Safety outcomes in meta-analyses of phase 2 vs phase 3 randomized trials: Intracranial hemorrhage in trials of bolus thrombolytic therapy

CONTEXT: Recent studies have reported disagreement between meta-analysis of small trials and subsequent large trials addressing the same question. However, disagreement for uncommon but serious adverse safety outcomes has not been examined. OBJECTIVE: To explore disagreement for serious adverse safety (intracranial hemorrhage [ICH]) and efficacy outcomes between meta-analysis of phase 2 (small) vs meta-analysis of phase 3 (large) randomized controlled trials comparing the efficacy of bolus thrombolytic therapy with infusion for acute myocardial infarction (AMI). DATA SOURCES: Electronic databases (MEDLINE, Cochrane Database of Clinical Trials) between January 1980 and December 1999 using the search terms thrombolysis, thrombolytic therapy, and myocardial infarction; conference proceedings; and reference lists. STUDY SELECTION: Fifteen randomized trials comparing thrombolytic agents administered by bolus injection with standard infusion therapy in patients with AMI. DATA EXTRACTION: Data on ICH, other causes of stroke, total mortality, and reinfarction were independently extracted from each study by 2 observers. DATA SYNTHESIS: Meta-analysis of 9 phase 2 trials (n = 3956) revealed a lower risk of ICH with bolus thrombolytic therapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.27-1.01), which was not statistically significant. Meta-analysis of 6 phase 3 trials (n = 62 673) indicated a significant increase in risk of ICH (OR, 1.25; 95% CI, 1.06-1.49). These results were significantly different (P =.01). There was no disagreement for efficacy outcomes. Phase 2 trials included younger and heavier patients with lower baseline blood pressures, and were more often open-label. Subgroup analyses suggested that each of these factors was associated with a lower estimate of risk of ICH with bolus agents. CONCLUSIONS: Our results suggest that when therapeutic interventions are associated with a potential for uncommon but serious adverse safety outcomes, there may be differences between small phase 2 and large phase 3 trials that result in their disagreement for safety but not necessarily efficacy outcomes. Further investigation of the frequency and causes of disagreement between small and large trials for safety outcomes is warranted.     

Meta-analysis of benzodiazepine use in the treatment of insomnia

OBJECTIVE: To systematically review the benefits and risks associated with the use of benzodiazepines to treat insomnia in adults. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1998 that described randomized controlled trials of benzodiazepines for the treatment of insomnia. Key words included "benzodiazepines" (exploded), "randomized controlled trial" and "insomnia." Bibliographies of relevant articles were reviewed for additional studies and manufacturers of benzodiazepines were asked to submit additional randomized controlled trial reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were randomized controlled trials involving patients with insomnia and compared a benzodiazepine with placebo or another active agent. Of the 89 trials originally identified, 45 met our criteria, representing a total of 2672 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analyses of sleep records indicated that, when compared with placebo, benzodiazepines decreased sleep latency by 4.2 minutes (non-significant; 95% confidence interval (CI -0.7 to 9.2) and significantly increased total sleep duration by 61.8 minutes (95% CI 37.4 to 86.2). Patient-reported outcomes were more optimistic for sleep latency; those randomized to benzodiazepine treatment estimated a sleep latency decrease of 14.3 minutes (95% CI 10.6 to 18.0). Although more patients receiving benzodiazepine treatment reported adverse effects, especially daytime drowsiness and dizziness or light-headedness (common odds ratio 1.8, 95% CI 1.4 to 2.4), dropout rates for the benzodiazepine and placebo groups were similar. Cognitive function decline including memory impairment was reported in several of the studies. Zopiclone was not found to be superior to benzodiazepines on any of the outcome measures examined. INTERPRETATION: The use of benzodiazepines in the treatment of insomnia is associated with an increase in sleep duration, but this is countered by a number of adverse effects. Additional studies evaluating the efficacy of nonpharmacological interventions would be valuable.     

Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal

OBJECTIVE: To analyse the evidence for the efficacy and potential harmful effects of benzodiazepines compared with other therapies in the treatment of acute alcohol withdrawal. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1997 that described randomized controlled trials (RCTs) of benzodiazepines in the treatment of acute alcohol withdrawal. Key words included "benzodiazepines" (exploded) and "randomized controlled trial." Bibliographies of relevant articles were reviewed for additional RCTs, and manufacturers of benzodiazepines were asked to submit additional RCT reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were RCTs involving patients experiencing acute alcohol withdrawal and comparing a benzodiazepine available in Canada with placebo or an active control drug. Of the original 23 trials identified, 11 met these criteria, representing a total of 1286 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analysis of benefit (therapeutic success within 2 days) showed that benzodiazepines were superior to placebo (common odds ratio [OR] 3.28, 95% confidence interval [CI] 1.30-8.28). Data on comparisons between benzodiazepines and other drugs, including beta-blockers, carbamazepine and clonidine, could not be pooled, but none of the alternative drugs was found to be clearly more beneficial than the benzodiazepines. The meta-analysis of harm revealed no significant difference between benzodiazepines and alternative drugs in terms of adverse events (common OR 0.67, 95% CI 0.34-1.32) or dropout rates (common OR 0.68, 95% CI 0.47-0.97). INTERPRETATION: Benzodiazepines should remain the drugs of choice for the treatment of acute alcohol withdrawal.     

Effectiveness of interventions to prevent delirium in hospitalized patients: a systematic review.

OBJECTIVE: To determine the effectiveness of interventions to prevent delirium in hospitalized patients. DATA SOURCES: Two databases, MEDLINE and CINAHL, were searched for relevant articles published from January 1966 to May 1995 and from January 1982 to May 1995 respectively. The bibliographies of identified articles were searched for additional references. STUDY SELECTION: Ten articles met the following three inclusion criteria: (a) original research article, (b) published in English or French and (c) controlled trial (nonrandomized or randomized) of an intervention to prevent delirium in hospitalized patients. The validity of the studies was independently assessed according to the criteria for intervention studies proposed by the Evidence-Based medicine Working Group. DATA EXTRACTION: Information about study design, patient population, sample size, diagnostic criteria, interventions and results was systematically abstracted from each report. Absolute risk reduction (ARR) for delirium was calculated for each study. DATA SYNTHESIS: Eight trials involved surgical patients and two involved elderly medical patients; most of the studies had serious methodological limitations. Among the surgical patients the ARRs ranged from -13% to 81% and were not related to the type or timing of the intervention, or to the personnel involved. Among the elderly medical patients the ARRs ranged from -3% to 3%. CONCLUSION: Interventions to prevent delirium among surgical patients may be modestly effective, but further trials are necessary.     

Hormone replacement therapy and cognition: systematic review and meta-analysis

CONTEXT: Some observational data suggest that hormone replacement therapy (HRT) may reduce the risk of cognitive decline and dementia but results have been conflicting. OBJECTIVE: To review and evaluate studies of HRT for preventing cognitive decline and dementia in healthy postmenopausal women. DATA SOURCES: Studies with English-language abstracts identified in MEDLINE (1966-August 2000), HealthSTAR (1975-August 2000, PsychINFO (1984-August 2000); Cochrane Library databases; and articles listed in reference lists of key articles. STUDY SELECTION: Randomized controlled trials and cohort studies were reviewed for the effects of HRT on cognitive decline; cohort and case-control studies were reviewed for dementia risk. No randomized controlled trials regarding dementia risk were identified. DATA EXTRACTION: Twenty-nine studies met inclusion criteria and were rated. Two reviewers rated study quality independently and 100% agreement was reached on Jadad scores and 80% agreement was reached on US Preventive Services Task Force quality scores. A final score was reached through consensus if reviewers disagreed. DATA SYNTHESIS: Studies of cognition were not combined quantitatively because of heterogeneous study design. Women symptomatic from menopause had improvements in verbal memory, vigilance, reasoning, and motor speed, but no enhancement of other cognitive functions. Generally, no benefits were observed in asymptomatic women. A meta-analysis of observational studies suggested that HRT was associated with a decreased risk of dementia (summary odds ratio, 0.66; 95% confidence interval, 0.53-0.82). However, possible biases and lack of control for potential confounders limit interpretation of these studies. Studies did not contain enough information to assess adequately the effects of progestin use, various estrogen preparations or doses, or duration of therapy. CONCLUSIONS: In women with menopausal symptoms, HRT may have specific cognitive effects, and future studies should target these effects. The meta-analysis found a decreased risk of dementia in HRT users but most studies had important methodological limitations.     

