Treating alcohol withdrawal with oral baclofen: a randomized, double-blind, placebo-controlled trial. Oxcarbazepine--efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study. Baclofen for the treatment of acute low-back syndrome. A double-blind comparison with placebo. Examination of the analytic quality of behavioral health randomized clinical trials. Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome: a randomized comparative study versus benzodiazepine. A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection. Abstracts of randomized controlled trials presented at the society for pediatric research meeting: an example of publication bias. Alcohol withdrawal severity is decreased by symptom-orientated adjusted bolus therapy in the ICU. Improving the quality of randomized controlled trials in Chinese herbal medicine, part IV: applying a revised CONSORT checklist to measure reporting quality. Randomized controlled trials in pediatric surgery: could we do better? Multi-centre, double-blind trial of a novel antispastic agent, tizanidine, in spasticity associated with multiple sclerosis.
Abrupt cessation of alcohol intake causes habituated drinkers to experience symptoms of alcohol withdrawal syndrome (AWS).
                To determine the effect of the gamma-aminobutyric acid (GABA)-B agonist baclofen on the course of acute symptomatic AWS.
                Prospective, randomized, double-blind, placebo-controlled clinical study.
                Two tertiary-care hospitals in Duluth, Minnesota.
                Inpatient adults admitted for any reason (including AWS) judged to be at high risk for AWS.
                Inpatients who developed symptoms of AWS received symptom-triggered benzodiazepine treatment using lorazepam by standard protocol, and were randomized to receive baclofen 10 mg or placebo, 3 times per day, orally.
                AWS severity was assessed using the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar); lorazepam dose was monitored.
                Seventy-nine subjects were enrolled. The 44 subjects who developed symptoms of AWS were randomized to baclofen or placebo. Thirty-one subjects (18 baclofen, 13 placebo) completed 72 hours of assessments, either entirely as inpatients or with outpatient follow-up. The need for high doses of benzodiazepines (20 mg or more of lorazepam over 72 hours) to control AWS was less likely in the baclofen treatment group (1 of 18) than in the placebo-treated group (7 of 13) (P = 0.004).
                We found that the use of baclofen was associated with a significant reduction in the use of high doses of benzodiazepine (lorazepam) in the management of symptomatic AWS. The use of low-dose baclofen in the management of AWS deserves further study, as reduced dependence on high-dose benzodiazepines in AWS management could improve patient safety.
                Copyright © 2011 Society of Hospital Medicine. Alcohol withdrawal syndrome (AWS) is a serious complication of alcohol dependence and often requires intensive medical treatment. Antiepileptic drugs (AEDs) have been shown to be as efficacious in the treatment of AWS in several controlled trials as benzodiazepines and superior to placebo in relieving alcohol withdrawal symptoms. Oxcarbazepine (OXC), a newer anticonvulsive drug, has a favorable safety profile over carbamazepine (CBZ) and other older AEDs due to its excellent efficacy and better side-effect profile.
                The efficacy and tolerability of OXC versus placebo were investigated in 50 inpatients during a 6-day treatment of alcohol withdrawal in a 4-site, double-blind, randomized, placebo-controlled pilot study. The amount of rescue medication of clomethiazole (CLO) capsules needed was chosen as the primary variable. The data were collected between May 2003 and September 2004.
                No initial differences were found regarding sociodemographic data and alcohol-related parameters, indicating successful randomization. No differences were found in the need for rescue medication CLO, decrease of withdrawal symptoms, or craving for alcohol between the OXC and the placebo group. Subjectively experienced side effects, normalization of vegetative parameters, craving, or improvement of psychopathological parameters were not different between the groups.
