Showing papers on "Publication bias published in 2008"
TL;DR: There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported.
Abstract: Background
The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention.
1,373 citations
TL;DR: The contour-enhanced funnel plot is proposed as an aid to differentiating asymmetry due to publication bias from that due to other factors and is simple to implement, widely applicable, and greatly improves interpretability.
1,211 citations
TL;DR: Support is provided for the association of the 5-HTTLPR polymorphism and amygdala activation and it is suggested that this locus may account for up to 10% of phenotypic variance and most studies to date are nevertheless lacking in statistical power.
775 citations
TL;DR: This study examines the relationship between delivery by caesarean section and the offspring's risk of allergic diseases and reports inconsistent findings.
Abstract: Summary
Background Studies of delivery by caesarean section (c-section) and the offspring's risk of allergic diseases are of current interest due to concerns about the increased use of c-section in many countries. However, previous studies have reported inconsistent findings.
Objective We investigated whether delivery by c-section is associated with an increased risk of atopy and allergic disease by reviewing the literature, performing a meta-analysis, and assessing publication bias.
Methods We used a systematic literature search of MEDLINE (1966 to May 2007). Six common allergic outcomes were included: food allergy/food atopy, inhalant atopy, eczema/atopic dermatitis, allergic rhinitis, asthma, and hospitalization for asthma. For each outcome a meta-analysis was performed, where a summary odds ratio (OR) was calculated taking into account heterogeneity between the study-specific relative risks. Publication bias was assessed using the funnel plot method.
Results We identified 26 studies on delivery by c-section and one or more of the six allergic outcomes. C-section was associated with an increased summary OR of food allergy/food atopy (OR 1.32, 95% CI 1.12–1.55; six studies), allergic rhinitis (OR 1.23, 95% CI 1.12–1.35; seven studies), asthma (OR 1.18, 95% CI 1.05–1.32; 13 studies), and hospitalization for asthma (OR 1.21, 95% CI 1.12–1.31; seven studies), whereas there was no association with inhalant atopy (OR 1.06, 95% CI 0.82–1.38; four studies) and eczema/atopic dermatitis (OR 1.03, 95% CI 0.98–1.09; six studies). Funnel plots indicated that the association with food allergy/food atopy could be difficult to interpret due to publication bias. For each significant association with an allergic outcome, only 1–4% of cases were attributable to c-section.
Conclusion Delivery by c-section is associated with a moderate risk increase for allergic rhinitis, asthma, hospitalization for asthma, and perhaps food allergy/food atopy, but not with inhalant atopy or atopic dermatitis. The increased use of c-section during the last decades is unlikely to have contributed much to the allergy epidemic observed during the same period.
467 citations
TL;DR: The authors found moderate evidence for a relation between the psychological demands of the job and the development of depression, with relative risks of approximately 2.0, but indication of publication bias weakens the evidence.
Abstract: This review is based on a literature search made in January 2007 on request by the Danish National Board of Industrial Injuries. The search in PubMed, EMBASE, and PsycINFO resulted in more than 1,000 publications. This was reduced to 14 after the titles, abstracts, and papers were evaluated by using the following criteria: 1) a longitudinal study, 2) exposure to work-related psychosocial factors, 3) the outcome a measure of depression, 4) relevant statistical estimates, and 5) nonduplicated publication. Of the 14 studies, seven used standardized diagnostic instruments as measures of depression, whereas the other seven studies used self-administered questionnaires. The authors found moderate evidence for a relation between the psychological demands of the job and the development of depression, with relative risks of approximately 2.0. However, indication of publication bias weakens the evidence. Social support at work was associated with a decrease in risk for future depression, as all four studies dealing with this exposure showed associations with relative risks of about 0.6. Even if this literature study has identified work-related psychosocial factors that in high-quality epidemiologic studies predict depression, studies are still needed that assess in more detail the duration and intensity of exposure necessary for developing depression.
