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ABSTRACTBecause of the large number of infected individuals, an estimate of the future burdens of the long-term consequences of SARS-CoV-2 infection is needed. This systematic review examined associations between SARS-CoV-2 infection and incidence of categories of and selected chronic conditions, by age and severity of infection (inpatient vs. outpatient/mixed care). MEDLINE and EMBASE were searched (1 January 2020 to 4 October 2022) and reference lists scanned. We included observational studies from high-income OECD countries with a control group adjusting for sex and comorbidities. Identified records underwent a two-stage screening process. Two reviewers screened 50% of titles/abstracts, after which DistillerAI acted as second reviewer. Two reviewers then screened the full texts of stage one selections. One reviewer extracted data and assessed risk of bias; results were verified by another. Random-effects meta-analysis estimated pooled hazard ratios (HR). GRADE assessed certainty of the evidence. Twenty-five studies were included. Among the outpatient/mixed SARS-CoV-2 care group, there is high certainty of a small-to-moderate increase (i.e. HR 1.26–1.99) among adults ≥65 years of any cardiovascular condition, and of little-to-no difference (i.e. HR 0.75–1.25) in anxiety disorders for individuals

Abstract Background To inform recommendations by the Canadian Task Force on Preventive Health Care, we reviewed evidence on the benefits, harms, and acceptability of screening and treatment, and on the accuracy of risk prediction tools for the primary prevention of fragility fractures among adults aged 40 years and older in primary care. Methods For screening effectiveness, accuracy of risk prediction tools, and treatment benefits, our search methods involved integrating studies published up to 2016 from an existing systematic review. Then, to locate more recent studies and any evidence relating to acceptability and treatment harms, we searched online databases (2016 to April 4, 2022 [screening] or to June 1, 2021 [predictive accuracy]; 1995 to June 1, 2021, for acceptability; 2016 to March 2, 2020, for treatment benefits; 2015 to June 24, 2020, for treatment harms), trial registries and gray literature, and hand-searched reviews, guidelines, and the included studies. Two reviewers selected studies, extracted results, and appraised risk of bias, with disagreements resolved by consensus or a third reviewer. The overview of reviews on treatment harms relied on one reviewer, with verification of data by another reviewer to correct errors and omissions. When appropriate, study results were pooled using random effects meta-analysis; otherwise, findings were described narratively. Evidence certainty was rated according to the GRADE approach. Results We included 4 randomized controlled trials (RCTs) and 1 controlled clinical trial (CCT) for the benefits and harms of screening, 1 RCT for comparative benefits and harms of different screening strategies, 32 validation cohort studies for the calibration of risk prediction tools (26 of these reporting on the Fracture Risk Assessment Tool without [i.e., clinical FRAX], or with the inclusion of bone mineral density (BMD) results [i.e., FRAX + BMD]), 27 RCTs for the benefits of treatment, 10 systematic reviews for the harms of treatment, and 12 studies for the acceptability of screening or initiating treatment. In females aged 65 years and older who are willing to independently complete a mailed fracture risk questionnaire (referred to as “selected population”), 2-step screening using a risk assessment tool with or without measurement of BMD probably (moderate certainty) reduces the risk of hip fractures (3 RCTs and 1 CCT, n = 43,736, absolute risk reduction [ARD] = 6.2 fewer in 1000, 95% CI 9.0–2.8 fewer, number needed to screen [NNS] = 161) and clinical fragility fractures (3 RCTs, n = 42,009, ARD = 5.9 fewer in 1000, 95% CI 10.9–0.8 fewer, NNS = 169). It probably does not reduce all-cause mortality (2 RCTs and 1 CCT, n = 26,511, ARD = no difference in 1000, 95% CI 7.1 fewer to 5.3 more) and may (low certainty) not affect health-related quality of life. Benefits for fracture outcomes were not replicated in an offer-to-screen population where the rate of response to mailed screening questionnaires was low. For females aged 68–80 years, population screening may not reduce the risk of hip fractures (1 RCT, n = 34,229, ARD = 0.3 fewer in 1000, 95% CI 4.2 fewer to 3.9 more) or clinical fragility fractures (1 RCT, n = 34,229, ARD = 1.0 fewer in 1000, 95% CI 8.0 fewer to 6.0 more) over 5 years of follow-up. The evidence for serious adverse events among all patients and for all outcomes among males and younger females (

