Systematic review and network meta-analysis (NMA) for cladribine tablets in achieving sustained disability improvement (SDI) in multiple sclerosis.

INTRODUCTION: This study was performed to compare probabilities of SDI on the Expanded Disability Status Scale (EDSS) in patients with relapsing-remitting multiple sclerosis (RRMS), treated with cladribine tablets (CT) or fingolimod (FTY), natalizumab (NAT), alemtuzumab (ALE) and ocrelizumab (OCR). CLINICAL RATIONALE FOR THE STUDY: Progression of neurological disability as measured by the EDSS has been a common endpoint in multiple sclerosis (MS) trials. Novel therapies can not only slow this process, but in some patients even reverse it. This effect can be measured by the sustained disability improvement (SDI) - an endpoint that seems to continuously gain importance in clinical practice. Despite that, SDI has rarely been explored as an outcome in MS clinical studies, mostly as post-hoc analyses from randomised trials or as retrospective analyses based on patient registry records. MATERIAL AND METHODS: A systematic review was conducted in Medline, Embase and Cochrane to identify clinical trials (RCT or non-RCT) evaluating 6-month SDI. An indirect comparison via network meta-analysis (NMA) was performed. Bayesian inference with Markov chains Monte Carlo methods were applied. RESULTS: Eight trials presenting SDI results and applicable for NMA were included: six non-RCTs, with control groups selected by propensity score matching, and two RCTs. NMA results revealed that probability of achieving 6-month SDI with CT was significantly higher compared to all other high efficacy disease-modifying drugs with available data - HR (95% Crl - Bayesian Credibility Interval) vs. FTY: 4.98 (2.11-11.79); vs. NAT: 3.12 (1.31-7.27); vs. ALE: 9.29 (3.40-25.21). The main results were confirmed in the sensitivity analyses. CONCLUSIONS: Of all considered therapies, treatment with cladribine tablets was associated with a higher probability of sustained disability improvement in RRMS patients. As this conclusion is based on available clinical data of limited quality, future studies, as well as real-world data, would be valuable to provide further evidence regarding the comparative effectiveness of RRMS therapies.

Predictors of Higher Quality of Systematic Reviews Addressing Nutrition and Cancer Prevention.

Systematic reviews/meta-analyses (SR/MAs) are considered a reliable source of information in healthcare. We aimed to explore the association of several characteristics of SR/MAs addressing nutrition in cancer prevention and their quality/risk of bias (using assessments from AMSTAR-2 and ROBIS tools). The analysis included 101 SR/MAs identified in a systematic survey. Associations of each specified characteristic (e.g., information about the protocol, publication year, reported use of GRADE, or other methods for assessing overall certainty of evidence) with the number of AMSTAR-2 not met ('No' responses) and the number of ROBIS items met ('Probably Yes' or "Yes' responses) were examined. Poisson regression was used to identify predictors of the number of 'No' answers (indicating lower quality) for all AMSTAR-2 items and the number of 'Yes' or 'Probably Yes' answers (indicating higher quality/lower concern for bias) for all ROBIS items. Logistic regression was used to identify variables associated with at least one domain assessed as 'low concern for bias' in the ROBIS tool. In multivariable analysis, SR/MAs not reporting use of any quality/risk of bias assessment instrument for primary studies were associated with a higher number of 'No' answers for all AMSTAR-2 items (incidence rate ratio (IRR) 1.26, 95% confidence interval (CI) 1.09-1.45), and a lower number of 'Yes' or 'Probably Yes' answers for all ROBIS items (IRR 0.76, 95% CI 0.66-0.87). Providing information about the protocol and search for unpublished studies was associated with a lower number of 'No' answers (IRR 0.73, 95% CI 0.56-0.97 and IRR 0.75, 95% CI 0.59-0.95, respectively) and a higher number of 'Yes' or 'Probably Yes' answers (IRR 1.43, 95% CI 1.17-1.74 and IRR 1.28, 95% CI 1.07-1.52, respectively). Not using at least one quality/risk of bias assessment tool for primary studies within an SR/MA was associated with lower odds that a study would be assessed as 'low concern for bias' in at least one ROBIS domain (odds ratio 0.061, 95% CI 0.007-0.527). Adherence to methodological standards in the development of SR/MAs was associated with a higher overall quality of SR/MAs addressing nutrition for cancer prevention.

Are systematic reviews addressing nutrition for cancer prevention trustworthy? A systematic survey of quality and risk of bias.

