Fibrin Sealants in Dura Sealing: A Systematic Literature Review

BackgroundFibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks.MethodsA comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors.ResultsA total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure.ConclusionsA major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety.     

Using Multiple Types of Studies in Systematic Reviews of Health Care Interventions – A Systematic Review

Background

A systematic review may evaluate different aspects of a health care intervention. To accommodate the evaluation of various research questions, the inclusion of more than one study design may be necessary. One aim of this study is to find and describe articles on methodological issues concerning the incorporation of multiple types of study designs in systematic reviews on health care interventions. Another aim is to evaluate methods studies that have assessed whether reported effects differ by study types.

Methods and Findings

We searched PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Methodology Register on 31 March 2012 and identified 42 articles that reported on the integration of single or multiple study designs in systematic reviews. We summarized the contents of the articles qualitatively and assessed theoretical and empirical evidence. We found that many examples of reviews incorporating multiple types of studies exist and that every study design can serve a specific purpose. The clinical questions of a systematic review determine the types of design that are necessary or sufficient to provide the best possible answers. In a second independent search, we identified 49 studies, 31 systematic reviews and 18 trials that compared the effect sizes between randomized and nonrandomized controlled trials, which were statistically different in 35%, and not different in 53%. Twelve percent of studies reported both, different and non-different effect sizes.

Conclusions

Different study designs addressing the same question yielded varying results, with differences in about half of all examples. The risk of presenting uncertain results without knowing for sure the direction and magnitude of the effect holds true for both nonrandomized and randomized controlled trials. The integration of multiple study designs in systematic reviews is required if patients should be informed on the many facets of patient relevant issues of health care interventions.     

Impact of Including Korean Randomized Controlled Trials in Cochrane Reviews of Acupuncture

Objective

Acupuncture is commonly practiced in Korea and is regularly evaluated in clinical trials. Although many Cochrane reviews of acupuncture include searches of both English and Chinese databases, there is no information on the value of searching Korean databases. This study aimed to investigate the impact of searching Korean databasesand journals for trials eligible for inclusion in existing Cochrane acupuncture reviews.

Methods

We searched 12 Korean databases and seven Korean journals to identify randomised trials meeting the inclusion criteria for acupuncture reviews in the Cochrane Database of Systematic Reviews. We compared risk of bias assessments of the Korean trials with the trials included in the Cochrane acupuncture reviews. Where possible, we added data from the Korean trials to the existing meta-analyses in the relevant Cochrane review and conducted sensitivity analyses to test the robustness of the results.

Results

Sixteen Korean trials (742 participants) met the inclusion criteria for eight Cochrane acupuncture reviews (125 trials; 13,041 participants). Inclusion of the Korean trials provided data for 20% of existing meta-analyses (24 out of 120). Inclusion of the Korean trials did not change the direction of effect in any of the existing meta-analyses. The effect size and heterogeneity remained mostly unchanged. In only one meta-analysis did the significance change. Compared to the studies included in the Cochrane acupuncture reviews, the risk of bias in the Korean trials was higher in terms of outcome assessor blinding and allocation concealment.

Conclusions

Many Korean studies contributed additional data to the existing meta-analyses in Cochrane acupuncture reviews. Although inclusion of these studies did not alter the results of the meta-analyses, comprehensive searches of the literature are important to avoid potential language bias. The identification and inclusion of eligible Korean trials should be considered for reviews of acupuncture.     

Addressing Dichotomous Data for Participants Excluded from Trial Analysis: A Guide for Systematic Reviewers

Introduction

Systematic reviewer authors intending to include all randomized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data.

Objective

The objective of this paper is to provide systematic reviewer authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of randomized trials.

Methods

This guide is based on a review of the Cochrane handbook and published methodological research. The guide deals with participants excluded from the analysis who were considered ‘non-adherent to the protocol’ but for whom data are available, and participants with missing data.

Results

Systematic reviewer authors should include data from ‘non-adherent’ participants excluded from the primary study authors'' analysis but for whom data are available. For missing, unavailable participant data, authors may conduct a complete case analysis (excluding those with missing data) as the primary analysis. Alternatively, they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data. When the primary analysis suggests important benefit, sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis. The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta-analysis. The proposed guide does not take into account the uncertainty associated with assumed events.

Conclusions

This guide proposes methods for handling participants excluded from analyses of randomized trials. These methods can help in establishing the extent to which risk of bias impacts meta-analysis results.     