Interventions for the treatment and management of chronic fatigue syndrome: a systematic review

CONTEXT: A variety of interventions have been used in the treatment and management of chronic fatigue syndrome (CFS). Currently, debate exists among health care professionals and patients about appropriate strategies for management. OBJECTIVE: To assess the effectiveness of all interventions that have been evaluated for use in the treatment or management of CFS in adults or children. DATA SOURCES: Nineteen specialist databases were searched from inception to either January or July 2000 for published or unpublished studies in any language. The search was updated through October 2000 using PubMed. Other sources included scanning citations, Internet searching, contacting experts, and online requests for articles. STUDY SELECTION: Controlled trials (randomized or nonrandomized) that evaluated interventions in patients diagnosed as having CFS according to any criteria were included. Study inclusion was assessed independently by 2 reviewers. Of 350 studies initially identified, 44 met inclusion criteria, including 36 randomized controlled trials and 8 controlled trials. DATA EXTRACTION: Data extraction was conducted by 1 reviewer and checked by a second. Validity assessment was carried out by 2 reviewers with disagreements resolved by consensus. A qualitative synthesis was carried out and studies were grouped according to type of intervention and outcomes assessed. DATA SYNTHESIS: The number of participants included in each trial ranged from 12 to 326, with a total of 2801 participants included in the 44 trials combined. Across the studies, 38 different outcomes were evaluated using about 130 different scales or types of measurement. Studies were grouped into 6 different categories. In the behavioral category, graded exercise therapy and cognitive behavioral therapy showed positive results and also scored highly on the validity assessment. In the immunological category, both immunoglobulin and hydrocortisone showed some limited effects but, overall, the evidence was inconclusive. There was insufficient evidence about effectiveness in the other 4 categories (pharmacological, supplements, complementary/alternative, and other interventions). CONCLUSIONS: Overall, the interventions demonstrated mixed results in terms of effectiveness. All conclusions about effectiveness should be considered together with the methodological inadequacies of the studies. Interventions which have shown promising results include cognitive behavioral therapy and graded exercise therapy. Further research into these and other treatments is required using standardized outcome measures.     

The exclusion of the elderly and women from clinical trials in acute myocardial infarction.

OBJECTIVE--To determine the extent to which the elderly have been excluded from trials of drug therapies used in the treatment of acute myocardial infarction, to identify factors associated with such exclusions, and to explore the relationship between the exclusion of elderly and the representation of women. DATA SOURCES--We conducted a systematic search of the English-language literature from January 1960 through September 1991 to identify all relevant studies of specific pharmacotherapies employed in the treatment of acute myocardial infarction. To accomplish this, we searched MEDLINE, major cardiology textbooks, meta-analyses, reviews, editorials, and the bibliographies of all identified articles. STUDY SELECTION--Only trials in which patients were randomly allocated to receive a specific therapeutic regimen or a placebo or nonplacebo control regimen were included for review. DATA EXTRACTION--Studies were abstracted for year of publication, source of support, performance location, drug therapies to which patients were randomized, use of invasive diagnostic tests or therapeutic procedures, exclusion criteria, size and demographic characteristics of the randomized study population, and principal outcome measures. DATA SYNTHESIS--A total of 214 trials met inclusion criteria, involving 150,920 study subjects. Over 60% of trials excluded persons over the age of 75 years. Studies published after 1980 were more likely to have age-based exclusions compared with studies published before 1980 (adjusted odds ratio, 4.92; 95% confidence interval, 2.33 to 10.54). Trials of thrombolytic therapy involving an invasive procedure were more likely to exclude elderly patients compared with other studies (adjusted odds ratio, 2.45; 95% confidence interval, 1.10 to 5.47). Studies with age-based exclusions had a smaller percentage of women compared with those without such exclusions (18% vs 23%; P = .0002), with the mean age of the study population significantly associated with the proportion of women participants (P = .0001, R2 = .29). CONCLUSIONS--Age-based exclusions are frequently used in clinical trials of medications used in the treatment of acute myocardial infarction. Such exclusions limit the ability to generalize study findings to the patient population that experiences the most morbidity and mortality from acute myocardial infarction.     

Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials

CONTEXT: Hormone replacement therapy (HRT) is widely considered to reduce fractures, but this belief is based on observational data; evidence from randomized trials is lacking. OBJECTIVE: To conduct a systematic review of all randomized trials of HRT that have reported or collected nonvertebral fracture data but that may not have focused on fracture prevention. DATA SOURCES: The MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trials Register databases were searched from 1997 through 2000 and a search was conducted of all recent systematic reviews to identify older studies. Authors were contacted to establish whether fracture data had been collected but not reported. Researchers in the field and pharmaceutical companies also were contacted to try to identify unpublished studies. STUDY SELECTION: Trials were included in which participants had been randomized to at least 12 months of therapy and data on nonvertebral fractures at any other site and due to any cause were available. Of 70 initially identified studies, 22 were included in the analysis. DATA EXTRACTION: Both investigators extracted data independently and appraised trial quality according to the Jadad scale, which assesses the methods of randomization, concealment allocation, and reporting of withdrawals and dropouts. Disagreements were resolved by discussion. DATA SYNTHESIS: There was an overall 27% reduction in nonvertebral fractures in a pooled analysis (reduction favoring HRT in relative risk [RR], 0.73; 95% confidence interval [CI], 0.56-0.94; P =.02). This effect was greater among women randomized to HRT who had a mean age younger than 60 years (RR, 0.67; 95% CI, 0.46-0.98; P =.03). Among women with a mean age of 60 years or older, there was a reduced effect (RR, 0.88; 95% CI, 0.71-1.08; P =.22). For hip and wrist fractures alone, the effectiveness of HRT appeared more marked (RR, 0.60; 95% CI, 0.40-0.91; P =.02), particularly for women younger than 60 years (RR, 0.45; 95% CI, 0.26-0.79; P =.005). CONCLUSIONS: Our meta-analysis of randomized controlled trials of HRT noted a statistically significant reduction in nonvertebral fractures. However, this effect may be attenuated in older women.     

Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials

CONTEXT: Exercise is widely perceived to be beneficial for glycemic control and weight loss in patients with type 2 diabetes. However, clinical trials on the effects of exercise in patients with type 2 diabetes have had small sample sizes and conflicting results. OBJECTIVE: To systematically review and quantify the effect of exercise on glycosylated hemoglobin (HbA(1c)) and body mass in patients with type 2 diabetes. DATA SOURCES: Database searches of MEDLINE, EMBASE, Sport Discuss, Health Star, Dissertation Abstracts, and the Cochrane Controlled Trials Register for the period up to and including December 2000. Additional data sources included bibliographies of textbooks and articles identified by the database searches. STUDY SELECTION: We selected studies that evaluated the effects of exercise interventions (duration >/=8 weeks) in adults with type 2 diabetes. Fourteen (11 randomized and 3 nonrandomized) controlled trials were included. Studies that included drug cointerventions were excluded. DATA EXTRACTION: Two reviewers independently extracted baseline and postintervention means and SDs for the intervention and control groups. The characteristics of the exercise interventions and the methodological quality of the trials were also extracted. DATA SYNTHESIS: Twelve aerobic training studies (mean [SD], 3.4 [0.9] times/week for 18 [15] weeks) and 2 resistance training studies (mean [SD], 10 [0.7] exercises, 2.5 [0.7] sets, 13 [0.7] repetitions, 2.5 [0.4] times/week for 15 [10] weeks) were included in the analyses. The weighted mean postintervention HbA(1c) was lower in the exercise groups compared with the control groups (7.65% vs 8.31%; weighted mean difference, -0.66%; P<.001). The difference in postintervention body mass between exercise groups and control groups was not significant (83.02 kg vs 82.48 kg; weighted mean difference, 0.54; P =.76). CONCLUSION: Exercise training reduces HbA(1c) by an amount that should decrease the risk of diabetic complications, but no significantly greater change in body mass was found when exercise groups were compared with control groups.     

Patient outcomes after lumbar spinal fusions.

OBJECTIVES--To determine success and complication rates for lumbar spinal fusion surgery, predictors of good outcomes, and whether fusion improves success rates of laminectomy for specific low back disorders. DATA SOURCES--English-language journal articles published from 1966 through April 1991, identified through MEDLINE searching (spinal fusion plus limiting terms), bibliography review, and expert consultation. STUDY SELECTION--Articles were selected only if they reported at least 1 year of follow-up data enabling the classification of clinical outcomes as satisfactory or unsatisfactory for at least 30 patients. DATA EXTRACTION--Two reviewers independently extracted data on patient characteristics, surgical methods, patient outcomes, and quality of study methods. DATA SYNTHESIS--Of 47 articles, there were no randomized trials. Four nonrandomized studies compared surgery with and without fusion for herniated disks; three found no advantage for fusion. On average, 68% of patients had a satisfactory outcome after fusion, but the range was wide (16% to 95%), and the satisfactory outcome rate was lower in prospective than in retrospective studies. The most frequently reported complications were pseudarthrosis (14%) and chronic pain at the bone graft donor site (9%). Clinical outcomes did not differ by diagnosis or fusion technique, but were worse in studies with a greater number of previously operated patients. CONCLUSIONS--For several low back disorders no advantage has been demonstrated for fusion over surgery without fusion, and complications of fusions are common. Randomized controlled trials are needed to compare fusion, surgery without fusion, and nonsurgical treatments in rigorously defined patient groups.     

