomized, double-blind fashion. In 43 women the area of allodynia around the scar was mapped as a measure of the degree of central sensitization. A significant reduction in the area of allodynia was found in those receiving ketamine with morphine (42 cm2 [interquartile range (IQR) 57] compared with 57 cm2 [IQR 82] z = -2.0, P = 0.04) in those receiving morphine alone. There were no significant differences between the two groups with respect to age, or weight, or between the subgroups within which the area of allodynia was measured with respect to length of incision. No significant differences were found between the groups with respect to pain scores, total or hourly drug consumption, patient satisfaction, nausea scores or antiemetic use. Patients in group K were more likely to require PCA for a shorter period than those in group M (median 40 hours, IQR 26 versus 48 hours IQR 7). Ten patients in group K were withdrawn because of side-effects (dysphoria n = 4, nausea n = 2, pruritus n = 4) compared with one in group M (nausea n = 1) (P = 0.006). The potential usefulness of ketamine after hysterectomy was offset by a high incidence of adverse effects and a lack of opioid-sparing effects, such that combined intravenous ketamine and morphine PCA as used in this study cannot be recommended for routine care.", "Ketamine may prevent postoperative hyperalgesia. In patients undergoing arthroscopic meniscectomy using general anesthesia, we tested whether a single intraoperative dose of ketamine enhanced postoperative analgesia and improved functional outcome compared with a typical multimodal analgesic regimen. After the induction of anesthesia, 50 patients were randomly assigned to ketamine (0.15 mg/kg IV just after the induction of anesthesia) or a vehicle placebo. Standardized general anesthesia included propofol, alfentanil, and nitrous oxide. Bupivacaine (0.5%) and morphine (5 mg) were given intraarticularly at the end of surgery. Postoperative analgesia was initially provided with morphine and subsequently with naproxen sodium (550 mg orally twice daily) and Di-Antalvic (400 mg acetaminophen and 30 mg dextropropoxyphene) as needed. Pain scores, analgesic requirements, side effects, and ability to walk were assessed in the ambulatory unit and at home for three postoperative days. Times to awakening and to discharge were similar in the two groups. However, the Ketamine group had significantly less postoperative pain at rest and during mobilization on Days 0, 1, and 2. Furthermore, they consumed significantly fewer Di-Antalvic tablets than the control group (13 [7-17] vs 27 [16-32], median [25%-75% interquartile range]). Patients given ketamine were also able to walk for longer periods of time on the first postoperative day. In conclusion, adding small-dose ketamine to a multimodal analgesic regimen improved postoperative analgesia and functional outcome after outpatient knee arthroscopy.", "This randomised, double-blind, prospective study compared morphine (1 mg x m(-1)) with the combination of morphine (1 mg x m(-1)) and ketamine (0.75 mg x m(-1)) via a patient-controlled analgesia system (PCAS) for postoperative pain control. A total of 42 female patients, ASA grade I and II, undergoing elective total abdominal hysterectomy was studied. During a standardised anaesthetic, a loading dose from the PCA syringe of 10 ml x m(-2) of body surface area was given. A PCAS with a background infusion was commenced postoperatively. Pain and side-effects were assessed using numerical scoring systems and cardiovascular and respiratory parameters were recorded. There was no statistically significant difference between the groups in total morphine consumption or pain scoring. Side-effect profiles and time to mobilisation were similar. This study concludes that the addition of ketamine to morphine, in this dosage regimen, administered via PCAS for postoperative pain control, does not confer benefit following total abdominal hysterectomy.", "Reduction of nociceptive input through blockade of N-methyl-D-aspartate (NMDA) receptors has been reported. We compared the effects of epidural S(+)-ketamine versus placebo on postoperative pain in a randomized, double-blinded study in 37 patients undergoing unilateral knee arthroplasty. After lumbar epidural anesthesia with ropivacaine (10 mg/mL, 10-20 mL), 19 patients received 0.9% epidural saline, and 18 patients received 0.25 mg/kg epidural S(+)-ketamine 10 min before surgical incision. After surgery, patient-controlled epidural analgesia with ropivacaine was provided. During the first 8 h after surgery, visual analog scale pain rating was similar between groups. Twenty-four and 48 h after surgery, patients anesthetized with ropivacaine had higher visual analog scale ratings at rest and during movement (P < 0.05) than patients anesthetized with S(+)-ketamine and ropivacaine. Forty-eight hours after surgery, patients anesthetized with ropivacaine also consumed more ropivacaine (558 +/- 210 mg) (P < 0.01) than those anesthetized with S(+)-ketamine and ropivacaine (319 +/- 204 mg). Adverse events were similar between groups. Patients who received S(+)-ketamine and ropivacaine rated the quality of their pain therapy better than those who received ropivacaine alone (P < 0.05). We conclude that the combination of S(+)-ketamine and ropivacaine in epidural anesthesia increases postoperative pain relief when compared with ropivacaine.\n Epidural S(+)-ketamine applied with ropivacaine before surgery is a rational approach to decrease injury-induced pain sensitization. Epidural blockade with an N-methyl-D-aspartate receptor antagonist and a local anesthetic may provide better analgesia in the postoperative period than a local anesthetic alone.", "Small-dose ketamine may enhance the analgesic effect of opiates. We studied the effect of IV coadministration of small-dose ketamine 50-100 microg/kg with morphine 50 microg/kg on postoperative morphine requirements and pain in 140 patients undergoing outpatient surgery. Midazolam 1-2 mg was administered in the holding area. Anesthesia was induced with propofol 2-2.5 mg/kg and was maintained with desflurane in a nitrous oxide/oxygen mixture. Patients received morphine 50 microg/kg with placebo (Group 1, n = 35) or ketamine 50 microg/kg IV (Group 2, n = 35), 75 microg/kg IV (Group 3, n = 35), or 100 microg/kg IV (Group 4, n = 35) 15 min before the end of the operation. Pain and drowsiness were assessed using visual analog scales on arrival in the recovery room, then every 15 min until the time of discharge to phase 2 recovery (phase 1 recovery). Morphine consumption in Groups 3 and 4 was approximately 40% less than that in the control group (91+/-9 and 89+/-8 microg/kg vs. 145+/-9 microg/kg; P<0.05 for both). Pain scores in Groups 3 and 4 were approximately 35% less than those in the control group at all time periods (P<0.0001 for all). There was no significant group difference in drowsiness scores. Small-dose ketamine 75-100 microg/kg IV, enhanced morphine-induced analgesia after outpatient surgery. Simultaneous use of small doses of ketamine with morphine enhances the pain relief produced by morphine.\n Simultaneous use of small doses of ketamine with morphine enhances the pain relief produced by morphine.", "To study the analgesic effect of epidural ketamine on postoperative pain and epidural PCA consumption after total abdominal hysterectomy.\n Sixty-one ASA I-II patients, 34-60 yr were randomly assigned into three groups. Epidural catheters were inserted before induction of anaesthesia. Patients in group I and II received 30 mg ketamine epidurally before induction of anaesthesia or 20 min after skin incision: group III received placebo. Postoperatively, on first analgesia request, sedation score, Visual Analogue Scale (VAS), Prince Henry Score (PHS) and Bromage motor weakness score were taken and followed by an epidural bolus of 9 ml bupivacaine 0.25% + 50 micrograms fentanyl. Analgesia was maintained by PCA with a mixture of bupivacaine 0.1% + fentanyl 0.001% epidurally. Measurements were repeated at 1, 2, 4, 8, 12 and 24 hr.\n First analgesia request was 17 +/- 6.8 min in the control group compared with 31.4 +/- 23.8 and 44 +/- 23.1 min for groups I and II respectively. The differences between group III and group I (P < 0.05) and between group III and group II (P < 0.01) were statistically significant. Twenty four hour PCA consumption was 101.2 +/- 47.2, 87 +/- 27 and 162 +/- 38 ml for groups I, II and III respectively. The differences between group III and group I and that between group III and group II were statistically significant (P < 0.001).\n Epidural ketamine 30 mg reduces post hysterectomy pain as evidenced by prolongation of time to first analgesia request and reduction in postoperative epidural PCA consumption. This effect is manifest whether ketamine is given before induction or 20 min after skin incision.", "This double-blind randomized study tested whether the addition of magnesium or ketamine to morphine for intravenous patient-controlled analgesia resulted in improved analgesic efficacy and lower pain scores compared with morphine patient-controlled analgesia alone after major abdominal surgery.\n Ninety patients (3 x 30) were randomly allocated to receive either morphine 0.4 mg mL(-1) (Group M) by patient-controlled analgesia, morphine 0.4mg mL(-1) + MgSO4 30mg mL(-1) (Group MM) or morphine 0.4 mg mL(-1) + ketamine 1 mg mL(-1) (Group MK). Postoperative analgesia was started when the verbal rating scale was > or = 2. Patients were first given a standardized loading dose (0.05 mg kg(-1)) of the study solution. They were then allowed to use bolus doses of this solution (0.0125 mg kg(-1) every 20 min without time limit). Discomfort, sedation, pain scores, cumulative morphine consumption and adverse effects were recorded up to 24 h after the start of the patient-controlled analgesia.\n The level of discomfort, level of sedation and verbal rating scores decreased significantly with time in all groups (P < 0.05). Both verbal rating and discomfort scores were significantly lower in Groups MM and MK at 15, 30 and 60 min compared with Group M (P < 0.001). Cumulative morphine consumption after 12 and 24 h was significantly higher in Group M alone (median 26 and 49 mg, respectively) compared with Group MM (24.2 and 45.7 mg) and Group MK (24.4 and 46.5 mg).\n In the immediate postoperative period, the addition of magnesium or ketamine to morphine for intravenous patient-controlled analgesia led to a significantly lower consumption of morphine. However, these differences are unlikely to be of any clinical relevance.", "NMDA receptors are assumed to play an important role for neuronal plasticity. In vitro and animal experiments confirmed that NMDA antagonistic drugs can prevent hyperexitability of dorsal root neurons after strong pain stimuli. Clinical data, however, are more or less controversial in this respect. It was the aim of the present prospective, randomised, double-blind study to verify if low-dose preoperative ketamine, an NMDA antagonist, provides relevant postoperative analgesia in surgical patients and to re-examine positive results published by other investigators. 80 ASA I-II patients undergoing elective laparoscopic or proctologic surgery received at induction of general anaesthesia a single i.v. bolus dose of either ketamine 0.15 mg/kg or placebo (0.9% NaCl). Postoperative analgesia was provided by i.v. patient-controlled analgesia (PCA) using the opioid piritramide. Cardiovascular parameters, respiration, sedation, cumulative piritramide consumption and pain scores (visual analogue scale 1-10, verbal rating scale 0-4) were monitored at 1, 2, 3, 4, 5, 6, 12 and 24 hours after surgery. Additionally, a retrospective pain score was documented after the 24 hours observation period. There was no statistically significant difference in any study parameter. Cumulative PCA piritramide consumption after 24 hours was 25.0+/-16.2 mg in the ketamine group and 29.5+/-20.4 mg in the placebo group. Ketamine-specific side effects such as hallucinations or bad dreams were not observed. It is concluded that under the study conditions used, low dose ketamine, contrary to previously reported results [30], does not provide a clinically relevant pre-emptive analgesic effect in postoperative patients.", "The preincisional use of ketamine combined with local tissue infiltration with Ropivacaine may reduce noxious input during surgery. The goal of this study was to examine whether this combination improves postoperative pain control after laparoscopic cholecystectomy.\n A total of 55 patients were randomly assigned to one of three groups. Group 1 received placebos preincisional. Group 2 received preincisional saline IV and local infiltration with 20 ml ropivacaine (10 mg/ml). Group 3 received preincisional ketamine 1 mg/kg IV and local infiltration with 20 ml ropivacaine (10 mg/ml). Postoperative pain was rated at 0, 3, 6, 12, 24, and 48 h postoperatively by visual analogue scale scores (VAS). Cumulative analgesic consumption and time until first analgesic medication request were recorded.\n Group 3 experienced significantly (p < 0.05) less pain than group 2 at 6 h and 12 h postoperatively. Groups 2 and 3 did not differ significantly by VAS at 0 h, 3 h, 24 h, and 48 h. Group 1 had significantly higher VAS scores than groups 2 and 3 at 0 h, 3 h, 6 h, 12 h, and 24 h postoperatively. The consumption of analgesics was significantly higher in group 1 than in groups 2 and 3. Although the consumption of analgesics was higher in group 3 than in group 2, this difference did not reach statistical significance. The time to first request for analgesics was significantly longer in groups 2 and 3 than in group 1, with no statistical difference between groups 2 and 3. Conclusion: Preincisional treatment with low-dose IV ketamine and local infiltration with ropivacaine 1% reduces postoperative pain after laparoscopic cholecystectomy.", "In a randomized, double-blinded study with three parallel groups, we assessed the analgesic effect of intraoperative ketamine administration in 45 ASA physical status I or II patients undergoing elective arthroscopic anterior ligament repair under general anesthesia. The patients received either IV ketamine 0.15 mg/kg after the induction of anesthesia and before surgical incision and normal saline at the end of surgery (PRE group); normal saline after the induction of anesthesia and before surgical incision and IV ketamine at the end of surgery (POST group); or normal saline at the beginning and the end of surgery (CONT group). Anesthesia was performed with propofol (2 mg/kg for induction, 60-200 microg x kg(-1) x min(-1) for maintenance), sufentanil (0.2 microg/kg 10 min after surgical incision, followed by an infusion of 0.25 microg x kg(-1) x h(-1) stopped 30 min before skinclosure), vecuronium (0.1 mg/kg), and 60% N2O in O2 via a laryngeal mask airway. Postoperative analgesia was initially provided with IV morphine in the postanesthesia care unit, then with IV patient-controlled analgesia started before discharge from the postanesthesia care unit. Pain scores, morphine consumption, side effects, and degree of knee flexion were recorded over 48 h and during the first and second physiotherapy periods, performed on Days 1 and 2. Patients in the ketamine groups required significantly less morphine than those in the CONT group over 48 h postoperatively (CONT group 67.7+/-38.3 mg versus PRE group 34.3+/-23.2 mg and POST group 29.5+/-21.5 mg; P < 0.01). Better first knee flexion (CONT group 35+/-10 degrees versus PRE group 46+/-12 degrees and POST group 47+/-13 degrees; P < 0.05) and lower morphine consumption (CONT group 3.8+/-1.7 mg versus PRE group 1.2+/-0.4 mg and POST group 1.4+/-0.4 mg; P < 0.05) were noted at first knee mobilization. No differences were seen between the PRE and POST groups, except for an increase in morphine demand in the PRE versus the POST group (P < 0.05) in the second hour postoperatively.\n We found that intraoperative small-dose ketamine reduced postoperative morphine requirements and improved mobilization 24 h after arthroscopic anterior ligament repair. No differences were observed in the timing of administration. Intraoperative small-dose ketamine may therefore be a useful adjuvant to perioperative analgesic management.", "Tissue injury induces central sensitization in the spinal cord dorsal horn neurons via mechanisms involving N-methyl-D-aspartate (NMDA) receptors, leading to secondary hyperalgesia. Using punctuate mechanical hyperalgesia as a measure of central sensitization, we examined whether induction and maintenance of central sensitization after surgery could be prevented by a low-dose infusion of the NMDA-receptor antagonist ketamine.\n Twenty living kidney donors were included in a randomized, double-blind, parallel, two-group study. Before start of surgery 10 patients received an i.v. bolus of racemic ketamine 0.5 mg.kg-1, followed by a continuous i.v. infusion of ketamine 2 micrograms.kg-1.min-1 for 24 h, thereafter 1 microgram.kg-1.min-1 for another 48 h. The control group received placebo bolus and infusion. A standard general anaesthesia including fentanyl was used. Patient-controlled (PCA) i.v. morphine was used for postoperative analgesia. Punctuate mechanical hyperalgesia and temporal summation of mechanical stimuli causing \"wind-up pain\" were measured using von Frey filaments.\n The area of punctuate mechanical hyperalgesia was significantly reduced in the ketamine group 1, 3 and 7 d after the operation (P < 0.01-0.001). \"Wind-up pain\" was also reduced by ketamine (P < 0.05). PCA morphine consumption and pain intensity (visual analogue scale) differed between groups only during the first hours after surgery, in favour of ketamine. The ketamine patients scored significantly higher on a global satisfaction score. Side-effects were most frequent in the placebo group.\n Low-dose i.v. infusion of ketamine during and after surgery reduces mechanical punctuate hyperalgesia surrounding the surgical incision. These results indicate that blockade of NMDA receptors prevents the central sensitization caused by nociceptive input during and after surgery.", "In this study, we evaluated the preemptive effect of a small dose of ketamine on postoperative wound pain. In a randomized, double-blinded, controlled trial, we compared the analgesic requirement in patients receiving preincision ketamine with ketamine after skin closure or placebo after gynecologic laparoscopic surgery. One-hundred-thirty-five patients were randomly assigned to receive preincision or postoperative ketamine 0.15 mg/kg or saline IV. Anesthetic technique was standardized. Patients were interviewed regularly up to 4 wk after surgery. Pain score, morphine consumption, side effects, and quality of recovery score were recorded. Patients receiving preincision ketamine had a lower pain score in the first 6 h after operation compared with the postoperative (P = 0.001) or placebo groups (P < 0.001). The mean (95% confidence intervals) time to first request for analgesia in the preincision group, 1.8 h (1.4-2.1), was longer than the postoperative group, 1.2 h (0.9-1.5; P < 0.001), or the placebo group, 0.7 h (0.4-0.9; P < 0.001). The mean +/- SD morphine consumption in the preincision group, 1.5 +/- 2.0 mg, was less than that in the postoperative group, 2.9 +/- 3.1 mg (P = 0.04) and the placebo group, 3.4 +/- 2.7 mg (P = 0.003). There was no significant difference among groups with respect to hemodynamic variables or side effects. No patient complained of hallucinations or nightmares. We conclude that a small dose of ketamine is not only safe, but it also provides preemptive analgesia in patients undergoing gynecologic laparoscopic surgery.\n In women undergoing laparoscopic gynecologic surgery, a small preoperative dose of ketamine (0.15 mg/kg) produced preemptive analgesia. There were no significant hemodynamic and psychological side effects with this dose.", "In a randomized, double-blinded study, we evaluated the analgesic effect of ketamine in the management of pain in a surgical intensive care unit after major abdominal surgery. Patients received morphine patient-controlled analgesia with either placebo (Group M) or ketamine (Group K). Morphine was administered with initial loading doses of 2 mg until the visual analog scale (VAS) score was <30 and thereafter with bolus doses of 1 mg and a lockout time of 7 min. Ketamine was administered with an initial bolus of 0.5 mg/kg followed by a perfusion of 2 micro g x kg(-1) x min(-1) during the first 24 h and 1 micro g x kg(-1) x min(-1) during the following 24 h. The 4-h cumulative morphine doses were measured over 48 h. The VAS scores at rest and at mobilization were measured every 4 h during 48 h. A total of 101 patients were enrolled, and 93 were analyzed (41 in Group K and 52 in Group M). VAS scores at rest and at mobilization were similar. The cumulative consumption of morphine was significantly smaller in Group K (P < 0.05). We concluded that small doses of ketamine were a valuable adjunct to opioids in surgical intensive care unit patients after major abdominal surgery.", "We investigated whether intraoperative 'subanesthetic doses' of ketamine have a postoperative anti-hyperalgesic and an analgesic effect and which is the preferential route of administration, either systemic (intravenous, i.v.) or epidural. One hundred patients scheduled for rectal adenocarcinoma surgery under combined epidural/general anesthesia were included. Before skin incision all the patients received an epidural bolus followed by an infusion of continuous bupivacaine/sufentanil/clonidine mixture. They were randomly assigned to receive no ketamine (group 1), i.v. ketamine at the bolus dose of 0.25 mg/kg followed by an infusion of 0.125 mg/kg per h (group 2), 0.5 mg/kg and 0.25 mg/kg per h (group 3), epidural ketamine 0.25 mg/kg and 0.125 mg/kg per h (group 4), or 0.5 mg/kg and 0.25 mg/kg per h (group 5). All i.v. and epidural analgesics were stopped at the end of surgery and patients were connected to an i.v. morphine patient-controlled analgesia (PCA) device. Short-term postoperative analgesia (72 h) was assessed by pain visual analog scale scores at rest, cough, and movements as well as by PCA requirements. Wound mechanical hyperalgesia was evaluated and residual pain was assessed by asking the patients at 2 weeks, and 1, 6, and 12 months. The area of hyperalgesia and morphine PCA requirements were significantly reduced in group 3. These patients reported significantly less residual pain until the sixth postoperative month. These observations support the theory that subanesthetic doses of i.v. ketamine (0.5 mg/kg bolus followed by 0.25 mg/kg per h) given during anesthesia reduce wound hyperalgesia and are a useful adjuvant in perioperative balanced analgesia. Moreover, they show that the systemic route clearly is the preferential route.", "We designed this double-blinded, randomized, controlled study to evaluate the effect of small-dose ketamine IV in combination with epidural morphine and bupivacaine on postoperative pain after renal surgery. An epidural catheter was inserted, and the administration of morphine and bupivacaine was started before surgery. Forty patients were assigned to one of two groups (ketamine or control). The ketamine group was administered a ketamine bolus and infusion during surgery. The median visual analog pain scale (VAS) scores at rest were significantly lower in the ketamine group during the first 6 h (P < 0.01). VAS pain scores on coughing were also significantly lower in the ketamine group (P < 0.01). Cumulative postoperative total analgesic consumption was less in the ketamine group on Days 1 and 2 (P < 0.001). The first analgesic demand time was shorter in the control group (9.2 +/- 11.5 min) than in the ketamine group (22.3 +/- 17.1 min) (P < 0.0001). The incidence of nausea and pruritus was more frequent in the control group (P < 0.05). In conclusion, postoperative analgesia was more effective when spinal cord and brain sensitization were blocked by a combination of epidural morphine/bupivacaine and IV ketamine.\n Renal nociception conducted multisegmentally by both the spinal nerves (T10 to L1) and the vagus nerve cannot be blocked by epidural analgesia alone. We demonstrated that IV ketamine had an improved analgesic or opioid-sparing effect when it was combined with epidural bupivacaine and morphine after renal surgery.", "This study evaluated the pre-emptive analgesic effect of intravenous (i.v.) (R)-ketamine in laparoscopic cholecystectomy. (R)-ketamine was used due to the lower incidence of side-effects.\n Sixty patients who underwent surgery under general anesthesia were randomly allocated to 3 groups and studied in a double-blind manner. Two i.v. injections were administered: one after induction of anesthesia, approximately 3 min before surgery, and one after surgery. The placebo group (PLA, n = 20) received saline in both injections. The preoperative group (PRE, n = 20) received (R)-ketamine 1 mg/kg and then saline. The postoperative group (POST, n = 20) received saline and then (R)-ketamine 1 mg/kg. Postoperatively, the patients used a patient-controlled analgesia (PCA) pump. Pain was evaluated with a visual analog scale (VAS) at 30 min and every hour for 4 h and with a verbal rating scale (VRS) at 24 h and after 7 days.\n There were no occurrence of side-effects from (R)-ketamine. VAS and VRS at 1, 2, 3, and 4 h postoperatively showed no statistical differences. In the POST group, extubation was delayed and pain score (VAS) at 30 min postoperatively was significantly lower (P < 0.05) than the two other groups. There were no statistical differences in meperidine consumption during the first 4 h postoperatively and no differences in consumption of analgesics at 24 h and 7 days.\n In this study a 1 mg/kg dose of (R)-ketamine given at the end of surgery exerted a short-lasting hypnotic and analgesic effect. The same dose given preoperatively did not show postoperative analgesic effect or pre-emptive effect.", "The use of intraoperative racemic ketamine for pain prevention after abdominal surgery is controversial. We compared one preincisional i.v. injection of S(+)-ketamine with its preincisional and repeated intraoperative use in 45 patients undergoing surgery with epidural and general anesthesia. S(+)-ketamine is a new drug formulation that contains the more potent S(+)-stereoisomer of ketamine. Patients were randomized to receive placebo, 0.5 mg/kg preincisional S(+)ketamine, or 0.5 mg/kg preincisional and 0.2 mg/kg intraoperative S(+)-ketamine repeated at 20-min intervals. In the postoperative period, epidural ropivacaine (2 mg/mL; 0.12 mL.kg(-1).h(-1)) was infused for pain therapy. Patients who received repeated S(+)-ketamine reported smaller pain scores than those who received placebo after awakening and 3 and 6 h later (P < or = 0.05). Fewer patients with repeated S(+)-ketamine required additional analgesics than those with placebo (P < or = 0.05). Cumulative consumption of additional diclofenac and dextropropoxyphene at 24 h was less after single (P < 0.05) and repeated (P < 0.05) S(+)-ketamine versus placebo. After awakening, patients who received repeated S(+)-ketamine reported being in a better mood than those in the other groups (P < 0.05). No psychotomimetic side effects were noted. In conclusion, preincisional and repeated intraoperative small-dose S(+)-ketamine added to general and epidural anesthesia causes better postoperative pain relief than general and epidural anesthesia alone.\n After major visceral surgery, preincisional and repeated intraoperative small-dose S(+)-ketamine added to general and epidural anesthesia causes better postoperative pain relief than general and epidural anesthesia alone.", "To compare the analgesic and side effects of preemptively used epidural ketamine +bupivacaine, neostigmine +bupivacaine, and bupivacaine alone on postoperative analgesia after major abdominal surgery.\n Randomized, controlled study.\n Inpatient anesthesia at the department of surgery of a metropolitan hospital.\n 30 ASA physical status I, II, and III patients scheduled for abdominal surgery.\n Group K received 1 mL (50 mg) ketamine and 5 mL (25 mg) bupivacaine epidurally, Group N received 1 mL (0.5 mg) neostigmine and 5 mL (25 mg) bupivacaine epidurally, and Group B received 1 mL saline and 5 mL (25 mg) bupivacaine epidurally 30 minutes before operation. All patients underwent anesthesia induction with thiopental and vecuronium; anesthesia was maintained with isoflorane and vecuronium. For postoperative analgesia, all patients received epidural morphine for 48 hours postoperatively.\n Standard monitoring included: 48 hours of analgesic requirement, visual analog scale (VAS), mean arterial pressure (MAP), and heart rate (HR) in the 1st, 2nd, 6th, 12th, 24th, and 48th hours. Data were analyzed using Kruskall-Wallis and Mann Whitney U tests, with a p < 0.05 considered statistically significant. No significant differences were observed regarding MAP and HR among the groups during the study period. In Group N, VAS was significantly lower than Group K and Group B. The total opioid consumption in Group N was significantly lower than in Groups K and B in the first 48 hours after the operation.\n Preemptive neostigmine can be a good choice for postoperative analgesia.", "In a randomised, double-blind prospective study we compared the effects on postoperative pain and analgesic consumption of intra-operative s(+)-ketamine (100 microg.kg-1 bolus and a continuous infusion of 2 microg.kg-1.min-1) followed by postoperative patient-controlled analgesia with morphine (1 mg per bolus) plus s(+)-ketamine (0.5 mg per bolus), or intra-operative saline followed by postoperative patient-controlled analgesia morphine (1 mg per bolus) alone. A total of 28 male patients undergoing radical prostatectomy were studied. Morphine consumption, pain scores, pressure algometry and adverse effects were recorded for 48 h after surgery. Cumulative morphine consumption was significantly lower in the ketamine/morphine group (47.9 +/- 26.2 mg) than in the saline/morphine group (73.4 +/- 34.8 mg; p = 0.049). Pain scores at rest were significantly lower in the ketamine/morphine group across the 48-h study period (p = 0.01). No significant differences were found in pressure algometry measurements or the occurrence of adverse effects.", "The aim of this study was to compare the analgesic effects and pharmacokinetics of epidural versus intravenous administration of low doses of ketamine.\n 45 patients scheduled for selective gastrectomy were randomly assigned into 3 groups: 0.5mg/kg ketamine administered epidurally (Kepi group), 0.5 mg/kg ketamine administered intravenously (Kiv group), or 10ml normal saline administered epidurally (Ctr group). Analgesic effects were evaluated using Visual Analog Scale (VAS) pain scores at rest, time to first request for analgesic (TFA), and subsequent morphine consumption. The plasma concentration of ketamine was measured with high performance liquid chromatography (HPLC) in the Kepi and Kiv groups. The elimination half-life of ketamine was calculated.\n Patients in the Kepi group had significantly lower VAS pain scores, longer TFA, and lower morphine consumption than patients in the Kiv or Ctr groups. Compared with intravenous administration, epidural administration of ketamine resulted in higher plasma concentrations from 90 minutes to 48 hours after injection, and much longer elimination half-life of ketamine, but a lower maximum plasma concentration of ketamine.\n The results suggest that epidural administration of a low dose of ketamine provides more effective analgesic effects as seen post-operatively than intravenous administration. The prolonged half-life and high plasma sustained concentration of epidural ketamine might account for the difference in analgesic effects.", "We designed this double-blind study to evaluate the effect of adding small-dose ketamine in a multimodal regimen of postoperative patient-controlled epidural analgesia (PCEA). Ninety-one patients, ASA physical status I-III, undergoing major surgery, received a standardized general anesthesia and epidural catheterization in an appropriate intervertebral space after surgery. A PCEA device was programmed to deliver a regimen of morphine 0.02 mg/mL, bupivacaine 0.8 mg/mL, and epinephrine 4 microg/mL, with the addition of ketamine 0.4 mg/mL (ketamine, n = 45) or without (control, n = 46). The mean visual analog pain scale (VAS) scores during cough or movement for the first 3 days after surgery were higher in the control group than in the ketamine group (P < 0.05), whereas the mean VAS score at rest for the first 2 days were higher in the control group than in the ketamine group (P < 0.05). Furthermore, patients in the control group consumed more multimodal analgesics than patients in the ketamine group for the first 2 days (P < 0.05). The sedation scores and the incidence of side effects (pruritus, nausea, emesis, sleep deprivation, motor block, and respiration depression) were similar between the two groups. We conclude that adding ketamine 0.4 mg/mL in a multimodal PCEA regimen provides better postoperative pain relief and decreases consumption of analgesics. Implications: Many studies have evaluated one or a combination of two analgesics for postoperative pain control, but few have examined a multimodal approach using three or four different epidural analgesics. This study demonstrates an additive analgesic effect when ketamine is added to a multimodal analgesic treatment.", "Several studies report that when small-dose racemic ketamine, an N-methyl-D-aspartate receptor antagonist, is administered perioperatively, opioid consumption is reduced postoperatively. S(+)-ketamine has a higher affinity for the N-methyl-D-aspartate receptor and less-serious side effects than racemic ketamine. Thirty patients scheduled for elective arthroscopic anterior cruciate ligament repair were enrolled in this randomized, double-blinded clinical trial designed to determine the preemptive effect of S(+)-ketamine on postoperative analgesia requirements in a setting of clinically relevant perioperative analgesia. Total IV anesthesia was induced and maintained with remifentanil (0.125-1.0 microg x kg(-1) x min(-1)) and a propofol target-controlled infusion (target 2-4 microg/mL). The Ketamine group received a bolus of 0.5 mg/kg S(+)-ketamine before incision, followed by a continuing infusion of 2 microg x kg(-1) x min(-1) until 2 h after emergence from anesthesia. The Control group received NaCl in the same sequence. After IV morphine provided pain relief down to < or =3 on a visual analog scale scored from 0 to 10, patients were connected to a patient-controlled analgesia device. There were no significant differences between the two groups in terms of total morphine consumption or VAS scores, either at rest or with movement. In our study, S(+)-ketamine did not contribute to postoperative pain reduction, possibly because of the clinically routine perioperative opioid analgesia.\n Small-dose S(+)-ketamine had no positive effect on postoperative analgesia when administered perioperatively for elective arthroscopic anterior cruciate ligament repair. Unlike investigations of the racemic mixture of ketamine, our study methods included timely standard-practice perioperative opioid analgesia, which seems to make supplemental analgesia unnecessary.", "Morphine and ketamine may prevent central sensitization during surgery and result in preemptive analgesia. The reliability of preemptive analgesia, however, is controversial.\n Gastrectomy patients were given preemptive analgesia consisting of epidural morphine, intravenous low-dose ketamine, and combinations of these in a randomized, double-blind manner. Postsurgical pain intensity was rated by a visual analog scale, a categoric pain evaluation, and cumulative morphine consumption.\n Preemptive analgesia by epidural morphine and by intravenous low-dose ketamine were significantly effective but not definitive. With epidural morphine, a significant reduction in visual analog scale scores at rest was observed at 24 and 48 h, and morphine consumption was significantly lower at 6 and 12 h, compared with control values. With intravenous ketamine, visual analog scale scores at rest and morphine consumption were significantly lower at 6, 12, 24, and 48 h than those in control subjects. The combination of epidural morphine and intravenous ketamine provided definitive preemptive analgesia: Visual analog scale scores at rest and morphine consumption were significantly the lowest at 6, 12, 24, and 48 h, and the visual analog scale score during movement and the categoric pain score also were significantly the lowest among the groups.\n The results suggest that for definitive preemptive analgesia, blockade of opioid and N-methyl-d-aspartate receptors is necessary for upper abdominal surgery such as gastrectomy; singly, either treatment provided significant, but not definitive, postsurgical pain relief. Epidural morphine may affect the spinal cord segmentally, whereas intravenous ketamine may block brain stem sensitization via the vagus nerve during upper abdominal surgery.", "The purpose of this study was to compare morphine with ketamine to morphine alone in a double-blind investigation of postsurgical pain control.\n Forty-two ASA 1 and 2 patients undergoing elective microdiscectomy were administered either 1 mg.ml-1 of morphine (n = 20) or 1 mg.ml-1 of both morphine and ketamine (n = 22) via iv patient controlled analgesia (IVPCA). Pain relief and side effects were assessed at 24 hr after surgery.\n The mean (SD) visual analogue scale (VAS) pain rating of 2.3 (1.67) for patients receiving morphine with ketamine was lower (P < 0.001) than the VAS scores of patients receiving only morphine 4.5 (1.54). Patients receiving morphine and ketamine also had less difficulty with side effects, reporting less nausea (P < 0.05), pruritus (P < 0.001), and urinary retention (P < 0.05). Although dysphoria is reported to be a common side effect of ketamine, complaints of dysphoria were rare in both groups, with only one subject (5%) in the morphine with ketamine group and three (15%) subjects receiving morphine alone reporting this side effect.\n IVPCA ketamine in combination with morphine provides superior postsurgical pain relief at lower dosage and with fewer side effects than morphine alone.", "In this prospective, randomized, and double-blinded clinical trial, we evaluated the efficacy of preincisional administration of epidural ketamine with morphine compared with epidural morphine alone for postoperative pain relief after major upper-abdominal surgery. We studied 50 ASA I and II patients undergoing major upper-abdominal procedures. These patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg, whereas those in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine 30 min before incision. Intraoperative analgesia was provided in addition, with IV morphine, and the requirement was noted. A blinded observer using a visual analog scale for pain assessment observed patients for 48 h after surgery. Additional doses of epidural morphine were provided when the visual analog scale score was more than 4. Analgesic requirements and side effects were compared between the two groups. There were no differences between the two groups with respect to age, sex, weight, or duration or type of the surgical procedures. The intraoperative morphine requirement was significantly (P = 0.018) less in Group 2 patients (median, 6.8 mg; range, 3-15 mg) compared with patients in Group 1 (median, 8.3 mg; range, 4.5-15 mg). The time for the first requirement of analgesia was significantly (P = 0.021) longer (median, 17 h; range, 10-48 h) in Group 2 patients than in Group 1 (median, 12 h; range, 4-36 h). The total number of supplemental doses of epidural morphine required in the first 48 h after surgery was comparable (P = 0.1977) in both groups. Sedation scores were similar in both groups. One patient in Group 2 developed hallucinations after study drug administration. None of the patients in either group developed respiratory depression. Other side effects, such as pruritus, nausea, and vomiting, were also similar in both groups. Although the addition of ketamine had synergistic analgesic effects with morphine (reduced intraoperative morphine consumption and prolonged time for first requirement of analgesia), there was no long- lasting preemptive benefit seen with this combination (in terms of reduction in supplemental analgesia) for patients undergoing major upper-abdominal procedures.\n Ketamine added to epidural morphine given before surgery can decrease postoperative pain by its preemptive effect, opioid potentiation, and prevention of acute opioid tolerance. A single epidural bolus of 1 mg/kg of ketamine with morphine given before major upper-abdominal surgery did not result in a clinically relevant reduction in postoperative pain relief.", "To evaluate the efficacy of the combination of epidural ketamine and morphine compared with epidural morphine alone for postoperative pain relief following major upper abdominal surgery.\n Prospective, randomized, double-blinded study.\n Tertiary care referral and teaching hospital.\n 46 ASA physical status I and II patients who underwent major upper abdominal procedures.\n Patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg whereas patients in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine postoperatively.\n A blinded observer using a visual analog scale (VAS) for pain assessment followed up patients for 48 hours postoperatively. Top-up dose of epidural morphine was provided when VAS was higher than 4. Analgesic requirements and side effects were compared between the two groups.\n Only 40 patients completed the study. There were no differences between the two groups with respect to age, gender, weight, duration, or type of surgical procedure or intraoperative opioid requirements. Onset of analgesia was faster (p < 0.001) in Group 2 (11 min) than in Group 1 patients (25 min). The time for first requirement of analgesia was significantly (p < 0.01) longer (19.8 +/- 9.8 hours) in Group 2 patients than Group 1 (12.8 +/- 6.2 hours). Total number of supplemental doses of epidural morphine required in the first 48 hours postoperatively was also significantly less (p < 0.005) in Group 2 compared to Group 1. Patients in Group 2 had higher sedation scores than Group I patients for the first 2 hours postoperatively. None of the patients in either group developed hallucinations or respiratory depression. Other side effects such as pruritus, nausea, and vomiting were also similar in both groups.\n The addition of epidural ketamine 1 mg/kg to morphine 50 microg/kg improved analgesia after major upper abdominal surgery without increasing side effects.", "We studied 60 patients undergoing operation on the kidney with combined general and epidural anaesthesia, in a double-blind, randomized, controlled study. Patients were allocated to receive a preoperative bolus dose of ketamine 10 mg i.v., followed by an i.v. infusion of ketamine 10 mg h-1 for 48 h after operation, or placebo. During the first 24 h after surgery, all patients received 4 ml h-1 of epidural bupivacaine 2.5 mg ml-1. From 24 to 48 h after operation, patients received epidural morphine 0.2 mg h-1 preceded by a bolus dose of 2 mg. In addition, patient-controlled analgesia (PCA) with i.v. morphine (2.5 mg, lockout time 15 min) was offered from 0 to 48 h after operation. Patients who received ketamine felt significantly more sedated at 0-24 h, but not at 24-48 h after operation, compared with patients who received placebo (P = 0.002 and P = 0.127, respectively). There were no significant differences in pain (VAS) at rest, during mobilization or cough, PCA morphine consumption, sensory block to pinprick, pressure pain detection threshold assessed with an algometer, touch and pain detection thresholds assessed with von Frey hairs, peak flow or side effects other than sedation. The power of detecting a reduction in VAS scores of 20 mm in our study was 80% at the 5% significance level. We conclude that we were unable to demonstrate an (additive) analgesic or opioid sparing effect of ketamine 10 mg h-1 i.v. combined with epidural bupivacaine at 0-24 h, or epidural morphine at 24-48 h after renal surgery.", "Relative large-dose intraoperative remifentanil could lead to the need for more postoperative analgesics. Intraoperative N-methyl-D-aspartate receptor antagonists, such as ketamine, decrease postoperative opioid use. We therefore tested the hypothesis that intraoperative small-dose ketamine improves postoperative analgesia after major abdominal surgery with remifentanil-based anesthesia. Fifty patients undergoing abdominal surgery under remifentanil-based anesthesia were randomly assigned to intraoperative ketamine or saline (control) supplementation. The initial ketamine dose of 0.15 mg/kg was followed by 2 microg. kg(-1). min(-1). In both groups, desflurane was kept constant at 0.5 minimum alveolar anesthetic concentration without N(2)O, and a remifentanil infusion was titrated to autonomic responses. All patients were given 0.15 mg/kg of morphine 30 min before the end of surgery. Pain scores and morphine consumption were recorded for 24 postoperative h. Less of the remifentanil was required in the Ketamine than in the Control group (P < 0.01). Pain scores were significantly larger in the Control group during the first 15 postoperative min but were subsequently similar in the two groups. The Ketamine patients required postoperative morphine later (P < 0.01) and received less morphine during the first 24 postoperative h: 46 mg (interquartile range, 34-58 mg) versus 69 mg (interquartile range, 41-87 mg, P < 0.01). No psychotomimetic symptoms were noted in either group. In conclusion, supplementing remifentanil-based anesthesia with small-dose ketamine decreases intraoperative remifentanil use and postoperative morphine consumption without increasing the incidence of side effects. Thus, intraoperative small-dose ketamine may be a useful adjuvant to intraoperative remifentanil.\n Supplementing remifentanil-based anesthesia with small-dose ketamine decreased intraoperative remifentanil use and postoperative morphine consumption. These data demonstrate that N-methyl-D-aspartate antagonists, such as ketamine, can be a useful adjuvant to intraoperative remifentanil." ]

[ "8798372" ]

[ "Selective nonoperative management of abdominal stab wounds: prospective, randomized study." ]

[ "In a prospective, randomized trial the safety and cost-effectiveness of selective nonoperative management was compared to mandatory laparotomy in patients with abdominal stab wounds not requiring immediate laparotomy for hemodynamic instability, generalized peritonitis, or evisceration of abdominal contents. Fifty-one patients were randomly assigned to mandatory laparotomy or expectant nonoperative management and compared for early (<90 days) mortality and morbidity, length of hospital stay, and hospital costs. There was no early mortality. The morbidity rate was 19% following mandatory laparotomy and 8% after observation (p = 0.26). Four patients (17%) managed nonoperatively required delayed laparotomy. The hospital stay was shorter in the observation group (median 2 days versus 5 days;p = 0.002). About $2800 (US) was saved for every patient who underwent successful nonoperative management. It is concluded that selective nonoperative management of abdominal stab wounds, although resulting in delayed laparotomy in some patients, is safe and the preferred strategy for minimizing the days in hospital with concomitant savings in hospital costs. Mandatory laparotomy detects some unexpected organ injuries earlier and more accurately but results in a high nontherapeutic laparotomy rate and surgical management of minor injuries that in many cases could be managed nonoperatively." ]

[ "2045259" ]

[ "The management of bleeding in early pregnancy." ]

[ "Ultrasound scan findings were analysed for 187 women referred to an emergency gynaecological scanning clinic during a seven month period, with bleeding in early pregnancy. One sixth of the women were not pregnant, one third had non-viable pregnancies and one half had viable pregnancies; 9% of this latter group subsequently miscarried. For the majority of women referred to the clinic, bed rest would have been inappropriate. In this study the value of bed rest and hospitalisation was considered uncertain for women with viable singleton pregnancies of 7-14 weeks gestation and bleeding in the previous 24 hours. Only 23 women with otherwise uncomplicated pregnancies met these criteria and consented to recruitment to a randomized controlled trial: three subsequently miscarried. Emergency scanning as a routine part of the gynaecological service is recommended, thus confining bed rest to those women with viable pregnancies. Reliable evaluation of bed rest and hospitalisation for such women will require a multicentre study." ]

[ "8101589", "1544759" ]

[ "Evaluation of effectiveness of good growth monitoring in south Indian villages.", "Impact of a clinic-based growth monitoring programme on maternal nutrition knowledge in Lesotho." ]

[ "We conducted a community intervention trial in 12 villages in Tamil Nadu, India to evaluate the benefits of growth monitoring. The villages were divided into 6 \"growth-monitoring package\" of intervention villages (GMP) and 6 \"non-growth-monitoring package\" of intervention villages (NGM). A functioning primary health care system was in place in all 12 villages implemented a set of interventions including health and nutritional education. About 550 children under the age of 60 months were studied over 4 years in GMP villages and a similar number of children in NGM villages. The interventions were identical in the two sets of villages except for the use of growth charts in education in the 6 GMP villages. The nutrition worker in the NGM villages had the same contact time as in the GMP villages but advised mothers without the benefit of growth charts. The research team, independently of the nutrition worker, did anthropometric studies on children in all villages every 4 to 5 months. Comparisons were done by calculating monthly gains in stature, and weight, and the significance of differences observed was adjusted for age and sex. After 30 months of interventions, similar improvements in growth were seen in GMP and NGM children. The interventions seemed to have improved the nutritional status of young children in both groups of villages. In view of the lack of additional benefit from growth monitoring over other educational interventions, we question its use as part of child survival programmes in India.", "An evaluation of the impact of a nationwide clinic-based growth monitoring (GM) programme was done in Lesotho to determine if clinic attendance was associated with improved maternal knowledge of weaning practices and diarrhoea. A total of 907 mothers from eight clinics were included in the study. Our results showed that mothers who had attended the clinics knew more about the appropriate timing for introducing animal protein-rich foods in the child's diet and about the use of oral rehydration salts for diarrhoea, than those who had not. The difference in knowledge between previous clinic attendants and new attendants was particularly marked among mothers with less than secondary schooling and mothers with young babies (less than 6 months). From observation in the clinics, we believe that group nutrition education, although it was not integrated with growth monitoring, was probably responsible for the positive association between clinic attendance and maternal knowledge. Prior clinic attendance was not specifically associated with improved knowledge about feeding during diarrhoea or the need to stop breastfeeding gradually. These need to be better incorporated into present clinic nutrition education. Whether improvements in growth monitoring would further significantly improve nutrition education remains to be seen." ]

[ "17251802", "18434839", "15939391", "12502940", "14644860" ]

[ "Lacrimal punctum occlusion in the treatment of severe keratoconjunctivitis Sicca caused by Sjögren syndrome: a uniocular evaluation.", "SmartPlug versus silicone punctal plug therapy for dry eye: a prospective randomized trial.", "Silicone versus collagen plugs for treating dry eye: results of a prospective randomized trial including lacrimal scintigraphy.", "Effects of lacrimal occlusion with collagen and silicone plugs on patients with conjunctivitis associated with dry eye.", "Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren's syndrome: a randomised 12 week controlled study." ]

[ "A controlled uniocular study to evaluate the short-term efficacy of lacrimal punctum occlusion in the treatment of severe dry eye caused by Sjögren syndrome.\n Uniocular punctum occlusion by punctum plug in the upper and lower puncta in 1 eye was performed in 20 patients with severe keratoconjunctivitis Sicca caused by Sjögren syndrome. To overcome possible interindividual variability between patients, the other eye, in the same patient, was not occluded and served as a control eye. The eye to be occluded was randomly selected. The patients were instructed to continue using their dry eye medications. Tear function tests (Schirmer test, rose Bengal test, and debris in de cul-de-sac) were performed in both eyes. Subjective complaints (discomfort) were registered for both eyes. All the above-mentioned data were collected before starting the treatment and at least 6 weeks later. The above-mentioned parameters were compared and statistically analyzed in both eyes.\n Of the 20 patients, 7 patients dropped out. The remaining 13 patients completed the final analysis. In the occluded eye, we found a significant improvement in both the subjective complaints and the rose Bengal score, but the Schirmer test and the tear mucus score did not change.\n Punctum occlusion therapy in a short-term study improved the rose Bengal score and discomfort score in our patients and thus may be helpful in the treatment of severe dry eye caused by Sjögren syndrome.", "To evaluate the clinical efficacy, retention rates, and complications of SmartPlug insertion compared with silicone punctal plugs in patients with dry eye.\n Thirty-six eyes with subjective symptoms of dry eye in addition to a tear film breakup time (TBUT) <5 seconds and evidence of ocular surface damage on rose Bengal or fluorescein staining were included. Treated eyes were randomized to either a silicone plug or SmartPlug inferior punctal occlusion. Pre- and posttreatment evaluations included subjective symptom scoring, tear meniscus height, TBUT, Schirmer test, fluorescein and rose Bengal staining, and artificial tear use.\n After a mean follow-up period of 11.2 weeks, both the silicone plug- and SmartPlug-treated eyes showed significant improvement in symptom scoring (P = 0.002 and P = 0.005, respectively), TBUT (P = 0.035 and P = 0.009, respectively), and fluorescein (P = 0.024 and P = 0.016, respectively) and rose Bengal (P = 0.008 and P = 0.046, respectively) staining. There was no significant difference in these parameters between the 2 plugs. SmartPlug-, but not the silicone plug-treated eyes showed significant improvement in mean tear meniscus height (P = 0.037). The use of artificial tear supplements was reduced in 10 (55.6%) silicone- and 11 (61.1%) SmartPlug-treated eyes. Minor complications related to plug insertion were experienced in 4 (22%) silicone- and 2 (11%) SmartPlug-treated eyes. Spontaneous plug loss occurred with 6 (33%) silicone plugs.\n This prospective randomized trial shows that SmartPlug insertion has equivalent clinical efficacy to the use of conventional silicone plugs. Both SmartPlug and silicone plug use can reduce dependency on tear supplements in >55% of patients with dry eye.", "To compare the short-term efficacy of collagen and silicone plugs for treating dry eye using quantitative lacrimal scintigraphy.\n Prospective randomized clinical trial.\n In this institutional study, 24 dry eye patients were evaluated in two groups: group I (n = 22 eyes) received collagen plugs and group II (n = 26 eyes) received silicone plugs. Comparisons were made with normal control subjects (n = 22 eyes). Data for the Schirmer I test, tear break-up time, and ocular surface staining with rose bengal dye were recorded before and after punctal occlusion. Lacrimal scintigraphy was performed at each time point, and the time to half maximum activity on the ocular surface (T(1/2)), and the percentage retention of activity on the ocular surface at the end of the dynamic study (RI) were recorded.\n In both patient groups, Schirmer I results, tear break-up times, and rose bengal staining scores improved significantly after plug insertion. Mean T(1/2) values and RI values increased significantly in both groups (P < .0001 for both). The differences for these values between groups I and II was statistically insignificant (P > .05).\n Collagen and silicone plugs both resulted in significant increases in aqueous tear volume, half-life of nuclear material on the ocular surface, and percentage of nuclear material retention. The groups' post-insertion values for all parameters were similar. These results suggest that these two plug types have similar efficacy as treatments for dry eye in the short term. Further studies evaluating long-term results are required.", "To determine whether canalicular occlusion with collagen and silicone plugs reduces the severity of symptoms in patients with conjunctivitis secondary to dry eye.\n This was a prospective, randomized, double-masked study conducted at a single center in Mexico, in which 61 patients with dry eye/conjunctivitis were assigned to progressive lacrimal occlusion with collagen and silicone plugs or a sham procedural group. Outcome variables included total and individual dry eye and conjunctivitis symptom scores, moisturizing agent usage, best-corrected visual acuity, ocular comfort level, visual performance, corneal/conjunctival fluorescein staining, and incidence of adverse events.\n Total dry eye and conjunctival symptom scores were reduced by 43.7 and 33.7%, respectively 2 weeks after occlusion of all four lacrimal canaliculi with collagen plugs, increasing to 77.4 and 72.1% 2 weeks later following superior canalicular occlusion of both eyes with silicone plugs and inferior placement of collagen plugs. At the 8-week visit (4 weeks after silicone plug implantation of the inferior canaliculi of both eyes), the reduction in total dry eye and conjunctival symptom scores further increased to 94.2 and 93.0%, respectively, accompanied by a marked decline in each of the seven individual symptom scores (dryness, watery eyes, itching, burning, foreign body, fluctuating vision, and light sensitivity). In concert with these changes, moisturizing agent usage and corneal/conjunctival fluorescein staining decreased in a progressive fashion over the 8-week study period, and best-corrected visual acuity, ocular comfort, and visual performance improved in the absence of any treatment-related adverse events except for one case of epiphora. The response of patients to lacrimal occlusion can be sharply contrasted with the sham procedure group, which remained relatively unchanged from baseline at each of the study visits.\n Progressive lacrimal occlusion with collagen and silicone plugs was of clinical benefit to patients with dry eye and conjunctivitis.", "To evaluate the efficacy and side effects of oral pilocarpine for the treatment of ocular symptoms in patients with primary Sjögren's syndrome (SS).\n A 12 week, single centre, randomised controlled study was performed. Twenty nine patients were randomly assigned to receive oral pilocarpine (5 mg twice a day), 28 only artificial tears, and 28 inferior puncta occlusion. Patients receiving oral pilocarpine and those with inferior puncta occlusion also received artificial tears. Patients were evaluated at baseline and throughout the study for their subjective global assessment of dry eyes and for their objective assessment of dry eyes (Schirmer's-I test, rose bengal test, and imprint test).\n Patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes, as was evaluated by improvement of >55 mm on a visual analogue scale (VAS) for responses to the eye questionnaire, compared with patients treated with artificial tears (p<0.001) and those with inferior puncta occlusion (p<0.05). Furthermore, patients receiving oral pilocarpine also showed greater objective improvement, as measured by the rose bengal test (p<0.05), while Schirmer's-I test showed no differences between the treated groups. Commonly reported adverse events were headache, increased sweating, nausea, and vomiting in the pilocarpine group, while one patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study.\n 10 mg of pilocarpine daily given to patients with SS for 12 weeks had a beneficial effect on subjective eye symptoms, as evaluated by improvement >55 mm on a VAS. Additionally, an improvement of rose bengal staining was noted, but an increase in tear production, as measured by the Schirmer-I test, was not substantiated." ]

[ "19299299", "16627487", "21596845", "21123487", "11303262", "11556595", "17128838" ]

[ "Atypical bacterial pathogens in community-acquired pneumonia in children: a hospital-based study.", "Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired pneumonia in Istanbul, Turkey.", "Rapid diagnosis of Mycoplasma pneumoniae by polymerase chain reaction in community-acquired lower respiratory tract infections.", "Detection of Mycoplasma pneumoniae in children with lower respiratory tract infections.", "Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired lower respiratory tract infections.", "Mycoplasma Pneumoniae infection in Malaysian children admitted with community acquired pneumonia.", "Prevalence and clinical features of mycoplasma pneumoniae in Thai children." ]

[ "A total of 243 children aged one month to five years with World Health Organization defined severe community acquired pneumonia were studied for the presence of atypical bacterial pathogens: 24 were found positive for mycoplasma infection. There was no significant association with any of the clinical, laboratory and radiological variables in children with pneumonia by the atypical pathogen.", "To investigate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae infection in pediatric pneumonia, in Istanbul, Turkey, we conducted a prospective study covering all the children between 2 months and 15 years hospitalized for community-acquired pneumonia.\n A total of 140 children (85 males, median age 2.5 years) with community-acquired pneumonia were enrolled. Acute and convalescent sera were tested for IgM and IgG antibodies to M. pneumoniae (enzyme-linked immunosorbent assay, Serion ELISA classic) and for IgM and IgG antibodies to C. pneumoniae (microimmunofluorescence, Savyon, Israel).\n Mycoplasma pneumoniae infection was diagnosed in 38 patients (27%) and C. pneumoniae infection in 7 (5%). In 2 children M. pneumoniae and C. pneumoniae co infection was observed. The average age of the M. pneumoniae cases was 5.3 years and that of the C. pneumoniae was 1.5 years. The average age of pneumonia cases caused by other pathogens was 3.4 years (p<0.05). No significant difference was observed in clinical onset, signs, symptoms and laboratory parameters in children with M. pneumoniae and C. pneumoniae infection and in those without M. pneumoniae and C. pneumoniae infection.\n The results of this study suggest a remarkable role for M. pneumoniae and C. pneumoniae in childhood community-acquired pneumonia, and the knowledge of the true prevalence of these two types of infections discovered in the community might lead to modifications in the present empirical treatment of bacterial pneumonia.", "Two hundred children hospitalized for community-acquired lower respiratory tract infections (LRTIs) were investigated for Mycoplasma pneumoniae employing serological tests and a P1 adhesin gene-based polymerase chain reaction assay (PCR) on nasopharyngeal aspirates. Serological evidence of M. pneumoniae infection was observed in 68 (34%) patients and PCR was positive in 20 (10%) children. Together PCR and/or enzyme immuno assay detected M. pneumoniae in 71(35.5%) children. Our data underline the role of M. pneumoniae in Indian children with community-acquired LRTIs even in children aged < 24 months.", "Mycoplasma pneumoniae is known to be a major cause of lower respiratory tract infections (LRTIs) in children. We studied 75 children who had been hospitalized for community-acquired LRTIs for the detection of M. pneumoniae by serological analysis and polymerase chain reaction (PCR) to amplify a 277-base pair region of 16S rDNA gene of M. pneumoniae applied to throat swab specimens. Serological and/or PCR positive results diagnosed M. pneumoniae infection in 23 (30.7%) patients.", "In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.", "Mycoplasma pneumoniae is increasingly recognized as an important cause of community acquired pneumonia (CAP) in children. We determined the importance of M. pneumoniae as a causative agent in 170 children aged 1 month to 15 years who were hospitalized with CAP over a 6-month period. The diagnosis of M. pneumoniae infection was based on serological evidence obtained by a particle agglutination test (SERODIA-MYCO II). A positive serological diagnosis was made if the acute phase serum titer was more than 1:160 or paired samples taken 2-4 weeks apart showed a four-fold or greater rise in the serum titer. M. pneumoniae was identified as the causative agent in 40 (23.5%) children. Children with M. pneumoniae infection were more likely to be older than 3 years (OR 4.0 95%CI 1.8-9.1, p<0.001), Chinese (OR 4.3 95%CI 2.0-8.9, p<0.001), have a duration of illness longer than 7 days prior to admission (OR 6.0 95%CI 2.7-13.5, p<0.001) and have perihilar interstitial changes on chest X-ray (OR 4.6 95%CI 2.2-9.9, p<0.001). A significant number of hospital admissions for CAP in Malaysian children can be attributed to M. pneumoniae. It is important to identify these children so as to administer the most appropriate antibiotic treatment.", "To determine the prevalence and clinical features of mycoplasma pneumoniae in Thai children with community acquired pneumonia (CAP).\n Diagnosis of current infection was based on > or = 4 fold rise in antibody sera or persistently high antibody titers together with the presence of mycoplasma DNA in respiratory secretion. The clinical features were compared between children who tested positive for M pneumoniae, and those whose results were negative.\n Current infection due to M. pneumoniae was diagnosed in 36 (15%) of 245 children with paired sera. The sensitivity and specificity of polymerase chain reaction (PCR) in diagnosing current infection in the present study were 78% and 98% respectively. The mean age of children with mycoplasma pneumoniae was higher than CAP with unspecified etiology. The presenting manifestations and initial laboratory finding were insufficient to predict mycoplasma pneumoniae precisely, the presence of chest pain and lobar consolidation on chest X-ray, however, were significant findings in children with mycoplasma pneumoniae.\n The present study confirms that M. pneumoniae plays a significant role in CAP in children of all ages. Children with this infection should be identified in order to administer the appropriate antibiotic treatment." ]

[ "11689811", "10962425", "16153933" ]

[ "A prospective randomized clinical study of thyroid hormone treatment after operations for complex congenital heart disease.", "Triiodothyronine repletion in infants during cardiopulmonary bypass for congenital heart disease.", "A randomized, double-blind, placebo-controlled pilot trial of triiodothyronine in neonatal heart surgery." ]

[ "nan", "Cardiopulmonary bypass suppresses circulating thyroid hormone levels. Although acute triiodothyronine repletion has been evaluated in adult patients after cardiopulmonary bypass, triiodothyronine pharmacokinetics and effects have not previously been studied in infants undergoing operations for congenital heart disease. We hypothesized that triiodothyronine deficiency in the developing heart after bypass may adversely affect cardiac function reserve postoperatively.\n Infants less than 1 year old undergoing ventricular septal defect or tetralogy of Fallot repair were randomized into 2 groups. Group T (n = 7) received triiodothyronine (0.4 microg/kg) immediately before the start of cardiopulmonary bypass and again with myocardial reperfusion. Control (NT, n = 7) patients received saline solution placebo or no treatment.\n These groups underwent similar ischemic and bypass times and received similar quantities of inotropic agents after the operation. The NT group demonstrated significant depression in circulating levels, compared with prebypass levels, for free triiodothyronine and total triiodothyronine at 1, 24, and 72 hours after bypass. Group T demonstrated similar low thyroxine values, but free and total triiodothyronine levels were maintained at prebypass levels for 24 hours and remained elevated over those of group NT (P <.05) at 72 hours. Heart rate was transiently elevated in group T compared with group NT (P <.05), and peak systolic pressure-rate product increased after 6 hours.\n These data imply that (1) triiodothyronine in the prescribed dose prevents circulating triiodothyronine deficiencies and (2) triiodothyronine repletion promotes elevation in heart rate without concomitant decrease in systemic blood pressure. Elevation of peak systolic pressure-rate product implies that triiodothyronine repletion improves myocardial oxygen consumption and may enhance cardiac function reserve after cardiopulmonary bypass in infants.", "This study was undertaken to evaluate the effect of triiodothyronine replacement on the early postoperative course of neonates undergoing aortic arch reconstruction.\n We performed a randomized, double-blind, placebo-controlled trial of triiodothyronine supplementation in neonates undergoing either a Norwood procedure or two-ventricle repair of interrupted aortic arch and ventricular septal defect. Patients were assigned to receive a continuous infusion of triiodothyronine (0.05 micro/kg/h) or placebo for 72 hours after cardiopulmonary bypass. Primary end points were a composite clinical outcome score and cardiac index at 48 postoperative hours.\n We enrolled 42 patients (triiodothyronine n = 22, placebo n = 20). Baseline characteristics were similar in the treatment groups. Study drug was discontinued prematurely because of hypertension (n = 1) and ectopic atrial tachycardia (n = 1), both cases in the triiodothyronine group. Free and total triiodothyronine levels were higher in the triiodothyronine group than in the placebo group at 24, 48, and 72 postoperative hours (P < .001). The median clinical outcome scores were 2.0 (range 0-4) with triiodothyronine and 2.0 (range 0-7) with placebo (P = .046). Compared with those in the placebo group, neonates assigned to triiodothyronine had shorter median time to negative fluid balance (2.0 vs 2.5 days, P = .027). Cardiac index values were 2.11 +/- 0.64 L/min x m2 with triiodothyronine and 2.05 +/- 0.72 L/min x m2 with placebo (P = .81). Heart rate and diastolic blood pressure were not influenced by triiodothyronine supplementation, but systolic blood pressure was higher in the triiodothyronine group (P < .001). No serious adverse events were attributed to triiodothyronine administration.\n Triiodothyronine supplementation was safe and resulted in more rapid achievement of negative fluid balance after aortic arch reconstruction. Cardiac index at 48 hours was not significantly improved." ]

[ "12712781", "19843790", "17006066", "11412288", "10325828", "19403595", "384738" ]

[ "The effect of an alveolar recruitment strategy on oxygenation during laparascopic cholecystectomy.", "Intraoperative ventilatory strategies for prevention of pulmonary atelectasis in obese patients undergoing laparoscopic bariatric surgery.", "Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents alveolar coagulation in patients without lung injury.", "Optimizing peroperative compliance with PEEP during upper abdominal surgery: effects on perioperative oxygenation and complications in patients without preoperative cardiopulmonary dysfunction.", "'Alveolar recruitment strategy' improves arterial oxygenation during general anaesthesia.", "Effects of four intraoperative ventilatory strategies on respiratory compliance and gas exchange during laparoscopic gastric banding in obese patients.", "Postoperative arterial oxygen tension after peroperative PEEP-ventilation." ]

[ "This prospective randomized controlled trial examined the effect of an \"alveolar recruitment strategy\" (ARS) in healthy patients having laparoscopic cholecystectomy. Twenty-four consecutive ASA 1 or 2 patients were randomly allocated to an ARS or control group. All patients were manually ventilated to a maximal airway pressure of 25 to 30 cmH2O or a tidal volume of 10 ml/kg during induction of general anaesthesia. After intubation, the control group was ventilated with standardized mechanical ventilation settings. The ARS group was manually ventilated to an airway pressure of 40 cmH2O for 10 breaths over one minute, followed by mechanical ventilation with similar standardized settings plus 5 cmH2O positive end-expiratory pressure. Blood pressure, heart rate, arterial oxygen and carbon dioxide tension (PaO2 and PaCO2) was measured pre-induction, 20 minutes post induction but before abdominal insufflation, 20 minutes after abdominal insufflation, and 20 minutes after arrival in the recovery room. Demographic and operation data were similar. The ARS group pre-insufflation PaO2 [30.16 (9.43)] was higher than the control group [22.19 (9.08)] (P = 0.047). There was a significant difference in PaO2 between the ARS [23.94 (4.87)] and control [17.26 (3.93)] groups during the post-insufflation period (P = 0.001). There were no significant differences in PaO2 between the groups during baseline and recovery periods. No adverse effects were reported. ARS improved arterial oxygenation intraoperatively in healthy patients having laparoscopic cholecystectomy, without clinical cardiovascular compromise or respiratory complication. We conclude that this alveolar recruitment strategy is a useful method of increasing arterial oxygenation.", "Atelectasis occurs regularly after induction of general anesthesia, persists postoperatively, and may contribute to significant postoperative morbidity and additional health care costs. Laparoscopic surgery has been reported to be associated with an increased incidence of postoperative atelectasis. It has been shown that during general anesthesia, obese patients have a greater risk of atelectasis than nonobese patients. Preventing atelectasis is important for all patients but is especially important when caring for obese patients.\n We randomly allocated 66 adult obese patients with a body mass index between 30 and 50 kg/m(2) scheduled to undergo laparoscopic bariatric surgery into 3 groups. According to the recruitment maneuver used, the zero end-expiratory pressure (ZEEP) group (n = 22) received the vital capacity maneuver (VCM) maintained for 7-8 s applied immediately after intubation plus ZEEP; the positive end-expiratory pressure (PEEP) 5 group (n = 22) received the VCM maintained for 7-8 s applied immediately after intubation plus 5 cm H(2)O of PEEP; and the PEEP 10 group (n = 22) received the VCM maintained for 7-8 s applied immediately after intubation plus 10 cm H(2)O of PEEP. All other variables (e.g., anesthetic and surgical techniques) were the same for all patients. Heart rate, noninvasive mean arterial blood pressure, arterial oxygen saturation, and alveolar-arterial Pao(2) gradient (A-a Pao(2)) were measured intraoperatively and postoperatively in the postanesthesia care unit (PACU). Length of stay in the PACU and the use of a nonrebreathing O(2) mask (100% Fio(2)) or reintubation were also recorded. A computed tomographic scan of the chest was performed preoperatively and postoperatively after discharge from the PACU to evaluate lung atelectasis.\n Patients in the PEEP 10 group had better oxygenation both intraoperatively and postoperatively in the PACU, lower atelectasis score on chest computed tomographic scan, and less postoperative pulmonary complications than the ZEEP and PEEP 5 groups. There was no evidence of barotrauma in any patient in the 3 study groups.\n Intraoperative alveolar recruitment with a VCM followed by PEEP 10 cm H(2)O is effective at preventing lung atelectasis and is associated with better oxygenation, shorter PACU stay, and fewer pulmonary complications in the postoperative period in obese patients undergoing laparoscopic bariatric surgery.", "Alveolar fibrin deposition is a hallmark of acute lung injury, resulting from activation of coagulation and inhibition of fibrinolysis. Previous studies have shown that mechanical ventilation with high tidal volumes may aggravate lung injury in patients with sepsis and acute lung injury. The authors sought to determine the effects of mechanical ventilation on the alveolar hemostatic balance in patients without preexistent lung injury.\n Patients scheduled for an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h later bronchoalveolar lavage fluid and blood samples were obtained, and markers of coagulation and fibrinolysis were measured.\n In contrast to mechanical ventilation with lower tidal volumes and PEEP (n = 21), the use of higher tidal volumes without PEEP (n = 19) caused activation of bronchoalveolar coagulation, as reflected by a marked increase in thrombin-antithrombin complexes, soluble tissue factor, and factor VIIa after 5 h of mechanical ventilation. Mechanical ventilation with higher tidal volumes without PEEP caused an increase in soluble thrombomodulin in lavage fluids and lower levels of bronchoalveolar activated protein C in comparison with lower tidal volumes and PEEP. Bronchoalveolar fibrinolytic activity did not change by either ventilation strategy.\n Mechanical ventilation with higher tidal volumes and no PEEP promotes procoagulant changes, which are largely prevented by the use of lower tidal volumes and PEEP.", "Late postoperative hypoxaemia after upper abdominal surgery is common even among cardiopulmonary healthy patients. Atelectasis may develop after intubation and persist into or reveal a disposition for atelectasis in the postoperative period. Positive end-expiratory pressure (PEEP) eliminates peroperative atelectasis but the effect on perioperative oxygenation is controversial. This study evaluated the effect of peroperative PEEP optimized pulmonary compliance on perioperative oxygenation and complications.\n Forty patients assessed by electrocardiography, spirometry, functional residual capacity and diffusion capacity were randomly assigned to receive positive end-expiratory pressure (PEEP) or zero end-expiratory pressure (ZEEP) during surgery. PaO2, SPO2 and complications in the postoperative period were evaluated without knowledge of peroperative PEEP or ZEEP application.\n Peroperative arterial oxygenation improved for all patients receiving PEEP, mean 2.1 kPa (0.7-3.5 kPa). There was no difference in postoperative median PaO2 between the groups. The differences in the incidence of late prolonged postoperative hypoxaemia and complications were 25% (-5% to 55%) and -1% (-31% to 29%) between the ZEEP and the PEEP group, but were not statistically significant.", "Abnormalities in gas exchange during general anaesthesia are caused partly by atelectasis. Inspiratory pressures of approximately 40 cm H2O are required to fully re-expand healthy but collapsed alveoli. However, without PEEP these re-expanded alveoli tend to collapse again. We hypothesized that an initial increase in pressure would open collapsed alveoli; if this inspiratory recruitment is combined with sufficient end-expiratory pressure, alveoli will remain open during general anaesthesia. We tested the effect of an 'alveolar recruitment strategy' on arterial oxygenation and lung mechanics in a prospective, controlled study of 30 ASA II or III patients aged more than 60 yr allocated to one of three groups. Group ZEEP received no PEEP. The second group received an initial control period without PEEP, and then PEEP 5 cm H2O was applied. The third group received an increase in PEEP and tidal volumes until a PEEP of 15 cm H2O and a tidal volume of 18 ml kg-1 or a peak inspiratory pressure of 40 cm H2O was reached. PEEP 5 cm H2O was then maintained. There was a significant increase in median PaO2 values obtained at baseline (20.4 kPa) and those obtained after the recruitment manoeuvre (24.4 kPa) at 40 min. This latter value was also significantly higher than PaO2 measured in the PEEP (16.2 kPa) and ZEEP (18.7 kPa) groups. Application of PEEP also had a significant effect on oxygenation; no such intra-group difference was observed in the ZEEP group. No complications occurred. We conclude that during general anaesthesia, the alveolar recruitment strategy was an efficient way to improve arterial oxygenation.", "Respiratory function is impaired in obese patients undergoing laparoscopic surgery. This study was performed to determine whether repeated lung recruitment combined with PEEP improves respiratory compliance and arterial partial pressure of oxygen (Pa(O2)) in obese patients undergoing laparoscopic gastric banding.\n Sixty patients with BMI >30 kg m(-2) were randomized, after induction of pneumoperitoneum, to receive either PEEP of 10 cm H2O (Group P), inspiratory pressure of 40 cm H2O for 15 s once (Group R), Group R recruitment followed by PEEP 10 cm H2O (Group RP), or Group RP recruitment but with the inspiratory manoeuvre repeated every 10 min (Group RRP). Static respiratory compliance and Pa(O2) were determined after intubation, 10 min after pneumoperitoneum (before lung recruitment), and every 10 min thereafter (after recruitment). Results are presented as mean (SD).\n Pneumoperitoneum decreased respiratory compliance from 48 (3) to 30 (1) ml cm H2O(-1) and decreased Pa(O2) from 12.4 (0.3) to 8.8 (0.3) kPa in all groups (P<0.01). Immediately after recruitment, compliance was 32 (1), 32 (2), 40 (2), and 40 (1) ml cm H2O(-1) and Pa(O2) was 9.1 (0.3), 9.1 (0.1), 11.9 (0.1), and 11.9 (0.1) kPa in Groups P, R, RP, and RRP, respectively (P<0.01). Ten and 20 min later, Pa(O2) in Group R decreased to 9.2 (0.1) kPa and compliance in Group PR decreased to 33 (2) ml cm H2O(-1), respectively (P<0.01).\n Group RRP recruitment strategy was associated with the best intraoperative respiratory compliance and Pa(O2) in obese patients undergoing laparoscopic gastric banding.", "Forty otherwise healthy patients (29 women and 11 men), undergoing elective cholecystectomy, were randomly allocated to be ventilated during the operation either with a positive end-expiratory pressure of 1 kPa (10 cmH2O) (PEEP group) or with intermittent positive pressure ventilation without PEEP (control group). During the operation the mean arterial oxygen tension (PaO2) in the PEEP group increased from 14.6 to 16.5 kPa, while no changes occurred in the control group (13.5 and 13.6 kPa). On the first postoperative day, PaO2 decreased by 12% of the preoperative values in the PEEP group; the decrease was 20% in the control group. On the third postoperative day, the PaO2 in the control group was still 9% below the preoperative values, but on the fifth day, both groups had reached their preoperative PaO2 values. In the postoperative period, no statistically significant difference in PaO2 could be demonstrated between the groups. Determinations of the forced vital capacity and forced expiratory volume in the first second showed no difference between the groups pre- or postoperatively. The present study demonstrated no clinically relevant beneficial effect of peroperative PEEP ventilation on the postoperative arterial hypoxaemia after an upper abdominal laparotomy." ]

[ "10211504", "9514434", "7813338", "15339325", "15622577", "15449263", "8330179", "12847369" ]

[ "A pilot study of total pelvic floor repair or gluteus maximus transposition for postobstetric neuropathic fecal incontinence.", "Pelvic floor procedures produce no consistent changes in anatomy or physiology.", "Randomized trial of internal anal sphincter plication with pelvic floor repair for neuropathic fecal incontinence.", "Adjuvant biofeedback following anal sphincter repair: a randomized study.", "A prospective, randomized, controlled clinical trial of placement of the artificial bowel sphincter (Acticon Neosphincter) for the control of fecal incontinence.", "Randomized clinical trial comparing conservative and surgical treatment of neurogenic faecal incontinence.", "Randomized trial comparing three forms of pelvic floor repair for neuropathic faecal incontinence.", "Direct repair vs. overlapping sphincter repair: a randomized, controlled trial." ]

[ "The aim of this study was to report pilot data comparing the morbidity and functional outcome of total pelvic floor repair with gluteus maximus transposition for women with postobstetric fecal incontinence.\n This is a prospective, randomized trial of two surgical procedures in 24 women so far. Functional assessment was performed with use of a 20-point clinical incontinence score and patient questionnaire before and after operation. The physiologic parameters, before and after operation, included resting and squeeze anal pressures, length of the high pressure zone, anal and rectal mucosal sensitivity, and pudendal nerve latency.\n So far, 12 patients have been treated by total pelvic floor repair and 12 by gluteus maximus transposition. Of these, three patients developed wound complications after gluteus maximus transposition compared with none after total pelvic floor repair. Among these cases there was a significant overall improvement in functional score (given as mean +/- standard deviation) after both total pelvic floor repair (13.1 +/- 2.7 vs. 6.6 +/- 4.5; P < 0.001) and gluteus maximus transposition (13.8 +/- 3.8 vs. 7.7 +/- 6.1; P < 0.01), although no difference existed between the groups. There was no change in any of the physiologic measurements after either operation, and preoperative measurements did not identify patients likely to do badly.\n We conclude from these preliminary data that both total pelvic floor repair and gluteus maximus transposition significantly improve continence in women with postobstetric neuropathic fecal incontinence. Gluteus maximus transposition gives equivalent results to total pelvic floor repair. Neither procedure has any influence on anorectal physiologic parameters.", "Postanal repair was designed to restore both anatomy and function of the anal canal in neurogenic fecal incontinence. In most series, the degree of continence is improved in fewer than 50 percent of patients. Adding anterior levatorplasty and sphincter plication (total pelvic floor repair) is claimed to improve functional results. We performed a randomized trial comparing postanal and total pelvic floor repair for neurogenic incontinence.\n Twenty female patients were studied. All had Type D incontinence (Parks and Browning). Anal manometry, defecography, and grading of the degree of continence were repeated 12 weeks after surgery to assess changes in clinical, manometric, and radiologic parameters. Statistical analysis was done using Wilcoxon's signed-rank test and Wilcoxon's two-sample test.\n Continence improved in eight patients. Differences among clinical, manometric, and radiologic data were not statistically significant.\n Pelvic floor repair procedures produce no consistent changes in anatomy or physiology. Clinical improvement is caused by creation of a local stenosis or by the placebo effect rather than by improvement of muscle function.", "This study was designed to examine the role of adjuvant internal anal sphincter plication in women with neuropathic fecal incontinence undergoing pelvic floor repair.\n We completed a randomized trial with symptomatic and physiologic assessment before and after surgery.\n There was no symptomatic advantage of adding internal sphincter plication; the mean improvement of functional score was 3.61 +/- 1.82 (standard deviation; P < 0.01) following pelvic floor repair alone compared with 2.80 +/- 1.66 (standard deviation; P < 0.01) when adjuvant internal and sphincter plication was added. The addition of internal sphincter plication was associated with a significant fall in maximum anal resting and squeezing pressures (P < 0.01).\n Addition of internal sphincter plication is not advised in women with neuropathic fecal incontinence treated by pelvic floor repair.", "To evaluate the impact of adjuvant biofeedback following sphincter surgery.\n Thirty-eight patients were randomized into sphincter repair or sphincter repair plus biofeedback groups. Outcome measures included a symptom questionnaire, patient's rating of satisfaction with continence function and improvement, change in continence score, quality of life and anorectal physiology. Endoanal ultrasonography was also performed pre- and post-operatively.\n Immediately following surgery, there was no statistically significant difference in any of the functional or physiological variables between the groups. Continence and patient satisfaction scores improved with a mean difference of -0.48 (95% CI: -3.30-2.33, P = 0.73) and 1.03 (95% CI: -1.40-3.46, P = 0.39), respectively. Only the difference in embarrassment scores reached statistical significance (mean) 0.56 (95% CI: 0.12-0.99, P = 0.014). Resting and squeeze pressures also improved. Thirteen of 14 in the biofeedback and 11 of 17 (control) reported symptomatic improvement. In the biofeedback group, although not statistically significant continence and satisfaction scores improved and were sustained over time. In the control group, continence and satisfaction scores changed little between 3 and 12 months (P = NS). Quality of life measures improved within the biofeedback group but there was no statistical difference between the groups.\n Following surgery continence function improves in all patients but adjuvant biofeedback therapy improves quality of life and maintains symptomatic improvement over time.\n Copyright 2004 Blackwell Publishing Ltd", "Severe fecal incontinence remains a disabling condition for the patient and a major therapeutic challenge for the physician. A series of observational studies have indicated that placement of an artificial bowel sphincter is associated with marked improvement of continence and quality of life. We have performed a prospective, randomized, controlled trial to evaluate the effect of placement of an artificial bowel sphincter (Acticon Neosphincter) on continence and quality of life in a group of severely incontinent adults.\n Fourteen adults (male:female, 1:13; age range, 44-75 years) were randomized to placement of the artificial bowel sphincter or to a program of supportive care and were followed for six months from operation or entry into the study. The principal outcome measure was the level of continence, measured with the Cleveland Continence Score, which provides a scale from 0 to 20, representing perfect control through to total incontinence. Secondary outcome measures were perioperative and late complications in the artificial bowel sphincter group, and the changes in quality of life in both groups.\n In the control group, the Cleveland Continence Score was not significantly altered, with an initial value of 17.1 +/- 2.3 and a final value of 14.3 +/- 4.6 at six months. The artificial bowel sphincter group showed a highly significant improvement, changing from 19.0 +/- 1.2 before placement to 4.8 +/- 4.0 at six months after placement. One patient in the artificial bowel sphincter group had failure of healing of the perineal wound and explantation of the device (14 percent explantation rate). There were two other significant perioperative events of recurring fecal impaction initially after placement in one patient and additional suturing of the perineal wound in another. There were major improvements in the quality of life for all measures in the artificial bowel sphincter group. There was significant improvement in all eight subscales of the Medical Outcome Study Short Form-36 measures. The American Medical Systems Quality of Life score was raised from 39 +/- 6 to 83 +/- 14 and the Beck Depression Inventory showed reduction from a level of mild depression (10.8 +/- 9.3) to a normal value (6.8 +/- 8.7). No significant changes in any of the quality of life measures occurred for the control group.\n Through a prospective, randomized trial format, we have shown that placement of an artificial bowel sphincter is safe and effective when compared with supportive care alone. Perioperative and late problems are likely to continue to occur and between 15 percent and 30 percent of patients may require permanent explantation. For the remainder, the device is easy and discrete to use, highly effective in achieving continence, and able to generate a major improvement in the quality of life.", "The treatment of choice in idiopathic (neurogenic) faecal incontinence is controversial. In a randomized study levatorplasty was compared with anal plug electrostimulation of the pelvic floor with respect to functional outcome and physiological variables.\n Thirty-one patients underwent levatorplasty and 28 anal plug electrostimulation of the pelvic floor over 3 years. The results were evaluated at 3, 12 and 24 months after completion of treatment by means of a validated questionnaire and anorectal manometry and manovolumetry.\n Incontinence scores were significantly reduced during the entire observation period in both groups (P < 0.001) as was the use of pads (P = 0.003 to P < 0.001). The proportion of patients reporting improvement in physical and social handicap was greater in the levatorplasty group after 3, 12 and 24 months (P = 0.036 to P < 0.001). No significant changes in physiological variables were observed in either group.\n Better results were obtained with levatorplasty than with anal plug electrostimulation of the pelvic floor in patients with idiopathic (neurogenic) faecal incontinence. Levatorplasty should be therefore be considered the treatment of choice for this condition.\n Copyright 2004 British Journal of Surgery Society Ltd.", "A randomized controlled trial in women with neuropathic faecal incontinence compared total pelvic floor repair (n = 12) with anterior levatorplasty and sphincter plication alone (n = 12) and postanal repair alone (n = 12). Review at 6 and 24 months indicated that results were significantly better for total pelvic floor repair than either of the other procedures. Complete continence was achieved in eight of the 12 patients 2 years after total pelvic floor repair. Only total repair significantly elongated the anal canal. Both total pelvic floor repair and anterior levatorplasty improved sensation in the upper anal canal.", "The aim of this study was to compare the results of two surgical techniques (direct end-to-end vs. overlapping) of delayed repair of a localized anterior defect of external anal sphincter after an obstetric trauma.\n During a five-year period, 23 patients were randomly assigned to direct end-to-end repair (n = 12) or overlapping sphincter repair (n = 11), using 2-0 PDS sutures. Two patients from each group had an internal anal sphincter defect that also was repaired. All patients had a normal pudendal nerve terminal motor latency preoperatively. Evaluations included endoanal ultrasound, anorectal manometry, and neurophysiologic evaluation. Continence was assessed by the Cleveland Clinic Continence Score (0-20; 0, perfect continence; 20, complete incontinence).\n The two groups were comparable with regard to age (median, 45 years), past history of sphincter repair (n = 2), and posterior vaginal repair. There was no major morbidity. The wound-healing rate was identical between the two groups. However, of the patients undergoing overlapping repair, two had fecal impaction, and one had a urinary retention. Median preoperative continence score was 17 in both the direct-repair group (score, 8-20) and the overlap group (score, 7-20). At a median follow-up of 18 months, the improvement in continence was similar between the two surgical groups, with a median continence score of 3, respectively. In both surgical groups there was a significant and similar improvement in maximum squeeze pressure and in the functional anal canal length postoperatively (P < 0.05), but the mean resting pressure was relatively unchanged. In the overlap group, one patient developed a unilaterally prolonged pudendal nerve terminal motor latency that was persistent 22 months after surgery, and two patients had impaired fecal evacuation postoperatively.\n This randomized, controlled study suggests that the outcome is similar whether direct end-to-end or overlapping repair of a sphincter defect is performed. Overlapping repair might be associated with more difficulties with fecal evacuation and a prolonged pudendal nerve terminal motor latency postoperatively." ]

[ "4583792", "5443653", "16818861" ]

[ "A double-blind comparison of fluphenazine and haloperidol in outpatient schizophrenic children.", "Comparison of haloperidol and fluphenazine in disturbed children.", "Childhood-onset schizophrenia: A double-blind, randomized clozapine-olanzapine comparison." ]

[ "nan", "nan", "Childhood-onset schizophrenia is a rare but severe form of the disorder that is frequently treatment resistant. The psychiatrist has a limited evidence base to guide treatment, particularly as there are no trials in children comparing atypical antipsychotics, the mainstay of current treatment.\n To compare the efficacy and safety of olanzapine and clozapine, hypothesizing that clozapine would be more efficacious.\n Double-blind randomized 8-week controlled trial, with a 2-year open-label follow-up.\n National Institute of Mental Health study, January 1998 to June 2005. Patients underwent reassessment 2 years after discharge.\n Children and adolescents recruited nationally, aged 7 to 16 years, meeting unmodified DSM-IV criteria for schizophrenia, and resistant to treatment with at least 2 antipsychotics.\n After drug washout and a 1- to 3-week antipsychotic-free period, patients were randomized to treatment with clozapine (n = 12) or olanzapine (n = 13).\n The Clinical Global Impression Severity of Symptoms Scale and Schedule for the Assessment of Negative/Positive Symptoms.\n Clozapine was associated with a significant reduction in all outcome measures, whereas olanzapine showed a less consistent profile of clinical improvement. While there were moderate to large differential treatment effects in favor of clozapine, these reached significance only in the alleviation of negative symptoms from an antipsychotic-free baseline (P = .04; effect size, 0.89). Clozapine was associated with more overall adverse events. At 2-year follow-up, 15 patients were receiving clozapine with evidence of sustained clinical improvement, but additional adverse events emerged, including lipid anomalies (n = 6) and seizures (n = 1).\n While not demonstrating definitively the superiority of clozapine compared with olanzapine in treatment-refractory childhood-onset schizophrenia, the study suggests that clozapine has a more favorable profile of clinical response, which is balanced against more associated adverse events." ]

[ "10477776", "9339943", "8625627", "16625008", "17138955", "16358138", "15851721", "8339645" ]

[ "Increased mortality associated with growth hormone treatment in critically ill adults.", "Immediate postoperative enteral feeding results in impaired respiratory mechanics and decreased mobility.", "Lack of effects of recombinant growth hormone on muscle function in patients requiring prolonged mechanical ventilation: a prospective, randomized, controlled study.", "Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.", "Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit.", "Inspiratory muscle training is ineffective in mechanically ventilated critically ill patients.", "Insulin therapy protects the central and peripheral nervous system of intensive care patients.", "The lack of effect of routine magnesium administration on respiratory function in mechanically ventilated patients." ]