Cluster Randomised Trials in Cochrane Reviews: Evaluation of Methodological and Reporting Practice

Objective

Systematic reviews can include cluster-randomised controlled trials (C-RCTs), which require different analysis compared with standard individual-randomised controlled trials. However, it is not known whether review authors follow the methodological and reporting guidance when including these trials. The aim of this study was to assess the methodological and reporting practice of Cochrane reviews that included C-RCTs against criteria developed from existing guidance.

Methods

Criteria were developed, based on methodological literature and personal experience supervising review production and quality. Criteria were grouped into four themes: identifying, reporting, assessing risk of bias, and analysing C-RCTs. The Cochrane Database of Systematic Reviews was searched (2^nd December 2013), and the 50 most recent reviews that included C-RCTs were retrieved. Each review was then assessed using the criteria.

Results

The 50 reviews we identified were published by 26 Cochrane Review Groups between June 2013 and November 2013. For identifying C-RCTs, only 56% identified that C-RCTs were eligible for inclusion in the review in the eligibility criteria. For reporting C-RCTs, only eight (24%) of the 33 reviews reported the method of cluster adjustment for their included C-RCTs. For assessing risk of bias, only one review assessed all five C-RCT-specific risk-of-bias criteria. For analysing C-RCTs, of the 27 reviews that presented unadjusted data, only nine (33%) provided a warning that confidence intervals may be artificially narrow. Of the 34 reviews that reported data from unadjusted C-RCTs, only 13 (38%) excluded the unadjusted results from the meta-analyses.

Conclusions

The methodological and reporting practices in Cochrane reviews incorporating C-RCTs could be greatly improved, particularly with regard to analyses. Criteria developed as part of the current study could be used by review authors or editors to identify errors and improve the quality of published systematic reviews incorporating C-RCTs.     

A framework for prospective,adaptive meta-analysis (FAME) of aggregate data from randomised trials

BackgroundThe vast majority of systematic reviews are planned retrospectively, once most eligible trials have completed and reported, and are based on aggregate data that can be extracted from publications. Prior knowledge of trial results can introduce bias into both review and meta-analysis methods, and the omission of unpublished data can lead to reporting biases. We present a collaborative framework for prospective, adaptive meta-analysis (FAME) of aggregate data to provide results that are less prone to bias. Also, with FAME, we monitor how evidence from trials is accumulating, to anticipate the earliest opportunity for a potentially definitive meta-analysis.MethodologyWe developed and piloted FAME alongside 4 systematic reviews in prostate cancer, which allowed us to refine the key principles. These are to: (1) start the systematic review process early, while trials are ongoing or yet to report; (2) liaise with trial investigators to develop a detailed picture of all eligible trials; (3) prospectively assess the earliest possible timing for reliable meta-analysis based on the accumulating aggregate data; (4) develop and register (or publish) the systematic review protocol before trials produce results and seek appropriate aggregate data; (5) interpret meta-analysis results taking account of both available and unavailable data; and (6) assess the value of updating the systematic review and meta-analysis. These principles are illustrated via a hypothetical review and their application to 3 published systematic reviews.ConclusionsFAME can reduce the potential for bias, and produce more timely, thorough and reliable systematic reviews of aggregate data.

Jayne Tierney and coauthors discuss FAME, an approach for adaptive meta-analysis of data from randomised trials.     

Current protocols and clinical efficacy of human fetal liver cell therapy in patients with liver disease: A literature review

The fetal liver is unique because of the coexistence of cells with endodermal and mesenchymal origins, making it a potential source of hepatic and pancreatic regenerative medicine. The liver appears at about the third week of gestation, growing rapidly from the fifth to the 10th week. We define fetal liver from 10 weeks of gestation, when hematopoietic progenitor cells gradually migrate from the aorta-mesonephros-gonad region to colonize the liver. Indeed, the fetal liver may be the most available source of cell therapy for liver disease. We conducted a review of the literature using Medline and EMBASE (up to May 2021) to identify clinical studies in which patients with liver disease had been given fetal liver cell therapy. This literature review highlighted the heterogeneity of cell isolation and selection protocols, which hinders the ability to pool data and perform a meta-analysis. A limitation of the studies analyzed was the scarcity of reports (n = 8) and the extremely small sample sizes (median sample size of treated patients was two), although there was a fairly long follow-up (median 12 months). The weeks after conception ranged from 16 to 34. There were no randomized controlled trials, and therefore no study was stratified as being of good methodological quality. Cryopreservation may help to circumvent the critical logistic issues that hamper the use of fetal liver cell therapy in clinical practice. To help consolidate the role of the fetal liver in regenerative medicine, good preclinical translational studies are necessary, whereas tracing strategies and biopsy-based endpoints are crucial in the clinic, along with well-designed, large, multicenter, randomized controlled trials using clinically applicable primary outcomes and refined imaging assessment.     