                Despite the negative finding, which may be attributable to the design of the study, OXC still poses an interesting alternative to CBZ and other drugs because other studies have found it not only as efficient but also as having no addictive potential, while additionally possessing an anti-craving effect. Therefore, well-designed investigations with larger cohorts are required to further elucidate this issue. The efficacy and safety of baclofen (30-80 mg daily) for the treatment of acute low-back syndrome were evaluated in a 14-day, double-blind, randomized study of 200 patients (100 baclofen, 100 placebo). Patients with initially severe or extremely severe symptoms (as opposed to moderate symptoms) benefitted most from treatment with baclofen. The incidence of adverse effects was significantly higher in the baclofen group; however, most were mild to moderate and disappeared in all but two patients who required a reduction in dosage, without reduced drug efficacy. Baclofen was shown to be effective, safe, and well-tolerated for the treatment of patients with acute low-back syndrome. Adoption of evidence-based practice (EBP) policy has implications for clinicians and researchers alike. In fields that have already adopted EBP, evidence-based practice guidelines derive from systematic reviews of research evidence. Ultimately, such guidelines serve as tools used by practitioners. Systematic reviews of treatment efficacy and effectiveness reserve their strongest endorsements for treatments that are supported by high-quality randomized clinical trials (RCTs). It is unknown how well RCTs reported in behavioral science journals fare compared to quality standards set forth in fields that pioneered the evidence-based movement. We compared analytic quality features of all behavioral health RCTs (n = 73) published in three leading behavioral journals and two leading medical journals between January 2000 and July 2003. A behavioral health trial was operationalized as one employing a behavioral treatment modality to prevent or treat an acute or chronic physical disease or condition. Findings revealed areas of weakness in analytic aspects of the behavioral health RCTs reported in both sets of journals. Weaknesses were more pronounced in behavioral journals. The authors offer recommendations for improving the analytic quality of behavioral health RCTs to ensure that evidence about behavioral treatments is highly weighted in systematic reviews.
                (c) 2006 Wiley Periodicals, Inc. Benzodiazepine has been shown to be one of the most effective class of drugs in the management of alcohol withdrawal syndrome (AWS). Gamma-hydroxybutyric acid (GHB) has recently been introduced in the treatment of alcohol problems, including AWS. At present there are no comparative studies between benzodiazepines and GHB in AWS treatment. The aim of the present randomized, controlled, single-blind study was to evaluate the efficacy and safety of GHB compared with diazepam in the treatment of AWS.
                Sixty alcoholics affected by AWS were enrolled in the study. Diazepam (0.5-0.75 mg/kg body weight for 6 days, tapering the dose 25% daily until day 10) was administered orally to 30 patients (25 males, 5 females; mean age 44.3 +/- 10.9 years); GHB (50 mg/kg body weight for 10 days) was administered orally to 30 patients (26 males,4 females; mean age 41.7 +/- 10.4 years). The Clinical Institute Withdrawal Assessment for Alcohol-revised scale (CIWA-Ar) was used to evaluate the AWS physical symptoms. The State Anxiety Inventory test for current anxiety assessment and the Zung self-rating Depression Scale for current depression assessment were performed.
                Eight patients (26.6%) in the diazepam group and 4 patients (13.3%) in the GHB group dropped out. Both treatments were effective in reducing AWS. No significant difference was found between the groups in CIWA-Ar total score at baseline and at the different times of observation. Considering the CIWA-Ar subscore and Zung scale, a significant reduction of anxiety on day 4 (p < 0.02), agitation on day 5 (p < 0.02) and time of recovery of depression on day 5 (p < 0.02) was observed in the GHB group with respect to the diazepam group. Drowsiness and vertigo developed after initial drug administration in the GHB (19.2%) and diazepam (36.4%) groups and quickly resolved in both groups.
                GHB is as effective in the management of AWS as benzodiazepine and it seems to be quicker in reducing anxiety, agitation, and depression. Both drugs are safe and well-tolerated in AWS management. To evaluate whether ischemic preconditioning (IP) with continuous clamping or intermittent clamping (IC) of the portal triad confers better protection during liver surgery.
                IP and IC are distinct protective approaches against ischemic injury. Since both strategies proved to be superior in randomized controlled trials (RCTs) to continuous inflow occlusion alone, we designed a RCT to compare IP and IC in patients undergoing major liver resection.