[ "The administration of growth hormone can attenuate the catabolic response to injury, surgery, and sepsis. However, the effect of high doses of growth hormone on the length of stay in intensive care and in the hospital, the duration of mechanical ventilation, and the outcome in critically ill adults who are hospitalized for long periods is not known.\n We carried out two prospective, multicenter, double-blind, randomized, placebo-controlled trials in parallel involving 247 Finnish patients and 285 patients in other European countries who had been in an intensive care unit for 5 to 7 days and who were expected to require intensive care for at least 10 days. The patients had had cardiac surgery, abdominal surgery, multiple trauma, or acute respiratory failure. The patients received either growth hormone (mean [+/-SD] daily dose, 0.10 +/- 0.02 mg per kilogram of body weight) or placebo until discharge from intensive care or for a maximum of 21 days.\n The in-hospital mortality rate was higher in the patients who received growth hormone than in those who did not (P<0.001 for both studies). In the Finnish study, the mortality rate was 39 percent in the growth hormone group, as compared with 20 percent in the placebo group. The respective rates in the multinational study were 44 percent and 18 percent. The relative risk of death for patients receiving growth hormone was 1.9 (95 percent confidence interval, 1.3 to 2.9) in the Finnish study and 2.4 (95 percent confidence interval, 1.6 to 3.5) in the multinational study. Among the survivors, the length of stay in intensive care and in the hospital and the duration of mechanical ventilation were prolonged in the growth hormone group.\n In patients with prolonged critical illness, high doses of growth hormone are associated with increased morbidity and mortality.", "The authors set out to determine whether immediate enteral feeding minimizes early postoperative decreases in handgrip and respiratory muscle strength.\n Muscle strength decreases considerably after major surgical procedures. Enteral feeding has been shown to restore strength rapidly in other clinical settings.\n A randomized, controlled, nonblinded clinical trial was conducted in patients undergoing esophagectomy or pancreatoduodenectomy who received immediate postoperative enteral feeding via jejunostomy (fed, n = 13), or no enteral feeding during the first 6 postoperative days (unfed, n = 15). Handgrip strength, vital capacity, forced expiratory volume in one second (FEV1), and maximal inspiratory pressure (MIP) were measured before surgery and on postoperative days 2, 4, and 6. Fatigue and vigor were evaluated before surgery and on postoperative day 6. Mobility was assessed daily after surgery using a standardized descriptive scale. Postoperative urine biochemistry was evaluated in daily 24-hour collections.\n Postoperative vital capacity (p < 0.05) and FEV1 (p = 0.07) were consistently lower (18%-29%) in the fed group than in the unfed group, whereas grip strength and maximal inspiratory pressure were not significantly different. Postoperative mobility also was lower in the fed patients (p < 0.05) and tended to recover less rapidly (p = 0.07). Fatigue increased and vigor decreased after surgery (both p < or = 0.001), but changes were similar in the fed and unfed groups. Intensive care unit and postoperative hospital stay did not differ between groups.\n Immediate postoperative jejunal feeding was associated with impaired respiratory mechanics and postoperative mobility and did not influence the loss of muscle strength or the increase in fatigue, which occurred after major surgery. Immediate postoperative enteral feeding should not be routine in well-nourished patients at low risk of nutrition-related complications.", "To evaluate the benefit of recombinant human growth hormone administration on muscle strength and duration of weaning in critically ill patients undergoing prolonged mechanical ventilation.\n Prospective, randomized, controlled, single-blind study.\n Intensive care unit. Patients: Twenty patients requiring > or = 7 days of mechanical ventilation for acute respiratory failure.\n Random assignment to receive either 0.43 IU (approximately 0.14 mg) recombinant growth hormone/kg body weight/day (treated group), or saline (nontreated group) for 12 days.\n Nutritional support was guided by indirect calorimetry. Cumulative nitrogen balance was positive throughout the study period in the treated group 17.3 (44.9 +/- 17.3[SEM] g/12 days) vs. the nontreated group (-65.8 +/- 11.8 g/12 days) (p<.0001). Despite similar initial plasma concentrations, recombinant growth hormone supplementation resulted in marked increases in growth hormone, insulin like growth factor-1, and insulin concentrations (p<.05, .02, and .0001, respectively, vs. nontreated group). Body impedance determined net fat-free mass increased in the treated group (0.8 +/- 0.6 kg) vs. the nontreated group (-1.1 +/- O.5 kg) (p<.03). Initial peripheral muscle function, assessed by computer-controlled electrical stimulation of the adductor pollicis, was similarly lower in treated and nontreated groups than sex and age-matched normal controls, and decreased further during the study period. Arterial blood gases, cumulative total mechanical ventilation time, and number of hrs/day of mechanical ventilation during weaning were similar in both patient groups. Only three of the ten patients in each group were weaned from mechanical ventilation by day 12.\n Daily administration of recombinant growth hormone in mechanically ventilated patients with acute respiratory failure promotes a marked nitrogen retention. However, this reaction is accompanied neither by an improvement in muscle strength nor by a shorter duration of ventilatory supports.", "Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.\n We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications.\n At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness.\n These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, NCT00295269.).\n Copyright 2006 Massachusetts Medical Society.", "Critical illness polyneuropathy/myopathy causes limb and respiratory muscle weakness, prolongs mechanical ventilation, and extends hospitalization of intensive care patients. Besides controlling risk factors, no specific prevention or treatment exists. Recently, intensive insulin therapy prevented critical illness polyneuropathy in a surgical intensive care unit.\n To investigate the impact of intensive insulin therapy on polyneuropathy/myopathy and treatment with prolonged mechanical ventilation in medical patients in the intensive care unit for at least 7 days.\n This was a prospectively planned subanalysis of a randomized controlled trial evaluating the effect of intensive insulin versus conventional therapy on morbidity and mortality in critically ill medical patients. All patients who were still in intensive care on Day 7 were screened weekly by electroneuromyography. The effect of intensive insulin therapy on critical illness polyneuropathy/myopathy and the relationship with duration of mechanical ventilation were assessed.\n Independent of risk factors, intensive insulin therapy reduced incidence of critical illness polyneuropathy/myopathy (107/212 [50.5%] to 81/208 [38.9%], p = 0.02). Treatment with prolonged (> or = 14 d) mechanical ventilation was reduced from 99 of 212 (46.7%) to 72 of 208 (34.6%) (p = 0.01). This was statistically only partially explained by prevention of critical illness polyneuropathy/myopathy.\n In a subset of medical patients in the intensive care unit for at least 7 days, enrolled in a randomized controlled trial of intensive insulin therapy, those assigned to intensive insulin therapy had a reduced incidence of critical illness polyneuropathy/myopathy and were treated with prolonged mechanical ventilation less frequently.", "Invasive mechanical ventilation is associated with complications, and its abbreviation is desirable. The imbalance between increased workload, decreased inspiratory muscle strength and endurance is an important determinant of ventilator dependence. Low endurance may be present due to respiratory muscle atrophy, critical illness, or steroid use. Specific inspiratory muscle training may increase or preserve endurance. The objective of the study was to test the hypothesis that inspiratory muscle training from the beginning of mechanical ventilation would abbreviate the weaning duration and decrease reintubation rate. As a secondary objective, we described the evolution of inspiratory muscle strength with and without inspiratory muscle training.\n Prospective, randomized clinical trial in an adult clinical-surgical intensive care unit. Twelve patients trained the inspiratory muscles twice a day, and 13 patients did not (control). Training was performed adjusting the sensitivity of the ventilator based on the maximal inspiratory pressure. Patients underwent daily surveillance of the maximal inspiratory pressure.\n The weaning duration (31 +/- 22 hr, control and 23 +/- 11 hr, training group; P = .24) and reintubation rate (5 control and 3 training group; P = .39) were not statistically different. The maximal inspiratory pressure of the control group showed a trend toward a modest increase. In contrast, the training group showed a small decrease (P = .34).\n In acute critically ill patients, inspiratory muscle training from the beginning of mechanical ventilation neither abbreviated the weaning duration, nor decreased the reintubation rate. Inspiratory muscle strength tended to stay constant, along the mechanical ventilation, with or without this specific inspiratory muscle training.", "To investigate the effectiveness of maintaining blood glucose levels below 6.1 mmol/L with insulin as prevention of secondary injury to the central and peripheral nervous systems of intensive care patients.\n The authors studied the effect of intensive insulin therapy on critical illness polyneuropathy (CIPNP), assessed by weekly EMG screening, and its impact on mechanical ventilation dependency, as a prospectively planned subanalysis of a large randomized, controlled trial of 1,548 intensive care patients. In the 63 patients admitted with isolated brain injury, the authors studied the impact of insulin therapy on intracranial pressure, diabetes insipidus, seizures, and long-term rehabilitation at 6 and 12 months follow-up.\n Intensive insulin therapy reduced ventilation dependency (p = 0.0007; Mantel-Cox log rank test) and the risk of CIPNP (p < 0.0001). The risk of CIPNP among the 405 long-stay (> or =7 days in intensive care unit) patients was lowered by 49% (p < 0.0001). Of all metabolic and clinical effects of insulin therapy, and corrected for known risk factors, the level of glycemic control independently explained this benefit (OR for CIPNP 1.26 [1.09 to 1.46] per mmol blood glucose, p = 0.002). In turn, prevention of CIPNP explained the ability of intensive insulin therapy to reduce the risk of prolonged mechanical ventilation (OR 3.75 [1.49 to 9.39], p = 0.005). In isolated brain injury patients, intensive insulin therapy reduced mean (p = 0.003) and maximal (p < 0.0001) intracranial pressure while identical cerebral perfusion pressures were obtained with eightfold less vasopressors (p = 0.01). Seizures (p < 0.0001) and diabetes insipidus (p = 0.06) occurred less frequently. At 12 months follow-up, more brain-injured survivors in the intensive insulin group were able to care for most of their own needs (p = 0.05).\n Preventing even moderate hyperglycemia with insulin during intensive care protected the central and peripheral nervous systems, with clinical consequences such as shortening of intensive care dependency and possibly better long-term rehabilitation.", "We wished to determine if magnesium infusion would improve respiratory muscle function in long-term ventilated patients even in the absence of hypomagnesemia.\n Prospective study of mechanically ventilated patients using a double-blind crossover design.\n A combined medical-surgical ICU of a university teaching hospital.\n Twenty-one separate admissions to the ICU in 20 patients were studied. Patients who were selected had been intubated and mechanically ventilated for at least 6 days with the admitting diagnosis of respiratory failure.\n Twelve patients received 6 g MgSO4 intravenous (i.v.) infusion over 16 h on day 1 followed by placebo infusion on day 2. Nine patients received placebo on day 1 followed by MgSO4 (6 g i.v.) on day 2.\n We measured vital capacity (VC), maximal inspiratory pressure (Pmax) and maximal expiratory pressure (Pemax) in all patients. There were no significant differences in Pimax (37 +/- 14 vs 42 +/- 20 cm H2O), Pemax (59 +/- 32 vs 61 +/- 38 cm H2O), and VC (850 +/- 460 vs 960 +/- 490 ml) comparing values before and after magnesium infusion. We could not find a subgroup of patients with a marked improvement in Pimax or Pemax.\n In patients requiring mechanical ventilation for respiratory failure, magnesium infusion is not associated with increased respiratory muscle strength. Although a trial of MgSO4 administration may be considered for patients with difficulty weaning from mechanical ventilation, it is unlikely to result in clinical improvement." ]

[ "1432282", "2809781", "1403397" ]

[ "Effects of dexamethasone on pulmonary function following extubation.", "Routine use of dexamethasone for the prevention of postextubation respiratory distress.", "Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema." ]

[ "Dexamethasone is often given to intubated neonates to facilitate successful extubation. To study the effects of dexamethasone on pulmonary function immediately following extubation, we conducted a randomized, blinded, placebo-controlled trial in 51 infants. All infants had been intubated for a minimum of 3 days but no more than 30 days. Mean weight at extubation was 2.41 kg in treated infants, 2.25 kg in control infants. When infants were deemed ready for extubation, dexamethasone 0.5 mg/kg/dose or an equal volume of normal saline was given in three doses 8 hours apart. The final dose was given 1 hour before extubation. Esophageal pressure, air flow integrated to tidal volume (Vt), respiratory rate, and heart rate were measured before extubation, immediately following extubation, and every 20 minutes for 80 minutes. Total pulmonary resistance (RTP), dynamic lung compliance (CL), and minute ventilation (VE) were calculated. Forty-two infants completed the study; 19 infants received dexamethasone and 23 received placebo. There was no difference between the two groups in gestational age, weight at study, or length of intubation. Vt, RTP, VE, and CL were not significantly different between the two groups over time; however, RTP increased over time in the placebo group. Heart rate was significantly lower in the dexamethasone group. We conclude that dexamethasone appears to have limited effect on pulmonary function immediately following extubation in the population studied. Further studies should evaluate the drug effect beginning at least 1 hour after extubation.", "We evaluated the routine use of dexamethasone for the prevention of postextubation respiratory distress by entering 60 ventilated infants into a prospective, randomized, blinded study. Thirty minutes before extubation, 30 infants were given a single dose of intravenous dexamethasone (0.25 mg/kg), and 30 infants received saline placebo. Infants were intubated orotracheally for at least 48 hours following a single intubation and were maintained on low ventilator settings (F10(2) less than 0.35, intermittent mandatory ventilation [IMV] less than 6, positive end-expiratory pressure [PEEP] less than 4) at least 12 hours before extubation. Following extubation, all infants weighing less than 1500 g were routinely placed on nasal continuous positive airway pressure (NCPAP). There was no difference between the two groups in postextubation Downes' score, serum pH, PCO2, or oxygen requirement at 30 minutes, 6 hours, and 24 hours. Respiratory acidosis occurred in one steroid-treated patient and in two placebo-treated infants. Stridor occurred in four infants in each group. No infant developed postextubation lobar atelectasis or required reintubation. We conclude that prophylactic administration of dexamethasone does not improve the immediate postextubation course of infants following a single intubation and that its routine use at the time of extubation is not indicated.", "We studied 50 preterm infants who had multiple or traumatic endotracheal intubations, or whose duration of endotracheal intubation was > or = to 14 days, and who were considered at high risk for airway edema. These infants were enrolled in a prospective, randomized, controlled clinical trial to assess whether prophylactic dexamethasone therapy would be effective in the prevention of postextubation stridor and respiratory distress. At study entry, both groups had similar weights, postnatal ages, methylxanthine use, ventilator settings, blood gas values, and pulmonary function test results (dynamic compliance, total respiratory resistance, tidal volume, peak-to-peak transpulmonary pressure, minute ventilation, and peak inspiratory and expiratory flow rates). Patients underwent blood gas studies, physical examinations, and pulmonary function testing at baseline (4 hours before extubation) and again 2 to 4 hours and 18 to 24 hours after extubation. Twenty-seven infants received dexamethasone, 0.25 mg/kg per dose, at baseline, and then every 8 hours for a total of three doses; 23 infants received saline solution at corresponding times. Eighteen to twenty-four hours after extubation, total pulmonary resistance increased by 225% from baseline in the control group compared with 33% in the dexamethasone group (p < 0.006), and the dexamethasone group had a greater tidal volume, a greater dynamic compliance, and a lower arterial carbon dioxide pressure. Of 23 control infants, 10 had postextubation stridor compared with 2 of 27 dexamethasone-treated patients (p < 0.006). Of the 23 control patients, 4 required reintubation compared with none of the treated group (p < 0.05). We conclude that the prophylactic use of corticosteroids for the prevention of postextubation stridor and respiratory distress is efficacious in low birth weight, high-risk preterm infants." ]

[ "1353192", "8436094", "3359804", "11119336", "8632216", "7913157", "20038852", "7762534", "17684522", "7752754", "2403062", "7713054", "1082238", "1739794", "11498488", "19640958", "9228962", "12649946", "8593380", "10376776", "3067695", "2205798", "1676467", "3524531", "8102720", "1978164", "11463965", "12744873", "8772901", "16522919", "17298703", "10419992", "10421302", "9687551", "8100345", "9002334", "3534284", "10390287" ]

[ "Vitamin A supplementation and child survival.", "Impact of large-dose vitamin A supplementation on childhood diarrhoea, respiratory disease and growth.", "The effect of vitamin A supplementation on tear fluid retinol levels of marginally nourished preschool children.", "Evaluation of safety of oral vitamin 'A' megadose co-administered with measles vaccination.", "Vitamin A supplementation fails to reduce incidence of acute respiratory illness and diarrhea in preschool-age Indonesian children.", "Effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections in young children in Brazil.", "Effects of vitamin A supplementation on intestinal barrier function, growth, total parasitic, and specific Giardia spp infections in Brazilian children: a prospective randomized, double-blind, placebo-controlled trial.", "Vitamin A supplementation and morbidity among preschool children in south India.", "Effect of vitamin A supplementation on immune function of well-nourished children suffering from vitamin A deficiency in China.", "Reduced seroconversion to measles in infants given vitamin A with measles vaccination.", "Tolerance of preschoolers to two dosage strengths of vitamin A preparation.", "No evidence of fontanelle-bulging episodes after vitamin A supplementation of 6- and 9-month-old infants in Guinea Bissau.", "The effect of massive doses of vitamin A on the signs of vitamin A deficiency in preschool children.", "Childhood mortality after a high dose of vitamin A in a high risk population.", "Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomised double blind controlled trial.", "Does vitamin A supplementation interact with routine vaccinations? An analysis of the Ghana Vitamin A Supplementation Trial.", "Randomised trial of effect of vitamin A supplementation on antibody response to measles vaccine in Guinea-Bissau, west Africa.", "Effect of vitamin A supplementation on childhood morbidity and mortality.", "Plasma retinol level, vitamin A supplementation and acute respiratory infections in children of 1-5 years old in a developing country. Respiratory Diseases Working Group.", "Vitamin A and zinc supplementation of preschool children.", "Vitamin A status of children with a history of respiratory syncytial virus infection in infancy.", "Reduced mortality among children in southern India receiving a small weekly dose of vitamin A.", "Efficacy of vitamin A in reducing preschool child mortality in Nepal.", "Vitamin A status in children who are prone to respiratory tract infections.", "Vitamin A supplementation and increased prevalence of childhood diarrhoea and acute respiratory infections.", "Effect of massive dose vitamin A on morbidity and mortality in Indian children.", "Vitamin A supplementation in children with recurrent respiratory infections.", "Effect of Vitamin A supplementation on the immune response to measles vaccination.", "Effect of vitamin A supplementation to mother and infant on morbidity in infancy.", "A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico.", "Supplementation with vitamin A reduces watery diarrhoea and respiratory infections in Mexican children.", "Vitamin A administered with measles vaccine to nine-month-old infants does not reduce vaccine immunogenicity.", "Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea: a randomised trial.", "Vitamin A supplementation but not deworming improves growth of malnourished preschool children in eastern Zaire.", "Vitamin A supplementation in northern Ghana: effects on clinic attendances, hospital admissions, and child mortality. Ghana VAST Study Team.", "Impact of nutrition education and mega-dose vitamin A supplementation on the health of children in Nepal.", "Effect of deworming and vitamin A administration on serum vitamin A levels in preschool children.", "The beneficial effects of weekly low-dose vitamin A supplementation on acute lower respiratory infections and diarrhea in Ecuadorian children." ]

[ "Previous studies of the effect of 6-monthly vitamin A supplementation on child mortality have given conflicting results. In other trials, more frequent doses of vitamin A have significantly reduced mortality among children at risk of vitamin A deficiency. We have done a double-blind, placebo-controlled trial of vitamin A supplementation in the Sudan among 28,753 children aged 9-72 months at risk of vitamin A deficiency. Children were assigned to receive either 200,000 IU vitamin A and 40 IU vitamin E every 6 months (vitamin A group) or 40 IU vitamin E alone (placebo group). During the 18 months of follow-up, there were 120 deaths (8.4/1000) in the vitamin A group and 112 (7.9/1000) in the placebo group (relative risk 1.06, 95% confidence interval 0.82-1.37). Controlling for geographic site, round of observation, anthropometry, morbidity, dietary intake of vitamin A, sex, and all baseline differences between the two groups did not change the results. Children living in poor and unsanitary environments, younger children, and those sick, stunted, wasted, or consuming diets low in vitamin A were at a significantly higher risk of dying. The lack of an effect of large-dose vitamin A supplementation on mortality, despite a clear association between dietary vitamin A and mortality, underscores the need to identify factors that modify the efficacy of vitamin A supplements as a public-health measure. Reducing poverty, improvements in sanitation, and access to adequate diets should remain the main goals to improve child survival.", "One hundred and seventy-two 0.5-3.0-year-old children in a mountainous area of northern Hebei Province of China were randomly assigned to a vitamin A supplementation group (n = 98) or a control group (n = 74) for a 1 year double-blind study. Capsules containing 200,000 IU vitamin A and 40 IU vitamin E were given to the children in the experimental group 3 and 9 months after baseline examination. During the 12 month study period, there was a significant reduction in the incidence of diarrhoea (P < 0.01) and respiratory disease (P < 0.01) in the children of the experimental group compared to the control. Risk of diarrhoea and respiratory disease were respectively 2.5 and 3.4 times higher in the control children. Serum retinol and IgA levels of the treatment group were significantly higher than that of control group (P < 0.01) 7 weeks after first supplementation. There was no significant difference in saliva IgA level between groups. No significant differences in growth were observed. It was concluded that supplementation with large doses of vitamin A decreased the incidence and severity of diarrhoea and respiratory disease in these children, possibly through enhanced activity of the immune system, but had no effect on growth over 1 year.", "Vitamin A has been determined in tear fluid and blood plasma of marginally nourished Thai children before and after supplementation with a single, oral dose of 110 mg retinyl palmitate. After two months a significant rise of tear fluid retinol levels of the supplemented group was observed as compared to the non-supplemented group, while after four months no difference could be found. Determination of vitamin A levels in tear fluid may be useful in clinical eye research, with special regard to xerophthalmia.", "nan", "Vitamin A supplementation of populations of vitamin A-deficient preschool-age children has been shown to reduce childhood mortality, but the primary preventive effects of such supplements on childhood infectious diseases have not been carefully evaluated. We conducted an individually randomized, placebo-controlled, double-masked trial among 1,407 Indonesian preschool-age children, to measure the effects of high dose vitamin A on acute respiratory and diarrheal illnesses. Signs and symptoms of morbidity were monitored using every other day home surveillance by trained interviewers. High dose vitamin A supplements increased the incidence of acute respiratory illnesses (ARI) by 8%, and acute lower respiratory illnesses (ALRI) by 39%. These detrimental effects on acute lower respiratory illnesses were most marked in children with adequate nutritional status (rate ratio 1.83, 95% confidence interval 1.257-2.669). In contrast, vitamin A tended to be protective of ALRI in chronically malnourished children (rate ratio 0.71, 95% confidence interval 0.375-1.331). There was no overall effect of high-dose vitamin A supplements on the incidence of diarrheal disease (rate ratio 1.06, 95% confidence interval 0.920-1.225). However, we found a significant interaction between supplementation and age: vitamin A increased the incidence of diarrhea in children < 30 mo of age, but tended to reduce the incidence in older children. The finding of a significant adverse effect of vitamin A supplements in adequately nourished children highlights the need to review the criteria for selecting populations of preschool-age children for vitamin A supplementation.", "A beneficial effect of periodic vitamin A supplementation on childhood mortality has been demonstrated, but the effect on morbidity is less clear. We investigated the effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections (ALRI) in children from northeastern Brazil in a randomised, double-blind, placebo-controlled community trial. 1240 children aged 6-48 months were assigned vitamin A or placebo every 4 months for 1 year. They were followed up at home three times a week, and data about the occurrence and severity of diarrhoea and ALRI were collected. Any child with cough and respiratory rate above 40 breaths per min was visited by a paediatrician. The overall incidence of diarrhoea episodes was significantly lower in the vitamin-A-supplemented group than in the placebo group (18.42 vs 19.58 x 10(-3) child-days; rate ratio 0.94 [95% Cl 0.90-0.98]). The benefit of supplementation was greater as regards severe episodes of diarrhoea; the incidence was 20% lower in the vitamin A group than in the placebo group (rate ratio 0.80 [0.65-0.98]). With the standard definition of diarrhoea (> or = 3 liquid or semi-liquid stools in 24 h) the effect of vitamin A on mean daily prevalence did not reach significance, but as the definition of diarrhoea was made more stringent (increasing number of stools per day), a significant benefit became apparent, reaching for diarrhoea with 6 or more liquid or semi-liquid stools in 24 h a 23% lower prevalence. We found no effect of vitamin A supplementation on the incidence of ALRI. The reduction in severity of diarrhoea may be the most important factor in the lowering of mortality by vitamin A supplementation.", "This study evaluates the effects of retinol on intestinal barrier function, growth, total parasites, and Giardia spp infections in children in northeastern Brazil.\n The study was a double-blind, randomized placebo-controlled trial (http://clinicaltrials.gov; register no. #NCT00133406) involving 79 children who received vitamin A 100,000-200,000 IU (n = 39) or placebo (n = 40) at enrollment, 4, and 8 months and were followed for 36 months. Intestinal barrier function was evaluated using the lactulose:mannitol ratio test. Stool lactoferrin was used as a marker for intestinal inflammation.\n The groups were similar with regard to age, sex, nutritional parameters (z scores), serum retinol concentrations, proportion of lactoferrin-positive stool samples, and intestinal barrier function. The lactulose:mannitol ratio did not change during the same time of follow-up (P > 0.05). The proportion of lactoferrin-positive samples evaluated at 1 month did not change between groups (P > 0.05). Total intestinal parasitic, specifically new, infections were significantly lower in the vitamin A treatment compared with control group; these were accounted for entirely by significantly fewer new Giardia infections in the vitamin A treatment group. The cumulative z scores for weight-for-length or height, length or height-for-age z scores, and weight-for-age did not change significantly with vitamin A intervention for 36 months of follow-up.\n These data showed that total parasitic infection and Giardia spp infections were significantly lower in the vitamin A treatment group when compared with the placebo group, suggesting that vitamin A improves the host's defenses against Giardia infections.", "A randomized, double-blind, placebo-controlled trial was conducted in an ongoing Growth Monitoring Research project in TamilNadu, India, to assess the impact of high-dose vitamin A supplementation on morbidity among mildly to moderately malnourished children aged < 3 y. Every 4 mo, the treatment group received 60 mg vitamin A (200,000 IU) whereas the control group received a placebo. Cases of xerophthalmia and severe malnutrition were excluded. Anthropometric measurements and serum retinol determinations were made at baseline and at the end of 1 y. Morbidity data were collected by trained village-level workers throughout the study period by using the weekly recall method. The two groups had similar nutritional status, serum retinol concentrations, age-sex composition, and other sociodemographic indicators at baseline. The mean number of episodes per child-year was 2.62 +/- 2.95 and 2.56 +/- 2.5 for respiratory illness and 1.9 +/- 2.2 and 1.77 +/- 1.77 for diarrhea for the vitamin A (n = 309) and placebo (n = 274) groups, respectively. The differences in respiratory and diarrheal morbidity between the two groups were not statistically significant and these findings remained unaltered after multivariate analysis in which the effects of age, sex, socioeconomic status, sanitation, etc, were considered. These findings are similar to other recent findings and indicate that vitamin A supplementation does not reduce common morbidity in children with mild-to-moderate vitamin A deficiency in areas where access to health care and immunization are good.", "To clearly clarify the protective effect of vitamin A supplementation on immune function of well-nourished children suffering from vitamin A deficiency.\n Three hundred sixty-two children in two kindergartens in Wuhan China were enrolled. Detailed dietary assessment and anthropometry were undertaken to facilitate the exclusion of malnourished children. Seventy vitamin A-deficient children with informed consent were randomly divided into the vitamin A-deficient-supplemented group and vitamin A-deficient placebo group, 35 vitamin A-sufficient children (age- and sex-matched with the vitamin A-deficient-supplemented group children) were selected as vitamin A-sufficient placebo group. The baseline and follow-up level of selected immune parameters of the 105 children in three intervention groups were compared.\n The total proportion of severe and marginal vitamin A-deficient children was 10.9 and 21.96%, respectively. At baseline, the serum complement C3 and sIgA level of vitamin A-sufficient children was significantly higher than that of vitamin A-deficient children (P < 0.05). However, the serum lysozyme level of vitamin A-sufficient children was inversely lower. After intervention, vitamin A-deficient-supplemented children increased serum vitamin A, complement C3 and sIgA level, but their serum lysozyme level inversely decreased.\n Vitamin A deficiency was still a serious health problem in children in China cities. Vitamin A supplementation was efficacious in ameliorating serum vitamin A status and partially impaired immune function of well-nourished children suffering from vitamin A deficiency.", "Administration of 100,000 IU vitamin A at the time of measles immunisation is currently recommended for infants in developing countries. However, the safety and value of giving vitamin A, a potent immune enhancer, with live measles virus vaccines are unknown. We conducted a randomised, double-blind, placebo-controlled clinical trial in Indonesia to evaluate the effect of simultaneous vitamin A supplementation on the immune response to measles immunisation at six months of age. 336 infants received either vitamin A (100,000 IU) or placebo when immunised with standard-titre Schwarz measles vaccine. 82% of infants seroconverted to measles. In a multiple logistic regression model adjusting for maternal antibody titres, vitamin A supplementation was associated with a lower likelihood of seroconversion to measles (odds ratio 0.40, 95% CI 0.19-0.88), and girls were less likely to seroconvert than boys (0.34, 0.15-0.76). Immunisation with standard-titre Schwarz vaccine at six months of age in this study population is characterised by high seroconversion rates. However, simultaneous high-dose vitamin A may interfere with seroconversion to live measles vaccine in infants with maternal antibody.", "The tolerance to two alternative large-dosage strengths of vitamin A preparation was determined in a double-blind study involving 2471 children in two municipalities in the Philippines. Each child, aged 1-6 y, not suffering from active xerophthalmia or from nausea and/or vomiting, headache, diarrhea, and fever, was randomly given 1 mL of a syrupy suspension later identified to contain 0, 60, or 30 mg vitamin A. Clinical evaluation of subjects was done by physicians 24 h and 1 wk after dosing. Nausea and/or vomiting and headache were twice as common among children given 60 mg than those given 30 mg. Severe vomiting (1.2%) was confined to those given 60 mg. Almost all experienced their symptoms within 24 h after dosing; symptoms lasted for no more than 12-24 h. The incidence of diarrhea and fever for vitamin A recipients was not significantly different from that of those receiving placebo.", "nan", "Marked seasonal variation in the prevalence of signs of vitamin A deficiency was found in the 2nd year of a continuing study of children age 0 to 4-1/2 years in a village in West Bengal, confirming results of a previous 18-month study. Administration of 200,000 IU of vitamin A every 4 months completely eliminated night blindness and prevented the development of new cases of Bitot's spot in a statistically significant number of children. The effectiveness of massive doses of vitamin A, administered at intervals of 4 months, as a short-term measure to fight the problem, was confirmed in this village. The study yielded additional evidence of the complex etiology of Bitot's spot, since alternate day dose of vitamin A in addition to massive therapy failed to eliminate these spots.", "To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme.\n Opportunistic controlled trial.\n Jumla district, Nepal.\n All children aged under 5 years; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation.\n Mortality and cause of death in the five months after supplementation.\n Risk of death for children aged 1-59 months in supplemented communities was 26% lower (relative risk 0.74, 95% confidence interval 0.55 to 0.99) than in unsupplemented communities. The reduction in mortality was greatest among children aged 6-11 months: death rate (deaths/1000 child years at risk) was 133.8 in supplemented children and 260.8 in unsupplemented children (relative risk 0.51, 0.30 to 0.89). The death rate from diarrhoea was also reduced (63.5 supplemented v 97.5 unsupplemented; relative risk 0.65, 0.44 to 0.95). The extra cost per death averted was about $11.\n The results support a role for Vitamin A in increasing child survival. The supplementation programme was readily integrated with the ongoing community health programme at little extra cost.", "To evaluate the effect of simultaneous zinc and vitamin A supplementation on diarrhoea and acute lower respiratory infections in children.\n Randomised double blind placebo controlled trial.\n Urban slums of Dhaka, Bangladesh.\n 800 children aged 12-35 months were randomly assigned to one of four intervention groups: 20 mg zinc once daily for 14 days; 200 000 IU vitamin A, single dose on day 14; both zinc and vitamin A; placebo. The children were followed up once a week for six months, and morbidity information was collected.\n The incidence and prevalence of diarrhoea were lower in the zinc and vitamin A groups than in the placebo group. Zinc and vitamin A interaction had a rate ratio (95% confidence interval) of 0.79 (0.66 to 0.94) for the prevalence of persistent diarrhoea and 0.80 (0.67 to 0.95) for dysentery. Incidence (1.62; 1.16 to 2.25) and prevalence (2.07; 1.76 to 2.44) of acute lower respiratory infection were significantly higher in the zinc group than in the placebo group. The interaction term had rate ratios of 0.75 (0.46 to 1.20) for incidence and 0.58 (0.46 to 0.73) for prevalence of acute lower respiratory infection.\n Combined zinc and vitamin A synergistically reduced the prevalence of persistent diarrhoea and dysentery. Zinc was associated with a significant increase in acute lower respiratory infection, but this adverse effect was reduced by the interaction between zinc and vitamin A.", "The World Health Organization recommends vitamin A supplementation (VAS) at vaccination contacts after 6 mo of age to reduce mortality. However, it is unknown whether the effect of VAS is independent of vaccinations. One of the original VAS trials from Ghana had collected vaccination information.\n We reanalyzed the data to explore the hypothesis that VAS reduces mortality in children who had bacille Calmette-Guérin or measles vaccine as their most recent vaccine but increased mortality when diphtheria-tetanus-pertussis vaccine (DTP) was the most recent vaccine. On the basis of previous studies, we expected the effects to be strongest in girls.\n At enrollment, children aged 6-90 mo were randomly assigned to receive VAS or placebo every 4 mo for 2 y. Vaccination status was assessed at enrollment and after 1 and 2 y by reviewing the children's health cards. Lack of a health card was presumed to mean that the child had not been vaccinated.\n VAS had a beneficial effect only in children with no record of vaccination at enrollment (n = 5066); the mortality rate ratio (MRR) was 0.64 (95% CI: 0.47, 0.88) compared with 0.95 (95% CI: 0.72, 1.26) in children with one or more vaccinations (n = 6656). Among vaccinated children, the effect of VAS differed between boys (MRR: 0.74; 95% CI: 0.51, 1.08) and girls (MRR: 1.18; 95% CI: 0.84, 1.67) (P = 0.046 for interaction). VAS had a negative effect in measles-vaccinated girls who were missing one or more doses of DTP at enrollment, a group who often received DTP during follow-up (MRR: 2.60; 95% CI: 1.41, 4.80).\n The effect of VAS differed by vaccination status. This is potentially problematic because VAS is provided at vaccination contacts.", "WHO has recommended vitamin A supplementation for children aged 6 months or older in developing countries at the same time as immunisation. One study has reported significantly lower seroconversion ratios among children who have received vitamin A supplements with measles vaccine at age 6 months. The aim of our study was to assess the effect of vitamin A supplementation on antibody response to measles vaccination at age 9 months, which is the more common age for immunisation in developing countries.\n In an urban community in Guinea-Bissau, we did a randomised, double-blind, placebo-controlled study of the effect of simultaneous vaccination and vitamin A supplementation in 462 children who received either a two-dose schedule of measles vaccine at the ages of 6 months and 9 months (150 infants) or one dose of measles vaccine at age 9 months (312 infants). Children were followed up to the age of 18 months and a blood sample was then collected to assess the antibody response.\n 397 (86%) of the children took part in the follow-up (52 [11%] had moved and 13 [3%] had died). Among children who received a two-dose vaccine schedule, seroconversion was 98%. There was no difference in seroconversion or geometric mean titre (GMT) for children receiving vitamin A compared with children receiving no supplement. Among children receiving only one dose of measles vaccine at age 9 months, seroconversion was 95%. The GMT was significantly higher in children receiving vitamin A than in those receiving no supplement (3704 vs 2439 mIU; GMT ratio 1.52 [1.22-1.88]). The effect on plasma antibody concentration in the blood was stronger for boys (3902 vs 1916 mIU; GMT ratio 2.04 [1.53-2.72]) than for girls (3502 vs 3017 mIU; GMT ratio 1.16 [0.85-1.58]) who had received vitamin A with measles vaccine. In a multivariate analysis of variance adjusted for sex, vitamin A supplementation was associated with higher antibody titres (p < 0.001). There was a significant interaction between vitamin A supplementation and sex (p = 0.02).\n There is no indication that simultaneous administration of measles vaccine and vitamin A supplements has a negative effect on measles immunity. Among the children who had received two doses of measles vaccine at the ages of 6 months and 9 months, supplements of vitamin A had no significant effect. Among children only receiving one dose of measles vaccine at age 9 months, 100,000 IU vitamin A increased antibody concentrations, especially for boys.", "In a double blind design, 1520 children aged < 10 years were individually randomised in vitamin A and placebo group in slums of Chandigarh. Children > 12, 6-12 and < 6 months of age received 200,000, 100,000, 500,000 I.U. of vitamin A respectively every 4 to 6 months during 15 months trial period. The prevalence of vitamin A deficiency was significantly reduced in vitamin A compared to placebo group during the follow-up period. In vitamin A group, incidence of diarrhoea and measles was significantly reduced but incidence of acute respiratory infections was not significantly different compared to control group. Risk of death was also significantly less in vitamin A group. Therefore, promotion of vitamin A rich diet or supplementation with synthetic vitamin A at 4-6 month interval should be a priority in populations where risk of vitamin A deficiency is high.", "To evaluate the relationship between vitamin A supplementation, plasma retinol level (PRL) and incidence, severity and duration of acute respiratory infect ions (ARI) in children 1-5 years old.\n A one year prospective randomized intervention study from June 1989 to May 1990 in Cikutra, a suburb of Bandung, Indonesia.\n Out of almost 2000 children aged 12-54 months, 269 were selected by stratified randomization. Vitamin A (200,000 IU orally) was administered at 6-monthly intervals in a double blind, placebo controlled programme. Every 2 weeks, primary health care workers collected data on respiratory symptoms in the children, and every month a pediatrician examined the children. Venous blood samples were obtained at the start and at 3 and 6 months for plasma retinol levels (PRL).\n The mean PRL at the start of the study was 20 +/- 8 micrograms/dl; 8% of the children showed a deficient level of less than 10 micrograms/dl. The incidence or ARI was 6.7 +/- 3.5 episodes per child per year with a mean duration of 5.3 +/- 3.1 days per episode. In vitamin A supplemented children the duration of ARI was slightly shorter (5.2 +/- 3.1 versus 5.6 +/- 3.1 days, P < 0.01) but no effect on the incidence or severity of ARI was detected. Low, and especially deficient, PRL had improved after 3 months and even after 6 months, but this was unrelated to vitamin A supplementation. There was also no relationship between PRL and incidence, severity or duration of ARI.\n Only a slight relationship is found between vitamin A supplementation and ARI duration in under-fives.", "To determine whether supplementation of vitamin A and/or zinc (Zn) improved serum levels of these nutrients and/or height and weight gains in preschool children, 22 to 66 months, living in Belize, Central America.\n Subjects received either Zn, vitamin A, Zn and vitamin A or a placebo, (70 mg Zn and/or 3030 RE vitamin A, once per week) for 6 months in a 2x2 factorial design. Forty-three children, from a population of 104 prescreened, completed the study; they were selected, prior to treatment, for low/marginal serum concentrations of these micronutrients.\n Serum Zn levels were greater (16%, p<0.001) for those who received Zn. In contrast, after vitamin A treatment there were no differences in serum vitamin A among groups. Although increases in height (+4.4 cm, p<0.001) and weight (+0.79 kg, p<0.001), compared with baseline values, were numerically greatest for children who received both supplements, only the vitamin A supplementation effect was significant, resulting in increased height (+1.4 cm, p<0.002) and greater weight gain (+0.15 kg, p<0.03) compared to those receiving no vitamin A. Vitamin A supplementation alone significantly increased (p<0.001) hemoglobin concentration.\n The results suggest that the preschool children in this study, prescreened for low/marginal serum concentrations from a larger population prior to treatment, were enduring inadequate vitamin A and, to a lesser degree, Zn nutriture. Height and weight gain were significantly increased in the subjects who received a single weekly supplement 3030 RE of vitamin A.", "In order to extend our earlier observation that children who experience frequent respiratory episodes may benefit from Vitamin A supplementation, 206 children aged 2-7 years who had been hospitalized for bronchiolitis during infancy were randomized into a controlled trial of Vitamin A supplementation. Of these, 149 met the criteria of protocol compliance after 12 months of follow-up. Mean plasma retinol at baseline was 39.2 micrograms/100 ml (s.e.m. = 1.0) and did not increase after 12 months (mean = 36.0 micrograms/100 ml, s.e.m. = 0.7) despite the older age of the cohort. The range observed (11.7-73.9 micrograms/100 ml) included some children at risk of marginal Vitamin A deficiency. Mean plasma retinol levels were 20% lower than those of children experiencing frequent respiratory episodes recorded earlier. Oral supplementation did not change plasma retinol levels, nor did it affect respiratory morbidity.", "Clinical vitamin A deficiency affects millions of children worldwide, and subclinical deficiency is even more common. Supplemental vitamin A has been reported to reduce mortality among these children, but the results have been questioned.\n We conducted a randomized, controlled, masked clinical trial for one year in southern India involving 15,419 preschool-age children who received either 8.7 mumol (8333 IU) of vitamin A and 46 mumol (20 mg) of vitamin E (the treated group) or vitamin E alone (the control group). Vitamin supplements were delivered weekly by community health volunteers who also recorded mortality and morbidity. Weekly contact was made with at least 88 percent of the children in both study groups. The base-line characteristics of the children were similar and documented a high prevalence of vitamin A deficiency and undernutrition.\n One hundred twenty-five deaths occurred, of which 117 were not accidental. The risk of death in the group treated with vitamin A was less than half that in the control group (relative risk, 0.46; 95 percent confidence interval, 0.30 to 0.71). The risk was most reduced among children under 3 years of age (6 to 11 months--relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.85; 12 to 35 months--relative risk, 0.46; 95 percent confidence interval, 0.26 to 0.81) and among those who were chronically undernourished, as manifested by stunting (relative risk, 0.11; 95 percent confidence interval, 0.03 to 0.36). The symptom-specific risk of mortality was significantly associated with diarrhea, convulsions, and other infection-related symptoms.\n The regular provision of a supplement of vitamin A to children, at a level potentially obtainable from foods, in an area where vitamin A deficiency and under-nutrition are documented public health problems contributed substantially to children's survival; mortality was reduced on average by 54 percent.", "Community trials of the efficacy of vitamin A supplementation in reducing preschool childhood mortality have produced conflicting results. To resolve the question, a randomised, double-masked, placebo-controlled community trial of 28,630 children aged 6-72 months was carried out in rural Nepal, an area representative of the Gangetic flood plain of South Asia. Randomisation was carried out by administrative ward; the vitamin-A-supplemented children received 60,000 retinol equivalents every 4 months and placebo-treated children received identical capsules containing 300 retinol equivalents. After 12 months, the relative risk of death in the vitamin-A-supplemented compared with the control group was 0.70 (95% confidence interval 0.56-0.88), equivalent to a 30% reduction in mortality. The trial, which had been planned to last 2 years, was discontinued. The reduction in mortality was present in both sexes (relative risk for boys 0.77; for girls 0.65), at all ages (range of relative risks 0.83-0.50), and throughout the year (0.76-0.67). The reduction in mortality risk was not affected by acute nutritional status, as measured by arm circumference. Thus, periodic vitamin A delivery in the community can greatly reduce child mortality in developing countries.", "The effect of Vitamin A supplementation on susceptibility to acute respiratory infections was investigated in a randomized controlled trial. One hundred and forty-seven preschool-age children with a history of frequent respiratory illness were randomized into Vitamin A supplemented (450 micrograms/day) and placebo groups. Respiratory symptoms were recorded on a daily basis over a period of 11 months. The children who received the supplement experienced 19% fewer episodes of respiratory symptomatology (P less than 0.05) than their placebo counterparts, despite the fact that their plasma retinol levels did not change. Children with a prior history of lower respiratory illness or of allergy benefited most from supplementation. The plausibility of a role for Vitamin A in the aetiology of respiratory proneness is reviewed.", "There is uncertainty over whether vitamin A supplementation reduces morbidity among children with subclinical deficiency of the vitamin. Hence a double-blind, placebo-controlled trial of the effect of vitamin A supplementation on childhood morbidity was conducted among 11,124 children aged 6-83 months in the northwest of Haiti. After a random start, children were sequentially assigned by household units to receive either megadose vitamin A or placebo in three distribution cycles 4 months apart. 2 to 8 weeks after each administration of the vitamin A and placebo capsules, indicators of childhood morbidity were reassessed through interviews conducted in the homes of participating families. The vitamin A group was found to have an increased 2-week prevalence of all symptoms and signs of childhood morbidity assessed, including diarrhoea (rate ratio [RR] = 1.09, 95% confidence interval 1.05-1.14), rhinitis (RR = 1.02, 95% confidence interval 1.00-1.04), cold/flu symptoms (RR = 1.04, 95% confidence interval 1.01-1.06), cough (RR = 1.07, 95% confidence interval 1.03-1.11), and rapid breathing (RR = 1.18, 95% confidence interval 1.09-1.27). The study shows an increased 2-week prevalence of diarrhoea and the symptoms of respiratory infections after vitamin A supplementation.", "The effect of vitamin A supplementation on preschool child morbidity and mortality was assessed in a prospective double-blind placebo-controlled study around Hyderabad, India. Every six months 200,000 IU vitamin A was given to 7691 children (treatment group) whereas 8084 children received a placebo (control group). Morbidity and mortality data were collected every three months. Risk of respiratory infection was higher in children with mild xerophthalmia than in children with normal eyes. Vitamin A supplementation had no effect on morbidity status. Mortality rates were similar in the two groups; it was highest in children who did not receive either vitamin A or placebo. The findings suggest that vitamin A supplementation alone may not reduce child mortality.", "nan", "A randomized controlled trial was conducted in 395 infants aged 9-12 months to determine the effect of Vitamin A supplementation on concurrently administered measles vaccine. Antibody response was measured using the plaque reduction neutralization assay. No statistically significant differences were demonstrated between the immune response in Vitamin A supplemented and unsupplemented children. Unlike some recent studies, we were unable to demonstrate an immune enhancing effect of Vitamin A supplementation. On the contrary, among children who were given Vitamin A, a lower, but statistically non-significant, proportion had protective antibody levels 6 months after vaccination.", "To assess the impact of Vitamin A supplementation to the mother soon after delivery and to the infant at six months on morbidity in infancy.\n Randomized double blind placebo controlled field trial.\n 51 villages in two contiguous Primary Health Centers in Villupuram Health Unit District of Tamil Nadu, South India.\n 909 newly delivered mother-and-infant pairs.\n Both mother and infant received Vitamin A (300,000 IU for mothers and 200,000 IU for children) in 311 instances (AA); mother received Vitamin A but infant received Placebo in 301 instances (AP); and both mother and infant received Placebo in the remaining 297 instances (PP).\n Incidence of diarrhea and Acute Respiratory Infection (ARI); distributions of infants by frequency of episodes and number of infected days.\n 233 in the AA Group and 228 each in the AP and PP Groups were followed up regularly. The incidence of diarrhea in these infants was 97.4%, 96.9% and 94.7% in the three groups, mean number of diarrheal episodes was 4.4, 4.6 and 4.2 and median number of days in infancy with diarrhea was 26, 26 and 22 days, respectively. For ARI, the incidences were 96.6%, 95.6% and 96.1%, means were 4.8, 5.1 and 4.8 episodes, and the medians were 32, 34 and 34 days, respectively.\n Prophylactic administration of mega doses of Vitamin A to the mother soon after delivery and to the infant at six months do not have any beneficial impact on the incidence of diarrhea and ARI in infancy.", "The efficacy of micronutrient supplementation in improving childhood health and survival in developing countries may be specific to the micronutrient used and health outcome measured.\n We evaluated the effect of vitamin A and zinc supplementation on overall rates of childhood diarrheal disease and respiratory tract infections and rates stratified by household and personal characteristics.\n A double-blind, randomized, placebo-controlled trial was carried out in which 736 children aged 6-15 mo living in a periurban area of Mexico City were assigned to receive vitamin A every 2 mo, zinc daily, vitamin A and zinc together, or placebo. Children were followed for 12 mo to determine overall counts of diarrheal episodes and respiratory tract infections.\n Vitamin A supplementation was associated with a 27% increase in diarrheal disease [risk ratio (RR): 1.27; 95% CI: 1.10, 1.45; P < 0.001] and a 23% increase in cough with fever (RR: 1.23; 95% CI: 1.02, 1.47; P = 0.02), whereas zinc had no effect on these outcomes. Vitamin A supplementation decreased diarrhea in children from households with dirt floors but increased diarrhea in children from households with nondirt floors, piped water, and indoor bathrooms. Zinc supplementation decreased diarrhea in children from households with dirt floors and whose mothers were more educated. Vitamin A supplementation increased cough with fever in children from less-crowded households that lacked indoor bathrooms and in children of less-educated mothers.\n Vitamin A increases diarrheal disease and respiratory tract infections in young children in periurban areas of Mexico City. Vitamin A and zinc have more heterogeneous effects in different subgroups of children.", "Previous clinical vitamin A trials have found no consistent effect on diarrhoeal disease and respiratory tract infection. These inconsistent results may be due to the distinct effects vitamin A supplementation has among children stratified by factors related to socio-economic status, nutritional status and season. We evaluated the effect of supplementation on the overall incidence of diarrhoeal disease and respiratory tract infections and on the incidence among children stratified by these factors. A total of 188 children, aged 6-15 months, from periurban, marginalized communities of Mexico City were assigned to receive vitamin A ( < 12 months of age, 20,000 IU retinol; >or= 12 months, 45,000 IU retinol) or a placebo every 2 months, and were followed for up to 15 months. Project personnel visited households twice a week to determine the onset and duration of diarrhoeal disease and respiratory tract infections. Vitamin A supplementation had no significant effect on risk of overall diarrhoeal disease but reduced mild watery diarrhoea (incidence rate ratio (RR) 0.69; 95 % CI 0.50, 0.93) and cough with fever (RR 0.69; 95 % CI 0.48, 0.98). Vitamin A supplementation decreased diarrhoeal disease during the summer (RR 0.74; 95 % CI 0.57, 0.94), among non-stunted children (RR 0.69; 95 % CI 0.52, 0.93) and among children from households with better socio-economic measures. Heterogeneity in the response to vitamin A supplementation may reflect heterogeneity in the aetiology and epidemiology of diarrhoeal disease and respiratory tract infections and the impact that supplementation has on the immune response.", "After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1. 18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs.", "Many individuals at risk of malaria also have micronutrient deficiencies that may hamper protective immunity. Vitamin A is central to normal immune function, and supplementation has been shown to lower the morbidity of some infectious diseases. We investigated the effect of vitamin A supplementation on malaria morbidity.\n This randomised double-blind placebo-controlled trial of vitamin A supplementation took place in a P. falciparum endemic area of Papua New Guinea. Of 520 potentially eligible children aged 6-60 months, 480 were randomly assigned high-dose vitamin A (n=239) or placebo (n=241), every 3 months for 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by intention to treat.\n The number of P. falciparum febrile episodes (temperature > or = 37.5 degrees C with a parasite count of at least 8000/microL) was 30% lower in the vitamin A group than in the placebo group (178 vs 249 episodes; relative risk 0.70 [95% CI 0.57-0.87], p=0.0013). At the end of the study P. falciparum geometric mean density was lower in the vitamin A than the placebo group (1300 [907-1863] vs 2039 [1408-2951]) as was the proportion with spleen enlargement (125/196 [64%] vs 148/207 [71%]); neither difference was significant (p=0.093 and p=0.075). Children aged 12-36 months benefited most, having 35% fewer febrile episodes (89 vs 141; relative risk 0.65 [14-50], p=0.0023), 26% fewer enlarged spleens (46/79 [58%] vs 67/90 [74%], p=0.0045), and a 68% lower parasite density (1160 [95% CI 665-2022] vs 3569 [2080-6124], p=0.0054). Vitamin A had no consistent effect on cross-sectional indices of proportion infected or with anaemia.\n Vitamin A supplementation may be an effective low-cost strategy to lower morbidity due to P. falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density are influenced by different immunological mechanisms from infection and anaemia.", "A randomized controlled trial was conducted in eastern Zaire to assess the effects of high dose vitamin A supplementation and regular deparasitation on the growth of 358 moderately malnourished preschool children, discharged from the hospital. The treatment groups received either vitamin A (60 mg of oily solution of retinyl palmitate, 30 mg if aged <12 mo) every 6 mo or mebendazole (500 mg) every 3 mo; the control group received no supplementation. Anthropometric data were gathered at baseline and after 6 and 12 mo of follow-up. Serum retinol concentrations were measured at baseline and after 3 mo. The three groups did not differ in sociodemographic indicators, age and sex composition, nutritional status and serum retinol concentrations at baseline. In children who were vitamin A deficient at baseline, adjusted mean weight and mid-upper arm circumference (MUAC) increments were higher in the vitamin A-supplemented group than in the control group [annual increment in weight and MUAC in vitamin A vs. control group: 2.088 vs. 1.179 kg (P = 0.029) and 2.24 vs. 0.95 cm (P = 0.012), respectively], whereas growth increment did not differ between the dewormed group and the control group. In children who were not vitamin A deficient at baseline, growth increment did not differ between the vitamin A-supplemented and control groups, whereas weight gain was lower in the dewormed group than in the control group. Vitamin A-supplemented boys gained more weight and height than control boys, whereas vitamin A-supplemented girls gained less height than control girls. Dewormed boys and girls gained less weight than control boys and girls. Programs to improve vitamin A status by high dose vitamin A supplementation may improve growth of preschool children who are vitamin A deficient, whereas deworming does not.", "Although most studies on the effect of vitamin A supplementation have reported reductions in childhood mortality, the effects on morbidity are less clear. We have carried out two double-blind, randomised, placebo-controlled trials of vitamin A supplementation in adjacent populations in northern Ghana to assess the impact on childhood morbidity and mortality. The Survival Study included 21,906 children aged 6-90 months in 185 geographical clusters, who were followed for up to 26 months. The Health Study included 1455 children aged 6-59 months, who were monitored weekly for a year. Children were randomly assigned either 200,000 IU retinol equivalent (100,000 IU under 12 months) or placebo every 4 months; randomisation was by individual in the Health Study and by cluster in the Survival Study. There were no significant differences in the Health Study between the vitamin A and placebo groups in the prevalence of diarrhoea or acute respiratory infections; of the symptoms and conditions specifically asked about, only vomiting and anorexia were significantly less frequent in the supplemented children. Vitamin-A-supplemented children had significantly fewer attendances at clinics (rate ratio 0.88 [95% CI 0.81-0.95], p = 0.001), hospital admissions (0.62 [0.42-0.93], p = 0.02), and deaths (0.81 [0.68-0.98], p = 0.03) than children who received placebo. The extent of the effect on morbidity and mortality did not vary significantly with age or sex. However, the mortality rate due to acute gastroenteritis was lower in vitamin-A-supplemented than in placebo clusters (0.66 [0.47-0.92], p = 0.02); mortality rates for all other causes except acute lower respiratory infections and malaria were also lower in vitamin A clusters, but not significantly so. Improving the vitamin A intake of young children in populations where xerophthalmia exists, even at relatively low prevalence, should be a high priority for health and agricultural services in Africa and elsewhere.", "The impact on vitamin A deficiency (VAD), wasting malnutrition, and excessive childhood mortality of two alternative approaches-nutrition education and mega-dose capsule distribution (6-12-month-olds: 100,000 IU; 1-5-year-olds: 200,000 IU)-in communities in Nepal are compared. Approximately 40,000 children from 75 locations in seven districts in two ecological settings (lowland and hills) took part in the study and were randomly allocated to intervention cohorts or a control group. At 24 months after the implementation of the project the reduction of risk for xerophthalmia was greater among children whose mothers were able to identify vitamin-A-rich foods (relative risk (RR) = 0.25; 95% confidence interval (CI) = 0.10-0.62) than among the children who received mega-dose capsules (RR = 0.59; 95% CI = 0.41-0.84). The risk of mortality at 2 years was reduced for both the nutrition education (RR = 0.64; 95% Cl = 0.48-0.86) and capsule distribution (RR = 0.57; 95% CI = 0.42-0.77) cohorts. The nutrition education programme was, however, more expensive to deliver than the capsule distribution programme. High rates of participation for children in the supplementation programme were achieved quickly. The nutrition education messages also spread rapidly throughout the study population (regardless of intervention cohort assignment). Practices, however, were slower to change. In communities where maternal literacy was low and channels of communication were limited the capsule distribution programme appeared to be more economical. However, there are economies of scale for nationwide education programmes that do not exist for capsule distribution programmes. Although nutrition education provides economies of scale and the promise of long-term sustainability, a comprehensive national programme requires both dietary supplementation and nutrition education components.", "nan", "Previous studies of large-dose vitamin A supplementation on respiratory morbidity have produced conflicting results in a variety of populations. The influence of malnutrition has not been examined in the majority of these trials. We hypothesized that weekly low-dose vitamin A supplementation would prevent respiratory and diarrheal disease morbidity and that malnutrition might influence the efficacy of vitamin A supplementation.\n In a randomized, double-blind, placebo-controlled field trial of 400 children, 6 to 36 months of age in a high Andean urban slum, half of the children received 10 000 IU of vitamin A weekly and half received placebo for 40 weeks. Children were visited weekly at home by physicians and assessed for acute diarrheal disease and acute respiratory infections.\n Acute diarrheal disease and acute respiratory infection did not differ globally or by severity between supplement-treated and placebo groups. However, the incidence of acute lower respiratory infection (ALRI) was significantly lower in underweight (weight-for-age z score [WAZ] <-2 SD) supplement-treated children than in underweight children on placebo (8.5 vs 22.3 per 10(3) child-weeks; rate ratio: 0.38 [95% CI: 0.17-0.85]). ALRI incidence was significantly higher in normal-weight (WAZ >-2 SD) supplement-treated children than in normal-weight children on placebo (9.8 vs 4.4 per 10(3) child-weeks; rate ratio: 2.21 [95% CI: 1.24-3.93]). By logistic regression analysis the risk of ALRI was lower in underweight supplement-treated children than in underweight children on placebo (point estimate 0.148 [95% CI: 0.034-0.634]). In contrast, risk of ALRI was higher in normal-weight supplement-treated children (WAZ >-1 SD to mean) than in normal-weight children on placebo in the same WAZ stratum (point estimate: 2.51 [95% CI: 1.24-5.05]). The risk of severe diarrhea was lower in supplement-treated children 18 to 23 months of age than in children on placebo in this age group (point estimate: 0.26 [95% CI: 0.06-1.00]).\n Weekly low-dose (10 000 IU) vitamin A supplementation in a region of subclinical deficiency protected underweight children from ALRI and paradoxically increased ALRI in normal children with body weight over -1 SD. Protection from severe diarrhea was consistent with previous trials. Additional research is warranted to delineate potential beneficial and detrimental interactions between nutritional status and vitamin A supplementation regarding ALRI." ]

[ "17983881", "19800329", "11511016", "11062571", "10429608", "17119800", "7797977", "15336749", "12562974", "7574280", "22133704", "17660155", "17617802", "19375278", "11892685", "17923296", "10639613" ]

[ "The impact of dressings on recovery from carpal tunnel decompression.", "Brief post-surgical electrical stimulation accelerates axon regeneration and muscle reinnervation without affecting the functional measures in carpal tunnel syndrome patients.", "A randomized prospective study to assess the efficacy of two cold-therapy treatments following carpal tunnel release.", "Does splintage help pain after carpal tunnel release?", "No advantage from splinting the wrist after open carpal tunnel release. A randomized study of 82 wrists.", "Wrist immobilization after carpal tunnel release: a prospective study.", "Early mobilization following carpal tunnel release. A prospective randomized study.", "A controlled clinical trial of postoperative hand elevation at home following day-case surgery.", "Homeopathic arnica for prevention of pain and bruising: randomized placebo-controlled trial in hand surgery.", "Prospective, randomized trial of splinting after carpal tunnel release.", "Duration of postoperative dressing after mini-open carpal tunnel release: a prospective, randomized trial.", "Use of a splint following open carpal tunnel release: a comparative study.", "Postoperative splinting after open carpal tunnel release does not improve functional and neurological outcome.", "A randomized controlled study of contrast baths on patients with carpal tunnel syndrome.", "Use of Arnica to relieve pain after carpal-tunnel release surgery.", "Outcomes of carpal tunnel surgery with and without supervised postoperative therapy.", "Usefulness of hand rehabilitation after carpal tunnel surgery." ]

[ "This study assesses the impact on outcome of wearing a bulky dressing following carpal tunnel decompression. One hundred patients were randomised for having a bulky dressing removed at either 24h or 2 weeks postoperatively. A Levine score was measured preoperatively and postoperatively at 2 weeks. The surgery and other dressings used were standardised as per the protocol. Comparison was made between the symptom and functional severity scores for each group to assess the impact of duration of wearing the dressing on resolution of symptoms. The results indicate no difference in outcome between the 2 week and 24h groups. We therefore feel that patients should be given the choice as to when to remove their dressing. If they feel restricted, they are free to remove the bulky dressing without an increased risk of a worse outcome. If they feel secure in the dressing, they will not suffer leaving it in place for 2 weeks.", "Electrical stimulation (ES) of injured peripheral nerves accelerates axonal regeneration in laboratory animals. However, clinical applicability of this intervention has never been investigated in human subjects. The aim of this pilot study was to determine the effect of ES on axonal regeneration after surgery in patients with median nerve compression in the carpal tunnel causing marked motor axonal loss. A randomized control trial was conducted to provide proof of principle for ES-induced acceleration of axon regeneration in human patients. Carpel tunnel release surgery (CTRS) was performed and in the stimulation group of patients, stainless steel electrode wires placed alongside the median nerve proximal to the surgical decompression site for immediate 1 h 20 Hz bipolar ES. Subjects were followed for a year at regular intervals. Axonal regeneration was quantified using motor unit number estimation (MUNE) and sensory and motor nerve conduction studies. Purdue Pegboard Test, Semmes Weinstein Monofilaments, and Levine's Self-Assessment Questionnaire were used to assess functional recovery. The stimulation group had significant axonal regeneration 6-8 months after the CTRS when the MUNE increased to 290+/-140 (mean+/-SD) motor units (MU) from 150+/-62 MU at baseline (p<0.05). In comparison, MUNE did not significantly improve in the control group (p>0.2). Terminal motor latency significantly accelerated in the stimulation group but not the control group (p>0.1). Sensory nerve conduction values significantly improved in the stimulation group earlier than the controls. Other outcome measures showed a significant improvement in both patient groups. We conclude that brief low frequency ES accelerates axonal regeneration and target reinnervation in humans.\n Copyright 2009 Elsevier Inc. All rights reserved.", "A prospective randomized study was performed comparing the efficacy of controlled cold therapy (CCT) with the efficacy of ice therapy in the postoperative treatment of 72 patients with carpal tunnel syndrome. Immediately after surgery, patients applied either a temperature-controlled cooling blanket (CCT) or a standard ice pack over their surgical dressings. Pain was assessed by visual analog scale and swelling by wrist circumference preoperatively, immediately after surgery, and on postoperative day 3. Patients kept log books of daily treatment times. Narcotic use (of Vicodin ES) was determined by pill count at day 3 and by daily log book recordings. Patients who used CCT showed significantly greater reduction in pain, edema (wrist circumference), and narcotic use at postoperative day 3 than did those using ice therapy. This study indicates that after carpal tunnel surgery, the use of CCT, compared with traditional ice therapy, provides patients with greater comfort and lessens the need for narcotics.", "A prospective randomized single blind trial was performed of 102 patients undergoing carpal tunnel release. Patients received either a palmar plaster of Paris splint or a bulky wool and crepe bandage postoperatively for the first 48 h, to determine whether the plaster slab reduced postoperative pain. There were no statistically significant differences between the two groups in postoperative pain scores or analgesic use.\n Copyright 2000 The British Society for Surgery of the Hand.", "To study the value of postoperative splinting after open carpal tunnel surgery, we randomly selected 82 wrists for 4 weeks of postoperative immobilization or no immobilization. The distributions of scar discomfort or pain and \"pillar pain\" were equal in the two groups both at 6 weeks and 6 months. Median sick leave was 6 weeks in both groups. Median VAS values for persistent discomfort and pain at 2 weeks, 6 weeks and 6 months were similar in the two groups. Grip strength was reduced compared to preoperative values by about 20% and keypinch strength by about 10% in both groups at 6 weeks and had returned to normal by 6 months. Pinch between the thumb and the tips of fingers 4 and 5 was considerably reduced postoperatively, but similar in both groups. We conclude that 4 weeks of postoperative immobilization confers no detectable benefit.", "This prospective study evaluates the possible advantages of wrist immobilization after open carpal tunnel release comparing the results of two weeks immobilization and no immobilization. Fifty two patients with idiopathic carpal tunnel syndrome were randomly selected in two groups after open carpal tunnel release. In one group (A, n=26) the patients wore a neutral-position wrist splint continuously for two weeks. In the other group (B, n=26) no wrist immobilization was used. Clinical assessment was done pre-operatively and at 2 weeks follow-up and included the two-point discrimination test at the second finger and two questionnaires as an outcome measurement of symptoms severity and intensity. All the patients presented improvement in the postoperative evaluations in the three analyzed parameters. There was no significant difference between the two groups for any of the outcome measurements at the final follow-up. We conclude that wrist immobilization in the immediate post-operative period have no advantages when compared with no immobilization in the end result of carpal tunnel release.", "A prospective randomized study was undertaken of 50 consecutive patients undergoing surgery for idiopathic carpal tunnel syndrome to determine the value of splintage of the wrist following open carpal tunnel release. Patients were randomized to either be splinted for 2 weeks following surgery or to begin range-of-motion exercises on the first post-operative day. Subjects were evaluated at 2 weeks, 1 month, 3 months, and 6 months after surgery by motor and sensory testing, physical examination, and a questionnaire. Variables assessed included date of return to activities of daily living, dates of return to work at light duty and at full duty, pain level, grip strength, key pinch strength, and occurrence of complications. Patients who were splinted had significant delays in return to activities of daily living, return to work at light and full duty, and in recovery of grip and key pinch strength. Patients with splinted wrists experienced increased pain and scar tenderness in the first month after surgery; otherwise there was no difference between the groups in the incidence of complications. We conclude that splinting the wrist following open release of the flexor retinaculum is largely detrimental, although it may have a role in preventing the rare but significant complications of bowstringing of the tendons or entrapment of the median nerve in scar tissue. We recommend a home physiotherapy programme in which the wrist and fingers are exercised separately to avoid simultaneous finger and wrist flexion, which is the position most prone to cause bowstringing.", "Although elevation of the upper limb is considered valuable for the prevention and of the reduction of swelling following major surgery or severe injuries to the hand, it is not clear how much elevation, if any, is required following minor surgery such as carpal tunnel decompression. We investigated this by randomizing patients undergoing carpal tunnel decompression into two groups - one having high elevation at home and one being treated with a simple sling. Volumetric analysis of the swelling of the hand 5 days postoperatively showed no significant difference between the two groups. In the trial group, the mean increase in volume of the operated hand was 11 ml (95% CI +4 to +17) or 2.7%. In the control group, the mean swelling was 13 ml (95% CI +4 to +21) or 3.6%. The findings of this study do not support the use of routine high arm elevation following day-case surgery of the hand.", "Homeopathic arnica is widely believed to control bruising, reduce swelling and promote recovery after local trauma; many patients therefore take it perioperatively. To determine whether this treatment has any effect, we conducted a double-blind, placebo-controlled, randomized trial with three parallel arms. 64 adults undergoing elective surgery for carpal tunnel syndrome were randomized to take three tablets daily of homeopathic arnica 30C or 6C or placebo for seven days before surgery and fourteen days after surgery. Primary outcome measures were pain (short form McGill Pain Questionnaire) and bruising (colour separation analysis) at four days after surgery. Secondary outcome measures were swelling (wrist circumference) and use of analgesic medication (patient diary). 62 patients could be included in the intention-to-treat analysis. There were no group differences on the primary outcome measures of pain (P=0.79) and bruising (P=0.45) at day four. Swelling and use of analgesic medication also did not differ between arnica and placebo groups. Adverse events were reported by 2 patients in the arnica 6C group, 3 in the placebo group and 4 in the arnica 30C group. The results of this trial do not suggest that homeopathic arnica has an advantage over placebo in reducing postoperative pain, bruising and swelling in patients undergoing elective hand surgery.", "To determine the possible beneficial effect of postoperative splint immobilization after open carpal tunnel release, we performed a prospective, randomized study comparing 2 weeks of postoperative wrist splinting versus a bulky dressing only. Forty patients with 43 carpal tunnel releases were evaluated. There were no statistically significant differences between the two groups using subjective parameters of patient satisfaction with their outcome and objective parameters of grip and lateral pinch strength, complication rates, and digital and wrist range of motion. No clinical evidence of bowstringing could be noted in either group of patients. We found no beneficial effect from postoperative splinting after open carpal tunnel release when compared to a bulky dressing alone.", "In this prospective, randomized, controlled study, we hypothesized that there would be no difference in short-term functional, subjective, and blinded wound outcome measures between patients treated after mini-open carpal tunnel release (CTR) with a postoperative bulky dressing for 2 weeks and those with dressing removal and placement of an adhesive strip after 48 to 72 hours.\n A total of 94 consecutive patients underwent mini-open CTR and placement of a bulky dressing and were randomized to either bandage removal at 48 to 72 hours with placement of an adhesive strip or continuation of the postoperative dressing until initial follow-up at approximately 2 weeks. We evaluated patient demographics, Levine-Katz scores, range of motion, strength, and a blinded assessment of wound healing at approximately 2 weeks and between 6 and 12 weeks. We conducted paired and independent sample t-tests to evaluate for statistical significance.\n There was no significant difference in Levine-Katz scores between groups at either the first follow-up or final visit. One patient with a longer dressing duration had evidence of a wound dehiscence.\n Removal of a bulky dressing after mini-open CTR and replacement with an adhesive strip at 48 to 72 hours causes no wound complications and results in equal short-term clinical and subjective outcome measures compared with using a bulky dressing for 2 weeks.\n Therapeutic I.\n Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.", "This study was undertaken to compare the clinical effectiveness and costs of postoperative splintage and late rehabilitation with a bulky bandage dressing versus early rehabilitation after carpal tunnel release. In this comparative study, 46 patients were randomly divided into 2 groups. In each group, 3 patients were excluded because of improper follow-up, leaving a total of 40 patients. Group 1 used a splint (exercises given 3 wk postoperatively) and group 2 was given a bulky bandage (exercises provided immediately) after open release. Patients were assessed preoperatively and at the first and third postoperative months with the Questionnaire of Levine for Clinical Assessment of Carpal Tunnel Syndrome. The 2 groups were similar in terms of preoperative functional status scores and in controls at the first and third months (P=.549, P=.326, P=.190). When both groups were compared, no statistical significance was found regarding symptom severity scale scores preoperatively and at the first postoperative month (P=.632 vs P=.353). At the third month, scores were lower in favor of group 2 (P=.023). Additionally, 16 of 20 patients (80%) in group 1 reported a heavy feeling and discomfort caused by the splint. This problem was not reported by the patients in group 2. The cheapest splint on the market was 9 times more expensive than a bulky dressing. The investigators concluded that postoperative immobilization with a splint has no detectable benefits. Use of bulky dressings and abandonment of the use of postoperative splints may prevent unnecessary expenditures without sacrificing patient comfort or compromising the course of healing in carpal tunnel surgery.", "Although surgical division of the transverse carpal ligament is the operative treatment of choice for carpal tunnel syndrome (CTS), controversy exists about the immediate postoperative treatment regimen. Splinting for up to 6 weeks after surgery is recommended by some investigators. We therefore evaluated effectiveness of splinting after open carpal tunnel surgery by a randomized, controlled trial. Fifty consecutive patients with clinically and electrophysiologically confirmed idiopathic CTS were assigned to open carpal tunnel release and randomized to receiving a light bandage (25 patients) or a bulky dressing with a volar splint (25 patients) for 2 days each. All patients were followed up at 3 months. Parameters retrieved were pain as measured using a visual analog scale, two-point discrimination, and grip strength, and nerve conduction studies. At follow-up, all patients reported definite improvement of symptoms, but there was no statistically significant difference between the two groups for any of our outcome measures. Thus, postoperative splinting after open carpal tunnel release does not yield any benefit to eventual outcome. In fact, it adds to the overall operating time and can safely be abandoned.", "Randomized clinical trial. Introduction: Contrast baths are a treatment modality commonly used in hand clinics. Yet the benefits of contrast baths have been poorly substantiated. Contrast baths have been suggested for the purposes of reducing hand volume, alleviating pain, and decreasing stiffness in affected extremities.\n To determine the effects of specific contrast bath protocols on hand volume in patients diagnosed with Carpal Tunnel Syndrome.\n Study participants were randomly assigned to one of three treatment group protocols--contrast baths with exercise, contrast baths without exercise, and an exercise-only control treatment group. Study participants were evaluated with hand volumetry, before and after treatment at two different data collection periods-pre- and postoperatively.\n Data were gathered on 58 participants before Carpal Tunnel Release surgery and on 56 participants after Carpal Tunnel Release surgery, for a total of 114 treatments. The changes in hand volume (the after treatment volume minus the before treatment volume) were analyzed using one-way and multi-way analysis of variance (ANOVA). Although all three treatments resulted in a slight increase in hand volume both pre- and postsurgery, the increase was not clinically significant with regard to hand volumes. Also no significant differences were noted among the three treatments. Specifically, the ANOVA for presurgery differences among treatments had F=0.155 (2 and 55 df), p=0.857. The ANOVA for postsurgery difference among treatments had F=0.544 (2 and 53 df), p=0.584.\n The use of contrast bath treatment has no significant effect on increase or decrease of hand volume in Carpal Tunnel Syndrome patients, pre- and/or postoperatively.\n 1B.", "Arnica is commonly used by the public as a treatment for bruising and swelling.\n To assess whether Arnica administration affects recovery from hand surgery.\n Double-blind, randomized comparison of Arnica administration versus placebo.\n Specialist hand surgery unit at the Queen Victoria NHS Trust.\n Thirty-seven patients undergoing bilateral endoscopic carpal-tunnel release between June 1998 and January 2000.\n Homeopathic Arnica tablets and herbal Arnica ointment compared to placebos.\n Grip strength, wrist circumference, and perceived pain measured 1 and 2 weeks after surgery.\n No difference in grip strength or wrist circumference was found between the 2 groups. However, there was a significant reduction in pain experienced after 2 weeks in the Arnica-treated group (P<.03).\n The role of homeopathic and herbal agents for recovery after surgery merits further investigation.", "To assess if a formal 2-week hand therapy improves outcomes and justifies its expense.\n A prospective randomized study was completed using a contemporary short incision and a 2-week program of therapy. Patients were randomized into 2 treatment groups: one group received instruction on home therapy exercises to be followed after carpal tunnel release, and a second group received the home program in addition to a therapist-directed program for 2 weeks. Variables measured were patient age, gender, preoperative and postoperative pain scores, grip and pinch strengths, return to modified and regular work, insurance coverage, and job category. Both groups were followed for 6 months postoperatively.\n One hundred fifty patients (110 women and 40 men) entered and completed the study. The average age was 46 years (range, 29-70 years). The average age, gender distribution, insurance coverage, and breakdown of job categories between groups was not statistically significant. There was no difference in return to work times between those with and without postoperative therapy; however, patients covered by workers' compensation insurance were slower to return to both modified and regular work compared with the other groups. The postoperative grip and pinch strengths, pain and Disabilities of the Arm, Shoulder, and Hand scores did not show statistical differences between groups at any of the measured time periods. Depending on insurance carrier, directed therapy added $600 to $900 to the cost of care.\n The current randomized study failed to show benefit in a 2-week course of hand therapy after carpal tunnel release using a short incision. The cost of supervised therapy for an uncomplicated carpal tunnel release seems unjustified.", "The purpose of this randomized trial was to assess the clinical evolution after carpal tunnel release in subjects with long-term carpal tunnel syndrome. The evaluation criteria were symptom occurrence, motor performance, and delay in returning to work. A total of 100 subjects were assessed four times (prior to surgery, and 12 days, 1 month, and 3 months after surgery) using the Boston carpal tunnel questionnaire, the nine-hole peg test (NHPT), and the Jebsen-Taylor test (JTT). Subjects were randomized to a rehabilitation program or to a progressive home exercise program. No difference in symptom occurrence between the two groups was detected after 1 and 3 months. One month after surgery, only patients in the first group showed motor dexterity improvement according to NHPT and JTT scores. At the 3-month follow-up, the two groups did not differ but the group undergoing rehabilitation showed a shorter return-to-work interval. A rehabilitation approach after hand surgery is clinically relevant to accelerate recovery but neither modifies functional recovery nor reduces symptom occurrence.\n Copyright 2000 John Wiley & Sons, Inc." ]

[ "12389657", "1448244", "15511994", "10804490", "12066083", "7862382" ]

[ "Closure of the subcutaneous dead space and wound disruption after Cesarean delivery.", "Does closure of Camper fascia reduce the incidence of post-cesarean superficial wound disruption?", "Blunt-tipped versus sharp-tipped needles: wound morbidity.", "Subcutaneous drain vs. suture in obese women undergoing cesarean delivery. A prospective, randomized trial.", "Subcutaneous stitch closure versus subcutaneous drain to prevent wound disruption after cesarean delivery: a randomized clinical trial.", "Subcutaneous tissue approximation in relation to wound disruption after cesarean delivery in obese women." ]

[ "To determine whether suture closure of subcutaneous dead space decreases wound disruption after Cesarean delivery.\n All patients undergoing Cesarean delivery at the New England Medical Center from September 1995 to June 1997 were eligible. One group (162 patients) was randomly assigned to have the subcutaneous fat layer closed with a running 3-0 plain suture. The other group (165 patients) had this layer left unclosed. Both groups had careful hemostasis of this layer with cautery and copious irrigation. All laboring and ruptured patients received prophylactic antibiotics. The patients were followed for 6 weeks after delivery for wound disruption.\n No significant differences were noted between the two groups with respect to demographic, obstetric, or surgical characteristics or loss to follow-up. Excluding those lost to follow-up (27 closed vs. 22 unclosed), there was no difference in wound infection (11 (8.1%) closed vs. 13 (9.1%) unclosed, RR 0.90, 95% CI 0.14, 2.08). There were decreases in risk of skin separation (three (2.2%) vs. six (4.2%), RR 0.53, 95% CI 0.42, 1.93) and seroma or hematoma formation (two (1.5%) vs. seven (4.9%), RR 0.30, 95% CI 0.06, 1.43) that were not statistically significant. Decreases that were not statistically significant were also noted for any wound disruption (14 (10.4%) vs. 21 (14.7%), RR 0.71, 95% CI 0.37, 1.33) and non-infected wound complication (three (2.2%) vs. eight (5.6%), RR 0.40, 95% CI 0.11, 1.47). Increasing gravidity and parity, and Cesarean delivery performed for failure to progress were independent risk factors for any wound complication. Controlling for these factors did not alter the effect of subcutaneous closure.\n Closure of the subcutaneous space does not increase and may protect against wound complications in patients undergoing Cesarean delivery.", "To determine whether closure of Camper fascia prevents the development of superficial wound disruption after cesarean delivery.\n During a 1-year period, 438 women undergoing cesarean delivery were randomized into groups with and without approximation of Camper fascia with absorbable suture during closure of the abdominal incision. All women received routine postoperative care following our departmental guidelines. We reviewed charts after the puerperium to identify women with postoperative superficial wound disruption and to obtain demographic and delivery information for analysis.\n We found a significantly higher incidence of wound disruption in the group without the suture than in those in whom the tissue was approximated (P = .03). Four or more vaginal examinations and higher body mass index were also associated with a higher incidence of wound disruption (P = .05 and P = .04, respectively). Logistic regression correction for covariables that might influence the results of our main analysis revealed no effect of maternal age, parity, indications for cesarean delivery, duration of labor, duration of ruptured membranes, duration of surgery, use of internal monitoring, type of incision, use of antibiotic prophylaxis, surgeon's level of training, or maternal diabetes mellitus and/or hypertension.\n Approximation of Camper fascia with absorbable suture at closure of the abdominal incision during cesarean delivery appears to protect against postoperative superficial wound disruption and is therefore recommended.", "Blunt-tipped needles have previously been shown to reduce needle-stick injury but the issue of morbidity had not been addressed. As awareness of the need for universal precautions heightens, concerns have been raised about any possible morbidity brought about by their use. We present the results of a randomised, controlled study which investigated wound morbidity following caesarean section. Of the 204 women randomised to closure with sharp or blunt-tipped needles, none developed anything other than superficial infection and there were no significant differences between the two groups. We conclude that the use of blunt-tipped needles does not cause an increase in wound morbidity.", "To determine if subcutaneous drain or closure of the subcutaneous layer decreases the incidence of wound complications in obese women undergoing cesarean delivery.\n Seventy-six obese women undergoing cesarean delivery and with at least 2 cm of subcutaneous fat were randomized to one of three groups: group 1 had suture closure of the subcutaneous tissue, group 2 had placement of a subcutaneous closed suction drain, and group 3 had neither suture closure nor drainage.\n Wound separation occurred in 12 (15.8%), seroma in 5 (6.6%) and infection in 3 (4%). There were no reports of wound hematoma. The overall incidence of any wound complication (infection, separation, seroma, hematoma) was higher in obese women who received neither subcutaneous suture nor drain as compared to obese women who received either subcutaneous suture closure or subcutaneous drain. The incidence of major wound complications (infection or separation) was also higher in obese women who received neither subcutaneous suture or drain compared to obese women who received either subcutaneous suture closure or subcutaneous drain.\n The use of closed suction drainage in the subcutaneous space may reduce the incidence of postoperative wound complications in obese women who have at least 2 cm of subcutaneous fat and undergo cesarean delivery.", "The purpose of this study was to compare a subcutaneous stitch closure and subcutaneous drain placement for the risk of wound disruption after cesarean delivery.\n This was a prospective randomized clinical trial that evaluated subcutaneous stitch closure, placement of a subcutaneous drain, or no closure for subsequent wound disruption risk in women with subcutaneous depth at >or=2 cm.\n The maternal demographics and intrapartum risk factors for postoperative wound disruptions were similar among the 964 study subjects, who were divided into 3 groups. Wound disruptions that required opening of the wound, irrigation, debridement, packing, and/or secondary delayed closure occurred in 9.7% of the women with no closure, 10.4% of the women in the stitch closure group, and 10.3% of the women in the closed drain group (P =.834).\n There appears to be no difference in the subsequent risk of wound complications when no closure of the subcutaneous tissue layers occurs versus suture closure or a closed drainage system.", "To test the hypothesis that closure of the subcutaneous fat decreases the incidence of wound disruption after cesarean delivery.\n Two hundred forty-five women with at least 2 cm of subcutaneous fat were randomized to closure of the Camper fascia or no closure with cesarean delivery.\n Complications leading to disruption or opening of the incision were classified as wound seromas in 28 women (11.4%) and as wound infections in 17 (7.0%). The relative risk (RR) of seroma formation in the subcutaneous closure group was 0.3 with a 95% confidence interval (CI) of 0.1-0.7 (5.1 versus 17.2%), a statistically significant difference. There was no significant difference in the incidence of wound infections in the two study groups. Overall, there was a significant difference in the incidence of wound disruption from all causes between the two groups: 14.5% in the subcutaneous closure group compared with 26.6% when the subcutaneous tissues were not reapproximated (RR 0.5, 95% CI = 0.3-0.9).\n Closure of the subcutaneous tissue can significantly reduce the rate of postoperative wound disruption in women with at least 2 cm of subcutaneous adipose tissue." ]

[ "19013598", "15834030" ]

[ "Evaluation of the safety and efficacy of sildenafil citrate for erectile dysfunction in men with multiple sclerosis: a double-blind, placebo controlled, randomized study.", "A double blind, randomised study of sildenafil citrate for erectile dysfunction in men with multiple sclerosis." ]

[ "We evaluated the safety and efficacy of sildenafil citrate for treating erectile dysfunction in patients with multiple sclerosis.\n A total of 203 patients with multiple sclerosis (age range 18 to 50 years old) with erectile dysfunction were randomly assigned to receive 50 to 100 mg sildenafil (102 patients in group 1) or a similar regimen of placebo (101 patients in group 2) 45 minutes to 2 hours before sexual stimulation. Patients were asked to use at least 24 doses/attempts at home. Primary outcome measures consisted of responses to questions 3 and 4 from the International Index of Erectile Function questionnaires well as responses to Sexual Encounter Profile diary questions 2 and 3. We also assessed the number of attempts at sexual intercourse, the number of attempts that were successful and adverse drug effects.\n Improved erections (positive response to the Global Assessment Questionnaire) were reported by 32.8% of patients receiving sildenafil and 17.6% of those receiving placebo (p = 0.04). For Sexual Encounter Profile question 2 (successful penetration) the increase from baseline in mean per patient percentage of yes responses was 29.4% after sildenafil vs 18.8% after placebo (p = 0.04). The proportion of successful sexual attempts ranged from 12% to 26% for sildenafil and from 9% to 21% for placebo, respectively (p = 0.044). Of patients taking sildenafil and placebo 24 (23.5%) and 9 (8.9%) experienced 81 and 31 adverse events, respectively (p = 0.01).\n Compared with placebo, sildenafil has little effect on multiple sclerosis emergent erectile dysfunction and, therefore, cannot be recommended for the routine treatment of erectile dysfunction in patients with multiple sclerosis. This finding implies that there must be other mechanisms that are not affected by sildenafil or are resistant to the effects of sildenafil.", "Identifying and effectively treating erectile dysfunction (ED) can result in an improvement of the quality of life (QoL) in men with multiple sclerosis (MS).\n This randomised, double blind (DB), placebo controlled, flexible dose study with an open label extension (OLE) assessed efficacy, QoL, and safety of sildenafil citrate in men with MS and ED. Overall, 217 men received sildenafil (25-100 mg; n = 104) or placebo (n = 113) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire that includes questions on achieving (Q3) and maintaining (Q4) an erection as well as a global efficacy question (GEQ). QoL was also assessed.\n After 12 weeks, patients receiving sildenafil had higher mean scores for IIEF Q3 and Q4 compared with those receiving placebo (p<0.0001), and 89% (92/103) reported improved erections compared with 24% (27/112) of patients receiving placebo (p<0.0001). At the end of the OLE phase, 95% of men reported improved erections. Patients receiving placebo during the DB phase showed a nearly fourfold increase in improved erections (97% v 26%). Men receiving sildenafil also showed improvements in five of the eight general QoL questions compared with men receiving placebo (p<0.05). The total mean score for the QoL questionnaire improved by 43% for the sildenafil group versus 13% for the placebo group (p<0.0001). Treatment related AEs were predominantly mild in nature, and no patient discontinued due to an AE.\n Sildenafil treatment for ED in men with MS was effective and well tolerated, and resulted in significant improvements in both general and disease specific QoL variables." ]

[ "11147154", "12859607", "17304001", "8238713", "18390492" ]

[ "Balance board training: prevention of traumatic injuries of the lower extremities in female soccer players? A prospective randomized intervention study.", "Hamstring injury occurrence in elite soccer players after preseason strength training with eccentric overload.", "A prevention strategy to reduce the incidence of injury in high school basketball: a cluster randomized controlled trial.", "Prevention of running injuries by warm-up, cool-down, and stretching exercises.", "Prevention of injuries among male soccer players: a prospective, randomized intervention study targeting players with previous injuries or reduced function." ]

[ "This prospective randomized intervention investigated whether training on a balance board could reduce the amount of traumatic injuries of the lower extremities in female soccer players. A total of 221 female soccer players from 13 different teams playing in the second and third Swedish divisions volunteered to participate in the study. Seven teams (n = 121) were randomized to an intervention group and six teams (n = 100) to a control group and were followed during one outdoor season (April-October). Before and after the season muscle flexibility and balance/postural sway of the lower extremities were measured in the players. There were no significant differences in age, height, weight, muscle flexibility and balance/postural sway of the lower extremities between the intervention and the control group. During the season the players in the intervention group performed a special training program consisting of 10-15 min of balance board training in addition to their standard soccer practice and games. After a 37% drop-out the intervention group consisted of 62 players and the control group of 78 players. The results showed no significant differences between the groups with respect either to the number, incidence, or type of traumatic injuries of the lower extremities. The incidence rate of \"major\" injuries was higher in the intervention group than in the control group. Four of five anterior cruciate ligament injuries occurred in the intervention group, which means that we could not prevent severe knee injuries in female soccer players with balance board training. However, among the players who had been injured during the 3-month period prior to this investigation there were significantly more players from the control group than from the intervention group who sustained new injuries during the study period.", "The primary purpose of this study was to evaluate whether a preseason strength training programme for the hamstring muscle group - emphasising eccentric overloading - could affect the occurrence and severity of hamstring injuries during the subsequent competition season in elite male soccer players. Thirty players from two of the best premier-league division teams in Sweden were divided into two groups; one group received additional specific hamstring training, whereas the other did not. The extra training was performed 1-2 times a week for 10 weeks by using a special device aiming at specific eccentric overloading of the hamstrings. Isokinetic hamstring strength and maximal running speed were measured in both groups before and after the training period and all hamstring injuries were registered during the total observational period of 10 months. The results showed that the occurrence of hamstring strain injuries was clearly lower in the training group (3/15) than in the control group (10/15). In addition, there were significant increases in strength and speed in the training group. However, there were no obvious coupling between performance parameters and injury occurrence. These results indicate that addition of specific preseason strength training for the hamstrings - including eccentric overloading - would be beneficial for elite soccer players, both from an injury prevention and from performance enhancement point of view.", "To examine the effectiveness of a sport-specific balance training program in reducing injury in adolescent basketball.\n Cluster randomized controlled trial.\n Twenty-five high schools in Calgary and surrounding area.\n Nine hundred and twenty high school basketball players (ages 12-18).\n Subjects were randomly allocated by school to the control (n = 426) and training group (n = 494). Both groups were taught a standardized warm-up program. The training group was also taught an additional warm-up component and a home-based balance training program using a wobble board.\n All injuries occurring during basketball that required medical attention and/or caused a player to be removed from that current session and/or miss a subsequent session were then recorded and assessed by a team therapist who was blinded to training group allocation.\n A basketball-specific balance training program was protective of acute-onset injuries in high school basketball [RR = 0.71 (95% CI; 0.5-0.99)]. The protective effect found with respect to all injury [RR = 0.8 (95% CI; 0.57-1.11)], lower-extremity injury [RR = 0.83 (95% CI; 0.57-1.19)], and ankle sprain injury [RR = 0.71 (95% CI; 0.45-1.13)] were not statistically significant. Self-reported compliance to the intended home-based training program was poor (298/494 or 60.3%).\n A basketball-specific balance training program was effective in reducing acute-onset injuries in high school basketball. There was also a clinically relevant trend found with respect to the reduction of all, lower-extremity, and ankle sprain injury. Future research should include further development of neuromuscular prevention strategies in addition to further evaluation of methods to increase compliance to an injury-prevention training program in adolescents.", "The purpose of this study was to evaluate the effect of a health education intervention on running injuries. The intervention consisted of information on, and the subsequent performance of, standardized warm-up, cool-down, and stretching exercises. Four hundred twenty-one male recreational runners were matched for age, weekly running distance, and general knowledge of preventing sports injuries. They were randomly split into an intervention and a control group: 167 control and 159 intervention subjects participated throughout the study. During the 16-week study, both groups kept a daily diary on their running distance and time, and reported all injuries. In addition, the intervention group was asked to note compliance with the standardized program. At the end of the study period, knowledge and attitude were again measured. There were 23 injuries in the control group and 26 in the intervention group. Injury incidence for control and intervention subjects was 4.9 and 5.5 running injuries per 1000 hours, respectively. The intervention was not effective in reducing the number of running injuries; it proved significantly effective (P < 0.05) in improving specific knowledge of warm-up and cool-down techniques in the intervention group. This positive change can perhaps be regarded as a first step on the way to a change of behavior, which may eventually lead to a reduction of running injuries.", "This study was conducted to investigate whether the most common injuries in soccer could be prevented, and to determine if a simple questionnaire could identify players at increased risk.\n Introduction of targeted exercise programs to male soccer players with a history of previous injury or reduced function in the ankle, knee, hamstring, or groin will prevent injuries.\n Randomized controlled trial; Level of evidence, 2.\n A total of 508 players representing 31 teams were included in the study. A questionnaire indicating previous injury and/or reduced function as inclusion criteria was used to divide the players into high-risk (HR) (76%) and low-risk (LR) groups. The HR players were randomized individually into an HR intervention group or HR control group.\n A total of 505 injuries were reported, sustained by 56% of the players. The total injury incidence was a mean of 3.2 (95% confidence interval [CI], 2.5-3.9) in the LR control group, 5.3 (95% CI, 4.6-6.0) in the HR control group (P = .0001 vs the LR control group), and 4.9 (95% CI, 4.3-5.6) in the HR intervention group (P = .50 vs the HR control group). For the main outcome measure, the sum of injuries to the ankle, knee, hamstring, and groin, there was also a significantly lower injury risk in the LR control group compared with the 2 other groups, but no difference between the HR intervention group and the HR control group. Compliance with the training programs in the HR intervention group was poor, with only 27.5% in the ankle group, 29.2% in the knee group, 21.1% in the hamstring group, and 19.4% in the groin defined as having carried out the minimum recommended training volume.\n The players with a significantly increased risk of injury were able to be identified through the use of a questionnaire, but player compliance with the training programs prescribed was low and any effect of the intervention on injury risk could not be detected." ]