A systematic review of reviews comparing the effectiveness of endoscopic and open carpal tunnel decompression

Controversy persists regarding the benefit of endoscopic carpal tunnel release compared with open carpal tunnel release for pain, numbness, strength, return to work and function, scar tenderness, and complications. For surgeons, a recommended first source of information on treatment effectiveness is a review of high-methodologic-quality articles. This review of reviews was undertaken to answer this clinical question regarding these outcomes. Cochrane, MEDLINE, EMBASE, CINAHL, and HealthSTAR databases were searched using the key words "endoscopic carpal tunnel," with limits "review or overview" and dates from 1989 to present. Five key journals were hand-searched. Any review with a reference to at least one randomized controlled trial that compared endoscopic carpal tunnel release to open carpal tunnel release was to be included. Two reviewers independently scanned titles and abstracts for potential relevance. Selection as relevant was confirmed through a review of full texts. Disagreements were resolved through discussion and consensus. The selected reviews were assessed for methodologic quality on the basis of the scale of Hoving et al. Of 48 articles initially identified, seven pertinent reviews were selected. Of these seven, three reviews of high methodologic quality concurred that there is no difference between the two techniques in symptom relief and that the evidence is conflicting for return to work and function. The risk of permanent median nerve injury does not differ between the techniques. The reviews indicated that the endoscopic carpal tunnel release technique is worse in terms of reversible nerve injury but superior in terms of grip strength and scar tenderness, at least in short-term follow-up. Several trials have not been incorporated in these reviews and statistical pooling has not been conducted. Further systematic review with meta-analysis may permit more definitive conclusions about the relative effectiveness of these two techniques, particularly with regard to return to work and function.     

Role of multivitamins and mineral supplements in preventing infections in elderly people: systematic review and meta-analysis of randomised controlled trials

Objective To evaluate the effectiveness of multivitamins and mineral supplements in reducing infections in an elderly population.Design Systematic review and meta-analysis of randomised controlled trials.Data sources Medline and other databases. Reference lists of identified articles were inspected for further relevant articles.Selection of studies Trials were included if they evaluated the effect of multivitamins and mineral supplements on infections in an elderly population.Review methods Studies were assessed for the methodological quality by using the Jadad instrument. If the data required for the analyses were not available from the published articles we requested them from the original study authors. Meta-analysis was undertaken on three outcomes: the mean difference in number of days spent with infection, the odds ratio of at least one infection in the study period, and the incidence rate ratio for the difference in infection rates. Data on adverse events were also extracted.Results Eight trials met our inclusion criteria. Owing to inconsistency in the outcomes reported, only a proportion of the trials could be included in each meta-analysis. Multivitamins and mineral supplements were found to reduce the mean annual number of days spent with infection (three studies) by 17.5 (95% confidence interval 11 to 24, P < 0.001). The odds ratio for at least one infection in the study period (three studies) was 1.10 (0.81 to 1.50, P = 0.53). The infection rate ratio (four studies) was 0.89 (0.78 to 1.03, P = 0.11). Reporting of adverse events was poor.Conclusion The evidence for routine use of multivitamin and mineral supplements to reduce infections in elderly people is weak and conflicting. Study results are heterogeneous, and this is partially confounded by outcome measure.     

Evaluation of Zhilong Huoxue Tongyu capsule in the treatment of acute cerebral infarction: A systematic review and meta-analysis of randomized controlled trials