CONTEXT: The last 30 years have yielded a vast number of systematic reviews and/or meta-analyses addressing the link between nutrition and cancer risk. OBJECTIVE: The aim of this survey was to assess overall quality and potential for risk of bias in systematic reviews and meta-analyses (SRMAs) that examined the role of nutrition in cancer prevention. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library databases were searched (last search performed November 2018). STUDY SELECTION: Studies identified as SRMAs that investigated a nutritional or dietary intervention or exposure for cancer prevention in the general population or in people at risk of cancer and in which primary studies had a comparison group were eligible for inclusion. Screening, data extraction, and quality assessment were conducted independently by 2 reviewers. DATA EXTRACTION: Altogether, 101 studies were randomly selected for analysis. The methodological quality and risk of bias were evaluated using the AMSTAR-2 and ROBIS tools, respectively. RESULTS: Most SRMAs included observational studies. Less than 10% of SRMAs reported a study protocol, and only 51% of SRMAs assessed the risk of bias in primary studies. Most studies conducted subgroup analyses, but only a few reported tests of interaction or specified subgroups of interest a priori. Overall, according to AMSTAR-2, only 1% of SRMAs were of high quality, while 97% were of critically low quality. Only 3% had a low risk of bias, according to ROBIS. CONCLUSIONS: This systematic survey revealed substantial limitations with respect to quality and risk of bias of SRMAs. SRMAs examining nutrition and cancer prevention cannot be considered trustworthy, and results should be interpreted with caution. Peer reviewers as well as users of SRMAs should be advised to use the AMSTAR-2 and/or ROBIS instruments to help to determine the overall quality and risk of bias of SRMAs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42019121116.

Similarities, reliability and gaps in assessing the quality of conduct of systematic reviews using AMSTAR-2 and ROBIS: systematic survey of nutrition reviews.

BACKGROUND: AMSTAR-2 ('A Measurement Tool to Assess Systematic Reviews, version 2') and ROBIS ('Risk of Bias in Systematic Reviews') are independent instruments used to assess the quality of conduct of systematic reviews/meta-analyses (SR/MAs). The degree of overlap in methodological constructs together with the reliability and any methodological gaps have not been systematically assessed and summarized in the field of nutrition. METHODS: We performed a systematic survey of MEDLINE, EMBASE, and the Cochrane Library for SR/MAs published between January 2010 and November 2018 that examined the effects of any nutritional intervention/exposure for cancer prevention. We followed a systematic review approach including two independent reviewers at each step of the process. For AMSTAR-2 (16 items) and ROBIS (21 items), we assessed the similarities, the inter-rater reliability (IRR) and any methodological limitations of the instruments. Our protocol for the survey was registered in PROSPERO (CRD42019121116). RESULTS: We found 4 similar domain constructs based on 11 comparisons from a total of 12 AMSTAR-2 and 14 ROBIS items. Ten comparisons were considered fully overlapping. Based on Gwet's agreement coefficients, six comparisons provided almost perfect (> 0.8), three substantial (> 0.6), and one a moderate level of agreement (> 0.4). While there is considerable overlap in constructs, AMSTAR-2 uniquely addresses explaining the selection of study designs for inclusion, reporting on excluded studies with justification, sources of funding of primary studies, and reviewers' conflict of interest. By contrast, ROBIS uniquely addresses appropriateness and restrictions within eligibility criteria, reducing risk of error in risk of bias (RoB) assessments, completeness of data extracted for analyses, the inclusion of all necessary studies for analyses, and adherence to predefined analysis plan. CONCLUSIONS: Among the questions on AMSTAR-2 and ROBIS, 70.3% (26/37 items) address the same or similar methodological constructs. While the IRR of these constructs was moderate to perfect, there are unique methodological constructs that each instrument independently addresses. Notably, both instruments do not address the reporting of absolute estimates of effect or the overall certainty of the evidence, items that are crucial for users' wishing to interpret the importance of SR/MA results.

Systematic review and meta-analysis of perioperative behavioral lifestyle and nutritional interventions in bariatric surgery: a call for better research and reporting.