[ "3914885", "8678158", "9743881", "2014076", "3526572", "9119091", "3051043", "2264174", "1785268", "3535364", "10554936", "1525095", "9621474", "1398272", "2335312", "6584028", "8760703", "7778622", "8259749", "1432827", "2714503", "6576807", "3475231", "3480840", "10582392", "6717874", "3548209", "7943077", "1953853", "3556308", "8841214", "1586329", "2913680", "6582419", "9404911", "2712914", "367426", "3514368", "3860789", "8827572", "7956549", "338022", "2242793", "2733949", "8560997", "1550149" ]

[ "A comparison of intravaginal PGF2 alpha and intravenous oxytocin to stimulate labour after membrane rupture.", "Randomized, double-blind trial of prostaglandin E2 intravaginal gel versus low-dose oxytocin for cervical ripening before induction of labor.", "A randomized trial of intracervical prostaglandin gel and intravenous oxytocin in prelabor rupture of membranes with unripe cervix at term.", "Does prostaglandin confer significant advantage over oxytocin infusion for nulliparas with pre-labor rupture of membranes at term?", "Expectant management of rupture of membranes at term.", "Prelabour rupture of membranes at term: early induction of labour versus expectant management.", "Prostaglandin E2 gel compared to oxytocin for medically-indicated labour induction at term: a controlled clinical trial.", "[Induction of labor. Prostaglandin E2 vaginal tablets compared with intravenous oxytocin for induction of labor in premature rupture of the membranes and immature cervix].", "No benefit from conservative management in nulliparous women with premature rupture of the membranes (PROM) at term. A randomized study.", "Induction of labor by intra-cervical PGE2 in viscous gel. Mechanism of action and clinical treatment routines.", "Prelabour rupture of the membranes at term--no advantage of delaying induction for 24 hours.", "Management of prelabour rupture of the membranes in term primigravidae: report of a randomized prospective trial.", "Induction of labor by intracervical prostaglandin gel and oxytocin infusion in primigravid women with unfavorable cervix.", "Labor characteristics of uncomplicated prolonged pregnancies after induction with intracervical prostaglandin E2 gel versus intravenous oxytocin.", "Premature rupture of the membranes--intervention or not.", "The effect of vaginal prostaglandin E2 pessaries on induction of labor.", "A randomised trial of two expectant managements of prelabour rupture of the membranes at 34 to 42 weeks.", "Cervical ripening before medical induction of labor: a comparison of prostaglandin E2, estradiol, and oxytocin.", "Management of prelabor rupture of membranes at term. A randomized study.", "Evaluation of two methods employed for cervical ripening.", "Lamicel does not promote induction of labour. A randomized controlled study.", "Controlled study comparing vaginal prostaglandin E2 pessaries with intravenous oxytocin for the stimulation of labour after spontaneous rupture of the membranes.", "[Comparison between prostaglandin E2 gel and oxytocin in medically indicated labor induction].", "Prostaglandin E2 vaginal suppository for induction of labour: an efficient, safe and popular method.", "[Induction of labor in patients with premature rupture of membranes in term pregnancy using dinoprostone vs oxytocin. An aleatory study].", "Management of premature rupture of membranes and unfavorable cervix in term pregnancy.", "Induction of labor with intravenous oxytocin or vaginal PGE2 suppositories. A randomized study.", "Cervical ripening before induction of labor: a randomized trial of prostaglandin E2 gel versus low-dose oxytocin.", "Comparison of intravenous oxytocin with and without vaginal prostaglandin E2 gel in term pregnancy with premature rupture of membranes and unfavorable cervix.", "[Cervix ripening using drugs before oxytocin labor induction. Clinical study of a new prostaglandin E2 triacetin gel].", "Clinical amnionitis and endometritis in patients with premature rupture of membranes: endocervical prostaglandin E2 gel versus oxytocin for induction of labor.", "A comparison of Syntocinon infusion with prostaglandin vaginal pessaries when spontaneous rupture of the membranes occurs without labour after 34 weeks gestation.", "Management of term pregnancy with premature rupture of the membranes and unfavourable cervix.", "Role of prostaglandin-induced cervical changes in labor induction.", "Premature rupture of membranes at term with an unfavorable cervix: comparison of expectant management, vaginal prostaglandin, and oxytocin induction.", "Premature rupture of membranes near term: induction of labor with endocervical prostaglandin E2 gel or intravenous oxytocin.", "A comparison of four methods of ripening the unfavourable cervix.", "[Multicenter experiences with the intracervical administration of a new PGE2 gel in labor induction].", "Comparison of intravenous oxytocin and vaginal prostaglandin E2 gel in women with unripe cervixes and premature rupture of the membranes.", "Controlled comparison of induction versus expectant care for prelabor rupture of the membranes at term.", "[15-Methyl-PGF2 alpha vaginal suppository for induction of term labor].", "Intravenous oxytocin and oral prostaglandin E2 for ripening of the unfavourable cervix.", "Induction of labour: the effect of vaginal prostaglandin or i.v. oxytocin--a matter of time only?", "A comparison of early and delayed induction of labor with spontaneous rupture of membranes at term.", "Premature rupture of the membranes (PROM) at term in nulliparous women with a ripe cervix. A randomized trial of 12 or 24 hours of expectant management.", "Prostaglandin E2 for induction of labor in patients with premature rupture of membranes at term." ]

[ "A prospective randomized controlled trial of 202 patients was set up to examine the efficiency and safety of 40 mg of intravaginal prostaglandin F2 alpha (PGF2 alpha) in a tylose gel to stimulate labour after artificial or spontaneous membrane rupture. The control group received a standard intravenous oxytocin regimen. The PGF2 alpha treated group had a significantly shorter length of labour (6.2 +/- 3.6 hours) compared to the oxytocin group (7.5 +/- 4.3 hours) (p less than 0.05). The analgesic requirements were significantly reduced in the PGF2 alpha treated patients. In PGF2 alpha treated patients 46 of 105 required no analgesia whereas 17 of 97 oxytocin treated patients required no analgesia (p less than 0.001). There were similar reductions for epidural (p less than 0.005) and pethidine requirements (p less than 0.005). No differences were found between groups with regards mode of delivery. There were no adverse maternal side-effects associated with PGF2 alpha usage. A significant reduction (p less than 0.05) in the incidence of neonatal jaundice requiring phototherapy occurred in the PGF2 alpha group. Prostaglandin F2 alpha appears to be a safe, efficient and better alternative to intravenous oxytocin to stimulate labour in the presence of ruptured membranes, allowing ambulation, a reduction in length of labour and less need for analgesia and intravenous therapy.", "Our purpose was to compare two methods of preinduction cervical ripening in a randomized, double-blind clinical trial.\n Two intravaginal, 4 mg prostaglandin E2 gel applications administered 4 hours apart were compared with 10 hours of low-dose oxytocin (2 mU/min) in 200 patients undergoing preinduction cervical ripening.\n There were no differences in parity, initial Bishop scores, estimated gestational ages, indications for induction, or birth weights. Prostaglandin E2 gel was significantly better (p < 0.0001) at achieving a change in the Bishop score of 3 or more. The number of successful inductions was significantly greater (p < 0.0003) and the mean time to active labor was significantly shorter (p < 0.0002) in the prostaglandin E2 group than in the oxytocin group. More multiple-day inductions (p < 0.01) occurred in the oxytocin group, and fewer discharged patients who did not deliver infants (p < 0.03) were seen in the prostaglandin E2 gel group. There were no differences between patient groups in the cesarean section rate, meconium staining, hyperstimulation, and Apgar scores.\n Two 4 mg doses of prostaglandin E2 intravaginal gel applied 4 hours apart are superior to low-dose oxytocin in producing cervical ripening and preparing for successful induction.", "In order to compare the efficacy of immediate intravenous oxytocin administration and intracervical prostaglandin E2 gel application in premature rupture of membranes with unfavorable cervices at term, 45 term pregnant patients with premature rupture of membranes were randomized into two groups. Twenty women received immediate intravenous oxytocin after cleansing enema while the rest were treated with intracervical prostaglandin E2 gel. Means of maternal age, gestational age, Bishop score at admission and the rates of nulliparity did not show any significant differences between the two groups (p > 0.05). The mean rupture to delivery time was 12.6 +/- 4.4 hours in the oxytocin group and 16.5 +/- 4.5 hours in the prostaglandin group (p < 0.01). Mean birth weights and Apgar scores were insignificant. Cesarean section rates were 24% in the oxytocin group and 5% in the other (p < 0.05). No infectious morbidity was seen in any case. In conclusion, although delivery is delayed with the intracervical prostaglandin approach, cesarean section rate is lowered without an increase in infectious morbidity.", "Ninety-four nulliparous women with a poor cervical score (less than 6) who had premature rupture of membranes at term were randomized by sealed envelope into two groups. One group received immediate stimulation of labor with oxytocin infusion. The second group received two prostaglandin E2 (PGE2) 3-mg pessaries 4 hours apart, followed by oxytocin infusion, if necessary. The interval between initiation of therapy to onset of labor was significantly longer in the PG group, but the length of labor was similar in both groups. The maximum dose of oxytocin needed was significantly higher in the oxytocin group. The cesarean delivery rate in the oxytocin group was 14.9%, compared with 19.1% in the PG group (not significantly different). All seven cesareans in the oxytocin group and seven of nine in the PG group were for failed stimulation of labor. Neonatal Apgar scores at 1 and 5 minutes and admission to the neonatal intensive care unit were similar in the two groups. The incidence of maternal and neonatal infection was small and was not different in the two groups. The use of PGE2 3-mg pessaries 4 hours apart, followed by oxytocin infusion if necessary, did not confer any benefit over the use of intravenous oxytocin in obstetric or neonatal outcome when both agents were started a few hours after admission.", "We conducted a prospective randomized study involving 317 patients with term gestations (greater than 36 weeks) and premature rupture of membranes (PROM). Eighty-five percent of the 167 patients managed conservatively began labor within 48 hours. The cesarean section rate in this group was 7% as opposed to 21% in the group managed by oxytocin induction. There were no neonatal infections, and the maternal intrauterine infection rate was lower in the group managed expectantly, 4% vs 12%. There was no difference in the average time of hospitalization for the two groups. Conservative management of patients with PROM at term will significantly reduce the incidence of cesarean section without placing the mother or infant at a higher risk of infection.", "To compare expectant management with early induction of labour in pregnant patients with prelabour rupture of membranes at term and unfavourable cervix.\n A prospective, randomised study of 154 women with prelabour rupture of membranes at term of whom 80 had been managed expectantly, and 74 had undergone oxytocin induction at a rate of 2.5 mU/min. Digital examination was not performed before oxytocin infusion, and the first was delayed until 4 h (nulliparae), or 2 h (multiparae) of regular uterine contractions.\n The mean period from rupture of membranes to delivery was significantly shorter in the induction group. The mean duration of labour was significantly shorter in the expectant group. Operative vaginal deliveries were more common in the induction group, and fetal distress was the most common cause of operative vaginal deliveries. The caesarean rates were low and similar in both groups. Maternal and neonatal infectious morbidity was similar and no difference was found in the length of hospitalisation.\n Expectant management in patients with ruptured membranes at term is safe and reduces the frequency of operative vaginal deliveries.", "A clinical trial was carried out to compare the efficacy and tolerance of two modes of induction of labour: vaginally administered prostaglandin E2 gel vs intravenous perfusion of synthetic oxytocin. Fifty women with pregnancy at or near term in whom prompt vaginal delivery was clinically indicated were divided at random into sub-groups of 25 each. Initial dose of PGE2 gel was 1 mg followed by another application of 1 mg or 2 mg 6 hours later in case active labour stage has not been reached. Progressive oxytocin perfusion began with 1 mU/min., being increased gradually every 20 minutes until efficacious uterine dynamics were attained. Data were recorded on entry of age, parity, gestation age, cervical dilatation, Bishop score, indication for induction. Continuous materno-foetal monitoring was carried out during the induction period. Results were evaluated from induction/delivery time, type of delivery, maternal and foetal condition, and any side-effects which developed. Apart from a higher number of instrumental deliveries in the PGE2 gel series, which was not related to the induction method, there was no significant difference between any of the variables evaluated, both methods producing active labour in approximately 70% of the patients within 12 hours. The authors stress, however, the convenience, both for patients and hospital staff, of the administration of an intravaginal induction agent over a systemic therapeutic method of induction.", "In a material of 88 patients with premature rupture of the membranes and unripe cervix, a comparative investigation was undertaken to compare the effects of prostaglandin E2 (PGE2) vaginal tablets and intravenous oxytocin on induction of labour. The patients were subdivided at random into two groups: 42 patients treatment with PGE2 and 46 treatment with intravenous oxytocin. The results did not reveal any significant differences in the numbers of successful inductions regardless of the Bishop score at the commencement of stimulation but the duration of induction was found to be briefer in the oxytocin group. No significant differences were observed in the numbers of instrumental interventions in the two groups nor in the frequencies of side effects and in the employment of analgesics. Treatment with PGE2 vaginal tablets is considered to be more acceptable by the patients and easier for the staff to use. The tablets were just as safe and reliable in use as intravenous oxytocin for induction of labour in cases of premature rupture of the membranes and Bishop scores less than 6, but the duration of induction was significantly longer.", "To compare maternal and fetal outcome in pregnancies with premature rupture of the membranes (PROM) at term with either early induction of labor or conservative management awaiting spontaneous labor.\n A prospective randomized trial.\n The University Hospital of Lund, Sweden.\n Altogether 369 women with singleton pregnancy, cephalic presentation, gestational duration 36-41 weeks, were randomized either to induction of labor (n = 139) or conservative management up to 3 days (n = 138). Those eligible but not participating in the study totalled 92. MAIN OBSTETRIC MEASURES: Obstetric intervention rate (cesarean section or instrumental delivery) and short-term neonatal morbidity.\n No difference was found in the rate of obstetric intervention between the induction of labor group and the group with conservative management (12.2 vs. 18.8%; chi 2 = 2.3, p greater than 0.05). A slightly increased rate of neonatal infections was seen in the latter group (0.7 vs. 4.3%; chi 2 = 3.2, p less than 0.05).\n We found no benefit from conservative management for up to 3 days in women with PROM at term, compared with immediate induction of labor. There was no difference in the number of obstetric interventions during labor. The neonatal infectious morbidity was slightly higher in conservatively managed cases.", "Induction of labor in women with immature cervix was accomplished by four different treatment schedules. The case material included a total of 100 subjects, each treatment group having 25 cases: Group A: Intravenous oxytocin; Group B: Intracervical PGE2-gel followed by intravenous oxytocin; Group C: Intracervical PGE2-gel twice with a 12-hour interval; Group D: Intracervical placebo gel twice with 12-hour interval. Oxytocin did not influence the Bishop score (B.S.) unless in the presence of active labor contractions. In contrast, there was an increment in B.S. by 3.6 points on average within 12 hours following PGE2-gel as calculated from data of subjects without signs of contractions. These results support the concept of a local action of PGE2-gel. The increment in B.S. was larger in subjects with very immature cervices (B.S. less than or equal to 2) than in those with moderately immature scores (B.S. 4). A second PGE2-gel instillation did not increase the B.S. above the level achieved by the first application, indicating that pharmacological ripening of the cervix by a single dose of PGE2 results in an effect approaching maximum. The success rate was the same for oxytocin and PGE2-gel treated women during the first 24 hours, when approximately 40% of the women had given birth. The oxytocin group remained at that level of success rate, whereas the PGE2-gel-oxytocin and PGE2-gel X 2 series continued to improve their success rate up to 75%. An interesting finding in the study was that women given PGE2-gel twice did not need intravenous oxytocin stimulation except in a few cases.", "We performed a prospective randomized study to compare maternal and fetal outcomes in pregnancies with prelabour rupture of the membranes (PROM) at term with early induction of labour or expectant management, 126 women with singleton pregnancy, cephalic presentation and gestational duration > or = 37 weeks, were randomized either to immediate induction of labour with oxytocin (Group 1) (n=52), or conservative management (Group 2) (n=74). Women who constituted Group 2 were divided into 2 groups. The first group (Group 2A) (n=25) included women in whom spontaneous labour did not begin after a waiting period of 24 hours, in which case labour was induced with oxytocin i.e. expectant management. The second group consisted of women (Group 2B) (n=49) in whom labour began spontaneously within 24 hours. The base Caesarean section rate was significantly higher in Group 2 (28.4%) (p<0.05). The rates of Caesarean section in the Groups 1-2A-2B were 19.2%, 60%, and 12.2%, respectively for nulliparous and parous women together. The rate of fetal distress was significantly higher in Group 2 (p<0.05). For determining maternal outcomes, the other parameters such as clinical chorioamnionitis, fever before or during labour, receiving antibiotics before or during labour, postpartum fever, analgesia, anaesthesia did not differ in Groups 1 and 2. Women in Group 1 went into active labour sooner, had fewer digital vaginal examinations, had a shorter interval between membrane rupture and delivery, and spent less time in the hospital before delivery than those in Group 2 (p<0.05). Babies in Group 2 were more likely to receive antibiotics, and more likely to stay in an intensive care nursery for more than 24 hours, and more likely to receive ventilation after initial resuscitation than those babies in Group 1. For developing apnoea and hypotonia, there was no significant difference between Groups 1 and 2. However, for babies in Group 2A there was a significant difference. We conclude that immediate induction of labour with oxytocin does not increase the risk of Caesarean section, compared with a practice of expectant management. Women at term with prelabour rupture of the membranes should therefore be reassured that immediate induction with oxytocin currently appears to be the best policy with respect to maternal and neonatal morbidity.", "To compare a conservative and an active policy (immediate oxytocin infusion) of management of prelabour rupture of the membranes in term primigravidae.\n Randomized trial involving 444 women.\n District maternity hospital.\n Caesarean section rate in each group; also the rate of forceps deliveries, spontaneous deliveries, length of labour, number of vaginal examinations, type of analgesia, pyrexia in labour or the puerperium and antibiotic use in the mother and the infant in each group. The caesarean section rate for the whole trial where the latent period was greater than 12 h was compared to that where the latent period was less than or equal to 12 h.\n There were fewer caesarean sections in the conservative group (odds ratio (OR) 0.60, 95% confidence interval (CI) 0.35 to 1.02; P = 0.06). There was a similar number of forceps deliveries (OR 0.79; 95% CI 0.52 to 1.19; P = 0.26) but more spontaneous deliveries (OR 1.57; 95% CI 1.08 to 2.29; P = 0.02) in the conservative group. More women managed conservatively required inhalational analgesia only for pain relief in labour (OR 2.88; 95% CI 1.46 to 5.68; P = 0.003), a similar number required pethidine (OR 1.29; 95% CI 0.85 to 1.94; P = 0.23), and fewer required epidural analgesia (OR 0.57; 95% CI 0.39 to 0.84; P = 0.005). The number of vaginal examinations was less in the conservative group (difference between mean 0.53; 95% CI 0.25 to 0.80; P less than 0.001). Fewer women managed conservatively experienced four or more vaginal examinations in labour (OR 0.58; 95% CI 0.39 to 0.86; P = 0.007). There were no differences in the lengths of labour, the proportions of women who developed pyrexia in labour or the puerperium or who required antibiotics or in the proportions of infants who required antibiotics.\n These results argue in favour of a conservative policy in managing primigravidae at term with prelabour rupture of the membranes.", "The rate of Cesarean Section for failed induction of labor and maternal and fetal compilations are high when labor is induced in a nulliparas women with an unripe cervix by amniotomy and oxytocin infusion. Prostaglandins (PG) in different forms have been used for ripening the cervix with an aim of reducing these problems. A prospective randomized trial was performed on one hundred primigravid women between 37 and 42 weeks of gestation with singleton pregnancy, cephalic presentation and unfavorable cervix (Modified Bishop Score < or = 5) in the department of Obstetrics & Gynaecology of Institute of Postgraduate Medicine & Research from 1st May 1996 to 30th April 1997. In this study the efficiency of prostaglandin E2 intracervical (PGE2 IC) gel in induction of labor in a group of primigravid women with unripe cervix was assessed and compared with another group with similar characteristics using oxytocin infusion and artificial rupture of membrane (ARM). The Modified Bishop Score (MBS), interval between IOL and onset of labor and the duration of labor after insertion of PGE2 gel was significantly different from those of oxytocin infusion group. But the Apgar Score at 1 & 5 min had shown no statistically significant difference. Any significant difference could also not be detected in the mode of delivery between the two induction group. The proportion of emergency Cesarean Section (CS) was high in the oxytocin infusion group than that of in the prostaglandin group. There was also no significant difference regarding the acceptability of both the induction methods.", "Labor characteristics after intracervical application of 0.5 mg prostaglandin (PG) E2 gel (n = 83) versus intravenous administration of oxytocin (n = 82) for labor induction were investigated in uncomplicated prolonged pregnancies with unripe cervix. The induction to delivery time as well as the total oxytocin dose were significantly reduced in the PGE2 group (p < 0.001). Cesarean sections, instrumental deliveries and fetal distress had the same frequency, but the failures of trial were significantly higher in the oxytocin group than in the PGE2 group (20.7 vs. 6%, p < 0.01). Twenty-four percent of women needed a second PGE2 dose, and almost half of the women in the PGE2 group experienced 'spontaneous' labor. More neonates in the oxytocin group had 5-min Apgar scores < 7 (p < 0.05). Intracervical PGE2 gel application is superior to intravenous oxytocin in terms of shortening the induction-delivery interval and increasing the frequency of successful vaginal delivery. In addition, it is safe for mother and fetus.", "Premature rupture of the membranes (PROM) in otherwise uncomplicated full-term single pregnancies was studied in a prospective randomized study. Ninety-three women were randomized to either induction with oxytocin infusion (n = 43) or expectant management (n = 50). Twenty-four and 26 respectively were nulliparas. In the induction group, all but 3 were delivered within 24 h from PROM. There were 3 vacuum extractions (VE), all in nulliparous women. No cesarean section (CS) was performed. In the expectancy group, 23 of 50 were delivered within 24 h. There were 5 VE and 3 CS in nulliparas and 1 VE and 1 CS in paras. The instrumental actions were mainly due to arrest of 1st or 2nd stage labor. The only clinical infections occurred in nulliparas in the expectancy group. Our conclusion is that parous women with PROM can be treated by either induction or expectancy while in nulliparas, induction after some hours' expectation seems preferable.", "In a prospective randomized study, patients with a valid obstetric indication for induction of labor received either 3 mg prostaglandin E2 vaginal pessaries immediately prior to oxytocin (prostaglandin group, n = 99), or oxytocin alone (oxytocin group, n = 103). At the conclusion of the second day of induction, a significant reduction was noted in the incidence of failed induction in the prostaglandin group (4%) as compared to the oxytocin group (13%) (p less than 0.05). Twenty percent of patients in the prostaglandin group experienced successful induction with prostaglandin pessaries only. When oxytocin was required in the prostaglandin group, the maximal concentration of oxytocin infused and the duration at this concentration were significantly less than in the oxytocin group. No perinatal complications were attributed to the use of prostaglandin. Three minor maternal complications that were attributed to vaginal prostaglandin E2 did not require treatment. Our conclusion is that patients who require an induction of labor, when artificial rupture of the membranes is not feasible, benefit from the use of prostaglandin pessaries before the administration of oxytocin.", "To compare obstetric and perinatal outcome between two different expectant managements in women with prelabour rupture of the membranes (PROM).\n A randomised study.\n One thousand three hundred and eighty-five women with rupture of the membranes at 34 to 42 weeks without contractions.\n Women without contractions 2 h after admission were randomised to early induction the following morning after PROM (early induction group) or induction two days later (late induction group). Women with contractions starting within 2 h after admission were included in the calculations as a short latency group. Digital examinations of the cervix were avoided until onset of active labour. Labour was induced with oxytocin in both groups if no spontaneous contractions occurred or if chorioamnionitis or fetal distress was detected.\n The frequency of spontaneous deliveries, operative deliveries, maternal and neonatal infections.\n In nulliparous women, a higher rate of spontaneous deliveries was found in the late induction group (89%) compared with the early induction group (81%) (P < 0.05). The ventouse extraction rate was 7% and 14% respectively (P < 0.05). A low (2-4%) caesarean section rate was recorded and did not differ between the groups. Endometritis was detected in six women after delivery. Sixty-one children were treated with antibiotics, and no difference could be detected between the groups.\n A higher rate of spontaneous deliveries was found among nulliparous women with prolonged latency as compared with brief latency prior to induction. A protocol of no digital examination before labour was associated with infrequent maternal and fetal morbidity, regardless of latency.", "Our purpose was to evaluate the effectiveness of oxytocin, prostaglandin E2 intracervical gel, and estradiol cream for ripening the very unfavorable cervix in patients requiring induction of labor at term.\n This prospective, randomized study was conducted in a population of women with a very unfavorable cervix (Bishop score < 4) requiring induction of labor. The patients received prostaglandin E2 gel (0.5 mg) intracervically (three doses 6 hours apart), 4 mg estradiol cream in the anterior fornix of the vagina (three doses 6 hours apart), or oxytocin at induction per protocol with an infusion pump.\n Ninety-nine women were recruited into this trial and evenly distributed among the three groups. The demographics of maternal age, race, parity, gestational age, initial Bishop score, and indication for induction were similar among the groups. The incidence of cesarean deliveries was similar in the three groups with approximately 59% of pregnancies delivered abdominally. For patients undergoing abdominal delivery the maximum cervical dilatation among the oxytocin, estradiol, and prostaglandin E2 groups was similar (3.90 +/- 3.02 cm, 3.63 +/- 2.79 cm, and 4.65 +/- 2.78 cm, respectively; p > 0.05). For all patients birth weight and Apgar scores at 1 and 5 minutes were comparable across all regimens (p > 0.05). In the subset of patients delivered vaginally patients receiving oxytocin for cervical ripening had the greatest improvement in Bishop score over baseline (p = 0.023) with an improvement of 7.08 +/- 2.42.\n No differences were detected among prostaglandin E2 gel, estrogen, and oxytocin in relation to cervical ripening in patients with an unfavorable cervix at term who require an induction of labor. Patients with a very unfavorable cervix at term who require delivery may benefit from serial ripening and inductions.", "To compare the rate of obstetric interventions, length of labor, and maternal morbidity in pregnancies with prelabor rupture of membranes at term after either early or late induction of labor in both primiparous and pluriparous women.\n Prospective, randomized study.\n 362 women with singleton pregnancies, cephalic presentations, gestational age of 36 completed weeks or more were allocated at random to induction with oxytocin either 6 hours after PROM (n = 62) (early) or 24 hours (n = 62) (late). Those eligible, but not participating in the study, totalled 238 women. MAIN OBSTETRIC MEASURES: Time of spontaneous labor in the late induction group, length of labor, obstetric intervention rate, maternal morbidity, and the degree of histologic chorioamnionitis.\n The length of labor was longer in the late induction group than in the early induction group in both primiparous and pluriparous (p < 0.05). There were no overall differences in the rate of obstetric interventions or maternal morbidity, but there were marked differences between primiparous and pluriparous women. Increasing time span between the period from rupture of membranes to delivery increased the degree of histologic chorioamnionitis.\n If a woman wants a short labor, she will benefit from early induction. We did not find statistical differences in the rate of obstetric intervention or in the maternal morbidity, but there was a tendency towards adverse effects of late induction.", "The study evaluates breast stimulation and oxytocin infusion as methods for cervical ripening in patients where an obstetric indication for induction of labour exists. Forty patients with a Bishop score of 5 or 6 were randomly selected for either breast stimulation or oxytocin infusion. In a similar group of 20 cases, no method was employed. The Bishop score improved in 41.2% of cases where breast stimulation was used as compared to 75% where an oxytocin infusion was given. Three foetal deaths in the breast stimulation group brought the study to a stop after 17 cases. Cervical ripening with an oxytocin infusion drip appears to be a better method since infusion dosage can be precisely controlled making the technique more predictable and reliable. Though breast stimulation is effective in ripening the cervix, it may be used only in cases of intrauterine foetal death as it may otherwise adversely affect foetal outcome.", "Lamicel is a synthetic tent, which, when inserted in the cervical canal, dilates the cervix by osmosis. Lamicel as an adjunct to induction of labour with intravenous oxytocin or vaginal prostaglandin E2 has been examined in a randomized controlled trial. Ninety-one pregnant women with an unripe cervix participated in the study. No improvement in efficacy was observed in the Lamicel groups compared to the control groups, neither when induction of labour was performed with oxytocin nor with vaginal prostaglandin.", "In a prospective randomized study, 36 patients with spontaneous rupture of the membranes of greater than or equal to 4 h duration were stimulated with 3 mg vaginal prostaglandin E2 pessaries or intravenous oxytocin. Oxytocin stimulation was associated with shorter labours and a lower incidence of abnormal cervimetric progress. Of the patients given prostaglandin pessaries, 40% required a second dose after 4 h for slow progress; 45% of the primigravidae subsequently developed abnormal labour which was corrected by augmentation with oxytocin in all cases. One caesarean section was carried out for disproportion, and the remaining 35 patients were delivered vaginally. Prostaglandin pessaries were not associated with an increased incidence of hyperstimulation or sepsis. In conclusion, although PGE2 pessaries are safe in spontaneous rupture of the membranes, intravenous oxytocin is more efficient in stimulating labour.", "The use of prostaglandins (PG) increasingly replaces the \"classical\" method of induction of labour by means of oxytocin and amniotomy, the last-named method being associated, especially in women with an unripe cervix, with side effects like prolonged labour and a higher rate of obstetric surgery. In this study the point of interest was whether prostaglandins offer any advantages over the classical method in respect of efficacy and maternal and foetal tolerance. 99 patients subdivided into primiparae and multiparae were randomly assigned to group A or B. In group A labour was induced with 1 mg resp. 2 mg PGE2 intravaginally at an interval of 6 hours. In group B the method of induction consisted of intravenous oxytocin and amniotomy. The success rate of induction was almost equal in both groups. However, in those patients where PGE2 induction did not succeed and who could not be delivered within 12 hours the cervical score was significantly improved in comparison to the oxytocin group. Based on the experience reported in the literature, one might speculate that an increased dosage could still improve the results of vaginally administered PGE2 gel.", "Two different methods for induction of labour were randomly used in 100 women with a favourable cervix. The patients were treated with either prostaglandin vaginal suppositories containing 2.5 mg PGE2 in a base of Witepsol S55 (Dynamit Nobel) or intravenous infusion of oxytocin. The PGE2 vaginal suppository was significantly more efficient than the intravenous infusion of oxytocin in relation to the time interval from the start of induction of labour to delivery. Also the percentage of women who delivered within 48 hours (success rate) was higher in the suppository group. Significantly more women in the suppository group found this induction method recommendable.", "It was accomplished a random comparative study to evaluate the effects of dinoprostone in the Hospital de Gineco Obstetricia No. 60 of the Mexican Institute of the Social Security, from June of 1997 to December of the same year, in relationship to the inducement cervical repening and vaginal delivery in patients with score less than or equal Bishop to 4. They were studied a total of 156 patients split into two groups: 78 patients who were administered by intracervical gel of Dinoprostone and to the remainders 78 were administered oxitocin with the same purpose, being this last the control group. We found that the duration time of induction with dinoprostone is 2 hours in average less than the inducement with oxitocin (p > 0.05). The were achieved 67 deliveries with dinoprostone and 65 deliveries with oxitocina, being not significantly. (p < 0.05) The percentage of inducement defect was considered in relationship to the absence of cervical modifications in 12 hours of administration of dinoprostone or oxitocin, being only 3 patients in each group in these conditions. The observed complications were the same in both groups and the conditions of the newborn were better in the Dinoprostone group. The septic complications of mothers were smaller in Dinoprostone group than Oxitocin group and were significantly (p > 0.05). We can conclude that the dinoprostone intracervical application reduce the induction and expulsion time, with better conditions of the new born, and less percent of infectious complications, in relationship to the Oxitocin control group.", "One hundred thirty-four indigent patients at term who had premature rupture of membranes and a cervix unfavorable for induction of labor (80% effacement or less, 2 cm dilation or less) were randomized to compare expectant with intervention management. Women with any medical or obstetric condition warranting immediate intervention were excluded from the study. Patients treated expectantly were placed at bed rest and observed for labor or infection. Patients managed by intervention were given oxytocin if labor did not ensue within 12 hours of rupture of the membranes. Patients in the intervention protocol had longer labor (P less than .02) and a higher incidence of both cesarean delivery (P less than .05) and intraamniotic infection (P less than .05). There was only one case of proven neonatal sepsis, and this occurred in a patient managed by induction of labor. There was no statistically significant difference between groups in mean length of maternal hospitalization.", "Thirty-eight term pregnant women with a moderately unfavorable cervix (cervical score 4-5 p.) were randomly given intravenous oxytocin (Group A) or 3 mg PGE2 as a vaginal suppository (Group B) for labor induction. Eight out of 19 in Group A and 17 out of 19 in Group B gave birth vaginally within 24 h. The remaining 11 women in Group A had still an unfavorable cervix after 24 h. They were then given 3 mg PGE2 as a vaginal suppository and all but one had given birth vaginally without complications within 24 h. In Group B only 2 were still undelivered after 24 h. Both had a favorable cervix and were delivered vaginally within 12 h after intravenous infusion of oxytocin. The number of instrumental deliveries in Group A was one cesarean section and two vacuum extractions and in Group B three vacuum extractions. One woman in Group B reported nausea and vomiting and in one had strong uterine contractions in the second stage of labor. Otherwise no side effects were registered. All babies were born in good condition with Apgar scores greater than or equal to 7. In conclusion, vaginal application of 3 mg PGE2 as a suppository seems to be more effective than intravenous infusion of oxytocin for labor induction in women with half-ripened cervices, i.e. cervical scores of 4-5 p.", "The purpose of this study was to compare prostaglandin E2 gel and a low-dose infusion of oxytocin for cervical ripening before labor induction.\n A total of 158 women were randomized to receive either two intracervical doses of 0.5 mg prostaglandin E2 gel 6 hours apart or 12 hours of intravenous oxytocin up to 4 mlU/min. After cervical ripening labor was induced with high-dose oxytocin infusion and amniotomy.\n There was no difference between the prostaglandin E2 and low-dose oxytocin groups in the likelihood of being in labor or having a Bishop score favorable for induction after ripening (64.2% vs 52.0%, p = 0.12) or in the incidence of vaginal delivery (75.9% vs 74.7%). Prostaglandin E2-treated patients were delivered sooner (20.2 +/- 8.1 hours vs 25.0 +/- 10.5 hours, p = 0.002). Among delivered patients the likelihood of vaginal delivery within 24 hours was greater with prostaglandin E2 ripening (63.7% vs 47.2%, p = 0.04), but there was no difference at 36 hours (76.2% vs 75.0%). Uterine hyperstimulation and fetal distress during ripening occurred only in the prostaglandin E2 group, at a rate of 4.8%.\n After cervical ripening with prostaglandin E2 gel or low-dose oxytocin vaginal delivery can be expected in three fourths of patients within 24 to 36 hours. We recommend that patients with an unfavorable cervix who require delivery undergo cervical ripening and induction of labor rather than automatic delivery by cesarean section.", "Forty-seven nulliparous term pregnant women with PROM and unfavorable cervix, were randomly divided into 23 patients who were observed for four hours then followed by intravenous oxytocin, and 24 patients who were given 3 mg PGE2 gel intravaginally then followed by intravenous oxytocin four hours later. No statistically significant difference was observed between the two treatment groups with regard to Bishop score four hours after observation, intravenous oxytocin to delivery time, Apgar score at 1 and 5 minutes and maternal puerperal complications in both groups. It can be concluded that PGE2 did not significantly improve Bishop score or shorten the induction to delivery time in cases of PROM with unfavorable cervix. Intravenous oxytocin is still preferable both in terms of cost and effectiveness.", "In an open randomized clinical study, 50 of 100 gravidae with a low Bishop score (less than or equal to 5) at term were treated with prostaglandin E2 (0.5 mg PGE2 in 2.5 ml Triacetin gel. Prepidil, intracervically) 12 hours before the indicated i.v. oxytocin induction. In 50 patients labor was induced intravenously without any pretreatment. In 46 of 50 pretreated women (92%) there was an increase in the Bishop score of at least three points, and of only two points in the remaining four. In the control group no significant increase in the Bishop score was measurable. Sixteen patients delivered within the first 12 hours after PGE2 gel administration, before oxytocin induction. Three women in the untreated control group also delivered during this pre-observation period. In 14 (64%) of 22 women in whom cervical priming with PGE2 was performed and 26 (57%) of 47 patients in whom it was not the first intravenous oxytocin induction was successful. The frequency of cesarean sections was 10% (n = 5) in the PGE2 gel group and 12% (n = 6) in the oxytocin group. The oxytocin dose needed to induce labor was significantly lower after cervical priming. No severe side effects were observed during and after PGE2 treatment, in either the mothers or the children.", "To compare the rates of clinical amnionitis and endometritis in patients with premature rupture of membranes (PROM), using endocervical prostaglandin E2 (PGE2) gel for induction of labor versus immediate oxytocin induction of labor.\n We randomized 118 patients to receive either endocervical 0.5 mg of PGE2 gel (study group) or immediate oxytocin induction of labor (control group). If labor was not established in the group receiving PGE2 gel in 24 hours, intravenous oxytocin was given in incremental doses. The rates of clinical amnionitis and endometritis in the two groups were analyzed. Also compared were hours of labor, duration of rupture of membranes and number of vaginal examinations. Student t test, chi 2, or Wilcoxon rank-sum test were used for statistical analysis, as appropriate. P < .05 was considered significant.\n The rates of clinical amnionitis were 5.3% in the PGE2 group and 8% in the control group. Endometritis developed in 1.7% of PGE2 patients and 3.2% of controls. These differences in maternal infection rates were not statistically significant. The two groups were comparable with respect to age, parity, and antepartum group B streptococcal colonization. No significant differences in hours of labor, duration of ruptured membranes, or vaginal examinations were observed. Neonatal outcome data (mean birth weight, Apgar scores at 1 and 5 minutes, Apgar score less than 7 at 5 minutes) were not statistically significant.\n Endocervical placement of 0.5 mg of PGE2 gel does not increase the incidence of clinical amnionitis and endometritis in patients with PROM at term when compared with immediate induction of labor with oxytocin.", "In a prospective randomized trial of 106 patients who had spontaneously ruptured their membranes greater than or equal to 4 hours in the absence of labour, vaginal prostaglandin E2 pessaries and intravenous Syntocinon were compared. There was no significant difference in the treatment to delivery times between the 2 groups. The number of operative deliveries in each group were comparable. No untoward side-effects were noted. The use of vaginal prostaglandin E2 tablets appears to be a safe alternative to Syntocinon for induction of labour when spontaneous rupture of membranes has occurred in the absence of uterine contractions.", "Sixty pregnant patients at term, who had premature rupture of the membranes and an unfavourable cervix were randomised to compare expectant management with oxytocin induction and with the use of prostaglandin E2 vaginal tablets for cervical ripening/induction of labour. Patients treated expectantly were placed on bed rest and observed for labour and infection. Patients managed by intervention were given intravenous oxytocin or 2 prostaglandin E2 tablets (0.5 mg) intravaginally every 6 hours. Between the three groups the duration of labour was longer in the oxytocin group and all 6 caesarean sections were performed on patients in this group. There was only 1 case of proven neonatal sepsis; this occurred in the oxytocin group. Patients with prostaglandin cervical ripening had a shorter hospital stay compared with patients treated expectantly. It is concluded that prostaglandin-induced cervical ripening is the method of choice in handling term patients with premature rupture of the membranes and an unfavourable cervix.", "The role of the cervix in labor induction has been studied in a previous report. Cervical preparation by mechanical methods did not alter the course of induced labor. The same hypothesis is further elucidated in the present study using prostaglandin E2 vaginal suppositories for cervical preparation. Forty-seven pregnant women near term with Bishop scores of 4 or less were divided into three study groups: control subjects, oxytocin-treated patients, and prostaglandin group. A 12-hour preparation phase procedure was carried out to produce cervical and/or myometrial changes. All women had continuous measurement of uterine activity by an extraovular catheter. At the end of the preparation phase, the Bishop score was reevaluated, amniotomy carried out in all patients, and oxytocin infusion either started or continued. Although prostaglandin and oxytocin both significantly changed the cervix, oxytocin had the shortest induction-to-delivery interval, though the prostaglandin-treated group required lower concentrations of oxytocin. The authors conclude that with rigid control of Bishop score and timing of amniotomy and oxytocin infusion rates, prostaglandin-induced cervical changes alone did not uniquely benefit labor induction in the doses used, or within the time frame of the study.", "Our objective was to determine the best treatment for parturients at term with an unfavorable cervix and premature rupture of membranes (PROM).\n In this prospective study, 96 women with PROM and an unfavorable cervix were randomized into one of three treatment groups: oxytocin induction, vaginal prostaglandin E2 gel followed by oxytocin, or expectant management.\n Length of labor, cesarean section rate, and maternal/neonatal morbidity were not significantly different. In contrast, the interval from PROM until delivery and length of hospital stay were significantly longer in the expectantly managed group than in the other groups. Four of the patients who received expectant management required delivery because of nonreassuring fetal assessments.\n Expectant management of PROM at term significantly prolongs hospital stay without decreasing the incidence of abdominal delivery or infectious morbidity. There appears to be potential for cord compression in patients managed expectantly without continuous electronic fetal surveillance.", "We have studied the influence of endocervical application of 0.4 mg prostaglandin E2 (PGE2) in gel on the clinical outcome of pregnancies of at least 36 weeks' duration complicated with premature rupture of the membranes (PROM) and unripe cervix, (modified Bishop score of 7 or less). There were 579 women in the study. The PGE2 gel was applied within the first 12 hours after PROM. The first 60 women were randomly divided into controls given oxytocin infusions and experimental subjects given PGE2 gel. All others were given PGE2 gel, and the results were compared with those obtained in patients with similar criteria who were treated with oxytocin infusions during the preceding year. The clinical outcome was significantly better in the PGE2-treated patients than oxytocin-infused patients. PROM to delivery interval and the incidence of operative deliveries were significantly reduced. No adverse effects on the neonates were observed and the incidence of neonatal infection declined. It is concluded that cervical ripening with PGE2 gel in patients with PROM and unripe cervix near term significantly improves the outcome for both mother and child.", "A comparison was made between four methods of ripening the unfavourable cervix (extra-amniotic prostaglandin E2 gel, oral prostaglandin E2, intravaginal prostaglandin E2 and intravenous oxytocin) in a clinical trial involving 60 primigravidae. In all groups there was an improvement in cervical status. This was significantly greater in those patients who received extra-amniotic prostaglandin gel and they also showed significant decreases in the mean induction-delivery interval and in the incidence of Caesarean section.", "With the participation of four Swiss obstetric clinics, medically indicated inductions of birth (with living fetuses) were performed using a new, stable PGE2 gel, and documented according to a uniform protocol. The study was conducted to investigate the efficacy of 0.5 mg of PGE2, in 2.5 ml of a vehicle (Triacetin) not yet commercially available, for local cervical maturation (n = 41). Thirty-nine patients selected by prospective randomization, in whom birth was induced conventionally, served as a control group. The efficiency of the prostaglandin gel alone or respectively with additional administration of oxytocin was evaluated on the basis of the clear changes in the cervical findings observed within 12 or respectively 24 hours, the spontaneous births, or, in the case of cesarean deliveries, according to the pelvic score. Application of PGE2 alone led to impressive changes of the cervix score and, in 34 of the 41 cases, to regular contractions after an average time of 87 minutes. After 12 hours, prior to administration of oxytocin, 43% of the patients were already delivered. The combination of locally applied PGE2 gel with conventional oxytocin induction significantly increases the number of successful inductions. The percentage of unsuccessfully attempted inductions was reduced to 24% in the PGE2 gel group as compared to 44% in the control group.", "To induce cervical priming and labor, 20 nulliparous term pregnant women with premature rupture of the membranes and unfavorable cervical states were randomly given either oxytocin intravenously or 4 mg prostaglandin E2 in gel intravaginally. One of ten women receiving oxytocin had a favorable cervical state within five hours and vaginal delivery within 24 hours after the start of the infusion compared with six of ten women after prostaglandin E2 gel application. This difference is statistically significant (P less than .01). The number of instrumental deliveries was nine (four cesarean sections and five vacuum extractions) in the oxytocin-treated patients compared with only two vacuum extractions in women who received prostaglandin E2 gel. This difference is also statistically significant (P less than .01, Fischer exact test). In a subsequent open study, 4 mg prostaglandin E2 gel was applied vaginally to 17 term pregnant women of mixed parity with premature rupture of the membranes and unfavorable cervixes. In 12 women a favorable cervical state was achieved within five hours after gel application, and all these women were delivered within 24 hours. None of the women required cesarean section but two required delivery by vacuum extraction. There were no perinatal losses, but two infants in the oxytocin-treated group had Apgar scores less than 7 at five minutes. At pediatric follow-up after two and six months, all infants were normal. In both obstetric and perinatal outcome prostaglandin E2 gel thus seems to be superior to oxytocin for labor induction in term pregnant patients with premature rupture of the membranes and unfavorable cervixes.", "This randomized clinical trial compared oxytocin induction of labor with expectant care for 48 hours after prelabor rupture of the membranes at term. Women at term with prelabor rupture of the membranes for at least 8 hours were assigned at random to induction with oxytocin or to expectant management for 48 hours followed by induction if necessary. Of 168 eligible women, 123 (73%) agreed to participate. More women in the induction group (23%) than in the expectant group (10%) had operative delivery, either cesarean section or instrumental vaginal delivery. In the induction group 41% received analgesia versus 24% in the expectant group (p < 0.005). There was no difference in the rate of maternal and neonatal infection between groups and sepsis was not observed. The active policy of oxytocin induction exposed the mother to a higher risk of operative delivery and a less comfortable labor than the 48 hours expectant care option.", "The results of intravaginal 15-methyl PGF2 alpha (PG05) were compared with gemeprost (ONO-802, PGE1 analogue) pessary and oxytocin intravenous infusion for induction of labor at term. A total of 99 primipara with singleton pregnancy and cephalic presentation, accepted for induction, was randomly allocated into 3 groups: group 1, PG05 0.25 mg (n = 33), group 2, ONO-802 0.125 mg (n = 33), and group 3, oxytocin i.v. (n = 33). Among these, 30 cases had plasma PGs (PGE2 and PGF2 alpha) concentration determined before and after induction. Successful treatment was defined as active labor starting within 24 hours following induction or an increase of cervical Bishop score > 3. The success rates were not significantly different among the 3 groups (PG05 88%, ONO-802 100%, and oxytocin 79%), (P > 0.05). No significant difference existed in the plasma prostaglandin concentrations as well. It is suggested that PG05 may be used for induction of labor at term.", "A clinical trial involving 60 patients was conducted to assess the relative efficacy of intravenous oxytocin and oral prostaglandin E2 in ripening the unfavourable cervix, when given as a priming dose on the day before induction of labour. There was significant improvement in the Bishop score, and the subsequent induction-delivery interval following priming with prostaglandin. This improvement appeared to be dose-related.", "Ninety-one pregnant women with unfavourable cervix (Bishop score no higher than 6) were randomly allocated to induction of labour with either prostaglandin E2 suppositories 2.5 mg 1-2 a day or i.v. oxytocin 4-32 mU/min. The induction procedure was carried on for 2 days. For statistical comparison of efficacy, life table analysis and the logrank test were used with vaginal delivery as the aimed 'event'. Prostaglandin suppositories were more efficient after 12 h (p less than 0.025) and 24 h (p less than 0.005), whereas no difference in efficacy was observed after 48 h. Vaginal delivery was obtained within 48 h in 74% of the women in the prostaglandin group and in 70% in the oxytocin group. No difference was observed in methods of delivery or neonatal Apgar scores, though, in neonates delivered vaginally within 2 days, lowered umbilical artery blood pH values were found after prostaglandin E2 suppositories (p less than 0.05). The patients attitude toward the method of induction was highly in favour of the prostaglandin suppositories. Prostaglandin E2 suppositories are considered excellent for induction of labour if delivery has to be within 24 h, whereas the two methods are equally effective after 48 h.", "The management of women with spontaneous rupture of membranes at term in the absence of labor and with a cervix unfavorable for induction of labor is controversial. In this randomized study of 182 patients, we report the effects of delayed versus early induction of labor on maternal and neonatal outcome. Qualifying patients not in labor at 6 hours after spontaneous rupture of membranes were randomized to either immediate oxytocin induction (86 women) or expectant management with oxytocin induction at 24 hours if labor had not occurred spontaneously (96 women). The cesarean section rate did not differ between the two groups. Women in the delayed group had significantly longer hospitalization (P less than .003), and their infants were significantly more likely to receive antibiotics (P = .006). Infectious morbidity (positive cultures or x-ray-documented pneumonia) occurred in five of the neonates in the delayed group, all of whose mothers had an initial digital cervical examination, but in none of the neonates in the early group, a difference that did not reach statistical significance (P = .061). Five (28%) of 18 infants from the delayed group whose mothers had received an initial digital cervical examination became infected, compared with none of the 78 infants from the delayed group whose mothers did not have digital examinations (P less than .001). We conclude that there is no advantage to delaying induction of labor when women present at term with spontaneous rupture of membranes.", "To compare maternal and neonatal outcomes after 12 or 24 hours of expectant management in healthy nulliparous women with a ripe cervix and PROM at term.\n A prospective, randomized study.\n Karolinska Hospital, Stockholm, Sweden.\n Two hundred and five healthy nulliparous women with singleton pregnancies, cephalic presentation, gestational duration 36 to 42 weeks, randomized to 12 or 24 hours of expectant management after evaluation of the cervical score (> 5). If spontaneous labor did not occur, induction was performed with oxytocin after 12 or 24 hours, respectively. MAIN PARAMETERS: Maternal early morbidity and neonatal infections, obstetric intervention rate (cesarean section or instrumental delivery).\n The cesarean section rate was 4% in each group. The vacuum extraction rate was 21% in each group. Induction of labor was performed in 47% of the women allocated to 12 hours of expectant management vs 17% of the women allocated to 24 hours of expectant management (p < 0.05). The maternal morbidity rate was almost negligible. Only a few fetal infections occurred and no difference was noted between the groups.\n In healthy nulliparous women at term with a ripe cervix, expectant management over 24 hours vs 12 hours resulted in fewer inductions of labor and no increase in instrumental deliveries, without any increase in neonatal or maternal morbidity.", "A prospective study comparing three management schemes for patients at term with premature rupture of membranes was performed.\n One hundred forty patients were randomized to one of three study groups: prostaglandin E2, placebo, or oxytocin. Patients randomized to prostaglandin E2 and placebo received vaginal suppositories containing 3 mg prostaglandin E2 or glycerin only, respectively; suppositories were administered in a double-blind fashion, on one or two occasions, 6 hours apart. Oxytocin was given only if labor was not established after 12 hours or to augment inadequate labor. In patients randomized to oxytocin labor was induced with intravenous oxytocin. The time interval to delivery, delivery outcome, and complications were analyzed.\n Patients receiving prostaglandin E2 were more likely to be in labor after one suppository and to be delivered without the addition of oxytocin when compared with placebo. The time interval to delivery was shorter with prostaglandin E2 and oxytocin induction versus placebo (\"expectant management\"). The incidence of maternal infection was lowest in patients with labor induced by prostaglandin E2. Although the overall cesarean section rate was low, there was a trend toward a lower rate with prostaglandin E2 induction. No adverse effects were observed with prostaglandin E2.\n Prostaglandin E2 can be used successfully to induce labor after premature rupture of membranes at term with greater ease of administration when compared with oxytocin." ]

[ "11509086" ]

[ "Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized clinical trial." ]

[ "The aim of the study was to assess the safety and feasibility of a clinical trial on the effect of vinpocetine, a synthetic ethyl ester of apovincamine, in acute ischaemic stroke. Thirty consecutive patients with computed tomography verified diagnosis of acute ischaemic stroke, who could receive drug treatment within 72 h of stroke onset, were enrolled. The patients were randomly allocated to receive either low-molecular weight dextran alone or in combination with vinpocetine. Poor outcome was defined as being dead or having a Barthel index of < 70 or a Rankin score of 3--5. Intention-to-treat analysis was applied. One-tenth of all hospitalized patients with acute ischaemic stroke were eligible for the trial. Thirty eligible patients were treated with either low-molecular weight dextran alone (mean age 57.9 +/- 11.6 years, n = 15) or in combination with vinpocetine (mean age 60.8 +/- 6.6 years, n = 15). The two treatment groups were comparable with respect to major prognostic variables. A relative risk (RR) reduction of poor outcome at 3 months follow-up was 30% (RR = 0.7; 95% confidence interval [CI] 0.1--3.4), as defined by the modified Barthel Index, and 60% as defined by the modified Ranking score (RR = 0.4, 95% CI: 0.1--1.7). The National Institute of Health (NIH--NINDS) Stroke Scale score was marginally significantly better in the vinpocetine treated group at 3 months of follow-up (P = 0.05, ANOVA). No significant adverse effects were seen. This pilot study shows that a full-scale randomized double-blind, placebo-controlled trial of vinpocetine treatment in acute ischaemic stroke is feasible and warranted." ]

[ "18670219", "16267767", "17827369" ]

[ "Albendazole treatment of HIV-1 and helminth co-infection: a randomized, double-blind, placebo-controlled trial.", "Schistosomiasis and HIV-1 infection in rural Zimbabwe: effect of treatment of schistosomiasis on CD4 cell count and plasma HIV-1 RNA load.", "Effect of diethylcarbamazine on HIV load, CD4%, and CD4/CD8 ratio in HIV-infected adult Tanzanians with or without lymphatic filariasis: randomized double-blind and placebo-controlled cross-over trial." ]

[ "Several co-infections have been shown to impact the progression of HIV-1 infection. We sought to determine if treatment of helminth co-infection in HIV-1-infected adults impacted markers of HIV-1 disease progression.\n To date, there have been no randomized trials to examine the effects of soil-transmitted helminth eradication on markers of HIV-1 progression.\n A randomized, double-blind, placebo-controlled trial of albendazole (400 mg daily for 3 days) in antiretroviral-naive HIV-1-infected adults (CD4 cell count >200 cells/microl) with soil-transmitted helminth infection was conducted at 10 sites in Kenya (Clinical Trials.gov NCT00130910). CD4 and plasma HIV-1 RNA levels at 12 weeks following randomization were compared in the trial arms using linear regression, adjusting for baseline values.\n Of 1551 HIV-1-infected individuals screened for helminth infection, 299 were helminth infected. Two hundred and thirty-four adults were enrolled and underwent randomization and 208 individuals were included in intent-to-treat analyses. Mean CD4 cell count was 557 cells/microl and mean plasma viral load was 4.75 log10 copies/ml at enrollment. Albendazole therapy resulted in significantly higher CD4 cell counts among individuals with Ascaris lumbricoides infection after 12 weeks of follow-up (+109 cells/microl; 95% confidence interval +38.9 to +179.0, P = 0.003) and a trend for 0.54 log10 lower HIV-1 RNA levels (P = 0.09). These effects were not seen with treatment of other species of soil-transmitted helminths.\n Treatment of A. lumbricoides with albendazole in HIV-1-coinfected adults resulted in significantly increased CD4 cell counts during 3-month follow-up. Given the high prevalence of A. lumbricoides infection worldwide, deworming may be an important potential strategy to delay HIV-1 progression.", "To determine whether treatment of schistosomiasis has an effect on the course of human immunodeficiency virus type 1 (HIV-1) infection, individuals with schistosomiasis and with or without HIV-1 infection were randomized to receive praziquantel treatment at inclusion or after a delay of 3 months; 287 participants were included in the study, and 227 (79%) were followed up. Among the 130 participants who were coinfected, those who received early treatment (n=64) had a significantly lower increase in plasma HIV-1 RNA load than did those who received delayed treatment (n=66) (P<.05); this difference was associated with no change in plasma HIV-1 RNA load in the early intervention group (P=.99) and an increase in plasma HIV-1 RNA load in the delayed intervention group (P<.01). Among the 227 participants who were followed up, those who received early treatment (n=105) had an increase in CD4 cell count, whereas those who received delayed treatment (n=122) did not (P<.05); this effect did not differ between participants when stratified by HIV-1 infection status (P=.17). The present study suggests that treatment of schistosomiasis can reduce the rate of viral replication and increase CD4 cell count in the coinfected host.", "We assessed the effect of anti-filarial treatment (diethylcarbamazine, DEC) on HIV load, CD4%, and CD4/CD8 ratio in HIV-positive individuals with and without infection with the filarial parasite Wuchereria bancrofti in a randomized, double-blind, placebo-controlled cross-over trial. The study was conducted in Tanga Region, Tanzania, in 2002 and involved 27 adults. A significant decrease in HIV load (54%) and an insignificant increase in CD4% were observed in the HIV-positive individuals with filarial co-infection at 12 weeks after treatment. HIV load and CD4% both increased, although not statistically significantly, in the HIV-positive individuals without filarial infection. The findings suggest that DEC affected HIV load through its effect on the filarial infection rather than through a direct (pharmacodynamic) effect on HIV. Global efforts to control lymphatic filariasis by annual mass treatment with DEC may have a beneficial effect on the HIV/AIDS epidemic in areas where HIV and lymphatic filariasis co-exist." ]

[ "10700949", "1721361", "9503547", "10755536", "11956848", "9275110", "12176589", "11267285", "11583721", "9636525", "11119899", "12270445", "12431623", "11888584", "12176511", "9112351", "12176523", "12591319", "10083501", "10326847", "11119902", "7533431", "11752040" ]

[ "Effect of acute rejection on expression of fibrosis associated genes in renal transplant recipients.", "FK 506 in clinical kidney transplantation.", "Pronounced renal vasoconstriction and systemic hypertension in renal transplant patients treated with cyclosporin A versus FK 506.", "Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation.", "Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation.", "Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.", "One year evolution of bone mineral density in kidney transplant recipients receiving tacrolimus versus cyclosporine.", "Canadian multicentre trial of tacrolimus/azathioprine/steroids versus tacrolimus/mycophenolate mofetil/steroids versus neoral/mycophenolate mofetil/steroids in renal transplantation.", "Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus.", "Prospective randomized study comparing FK 506 (Prograft) and cyclosporine A (Neoral) as primary immunosuppression in cadaveric renal transplants at a single institution: interim report of the first 80 cases.", "Tacrolimus vs CyA Neoral in combination with MMF and steroids after cadaveric renal transplantation.", "Effects of three immunosuppressive regimens on CD4 helper function, B cell monocyte and cytokine responses in renal transplant recipients: 4-month follow-up of a prospective randomized study.", "Arterial hypertension in renal transplant recipients treated with tacrolimus or cyclosporine-Neoral.", "Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study.", "A three arm study comparing immediate tacrolimus therapy with ATG induction therapy followed by either tacrolimus or cyclosporine in adult renal transplant recipients.", "A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group.", "One-year follow-up of a Brazilian randomized multicenter study comparing tacrolimus versus cyclosporine in kidney transplantation.", "Randomized trial of tacrolimus in combination with mycophenolate mofetil versus cyclosporine with mycophenolate mofetil in cadaveric renal transplant recipients with delayed graft function.", "Tacrolimus/\"low-dose\" mycophenolate mofetil versus microemulsion cyclosporine/\"low-dose\" mycophenolate mofetil after kidney transplantation--1-year follow-up of a prospective, randomized clinical trial.", "A prospective randomized trial comparing the efficacy of tacrolimus versus cyclosporine in black recipients of primary cadaveric renal transplants.", "Clinical experience with Prograf (tacrolimus, FK 506) in Chinese patients after renal transplantation.", "Phase II FK 506 multicenter concentration control study: one-year follow-up.", "Glucose metabolism in the first 3 years after renal transplantation in patients receiving tacrolimus versus cyclosporine-based immunosuppression." ]

[ "nan", "nan", "This prospective study investigated hypertension and renal vasoconstriction developing during the 1st year after renal transplantation in patients randomly allocated to treatment with FK 506 (n = 28) or CyA (n = 13). Starting doses were 0.2-0.3 mg/kg per day for FK 506 and 5-8 mg/kg per day for CyA: doses were subsequently adjusted to trough levels (5-15 ng/ml for FK 506 and 100-150 ng/ml for CyA). We compared 24-h ambulatory blood pressure measurement, antihypertensive treatment, serum creatinine, and resistance index (RI), measured by Doppler ultrasound at the level of the interlobar artery. Until month 2 of treatment, FK 506-treated patients had a significantly lower RI (8%) and better renal graft function, as evidenced by significantly lower serum creatinine values. Some 13% of FK 506-treated patients, compared to 70% of CyA-treated patients (P < 0.01), needed additional antihypertensive drugs after transplantation to keep blood pressure stable. FK 506 treatment, at the above-mentioned dosages, was associated with a significantly higher number of infections (urinary tract infection, pyelonephritis, and pneumonia). We conclude that CyA produces greater renal vasoconstriction and systemic hypertension than FK 506, as reflected in higher renal interlobar artery RI values and a greater need for antihypertensive treatment. After 2 months of treatment and a reduction in CyA trough levels, the renal effects (i.e., lower RI and lower creatinine values), but not the systemic hypertensive effects, disappear.", "Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation.\n A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year.\n There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups.\n All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.", "This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with the microemulsion formulation of cyclosporin (CyA) in children undergoing renal transplantation. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 years) were randomly assigned (1:1) to receive either Tac ( n=103) or CyA microemulsion ( n=93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection. Baseline characteristics were comparable between treatment groups. Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA therapy (59.1%) ( P=0.003). The incidence of corticosteroid-resistant rejection was also significantly lower in the Tac group compared with the CyA group (7.8% vs. 25.8%, P=0.001). The differences were also significant for biopsy-confirmed acute rejection (16.5% vs. 39.8%, P<0.001). At 1 year, patient survival was similar (96.1% vs. 96.6%), while 10 grafts were lost in the Tac group compared with 17 graft losses in the CyA group ( P=0.06). At 1 year, mean glomerular filtration rate (Schwartz estimate) was significantly higher in the Tac group (62+/-20 ml/min per 1.73 m(2), n=84) than in the CyA group (56+/-21 ml/min per 1.73 m(2), n=74, P=0.03). The most frequent adverse events during the first 6 months were hypertension (68.9% vs. 61.3%), hypomagnesemia (34.0% vs. 12.9%, P=0.001), and urinary tract infection (29.1% vs. 33.3%). Statistically significant differences ( P<0.05) were observed for diarrhea (13.6% vs. 3.2%), hypertrichosis (0.0% vs. 7.5%), flu syndrome (0.0% vs. 5.4%), and gum hyperplasia (0.0% vs. 5.4%). In previously non-diabetic children, the incidence of long-term (>30 days) insulin use was 3.0% (Tac) and 2.2% (CyA). Post-transplant lymphoproliferative disease was observed in 1 patient in the Tac group and 2 patients in the CyA group. In conclusion, Tac was significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population. The overall safety profiles of the two regimens were comparable.", "To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection.\n A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids.\n At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment.\n The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.", "nan", "nan", "Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patient's prognosis. In study 1, the effects of immunosuppressants, cyclosporine (CsA) and tacrolimus on serum lipids were compared in-patients undergoing renal transplantation. The study included 32 cases of renal transplantation recipients who randomized to the CsA treatment group (15 patients) and the tacrolimus group (17 patients). Before and 1 month after the transplantation, we assessed the serum lipid levels, apolipoprotein levels, the concentrations of cholesterol in the respective lipoprotein fractions and the enzyme activities related to lipid-metabolism. The serum lipid levels in both groups were significantly increased at 1 month after renal transplantation. In the CsA group, there were significant increases in cholesterol contents in very-low-density lipoprotein (VLDL), LDL2 and HDL2 fractions, whereas, in the tacrolimus group, cholesterol content was increased in VLDL and HDL2 fractions. In study 2, 1 month after renal transplantation, 19 patients with hypercholesterolemia (total cholesterol (TC) >200 mg/dl) and hypertriglyceridemia (triglyceride (TG) >150 mg/dl) were treated with simvastatin 5-10 mg/day for 6 months. Simvastatin treatment significantly decreased serum TC (240+/-29-200+/-22 mg/dl, P<0.001), low-density lipoprotein cholesterol (LDL-C; 114+/-20-99+/-17 mg/dl, P<0.05) and TG levels (217+/-103-130+/-38 mg/dl, P<0.01). In addition, there were significant decreases in very-low-density lipoprotein cholesterol (VLDL-C; 53+/-20-34+/-15 mg/dl, P<0.001). The Cmax and AUC of simvastatin were increased about eight-fold, when simvastatin was given in combination with CsA. In contrast, no significant changes in simvastatin levels were observed when combination with tacrolimus. Although simvastatin levels were increased with CsA, there were no abnormal changes in renal and liver functions, creatinine phosphokinase (CPK) levels or in incidence of adverse effects.", "nan", "nan", "nan", "nan", "In previous comparative studies tacrolimus was superior to the standard formulation of ciclosporin in preventing acute rejection after renal transplantation. We have compared the microemulsion formulation of ciclosporin with tacrolimus in a multicentre randomised trial.\n The 6-month open study involved 560 patients in 50 European centres. 287 patients were randomly assigned tacrolimus and 273 ciclosporin microemulsion plus azathioprine and corticosteroids. The initial oral daily doses were 0.30 mg/kg for tacrolimus and 8-10 mg/kg for ciclosporin. The primary endpoint was the proportion of patients with biopsy-proven acute rejection and the time to this event.\n The two study groups were similar in terms of baseline characteristics. Three patients did not receive study treatment or did not undergo transplantation (one tacrolimus, two ciclosporin). The rate of biopsy-confirmed acute rejection was significantly lower with tacrolimus than with ciclosporin microemulsion (56 patients [19.6%] vs 101 [37.3%]; 17.7% difference [95% CI 10.3-25.1]; p<0.0001). Biopsy-confirmed corticosteroid-resistant rejection was also significantly lower with tacrolimus (27 [9.4%] vs 57 [21.0%]; 11.6% difference [5.7-17.5]; p<0.0001). Cross-over between therapies because of biopsy-proven rejection was judged necessary in one of 286 (0.3%) tacrolimus-group patients and 27 of 271 (10.0%) ciclosporin-group patients (p<0.0001). There were no significant differences in survival of patients or grafts or in renal function. The overall frequency of adverse events was similar in the two groups, though hypertension and hypercholesterolaemia were more common in the ciclosporin group and tremor and hypomagnesaemia were more frequent in the tacrolimus group.\n Tacrolimus was significantly more effective than ciclosporin microemulsion in preventing acute rejection after renal transplantation and had a superior cardiovascular-risk profile.", "nan", "Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immunosuppression in patients receiving cadaveric kidney transplants.\n A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were followed for 1 year for patient and graft survival and the incidence of acute rejection.\n One-year patient survival rates were 95.6% for tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-year graft survival rates were 91.2% and 87.9% (P=0.289). There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the tacrolimus group (30.7%) compared with the cyclosporine group (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respectively; P<0.001). Impaired renal function, gastrointestinal disorders, and neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolimus group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients.\n Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.", "nan", "nan", "nan", "We performed a prospective randomized trial to compare the efficacy and safety of tacrolimus (FK506) versus cyclosporine (CSA) in black primary cadaveric renal transplant (CRT) recipients.\n Between December 1994 and February 1997, 35 black primary CRT recipients were enrolled in this trial. All patients received 7 days of induction therapy with OKT3. Fourteen patients received FK506 and prednisone only. Twenty-one patients received CSA, azathioprine, and prednisone. The two groups were comparable in terms of age, gender, plasma renin activity, human leukocyte antigen mismatches, and cause of renal failure.\n Patient and graft survival were 12 of 14 (86%) for the FK506 group and 20 of 21 (95%) for the CSA group (P = 0.71). Three patients died owing to cardiac events with functioning grafts. Acute rejection was 2 of 14 (14%) for the FK506 and 8 of 21 (38%) for the CSA group (P = 0.25). Two other patients on CSA were converted to FK506 as rescue for OKT3-resistant rejection. Mean serum cholesterol at 1 year was 198 +/- 45 mg/dL for the FK506 group and 244 +/- 49 mg/dL for the CSA group (P = 0.03). Mean serum creatinine at 1 year was 1.39 +/- 0.38 mg/dL for the FK506 group and 1.94 +/- 0.64 mg/dL for the CSA group (P = 0.02).\n Patient and graft survival were similar in both groups at 1 year posttransplant. Although statistically not significant, the incidence of acute rejection was lower in the FK506 group. Furthermore, FK506-treated patients had significantly lower serum creatinine and cholesterol levels at 1 year posttransplant.", "nan", "nan", "The long-term effects of tacrolimus and cyclosporine on pancreatic islet cell function in renal transplant recipients are unclear. Therefore, a prospective, randomized, longitudinal study was performed that compared glucose metabolism in adult kidney allograft recipients on tacrolimus versus cyclosporine-based immunosuppression. Twenty-three white renal allograft recipients, randomized for either therapy with cyclosporine or tacrolimus, underwent intravenous glucose tolerance tests 6 times during the first 3 yr after transplantation. Concomitant therapy (low-dose steroids and azathioprine) was the same in both groups. Insulin sensitivity index (kG), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus and cyclosporine were measured. The occurrence of posttransplantation diabetes mellitus was prospectively monitored. Statistical analysis was performed by ANOVA for repeated measures, and parametric and nonparametric tests were also performed. Although only one patient treated with cyclosporine developed posttransplantation diabetes mellitus, kG levels were below normal in up to one-third of both patients who received tacrolimus and cyclosporine. The only significant difference between patients who received tacrolimus and those who received cyclosporine was in pancreatic secretion capacity at week 3 after transplantation, when the increment of C-peptide secretion was 57% lower and the increment of insulin secretion was 48% lower for patients receiving tacrolimus. In both groups, from week 3 to month 6, there was a tendency toward an increase in kG, despite a significant increase in fasting glucose and insulin resistance calculated by homeostasis model assessment. After month 6, there were no significant changes in any of the parameters of glucose metabolism, indicating that long-term use of either tacrolimus or cyclosporine does not cause chronic, cumulative pancreatic toxicity." ]

[ "11815967", "8276647", "8402457", "15275728" ]

[ "High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial.", "Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial.", "High-dose rate and low-dose rate intracavitary therapy for carcinoma of the uterine cervix. Final results of Osaka University Hospital.", "Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma." ]

[ "This was a prospective randomized clinical trial undertaken at our institution to compare low-dose-rate (LDR) intracavitary radiation therapy versus high-dose-rate (HDR) intracavitary radiation therapy for the treatment of cervical carcinoma.\n From January 1984 to December 1997, a total of 132 patients with Stage II or IIIB of invasive carcinoma of the uterine cervix were entered into this randomized study. Treatment arm by HDR or LDR was allocated according to the month of each patient's birth. External irradiation consisted of whole pelvis irradiation and pelvic irradiation. Doses of external irradiation for both groups were identical. The authors used 0.588 as the conversion factor of total intracavitary dose from LDR to HDR.\n The 5-year disease specific survival rates of Stage II and III patients treated with HDR were 69% and 51% whereas those with LDR were 87% and 60%, respectively. The 5-year pelvic recurrence free survival rates of Stage II and III patients treated with HDR were 89% and 73% whereas those with LDR were 100% and 70%, respectively. There was no significant difference in disease specific survival or pelvic recurrence free survival rates between HDR and LDR. The actuarial complication rate (Radiation Therapy Oncology Group Grade 3, 4, or 5) at 5 years was 10% in the HDR group and 13% in the LDR group, and the difference between the HDR and LDR groups was not statistically significant.\n The pelvic control or actuarial complication rates were comparable between HDR and LDR treatment. The difference between the disease specific survival rates for HDR and LDR was not statistically significant for Stage II or III, although in Stage II, patients treated with LDR appeared to have a better survival rate than those treated with HDR.\n Copyright 2002 American Cancer Society.", "This study is a prospective randomized clinical trial undertaken at our center to compare low dose rate versus high dose rate intracavitary brachytherapy for the treatment of carcinoma uterine cervix.\n From June 1986 to June 1989, 482 patients with previously untreated invasive squamous cell carcinoma of the uterine cervix were entered into the study. After an initial clinical examination and investigative work-up the patients were staged according to FIGO staging system. Depending upon the stage of the disease, the size of the local growth and the local cervical anatomy, the patients were divided into two main groups. In group I patients, the predominant treatment was by intracavitary therapy and in group II patients, the predominant therapy was by external beam radiation. In both the groups at the time of intracavity brachytherapy the patients were alternately randomized to receive either low dose rate or high dose rate brachytherapy. There were thus two hundred forty-six patients in the low dose rate group and two hundred thirty-six patients in the high dose rate group. The patients were analyzed for local control, 5 years survival and late radiation morbidity.\n Stage for stage the local control rates in the low dose rate group and high dose rate group were similar. The overall local control achieved in the low dose rate group was 79.7% as compared to 75.8% in the high dose rate group. The 5 years survival figures in the low dose rate and high dose rate group were also comparable. In Stage I, it was 73% for low dose rate patients and 78% for high dose rate patients, for Stage II it was 62% and 64% respectively and for Stage III patients it was 50% and 43%. The only statistically significant difference was found in the incidence of overall rectal complications which was 19.9% for the low dose rate group as compared to only 6.4% for the high dose rate group. However, the more severe grade 3-4 complications were not significantly different between the two groups (2.4% vs. 0.4%, respectively). The bladder morbidity in both the groups was similar.\n Thus high dose rate intracavitary brachytherapy is an equally good alternative to conventional low dose rate brachytherapy in the treatment of carcinoma of the uterine cervix.", "High-dose rate (HDR) intracavitary radiation therapy for carcinoma of the uterine cervix has gradually found wider acceptance. In 1983, the authors first presented the results of prospective randomized comparative study of HDR versus low-dose rate (LDR) therapy. In the current study, the final results of this study with a longer follow-up are presented.\n From January 1975 through August 1983, 430 previously untreated patients with carcinoma of the uterine cervix in Stages I-III were treated with either HDR 60Co therapy or LDR 137Cs therapy at our department. HDR was administered to a total of 259 patients: 32 patients in Stage I, 80 in Stage II, and 147 in Stage III. LDR was administered to a total of 171 patients: 28 patients in Stage I, 61 in Stage II, and 82 in Stage III.\n The 5-year cause-specific survival rates of Stage I-III patients treated with HDR were 85%, 73%, and 53%, respectively. The corresponding figures for LDR were 93%, 78%, and 47%, respectively. There was no significant difference between these survival rates. Moderate-to-severe complications developed in 10% of the patients treated with HDR and 4% of those with LDR. This difference in the incidence of complications was statistically significant (P = 0.023).\n Treatment results in terms of cause-specific survival were equivalent for HDR and LDR treatment. However, the incidence of complications was higher for the HDR group, although within acceptable levels, than for the LDR group.", "Intracavitary brachytherapy plays an important role in the treatment of cervical carcinoma. Previous results have shown controversy between the effect of dose rate on tumor control and the occurrence of complications. We performed a prospective randomized clinical trial to compare the clinical outcomes between low-dose-rate (LDR) and high-dose-rate (HDR) intracavitary brachytherapy for treatment of invasive uterine cervical carcinoma.\n A total of 237 patients with previously untreated invasive carcinoma of the uterine cervix treated at King Chulalongkorn Memorial Hospital were randomized between June 1995 and December 2001. Excluding ineligible, incomplete treatment, and incomplete data patients, 109 and 112 patients were in the LDR and HDR groups, respectively. All patients were treated with external beam radiotherapy and LDR or HDR intracavitary brachytherapy using the Chulalongkorn treatment schedule.\n The median follow-up for the LDR and HDR groups was 40.2 and 37.2 months, respectively. The actuarial 3-year overall and relapse-free survival rate for all patients was 69.6% and 70%, respectively. The 3-year overall survival rate in the LDR and HDR groups was 70.9% and 68.4% (p = 0.75) and the 3-year pelvic control rate was 89.1% and 86.4% (p = 0.51), respectively. The 3-year relapse-free survival rate in both groups was 69.9% (p = 0.35). Most recurrences were distant metastases, especially in Stage IIB and IIIB patients. Grade 3 and 4 complications were found in 2.8% and 7.1% of the LDR and HDR groups (p = 0.23).\n Comparable outcomes were demonstrated between LDR and HDR intracavitary brachytherapy. Concerning patient convenience, the lower number of medical personnel needed, and decreased radiation to health care workers, HDR intracavitary brachytherapy is an alternative to conventional LDR brachytherapy. The high number of distant failure suggests that other modalities such as systemic concurrent or adjuvant chemotherapy might lower this high recurrence, especially in Stage IIB and IIIB." ]

[ "11277825", "12372577", "11452676", "10385495", "12473255", "11113401", "15215811", "19640331", "20500832", "18219956", "12076217", "15326073", "15864233", "18159093", "16616020", "9187418", "12222700" ]

[ "Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.", "Effects of atorvastatin 80 mg daily early after onset of unstable angina pectoris or non-Q-wave myocardial infarction.", "Pravastatin in acute ischaemic syndromes: results of a randomised placebo-controlled trial.", "Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial.", "Effect of fluvastatin on ischaemia following acute myocardial infarction: a randomized trial.", "Beneficial effects of pravastatin (+/-colestyramine/niacin) initiated immediately after a coronary event (the randomized Lipid-Coronary Artery Disease [L-CAD] Study).", "Effect of pravastatin compared with placebo initiated within 24 hours of onset of acute myocardial infarction or unstable angina: the Pravastatin in Acute Coronary Treatment (PACT) trial.", "Effect of simvastatin on plasma interleukin-6 in patients with unstable angina.", "Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial).", "[The effects of early application of simvastatin on C-reactive protein level, blood lipids, and the clinical course of acute coronary syndrome].", "Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial.", "Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study.", "Atorvastatin has an important acute anti-inflammatory effect in patients with acute coronary syndrome: results of a randomized, double-blind, placebo-controlled study.", "Effect of early use of low-dose pravastatin on major adverse cardiac events in patients with acute myocardial infarction: the OACIS-LIPID Study.", "Effects of early statin treatment on symptomatic heart failure and ischemic events after acute myocardial infarction in Japanese.", "Time course of serum lipids and apolipoproteins after acute myocardial infarction: modification by pravastatin.", "Early use of pravastatin in patients with acute myocardial infarction undergoing coronary angioplasty." ]

[ "Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events.\n To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events.\n A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia.\n A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction.\n Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission.\n Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization.\n A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12 vs 24 events; P =.045). In the atorvastatin group, mean low-density lipoprotein cholesterol level declined from 124 mg/dL (3.2 mmol/L) to 72 mg/dL (1.9 mmol/L). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P<.001).\n For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization.", "nan", "Therapy with individual 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been shown conclusively to diminish coronary event rates and mortality in both primary and secondary prevention. To date, scant attention has been paid to whether initiation of such regimens in the hospital phase of acute coronary syndromes might confer cardioprotective benefits. The purpose of this study was to determine the safety and tolerability of early initiation of statin therapy in patients with acute coronary syndromes. In this randomised, double-blind, three-month, pilot study, 100 patients with acute myocardial infarction or unstable angina and low-density lipoprotein cholesterol > 3.5 mmol/l were randomly assigned to pravastatin 40 mg daily or placebo initiated within 48 hours of hospital admission. Pravastatin proved safe and well tolerated in these patients, who were well matched at baseline. No statistically significant differences in death, MI and drug-related adverse events were observed in the pravastatin group compared with control subjects. This pilot study shows that therapy with pravastatin early after an acute coronary event is safe and well tolerated. Larger, long-term studies are needed to confirm these findings.", "Cholesterol lowering reduces coronary events. One mechanism could be improvement of endothelial function. In line with this hypothesis, this study investigates whether cholesterol reduction can result in rapid improvement of endothelial function after acute coronary syndromes.\n Patients with acute myocardial infarction or unstable angina and total cholesterol levels at admission >/=5.2 mmol/L or LDL >/=3.4 mmol/L were randomized to placebo (n=30) or pravastatin 40 mg daily (n=30) for 6 weeks. Brachial ultrasound was used to measure endothelium-dependent flow-mediated dilatation (FMD) and response to endothelium-independent nitroglycerin. Changes in the levels of markers of platelet activation, coagulation factors, and plasma endothelin levels were also assessed. Total and LDL cholesterol levels were similar at admission and before randomization in both groups. With pravastatin, but not with placebo, they decreased by 23% (P<0.05) and 33% (P<0.01), respectively. FMD was unchanged with placebo, 5.43+/-0.74% (mean+/-SEM) to 5.84+/-0.81%, but increased with pravastatin, 4.93+/-0.81% to 7.0+/-0.79% (P=0.02), representing a 42% relative increase. Responses to nitroglycerin were similar during the time course of the study in the 2 groups. Markers of platelet activity, coagulation factors, and endothelin levels were not affected by pravastatin.\n Cholesterol reduction with pravastatin initiated early after acute coronary syndromes rapidly improves endothelial function after 6 weeks of therapy.", "Residual ischaemia following acute myocardial infarction (AMI) is related to an adverse outcome, although the effect of early initiation of statin therapy is unknown.\n A randomized, placebo-controlled, double-blind, parallel study was performed, which compared fluvastatin 80 mg daily with placebo in patients with an AMI and total cholesterol of <6.5 mmol.l(-1). Ischaemia was measured by ambulatory electrocardiographic (AECG) monitoring over 48-h at baseline, after 6 weeks and at 12 months.\n Five hundred and forty patients were included (83% male, age 61+/-11 years); 43% had an anterior AMI and 50% were treated with fibrinolytics in the acute phase. After 12 months, the total cholesterol (TC) level was reduced by 13% and LDL-C (low-density-lipoprotein cholesterol) by 21% (from 3.5 mmol.l(-1) to 2.7 mmol.l(-1)) in the fluvastatin treatment group. Both TC and LDL increased by 9% in the placebo group (P<0.001 between groups). At baseline, ischaemia on AECG was present in only 11% of patients, and absent in 77%; in the remaining 11%, recordings were technically inadequate. After 6 weeks, 32/48 (67%), and 12 months 35/46 (76%) of the patients with ischaemia on the baseline AECG, no longer showed signs of ischaemia. Nevertheless, ischaemia at baseline was predictive for the occurrence of any major clinical event (RR=2.35; 95% CI 1.39-3.2;P <0.001). Fluvastatin treatment did not affect ischaemia on AECG, nor the occurrence of any major clinical events as compared to placebo. Post-hoc analysis in patients with the most pronounced ischaemia at baseline showed a trend for a beneficial effect of fluvastatin on major clinical events (P=0.084).\n Residual ischaemia after AMI is observed less frequently in the present study, than in earlier studies, although it is predictive for future cardiovascular events. As a result, the present study was underpowered, and no effect of fluvastatin on AECG ischaemia, or major clinical events in the first year after AMI, could be detected. The present data do not confirm other reports which support widespread use of statin treatment early after AMI.\n Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd.", "Secondary prevention of coronary heart disease by antilipidemic therapy beginning at > or =3 months after an acute coronary syndrome is well documented. The impact, however, of immediate initiation of antilipidemic therapy on coronary stenoses and clinical outcome in patients with acute coronary syndrome is unknown. In our study, patients were randomized, on average, 6 days after an acute myocardial infarction and/or percutaneous transluminal coronary angioplasty secondary to unstable angina, to pravastatin (combined, when necessary, with cholestyramine and/or nicotinic acid) to achieve low-density lipoprotein cholesterol levels of < or =130 mg/dl (group A, n = 70). In controls (group B, n = 56), antilipidemic therapy was determined by family physicians. Quantitative coronary angiography was performed at inclusion, and at 6- and 24-month follow-up. The combined clinical end points were total mortality, cardiovascular death, nonfatal myocardial infarction, need for coronary intervention, stroke, and new onset of peripheral vascular disease. Minimal lumen diameter in group A increased by 0.05 +/- 0.20 mm after 6 months and 0.13 +/- 0.29 mm after 24 months, whereas it decreased by 0.08 +/- 0.20 mm and 0.18 +/- 0.27 mm, respectively, in group B (p = 0.004 at 6 months and p <0.001 at 24 months). After 2 years, 29 patients of 56 patients in group B, but only 16 of 70 patients in group A, experienced a clinical end point (p = 0.005; odds ratio 0.28, confidence intervals 0.13 to 0.6). We conclude that pravastatin-based therapy initiated immediately after an acute coronary syndrome is well tolerated and safe, lessens coronary atherosclerosis, and has a pronounced clinical benefit.", "The efficacy of statin drugs after an acute coronary event is now well established, but the evidence for statin use in the early treatment of acute coronary events remains unclear.\n We tested the effects of administering pravastatin within 24 hours of the onset of symptoms in patients with unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction. Patient recruitment of 10,000 with 1200 end points was planned, but the trial was stopped early. A total of 3408 patients were randomly assigned to treatment with pravastatin (1710 patients) or matching placebo (1698 patients). Treatment was continued for 4 weeks. The primary end point of the study was a composite of death, recurrence of myocardial infarction, or readmission to hospital for unstable angina within 30 days of random assignment.\n The primary end point occurred in 199 of patients allocated to pravastatin (11.6%) and in 211 patients allocated to placebo (12.4%). A relative risk reduction of 6.4% favored allocation to pravastatin but was not statistically significant (95% CI, -13.2% to 27.6%). No adverse effects were seen.\n We conclude that 20 to 40 mg of pravastatin can be safely administered within 24 hours of the onset of symptoms of an acute coronary event, with a favorable but not significant trend in outcome at 30 days compared with placebo.", "The primary aim of the study was to investigate the effect of sinvastatin on plasma interleukin-6 (IL-6) in patients with unstable angina pectoris (UAP).\n Eighty-six patients with UAP were randomized into simvastatin (40 mg/d for 4 weeks) and the placebo group. Plasma IL-6 was measured by ELISA.\n There was a reduction in the plasma total cholesterol and LDL in the simvastatin group (P < 0.01). The simvastatin group also had better angina control than the placebo group (post-treatment angina score, 0.72+/-0.59 vs 1.07+/-0.76, P < 0.05). Following treatment, the average left ventricular ejection fraction in the simvastatin group was higher than in the placebo group (0.54+/-0.06 vs 0.51+/-0.05, P < 0.05), whereas the plasma BNP levels were lower (16.8+/-6.6 vs 26.4+/-1.4, P < 0.01). Before treatment, there was no difference in the plasma levels of IL-6 between the simvastatin and the placebo groups (P > 0.05). Following treatment, the IL-6 levels in the simvastatin group were lower than in the placebo group (0.7+/-0.4 vs 1.2+/-0.4 pg/ml, P < 0.05).\n Short-term treatment with simvastatin reduces plasma IL-6. The anti-inflammatory effect of simvastatin may contribute to its beneficial effects on the ventricular function and angina control.", "Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS.\n The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy.\n We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037).\n This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS.\n NCT00171275.", "In spite of a large number of studies on the use of HMG-CoA-reductase inhibitors (statins) in treatment of different forms of coronary artery disease, the efficacy of their early administration in acute coronary syndrome (ACS) is still unclear. The purpose of the present investigation was to study the effects of medium doses (40 mg per day) of simvastatin on the clinical course of ACS and blood levels of C-reactive protein (CRP) and lipids in ACS patients to whom the drug was administered on the first day of the disease. One hundred and eight patients with ACS were randomized into two groups: the control group receiving standard therapy, and the main group receiving in addition 40 mg of simvastatin beginning on the first day of the disease. Blood levels of lipids and CRP were measured by a precise qualitative technique on the first and fourteenth days of the disease. The clinical course of the disease was evaluated during six months from the first day of hospital stay. Mean CRP level decreased significantly within two weeks in the group of patients receiving simvastatin (from 14.9 +/- 9.7 to 7.6 +/- 6.0 mg/l; p = 0.02). In the control group CRP concentration decreased less and not significantly (from 16.1 +/- 7.3 to 13.2 +/- 6.8 mg/l; p = 0.18). Two main types of the dynamics of CRP level were revealed in the ACS patients. Most patients in both groups displayed a decrease in CRP level by the fourteenth day of the disease. At the same time, in some patients CRP level grew during this period, and these patients had stenocardia and required repeated hospital admissions due to ACS recurrence significantly more frequently during the following six months (relative risk 1.4; 95% confidence interval 1.1 to 1.8). The frequency of postinfarction stenocardia was the most substantial and significant clinical difference between the groups (50.9% in the control group, and 23.6% in the main group, p = 0.04). Thus, early therapy with simvastatin in ACS lowers SRP level and the frequency of postinfarction stenocardia. The elevation of CRP level during the first two weeks of the disease is a poor prognostic sign.", "Percutaneous coronary intervention (PCI) is associated with excellent short-term improvements in ischemic symptoms, yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events (MACE).\n To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI.\n Randomized, double-blind, placebo-controlled trial conducted at 77 referral centers in Europe, Canada, and Brazil.\n A total of 1677 patients (aged 18-80 years) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL (3.5-7.0 mmol/L), with fasting triglyceride levels of less than 400 mg/dL (4.5 mmol/L).\n Patients were randomly assigned to receive treatment with fluvastatin, 80 mg/d (n = 844), or matching placebo (n = 833) at hospital discharge for 3 to 4 years.\n Survival time free of MACE, defined as cardiac death, nonfatal myocardial infarction, or reintervention procedure, compared between the treatment and placebo groups.\n Median time between PCI and first dose of study medication was 2.0 days, and median follow-up was 3.9 years. MACE-free survival time was significantly longer in the fluvastatin group (P =.01). One hundred eighty-one (21.4%) of 844 patients in the fluvastatin group and 222 (26.7%) of 833 patients in the placebo group had at least 1 MACE (relative risk [RR], 0.78; 95% confidence interval [CI], 0.64-0.95; P =.01). This result was independent of baseline total cholesterol levels (above [RR, 0.76; 95% CI, 0.56-1.04] vs below [RR, 0.77; 95% CI, 0.57-1.02] the median). In subgroup analysis, the risk of MACE was reduced in patients with diabetes (n = 202; RR, 0.53; 95% CI, 0.29-0.97; P =.04) and in those with multivessel disease (n = 614; RR, 0.66; 95% CI, 0.48-0.91; P =.01) who received fluvastatin compared with those who received placebo. There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group.\n Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events.", "Recent clinical trials have demonstrated that aggressive lipid lowering by statins could prevent recurrent events after acute coronary syndrome (ACS). We hypothesized that this efficacy was caused by a significant reduction in plaque volume by aggressive LDL cholesterol (LCL-C) lowering. The present study investigated the effect of early statin treatment on plaque volume of a nonculprit lesion by serial volumetric intravascular ultrasound in patients with ACS.\n Seventy patients with ACS were enrolled. All patients underwent emergency coronary angiography and percutaneous coronary intervention (PCI). They were randomized to intensive lipid-lowering therapy (n=35; atorvastatin 20 mg/d) or control (n=35) groups after PCI. Volumetric intravascular ultrasound analyses were performed at baseline and 6-month follow-up for a non-PCI site in 48 patients (atorvastatin, n=24; control, n=24). LDL-C level was significantly decreased by 41.7% in the atorvastatin group compared with the control group, in which LDL-C was increased by 0.7% (P<0.0001). Plaque volume was significantly reduced in the atorvastatin group (13.1+/-12.8% decrease) compared with the control group (8.7+/-14.9% increase; P<0.0001). Percent change in plaque volume showed a significant positive correlation with follow-up LDL-C level (R=0.456, P=0.0011) and percent LDL-C reduction (R=0.612, P<0.0001), even in patients with baseline LDL-C <125 mg/dL.\n Early aggressive lipid-lowering therapy by atorvastatin for 6 months significantly reduced the plaque volume in patients with ACS. Percent change in plaque volume showed a significant positive correlation with percent LDL-C reduction, even in patients with low baseline LDL-C.", "C-reactive protein (CRP) levels are associated with cardiovascular risk. We assessed the hypothesis that atorvastatin might have anti-inflammatory effects in acute coronary syndromes (ACS) as shown by CRP reduction.\n This study was a prospective, randomized, double-blind, placebo-controlled study of 90 consecutive patients admitted within 48 hours of onset of ACS with CRP levels > or =1.4 mg/dL. Patients were assigned to atorvastatin 40 mg daily or placebo over 30 days. C-reactive protein levels, lipid profiles, serum fibrinogen, white cell count, and erythrocyte sedimentation rate were measured at entry, hospital discharge, and 1 month later.\n Baseline clinical characteristics did not differ between atorvastatin and placebo groups (mean age 59.3 +/- 13.4 vs 61.1 +/- 11.5, P = ns); myocardial infarction 52.3% versus 67.4% ( P = ns). In both groups, median baseline CRP levels were comparable (5.97 +/- 6.2 vs 4.64 +/- 4.2 mg/dL, P = ns). C-reactive protein levels were lower in the atorvastatin group versus control group at discharge (1.68 +/- 1.65 vs 4.12 +/- 4.18 mg/dL) and at 30 days (0.50 +/- 0.71 vs 2.91 +/- 2.68 mg/dL, both P < .0001). C-reactive protein levels significantly decreased from baseline to discharge and 1 month later in placebo and atorvastatin groups (both P < .0001); however, the reduction was greater in the atorvastatin group (62% vs 11% at discharge [P < .0001]; 84% vs 30% at 1 month [P < .0001]). In addition, atorvastatin was associated with a reduction in total and low-density lipoprotein cholesterol and erythrocyte sedimentation rate at discharge and at 30 days (P < .0001 for all comparisons). No correlation was found between changes in CRP and cholesterol levels.\n C-reactive protein levels in ACS were rapidly reduced with atorvastatin. These data provide evidence that statins have fast and early anti-inflammatory effects in addition to lipid-lowering effects in ACS.", "It is unclear whether early initiation of low-dose pravastatin therapy can reduce the occurrence of major adverse cardiac events after acute myocardial infarction (AMI).\n The study group comprised 353 patients with AMI who had plasma total cholesterol levels of 200-250 mg/dl and triglyceride levels <300 mg/dl. The patients were randomly assigned to either receive pravastatin (10 mg/daily, n=176) or not (n=177). The primary endpoint was a composite of death, nonfatal myocardial infarction (MI), unstable angina (UA), stroke, revascularization, and rehospitalization because of other cardiovascular disease. The follow-up period was 9 months. The primary endpoint occurred in 31 patients (17.9%) in the pravastatin group and 55 patients (31.4%) in the non-pravastatin group (relative risk, 0.56; 95% confidence interval, 0.36-0.87). There were no significant differences in the risk of death, nonfatal MI, UA, and stroke between the 2 groups, although the pravastatin group had a lower risk of need for revascularization.\n For patients with AMI, early and low-dose pravastatin therapy (10 mg/daily) reduces recurrent major adverse cardiac events, mostly the requirement for revascularization.", "Statins have been shown to prevent coronary artery disease and to preserve left ventricular function in dilated cardiomyopathy. We hypothesized that early use of statins would decrease cardiovascular events, including heart failure in patients with acute myocardial infarction (AMI). To examine the effect of statins in Japanese patients with AMI, a prospective, randomized, open-label trial was conducted in 486 patients with normal total cholesterol levels. Patients were randomly assigned to receive any available statin (n = 241) within 96 hours of AMI onset or no statin (n = 245) and were followed for up to 24 months. The primary end point was a composite of cardiovascular death, nonfatal AMI, recurrent symptomatic myocardial ischemia, congestive heart failure, and stroke. Event rate for the primary end point was lower in the statin group than in the nonstatin group (6.1% vs 11.4%, p = 0.0433). The statin group had a lower risk of congestive heart failure and symptomatic myocardial ischemia (p = 0.0154 and 0.0264, respectively). In conclusion, early lipid-lowering therapy with statins decreases recurrent cardiovascular events, in particular, congestive heart failure.", "Pravastatin was administered to patients suffering an acute myocardial infarction starting with a dose of 10 mg/day at day 3 and continuing with a dose of 20 mg/day up to a period of 3 months. The study was performed on the basis of a randomized placebo-controlled double-blind trial. At the dosage used pravastatin significantly lowered the total cholesterol and LDL-cholesterol levels and increased the HDL-cholesterol levels compared to placebo. A prospective clinical trial in order to examine the possible clinical relevance of these findings is recommended.", "To determine whether statin therapy initiated early in acute myocardial infarction together with thrombolytic therapy in patients with acute myocardial infarction results in clinical benefit through early plaque stabilization.\n The study population consisted of 77 patients who underwent coronary balloon angioplasty of the infarct-related artery during the first month of acute myocardial infarction. These patients belonged to the cohort of the Pravastatin Turkish Trial (PTT). Forty of them were assigned randomly to have immediate pravastatin (40 mg/day) therapy adjunctive to thrombolytic therapy regardless of serum lipid levels and received statin treatment throughout the study. Lipid levels were determined immediately after admission and before angioplasty and at the end of 6 months. Patients were re-evaluated clinically and angiographically for cardiovascular adverse events and restenosis after a 6-month follow-up period. The baseline angiographic and clinical characteristics of the two groups were similar. The incidence of angina was significantly lower in the pravastatin group (30.0%, 12 patients) compared to the control group (59.5%, 22 patients) (p = 0.018). The cumulative major adverse cardiac events in the pravastatin group were significantly lower when compared to the control group (32.5% vs. 75.6%, p = 0.0001).\n Early initiation of pravastatin therapy immediately after an acute myocardial infarction significantly decreased the frequency of major cardiac adverse events. Such early potential clinical benefits further strengthen the rationale for starting statin treatment as soon as possible after acute coronary events particularly in patients in whom invasive intervention is planned." ]