重症急性肾损伤早期与晚期应用肾脏替代法疗效的Meta分析

目的 对比重症急性肾损伤(acute kidney injury, AKI)早期与晚期应用肾脏替代法(renal replacement therapy, RRT)治疗后的生存率与肾功能恢复情况。方法 使用Meta分析方法,检索中国知网、万方、MEDLINE、PubMed、EMBASE、Web of Science(1985年1月至2015年5月)数据库中相关随机对照试验(randomized controlled trial,RCT)及观察性研究文献,并扩展至所有涉及的参考文献,进行双人交叉文献纳入、排除,提取最终获得的文献的效应量,使用STAT11.0进行合并、数据分析。结果 获得参考文献1 494篇,经过纳入、排除后,最终获得符合要求的文献15篇(2篇RCT、4篇前瞻队列研究、9篇回顾队列研究)。文献整体方法学质量不高。早期应用肾脏替代法患者比晚期应用患者的28日存活率显著提高(合并OR值=0.45,95%CI:0.28~0.72, P<0.001)。各研究间异质性较大(I²=78%)。以收治重症加强护理病房(intensive care unit, ICU)类别、研究设计分别进行亚组分析未发现各亚组差异有统计学意义(P<0.05)。提取有次要结局指标的报道(7篇)的肾功能恢复效应量进行合并,并未发现早期应用比晚期应用肾脏替代法对肾功能恢复有显著提升(OR=0.62,95%CI:0.34~1.13,I²=69.6%)。结论 1)早期应用体外RRT治疗重症急性肾损伤,有助于提高患者存活率,提高幅度明显;2)现有证据表明,早期开展RRT无助于重症AKI患者肾功能恢复;3)提供现有证据的研究大部分样本量较小,研究设计不统一,质量参差不齐。在设计合理的大规模多中心RCT证据出现之前,现有的关于RRT使用时机的结论并不一定能完全代表客观事实;4)有必要展开相关研究,明确定义RRT治疗时机中的"早期"与"晚期"。     

An overview of interventions to improve compliance with appointment keeping for medical services.

OBJECTIVE--To determine, by a quantitative meta-analysis of randomized trials, the effectiveness of strategies to improve patient compliance with screening, referral, and clinic appointments for health services that are provided at the time of the visit. DATA SOURCES--Computerized searches of MEDLINE (1966 through 1990) were done using two search strategies: (1) (Patient Compliance OR Adhere* OR Dropout*) AND (Appointment*) AND (Screen* OR Follow* OR Refer*); and (2) (Patient Compliance OR Adhere* OR Dropout*) AND (Attend* OR Screen*) OR (Appointment*). A computerized search of PSYCHLIT was done with the terms Compliance AND Appointment*. In addition, the reference list of each retrieved article was reviewed and relevant citations retrieved. STUDY SELECTION--Only randomized trials with quantitative data concerning the effect of interventions to improve attendance at appointments for supervised administration of care were considered for detailed review. Studies of appointment keeping for self-administered treatments or tests were excluded. Two independent reviewers assessed each article for inclusion (kappa, for agreement, 0.66 for MEDLINE; 0.95 for PSYCHLIT) and validity (kappa, 0.62) using a priori criteria. Twenty-three (26%) of 88 relevant articles met all criteria. DATA EXTRACTION--Data on study populations, interventions, and outcomes were extracted and analyzed using pooled odds ratios (ORs). DATA SYNTHESIS--The average rate of compliance with appointments was 58%. Mailed reminders and telephone prompts were consistently useful in reducing broken appointments (OR, 2.2; 95% confidence interval [CI], 1.7 to 2.9; and OR, 2.9, CI, 1.9 to 4.3, respectively). An "orientation statement" (OR, 2.9; CI, 1.5 to 5.6), "contracting" with patients (OR, 1.9; CI, 1.04 to 3.5), and prompts from physicians (OR, 1.6; CI, 1.4 to 2.0) showed positive effects as well. CONCLUSIONS--In clinic settings where kept appointments can be an accurate measure of patient compliance with health care interventions, broken appointments can be reduced by mail, telephone, or physician reminders; orienting patients to the clinic; or contracting with patients.     