458 citations
TL;DR: The major common challenges and flaws that emerge in using and interpreting statistical tests of heterogeneity and bias in meta-analyses are discussed and suggestions are made on how to avoid these flaws, use these tests properly and learn from them.
Abstract: Statistical tests of heterogeneity and bias, in particular publication bias, are very popular in meta-analyses. These tests use statistical approaches whose limitations are often not recognized. Moreover, it is often implied with inappropriate confidence that these tests can provide reliable answers to questions that in essence are not of statistical nature. Statistical heterogeneity is only a correlate of clinical and pragmatic heterogeneity and the correlation may sometimes be weak. Similarly, statistical signals may hint to bias, but seen in isolation they cannot fully prove or disprove bias in general, let alone specific causes of bias, such as publication bias in particular. Both false-positive and false-negative signals of heterogeneity and bias can be common and their prevalence may be anticipated based on some rational considerations. Here I discuss the major common challenges and flaws that emerge in using and interpreting statistical tests of heterogeneity and bias in meta-analyses. I discuss misinterpretations that can occur at the level of statistical inference, clinical/pragmatic inference and specific cause attribution. Suggestions are made on how to avoid these flaws, use these tests properly and learn from them.
414 citations
TL;DR: Despite initially promising results, the COMT Val158/108Met polymorphism appears to have little if any association with cognitive function and publication bias may hamper attempts to understand the genetic basis of psychological functions and psychiatric disorders.
397 citations
TL;DR: Although these results appear optimistic in advocating the use of CBT in ameliorating suicidal thoughts, plans, and behaviors, evidence of a publication bias tempers such optimism.
Abstract: Suicide behavior is a serious clinical problem worldwide, and understanding ways of reducing it is a priority. A systematic review and meta-analysis were carried out to investigate whether Cognitive-behavioral therapies (CBTs) would reduce suicide behavior. From 123 potential articles, 28 studies met the entry criteria. Overall, there was a highly significant effect for CBT in reducing suicide behavior. Subgroup analysis indicates a significant treatment effect for adult samples (but not adolescent), for individual treatments (but not group), and for CBT when compared to minimal treatment or treatment as usual (but not when compared to another active treatment). There was evidence for treatment effects, albeit reduced, over the medium term. Although these results appear optimistic in advocating the use of CBT in ameliorating suicidal thoughts, plans, and behaviors, evidence of a publication bias tempers such optimism.
346 citations
TL;DR: The size of one of the new tests is comparable to those of the best existing tests, including those recently published, and among such tests it has slightly greater power, especially when the effect size is small and heterogeneity is present.
Abstract: In meta-analyses, it sometimes happens that smaller trials show different, often larger, treatment effects. One possible reason for such 'small study effects' is publication bias. This is said to occur when the chance of a smaller study being published is increased if it shows a stronger effect. Assuming no other small study effects, under the null hypothesis of no publication bias, there should be no association between effect size and effect precision (e.g. inverse standard error) among the trials in a meta-analysis.A number of tests for small study effects/publication bias have been developed. These use either a non-parametric test or a regression test for association between effect size and precision. However, when the outcome is binary, the effect is summarized by the log-risk ratio or log-odds ratio (log OR). Unfortunately, these measures are not independent of their estimated standard error. Consequently, established tests reject the null hypothesis too frequently. We propose new tests based on the arcsine transformation, which stabilizes the variance of binomial random variables. We report results of a simulation study under the Copas model (on the log OR scale) for publication bias, which evaluates tests so far proposed in the literature. This shows that: (i) the size of one of the new tests is comparable to those of the best existing tests, including those recently published; and (ii) among such tests it has slightly greater power, especially when the effect size is small and heterogeneity is present. Arcsine tests have additional advantages that they can include trials with zero events in both arms and that they can be very easily performed using the existing software for regression tests.
334 citations
TL;DR: The publication rate of efficacy trials submitted to the Food and Drug Administration in approved New Drug Applications (NDAs) is determined and the trial characteristics as reported by the FDA with those reported in publications are compared.