[ "3465448", "4395021", "7016089", "3476237", "3910338", "356989", "6572128", "288179", "8521431", "3475184", "3895545", "1890532", "271002", "284065" ]

[ "Caries-preventive effect of Duraphat varnish applications versus fluoride mouthrinses: 5-year data.", "The effect of a fluoride gel used for supervised toothbrushing 15 or 30 times per year.", "The anticaries effect of single and combined topical fluoride systems in school children.", "Effect of fluoride containing dentifrice, mouthrinsing, and varnish on approximal dental caries in a 3-year clinical trial.", "Three-year caries increments after fluoride rinses or topical applications with a fluoride varnish.", "A three-year clinical study to determine the separate and combined caries-inhibiting effects of sodium monofluorophosphate toothpaste and an acidulated phosphate-fluoride gel.", "Combined effects of a fluoride dentifrice and mouthrinse on the incidence of dental caries.", "Effect of flouride varnish (Duraphat) treatment every six months compared with weekly mouthrinses with 0.2 per cent NaF solution on dental caries.", "Fluoride varnish versus acidulated phosphate fluoride gel: a 3-year clinical trial.", "Caries preventive effect of two fluoride varnishes and a fluoride mouthrinse.", "Effect on caries of different fluoride prophylactic programs in preschool children. A two year clinical study.", "Effectiveness of fortnightly tooth brushing with amine fluorides in caries-prone subjects.", "Clinical testing of a mouthrinse and a dentifrice containing fluoride. A two-year supervised study in school children.", "The caries-preventive effect of amine fluorides and inorganic fluorides in a mouthrinse or dentifrice after 30 months of use." ]

[ "nan", "nan", "nan", "The purpose of this study was to evaluate the separate effect of fluoride dentifrice, fluoride mouthrinsing and fluoride varnish on approximal dental caries. All 252 13-14-yr-old children at an elementary school were selected at random and divided among four groups for a 3-yr longitudinal study. Group 1 received a fluoride dentifrice for home care and a fluoride mouthrinse once a week. Group 2 received a fluoride dentifrice for home care and a placebo mouthrinse once a week. Group 3 received a fluoride dentifrice for home care and a fluoride varnish once every 3 months. Group 4 received a placebo dentifrice for home care and a fluoride rinse once a week. Fluoride rinsing did not give any additional effect compared with placebo-rinsing when a fluoride dentifrice was used for home care. Fluoride varnish gave a significant caries reduction compared with fluoride rinsing.", "251 9-12-yr-old children completed a 3-yr, double-blind, clinical trial of two caries preventive fluoride programs. Caries increments and progression patterns were compared in two groups of children who rinsed every fortnight with a 0.2% NaF solution or received biannual topical applications with a fluoride varnish (Fluor-Protector). Clinically recorded mean DFS increments were 3.3 +/- 0.2 (SE) in the rinse group and 3.5 +/- 0.2 in the varnish group. In both groups nearly half of these increments were recorded in the occlusal surfaces of second molars. The mean incremental DFS recorded radiographically on approximal surfaces of posterior teeth were 1.1 +/- 0.2 and 1.5 +/- 0.2 in the rinse and varnish group, respectively. None of the inter-group differences were statistically significant (P greater than 0.05). Detailed analyses of the radiographic scores revealed a similar and extremely slow caries progression in the two study groups and they strengthened the conclusion of equal clinical efficacy of the two treatments. None of the fluoride programs had been able to change preestablished patterns of caries development among the children.", "nan", "751 14- and 15-year old children completed a 3-year, double-blind, caries preventive program. The effects of daily, supervised toothbrushing with an 0.76% sodium monofluorophosphate dentifrice, rinsing with a 0.05% sodium fluoride mouthrinse, and the combined effects of the two treatments were investigated. Both the dentifrice and mouthrinse reduced the incidence of dental caries, but their combined use at the same time had no greater effect than either used alone.", "Recent studies have shown a high fluorine uptake in the enamel and a considerable caries reduction following the application of varnished containing fluoride. As the application is easy to carry out it may in certain situations serve as an alternative to other topical fluoride school programmes. The aim of the present study, therefore, was to compare the caries increment in schoolchildren exposed to a fluoride varnish (Duraphat) every six months and in children receiving the conventional weekly fluoride mouthrinsing programme with 0.2 per cent sodium fluoride over a two-year period. Two hundred 14-year-old children, divided into one test and one control group took part in the study. They were clinically and radiographically examined every year. Preexperimental data revealed no differences between the groups. During the experimental period the children in the fluoride varnish group developed a statistically significant lower number of new carious lesions compared with those in the mouthrinsing group. The difference in caries increment was about 30 per cent. Further clinical studies to compare the effects of various topical fluoride programmes are recommended.", "The aim of this trial was to compare the caries-preventive effect of sodium fluoride varnish and acidulated phosphate fluoride (APF) gel. A total of 254 children aged 12-13 years with high past caries experience were randomly divided into two groups. The participants received semi-annual applications of either fluoride varnish or APF gel for 3 years. During the study, the mean (+/- SD) total DMFS increments of the varnish and gel groups were 6.8 +/- 5.6 and 7.7 +/- 6.4, respectively, when initial caries was included, and 3.1 +/- 3.7 and 3.6 +/- 4.6 when initial caries was excluded. The difference was most evident on the approximal surfaces (varnish: 1.4 +/- 2.4; gel: 1.9 +/- 3.1). However, this difference was not statistically significant. Although larger studies are needed for firm conclusions about the comparative effect of the two fluoride measures, the results suggest that fluoride varnish is as effective as fluoride gel at least in preventing approximal caries. Taking into account the shorter treatment time, using fluoride varnish for professional applications seems justified.", "nan", "376 three-year old children were divided into four experimental groups and exposed to different combinations of preventive programs for a period of two years. All the groups were given the same basic prophylactic information. Additionally Group I received fluoride tablets (FLUDENT) for daily sucking twice a day plus a placebo dentifrice free of fluoride. Group II was given a fluoride dentifrice containing 0.025% F, (ACTA). Group III was given a placebo dentifrice plus fluoride varnish (Duraphat) twice a year. Group IV a fluoride dentifrice containing 0.025% F (ACTA) plus fluoride varnish (Duraphat) twice a year. No statistically significant difference in caries increment during the two experimental years was found between the groups. A tendency to lower caries increment was found in Group IV, i.e. in the children using the low fluoride dentifrice and treated twice a year with fluoride varnish.", "The aim of this study was to assess the caries incidence and plaque accumulation in schoolchildren at caries risk, after brushing the teeth fortnightly with gels containing 0, 0.4% F, 1.25% F as amine fluoride (AmF) or the common amine fluoride toothpaste containing 0.125% F. The study was conducted double blind over an 18-month period, and after 6 months discontinuation of brushing. Only the group that brushed with the 1.25% AmF gel showed a significant decrease in caries development compared to the group that brushed with the 0.125% AmF toothpaste. During the 6-month discontinuation period, the incidence of caries increased in all groups; the differences in caries development between all groups were not significant. Plaque indices were significantly lower in the AmF-treated groups. The highest fluoride concentration in the gel reduced the development of caries to zero, probably due to increased fluoride levels in the oral milieu of caries risk children. In order to maintain a positive effect of fluoride over an extended time period, caries-prone subjects should continue an initiated fluoride programme.", "nan", "The study groups using a dentifrice and mouthrinse both containing fluorides, a dentifrice containing stannous fluoride and a mouthrinse containing sodium fluoride, or a mouthrinse containing sodium fluoride with a placebo dentifrice had a 20.7% to 29.0% lower DMF increment than the control group after 30 months. These differences were significant. The study groups using a dentifrice containing amine fluorides and a placebo mouthrinse, a mouthrinse containing amine fluorides and a placebo dentifrice, or a dentifrice containing stannous fluoride and a placebo mouthrinse had a 13.6% to 22.4% lower DMF increment than the control group. These differences were not statistically significant. There was no significant difference in effectiveness against caries between the use of the organic or inorganic fluoride products." ]

[ "1463951", "8013170", "9115527", "5504074", "3978484", "2320489" ]

[ "Management of feverish children at home.", "Tepid sponging to reduce temperature in febrile children in a tropical climate.", "The efficacy of tepid sponge bathing to reduce fever in young children.", "Evaluation of sponging and of oral antipyretic therapy to reduce fever.", "Evaluation of sponging to reduce body temperature in febrile children.", "Efficacy of sponging vs acetaminophen for reduction of fever. Sponging Study Group." ]

[ "To compare the acceptability and effects on temperature of advice to unwrap children and give paracetamol or warm sponging treatments in the management of feverish illness at home.\n A randomised, open, parallel group study using factorial design comparison of unwrapping, warm sponging plus unwrapping, paracetamol plus unwrapping, and paracetamol and warm sponging plus unwrapping.\n Homes of willing families with a feverish child recruited after consulting one of 21 participating general practitioners in Southampton.\n 52 children aged from 3 months to 5 years with axillary temperatures before treatment of > or = 37.8 degrees C and < 40 degrees C.\n Response to advice assessed over four hours; temperature assessed by continuous data logging from an axillary thermistor; acceptability of treatment to child and parent scored on Likert scales immediately after treatment and on return to health.\n Response to treatment advice varied; unwrapping alone had little effect on temperature. Paracetamol increased the time below 37.2 degrees C in four hours by 109 (95% confidence interval 74 to 145) minutes compared with unwrapping; warm sponging caused the fastest reduction in temperature. Parents discriminated between treatments, preferring paracetamol.\n Advice to give paracetamol is more effective than sponging or unwrapping in controlling temperature in children at home and is more acceptable to parents. Warm sponging has an additive effect and reduces fever more quickly than paracetamol.", "The effectiveness of tepid sponging, in addition to antipyretic medication, in the reduction of temperature in febrile children living in a tropical environment, was assessed in a prospective, randomized, open trial. Seventy-five children aged between 6 and 53 months who attended the casualty department of the Children's Hospital, Bangkok, Thailand, with fever (rectal temperature > or = 38.5 degrees C) of presumed viral origin were randomized to received either tepid sponging and oral paracetamol (sponged group) or paracetamol alone (control group). Rectal temperature and the occurrence of crying, irritability, and shivering were recorded over the following 2 hours. A greater and more rapid fall in mean rectal temperature occurred in the sponged group than in the control group. Temperature fell below 38.5 degrees C sooner in children in the sponged group than in control children (P < 0.001). At 60 minutes, 38 (95.0%) of the controls still had a temperature of 38.5 degrees C or greater, compared with only 15 children (42.9%) in the sponged group (P < 1 x 10(-5). Crying was associated with sponging, but shivering and irritability occurred in only one child who was being sponged. It is concluded that tepid sponging, in addition to antipyretic medication, is clearly more effective than antipyretic medication alone in reducing temperature in febrile children living in a tropical climate.", "Tepid sponge baths distress febrile children, and their efficacy at reducing fever has not been established. This study compared fever reduction and with (1) acetaminophen alone and (2) acetaminophen plus a 15-minute tepid sponge bath. Twenty children, ages 5 to 68 months, who presented to the emergency department or urgent care center with fever of > or = 38.9 degrees C were randomized to receive (1) acetaminophen alone or (2) acetaminophen plus a 15-minute tepid sponge bath. All subjects received a 15-mg/kg dose of acetaminophen. Tympanic temperature was monitored every 30 minutes for 2 hours. Subjects were monitored for signs of discomfort (crying, shivering, goosebumps). Sponge-bathed subjects cooled faster during the first hour but there was no significant temperature difference between the groups over the 2-hour study period (P = .871). Subjects in the sponge bath group had significantly higher discomfort scores (P = .009).", "nan", "A study was conducted to evaluate the efficacy of sponging as a way of reducing body temperature in febrile children. Of 130 children 73 received antipyretic medication and sponging and 57 received antipyretic medication alone. No difference in temperature reduction was noted between the two groups. It is therefore suggested that sponging be abandoned as a mode of temperature reduction in febrile children whose increased temperature is due to an infectious process.", "Seventy-three children with acute febrile illnesses were enrolled in a study to compare the efficacy of sponging, sponging plus acetaminophen, and acetaminophen alone as methods of lowering body temperature. The greatest temperature reduction was seen in the combined acetaminophen plus sponging group. The smallest temperature reduction was noted in children who received sponging alone. We urge reconsideration of routine sponging of febrile young patients." ]

[ "15681939", "8029811", "16432349", "16442954", "12514144" ]

[ "Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial.", "Modulation of coagulation and fibrinolysis in hepatic resection: a randomized prospective control study using antithrombin III concentrates.", "Perioperative parenteral tranexamic acid in liver tumor resection: a prospective randomized trial toward a \"blood transfusion\"-free hepatectomy.", "Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial.", "Desmopressin does not decrease blood loss and transfusion requirements in patients undergoing hepatectomy." ]

[ "Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.\n Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.\n The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04).\n Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.", "A randomized prospective control trial for determining the efficacy of antithrombin III concentrates in hepatic resection was performed using 24 patients with hepatocellular carcinoma. Thirteen patients were given antithrombin III concentrates (1,500 IU) immediately before operation, during hepatectomy and immediately after operation. Coagulant and fibrinolytic profiles were determined by molecular markers such as thrombin-antithrombin III complex and plasmin-alpha 2plasmin inhibitor complex. During hepatic resection, both hypercoagulability and mainly primary hyperfibrinolysis occurred. Regarding the effectiveness of antithrombin III concentrates, in the antithrombin III treatment group, only a significant lower incidence of positive soluble fibrin monomer complex at postoperative days 1 and 5 was found among all the parameters studied. Therefore, no definite evidence of clinical usefulness of the perioperative administration of antithrombin III concentrates in hepatic resection was proved.", "To examine the feasibility of a real \"blood transfusion\"-free hepatectomy in a large group of patients with liver tumors.\n Bleeding control and blood transfusion remains problematic in liver resection. A real \"blood transfusion\"-free hepatectomy in a large group of patients has rarely been reported. The impact of tranexamic acid (TA), an antifibrinolytic agent, on blood transfusion in liver resection is unknown.\n A prospective double-blind randomized trial was performed on elective liver tumor resections. In group A, TA 500 mg was intravenously administered just before operation followed by 250 mg, every 6 hours, for 3 days. In group B, only placebo was given. The patients' background, blood transfusion rates, and early postoperative results in the 2 groups were compared. Factors that influenced blood requirement were analyzed.\n There were 108 hepatectomies in group A and 106 hepatectomies in group B. The patients' backgrounds, operative procedures, and hepatectomy extent did not significantly differ between the 2 groups. Although the differences of the operative morbidity and postoperative stay were not significant, a significantly lower amount of operative blood loss, lower blood transfusion rate, shorter operative time, and lower hospital costs were found in group A patients. No patient in group A received blood transfusion. No hospital mortality occurred in either group. Tumor size and use of TA were independent factors that influenced blood transfusion.\n Perioperative parenteral use of TA reduced the amount of operative blood loss and the need for blood transfusion in elective liver tumor resection. A real \"blood transfusion\"-free hepatectomy may be feasible with the assistance of parenteral TA.", "Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy. We evaluated the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy.\n Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo, administered intravenously 10 minutes before surgery and every second hour during surgery. The primary efficacy end points were the proportion of patients receiving red blood cell (RBC) transfusions and the amount of RBCs transfused. The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events.\n No statistically significant effect of rFVIIa treatment on efficacy end points was observed. Serious and thromboembolic adverse events occurred at similar incidences in the study groups.\n Using blood loss as a transfusion trigger, the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study. No safety concerns were identified.", "To determine the effects of desmopressin on coagulation and blood loss in patients undergoing elective partial hepatectomy.\n A randomized, controlled and double-blind study on 59 patients who received either 0.3 micro g x kg(-1) of desmopressin or an equal volume of normal saline (control) infused intravenously over 20 min after induction of general anesthesia.\n There was an increase in plasma levels of factors VIII and von Willebrand after the infusion of study drug in both groups (P < 0.001). The activated partial thromboplastin time was shortened in Group D whereas prothrombin time was prolonged in Group C; (P = 0.02). A large range of intraoperative blood loss (400-7128 mL) was observed, with no significant differences between groups. There were no changes in plasma electrolyte levels or osmolality. Transfusion requirements were similar in both groups.\n Desmopressin did not reduce intraoperative blood loss or transfusion requirements during hepatectomy despite raising clotting factor levels and improving tests of hemostasis." ]

[ "1996888", "16275171" ]

[ "Neonatal screening for cystic fibrosis in Wales and the West Midlands: clinical assessment after five years of screening.", "Cystic fibrosis mutations and genotype-pulmonary phenotype analysis." ]

[ "Screening of the newborn for cystic fibrosis by measurement of immunoreactive trypsin has been undertaken on alternate weeks in Wales and the West Midlands for five years since 1985 to evaluate the possible clinical benefits of early diagnosis. Patients detected by screening and those diagnosed by clinical symptoms alone were assessed annually for differences in clinical, anthropometric, and biochemical variables. Fifty eight infants not considered to be at risk of cystic fibrosis (they did not present with meconium ileus and do not have a sibling with cystic fibrosis) have been detected by screening and they have been compared with 44 children who were diagnosed clinically. This latter group includes nine children whose screening was negative but who were recognised subsequently to have cystic fibrosis. The mean age at diagnosis of the screened group was significantly lower than that of the group diagnosed clinically. Excluding admissions for diagnostic tests for cystic fibrosis, the screened group spent a significantly shorter time in hospital during the first year of life. The results of all other comparisons made between the screened group and those diagnosed clinically were similar up to the age of 4 years.", "Although there are more than 1000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, most of them are uncommon and only limited information exists regarding genotype-pulmonary phenotype relationships.\n We determined and classified the CFTR mutations using denaturing high-performance liquid chromatography and developed new, quantitative methods to categorize pulmonary phenotypes.\n Two novel alleles were discovered, namely G1047R and 1525-2A-->G, which were accompanied by F508del and G551D mutations, respectively. Assessment of numerous options revealed that CF pulmonary phenotype categorization in children cannot be accomplished with clinical or pulmonary function data but is facilitated by longitudinal quantitative chest radiology. It was most useful to categorize pulmonary disease status by evaluating the typical pattern of abnormalities in patients homozygous for the F508del mutation, and then compare patients with minor mutations to this typical CF pulmonary phenotype. By this method, both patients with novel mutations have pulmonary phenotypes typical of F508del homozygotes. However, patients with class IV mutations (e.g., R347P) or with pancreatic sufficiency showed serial chest radiographs that were atypically mild.\n Longitudinal quantitative chest radiography provides a new strategy for CF pulmonary phenotype categorization that should be useful for genotype-phenotype delineation in individual patients and in both epidemiologic studies and clinical trials involving groups of children with CF." ]

[ "10691121" ]

[ "A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy." ]

[ "To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy.\n One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated.\n Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2-year follow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12-month remission. Frequency of adverse effects was almost identical in the two groups.\n Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome. and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population." ]

[ "3886308", "3058537", "162660", "11128665", "3236298", "10534546", "3519096", "3057482" ]

[ "Controlled, double-blind, randomized trial of amitriptyline in relieving articular pain and tenderness in patients with rheumatoid arthritis.", "A comparison of dothiepin versus placebo in the treatment of pain in rheumatoid arthritis and the association of pain with depression.", "Imipramine, rheumatoid arthritis and rheumatoid factor.", "Paroxetine versus amitriptyline for treatment of depression associated with rheumatoid arthritis: a randomized, double blind, parallel group study.", "Antidepressant analgesia in rheumatoid arthritis.", "The effects of dothiepin on subjects with rheumatoid arthritis and depression.", "Trimipramine in rheumatoid arthritis: a randomized double-blind trial in relieving pain and joint tenderness.", "Psychomotor performance of patients with rheumatoid arthritis: cross-over comparison of dextropropoxyphene, dextropropoxyphene plus amitriptyline, indomethacin, and placebo." ]

[ "Thirty-six patients with definite or classical rheumatoid arthritis participated in a double-blind, randomized, placebo-controlled trial to assess the effectiveness of adding amitriptyline to the treatment regimen for the relief of pain not adequately controlled by non-steroidal anti-inflammatory drugs. Dosage of amitriptyline was increased gradually up to 25 mg 3-times daily and patients were followed up for 12 weeks. Assessments were made of joint pain and tenderness every 4 weeks. The results showed no difference between the amitriptyline and placebo-treated patients for either parameter.", "The effectiveness of dothiepin (a tricyclic anti-depressant) at a dose of 75 mg given orally at night was compared with placebo for 4 weeks in alleviating pain in 60 patients with classical or definite active rheumatoid arthritis. Patients were classified as either 'depressed' or 'not depressed'. The week before, during and 2 weeks after the study, 600 mg ibuprofen was given orally three times daily to all patients. Compared with placebo, dothiepin produced a significant reduction in daytime pain by the end of the treatment period. The Hamilton rating scale in 'depressed' patients was significantly improved in patients given dothiepin. The Cassano-Castrogiovanni self-evaluation rating scale in both 'depressed' and 'not depressed' patients showed a tendency (not significant) to be improved following dothiepin treatment compared with placebo. These results suggest that patients with rheumatoid arthritis may experience an increase in pain symptoms due to an alteration of mood. Therapy with tricyclic anti-depressants, such as dothiepin, therefore, may determine an improvement of pain indexes besides having an anti-depressant effect.", "nan", "To compare the efficacy and tolerability of paroxetine (a selective serotonin reuptake inhibitor) with that of amitriptyline (a tricyclic antidepressant) in the treatment of depression in 191 patients with rheumatoid arthritis (RA).\n A randomized, double blind, double dummy, parallel group study. A placebo washout period of 3-7 days was followed by an 8 week active treatment phase during which patients received either paroxetine (20-40 mg daily) or amitriptyline (75-150 mg daily). The primary efficacy variable was the change from baseline in Montgomery Asberg Depression Rating Scale score at endpoint.\n Paroxetine was as effective as amitriptyline for the treatment of depression, with similar improvements in RA associated pain and disability also seen in both groups. However, paroxetine was better tolerated than amitriptyline, with an overall frequency of adverse experiences of 56.4% and 67.7% in the 2 groups, respectively. The frequency of anticholinergic adverse experiences was much lower in the paroxetine treatment group (18.1% vs 43.8% taking amitriptyline) and paroxetine treated patients also experienced fewer severe (16.0% vs 21.9%), serious nonfatal (0% vs 4.2%), and drug related adverse experiences (12.8% vs 29.2%).\n Tolerability is an important consideration in this patient population, which is largely composed of elderly patients who are taking additional medications for RA. Paroxetine shows a number of advantages in the management of depression comorbid with RA.", "Forty-seven patients with definite rheumatoid arthritis (RA) were treated in a 32 week, double blind, crossover trial of amitriptyline, desipramine, trazodone, and placebo. All drug regimens produced significant changes on pain measures relative to baseline, but only amitriptyline exceeded placebo. Amitriptyline was associated with a significant reduction in the number of painful/tender joints. Our study supports the efficacy of a moderate dose of amitriptyline as an adjunct drug for the treatment of pain in both depressed and nondepressed patients with RA.", "The relative importance of direct analgesic and antidepressant effects of antidepressant drugs in rheumatoid arthritis (RA) is not clear.\n Forty-eight female out-patients with RA, with depression and/or anxiety, were entered into a double-blind, placebo-controlled study of dothiepin in doses up to 150 mg daily to assess the effects on mood [Hospital Anxiety and Depression (HAD) scale and Hamilton Rating Scale (HRS) for Depression], pain [visual analogue scale (VAS)] and disability [Health Assessment Questionnaire (HAQ)].\n Repeated measures multivariate analysis of variance revealed that treatment had a significant effect on pain (F(d.f. 1,39) =5.7, P=0.02). There were further interaction effects between treatment and time on pain (F(d. f. 3,117) =3.3, P=0.03), disability (F(d.f. 3,117)=4.2, P=0.008) and duration of early morning stiffness (F(d.f. 3,117) =3.3, P=0.03). Depression (HRS) was considerably reduced in both the dothiepin and placebo groups, and there was no significant difference between groups. Post hoc analyses using analysis of covariance revealed that, in the dothiepin group, pain was significantly reduced by week 4 and remained so at week 12. Disability scores and duration of early morning stiffness were consistently lower in the dothiepin group, although differences failed to reach statistical significance at any follow-up assessment. In the group as a whole, reductions in pain were highly significantly correlated with reductions in HAD depression (r =0.63, P<0.0005), HAD anxiety (r=0.46, P=0.001) and HRS depression (r=0.37, P=0.01).\n Dothiepin is effective in relieving pain, disability and reducing the duration of early morning stiffness in out-patients with RA. Although there is a general association between pain reduction and improved anxiety and depression, the analgesic effect of dothiepin is independent of its antidepressant effect. Individual variation is considerable and further research should try to identify mechanisms of interaction between the antidepressant and analgesic effects of treatment in different patient groups.", "The effect of low-dose trimipramine (25 to 75 mg/day) on joint pain and tenderness in 36 patients with rheumatoid arthritis was studied in a randomized double-blind trial carried out over a period of 12 weeks. The patients were pre-selected to include only patients who were depressed on a 'self-rating depression scale' but had no evidence of fibrositic 'trigger-points'. The results showed that joint pain and tenderness were significantly reduced with trimipramine, but depression scores remained unchanged.", "Actions on performance of dextropropoxyphene (DXP) alone and in combination with amitriptyline (AMI), indomethacin (IN), and placebo were compared in 15 patients with rheumatoid arthritis. The patients were on their prescribed maintenance regimen excluding analgesics. In four randomized test sessions at two-week intervals, they received double blind and crossover single oral doses of DXP 130 mg, IN 50 mg, DXP 65 mg + AMI 25 mg or placebo, each after two days' pretreatment with the same drug. Objective and subjective effects were measured at baseline and 2 and 4 hours after drug administration. DXP impaired critical flicker discrimination, symbol copying and body balance without modifying tracking, choice reactions or attention. It rendered the subjects elated, muzzy, mentally slow and calm. Actions of AMI + DXP were about the same. IN impaired body balance and critical flicker recognition. Plasma concentrations of DXP were moderate to high whilst those of IN and AMI were fairly low. We conclude that therapeutic doses of DXP and IN are relatively safe in regard to driving skills. Small doses of AMI may not enhance the mild psychomotor effects of DXP. Earlier single dose studies carried out with healthy volunteers might have overestimated the decremental effects of analgesics on psychomotor performance." ]

[ "6343149", "3888246", "2064943", "6343148", "8215491", "3904810", "3539171", "11703279", "1685841", "4582718", "2974306", "4133022", "6696838", "9990362", "7000136", "2184179", "7039659", "1981434", "3300565", "6203289", "788767" ]

[ "A randomized trial of etretinate (Tigason) in palmoplantar pustulosis.", "The effect of etretinate compared with different regimens of PUVA in the treatment of persistent palmoplantar pustulosis.", "A double-blind, placebo-controlled trial of topical PUVA in persistent palmoplantar pustulosis.", "Efficacy of etretinate (Tigason) in clearing and prevention of relapse of palmoplantar pustulosis.", "Cyclosporine in the treatment of palmoplantar pustulosis. A randomized, double-blind, placebo-controlled study.", "Etretinate in pustular psoriasis of palms and soles.", "Low-dose etretinate in the maintenance of remission of palmoplantar pustular psoriasis.", "Oral liarozole in the treatment of palmoplantar pustular psoriasis: a randomized, double-blind, placebo-controlled study.", "A hydrocolloid occlusive dressing plus triamcinolone acetonide cream is superior to clobetasol cream in palmo-plantar pustulosis.", "Pustulosis palmaris et plantaris.", "Acitretin and etretinate in the treatment of palmoplantar pustulosis: a double-blind comparative trial.", "Pustulosis palmaris et plantaris treated with hydroxyurea.", "A comparison of PUVA-etretinate and PUVA-placebo for palmoplantar pustular psoriasis.", "Double-blind placebo-controlled study of long-term low-dose cyclosporin in the treatment of palmoplantar pustulosis.", "A controlled trial of photochemotherapy for persistent palmoplantar pustulosis.", "Topical PUVA, etretinate, and combined PUVA and etretinate for palmoplantar pustulosis: comparison of therapeutic efficacy and the influences of tonsillar and dental focal infections.", "Failure of colchicine for palmo-plantar pustulosis.", "The effect of grenz ray therapy on pustulosis palmoplantaris. A double-blind bilateral trial.", "PUVA, etretinate, and PUVA-etretinate therapy for pustulosis palmoplantaris. A placebo-controlled comparative trial.", "Treatment of pustulosis palmaris et plantaris with colchicine. A double-blind cross-over trial.", "A double-blind trial of clomocycline in the treatment of persistent palmoplantar pustulosis." ]

[ "5 patients with palmoplantar pustulosis (PPP) were randomized to 8 weeks of daily treatment with either oral etretinate, 1 mg/kg b.w. or placebo. Good or moderate effect was obtained in 18 or 20 patients on etretinate compared o 6 of 21 patients on placebo (p less than 0.001). Etretinate proved to be significantly superior to placebo with regard to influence on the individual symptoms and signs of pustulosis. All patients on etretinate experienced some side effects from the mucous membranes, but they were generally mild. Treatment was discontinued after 4 weeks in 3 patients for reasons unrelated to treatment, in 4 for lack of effect (all on placebo) and in 2 for side effects (both or etretinate). Etretinate is a good alternative to other systemic treatments of PPP.", "Eighty-four patients with persistent palmoplantar pustulosis (PPP) of long duration were treated with either etretinate or one of three PUVA regimens. PUVA was given either with oral methoxsalen (thirteen cases), with a 1% methoxsalen cream (thirty-three cases) or with trioxsalen baths (eighteen cases). Twenty patients were treated with etretinate. Patients were assessed every fourth week. A mean score for each group was calculated at each visit based on erythema, desquamation, induration and pustulation. In addition, the number of pustules was calculated at each visit. After 12 weeks four of twenty-eight patients treated with local methoxsalen and fourteen of seventeen patients treated with etretinate had completely cleared. At this stage no patient treated with local trioxsalen or oral methoxsalen showed complete clearance.", "The effect of topical PUVA was investigated in the treatment of patients with persistent palmoplantar pustulosis (PPP). In this double-blind, placebo-controlled trial of 27 patients with PPP there was an overall improvement of the hands and feet in both the active and placebo-treated areas and little difference between them.", "A total of 40 patients with palmoplantar pustulosis (PPP) were initially treated with oral etretinate (Tigason) in an open trail with a maximum treatment period of 16 weeks. Remission, with only slight residual changes in some cases, was achieved in 26 patients (65%) who were randomized to either a low dose of Tigason or placebo. In the Tigason group, 7 of 11 patients were still in remission afer 6 months while in the placebo group, remission persisted in 4 of the 10 patients who stayed in the study throughout the whole 6 months' period. Alopecia led to stopping the treatment in 6 patients and desquamation of the healthy skin in 2 patients. Other side-effects were only mild. As a conclusion, Tigason shows a beneficial effect in the majority of patients with PPP and is better than placebo in preventing relapse of the disease but intolerable side-effects restrict its use in many patients.", "Palmoplantar pustulosis (PPP) is an inflammatory skin disease characterized by pustule formation, erythema, induration, and scaling of the affected skin of the palms and soles. Palmoplantar pustulosis is usually resistant to treatment. In a double-blind study (phase 1) of 4 weeks, 40 patients with PPP were randomized to receive oral cyclosporine, 2.5 mg/kg per day, or placebo. An open-label dose-finding phase 2 with cyclosporine doses of 1.25, 2.5, and 3.75 mg/kg per day was performed in the following 3 months. The patients were then followed for at least 2 months after termination of cyclosporine treatment. Response to treatment was judged by the number of fresh pustules. Patients displaying a reduction of 50% or greater in the number of pustules, compared with baseline, were defined as responders.\n Of the patients who completed phase 1, 17 of 19 patients in the cyclosporine group and four of 15 in the placebo group were classified as responders (P < .001). Cyclosporine, but not placebo, significantly reduced formation of new pustules (P = .001). In the subsequent open phase, a daily cyclosporine dose of 1.25 mg/kg appeared to be an effective treatment of PPP in approximately half of the treated patients. Many patients relapsed after initial success with cyclosporine. However, only one patient studied totally failed to respond to cyclosporine treatment. At the end of phase 3, most of the studied parameters had returned to pretreatment levels. The most common side effect was headache in the 2.5 mg/kg per day dosage group; no significant side effects were observed in the 1.25 mg/kg per day dosage group.\n Low-dose cyclosporine treatment (1.25 to 2.5 mg/kg per day) is effective in PPP.", "In a double-blind controlled study of patients with pustular psoriasis of palms and soles who were allocated at random to etretinate or placebo, we found that etretinate improved the condition as assessed by pustule count and overall clinical response. Side-effects occurred but were accepted by the patients in the short-term. The clinical usefulness of etretinate in this condition will depend on time to relapse, and whether this can be prevented or postponed by continuous treatment. Toxicity in the long-term will also be important.", "Twenty patients with palmoplantar pustular psoriasis were treated initially for 4 weeks with 70 mg etretinate daily. This led to clinical improvement and a significant fall in pustule count. The patients were then allocated randomly to 30 mg etretinate daily or placebo for a further 12 weeks. There was a rapid deterioration in the clinical condition and a rise in pustule count in the placebo group. The etretinate-treated group still showed clinical improvement and a significantly lower pustule count after 12 weeks. Clinical side-effects were few and adverse effects on liver function and serum lipids were not found.", "Palmoplantar pustular psoriasis (PPP) is a chronic, relapsing condition often recalcitrant to therapy. Synthetic retinoids have been found to be efficacious in the treatment of PPP, but their use is limited by side-effects. Liarozole is an imidazole-like compound that inhibits the retinoic acid (RA) 4-hydroxylase-mediated breakdown of all-trans RA, causing elevation of plasma and cutaneous levels of RA. Thus liarozole acts as a retinoid-mimetic drug. Liarozole has already been found to be effective in the treatment of retinoid-responsive conditions such as chronic plaque psoriasis and ichthyoses.\n To assess the efficacy and side-effect profile of liarozole in the treatment of PPP.\n We performed a double-blind, randomized, placebo-controlled trial of oral liarozole 75 mg twice daily for 12 weeks in the treatment of PPP. The trial was conducted at two centres and involved 15 patients.\n Using the PPP Area and Severity Index we found a statistically significant (P = 0.02) improvement in PPP in subjects on liarozole (median 3, range 1.8-14.1) as compared with placebo (median 12.1, range 5-18) by the end of the treatment phase. There was also a statistically significant difference (P = 0.006) in the number of fresh pustules after treatment for the two study groups (liarozole median 2, range 0-18; placebo median 38, range 2-75). The severity of disease (on a scale of 0-8) between the two groups was significantly different at the end of treatment (liarozole median 1, range 1-5; placebo median 3, range 2-6; P = 0.04). No patients withdrew from the trial because of adverse events. The most commonly reported side-effects were pruritus, cheilitis and xerosis but these were rarely severe and resolved rapidly on discontinuation of treatment. Laboratory results, including haematology, liver function tests and serum cholesterol and triglycerides were not significantly different between the liarozole and placebo groups.\n The results of this pilot study suggest that liarozole 75 mg twice daily is an effective and well-tolerated therapy for PPP. In addition, the pharmacokinetics of liarozole may help to circumvent side-effects associated with synthetic retinoids and allow its use in premenopausal women.", "The purpose of this study was to compare the therapeutic efficacy of a hydrocolloid dressing (Actiderm) over a medium strength corticosteroid (triamcinolone acetonide (TAA) 0.1% cream) with that of a highly potent corticosteroid (clobetasol propionate 0.05% cream) in palmo-plantar pustulosis and localized pustular psoriasis. It was a randomized, open, prospective, right-left comparative trial in 19 patients. The Actiderm dressing and the TAA cream were applied every third day, whereas the clobetasol cream was applied twice daily for 4 weeks. Both treatments resulted in a significant improvement. On completion of treatment, complete clearance was found in 13 patients (63%) with Actiderm plus TAA, but in only 3 patients (21%) with clobetasol (p = 0.001). Four weeks after stopping therapy, the clinical parameters had returned to their pre-treatment level, except for erythema on the Actiderm plus TAA treated lesions (p less than 0.05). No clinically important adverse effects were reported or observed; in particular there was no sign of skin atrophy at the end of study. The results of this study demonstrate that Actiderm applied over a medium strength corticosteroid every third day is highly effective against palmoplantar pustulosis and localized pustular psoriasis. However, it is necessary to develop treatment regimens to maintain the improvement achieved.", "nan", "Sixty patients with palmoplantar pustulosis were treated in a double-blind trial with either acitretin (etretin, Ro 10-1670) or with etretinate. The study consisted of 4 weeks of therapy with three 10 mg capsules/day followed by 8 weeks of therapy with a varying number of capsules given daily according to therapeutic response. At the end of the 12-week treatment period, the mean number of pustules (+/- SEM) had decreased from 57.8 (+/- 8.6) to 3.9 (+/- 1.6) in the acitretin group and from 57.1 (+/- 14.1) to 5.7 (+/- 2.7) in the etretinate group. With regard to influence on erythema, infiltration, scaling, and area involved, similar improvements were obtained in both treatment groups. Adverse reactions of the hypervitaminosis A type were observed with almost the same frequency and severity in both treatment groups. The mean number of 10 mg capsules used daily was comparable in the two groups: 2.82 (range 1.23-4.67) for acitretin and 2.77 (range 1.60-4.82) for etretinate. It can be concluded that acitretin and etretinate do not significantly differ with regard to efficacy and overall safety in the treatment of patients with palmoplantar pustulosis.", "nan", "Seventeen patients with palmoplantar pustular psoriasis and three with hyperkeratotic psoriasis of palms and soles were treated with either PUVA-etretinate (1 mg/kg) or PUVA-placebo. Patients were randomly allocated to each group and the trial was conducted according to a double-blind protocol, so far as the side-effects of etretinate made this possible. PUVA was given three times a week for a maximum of 18 weeks, after 2 weeks on daily placebo or etretinate alone. All ten patients in the PUVA-etretinate group cleared, but there were four failures in the PUVA-placebo group (P = 0.03). The PUVA-etretinate treated patients required significantly fewer PUVA treatments (13.1 +/- 2.9; mean +/- s.e.) and cleared in a significantly shorter time (30.3 +/- 7.1 days) than the PUVA-placebo group (23.2 +/- 4.2 treatments; 59.2 +/- 11.5 days, P less than 0.05). The cumulative UV-A dose to clear was less in the PUVA-etretinate group (53.9 +/- 18.5 J/cm2) than the PUVA-placebo group (113.1 +/- 33.4 J/cm2). This difference was not significant due to the exceptionally large dose of UV-A used on one patient but the results were significant when it was excluded. The therapeutic advantage of adding etretinate to PUVA is offset by the side-effects of cheilitis, hair loss and peeling skin which occurred in eight of the ten PUVA-etretinate patients, and an increase in fasting triglyceride concentrations and serum alkaline phosphatase activity.", "We previously showed in a double-blind, placebo-controlled study that cyclosporin at a dose of 2.5 mg/kg per day is an effective treatment for palmoplantar pustulosis (PPP). In the present randomized, double-blind, placebo-controlled multicentre study we treated 58 PPP patients with placebo or cyclosporin at an initial dose of 1 mg/kg per day. Disease activity was calculated from the number of fresh pustules. Treatment success was defined as the number of fresh pustules not exceeding 50% of the patients' own baseline pustule number. In cases of treatment success the dose of the test medication was not increased and the treatment was kept blinded for a maximum of 12 months. Blinding was broken only on treatment failure of the initial test medication dose. The mean blinded treatment time was 5.1 months for the patients receiving cyclosporin and 2.1 months for placebo (P < 0.01). Treatment was kept blinded for 12 months for seven patients in the cyclosporin and two in the placebo group (P < 0.05). Patients whose treatment code was broken continued in an open dose-finding part of the study with dose adjustments of cyclosporin every second month. In cases of treatment failure the dose of cyclosporin was increased in steps of 1 mg/kg per day; in cases of treatment success the cyclosporin dose was decreased by 1 mg/kg per day. The minimum and maximum doses were 1 and 4 mg/kg per day, respectively. The mean effective dose during the dose-finding part was between 1.2 and 1.7 mg/kg per day. Two patients did not respond to the highest dose of 4 mg/kg per day. In two patients serum creatinine levels increased by > 30% of their own baseline. The other main adverse events were hypertension (seven patients) and hypertrichosis (six patients). After stopping cyclosporin treatment the mean number of fresh pustules showed a maximum after 2 weeks with a continuous decline after that. Twelve months after completing the treatment the mean number of pustules was reduced to 20.0 compared with 63.6 at baseline (P < 0.001); 11 patients were free from pustules and two of these were totally cleared. We conclude that cyclosporin at 1-2 mg/kg per day is an effective and well tolerated treatment for PPP in most patients.", "Twenty-two patients with bilaterally symmetrical persistent palmoplantar pustulosis were treated on one randomly selected side with oral psoralen and long-wave ultraviolet light. The treated side cleared completely in twelve patients, almost cleared in five patients and improved in four. One patient improved on both sides. Fifteen of the twenty-two patients were then treated with topical psoralen and long-wave ultraviolet light on the side that had previously been used as a control. Similar results were obtained. Seven patients cleared completely, six patients were much improved and two were improved. These results are significantly different from those liable to occur by chance (P < 0.001).", "Twenty patients with palmoplantar pustulosis (PPP) were treated with topical PUVA, oral etretinate (Re), or combined PUVA and etretinate (Re-PUVA). Re and Re-PUVA treated sites improved and/or cleared more rapidly than PUVA treated sites. Complete clearance was observed in six of ten sites treated with Re-PUVA, two of ten with Re, and one of ten sites with PUVA within 12 weeks. UVA-control sites failed to be cleared within 12 weeks. Remission periods after stopping the treatment were 1.5 +/- 0.5 weeks (n = 2) with Re, 10.5 +/- 11.4 weeks (n = 6) with Re-PUVA, and one year (n = 1) with PUVA. These results overall suggested that Re-PUVA is the most effective treatment for PPP. Tonsillar focal infection (TFI) and dental focal infection (DFI) were found in 6/20 and 17/20 patients, respectively. However, the presence of focal infection (FI), TFI and/or DFI, did not appear to interfere with the therapeutic activities of Re and/or PUVA, because the complete clearance rates and remission periods in FI(+) patients were comparable with those in FI(-) patients.", "nan", "The effect of grenz ray therapy in the treatment of pustulosis palmoplantaris was assessed in 15 patients by randomly allocating active treatment of the lesions of one side of the body, while the lesions on the other side, which received stimulated therapy, served as a control. Four Gy of grenz rays 10 kV were applied on 6 occasions at intervals of 1 week. A significantly better therapeutic result was recorded on the lesions which had received active grenz ray therapy. However, the therapeutic response was moderate. It is concluded that grenz ray therapy could be useful in pustulosis palmoplantaris mainly as an adjunct to other therapies.", "Thirty patients with severe pustulosis palmoplantaris completed a placebo-controlled comparative trial. Patients were randomly allocated to placebo or etretinate therapy; after two weeks, psoralen plus long-wave ultraviolet light (PUVA) treatment was instituted on one hand or foot, while the other hand or foot served as an untreated control. Fourteen of 18 hands or feet cleared with the combined treatment, compared with three of 18 with etretinate treatment and three of 12 with PUVA treatment. Follow-up showed a high relapse rate. Treatment of severe pustulosis palmoplantaris must be individualized to minimize short- and long-term side effects.", "27 patients with pustulosis palmaris et plantaris were treated daily with colchicine 0.5 mg X 3 for four weeks in a double-blind study. Only ten patients experienced a halt of pustule formation, whereas redness, scaling, and subjective symptoms were unchanged. Colchicine seems of limited value in patients with pustulosis palmaris et plantaris.", "Sixty patients with persistent palmoplantar pustulosis (PPP) were treated with clomocycline (Megaclor) in a double-blind, cross-over trial in an attempt to establish whether the condition responds to tetracycline. Each patient received 3 months each of clomocycline and placebo in random order. Forty patients completed the trial. Twenty-two failed to respond to either treatment, fifteen improved on clomocycline, two improved on placebo and one placebo and one improbed on both treatments. These results are highly significant (P = 0-003) and suggest that clomocycline may suppress pustulation in some patients. The twenty-two 'non-responders' were compared with the eighteen 'responders' for sex, age, length of history and associated psoriasis but no significant differences were found. Difficulties in assessment and the possiblity of improvement deing due to spontaneous remission are discussed. Further follow-up of both groups suggested that clomocycline used over long periods favourably influenced the course of the disease in the 'responder' group." ]

[ "17218230", "18487215", "9363727" ]

[ "Pentoxifylline therapy after laparoscopic surgery for different stages of endometriosis: a prospective, double-blind, randomized, placebo-controlled study.", "Combined laparoscopic surgery and pentoxifylline therapy for treatment of endometriosis-associated infertility: a preliminary trial.", "Pentoxifylline versus placebo in the treatment of infertility associated with minimal or mild endometriosis: a pilot randomized clinical trial." ]

[ "To evaluate the effects of pentoxifylline administration on patients with different stages of endometriosis on whom laparoscopy was performed.\n Prospective, double-blind, randomized, placebo-controlled clinical (Canadian Task Force classification I).\n University and private hospitals.\n Eighty-eight women, all with infertility, some with dysmenorrhea, dyspareunia, or pelvic pain, on whom a laparoscopic diagnosis of endometriosis was made.\n The treatment group received 800 mg pentoxifylline daily for 6 months immediately after surgery. The control group received placebo capsules. All patients were followed-up for 1 year thereafter.\n A comparison of pregnancy rate and recurrence of signs and symptoms in the 2 groups was performed. Forty-three patients were studied in the pentoxifylline group and 45 in the placebo group. The cumulative pregnancy rate was 39.5% and 35.6% in the treatment and control groups, respectively. The overall recurrence of signs and symptoms was 14% in the former group and 15.6% in the latter. There were no statistically significant differences between the 2 groups in rates of pregnancy and recurrence (p = .700 and .832, respectively). Nor was there any significant statistical difference between the same stages in the 2 groups regarding immunomodulation.\n According to the results of this study, and while keeping in mind that appropriate surgery is the main aspect of endometriosis treatment, there is no evidence that immunomodulation with pentoxifylline aids fertility or lessens recurrence of signs and symptoms in women with different stages of endometriosis (i.e., minimal, mild, moderate, or severe).", "Surgical treatment has modest efficacy for the treatment of infertility associated with early-stage endometriosis. Immunomodulation with pentoxifylline is considered as a new strategy potentially useful in treating endometriosis. Thus, this study investigated the usefulness of combined laparoscopic surgery and pentoxifylline therapy in the treatment of infertility associated with minimal to mild endometriosis.\n A prospective, randomized, controlled blind trial was conducted. Patients entered the study immediately after laparoscopic surgery and were randomly assigned to the treatment with either oral pentoxifylline (800 mg/day) (pentoxifylline group, n = 51) or an oral placebo (placebo group, n = 53). Patients were then observed for pregnancy for 6 months.\n Among 98 patients finally considered in the evaluation of the results, the 6 month overall pregnancy rates were 28 and 14% in the pentoxifylline and placebo groups, respectively. Thus, an absolute difference of 14% (95% CI -2 to 30) (Chi-squared test, P = 0.1) in the cumulative probability of pregnancy in 6 months after laparoscopic surgery in patients receiving pentoxifylline versus placebo post-operatively was observed.\n Our findings provide preliminary clinical evidence to suggest the new experimental treatment approaches, toward endometriosis, that are based on immunomodulation deserve further attention. Well-designed multicenter trials are warranted to confirm or refute our results.", "The present study is the first prospective randomized controlled trial of the effect of pentoxifylline on future fertility in infertile women with asymptomatic minimal or mild endometriosis. After completion of a basic infertility workup and laparoscopy, patients were entered into the study and randomly allocated to receive either a 12 month course of oral pentoxifylline (800 mg/day) (n = 30) or an oral placebo (n = 30). Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be non-contributory. Life-table analysis was used to compare pregnancy rates between the two groups over a 12 month period that started immediately after laparoscopy. The 12 month actuarial overall pregnancy rates were 31 and 18.5% in the pentoxifylline and placebo groups respectively. However, this difference was not statistically significant by the chi(2)-test. Similarly, the Cox regression method showed no differences between the hazard of pregnancy in the two groups studied (odds ratio, 0.56; 95% confidence interval, 0.18-1.67). Therefore, there is no evidence from this study that immunomodulation with pentoxifylline aids fertility in those women with minimal or mild endometriosis. Further studies including more infertile patients with endometriosis are desirable in order to confirm our results." ]

[ "16899964", "12583920", "3084975", "7872852", "1518313", "1592254" ]

[ "Randomised controlled trial of a collaborative care model with psychiatric consultation for persistent medically unexplained symptoms in general practice.", "The somatization in primary care study: a tale of three diagnoses.", "Psychiatric consultation in somatization disorder. A randomized controlled study.", "A trial of the effect of a standardized psychiatric consultation on health outcomes and costs in somatizing patients.", "An analysis of panel data. The impact of a psychiatric consultation letter on the expenditures and outcomes of care for patients with somatization disorder.", "A randomized trial of psychiatric consultation with distressed high utilizers." ]

[ "Patients with persistent medically unexplained symptoms often exhibit general dysfunction and psychiatric comorbidity and frequently resist psychiatric referral. The aim of this study was to evaluate the efficacy of a collaborative care model including training for general practitioners (GPs) and a psychiatric consultation model for patients with persistent medically unexplained symptoms in general practice.\n Randomised controlled trial. Cluster randomisation at GP practices and multilevel analysis were performed. A total of 81 patients from 36 general practices completed the study. A collaborative care model of training and psychiatric consultation in general practice in the presence of the GP was compared with training plus care as usual by the GP. Outcome assessment on the patients' well-being, functioning and utilisation of health care services was performed 6 weeks and 6 months later.\n All the patients had somatoform disorders (Whitely Index 7.46), and 86% had comorbid psychiatric disorders. In the intervention group, the severity of the main medically unexplained symptoms decreased by 58%. The patients' social functioning improved. The utilization of health care was lower than in the care as usual group.\n A collaborative care model combining training with psychiatric consultation in the general practice setting is an effective intervention in the treatment of persistent medically unexplained symptoms. Anxiety and depressive disorders are highly comorbid in this group. The findings warrant a larger study.", "Somatization is a common phenomenon that has been defined in many ways. The two most widely used diagnoses, Somatization Disorder (SD) and Abridged Somatization Disorder (ASD), are based on lifetime unexplained symptoms. However, reports indicate instability in lifetime symptom recall among somatizing patients. Multisomatoform disorder (MSD) is a new diagnosis based on current unexplained symptoms. To understand how knowledge about SD and ASD translates to MSD, we examined the diagnostic concordance, impairment and health care utilization of these groups in a sample from the Somatization in Primary Care Study. The diagnostic concordance was high between MSD and SD, but lower between MSD and ASD. All three groups reported considerable physical impairment (measured using the PCS subscale of the SF-36). The mental health (MCS) scores for the three groups were only slightly lower than those of the general population. Over the course of one year, physical functioning fell significantly for all three groups. Mental functioning did not change significantly for any of the three groups over this period. Utilization patterns were very similar for the three groups. The high prevalence, serious impairment, and worsening physical functioning over the course of one year suggest the importance of developing interventions in primary care to alleviate the impaired physical functioning and reduce utilization in somatizing patients. MSD should be a useful diagnosis for targeting these interventions because it identifies a sizable cohort of somatizing patients reporting impairment of comparable severity to full SD, using a more efficient diagnostic algorithm based on current symptoms.", "The per capita expenditure for health care of patients with multiple physical symptoms but no apparent physical disease (somatization disorder) is up to nine times the average per capita amount. We conducted a randomized controlled trial to determine whether psychiatric consultation would reduce the medical costs of these patients, without effecting a substantial change in patient outcome. Thirty-eight patients were randomly assigned to treatment or control groups and studied prospectively for 18 months. Treatment consisted of a psychiatric consultation and suggestions on management given to primary physicians. After nine months, the control group was crossed over to receive treatment with the same intervention. After the psychiatric consultation, the quarterly health care charges in the treatment group declined by 53 percent (P less than 0.05). In contrast, the charges in the control group showed wide variations but no overall change. The quarterly charges in the control group were significantly higher than those in the treatment group (P less than 0.05). After the control group was crossed over to receive treatment, their quarterly charges declined by 49 percent (P less than 0.05). The reductions in expenditures in both groups were due largely to decreases in hospitalization. We conclude that psychiatric consultation in the care of patients with somatization disorder reduced subsequent health care expenditures without inducing changes in health status or patients' satisfaction with their health care.", "Patients who somatize but who do not meet criteria for somatization disorder are common in the community. Virtually no research has been conducted to determine how to treat these patients.\n We conducted a randomized controlled clinical trial of a psychiatric consultation intervention we had previously shown to improve the management of somatization disorder. The study population included 51 physicians treating 56 somatizing patients who had a history of seeking help for six to 12 lifetime unexplained physical symptoms. At the onset of the experiment, physicians randomized to the treatment condition received a consultation letter recommending a specific management approach; physicians randomized to the control/crossover condition received the consultation letter after 12 months. Data on health outcomes and charges were collected every 4 months for 2 years after randomization for 96% of subjects who entered the study.\n Patients of physicians who received the intervention reported significantly increased physical functioning, an improvement that remained stable during the year after the intervention. The intervention reduced annual medical care charges by $289 (95% confidence interval, $40 to $464) in 1990 constant dollars, which equates to a 32.9% reduction in the annual median cost of their medical care.\n Somatizing patients with a lifetime history of six to 12 unexplained physical symptoms reported better physical functioning after their primary care physician was provided appropriate treatment recommendations via a psychiatric consultation. Such a consultation is cost-effective because it reduces subsequent charges for medical care, while improving health outcomes in a chronically impaired population.", "In this study, the cost and health outcomes of a psychiatric consultation letter to primary care physicians caring for a sample of patients diagnosed with somatization disorder, a psychiatric condition associated with multiple, unexplained medical complaints, was assessed. To accommodate the small sample size of 73 patients, outcome effects were calculated using panel analysis. Study patients were randomized to a consultation or noconsultation group, and were repeatedly assessed at equal time intervals. Data were analyzed using parsimonious regression models derived from economic theory. During the 1-year follow-up period, a psychiatric consultation letter was associated with a 12% reduction in health care costs ($455 per patient within first year), with no evidence of deterioration in physical, mental, or general health. Less powerful t-test comparisons between treated and control groups lead to different conclusions. Reasons for these differences are discussed.", "This study reports the results of a randomized trial of a psychiatric consultation intervention with distressed, high utilizing patients of 18 physicians in two primary care clinics. Psychiatric consultation was associated with a significant increase in the use of antidepressants in intervention patients compared with controls in the first 6 months after intervention. Intervention patients were also significantly more likely to continue antidepressant treatment than control patients. The primary care physicians receiving psychiatric consultations increased the rate of prescribing antidepressant medications in their practice from 32 prescriptions filled per 1,000 visits before their participation in four consultations to 44 new prescriptions per 1,000 visits in the 12-month period after. There were no significant differences between intervention patients and controls at 6 and 12 months after randomization in psychiatric distress, functional disability, or utilization of health care (ambulatory visits, radiographic and laboratory testing services, admissions to inpatient medical care)." ]

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[ "A 3-year follow-up of a multidisciplinary rehabilitation programme for back and neck pain.", "Comparison of operant behavioral and cognitive-behavioral group treatment for chronic low back pain.", "Incorporation of cognitive-behavioral treatment into the medical care of chronic low back patients: a controlled randomized study in German pain treatment centers.", "Two psychological interventions are effective in severely disabled, chronic back pain patients: a randomised controlled trial.", "The effect of cognitive behavior therapy in patients with rheumatoid arthritis.", "A comparison of behavioral and educational interventions for fibromyalgia.", "Tailored cognitive-behavioral therapy in early rheumatoid arthritis for patients at risk: a randomized controlled trial.", "Does systematic graded exposure in vivo enhance outcomes in multidisciplinary chronic pain management groups?", "Tailored cognitive-behavioral therapy and exercise training for high-risk patients with fibromyalgia.", "Multimodal cognitive behavioral treatment of patients sicklisted for musculoskeletal pain: a randomized controlled study.", "Subacute and chronic, non-specific back and neck pain: cognitive-behavioural rehabilitation versus primary care. A randomized controlled trial.", "A randomized, controlled trial of acceptance and commitment therapy and cognitive-behavioral therapy for chronic pain.", "Chronic low-back pain: what does cognitive coping skills training add to operant behavioral treatment? Results of a randomized clinical trial.", "The effectiveness of psychological interventions for the rehabilitation of low back pain: a randomized controlled trial evaluation.", "Group therapies for rheumatoid arthritis. A controlled study of two approaches.", "Exposure in vivo versus operant graded activity in chronic low back pain patients: results of a randomized controlled trial.", "Momentary pain and coping in temporomandibular disorder pain: exploring mechanisms of cognitive behavioral treatment for chronic pain.", "The relative efficacy of three cognitive-behavioral treatment approaches to temporomandibular disorders.", "Is surface EMG biofeedback an effective training method for persons with neck and shoulder complaints after whiplash-associated disorders concerning activities of daily living and pain -- a randomized controlled trial.", "Multidisciplinary group rehabilitation versus individual physiotherapy for chronic nonspecific low back pain: a randomized trial.", "Treating fibromyalgia with mindfulness-based stress reduction: results from a 3-armed randomized controlled trial.", "A comparative study of 2 manual-based self-help interventions, acceptance and commitment therapy and applied relaxation, for persons with chronic pain.", "Spouse-assisted coping skills training in the management of osteoarthritic knee pain.", "Operant behavioral treatment of fibromyalgia: a controlled study.", "Short- and long-term efficacy of brief cognitive-behavioral therapy for patients with chronic temporomandibular disorder pain: a randomized, controlled trial.", "Results of a randomized controlled trial to examine the efficacy of a chronic pain self-management group for older adults [ISRCTN11899548].", "One-year outcomes of a randomized controlled trial of an educational-behavioural joint protection programme for people with rheumatoid arthritis.", "Biofeedback/relaxation training and exercise interventions for fibromyalgia: a prospective trial.", "Inpatient vs. outpatient pain management: results of a randomised controlled trial.", "Intensive physical and psychosocial training program for patients with chronic low back pain. A controlled clinical trial.", "Cognitive-educational treatment of fibromyalgia: a randomized clinical trial. I. Clinical effects.", "A behavioural treatment for chronic shoulder complaints: concepts, development, and study design.", "A randomized controlled component analysis of a behavioral medicine rehabilitation program for chronic spinal pain: are the effects dependent on gender?", "Effects of a stress-reduction program on psychological function, pain, and physical function of systemic lupus erythematosus patients: a randomized controlled trial.", "Chronic pain management in a health maintenance organization.", "Comparison of cognitive behavioral and mindfulness meditation interventions on adaptation to rheumatoid arthritis for patients with and without history of recurrent depression.", "Age analysis of cognitive-behavioral group therapy for chronic pain outpatients." ]

[ "The aim of the present study was to evaluate the long-term outcome of a behavioural medicine rehabilitation programme and the outcome of its two main components, compared to a 'treatment-as-usual' control group. The study employed a 4 x 5 repeated-measures design with four groups and five assessment periods during a 3-year follow-up. The group studied consisted of blue-collar and service/care workers on sick leave, identified in a nationwide health insurance scheme in Sweden. After inclusion, the subjects were randomised to one of the four conditions: behaviour-oriented physiotherapy (PT), cognitive behavioural therapy (CBT), behavioural medicine rehabilitation consisting of PT+CBT (BM) and a 'treatment-as-usual' control group (CG). Outcome variables were sick leave, early retirement and health-related quality of life. A cost-effectiveness analysis, comparing the programmes, was made. The results showed, consistently, the full-time behavioural medicine programme being superior to the three other conditions. The strongest effect was found on females. Regarding sick leave, the mean difference in the per-protocol analysis between the BM programme and the control group was 201 days, thus reducing sick leave by about two-thirds of a working year. Rehabilitating women has a substantial impact on costs for production losses, whereas rehabilitating men seem to be effortless with no significant effect on either health or costs. In conclusion, a full-time behavioural medicine programme is a cost-effective method for improving health and increasing return to work in women working in blue-collar or service/care occupations and suffering from back/neck pain.", "nan", "Cognitive behavioral treatment has been incorporated into standard medical treatment procedures in German pain centers. Acceptance of the treatment by patients and outcome in terms of pain, coping, and disability was investigated. Components of the psychological treatment are education, relaxation and imagery, modifying thoughts and feelings, enhancement of pleasant activities, and training of good postural habits. The program was conducted in a group setting in accordance with a treatment manual and consists of 12 weekly 2.5-h sessions. A two-factor experiment with repeated measures on one factor was applied. Ninety-four consecutive patients with low-back pain were randomly assigned to an experimental group having a combined medical and cognitive-behavioral treatment, or to a control group with medical treatment only. Assessments were taken pre-treatment, post-treatment, and--in the treated group only--at a 6-months follow-up. At each assessment, patients kept a pain diary over a period of 4 weeks, and filled in self-report questionnaires. The sample consisted of 36 experimental and 40 control subjects at post-treatment. Experimental subjects reported less pain, better control over pain, more pleasurable activities and feelings, less avoidance and less catastrophizing. In addition, disability was reduced in terms of social roles, physical functions and mental performance. The results were maintained at follow-up. Patients who only received medical treatment showed little improvement. Data indicate that the program meets the needs of the patients and should be continued.", "Many pain patients appreciate biofeedback interventions because of the integration of psychological and physiological aspects. Therefore we wanted to investigate in a sample of chronic back pain patients whether biofeedback ingredients lead to improved outcome of psychological interventions.\n One hundred and twenty-eight chronic back pain patients were randomly assigned to cognitive-behavioural therapy (CBT), cognitive-behavioural therapy including biofeedback tools (CBT-B) or waitlist control (WLC). The sample was recruited from a highly disabled group including many patients with low education status and former back surgeries. Measures on pain, physical functioning, emotional functioning, coping strategies and health care utilisation were taken at pretreatment, posttreatment and 6 months of follow-up.\n The results indicated significant improvements on most outcome measures for CBT-B and CBT in comparison to WLC. CBT-B and CBT were equally effective (e.g. ITT effect sizes for pain intensity: CBT-B, 0.66 (95% CI 0.39-0.95); CBT, 0.60 (95% CI 0.33-0.87)).\n In conclusion, biofeedback ingredients did not lead to improved outcome of a psychological intervention. Cognitive-behavioural treatment as a \"package\" of respondent, operant and cognitive interventions was effective for ameliorating pain-related symptoms for chronic back pain patients treated in an outpatient setting. The high treatment acceptability associated with biofeedback ingredients can also be achieved with pure psychological interventions.", "In order to examine the effectiveness of cognitive behavioral therapy for patients with rheumatoid arthritis (RA) three patients groups were studied: a cognitive behavioral therapy group (CBT), an occupational therapy group (OT), and a waiting-list control group. The CBT received a comprehensive, 10-session treatment package that taught progressive relaxation, rational thinking and the differential use of pain coping strategies. CBT resulted in minor changes in pain coping behavior at posttreatment, while CBT and OT showed an increase of knowledge of RA. No therapeutic effects with regard to health status were demonstrated at posttreatment and at 6 months follow-up. Clinical and laboratory measures of disease activity revealed progressive deterioration of the patients during the course of the study. It is suggested that the ineffectiveness of CBT might be due to the progressive course of RA in the patients studied, as well as to the rather small changes in coping behavior.", "To compare a comprehensive behavioral intervention with an education/control condition in the treatment of patients with fibromyalgia (FM), and to explore the role of mediators of clinical improvement in both groups.\n The effects of the behavioral and education/control interventions were evaluated across a 10 week treatment period and at 6 month followup on measures of pain, depression, disability, pain behaviors, and intervening variables. The behavioral intervention focused on the development of diverse pain coping skills, while the education/control condition presented information on a range of health related topic without emphasizing skill acquisition.\n Although improvement across time was found in depression, self-reported pain behaviors, observed pain behaviors, and myalgia scores, no differences in these criteria were found between the behavioral and education/control conditions. Multiple regression analyses revealed that changes in helplessness and passive coping were associated with improvement in a number of clinical outcomes.\n The findings illustrate the value of psychoeducational interventions in decreasing the psychological and behavioral effect of FM, and the value of reducing dysfunctional coping and helplessness in future intervention research.", "Recent developments in chronic pain research suggest that effectiveness of cognitive-behavioral therapy (CBT) may be optimized when applying early, customized treatments to patients at risk. For this purpose, a randomized, controlled trial with tailor-made treatment modules was conducted among patients with relatively early rheumatoid arthritis (RA disease duration of <8 years), who had been screened for psychosocial risk profiles. All participants received standard medical care from a rheumatologist and rheumatology nurse consultant. Patients in the CBT condition additionally received an individual CBT treatment with two out of four possible treatment modules. Choice of treatment modules was determined on the basis of patient priorities, which resulted in most frequent application of the fatigue module, followed by the negative mood, social relationships and pain and functional disability modules. Analyses of completers and of intention-to-treat revealed beneficial effects of CBT on physical, psychological and social functioning. Specifically, fatigue and depression were significantly reduced at post-treatment and at the 6-month follow-up in the CBT condition in comparison to the control condition, while perceived support increased at follow-up assessment. In addition, helplessness decreased at post-treatment and follow-up assessment, active coping with stress increased at post-treatment, and compliance with medication increased at follow-up assessment in the CBT condition in comparison to the control condition. Results indicate the effectiveness of tailor-made CBT for patients at risk in relatively early RA, and supply preliminary support for the idea that customizing treatments to patient characteristics may be a way to optimize CBT effectiveness in RA patients.", "Graded exposure in vivo (GEXP) treatment has been successfully used to reduce levels of pain-related fear and disability in some chronic pain patients, but its effectiveness has not been evaluated in general clinical settings using group-design studies. The purpose of this study was to determine if the systematic incorporation of GEXP into a multidisciplinary chronic pain management group (PMG) treatment program would result in better treatment outcomes than usual PMG treatment.\n One hundred forty-three chronic pain patients who were assessed as suitable for an outpatient multidisciplinary chronic PMG program were randomly allocated to 3 experimental conditions; usual PMG, PMG incorporating systematic graded exposure, and wait-list control.\n The clinical outcomes of the 2 treatment conditions were not significantly different, suggesting that the systematic incorporation of GEXP into a multidisciplinary PMG program did not result in better treatment outcomes than usual PMG treatment. Both group treatment programs were associated with significant treatment effects when compared with the wait-list control on measures of pain intensity, fear of movement/(re)injury, pain self-efficacy, activity level, and depression. No treatment effects were found on self-report measures of pain disability or anxiety.\n The addition of systematic graded exposure into a multidisciplinary chronic pain management program did not result in better clinical outcomes than the usual group treatment program. The validity of GEXP to the broader population of chronic pain patients warrants further investigation.", "The treatment of patients with fibromyalgia (FM), a high-prevalence chronic pain condition with a high impact on both patients and society, poses a great challenge to clinicians due to a lack of effective treatments. In view of the large individual variability in outcome, selecting patients at risk of long-term dysfunction and offering tailored treatment may be promising for beneficial treatment effects.\n High-risk patients were selected and classified into 2 groups (pain-persistence and pain-avoidance groups) and subsequently randomized in groups to either a treatment condition (TC) or a waiting list control condition (WLC). Treatment consisted of 16 sessions of cognitive-behavioral therapy (CBT) and exercise training in groups, tailored to the patient's specific cognitive-behavioral pattern, delivered within 10 weeks. Physical and psychological functioning and impact of FM were assessed at baseline, posttreatment, and 6-month followup. Treatment effects were evaluated using a linear mixed model.\n The treatment effects were significant for all primary outcomes, showing significant differences in physical (pain, fatigue, and functional disability) and psychological (negative mood and anxiety) functioning, and impact of FM for the TC in comparison with the WLC. Effect sizes in the TC were overall large, and reliable change indices indicated a clinically relevant improvement among the TC.\n The presented results demonstrate for the first time that tailored CBT and exercise training for high-risk patients with FM is effective in improving short- and long-term physical and psychological functioning, indicating that tailoring treatment is likely to promote beneficial outcomes in FM and reduce the burden for patients and society.", "In a randomized controlled study multimodal cognitive behavioral treatment (MMCBT), including physical treatment, cognitive behavioral modification, education, and examination of the work situation for each patient, was given to patients sick-listed for musculoskeletal pain (n = 469). Patients were recruited through the National Insurance System. After a pre-test by an independent physiotherapist the patients were allocated at random to the intervention group (n = 312) or the control group (n = 157). The MMBCT program lasted for 4 weeks. The control group returned to their general practitioners, without any feedback or advice on therapy from the project. At the one year follow-up the MMCBT group had not returned to work at a higher rate than the control group receiving ordinary treatment available through their general practitioners. However, the MMCBT group had improved their ergonomic behavior, work potential, life quality, physical, and psychological health.", "In the industrial world, non-specific back and neck pain (BNP) is the largest diagnostic group underlying sick-listing. For patients with subacute and chronic (= full-time sick-listed for 43 - 84 and 85 - 730 days, respectively) BNP, cognitive-behavioural rehabilitation was compared with primary care. The specific aim was to answer the question: within an 18-month follow-up, will the outcomes differ in respect of sick-listing and number of health-care visits?\n After stratification by age (< or = 44/> or = 45 years) and subacute/chronic BNP, 125 Swedish primary-care patients were randomly allocated to cognitive-behavioural rehabilitation (rehabilitation group) or continued primary care (primary-care group). Outcome measures were Return-to-work share (percentage) and Return-to-work chance (hazard ratios) over 18 months, Net days (crude sick-listing days x degree), and the number of Visits (to physicians, physiotherapists etc.) over 18 months and the three component six-month periods. Descriptive statistics, Cox regression and mixed-linear models were used.\n All patients: Return-to-work share and Return-to-work chance were equivalent between the groups. Net days and Visits were equivalent over 18 months but decreased significantly more rapidly for the rehabilitation group over the six-month periods (p < .05). Subacute patients: Return-to-work share was equivalent. Return-to-work chance was significantly greater for the rehabilitation group (hazard ratio 3.5 [95%CI1.001 - 12.2]). Net days were equivalent over 18 months but decreased significantly more rapidly for the rehabilitation group over the six-month periods and there were 31 days fewer in the third period. Visits showed similar though non-significant differences and there were half as many in the third period. Chronic patients: Return-to-work share, Return-to-work chance and Net days were equivalent. Visits were equivalent over 18 months but tended to decrease more rapidly for the rehabilitation group and there were half as many in the third period (non-significant).\n The results were equivalent over 18 months. However, there were indications that cognitive-behavioural rehabilitation in the longer run might be superior to primary care. For subacute BNP, it might be superior in terms of sick-listing and health-care visits; for chronic BNP, in terms of health-care visits only. More conclusive results concerning this possible long-term effect might require a longer follow-up.", "Individuals reporting chronic, nonmalignant pain for at least 6 months (N=114) were randomly assigned to 8 weekly group sessions of acceptance and commitment therapy (ACT) or cognitive-behavioral therapy (CBT) after a 4-6 week pretreatment period and were assessed after treatment and at 6-month follow-up. The protocols were designed for use in a primary care rather than specialty pain clinic setting. All participants remained stable on other pain and mood treatments over the course of the intervention. ACT participants improved on pain interference, depression, and pain-related anxiety; there were no significant differences in improvement between the treatment conditions on any outcome variables. Although there were no differences in attrition between the groups, ACT participants who completed treatment reported significantly higher levels of satisfaction than did CBT participants. These findings suggest that ACT is an effective and acceptable adjunct intervention for patients with chronic pain.\n Published by Elsevier B.V.", "This study examined the supplemental value of a cognitive coping skills training when added to an operant-behavioral treatment for chronic low-back pain patients. The complete treatment package (OPCO) was compared with an operant program + group discussion (OPDI) and a waiting-list control (WLC). After the WL period, the WLC patients received a less protocolized operant program usually provided in Dutch rehabilitation centers (OPUS). Regression analyses showed that, compared with WLC, both OPCO and OPDI led to less negative affect, higher activity tolerance, less pain behavior, and higher pain coping and pain control. At posttreatment, OPCO led to better pain coping and pain control than OPDI. Calculation of improvement rates revealed that OPCO and OPDI had significantly more improved patients than OPUS on all the dependent variables. The discussion includes findings regarding treatment credibility, compliance, and contamination bias.", "Forty-five low back pain patients were randomly assigned to either a standard inpatient rehabilitation program or the standard program with additional psychological components. The standard program emphasized education, support, and physical reconditioning through exercise. Patients receiving the psychological program were given additional training in relaxation and other coping skills and received contingent reinforcement for exercise. Both programs included reduction of medication intake and an emphasis on family involvement after discharge. Measures of functional status were taken prior to the program, at discharge from the 3-week inpatient program, and at a 6-month follow-up appointment. These data revealed that patients improved their overall functioning at discharge and maintained these gains at the follow-up assessment. A similar pattern of findings was obtained for self-reported pain and interference. Furthermore, 81% of the patients had returned to work or were engaged in active job retraining by the follow-up. Using a conservative measure of full-time return to the same or an equivalent job, 57% were employed by the follow-up. Patient improvement, however, was not differentially affected by treatment group assignment, suggesting that the psychological treatment failed to add to the effectiveness obtained by the standard rehabilitation program. Results are discussed in the context of improving patient outcomes from rehabilitation for low back pain.", "An important unanswered question about rheumatoid arthritis (RA) is how the patient's psychological or emotional state relates to disease activity and functional status. No controlled studies of psychotherapeutic interventions in RA have been reported. To test the hypothesis that a psychosocial intervention would lead to improvement in functional status or disease activity, 57 RA patients were randomly assigned to 1 of 3 groups, which received: 1) conventional group psychotherapy; 2) group assertion/relaxation training; or 3) no treatment (control group). Patient and physician questionnaires collected at baseline, immediately after the interventions, and 12 months after baseline provided outcome data on functional status, social and psychological adaptation, psychological symptoms, and disease activity. There were few outcome measures for which either treatment resulted in significantly higher scores than were seen in controls, though more improvement did occur among patients who received conventional group psychotherapy.", "Since pain-related fear may contribute to the development and maintenance of chronic low back pain (CLBP), an exposure in vivo treatment (EXP) was developed for CLBP patients. We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant graded activity (GA) directly and 6 months post-treatment in a multi-centre randomized controlled trial. In total, 85 patients suffering from disabling non-specific CLBP reporting at least moderate pain-related fear were randomly allocated to EXP or GA. It was demonstrated that EXP, despite excelling in diminishing pain catastrophizing and perceived harmfulness of activities, was equally effective as GA in improving functional disability and main complaints, although the group difference almost reached statistical significance favouring EXP. Both treatment conditions did not differ in pain intensity and daily activity levels either. Nor was EXP superior to GA in the subgroup of highly fearful patients. Irrespective of treatment, approximately half the patients reported clinically relevant improvements in main complaints and functional disability, although for the latter outcome the group difference was almost significant favouring EXP. Furthermore, the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities. In sum, this study demonstrates that up to 6 months after treatment EXP is an effective treatment, but not more effective than GA, in moderately to highly fearful CLBP patients, although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established. Possible explanations for these findings are discussed.", "The purpose of this study was to determine whether cognitive-behavioral treatment (CBT) operates by effecting changes in cognitions, affects, and coping behaviors in the context of painful episodes. Patients were 54 men and women with temporomandibular dysfunction-related orofacial pain (TMD) enrolled in a study of brief (6 weeks) standard conservative treatment (STD) or standard treatment plus CBT (STD+CBT). Momentary affects, pain, and coping processes were recorded on a cell phone keypad four times per day for 7 days prior to treatment, and for 14 days after treatment had finished, in an experience sampling paradigm. Analyses indicated no treatment effects on general retrospective measures of pain, depression, or pain-related interference with lifestyle at post-treatment. However, mixed model analyses on momentary pain and coping recorded pre- and post-treatment indicated that STD+CBT patients reported greater decreases in pain than did STD patients, significantly greater increases in the use of active cognitive and behavioral coping, and significantly decreased catastrophization. Analyses of experience sampling data indicated that post-treatment momentary pain was negatively predicted by concurrent active coping, self-efficacy, perceived control over pain, and positive-high arousal affect. Concurrent catastrophization was strongly predictive of pain. Active behavioral coping and self-efficacy reported at the prior time point (about 3h previously) were also protective, while prior catastrophization and negative-high arousal mood were predictive of momentary pain. The results suggest that CB treatment for TMD pain can help patients alter their coping behaviors, and that these changes translate into improved outcomes.", "The purpose of this study was to evaluate the relative efficacy of different biopsychosocial treatment conditions on patients with chronic temporomandibular disorder. Ninety-four patients with chronic temporomandibular disorder were assigned to either a biofeedback treatment group, a cognitive-behavioral skills training (CBST) treatment group, a combined (combination of biofeedback/CBST) treatment group, or a no-treatment control group. Pain scores were analyzed pretreatment and posttreatment to determine group and within-subjects treatment effects. Results demonstrated that, in terms of a self-reported pain score, all three treatment groups had significantly decreased pain scores from pretreatment to posttreatment, while the no-treatment group did not. Moreover, patients in the biofeedback group were the most significantly improved compared to the no-treatment group. Finally, participants in the three treatment groups displayed significant improvement in mood states.", "To evaluate the effectiveness of surface electromyographic (EMG) biofeedback training as a supplement to an interdisciplinary rehabilitation programme regarding consequences for activities of daily living and pain.\n A randomized controlled unblinded trial.\n The study was carried out in a pain unit at a rehabilitation centre.\n Sixty-five people with chronic whiplash-associated disorders consecutively referred to the pain unit agreed to participate in the study. Participants were randomly assigned to either the treatment or control group.\n All participants received interdisciplinary rehabilitation and the treatment group also had four weeks of surface EMG biofeedback training.\n The Canadian Occupational Performance Measure was used at admission discharge and at six-month follow-up to register changes in activities of daily living. The Multidimensional Pain Inventory, Swedish version, was used at admission and at six-month follow-up to capture the multidimensional aspects of pain.\n Sixty-two people completed the study. Both treatment and control groups improved significantly according to the Canadian Occupational Performance Measure at discharge and the results remained after six months (P<0.001). The subscale 'Interference' on the Multidimensional Pain Inventory was significantly decreased at six months for the treatment group (P<0.001). No differences were found between the two groups for activities of daily living (performance P = 0.586; satisfaction P = 0.988) at follow-up or for pain level (P = 0.914), indicating no additional effect of the surface EMG biofeedback training.\n In this study there was no support for the effectiveness of surface EMG biofeedback training as a supplement to an interdisciplinary rehabilitation programme for people with long-lasting pain after whiplash.", "A randomized trial.\n To evaluate the effectiveness of a semi-intensive multidisciplinary rehabilitation for patients with chronic low back pain in an outpatient setting.\n Systematic reviews have shown that there is strong evidence that intensive multidisciplinary treatment (>100 hours), which includes functional restoration, improves function among chronic patients with low back pain, and moderate evidence that it reduces pain but contradictory evidence regarding improvement of working ability. However, there is paucity of data whether semi-intensive outpatient multidisciplinary rehabilitation in groups is more effective than individual physiotherapy.\n A total of 120 women employed as healthcare and social care professionals with nonspecific chronic low back pain were recruited from two occupational healthcare centers. The patients were randomized into two intervention programs. Multidisciplinary rehabilitation (n = 59) was conducted in groups and comprised of physical training, workplace interventions, back school, relaxation training, and cognitive-behavioral stress management methods for 70 hours. The individual physiotherapy (n = 61) included physical exercise and passive treatment methods administered for 10 hours. Main outcome measures were: back pain and sciatic pain intensity, disability, sick leaves, healthcare consumption, symptoms of depression, and beliefs of working ability after 2 years.\n There were no statistically significant differences between the two treatment groups in main outcome measures just after rehabilitation, at 6-, at 12-, or 24-month follow-up. In both intervention arms, however, the before-and-after comparison showed favorable effects, and the effects were still maintained at 2 years follow-up.\n The results of this study indicate that semilight outpatient multidisciplinary rehabilitation program for female chronic low back pain patients does not offer incremental benefits when compared with rehabilitation carried out by a physiotherapist having a cognitive-behavioral way of administering the treatment.", "Mindfulness-based stress reduction (MBSR) is a structured 8-week group program teaching mindfulness meditation and mindful yoga exercises. MBSR aims to help participants develop nonjudgmental awareness of moment-to-moment experience. Fibromyalgia is a clinical syndrome with chronic pain, fatigue, and insomnia as major symptoms. Efficacy of MBSR for enhanced well-being of fibromyalgia patients was investigated in a 3-armed trial, which was a follow-up to an earlier quasi-randomized investigation. A total of 177 female patients were randomized to one of the following: (1) MBSR, (2) an active control procedure controlling for nonspecific effects of MBSR, or (3) a wait list. The major outcome was health-related quality of life (HRQoL) 2 months post-treatment. Secondary outcomes were disorder-specific quality of life, depression, pain, anxiety, somatic complaints, and a proposed index of mindfulness. Of the patients, 82% completed the study. There were no significant differences between groups on primary outcome, but patients overall improved in HRQoL at short-term follow-up (P=0.004). Post hoc analyses showed that only MBSR manifested a significant pre-to-post-intervention improvement in HRQoL (P=0.02). Furthermore, multivariate analysis of secondary measures indicated modest benefits for MBSR patients. MBSR yielded significant pre-to-post-intervention improvements in 6 of 8 secondary outcome variables, the active control in 3, and the wait list in 2. In conclusion, primary outcome analyses did not support the efficacy of MBSR in fibromyalgia, although patients in the MBSR arm appeared to benefit most. Effect sizes were small compared to the earlier, quasi-randomized investigation. Several methodological aspects are discussed, e.g., patient burden, treatment preference and motivation, that may provide explanations for differences. In a 3-armed randomized controlled trial in female patients suffering from fibromyalgia, patients benefited modestly from a mindfulness-based stress reduction intervention.\n Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.", "The aim of this study was to compare 2 self-help-based interventions; a coping-oriented approach, applied relaxation (AR) and an acceptance-oriented approach, acceptance and commitment therapy (ACT), for persons with chronic pain.\n This study is a randomized control trial (N=90) with a mixed between-within participants design with repeated measures. Interventions in both conditions comprised an initial face-to-face session, a 7-week manual-based self-help intervention including weekly therapist telephone support and a concluding face-to-face session. Outcome measures included satisfaction with life, depression, anxiety, acceptance of chronic pain, level of function, and pain intensity. Effects were measured at preintervention and postintervention and at 6 and 12 months after the end of intervention.\n The results show that the ACT condition increased their level of acceptance significantly compared with the AR condition. There was also a marginally significant interaction effect regarding satisfaction with life in which the ACT condition had improved in comparison to the AR condition. Further, the ACT condition reported a higher level of function and decreased pain intensity compared with the AR condition. Both conditions improved significantly regarding depression and anxiety.\n A manual-based self-help intervention with weekly therapist support in an ACT format adds value to the treatment repertoire for persons suffering with chronic pain.", "To evaluate the effects of a spouse-assisted pain-coping skills training intervention on pain, psychological disability, physical disability, pain-coping, and pain behavior in patients with osteoarthritis (OA) of the knees.\n Eighty-eight OA patients with persistent knee pain were randomly assigned to 1 of 3 conditions: 1) spouse-assisted pain-coping skills training, (spouse-assisted CST), 2) a conventional CST intervention with no spouse involvement (CST), or 3) an arthritis education-spousal support (AE-SS) control condition. All treatment was carried out in 10 weekly, 2-hour group sessions.\n Data analysis revealed that at the completion of treatment, patients in the spouse-assisted CST condition had significantly lower levels of pain, psychological disability, and pain behavior, and higher scores on measures of coping attempts, marital adjustment, and self-efficacy than patients in the AE-SS control condition. Compared to patients in the AE-SS control condition, patients who received CST without spouse involvement had significantly higher post-treatment levels of self-efficacy and marital adjustment and showed a tendency toward lower levels of pain and psychological disability and higher scores on measures of coping attempts and ratings of the perceived effectiveness of pain-coping strategies.\n These findings suggest that spouse-assisted CST has potential as a method for reducing pain and disability in OA patients.", "To evaluate the efficacy of operant pain treatment for fibromyalgia syndrome (FMS) in an inpatient setting.\n Sixty-one patients who fulfilled the American College of Rheumatology criteria for FMS were randomly assigned to the operant pain treatment group (OTG; n = 40) or a standardized medical program with an emphasis on physical therapy (PTG; n = 21). Pain assessments were performed before, immediately after, 6 months after, and 15 months after treatment.\n The OTG patients reported a significant and stable reduction in pain intensity, interference, solicitous behavior of the spouse, medication, pain behaviors, number of doctor visits, and days at a hospital as well as an increase in sleeping time. Sixty-five percent of the OTG compared with none of the patients in the PTG showed clinically significant improvement.\n These results suggest that operant pain treatment provided in an inpatient setting is an effective treatment for FMS, whereas a purely somatically oriented program may lead to a deterioration of the pain problem.", "We evaluated the short- and long-term efficacy of a brief cognitive-behavioral therapy (CBT) for chronic temporomandibular disorder (TMD) pain in a randomized controlled trial. TMD clinic patients were assigned randomly to four sessions of either CBT (n=79) or an education/attention control condition (n=79). Participants completed outcome (pain, activity interference, jaw function, and depression) and process (pain beliefs, catastrophizing, and coping) measures before randomization, and 3 (post-treatment), 6, and 12 months later. As compared with the control group, the CBT group showed significantly greater improvement across the follow-ups on each outcome, belief, and catastrophizing measure (intent-to-treat analyses). The CBT group also showed a greater increase in use of relaxation techniques to cope with pain, but not in use of other coping strategies assessed. On the primary outcome measure, activity interference, the proportion of patients who reported no interference at 12 months was nearly three times higher in the CBT group (35%) than in the control group (13%) (P=0.004). In addition, more CBT than control group patients had clinically meaningful improvement in pain intensity (50% versus 29% showed > or =50% decrease, P=0.01), masticatory jaw function (P<0.001), and depression (P=0.016) at 12 months (intent-to-treat analyses). The two groups improved equivalently on a measure of TMD knowledge. A brief CBT intervention improves one-year clinical outcomes of TMD clinic patients and these effects appear to result from specific ingredients of the CBT.", "Chronic pain is a common, disabling problem in older adults. Pain self-management training is a multimodal therapy that has been found to be effective in young to middle-aged adult samples; however, few studies have examined the effectiveness of this therapy in older adults. In this randomized, controlled trial, we evaluated a pain self-management training group (SMG) intervention as compared with an education-only (BOOK) control condition. Participants, 65 years of age or older who experienced persistent, noncancer pain that limited their activities, were recruited from 43 retirement communities in the Pacific Northwest of the United States. The primary outcome was physical disability, as measured by the Roland-Morris Disability Questionnaire. Secondary outcomes were depression (Geriatric Depression Scale), pain intensity (Brief Pain Inventory), and pain-related interference with activities (Brief Pain Inventory). Randomization occurred by facility to minimize cross-contamination between groups. Two-hundred and fifty-six individuals, mean age=81.8 (SD: 6.5), enrolled and 218 completed the study. No significant differences in outcomes were found between groups at post-intervention, 6-month follow-up, or 12-month follow-up. The SMG group showed a significantly greater increase over time, relative to the BOOK group, in two process measures, as measured by the Chronic Pain Coping Inventory: use of relaxation and use of exercise/stretching. In both cases, the increase was greatest from baseline to the post-intervention assessment. Study findings indicate that additional research is needed to determine the most effective content and delivery methods for self-management therapies targeted at older adults with chronic pain.", "Joint protection aims to reduce pain and local inflammation, preserve the integrity of joint structures and improve function. There is evidence that it can improve pain and function in the short term, but the long-term effects are uncertain. This study evaluated the effects of joint protection in early rheumatoid arthritis (RA).\n A randomized, controlled, assessor-blinded trial of duration 1 yr was conducted. Two interventions (both 8 h) were compared: standard arthritis education, including 2.5 h of joint protection education based on typical UK practice; and a joint protection arthritis education programme, using educational-behavioural teaching methods. Assessments were made at entry and 6 and 12 months.\n Sixty-five people with RA attended the joint protection programme and 62 the standard programme. The groups were matched for age (51 and 49 yr), disease duration (21 and 17.5 months) and use of non-steroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs. In comparison with the standard group, the joint protection group significantly improved with respect to adherence to the joint protection programme (P=0.001), hand pain (P=0.02), general pain (P=0.05), early morning stiffness (P=0.01), self-reported number of disease flare-ups (P=0.004), visits to the doctor for arthritis (P<0.01), and the AIMS2 (Arthritis Impact Measurement Scales) activities of daily living scale (P=0.04). A trend to improved swollen joint counts was identified (P=0.07). Within-group analyses also showed improvements in arthritis self-efficacy and perceived control. Hand deformity scores continued to increase in both groups.\n We found significant improvements in adherence, pain, disease status and functional ability amongst those attending the joint protection programme. Benefits became more apparent with time, suggesting that joint protection can help slow the progression of the effects of RA over and above the effects of drug therapy.", "To compare the effectiveness of biofeedback/relaxation, exercise, and a combined program for the treatment of fibromyalgia.\n Subjects (n = 119) were randomly assigned to one of 4 groups: 1) biofeedback/relaxation training, 2) exercise training, 3) a combination treatment, or 4) an educational/attention control program.\n All 3 treatment groups produced improvements in self-efficacy for function relative to the control condition. In addition, all treatment groups were significantly different from the control group on tender point index scores, reflecting a modest deterioration by the attention control group rather than improvements by the treatment groups. The exercise and combination groups also resulted in modest improvements on a physical activity measure. The combination group best maintained benefits across the 2-year period.\n This study demonstrates that these 3 treatment interventions result in improved self-efficacy for physical function which was best maintained by the combination group.", "Inpatient and outpatient cognitive behavioural pain management programmes for mixed chronic pain patients were compared. Patients were randomly allocated to the 4 week inpatient programme or to the 8 half day per week outpatient programme, or to a waiting list control group. Staff, teaching materials, and setting were the same for the two treatment groups. Patients were assessed pre-treatment, and at 1 month after discharge, and treated patients also at 6 months and 1 year after discharge, by assessors blind to treatment group; assessments included physical, functional and psychological measures, and medication use. In total, 121 mixed chronic pain patients (mean age 50 years; mean chronicity 8.1 years) were included in the study, following medical examination to ensure that no further medical treatment was appropriate. There was no change in the control group; inpatients and outpatients, comparable before treatment, both made significant improvements in physical performance and psychological function, and reduced medication use. Inpatients made greater gains, and maintained them better at 1 year; they also used less health care than outpatients. There were no outstanding predictors of improvement other than treatment group.", "The authors conducted a controlled clinical trial with 1-year follow-up to define the effectiveness of an intensive physical and psychosocial training program on patients with low back pain.\n The intervention group included 152 patients (mean age 40.5 yr, Million index 45.1/100), and the reference group included 141 patients (mean age 40.4 yr, Million-index 44.5/100).\n The progressive intervention program consisted of intensive physical training and psychosocial activation. The outcomes were physical and psychosocial measures, the pain and disability index (Million), sick leaves, and occupational handicap.\n The intervention was more efficient with respect to physical measures and pain and disability index. There were only mild or no differences in changes between the study groups in psychologic variables, sick leaves, or retirement.\n The intervention program could improve physical disability, but to improve occupational handicap, activities of the whole society (social legislation, labor market policy) are needed.", "This randomized controlled clinical trial evaluates the effectiveness of outpatient group cognitive/educational treatment for patients with the fibromyalgia (FM) syndrome. We hypothesized that the combination of group education with cognitive treatment aimed at developing pain coping skills would be more effective than group education alone.\n 131 patients with FM were randomly assigned to 3 conditions: an experimental condition, which was the combined cognitive/educational intervention (ECO); an attention control condition consisting of group education plus group discussion (EDI); and a waiting list control (WLC). For the treatment conditions ECO and EDI, assessments were made 2 weeks before treatment, at start of treatment, at post-treatment, and at 6 and 12 mo followup. WLC patients received only 3 assessments.\n There were no pretreatment differences between the groups, or between dropouts and patients who remained in the study. At post-treatment, and compared with the WLC, the ECO patients improved in knowledge about FM (p = 0.007) and pain coping (p < 0.001). EDI patients improved on pain coping (p = 0.005) and pain control (p = 0.002). EDI patients reported significantly less fear than ECO patients (p = 0.005). There were no other differential effects between ECO and EDI at post-treatment or 6 mo or 12 mo followup. Based on the reliability of change index for clinical significance, the relative short term success rates are 6.4 and 18.4% for ECO and EDI, respectively.\n The surplus value of a highly structured, 12 session group cognitive treatment added to group education cannot be supported by our study. In EDI, fear reduction might have enhanced pain coping and pain control, while poor compliance, the difficulty of homework assignments, and lack of individual support may have limited the effectiveness of ECO.", "This paper discusses the rationale for and content of a newly developed treatment for shoulder complaints, and describes a randomised study which is currently being conducted to test effectiveness of the treatment. In current practice, approximately 50% of all patients with shoulder complaints mention limitations in the performance of daily activities and persisting pain after six months. To improve the functional ability of patients with chronic shoulder complaints, despite their pain, we have developed an operant behavioural and time-contingent graded exercise therapy programme for use in a primary care setting. We present the theory and conceptual model underlying this programme, report on its development and content, and describe the design of a randomised clinical trial to evaluate the programme's effectiveness and cost-effectiveness. One hundred and thirty-two patients who suffer from shoulder complaints for at least 3 months are being recruited in general practice. After inclusion in the study, patients are allocated randomly to the graded exercise therapy programme or to usual care. Questionnaires will be used to measure factors like severity of the main complaint, functional limitations of daily activities, perceived recovery, global health status, shoulder pain, generic health-related quality of life, and costs. These factors will be assessed at baseline, during treatment (6 weeks), and after treatment (12, 26, and 52 weeks).", "The aim of the present study was to evaluate the outcome of a behavioral medicine (BM) rehabilitation program and the outcome of its two main components, compared to a 'treatment-as-usual' control group (CG). The study employed a 4x4 repeated-measures design with four groups and four assessment periods (pre-treatment, post-treatment, 6-month follow-up, and 18-month follow-up). The group studied consisted of subjects on sick leave identified in a nationwide health insurance scheme in Sweden. After inclusion, the subjects were randomized to one of four conditions, which were: (1) behavior-oriented physical therapy (PT); (2) cognitive behavioral therapy (CBT); (3) BM rehabilitation consisting of PT+CBT (BM); (4) a 'treatment-as-usual' CG. The treatments were given over a period of 4 weeks, PT and CBT on a part-time basis and BM on a full-time basis. Outcome variables were sick leave, early retirement, and health-related quality of life (measured using the Short Form Health Survey, SF-36). The results showed that the risk of being granted full-time early retirement was significantly lower for females in PT and CBT compared to the CG during the 18-month follow-up period. However, the total absence from work (sick listing plus early retirement) in days over the 18-month follow-up period was not significantly different in the CG compared to the treatments. On the SF-36, women in CBT and BM reported a significantly better health-related quality of life than women in the CG at the 18-month follow-up. No significant differences for men were found on the SF-36 scales. In conclusion, the results revealed gender differences in the outcome of the treatments and that the components of this BM program yielded as good results as the whole program.", "To assess the effects of a stress-reduction program on pain, psychological function, and physical function in persons with systemic lupus erythematosus (SLE) who experience pain.\n Ninety-two SLE patients were assigned randomly to receive either biofeedback-assisted cognitive-behavioral treatment (BF/CBT), a symptom-monitoring support (SMS) intervention, or usual medical care (UC) alone.\n BF/CBT participants had significantly greater reductions in pain and psychological dysfunction compared with the SMS group (pain, P = 0.044; psychological functioning, P < 0.001) and the UC group (pain, P = 0.028; psychological functioning, P < 0.001). BF/CBT had significantly greater improvement in perceived physical function compared with UC (P = 0.035), and improvement relative to SMS was marginally significant (P = 0.097). At a 9-month followup evaluation, BF/CBT continued to exhibit relative benefit compared with UC in psychological functioning (P = 0.023).\n This study supports the utility of a brief stress management program for short-term improvement in pain, psychological function, and perceived physical function among persons with SLE who experience pain.", "The purpose of this study is to investigate the management of chronic pain in a large health maintenance organization using cognitive-behavioral techniques and a blinded control group.\n Subjects were randomized into two groups. All participants completed a self-administered baseline questionnaire and were mailed a self-administered 6-month follow-up questionnaire.\n This study examines chronic pain management in a large, established health maintenance organization.\n Patients were members of a health maintenance organization, had pain for at least 6 months, and had failed all known treatment regimens.\n The treatment group participated in a 16-hour, 8-week class teaching cognitive-behavioral techniques, the relaxation response, meditation, and stress management. The minimal treatment group received a home-study manual.\n Behavioral outcomes, function, and pain severity and also patient satisfaction were measured.\n Both the treatment and minimal treatment groups exhibited improvement in pain severity, negative mood, pain affect, and pain interference with the patient's life.\n Gains were achieved in pain severity, negative mood, pain affect, self-control, and pain interference with the patient's life. Other behavioral variables and activity did not improve. Except in self-control, pain affect, and distracting responses from their significant others, the blinded minimal treatment group demonstrated similar findings. Patient satisfaction with treatment strongly favored the treatment group with over 78% of the treatment participants satisfied with the care provided.", "This research examined whether cognitive behavioral therapy and mindfulness interventions that target responses to chronic stress, pain, and depression reduce pain and improve the quality of everyday life for adults with rheumatoid arthritis (RA). The 144 RA participants were clustered into groups of 6-10 participants and randomly assigned to 1 of 3 treatments: cognitive behavioral therapy for pain (P); mindfulness meditation and emotion regulation therapy (M); or education-only group (E), which served as an attention placebo control. The authors took a multimethod approach, employing daily diaries and laboratory assessment of pain and mitogen-stimulated levels of interleukin-6 (IL-6), a proinflammatory cytokine. Participants receiving P showed the greatest Pre to Post improvement in self-reported pain control and reductions in the IL-6; both P and M groups showed more improvement in coping efficacy than did the E group. The relative value of the treatments varied as a function of depression history. RA patients with recurrent depression benefited most from M across several measures, including negative and positive affect and physicians' ratings of joint tenderness, indicating that the emotion regulation aspects of that treatment were most beneficial to those with chronic depressive features.\n (c) 2008 APA, all rights reserved", "This study explored the effectiveness, in terms of age of the client, of a 10-week cognitive-behavioral group therapy (stress inoculation training) for chronic pain. A total of 69 outpatients between the ages of 27 and 80 (M = 52.74 years, SD = 14.40) with diverse types of chronic pain were assigned randomly to immediate or wait-list-delayed therapy. Self-report measures of pain, activities, coping, and the use of medications and other physical pain control techniques were obtained at baseline, during therapy, and at 1- and 6-month follow-up. Treatment decreased the degree to which pain interfered with activity, increased ability to cope with pain, and decreased use of some medications and other physical treatments. It had little effect on perceived pain intensity. Gains were maintained through 6-month follow-up. Age was unrelated to outcome. Stress inoculation training appears to be an effective method of ameliorating the interference of chronic pain with the daily activities of life for adults of all ages." ]