BackgroundZhilong Huoxue Tongyu capsule (ZL) is a Chinese patent medicine and used for the treatment of acute cerebral infarction (ACI) and its clinical application has gradually been widely recognized in China. However, the effects of ZL for patients with ACI have never been systematically evaluated.PurposeA systematic review and meta-analysis was performed to evaluate the efficacy of ZL in ACI.Study designA systematic review and meta-analysis of randomized clinical trials (RCTs).Materials and methodsA systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The comprehensive literature search was accomplished in 6 electronic databases to find relevant randomized controlled trials from their inception until October 31, 2020. The Cochrane Handbook for Systematic Reviews of Interventions was used for methodological quality and independent evaluation. Review Manager 5.3 was used to analyze all the data obtained. The Clinical Effective Rate (CER) was the primary outcome, and the National Institutes of Health Stroke Score (NIHSS), Barthel Index (BI), and Modified Rankin Scale (MRS) were the secondary outcomes.ResultsSeven clinical studies recruiting 571 eligible patients were included in this meta-analysis. The results of meta-analysis suggested that compared with conventional treatment alone, ZL combined with conventional treatment significantly improved CER (RR = 1.20, 95% CI: 1.12-1.29, p < 0.00001), decrease National Institutes of Health Stroke Scale Score (NIHSS) (MD = -2.60, 95% CI: -3.41–1.79, p < 0.00001), Barthel Index (BI) (MD = -9.75, 95% CI: 7.15-12.36, p < 0.00001) and Modified Rankin Scale (MRS) (MD = -0.57, 95% CI: -0.84–0.30, p < 0.00001). There were no reported adverse events in the studies. Most results were robust and the quality of evidence was from moderate to low.ConclusionZL combined with conventional treatment can improve the short-term outcomes of ACI patients, indicating ZL is a promising treatment choice for ACI and may be used as adjunctive treatment to the conventional treatment of ACI. However, due to the limitations of included clinical trials, high-quality clinical trials with longer follow-ups are still needed to further assess the effectiveness and safety of ZL for ACI patients.     

Effect of electrical stimulation on musculoskeletal systems; a meta-analysis of controlled clinical trials

This study was a meta-analysis to examine whether electrical stimulation has specific effects in the healing of musculoskeletal repair process and in the diminution of symptoms with bone and joint disorders. Using MEDLINE (1966-1999) and EMBASE (1985-1999) a search for articles was carried out with four medical subject headings. Data were extracted from all the accessed articles and additionally collected from appropriate journal lists. A total of 20 randomized controlled trials on bones was identified which assessed healing of fractures, bone graft, and other conditions; and 29 randomized controlled trials on soft tissues and joints were also found, dealing with healing of skin wounds or dermal ulcers, soft tissue injury, and other conditions. Using criteria through which the quality of studies was assessed, the content of the articles was reorganized into a tabular form. The majority of the identified articles reported positive findings, but all the trials showed methodological flaws to some extent. Because of heterogeneity of the studies and the various outcome measurements, pooling of only part of the data was performed. The combined results of 12 trials on bones and 16 trials on soft tissues, the cases in which major endpoints were mainly union or healing rate, revealed statistically significant effects. The studies in this review had some methodological limitations, and the selected pooled trials do not constitute acceptable proof that electrical stimulation has specific effects on health. However, one cannot ignore the statistically significant positive findings reported in the trials, from which extracted data were able to be combined.     

Diet and calcium stones.

OBJECTIVE: To review the current literature on the dietary modification of urinary risk factors as a means of reducing the likelihood of recurrent stone formation and to develop practical dietary recommendations that might be useful to this end. DATA SOURCES: MEDLINE was searched for English-language articles published from 1983 to 1990. Additional references were selected from the bibliographies of identified articles. STUDY SELECTION: Nonrandomized trials and retrospective reviews were included because of a paucity of randomized controlled trials. DATA SYNTHESIS: Information on the dietary intake of calcium, oxalate, protein, sodium and fibre and on alcohol and fluid intake was used to develop practical guidelines on dietary modification. CONCLUSION: Dietary modification plays an important role in the reduction of urinary risk factors in patients with calcium stone disease of the urinary tract. As an initial form of prevention attention should be directed toward moderating the intake of calcium, oxalate, protein, sodium and alcohol and increasing the intake of fibre and water. Future research should include an assessment of the long-term reduction of dietary and urinary risk factors and the rates of recurrence of calcium stones.     

Missing Data in Randomized Clinical Trials for Weight Loss: Scope of the Problem,State of the Field,and Performance of Statistical Methods

Background

Dropouts and missing data are nearly-ubiquitous in obesity randomized controlled trails, threatening validity and generalizability of conclusions. Herein, we meta-analytically evaluate the extent of missing data, the frequency with which various analytic methods are employed to accommodate dropouts, and the performance of multiple statistical methods.