Abstract: Background Previous studies of drug trials submitted to regulatory authorities have documented selective reporting of both entire trials and favorable results. The objective of this study is to determine the publication rate of efficacy trials submitted to the Food and Drug Administration (FDA) in approved New Drug Applications (NDAs) and to compare the trial characteristics as reported by the FDA with those reported in publications.
320 citations
TL;DR: The proportion of trials submitted to the FDA in support of newly approved drugs that are published in biomedical journals that a typical clinician, consumer, or policy maker living in the US would reasonably search is determined.
Abstract: Author(s): Lee, Kirby; Bacchetti, Peter; Sim, Ida | Abstract: BackgroundThe United States (US) Food and Drug Administration (FDA) approves new drugs based on sponsor-submitted clinical trials. The publication status of these trials in the medical literature and factors associated with publication have not been evaluated. We sought to determine the proportion of trials submitted to the FDA in support of newly approved drugs that are published in biomedical journals that a typical clinician, consumer, or policy maker living in the US would reasonably search.Methods and findingsWe conducted a cohort study of trials supporting new drugs approved between 1998 and 2000, as described in FDA medical and statistical review documents and the FDA approved drug label. We determined publication status and time from approval to full publication in the medical literature at 2 and 5 y by searching PubMed and other databases through 01 August 2006. We then evaluated trial characteristics associated with publication. We identified 909 trials supporting 90 approved drugs in the FDA reviews, of which 43% (394/909) were published. Among the subset of trials described in the FDA-approved drug label and classified as "pivotal trials" for our analysis, 76% (257/340) were published. In multivariable logistic regression for all trials 5 y postapproval, likelihood of publication correlated with statistically significant results (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.78-5.17); larger sample sizes (OR 1.33 per 2-fold increase in sample size, 95% CI 1.17-1.52); and pivotal status (OR 5.31, 95% CI 3.30-8.55). In multivariable logistic regression for only the pivotal trials 5 y postapproval, likelihood of publication correlated with statistically significant results (OR 2.96, 95% CI 1.24-7.06) and larger sample sizes (OR 1.47 per 2-fold increase in sample size, 95% CI 1.15-1.88). Statistically significant results and larger sample sizes were also predictive of publication at 2 y postapproval and in multivariable Cox proportional models for all trials and the subset of pivotal trials.ConclusionsOver half of all supporting trials for FDA-approved drugs remained unpublished g/= 5 y after approval. Pivotal trials and trials with statistically significant results and larger sample sizes are more likely to be published. Selective reporting of trial results exists for commonly marketed drugs. Our data provide a baseline for evaluating publication bias as the new FDA Amendments Act comes into force mandating basic results reporting of clinical trials.
TL;DR: This work has suggested that adding contours of statistical significance to funnel plots should be used routinely for meta-analyses where it is possible that results could be suppressed on the basis of their statistical significance.
Abstract: Funnel plots are commonly used to investigate publication and related biases in meta-analysis. Although asymmetry in the appearance of a funnel plot is often interpreted as being caused by publication bias, in reality the asymmetry could be due to other factors that cause systematic differences in the results of large and small studies, for example, confounding factors such as differential study quality. Funnel plots can be enhanced by adding contours of statistical significance to aid in interpreting the funnel plot. If studies appear to be missing in areas of low statistical significance, then it is possible that the asymmetry is due to publication bias. If studies appear to be missing in areas of high statistical significance, then publication bias is a less likely cause of the funnel asymmetry. It is proposed that this enhancement to funnel plots should be used routinely for meta-analyses where it is possible that results could be suppressed on the basis of their statistical significance.
TL;DR: Do Statistical Reporting Standards Affect What Is Published? Publication bias in Two Leading Political Science Journals as mentioned in this paper was found to be significant in two leading political science journals in the United Kingdom and Ireland.
Abstract: Do Statistical Reporting Standards Affect What Is Published? Publication Bias in Two Leading Political Science Journals
TL;DR: Funding's effects areSituating funding's effects in the context of the ghost-management of research and publication by pharmaceutical companies, and the creation of social ties between those companies and researchers is built on.