[ "3549879", "12610718", "18605811" ]

[ "Weight gain and prolactin levels in patients on long-term antipsychotic medication: a double-blind comparative trial of haloperidol decanoate and fluphenazine decanoate.", "Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study.", "A multicenter, randomized, double-blind study of the effects of aripiprazole in overweight subjects with schizophrenia or schizoaffective disorder switched from olanzapine." ]

[ "A one year double-blind trial of haloperidol decanoate and fluphenazine decanoate was conducted in nineteen out-patients who had previously received at least one year's treatment with fluphenazine decanoate and were already overweight, as judged by a Body Mass Index of 25+. Although the difference was not statistically significant, patients treated with haloperidol decanoate showed a trend to less weight gain than patients who continued on fluphenazine decanoate, even though the haloperidol to fluphenazine dose ratio was 4:1. No statistically significant changes in mental state were observed and the incidence of extrapyramidal side-effects in the two treatment groups was similar.", "Switching patients from one antipsychotic to another can lead to tolerability problems or transient symptom exacerbations. It is important to compare switching strategies to determine which methods produce the best possible patient outcomes.\n To investigate the efficacy, safety and tolerability of three dosing strategies for switching chronic, stable patients with schizophrenia from current oral antipsychotic monotherapy to once-daily oral aripiprazole monotherapy.\n Patients in this 8-week, open-label, outpatient study were randomized to: 1). immediate initiation of 30 mg/day aripiprazole with simultaneous immediate discontinuation of current antipsychotic; 2). immediate initiation of 30 mg/day aripiprazole while tapering off current antipsychotic over 2 weeks; or 3). up-titrating aripiprazole to 30 mg/day over 2 weeks, while simultaneously tapering off current antipsychotic. Efficacy assessments included PANSS, CGI-S, and CGI-I scores. Safety assessments included: adverse events (AEs) recording, evaluation of extrapyramidal symptoms (EPS), vital signs, ECG, and clinical laboratory tests.\n Efficacy with aripiprazole was maintained during the study with numerical improvements compared with baseline in all three groups. The overall incidence of AEs was broadly comparable across all groups, and AEs were generally mild to moderate in severity and time-limited. Discontinuations due to AEs were comparable across the groups. No deterioration in EPS occurred in any group. The reduction in body weight and plasma prolactin levels following switch to aripiprazole were comparable across the three groups.\n Any of the three strategies evaluated can be used safely for switching patients to aripiprazole from antipsychotic monotherapy. Furthermore, patients' symptoms may continue to improve after switching to aripiprazole.", "Major mental disorders are associated with an increased risk for obesity-related cardiovascular mortality, leading to interest in risk-reduction approaches that target weight and risk-related plasma lipids, including use of antipsychotic agents with low metabolic risk. This multicenter, randomized, double-blind study compared the metabolic effects of aripiprazole versus olanzapine in overweight persons with schizophrenia or schizoaffective disorder who were previously on olanzapine treatment.\n In total, 173 subjects with DSM-IV-TR-defined schizophrenia or schizoaffective disorder were randomly assigned to receive aripiprazole (N = 88) or olanzapine (N = 85) for 16 weeks in a study conducted from March 30, 2004, to August 8, 2006. Primary and secondary endpoints were mean weight change from baseline and percentage change from baseline in fasting triglyceride levels, respectively.\n At week 16, weight decreased significantly with aripiprazole versus olanzapine (-1.8 vs. +1.41 kg; p < .001). Significant differences in percentage change in triglyceride levels were observed with aripiprazole (decreases) versus olanzapine (increases) at all time-points. In addition, significantly more subjects receiving aripiprazole had clinically relevant (> or = 7%) weight loss versus olanzapine (11.1% vs. 2.6%; p = .038), and a lower percentage of subjects receiving aripiprazole had clinically relevant weight gain (2.5% vs. 9.1%; p = .082). Mean percentage changes in fasting total cholesterol and high-density lipoprotein cholesterol at week 16 were significantly different with aripiprazole versus olanzapine, with no significant effects on glycemic laboratory measures. Mean Clinical Global Impressions-Improvement (CGI-I) scores for both groups were in the range of \"no change\" to \"minimal improvement.\" CGI-I endpoint scores were statistically significantly better with olanzapine (mean +/- SE = 3.09 +/- 0.16) versus aripiprazole (mean +/- SE = 3.74 +/- 0.15; p < .001), and more subjects discontinued aripiprazole (N = 32/88; 36%) than olanzapine (N = 22/85; 26%).\n Significant improvements in weight and lipids observed during discontinuation of olanzapine and switch to aripiprazole treatment occurred with limited evidence of negative psychiatric effects, relative to uninterrupted continuation of olanzapine treatment. The results suggest that the potential value of therapeutic substitutions involving specific antipsychotic medications should be considered in overall efforts to reduce cardiovascular risk in this population." ]

[ "4557585", "3571940", "16855454", "476223", "391753", "3905773", "10901342", "14628981", "17110825", "7755127", "2664088", "13904675", "14097430", "5502782", "13514499", "15669893", "15641125", "10084641" ]

[ "Methylphenidate in mildly depressed outpatients.", "The effects of methylamphetamine on mood and appetite in depressed patients: a placebo-controlled study.", "Modafinil for atypical depression: effects of open-label and double-blind discontinuation treatment.", "d-Amphetamine: effects on memory in a depressed population.", "The clinical and psychological effects of pemoline in depressed patients--a controlled study.", "Methylphenidate in mild depression: a double-blind controlled trial.", "Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial.", "Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study.", "A randomized, double-blind, placebo-controlled trial of augmentation with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression.", "Double-blind, placebo-controlled trial of methylphenidate in older, depressed, medically ill patients.", "Major depression in Parkinson's disease and the mood response to intravenous methylphenidate: possible role of the \"hedonic\" dopamine synapse.", "Phenelzine and dexamphetamine in depressive illness. A comparative trial.", "IMIPRAMINE AND \"DRINAMYL\" IN DEPRESSIVE ILLNESS: A COMPARATIVE TRIAL.", "A controlled study of the antidepressant effect of p-Chloro-N-methylamphetamine, a compound with a selective effect on the central 5-hydroxytryptamine metabolism.", "A controlled trial of methyl phenidate (ritalin) in the treatment of depressive states.", "A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness.", "Comparing effects of methylphenidate, sertraline and placebo on neuropsychiatric sequelae in patients with traumatic brain injury.", "Early augmentation of sertraline with methylphenidate." ]

[ "nan", "Methylamphetamine given intravenously as a single 15 mg dose led to a pronounced elevation of mood in 7 out of 21 depressed patients compared to a control injection of sterile water administered on another occasion in random order under double-blind conditions. All 7 responders experienced an increase of VAS self-ratings of hunger in contrast to what has been observed in normal subjects who show a decrease in hunger after amphetamine. The implications of these findings are discussed in the light of monoamine theories of depression and appetite control.", "Atypical depression, with features of hypersomnia, hyperphagia, anergia, and rejection sensitivity, is a common presentation of major depressive disorder. There are few available effective therapies for this disorder. We test modafinil, a novel wake-promoting agent, as monotherapy for atypical depression in a double-blind, placebo-controlled, relapse prevention trial after open-label treatment. We found that modafinil significantly improved atypical depression symptoms during 12 weeks of open-label treatment (mean +/- SD Hamilton Depression Scale (29-item version) score changed from 34 +/- 8.2 at baseline to 9.7 +/- 9.3, P < 0.0001), and that benefits were maintained alike in both the continuation and placebo arms during the double-blind treatment phase (P = 0.92). Modafinil was well tolerated and the drug was associated with significant weight loss compared with placebo (P = 0.01).", "The effect of intravenous d-amphetamine on memory functions in a group of depressed patients was examined in a double-blind placebo-controlled study. Active drug administration resulted in an increase in verbal free recall but no change in cued recall, suggesting specific effects on memory processes. The level of psychological processing of the presented stimulus was shown to interact with drug-induced facilitation of recall. Improvement in memory of more shallowly processed material under amphetamine related significantly to subjects' base-line indices of noradrenergic function. Drug-induced changes in mood did not correlate with improvement in cognitive functioning. The interrelationships between biochemical determinants of mood and memory are discussed in light of these findings.", "The clinical and psychological effects of pemoline were compared with placebo in a double-blind study of 20 depressed patients. Target symptoms were disturbances of concentration and memory, tension, depression, fatigue, decreased libido, anorexia and insomnia. The two groups were matched for their clinical picture, age, sex, and duration of illness. During the three-week study period the pemoline group received 50 mg daily. Significant differences in some clinical symptoms were found between the groups, but not in the performance of psychological tests, administered before and after the three-week study period. These differences proved the effectiveness of pemoline in combating symptoms of disturbances in concentration, memory, tension, depression and fatigue.", "The literature on the use of stimulants in depression is reviewed, and a controlled study is described. Twenty mildly depressed outpatients with Hamilton Depression Rating Scale scores of 14-24 were entered into a double-blind crossover study with randomized order, comparing methylphenidate (up to 60 mg/day) and placebo. No antidepressant effect was found. A beneficial effect of stimulants in subgroups of depressed patients remains to be proven.", "This report documents findings from a small placebo-controlled trial of dextroamphetamine for depression and fatigue in men with the human immunodeficiency virus (HIV). Dextroamphetamine offers the potential for rapid onset of effect and activation properties, both of which are important to persons with medical illness and an uncertain, but limited, life expectancy.\n Primary inclusion criteria included the presence of a DSM-IV depressive disorder, debilitating fatigue, and no history of dependence on stimulants. The study consisted of a 2-week randomized, placebo-controlled trial, with the blind maintained until week 8 for responders, followed by open treatment through the completion of 6 months.\n Of 23 men who entered the study, 22 completed the 2-week trial. Intent-to-treat analysis indicated that 73% of patients (8/11) randomly assigned to dextroamphetamine reported significant improvement in mood and energy, compared with 25% (3/12) among placebo patients (Fisher exact test, p < .05). Both clinician- and self-administered measures indicated significantly improved mood, energy, and quality of life among patients taking dextroamphetamine. There was no evidence of the development of tolerance of, abuse of, or dependence on the medication.\n These results suggest that dextroamphetamine is a potentially effective, fast-acting antidepressant treatment for HIV patients with depression and debilitating fatigue.", "Fatigue and sleepiness are primary symptoms of depression that may not resolve with antidepressant therapy. Modafinil is a novel agent that has been shown to improve wakefulness and lessen fatigue in a variety of conditions. In this study, we examined the utility of modafinil as an adjunct therapy to treat fatigue and sleepiness in patients with major depression who are partial responders to antidepressants.\n Patients with partial response to anti-depressant therapy given for at least a 6-week period for a current major depressive episode (DSM-IV criteria) were enrolled in this 6-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Patients received once-daily doses (100-400 mg) of modafinil or matching placebo as adjunct treatment to ongoing antidepressant therapy. The effects of modafinil were evaluated using the Hamilton Rating Scale for Depression (HAM-D), the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Change (CGI-C), and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Adverse events were monitored throughout the study.\n One hundred thirty-six patients were randomized to treatment, with 118 patients (87%) completing the study. Most patients (82%) were fatigued, and one half of patients (51%) were sleepy. Modafinil rapidly improved fatigue and daytime wakefulness, with significantly greater mean improvements from baseline than placebo in fatigue (FSS) scores at week 2 (p < .05) and sleepiness (ESS) scores at week 1 (p < .01); the differences between modafinil and placebo at week 6 were not statistically significant. Assessment of the augmentation effects of modafinil (HAM-D, CGI-C, and SF-36) did not significantly distinguish modafinil from placebo. Modafinil was well tolerated in combination with a variety of antidepressants.\n Modafinil may be a useful adjunct therapy for the short-term management of residual fatigue and sleepiness in patients who are partial responders to antidepressant therapy.", "We examined the efficacy and tolerability of augmentation with an extended release formulation of methylphenidate (OROS MPH, Concerta) in patients with major depression who were nonresponders or partial responders to antidepressants. Sixty subjects with treatment-resistant depression (TRD) participated in a 4-week, randomized, double-blind, placebo-controlled study of augmentation with methylphenidate (18-54 mg/d). The preexisting antidepressant dose was unchanged. The primary efficacy measure was change in the 21-item Hamilton Depression Rating Scale from randomization to end of treatment. Data were analyzed with intent-to-treat with last observation carried forward approach. There were no statistically significant differences between the methylphenidate (n = 30) and placebo (n = 30) groups in reduction in 21-item Hamilton Depression Rating Scale scores (drug, -6.9; placebo, -4.7) from baseline to end of treatment (F1,47 = 1.24, P = 0.22), although responders were numerically higher in the extended-release methylphenidate group (40.0%) than in the placebo group (23.3%). On the secondary efficacy measures of changes in Clinical Global Impression-Improvement and Severity scores and Beck Depression Inventory-Second Edition, the drug failed to separate from placebo, although the proportion of responders in the drug group were numerically higher than placebo. There were no significant differences in weight, heart rate, and blood pressure changes between the 2 groups. The common adverse events were loss of appetite, nausea, headache, and anxiety. The mean dose of drug was 34.2 mg/d. The study did not demonstrate a statistically significant benefit for augmentation with methylphenidate in TRD. Combination of methylphenidate with antidepressants was well tolerated. Adequately powered, randomized, controlled trials are necessary to fully evaluate the efficacy of extended-release methylphenidate in TRD.", "The authors examined the efficacy of methylphenidate in the treatment of depression in a group of older, medically ill patients.\n Sixteen patients underwent an 8-day double-blind, randomized, placebo-controlled crossover trial; 13 completed the trial.\n Statistically and clinically significant treatment responses were found.\n These results support the use of methylphenidate in older, medically ill patients in whom rapid resolution of depressive symptoms is crucial.", "The euphoric response to equivalent doses of intravenous methylphenidate (MTP) was assessed in a group of 13 Parkinsonian patients affected by major depression, in a group of 11 nondepressed Parkinsonians, in a group of 14 nonparkinsonian subjects suffering from major depression, and finally in a group of 12 controls with no CNS or psychiatric disease. Subjects of all four groups were matched for age, sex and other main characteristics. Depressed and nondepressed Parkinsonians were also matched for duration and severity of illness, and for the type of antiparkinsonian treatment. The response to MTP was evaluated in the context of a double-blind, placebo-controlled study. Parkinsonian patients with major depression exhibited a significant lack of sensitivity to the euphoriant effects of MTP, in comparison with the other three groups. Euphoria produced by central stimulants has been shown to depend on the activity of a dopamine synapse in humans, which is thought to be situated at the limbic terminals of dopamine neurons located in the ventral tegmental area. Degeneration of this system may have predisposed our Parkinsonian patients to major depression.", "nan", "nan", "nan", "nan", "Up to one half of depressed patients have partial or no response to antidepressant monotherapy. This multicenter, placebo-controlled study evaluated the efficacy of modafinil augmentation in major depressive disorder (MDD) patients with fatigue and excessive sleepiness despite selective serotonin reuptake inhibitor (SSRI) monotherapy.\n Patients (18-65 years) with a DSM-IV diagnosis of MDD and partial response to SSRI monotherapy (> or = 8 weeks) at a stable dose for > or = 4 weeks were eligible. Patients had screening/baseline 31-item Hamilton Rating Scale for Depression (HAM-D) scores of 14 to 26, Epworth Sleepiness Scale (ESS) scores > or = 10, and Fatigue Severity Scale (FSS) scores > or = 4. Patients were randomly assigned to augmentation therapy with modafinil 200 mg/day or placebo for 8 weeks. Assessments included the ESS, Clinical Global Impressions-Improvement scale (CGI-I), 31- and 17-item HAM-D, FSS, Brief Fatigue Inventory (BFI), and Montgomery-Asberg Depression Rating Scale (MADRS).\n Of 311 enrolled patients who received > or = 1 dose of study drug, 158 were randomly assigned to modafinil (70% women) and 153 to placebo (72% women); 85% of each treatment group completed the study. At final visit, modafinil significantly improved patients' overall clinical condition compared with placebo on the basis of CGI-I scores (p = .02), and there were trends toward greater mean reductions in ESS, 31- and 17-item HAM-D, and MADRS scores versus placebo. Modafinil significantly reduced BFI scores for worst fatigue at final visit (p < .05 vs. placebo). There were no significant differences between modafinil and placebo at final visit in FSS or BFI total scores. Adverse events significantly more common during modafinil compared with placebo treatment were nausea (9% vs. 2%; p = .01) and feeling jittery (4% vs. 1%; p = .03).\n These findings suggest that modafinil is a well-tolerated and potentially effective augmenting agent for SSRI partial responders with fatigue and sleepiness.", "This study aimed to investigate the effects of methylphenidate and sertraline compared with placebo on various neuropsychiatric sequelae associated with traumatic brain injury (TBI).\n This was a 4 week, double-blind, parallel-group trial. Thirty patients with mild to moderate degrees of TBI were randomly allocated to one of three treatment groups (n = 10 in each group) with matching age, gender and education, i.e. methylphenidate (starting at 5 mg/day and increasing to 20 mg/day in a week), sertraline (starting at 25 mg/day and increasing to 100 mg/day in a week) or placebo. At the baseline and at the 4 week endpoint, the following assessments were administered: subjective (Beck Depression Inventory) and objective (Hamilton Depression Rating Scale) measures of depression; Rivermead Postconcussion Symptoms Questionnaire for postconcussional symptoms; SmithKline Beecham Quality of Life Scale for quality of life; seven performance tests (Critical Flicker Fusion, Choice Reaction Time, Continuous Tracking, Mental Arithmetic, Short-Term memory, Digit Symbol Substitution and Mini-Mental State Examination); subjective measures of sleep (Leeds Sleep Evaluation Questionnaire) and daytime sleepiness (Epworth Sleepiness Scale). All adverse events during the study period were recorded and their relationships to the drugs were assessed.\n Neuropsychiatric sequelae seemed to take a natural recovery course in patients with traumatic brain injury. Methylphenidate had significant effects on depressive symptoms compared with the placebo, without hindering the natural recovery process of cognitive function. Although sertraline also had significant effects on depressive symptoms compared with the placebo, it did not improve many tests on cognitive performances. Daytime sleepiness was reduced by methylphenidate, while it was not by sertraline.\n Methylphenidate and sertraline had similar effects on depressive symptoms. However, methylphenidate seemed to be more beneficial in improving cognitive function and maintaining daytime alertness. Methylphenidate also offered a better tolerability than sertraline.\n 2005 John Wiley & Sons, Ltd.", "nan" ]

[ "2832935", "7508066", "1638340", "16749588", "9720517" ]

[ "Unprocessed bran and intermittent thiazide therapy in prevention of recurrent urinary calcium stones.", "Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing calcium stone recurrences.", "Thiazide treatment for calcium urolithiasis in patients with idiopathic hypercalciuria.", "[The role of thiazides in the prophylaxis of recurrent calcium lithiasis].", "Physiological effects of slow release potassium phosphate for absorptive hypercalciuria: a randomized double-blind trial." ]

[ "Both urinary calcium excretion and renal stone episodes are increased during the summer in Finland. Since thiazide and unprocessed bran are known to decrease urinary calcium excretion, we treated 73 patients with recurrent urinary stone formation by giving them unprocessed bran and intermittent thiazide. Of the patients, 32 had absorptive hypercalciuria and 41 had normal urinary calcium values. All patients were on a low-calcium and low-oxalate diet and took 40 g bran daily. Fourteen of the hypercalciuric and 14 of the normocalciuric patients were randomly allocated to use hydrochlorothiazide 50 mg b.i.d. from May to September. Reduction of stone formation was seen in all groups. The combination of thiazide + bran was superior to the bran on its own in inhibition of stone formation. Only 3/11 (27%) stones passed through during the summer in the thiazide + bran group as compared with the 11/17 (65%) in the bran group.", "We examined the biochemical changes and the efficacy of indapamide in the prevention of calcium stone recurrences. Seventy-five patients with calcium nephrolithiasis and hypercalciuria were randomly assigned to three different therapies: diet and fluid (group A), diet and fluid plus indapamide 2.5 mg/day (group B), and diet and fluid plus indapamide 2.5 mg/day plus allopurinol 300 mg/day (group C). Before treatment and after 6, 12, 24, and 36 months of therapy, we evaluated blood pressure, serum and urine risk parameters (including relative supersaturations of calcium oxalate, calcium phosphate and uric acid), stone rate, and the proportion of calculi-free patients. During the 3 years of treatment, urinary calcium greatly decreased in groups B and C, dropping to 50% of the pretreatment values; urinary oxalate also significantly declined in group B (-24%) and group C (-27%). Relative supersaturations of calcium oxalate and calcium phosphate decreased to the same extent in groups B and C (about one-half of the pretreatment value), and relative supersaturation of uric acid was particularly reduced in group C (-65% of the pretreatment value). The stone rate improved in all three groups (p < 0.005), but using actuarial analysis in the evaluation of calculi-free patients, indapamide, and indapamide plus allopurinol groups were found to have a significantly more favorable effect than diet and fluid treatment (p < 0.02), without any difference between the two drug groups. Because indapamide has fewer side effects than thiazide diuretics, we conclude that indapamide could be an interesting alternative to thiazides in the prevention of calcium stones in hypercalciuric patients.", "In a randomised trial based on a parallel design to determine the prophylactic effect of thiazide on stone formation, 210 calcium urolithiasis patients with idiopathic hypercalciuria were allocated either to treatment with trichlormethiazide (4 mg/day) or no treatment with only close follow-up; 35 patients were excluded for various reasons, including voluntary withdrawal. The background of the remaining 175 patients (82 in the thiazide group and 93 in the control group), including age and sex, was similar for both groups. In patients treated with thiazide there was a statistically significant fall in urinary calcium output. Statistical analyses also demonstrated that the stone formation rate in the thiazide group was significantly less than that in the control group. Adverse clinical reactions probably due to the drug were observed in 9 patients. These findings indicate that trichlormethiazide has a prophylactic effect on calcium urolithiasis in patients with idiopathic hypercalciuria.", "To show the prolonged efficacy of thiazides in the prophylaxis and treatment of recurrences in patients with calcium oxalate and phosphate lithiasis.\n A randomised prospective study is conducted, with a three-year follow-up, in 150 patients diagnosed with recurrent calcium lithiasis. The patients are divided into three groups: A) 50 cases subject to observation with no treatment, B) 50 cases treated with 50 mg/day of hydrochlorothiazide, and C) 50 cases treated with 50 mg of hydrochlorothiazide and 20 mlEq of potassium citrate/day. Each group is subject to a renal study with imaging techniques and a urinary metabolic study at baseline, 12, 24 and 36 months.\n The patients treated with thiazides (Groups B and C) obtain a significant reduction in lithiasis recurrence compared with the control group (Group A). The most common abnormality found in the metabolic study was hypercalciuria, 52% of cases; 16% present a mixed lithogenic pattern. The number of recurrences and need for new sessions of extracorporeal lithotripsy in patients with hypercalciuria treated with thiazides is significantly smaller than in Group A (p=0.003).\n We observe a significant relation between lithogenic pattern and lithiasis recurrence. Thiazides help us to control lithogenic factors and recurrences in patients with calcium lithiasis. This effect is prolonged and significant in patients with hypercalciuria.", "We examined the physiological effects and tolerance of UroPhos-K, a slow release neutral form of potassium phosphate (155 mg. phosphate and 8 mEq. potassium per tablet) in patients with absorptive hypercalciuria.\n A total of 31 patients with absorptive hypercalciuria were studied at baseline and after 3 months of treatment with 4 tablets twice daily of UroPhos-K or placebo (identical in appearance) in a prospective randomized, placebo controlled, double-blind trial during a 4-day inpatient study with a daily constant metabolic diet containing 400 mg. calcium, 100 mEq. sodium and 800 mg. phosphate.\n Treatment with UroPhos-K did not cause significant gastrointestinal side effects, increase fasting serum potassium or phosphorus, or reduce hemoglobin or creatinine clearance. It reduced urinary calcium excretion from 277 +/- 72 to 166 +/- 43 mg. per day (p < 0.001), associated with a reduction in serum 1,25-dihydroxyvitamin D concentration from 50 +/- 11 to 42 +/- 9 pg./ml. (p < 0.001). Indexes of intestinal calcium absorption and markers of bone turnover also decreased modestly. None of these changes was seen in the placebo group.\n In patients with absorptive hypercalciuria UroPhos-K seems to correct hypercalciuria by a combination of reduced intestinal absorption, bone resorption and improved renal calcium reabsorption. The drug is well tolerated compared to placebo." ]

[ "10327712", "20801071", "15820586", "11470223", "2260182", "17324975", "11114752", "16343973", "13845013", "18701729", "22054336", "21563714", "18812366", "17325397", "12848239", "17699530" ]

[ "Chagas disease vector control through different intervention modalities in endemic localities of Paraguay.", "Health impact assessment and evaluation of a Roma housing project in Hungary.", "Housing improvement and self-reported mental distress among council estate residents.", "Neighbourhood renewal and health: evidence from a local case study.", "Reduction in diarrhoeal diseases in children in rural Bangladesh by environmental and behavioural modifications.", "Effect of insulating existing houses on health inequality: cluster randomised study in the community.", "Housing and health: does installing heating in their homes improve the health of children with asthma?", "\"The walls were so damp and cold\" fuel poverty and ill health in Northern Ireland: results from a housing intervention.", "Housing as an environmental factor in mental health: the Johsn Hopkins longitudinal study.", "The effect of improving the thermal quality of cold housing on blood pressure and general health: a research note.", "Enhancing ventilation in homes of children with asthma: pragmatic randomised controlled trial.", "Health outcomes and green renovation of affordable housing.", "Effects of improved home heating on asthma in community dwelling children: randomised controlled trial.", "The health impacts of housing-led regeneration: a prospective controlled study.", "Evaluating the effectiveness of a multi-component intervention to improve health in an inner-city Havana community.", "The Watcombe Housing Study: the short term effect of improving housing conditions on the health of residents." ]

[ "In a field study carried out in three rural communities in Paraguay in a zone endemic for Chagas disease, we implemented three different vector control interventions--spraying, housing improvement, and a combination of spraying plus housing improvement--which effectively reduced the triatomine infestation. The reduction of triatomine infestation was 100% (47/47) in the combined intervention community, whereas in the community where housing improvement was carried out it was 96.4% (53/55). In the community where fumigation alone was used, the impact was 97.6% (40/41) in terms of domiciliary infestation. In all the houses where an intervention was made, an 18-month follow-up showed reinfestation rates of less than 10%. A serological survey of the population in the pre- and post-intervention periods revealed a shift in positive cases towards older age groups, but no significant differences were observed. The rate of seroconversion was 1.3% (three new cases) in the community with housing improvement only, but none of these cases could have resulted from vector transmission. The most cost-effective intervention was insecticide spraying, which during a 21-month follow-up period had a high impact on triatomine infestation and cost US$ 29 per house as opposed to US$ 700 per house for housing improvement.", "An outstanding feature of marginalized Roma communities is their severely substandard living conditions, which contribute to their worse health status compared to the majority. However, health consequences of international and local-level housing initiatives in most cases fail to be assessed prospectively or evaluated after implementation. This paper summarizes the result of a retrospective health impact assessment of a Roma housing project in Hungary in comparison with the outcome evaluation of the same project. Positive impacts on education, in- and outdoor conditions were noted, but negative impacts on social networks, housing expenses and maintenance, neighbourhood satisfaction and no sustained change in health status or employment were identified. Recommendations are made to improve efficiency and sustainability of housing development initiatives among disadvantaged populations.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "This paper is concerned with how housing improvements instigated either publicly or privately influence the degree of psychological stress reported by council estate residents in South Manchester. Stress is measured on the GHQ12 scale containing standard symptomatic items. Potential sources of variation in this indicator are analysed within a geographical setting where repeated samples of residents were drawn from two adjacent suburban council housing estates before and after the implementation of a single regeneration budget (SRB) housing initiative in late 1999. The residents of one of these estates (Wythenshawe) were targeted by this funding while those in the other (Mersey Bank) were not. The latter, therefore, serve as a control for the effects of the enhanced incidence of housing improvement activity promoted by this SRB. Regression analyses revealed that stress was raised significantly among the SRB residents perhaps on account of the additional environmental nuisance they encountered. The experience of stress among all residents, however, was dominated by measures of personal psychosocial risk and it is argued that future regeneration initiatives should address the manifestation of these risks in the effort to achieve better mental health.", "This article presents findings from a before-and-after study of the effects of neighbourhood renewal on residents' health. Survey data were analysed using multivariate logistic regression. Before the renewal programme, damp and draughts had significant independent effects on respiratory health problems. Draughts and perceived community safety were associated with mental health problems. Children's mental health was associated with parental mental health. Following the renewal work, improvements occurred in both adults' and children's mental health, and smoking declined sharply. Respiratory health did not improve and there was no change in use of health services. Neighbourhood renewal in deprived areas can have an important role in improving community health.", "The impact of a water, sanitation and hygiene education intervention project on diarrhoeal morbidity in children under 5 years old was evaluated in a rural area of Bangladesh. Data were collected throughout 1984-1987, covering both pre- and post-intervention periods, from an intervention and a control area. The 2 areas were similar with respect to most socio-economic characteristics and baseline levels of diarrhoeal morbidity. The project showed a striking impact on the incidence of all cases of diarrhoea, including dysentery and persistent diarrhoea. By the end of the study period, children in the intervention area were experiencing 25% fewer episodes of diarrhoea than those in the control area. This impact was evident throughout the year, but particularly in the monsoon season, and in all age groups except those less than 6 months old. Within the intervention area, children from households living closer to handpumps or where better sanitation habits were practised experienced lower rates of diarrhoea. These results suggest that an integrated approach to environmental interventions can have a significant impact on diarrhoeal morbidity.", "To determine whether insulating existing houses increases indoor temperatures and improves occupants' health and wellbeing.\n Community based, cluster, single blinded randomised study.\n Seven low income communities in New Zealand.\n 1350 households containing 4407 participants.\n Installation of a standard retrofit insulation package.\n Indoor temperature and relative humidity, energy consumption, self reported health, wheezing, days off school and work, visits to general practitioners, and admissions to hospital.\n Insulation was associated with a small increase in bedroom temperatures during the winter (0.5 degrees C) and decreased relative humidity (-2.3%), despite energy consumption in insulated houses being 81% of that in uninsulated houses. Bedroom temperatures were below 10 degrees C for 1.7 fewer hours each day in insulated homes than in uninsulated ones. These changes were associated with reduced odds in the insulated homes of fair or poor self rated health (adjusted odds ratio 0.50, 95% confidence interval 0.38 to 0.68), self reports of wheezing in the past three months (0.57, 0.47 to 0.70), self reports of children taking a day off school (0.49, 0.31 to 0.80), and self reports of adults taking a day off work (0.62, 0.46 to 0.83). Visits to general practitioners were less often reported by occupants of insulated homes (0.73, 0.62 to 0.87). Hospital admissions for respiratory conditions were also reduced (0.53, 0.22 to 1.29), but this reduction was not statistically significant (P=0.16).\n Insulating existing houses led to a significantly warmer, drier indoor environment and resulted in improved self rated health, self reported wheezing, days off school and work, and visits to general practitioners as well as a trend for fewer hospital admissions for respiratory conditions.", "The objective of this study was to evaluate the use of NHS money to improve health by improving housing conditions. A pilot study assessing health outcomes before and after improving housing conditions was conducted, studying 72 children with previously diagnosed asthma living in 59 damp houses in Cornwall. The intervention was the installation of central heating. This improved the energy efficiency of the housing. The children's health was a symptom-based outcome measure for asthma and time lost from school. Improvements comprised installation of gas central heating in 28/59 (47%) houses, electric storage heaters in 22/59 (37%), solid fuel central heating in 7/59 (12%) and oil-fired central heating in 2/59 (4%) houses. Energy efficiency improved by a mean of 2.1 on the National Home Energy Rating scale (95% CI 1.68-2.47, P<0.001) in the 37/59 (62%) houses for which two readings were available. Initially, 69/72 (92%) children's bedrooms were unheated and 44/72 (61%) were damp; following improvements, the proportions were 10/72 (14%) and 15/72 (21%) respectively. All respiratory symptoms were significantly reduced after intervention; the greatest reduction was seen in nocturnal cough from a median score of 3 (most nights) to 1 (on one or several nights) (P<0.001) in the previous month. School-age children lost significantly less time from school for asthma in the previous 3 months (9.3 days per 100 school days before intervention and 2.1 days afterwards, P<0.01) but not for other reasons (1.4 days per 100 school days before and 3.2 after, P>0.05). In conclusion, this study provides the first evaluation of health outcomes following housing improvements. Lack of a comparison group means that effects of age, season and biased reporting cannot be eliminated. More work is needed to substantiate these results.", "This article reports the findings from an evaluation of a fuel poverty programme in the Armagh and Dungannon Health Action Zone in Northern Ireland. Focusing on a rural community, it adds to the debate surrounding the hidden nature of rural fuel poverty. As part of the programme, energy efficiency measures, including some central heating systems, were installed in 54 homes. Surveys were conducted both pre and post intervention and analysed to assess any changes. The programme demonstrated that energy efficiency intervention can lead to improvements in health and well being, increased comfort levels in the home and a reduction in the use of health services, therefore having potential cost savings for the NHS. Some households, however, remain in fuel poverty after having full central heating installed, reflecting the significant contribution of low income on the production of fuel poverty. The article concludes by suggesting that interventions in this area require commitment from multiple sectors of society, including health professionals and local communities.", "nan", "To examine the effect of improving the thermal quality of housing on blood pressure (BP) and general health.\n A before and after study comparing the changes of the intervention with controls.\n Four blocks of flats in the Easthall area of Easterhouse in Glasgow.\n Residents of the four blocks who agreed to participate.\n Two blocks of flats were upgraded from being cold, damp and mouldy to being comfortably warm, dry and mould free throughout.\n Changes in BP, general health and financial status.\n In the intervention subjects, systolic and diastolic blood pressures fell very significantly (p<0.000). There was also an improvement in general health as reported subjectively, and as indicated by a reduction in the use of medication and in hospital admissions. In addition, there was a markedly reduced expenditure on heating costs and other previous expenses. There were no changes in the control subjects in any of these measures.\n Improving the thermal quality of housing to eliminate damp and mould and produce a comfortable temperature throughout the house has a major impact on the health of the residents. There are also financial benefits for the residents, and indirectly for the NHS.", "Few robust studies have tested whether enhancing housing also improves health.\n To evaluate the effectiveness of installing ventilation systems, and central heating where necessary, in the homes of children with moderate or severe asthma.\n Pragmatic randomised controlled trial (RCT) in homes within Wrexham County Borough, Wales, UK.\n A pragmatic RCT was carried out, of a tailored package of housing improvements providing adequate ventilation and temperature, following inspection by a housing officer. One hundred and ninety-two children with asthma aged 5 to 14 years, identified from general practice registers, were randomised to receive this package, either immediately or a year after recruitment. At baseline, and after 4 and 12 months, parents reported their child's asthma-specific and generic quality of life, and days off school.\n The package improved parent-reported asthma-specific quality of life significantly at both 4 and 12 months. At 12 months, this showed an adjusted mean difference between groups of 7.1 points (95% confidence interval [CI] = 2.8 to 11.4, P= 0.001): a moderate standardised effect size of 0.42. The generic quality-of-life scale showed reported physical problems were significantly reduced at 4 months, but not quite at 12 months, when the mean difference was 4.5 (95% CI = -0.2 to 9.1, P= 0.061). The improvement in psychosocial quality of life at 12 months was not significant, with a mean difference of 2.2 (95% CI = -1.9 to 6.4, P= 0.292). Parent-reported school attendance improved, but not significantly.\n This novel and pragmatic trial, with integrated economic evaluation, found that tailored improvement of the housing of children with moderate to severe asthma significantly increases parent-reported asthma-related quality of life and reduces physical problems. Collaborative housing initiatives have potential to improve health.", "This study sought to determine whether renovating low-income housing using \"green\" and healthy principles improved resident health and building performance.\n We investigated resident health and building performance outcomes at baseline and one year after the rehabilitation of low-income housing using Enterprise Green Communities green specifications, which improve ventilation; reduce moisture, mold, pests, and radon; and use sustainable building products and other healthy housing features. We assessed participant health via questionnaire, provided Healthy Homes training to all participants, and measured ventilation, carbon dioxide, and radon.\n Adults reported statistically significant improvements in overall health, asthma, and non-asthma respiratory problems. Adults also reported that their children's overall health improved, with significant improvements in non-asthma respiratory problems. Post-renovation building performance testing indicated that the building envelope was tightened and local exhaust fans performed well. New mechanical ventilation was installed (compared with no ventilation previously), with fresh air being supplied at 70% of the American Society of Heating, Refrigerating, and Air-Conditioning Engineers standard. Radon was < 2 picocuries per liter of air following mitigation, and the annual average indoor carbon dioxide level was 982 parts per million. Energy use was reduced by 45% over the one-year post-renovation period.\n We found significant health improvements following low-income housing renovation that complied with green standards. All green building standards should include health requirements. Collaboration of housing, public health, and environmental health professionals through integrated design holds promise for improved health, quality of life, building operation, and energy conservation.", "To assess whether non-polluting, more effective home heating (heat pump, wood pellet burner, flued gas) has a positive effect on the health of children with asthma.\n Randomised controlled trial.\n Households in five communities in New Zealand.\n 409 children aged 6-12 years with doctor diagnosed asthma.\n Installation of a non-polluting, more effective home heater before winter. The control group received a replacement heater at the end of the trial.\n The primary outcome was change in lung function (peak expiratory flow rate and forced expiratory volume in one second, FEV(1)). Secondary outcomes were child reported respiratory tract symptoms and daily use of preventer and reliever drugs. At the end of winter 2005 (baseline) and winter 2006 (follow-up) parents reported their child's general health, use of health services, overall respiratory health, and housing conditions. Nitrogen dioxide levels were measured monthly for four months and temperatures in the living room and child's bedroom were recorded hourly.\n Improvements in lung function were not significant (difference in mean FEV(1) 130.7 ml, 95% confidence interval -20.3 to 281.7). Compared with children in the control group, however, children in the intervention group had 1.80 fewer days off school (95% confidence interval 0.11 to 3.13), 0.40 fewer visits to a doctor for asthma (0.11 to 0.62), and 0.25 fewer visits to a pharmacist for asthma (0.09 to 0.32). Children in the intervention group also had fewer reports of poor health (adjusted odds ratio 0.48, 95% confidence interval 0.31 to 0.74), less sleep disturbed by wheezing (0.55, 0.35 to 0.85), less dry cough at night (0.52, 0.32 to 0.83), and reduced scores for lower respiratory tract symptoms (0.77, 0.73 to 0.81) than children in the control group. The intervention was associated with a mean temperature rise in the living room of 1.10 degrees C (95% confidence interval 0.54 degrees C to 1.64 degrees C) and in the child's bedroom of 0.57 degrees C (0.05 degrees C to 1.08 degrees C). Lower levels of nitrogen dioxide were measured in the living rooms of the intervention households than in those of the control households (geometric mean 8.5 microg/m(3) v 15.7 microg/m(3), P<0.001). A similar effect was found in the children's bedrooms (7.3 microg/m(3) v 10.9 microg/m(3), P<0.001).\n Installing non-polluting, more effective heating in the homes of children with asthma did not significantly improve lung function but did significantly reduce symptoms of asthma, days off school, healthcare utilisation, and visits to a pharmacist.\n Clinical Trials NCT00489762.", "To evaluate self-reported changes in housing quality and health associated with housing-led area regeneration.\n A prospective study over 1 year using structured interviews with 50 households who moved to new housing and with 50 matched controls who did not move.\n Residents of two social rented housing schemes in the West of Scotland.\n Small but not statistically significant increases in levels of \"excellent\" or \"good\" self-reported health status were found in both groups. Both intervention and control groups experienced reductions in problems related to warmth, but no significant change in how they felt about their house.\n It is feasible to conduct prospective controlled studies to evaluate the health effects of housing improvement using matched control groups. The absence of marked improvement in health after moving to new housing might be due to the small sample size or to the limited potential to improve health through this intervention alone.", "The ecosystem approach to human health was applied to guide an evaluation of the effectiveness of a multi-component intervention to improve quality of life and health in an inner-city Havana community. A pre- versus post-intervention analysis was carried out in the study community of Cayo Hueso, and Colon, a concurrent comparison community. A household survey of 1,703 individuals was conducted in 30 neighborhoods, equally divided between the two areas. Greater improvements in housing, local infrastructure, and exposure to risk were perceived to have occurred in the targeted community, more so from the perspective of benefit to the community rather than with regard to the residents' own households. Improvements in some lifestyle-related risk factors and self-rated health in the most vulnerable subgroups (elderly and adolescents) were also achieved. Overall, the Cayo Hueso Plan was considered highly successful in improving the quality of life amid difficult circumstances. Its lessons are being embraced by other communities.", "To assess the short term health effects of improving housing.\n Randomised to waiting list.\n 119 council owned houses in south Devon, UK.\n About 480 residents of these houses.\n Upgrading houses (including central heating, ventilation, rewiring, insulation, and re-roofing) in two phases a year apart.\n All residents completed an annual health questionnaire: SF36 and GHQ12 (adults). Residents reporting respiratory illness or arthritis were interviewed using condition-specific questionnaires, the former also completing peak flow and symptom diaries (children) or spirometry (adults). Data on health service use and time lost from school were collected.\n Interventions improved energy efficiency. For those living in intervention houses, non-asthma-related chest problems (Mann-Whitney test, p = 0.005) and the combined asthma symptom score for adults (Mann-Whitney test, z = 2.7, p = 0.007) diminished significantly compared with control houses. No difference between intervention and control houses was seen for SF36 or GHQ12.\n Rigorous study designs for the evaluation of complex public health and community based interventions are possible. Quantitatively measured health benefits are small, but as health benefits were measured over a short time scale, there may have been insufficient time for measurable improvements in general and disease-specific health to become apparent." ]

[ "11044499", "11509774", "12237625", "15383112", "15559355", "11223708", "15374722", "12554989", "12386350", "12699795", "9166205", "12052587", "9823652", "9649102", "16962526", "10584722", "12849825", "17218227" ]

[ "One-year results of the vesta system for endometrial ablation.", "A multicenter evaluation of endometrial ablation by Hydro ThermAblator and rollerball for treatment of menorrhagia.", "Hysteroscopic transcervical endometrial resection versus thermal destruction for menorrhagia: a prospective randomized trial on satisfaction rate.", "Randomised controlled trial of bipolar radio-frequency endometrial ablation and balloon endometrial ablation.", "Microwave endometrial ablation vs. rollerball electroablation for menorrhagia: a multicenter randomized trial.", "Thermal balloon ablation in myoma-induced menorrhagia under local anesthesia.", "A randomized comparison of endometrial laser intrauterine thermotherapy and hysteroscopic endometrial resection.", "A randomized study comparing endometrial cryoablation and rollerball electroablation for treatment of dysfunctional uterine bleeding.", "A randomized, multicenter trial of safety and efficacy of the NovaSure system in the treatment of menorrhagia.", "A randomised controlled trial comparing the Cavaterm endometrial ablation system with the Nd:YAG laser for the treatment of dysfunctional uterine bleeding.", "A pragmatic randomised comparison of transcervical resection of the endometrium with endometrial laser ablation for the treatment of menorrhagia.", "Five-year follow-up of endometrial ablation: endometrial coagulation versus endometrial resection.", "[Therapy of recurrent menorrhagia--Cavaterm balloon coagulation versus roller-ball endometrium coagulation--a prospective randomized comparative study].", "Thermal balloon and rollerball ablation to treat menorrhagia: a multicenter comparison.", "Cavaterm thermal balloon endometrial ablation versus hysteroscopic endometrial resection to treat menorrhagia: the French, multicenter, randomized study.", "Comparison of microwave endometrial ablation and transcervical resection of the endometrium for treatment of heavy menstrual loss: a randomised trial.", "A double-blind randomized trial comparing the Cavaterm and the NovaSure endometrial ablation systems for the treatment of dysfunctional uterine bleeding.", "Comparison of the long-term histopathologic and morphologic changes after endometrial rollerball ablation and resection: a prospective randomized trial." ]

[ "To compare a distensible multielectrode balloon for endometrial ablation with electrosurgical ablation performed by a combined resection-coagulation technique.\n Randomized, prospective trial (Canadian Task Force classification I). Setting. Eight centers.\n Women with menorrhagia validated with a standardized pictorial blood loss assessment chart (PBAC), without intracavitary organic uterine disease, who failed or poorly tolerated medical therapy. Intervention. Results in 122 patients treated by Vesta and 112 treated surgically, evaluable at 1 year, were compared, with success defined as monthly blood loss of less than 80 ml and avoidance of additional therapy.\n Pretreatment PBAC scores for patients treated by Vesta and resection or rollerball were 535+/-612 and 445 +/- 313, respectively; at 1 year they were 18+/-37 and 28+/-60, respectively. With PBAC below 75 as the definition of success, 86.9% of Vesta-treated patients were successful compared with 83.0% treated by rollerball or resection. Total amenorrhea, defined as no visible bleeding and no use of protective products, was 31.1% and 34. 8%, respectively. None of the outcome comparisons between treatments showed statistical difference. Complications in both groups were few and minor. Most (86.6%) Vesta procedures were carried out with paracervical block with or without intravenous sedation in an office or outpatient setting, compared with 79.7% epidural or general anesthesia for rollerball or resection.\n The Vesta system of endometrial ablation is equally effective and safe as classic resectoscopic methods. Potential advantages include avoidance of fluid and electrolyte disturbance associated with intravasation of distending media, and ability to perform the procedure under local anesthesia in an office setting with less total operating time.", "To compare results of endometrial ablation using the Hydro ThermAblator (HTA) and rollerball.\n Prospective, randomized study (Canadian Task Force classification I).\n Nine private practice and university centers in the United States.\n Two hundred seventy-six women with menorrhagia due to benign causes.\n Endometrial ablation with the HTA (187 women) or rollerball (89).\n Menstrual diaries were kept for 2 weeks and 3, 6, and 12 months after treatment. Reduction in diary scores to 75 or lower at 12 months was considered a success. For patients treated and followed according to protocol, success rates were 77% for HTA and 82% for rollerball. Amenorrhea rates at 12 months were 40% and 51%, respectively.\n Endometrial ablation with the HTA is safe and effective. It offers an advantage over rollerball ablation of being an office-based procedure, which reduces anesthesia requirements and obviates problems of fluid absorption.", "The purpose of this study was to compare the satisfaction rate and the effectiveness of transcervical hysteroscopic endometrial resection and thermal destruction of the endometrium in the treatment of menorrhagia.\n A prospective randomized trial with 2 years of follow-up was carried out in the Department of Gynecology of the University of Naples. Eighty-two patients who were affected by menorrhagia that was unresponsive to medical treatment were respectively randomized to transcervical hysteroscopic endometrial resection or to thermal destruction of the endometrium. Satisfaction rate, operative time, discharge time, complication rate, reintervention rate, and resumption of normal activity were evaluated in each group.\n The satisfaction rate was significantly higher in the thermal destruction group. Operative time was significantly shorter in the thermal destruction group (24 +/- 4 minutes vs 37 +/- 6 minutes). Intraoperative blood loss was significantly lower in the thermal destruction group (7.2 +/- 2.8 mL vs 89 +/- 38 mL). Reintervention rates were higher in the transcervical hysteroscopic endometrial resection group, although postoperative pain was not significantly different between the two groups. Discharge time, complication rate, and resumption of normal activity were not significantly different between the two groups.\n Thermal destruction of the endometrium for the treatment of menorrhagia should be considered an effective therapeutic option because of its acceptability among patients, shorter operative time, and lower blood loss.", "To compare the effectiveness of two second-generation ablation techniques, bipolar radio-frequency impedance-controlled endometrial ablation (NovaSure) and balloon ablation (ThermaChoice), in the treatment of menorrhagia.\n Double-blind, randomised, controlled trial.\n A large teaching hospital with 500 beds in The Netherlands.\n Women suffering from menorrhagia referred by their general practitioner.\n Women suffering from menorrhagia, without intracavitary abnormalities, were randomly allocated to bipolar radio-frequency ablation (bipolar group) and balloon ablation (balloon group) in a 2:1 ratio. At follow up, both women and observers were unaware of the type of treatment that had been performed.\n The main outcome measure was amenorrhea at 3, 6 and 12 months after randomisation.\n One hundred and twenty-six women were included in the study, of which 83 were allocated to the bipolar group, and 43 to the balloon group. No complications occurred in either of the treatment groups. At the one-year follow up stage, amenorrhea rates were 43% (34/83) in the bipolar group and 8% (3/43) in the balloon group (treatment effect in time P < 0.001). At this stage, 90% of the patients in the bipolar group were satisfied with the result of the treatment against 79% in the balloon group (treatment effect in time P= 0.003).\n The bipolar radio-frequency impedance-controlled endometrial ablation system is more effective than balloon ablation in the treatment of menorrhagia.", "To compare the effectiveness, safety, and acceptability of microwave endometrial ablation (MEA) with those of rollerball electroablation (REA) for the treatment of menorrhagia.\n Randomized clinical trial (Canadian Task Force classification I).\n Eight academic medical centers and private medical practices.\n Three hundred twenty-two women with documented menorrhagia due to benign causes.\n MEA or REA.\n By intent-to-treat analysis, the success rate of MEA at 12 months (87.0%; CI 81.7%-91.2%) did not differ significantly (p = .40) from that of REA (83.2%; CI 74.7%-89.7%). Among evaluable patients, success rate was also similar (p = .24) in the MEA (96.4%; CI 92.7%-98.5%) and REA (92.7%; CI 85.6%-97%) groups. The amenorrhea rate in evaluable patients after MEA was 61.3% (CI 54.1 %-68.2%). In patients with myomas, the success and amenorrhea rates in evaluable patients after MEA were 90.3% (CI 74.2%-98%) and 61.3% (CI 42.2%-78.2%), respectively. In evaluable patients with body mass index of 30 kg/m2 or greater, MEA success rate was 96.7% (CI 88.5%-99.6%) compared with 81.8% (CI 59.7%-94.8%) for REA (p = .042). The ablation procedure was performed under IV sedation in 62% of patients in the MEA group versus 18% of patients in the REA group (p <.001); whereas, general anesthesia was employed more often in patients undergoing REA (37% vs. 76%, p <.001). No major complications were encountered. Patient satisfaction with results of treatment was high (98.5% of the MEA and 99.0% of the REA group).\n Microwave endometrial ablation is an efficacious and safe procedure for the treatment of menorrhagia. Over half of patients treated with MEA achieve amenorrhea, and the procedure is suitable for women with myomas and irregular uterine cavities. The procedure is easily learned and can be performed rapidly, under IV sedation in most cases.", "Our purposes were to compare the impact of surgery on menstrual blood flow reduction and on the increase in hemoglobin values as primary endpoints at 12 months, and operating time, complication rates, postoperative pain scores at 12 h and surgically induced amenorrhea rates at 12 months as secondary endpoints after roller ball endometrial ablation or thermal balloon ablation for myoma-induced menorrhagia.\n Menorrhagic women (documented by a validated pad scoring system) over 40 years of age, with a mobile myomatous uterus smaller than 12-week pregnancy, were enrolled in a prospective randomized trial to compare endometrial roller ball ablation and thermal balloon ablation after pharmacological endometrial thinning. One year after surgery, primary and secondary endpoints in both groups were compared.\n Forty-five subjects underwent endometrial thermal balloon ablation under local anesthesia and 48 underwent endometrial roller ball ablation under general anesthesia. Statistically significant but similar decreases in mean pictorial blood assessment score and increases in mean hemoglobin values were noted for both groups at 12 months. Those who underwent endometrial roller ball ablation had experienced significantly more intraoperative complications.\n Thermal balloon ablation under local anesthesia for myoma-induced menor- rhagia provided both significant and statistically similar reductions in menstrual blood flow and increases in hemoglobin values with no intraoperative complication compared to roller ball endometrial ablation.", "To investigate the difference of long-term amenorrhea rate in patients with menorrhagia treated by endometrial laser intrauterine thermal therapy (ELITT), a new nonhysteroscopic endometrial ablation procedure, versus transcervical hysteroscopic endometrial resection (TCRE).\n Randomized clinical study. Healthy volunteers in an academic research environment.\n Academic teaching hospital.\n Premenopausal women with abnormal uterine bleeding.\n Fifty-eight patients were treated with the ELITT procedure and 58 patients with TCRE; both groups were treated with GnRH agonists before the procedure.\n Bleeding status and patient satisfaction after treatment were evaluated as well as the intraoperative complication rate.\n At 12 months, the amenorrhea rate was 56% in the ELITT group and 23% in the TCRE group. At 36 months, the figures were 61% for ELITT and 24% for TCRE. No significant complications were recorded for either procedure.\n Results of this randomized study demonstrate that both procedures are equally effective in the treatment of menorrhagia. However, the ELITT procedure has proven to be superior in inducing amenorrhea.", "To determine the effectiveness of endometrial cryoablation in comparison with rollerball electroablation.\n Prospective, randomized study (Canadian Task Force classification I).\n Ten university and private medical centers in the United States.\n Two hundred seventy-nine women with menorrhagia due to benign causes.\n Endometrial ablation using a Her Option cryoablation device in 193 women and rollerball electroablation in 86.\n Women treated by cryoablation received significantly less general anesthesia (46%) than those treated by electroablation (92%). Subjects maintained menstrual diaries for at least one cycle before and for 12 months after the procedure. Success was defined as reduction of menstrual bleeding to a score of 75 or less in the absence of retreatment. Success rates in the cryoablation and electroablation groups were 77.3% and 83.8%, respectively. Bleeding declined by 92% and 94%, respectively. Both procedures led to significant improvements in a broad range of symptoms including menses-related pain, mood, and overall improvement in quality of life.\n Endometrial cryoablation is a safe and effective procedure in treatment of dysfunctional uterine bleeding. Its advantages include technical ease of performance, direct ultrasonographic view of depth of ablation, little anesthetic, and avoidance of potential complications related to distention media.", "To compare the safety and effectiveness of the NovaSure impedance-controlled endometrial ablation system with hysteroscopic wire loop resection plus rollerball ablation for treatment of excessive uterine bleeding in premenopausal women.\n Randomized, multicenter, double-arm study (Canadian Task Force classification I).\n Nine academic medical centers and private offices.\n Two hundred sixty-five premenopausal women with symptomatic menorrhagia.\n Ablation performed with the NovaSure system or wire loop resection and rollerball.\n Success [pictorial blood loss-assessment chart (PBLAC) score < or =75] was achieved in 88.3% of NovaSure-treated and 81.7% of rollerball-treated patients. One year after treatment 90.9% and 87.8%, respectively, reported normal bleeding or less (PBLAC < or =100) and 41% and 35%, respectively, experienced amenorrhea (PBLAC = 0). Mean procedure time was 4.2 minutes (average 84 sec) in the NovaSure group and 24.2 minutes in the rollerball group. Local and/or intravenous sedation was administered in 73% of NovaSure patients and 18% of rollerball patients. Intraoperative adverse events occurred less frequently with NovaSure (0.6%) than with rollerball (6.7%). Postoperative adverse events occurred in 13% and 25.3% of patients, respectively.\n The NovaSure system was safe and effective in treatment of women with menorrhagia. The procedure is both quick and effective, and eliminates the expense and side effects of endometrial pretreatment.", "To compare the effectiveness of the Cavaterm thermal balloon endometrial ablation system with the Nd:YAG laser for the treatment of dysfunctional uterine bleeding.\n Randomised controlled trial.\n Minimal access gynaecological surgery unit in a district general hospital.\n Seventy-two women with dysfunctional uterine bleeding requesting conservative surgical management of their condition.\n Women with a normal endometrial biopsy and normal uterine cavity were randomly allocated to endometrial ablation by Cavaterm or Nd:YAG laser. Patients completed pre-operative and 6- and 12-month post-operative questionnaires assessing menstrual symptoms, quality of life, sexual activity and procedural satisfaction and acceptability. All patients received a single dose of gonadotropin-releasing hormone analogue one month pre-operatively and kept blinded to the procedure performed until after the 6-month assessment.\n The primary outcome measure was amenorrhoea rate. Secondary outcomes were effect on blood loss, quality of life, sexual activity, patient satisfaction and procedure acceptability.\n Seventy-two women were randomised. Amenorrhoea rates at 12 months in the Cavaterm and endometrial laser ablation groups were 29% vs 39% (P = 0.286), with combined amenorrhoea and hypomenorrhoea rates of 73% vs 69%, respectively. At 12 months, repeat surgery rates were higher in the endometrial laser ablation group (15% vs 12%, P = 0.395). Cavaterm was an acceptable procedure and 93% of patients satisfied or very satisfied at 12 months (95% endometrial laser ablation). Both treatments were associated with an increase from baseline in the SF-12 physical score (Cavaterm mean difference -3.9, 95% CI -7.9, 0.2, ns; endometrial laser ablation mean difference -5.1, 95% CI -9.5, -0.7, P = 0.003) and mental health score (Cavaterm mean difference -5.6, 95% CI -9.9, -1.3, P = 0.001; endometrial laser ablation mean difference -5.9, 95% CI -11.7, -0.2, P = 0.04). Patient's own assessment of health (EQ-5D VAS) improved from baseline in both groups (Cavaterm mean difference -7.6, 95% CI -13.9, -1.3, P = 0.02; endometrial laser ablation mean difference -5.4, 95% CI -14.9, 4.2, ns). EQ-5D index scores also improved (Cavaterm mean difference -0.06, 95% CI -0.2, 0.005, ns; endometrial laser ablation mean difference -0.17, 95% CI -0.3, -0.02, P = 0.02). There were no major complications in either group.\n The results with the Cavaterm thermal balloon endometrial ablation system are as good as those obtained with the Nd:YAG laser when used for the treatment of dysfunctional uterine bleeding in the short term. It results in a significant reduction in menstrual blood loss, patient satisfaction and improvement in patient quality of life. Larger studies with longer follow up are required to determine its place in the modern treatment of dysfunctional uterine bleeding.", "To compare endometrial laser ablation (ELA) with transcervical resection of the endometrium (TCRE) in the treatment of menorrhagia.\n Randomised controlled trial.\n Gynaecology department of a large teaching hospital.\n Women with menorrhagia due to dysfunctional uterine bleeding (n = 372) were randomly allocated to ELA (n = 188) or TCRE (n = 184).\n Operative complications, post-operative recovery, relief of menstrual and other symptoms, need for further surgical treatment, satisfaction with treatment after 6 and 12 months, and differential resource use.\n TCRE was significantly quicker, with lower rates of fluid overload. Perioperative morbidity was low and similar in both groups. Outcome at 12 months was also similar: 72 women (45%) had either amenorrhoea or brown discharge in the ELA group compared with 71 (49%) in the TCRE group; 79 (49%) versus 68 (46%) had lighter periods. Thirty (16%) versus 36 (20%) had received further surgical treatment: 9 (5%) compared with 25 (14%) had had a hysterectomy and 21 (11%) versus 11 (6%) had received repeat ablation. Anxiety and depression, dysmenorrhoea and pre-menstrual symptoms were improved by both procedures and bladder symptoms were affected by neither. At 12 months 148 (90%) women in the ELA group and 140 (91%) women in the TCRE group were satisfied with their treatment. The estimated additional cost of ELA was Pound 145 per procedure.\n At one year there was no clear difference in clinical outcome between ELA and TCRE. Both procedures were associated with low morbidity. ELA was the more costly procedure. Despite the need for further surgery for about one in six women, satisfaction rates were high following both ELA and TCRE.", "A randomized, controlled trial was performed to compare the patient complication rate, effectiveness, and satisfaction rate of transcervical hysteroscopic endometrial coagulation versus endometrial resection in the treatment for heavy dysfunctional bleeding.\n One hundred and twenty women requiring endometrial ablation for the treatment of heavy bleeding disorders entered the study. All patients were offered a clinical examination 24 months postoperatively and had a questionnaire by mail 5 years after the initial treatment. The number of complications during and after the operation, re-ablations, and hysterectomies were registered. A bleeding index and the patient satisfaction rate were stated.\n Sixty-one patients were treated by endometrial coagulation, and 59 were treated by endometrial resection. No differences between the two groups were observed concerning fluid absorption, bleeding, perforation, and infection. At the 5-year follow-up, 64% of the patients had only one ablation, 15% were treated twice, 15% had a hysterectomy, and 6% were lost to follow-up. After 5 years, the bleeding index was halved in patients with menses. Seventy-nine percent of the women would recommend the treatment to their best female friend.\n We found no significant differences in the frequency of complications. Only 15% of the women had a hysterectomy after 5 years. No significant difference was observed with respect to bleeding reduction and patient satisfaction in the two groups.", "In a prospective study 20 patients suffering from recurrent, therapy-refractory menorrhagias were pre-treated for endometrial ablation after exclusion of intrauterine abnormalities and histological pathology. Two injections of GnRH-analogues (3.75 mg leuprorelinacetate depot, Enantone Gyn, Takeda Pharma GmbH Aachen, Germany). Two weeks after the last injection a hysteroscopic surgery by roller-ball-techniques was performed in 10 patients and a balloon-thermocoagulation by Cavaterm-technique (Wallsten Medical, Morges, Schweiz) was performed in 10 patients. Both patients groups were comparable according to age and anamnesis. In a follow-up of 9 to 15 months we found about identical results. All 20 patients were satisfied with the treatment. The Cavaterm-coagulation is in comparison to the operative hysteroscopy a simple method for endometrial coagulation, and can also be used by an hysteroscopically inexperienced gynaecologists with simple technical equipment. In strict indication the Cavaterm-coagulation is a simple method of endometrial ablation in many patients.", "To compare the clinical efficacy and safety of a thermal uterine balloon system with hysteroscopic rollerball ablation in the treatment of dysfunctional uterine bleeding.\n Two hundred fifty-five premenopausal women were treated in a randomized multicenter study comparing thermal uterine balloon therapy with hysteroscopic rollerball ablation for the treatment of menorrhagia. Preprocedural and postprocedural menstrual diary scores and quality-of-life questionnaires were obtained. Twelve-month follow-up data are presented on 239 women.\n Twelve-month results indicated that both techniques significantly reduced menstrual blood flow with no clinically significant difference between the two groups as reflected by return to normal bleeding or less (balloon 80.2% and rollerball ablation 84.3%). Multiple quality-of-life questionnaire results were also similar, including percent of patients highly satisfied with their results (balloon 85.6% compared with rollerball 86.7%). A 90% decrease in diary scores was seen in more than 60% of patients in both groups. Procedural time was reduced significantly in the uterine balloon therapy group. Intraoperative complications occurred in 3.2% of the hysteroscopic rollerball patients, whereas no intraoperative complications occurred in the thermal balloon group.\n In the treatment of dysfunctional uterine bleeding, uterine balloon therapy is as efficacious as hysteroscopic rollerball ablation and may be safer.", "To compare the efficacy and safety of Cavaterm thermal balloon endometrial ablation with hysteroscopic endometrial resection.\n Multicenter randomized trial (Canadian Task Force classification I).\n Departments of obstetrics and gynecology in French university hospitals.\n Fifty-one women with menorrhagia unresponsive to medical treatment.\n Women were randomized to thermal destruction of the endometrium or to hysteroscopic endometrial resection. Women completed preoperative, 6-, and 12-month postoperative pictorial charts to determine Higham blood loss scores and a satisfaction questionnaire. Operative time, discharge time, complication rate, and resumption of normal activities were evaluated for each group.\n Amenorrhea rates were 36% (95% CI 19%-56%) and 29% (95% CI 8%-51%) in the Cavaterm and the endometrial resection groups at 12 months, respectively (ns). Both treatments significantly reduced uterine bleeding. The median decrease in Higham score at 12 months was significantly higher in women treated by Cavaterm (377, range 108-1300) than in women treated by resection (255, range -82 to 555) (p=.006). A subsequent hysterectomy for recurrent bleeding was performed in 2 women, both previously treated by resection. The rate of women reporting good or excellent satisfaction was 89% (95% CI 72%-98%) in the Cavaterm group and 79% (95% CI 54%-94%) in the resection group at 12 months. Discharge time was significantly lower in women treated by Cavaterm, although postoperative pain at 1 hour was higher. There were no major complications in either group.\n Cavaterm thermal balloon ablation was as effective as hysteroscopic endometrial resection to treat menorrhagia, both resulting in a significant reduction in menstrual blood loss and high patient satisfaction.", "Various new endometrial ablation techniques have emerged for the treatment of menorrhagia. We undertook a randomised controlled trial comparing one new technique, microwave endometrial ablation (MEA), with a proven procedure, transcervical resection of the endometrium (TCRE), for women with heavy menstrual loss.\n 263 eligible and consenting women, referred for endometrial ablative surgery, were randomly assigned MEA (Microsulis plc, Waterlooville, Hampshire, UK; n=129) or TCRE (n=134). 230 participants were needed to give 80% power of demonstrating a 15% difference in satisfaction with treatment. All procedures were done under general anaesthesia 5 weeks after endometrial thinning with goserelin 3.6 mg. Questionnaires were completed at recruitment and at 12 months' follow-up. The primary outcome measures were patients' satisfaction with and the acceptability of treatment. Analysis was by intention to treat among women followed up to 12 months (n=116 MEA, n=124 TCRE).\n At 12 months, 89 (77%) women in the MEA group and 93 (75%) in the TCRE group were totally or generally satisfied with their treatment (95% CI for difference -12 to 17) and 109 (94%) versus 112 (90%) found it acceptable (-11 to 35). Mean operating times were shorter for MEA than for TCRE (11.4 vs 15.0 min, p=0.001) and the postoperative stay slightly but not significantly shorter. One blunt perforation occurred in each study group resulting in one immediate hysterectomy (TCRE group). Of eight health-related quality of life dimensions, all were improved after MEA (six significantly) and seven were improved after TCRE (all significantly).\n Both techniques achieved high rates of satisfaction and acceptability and both improved quality of life after 1 year. However, we cannot exclude a difference in satisfaction between the groups of less than 15%. MEA seems a suitable alternative to TCRE.", "To compare two second-generation endometrial ablation systems in women with dysfunctional uterine bleeding (DUB) who want conservative surgical treatment.\n A double-blind, randomized trial.\n A minimal access gynecological surgery unit in northeast England.\n Fifty-seven women diagnosed with DUB were recruited, with 55 undergoing surgery and completing 12-month follow-up.\n Thirty-seven women underwent a NovaSure endometrial ablation, and 18 had a Cavaterm endometrial ablation. Clinical and quality of life data were collected 6 and 12 months after treatment.\n Amenorrhea, menstrual change, quality of life, sexual activity, patient satisfaction, and procedure acceptability.\n Amenorrhea, hypomenorrhea, eumenorrhea, and menorrhagia rates for the Cavaterm and Novasure groups at 12 months were 2/18 (11%) vs. 16/37 (43%); 11/18 (61%) vs. 10/37 (27%); 5/18 (27%) vs. 6/37 (16%); and 0/18 vs. 5/37 (13%), respectively. At 12 months, 83% and 92% of women were either satisfied or very satisfied in the Cavaterm or Novasure groups, respectively. There were no major complications in either group.\n Both the Cavaterm and the Novasure endometrial ablation systems are effective in reducing menstrual loss in women with DUB and achieve high rates of patient satisfaction. The Novasure system achieved a statistically significantly higher rate of amenorrhea in this study.", "To compare long-term histologic features of endometrial rollerball ablation versus resection.\n Randomized clinical trial (Canadian Task Force classification I).\n Akdeniz University School of Medicine.\n Women with menorrhagia undergoing endometrial ablation.\n Comparison of patients with menorrhagia undergoing endometrial resection and ablation.\n Endometrial rollerball ablation (n = 23 women) and resection (n = 25) were followed by second-look office hysteroscopy with endometrial biopsy. Mean follow-up to second look hysteroscopy after rollerball ablation and loop resection was 33.4 +/- 2.1 and 31.1 +/- 2.6 months, respectively. Complete atrophy and partial adhesion or obliteration of the cavity and fibrosis were observed at second-look hysteroscopy and were similar in both groups. Whereas all random biopsy specimens after both ablation and resection revealed diminished endometrial glands with varied necrosis and scarring, the number of endometrial glands per field was not correlated with amount of bleeding or menstrual pattern. Bleeding patterns were similar between the groups. No precancerous or malignant lesion was found after the procedures.\n Although efficacy of both endometrial ablation and resection is related to initial thermal destruction and correlated with postablation hysteroscopic and histologic findings, endometrial regrowth may be expected and is not a failure of ablation. Both procedures revealed histopathologically and clinically similar results." ]

[ "10645355", "12571295", "16259175", "10069091", "8946182", "19781053", "3083644", "2516838", "8451961", "10150249", "18672751", "17206496", "10800385", "2492286", "7767451", "20688546", "8636173", "15954049", "17257532", "3132812", "17195934", "3577722", "3425284" ]

[ "Early mobilisation versus immobilisation of surgically treated ankle fractures. Prospective randomised control trial.", "Use of a cast compared with a functional ankle brace after operative treatment of an ankle fracture. A prospective, randomized study.", "No long-term effects of ultrasound therapy on bioabsorbable screw-fixed lateral malleolar fracture.", "Using hypnosis to accelerate the healing of bone fractures: a randomized controlled pilot study.", "Stable lateral malleolar fractures treated with aircast ankle brace and DonJoy R.O.M.-Walker brace: a prospective randomized study.", "Effects of a training program after surgically treated ankle fracture: a prospective randomised controlled trial.", "Immobilization of operated ankle fractures.", "Comparative study of functional bracing and plaster cast treatment of stable lateral malleolar fractures.", "Early mobilization of operated on ankle fractures. Prospective, controlled study of 40 bimalleolar cases.", "Protected early motion versus cast immobilization in postoperative management of ankle fractures.", "[Comparison between Robert Jones dressing and \"U\" splint in ankle fractures].", "The dynamic vacuum orthosis: a functional and economical benefit?", "[Cast immobilization versus vacuum stabilizing system. Early functional results after osteosynthesis of ankle joint fractures].", "Early postoperative weight-bearing and muscle activity in patients who have a fracture of the ankle.", "Ankle performance after ankle fracture: a randomized study of early mobilization.", "Use of noninvasive interactive neurostimulation to improve short-term recovery in patients with surgically repaired bimalleolar ankle fractures: a prospective, randomized clinical trial.", "Postoperative treatment of internally fixed ankle fractures: a prospective randomised study.", "Passive stretching does not enhance outcomes in patients with plantarflexion contracture after cast immobilization for ankle fracture: a randomized controlled trial.", "Early mobilization in a removable cast compared with immobilization in a cast after operative treatment of ankle fractures: a prospective randomized study.", "Mobilization after operation of ankle fractures. Good results of early motion and weight bearing.", "Aftertreatment of malleolar fractures following ORIF -- functional compared to protected functional in a vacuum-stabilized orthesis: a randomized controlled trial.", "Early weight bearing of malleolar fractures.", "Early weight bearing of displaced ankle fractures." ]