Analysis and reporting of factorial trials: a systematic review

CONTEXT: Although factorial trials have become common, standards for the analysis and reporting of such trials have not been established and, despite concerns about the possibility of unrecognized interactions between therapies in factorial trials, the magnitude of this potential problem is unknown. OBJECTIVE: To examine the rationale, methods, and analysis of randomized factorial trials. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register using the terms factorial, interaction, 2 x 2, 2 by 2, and incremental to identify factorial randomized trials published from January 2000 to July 2002. To identify trials missed by the electronic search, we performed a hand search of English-language trials in a defined topic area (using the term myocardial ischemia [exp]) listed in MEDLINE (1966-2002), EMBASE (1980-2002), and the Cochrane Controlled Trials Register, as well as all trials in any topic area published in December 2000, excluding trials reporting only continuous surrogate end points. The final set of 33 eligible publications described 29 unique trials. DATA EXTRACTION: Two investigators independently identified factorial trials, generated a list of items affecting validity of results, and abstracted these items from each trial. DATA SYNTHESIS: The sensitivity of electronic searching for identifying factorial trials was 76%. Our 3-pronged search strategy identified 44 factorial trials with clinically important binary outcomes: 36 (82%) were done for reasons of efficiency (testing 2 interventions in the same patient population), and 8 (18%) were done to assess the incremental benefits of combining the 2 treatments. All but 1 of the trials reported treatment effects by comparing all patients who received treatment A (ie, those receiving either A alone or both A and B) vs all those not receiving treatment A (ie, those receiving either B alone or neither A nor B). Twenty-nine of the 44 trials (66%) reported the data from each of the treatment groups separately; 26 trials (59%) reported testing for interactions between the treatments. Only 2 of 31 (6%) comparisons demonstrated a statistically significant interaction between the 2 treatments. CONCLUSIONS: Accurate interpretation of factorial trials depends on the transparent reporting of data for each treatment cell. Despite concerns about unrecognized interactions, our findings suggest that investigators are appropriately restricting their use of the factorial design to those situations in which 2 (or more) treatments do not have the potential for substantive interaction.     

小肝癌射频消融与手术切除疗效的Meta分析

目的:对于可以手术的小肝癌患者射频消融和手术切除哪种治疗更适合,一直没有统一的定论,为此本文对两者进行Meta分析?方法:对2000年1月~2009年12月在PubMed?Medline和CNKI上收录的关于小肝癌射频消融与手术切除疗效比较的文献数据进行系统回顾和Meta分析,利用固定效应模型和随机效应模型计算优势比(OR)和95%可信区间(95%Cl)?结果:共选取6篇随机对照研究(RCT)和9篇非随机对照研究(NRCT),这些研究总共包括了2 284例肝癌患者,其中1 213例行射频消融治疗,1 071例行肝切除治疗?射频消融组和肝切除组在1年生存率?1年复发率?3年复发率上没有显著差异(P > 0.05),3年生存率手术组明显高于射频组(P < 0.05)?结论:小肝癌的治疗中射频消融与肝切除相比1年累计生存率及复发率无明显差别,但是就远期生存情况来看,肝切除仍优于射频消融?     

Effectiveness of intrapartum penicillin prophylaxis in preventing early-onset group B streptococcal infection: results of a meta-analysis.

OBJECTIVE: To determine the effectiveness of intrapartum penicillin prophylaxis in preventing early-onset group B streptococcal (GBS) infection in neonates of women whose birth canals are colonized by group B streptococci. DATA SOURCES: Articles published between 1966 and 1992 identified from MEDLINE, EMBASE, the Science Citation Index and the Oxford Perinatal Database; the bibliographies of primary studies, textbooks and review articles and published abstracts from major conferences and symposia. DATA SELECTION: Studies were selected if four criteria were met: (a) the target population was intrapartum women and neonates, (b) the intervention was penicillin prophylaxis, (c) invasive early-onset GBS infection was an outcome measure, and (d) the studies were controlled trials or cohort studies. Seven primary studies were identified, four of which were randomized controlled trials. DATA EXTRACTION: Explicit methodologic criteria were used by two of the authors to assess independently the study quality; one of the reviewers was blind as to author, institution and journal. The baseline characteristics of the population, intervention and outcome were summarized twice and checked for accuracy by two of the authors. DATA SYNTHESIS: Five of the studies showed a trend toward a beneficial effect of penicillin prophylaxis, and two showed a statistically significant effect. The pooled odds ratio indicated a 30-fold reduction (95% confidence interval 0.0013 to 0.17) in the incidence of early-onset GBS infection with intrapartum penicillin prophylaxis. Subgroup analyses did not change these results. The magnitude of improvement observed did not differ between women with prenatal risk factors (premature rupture of the membranes and premature labour) and those without these risk factors. CONCLUSIONS: There is accumulative evidence that intrapartum penicillin prophylaxis is effective in preventing early-onset GBS infection. Such therapy is beneficial to women whose birth canals are colonized with group B streptococci. Further studies are needed to determine the optimum timing and method of detecting vaginal colonization during pregnancy.     