                Noncirrhotic patients undergoing major liver resection were randomized to receive IP with inflow occlusion (n = 36) or IC (n = 37). Primary endpoints were postoperative liver injury and intraoperative blood loss. Postoperative liver injury was assessed by peak values of AST (alanine aminotransferase) and ALT (aspartate aminotransferase), as well as the area under the curve (AUC) of the postoperative transaminase course. Secondary endpoints included resection time, the need of blood transfusion, ICU, and hospital stay as well as postoperative complications and mortality.
                Both groups were comparable regarding demographics, ASA score, type of hepatectomy, duration of inflow occlusion (range, 30-75 minutes), and resection surface. The transection-related blood loss was 146 versus 250 mL (P = 0.008), and when standardized to the resection surface 1.2 versus 1.8 mL/cm (P = 0.01) for IP and IC, respectively. Although peak AST, AUCAST, and AUCALT were lower for IC, the differences did not reach statistical significance. Overall (42% vs. 38%) and major (33 vs. 27%) postoperative complications as well as median ICU (1 vs. 1 day) and hospital stay (10 vs. 11 days) were similar between both groups.
                Both IP and IC appear to be equally effective in protecting against postoperative liver injury in noncirrhotic patients undergoing major liver resection. However, IP is associated with lower blood loss and shorter transection time. Therefore, both strategies can be recommended for noncirrhotic patients undergoing liver resection. Publication bias toward studies that favor new therapies has been known to occur for the past 40 years, yet its implications are not well studied in child health. The increased interest in meta-analyses has highlighted the need to identify the totality of evidence when addressing treatment questions.
                To measure the percentage of randomized controlled trials (RCTs) presented at a major pediatric scientific meeting that were subsequently published as full-length articles, to investigate factors associated with publication, and to describe the variables that change from abstract to manuscript form.
                The scientific proceedings from the Society for Pediatric Research were hand searched for RCTs (1992-1995). Subsequent publication was ascertained through a search of various electronic databases. Quality of abstracts and manuscripts was measured, and data were extracted using a structured form.
                A total of 264 (59.1%) of 447 abstracts were subsequently published. Almost 64% of RCTs that were subsequently published favored new therapy compared with 43.5% of studies that were never published (P<.001). Mean effect size for published vs unpublished RCTs was 0.74 vs 0.05 (P<.001). Median sample size was larger in published (n = 45) vs unpublished (n = 34) RCTs (P =.02). Quality was significantly lower for abstracts vs published RCTs (P<.001). For 5% of abstracts that were subsequently published, the conclusion regarding treatment efficacy changed.
                Publication bias is a serious threat to assessing the effectiveness of interventions in child health, as little more than half of RCTs presented at a major scientific meeting are subsequently published. There is a need to institute an international registry of RCTs in children so that the totality of evidence can be accessed when assessing treatment effectiveness. To examine the effect of bolus vs. continuous infusion adjustment on severity and duration of alcohol withdrawal syndrome (AWS), the medication requirements for AWS treatment, and the effect on ICU stay in surgical intensive care unit (ICU) patients.
                Prospective randomized, double-blind controlled trial in a surgical ICU.
                44 patients who developed AWS after admission to the ICU.
                Patients were randomized to either (a). a continuous infusion course of intravenous flunitrazepam (agitation), intravenous clonidine (sympathetic hyperactivity), and intravenous haloperidol (productive psychotic symptoms) if needed (infusion-titrated group), or (b). the same medication (flunitrazepam, clonidine, or haloperidol) bolus adjusted in response to the development of the signs and symptoms of AWS (bolus-titrated group).
                The administration of "as-needed" medication was determined using a validated measure of the severity of AWS (Clinical Institute of Withdrawal Assessment). Although the severity of AWS did not differ between groups initially, it significantly worsened over time in the infusion-titrated group. This required a higher amount of flunitrazepam, clonidine, and haloperidol. ICU treatment was significantly shorter in the bolus-titrated group (median difference 6 days) due to a lower incidence of pneumonia (26% vs. 43%).