TL;DR: The effect of the.05 significance level on the pattern of published findings is examined using a ''caliper'' test, and the hypothesis of no publication bias can be rejected at approximately the 1 in 10 million level.
Abstract: Despite great attention to the quality of research methods in individual studies, if publication decisions of journals are a function of the statistical significance of research findings, the published literature as a whole may not produce accurate measures of true effects. This article examines the two most prominent sociology journals (the American Sociological Review and the American Journal of Sociology) and another important though less influential journal (The Sociological Quarterly) for evidence of publication bias. The effect of the .05 significance level on the pattern of published findings is examined using a ``caliper'' test, and the hypothesis of no publication bias can be rejected at approximately the 1 in 10 million level. Findings suggest that some of the results reported in leading sociology journals may be misleading and inaccurate due to publication bias. Some reasons for publication bias and proposed reforms to reduce its impact on research are also discussed.
TL;DR: Using a rigorous process for the identification and extraction of data from a homogenous subset of the prognostic WAD literature, several factors for which information is easy to collect clinically and could provide clinicians with a good sense of prognosis following whiplash injury are identified.
Abstract: Study Design Systematic review and meta-analysis. Background Whiplash-associated disorder (WAD) is the most common reported injury following motor vehicle accident. Evidence for prognosis and intervention are difficult to interpret due to differences in inception times, outcomes used, and sample heterogeneity. Methods An extensive literature search was conducted to identify published studies of prognosis following whiplash. Rigorous inclusion criteria were applied to allow for meaningful results to be drawn. Data were extracted, transformed where necessary, and pooled to allow estimation of the odds ratio for any factor with at least 3 data points in the literature. Results From 11 cohorts (n = 3193), 25 factors were identified with at least 3 data points in the existing literature. Of these, 9 were found to be significant predictors based on the odds ratio and confidence limits: no postsecondary education, female gender, history of previous neck pain, baseline neck pain intensity greater than 55/100, pre...
TL;DR: A review of the evidence in support of the contention that publication bias is a potential threat to the validity of meta-analytic results in criminology and similar fields can be found in this article.
Abstract: This paper reviews the evidence in support of the contention that publication bias is a potential threat to the validity of meta-analytic results in criminology and similar fields. It then provides a critique of the traditional file drawer or failsafe N method for examining publication bias, and an overview of four newer methods that can be used to detect publication bias. These include two (trim and fill and cumulative meta-analysis) that enable the researcher to estimate the magnitude of the influence of publication bias on the overall mean effect size. Advantages and limitations of both traditional and newer methods are examined. The methods reviewed are illustrated through their application to a meta-analysis of the effects of drug courts on recidivism by Wilson et al. (Journal of Experimental Criminology, 2, 459–487, 2006).
TL;DR: The results do not support the hypothesis that statins reduce the risk of total prostate cancer, and further research is required to investigate whether the particular association of statin use with lower risk of advanced prostate cancer is indeed causal.
Abstract: Statins have been suggested to prevent prostate cancer. Our aim was to examine statin use in relation to both total prostate cancer and the more clinically important advanced prostate cancer, through a detailed metaanalysis of the epidemiologic studies published on the subject in peer-reviewed literature. A comprehensive search for articles published up to November 2007 was performed, reviews of each study were conducted and data were abstracted. Prior to metaanalysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. Subgroup and sensitivity analyses were also performed. Nineteen studies [6 randomized clinical trials (RCTs), 6 cohort and 7 case-control studies] contributed to the analysis. There was no evidence of an association between statin use and total prostate cancer among either RCTs (RR = 1.06, 95% CI: 0.93-1.20) or the observational studies (RR = 0.89, 95% CI: 0.65-1.24). However, high heterogeneity was detected among the observational studies. Moreover, long-term statin use did not significantly affect the risk of total prostate cancer (RR = 0.93, 95% CI: 0.77-1.13). In contrast, synthesis of the available reports that had specifically examined statin use in relation to advanced prostate cancer indicated a protective association (RR = 0.77, 95% CI: 0.64-0.93). Our results do not support the hypothesis that statins reduce the risk of total prostate cancer. However, further research is required to investigate whether the particular association of statin use with lower risk of advanced prostate cancer is indeed causal.