Les infections par le virus respiratoire syncytial sont fréquentes chez les jeunes enfants et représentent un fardeau important pour les patients, leurs familles et le système de santé canadien. Nous procédons ici à un examen rapide du fardeau lié au virus respiratoire syncytial chez les enfants âgés de 24 mois ou moins. Quatre bases de données (Medline, Embase, Cochrane Database of Clinical Trials, ClinicalTrials.gov de 2014 à 2018), la littérature grise et les listes de référence ont été examinées pour trouver des études portant sur les éléments suivants : enfants avec ou sans facteur de risque, sans prophylaxie et avec une infection par le virus respiratoire syncytial confirmée en laboratoire. Sur les 29 études trouvées, 10 ont fourni des comparaisons intraétudes et peu ont fait l’examen des conditions cliniques autres que la prématurité. Pour les nourrissons âgés de 33 à 36 semaines de grossesse (SG) par rapport aux nourrissons nés à terme, il existe des preuves de certitude faible à modérée d’une augmentation des hospitalisations dues au virus respiratoire syncytial (n = 599 535 nourrissons; RR 2,05 [IC 95 % 1,89 à 2,22]; 1,3 de plus pour 100 [1,1 à 1,5 de plus]) et de la durée d’hospitalisation (n = 7 597 nourrissons; différence moyenne de 1,00 jour [IC 95 % 0,88 à 1,12]). Il y avait des preuves de certitude faible à modérée d’une différence faible à nulle entre les nourrissons nés entre 29 à 32 SG et ceux nés entre 33 à 36 SG pour l’hospitalisation (n = 12 812 nourrissons; RR 1,20 [IC 95 % 0,92 à 1,56]). Il existe des preuves de faible certitude d’une ventilation mécanique accrue pour les nourrissons hospitalisés nés à 29 à 32 SG par rapport à 33 à 35 SG (n = 212 nourrissons; RR 1,58; IC 95 % 0,94 à 2,65). Chez les nourrissons nés entre 32 et 35 SG, l’hospitalisation pour le virus respiratoire syncytial dans la petite enfance peut être associée à une augmentation de la respiration sifflante et de l’utilisation de médicaments contre l’asthme au cours du suivi de six ans (RR de 1,3 à 1,7). Les enfants atteints du syndrome de Down peuvent avoir une durée d’hospitalisation plus longue que ceux qui n’en sont pas atteints (n = 7 206 enfants; différence moyenne de 3,00 jours, IC 95 % 1,95 à 4,05; certitude faible). Les preuves pour les autres comparaisons intraétudes étaient d’un niveau de certitude très faible. En résumé, la prématurité est associée à un risque plus élevé d’hospitalisation pour le virus respiratoire syncytial et à une durée d’hospitalisation plus longue, et le syndrome de Down peut être associé à une hospitalisation plus longue pour le virus respiratoire syncytial. L’hospitalisation due au virus respiratoire syncytial dans la petite enfance peut être associée à une plus grande respiration sifflante et à une plus grande utilisation de médicaments contre l’asthme dans la petite enfance. L’absence de groupe de comparaison a constitué une limite majeure pour de nombreuses études.

Respiratory syncytial virus (RSV) infections are common among young children and represent a significant burden to patients, their families and the Canadian health system. Here we conduct a rapid review of the burden of RSV illness in children 24 months of age or younger. Four databases (Medline, Embase, Cochrane Database of Clinical Trials, ClinicalTrials.gov from 2014 to 2018), grey literature and reference lists were reviewed for studies on the following: children with or without a risk factor, without prophylaxis and with lab-confirmed RSV infection. Of 29 studies identified, 10 provided within-study comparisons and few examined clinical conditions besides prematurity. For infants of 33–36 weeks gestation (wGA) versus term infants, there was low-to-moderate certainty evidence for an increase in RSV-hospitalizations (n=599,535 infants; RR 2.05 [95% CI 1.89–2.22]; 1.3 more per 100 [1.1–1.5 more]) and hospital length of stay (n=7,597 infants; mean difference 1.00 day [95% CI 0.88–1.12]). There was low-to-moderate certainty evidence of little-to-no difference for infants born at 29–32 versus 33–36 wGA for hospitalization (n=12,812 infants; RR 1.20 [95% CI 0.92–1.56]). There was low certainty evidence of increased mechanical ventilation for hospitalized infants born at 29–32 versus 33–35 wGA (n=212 infants; RR 1.58, 95% CI 0.94–2.65). Among infants born at 32–35 wGA, hospitalization for RSV in infancy may be associated with increased wheeze and asthma-medication use across six-year follow-up (RR range 1.3–1.7). Children with versus without Down syndrome may have increased hospital length of stay (n=7,206 children; mean difference 3.00 days, 95% CI 1.95–4.05; low certainty). Evidence for other within-study comparisons was of very low certainty. In summary, prematurity is associated with greater risk for RSV-hospitalization and longer hospital length of stay, and Down syndrome may be associated with longer hospital stay for RSV. Respiratory syncytial virus-hospitalization in infancy may be associated with greater wheeze and asthma-medication use in early childhood. Lack of a comparison group was a major limitation for many studies.