Bariatric surgery is considered the most effective treatment for people with morbid obesity, and certain interventions could enhance its long-term results. We searched MEDLINE, Embase, Web of Science, CENTRAL, and trial registers up to January 1, 2020. Randomized controlled trials, where behavioral lifestyle or nutritional interventions were provided perioperatively were included. Primary outcome was weight change. Two reviewers independently performed each stage of the review. Altogether 6652 references were screened. 31 studies were included for qualitative synthesis and 22 studies for quantitative synthesis. Interventions varied greatly, thus limiting possibility of synthesizing all results. Six groups of interventions were discerned, and we used standardized mean differences for synthesis. Low to very-low certainty evidence suggests that physical activity, nonvitamin nutritional interventions, vitamins, psychotherapy, and counseling but not combined interventions might bring some benefit regarding short-term postsurgery follow-ups (up to 12 mo), but the estimates varied and results were not statistically significant, except for 12 months follow-ups regarding counseling. Psychotherapy and counseling, but not vitamins and combined interventions, may provide some benefit at longer follow-ups (over 12 mo), but the certainty of evidence was low to very-low and statistically significant results were observed in comparisons including data from single studies with small sample sizes only. Included studies expressed an outcome "weight change" using 20 different measures. Misreporting of data and huge variety of outcomes do not benefit systematic analyses and may possibly lead to confusion of both researchers and readers. We suggest that authors follow a predefined set of outcomes when reporting the results of their studies. The initiative to produce "core outcome set" for clinical trials in bariatric surgery trials is currently underway.

Efficacy of probiotics in patients with morbid obesity undergoing bariatric surgery: a systematic review and meta-analysis.

Bariatric surgery is considered effective for morbid obesity, and probiotic supplementation might provide some benefits. We aimed to revise the evidence regarding probiotic supplementation in patients with morbid obesity undergoing bariatric surgery. MEDLINE, Embase, Web of Science, CENTRAL, and trial registers were searched up to April 1, 2020. We included randomized controlled trials and controlled clinical trials, and outcomes of interest were weight change, quality of life, gastrointestinal symptoms, and adverse events. All stages of the review were done by 2 authors independently and we followed Cochrane Handbook guidance. We screened 2541 references and included 5 studies. Probiotics may have minor to no effect regarding percentage excess weight loss (%EWL) at 6 weeks (mean difference [MD], .28; 95% CI, -9.53 to 10.09; 44 participants, 2 studies), 3 months (MD, 5.47; 95% CI, -3.22 to 14.17; 165 participants, 3 studies), 6 months (MD, .46; 95% CI, -8.14 to 9.07; 115 participants, 2 studies), and 12 months post surgery (MD, .35; 95% CI, -8.66 to 9.37; 123 participants, 2 studies). We observed short-term improvement in gastrointestinal symptoms. There was no important effect on quality of life and no meaningful adverse events. Because probiotic supplementation might provide some benefit with respect to weight loss, might alleviate some gastrointestinal symptoms, and is associated with minor or no adverse events, continuous supplementation might be worth considering in certain individuals. Our findings are based on the body of evidence of very low certainty, and further well-designed randomized controlled trials are required to elucidate the effect and strengthen the certainty in the estimates.

Mortality in patients after acute myocardial infarction managed by cardiologists and primary care physicians: a systematic review.

INTRODUCTION: Mortality following acute myocardial infarction (AMI) remains high despite of progress in invasive and noninvasive treatments. OBJECTIVES: This study aimed to compare the outcomes of ambulatory treatment provided by cardiologists versus general practitioners (GPs) in post­AMI patients. PATIENTS AND METHODS: We conducted a systematic search in 3 electronic databases for interventional and observational studies that reported all­cause mortality, mortality from cardiovascular causes, stroke, and myocardial infarction at long­term follow­up following AMI. We assessed the risk of bias of the included studies using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS­I) tool. For randomized trials, we used the revised Cochrane risk of bias tool (RoB 2.0). RESULTS: Two nonrandomized studies fulfilled the inclusion criteria. We assessed these studies as having a moderate risk of bias. We did not pool the results owing to significant heterogeneity between the studies. Patients consulted by both a cardiologist and a GP were at lower risk of all­cause death as compared with patients consulted by a cardiologist only (risk ratio [RR], 0.92; 95% CI, 0.85-0.99). Patients consulted by a cardiologist with or without GP consultation were at lower risk of all­cause death compared with those consulted by a GP only in both studies (RR, 0.8; 95% CI, 0.75-0.85 and RR, 0.44; 95% CI, 0.41-0.47). CONCLUSIONS: Patients after AMI consulted by both a cardiologist and a GP may be at lower risk of death compared with patients consulted by a GP or a cardiologist only. However, these findings are based on moderate­quality nonrandomized studies. We found no evidence on the relation between the specialization of the physician and the risk of cardiovascular death, stroke, or myocardial infarction in AMI survivors.