Journal Article•
TL;DR: Cross-sectional studies from around the world show a consistent increased risk of obesity amongst short sleepers in children and adults, and a estimate of the risk is obtained.
Abstract: Background: Recent epidemiological studies suggest that short sleep duration may be associated with the development of obesity from childhood to adulthood. Objectives: To assess whether the evidence supports the presence of a relationship between short sleep duration and obesity at different ages, and to obtain an estimate of the risk. Methods: We performed a systematic search of publications using MEDLINE (1996-2007 wk 40), EMBASE (from 1988), AMED (from 1985), CINHAL (from 1982) and PsyclNFO (from 1985) and manual searches without language restrictions. When necessary, authors were contacted. Criteria for inclusion were: report of duration of sleep as exposure, BMI as continuous outcome and prevalence of obesity as categorical outcome, number of participants, age, and gender. Results were pooled using a random effect model. Sensitivity analysis was performed, heterogeneity and publication bias were also checked. Results are expressed as pooled odds ratios (OR [95% confidence intervals, CIs]) and as pooled regression coefficients (β; 95% CIs). Results: Of 696 studies identified, 45 met the inclusion criteria (19 in children and 26 in adults) and 30 (12 and 18, respectively) were pooled in the meta-analysis for a total of 36 population samples. They included 634,511 participants (30,002 children and 604,509 adults) from around the world. Age ranged from 2 to 102 years and included boys, girls, men and women. In children the pooled OR for short duration of sleep and obesity was 1.89 (1.46 to 2.43; P < 0.0001). In adults the pooled OR was 1.55 (1.43 to 1.68; P < 0.0001). There was no evidence of publication bias. In adults, the pooled β for short sleep duration was -0.35 (-0.57 to -0.12) unit change in BMI per hour of sleep change. Conclusions: Cross-sectional studies from around the world show a consistent increased risk of obesity amongst short sleepers in children and adults. Causal inference is difficult due to lack of control for important confounders and inconsistent evidence of temporal sequence in prospective studies.
TL;DR: An-Wen Chan discusses the implications of a new study that suggests that the randomized trial literature is skewed towards reporting favorable results.
Abstract: An-Wen Chan discusses the implications of a new study inPLoS Medicine that suggests that the randomized trial literature is skewed towards reporting favorable results.
TL;DR: A systematic review and meta-analysis of published epidemiological studies on this subject was carried out in this paper, which revealed an association between occupational exposure to ELF-EMF and AD.
Abstract: Background Among potential environmental risk factors for Alzheimer disease (AD), occupational exposures have received some attention, including extremely low frequency electromagnetic fields (ELF-EMF). A systematic review and meta-analysis of published epidemiological studies on this subject was carried out. Methods The search was concluded in April 2006. Bibliographic databases consulted included PubMed, EMBASE, Cochrane Library and NIOSHTIC2. Pooled estimates were obtained using random-effects meta-analysis. Sources of heterogeneity between studies were explored, as was publication bias. Results Fourteen different studies (nine case-control and five cohort studies) accomplished inclusion criteria. All these studies followed standardized criteria for AD diagnosis and most of them obtained quantitative estimates of exposure. Pooled estimates suggest an increased risk of AD from case-control studies (OR(pooled) 2.03; 95% CI 1.38-3.00) and from cohort studies (RR(pooled) 1.62; 95% CI 1.16-2.27), with moderate to high statistical heterogeneity in both cases (respectively, I(2) = 58% and I(2) = 54%). Cohort studies showed consistently increased risks for exposed men (RR(pooled) 2.05; 95% CI 1.51-2.80, I(2) = 0%). Evidence of dose-response relationship was not present. Test for publication bias suggests small study effects, mostly for case-control studies. Conclusions Available epidemiological evidence suggests an association between occupational exposure to ELF-EMF and AD. However, some limitations affecting the results from this meta-analysis should be considered. More information on relevant duration and time windows of exposure, on biological mechanisms for this potential association and on interactions between electromagnetic fields exposure and established risk factors for AD is needed.