Methodology/Principal Findings

We searched PubMed and Cochrane databases (2000–2006) for articles published in English and manually searched bibliographic references. Articles of pharmaceutical randomized controlled trials with weight loss or weight gain prevention as major endpoints were included. Two authors independently reviewed each publication for inclusion. 121 articles met the inclusion criteria. Two authors independently extracted treatment, sample size, drop-out rates, study duration, and statistical method used to handle missing data from all articles and resolved disagreements by consensus. In the meta-analysis, drop-out rates were substantial with the survival (non-dropout) rates being approximated by an exponential decay curve (e^−λt) where λ was estimated to be .0088 (95% bootstrap confidence interval: .0076 to .0100) and t represents time in weeks. The estimated drop-out rate at 1 year was 37%. Most studies used last observation carried forward as the primary analytic method to handle missing data. We also obtained 12 raw obesity randomized controlled trial datasets for empirical analyses. Analyses of raw randomized controlled trial data suggested that both mixed models and multiple imputation performed well, but that multiple imputation may be more robust when missing data are extensive.

Conclusion/Significance

Our analysis offers an equation for predictions of dropout rates useful for future study planning. Our raw data analyses suggests that multiple imputation is better than other methods for handling missing data in obesity randomized controlled trials, followed closely by mixed models. We suggest these methods supplant last observation carried forward as the primary method of analysis.     

Formalized synthesis opportunities for ecology: systematic reviews and meta‐analyses

Narrative reviews are dead. Long live systematic reviews (and meta‐analyses). Synthesis in many forms is now a driving force in ecology. Advances in open data for ecology and new tools provide vastly improved capacity for novel, emergent knowledge synthesis in our discipline. Systematic reviews and meta‐analyses are two formal synthesis opportunities for ecologists that are now accepted as traditional publications, but the scope of validated syntheses will continue to expand. To date, systematic reviews are rarely used whilst the rate of meta‐analyses published in ecological journals is increasing exponentially. Systematic reviews provide an overview of the literature landscape for a topic, and meta‐analyses examine the strength of evidence integrated across different studies. Effective synthesis benefits from both approaches, but better data reporting and additional advances in the culture of sharing data, code, analytics, workflows, methods and also ideas will further energize these efforts. At this junction, synthetic efforts that include systematic reviews and meta‐analyses should continue as stand‐alone publications. This is a necessary step in the evolution of synthesis in our discipline. Nonetheless, they are still evolving tools, and meta‐analyses in particular are simply an extended set of statistical tests. Admittedly, understanding the statistics and assumptions influence how we conduct synthesis much as statistical choices often shape experimental design, i.e. ANOVA versus regression‐based experiments, but statistics do not make the paper. Current steps – primary research articles need to more effectively report evidence, sharing scientific products should expand, systematic reviews should be used to identify research gaps/delineate literature landscapes, and meta‐analyses should be used to examine evidence patterns to further predictive ecology.     

Selenium intake and cardiovascular risk: what is new?

PURPOSE OF REVIEW: Selenium is an essential element with a narrow safety margin. Adequate selenium intake is needed to maximize the activity of glutathione peroxidases and other selenoproteins. This review discusses recent experimental and epidemiologic contributions on the role of selenium for the prevention of atherosclerotic cardiovascular disease. RECENT FINDINGS: Few randomized trials have evaluated the efficacy of selenium supplementation on cardiovascular endpoints. Most trials, conducted in selenium-replete populations, found no evidence of cardiovascular protection. A meta-analysis of 13 prospective cohort studies found a moderate inverse relationship between plasma/serum selenium and coronary heart disease. The interpretation of these data is complicated, however, by potential residual confounding and publication bias. In contrast, recent data from trials of selenium-containing supplements and from epidemiologic studies suggest that chronically increased selenium intake in selenium-replete populations can induce diabetes and maybe also hypercholesterolemia. SUMMARY: Current evidence is insufficient to support a protective role for selenium in cardiovascular prevention. Large high-quality randomized controlled trials and observational studies are needed across populations with different levels of selenium intake. Furthermore, subjects living in regions with high selenium intake should be aware that selenium supplements may increase their risk of diabetes and hypercholesterolemia.     

High-dose chemotherapy followed by autologous stem cell transplantation for metastatic rhabdomyosarcoma--a systematic review

Introduction

Patients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy.

Methods

Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations.

Results

A total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years) were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws.

Conclusions

HDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials.     