Indications for treatment of Helicobacter pylori infection: a systematic overview.

OBJECTIVE: To determine (a) the advantages and disadvantages of treatment options for the eradication of Helicobacter pylori and (b) whether eradication of H. pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and gastric cancer. DATA SOURCES: A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric cancer, dyspepsia and clinical trial. Six journals and Current Contents were searched manually for pertinent articles published in that time frame. STUDY SELECTION: For duodenal ulcer the search was limited to studies involving adults, studies of H. pylori eradication and randomized clinical trials comparing anti-H. pylori therapy with conventional ulcer treatment. For nonulcer dyspepsia with H. pylori infection the search was limited to placebo-controlled randomized clinical trials. DATA EXTRACTION: The quality of each study was rated independently on a four-point scale by each author. For the studies of duodenal ulcer the outcome measures assessed were acute ulcer healing and time required for healing, H. pylori eradication and ulcer relapse. For the studies of nonulcer dyspepsia with H. pylori infection the authors assessed H. pylori eradication, the symptoms used as outcome measures and whether validated outcome measures had been used. DATA SYNTHESIS: Eight trials involving duodenal ulcer met our inclusion criteria: five were considered high quality, two were of reasonable quality, and one was weak. Six trials involving nonulcer dyspepsia met the criteria, but all were rated as weak. Among treatment options triple therapy with a bismuth compound, metronidazole and either amoxicillin or tetracycline achieved the highest eradication rates (73% to 94%). Results concerning treatment indications for duodenal ulcer were consistent among all of the studies: when anti-H. pylori therapy was added to conventional ulcer treatment acute ulcers healed more rapidly. Ulcer relapse rates were dramatically reduced after H. pylori eradication. All of the studies involving nonulcer dyspepsia assessed clearance rather than eradication of H. pylori. No study used validated outcome measures. A consistent decrease in symptom severity was no more prevalent in patients in whom the organism had been cleared than in those taking a placebo. Of the studies concerning gastric cancer none investigated the effect of eradication of H. pylori on subsequent risk of gastric cancer. CONCLUSIONS: There is sufficient evidence to support the use of anti-H. pylori therapy in patients with duodenal ulcers who have H. pylori infection, triple therapy achieving the best results. There is no current evidence to support such therapy for nonulcer dyspepsia in patients with H. pylori infection. Much more attention must be paid to the design of nonulcer dyspepsia studies. Also, studies are needed to determine whether H. pylori eradication in patients with gastritis will prevent gastric cancer.     

Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein thrombosis after total hip replacement.

OBJECTIVE: To compare the efficacy and cost-effectiveness of enoxaparin, a low-molecular-weight heparin derivative, with that of low-dose warfarin in the prevention of deep-vein thrombosis (DVT) after total hip replacement. DATA SOURCES: English-language articles on enoxaparin and warfarin prophylaxis is patients undergoing total hip replacement published from January 1982 to December 1992. STUDY SELECTION: Four trials of enoxaparin (involving 567 patients) and six trials of warfarin (involving 630) met the following criteria: randomized controlled trial, prophylaxis started no later than 24 hours after surgery and continued for at least 7 days, warfarin dose monitored and adjusted appropriately, enoxaparin dosage 30 mg twice daily, and DVT confirmed by bilateral venography. DATA EXTRACTION: Rates of DVT, cost of prophylaxis, diagnosis and treatment per patient, rate of pulmonary embolism (PE), number of deaths and incremental cost-effectiveness (cost per life-year gained). DATA SYNTHESIS: The pooled rate of DVT was 13.6% with enoxaparin (95% confidence interval [CI] 10.9% to 16.3%) and 20.6% with warfarin (95% CI 17.4% to 23.8%). At a cost of $19.55 per day for enoxaparin the total cost per patient, including prophylaxis and management of DVT, exceeded that per patient receiving warfarin by about $121. For every 10,000 patients treated the use of enoxaparin will prevent 47 cases of DVT, 3 cases of PE and 4 deaths. Thus, the estimated incremental cost-effectiveness of enoxaparin is $29 120 per life-year gained. CONCLUSION: On the basis of current Canadian cost-effectiveness guidelines the results of this study would be considered moderate to strong evidence to adopt enoxaparin prophylaxis against DVT after total hip replacement. However, because of the limited data the estimates are uncertain. Future trials should compare enoxaparin and warfarin and incorporate a prospective economic appraisal.     