                We conclude that symptom-orientated bolus-titrated therapy decreases the severity and duration of AWS and of medication requirements, with clinically relevant benefits such as fewer days of ventilation, lower incidence of pneumonia, and shorter ICU stay. To discuss the quality of reporting in randomized controlled trials (RCTs) of Chinese herbal medicine (CHM), and to provide suggestions for improving the reporting of future clinical studies in this therapeutic area.
                A search of the Cochrane Library was conducted to identify RCTs of CHM. A revised CONSORT checklist designed for CHM clinical studies was implemented. The revised CONSORT checklist contained 63 items, including the following new items added specifically for CHM: (1) "syndrome of disease" based on Chinese medicine theories; (2) rationale of CHM formula; (3) formula composition; (4) preparation form of CHM; (5) quality control of CHM.
                The overall reporting quality of the RCTs as assessed with the revised CONSORT checklist varied between 19% and 44%, with a median score of 32% (standard deviation 8%).
                The overall quality of reporting of RCTs of CHM evaluated with a revised CONSORT checklist was poor, reflecting the need for improvements in reporting future clinical trials in this area.
                To improve the quality of reporting of RCTs of CHM, we recommend adopting a revised CONSORT checklist that includes items specific to CHM. We also recommend that editors of CHM journals require authors to use a structured approach to presenting their trials as a condition of publication. Randomized controlled trials (RCTs) are accepted as the gold standard for assessing the effectiveness of clinical interventions but are rarely reported in pediatric surgery. Have RCTs submitted to the British Association of Paediatric Surgeons (BAPS) Annual Congress during the last 5 years been adequately designed and large enough to produce a valid result?
                Abstracts accepted by the Annual BAPS Congress meetings between 1996 and 2000 were examined in collaboration with a senior health services researcher. The quality of the design, methodology, statistical analysis and conclusions, and the adequacy of the sample size were assessed for all identifiable clinical RCTs.
                From 760 accepted abstracts, there were only 9 RCTs (1%) of clinical interventions. In only 4 trials was the relevant primary end-point specified at the outset of the study, and none documented the method of randomization. Only one abstract mentioned blinding with respect to the intervention or outcome measure. Sample sizes were inadequate to detect even large clinical differences. To date, only one of these RCTs has been published in an English-language, peer-reviewed journal.
                Clear guidelines exist for the conduct of RCTs, yet compliance with these standards was rarely documented in abstracts of pediatric surgical RCTs presented at BAPS. Sample sizes were inadequate. RCTs in pediatric surgery are difficult to perform, but the specialty would benefit from well-designed, carefully conducted, multicentre, clinical RCTs to advance evidence-based practice.
                Copyright 2003, Elsevier Science (USA). All rights reserved. A multi-centre, double-blind study was carried out in 100 patients suffering from chronic spasticity due to multiple sclerosis to compare the effectiveness of tizanidine hydrochloride with that of baclofen. Patients were allocated at random to receive treatment initially with daily doses of either 6 mg tizanidine or 15 mg baclofen and the dose was increased during the first 2 weeks up to a maximum of 24 mg tizanidine or 60 mg baclofen per day. Patients were then treated with the optimum dose for 6 weeks. Efficacy and tolerability parameters were evaluated after 2 and 8 weeks. Tizanidine and baclofen improved the functional status of patients in 80% and 76% of cases, respectively, but there were no significant differences between the two drugs. The antispastic efficacy of tizanidine was greater after 8 weeks than after 2 weeks, whereas the efficacy of baclofen decreased slightly with time. Both drugs showed good overall tolerability in more than 60% of patients. Thus, tizanidine is a well tolerated and effective muscle relaxant, the antispastic efficacy of which is well maintained over time, and it promises to be particularly useful in the treatment of spasticity due to multiple sclerosis.
The evidence for recommending baclofen for AWS is insufficient. More well designed RCTs are needed to prove its efficacy and safety.