TL;DR: Limited evidence was found for the effectiveness of a multifaceted safety campaign and aMultifaceted drug program, but no evidence is found that legislation is effective to prevent nonfatal or fatal injuries in the construction industry.
Posted Content•
TL;DR: In this paper, the publication decisions of journals are a function of the statistical significance of research findings, and the published literature may suffer from "publication bias" when compared to statistically insignificant results.
Abstract: If the publication decisions of journals are a function of the statistical significance of research findings, the published literature may suffer from "publication bias." This paper describes a method for detecting publication bias. We point out that to achieve statistical significance, the effect size must be larger in small samples. If publications tend to be biased against statistically insignificant results, we should observe that the effect size diminishes as sample sizes increase. This proposition is tested and confirmed using the experimental literature on voter mobilization.
TL;DR: Assessment of methods used to identify, analyze, and synthesize results of empirical research on intervention effects suggested that reviews were influenced by confirmation bias, the tendency to emphasize evidence that supports a hypothesis and ignore evidence to the contrary.
TL;DR: This work describes three types of selection biases (incidence-prevalence bias, loss-to-follow-up bias, and publication bias) and a series of information biases (i.e. misclassification bias--recall bias, interviewer bias, observer biased, and regression dilution bias--and lead-time bias).
TL;DR: Orthopaedic researchers should submit negative and neutral studies for publication, confident that the likelihood of acceptance will not be influenced by the direction of study findings, as positive and nonpositive studies were accepted at similar rates.
Abstract: Background: Positive outcomes are common in the orthopaedic literature, and there are many who believe it may be due to the preferential publication of studies with positive findings—a phenomenon known as publication bias. The purpose of this investigation was to determine whether positive findings rendered a manuscript submitted to The Journal of Bone and Joint Surgery (American Volume) more likely to be accepted for publication.
Methods: A total of 1181 manuscripts submitted to The Journal of Bone and Joint Surgery between January 1, 2004, and June 30, 2005, for publication as scientific articles were analyzed, with 855 meeting the inclusion criteria. The direction of the study findings (positive, neutral, or negative) was independently graded by three blinded reviewers. The final disposition (acceptance or rejection) was recorded, as was information on the scientific characteristics plausibly related to acceptance or rejection. Logistic regression was used to identify factors associated with acceptance for publication.
Results: The overall acceptance rate was 21.8% (186 of 855 studies). The study outcome was positive for 72.5% (620) of the manuscripts. The acceptance rate for the 235 manuscripts with nonpositive findings was 23.0% (fifty-four studies) compared with 21.3% (132) of the 620 studies with positive findings (crude odds ratio, 1.10 [95% confidence interval, 0.77 to 1.58]; p = 0.593). After controlling for all covariates, the adjusted odds ratio was 0.92 (95% confidence interval, 0.62 to 1.35; p = 0.652). In the multivariate analysis, the only factor significantly associated with acceptance for publication was level of evidence (p = 0.001).
Conclusions: We found no evidence of publication bias in the review of manuscripts for publication by The Journal of Bone and Joint Surgery , as positive and nonpositive studies were accepted at similar rates. The dearth of nonpositive studies in the orthopaedic literature is of concern, and may be due largely to investigator-based factors. Orthopaedic researchers should submit negative and neutral studies for publication, confident that the likelihood of acceptance will not be influenced by the direction of study findings.
TL;DR: Less than one in five studies in cancer that are registered with clinicaltrials.gov have been published in peer-reviewed journals, suggesting research sponsors, researchers, and journal editors should redouble their efforts to encourage publication of registered clinical trials in oncology.