[ "In a randomised prospective controlled trial of 52 patients aged 16 to 65 we compared early non-weightbearing ankle mobilisation with ankle immobilisation following surgical treatment of bimalleolar ankle fractures. At 3 months there was no significant difference between the two groups in the range of ankle movements or pain. There was however a significant difference in the gait pattern with a higher proportion of cases in the early ankle mobilisation group having a symmetrical gait (P = 0.0001).", "Controversy continues with regard to the optimal postoperative care after open reduction and internal fixation of an ankle fracture. The hypothesis of this study was that postoperative treatment of an ankle fracture with a brace that allows active and passive range-of-motion exercises would improve the functional recovery of patients compared with that after conventional treatment with a cast. Thus, the purpose of this prospective, randomized study was to compare the long-term subjective, objective, and functional outcome after conventional treatment with a cast and that after use of functional bracing in the first six weeks following internal fixation of an ankle fracture.\n One hundred patients with an unstable and/or displaced Weber type-A or B ankle fracture were treated operatively and then were randomly allocated to two groups: immobilization in a below-the-knee cast (fifty patients) or early mobilization in a functional ankle brace (fifty patients) for the first six postoperative weeks. The follow-up examinations, which consisted of subjective and objective (clinical, radiographic, and functional) evaluations, were performed at two, six, twelve, and fifty-two weeks and at two years postoperatively.\n There were no perioperative complications in either study group, but eight patients who were managed with a cast and thirty-three patients who were managed with a brace had postoperative complications, which were mainly related to wound-healing. Two patients in the group treated with a cast had deep-vein thrombosis. All fractures healed well in both groups. The difference between the two groups with respect to the complication rate was significant (p = 0.0005). No significant differences between the study groups were observed in the final subjective or objective (clinical) evaluation. At the two-year follow-up examination, the average score (and standard deviation) according to the ankle-rating scale of Kaikkonen et al. was 85 +/- 9 points for the group treated with a cast and 83 +/- 10 points for the group treated with a brace, and the average ankle score according to the system of Olerud and Molander was 87 +/- 8 points and 87 +/- 9 points, respectively.\n The long-term functional outcome after postoperative treatment of an ankle fracture with a cast and that after use of a functional brace are similar. Although early mobilization with use of a functional ankle brace may have some theoretical beneficial effects, the risk of postoperative wound complications associated with this treatment approach is considerably increased compared with that after conventional cast treatment. Thus, the postoperative protocol of treatment with a functional brace requires refinement before it can be generally advocated for use after operative treatment of an ankle fracture.", "The present study was initiated to evaluate the long-term effects of low-intensity ultrasound therapy on bioabsorbable screw-fixed lateral malleolar fractures, which has not been studied earlier.\n The study design was prospective, randomized, double-blinded, and placebo-controlled. Sixteen dislocated lateral malleolar fractures were fixed with one bioabsorbable self-reinforced poly-L-lactide screw. The patients used an ultrasound device 20 minutes daily for six weeks without knowing it was active (eight patients) or inactive (eight patients). The follow-up time was 18 months. The radiological bone morphology was assessed by multidetector computed tomography (MDCT) scans, the bone mineral density by dual-energy X-ray absorptiometry scans, and the clinical outcome by Olerud-Molander scoring and clinical examination of the ankle.\n The MDCT scans revealed that all fractures were fully healed, and no differences were observed in radiological bone morphology at the fracture site. The bone mineral density of the fractured lateral malleolus tended to increase slightly during the 18-month follow-up, the increase being symmetrical in both groups. No differences were observed in the clinical outcome or Olerud-Molander scores.\n The six-week low-intensity ultrasound therapy had no effect on radiological bone morphology, bone mineral density or clinical outcome in bioabsorbable screw-fixed lateral malleolar fractures 18 months after the injury.", "Hypnosis has been used in numerous medical applications for functional and psychological improvement, but has been inadequately tested for anatomical healing.\n To determine whether a hypnotic intervention accelerates bodily tissue healing using bone fracture healing as a site-specific test.\n Randomized controlled pilot study.\n Massachusetts General Hospital, Boston, Mass, and McLean Hospital, Belmont, Mass.\n Twelve healthy adult subjects with the study fracture were recruited from an orthopedic emergency department and randomized to either a treatment (n = 6) or a control group (n = 6). One subject, randomized to the treatment group, withdrew prior to the intervention.\n All 11 subjects received standard orthopedic care including serial radiographs and clinical assessments through 12 weeks following injury. The treatment group received a hypnotic intervention (individual sessions, audiotapes) designed to augment fracture healing.\n Radiological and orthopedic assessments of fracture healing 12 weeks following injury and hypnotic subjects' final questionnaires and test scores on the Hypnotic Induction Scale.\n Results showed trends toward faster healing for the hypnosis group through week 9 following injury. Objective radiographic outcome data revealed a notable difference in fracture edge healing at 6 weeks. Orthopedic assessments showing trends toward better healing for hypnosis subjects through week 9 included improved ankle mobility; greater functional ability to descend stairs; lower use of analgesics in weeks 1, 3, and 9; and trends toward lower self-reported pain through 6 weeks.\n Despite a small sample size and limited statistical power, these data suggest that hypnosis may be capable of enhancing both anatomical and functional fracture healing, and that further investigation of hypnosis to accelerate healing is warranted.", "Stable lateral malleolar fractures can be treated with dynamic braces and early mobilization. In a randomized clinical trial, 66 patients with supination-eversion stage II fractures were treated with Aircast Air-Stirrup ankle braces or DonJoy R.O.M.-Walker braces. Average bracing time was 5 weeks, and average time until return to work was 6 weeks. At 4 weeks, 70% to 80% of patients were able to walk without pain. Subjective satisfaction with comfort and ease of use was significantly higher with Aircast, although it was high in both groups. Pain relief and an inflammatory score were significantly better in the R.O.M.-Walker group after 4 weeks. Three months after injury, no differences were observed in grade of ambulation, pain, swelling, range of motion, or inflammatory score. Both braces can be recommended.", "Despite conflicting results after surgically treated ankle fractures few studies have evaluated the effects of different types of training programs performed after plaster removal. The aim of this study was to evaluate the effects of a 12-week standardised but individually suited training program (training group) versus usual care (control group) after plaster removal in adults with surgically treated ankle fractures.\n In total, 110 men and women, 18-64 years of age, with surgically treated ankle fracture were included and randomised to either a 12-week training program or to a control group. Six and twelve months after the injury the subjects were examined by the same physiotherapist who was blinded to the treatment group. The main outcome measure was the Olerud-Molander Ankle Score (OMAS) which rates symptoms and subjectively scored function. Secondary outcome measures were: quality of life (SF-36), timed walking tests, ankle mobility tests, muscle strength tests and radiological status.\n 52 patients were randomised to the training group and 58 to the control group. Five patients dropped out before the six-month follow-up resulting in 50 patients in the training group and 55 in the control group. Nine patients dropped out between the six- and twelve-month follow-up resulting in 48 patients in both groups. When analysing the results in a mixed model analysis on repeated measures including interaction between age-group and treatment effect the training group demonstrated significantly improved results compared to the control group in subjects younger than 40 years of age regarding OMAS (p = 0.028), muscle strength in the plantar flexors (p = 0.029) and dorsiflexors (p = 0.030).\n The results of this study suggest that when adjusting for interaction between age-group and treatment effect the training model employed in this study was superior to usual care in patients under the age of 40. However, as only three out of nine outcome measures showed a difference, the beneficial effect from an additional standardised individually suited training program can be expected to be limited. There is need for further studies to elucidate how a training program should be designed to increase and optimise function in patients middle-aged or older.\n Current Controlled Trials ACTRN12609000327280.", "Forty-three patients with stable internal fixation of fresh ankle fractures were treated at random with a plaster cast for 6 weeks without weight bearing or were only immobilized for 3 days, after which active movements were encouraged. The two groups were followed for a year. Only at 6 weeks were there significant differences between the groups.", "In a prospective, randomized study, the use of the Aircast pneumatic air stirrup was compared with a standard below-knee walking cast in the management of Lauge-Hansen supination-eversion, stage II ankle fractures. Forty patients were randomly allocated to the two treatment groups. The use of the air stirrup led to a significant improvement in early patient comfort, post-fracture swelling, range of ankle motion at union, and time to full rehabilitation. We advocate the use of pneumatic air stirrup in the cost-effective management of stable ankle fractures.", "40 patients with dislocated bimalleolar and trimalleolar ankle fractures took part in this randomized study. All ankles were operated on using cerclage, staples and pins. Active ankle movement with weight bearing in an orthosis was compared with active ankle movement without weight bearing using a dorsal splint. Stereophotogrammetric analysis showed small movements in the ankle mortise in both groups but conventional radiography revealed no fracture redislocation. The clinical results did not differ. This study was designed as the second part of a consecutive project. In the first part, early and late weight bearing in a cast without ankle movements was compared (Ahl et al. 1987b). In comparing the first and the second parts of the study, a small but significant increase in fracture instability was observed in the early motion group. No lasting superior clinical result was achieved by early ankle movement. After operation on dislocated bimalleolar ankle fractures, early postoperative weight bearing in a walking cast is recommended.", "Sixty-one active-duty military personnel with operatively treated ankle fractures were randomized into two postoperative immobilization regimens: Group I--six weeks short-leg cast, nonweight-bearing; Group II--six weeks removable orthosis, nonweightbearing. Group I began physical therapy at six weeks postoperatively, and Group II began physical therapy within the first postoperative week. Objective measurements of swelling, strength, range of motion, and functional tests were examined. Subjective scores of pain, function, cosmesis, and motion were recorded. Patients in Group II (early mobilization) had significantly better subjective scores at three and six months postoperatively; however, time to return to duty was not significantly different. Objective tests of swelling, strength, range of motion, and functional tests were not significantly different at three months postoperatively for either group. Early mobilization in a removable orthosis, while not objectively altering the postoperative course, provides a safe, preferable method of treatment in the reliable and cooperative patient.", "To compare the Robert Jones bandage with the \"U\" splint in edema control of ankle fractures.\n A prospective, longitudinal study, open, comparative and randomized made in 32 male patients (72%) and 16 female patients (28%), the average age was 36.9 years. Patients with an ankle fracture within 12 hours of evolution were registered. Both ankles previous to immobilization were measured, dividing the patients in 2 groups. Group 1 were treated with Robert Jones Bandage, and group 2 with \"U\" splint. The pain previous to immobilization was registered using an analogous visual scale. Twenty-four hours later the circumference and the pain was measured again.\n Group 1 displayed less edema, mean 17.69 mm, in comparison with group 2, of 8.33 mm (p < or = 0.36). Pain previous to immobilization in group 1 was a mean of 7 and in group 2 of 5.5 (p < or = 0.3); 24 hours later, a mean of 2 in both (p < or = 0.8).\n There were no significant differences between both immobilization methods.", "In a prospective, randomised study, 27 patients with internally fixed ankle fractures were treated post-operatively for a period of six weeks by application of either a new dynamic vacuum orthosis with permitted mobilisation to 10 degrees -0 degrees -10 degrees at the ankle joint or a synthetic cast. Full weight bearing was allowed in both groups after two weeks. The cast group was prescribed four weeks of physiotherapy following six weeks of immobilisation. After ten weeks, the Olerud and Molander score showed a significant difference in favour of the orthosis. Early functional outcomes were significantly better for this group after six weeks and ten weeks. Patients in the orthosis group who were in formal employment returned to work 24 days earlier than those in the control group. Treatment of the orthosis patients took up three to four times less working time for the medical personnel. A saving of 38 euros on directly ascertainable costs could be evaluated. Rehabilitation of ankle fractures with a dynamic vacuum orthosis leads to better early functional results and greater patient satisfaction. The orthosis fulfils the conditions for early return to work. Treatment with an orthosis not only reduces working time for medical personnel but economises on expenditure for treatment and rehabilitation.", "In a prospective randomized trial the early functional results after immobilisation in a cast were compared to those after using a vacuum stabilizing system. The vacuum stabilizing system Vacoped offers equivalent stability compared to a plaster cast. In contrast to the cast the Vacoped can be removed for body care and physical therapy. Additionally the range of motion for dorsal flexion/extention in the upper ankle joint can be adjusted. From 9/1996 to 7/1997 there were 40 patients included in the study with an operated ankle fracture as monotrauma. Six weeks postoperatively the patients with cast treatment showed significantly higher functional deficits for the upper ankle joint (20%), the lower ankle joint (40%) and muscle atrophy (2.1 cm side difference) than the group with the vacuum stabilizing system (upper ankle joint 15%, lower ankle joint 25%, 1.4 cm muscle atrophy). Five patients out of the group with the vacuum system were already at work three weeks postoperatively. Three months postoperatively the functional results for both groups were approximating. The vacuum stabilizing system Vacoped offers better early functional results than conventional cast treatment after osteosynthesis of ankle fractures. Because of the increased patient comfort and the early ability for physical therapy the vacuum stabilizing system is preferable to cast treatment.", "Fifty-six patients who had a displaced fracture of the ankle necessitating surgical fixation were randomly assigned to one of three postoperative treatment regimens: no plaster cast or weight-bearing, and active exercises of the ankle; a non-weight-bearing plaster cast; or a plaster walking cast for the first six postoperative weeks. At follow-up with a duration of as much as two years, there were no consistent differences in the clinical results between the three groups. The time lost from work and the proportion of excellent and good clinical results were also uninfluenced by the postoperative regimen. No adverse effects could be detected as a result of the patient's having walked before the syndesmosis screw had been removed. It was concluded that none of the three postoperative regimens has any advantage over the others in a patient who has a stable osteosynthesis of a fracture of the ankle.", "In a prospective, randomized study, 30 patients were evaluated after ankle fracture treated by means of open reduction and internal fixation. The patients were randomized to either postoperative immobilization in a plaster cast for 6 weeks or early mobilization (1-2 weeks after surgery) in an ankle brace. Both regimens allowed weightbearing. Evaluation after 10 weeks and after 12 months included clinical assessment and isokinetic muscle strength measurements. Patients with impaired ankle function, as shown by means of an ankle score at 12 months, were followed for 3 years. At 10 weeks, impaired muscle torque and restricted range of motion was found on the affected side. This impairment was significantly less in the brace group. At 12 months, range of motion of the ankle and subtalar joints was restored, but dorsiflexion was still better in the brace group. Score values from a functional score did not correlate with muscle strength.", "We undertook a trial with 60 patients who had undergone operative reduction and internal fixation of bimalleolar, AO type B2 ankle fractures with comminution. Patients were randomized into 2 groups, one of which received postoperative treatment using a noninvasive interactive neurostimulation device (InterX) and the other with a sham device. The trial was designed to test the hypothesis that incorporation of noninvasive interactive neurostimulation into the rehabilitation protocol would result in reduced pain, increased range of motion, reduced edema, and reduced consumption of pain medication, in comparison with the sham therapy group. Outcome measurements included the patient's subjective assessment of level of pain, range of motion, and the extent of edema in the involved ankle, and the use of ketorolac for postoperative control of pain. The results showed significantly better results in the patients receiving treatment with active neurostimulation (repeated measures analysis of variance, P < .001).\n Copyright 2010 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.", "In a prospective, randomised trial of 81 patients with fractures of the ankle of AO types A, B and C we compared two regimes of postoperative management after internal fixation. The patients were mobilised either non-weight-bearing with crutches or weight-bearing in a below-knee walking plaster. We found a temporary benefit in subjective evaluation only (65 v 50 points, Mann-Whitney test, cft, p=0.02) for those with a below-knee walking plaster. There were no significant differences between the groups in the loaded dorsal range of movement (25 degrees v 23 degrees, Mann-Whitney test, cft, p = 0.16) or in the overall clinical result. Both treatments were considered to be satisfactory and their choice depends on the ability to mobilise non-weight-bearing, wound healing, the type of work and personal preference.", "To compare the efficacy of short- and long-duration passive stretches with a control treatment for the management of plantarflexion contracture after cast immobilization for ankle fracture.\n Assessor-blinded, randomized controlled trial.\n Hospital physical therapy outpatient departments.\n Adults with plantarflexion contracture (N=150) after cast immobilization for ankle fracture. All subjects were weight bearing or partial weight bearing.\n Exercise only, exercise plus short-duration passive stretch, and exercise plus long-duration passive stretch. All subjects had a 4-week course of exercises. In addition, subjects in the short-duration stretch plus exercise group completed 6 minutes of stretching per day, and subjects in the long-duration stretch plus exercise group completed 30 minutes of stretching per day.\n Lower Extremity Functional Scale and passive dorsiflexion range of motion with the knee bent and straight at baseline, and at 4 weeks and 3 months postintervention.\n One hundred thirty-nine (93%) subjects completed the 4-week assessment and 134 (89%) subjects completed the 3-month assessment. There were no statistically significant or clinically important between-group differences for the primary outcomes.\n The addition of passive stretching confers no benefit over exercise alone for the treatment of plantarflexion contracture after cast immobilization for ankle fracture.", "The aim of operative treatment for ankle fractures is to allow early movement after internal fixation. The hypothesis of this study was that early mobilization would improve functional recovery in patients after surgery for ankle fractures.\n In a prospective randomized controlled study, 66 consecutive patients with ankle fractures that required open reduction and internal fixation (ORIF) were assigned to one of two postoperative regimens: immobilization in a nonweightbearing below-knee cast or early mobilization in a removable cast. Four patients were excluded from the study, leaving 62 for review.\n Patients who had early mobilization in a removable cast had higher functional scores (Olerud-Molander and AOFAS) at 9 and 12 weeks postoperatively. They also returned to work earlier (67 days) compared with those treated in nonweightbearing below-knee cast (95 days), p<0.05. There was no statistical difference in Quality of Life (SF-36 Questionnaire) at 6 months between the two groups. We had an approximately 10% postoperative infection trend (one superficial and two deep) in the early mobilization group.\n Despite the overall short-term benefit of early mobilization, we had three patients in the early mobilization group who had wound complications. Both the surgeon and patient should be aware of the higher risk of wound complications associated with this treatment, and thus the accelerated rehabilitation protocol should be individualized.", "Fifty-one patients with dislocated lateral malleolar fractures took part in this prospective randomized study. Active ankle movements with weight bearing in an orthosis were compared with active ankle movements without weight bearing using a dorsal splint. By using cerclage, staples, and pins (Cedell 1967), an exact reconstruction of the ankle mortise was achieved in 44/51 ankles. Radiographic and stereophotogrammetric analyses at 3 months showed no redislocation and only small movements in the ankle mortise. Better loaded dorsal flexion capacity at 3 months was found in the orthosis group. This study was designed as the second part of a consecutive study. In the first part, early or late weight bearing without ankle exercises was compared (Ahl et al. 1986). The results from the two consecutive parts indicate that active ankle movements in combination with weight bearing facilitate and improve the rehabilitation following operation for an ankle fracture.", "In a monocenter randomized controlled trial, 45 patients with isolated malleolar fracture type OTA/AO 44 A1-B2 undergoing ORIF were allocated randomly to a postoperative treatment either with a vacuum-stabilized orthesis with prescribed full weight bearing after the second week (23 patients) (orthesis group -- OG) or with functional aftertreatment with partial weight bearing of 15 kg for 6 weeks (22 patients) (control group -- CG). Outcomes were compared at 6- and 10-week follow-up examinations. The Olerud and Molander ankle (OMA) score, ankle swelling, usage of crutches, range of motion, Short Form 12, patient-reported visual analogue scales (VAS) (pain, comfort, walking confidence) and time to return to work were evaluated. All patients of OG showed reduced swelling at discharge. The median OMA scores after 6 weeks were 42 and 42.5 (p = 0.46) and after 10 weeks 69 and 72 (p = 0.55) in the OG and CG, respectively. The time to achieve secure walking capacity was reduced by 1 day (p = 0.03) in the OG. After ORIF of simple malleolar fractures, patients with a vacuum-stabilized orthesis can bear full weight 2 weeks postoperatively. This group experienced no adverse events. Postoperative swelling was significantly reduced and of the ability to walk on stairs confidently was shorter as compared to a functional aftertreatment without any external stabilization of the ankle.", "A prospective randomized investigation of early versus late weight bearing in 46 patients with fracture of the lateral malleolus was performed. In 43/46 patients an exact operative reconstruction of the ankle mortise could be achieved using pins, staples and cerclage (Cedell, 1967). Radiographic and stereophotogrammetric analysis of the ankles after 3 months showed no significant differences, nor did the clinical follow-up.", "A prospective randomized study was performed comparing immediate and late weight bearing in 53 dislocated bimalleolar and trimalleolar fractures. Using cerlage, staples, and pins (Cedell 1967), an exact reconstruction of the ankle mortise was achieved in 41/53 ankles. At follow-up after 3 and 6 months, the two groups were equal regarding clinical results. Evaluation radiographically and by roentgen stereophotogrammetric analysis (Selvik 1974) indicated that the stability of the ankle mortise was sufficient to allow early postoperative weight bearing." ]

[ "10802273", "12681033", "8706436", "8536451" ]

[ "Performance of the frameless GyneFix and the TCu380A IUDs in a 3-year multicenter, randomized, comparative trial in parous women.", "Randomised controlled trial assessing the acceptability of GyneFix versus Gyne-T380S for emergency contraception.", "Performance of the TCu380A and Cu-Fix IUDs in an international randomized trail.", "The TCu 380A IUD and the frameless IUD \"the FlexiGard\": interim three-year data from an international multicenter trial. UNDP, UNFPA, and WHO Special Programme of Research, Development and Research Training in Human Reproduction, World Bank: IUD Research Group." ]

[ "This study was conducted to evaluate a new and improved inserter (GyneFix) for the anchoring of the Frameless IUD in the uterine cavity. Previous studies conducted with a prototype inserter (Flexigard) did not show fully the advantages of the new anchoring concept because of the shortcomings of the Flexigard inserter and the complexity of the insertion technique. The GyneFix IUD was compared with the TCu380A IUD in six centers in China in approximately 300 women in each group. Only parous women were included in the study. The data from this 3-year, ongoing study demonstrate that the shortcomings of the inserter have been corrected, resulting in better performance and a much reduced rate of failed insertion/expulsion of the frameless and anchored device. The cumulative expulsion rate with the GyneFix IUD was 3.0 at 3 years (annual rates 2.67, 0.33, and 0.0, respectively) compared with a cumulative expulsion rate of 7.38 at 3 years with TCu380A (annual rates 4.63, 1.76, and 1.04, respectively). This difference is statistically significant. The majority of the expulsions with the anchored IUD occurred early in the study, indicating improper anchoring technique. The study also shows that both devices are highly efficacious. No pregnancies occurred with the GyneFix IUD (cumulative pregnancy rate 0.0 at 3 years) versus one pregnancy with TCu380A (cumulative pregnancy rate 0.34 at 3 years). The total use-related discontinuation rate at 3 years was significantly lower with the GyneFix IUD (8.34) than with the TCu380A IUD (14.13) and results in a higher rate of continuation with the GyneFix IUD compared to the TCu380A IUD (90.73 vs 85.25). Neither perforations nor pelvic inflammatory disease cases were encountered with either device in this study, demonstrating the safety of the anchoring system.", "To assess insertion-linked pain and the short-term user-acceptability and safety of the GyneFix as compared with T-framed intrauterine devices (IUDs).\n A randomised controlled trial in an outpatient clinic setting.\n Women requesting an IUD for emergency contraception (EC) were allocated to either the short-term arm (GyneFix versus Nova-T200, or the long-term arm (GyneFix versus Gyne-T380S, and then randomised within each group. Visual analogue scores were used to assess the women's perception of the pain associated with insertion, which was patient-blinded. Follow-up was double-blinded, at 6 weeks, with bleeding and pain recorded over this time.\n A total of 175 women received an IUD in the long-term arm. The short-term arm was discontinued due to low recruitment (17 women at 20 months) and therefore the results relate to the long-term arm only. Outcome was known in 98% of subjects. The actual insertion procedure was scored as more painful for the GyneFix, both by the women (p = 0.013) and the doctors making their assessment of the women's pain (p = 0.04). The women with GyneFix described less pain in the subsequent 30 days after insertion (p = 0.005). Only 13% of women with GyneFix requested removal as compared with 20% with Gyne-T380S, with the difference being attributed to removal due to pain. The bleeding pattern was similar for those using GyneFix and Gyne-T380S.\n Our study suggests that although the actual fitting may be more painful, pain is less during the 6 weeks after insertion of GyneFix and fewer women discontinue its use because of pain, as compared with Gyne-T380S. The high overall continuation rate of all emergency IUDs at 6 weeks and low morbidity seen in this study favours more frequent IUD insertion where unprotected intercourse has occurred, given also its higher efficacy over oral hormonal EC.", "To compare the clinical performance of the TCu380A, the most widely used copper IUD in the world today, and a new frameless device, the Cu-Fix, we report results from a randomized international two-year clinical trial involving 874 parous women followed for an average of fourteen months. Event rates at the end of two years (per 100 women) for pregnancy were 0.0 for the TCu380A and 1.5 for the Cu-Fix. Termination due to expulsion was significantly less for TCu380A as compared with Cu-Fix users (2.0 and 11.4 per hundred women, respectively); other medical reasons for termination (bleeding/pain, pelvic inflammatory disease (PID), and other) did not differ significantly. PID incidence rates at two years were 1.0 per hundred women for the TCu380A and 1.6 for the Cu-Fix (equivalent to 6.0 and 8.3 per 1,000 woman-years, respectively). The net cumulative continuation rates at two years per hundred women were 78.8 for TCu380A, and 71.9 for the Cu-Fix. Both IUDs provide highly effective protection against pregnancy, but the TCu380A has a lower expulsion rate. The low rate of PID indicates that it is an in-frequent occurrence in appropriately selected candidates.", "The TCu 380A and FlexiGard IUDs were compared in a randomized multicenter trial including 28 institutes in 13 countries. There were 53 insertion failures with the FlexiGard and one with the TCu 380A. There were 2184 successful insertions of the TCu380A and 2102 of the FlexiGard device. The three-year pregnancy rates for the TCu 380A and FlexiGard were similar (1.6 and 1.9 per 100 women, respectively) but the FlexiGard three-year expulsion rate (7.4 per 100 women) was significantly higher than that of the TCu 380A (4.4 per 100 women). The insertion technique for the FlexiGard needs to be improved in order to lower the expulsion rate." ]

[ "17185202", "12568841", "15994622", "16246657", "17540797" ]

[ "Depo Now: preventing unintended pregnancies among adolescents and young adults.", "Bleeding patterns after immediate vs. conventional oral contraceptive initiation: a randomized, controlled trial.", "Bleeding patterns after immediate initiation of an oral compared with a vaginal hormonal contraceptive.", "Same-day initiation of the transdermal hormonal delivery system (contraceptive patch) versus traditional initiation methods.", "Initiation of oral contraceptives using a quick start compared with a conventional start: a randomized controlled trial." ]

[ "We compared the immediate administration of DMPA (Depo Now) to the immediate use of short-term hormonal methods that served as a \"bridge method\" until later DMPA initiation. We examined whether Depo Now, as compared to initiating with a bridge method (pills, transdermal patch, or vaginal ring), resulted in greater DMPA continuation at six months.\n Young women aged 14 to 26 years seeking to use DMPA were randomized (nonblinded) after meeting eligibility criteria to either the Depo Now (n = 101) or bridge method (n = 232) group. Depo Now subjects received their first injection of DMPA at the conclusion of their first visit provided each was medically suitable and had a negative urine pregnancy test regardless of menstrual cycle day. Those assigned to the bridge method group were allowed to choose their starting contraceptive method and it was provided at the first visit. All subjects were told to return to the clinic in 21 days to repeat the urine pregnancy test, and among those who were assigned to use a bridge method, to receive their first injection of DMPA. All subjects were followed to their third injection, or about 6 months later.\n Those randomized to a bridge method were 1.8 (1.1, 2.9) times more likely than Depo Now subjects to return for their 21-day repeat pregnancy test, but only 55% (n = 125) of these young women actually received their first DMPA injection. Continuation rates at the third injection were 29.7% (n = 30) for those in the Depo Now group and 21.1% (n = 49) for those assigned to the bridge method (p = .09). Three factors were significantly associated with adherence to the third injection: randomized to Depo Now group, knowing more women who use DMPA, and returning to clinic for the 21-day repeat pregnancy test visit. Finally, 28 pregnancies were diagnosed during the study period, and those in the bridge method group were almost 4.0 (1.2, 13.4) times more likely to be diagnosed with a pregnancy than those in the Depo Now group.\n Immediate administration of DMPA is associated with improved adherence to DMPA continuation and fewer pregnancies.", "To compare bleeding patterns after immediate vs. conventional oral contraceptive (OC) initiation.\n Randomized controlled trial.\n University-based clinic.\n One hundred thirteen women initiating combination OCs.\n Participants received a 4-month supply of a monophasic 35-microg ethinyl E(2) (EE) OC and a bleeding diary, were randomized to immediate or conventional OC start, underwent monthly telephone follow-up, and after 90 days returned the diary and completed an exit interview.\n Total number of bleeding-spotting days, using the World Health Organization 90-day reference period method. Comparisons were made by trial assignment (immediate vs. conventional) and cycle day of OC initiation (day 8+ vs. days 1-7).\n There was no significant difference in the number of bleeding-spotting days (mean difference: -0.5 days; 95% CI: -3.4 to 2.3) or any other bleeding parameter between the immediate and conventional starters, or days 1-7 and day 8+ starters.\n Immediate start of OCs does not induce bleeding patterns different from conventional starting regimens. Concern about adverse bleeding patterns should not be considered a justification for instructing women to wait until menses before starting OCs.", "This study compared 84-day bleeding patterns after immediate initiation of a triphasic oral contraceptive with a 25-mug daily dose of ethinyl estradiol (E2) compared with the contraceptive vaginal ring, which has a 15-mug daily dose of ethinyl E2.\n This was an open-label controlled trial. We randomly assigned 201 women to immediate start of a contraceptive pill or immediate start of the ring in a 1:1 allocation ratio. Our primary outcome was difference in mean bleeding-spotting days per woman according to treatment assignment. Secondary outcomes were differences in World Health Organization-defined menstrual indices, differences in perceived bleeding changes, and differences in bleeding according to cycle day at the start of method.\n The mean bleeding-spotting days in the 84-day reference period for all subjects was 19.2 days (17.0 days for ring users and 21.4 days for pill users, mean difference 4.4 days). Using the World Health Organization menstrual indices, the ring users experienced fewer days or episodes of bleeding-spotting and shorter intervals. Among ring users, no baseline characteristics were associated with bleeding outcomes. Older nulliparous pill users, however, reported more bleeding-spotting days. Significantly more ring users reported a decrease in duration of bleeding compared with pill users (P < .01). We found no significant differences in bleeding patterns based on analysis of cycle day at study enrollment.\n Our study shows advantageous bleeding patterns for subjects using the contraceptive vaginal ring. It also confirms our previous findings that immediate start of hormonal contraception is an acceptable alternative to waiting for menses.\n II-1.", "Published comparisons of oral contraceptive pill (OCP) initiation methods demonstrate that OCP initiation at the office visit (\"Quick Start\") resulted in higher continuation rates into the second cycle. This trial was performed to investigate whether Quick Start with the contraceptive patch would provide similar results.\n Sixty women were randomized to initiate use of the contraceptive patch using Quick Start (Group 1, n=30) or on the first day of their next menses (Group 2, n=30). Telephone contact at 6 weeks occurred to ensure that the second cycle had been initiated. A single follow-up visit was scheduled after completion of the third patch cycle.\n Continuation rates for Groups 1 and 2 were 97% and 93% (p=1.0), respectively, into the second cycle, and 93% and 90%, respectively, into the third cycle (p=1.0). Only approximately half of the subjects planned to continue using the patch after the study.\n Quick Start for the contraceptive patch did not improve continuation rates into the second or third cycle.", "To estimate whether young women taking the first pill on the day of prescription had higher continuation rates and lower pregnancy rates than women who waited until menses to start the oral contraceptive pill (OCP).\n We recruited 1,716 women aged younger than 25 years seeking to initiate the oral contraceptive at three publicly funded family planning clinics, and randomly assigned them to conventional initiation of the pill (conventional start) or immediate, directly observed ingestion of the first pill (quick start) during the clinic visit. Women underwent follow-up interviews at 3 and 6 months.\n Sixty percent of participants discontinued the pill, and 8% became pregnant during follow-up. Women who took the first pill in the clinic were more likely to continue to the second OCP pack (odds ratio 1.5, 95% confidence interval 1.0-2.1.); however, the Quick Start approach did not improve OCP continuation rates at 3 and 6 months. Those assigned to Quick Start were slightly less likely to become pregnant within 6 months from the time they started the pill (hazard ratio 0.90, 95% confidence interval 0.64-1.25). Eighty-one percent of women rated the Quick Start approach as acceptable or preferable to waiting. Rates of serious adverse events were low and similar in the two groups.\n Protocols that require a woman to wait until the next menses to start hormonal contraceptives are an obstacle to contraceptive initiation. Directly observed, immediate initiation of the pill improves short-term continuation.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00068848" ]

[ "9519099" ]

[ "Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study." ]

[ "We hypothesised that a combined regimen of clozapine, a relatively weak D2-dopaminergic antagonist, and sulpiride, a selective D2 blocker, would demonstrate a greater antipsychotic efficacy by enhancing the D2 blockade of clozapine.\n Twenty-eight people with schizophrenia, previously unresponsive to typical antipsychotics and only partially responsive to current treatment with clozapine, received, double-blind, 600 mg/day sulpiride or placebo, in addition to an ongoing clozapine treatment. The clinical status was evaluated before, during, and at the end of 10 weeks of sulpiride addition using the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms, and Hamilton Rating Scale for Depression.\n The clozapine-sulpiride group exhibited substantially greater and significant improvements in positive and negative psychotic symptoms. About half of them, characterised by a younger age and lower baseline SAPS scores, had a mean reduction of 42.4 and 50.4% in their BPRS and SAPS scores, respectively.\n A subgroup of patients with chronic schizophrenia may substantially benefit from sulpiride addition to clozapine." ]

[ "6116084", "7305427", "3973786", "3907504", "17156694", "378504", "7381637", "3125773", "8660037", "2509264", "1260273", "19736332", "8510706", "7322717", "840556", "7776115", "2242106", "8282390", "6770760", "3531001", "5445067", "20890683", "7009019", "3218448", "6818516", "381616", "6424041", "2239131", "15120684", "8499051", "9794981", "2202804", "662511", "10416094" ]

[ "Placebo-controlled study of phenobarbitone and phenytoin in the prophylaxis of febrile convulsions.", "Behavioural effects of phenobarbitone and phenytoin in small children.", "Effective short-term diazepam prophylaxis in febrile convulsions.", "Recurrence risk after first febrile seizure and effect of short term diazepam prophylaxis.", "Effectiveness of intermittent diazepam prophylaxis in febrile seizures: long-term prospective controlled study.", "Sodium valproate in the prophylaxis of simple febrile convulsions.", "The first febrile seizure--antipyretic instruction plus either phenobarbital or placebo to prevent recurrence.", "[Preventing the recurrence of febrile seizures: intermittent prevention with rectal diazepam compared with continuous treatment with sodium valproate].", "Long term outcome of prophylaxis for febrile convulsions.", "Intention to treat febrile convulsions with rectal diazepam, valproate or phenobarbitone.", "Failure of phenobarbitone to prevent febrile convulsions.", "Antipyretic agents for preventing recurrences of febrile seizures: randomized controlled trial.", "A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures.", "Long-term effect of phenobarbital on cognitive function in children with febrile convulsions.", "The value of phenobarbital in the child who has had a single febrile seizure: a controlled prospective study.", "Effect of acetaminophen and of low intermittent doses of diazepam on prevention of recurrences of febrile seizures.", "Phenobarbital for febrile seizures--effects on intelligence and on seizure recurrence.", "Role of phenobarbitone in preventing recurrence of febrile convulsions.", "Continuous sodium valproate or phenobarbitone in the prevention of 'simple' febrile convulsions. Comparison by a double-blind trial.", "Long term prophylaxis of febrile seizures.", "Studies on prophylactic treatment of febrile convulsions in children. Is it feasible to inhibit attacks by giving drugs at the first sign of fever or infection?", "Diazepam versus clobazam for intermittent prophylaxis of febrile seizures.", "A controlled trial of pyridoxine supplementation in children with febrile convulsions.", "Frequent febrile episodes and recurrent febrile convulsions.", "[Efficacy of sodium dipropylacetate compared with phenobarbital and placebo in the prevention of recurrence of febrile convulsions].", "Side effects of phenobarbital in toddlers; behavioral and cognitive aspects.", "Prevention of recurrent febrile convulsions--a randomized therapeutic assay: sodium valproate, phenobarbital and placebo.", "Intermittent prophylaxis in febrile convulsions: diazepam or valproic acid?", "Intermittent oral diazepam prophylaxis in febrile convulsions: its effectiveness for febrile seizure recurrence.", "Does phenobarbital used for febrile seizures cause sleep disturbances?", "Randomized, controlled trial of ibuprofen syrup administered during febrile illnesses to prevent febrile seizure recurrences.", "Double-blind, randomized trial of diazepam versus placebo for prevention of recurrence of febrile seizures.", "Behavior disturbance, phenobarbital, and febrile seizures.", "Late cognitive effects of early treatment with phenobarbital." ]

[ "Of 138 children who had a first febrile convulsion before their second birthday, 48 were treated with phenobarbitone, 47 with phenytoin, and 43 with a placebo for 12 months. Drug levels were monitored and adverse effects of the drugs were noted. Compared with placebo, phenobarbitone significantly reduced recurrences among children under 14 months old at the time of their first convulsion, but nor among older children. Phenytoin was an ineffective prophylactic agent. Ideal drug levels were difficult to maintain, and many recurrences occurred when concentrations were suboptimal. Behavioural disturbance in children taking phenobarbitone was not a serious problem. The decision to give continuous prophylaxis for febrile convulsions is complex, and each case must be judged on its merits. For children who have a first seizure before 14 months of age prophylaxis may be advisable and phenobarbitone is effective.", "Mothers of 56 children under 2 years old taking phenobarbitone and mothers of 55 children taking phenytoin recorded on questionnaires changes they had noted in the children's behaviour 3 and 9 weeks after starting the drug. Severe behavioural disturbance was noted by many, but the pattern and incidence was similar to that recorded by the mothers of 50 children starting a placebo, and we attribute it to the effect of a recent hospital admission. There was a small improvement in the behaviour of 20% of children who had been taking phenobarbitone for a year when they stopped it, but in this age group the disturbance caused by phenobarbitone did not appear to have been great.", "The efficacy of short-term diazepam prophylaxis in febrile convulsions was evaluated in a prospective, controlled study. A total of 289 consecutive children admitted with their first febrile seizure were randomized into two groups. One group received short-term prophylaxis for 18 months with rectally administered diazepam in solution whenever the temperature was greater than or equal to 38.5 degrees C. The control group received no prophylaxis, but diazepam rectally in the event of new seizures. The short-term prophylaxis, a mean of five doses of diazepam per child per year, afforded effective seizure control; the 18-month recurrence rate was reduced from 39% to 12% (P less than 0.001), the total number of recurrences from 77 to 23 (P less than 0.001), the long-lasting recurrences from 5.0% to 0.7% (P less than 0.05). The risk of subsequent epilepsy within the first 2 years was the same, regardless of receiving prophylaxis (3%) or not (3%); it was low after simple febrile convulsions (no cases of epilepsy in 230 children) but considerable after complex febrile seizures (20%) or seizures associated with severe interictal EEG abnormalities (50%).", "In a prospective randomised study, 289 children admitted consecutively to hospital with their first febrile seizure were allocated, by date of admission, to short term diazepam prophylaxis (n = 152) or to no prophylaxis (n = 137) and followed for 18 months. In untreated children, five major risk factors for recurrent febrile convulsions were identified: age 15 months or less at the time of the first febrile seizure, epilepsy in first degree relatives, febrile convulsions in first degree relatives, a first complex febrile seizure, and day nursery care. The 18 month recurrence rate was 80 to 100% if three to five risk factors were present, 50% if two factors were identified, 25% where one factor was found, and 12% if there were no predictors. During prophylaxis the recurrence rate was uniformly low (mean 12%) in all risk groups. In high (three or more factors) and intermediate (two factors) risk children prophylaxis provided effective seizure control and reduced the recurrence rate from 80%, or more, to 12% and 50% to 12%, respectively. In children with one risk factor 50% of all recurrences were prevented (25% to 12%). Prophylaxis was ineffective in very low risk children (12% to 12%).", "The efficacy of intermittent rectal diazepam prophylaxis is assessed in the prevention of febrile seizures. In a prospective randomized cohort trial, 139 children (77 girls, 62 boys) who experienced a first febrile seizure were allocated to two groups: group A, which received intermittent diazepam (n = 68), and group B, which received no prophylaxis (n = 71). All children had a 3-year follow-up. The inclusion criteria were no personal history of afebrile seizures, normal neurodevelopment, no previous anticonvulsant therapy, and age between 6 months and 3 years. Each group was stratified to low, intermediate, and high risk according to the available clinical data. The 36-month recurrence rates in the no-prophylaxis group were 83% in high-risk patients, 55% in intermediate-risk patients, and 46% in low-risk patients. In the prophylaxis group, the recurrence rates were reduced in all risk groups: 38%, 35%, and 33%, respectively. Intermittent diazepam prophylaxis reduces the recurrence rate mainly in high-risk children provided that sufficient doses are given on time and adequately.", "Thirty children with simple febrile convulsions were treated with sodium valproate following their second convulsion. Twenty-two of the 30 (73%) had no further convulsions during the one-year period of observation compared with 17 of 28 in the control group (61%). This was not a statistically significant difference. Side effects attributed to sodium valproate treatment were noted in 7 patients (23%), although 4 of these showed only mild transient gastrointestinal symptoms at high dosage. The study did not confirm any advantage in the use of sodium valproate as a prophylaxis for febrile convulsions, although compliance was good and significant side effects infrequent.", "A randomized double-blind study was carried out comparing single daily dose phenobarbital plus antipyretic instruction to a placebo plus antipyretic instruction to prevent a recurrent seizure following an initial simple febrile seizure. Parents of 138 consecutive children presenting to an emergency room with a first simple febrile convulsion received verbal and written instructions about fever control. Seventy-nine then agreed to participate in this study. Children were randomized to receive either placebo with riboflavin tracer (n = 40) or phenobarbital 5 mg/kg in a single daily dose with a riboflavin tracer (n = 39) for 12 months or until another seizure occurred. Urine fluorescence for riboflavin was used to monitor compliance in all patients. Serum phenobarbital levels were obtained at each follow-up visit and averaged 1.4 mg/dl throughout the study. The significant difference (P less than 0.02) in the incidence of recurrent seizures between patients receiving phenobarbital (2/39) and those receiving placebo (10/40) suggests that a single daily dose of phenobarbital is more effective than counseling parents about antipyretic therapy in preventing recurrent seizures following an initial febrile seizure.", "Sixty nine children suffering from a first febrile seizure without evidence of neurologic disorder or associated risk factors were randomly assigned to one of three groups: no treatment; intermittent rectal diazepam; or continuous oral sodium valproate. All patients were followed for two years. Periodical controls were performed every three months in order to record febrile episodes, recurrent seizures, and treatment side affects. Rate of recurrent febrile seizures was 16% in control group, and 5.5% in diazepam group. Sodium valproate group showed no recurrences in the follow-up period. The low relapsing rate in control group suggests that prophylaxis should not be established even if it is requested by certain parental attitudes.", "A cohort of 289 children with febrile convulsions who had been randomised in early childhood to either intermittent prophylaxis (diazepam at fever) or no prophylaxis (diazepam at seizures) was followed up 12 years later. The study focused on the occurrence of epilepsy and on neurological, motor, intellectual, cognitive, and scholastic achievements in the cohort. At follow up the two groups were of almost identical age (14.0 v 14.1 years), body weight (58.2 v 57.2 kg), height (168.2 v 167.7 cm), and head circumference (55.9 v 56.2 cm). The occurrence of epilepsy (0.7% v 0.8%), neurological examination, fine and gross motor development on the Stott motor test, intellectual performance on the Wechsler intelligence scale for children verbal IQ (105 v 105), performance IQ (114 v 111), and full scale IQ (110 v 108), cognitive abilities on a neuropsychological test battery, including short and long term, auditory and visual memory, visuomotor tempo, computer reaction time, reading test, and scholastic achievement were also very similar. Children with simple and complex febrile convulsions had the same benign outcome. The long term prognosis in terms of subsequent epilepsy, neurological, motor, intellectual, cognitive, and scholastic ability was not influenced by the type of treatment applied in early childhood. Preventing new febrile convulsions appears no better in the long run than abbreviating them.", "One hundred and eighty-six consecutive children aged between six and 72 months admitted to the Manchester Children's Hospitals with a febrile convulsion in the first year of life, a complicated febrile convulsion, or more than one febrile convulsion within two years, were allocated randomly to one of three groups who were offered rectal diazepam in the event of a subsequent prolonged febrile convulsion, or prophylactic treatment with sodium valproate or phenobarbitone. Over-all risk of recurrence was 30 per cent and adequate prophylactic treatment did not lessen this risk. Side-effects in 24 per cent of the valproate group and 61 per cent of the phenobarbitone group did not justify the use of prophylactic treatment.", "One-hundred-sixty-five children without known neurological disorder who presented with their first febrile convulsion between the ages of six months and three years were assigned to daily phenobarbitone treatment or to a control group and followed up at a special clinic for six months. One-hundred-and-sixty-one-one children completed the trial, and of the 88 children assigned to phenobarbitone treatment 10 had further convulsions during this period compared with 14 of the 73 control children. Only 49 of those assigned to phenobarbitone took the drug regularly throughout the trial, and four of these had further febrile convulsions, a proportion not significantly different from that in the controls. All four had mean plasma phenobarbitone concentrations over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours of the repeat convulsion. Regular phenobarbitone does not seem to prevent febrile convulsions. Attention should instead be directed to organising emergency services to allow early termination of fevrile convulsions, whether first or subsequent, to prevent irreversible brain damage.", "To evaluate the efficacy of different antipyretic agents and their highest recommended doses for preventing febrile seizures.\n Randomized, placebo-controlled, double-blind trial.\n Five hospitals, each working as the only pediatric hospital in its region.\n A total of 231 children who experienced their first febrile seizure between January 1, 1997, and December 31, 2003. The children were observed for 2 years.\n All febrile episodes during follow-up were treated first with either rectal diclofenac or placebo. After 8 hours, treatment was continued with oral ibuprofen, acetaminophen, or placebo.\n Recurrence of febrile seizures.\n The children experienced 851 febrile episodes, and 89 of these included a febrile seizure. Febrile seizure recurrences occurred in 54 of the 231 children (23.4%). There were no significant differences between the groups in the main measure of effect, and the effect estimates were similar, as the rate was 23.4% (46 of 197) in those receiving antipyretic agents and 23.5% (8 of 34) in those receiving placebo (difference, 0.2; 95% confidence interval, -12.8 to 17.6; P = .99). Fever was significantly higher during the episodes with seizure than in those without seizure (39.7 degrees C vs 38.9 degrees C; difference, 0.7 degrees C; 95% confidence interval, -0.9 degrees C to -0.6 degrees C; P < .001), and this phenomenon was independent of the medication given.\n Antipyretic agents are ineffective for the prevention of recurrences of febrile seizures and for the lowering of body temperature in patients with a febrile episode that leads to a recurrent febrile seizure.", "Phenobarbital, once widely prescribed to prevent febrile seizures, is now in disfavor because of its side effects and lack of efficacy. Diazepam, administered only during episodes of fever, may be a safe, effective agent to prevent the recurrence of febrile seizures.\n We conducted a randomized, double-blind, placebo-controlled trial among 406 children (mean age, 24 months) who had at least one febrile seizure. Diazepam (0.33 mg per kilogram of body weight) or placebo was administered orally every eight hours during all febrile illnesses.\n During a mean follow-up of 1.9 years (a period during which 90 percent of febrile seizures recur), our intention-to-treat analysis showed a reduction of 44 percent in the risk of febrile seizures per person-year with diazepam (relative risk = 0.56; 95 percent confidence interval, 0.38 to 0.81; P = 0.002). A survival analysis of the length of time to the first recurrent febrile seizure did not show a significant difference between the treatment groups (P = 0.064 by the log-rank test), but after adjustment for covariates, diazepam was found to have a benefit (P = 0.027 by Cox regression analysis). An analysis restricted to children who had seizures while actually receiving the study medication (7 in the diazepam group and 29 in the placebo group) showed an 82 percent reduction in the risk of febrile seizures with diazepam (relative risk = 0.18; 95 percent confidence interval, 0.09 to 0.37; P < 0.001). Of the 153 children who took at least one dose of diazepam, 39 percent had ataxia, lethargy, or irritability or at least one other moderate side effect that was reversed after a reduction in the dose. There were no severe side effects.\n Oral diazepam, given only when fever is present, is safe and reduces the risk of recurrent febrile seizures.", "Psychometric tests were performed on 50 children with a history of febrile convulsions. Twenty-five of these had received daily phenobarbital for a mean of 35 months; 25 had received no phenobarbital. The two groups were matched for sex, age at the time of testing, race, and socioeconomic status. The tests used were the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), the Matching Familiar Figures Test, and the Children's Embedded Figures Test. There were no significant differences in test results between the two groups.", "A group of 355 children who were seen after a first febrile convulsion at the Kaiser Foundation Foundation Hospitals in Southern California from 1970 to 1975 were randomly assigned to three treatment groups-daily phenobarbital, \"intermittent\" phenobarbital given at the onset of fever, and no phenobarbital. We found that 42% had a relative with a febrile seizure and 16% a relative with an afebrile convulsion. 13% had seizures which were either lateralized or longer than ten minutes. Parents were unaware of the fever prior to the seizure in about 30% of the cases. In 81% the preseizure duration of fever was less than 24 hours. The mean follow-up was 28 months, with a range of 6 to 70 months. There was no significant difference in the recurrence rate between children receiving \"intermitent\" as compared with no phenobarbital. The recurrence rate in children receiving daily phenobarbital was significantly decreased compared to either of the other two groups. Severe recurrent febrile seizures occurred in no children on daily phenobarbital and in 4.4% of the children receiving either intermittent or no phenobarbital. Parental resistance, compliance, and reversible hyperactivity were the main problems encountered with the continuous phenobarbital regimen.", "Acetaminophen and low doses of diazepam were evaluated for the prevention of recurrences of febrile seizures in a placebo-controlled, double-blind trial. Children after their first febrile seizure were assigned to receive either one dose of rectally administered diazepam, and then, after 6 hours, oral doses of 0.2 mg/kg three times a day for the first 2 days if the fever stayed greater than 38.5 degrees C, or a placebo similarly during forthcoming febrile episodes. In addition, each febrile episode was randomly assigned to be treated with acetaminophen or the placebo. Thus four groups were examined for 2 years: patients receiving two kinds of placebo, patients receiving diazepam and a placebo, patients receiving acetaminophen and a placebo, and patients receiving both diazepam and acetaminophen. Of a total of 180 patients (102 boys), 161 were followed for the 2-year period and 157 were seen at the last outpatient examination: 80 in the diazepam group and 77 in the placebo group. The final analysis of the efficacy of the drugs was made on the basis of the data from 153 patients who had had at least one febrile episode during follow-up. There were 641 fever events during this period, and 38 children (21.1%) had 55 recurrences of febrile seizures. Acetaminophen had no effect on the recurrence rate. Seizures recurred at least once in 21 patients (28.4%) receiving diazepam and 17 (21.5%) receiving a placebo (p = 0.4138, log-rank test). The combination of antipyretic agents with anticonvulsant medication did not reduce the recurrence of febrile seizures. Our results show that low doses of acetaminophen or diazepam or both are ineffective for preventing febrile seizures.", "Phenobarbital is widely used in the treatment of children with febrile seizures, although there is concern about possible behavioral and cognitive side effects. In 217 children between 8 and 36 months of age who had had at least one febrile seizure and were at heightened risk of further seizures, we compared the intelligence quotients (IQs) of a group randomly assigned to daily doses of phenobarbital (4 to 5 mg per kilogram of body weight per day) with the IQs of a group randomly assigned to placebo. After two years, the mean IQ was 7.03 [corrected] points lower in the group assigned to phenobarbital than in the placebo group (95 percent confidence interval, -11.52 to -2.5, P = 0.0068 [corrected]). Six months later, after the medication had been tapered and discontinued, the mean IQ was 5.2 points lower in the group assigned to phenobarbital (95 percent confidence interval, -10.5 to 0.04, P = 0.052). The proportion of children remaining free of subsequent seizures did not differ significantly between the treatment groups. We conclude that phenobarbital depresses cognitive performance in children treated for febrile seizures and that this disadvantage, which may outlast the administration of the drug by several months, is not offset by the benefit of seizure prevention.", "A randomized double blind placebo controlled trial was carried out to study the effect of phenobarbitone (PB) in preventing recurrences of simple and atypical febrile convulsions among children in the age group 6 months to 6 years. Children with simple febrile convulsions were randomly allocated to receive either phenobarbitone or placebo. Children with atypical convulsions were treated with phenobarbitone, as a third group. Thirty children were admitted in each group. All the children were followed up for a period of twelve months. Recurrence of convulsions and side effects of PB were recorded. Recurrence occurred in only 7% (95% confidence interval: 1-22) of children on Phenobarbitone, suffering from either simple or atypical febrile convulsions, compared to 53% (95% confidence interval: 34-72) of children on placebo, suffering from simple febrile convulsions. With Phenobarbitone, 5% of children had intolerable side effects. These results suggest that long term prophylaxis with phenobarbitone, even in simple febrile convulsions will be useful.", "Of the 265 children aged between 6 and 18 months admitted to hospital in a 26-month period each with his first febrile convulsion, there were 64 who satisfied our criteria for a simple febrile convulsion. Of these, 43 (random) were entered into a double-blind trial of continuous sodium valproate versus phenobarbitone, and 21 were untreated. The dosage was phenobarbitone 3-6 mg/kg per day; sodium valproate 30-60 mg/kg per day. 39 completed treatment (21 phenobarbitone, 18 sodium valproate), 2 in each group being withdrawn because of unacceptable side effects. Close supervision and random serum drug estimations showed compliance to be good. After a mean treatment period of 12 months (mean age 25 months) there had been one recurrence in the sodium valproate group compared with 7 in the untreated group (P less than 0.05), and 4 recurrences in the phenobarbitone group. The difference between treatment and no treatment was significant (P less than 0.05). These results suggest that in simple febrile convulsions occurring between 6 and 18 months of age sodium valproate is as effective as phenobarbitone in preventing recurrence and that either treatment is better than none.", "nan", "nan", "To compare the effectiveness of intermittent clobazam versus diazepam therapy in preventing the recurrence of febrile seizures and assess adverse effects of each drug.\n This prospective randomized controlled trial was performed on neurologically normal children aged from 6 months to 5 years with a history of simple febrile seizures and normal electroencephalogram without any evidence of acute central nervous system infection. The patients were randomly prescribed with oral clobazam (37 cases) or diazepam (35 cases) when they developed a febrile disease. They were advised to use the medications during the first 48 h of the onset of fever. All the patients were monitored regarding developing seizure and adverse effects of the drugs. All patients were followed for 12 months.\n Overall, 243 episodes of fever occurred during the period, including 116 episodes in the clobazam group and 127 episodes in the diazepam group. Recurrence of seizures occurred in 2 (1.7%) subjects in the clobazam group, and in 4(3.1%) cases in the diazepam group. (P value=0.474). Twenty cases (54%) in the diazepam group and 5 (14.2%) cases in the clobazam group developed drowsiness and sedation during the follow-up period (P value=0.0001).\n Intermittent clobazam therapy seems advantageous to diazepam due to similar efficacy but significantly lower adverse effects such as drowsiness and sedation.", "A total of 107 children who had been hospitalized following a febrile convulsion were enrolled into the trial. By random allocation, 55 children were treated with pyridoxine hydrochloride (20 mgs twice daily) and the remaining 52 children were treated with a placebo until there had been either a further convulsion or a year had passed without recurrence. Eighty children were adequately followed up and of these, 17 had a recurrent febrile convulsion while receiving medication. Recurrences occurrences occurred in 7 of the 38 children receiving pyridoxine and in 10 of the 42 children receiving placebo (X2 = .346, p greater than 0.5). Initial tryptophan load tests had been abnormal in 34 children, and of these, recurrences occurred in 3 of the 17 who received pyridoxine and in 3 of the 17 who received placebo. It has yet to be shown that pyridoxine supplementation protects children from recurrent febrile convulsions.", "The relationship between the number of febrile episodes and recurrent febrile convulsions was studied prospectively in 289 children after their first febrile seizure. They were randomized to either short-term diazepam prophylaxis (n = 152) or to no prophylaxis (n = 137), and followed for 18 months. Among untreated children with many subsequent febrile episodes (greater than or equal to 4 per year) 29 of 37 (78%) had a recurrence vs. 17 of 100 (17%) with only few (less than 4 per year) feverish illnesses. The former group had a 4:1 chance of developing further febrile fits, compared with a 1:4 chance in the latter (P less than 0.0001). A similar pattern was observed in the prophylaxis group, but less recurrences were seen (30% vs. 6%, P less than 0.0001). By Cox regression analysis, the subsequent occurrence of many febrile episodes could be identified among several items, including young age at onset, as the adverse factor most highly associated with further febrile fits (P less than 0.0001).", "nan", "Cognitive and behavioral effects of phenobarbital in toddlers were assessed in a randomized, placebo-controlled study of patients who had had a febrile seizure. There were no significant differences in IQ (Binet or Bayley Scales) between placebo and phenobarbital groups after eight to 12 months of therapy. However, detrimental effects of phenobarbital were found in memory, for which serum level influenced scores, and in comprehension, in that length of treatment time affected performance. Hyperactivity was not seen. Behavioral changes, reported by parents, were increased fussiness and a characteristic disturbance of sleep. These changes varied in severity and were classified as transient, dose related, or unacceptable. After 12 months in the study, most parents could not distinguish between phenobarbital and placebo. Our data suggest that although most toddlers do not have major side effects from phenobarbital therapy when treated for a year, serum levels and length of time on phenobarbital should be kept at a minimum to reduce negative cognitive and behavioral effects.", "The purpose of this study was to compare three different modes of treatment in the prevention of relapses of febrile convulsions (Phenobarbital = PH, Sodium Valproate = SV, Placebo = PO) in a randomized therapeutic trial. The patients included in the study had shown their first generalized convulsive seizure during a bout of fever (greater than or equal to 38.5 degrees C) and were aged between 6 months and 4 years. They were subsequently followed up as outpatients, and Phenobarbital and sodium valproate levels were measured regularly to ascertain compliance with the treatment and to adjust the dosage accordingly. The patients' families were questioned with respect to the occurrence of feverish bouts and convulsive seizures during the interval between visits, as well as possible adverse reactions. An EEG was carried out yearly. Results were as follows: - 69 patients - 35 boys and 34 girls - with an average age of 24 months were divided into 3 groups according to treatment: 21 cases on PH, 22 cases on SV, and 26 cases on PO. - they were followed up for an average duration of 21 months. - the average number of feverish bouts per child and per year was evaluated at 2.5, no statistically significant difference being noticeable between the various modes of prophylaxis. - 15 relapses of febrile seizures were noted in 14 children, over an average duration of 23 months; on average, relapses occurred after 9 months; among the 14 children who had relapsed, one had been treated with SV, 4 with PH and 9 with PO, leading to estimated relapse rates of 4%, 19%, and 35% respectively. There is a statistically significant difference in the relapse rates between the treated groups (SV and PH) and the Placebo group, and a particularly significant difference between Sodium Valproate and Placebo.(ABSTRACT TRUNCATED AT 250 WORDS)", "In an open, prospective, randomized, and hospital-based study, comprising 219 consecutive children, 169 were given intermittent prophylaxis for one year, receiving either diazepam or valproic acid after their first febrile convulsion. Children admitted on odd dates (n = 89) were given rectal diazepam in solution every 12 h, whenever the temperature was 38.5 degrees C or more. Children admitted on even dates (n = 80) were given valproic acid as suppositories at times of fever. Twenty-three children in the diazepam group had a recurrence within 1 year versus 14 in the valproic acid group. On an intention-to-treat basis the 12-month recurrence rates in the 2 groups were similar, 27% vs 20%. The latter is well below figures for untreated controls from Denmark (32%), suggesting that intermittent valproic acid at times of fever may be effective, but further studies are needed. The number of complex recurrences, however, were significantly higher in the valproic acid group than in the diazepam group. Parental non-compliance was a major problem, and in the 2 study groups only 5 and 12 children, respectively, with recurrences were treated adequately. Sixty-nine children receiving diazepam had side-effects vs 37 receiving valproic acid. None were serious.", "In order to evaluate the effectiveness of diazepam for the reduction in the recurrence of febrile seizures we carried out a prospective study in two groups of children; Group A: 45 children (25 female, 20 male), receiving oral prophylaxis with diazepam, and Group B: 65 children (35 female, 30 male) who did not receive any oral prophylaxis. All subjects of both groups were followed for at least 4 years and finally re-evaluated at the mean age of 6.7+/-1.4 years. Among the patients of Group A, recurrent febrile seizures (FS) occurred in five of the 45 children (11.1%). Among the 65 children of Group B, 20 (30.7%) went on to have one or more additional episodes. In conclusion, our study demonstrates that oral diazepam, given only when fever is present, is an effective means of reducing the risk of recurrences of FS.", "The effect of phenobarbital on total sleep time, night awakenings, and lengthy awakenings was examined as part of a randomized trial of children with febrile seizures; information about sleep patterns was gathered by parental observation. Children were between ages 8-36 months at enrollment and were examined subsequently for 2 1/2 years. Night awakenings were not more common in children assigned to phenobarbital except for those who were poor sleepers at the beginning of the study. Total sleep time was no different in children assigned to phenobarbital than in those assigned to placebo. It is concluded that sleep problems reported in most young children with febrile seizures treated with phenobarbital did not exceed those reported in children treated with placebo, but a subset of predisposed children did experience an increase in night awakenings.", "Febrile seizures recur frequently. Factors increasing the risk of febrile seizure recurrence include young age at onset, family history of febrile seizures, previous recurrent febrile seizures, time lapse since previous seizure <6 months, relative low temperature at the initial seizure, multiple type initial seizure, and frequent febrile illnesses. Prevention of seizure recurrences serves two useful purposes: meeting parental fear of recurrent febrile seizures in general and reducing the (small) risk of a long-lasting and eventually injurious recurrent seizure. In daily practice, children with febrile seizures often are treated with antipyretics during fever to prevent febrile seizure recurrences. Thus far, no randomized placebo-controlled trial has been performed to assess the efficacy of intermittent antipyretic treatment in the prevention of seizure recurrence.\n We performed a randomized, double-blind, placebo-controlled trial. Children 1 to 4 years of age who had had at least one risk factor for febrile seizure recurrence were enrolled. They were randomly assigned to either ibuprofen syrup, 20 mg/mL, 0.25 mL (= 5 mg) per kilogram of body weight per dose, or matching placebo, to be administered every 6 hours during fever (temperature, >/=38.5 degrees C). Parents were instructed to take the child's rectal temperature immediately when the child seemed ill or feverish and to promptly administer the study medication when the temperature was >/=38.5 degrees C. Doses were to be administered every 6 hours until the child was afebrile for 24 hours. The parents were instructed not to administer any other antipyretic drug to the child. For measuring rectal temperature, a Philips HP5316 digital thermometer (Philips, Eindhoven, The Netherlands) was distributed. During subsequent treatment of the fever episode, parents had to call the investigator at least once each day to notify the investigator in case of febrile seizure recurrence. The investigator could be contacted by parents 24 hours per day. The primary outcome was the first recurrence of a febrile seizure. Kaplan-Meier curves and Cox regression were used for the statistical analysis. The treatment effect on the course of the temperature was assessed using analysis of covariance, with temperature at fever onset as covariate. Two analyses were performed. In an intention-to-treat analysis, all first recurrences were considered regardless of study medication compliance. A per-protocol analysis was limited to those recurrences that occurred in the context of study medication compliance.\n Between October 1, 1994, and April 1, 1996, 230 children were randomly assigned to ibuprofen syrup (111 children) or placebo (119 children). Median follow-up time was 1.04 years (25th-75th percentiles; 0.7-1.8 years) in the ibuprofen group and 0.98 years (0.7-1.6 years) in the placebo group. Of all children, 67 had a first febrile seizure recurrence, with 31 in the ibuprofen group and 36 in the placebo group. The 2-year recurrence probabilities were 32% and 39%, respectively. The recurrence risk in the ibuprofen group was 0.9 (95% confidence interval: 0.6-1.5) times the recurrence risk in the placebo group (intention to treat). Adjustment for baseline characteristics did not affect the risk-reduction estimate. Of the 67 recurrences, 30 occurred in the context of study medication compliance (13 ibuprofen, 17 placebo). The per-protocol analysis, which was limited to these events, showed similar results. A significant reduction in temperature (0.7 degrees C) after fever onset in the ibuprofen group compared with the placebo group was demonstrated if all 555 fever episodes were considered. In the fever episodes with a seizure recurrence, a similar temperature increase was shown in both groups, with no significant difference between the intention-to-treat and the per-protocol analysis.\n (ABSTRACT TRUNCATED)", "The aim of this study was to evaluate the efficacy and tolerance of intermittent oral administration of diazepam during hyperthermia for reducing the recurrence of febrile seizure: 185 children, between 8 months and 3 years of age, with a first febrile seizure and normal neurologic development, were randomly assigned in a double-blind fashion to receive orally administered diazepam (0.5 mg/kg, then 0.20 mg/kg, every 12 hours) or placebo, whenever the rectal temperature was more than 38 degrees C. The main criterion of efficacy was the seizure recurrence rate 1 year after the first seizure. The duration of the study was 3 years; eight different centers in France participated. There were 462 febrile episodes and 1000 days with prophylactic treatment. The recurrence rates did not differ between the diazepam group (16%) and the placebo (19.5%) group. The children with recurrent seizures were significantly younger at the time of the first seizure (17 +/- 6.9 months) than children without a recurrent seizure (21 +/- 8.5 months). In children with recurrent seizures, prophylactic treatment was correctly administered to only 1 of 15 children in the diazepam group and to 7 of 18 children in the placebo group. The following were the reasons for this poor cooperation: convulsion being the first manifestation of the fever (seven cases in each group), parents neglecting to give treatment (nine cases), and refusal to take treatment by two children. Side effects were similar in the two groups except for hyperactivity, which was more frequent in the diazepam (138 days) than in the placebo (34 days) group. Intermittent oral administration of diazepam at the onset of fever offered no advantage over placebo in preventing recurrence of seizure. This finding probably reflects a lack of efficacy of the intermittent method rather than of diazepam itself.", "Of 109 children treated daily with phenobarbital following the first fibrile convulsion, 42% developed a behavior disorder, usually hyperactivity. Daily phenobarbital therapy was prematurely discontinued in 54% of the children with behavior abnormality (20% of those treated). The behavior disturbance usually appeared within several months, was no correlated with high blood barbiturate levels, disappeared in 73%, and improved in all children when barbiturate therapy was discontinued. No characteristics of the child, the initial febrile seizure, or recurrence of febrile seizures were significantly correlated with the occurrence of the behavior disorder except for behavioral abnormality preceding the initial febrile convulsion. Eighteen percent of the children who received no phenobarbital developed behavior disorder, most often hyperactivity. The behavior disturbance spontaneously disappeared in 52%. Among these children not given phenobarbital, the group with normal behavior had a greater frequency of family history of seizures, especially febrile convulsions, and a lower frequency of preseizure behavior disturbance; abnormalities of pregnancy, labor, delivery, and neonatal period; delayed milestones; long seizures; abnormal results of neurological examination; abnormal EEG; and recurrent febrile seizures.", "We previously reported that IQ was significantly lowered in a group of toddler-aged children randomly assigned to receive phenobarbital or placebo for febrile seizures and there was no difference in the febrile seizure recurrence rate. We retested these children 3-5 years later, after they had entered school, to determine whether those effects persisted over the longer term and whether later school performance might be affected. On follow-up testing of 139 (of the original n = 217) Western Washington children who had experienced febrile seizures, we found that the phenobarbital group scored significantly lower than the placebo group on the Wide Range Achievement Test (WRAT-R) reading achievement standard score (87.6 vs 95.6; p = 0.007). There was a nonsignificant mean difference of 3.71 IQ points on the Stanford-Binet, with the phenobarbital-treated group scoring lower (102.2 vs 105.7; p = 0.09). There were five children in our sample with afebrile seizures during the 5-year period after the end of the medication trial. Two had been assigned to phenobarbital, and three had been in the placebo group. We conclude there may be a long-term adverse cognitive effect of phenobarbital on the developmental skills (language/verbal) being acquired during the period of treatment and no beneficial effect on the rate of febrile seizure recurrences or later nonfebrile seizures." ]

[ "19318702", "11812708", "10455830", "15890830" ]

[ "Effect of food intake during labour on obstetric outcome: randomised controlled trial.", "An evaluation of isotonic \"sport drinks\" during labor.", "Eating in labour. A randomised controlled trial assessing the risks and benefits.", "The effect of unrestricted oral carbohydrate intake on labor progress." ]

[ "To investigate the effect of feeding during labour on obstetric and neonatal outcomes.\n Prospective randomised controlled trial.\n Birth centre in London teaching hospital.\n 2426 nulliparous, non-diabetic women at term, with a singleton cephalic presenting fetus and in labour with a cervical dilatation of less than 6 cm.\n Consumption of a light diet or water during labour.\n The primary outcome measure was spontaneous vaginal delivery rate. Other outcomes measured included duration of labour, need for augmentation of labour, instrumental and caesarean delivery rates, incidence of vomiting, and neonatal outcome.\n The spontaneous vaginal delivery rate was the same in both groups (44%; relative risk 0.99, 95% confidence interval 0.90 to 1.08). No clinically important differences were found in the duration of labour (geometric mean: eating, 597 min v water, 612 min; ratio of geometric means 0.98, 95% confidence interval 0.93 to 1.03), the caesarean delivery rate (30% v 30%; relative risk 0.99, 0.87 to 1.12), or the incidence of vomiting (35% v 34%; relative risk 1.05, 0.9 to 1.2). Neonatal outcomes were also similar.\n Consumption of a light diet during labour did not influence obstetric or neonatal outcomes in participants, nor did it increase the incidence of vomiting. Women who are allowed to eat in labour have similar lengths of labour and operative delivery rates to those allowed water only.\n Current Controlled Trials ISRCTN33298015.", "We compared the metabolic effects of allowing women isotonic \"sport drinks\" rather than water to drink during labor. The effect of these drinks on gastric residual volume was also evaluated. Sixty women in early labor (cervical dilation <5 cm) were randomized to receive either isotonic sport drinks or water only. Plasma beta-hydroxybutyrate, nonesterified fatty acids, and glucose were measured in early labor and at the end of the first stage of labor. Residual gastric volume was assessed within 45 min of delivery by use of an ultrasound scanner. The incidence and volume of vomiting was recorded. At the end of the first stage of labor, plasma beta-hydroxybutyrate (P = 0.000) and nonesterified fatty acids (P = 0.000) had increased and plasma glucose (P = 0.007) had decreased significantly in the Water-Only group. Gastric antral cross-sectional area after delivery was similar in the two groups. The incidence of vomiting and the volume vomited during labor and within the hour of delivery were also similar. There was no difference between the groups in any maternal or neonatal outcome of labor. In conclusion, isotonic drinks reduce maternal ketosis in labor without increasing gastric volume.\n Solid foods may endanger a woman's life if consumed during labor. Isotonic sport fluids were evaluated as a nutritional alternative. Results demonstrate that mothers who have not received parenteral opioids can safely drink isotonic drinks in active labor.", "The aim of this study was to determine whether permitting women in labour to eat a light diet would: (i) alter their metabolic profile, (ii) influence the outcome of labour, and (iii) increase residual gastric volume and consequent risk of pulmonary aspiration. Women were randomised to receive either a light diet (eating group, n = 48) or water only (starved group, n = 46) during labour. The light diet prevented the rise in plasma beta-hydroxybutyrate (p = 2.3 x 10(-5)) and nonesterified fatty acids (p = 9.3 x 10(-7)) seen in the starved group. Plasma glucose (p = 0.003) and insulin (p = 0.017) rose in the eating group but there was no difference in plasma lactate (p = 0.167) between the groups. There were no differences between the groups with respect to duration of first or second stage of labour, oxytocin requirements, mode of delivery, Apgar scores or umbilical artery and venous blood samples. Relative gastric volumes estimated by ultrasound measurement of gastric antral cross-sectional area were larger (p = 0.001) in the eating group. This was supported by the observation that those from this group who vomited, vomited significantly larger volumes than those in the starved group (p = 0.001). We conclude that eating in labour prevents the development of ketosis but significantly increases residual gastric volume.", "To determine if unrestricted oral carbohydrate intake during labor reduced the incidence of dystocia in low-risk nulliparous women.\n A randomized clinical trial at a university-affiliated hospital in southeastern Ontario. Low-risk nulliparous women were randomized between 30 and 40 weeks gestation to either an intervention or usual care group.\n Women in the intervention group received, prenatally, guidelines about food and fluid intake during labor and were encouraged to eat and drink as they pleased during labor. Women in the usual care group received no prelabor information and were restricted to ice chips and water during labor in the hospital.\n The incidence of dystocia, defined as a cervical dilatation rate of less than 0.5 cm/hr for a period of 4 hrs after a cervical dilatation of 3 cm.\n Three hundred twenty-eight women were randomized to the intervention (n = 163) or usual care (n = 165) groups. Women in the intervention group reported a significantly different pattern of oral intake during early labor in the hospital (chi(2) = 40.7, p < .001). The incidence of dystocia was 36% (n = 58) in the intervention group and 44% (n = 72) in the usual care group and was not significantly different (OR = 0.71, 95% CI = 0.46, 1.11). There were no significant differences in the other secondary outcomes or in the incidence of adverse maternal or neonatal complications.\n Eating and drinking early in labor had no significant impact on the incidence of dystocia and/or adverse maternal or neonatal outcomes." ]

[ "11062278", "5903854", "12806495", "6731167", "1866749", "7740638", "6382700", "7134909", "7435253", "14563969", "3911506", "9448885", "3917584", "8378947", "12511758", "9506597", "16123546", "7831697", "13892131", "15198886", "15955756", "7482644", "11036894" ]

[ "Effect of acute stroke unit care integrated with care continuum versus conventional treatment: A randomized 1-year study of elderly patients: the Göteborg 70+ Stroke Study.", "Evaluation of rehabilitation methods in the hemiplegic patient.", "Study comparing the stroke unit outcome and conventional ward treatment: a randomized study in Joinville, Brazil.", "A randomized controlled trial of a stroke rehabilitation ward.", "Benefit of a stroke unit: a randomized controlled trial.", "[Intensive rehabilitation after apoplexy--a controlled pilot study].", "A randomized trial of team care following stroke.", "II. Early activation in stroke: does it make a difference?", "A study of stroke patients treated in a non-intensive stroke unit or in general medical wards.", "Role of monitoring in management of acute ischemic stroke patients.", "The significance of intensity of rehabilitation of stroke--a controlled trial.", "Stroke units: an Australian perspective.", "A non-intensive stroke unit reduces functional disability and the need for long-term hospitalization.", "Improving stroke rehabilitation. A controlled study.", "Admitting acute ischemic stroke patients to a stroke care monitoring unit versus a conventional stroke unit: a randomized pilot study.", "Stroke unit versus general medical wards, II: neurological deficits and activities of daily living: a quasi-randomized controlled trial.", "Patients with severe stroke benefit most by interdisciplinary rehabilitation team approach.", "Where and how should elderly stroke patients be treated? A randomized trial.", "A comparison of functionally orientated medical care and formal rehabilitation in the management of patients with hemiplegia due to cerebrovascular disease.", "Assessment of the early effectiveness of a stroke unit in comparison to the general ward.", "Early assessment by a mobile stroke team: a randomised controlled trial.", "Role of stroke rehabilitation units in managing severe disability after stroke.", "Alternative strategies for stroke care: a prospective randomised controlled trial." ]

[ "The aim of the study was to compare the effect of conventional treatment with the effect of acute stroke unit care integrated with geriatric stroke unit care continuum.\n A 1-year study was undertaken with 2:1 randomization to stroke unit care or conventional care, with assessment by an independent team. The study was composed of 249 elderly patients (aged >/=70 years) hospitalized for acute stroke, without previous cerebral lesion and without recognized need of care. Main outcome measures were patients at home after 1 year, ability in daily living activities, health-related quality of life score according to questionnaire, death or institutional care, and death or dependence.\n One hundred two patients (61%) in the stroke unit and 49 patients (59%) in the general ward group were alive and at home after 1 year (95% CI -10% to 16%). There were no significant differences in daily life activities or quality of life. In patients with concomitant cardiac disease, there was a reduction in death or institutional care after 3 months in the stroke unit group compared with the group receiving conventional care (28% versus 49%, respectively; 95% CI -40% to -3%). This effect did not remain after 1 year. Patients seeking care after 24 hours often had mild stroke and lived alone.\n There was no effect on the number of patients living at home after 1 year, but after 3 months of stroke unit care, a beneficial effect was found on mortality and the need for institutional care among those with concomitant heart disease. This study involved patients who were considerably older than those investigated in previous randomized studies of acute stroke unit care; thus, these findings will contribute to the specialized register of controlled trials in stroke.", "nan", "To assess the impact of a stroke unit (SU) on acute phase treatment when compared to a conventional general ward treatment (GW).\n Seventy-four patients with acute stroke were randomized between a SU and conventional general ward (GW). We compared both groups regarding the length of hospital stay, lethality and functional and clinical status within 6 months, using the Scandinavian scale and Barthel index.\n Thirty-five and thirty-nine patients were allocated at SU and GW, respectively. Lethality on the 10th day at SU and GW achieved 8.5% and 12.8% respectively (p= 0.41), whereas 30-days mortality rates achieved 14.2% and 28.2% (p= 0.24), 17.4% and 28.7% on the 3rd month (p= 0.39), and 25.7% and 30.7% on the 6th month (p= 0.41). Thirty-day survival curve achieved 1.8 log rank (p= 0.17), with a trend for lower lethality in the SU. In order to save one death in 6 months in SU, NNT (the number need to treat) was 20; to get one more home independent patient NNT was 15. No significant difference was found between the length of hospital stay and morbidity.\n No significant benefit was found in SU patients compared to GW group. However,an evident benefit in absolute numbers was observed in lethality, survival curve and NNT in thirty days period after stroke. Further collaborative studies or incresead number of patients are required to define the role of SU.", "In S.E. Kent, during 1978 and 1979, 225 patients, representing 228 occurrences of hemiplegia, were referred to a new 20-bed stroke rehabilitation ward. These patients were randomly allocated to treatment in the special ward (group A 112 strokes) or to remain in conventional treatment locations (group C 116 strokes); the two groups were closely similar, except for the initial level of consciousness. Survivors were observed at four-month intervals to one year. There are indications of benefit for patients in group A by comparison with Group C in terms of treatment received (number treated by remedial therapists, the extent of treatment, and the arrangements for after-care), and in outcome (survival and the proportion returned to the community). The direction of the trend of advantage is consistent with another recent controlled trial, although not all modes of improvement are identical in the two trials. It is suggested that every health district should develop a comprehensive policy of stroke management.", "In a randomized controlled trial we compared the clinical outcome of acute stroke patients, 110 of whom were allocated to treatment in a stroke unit and 110 to treatment in general medical wards. No significant difference existed between these groups with regard to sex, age, marital status, medical history, or functional impairment on admission. Outcome was measured at 6 and 52 weeks after the stroke by the proportion of patients at home, the proportion of patients in an institution, the mortality, and the functional state. After 6 weeks 56.4% of the patients randomized to the stroke unit and 32.7% of the patients randomized to the general medical wards were at home (p = 0.0004), and after 52 weeks 62.7% and 44.6%, respectively, were at home (p = 0.002). After 6 weeks 36.3% of the patients from the stroke unit and 50.0% from the general medical wards were in an institution (p = 0.02); after 52 weeks 12.7% and 22.7%, respectively, were institutionalized (p = 0.016). After 6 weeks mortality was 7.3% for the stroke unit group and 17.3% for the general medical wards group (p = 0.027). After 52 weeks mortality was 24.6% for the stroke unit group and 32.7% for the general medical wards group (difference not significant). Functional state was significantly better for patients treated in the stroke unit after both 6 and 52 weeks. We conclude that care of patients with acute stroke in a stroke unit improves clinical outcome compared with treatment in general medical wards.", "In a prospective, randomized, controlled trial we compared the clinical outcome for 65 acute stroke patients where 31 were treated in a stroke unit and 34 in general medical units. In the stroke unit the treatment principles of Bobath were used, and teamwork was essential in the treatment. The inclusion period was nine months. Patients were followed up at a control six months after hospital discharge. The two groups were comparable as concerned age, sex, number of patients > or = 75 years and functional impairment at hospital admission. The mortality was similar in the two groups of patients. Significantly fewer patients from the stroke unit group were referred to nursing homes, when the patients in function group five (those most severely ill) were excluded. The functional status at the six months post discharge control was similar in the two groups. The in-patient time was without significant difference between the two groups when patients referred to nursing homes were excluded. The need for primary nursing after discharge was similar in the two groups. We conclude from our pilot study that better organisation in a general medical ward would in some aspects improve the prognosis of a major proportion of stroke patients.", "A randomized controlled trial was conducted to examine the effects of interdisciplinary team care on acute hospitalized stroke patients. After obtaining baseline information on 42 stroke victims receiving conventional care in a general hospital, 130 stroke patients were stratified and randomly assigned either to Traditional or Team care. Assessments by independent evaluators permitted comparisons between Team and Traditional groups with reference to patient survival, motor performance and functional abilities. Data obtained prospectively from charts and treatment logs allowed the care process across groups to be compared. Results demonstrated that Team and Traditional patients fared similarly in survival. However there was an unexpected difference in survival depending upon sex. For motor performance, male survivors performed better with Team care and female survivors with the Traditional method. In terms of functional abilities, male patients receiving Team care again performed better than their Traditional counterparts, whereas in women there was no difference between the treatment groups.", "The effect of early systematic activation in daily nursing care was studied in an experimental group of patients with acute stroke. The staff had received an educational programme on stroke and its care. Sixty stroke patients were admitted to two general medical wards during a period of 9 months. Fifty-two stroke patients from two other such wards formed a control group. The functional capacity was measured by a specially constructed Activity Index (AI) at regular intervals in all patients. The functional capacity of the experimental group improved significantly with the special care in hospital up to 4 weeks after the stroke, while the change in the control group was non-significant according to the chosen level of significance. During the remainder of the 3-month study period with routine care in both groups, the two groups improved more equally. The activation programme may thus have had a stimulation effect while it was in progress.", "To study the representativity and outcome of patients admitted to a stroke unit (SU) (n = 269), a comparison was made with all stroke patients treated in general medical wards (GMW) (n = 225) in the same hospital during two years. There was no difference between the patient groups regarding sex, age, previous cardiovascular diseases or neurological deficit on admission. As expected, more diagnostic examinations were performed in the SU than in the GMW where a diagnosis of ill-defined stroke was very frequent. A higher frequency of lumbar puncture with CSF spectrophotometry would have increased considerably the number of specific diagnoses in the GMW. Acute and, particularly, secondary prophylactic treatment was more often given in the SU. There was no difference between the patient groups regarding mortality or length of hospital stay.", "Although several studies have demonstrated the effectiveness of specialist Stroke Unit (SU) care of stroke patients, there is still disagreement over how these units are best organized. We sought to clarify the role of continuous monitoring of physiological parameters in acute ischemic stroke.\n We conducted a prospective study of 268 first-ever ischemic stroke patients admitted to our Cerebrovascular Department and allocated, according to the availability of beds, to the SU or Cerebrovascular Unit (CU). Statistical analysis compared mortality and outcome at discharge, medical and neurological complications, and length of hospitalization in the 2 care settings.\n Two hundred sixty-eight patients were enrolled. A good outcome at discharge, observed in 114 SU patients (85%) and 78 CU patients (58%) (odds ratio, 2.63; 95% CI, 1.4 to 4.8; P<0.02), was found, on multivariate analysis, to be significantly related to type of care (SU versus CU). A significantly greater proportion of SU patients showed adverse changes in monitored parameters, which required acute medical treatment (SU: 64%; CU: 19%; P<0.0001). The mean duration of these complications was significantly shorter in the SU patients (SU: 1.0 day; CU: 2.4 days; P<0.02), and the outcome in patients experiencing complications covered by the monitoring protocol was significantly better in the SU (66%) than in the CU (35%) group (P<0.0001).\n Admission of acute stroke patients to a monitoring SU may positively influence their outcome at discharge. Confirmation of our findings in larger trials will indicate the need for a revision of the minimum requirements of SUs, with the addition of monitoring as a new requirement.", "Of the 373 stroke patients 95 were admitted to the feasibility study of stroke rehabilitation. The patients were divided into two groups, an intensive and a normal treatment group. In this study, the functional recovery of stroke, measured by ADL and motor function was significantly better in the intensive treatment group. There was no difference in institutionalization or incidence of death between the groups. The gain of ADL and motor function was greatest during the first three months after stroke in the intensive treatment group. The conclusion is that intensified physiotherapy seems to improve the functional recovery of stroke patients.", "nan", "In a prospective controlled trial we compared the clinical outcome for unselected acute stroke patients in a non-intensive stroke unit (n = 110) and in general medical wards (n = 183). The patients were comparable in age, marital state and functional impairment on admission. Case fatality rates over the first year after the stroke were similar in the two groups. By three months after the stroke, 15% of the survivors initially admitted to the stroke unit and 39% of those admitted to general medical wards remained hospitalized (p less than 0.001). The corresponding figures by one year after the cerebrovascular accident were 12% and 28%, respectively (p less than 0.05). A greater proportion of surviving stroke unit patients was independent in walking (0.10 greater than p greater than 0.05), personal hygiene (p less than 0.05) and dressing (p less than 0.001). Essential features of the stroke unit are team work headed by a stroke nurse, staff, patient and family education and very early onset of rehabilitation. We conclude that this strategy improves functional outcome and reduces the need for long-term hospital care.", "Assessment of stroke rehabilitation is complicated by the heterogeneity of patients and settings and by difficulties in disentangling effects of organization from effects of types and amounts of treatment input.\n A prospective controlled study was undertaken in 245 stroke patients stratified into three groups according to prognosis and managed on a stroke rehabilitation unit (n = 124) or general medical wards (n = 121). Patients were randomly allocated to either setting 2 weeks after stroke and were comparable for baseline characteristics.\n Patients on general medical wards received more physiotherapy on average (16.2 +/- 7.2 versus 14.3 +/- 3.2 hours; P < .05) but similar amounts of occupational therapy (9.3 +/- 2.8 versus 9.5 +/- 3.2 hours) compared with stroke unit patients. More time was spent on individual rehabilitation on the stroke unit compared with general wards (P < .001). Functional abilities at discharge, destination of discharge, and length of hospital stay in patients with good prognosis were comparable in both settings. Patients with poor prognosis managed on general wards showed higher mortality (P < .05) and longer hospital stay (123.2 +/- 48.2 versus 52.3 +/- 19.8 days; P < .001), but functional abilities at discharge in survivors were comparable with those of stroke unit patients. Patients with intermediate prognosis had significantly better outcome on the stroke unit, with more patients being discharged home (75% versus 52%; P < .001), shorter average length of hospital stay (48.7 +/- 17.2 versus 104.6 +/- 28.6 days; P < .001), and better functional abilities at discharge (P < .05).\n Stroke units improve outcome and reduce hospital stay without increasing therapy time. Their effectiveness may be enhanced by patient selection.", "Pathophysiological considerations and observational studies indicate that elevated body temperature, hypoxia, hypotension, and cardiac arrhythmias in the acute phase of ischemic stroke may aggravate brain damage and worsen outcome.\n Both units were organized with the same standard care and multidisciplinary approach to nursing and rehabilitation. A blinded observer assessed functional outcome at 3 months with the modified Rankin scale (mRS) and Barthel Index (BI). End points were (1) poor outcome, defined as either mRS > or =4 or BI <60 or the need for institutional care and (2) mortality.\n Fifty-four patients meeting the inclusion criteria were randomized. The groups were well matched for baseline characteristics, stroke subtype, stroke severity, vascular risk factors, and prognostic factors. Poor outcome was seen in 7 (25.9%) patients in the SCMU group and in 13 (48.1%) in the SU group (P=0.16). Mortality was lower in the SCMU group than in the SU group (1 [3.7%] vs 7 [25.9%]; odds ratio, 0.11 [95% CI, 0.02 to 0.96], P=0.05).\n This pilot study suggests that admission of acute stroke patients to an SCMU may reduce mortality and poor outcome. A larger trial is required to confirm these findings.", "The efficacy of stroke units has been extensively examined. It is unknown, however, whether the superiority of the stroke unit will remain after the increased focus on stroke treatment in general medicine. This study of patients admitted to the hospital early and with a short length of stay determines the effect and identifies certain important components of a stroke unit.\n Five hundred fifty patients aged 60 years or older with acute stroke were allocated by a quasi-randomized design to a stroke unit or a general medical ward based on date of birth in the month. Patients admitted within 24 hours of onset were enrolled. Outcomes after 7 months were death, proportion needing long-term care, and change in neurological and functional state assessed by the Scandinavian Stroke Scale and Barthel Index.\n Seven months after admission there was a trend in favor of the stroke unit in all outcome measures, but no significant differences in clinical outcomes were found except for change in the Scandinavian Stroke Scale score. Recurrent stroke during hospitalization occurred more often in the general medical ward (P = .03). The stroke unit was significantly more aggressive in mobilization out of bed (P<.01) and use of parenteral fluid (P<.0001), aspirin (P<.0001), antipyretics (P<.0001), and antibiotics (P<.0001).\n Our study confirms the benefit of the stroke unit, but the effects on the most reliable clinical outcomes were modest and insignificant. Treatment in this stroke unit hastened recovery. More aggressive rehabilitation and use of parenteral fluid, aspirin, antipyretics, and antibiotics appeared in the stroke unit.", "We evaluated the efficacy of a regular interdisciplinary stroke team approach on rehabilitation outcome.\n We compared a stroke rehabilitation unit (SRU) with regular interdisciplinary stroke team conferences with general rehabilitation ward (GRW) without such conferences in the same rehabilitation hospital. One hundred and seventy-eight patients within 3 months after stroke were allocated to SRU or GRW, based on bed availability. Main outcome measures were the Functional Independence Measure, Stroke Impairment Assessment Set, length of hospital stay, discharge disposition and cost of hospitalization.\n The interval between stroke onset and admission to our hospital was significantly longer in the SRU (n = 91) group compared with the GRW group (n = 87, p < 0.05). Although comparable numbers of patients were discharged home (74.7% in the SRU vs. 71.3% in the GRW), significantly more patients (p < 0.0001) with severe disability were discharged home in the SRU group (47.4%) compared with the GRW group (0%). There were no significant differences in the increase in Functional Independence Measure score, Stroke Impairment Assessment Set score,length of hospital stay, or cost.\n Patients with severe stroke appeared to benefit most from regular interdisciplinary stroke team conferences in the SRU and had an improved discharge disposition.\n Copyright (c) 2005 S. Karger AG, Basel.", "Elderly stroke patients in particular are at risk of receiving less than optimal care. We studied the effects of the department care (medicine versus neurology) on the outcome of elderly stroke patients in a randomized controlled trial with 1-year follow-up.\n A total of 243 consecutive patients aged 65 years or older with acute stroke were randomized to receive care in the Departments of Medicine or the Department of Neurology of a university teaching hospital with a referral area of 1.1 million. The outcome was assessed by mortality, length of hospital stay, ability to live at home on discharge, Barthel Index, and Rankin grades at 1 year.\n There were no differences in sex and age, severity or type of stroke, other diseases, or social factors between the two groups. One-year mortality was 21% in both patients treated by the Departments of Medicine and those treated by the Department of Neurology. Patients treated by the Department of Neurology were discharged an average of 16 days earlier (24 versus 40 days). The length of hospital stay of patients aged younger than 75 years differed significantly (P = .02). Patients randomized to neurological wards more often went directly home (75% versus 62%; P = .03), and their functional status was better as assessed with Barthel Index and Rankin grades at 1 year (P = .02 and P = .03, respectively). Independent predictors of a better functional outcome and shorter hospital stay by stepwise multivariate analysis included management by the Department of Neurology.\n Well-organized management of elderly stroke patients was associated with a better outcome. It was also the more economical alternative.", "nan", "Stroke unit is the most effective treatment method to benefit stroke patients. Our study is to evaluate the early effectiveness of a hospital stroke unit (SU).\n Three hundred and ninety-two patients who had suffered from acute strokes and who were admitted to our hospital between December 2001 and January 2003 were recruited for this controlled study. All patients were sent at random to either the SU or the general ward (GW) for treatment. The following indices were measured by: Barthel Index (BI), National Institute of Health Stroke Scale (NIHSS), Oxford Handicap Scale (OHS).\n The mean change in BI score between the day of admission and the day of discharge was 20.00 +/- 24.36 for the SU group and 10.63 +/- 23.59 for the GW group. A difference that is statistically significant (P = 0.000). The mean change in NIHSS score was -2.01 +/- 6.61 for the SU group and 0.55 +/- 7.44 for the GW group. A difference that is also statistically significant (P = 0.000). Finally, the mean change in OHS score was -0.74 +/- 1.04 for the SU group and -0.28 +/- 0.98 for the GW group, also a statistically significant difference (P = 0.000). Among SU patients, patient satisfaction was higher (P = 0.000), the rehabilitation success rate was higher (P = 0.000), and there were fewer complications (P = 0.000).\n Compared to GW patients, stroke patients treated in a special SU were able to return to normal daily activities earlier, with better social abilities, and have reduced neurological defects, without increasing the overall economic burden.", "There is overwhelming evidence of the effectiveness of specialist stroke rehabilitation, but more limited evidence of the effectiveness of organised stroke care during the acute phase of stroke.\n To determine the impact on outcome of access to a mobile team during the acute phase of stroke among patients admitted to general wards.\n 308 patients admitted to one of two hospitals within 5 days of the onset of a clinically diagnosed stroke.\n Randomised controlled trial. STUDY GROUPS: Following admission, patients in the intervention arm were visited by members of a mobile stroke team who advised clinical staff on appropriate and timely investigation and management. They co-ordinated early input from therapy groups and identified those ready for transfer to the stroke rehabilitation unit. Patients in the control arm were not visited by the mobile stroke team.\n All-cause mortality measured at 6 weeks and 12 months.\n There was no statistically significant difference observed between study groups in mortality at 6 weeks (95% CI(adj) -7.4 to 7.4%) nor at 12 months ( 95% CI(adj) -4.1 to 15.9%). There were also no differences observed between study groups in morbidity outcomes or health-related quality of life measured at 12 months.\n The trial was terminated before the necessary sample size was collected but findings suggest that the mobile stroke team failed to confer significant long-term mortality benefit compared with general ward-based care alone.", "Stroke unit rehabilitation tends to be directed toward stroke patients with moderately severe disabilities (\"the middle group\"). Data collected on a stroke rehabilitation unit, however, showed improving outcome over 3 years in patients with a poor prognosis (discharge home: 48% versus 16%, P < .02; discharge Barthel Index score: 9 versus 6, P < .05). The hypothesis that stroke rehabilitation units may improve outcome in severely disabled stroke patients was tested in this study.\n A randomized controlled study was undertaken in 71 patients with a poor prognosis who were treated either on a stroke rehabilitation unit (n = 34) or on general wards (n = 37) to compare outcome between the two groups. Data collected were also compared with those from a methodologically similar study undertaken 3 years ago.\n Severe stroke patients treated on the stroke rehabilitation unit had a significantly better outcome compared with general wards (mortality: 21% versus 46%, P < .05; discharge home 47% versus 19%, P < .01; median length of hospital stay: 43 versus 59 days, P < .02). The number of stroke unit patients being discharged home had increased significantly from the previous study, with a trend toward improvement in median discharge Barthel Index score.\n Stroke rehabilitation units may improve outcome in severe stroke patients. This improvement appears to be due to the development of innovative management strategies that reduce mortality and institutionalization and enable caregivers to support more disabled stroke patients at home.", "Organised specialist care for stroke improves outcome, but the merits of different methods of organisation are in doubt. This study compares the efficacy of stroke unit with stroke team or domiciliary care.\n A single-blind, randomised, controlled trial was undertaken in 457 acute-stroke patients (average age 76 years, 48% women) randomly assigned to stroke unit, general wards with stroke team support, or domiciliary stroke care, within 72 h of stroke onset. Outcome was assessed at 3, 6, and 12 months. The primary outcome measure was death or institutionalisation at 12 months. Analyses were by intention to treat.\n 152 patients were allocated to the stroke unit, 152 to stroke team, and 153 to domiciliary stroke care. 51 (34%) patients in the domiciliary group were admitted to hospital after randomisation. Mortality or institutionalisation at 1 year were lower in patients on a stroke unit than for those receiving care from a stroke team (21/152 [14%] vs 45/149 [30%]; p<0.001) or domiciliary care (21/152 [14%] vs 34/144 [24%]; p=0.03), mainly as a result of reduction in mortality. The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team (129/152 [85%] vs 99/149 [66%]; p<0.001) or domiciliary care (129/152 [85%] vs 102/144 [71%]; p=0.002). These differences were present at 3 and 6 months after stroke.\n Stroke units are more effective than a specialist stroke team or specialist domiciliary care in reducing mortality, institutionalisation, and dependence after stroke." ]