Automatic external defibrillators: changing the way we manage ventricular fibrillation

OBJECTIVE: To discuss recent developments in automatic defibrillation and to review the evidence that first-responders equipped with automatic external defibrillators (AEDs) improve survival from out-of-hospital cardiac arrest. DATA SOURCES: MEDLINE search from 1966 to 1999 (articles in English only) and examination of bibliographies. STUDY SELECTION: Published studies of out-of-hospital cardiac arrest and first-responders equipped with AEDs. Studies had to have a control group and to report survival to hospital discharge from ventricular fibrillation (VF). DATA EXTRACTION: Six studies met the selection criteria (two prospective randomised trials, two prospective controlled trials, and one cohort study and one retrospective study, both with historical controls). DATA SYNTHESIS: A random effects meta-analysis of odds ratios for survival from VF. CONCLUSIONS: Meta-analysis suggests that equipping first-responders with AEDs increases the probability of survival to hospital discharge after out-of-hospital cardiac arrest (odds ratio, 1.74; 95% CI, 1.27-2.38; P < 0.001). However, most of the studies lacked sufficient power to draw definitive conclusions. Until the impact of wide deployment of AEDs is fully understood, first-responder defibrillation in Australia should only occur as part of coordinated multicentre research studies.     

Preoperative radiotherapy for resectable rectal cancer: A meta-analysis

CONTEXT: The benefit of adjuvant radiotherapy for resectable rectal cancer has been extensively studied, but data on survival are still equivocal despite a reduction in the rate of local recurrence. OBJECTIVE: To assess the effectiveness of preoperative radiotherapy followed by surgery in the reduction of overall and cancer-related mortality and in the prevention of local recurrence and distant metastases. DATA SOURCES: Computerized bibliographic searches of MEDLINE and CANCERLIT (1970 to December 1999), including non-English sources, were supplemented with hand searches of reference lists. The medical subject headings used were rectal cancer, radiotherapy, surgery, RCT, randomized, and clinical trial. STUDY SELECTION: Studies were included if they were randomized controlled trials (RCTs) comparing preoperative radiotherapy plus surgery with surgery alone and if they included patients with resectable histologically proven rectal adenocarcinoma, without metastatic disease. Fourteen RCTs were analyzed. DATA EXTRACTION: Data on population, intervention, and outcomes were extracted from each RCT according to the intention-to-treat method by 3 independent observers and combined using the DerSimonian and Laird method. DATA SYNTHESIS: Radiotherapy plus surgery compared with surgery alone significantly reduced the 5-year overall mortality rate (odds ratio [OR] 0.84; 95% confidence interval [CI], 0.72-0.98; P =.03), cancer-related mortality rate (OR, 0.71; 95% CI, 0.61-0.82; P<.001), and local recurrence rate (OR, 0.49; 95% CI, 0.38-0.62; P<.001). No reduction was observed in the occurrence of distant metastases (OR, 0.93; 95% CI, 0.73-1.18; P =.54). CONCLUSIONS: In patients with resectable rectal cancer, preoperative radiotherapy significantly improved overall and cancer-specific survival compared with surgery alone. The magnitude of the benefit is relatively small and criteria are needed to identify patients most likely to benefit from adjuvant radiotherapy. JAMA. 2000;284:1008-1015     

临床试验中医生和患者对不同治疗方案疗效总体评估比较实证研究

目的 观察医生和患者对治疗方案疗效的总体评估是否一致。 设计 系统综述中入选的临床试验包含了各种不同的治疗方案。 数据来源 用于系统综述的Coehrane数据库。 数据收录 收录采用相同的对照标准比较医生和患者对同种治疗方案效果的总体评估数据。 结局评估指标 相对比值比（医生所评估的干预组和试验组的效果的比值比除以患者所评估的干预组和试验组的效果的比值比所得的率）及医生和患者各自所评估的治疗方案有效率。 结果 分别在18种不同的比较条件下，将医生和患者对63种不同治疗方案效果进行总体评估（共240次试验）。总体上讲，比较所得的相对比值比与1比较差别无统计学意义（相对比值比为0．98，95％可信区间为0．88～1．08；I^2=0％，95％可信区间0％-30％）。在63种治疗方案中，医生和患者对62种治疗方案效果的评估差异是由随机误差造成的，但其中1种治疗方案效果评估差异的可信区间较大。医生和患者对所有治疗方案效果的评估的平均值之间差异无统计学意义（总体相对比值比为0．98，0．88—1．06；I^2=0％，0％～24％）。 结论 医生和患者对治疗方案疗效的总体评估结果基本一致。