Trifolium pratense isoflavones in the treatment of menopausal hot flushes: A systematic review and meta-analysis

OBJECTIVE: To critically assess the evidence of supplements containing Trifolium pratense (red clover) isoflavones in the reduction of hot flush frequency in menopausal women. DATA SOURCES: Systematic literature searches were performed in (Medline (1951 - April 2006), Embase (1974 - April 2006), CINAHL (1982 - April 2006), Amed (1985 - April 2006) and The Cochrane Library (Issue 2, 2006). Reference lists located were checked for further relevant publications. Experts in the field and manufacturers of identified products were contacted for unpublished material. No language restrictions were imposed. REVIEW METHODS: Studies were selected according to predefined inclusion and exclusion criteria. All randomized clinical trials of monopreparations containing T. pratense isoflavones for treating hot flushes were included. Study selection, data extraction and validation were performed by at least two reviewers with disagreements being settled by discussion. Weighted means and 95% confidence intervals were calculated and sensitivity analyses were performed. RESULTS: Seventeen potentially relevant articles were retrieved for further evaluation. Five were suitable for inclusion in the meta-analysis. The meta-analysis indicates a reduction in hot flush frequency in the active treatment group (40-82 mg daily) compared with the placebo group (weighted mean difference -1.5 hot flushes daily; 95% CI -2.94 to 0.03; p=0.05). CONCLUSION: There is evidence of a marginally significant effect of T. pratense isoflavones for treating hot flushes in menopausal women. Whether the size of this effect can be considered clinically relevant is unclear. Whereas there is no apparent evidence of adverse events during short-term use, there are no available data on the safety of long-term administration.     

Surgical treatment of osteoarthritis of the carpometacarpal joint of the thumb: a systematic review

In most cases of basal joint osteoarthritis, surgery becomes an option at stages II, III, and IV, as classified by Eaton. Controversy exists regarding which technique achieves the best outcome. This systematic review was undertaken to address the question of which technique, if any, offers the best outcome to patients with osteoarthritis of the first carpometacarpal joint greater than stage II. A thorough search of the electronic databases Cochrane, Cinahl, Healthstar, and MEDLINE/PubMed was undertaken to identify reviews and articles on primary comparative studies of the different surgical options. The methodological quality of the retrieved articles was assessed on the basis of specific criteria. Inclusion criteria were applied to 44 of 254 possibly relevant articles. Eight reviews and 18 comparative studies met the criteria and were reviewed. Each of the techniques, arthrodesis, trapeziectomy with or without biological/synthetic interposition, osteotomy, and joint replacement, was associated with unique benefits and risks. There was great variability in outcome measurements. The majority of retrieved review articles claim that ligamentous reconstruction and tendon interposition may represent the best option; however, validity assessment of these studies revealed methodological flaws. Furthermore, results from the articles on comparative studies indicate that ligamentous reconstruction and tendon interposition may provide no additional benefit when compared with arthrodesis and trapeziectomy alone or with tendon interposition. There is no consensus as to which clinical outcomes are most important in thumb basal joint surgery and how these should be measured. This renders the appraisal and comparison of such studies a challenging task. Until large randomized controlled trials that compare techniques in similar populations with respect to staging and prognostic factors are undertaken and the clinical outcomes are clearly defined, surgeons will continue to claim superiority of one technique over another without supporting evidence.     

Review and Meta‐analysis of Pharmacotherapy for Binge‐eating Disorder

This study evaluated available controlled treatment studies to determine utility of pharmacotherapy for binge‐eating disorder (BED). The authors identified randomized placebo‐controlled trials testing pharmacotherapy‐only treatments and controlled trials testing pharmacotherapy with psychotherapy treatments. Meta‐analysis was performed on placebo‐controlled trials with data for attrition, remission, and weight loss. Qualitative review was performed on remaining controlled treatment literature. A total of 33 studies were considered of which 14 studies with a total of 1,279 patients were included in the meta‐analysis of pharmacotherapy‐only treatment and 8 studies with a total of 683 patients were included in the qualitative review of pharmacotherapy combined with psychotherapy interventions. No evidence suggested significant differences between medication and placebo for attrition. Evidence suggested that pharmacological treatments have a clinically significant advantage over placebo for achieving short‐term remission from binge eating (48.7% vs. 28.5%) and for weight loss, although weight losses are not substantial. No data exist to allow evaluation of longer‐term effects of pharmacotherapy‐only treatment for BED. Combining medications with psychotherapy interventions failed to significantly enhance binge outcomes, although specific medications (orlistat, topiramate) enhanced weight losses achieved with cognitive behavioral therapy and behavioral weight loss. In summary, BED patients can be advised that certain pharmacotherapies may enhance likelihood of stopping binge eating short term, but that longer‐term effects are unknown. Although some weight loss may occur, it is unlikely to be substantial with available medications. Combining medications with cognitive or behavioral treatments is unlikely to enhance binge outcomes, but specific medications (orlistat, topiramate) may enhance weight losses, albeit modestly.