[ "9925837", "7640316", "12538787", "18216861", "2895173", "10634838", "15210658", "1403464" ]

[ "Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method.", "Early minimal feedings promote growth in critically ill premature infants.", "Effect of minimal enteral feeding on splanchnic uptake of leucine in the postabsorptive state in preterm infants.", "The early use of minimal enteral nutrition in extremely low birth weight newborns.", "Beneficial effects of early hypocaloric enteral feeding on neonatal gastrointestinal function: preliminary report of a randomized trial.", "Randomised controlled study of clinical outcome following trophic feeding.", "Minimal enteral feeding, fetal blood flow pulsatility, and postnatal intestinal permeability in preterm infants with intrauterine growth retardation.", "Gastrointestinal priming prior to full enteral nutrition 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.", "Critically ill premature infants requiring mechanical ventilation and an umbilical artery catheter usually do not receive enteral feedings during the acute phase of their illness. We studied the safety and benefit of early minimal enteral feedings during this time in a prospective, controlled, and randomized study. Twenty-nine infants were randomly assigned to receive only standard intravenous fluid and nutrition (nothing per OS, NPO group; n = 13), or in addition to receive small-volume hypocaloric continuous feedings (1 ml/kg/h), beginning at 24 h of age (early-feeding group; n = 16). Standard enteral feedings were begun in both groups at the resolution of the acute phase of the illness and advanced by protocol. The two groups were of comparable birth weight, gestational age, and Apgar scores. There were no significant differences in the episodes of feeding intolerance. Two infants in the NPO group developed clinical signs of necrotizing enterocolitis. Serum diamine oxidase and somatomedin C were measured weekly until 30-60 days of age and were not different between the two groups. The early-feeding group required fewer days to reach 120 ml/kg/day enteral intake (early-feeding group 10 +/- 3 days, NPO group 13 +/- 4 days; p < 0.05). On day 30 of life the early-feeding group was 223 +/- 125 g above birth weight, while the NPO group was 95 +/- 161 g above birth weight (p < 0.05). The average intake (kcal/kg/day) from day 6 to day 30 was not different between the two groups. We conclude that early minimal feedings in critically ill very-low-birth-weight infants requiring mechanical ventilation are well tolerated and result in reduced time to reach 120 ml/kg/day of enteral feeding and in a greater weight gain by day 30 of life.", "We conducted a controlled, randomized trial to study the effect of minimal enteral feeding on leucine uptake by splanchnic tissues, as an indicator of maturation of these tissues, in preterm infants in the first week of life. Within a few hours after birth, while receiving only glucose, a primed constant infusion of [1-(13)C]-leucine was started and continued for 5 h via the nasogastric tube, whereas 5,5,5 D3-leucine was infused intravenously (for both tracers, priming dose 2 mg/kg, continuous infusion 2 mg/kg/h). Patients were thereafter randomized to receive solely parenteral nutrition (C), parenteral nutrition and 20 mL breast milk/kg/d (BM), or parenteral nutrition and 20 mL formula/kg/d (F). On d 7, the measurements were repeated, after discontinuing the oral intake for 5 h. Fourteen infants were included in group C, 12 in group BM, and 12 in group F. There was no difference in energy intake or nitrogen balance at any time. On d 1, plasma enrichment for the nasogastric tracer was lower than for the intravenous tracer for all three groups, both for leucine and for alpha-keto-isocaproic acid. On d 7, the enrichment for leucine and alpha-keto-isocaproic acid for the nasogastric tracer was lower than for the intravenous tracer for the groups BM and F (BM: 3.65 +/- 1.20 nasogastric versus 4.64 +/- 0.64 i.v.; F: 4.37 +/- 1.14 nasogastric versus 5.21 +/- 0.9 i.v.). In the control group, there was no difference between tracers. The lower plasma enrichment for the nasogastric tracer compared with the intravenous tracer suggests uptake of leucine by the splanchnic tissues. We conclude that minimal enteral feeding--even in low volumes of 20 mL/kg/d--increases the leucine uptake by the splanchnic tissue. We speculate that this reflects a higher protein synthesis of splanchnic tissues in the groups receiving enteral nutrition.", "To gather information regarding the efficacy of early minimal enteral nutrition on overall feeding tolerance in extremely low birth weight infants.\n Prospective randomized controlled trial comparing the early use of minimal enteral nutrition in extremely low birth weight infants from day 2 to day 7 vs control infants. On day 8, feeding volume in both groups were advanced by 10 ml kg(-1) day(-1) until full enteral feedings were reached. Time to full feeds, number of intolerance episodes, anthropometric measurements, peak total bilirubin levels, incidence of necrotizing enterocolitis and incidence of sepsis were compared between the two groups with t-test and chi (2) test.\n Eighty-four infants were enrolled in the study but only 61 infants completed the feeding protocol. No statistically significant differences were found between the groups with regards to growth patterns, feeding tolerance, mortality, length of hospital stay and incidence of sepsis and necrotizing enterocolitis.\n Early minimal enteral nutrition use in extremely low birth weight infants did not improve feeding tolerance.", "In a prospective randomized trial, we studied the effects of early hypocaloric enteral feedings (PO) begun at 48 hours of age in 19 infants compared with 20 infants who received no enteral feedings (NPO) for at least the first 9 days of life. Both groups initially received the majority of their calories by parenteral alimentation. The groups were similar with respect to birth weight, gestational age, sex, Apgar score, and major neonatal diagnoses. The early enteral feeds proved to be significantly beneficial without an increased incidence of complications. The PO group reached full enteral feedings faster than the NPO group (31.2 vs 47.3 days). The PO group had a greater decline in serum bilirubin concentration over the first 2 weeks of life and spent less time under phototherapy (6.8 vs 9.5 days). Less cholestasis was observed among the PO infants (6.7% vs 33%), and peak direct bilirubin levels were also lower (0.7 vs 2.5 mg/dL). Osteopenia of prematurity, manifested by significantly lower alkaline phosphatase activity, was also decreased in the PO group, perhaps because of greater calcium intake during the first month among PO infants (1.3 vs 0.8 g). Compared with complete bowel rest, early onset of hypocaloric enteral feedings has beneficial effects on indirect hyperbilirubinemia, cholestatic jaundice, and metabolic bone disease of very low birth weight infants.", "To determine the effect of trophic feeding on clinical outcome in ill preterm infants.\n A randomised, controlled, prospective study of 100 preterm infants, weighing less than 1750 g at birth and requiring ventilatory support and parenteral nutrition, was performed. Group TF (48 infants) received trophic feeding from day 3 (0.5-1 ml/h) along with parenteral nutrition until ventilatory support finished. Group C (52 infants) received parenteral nutrition alone. \"Nutritive\" milk feeding was then introduced to both groups. Clinical outcomes measured included total energy intake and growth over the first six postnatal weeks, sepsis incidence, liver function, milk tolerance, duration of respiratory support, duration of hospital stay and complication incidence.\n Groups were well matched for birthweight, gestation and CRIB scores. Infants in group TF had significantly greater energy intake, mean difference 41.4 (95% confidence interval 9, 73.7) kcal/kg p=0.02; weight gain, 130 (CI 1, 250) g p = 0.02; head circumference gain, mean difference 0.7 (CI 0.1, 1.3) cm, p = 0.04; fewer episodes of culture confirmed sepsis, mean difference -0.7 (-1.3, -0.2) episodes, p = 0.04; less parenteral nutrition, mean difference -11.5 (CI -20, -3) days, p = 0. 03; tolerated full milk feeds (165 ml/kg/day) earlier, mean difference -11.2 (CI -19, -3) days, p = 0.03; reduced requirement for supplemental oxygen, mean difference -22.4 (CI-41.5, -3.3) days, p = 0.02; and were discharged home earlier, mean difference -22.1 (CI -42.1, -2.2) days, p = 0.04. There was no significant difference in the relative risk of any complication.\n Trophic feeding improves clinical outcome in ill preterm infants requiring parenteral nutrition.", "To study the effect of minimal enteral feeding (MEF) on intestinal permeability and feeding tolerance in preterm infants with intrauterine growth retardation (gestational age < 37 weeks, birth weight for gestational age p < 10). Furthermore, to determine whether fetal blood flow pulsatility or intestinal permeability predict feeding tolerance in these infants.\n Randomised controlled trial.\n Within 48 hours of birth, infants were randomised to MEF or no enteral feeding (NEF) for five days in addition to parenteral feeding. Intestinal permeability was measured by the sugar absorption test before (SAT1) and after (SAT2) the study. The sugar absorption test measured the urinary lactulose/mannitol (LM) ratio after oral ingestion of a solution (375 mosm) containing mannitol and lactulose. Charts of all infants were assessed for measures of feeding tolerance. Fetal blood flow pulsatility index (U/C ratio) was measured within the seven days before birth.\n Of the 56 infants enrolled, 42 completed the study: 20 received MEF and 22 NEF. The decrease in LM ratio (LM ratio 1 - LM ratio 2) was not significantly different between the two groups (0.25 v 0.11; p = 0.14). Feeding tolerance, growth, and incidence of necrotising enterocolitis were not significantly different between the two groups. Neither the U/C nor the LM ratio 1 predicted feeding tolerance.\n The results suggest that MEF of preterm infants with intrauterine growth retardation has no effect on the decrease in intestinal permeability after birth. Neither fetal blood flow pulsatility nor intestinal permeability predicts feeding tolerance.", "Priming of the gastrointestinal (GI) tract with low-volume feedings before giving full enteral feedings to very premature, high-risk infants is a controversial practice. We designed a study of infants weighing less than 1,250 g and receiving total parenteral nutrition to determine whether GI priming would hasten weight gain, improve tolerance of subsequent feedings, enhance nutritional status, and increase serum concentration of gastrin, a hormone trophic for intestinal growth. Infants were randomly assigned to receive total parenteral nutrition (TPN) alone (N = 21) or GI priming plus TPN (N = 19) for 12 days beginning on day 3 of life. Full-strength premature infant formula was used for priming. Both groups received the same total nutrition. Beginning on day 15, feedings in both groups were increased daily to a maximum of 120 kcal/kg/day on day 20, where they were maintained until day 30. After day 30, the feedings were modified according to the infants' condition. The groups did not differ in birth weight, gestational age, or 5-min Apgar scores. GI-primed infants had improved feeding tolerance after day 20 and a faster rise in serum gastrin during the initial phase of the study. There was no significant difference in weight gain. GI priming improves tolerance of feedings, accelerates rate of rise of serum gastrin during the first weeks of life, and does not increase the risk of feeding complications when compared to TPN alone. This may lead to more rapid maturation of the GI tract in primed infants." ]

[ "2125153", "3532585", "2516669", "7283256", "2648911" ]

[ "Five year results of a 3-month and two 5-month regimens for the treatment of sputum-positive pulmonary tuberculosis in south India.", "[Daily ultrashort chemotherapy and intermittent short-term chemotherapy with 4 drugs of communicable pulmonary tuberculosis treated for the first time. Results of a cooperative multicenter study].", "Treatment of pulmonary tuberculosis with short course chemotherapy in south India--5-year follow up.", "Shortest possible acceptable, effective ambulatory chemotherapy in pulmonary tuberculosis: preliminary report I.", "A controlled trial of 3-month, 4-month, and 6-month regimens of chemotherapy for sputum-smear-negative pulmonary tuberculosis. Results at 5 years. Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council." ]

[ "A controlled study of three short-course regimens was undertaken in South Indian patients with newly diagnosed, sputum-positive pulmonary tuberculosis. The patients were allocated at random to one of three regimens: a) Rifampicin, streptomycin, isoniazid and pyrazinamide daily for 3 months (R3); b) the same regimen as above but followed by streptomycin, isoniazid and pyrazinamide twice-weekly for a further period of 2 months (R5); c) the same as R5 but without rifampicin (Z5). A bacteriological relapse requiring treatment occurred by 5 years in 16.8% of 113 R3, 5.2% of 97 R5, and 20.0% of 115 Z5 patients with organisms sensitive to streptomycin and isoniazid initially. The differences in the relapse rates between the R3 and R5 regimens and the R5 and Z5 regimens were statistically significant (p less than 0.01 for both). Considering patients with organisms initially resistant to streptomycin or isoniazid or both, 7 of 52 patients (4 R3, 2 R5, 1 Z5) had a bacteriological relapse requiring retreatment.", "Three short-course regimens, all comprising isoniazide (H), rifampicine (R), streptomycine (S) and pyrazinamide (Z), are compared in a randomized prospective cooperative clinical trial. The drugs are given daily in a 3-month regimen (3-HRSZ), twice a week in a 6-month regimen (6-HRSZ2), and in a further two-phase 6-month regimen the 4 drugs are administered 3 times a week for the first 3 months followed by the administration of HSZ twice a week (without R) for further 3 months (3-HRSZ3/3-HSZ2). The number of patients admitted to study is 80, 144 and 139 respectively. The 3-month regimen has been stopped because of a high rate of relapses. 17 p.c. of the patients admitted have to be excluded from analysis for various reasons, out of these 5.8 p.c. because of adverse reactions. Two thirds of the patients had heavily positive sputum cultures at the start. 300 patients completed therapy. At the end of therapy cultures were negative in 94 p.c., 100 p.c. and 99 p.c. respectively. The rate of bacteriological relapses is 19 p.c. in 3-HRSZ, 9 p.c. in 3-HRSZ3/3-HSZ2 and 3 p.c. in 6-HRSZ2, during a follow-up period of 3-4 years after completing therapy. The acceptability was good in all treatment groups. Adverse reactions like \"flu\" were rarely observed. Increased blood urea was common but in general without clinical symptoms. Elevation of ALAT and ASAT was relatively frequent but mostly transient and without clinical importance. The results served as basis for the new \"Recommendation for Treatment of Tuberculosis\" and are interpreted with regard to practical consequences and possibilities for further rationalisation of treatment.", "A controlled clinical trial of three short-course chemotherapy regimens was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis. The patients were randomly allocated to receive one of three regimens: rifampicin, streptomycin, isoniazid and pyrazinamide daily for 2 months, followed by streptomycin, isoniazid and pyrazinamide twice weekly for 3 months (R/5) or for 5 months (R/7), or the same regimen as R/7 but without rifampicin (Z/7). A bacteriological relapse requiring retreatment occurred by 5 years in 7.1% of 126 R/5, 4.0% of 124 R/7 and 6.7% of 253 Z/7 patients with organisms initially sensitive to streptomycin and isoniazid; none of these differences is statistically significant. Of the 31 relapses, 16 occurred within 2 years of the completion of chemotherapy and the remaining 15 between 2 and 5 years. Among 65 patients with initial drug resistance to streptomycin or isoniazid or both, there were six bacteriological relapses requiring retreatment.", "In two 4.5-month regimens and one 3-month regimen the four most potent antituberculous drugs (isoniazid, rifampin, pyrazinamide, and streptomycin) were given for the initial 3 months of chemotherapy. Acceptance by the patients was high, and bacillary sterilization was achieved in 96% of cases within 2 months. Addition of a fifth drug, ethionamide, during the initial 3 months was neither acceptable nor useful. No relapses were observed during a 12-month follow-up period after completion of the 4.5-month regimens. A relapse rate of 5% followed the 3-month regimen. The toxicity and side effects of antituberculous drugs were observed in 16% of patients during the initial 3-month period. In 3.4% of patients, toxicity necessitated cessation of treatment. In the remaining 13% of patients, adverse side effects could be managed without cessation of treatment. Even when patients were ambulatory and outpatient attendance was required for drug administration, the noncompliance rate was only approximately 10%. With the current over-all cost of drugs being limited to 100 United States dollars, the patients with moderately extensive disease must be treated for 100 days, or a maximum of 100 doses.", "Of 1,710 Chinese patients with radiologically active pulmonary tuberculosis but with sputum negative for acid-fast bacilli on four or more initial microscopic examinations who were studied for 5 yr, 592 (35%) had one or more initial sputum cultures positive for Mycobacterium tuberculosis. These 592 patients were randomly allocated to receive streptomycin, isoniazid, rifampin, and pyrazinamide daily for 4 months or 3 times a week for either 4 or 6 months. The remaining 1,118 patients with all their initial cultures negative were randomly allocated to receive the same four drugs daily for 3 months or 3 times a week for either 3 or 4 months. There were no bacteriologic failures during chemotherapy, and the relapse rates for the 4-month regimens during the 5 yr were 2% in 293 patients with drug-susceptible cultures initially (95% confidence limits, 1 to 5%); 8% in 59 patients with cultures resistant to isoniazid, streptomycin, or both drugs, but susceptible to rifampin initially; and 4% in 325 patients with all their cultures negative initially (95% confidence limits, 1 to 7%). The combined relapse rate for the 3-month regimens was 7% in 709 patients with all their cultures negative initially (95% confidence limits, 5 to 9%). In Hong Kong, 4 months of chemotherapy is now used routinely in the treatment of patients with smear-negative pulmonary tuberculosis, whether their initial sputum cultures are positive or negative." ]

[ "17463075", "19863647", "21286740", "19561035", "9395691", "12868251", "20371148", "17613573", "9050361" ]

[ "The effects of transcutaneous electrical nerve stimulation (TENS) on spasticity in multiple sclerosis.", "Effects of intermittent theta burst stimulation on spasticity in patients with multiple sclerosis.", "Transcranial magnetic stimulation primes the effects of exercise therapy in multiple sclerosis.", "Vibration therapy in multiple sclerosis: a pilot study exploring its effects on tone, muscle force, sensation and functional performance.", "Double-blind study of pulsing magnetic field effects on multiple sclerosis.", "Effects of a pulsed electromagnetic therapy on multiple sclerosis fatigue and quality of life: a double-blind, placebo controlled trial.", "Influence of sports climbing and yoga on spasticity, cognitive function, mood and fatigue in patients with multiple sclerosis.", "Early physiotherapy after injection of botulinum toxin increases the beneficial effects on spasticity in patients with multiple sclerosis.", "Treatment of spasticity with repetitive magnetic stimulation; a double-blind placebo-controlled study." ]

[ "Spasticity is a common and often disabling symptom associated with multiple sclerosis (MS). Transcutaneous electrical nerve stimulation (TENS) has been found effective in reducing spasticity in conditions such as stroke, but there is little evidence to support its use in MS. The aim of this study was to evaluate the effectiveness of TENS on spasticity in MS and, furthermore, to compare two different application times. Thirty-two subjects were randomized into two groups, and a single, blind, crossover design was used to compare two weeks of 60 minutes and 8 hours daily of TENS applications (100 Hz and 0.125 ms pulse width). Outcomes were examined using the Global Spasticity Score (GSS), the Penn Spasm Score (PSS), and a visual analogue scale (VAS) for pain. The results of the study demonstrated that there were no statistically significant differences in the GSS following either 60 minutes or 8 hours daily of TENS (P=0.433 and 0.217, respectively). The 8-hour application time led to a significant reduction in muscle spasm (P=0.038) and pain (P = 0.008). Thus, this study suggests that, whilst TENS does not appear to be effective in reducing spasticity, longer applications may be useful in treating MS patients with pain and muscle spasm.", "Spasticity is a common disorder and a major cause of long-term disability in patients with multiple sclerosis (MS). Our aim was to evaluate whether a recently developed repetitive transcranial magnetic stimulation protocol, the intermittent theta burst stimulation (iTBS) is effective in modulating lower limb spasticity in MS patients.\n Twenty MS patients were pseudorandomized to undergo a 2-week daily sessions of real or sham iTBS protocol. The H/M amplitude ratio of the Soleus H reflex, a reliable neurophysiological index of spinal excitability and the Modified Ashworth Scale (MAS) for spasticity were evaluated by blinded raters before and after the stimulation protocols.\n Patients receiving real iTBS showed a significant reduction of H/M amplitude ratio and MAS scores 1 week after the stimulation and persisting up to 2 weeks after the end of stimulation protocol. There were no significant effects for sham stimulation.\n These results show that iTBS, a safe, non-invasive, well-tolerated and feasible protocol, is a promising tool for the treatment of spasticity in MS.", "Exercise therapy (ET) can be beneficial in disabled multiple sclerosis (MS) patients. Intermittent transcranial magnetic theta burst stimulation (iTBS) induces long-term excitability changes of the cerebral cortex and may ameliorate spasticity in MS. We investigated whether the combination of iTBS and a program of ET can improve motor disability in MS patients. In a double-blind, sham-controlled trial, 30 participants were randomized to three different interventions: iTBS plus ET, sham stimulation plus ET, and iTBS alone. Before and after 2 weeks of treatment, measures of spasticity through the modified Ashworth scale (MAS) and the 88 items Multiple Sclerosis Spasticity Score questionnaire (MSSS-88), fatigue through the Fatigue Severity Scale (FSS), daily living activities (ADL) through the Barthel index and health-related quality of life (HRQoL) through the 54 items Multiple Sclerosis Quality of life inventory (MSQoL-54) were collected. iTBS plus ET reduced MAS, MSSS-88, FSS scores, while in the Barthel index and MSQoL-54, physical composite scores were increased. iTBS alone caused a reduction of the MAS score, while none of the measured scales showed significant changes after sham iTBS plus ET. iTBS associated with ET is a promising tool for motor rehabilitation of MS patients.", "To examine the effectiveness of whole body vibration (WBV) on tone, muscle force, sensation and functional performance in people with multiple sclerosis.\n A randomized cross-over pilot study.\n Revive MS Support Therapy Centre. Glasgow, UK.\n Sixteen people with multiple sclerosis were randomly allocated to one of two groups.\n Group 1 received four weeks of whole body vibration plus exercise three times per week, two weeks of no intervention and then four weeks of exercise alone three times per week. Group 2 were given the two treatment interventions in the reverse order to group 1.\n Ten-metre walk, Timed Up and Go Test, Modified Ashworth Scale, Multiple Sclerosis Spasticity Scale (MSSS-88), lower limb muscle force, Nottingham Sensory Assessment and Multiple Sclerosis Impact Scale (MSIS-29) were used before and after intervention.\n The exercise programme had positive effects on muscle force and well-being, but there was insufficient evidence that the addition of whole body vibration provided any further benefit. The Modified Ashworth Scale was generally unaffected by either intervention, although, for each group, results from the MSSS-88 showed whole body vibration and exercises reduced muscle spasms (P = 0.02). Although results for the 10-m walk and Timed Up and Go Test improved, this did not reach statistical significance (P = 0.56; P = 0.70, respectively). For most subjects sensation was unaffected by whole body vibration.\n Exercise may be beneficial to those with multiple sclerosis, but there is limited evidence that the addition of whole body vibration provides any additional improvements. Further larger scale studies into the effects of whole body vibration in people with multiple sclerosis are essential.", "We performed a double-blind study to measure the clinical and subclinical effects of an alternative medicine magnetic device on disease activity in multiple sclerosis (MS). The MS patients were exposed to a magnetic pulsing device (Enermed) where the frequency of the magnetic pulse was in the 4-13 Hz range (50-100 milliGauss). A total of 30 MS patients wore the device on preselected sites between 10 and 24 hours a day for 2 months. Half of the patients (15) randomly received an Enermed device that was magnetically inactive and the other half received an active device. Each MS patient received a set of tests to evaluate MS disease status before and after wearing the Enermed device. The tests included (1) a clinical rating (Kurtzke, EDSS), (2) patient-reported performance scales, and (3) quantitative electroencephalography (QEEG) during a language task. Although there was no significant change between pretreatment and posttreatment in the EDSS scale, there was a significant improvement in the performance scale (PS) combined rating for bladder control, cognitive function, fatigue level, mobility, spasticity, and vision (active group -3.83 +/- 1.08, p < 0.005; placebo group -0.17 +/- 1.07, change in PS scale). There was also a significant change between pretreatment and posttreatment in alpha EEG magnitude during the language task recorded at various electrode sites on the left side. In this double-blind, placebo-controlled study, we have demonstrated a statistically significant effect of the Enermed magnetic pulsing device on patient performance scales and on alpha EEG magnitude during a language task.", "There is a growing literature on the biological and clinical effects of pulsed electromagnetic fields. Some studies suggest that electromagnetic therapies may be useful in the treatment of chronic illnesses. This study is a follow-up to a placebo controlled pilot study in which multiple sclerosis (MS) patients exposed to weak, extremely low frequency pulsed electromagnetic fields showed significant improvements on a composite symptom measure.\n To evaluate the effects of a pulsed electromagnetic therapy on MS related fatigue, spasticity, bladder control, and overall quality of life.\n A multi-site, double-blind, placebo controlled, crossover trial. Each subject received 4 weeks of the active and placebo treatments separated by a 2-week washout period.\n The University of Washington Medical Center in Seattle Wash, the Neurology Center of Fairfax in Fairfax, Va, and the headquarters of the Multiple Sclerosis Association of America in Cherry Hill, NJ.\n 117 patients with clinically definite MS.\n Daily exposure to a small, portable pulsing electromagnetic field generator.\n The MS Quality of Life Inventory (MSQLI) was used to assess changes in fatigue, bladder control, spasticity, and a quality of life composite.\n Paired t-tests were used to assess treatment differences in the 117 subjects (81% of the initial sample) who completed both treatment sessions. Improvements in fatigue and overall quality of life were significantly greater on the active device. There were no treatment effects for bladder control and a disability composite, and mixed results for spasticity.\n Evidence from this randomized, double-bind, placebo controlled trial is consistent with results from smaller studies suggesting that exposure to pulsing, weak electromagnetic fields can alleviate symptoms of MS. The clinical effects were small, however, and need to be replicated. Additional research is also needed to examine the possibility that ambulatory patients and patients taking interferons for their MS may be most responsive to this kind of treatment.", "Spasticity, cognitive impairment, depression and fatigue significantly reduce the quality of life in multiple sclerosis (MS) patients. To find out whether nonpharmalogical treatment approaches can reduce these symptoms we investigated effects of sports climbing (SC) and yoga on spasticity, cognitive impairment, mood change and fatigue in MS patients. Sports climbing (SC) and yoga are aerobic physical activities comprised a series of stretching techniques, implementation of which demands body control and planning of complex movements.\n 20 subjects with relapsing-remitting or progressive MS, 26-50 years of age, with EDSS<or=6 and EDSS pyramidal functions score (EDSSpyr)>2 were enrolled in a randomized prospective study. The participants were randomly divided into SC and yoga group. We evaluated spasticity, cognitive function, mood and fatigue before and after both programs, that lasted 10 weeks, with standardized assessment methods.\n There were no significant improvements in spasticity after SC and yoga. In the SC group we found a 25% reduction (p=0.046) in EDSSpyr. There were no differences in executive function after the completion of both programs. There was a 17% increase in selective attention performance after yoga (p=0.005). SC reduced fatigue for 32.5% (p=0.015), while yoga had no effect. We found no significant impact of SC and yoga on mood.\n Yoga and SC might improve some of the MS symptoms and should be considered in the future as possible complementary treatments.", "To determine whether additional physiotherapy increases botulinum toxin type A effects in reducing spasticity in patients with multiple sclerosis.\n A single-blind, randomized, controlled pilot trial with a 12-week study period.\n Thirty-eight patients with progressive multiple sclerosis affected by focal spasticity and who were observed at the Multiple Sclerosis Centre operating in the S. Andrea Hospital in Rome.\n For intervention all patients received botulinum toxin type A; the treatment group also received additional physiotherapy to optimize management through passive or active exercise and stretching regimens.\n To measure objective and subjective level of spasticity, patients were assessed at baseline, 2, 4 and 12 weeks post treatment by Modified Ashworth Scale and visual analogue scale.\n When compared with the control group, we found a significant decrease of spasticity by Modified Ashworth Scale (P < 0.01 by t-test) in the treatment group at week 2 (2.73 versus 3.22), week 4 (2.64 versus 3.33) and week 12 (2.68 versus 3.33). The mean (%) difference in Modified Ashworth Scale score between baseline and the end of follow-up was -0.95 (26.1) in the treatment group and -0.28 (7.7) in the control group (P < 0.01). The combined treatment proved also to be more effective by visual analogue scale (P < 0.01) at week 4 (6.95 versus 5.50) and at week 12 (7.86 versus 6.56) but not at week 2 (5.18 versus 5.50; P = 0.41).\n Our data suggest that physiotherapy in combination with botulinum toxin type A injection can improve overall response to botulinum toxin.", "The effect of repetitive magnetic stimulation on spasticity was evaluated in 38 patients with multiple sclerosis in a double-blind placebo-controlled study. One group was treated with repetitive magnetic stimulation (n = 21) and the other group with sham stimulation (n = 17). Both groups were treated twice daily for 7 consecutive days. Primary end-points of the study were changes in the patients self-score, in clinical spasticity score, and in the stretch reflex threshold. The self-score of ease of daily day activities improved by 22% (P = 0.007) after treatment and by 29% (P = 0.004) after sham stimulation. The clinical spasticity score improved -3.3 +/- 4.7 arbitrary unit (AU) in treated patients and 0.7 +/- 2.5 AU in sham stimulation (P = 0.003). The stretch reflex threshold increased 4.3 +/- 7.5 deg/s in treated patients and -3.8 +/- 9.7 deg/s in sham stimulation (P = 0.001). The data presented in this study supports the idea that repetitive magnetic stimulation has an antispastic effect in multiple sclerosis. Future studies should clarify the optimal treatment regimen." ]

[ "8315230", "12550149", "1807303", "2203214", "9863850", "17944890", "10024253", "12867764", "18719756" ]

[ "A comparison of effectiveness of biofeedback and pelvic muscle exercise treatment of stress incontinence in older community-dwelling women.", "A comparison of effectiveness of bladder training and pelvic muscle exercise on female urinary incontinence.", "Controlled trial of pelvic floor exercises in the treatment of urinary stress incontinence in general practice.", "[The value of physical therapy in genuine female stress incontinence].", "Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial.", "Effectiveness of multidimensional exercises for the treatment of stress urinary incontinence in elderly community-dwelling Japanese women: a randomized, controlled, crossover trial.", "Single blind, randomised controlled trial of pelvic floor exercises, electrical stimulation, vaginal cones, and no treatment in management of genuine stress incontinence in women.", "Biofeedback and pelvic floor exercises for the rehabilitation of urinary stress incontinence.", "Single-blind, randomized, controlled trial of pelvic floor muscle training, electrical stimulation, vaginal cones, and no active treatment in the management of stress urinary incontinence." ]

[ "Research using biofeedback as a treatment for sphincteric incontinence began with Kegel's early studies using a perineometer and pelvic muscle exercises demonstrating a 90% improvement in urine loss symptoms. More recent studies using varying combinations of biofeedback and pelvic muscle exercises found symptom reduction rates of 78% to 90%, but these studies lacked the rigor of a \"phase three,\" or randomized controlled clinical trial.\n A randomized controlled trial assessed the efficacy of biofeedback for older women for treatment of sphincteric incompetence. One hundred thirty-five community-dwelling women were randomized in a single-blind trial to three groups: biofeedback, pelvic muscle exercise, or control. Incontinent episodes were monitored over 8 weeks of treatment and at 3 and 6 months thereafter.\n The number of incontinent episodes decreased significantly in the biofeedback and pelvic muscle exercise subjects but not in the control subjects for all severity of incontinence frequency subgroups. Improvement was maintained within the moderate and severe symptom subgroups for both treatments for at least 6 months but declined in subjects with mild incontinence frequency. Pelvic muscle activity (EMG) was significantly correlated with decreases in incontinent episodes, and only the biofeedback subjects showed significant improvement in EMGs.\n Biofeedback and pelvic muscle exercises are efficacious for sphincteric incompetence in older women. Benefits are maintained and improvement continues for at least 6 months postintervention. These therapies may be useful before considering invasive treatment.", "This study compared the effectiveness of bladder training versus pelvic muscle exercises in the treatment of urinary incontinence in women. It was revealed that the two intervention groups showed improvement compared with the control group, but differed in their effects on outcome measures. The pelvic muscle exercise group was more effective in increasing the peak and the average pressures of pelvic muscle contraction. The bladder-training group was more effective in reducing urinary frequency and in increasing voided volume. Further research is needed to explore the relationship among the various outcome measures of urinary incontinence.\n Copyright 2002 Elsevier Science Ltd.", "The aim of this study was to assess the usefulness of pelvic floor exercises in the treatment of urinary incontinence in women and to analyse the factors which determine a successful outcome. The study involved 66 women who had reported 'genuine stress incontinence' to their general practitioner. They were assigned at random to the treatment or control group. The treatment group received instructions in pelvic floor exercises from a general practitioner. The control group received no therapy. At the start of the trial the severity of the patients' incontinence was assessed objectively. This assessment was repeated after three months and patients were also asked for their own perception of whether their incontinence had improved. After the three months' evaluation the patients in the control group were also given instructions in pelvic floor exercises. After another three months they were assessed in the same way. About 60% of the patients in the treatment group were dry or mildly incontinent after three months compared with only one patient in the control group; the mean weekly frequency of incontinence episodes fell from 17 to five in the treatment group but remained virtually unchanged in the control group; and about 85% of the women in the treatment group felt that their incontinence had improved or was cured compared with no one in the control group. These results were later corroborated by those for the control group. The most important factor in the success of the treatment was the patients' motivation, as demonstrated by their adherence to the daily exercises.(ABSTRACT TRUNCATED AT 250 WORDS)", "In a prospective randomized study the efficiacy of physical therapy in female stress incontinence could be verified. The greatest success rate was achieved by medical gymnastics, whereas the perineal electrical stimulation should be used as supporting measure like a biofeedback mechanism because of its low effective intensity. Despite of the good therapeutic success (51.5%) with lasting effects no objective criteria to the use of physical therapy in female stress incontinence were found.", "Urinary incontinence is a common condition caused by many factors with several treatment options.\n To compare the effectiveness of biofeedback-assisted behavioral treatment with drug treatment and a placebo control condition for the treatment of urge and mixed urinary incontinence in older community-dwelling women.\n Randomized placebo-controlled trial conducted from 1989 to 1995.\n University-based outpatient geriatric medicine clinic.\n A volunteer sample of 197 women aged 55 to 92 years with urge urinary incontinence or mixed incontinence with urge as the predominant pattern. Subjects had to have urodynamic evidence of bladder dysfunction, be ambulatory, and not have dementia.\n Subjects were randomized to 4 sessions (8 weeks) of biofeedback-assisted behavioral treatment, drug treatment (with oxybutynin chloride, possible range of doses, 2.5 mg daily to 5.0 mg 3 times daily), or a placebo control condition.\n Reduction in the frequency of incontinent episodes as determined by bladder diaries, and patients' perceptions of improvement and their comfort and satisfaction with treatment.\n For all 3 treatment groups, reduction of incontinence was most pronounced early in treatment and progressed more gradually thereafter. Behavioral treatment, which yielded a mean 80.7% reduction of incontinence episodes, was significantly more effective than drug treatment (mean 68.5% reduction; P=.04) and both were more effective than the placebo control condition (mean 39.4% reduction; P<.001 and P=.009, respectively). Patient-perceived improvement was greatest for behavioral treatment (74.1% \"much better\" vs 50.9% and 26.9% for drug treatment and placebo, respectively). Only 14.0% of patients receiving behavioral treatment wanted to change to another treatment vs 75.5% in each of the other groups.\n Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence.", "To evaluate the effectiveness of pelvic floor muscle (PFM) and fitness exercises in reducing urine leakage in elderly women with stress urinary incontinence (UI).\n Randomized, crossover, follow-up trial.\n Urban community in Japan.\n Seventy women aged 70 and older who reported urine leakage one or more times per month; 35 were randomly assigned to intervention and the other 35 to control.\n The intervention group attended an exercise class aimed at enhancing PFMs and fitness. Duration of the exercise was 60 minutes per session twice a week for 3 months. After 3 months of exercise, the intervention group was followed for 1 year.\n Body mass index (BMI), urine leakage, walking speed, and muscle strength were measured at baseline, after the intervention, and at follow-up.\n In the intervention group, maximum walking speed and adductor muscle strength increased significantly after the intervention; there were no significant changes in the control group. After 3 months of exercise, 54.5% of the intervention group and 9.4% of the control group reported being continent. Within the cured group of UI, a significantly higher proportion had decreased their BMI at 3 months (P=.03) and increased walking speed at 3 (P=.04) and 12 (P=.047) months.\n Decrease in BMI and increase in walking speed may contribute to the treatment of UI, although the data do not support a positive correlation between strengthening of adductor muscle and improvement of UI, which needs more research.", "To compare the effect of pelvic floor exercises, electrical stimulation, vaginal cones, and no treatment for genuine stress incontinence.\n Stratified, single blind, randomised controlled trial.\n Multicentre.\n 107 women with clinically and urodynamically proved genuine stress incontinence. Mean (range) age was 49.5 (24-70) years, and mean (range) duration of symptoms 10.8 (1-45) years.\n Pelvic floor exercise (n=25) comprised 8-12 contractions 3 times a day and exercise in groups with skilled physical therapists once a week. The electrical stimulation group (n=25) used vaginal intermittent stimulation with the MS 106 Twin at 50 Hz 30 minutes a day. The vaginal cones group (n=27) used cones for 20 minutes a day. The untreated control group (n=30) was offered the use of a continence guard. Muscle strength was measured by vaginal squeeze pressure once a month.\n Pad test with standardised bladder volume, and self report of severity.\n Improvement in muscle strength was significantly greater (P=0.03) after pelvic floor exercises (11.0 cm H2O (95% confidence interval 7.7 to 14.3) before v 19.2 cm H2O (15.3 to 23.1) after) than either electrical stimulation (14.8 cm H2O (10. 9 to 18.7) v 18.6 cm H2O (13.3 to 23.9)) or vaginal cones (11.8 cm H2O (8.5 to 15.1) v 15.4 cm H2O (11.1 to 19.7)). Reduction in leakage on pad test was greater in the exercise group (-30.2 g; -43. 3 to 16.9) than in the electrical stimulation group (-7.4 g; -20.9 to 6.1) and the vaginal cones group (-14.7 g; -27.6 to -1.8). On completion of the trial one participant in the control group, 14 in the pelvic floor exercise group, three in the electrical stimulation group, and two in the vaginal cones group no longer considered themselves as having a problem. Conclusion: Training of the pelvic floor muscles is superior to electrical stimulation and vaginal cones in the treatment of genuine stress incontinence.", "We investigated the effectiveness of pelvic floor muscle (PFM) exercises or biofeedback for the treatment of urinary stress incontinence (USI). Fifty patients with USI were included in this randomized, controlled, prospective study. Twenty patients were taught PFM exercises via digital palpation and instructed to perform regularly as home program. The second group of 20 patients had PFM exercises via biofeedback three times a week for 2 months. The third group of 10 patients did not have any exercises. The patients were evaluated via pad test, perineometry, digital palpation based PFM strength, incontinence frequency, and visual analog scale based social activity index prior to and 8 weeks after the treatment. The first two groups had significant improvement in USI with respect to the control group (p < 0.001). The rise in PFM strength with perineometry of the biofeedback group was higher than in the digital palpation group after treatment (p < 0.001). PFM exercises are effective for the treatment of USI; the biofeedback method revealed better PFM strength results with respect to digital palpation.\n Copyright 2003 S. Karger AG, Basel", "To compare the effectiveness of pelvic floor exercises, electrical stimulation, vaginal cones, and no active treatment in women with urodynamic stress urinary incontinence.\n One hundred eighteen subjects were randomly selected to receive pelvic floor exercises (n=31), ES (n=30), vaginal cones (n=27), or no treatment (untreated control) (n=30). Women were evaluated before and after completion of six months of treatment by the pad test, quality of life questionnaire (I-QOL), urodynamic test, voiding diary, and subjective response.\n In the objective evaluation, we observed a statistically significant reduction in the pad test (p=0.003), in the number of stress urinary episodes (p<0.001), and a significant improvement in the quality of life (p<0.001) in subjects who used pelvic floor exercises, electrical stimulation, and vaginal cones compared to the control group. No significant difference was found between groups in the urodynamic parameters. In the subjective evaluation, 58%, 55%, and 54% of women who had used pelvic floor exercises, electrical stimulation, and vaginal cones, respectively, reported being satisfied after treatment. In the control group, only 21% patients were satisfied with the treatment.\n Based on this study, pelvic floor exercises, electrical stimulation, and vaginal cones are equally effective treatments and are far superior to no treatment in women with urodynamic stress urinary incontinence." ]

[ "17661855", "15222602", "14585550", "8502438", "15154151", "3633503", "9687125", "9789512", "17351024", "12484105", "12564350", "14713325", "11572538", "9766290" ]

[ "Does therapeutic touch ease the discomfort or distress of patients undergoing stereotactic core breast biopsy? A randomized clinical trial.", "Touch the pain away: new research on therapeutic touch and persons with fibromyalgia syndrome.", "A phase II trial of Reiki for the management of pain in advanced cancer patients.", "Therapeutic touch and postoperative pain: a Rogerian research study.", "Healing touch and quality of life in women receiving radiation treatment for cancer: a randomized controlled trial.", "Effects of therapeutic touch on tension headache pain.", "The effect of therapeutic touch on pain and anxiety in burn patients.", "The effects of therapeutic touch on patients with osteoarthritis of the knee.", "Pilot crossover trial of Reiki versus rest for treating cancer-related fatigue.", "Effects of integrating therapeutic touch into a cognitive behavioral pain treatment program. Report of a pilot clinical trial.", "Outcomes of touch therapies during bone marrow transplant.", "Therapeutic massage and healing touch improve symptoms in cancer.", "Therapeutic touch in the treatment of carpal tunnel syndrome.", "Effects of dialogue and therapeutic touch on preoperative and postoperative experiences of breast cancer surgery: an exploratory study." ]

[ "To determine whether therapeutic touch administered at the time of stereotactic core biopsy of suspicious breast lesions results in a reduction in anxiety and pain.\n Randomized, patient-blinded, controlled trial of either Krieger-Kunz therapeutic touch administered by a trained practitioner or a sham intervention mimicking therapeutic touch delivered during core biopsy.\n Stereotactic breast biopsy unit of a comprehensive breast center.\n Women with mammographically detected, nonpalpable breast lesions requiring biopsy.\n Changes in pain and anxiety measured by visual analog scales immediately before and after stereotactic core biopsy.\n A total of 82 patients were accrued: 42 received actual therapeutic touch and 40 sham therapeutic touch. No significant differences were found between the arms for age, ethnicity, educational background, or other demographic data. The sham arm had a preponderance of left breast biopsies (48% vs 58%; P = 0.07) and received a slightly higher volume of epinephrine-containing local anesthetic (6.5 +/- 6.1 vs 4.5 +/- 4.5 mL; P = 0.09). Therapeutic touch patients were more likely to have an upper breast lesion location (57% vs 53%; P = 0.022). No significant differences between the arms were seen regarding postbiopsy pain (P = 0.95), anxiety (P = 0.66), fearfulness, or physiological parameters. Similarly, no differences were seen between the arms when change in parameters from prebiopsy to postbiopsy was considered for any of the psychological or physiological variables measured. These findings persisted when confounding variables were controlled for.\n Women undergoing stereotactic core breast biopsy received no significant benefit from therapeutic touch administered during the procedure. Therapeutic touch cannot be routinely recommended for patients in this setting.", "This pilot study tested the effectiveness of 6 therapeutic touch treatments on the experience of pain and quality of life for persons with fibromyalgia syndrome. Its findings support that subjects who received therapeutic touch had a statistically significant decrease in pain for each pretherapeutic to posttherapeutic touch treatment, as well as significant improvement in quality of life from pre-first to pre-sixth treatment. Therapeutic touch may be an effective treatment for relieving pain and improving quality of life in this specific population of persons with fibromyalgia syndrome.", "This trial compared pain, quality of life, and analgesic use in a sample of patients with cancer pain (n=24) who received either standard opioid management plus rest (Arm A) or standard opioid management plus Reiki (Arm B). Participants either rested for 1.5 hr on Days 1 and 4 or received two Reiki treatments (Days 1 and 4) one hour after their first afternoon analgesic dose. Visual analogue scale (VAS) pain ratings, blood pressure, heart rate, and respirations were obtained before and after each treatment/rest period. Analgesic use and VAS pain scores were reported for 7 days. Quality of life was assessed on Days 1 and 7. Participants in Arm B experienced improved pain control on Days 1 and 4 following treatment, compared to Arm A, and improved quality of life, but no overall reduction in opioid use. Future research will determine the extent to which the benefits attributed to Reiki in this study may have been due to touch.", "This article details Meehan's research study concerning the conceptualization of therapeutic touch within Rogers' science of unitary human beings and an investigation of the effects of therapeutic touch on pain experience in postoperative patients. Using a single trial, single-blind, three-group design, 108 postoperative patients were randomly assigned to receive one of the following: therapeutic touch, a placebo control intervention which mimicked therapeutic touch, or the standard intervention of a narcotic analgesic. Using a visual analogue scale, pain was measured before and one hour following intervention. The hypothesis, that therapeutic touch would significantly decrease postoperative pain compared to the placebo control intervention, was not supported. Secondary analyses suggest that therapeutic touch may decrease patients' need for analgesic medication. Implications for further research and practice are suggested.", "nan", "Therapeutic touch (TT) is a modern derivative of the laying on of hands that involves touching with the intent to help or heal. This study investigated the effects of TT on tension headache pain in comparison with a placebo simulation of TT. Sixty volunteer subjects with tension headaches were randomly divided into treatment and placebo groups. The McGill-Melzack Pain Questionnaire was used to measure headache pain levels before each intervention, immediately afterward, and 4 hours later. A Wilcoxon signed rank test for differences indicated that 90% of the subjects exposed to TT experienced a sustained reduction in headache pain, p less than .0001. An average 70% pain reduction was sustained over the 4 hours following TT, which was twice the average pain reduction following the placebo touch. Using a Wilcoxon rank sum test, this was statistically significant, p less than .01. Study results indicated that TT may have potential beyond a placebo effect in the treatment of tension headache pain.", "The purpose of this single-blinded randomized clinical trial was to determine whether therapeutic touch (TT) versus sham TT could produce greater pain relief as an adjunct to narcotic analgesia, a greater reduction in anxiety, and alterations in plasma T-lymphocyte concentrations among burn patients. Therapeutic touch is an intervention in which human energies are therapeutically manipulated, a practice conceptually supported by Rogers' (1970) theory of unitary human beings. Data were collected at a university burn centre in the south-eastern United States. The subjects were 99 men and women between the ages of 15 and 68 hospitalized for severe burns, and they received either TT or sham TT once a day for 5 days. Baseline data were collected on day 1, data were collected before and after treatment on day 3, and post-intervention data were collected on day 6. Instruments included the McGill Pain Questionnaire, Visual Analogue Scales for Pain, Anxiety and Satisfaction with Therapy, and an Effectiveness of Therapy Form. Blood was drawn on days 1 and 6 for lymphocyte subset analysis. Medication usage for pain in mean morphine equivalents, and mean doses per day of sleep, anxiety and antidepressant medications were recorded. Subjects who received TT reported significantly greater reduction in pain on the McGill Pain Questionnaire Pain Rating Index and Number of Words Chosen and greater reduction in anxiety on the Visual Analogue Scale for Anxiety than did those who received sham TT. Lymphocyte subset analyses on blood from 11 subjects showed a decreasing total CD8 + lymphocyte concentration for the TT group. There was no statistically significant difference between groups on medication usage.", "The purpose of this study was to determine if therapeutic touch, an alternative medicine modality, is effective in the treatment of osteoarthritis of the knee.\n A single-blinded randomized control trial was conducted in a family practice center of a community hospital family practice residency program in Pennsylvania. The patients were between the ages of 40 and 80, had been given a diagnosis of osteoarthritis of at least one knee, had not had knee replacement, and had no other connective tissue disease. The patients were randomized to therapeutic touch, mock therapeutic touch, or standard care. The main outcome measures were pain and its impact, general well-being, and health status measured by standardized, validated instruments, as well as the qualitative measurement of a Depth interview.\n Twenty-five patients completed the study. The treatment group had significantly decreased pain and improved function as compared with the placebo and control groups. The qualitative Depth interview confirmed this result.\n Despite the small numbers, significant differences were found in improvement in function and pain for patients receiving therapeutic touch. A larger study is needed to confirm these results. Alternative therapies can neither be accepted nor rejected without being subjected to the scientific method.", "Fatigue is an extremely common side effect experienced during cancer treatment and recovery. Limited research has investigated strategies stemming from complementary and alternative medicine to reduce cancer-related fatigue. This research examined the effects of Reiki, a type of energy touch therapy, on fatigue, pain, anxiety, and overall quality of life. This study was a counterbalanced crossover trial of 2 conditions: (1) in the Reiki condition, participants received Reiki for 5 consecutive daily sessions, followed by a 1-week washout monitoring period of no treatments, then 2 additional Reiki sessions, and finally 2 weeks of no treatments, and (2) in the rest condition, participants rested for approximately 1 hour each day for 5 consecutive days, followed by a 1-week washout monitoring period of no scheduled resting and an additional week of no treatments. In both conditions, participants completed questionnaires investigating cancer-related fatigue (Functional Assessment of Cancer Therapy Fatigue subscale [FACT-F]) and overall quality of life (Functional Assessment of Cancer Therapy, General Version [FACT-G]) before and after all Reiki or resting sessions. They also completed a visual analog scale (Edmonton Symptom Assessment System [ESAS]) assessing daily tiredness, pain, and anxiety before and after each session of Reiki or rest. Sixteen patients (13 women) participated in the trial: 8 were randomized to each order of conditions (Reiki then rest; rest then Reiki). They were screened for fatigue on the ESAS tiredness item, and those scoring greater than 3 on the 0 to 10 scale were eligible for the study. They were diagnosed with a variety of cancers, most commonly colorectal (62.5%) cancer, and had a median age of 59 years. Fatigue on the FACT-F decreased within the Reiki condition (P=.05) over the course of all 7 treatments. In addition, participants in the Reiki condition experienced significant improvements in quality of life (FACT-G) compared to those in the resting condition (P <.05). On daily assessments (ESAS) in the Reiki condition, presession 1 versus postsession 5 scores indicated significant decreases in tiredness (P <.001), pain (P <.005), and anxiety (P<.01), which were not seen in the resting condition. Future research should further investigate the impact of Reiki using more highly controlled designs that include a sham Reiki condition and larger sample sizes.", "The purpose of this study was to investigate the effects of offering Therapeutic Touch (TT) as an adjunct to cognitive behavioral therapy (CBT) for people with chronic pain. Patients were randomized to relaxation training (control group) or TT plus relaxation (experimental). Subsequently, all participants attended a CBT program. Preprogram and postprogram data were examined to identify patterns of change in pain intensity, self-efficacy, unitary power, disability, and perceived distress. In addition, patterns of attrition were examined. Patients in this study who were randomized to receive TT fared better in terms of enhanced self-efficacy and unitary power, as well as having lower attrition rates. Trends associated TT with less distress and disability. This pilot study suggests that offering TT as an adjunct to CBT may help to improve clinical outcomes, reduce program attrition, and promote unitary power in those who suffer with chronic pain.", "The integration of complementary modalities into mainstream healthcare is gaining increasing emphasis. It is important, therefore, to document the effects of these interventions on patient outcomes.\n To investigate the effects of Therapeutic Touch and massage therapy on the outcomes of engraftment time, complications, and perceived benefits of therapy during bone marrow transplant.\n Randomized clinical trial.\n Subjects were adult patients on the bone marrow transplant unit of a large urban tertiary care center.\n Subjects were randomly assigned to 1 of 3 treatment groups: Therapeutic Touch (TT), massage therapy (MT), and a control group called the friendly visit (FV). Subjects (N = 88) were stratified by type of transplant (allogeneic or autologous). Twenty-seven subjects received MT; 31 received TT; and 30 received FV. Nurses with expertise in the 2 touch therapies administered them. The interventions of MT, TT, and FV were administered according to standarized protocols every third day beginning the day chemotherapy began until discharge from the program.\n Time for engraftment, complications, and patient perceptions of benefits of therapy were the main outcome measures. Analysis of variance and analysis of covariance were used to determine significant differences among the 3 groups with respect to time of engraftment.\n A significantly lower score for central nervous system or neurological complications was noted for subjects who received MT comppared with the control group; however, no differences were found among the 3 groups with respect to the other 10 complication categories or in the total mean score for complications. Patients' perception of the benefits of therapy (total score) was significantly higher for those who received MT compared with the FV control group. The mean scores on the comfort subscale were significantly higher for patients receiving both MT and TT compared with the FV control group.\n Massage therapy may be effective in altering the psychological and neurological complications associated with chemotherapy during bone marrow transplant. Both massage and Therapeutic Touch provide comfort to patients undergoing this challenging process.", "Complementary therapies are increasingly used to reduce side effects of cancer treatment, without evidence for their effectiveness. In a randomized, prospective, 2-period, crossover intervention study, the authors tested the effects of therapeutic massage (MT) and healing touch (HT), in comparison to presence alone or standard care, in inducing relaxation and reducing symptoms in 230 subjects. MT and HT lowered blood pressure, respiratory rate (RR), and heart rate (HR). MT lowered anxiety and HT lowered fatigue, and both lowered total mood disturbance. Pain ratings were lower after MT and HT, with 4-week nonsteroidal antiinflammatory drug use less during MT. There were no effects on nausea. Presence reduced RR and HR but did not differ from standard care on any measure of pain, nausea, mood states, anxiety, or fatigue. MT and HT are more effective than presence alone or standard care in reducing pain, mood disturbance, and fatigue in patients receiving cancer chemotherapy.", "Alternative medical therapies are widely utilized, but there are few objective data to evaluate the effectiveness of these techniques. The purpose of this study was to determine whether one alternative therapy, Therapeutic Touch (TT), can improve objective indices of median nerve function in patients with carpal tunnel syndrome.\n Participants with electrodiagnostically confirmed carpal tunnel syndrome were randomly assigned in single-blind fashion to receive either TT or sham therapeutic touch once weekly for 6 consecutive weeks. The distal latency of the median motor nerve along with visual analog assessments of pain and relaxation were measured before and after each treatment session.\n Twenty-one participants completed the study. Changes in median motor nerve distal latencies, pain scores, and relaxation scores did not differ between participants in the TT group and participants in the sham treatment group, either immediately after each treatment session or cumulatively. Immediately after each treatment session, however, there were improvements from baseline among all the outcome variables in both groups.\n In this small study, TT was no better than placebo in influencing median motor nerve distal latencies, pain scores, and relaxation scores. The changes in the outcome variables from baseline in both groups suggest a possible physiologic basis for the placebo effect.", "To obtain preliminary data and determine the feasibility of a large-scale experimental study to test the efficacy of the Rogerian Science of Unitary Human Beings-based intervention of dialogue and therapeutic touch (TT) on pre- and postoperative anxiety and mood and postoperative pain from breast cancer surgery.\n Experimental.\n Mid-Atlantic region; ambulatory.\n 29 Caucasian and 2 African American English-speaking women with positive breast cancer biopsy (experimental, n = 14; control, n = 17), ranging in age from 31-84 years old (F = 55.6).\n Treatments administered in subjects' homes within seven days prior to surgery and 24 hours after hospital discharge. Experimental treatment consisted of 10 minutes of TT and 20 minutes of dialogue. Control treatment consisted of 10 minutes of quiet time and 20 minutes of dialogue. Data (Spielberger State-Trait Anxiety Inventory. Affects Balance Scale, and Visual Analog Scale-Pain) were collected at the conclusion of each home visit.\n Anxiety, mood, and pain.\n The experimental group had lower preoperative state anxiety than the control groups (p = 0.008). No difference was found for preoperative mood. No differences were found for any postoperative measure.\n A large-scale study of dialogue and TT would require changes in design and recruitment strategies.\n Nurses may provide more comprehensive care by incorporating dialogue and TT or quiet time into their pre- and postoperative care. Additional research, however, is recommended to determine the differential effects of dialogue, TT, and quiet time on women's experiences with breast cancer prior to incorporating these noninvasive modalities into clinical practice." ]

[ "2191938", "8436497", "2861907", "2189328", "2251492", "3282670", "321395", "3510125", "3822681", "6519358", "6218003", "4839065", "3533271", "3313023", "6397729", "343489" ]

[ "A placebo-controlled crossover trial of nimodipine in pediatric migraine.", "A placebo-controlled crossover trial using trazodone in pediatric migraine.", "Flunarizine v. placebo in childhood migraine. A double-blind study.", "[Flunarizine and dihydroergotamine in the treatment of migraine in children].", "[The treatment of juvenile migraine using flunarizine or propranolol].", "Flunarizine in prophylaxis of childhood migraine. A double-blind, placebo-controlled, crossover study.", "Clonidine prophylaxis of childhood migraine and other vascular headache. A double blind study of 57 children;.", "Pizotifen (Sanomigran) in childhood migraine. A double-blind controlled trial.", "Comparison of self-hypnosis and propranolol in the treatment of juvenile classic migraine.", "Propanolol ('Inderal') in the treatment of childhood migraine.", "Clonidine and childhood migraine: a pilot and double-blind study.", "Propranolol used in prophylaxis of migraine in children.", "L-5-hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study.", "[Prevention of migraine with flunarizine and acetylsalicylic acid. A double-blind study].", "[Treatment of essential headache in developmental age with L-5-HTP (cross over double-blind study versus placebo)].", "Papaverine in the prophylaxis of migraine and other vascular headache in children." ]

[ "An 8-month, double-blind, placebo-controlled crossover trial was carried out on the use of nimodipine in migraine prophylaxis in 37 patients aged 7 to 18 years old. After a 4-week medication-free run-in period, 19 subjects (Group 1) received a placebo while 18 (Group 2) received nimodipine (10-20 mg t.i.d., according to body weight), for 12 weeks. After a 4-week wash-out period, the groups switched therapy for a further 12 weeks. 30 patients completed the trial and the number of dropouts was comparable in the 2 groups. The only side-effect during nimodipine treatment was mild abdominal discomfort (3 cases). The treatments were evaluated on the basis of frequency and duration of attacks. There was a significant reduction in both parameters during the first period of treatment. During the second period of treatment, nimodipine proved to have a significantly greater effect than the placebo with regard to frequency, whereas the response was similar with the placebo as regards duration of attacks. The latter parameter shows a significant decrease during the treatment periods, regardless of type of therapy.", "An 8-month, double-blind, placebo-controlled cross-over trial was carried out on the use of trazodone in pediatric migraine prophylaxis. It involved 40 patients aged 7 to 18 years old and suffering from migraine without aura, randomly divided into 2 groups. After a 4-week run-in period, Group A received oral trazodone (1 mg/kg a day divided into 3 doses) for 12 weeks, while Group B received a placebo. After a further 4-week washout period, Group A was given the placebo and Group B was treated with trazodone for a further 12 weeks. The trial was completed by 35 patients, the number of drop-outs being comparable in the two groups. During the first treatment period, both the frequency and the duration of the migraine episodes were significantly reduced in both groups. During the second, a significant further improvement in both parameters was only observed in Group B. No side-effects were observed at any time. Our results showed that, like other antidepressants, trazodone is a valid prophylactic agent for juvenile migraine.", "Successful migraine prophylaxis with flunarizine has been reported in adults by several authors. We used flunarizine in a double-blind, placebo controlled, randomized trial in childhood migraine. Twenty-four children with classical or common migraine were followed by a 12-week flunarizine treatment period. Each patient took 5 mg/day of the drug before going to sleep. Twenty-four children with similar clinical characteristics were assigned to placebo treatment. Efficacy of flunarizine versus placebo was assessed on the basis of the reduction of headache frequency and duration. A statistical comparison was performed between values reported in the treatment period and those in the three months before. Children treated with flunarizine experienced a statistically significant reduction in headache (66%) and duration (51%). These results were statistically superior to those observed in the placebo group. Sixteen patients on flunarizine therapy experienced an improvement of more than 50% of both parameters. We found flunarizine is an effective agent in children's migraine prophylaxis. Moreover it is suitable for the low incidence of mild side effects.", "We administer during 6 months in randomised way dihydroergotamine or flunarizine to 50 children affects of classical or common migraine. A significative improvement was estimated in frequency, intensity and duration of their crisis in 87% with dihydroergotamine and 79% with flunarizine, without significative differences from one to other. Dihydroergotamine was specially effective in children with vegetative lability. The secondary effects, 12% with dihydroergotamine and 20% with flunarizine, were trivial and advantageous even, without the necessity of stop the treatment in not any case.", "The clinical efficacy of flunarizine and propranolol for the prevention of migraine attacks was assessed in 33 children in a double blind study. After a run-in phase of one month, 32 patients started the active medication. A reduction in the number of migraine attacks was observed in 75% of the flunarizine group and in 73.8% of the propranolol group. Propranolol also reduced the severity of attacks. Transient side effects were observed in 3 of 17 of the flunarizine group and in 5 of 15 of the propranolol group. The most frequent side effect was increased fatigue, which required interruption of therapy in 2 patients of the propranolol group.", "An 8-month, double-blind, placebo-controlled, crossover trial of flunarizine in the prophylaxis of migraine has been performed in 70 children. After 4 weeks of medication-free base-line observation, 35 children (group A) received flunarizine (5 mg/day) and 35 (group B) received placebo over a 12-week period. After a 4-week washout they crossed treatments for another 12 weeks. Sixty-three patients completed the trial. In both groups flunarizine significantly reduced the frequency and average duration of headache attacks. In group A efficacy was maintained after placebo crossover for the last 4 months of the study. Five subjects in group B stopped placebo because of ineffectiveness; two children in group A discontinued flunarizine treatment, one because of excessive daytime sedation and the other because therapy was ineffective. The main side effects were daytime sedation and weight gain. It is concluded that flunarizine is an effective drug for the treatment of childhood migraine. In a study of this length no serious side effects were discovered.", "nan", "Forty-seven children with migraine have been included in a double-blind cross-over study with pizotifen and placebo. The children received either pizotifen for 3 months followed by placebo or vice versa. Thirty-nine children completed the trial and there was no significant difference between active and placebo treatment as regards reduction of number of attacks, total and mean duration of attacks and duration of longest attacks. Pizotifen was well tolerated by the children.", "In a prospective study we compared propranolol, placebo, and self-hypnosis in the treatment of juvenile classic migraine. Children aged 6 to 12 years with classic migraine who had no previous specific treatment were randomized into propranolol (at 3 mg/kg/d) or placebo groups for a 3-month period and then crossed over for 3 months. After this 6-month period, each child was taught self-hypnosis and used it for 3 months. Twenty-eight patients completed the entire study. The mean number of headaches per child for 3 months during the placebo period was 13.3 compared with 14.9 during the propranolol period and 5.8 during the self-hypnosis period. Statistical analysis showed a significant association between decrease in headache frequency and self-hypnosis training (P = .045). There was no significant change in subjective or objective measures of headache severity with either therapy.", "In a double-blind crossover study of 39 children with established migraine, there was no difference between treatment with propanolol and placebo as regards frequency, severity or average duration of migraine attacks. There was some evidence that propanolol increased the average length of headaches.", "nan", "nan", "L-5HTP was tested versus placebo in a double-blind crossover study of 27 migraine children aged 6-12 years, who recorded their headaches in a headache diary for 1 month. Twenty-one patients subsequently started the trial. The mean daily dose of L-5HTP was 5 mg/kg body weight, and each treatment period with either L-5HTP or placebo lasted 12 weeks. In group A (L-5HTP-placebo; 10 patients) and group B (placebo-L-5HTP; 11 patients) both L-5HTP and placebo led to a significant reduction of the migraine index and frequency of migraine attacks during the 3rd month of each treatment period. However, we found a treatment X period interaction because the efficacy determinants decreased significantly during the first and the second treatment periods in both groups irrespective of the sequence of treatments. No differences were found between L-5HTP (first period of group A) and placebo (first period of group B).", "30 children between 7 and 17 years suffering from at least 2 attacks/month of common or classical migraine since more than 1 year were studied. After clinical exclusion of symptomatic headache 4 weeks were documented by means of a migraine diary. Prophylaxis with Calcium entry blocker Flunarizine (Sibelium) or Thromboxane A inhibitor Acetylsalicylic acid (ASS) was carried out in a double blind design for 3 months. Medication was given as one dosage in the evening: 2-5 mg/kg KG ASS or 5-10 mg Flunarizine. Documented attack frequency and duration were controlled at monthly physical examinations. Final results showed no differences in significant reduction of attack frequency or symptoms between both different therapeutic principals. 72.4% (ASS 73.3%; Flunarizine 71.4%) of patients were attack-free or had at least a 50% reduction. Migraine frequency of initially 7-8 was reduced to 1-2 attacks/month. Duration remained constant in both groups (1-3 h). Side effects were slight body weight gain or abdominal pain after intake, prophylaxis had not to be interrupted therefore. Longtime prognosis is not yet possible because the time of observation is too short so far. Conclusion: Both substances are definitely useful and have few side effects in childhood migraine. If the response to one is insufficient the other substance should be tried.", "Thirty patients (mean age: 10.38 years) affected by primary headache were selected for a double-blind cross-over clinical trial. The patients were randomized into 2 homogeneous groups of 15 and treated for 12 weeks with L-5-HTP (100 mg/day) and placebo as per the following design: placebo - L-5-HTP (group A) and L-5-HTP - placebo (group B). Evaluation was carried out every 3 weeks by the Migraine Index supplying a general assessment of the attacks, i.e. severity, duration and frequency. The decrease in mean score values was directly proportional to L-5-HTP treatment, and statistical significance (Wilcoxon's test) was observed only for L-5-HTP in both groups, from 0.05 to 0.01. Improvement, as evaluated by CGI on percentage distribution of the patients, was homogeneous in both groups.", "A daily dose of papaverine (5--10 mg per kg body weight) was administered on a double-blind basis for two months to 42 successive child patients suffering from migraine or other vascular headache attacks not less than twice a month. Thirty-seven patients received the drug for the whole period of two months and 31 of these could be followed for a period of one to 10 months (mean 4.5 months) after the cessation of the treatment. Nineteen received papaverine and 18 placebo. Six out of 19 papaverine patients and none of 18 placebo patients were completely free from attacks during the treatment. Altogether 11 patients in the papaverine group and 5 in the placebo group experienced a 75--100% reduction in attack frequency which was accompanied by lower intensity and shorter duration of attacks. The results were best in cases with classical migraine. An \"excellent\" or \"good\" drug effect was experienced by 58% of papaverine patients and 17% of placebo patients." ]

[ "15316798", "9439944", "8164818", "11985388", "4905910", "9311358", "12058094", "12389143", "9137847", "11251695", "7872882", "15096395", "16643559", "1576648", "15624081", "511533", "11576201", "14982912", "11903524", "10958046", "9137848" ]

[ "Topiramate in migraine prophylaxis--results from a placebo-controlled trial with propranolol as an active control.", "Valproate versus flunarizine in migraine prophylaxis: a randomized, double-open, clinical trial.", "Sodium valproate has a prophylactic effect in migraine without aura: a triple-blind, placebo-controlled crossover study.", "Efficacy and tolerability of acetazolamide in migraine prophylaxis: a randomised placebo-controlled trial.", "Aetiology of migraine and prevention with carbamazepine (Tegretol): results of a double-blind, cross-over study.", "A comparison of divalproex with propranolol and placebo for the prophylaxis of migraine without aura.", "A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis.", "[Effectiveness and safety of gabapentin in the preventive treatment of migraine].", "Divalproex sodium in migraine prophylaxis: a dose-controlled study.", "Efficacy of gabapentin in migraine prophylaxis.", "Migraine prophylaxis with divalproex.", "Topiramate in migraine prevention: results of a large controlled trial.", "Comparison of the effect of topiramate and sodium valporate in migraine prevention: a randomized blinded crossover study.", "Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo.", "Topiramate in migraine prophylaxis: a randomised double-blind versus placebo study.", "Clonazepam (rivotril) in migraine prophylaxis.", "Valproic acid is effective in migraine prophylaxis at low serum levels: a prospective open-label study.", "Topiramate for migraine prevention: a randomized controlled trial.", "Topiramate in migraine prevention: a double-blind, placebo-controlled study.", "Gabapentin in the prophylaxis of migraine: a double-blind randomized placebo-controlled study.", "Lamotrigine versus placebo in the prophylaxis of migraine with and without aura." ]

[ "Topiramate (TPM) has shown efficacy in migraine prophylaxis in two large placebo-controlled, dose-ranging trials. We conducted a randomised, double-blind, multicentre trial to evaluate the efficacy and safety of two doses of topiramate vs placebo for migraine prophylaxis, with propranolol (PROP) as an active control. Subjects with episodic migraine with and without aura were randomised to TPM 100 mg/d, TPM 200 mg/d, PROP 160 mg/d (active control), or placebo. The primary efficacy measure was the change in mean monthly migraine frequency from the baseline phase relative to the double-blind treatment phase. Five hundred and seventy-five subjects were enrolled from 61 centres in 13 countries. TPM 100 mg/d was superior to placebo as measured by reduction in monthly migraine frequency, overall 50% responder rate, reduction in monthly migraine days, and reduction in the rate of daily rescue medication use. The TPM 100 mg/d and PROP groups were similar with respect to reductions in migraine frequency, responder rate, migraine days, and daily rescue medication usage. TPM 100 mg/d was better tolerated than TPM 200 mg/d, and was generally comparable to PROP. No unusual or unexpected safety risks emerged. These findings demonstrate that TPM 100 mg/d is effective in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d exhibited similar efficacy profiles.", "The aim of this study was to compare the efficacy and safety of valproate versus flunarizine in migraine prophylaxis in a randomized double-open clinical trial. Twenty-two migraine sufferers were treated with valproate (1 g per day) for 8 weeks; a parallel group of 22 migraine sufferers was treated with flunarizine (10 mg per day). The main admission criterion was a minimum of 3 migraine (with, or without aura) attacks per month. The major clinical parameters evaluated were the frequency of headache attacks, the frequency of use of drugs for the acute management of migraine, the patients' opinion of treatment and the Hamilton anxiety and depression rating scales. During the study 3 patients dropped out (1 from the valproate and 2 from the flunarizine groups). Fifteen patients (71.4%) from the valproate group responded to therapy, compared to 14 patients (65%) from the flunarizine group. In the valproate group 12 patients (57.1%) reported various side effects (prevalently gastric symptoms) versus 10 patients (47.6%) in the flunarizine group (prevalently somnolence). The patients who were treated with flunarizine showed an increase in the mean score of the 21-item Hamilton rating scale for depression, but the difference was not significant; morning dysthymia however, was significantly more often observed in the flunarizine patients, compared to the valproate patients. These results suggest that both drugs are effective and safe in migraine prophylaxis.", "We included 43 patients with migraine without aura in a triple-blind, placebo- and dose-controlled, crossover study of the prophylactic effect of slow-release sodium valproate; 34 patients completed the trial. The number of days with migraine was 3.5 per 4 weeks during treatment with sodium valproate and 6.1 during placebo (p = 0.002). The severity and duration of the migraine attacks that did occur were not affected by sodium valproate when compared with placebo. Fifty percent of the patients were responders, ie, their initial migraine frequency was reduced to 50% or less during sodium valproate as compared with 18% during placebo. The number of responders increased during the trial to 65% in the last 4 weeks of the active treatment period. There were no serious side effects requiring withdrawal of patients from the study. We conclude that sodium valproate is an effective and well-tolerated prophylactic medication for migraine without aura.", "Familial hemiplegic migraine and episodic ataxia type 2 (EA2) are allelic disorders with distinct types of mutations in the CACNA1A gene. EA2 attacks are remarkably sensitive to acetazolamide, a carbonic anhydrase inhibitor. The effectiveness of acetazolamide in migraine prophylaxis is unknown.\n To evaluate the efficacy and the tolerability of acetazolamide in migraine prophylaxis.\n We compared daily oral 500 mg acetazolamide and placebo in patients with migraine in a multicentre, double-blind, randomised trial of 12 weeks duration after a run-in period of 4 weeks without treatment. Frequency of attacks at the last trial period of 4 weeks was the primary efficacy criterion. Secondary efficacy criteria were the frequency of attacks per 4 weeks, the severity and duration of attacks, the number of hours with migraine as well as the number of responders with more than 50% reduction in attack frequency.\n 53 patients had been enrolled when the study was prematurely stopped because of a high number of withdrawals (34%), primarily linked to acetazolamide related side effects. Considering the primary and secondary efficacy criteria, among the 53 included patients (27 in the placebo group and 26 in the acetazolamide group), no difference between the 2 study groups could be demonstrated. The most frequent adverse events related to acetazolamide were paresthesias and asthenia.\n In this trial, migraine sufferers poorly tolerated acetazolamide given in an oral dose of 500 mg daily. No obvious prophylactic beneficial effect of acetazolamide appeared on migraine attacks.", "nan", "To compare the efficacy of divalproex sodium (Depakote) with that of propranolol hydrochloride (and placebo) for the prophylaxis of migraine without aura.\n Single-investigator, randomized, single-blind, placebo-controlled study with 5 phases: baseline (weeks 1-4); placebo (weeks 5-8); first treatment, 1 agent (weeks 9-20); washout (weeks 21-24); and second treatment, crossover to other agent (weeks 25-36).\n Private practice of a general neurologist with a special interest in headache disorders.\n Of 37 patients (30 women and 7 men) selected, 32 completed the study. All received placebo, after which half were randomized to receive divalproex or propranolol, then crossed over after washout.\n Divalproex and propranolol doses were titrated during the initial 8 weeks of each 12-week treatment cycle. For divalproex, doses were titrated to 1500 mg/d in 23 patients, to 2000 mg/d in 2, and downward in 7; the mean valproate sodium trough level was 68.5 mg/L. Propranolol was titrated to 180 mg/d in 28 patients, to 240 mg/d in 1, and downward in 3.\n Migraine frequency was reduced in 19% (6/ 32) of placebo-treated, 66% (21/32) of divalproex-treated, and 63% (20/32) of propranolol-treated patients. Assessment of migraine-days per month revealed significant response to placebo in 22% (7/32) of patients, to divalproex in 66% (21/32), and to propranolol in 69% (22/32). When results were limited to the third month of each active-agent treatment phase, 75% (24/ 32) of patients receiving divalproex and 78% (25/32) of those receiving propranolol had reduction in migraine frequency.\n No significant difference was identified between divalproex and propranolol for the prophylaxis of migraine without aura.", "To evaluate the efficacy and safety of extended-release divalproex sodium compared with placebo in prophylactic monotherapy treatment of migraine headache.\n This was a double-blind, randomized, placebo-controlled, parallel-group study. Subjects with more than two migraine headache attacks during a 4-week baseline were randomly assigned in a 1:1 ratio at each center to receive either extended-release divalproex sodium or matching placebo once daily for 12 weeks. Subjects initiated treatment on 500 mg once daily for 1 week, and the dose was then increased to 1,000 mg once daily with an option, if intolerance occurred, to permanently decrease the dose to 500 mg during the second week. Reduction from baseline in 4-week migraine headache rate was the primary efficacy variable. Migraine headaches separated by a < 24-hour headache-free interval were counted as single migraines in calculating migraine headache rates. Tolerance and safety were also evaluated.\n The mean reductions in 4-week migraine headache rate were 1.2 (from a baseline mean of 4.4) in the extended-release divalproex sodium group and 0.6 (from a baseline mean of 4.2) in the placebo group (p = 0.006); reductions with extended-release divalproex sodium were significantly greater than with placebo in all three 4-week segments of the treatment period. No significant differences were detected between treatment groups in either the overall incidence or in the incidence of any specific treatment-emergent adverse event; 8% of subjects treated with extended-release divalproex sodium and 9% of those treated with placebo discontinued for adverse events.\n Extended-release divalproex sodium is an efficacious, well-tolerated, safe, and easy-to-use once-a-day prophylactic antimigraine medication.", "Migraine is a frequent and disabling pathological condition with important socioeconomic repercussions. Recent studies have explored the use of antiepileptic drugs in the prophylactic treatment of migraine. Preliminary studies have shown that gabapentin is a drug that is effective and well tolerated by patients. AIM. To evaluate the effectiveness and safety of gabapentin in the prophylactic treatment of migraine.\n A prospective, open, multicentre, random clinical study, carried out according to IHS criteria, which compares the effectiveness and safety of gabapentin in 1,200 mg/day and 2,000 mg/day doses as a preventive treatment for migraine over a 16 week period.\n Significant differences were found in patients treated with gabapentin, as compared with their basal state, in the following: a lower number of attacks (reduction in weeks 4, 10 and 16: 2.4 2.8, 2.9 2.9 and 3.1 2.9 attacks/month on a basal rate of 5.3 3.5 attacks/month), lower intensity (on a scale of 0 3 of increasing pain intensity: basal rate: 2.7 0.4, week 4: 1.8 0.9, week 10: 1.7 0.9, week 16: 1.4 1.0) and how long the pain lasts (basal rate 390 hours/month, week 4: 180 hours/month, week 10: 180 hours/month, week 16: 120 hours/month). No statistically significant differences were found between doses of 1,200 or 2,000 mg/day. Mild adverse effects were seen in 62 patients (37.8%): drowsiness (22.6%), asthenia (7.9%), dizziness (4.9%), abdominal pain (3.7%) and dazedness (3.7%). No serious adverse events occurred.\n Gabapentin can be considered an effective and safe drug in the preventive treatment of migraine.", "To evaluate the efficacy and safety of divalproex sodium (DVPX) when used as prophylactic monotherapy in patients with migraine.\n Multicenter, double-blind, placebo-controlled, parallel group. Patients were previously untreated or had failed no more than two adequate trials of prophylactic therapy. During the 4-week (single-blind) baseline, patients received placebo and completed a headache diary. Patients with two or more migraine attacks during the baseline were randomized to receive a DVPX daily dose of 500, 1000, or 1500 mg, or to placebo. The experimental phase (EP) lasted 12 weeks, the first 4 weeks for dose escalation to randomized dose, and the remaining 8 weeks for maintenance at that dose. The primary efficacy variable was 4-week migraine attack frequency during the EP.\n One-hundred-and-seventy-six patients (44 placebo, 132 DVPX) were randomized; 171 provided efficacy data and 137 completed the study. During the EP, after adjustment for differences in baseline migraine attack frequencies, mean reductions in the DVPX groups were 1.7 (500 mg), 2.0 (1000 mg) and 1.7 (1500 mg) migraine attacks per 4 weeks compared to a mean reduction of 0.5 migraine attacks in the placebo group (p < or = 0.05 vs placebo). Forty-four to 45% of DVPX-treated patients compared to 21% of patients in the placebo group achieved > or = 50% reduction in their migraine attack frequencies (p < or = 0.05 vs placebo). The recommended initial dose of DVPX in migraine prophylaxis is 500 mg per day, although some patients may benefit from higher doses. Adverse events were similar in the DVPX and placebo treatment groups except for nausea, dizziness and tremor in which incidence rates were significantly higher in the DVPX 1500 mg group (nausea was also higher in 500 mg group) than in the placebo group.\n Divalproex sodium is an effective prophylactic treatment in migraine and is generally well tolerated.", "To compare gabapentin with placebo for use as a prophylactic agent in patients with migraine (with or without aura). STUDY DESIGN AND TREATMENT: After screening, a 4-week, single-blind, placebo baseline period was followed by a 12-week, double-blind, treatment period. The 12-week treatment period consisted of a 4-week titration phase and an 8-week stable-dosing phase. During the 4-week titration phase, patients were started on one 300-mg capsule of gabapentin or matching placebo. Patients were titrated weekly from 900 mg/day (end of week 1) to 2400 mg/day (end of week 4) and had to be receiving a stable dose of study medication by the end of the titration period. Study medication was to be given on a three-times-a-day dosing regimen.\n The study hypothesis was defined a priori as a lower 4-week migraine rate during the second stabilization period for the gabapentin-treated patients as compared with the placebo-treated patients. The analyses were performed with the 4-week migraine rate at baseline as a covariate and center as a blocking factor.\n At seven participating centers, 143 patients with migraine were randomized in a 2:1 ratio and received either gabapentin (n = 98) or matching placebo (n = 45). Thirty-three patients (24.1%) discontinued prematurely from the study, including 24 (24.5%) of 98 gabapentin-treated patients and 9 (20.0%) of 45 placebo-treated patients; the majority of patients discontinued due to adverse events (16 [16.3%] of 98 gabapentin-treated patients; 4 [8.9%] of 45 placebo-treated patients). Patients included in the analysis were evenly balanced for age, sex, race, weight, and height. The majority of these patients were white (80 [92.0%] of 87) and women (72 [82.8%] of 87), with a mean age of approximately 39.4 years and a history of migraine episodes for a mean of about 21 years. At the end of the 12-week treatment phase, the median 4-week migraine rate was 2.7 for the gabapentin-treated patients maintained on a stable dose of 2400 mg/day and 3.5 for the placebo-treated patients (P =.006), compared with 4.2 and 4.1, respectively, during the baseline period. Additionally, 26 (46.4%) of 56 patients receiving a stable dose of 2400 mg/day gabapentin and 5 (16.1%) of 31 patients receiving placebo showed at least a 50% reduction in the 4-week migraine rate (P =.008). The average number of days per 4 weeks with migraine was also statistically significant and favored gabapentin (P =.006) during stabilization period 2. The median change in 4-week headache rate was statistically significant as well (P =.013). The most frequently reported adverse events for both treatment groups were asthenia, dizziness, somnolence, and infection. Adverse events determined by the investigator to be associated with study drug resulted in patient withdrawal in 13 (13.3%) of 98 gabapentin-treated patients and 3 (6.7%) of 45 placebo-treated patients. Somnolence and dizziness accounted for many of the premature withdrawals among those taking gabapentin.\n Gabapentin is an effective prophylactic agent for patients with migraine. In addition, gabapentin appears generally well tolerated with mild to moderate somnolence and dizziness.", "To compare the effectiveness and safety of divalproex sodium (Depakote) and placebo in the prophylaxis of migraine headache.\n Multicenter, double-blind, randomized, placebo-controlled investigation, having a 4-week, single-blind placebo baseline phase and a 12-week treatment phase (4-week dose adjustment, 8-week maintenance).\n Eight headache/neurology clinics throughout the United States.\n One hundred seven patients randomized to divalproex or placebo (2:1 ratio): 70 receiving divalproex and 37 receiving placebo.\n Divalproex and placebo dosages titrated in blinded fashion during dose adjustment period to achieve actual/sham trough valproate sodium concentrations of approximately 70 to 120 mg/L.\n During the treatment phase, the mean migraine headache frequency per 4 weeks was 3.5 in the divalproex group and 5.7 in the placebo group (p < or = .001), compared with 6.0 and 6.4, respectively, during the baseline phase. Forty-eight percent of divalproex-treated patients and 14% of placebo-treated patients showed a 50% or greater reduction in migraine headache frequency from the baseline phase (P < .001). Among those with migraine headaches, divalproex-treated patients reported significantly less functional restriction than placebo-treated patients and used significantly less symptomatic medication per episode. No significant treatment group differences were observed in average peak severity or duration of individual migraine headaches. Treatment was stopped in 13% of divalproex-treated patients and 5% of placebo-treated patients because of intolerance (P, not significant).\n Divalproex is an effective prophylactic drug for patients with migraine headaches and is generally well tolerated.", "Open-label trials and small controlled studies report topiramate's efficacy in migraine prevention.\n To assess the efficacy and safety of topiramate as a migraine-preventive therapy.\n A 26-week, randomized, double-blind, placebo-controlled study.\n Outpatient treatment at 49 US clinical centers. Patients Patients were aged 12 to 65 years, had a 6-month International Headache Society migraine history, and experienced 3 to 12 migraines per month, but had 15 or fewer headache days per month during the 28-day baseline period.\n Participants were randomized to placebo or topiramate, 50, 100, or 200 mg/d, titrated by 25 mg/wk to the assigned dose or as tolerated in 8 weeks; maintenance therapy continued for 18 weeks.\n The primary efficacy assessment was a reduction in mean monthly migraine frequency across the 6-month treatment phase. Secondary end points were responder rate, time to onset of action, mean change in migraine days per month, and mean change in rescue medication days per month.\n Four hundred eighty-seven patients were randomized, and 469 composed the intent-to-treat population. The mean +/- SD monthly migraine frequency decreased significantly for the 100-mg/d group (from 5.4 +/- 2.2 to 3.3 +/- 2.9; P <.001) and the 200-mg/d group (from 5.6 +/- 2.6 to 3.3 +/- 2.9; P <.001) vs the placebo group (from 5.6 +/- 2.3 to 4.6 +/- 3.0); improvements occurred within the first treatment month. Significantly more topiramate-treated patients (50 mg/d, 35.9% [P =.04]; 100 mg/d, 54.0% [P <.001]; and 200 mg/d, 52.3% [P <.001]) exhibited a 50% or more reduction in monthly migraine frequency than placebo-treated patients (22.6%). Adverse events included paresthesia, fatigue, nausea, anorexia, and taste per version.\n Topiramate, 100 or 200 mg/d, was effective as a preventive therapy for patients with migraine.", "Topiramate and sodium valporate are anticonvulsants, demonstrated to be effective as monotherapy for migraine prevention in placebo-controlled trials.\n To compare the relative efficacy of topiramate and sodium valporate in the prevention of migraine.\n A 24-week, randomized, double-blind, crossover, clinical trial was conducted from October 2003 to September 2004. A total of 64 patients with migraine headache, aged 14 to 57 years, were randomly allocated to the 2 treatment groups. The first group received topiramate (25 mg daily increment over 1 week to 50 mg) for a total of 2 months. The second group received sodium valporate (200 mg daily increment over 1 week to 400 mg) for 2 months. Response to treatment was assessed at 0, 1, 8, 16, and 24 weeks after start of therapy.\n Topiramate appeared to be equivalent in efficacy and safety to sodium valporate. A significant decrease in duration, monthly frequency, and intensity of headache occurred in both groups. Of the 32 patients treated with sodium valporate, the mean standard deviation (SD) of monthly migraine frequency decreased from 5.4 (2.5) to 4.0 (2.8) episode per month, headache intensity from 7.7 (1.2) to 5.8 (1.7) by visual analog scale (VAS), and headache duration from 21.3 (14.6) to 12.3 (10.7) hours (P < .001). Correspondingly, in the 32 patients treated with topiramate, the mean SD of monthly headache frequency decreased from 5.4 (2.0) to 3.2 (1.9) per month, headache intensity from 6.9 (1.2) to 3.7 (1.3), and headache duration from 17.3 (8.4) to 3.9 (2.7) hours (P < .001).\n This study demonstrates that treatment with topiramate and sodium valporate both significantly reduce migraine headache. This effect of topiramate and sodium valporate has previously been shown to reduce migraine headache, and we postulate that treatment with topiramate and sodium valporate may have a similar benefit.", "The efficacy of sodium valproate (Depalept) versus placebo in the treatment of migraine was evaluated in a double-blind randomized cross-over study in twenty-nine patients. The patients were divided into two groups each of which was alternately given 400 mg of sodium valproate B.I.d or placebo for eight weeks and then crossed over for an additional eight weeks. Our results show that in 86.2% of the patients sodium valproate was effective in preventing migraine or reducing the frequency, severity and duration of the attacks. In general, the drug was well tolerated and proved to be an effective treatment in migraine.", "The objectives of this paper are to evaluate the efficacy and tolerability of topiramate, given at the dose of 100 mg/day, in the prophylactic treatment of migraine. The hypothesis that migraine is the result of a condition of neuronal hyperexcitability and the quest for drugs that are able to limit the number of crises justifies the attempt to utilise the new antiepileptic drugs in the prophylaxis of this pathology, which is so important due to its high prevalence and due to the high disability it causes. The study was randomised double-blind versus placebo, lasting 16 weeks, and was preceded by a run-in period of 4 weeks. One hundred and fifteen patients were randomly allocated to treatment with topiramate (TPM) or placebo: 35 patients completed the study in the TPM group and 37 patients in the placebo group. At the end of the double-blind phase of study, in the TPM group, we recorded a significant reduction in the frequency of migraine crises (from 5.26 at baseline to 2.60 in the last 4 weeks), a significant reduction in the quantity of symptomatic drugs taken as compared to the placebo control group (from 6.17+/-1.80 SD to 2.57+/-0.80) and a significant downward trend in the number of days of disability over the 16-week period of therapy. In the TPM group, side effects were transient and well tolerated. TPM has thus proven its efficacy and tolerability in the prophylaxis of migraine.", "nan", "We evaluated the efficacy of prophylactic valproic acid treatment (6 months) on the frequency of migraine attacks and the number of migraine headache days with respect to serum levels.\n Valproic acid, a GABAergic drug, has been shown to be effective for migraine prophylaxis. Results from several dose- and serum level-adjusted studies have recommended valproic acid doses within a range of 500 to 1500 mg per day for migraine prophylaxis. Design and\n In this prospective open-label study, 52 patients received valproic acid doses of 300 to 1200 mg per day; 45 patients were treated per protocol. Valproic acid serum levels increased linearly in relation to the valproic acid dose and were between 21 and 107 microg/mL at the end of the treatment period. Patients were divided into two groups: those with valproic acid serum levels less than 50 microg/mL (group 1) and those with serum levels greater than 50 microg/mL (group 2).\n The frequency of migraine attacks was significantly reduced in group 1 from 3.5 +/- 0.9 to 2.0 +/- 0.9 attacks per month. Migraine headache days also decreased (6.4 +/- 3.5 to 4.6 +/- 2.9 days per month). In the high serum level group, a reduction of migraine attacks from 3.5 +/- 0.9 to 2.8 +/- 1.0 attacks per month and only a slight decrease in headache days (6.4 +/- 3.5 to 6.1 +/- 2.4 days per month) was observed. The outcome of group 1 (low serum level) was significantly better than that of group 2 with respect to both parameters (P<.05). Side effects were generally mild and temporary.\n Due to the lack of additional benefit from higher valproic acid doses (more than 600 mg per day), we recommend daily valproic acid doses of 500 to 600 mg with a target serum level less than 50 microg/mL for the prophylactic treatment of migraine.", "Small open-label and controlled trials suggest that the antiepileptic drug topiramate is effective for migraine prevention.\n To assess the efficacy and safety of topiramate for migraine prevention in a large controlled trial.\n A 26-week, randomized, double-blind, placebo-controlled study was conducted during outpatient treatment at 52 North American clinical centers. Patients were aged 12 to 65 years and had a 6-month history of migraine (International Headache Society criteria) and 3 to 12 migraines a month but no more than 15 headache days a month during a 28-day prospective baseline phase.\n After a washout period, patients meeting entry criteria were randomized to topiramate (50, 100, or 200 mg/d) or placebo. Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or maximum tolerated dose, whichever was less. Patients continued receiving that dose for 18 weeks.\n The primary efficacy measure was change from baseline in mean monthly migraine frequency. Secondary efficacy measures included responder rate (proportion of patients with > or =50% reduction in monthly migraine frequency), reductions in mean number of monthly migraine days, severity, duration, and days a month requiring rescue medication, and adverse events. The month of onset of preventive treatment action was assessed.\n Of 483 patients randomized, 468 provided at least 1 postbaseline efficacy assessment and comprised the intent-to-treat population. Mean monthly migraine frequency decreased significantly for patients receiving topiramate at 100 mg/d (-2.1, P =.008) and topiramate at 200 mg/d (-2.4, P<.001) vs placebo (-1.1). Statistically significant reductions (P<.05) occurred within the first month with topiramate at 100 and 200 mg/d. The responder rate was significantly greater with topiramate at 50 mg/d (39%, P =.01), 100 mg/d (49%, P<.001), and 200 mg/d (47%, P<.001) vs placebo (23%). Reductions in migraine days were significant for the 100-mg/d (P =.003) and 200-mg/d (P<.001) topiramate groups. Rescue medication use was reduced in the 100-mg/d (P =.01) and 200-mg/d (P =.005) topiramate groups. Adverse events resulting in discontinuation in the topiramate groups included paresthesia, fatigue, and nausea.\n Topiramate showed significant efficacy in migraine prevention within the first month of treatment, an effect maintained for the duration of the double-blind phase.", "To evaluate the efficacy of topiramate in the preventative treatment of episodic migraine.\n Topiramate is a broad-spectrum antiepileptic drug effective for treatment of multiple seizure types in adults and children. Antiepileptic agents have demonstrated efficacy in migraine prevention, and open-label experience from our clinic has suggested that topiramate might be effective for this use. We consequently conducted a single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate for the preventative treatment of migraine.\n Forty patients, aged 19 to 62 years (mean, 38.2 years), were randomly assigned in a 1:1 ratio to receive topiramate (n = 19; all women) or placebo (n = 21; 20 women, 1 man). Following a prospective baseline phase of 4 weeks, the study drug dose was titrated weekly in 25-mg increments over 8 weeks to 200 mg per day or to the maximum tolerated dose. The titration phase was followed by an 8-week maintenance phase.\n During the entire double-blind phase, topiramate-treated patients experienced a significantly lower 28-day migraine frequency (3.31 +/- 1.7 versus 3.83 +/- 2.1; P =.002) compared to placebo, irrespective of use of concomitant migraine prevention medications. The mean 28-day migraine frequency was reduced by 36% in patients receiving topiramate as compared with 14% in patients receiving placebo (P =.004). Twenty-six percent of the patients on topiramate and 9.5% of the patients on placebo achieved a 50% reduction in migraine frequency (P >.05). The mean dose of topiramate was 125 mg per day (range, 25 to 200 mg per day). Topiramate was well tolerated; 2 of 19 topiramate-treated patients discontinued treatment due to adverse events. Adverse effects that occurred more frequently in topiramate-treated patients included paresthesia, weight loss, altered taste, anorexia, and memory impairment.\n Preventative therapy with topiramate significantly reduced migraine frequency. Larger multicenter clinical studies may further delineate the role of topiramate in migraine prevention.", "Gabapentin is an antiepileptic drug of new generation that increases brain GABA levels. We report the results of a three-month randomised double-blind placebo-controlled study on the effects of gabapentin in the prophylaxis of patients with migraine meeting the IHS criteria.\n We treated 63 patients suffering from migraine with or without aura. Patients treated their attack at home using symptomatic drugs and clinical assessment was recorded on a diary. After a washout of 8 week from any other prophylactic treatment, all patients were treated with 1200 mg/day of gabapentin; this is our therapeutic plan: 400 mg/day from 1st to 3rd day, 800 mg/day from 4th to 6th day and 1200 mg/day from 7th day.\n No patients withdrew, gabapentin was well tolerated; adverse events (somnolence, dizziness, tremor, fatigue and ataxia) generally were transient and mild to moderate in severity and in 13 patients (27%) only occurred. At the end of treatment, in such case, we reported a significative reduction of frequency and intensity of migraine in 30 patients treated with gabapentin.\n Our observations indicate that gabapentin is well tolerated by patients and that reduces headache frequency and use of symptomatic drugs in both groups. Gabapentin shows to have an effective therapeutic action in the prophylactic treatment of migraine.", "Lamotrigine blocks voltage-sensitive sodium channels, leading to inhibition of neuronal release of glutamate. Release of glutamate may be essential in the propagation of spreading cortical depression, which some believe is central to the genesis of migraine attacks. This study compared safety and efficacy of lamotrigine and placebo in migraine prophylaxis in a double-blind randomized parallel-groups trial. A total of 110 patients entered; after a 1-month placebo run-in period, placebo-responders and non-compliers were excluded, leaving 77 to be treated with lamotrigine (n = 37) or placebo (n = 40) for up to 3 months. Initially, lamotrigine therapy was commenced at the full dose of 200 mg/day, but, following a high incidence of skin rashes, a slow dose-escalation was introduced: 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, then 200 mg/day. Attack rates were reduced from baseline means of 3.6 per month on lamotrigine and 4.4 on placebo to 3.2 and 3.0 respectively during the last month of treatment. Improvements were greater on placebo and these changes, not statistically significant, indicate that lamotrigine is ineffective for migraine prophylaxis. There were more adverse events on lamotrigine than on placebo, most commonly rash. With slow dose-escalation their frequency was reduced and the rate of withdrawal for adverse events was similar in both treatment groups." ]