Abstract: Objective. Members of the International Committee of Medical Journal Editors require, as a condition of consideration for publication, that all clinical trials be registered in a public trials registry. We evaluated the proportion of registered trials that are published in the peer-reviewed literature. Methods. After downloading the contents of the National Institutes of Health’s ClinicalTrials.gov registry, we used key words to identify trials in oncology. We then evaluated the proportion of trials that had been published in journals listed in PubMed.gov. Among trials with published results, we determined the proportion that reported positive versus negative results. Results. Among the 2,028 trials meeting the inclusion
TL;DR: Antibiotic therapy with adjunctive loperamide offers an advantage over antibiotics alone by decreasing the illness duration and increasing the probability of early clinical cure.
Abstract: Background. A previous Cochrane Collaboration review established an effective advantage of antibiotic therapy, compared with placebo, for treatment of traveler's diarrhea. The goal of the present study was to conduct a systematic review of the literature to establish the effect on treatment outcomes of using antimotility agents in conjunction with antibiotic therapy. Methods. The meta-analysis was conducted through searches of electronic databases and pertinent reference lists (including other review articles) and consultation with experts in the field. Clinical trials on therapy of infectious diarrhea in adult populations that met eligibility criteria were studied. Data were extracted and verified by 2 independent investigators and were analyzed for outcomes of clinical cure at 24 h, 48 h, and 72 h and time to last unformed stool. Study quality, heterogeneity, and publication bias were assessed. When appropriate, effect estimates among studies were pooled and sensitivity analyses were performed. Results. Nine studies consisting of 12 different adjunctive loperamide antibiotic regimens were included for analysis. Among 6 paired studies comparing antibiotics alone versus antibiotics in combination with loperamide, the odds of clinical cure at 24 h and 48 h favored combination therapy, with summary odds ratios of 2.6 (95% confidence interval, 1.8-3.6; P = .20, by x 2 heterogeneity statistic) and 2.2 (95% confidence interval, 1.5-3.1; P = .20, by x 2 heterogeneity statistic), respectively, with no evidence of heterogeneity. Factors that possibly affect advantage of combination therapy over solo therapy included increased frequency of pretreatment diarrhea and higher prevalence of noninvasive pathogens. Conclusion. Antibiotic therapy with adjunctive loperamide offers an advantage over antibiotics alone by decreasing the illness duration and increasing the probability of early clinical cure.
TL;DR: This meta-analysis of randomized clinical trials was performed to determine whether hydration therapy using sodium bicarbonate consistently differs from control hydration regimens with normal saline in its preventive effects upon radiocontrast media-induced renal dysfunction.
Abstract: BACKGROUND: The clinical value of hydration therapy using sodium bicarbonate in the prevention of contrast media-induced nephropathy is subject of controversy. OBJECTIVE: This meta-analysis of randomized clinical trials was performed to determine whether hydration therapy using sodium bicarbonate consistently differs from control hydration regimens with normal saline in its preventive effects upon radiocontrast media-induced renal dysfunction. METHODS: Randomized clinical trials comparing sodium bicarbonate with a control regimen for prevention of contrast media-induced nephropathy were selected by multiple methods, including computer searches of bibliographic databases, perusal of reference lists, and manual searching. Major findings were qualitatively summarized. In addition, a quantitative meta-analysis was performed on renal dysfunction data. RESULTS: Altogether, 9 randomized clinical trials with a total of 2,043 patients were included. The pooled odds ratio was 0.45 (confidence interval, 0.26–0.79), indicating a significant treatment benefit of sodium bicarbonate compared to normal saline. Heterogeneity was detectable (p = 0.016) and evidence of publication bias was present (p = 0.012). After adjustment for presumed unpublished trials after trim-and-fill analysis, the estimated pooled odds ratio was 0.65 (confidence interval, 0.36–1.20). CONCLUSION: This meta-analysis confirms that, based on currently available randomized trials, bicarbonate therapy is effective in preventing contrast media-induced nephropathy. However, study heterogeneity and publication bias are substantial, and therefore further controlled clinical trials are needed.