[ "12544527", "18231834", "12525911", "16696389", "12549689", "17636512", "18273670", "11856126", "15206964", "15932557", "18545884", "14530679", "16479346", "11952582" ]

[ "Clinical experience of sutureless closed hemorrhoidectomy with LigaSure.", "Ligasure Precise vs. conventional diathermy for Milligan-Morgan hemorrhoidectomy: a prospective, randomized, multicenter trial.", "Randomised trial comparing LigaSure haemorrhoidectomy with the diathermy dissection operation.", "Closed vs ligasure hemorrhoidectomy: a prospective, randomized clinical trial.", "Haemorrhoidectomy: randomised controlled clinical trial of Ligasure compared with Milligan-Morgan operation.", "Randomized clinical trial of LigaSure and conventional diathermy haemorrhoidectomy.", "Ligasure vs. conventional diathermy in excisional hemorrhoidectomy: a prospective, randomized study.", "Randomized clinical trial of Ligasure versus open haemorrhoidectomy.", "One year follow up of a randomized trial comparing Ligasure with open haemorrhoidectomy.", "Ligasure trademark vs conventional diathermy haemorrhoidectomy: long-term follow-up of a randomised clinical trial.", "Randomized clinical trial comparing LigaSure haemorrhoidectomy with open diathermy haemorrhoidectomy.", "Randomized, clinical trial of Ligasure vs conventional diathermy in hemorrhoidectomy.", "Randomized controlled trial of LigaSure with submucosal dissection versus Ferguson hemorrhoidectomy for prolapsed hemorrhoids.", "Randomized clinical trial of Ligasure versus conventional diathermy for day-case haemorrhoidectomy." ]

[ "The purpose of this study was to evaluate the LigaSure vessel sealing system as an alternative to closed hemorrhoidectomy.\n Sixty-one patients with Grade 3 or 4 symptomatic hemorrhoids were prospectively randomly assigned to undergo hemorrhoidectomy with the LigaSure vessel sealing system or hemorrhoidectomy using the conventional Ferguson procedure. We determined the operation time, postoperative pain, amount of time taken off from work, and complications associated with both techniques.\n Mean operative time for the LigaSure hemorrhoidectomy was 15 +/- 5.4 minutes and for the Ferguson operation, 21.2 +/- 8.2 minutes. The difference was significant (P < 0.01). There was also a significant decrease in pain measurements reported on postoperative Days 1 and 2 (P < 0.05) in the LigaSure group. The incidence of postoperative wound swelling and complications were similar between two groups. There was no difference in the period of time off from work between patient groups.\n This study confirms that LigaSure system can achieve a radical ablation of hemorrhoids, reduce operative time, and result in less postoperative pain on postoperative Days 1 and 2.", "Milligan-Morgan hemorrhoidectomy using radiofrequency dissection (Ligasure) has been proposed instead of conventional diathermy in view of its potential benefits in terms of postoperative anal pain and better hemostatic control, but the medical literature is still controversial. This multicenter, randomized, controlled trial was designed to compare the outcomes between Ligasure and conventional diathermy hemorrhoidectomy in the Milligan-Morgan procedures in a sufficient number of patients.\n Patients with Grades III and IV hemorrhoids were randomized to two groups: Ligasure hemorrhoidectomy and conventional diathermy. Postoperative anal pain was measured by the Visual Analog Scale (VAS) and the analgesia required. Postoperative complications, wound healing, and return to working activities also were evaluated as secondary outcomes.\n A total of 273 patients, well matched for age, gender, working activity and grade of hemorrhoids, were randomized to two groups: Ligasure 146, and diathermy 127. The severity of postoperative anal pain was significantly less in the Ligasure group when measured at least 12 hours after defecation (P < 0.01), whereas it was similar at the time of defecation. The Ligasure group had significantly lower requirements for painkiller pills. There were no significant differences in early and late complications. Return to work and normal activities was significantly faster in the Ligasure group.\n Ligasure hemorrhoidectomy is an effective procedure for Grades III and IV hemorrhoids and facilitates a faster return to work and normal activities by reducing postoperative pain.", "The study was designed to compare LigaSure haemorrhoidectomy with open haemorrhoidectomy performed by means of diathermy excision. Fifty-sixty consecutive patients with third- and fourth-degree haemorrhoids were randomly allocated to undergo either LigaSure haemorrhoidectomy (29 patients) or diathermy haemorrhoidectomy (27 patients). All patients were evaluated for operative time, pain, post-operative analgesic requirements, time to first bowel movement, length of hospital stay, wound healing period, time to return to work, and occurrence of early postoperative complications (such as urinary dysfunction, bleeding, soiling, seepage, continence disorders) and late complications (such as stenosis). A statistically significant advantage was observed in the patients who received the LigaSure technique as far as concerns length of operative time (9.2 vs. 12.2 min, p<0.001), post-operative analgesic requirements (14.1 vs. 16.8 administrations, p<0.001), wound healing period (16.3 vs. 37.5 days, p< 0.0001), and time to return to work (8.3 vs. 18.3 days, p<0.01). No significant difference was seen in the postoperative pain score, complications rate, first bowel motion or hospital stay. No recurrence was observed at the 6-month follow-up. In conclusion, our experience shows that the LigaSure haemorrhoidectomy offers definite advantages over the classic diathermy technique. This procedure is easier, safer, and more rapid to perform and is followed by a faster wound healing time, a significantly shorter hospital stay, less postoperative pain and faster wound healing.", "To compare the operative time, postoperative complications, and analgesic requirement between closed hemorrhoidectomy and Ligasure hemorrhoidectomy.\n The study was conducted in a prospectively randomized controlled fashion. Forty-seven patients with grade 3 or 4 hemorrhoids plus external component or skin tag were operated on by either hemorrhoidectomy with Ligasure (24 patients) or closed hemorrhoidectomy (23 patients). One patient in each group was lost to follow up. The operative time, postoperative verbal numeric pain score, analgesic requirement, bleeding, and wound dehiscence between the two groups were compared Unpaired t-tests, Mann-Whitney U tests, or Fisher's Exact tests were used where appropriate.\n Demographic and clinical data between two groups were comparable. Operative time for the Ligasure hemorrhoidectomy was significantly shorter than the closed hemorrhoidectomy group (21.70 +/- 11.76 vs 35.68 +/- 14.25 min, p < 0. 001), while the number of resected hemorrhoids in the study group were 2.91 versus 2.18 in the control group. However, there were no differences in post-operative pain score, analgesic requirement, bleeding, or wound dehiscence between the two groups.\n Ligasure hemorrhoidectomy is superior to closed hemorrhoidectomy in terms of reducing the operative time without affecting postoperative complications.", "To evaluate the efficacy of the Ligasure system in the management of haemorrhoids.\n Unblinded randomised clinical trial.\n Teaching hospital, Spain.\n 112 patients with third and fourth degree haemorrhoids.\n For 56 patients we used Ligasure system and a variant of Milligan and Morgan's technique. For the other 56, we used the traditional technique.\n Postoperative pain.\n Operating times varied from 100 seconds for each haemorrhoidal cushion with Ligasure system to the 313 seconds by the traditional technique. The blood loss was not quantifiable in patients operated on with Ligasure. Pain was scored on a visual analogue scale. In the Ligasure group, the mean scores were 4.9 (immediate postoperative period) and 2.3 (24 hours later). In the other group, the scores were 7.8 and 6.9. These differences were significant.\n Haemorrhoidectomy using Ligasure as a technical variant of Milligan and Morgan's technique has important advantages.", "The aim of this randomized prospective trial was to compare LigaSure and conventional diathermy haemorrhoidectomy.\n Two hundred and eighty-four patients with grade III or IV haemorrhoids were randomized to LigaSure or diathermy (Milligan-Morgan) haemorrhoidectomy as a day-case procedure. Operating time, postoperative pain score, hospital stay, postoperative complications, wound healing time and time to return to normal activities were assessed. Thirty-four patients were lost to follow-up.\n The mean operating time for LigaSure haemorrhoidectomy was significantly shorter than that for diathermy (P = 0.011). Patients treated with LigaSure had significantly less postoperative pain (measured on a visual analogue scale; P = 0.010), a shorter wound healing time (defined as time to absence of swelling; P = 0.012) and less time off work (P = 0.010) than patients who had diathermy. Neither postoperative complications nor mean hospital stay (day-case surgery) were significantly different.\n LigaSure haemorrhoidectomy demonstrates simplicity, reproducibility, a low complication rate, fast wound healing, a quick return to work and reduced postoperative pain.\n Copyright (c) 2007 British Journal of Surgery Society Ltd.", "This study was designed to compare the surgical outcomes of hemorrhoidectomy performed by the Ligasure with that performed by the conventional diathermy.\n A total of 110 patients were randomized to Ligasure (55 patients) or diathermy (55 patients) hemorrhoidectomy. The operative time, postoperative pain scores, parenteral analgesic requirements in the first 24 hours, postoperative complications, and wound healing rates at six weeks postoperatively were documented.\n The median operative time was 8 (range, 7-10) minutes for the Ligasure group and 18 (range, 15-21) minutes for the diathermy group (P < 0.001). Throughout the first postoperative week, the daily median pain score was lower in the Ligasure group than in the diathermy group (P < 0.001). The median number of analgesic ampoules during the first 24 hours postoperatively was lower in the Ligasure group (P < 0.001). There was no statistically significant difference in the incidence of postoperative complications. At six weeks postoperatively, more patients in the Ligasure group had complete healing of wounds (P = 0).\n Ligasure provides a superior alternative to conventional diathermy in hemorrhoidectomy by reducing the operative time, postoperative pain, parenteral analgesic requirements during the first 24 hours postoperatively, and the time to complete healing of wounds.", "Postoperative pain associated with open haemorrhoidectomy remains problematic. Haemorrhoidectomy performed using bloodless bipolar diathermy--Ligasure--may have advantages over conventional open haemorrhoidectomy in terms of operating time and postoperative pain.\n Thirty-four patients were randomized to undergo Ligasure (18 patients) or diathermy (16) haemorrhoidectomy. The operating time, amount of pain and postoperative analgesic requirement, postoperative complications and overall patient satisfaction were documented.\n The median duration of operation was shorter in the Ligasure haemorrhoidectomy group (5.1 versus 9.2 min; P < 0.001). There was no statistically significant difference in the postoperative pain score, but the median analgesic requirement was lower in the Ligasure group (850 versus 1600 mg tramadol; P = 0.013). Patient satisfaction was similar in both groups.\n Ligasure haemorrhoidectomy is quick and bloodless and, although as painful as diathermy haemorrhoidectomy, is associated with a reduced analgesic requirement.", "Ligasure haemorrhoidectomy is an effective treatment for prolapsing haemorrhoids, however, concerns exist regarding potential damage to the anal sphincters.\n Patients previously included into a randomized trial comparing open and Ligasure haemorrhoidectomy were contacted by postal questionnaire to evaluate their overall satisfaction and continence at 12 months post operatively.\n Thirteen patients who underwent open and 17 who underwent Ligasure haemorrhoidectomy were evaluated. Three patients from the open group and 2 from the Ligasure group were unhappy with the result (P = 0.37) and minor incontinence was reported in 5 Ligasure and 2 open patients (P = 0.42).\n Patient satisfaction and post operative continence scores at 1 year post operatively are comparable for open and Ligasure haemorrhoidectomy.", "Ligasure haemorrhoidectomy has short-term benefits over conventional diathermy haemorrhoidectomy. The current study aimed to determine the long-term efficacy of Ligasure haemorrhoidectomy.\n Forty patients, previously randomised to Ligasure or diathermy haemorrhoidectomy in 2002, were invited to participate in the study. Haemorrhoidal symptoms and patient satisfaction were recorded. Incontinence was quantified and sphincter anatomy and function assessed by endoanal ultrasound and anorectal manometry.\n Thirty (75%) patients participated in the study (14 Ligasure, 16 conventional). There was no difference in age, sex distribution, or length of follow-up (Ligasure : 37 months; conventional: 36 months) between the groups. Both techniques achieved good symptom control, but with a trend to less recurrent bleeding following Ligasure. Incontinence scores and patient satisfaction were similar. A significant difference was observed in internal sphincter thickness (Ligasure : 2.5 mm, 2.2-2.8 (mean, 95%CI) vs conventional: 1.88 mm, 1.7-2.1, P = 0.005) and rectal urge sensation (Ligasure : 284 mls, 211-378 vs conventional: 173 mls, 129-217, P = 0.08).\n Ligasure is as effective as conventional diathermy haemorrhoidectomy in achieving long-term symptom control. Less radical haemorrhoidal excision with the Ligasure could explain the differences in internal sphincter thickness and urge sensation, and might make it the preferred method for patients with compromised sphincter function.", "Milligan-Morgan excision haem-orrhoidectomy remains a very popular treatment modality for third and fourth degree haemorrhoids due to its cost effectiveness and good long-term results. The LigaSure tissue-sealing device is an alternative technique used in haemorrhoidectomy that has been shown to produce favourable results. The aim of this study was to assess the effectiveness of the LigaSure tissue sealing device in comparison with conventional diathermy haemorrhoidectomy.\n A prospective clinical trial was conducted. Patients with newly diagnosed haemorrhoids requiring haemorrhoidectomy were randomized to either LigaSure haemorrhoidectomy or diathermy haemorrhoidectomy. Surgical technique and postoperative care was standardized. Outcome measures were operative time and bleeding, postoperative pain (measured on a visual analogue scale) and rate of wound healing.\n We randomized 44 patients, 22 to LigaSure and 22 to diathermy; 43 patients were evaluated. They were aged between 19 and 71 years. There were no differences in patient demographics or type of haemorrhoid being operated on. LigaSure haemorrhoidectomy had a significantly lower mean operative time and intraoperative bleeding. At 3 weeks after surgery, haemorrhoidectomy performed with LigaSure had an odds ratio for complete epithelialization of 3.1 over diathermy (95% CI 1.2-8.2). There was no difference in postoperative pain.\n LigaSure haemorrhoidectomy is superior to diathermy for open haemorrhoidectomy.", "Hemorrhoidectomy is frequently associated with significant postoperative pain, and new techniques to reduce this pain are constantly under evaluation. The present study was conducted to determine the usefulness of the Ligasure system and compare it with conventional diathermy for hemorrhoidectomy.\n Thirty-four consecutive patients with Grade 3 or 4 hemorrhoids requiring surgery were recruited and randomized into two groups by preoperative assignment of sealed envelopes. Patients with coexisting perianal disease, previous perianal surgery, or thrombosed hemorrhoids were excluded. All patients were anesthetized and operated on by a single team. In one group, monopolar diathermy in the coagulation mode was used to dissect hemorrhoidal tissue from the internal sphincter. In the second group, tissue was coagulated by Ligasure and then divided with scissors. Operating time was documented by theater staff. Postoperatively, pain scores and Cleveland Clinic incontinence scores were documented.\n Seventeen patients were randomized into each group. There were no significant differences in age, gender, or clinical symptoms between the groups. The mean operating time in the Ligasure group was 6 (range, 4-10) minutes compared with 11 (range, 7-20) minutes in the other group, and this was statistically significant (P < 0.001). Patients in the Ligasure group reported significantly less pain with first defecation and at postoperative Days 1 and 14 (P < 0.001). The mean hospital stay in both groups was one (range, 1-5) day, and there was no difference in the incontinence scores.\n Ligasure diathermy provides a superior alternative to conventional diathermy in hemorrhoidectomy by reducing operating time and postoperative pain.", "The aim of this study was to compare the outcomes between the LigaSure vessel sealing system and the conventional closed Ferguson hemorrhoidectomy procedure performed by diathermy.\n A series of 84 patients with grades III and IV hemorrhoids were randomized into two groups: (1) LigaSure hemorrhoidectomy with submucosal dissection (42 patients) and (2) Ferguson hemorrhoidectomy (42 patients). The patient demographics, operative details, parenteral analgesic requirement, postoperative pain score (assessed by an independent assessor), operating time, intraoperative blood loss, hospital stay, early and delayed complications, and time off from work or normal activity were recorded. The patients were regularly followed up at 1, 2, 4, 6, and 8 weeks after surgery.\n There were no statistically significant differences between the two groups in terms of age, gender, duration of symptoms, grade of the hemorrhoid(s), or number of hemorrhoids resected. The mean operating time for LigaSure hemorrhoidectomy with submucosal dissection was significantly shorter than that for the Ferguson hemorrhoidectomy (11.3 +/- 0.4 vs. 34.2 +/- 0.7 minutes; P < 0.0001). Patients treated with the LigaSure method had significantly less blood loss (P < 0.0001), a better pain score (P < 0.0001), less parenteral analgesic requirement (P < 0.0001), shorter hospital stay (P < 0.0001), and less time off from work or normal activity (P < 0.0001). There was no difference in the early and delayed postoperative complications between the two groups.\n LigaSure hemorrhoidectomy with submucosal dissection is a safe, effective procedure for grade III and IV hemorrhoids. Patients derive greater short-term benefits: reduced intraoperative blood loss, operating time, and postoperative pain as well as earlier resumption of work or normal activity. Long-term follow-up with a larger number of patients is required to confirm the long-term results of this procedure.", "Haemorrhoidectomy is frequently associated with postoperative pain and prolonged hospital stay. A new technique of haemorrhoidectomy using the Ligasure device suited to day-case surgery is described. This technique was compared with conventional open diathermy haemorrhoidectomy.\n Forty patients with grade III or IV haemorrhoids were randomized to Ligasure (group 1) or conventional diathermy (group 2) haemorrhoidectomy. Operative details were recorded and patients recorded daily pain scores on a linear analogue scale. Follow-up was at 1, 3, 6 and 12 weeks to evaluate complications, return to normal activity, ongoing symptoms and patient satisfaction.\n Reduced intraoperative blood loss (median (range) 0 (0-5) ml versus 20 (12-22) ml; P < 0.001) and a shorter operating time (10 (8-11) versus 20 (18-25) min; P < 0.001) was observed in group 1 compared with group 2. More patients in group 1 were discharged on the day of operation (18 of 20 versus 11 of 20; P < 0.05) and there was a trend towards lower postoperative pain scores on day 1 (group 1 median 5 (95 per cent confidence interval (c.i.) 2.6 to 6.8) versus group 2 7 (95 per cent c.i. 4.2 to 7.7); P = 0.36). There was no difference between the two groups in the degree of patient satisfaction or number of postoperative complications.\n Ligasure diathermy may be used safely in the treatment of patients with grade III or IV haemorrhoids. It reduces intraoperative blood loss and operating time, and facilitates same-day discharge." ]

[ "9834259", "10233192", "17944740" ]

[ "Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: a controlled study in normal subjects.", "Bedtime ranitidine does not eliminate the need for a second daily dose of omeprazole to suppress nocturnal gastric pH.", "Clinical trial: the effects of adding ranitidine at night to twice daily omeprazole therapy on nocturnal acid breakthrough and acid reflux in patients with systemic sclerosis--a randomized controlled, cross-over trial." ]

[ "Proton pump inhibitors administered twice daily do not provide complete nocturnal acid suppression. Acid breakthrough, or decrease in intragastric pH to <4 for an hour or longer, occurs in three quarters of normal subjects and patients at night. We compared the effect of a third dose of omeprazole at bedtime with that of a dose of ranitidine at bedtime on residual nocturnal acid secretion in patients receiving omeprazole twice daily.\n Twelve volunteers underwent overnight intragastric pH monitoring after 7 days of treatment with omeprazole, 20 mg twice daily, followed by different treatment supplements at bedtime: placebo; additional omeprazole, 20 mg; ranitidine, 150 mg; and ranitidine, 300 mg.\n Additional omeprazole at bedtime reduced the percentage of time with intragastric pH of <4 from 48% to 31% (P < 0.005) compared with omeprazole twice daily with placebo at bedtime. Ranitidine at bedtime reduced this parameter more, 5% with 150 mg and 6% with 300 mg (P <0.01 vs. omeprazole twice daily plus bedtime). Results for percentage of time with intragastric pH <3 were similar. Eleven subjects had acid breakthrough with placebo at bedtime; 7 with omeprazole at bedtime (P = NS); 4 with ranitidine, 150 mg at bedtime; and 3 with ranitidine, 300 mg at bedtime (P < 0. 05, ranitidine vs. placebo).\n Bedtime ranitidine is more effective than bedtime omeprazole on residual nocturnal acid secretion in patients receiving omeprazole twice daily. This finding suggests that fasting breakthrough nocturnal acid secretion in patients receiving omeprazole twice daily is most likely histamine related.", "We have previously shown that 70% of patients experience nocturnal gastric acid breakthrough (defined as pH<4 for more than 60 min between 22.00 and 06.00 hours) on twice a day (b.d.) proton pump inhibitor. Adding 150 or 300 mg of ranitidine at bedtime is more effective than additional omeprazole at bedtime in control of night-time acid breakthrough.\n To assess whether omeprazole 20 mg AM plus ranitidine 150 mg HS would be as effective as omeprazole 20 mg before breakfast and dinner (b.d. AC) in intragastric pH control, particularly during the overnight period.\n Twenty healthy volunteers (11 males, 9 females, mean age 32.7 years) were treated with omeprazole (OME) 20 mg b.d. AC and placebo HS or omeprazole 20 mg AM and placebo before dinner plus ranitidine (RAN) 150 mg HS for 7 days, in a randomized, double-blind, crossover design, with a 1 week washout between study periods. On day 8 subjects were monitored for 24 h with a single channel pH probe placed in the stomach 10 cm below the proximal border of the LES. Percentage time pH<4 for total, upright and recumbent positions were compared between the two regimens using Wilcoxon matched pairs testing.\n Expressed in median values of percentage time pH<4: upright time intragastric pH<4 on OME 20 mg b.d. AC was 18.9 compared to 29.7 on OME AM + RAN HS (P = 0.003). Recumbent time pH<4 on OME 20 mg b.d. AC was 23.45 compared to 44.75 on OME AM + RAN HS (P = 0.02).\n Bedtime ranitidine does not eliminate the need for an evening dose of omeprazole to control intragastric pH in patients requiring more than a single daily dose of omeprazole.", "Gastro-oesophageal reflux disease (GERD) is an important problem in systemic sclerosis due to impaired salivation and oesophageal function.\n To determine the efficacy of adding ranitidine at bedtime to control nocturnal acid breakthrough (NAB) and GERD in patients with systemic sclerosis already prescribed high-dose omeprazole.\n Patients with systemic sclerosis and GERD symptoms (n = 14) were treated with omeprazole 20 mg b.d. and either placebo or ranitidine 300 mg at bedtime for 6 weeks in a randomized, cross-over, placebo controlled study. At the end of each period a 24 h pH-study with intragastric and oesophageal pH measurement was performed.\n Pathological acid reflux occurred in eight patients with omeprazole/placebo and in seven with omeprazole/ranitidine (P = ns) with technically adequate oesophageal pH-studies (n = 13). NAB was present in eight patients with omeprazole/placebo and six with omeprazole/ranitidine (P = ns) in whom technically adequate gastric pH-studies were obtained (n = 10). The addition of ranitidine had no consistent effect on patient symptoms or quality of life.\n Many patients with systemic sclerosis experienced NAB and pathological oesophageal acid exposure despite high-dose acid suppression with omeprazole b.d. Adding ranitidine at bedtime did not improve NAB, GERD or quality of life in this population." ]

[ "11584487", "4948652", "17621727", "12850618", "17957907", "14712970", "11165579", "11275030", "7573262", "8623811", "14125507", "8041539", "17318558", "2047064", "19250006", "12233808", "13827111", "11303547", "14649969", "18272271", "14116305", "11843784", "19127781", "15051552", "14566347" ]

[ "Effect of acupressure on nausea and vomiting during pregnancy. A randomized, placebo-controlled, pilot study.", "Double-blind evaluation of hydroxyzine as an antiemetic in pregancy.", "Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial.", "A randomized controlled trial of nerve stimulation for relief of nausea and vomiting in pregnancy.", "A randomized comparison of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy.", "Effect of a ginger extract on pregnancy-induced nausea: a randomised controlled trial.", "Effect of acupuncture on nausea of pregnancy: a randomized, controlled trial.", "Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial.", "Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial.", "Efficacy of P6 acupressure in the treatment of nausea and vomiting during pregnancy.", "A DOUBLE BLIND STUDY OF FLUPHENAZINE WITH PYRIDOXINE.", "Acupressure for nausea and vomiting of pregnancy: a randomized, blinded study.", "Acupressure and vitamin B6 to relieve nausea and vomiting in pregnancy: a randomized study.", "Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study.", "Effects of ginger capsules on pregnancy, nausea, and vomiting.", "Ginger syrup as an antiemetic in early pregnancy.", "Bendectin in the treatment of nausea and vomiting in pregnancy.", "Acupressure treatment of morning sickness in pregnancy. A randomised, double-blind, placebo-controlled study.", "A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy.", "Comparing ginger and vitamin B6 for the treatment of nausea and vomiting in pregnancy: a randomised controlled trial.", "NAUSEA AND VOMITING IN PREGNANCY: A TRIAL OF THIETHYLPERAZINE.", "Acupuncture to treat nausea and vomiting in early pregnancy: a randomized controlled trial.", "Effectiveness of auricular acupressure in the treatment of nausea and vomiting in early pregnancy.", "A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy.", "Comparison of three outpatient regimens in the management of nausea and vomiting in pregnancy." ]

[ "To compare the antiemetic effect of acupressure at the Neiguan point (P6) in a group of healthy women with normal pregnancy and nausea and vomiting during pregnancy (NVP) with a similar group receiving acupressure at a placebo point and another, similar group not receiving any treatment.\n A randomized, placebo-controlled, pilot study involving 60 women.\n It is possible to reduce NVP significantly with acupressure at P6 as compared to acupressure at a placebo point or no treatment at all in healthy women with normal pregnancies. Relief from nausea appeared one day after starting treatment in both the P6 and placebo groups but lasted for only six days in the placebo group. The P6 group, however, experienced significantly less nausea after 14 days as compared to the other two groups.\n This study involved 60 healthy women with normal pregnancy and suffering from NVP. According to the results, in healthy women with normal pregnancy it is possible to reduce NVP significantly at P6 as compared to acupressure at a placebo point and to no treatment.", "nan", "To compare the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in pregnancy.\n Randomized double-blind controlled trial.\n Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital.\n One hundred and twenty-six pregnant women, with a gestational age of < or = 16 weeks who had nausea and vomiting, required anti-emetics, had no medical complication, and were not hospitalized. Pregnant women were randomly allocated to receive either 650 mg of ginger or 25 mg of vitamin B6. They were given three times per day for 4 days. The degree of nausea and vomiting were assessed by three physical symptoms of Rhode's score (episodes of nausea, duration of nausea and number of vomits). These were recorded 24 hours before treatment for baseline and each subsequent day of treatment. Difference of baseline and post-treatment nausea vomiting scores were calculated for both groups during 4 days of treatment.\n One hundred and twenty-three women returned to follow-up. Ginger and vitamin B6 significantly reduced nausea and vomiting scores from 8.7 +/- 2.2 to 5.4 +/- 2.0 and 8.3 +/- 2.5 to 5.7 +/- 2.3 respectively, (p < 0.05). The mean score change after treatment with ginger was greater than with vitamin B6 (3.3 +/- 1.5 versus 2.6 +/- 1.3), (p < 0.05). There were some minor side effects in both groups 25.4% and 23.8% (p = 0.795) respectively, such as sedation, heartburn, arrhythmia.\n Both ginger and vitamin B6 were effective for treatment of nausea and vomiting in pregnancy. Moreover, ginger was more effective than vitamin B6. Side effects from ginger were reported to be minor and did not need any treatment.", "To evaluate the effectiveness of low-level nerve stimulation therapy over the volar aspect of the wrist at the P6 point to treat nausea and vomiting in early pregnancy.\n Pregnant volunteers (n = 230) with symptoms of mild to severe nausea and vomiting between 6 and 12 weeks' gestation participated in a 21-day clinical trial. Participants were randomly assigned to receive a device for nerve stimulation therapy or an otherwise identical but nonstimulating placebo device. The primary outcome measure was self-recorded symptoms according to the Rhodes Index of Nausea, Vomiting, and Retching (Rhodes Index). Secondary outcome measures were medication use, weight gain, and presence of urinary ketones.\n Baseline characteristics were similar in both groups. A total of 187 women (81%) completed the trial. Pretreatment Rhodes Index scores for the entire population demonstrated no significant differences between study and control groups. The time-averaged change in Rhodes Index total experience of 6.48 for the study group was significantly better than the control value of 4.65 (P =.02). Study patients gained more weight than controls (2.9 versus 1.2 lb, P =.003). There were no statistically significant differences in medication use or urinary ketone measurements.\n Nerve stimulation therapy is effective in reducing nausea and vomiting and promoting weight gain in symptomatic women in the first trimester of pregnancy.", "To study the efficacy of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy.\n Double blind randomized controlled trial.\n Department of Obstetrics and Gynecology, Thammasat Hospital, Faculty of Medicine, Thammasat University.\n Between January 2005 and December 2005, 170 pregnant women who attended at antenatal clinic Thammasat University Hospital with the symptoms of nausea and vomiting in pregnancy were randomly allocated into group A (n = 85) and group B (n = 85). The patients in group A received one capsule of ginger twice daily (one capsule contained 0.5 gm of ginger powder) while the patients in group B received the identical capsule of 50 mg dimenhydrinate twice daily. The visual analogue nausea scores (VANS) and vomiting times were evaluated at day 0-7 of the treatment.\n There was no significant difference in the visual analogue nausea scores (VANS) between group A and group B in day 1-7 of the treatment. The vomiting episodes of group A were greater than group B during the first and second day of the treatment with statistically significant difference. No difference in vomiting episodes during the day 3-7 of treatment was found in both groups. There was a statistically significant difference in the side effect of drowsiness after treatment in group B greater (77.64%) than group A (5.88%) (p < 0.01).\n From the presented data, ginger is as effective as dimenhydrinate in the treatment of nausea and vomiting during pregnancy and has fewer side effects.", "To investigate the effect of a ginger extract (EV.EXT35) on the symptoms of morning sickness.\n Double-blind randomised placebo-controlled trial.\n A tertiary metropolitan teaching hospital, March 1999-November 1999.\n The participants included 120 women less than 20 weeks pregnant, who had experienced morning sickness daily for at least a week and had had no relief of symptoms through dietary changes.\n Random allocation of 125 mg ginger extract (EV.EXT35; equivalent to 1.5 g of dried ginger) or placebo given four times per day for 4 days.\n Nausea, vomiting and retching as measured by the Rhodes Index of Nausea, Vomiting and Retching.\n The nausea experience score was significantly less for the ginger extract group relative to the placebo group after the first day of treatment and this difference was present for each treatment day. Retching was also reduced by the ginger extract although to a lesser extent. No significant effect was observed on vomiting. Follow-up of the pregnancies revealed normal ranges of birthweight, gestational age, Apgar scores and frequencies of congenital abnormalities when the study group infants were compared to the general population of infants born at the Royal Hospital for Women for the year 1999-2000.\n Ginger can be considered as a useful treatment option for women suffering from morning sickness.", "To compare acupuncture with sham (placebo) acupuncture for treatment of nausea of pregnancy.\n In a subject- and observer-masked, randomized, controlled trial in the maternity unit at Exeter Hospital, we gave 55 women between 6 and 10 weeks' gestation genuine, traditional-style acupuncture or sham treatment with a cocktail stick on three or four occasions over 3 weeks. The main outcome measure was nausea score, as determined by subject report on a visual analogue scale in a daily diary. Anxiety and depression also were assessed.\n Nausea scores decreased from a median of 85.5 (interquartile range 71.25-89.75) to 47.5 (interquartile range 29.25-69.5) in the acupuncture group and from 87.0 (interquartile range 73.0-90.0) to 48.0 (interquartile range 14.0-80.0) in the sham treatment group. There was strong evidence of a time effect (P <.001) but no evidence of a group effect (P =.9) or a group-time interaction (P =.8). Similarly, there was evidence of time effects in scores for anxiety and depression but no group differences. The study had a power of 95% to detect significant differences in nausea scores.\n Acupuncture was as effective in treating nausea of pregnancy as a sham procedure.", "To determine the effectiveness of ginger for the treatment of nausea and vomiting of pregnancy.\n Women with nausea and vomiting of pregnancy, who first attended an antenatal clinic at or before 17 weeks' gestation, were invited to participate in the study. During a 5-month period, 70 eligible women gave consent and were randomized in a double-masked design to receive either oral ginger 1 g per day or an identical placebo for 4 days. Subjects graded the severity of their nausea using visual analog scales and recorded the number of vomiting episodes in the previous 24 hours before treatment, and again during 4 consecutive days while taking treatment. At a follow-up visit 7 days later, five-item Likert scales were used to assess the severity of their symptoms.\n All participants except three in the placebo group remained in the study. The visual analog scores of posttherapy minus baseline nausea decreased significantly in the ginger group (2.1 +/- 1.9) compared with the placebo group (0.9 +/- 2.2, P =.014). The number of vomiting episodes also decreased significantly in the ginger group (1.4 +/- 1.3) compared with the placebo group (0.3 +/- 1.1, P <.001). Likert scales showed that 28 of 32 in the ginger group had improvement in nausea symptoms compared with 10 of 35 in the placebo group (P <.001). No adverse effect of ginger on pregnancy outcome was detected.\n Ginger is effective for relieving the severity of nausea and vomiting of pregnancy.", "Our purpose was to determine the effectiveness of pyridoxine for nausea and vomiting of pregnancy.\n During an 11-month period 342 women who first attended Chiang Mai University Hospital antenatal clinic at < or = 17 weeks' gestation were randomized to received either oral pyridoxine hydrochloride, 30 mg per day, or placebo in a double-blind fashion. Patients graded the severity of their nausea by a visual analog scale and recorded the number of vomiting episodes over the previous 24 hours before treatment and again during 5 consecutive days on treatment.\n There was a significant decrease in the mean of posttherapy minus baseline nausea scores in the pyridoxine compared with that in the placebo group (t test, p = 0.0008). There was also a greater reduction in the mean number of vomiting episodes, but the differences did not reach statistical significance (p = 0.0552).\n Pyridoxine is effective in relieving the severity of nausea in early pregnancy.", "Our purpose was to investigate the efficacy of P6 acupressure in reducing or relieving symptoms of nausea with or without vomiting and retching during pregnancy.\n Symptomatic pregnant volunteers (n=161) participated in a 7-day community-based clinical trial. All participants were assigned to one of three groups (i.e., P6 acupressure, placebo [acupressure bands inappropriately placed], or control) on the basis of a process of blocked randomization. Data were analyzed by error bar charts and analysis of variance of difference scores.\n Of 161 women, 149 (92.5%) completed the protocol. Irrespective of group assignment, participants reported significant decreases in nausea (p<0.0009) and vomiting or retching (p<0.0009). However, there was no differential treatment effect as a result of acupressure.\n There was no apparent medical benefit from the use of P6 acupressure. Our findings differ from other recently published studies that did not include a control group.", "nan", "To evaluate the effectiveness of acupressure in reducing nausea and vomiting of pregnancy.\n Symptomatic pregnant women were randomized to one of two acupressure groups: one treatment group using an acupressure point (PC-6) and one sham control group using a placebo point. Subjects were blind to the group assignment. Each evening for 10 consecutive days, the subjects completed an assessment scale describing the severity and frequency of symptoms that occurred. Data from the first 3 days were used as pre-treatment scores. Beginning on the morning of the fourth day, each subject used acupressure at her assigned point for 10 minutes four times a day. Data from day 4 were discarded to allow 24 hours for the treatment to take effect. Data from days 5-7 were used to measure treatment effect.\n Sixty women completed the study. There were no differences between groups in attrition, parity, fetal number, maternal age, gestational age at entry, or pre-treatment nausea and emesis scores. Analysis of variance indicated that both groups improved significantly over time, but that nausea improved significantly more in the treatment group than in the sham control group (F1,58 = 10.4, P = .0021). There were no differences in the severity or frequency of emesis between the groups. There was a significant positive correlation (r = 0.261, P = .044) between maternal age and severity of nausea.\n Our results indicate that acupressure at the PC-6 anatomical site is effective in reducing symptoms of nausea but not frequency of vomiting in pregnant women.", "To compare the effectiveness of acupressure and vitamin B6 in the outpatient treatment of nausea and vomiting in early pregnancy.\n Pregnant volunteers with symptoms of mild to moderate nausea and vomiting between 6 and 12 weeks' gestation participated in a 7-day clinical trial. Participants were randomly assigned to receive a device for acupressure therapy and placebo drug or an otherwise identical but non-stimulating placebo device and vitamin B6. The primary outcome measure was self-recorded symptoms according to Rhodes index. Secondary outcome measures were weight gain and medication use.\n The mean change in Rhodes index was not significantly different between the two groups. There were no statistically significant differences in weight gain and medication use between the two groups.\n Acupressure therapy is not more effective than vitamin B6 in reducing nausea and vomiting in symptomatic women in the first trimester of pregnancy.", "Fifty-nine women completed a randomized, double-blind placebo-controlled study of pyridoxine hydrochloride (vitamin B6) for the treatment of nausea and vomiting of pregnancy. Thirty-one patients received vitamin B6, 25-mg tablets orally every 8 hours for 72 hours, and 28 patients received placebo in the same regimen. Patients were categorized according to the presence of vomiting: severe nausea (score greater than 7) or mild to moderate nausea (score of 7 or less). The severity of nausea (as graded on a visual analogue scale of 1-10 cm) and the number of patients with vomiting over a 72-hour period were used to evaluate response to therapy. Twelve of 31 patients in the vitamin B6 group had a pre-treatment nausea score greater than 7 (severe) (mean 8.2 +/- 0.8), as did ten of 28 patients in the placebo group (mean 8.7 +/- 0.9) (not significant). Following therapy, there was a significant difference in the mean \"difference in nausea\" score (ie, baseline - post-therapy nausea) between patients with severe nausea receiving vitamin B6 (mean 4.3 +/- 2.1) and placebo (mean 1.8 +/- 2.2) (P less than .01). In patients with mild to moderate nausea and in the group as a whole, no significant difference between treatment and placebo was observed. Fifteen of 31 vitamin B6-treated patients had vomiting before therapy, compared with ten of 28 in the placebo group (not significant). At the completion of 3 days of therapy, only eight of 31 patients in the vitamin B6 group had any vomiting, compared with 15 of 28 patients in the placebo group (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)", "The aim of this study was to determine the effects of ginger in nausea and vomiting of pregnancy.\n This was a single blind clinical trial study.\n The study was conducted in a selected prenatal care clinic of Isfahan City hospitals.\n The subjects included 67 pregnant women who complained of nausea and vomiting from Isfahan city hospitals participated in the study.\n The participants were randomly assigned to two groups, an experimental group and a control group. The groups were matched according to the age, gestational age, parity, occupational status, and educational level of the participants. The experimental group received ginger 250 mg capsules for 4 days, and the control group received placebo with the same prescription form.\n Effects of treatment of nausea were evaluated twice daily for 4 days by a before-and-after treatment questionnaire.\n The mean ages of the experimental and control groups were 24.1 +/- 4.8 and 23.3 +/- 5 years, respectively. The mean gestational age was 13 +/- 3 weeks, and the mean parity was 1.6 +/- 0.8. The ginger users demonstrated a higher rate of improvement than the placebo users did (85% versus 56%; p < 0.01). The decrease in vomiting times among ginger users was also significantly greater than among the women who received the placebo (50% versus 9%; p < 0.05).\n A daily total of 1000 mg of ginger in a capsule preparation can be suggested by care providers as a means of decreasing pregnancy nausea and vomiting in women who tend to herbal medicines.\n Ginger is an effective herbal remedy for decreasing nausea and vomiting during pregnancy.", "Ginger (Zingiber officinale) has been used to ameliorate symptoms of nausea. A beverage containing ginger in a syrup may be easier to consume than a capsule or solid food.\n To determine if ginger syrup mixed in water is an effective remedy for the relief of nausea and vomiting in the first trimester of pregnancy.\n Double-blind, placebo-controlled, randomized clinical trial.\n Subjects were enrolled from the University of South Florida department of obstetrics and gynecology private practice office.\n 26 subjects in the first trimester of pregnancy.\n Subjects ingested 1 tablespoon of commercially prepared study syrup (or placebo) in 4 to 8 ounces of hot or cold water 4 times daily.\n Duration and severity of nausea and vomiting over a 2-week period measured on a 10-point scale.\n After 9 days, 10 of the 13 (77%) subjects receiving ginger had at least a 4-point improvement on the nausea scale. Only 2 of the 10 (20%) remaining subjects in the placebo group had the same improvement. Conversely, no woman in the ginger group, but 7 (70%) of the women in the placebo group, had a 2-point or less improvement on the nausea scale. Eight of the 12 (67%) women in the ginger group who were vomiting daily at the beginning of the treatment stopped vomiting by day 6. Only 2 of the 10 (20%) women in the placebo group who were vomiting stopped by day 6.\n The ingestion of 1 g of ginger in syrup in a divided dose daily may be useful in some patients experiencing nausea and vomiting in the first trimester of pregnancy.", "nan", "To find out whether acupressure wristband can alleviate nausea and vomiting in early pregnancy.\n Double-blind, placebo-controlled study.\n 97 women with mean gestational length completed 8-12 weeks.\n Symptoms were recorded according to intensity, duration and nature of complaints.\n 71% of women in the intervention group reported both less intensive morning sickness and reduced duration of symptoms. The same tendency was seen in the placebo group, with 59% reporting less intensity and 63% shorter duration of symptoms. However, a significance level of 5% was reached only in the case of duration of symptoms, which was reduced by 2.74 hours in the intervention group compared to 0.85 hours in the placebo group (p = 0.018).\n Acupressure wristband might be an alternative therapy for morning sickness in early pregnancy, especially before pharmaceutical treatment is considered.", "To compare the efficacy of ginger to vitamin B6 in the treatment of nausea and vomiting of pregnancy.\n A randomized double-blind controlled trial.\n The Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital.\n Women with nausea and vomiting of pregnancy at or before 16 weeks of gestation, who attended the antenatal care clinic. The subjects requested anti-emetics, had no medical complications, non-hospitalized and were able to attend a one week follow-up visit. From November, 1999 to November 2000, 138 women participated and gave consent for the study.\n The subjects were randomly allocated into two groups to take either 500 mg of ginger orally or an identical 10 mg of vitamin B6 one capsule three times daily for three days. Subjects graded the severity of their nausea using visual analogue scales before treatment and recorded the number of vomiting episodes in the previous 24 hours and again during three consecutive days of treatment.\n The change of nausea scores and the number of vomiting episodes during three days of treatment.\n The 64 subjects in each group remained in the study. The demographic data were comparable in both groups. The ginger and vitamin B6 significantly reduced the nausea scores from 5.0 (SD, 1.99) to 3.6 (SD, 2.48) and 5.3 (SD, 2.08) to 3.3 (SD, 2.07) respectively, with p < 0.001. The mean score change after treatment with ginger was 1.4 (2.21), less than with vitamin B6, which was 2.0 (2.19) but with no statistically significant difference (95% CI -1.4 to 0.2, p = 0.136). The ginger and vitamin B6 also significantly reduced the number of vomiting episodes from 1.9 (2.06) to 1.2 (1.75) and 1.7 (1.81) to 1.2 (1.50) respectively, with p < 0.01. The mean number change after treatment with ginger was 0.7 (2.18), more than with vitamin B6, which was 0.5 (1.44) but with no statistically significant difference, (p = 0.498). There were some minor side effects in both groups such as sedation (26.6% vs 32.8%, p = 0.439), and heartburn (9.4% vs 6.3%, p = 0.510), a non-significant difference.\n The nausea score and the number of vomiting episodes were significantly reduced following ginger and vitamin B6 therapy. Comparing the efficacy, there was no significant difference between ginger and vitamin B6 for the treatment of nausea and vomiting during pregnancy.", "to compare the effectiveness of ginger and vitamin B6 for the treatment of nausea and vomiting in early pregnancy.\n double-blind randomised controlled trial. Pregnant women with nausea, who first attended the antenatal clinic at or before 17 weeks gestation, were invited to participate in the study. Over a 3-month period, 70 women were randomised to receive either ginger 1g/day or vitamin B6 40 mg/day for 4 days. Subjects graded the severity of their nausea using a visual analogue scale, and recorded the number of vomiting episodes in the 24 hours before treatment and during 4 consecutive days while taking treatment. At 7-day follow-up, women reported any changes in the severity of their symptoms.\n compared with baseline, the decrease in the visual analogue scores of post-therapy nausea in the ginger group was significantly greater than that for the vitamin B6 group (p = 0.024). The number of vomiting episodes decreased in both groups, and there was no significant difference between the groups. In the ginger group, 29/35 women reported an improvement in nausea symptoms, compared with 23/34 women in the vitamin B6 group (p = 0.52).\n ginger is more effective than vitamin B6 for relieving the severity of nausea, and is equally effective for decreasing the number of vomiting episodes in early pregnancy.", "nan", "Nausea and vomiting in early pregnancy are troublesome symptoms for some women. We undertook a single blind randomized controlled trial to determine whether acupuncture reduced nausea, dry retching, and vomiting, and improved the health status of women in pregnancy.\n The trial was undertaken at a maternity teaching hospital in Adelaide, Australia, where 593 women less than 14 weeks' pregnant with symptoms of nausea or vomiting were randomized into 4 groups: traditional acupuncture, pericardium 6 (p6) acupuncture, sham acupuncture, or no acupuncture (control). Treatment was administered weekly for 4 weeks. The primary outcomes were nausea, dry retching, vomiting, and health status. Comparisons were made between groups over 4 consecutive weeks.\n Women receiving traditional acupuncture reported less nausea (p < 0.01) throughout the trial and less dry retching (p < 0.01) from the second week compared with women in the no acupuncture control group. Women who received p6 acupuncture (p < 0.05) reported less nausea from the second week of the trial, and less dry retching (p < 0.001) from the third week compared with women in the no acupuncture control group. Women in the sham acupuncture group (p < 0.01) reported less nausea and dry retching (p < 0.001) from the third week compared with women in the no acupuncture group. No differences in vomiting were found among the groups at any time.\n Acupuncture is an effective treatment for women who experience nausea and dry retching in early pregnancy. A time-related placebo effect was found for some women.", "To evaluate the effectiveness of auricular acupressure in the treatment of nausea and vomiting in early pregnancy.\n Ninety-eight volunteer pregnant women with symptoms of nausea and vomiting in early pregnancy before 14 weeks gestation were enrolled. The participants were randomized into two groups: treatment group and control group. Each patient in the treatment group received magnet pellets, placed at both auricles. They were taught to start acupressure from the third to the sixth day. Outcome measurement was Rhodes index score, which describe the severity and frequency of nausea and vomiting in the form of a questionnaire. The patients from both groups were asked to complete and return the forms including the amount of anti-emetic drug taken. Mean Rhodes index score and total number of anti-emetic drug taken from day 4-6 were used to compare the treatment effect. Student's t test, Chi-square test and Mann-Whitney U test were used for statistical analysis.\n Ninety-one pregnant women who returned the questionnaires were evaluated. The Rhodes index scores of the treatment group were lower than that of the control group especially after day 4 to day 6 when the acupressure was started. However when comparing the mean score between the two groups, there were no statistically significant differences (p > 0.05). The total amount of anti-emetic tablets in day 4-6 after acupressure intervention was compared and there were no statistically significant differences (p > 0.05) between the groups.\n Auricular acupressure therapy in treatment of nausea and vomiting in early pregnancy may not relieve nausea and vomiting in early pregnancy and need further clinical research to confirm the effectiveness.", "To estimate whether the use of ginger to treat nausea or vomiting in pregnancy is equivalent to pyridoxine hydrochloride (vitamin B6).\n A randomized, controlled equivalence trial involving 291 women less than 16 weeks pregnant was undertaken at a teaching hospital in Australia. Women took 1.05 g of ginger or 75 mg of vitamin B6 daily for 3 weeks. Differences from baseline in nausea and vomiting scores were estimated for both groups at days 7, 14, and 21.\n Ginger was equivalent to vitamin B6 in reducing nausea (mean difference 0.2, 90% confidence interval [CI] -0.3, 0.8), retching (mean difference 0.3; 90% CI -0.0, 0.6) and vomiting (mean difference 0.5; 90% CI 0.0, 0.9), averaged over time, with no evidence of different effects at the 3 time points.\n For women looking for relief from their nausea, dry retching, and vomiting, the use of ginger in early pregnancy will reduce their symptoms to an equivalent extent as vitamin B6.\n I", "This study compares pyridoxine-metoclopramide combination therapy to prochlorperazine and promethazine monotherapies in the outpatient treatment of nausea and vomiting in pregnancy.\n In total, 174 first trimester, singleton pregnancies were evaluated for nausea and vomiting. Patients were prospectively randomized into three treatment groups: pyridoxine-metoclopramide, prochlorperazine, or promethazine. Prior to, and on the third day, patients recorded their subjective responses to the given treatment and their number of emesis episodes. The three treatment groups were compared for therapy response.\n There were no differences in the number of emesis episodes prior to treatment. Both subjective and objective responses to treatment differed among the three groups when comparing the combination therapy to the monotherapies (p<0.05).\n Combination therapy with pyridoxine and metoclopramide appears to be superior to either monotherapy in the treatment of nausea and vomiting in pregnancy." ]

[ "10493479", "14631226" ]

[ "Is prophylactic gastrojejunostomy indicated for unresectable periampullary cancer? A prospective randomized trial.", "The need for a prophylactic gastrojejunostomy for unresectable periampullary cancer: a prospective randomized multicenter trial with special focus on assessment of quality of life." ]

[ "This prospective, randomized, single-institution trial was designed to evaluate the role of prophylactic gastrojejunostomy in patients found at exploratory laparotomy to have unresectable periampullary carcinoma.\n Between 25% and 75% of patients with periampullary cancer who undergo exploratory surgery with intent to perform a pancreaticoduodenectomy are found to have unresectable disease. Most will undergo a biliary-enteric bypass. Whether or not to perform a prophylactic gastrojejunostomy remains unresolved. Retrospective reviews of surgical series and prospective randomized trials of endoscopic palliation have demonstrated that late gastric outlet obstruction, requiring a gastrojejunostomy, develops in 10% to 20% of patients with unresectable periampullary cancer.\n Between May 1994 and October 1998, 194 patients with a periampullary malignancy underwent exploratory surgery with the purpose of performing a pancreaticoduodenectomy and were found to have unresectable disease. On the basis of preoperative symptoms, radiologic studies, or surgical findings, the surgeon determined that gastric outlet obstruction was a significant risk in 107 and performed a gastrojejunostomy. The remaining 87 patients were thought by the surgeon not to be at significant risk for duodenal obstruction and were randomized to receive either a prophylactic retrocolic gastrojejunostomy or no gastrojejunostomy. Short- and long-term outcomes were determined in all patients.\n Of the 87 patients randomized, 44 patients underwent a retrocolic gastrojejunostomy and 43 did not undergo a gastric bypass. The two groups were similar with respect to age, gender, procedure performed (excluding gastrojejunostomy), and surgical findings. There were no postoperative deaths in either group, and the postoperative morbidity rates were comparable (gastrojejunostomy 32%, no gastrojejunostomy 33%). The postoperative length of stay was 8.5+/-0.5 days for the gastrojejunostomy group and 8.0+/-0.5 days for the no gastrojejunostomy group. Mean survival among those who received a prophylactic gastrojejunostomy was 8.3 months, and during that interval gastric outlet obstruction developed in none of the 44 patients. Mean survival among those who did not have a prophylactic gastrojejunostomy was 8.3 months. In 8 of those 43 patients (19%), late gastric outlet obstruction developed, requiring therapeutic intervention (gastrojejunostomy 7 patients, endoscopic duodenal stent 1 patient; p < 0.01). The median time between initial exploration and therapeutic intervention was 2 months.\n The results from this prospective, randomized trial demonstrate that prophylactic gastrojejunostomy significantly decreases the incidence of late gastric outlet obstruction. The performance of a prophylactic retrocolic gastrojejunostomy at the initial surgical procedure does not increase the incidence of postoperative complications or extend the length of stay. A retrocolic gastrojejunostomy should be performed routinely when a patient is undergoing surgical palliation for unresectable periampullary carcinoma.", "To evaluate the effect of a prophylactic gastrojejunostomy on the development of gastric outlet obstruction and quality of life in patients with unresectable periampullary cancer found during explorative laparotomy.\n Several studies, including one randomized trial, propagate to perform a prophylactic gastrojejunostomy routinely in patients with periampullary cancer found to be unresectable during laparotomy. Others suggest an increase of postoperative complications. Controversy still exists in general surgical practice if a double bypass should be performed routinely in these patients.\n Between December 1998 and March 2002, patients with a periampullary carcinoma who were found to be unresectable during exploration were randomized to receive a double bypass (hepaticojejunostomy and a retrocolic gastrojejunostomy) or a single bypass (hepaticojejunostomy). Randomization was stratified for center and presence of metastases. Patients with gastrointestinal obstruction and patients treated endoscopically for more than 3 months were excluded. Primary endpoints were development of clinical gastric outlet obstruction and surgical intervention for gastric outlet obstruction. Secondary endpoints were mortality, morbidity, hospital stay, survival, and quality of life, measured prospectively by the EORTC-C30 and Pan26 questionnaires. It was decided to perform an interim analysis after inclusion of 50% of the patients (n = 70).\n Five of the 70 patients randomized were lost to follow-up. From the remaining 65 patients, 36 patients underwent a double and 29 a single bypass. There were no differences in patient demographics, preoperative symptoms, and surgical findings between the groups. Clinical symptoms of gastric outlet obstruction were found in 2 of the 36 patients (5.5%) with a double bypass, and in 12 of the 29 patients (41.4%) with a single bypass (P = 0.001). In the double bypass group, one patient (2.8%) and in the single bypass group 6 patients (20.7%) required (re-)gastrojejunostomy during follow-up (P = 0.04). The absolute risk reduction for reoperation in the double bypass group was 18%, and the numbers needed to treat was 6. Postoperative morbidity rates, including delayed gastric emptying, were 31% in the double versus 28% in the single bypass group (P = 0.12). Median postoperative length of stay was 11 days (range 4-76 days) in the double versus 9 days (range 6-20 days) in the single bypass group (P = 0.06); median survival was 7.2 months in the double versus 8.4 months in the single bypass group (P = 0.15). No differences were found in the quality of life between both groups. After surgery most quality of life scores deteriorated temporarily and were restored to their baseline score (t = -1) within 4 months.\n Prophylactic gastrojejunostomy significantly decreases the incidence of gastric outlet obstruction without increasing complication rates. There were no differences in quality of life between the two groups. Together with the previous randomized trial from the Hopkins group, this study provides sufficient evidence to state that a double bypass consisting of a hepaticojejunostomy and a prophylactic gastrojejunostomy is preferable to a single bypass consisting of only a hepaticojejunostomy in patients undergoing surgical palliation for unresectable periampullary carcinoma. Therefore, the trial was stopped earlier than planned." ]

[ "7011688", "4899587", "8252318", "4555545", "241072", "866904", "7017917", "389264", "3365530", "350499", "3548732", "1106038", "4571392", "3057482" ]

[ "Clinical therapeutic trial of aspirin and azapropazone in rheumatoid arthritis when prescribed singly and in combination.", "Comparison of aspirin and dextropropoxyphene-with-aspirin as analgesics in rheumatoid arthritis.", "Additive effect of combined naproxen and paracetamol in rheumatoid arthritis.", "Comparison of aspirin and benorylate in the treatment of rheumatoid arthritis.", "Comparison of benorylate and indomethacin in the symptomatic control of arthritic disorders.", "Night medication in rheumatoid arthritis: II. Combined therapy with indomethacin and diazepam.", "Additive clinical effect of indomethacin suppositories during salicylate therapy in rheumatoid patients.", "The aspirin-ibuprofen interaction in rheumatoid arthritis.", "Equianalgesic effects of paracetamol and indomethacin in rheumatoid arthritis.", "Night medication in rheumatoid arthritis. III. the use of sulindac.", "A controlled study of concurrent therapy with a nonacetylated salicylate and naproxen in rheumatoid arthritis.", "[Clinical study on a new acetylsalicylic acid/paracetamol preparation with gastric acid resistant coating (Safapryn), and on two various phenylbutazone dosages in patients with primary chronic polyarthritis as based on a new evaluation method].", "Double-blind comparison of aspirin and 4-(acetamido) phenyl-2-acetoxy-benzoate (benorylate) in rheumatoid arthritis.", "Psychomotor performance of patients with rheumatoid arthritis: cross-over comparison of dextropropoxyphene, dextropropoxyphene plus amitriptyline, indomethacin, and placebo." ]

[ "A double-blind, crossover trial was carried out to assess the clinical efficacy of 3.6 g aspirin, 1200 mg azapropazone and the two drugs together in 24 adult patients with classical or definite rheumatoid disease. Pain score, morning stiffness and patients' assessment of pain were significantly improved for each drug regimen when compared to placebo. There was no significant difference among the individual drug regimens. Azapropazone was the best drug regimen in terms of improving pain score, morning stiffness and patient assessment of pain, but this was not statistically significant. It is concluded that there is no justification for prescribing aspirin with azapropazone in patients with rheumatoid disease.", "nan", "The clinical effect and plasma naproxen levels were studied in 20 patients with RA receiving three doses of naproxen and two naproxen doses combined with paracetamol (acetaminophen) in a randomized, double-blind, comparison in five 2-wk treatment periods. A significant dose-concentration effect relationship was found for the three naproxen doses (500, 1000 and 1500 mg daily). The following variables were measured: global clinical effect, joint index, morning stiffness, activity of daily living (ADL), pain during movement and at rest. The naproxen dose-concentration effect relationship curve was moved to the left by the addition of 4 g paracetamol daily. No major side effects were observed, but complaints concerning the gastrointestinal tract were fewer on lower naproxen doses and these were not increased by concomitant paracetamol treatment. The results show that the clinical effect of naproxen in RA may be significantly increased by concomitant paracetamol administration.", "In a double-blind between-patient study of aspirin and benorylate carried out in 72 outpatients with rheumatoid arthritis, benorylate 4 g twice daily was shown to be an effective analgesic and anti-inflammatory drug, its effects being indistinguishable from those of aspirin 1.2 g four times daily. Compared with the pretreatment values both drugs produced a statistically significant improvement (P < 0.01) in functional grade, overall pain, articular index, and grip strength at the end of the first and second weeks. The overall incidence of side effects was less with benorylate, though this difference was not significant at the 5% level.", "nan", "Seventeen of eighteen patients hospitalized for active rheumatoid arthritis completed a three-day randomized, double-blind comparison of 100 mg indomethacin, 100 mg indomethacin with 10 mg diazepam and matching placebo as night medication. The results showed a consistent pattern in the four functions measured--pain, morning stiffness, sleep score and patient preference. In each, indomethacin proved superior to placebo and the combined therapy better than indomethacin alone. From this it has been concluded that the combination of indomethacin and diazepam should now be considered the treatment of choice for maximum control of night pain and morning stiffness in rheumatoid arthritis.", "Twelve rheumatic patients were given 2.0 and 4.5 g acetylsalicylic acid daily in two 3-week periods. On days 13 and 20 of each period the patients took a suppository containing either placebo or 50 mg of indomethacin. The study was performed double-blind. Indomethacin had a significant additive effect during ASA therapy with 2 g daily as estimated by articular index and subjective ratings of pain and morning stiffness. On the 4.5 g ASA dose there was a significant improvement only for articular index. The patients experienced less pain during maintenance therapy with 4.5 g of ASA compared with 2.0 g daily. Both ASA doses induced complete inhibition of prostaglandin PGF2 alpha release from platelets. Thus the suppression of PGF2 alpha release does not reflect the therapeutic response of these drugs. Side effects observed comprised tinnitus, dizziness and gastritis. In 2 of the patients the aminotransferase levels increased, indicating hepatotoxicity. The protein binding of salicylate decreased with increasing salicylate concentration. As the dose was increased from 2.0 to 4.5 g/day the unbound concentration increased 5 to 24 times. This reflects the combined effect of capacity-limited metabolism and capacity-limited protein binding of salicylate.", "1 This was a double-blind crossover trial of ibuprofen and soluble aspirin against each drug alone and against placebo in patients with rheumatoid arthritis. Two dosage regimes were tested. 2 A weak clinical additive effect was demonstrated between soluble aspirin and ibuprofen in patients with rheumatoid arthritis using moderate (1600 mg ibuprofen and 3.6 g aspirin daily) but not low (800 mg ibuprofen and 2.4 g aspirin daily) dosages of both drugs. 3 A significant correlation between clinical efficacy and serum ibuprofen but not salicylate level was found in the single drug periods of the trial. 4 No consistent effect of ibuprofen administration on serum salicylate levels was found. 5 Concurrent salicylate administration produced significant lowering of serum ibuprofen levels without affecting elimination half-lives of the drug.", "The therapeutic and adverse effects of 2 weeks of treatment with high-dose indomethacin (150 mg/day) were compared with those of low-dose indomethacin (50 mg/day) combined with paracetamol (4 g/day) in a double-blind, double-dummy, cross-over study in 17 patients with active rheumatoid arthritis. Grip strength, Ritchie's index, joint circumference, joint pain, and patient's and physician's global assessments were estimated, and conventional laboratory parameters were followed. In addition, the time-concentration profiles of indomethacin and paracetamol were assessed during steady state. All patients had measurable plasma drug levels, indicating adequate compliance, and responders and nonresponders (five on each treatment) had equal drug levels, indicating that the variation in therapeutic efficacy was not secondary to pharmacokinetic differences. While there were fewer and milder side-effects during treatment with the drug combination, there was no difference in therapeutic efficacy. Hence, it appears that the main therapeutic profit of indomethacin in daily doses greater than 50 mg is enhanced analgesia. As such dosage involves pronounced side-effects, it seems more appropriate to employ the combination of 50 mg indomethacin and 4 g paracetamol, whereby similar analgesia can be obtained without an increase in side-effects.", "A double-blind controlled trial was carried out in 18 in-patients with classical or definite rheumatoid arthritis to assess the effectiveness of night-time medication with 100 mg indomethacin plus 10 mg diazepam, 200 mg sulindac, and 200 mg sulindac plus 10 mg diazepam in improving sleep and reducing night pain and the duration of morning stiffness. Patients received each treatment regimen for 1 night. The results from the 17 patients completing the full trial protocol indicated that indomethacin plus diazepam was the most effective of the three regimens, although the differences did not reach conventional statistical significance. It is suggested that in further such studies with sulindac a larger dose and a longer duration of treatment should be used.", "Previous studies of combinations of nonsteroidal drugs used in the treatment of rheumatoid arthritis (RA) have yielded conflicting results. We used standard methods to measure disease activity and high pressure liquid chromatography to measure plasma drug concentrations. We used doses of choline magnesium trisalicylate, adjusted to achieve therapeutic serum salicylate concentrations, and naproxen in a randomized, double-blind, placebo-controlled cross-over study of full dose trisalicylate (CMT), full dose naproxen (N), full dose of both (CMT-N), and half dose of both (cmt-n) to examine their relative efficacy and toxicity in treating RA. CMT-N was statistically superior to all other treatments in only 1 of 12 efficacy variables, but was equal to N and better than CMT or cmt-n for 7 variables. There were minimal differences among treatments for the other 4 efficacy variables. The mean percentage difference for the efficacy variables between CMT-N and N was 3%, between CMT-N and CMT was 10.6%, and between CMT-N and cmt-n was 10.5%. Thirteen percent of patients manifested toxic reactions during the initial open dose-adjustment salicylate run-in phase. During the double-blind phases of the study, CMT-N was more toxic than N, CMT, or cmt-n (7.5% versus 3.4%, 1.8%, and 3.7%, respectively). Tinnitus was more common when full-dose CMT was used; N (N or CMT-N) was associated with increased skin toxicity. Gastrointestinal complaints were equally common with all regimens. CMT-N, although sometimes statistically superior to CMT, N, or cmt-n, showed no clinically important additive or synergistic effect versus N or CMT alone.", "The authors describe a simple non-crossover-blind test for the evaluation of subjective indices. A table for recording pains during the 14 days' study is described. The patient's satisfaction with the treatment and the number of days until withdrawal from the trial are recorded. The statistical procedure takes into consideration differences between the treatment groups and makes possible a valuable comparison with drugs tested in other clinical trials. The three dose schedules of antirheumatic treatment were tested on 122 patients and the results compared with those of 342 patients treated with the 6 other antirheumatic drugs (enteric-coated aspirin, paracetamol, indomethacin, flurbiprofen, mefenamic acid, and prednisolone) and those of 41 patients who received placebos. The results show that Safapryn (3,6 g aspirin + 3.0 g paracetamol daily) compared with 3.9 g enteric coated aspirin does not offer any advantage in its analgesic effect, although it gives rise to fewer side effects. Phenylbutazone (3000 mg) was almost as effective as 15 mg prednisolone daily. Between the effects of this dosage of phenylbutazone and other non-steroidal antirheumatic drugs, however, no significant difference could be detected. 50 mg phenylbutazone daily and placebo treatment could not be distinguished. The authors thank the Arthritis and Rheumatism Council for Research in Great Britain for its financial support. One of the authors (PL) was a Merck, Sharp, and Dohme Research Fellow and another one (PMB) received a Robins research scholarship.", "nan", "Actions on performance of dextropropoxyphene (DXP) alone and in combination with amitriptyline (AMI), indomethacin (IN), and placebo were compared in 15 patients with rheumatoid arthritis. The patients were on their prescribed maintenance regimen excluding analgesics. In four randomized test sessions at two-week intervals, they received double blind and crossover single oral doses of DXP 130 mg, IN 50 mg, DXP 65 mg + AMI 25 mg or placebo, each after two days' pretreatment with the same drug. Objective and subjective effects were measured at baseline and 2 and 4 hours after drug administration. DXP impaired critical flicker discrimination, symbol copying and body balance without modifying tracking, choice reactions or attention. It rendered the subjects elated, muzzy, mentally slow and calm. Actions of AMI + DXP were about the same. IN impaired body balance and critical flicker recognition. Plasma concentrations of DXP were moderate to high whilst those of IN and AMI were fairly low. We conclude that therapeutic doses of DXP and IN are relatively safe in regard to driving skills. Small doses of AMI may not enhance the mild psychomotor effects of DXP. Earlier single dose studies carried out with healthy volunteers might have overestimated the decremental effects of analgesics on psychomotor performance." ]

[ "7600346", "15160576", "11938346", "12430368", "3304523", "12066081", "2459870", "3524644", "6204377", "7947061", "6344906", "3926169", "2437713", "9091151", "1938398" ]

[ "Comparison of two dressings in the treatment of venous leg ulcers.", "An evaluation of Hyalofill-F plus compression bandaging in the treatment of chronic venous ulcers.", "Controlled, randomized clinical trial of 2 hydrocolloid dressings in the management of venous insufficiency ulcers.", "The healing properties of Promogran in venous leg ulcers.", "Controlled trial of occlusive dressings in healing chronic venous ulcers.", "Randomised, comparative study of three primary dressings for the treatment of venous ulcers.", "Cadexomer iodine (Iodosorb) compared with dextranomer (Debrisan) in the treatment of chronic leg ulcers.", "A controlled comparative trial of Actisorb activated charcoal cloth dressings in the community.", "The clinical significance of bacterial growth in venous leg ulcers.", "Prospective, multicenter study of managing lower extremity venous ulcers.", "A randomized trial comparing cadexomer iodine and standard treatment in the out-patient management of chronic venous ulcers.", "Controlled trial of Iodosorb in chronic venous ulcers.", "[Therapy of varicose ulcer using crilanomer and dextranomer].", "The influence of dressings on venous ulcer healing--a randomised trial.", "[Treatment of venous ulcera cruris with dry wound dressings. Phase overlapping use of silver impregnated activated charcoal xerodressing]." ]

[ "nan", "Hyaluronan, a component of the extracellular matrix, plays a significant role in several aspects of tissue repair and the wound healing process.\n In this Italian study Hyalofill-F, a partial benzyl ester derivative of hyaluronan, used in combination with compression bandaging, was compared with the well-established therapy in Italy of non-adherent gauze plus compression therapy in the treatment of chronic venous leg ulcers.\n Hyalofill-F plus compression bandaging performed significantly better than non-adherent gauze plus compression bandage in all of the clinically relevant efficacy parameters. Mean reduction in ulcer area in the hyaluronan-derivative group was 8.1 cm2 after eight weeks of treatment, compared with 0.4 cm2 in the comparator group. The resulting difference of 7.7 cm2 between the two groups was statistically significant (p = 0.0019). Furthermore, statistically significant results in favour of the hyaluronan-derivative group were obtained in the following: speed of epithelialisation; leveling of the margins; degree of maceration; pain intensity and frequency.\n Hyalofill-F plus compression bandaging resulted in an earlier and greater decrease in ulcer area compared with non-adherent gauze plus compression bandaging, therapy supporting its use in the treatment of chronic venous ulcers.", "A prospective, randomized study was conducted to compare the performance of 2 hydrocolloid dressings, hydrocolloid A and hydrocolloid B, in the treatment of venous insufficiency ulcers. A total of 31 patients were enrolled at 2 clinical sites. Complete wound closure (100% epithelialization) was observed in 59% of the patients treated with hydrocolloid A, compared with complete wound closure in 15% of the patients in the hydrocolloid B group (P <or=.03). Investigators also rated hydrocolloid A significantly better in ease of application, adhesion, conformability, exudate absorption, barrier properties, transparency, and patient comfort (P <or=.02). Significantly fewer patients in the hydrocolloid A group required unscheduled, product-related dressing changes (P <or=.02). In this clinical study, hydrocolloid A demonstrated excellent performance characteristics and was highly effective in treating venous insufficiency ulcers.", "To evaluate the healing rate of venous leg ulcers treated with Promogran.\n Patients with stagnating venous leg ulcers were recruited. Target wounds were > or = 2 cm but < or = 10 cm in any one dimension. Subjects were randomly allocated to receive either Promogran or a non-adherent dressing (Adaptic) with a secondary dressing of gauze followed by short-stress compression (Biflex). Weekly wound assessments occurred over 12 weeks and dressings were changed twice weekly by the investigator and/or nurse team. Planimetry tracings and photographs were blindly reviewed and assessed by two independent investigators. An intent-to-treat analysis was performed.\n Seventy-three patients were included. Thirty-seven were randomly allocated Promogran and 36 Adaptic. Twenty-nine patients completed the 12-week follow-up visit, 25 healed before week 12 and 19 stopped follow-up before week 12 for reasons unrelated to healing. Significantly more patients in the Adaptic group than in the Promogran group switched to another dressing (22.2% versus 5.4%; p = 0.035). Eleven venous leg ulcers healed in the control group (31%) and 15 in the Promogran group (41%) (p = 0.373). Overall, 15 venous leg ulcers healed or improved in the control group (42%) and 23 in the Promogran group (62%) (p = 0.079). Surface area decreased, on average, by 36.5 +/- 11.4% (median decrease: 44.6%) in the Adaptic group and by 54.4 +/- 10.9% (median decrease: 82.4%) in the Promogran group (p < 0.001). A < or = 20% surface area reduction was observed in 15 patients in the Adaptic group and in seven in the Promogran group (42% versus 19%; p = 0.034). No severe local adverse events were noted in either group, although poor tolerability caused a dressing switch in five patients in the control group and three in the Promogran group. Dressing acceptability was good or excellent in more than 60% of subjects in both groups.\n The results suggest that Promogran may accelerate healing in venous leg ulcers and was well tolerated compared with the current standard of care.", "Fifty-six patients with chronic venous ulcers present for a mean of 2.4 years were randomized to either a new occlusive hydrocolloid dressing (Granuflex, Squibb Surgicare) or a porous non-adherent dressing (N A, Johnson and Johnson). In all patients, dressings were applied beneath a standard graduated compression bandage. There was no difference between the two groups, with complete healing in 21 out of 28 (75 per cent) of occlusive dressing patients and 22 out of 28 (78 per cent) with N A dressings by 12 weeks. Careful graduated compression bandaging achieves healing even in the majority of so-called resistant chronic venous ulcers; there was no additional benefit from applying occlusive dressings which tend to be expensive.", "In this article, we describe a randomised trial in which two established primary dressings - Comfeel (Coloplast, UK) and Granuflex improved formulation (Convatec, UK) - were compared to Cutinova foam (Beiersdorf Medical, UK) in the management of venous leg ulcers. Patients that met the study trial criteria were randomised to receive one of the three primary dressings. All ulcers were secondarily bandaged with Comprilan (Beiersdorf Medical, UK) short-stretch compression. The three dressings were compared in terms of their ability to promote ulcer healing (closure rate and healing rate) and reduce the prevalence and severity of ulcer-associated pain, over a 12-week period. The ease with which dressings could be used in a busy outpatient clinic setting was also considered. On enrollment, groups were well matched in terms of all of the patient and ulcer parameters studies. Six patients were withdrawn for reasons unrelated to study dressings or trial procedures. Following non-parametric analysis of the study data, the three dressings were found to be equally effective at promoting ulcer healing and alleviating ulcer-associated pain. Study personnel rated Cutinova Foam as easy, if not easier, to use than Comfeel or Granuflex. This study suggests that Cutinova Foam is as safe and effective as both Comfeel and Granuflex, in the treatment of venous leg ulcers.", "nan", "nan", "The importance of pathogenic bacteria in venous leg ulcers was analysed in a randomized open trial divided into 2 parts. During the first 2-week period the effects of physiological saline and dextranomer beads were compared. During the following 8 weeks the effect of porcine skin, aluminium foil and a double layer bandage were compared. The assessment of the results of treatment was based on the area and volume of the ulcer measured by stereophotogrammetry and the bacteriological findings. Staphylococcus aureus was the commonest isolated species. Mixed cultures comprising Staph. aureus and gram-negative bacteria were the next commonest finding. There was a low frequency of isolation of anaerobic bacteria. The bacteriological findings were similar in the different treatment groups. The nature of the bacterial isolates and the colonization estimated by a contact-transfer procedure bore no relationship to the clinical assessment as to whether the ulcer was clean or purulent. Healing of the ulcer was not influenced by the bacteria present. The findings seem to indicate that as a rule the bacteria in the ulcers are saprophytic and will disappear when the favourable environment for their growth is lost.", "Seventy patients with 90 venous ulcers were randomly assigned to hydrocolloid or conventional dressing and compression therapy at four study centers. The ulcers had been present for a mean of 47.8 in the control and 46.2 weeks in the treatment group and 42% of all patients had recurrent ulcers. Ulcers treated with hydrocolloid dressings reduced 71% and control treated wounds reduced 43% in area after 7.2 weeks of treatment. Thirty-four percent of all ulcers healed. Mean time to healing was 7 weeks for the hydrocolloid dressing group and 8 weeks for the control group. Most ulcers were less painful at final evaluation, but reduction in pain was more pronounced in hydrocolloid-dressed ulcers (p = 0.03). At baseline as well as during follow-up, significant differences between study centers were observed. Ulcers in patients in the United Kingdom were larger and less likely to heal (p = 0.001). Size of the ulcer at baseline was associated with treatment response and time to healing (p = 0.002). Percent reduction in ulcer area after 2 weeks was also correlated with treatment outcome (p = 0.004) and time to healing (p = 0.002). When all treatment outcome predictors were analyzed together, only percent reduction in area after 2 weeks remained statistically significant (p = 0.002), with percent reduction during the first 2 weeks of treatment > 30% predicting healing.", "Ninety-three patients with treatment-resistant venous ulcers were included in a multicentre randomized trial to compare cadexomer iodine and the standard treatment used in each centre combined with compression bandages, in healing venous ulcers. The mean duration of ulcers before the trial was more than 2 years. With standard treatment the mean ulcer size increased slightly during the 6-week trial whereas with cadexomer iodine the ulcer size was significantly reduced. Cadexomer iodine was more effective than standard treatment for reduction of pain, removal of pus and debris, removal of exudate, stimulation of granulation and reduction of surrounding erythema. Bacterial infection of ulcers increased or did not change during treatment with the standard therapy whereas cadexomer iodine significantly reduced infection with Staphylococcus aureus, Pseudomonas aeruginosa and other pathogenic organisms. A correlation was seen between the time taken to reduce or eliminate infection with Staphylococcus aureus and rate of ulcer healing. Four patients complained of transient pain in the ulcer after application of the cadexomer iodine. It is concluded that cadexomer iodine increased the rate of healing of infected chronic venous ulcers.", "Cadexomer iodine (Iodosorb) is a hydrophilic starch powder containing iodine, which is a suitable dressing for granulating wounds such as venous ulcers. A total of 61 outpatients with chronic venous ulcers participated in a randomised optional crossover trial using cadexomer iodine or a standard dressing for their ulcers. The trial lasted for 24 weeks or until the ulcer had healed. Two patients withdrew during the course of the trial. Both treatments were highly effective, but the epithelium of ulcers dressed with cadexomer iodine grew again significantly faster (p less than 0.001). At the midpoint of the trial (12th week) 13 of 30 patients receiving standard treatment were changed to cadexomer iodine, while only three of 29 receiving cadexomer iodine changed to the standard dressing (p less than 0.02). In most cases ulcers were dressed and rebandaged daily by the patients themselves after instruction and supervision. This may be better than having dressings and bandages applied by professionals less regularly.", "148 patients with leg ulcers were treated in 14 clinics with Clinagel or with Debrisan Paste for four weeks. The size of the surface of the ulcer and the overall evaluation of the ulcer by physician before and after treatment were the most important criteria for the assessment of efficacy. The comparison between the two treatments was carried out by t- and x2-test at the level of a = 0.05. Clinagel was shown to be better than Debrisan. Its superiority was statistically significant in regard to reduction of area, depth, pain and swelling, increase of granulation tissue, reepithelialisation of ulcer and the subjective judgement of physician and patient. No systemic side effects were observed in any of the patients and only slight local side effects were registered.", "To assess the effect of different dressings on venous ulcer healing.\n A randomised clinical trial.\n Patients were randomised to treatment with one of three dressings: a zinc oxide impregnated bandage, a zinc oxide impregnated stockingette, or an alginate dressing. All patients were treated as outpatients and had compression bandaging with two minimal stretch bandages (Elastocrepe) and a stockingette (Tubigrip) to keep the bandages in place.\n One hundred and thirteen patients (133 ulcerated limbs) with chronic ulceration of the leg due to venous disease alone, and attending Fremantle Hospital Leg Ulcer Clinic, Western Australia were entered into the study. Healing was measured as complete healing of the ulcerated limb or failure of the limb to heal within 9 months.\n There was no significant difference between the three groups in ulcer size, duration, and other parameters compared. Healing was affected significantly by ulcer size and which leg was ulcerated. There was significantly faster healing with the paste bandage.\n The use of a paste bandage significantly improved the healing of chronic venous ulcers when used in combination with compression bandaging, and compared to an alginate dressing and a zinc oxide impregnated stockingette.", "In a controlled randomized study on 40 patients with venous leg ulcers, monotherapy with a dry wound dressing (silver-impregnated--activated charcoal xerodressing; SIAX) was tested. The xerodressing was applied throughout the entire study and was compared with the conventional phase-adapted therapy using diverse topical modalities, e.g. as granulating ointments, zinc paste. etc. The parameters of wound healing were documented in the two randomized groups over 6 weeks and were statistically evaluated. In the statistical comparison of SIAX therapy (n = 19) and conventional therapy (n = 19) significant differences were found in favour of the SIAX group (increase of epithelialization, reduction of ulcer size; P less than 0.05). In addition, the ulcers of 6/19 patients (= 31.6%) treated with SIAX healed completely within the study period, in contrast to only 2/19 patients (= 10.5%) receiving conventional therapy. Exudate, granulation and colonization of the ulcers as well as odour, necroses, erythema and oedema of the surrounding areas were not significantly different. The study shows that a consistent therapy performed with dry wound dressings such as SIAX is superior to the conventional topical therapy of venous leg ulcers in some cases. Wound dressings provide new therapeutic modalities, being easy to apply and fully efficient, without side-effects." ]