Abstract Background We conducted systematic reviews on the benefits and harms of screening compared with no screening or alternative screening approaches for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in non-pregnant sexually active individuals, and on the relative importance patients’ place on the relevant outcomes. Findings will inform recommendations by the Canadian Task Force on Preventive Health Care. Methods We searched five databases (to January 24, 2020), trial registries, conference proceedings, and reference lists for English and French literature published since 1996. Screening, study selection, and risk of bias assessments were independently undertaken by two reviewers, with consensus for final decisions. Data extraction was conducted by one reviewer and checked by another for accuracy and completeness. Meta-analysis was conducted where appropriate. We used the GRADE approach to rate the certainty of the evidence. The Task Force and content experts provided input on determining thresholds for important effect sizes and on interpretation of findings. Results Of 41 included studies, 17 and 11 reported on benefits and harms of screening, respectively, and 14 reported on patient preferences. Universal screening for CT in general populations 16 to 29 years of age, using population-based or opportunistic approaches achieving low screening rates, may make little-to-no difference for a female’s risk of pelvic inflammatory disease (PID) (2 RCTs, n=141,362; 0.3 more in 1000 [7.6 fewer to 11 more]) or ectopic pregnancy (1 RCT, n=15,459; 0.20 more per 1000 [2.2 fewer to 3.9 more]). It may also not make a difference for CT transmission (3 RCTs, n=41,709; 3 fewer per 1000 [11.5 fewer to 6.9 more]). However, benefits may be achieved for reducing PID if screening rates are increased (2 trials, n=30,652; 5.7 fewer per 1000 [10.8 fewer to 1.1 more]), and for reducing CT and NG transmission when intensely screening high-prevalence female populations (2 trials, n=6127; 34.3 fewer per 1000 [4 to 58 fewer]; NNS 29 [17 to 250]). Evidence on infertility in females from CT screening and on transmission of NG in males and both sexes from screening for CT and NG is very uncertain. No evidence was found for cervicitis, chronic pelvic pain, or infertility in males from CT screening, or on any clinical outcomes from NG screening. Undergoing screening, or having a diagnosis of CT, may cause a small-to-moderate number of people to experience some degree of harm, mainly due to feelings of stigmatization and anxiety about future infertility risk. The number of individuals affected in the entire screening-eligible population is likely smaller. Screening may make little-to-no difference for general anxiety, self-esteem, or relationship break-up. Evidence on transmission from studies comparing home versus clinic screening is very uncertain. Four studies on patient preferences found that although utility values for the different consequences of CT and NG infections are probably quite similar, when considering the duration of the health state experiences, infertility and chronic pelvic pain are probably valued much more than PID, ectopic pregnancy, and cervicitis. How patients weigh the potential benefits versus harms of screening is very uncertain (1 survey, 10 qualitative studies); risks to reproductive health and transmission appear to be more important than the (often transient) psychosocial harms. Discussion Most of the evidence on screening for CT and/or NG offers low or very low certainty about the benefits and harms. Indirectness from use of comparison groups receiving some screening, incomplete outcome ascertainment, and use of outreach settings was a major contributor to uncertainty. Patient preferences indicate that the potential benefits from screening appear to outweigh the possible harms. Direct evidence about which screening strategies and intervals to use, which age to start and stop screening, and whether screening males in addition to females is necessary to prevent clinical outcomes is scarce, and further research in these areas would be informative. Apart from the evidence in this review, information on factors related to equity, acceptability, implementation, cost/resources, and feasibility will support recommendations made by the Task Force. Systematic review registration International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42018100733 .

Abstract Background There is an unresolved debate about the reliability of the interpretation of P value. Some investigators have suggested that an alternative Bayesian method is preferred in conducting health research. As randomized-controlled trials (RCTs) are important in generating research evidence, we decided to investigate the extent, if any, the inferential statistical framework in published RCTs in child health research have changed over 10 years. We aim to examine the change in P value and Bayesian analysis in RCTs in child health research papers published from 2007 to 2017. Methods We will search the Cochrane Central Register of Controlled Trials (Wiley) to identify relevant citations. We will leverage a pre-existing sample of child health RCTs published in 2007 (n=300) used in our previous study of reporting quality of pediatric RCTs. Using the same strategy and study selection methods, we will identify a comparable random sample of child health RCTs published in 2017 (n=300). Eligible studies will include RCTs in health research among individuals aged 21 years and below. One reviewer will select studies for inclusion and extract the data and another reviewer will verify these. Disagreements will be resolved by a discussion between reviewers or by involving another reviewer. We will perform a descriptive analysis of 2007 and 2017 samples and analyze the results using both the frequentist and Bayesian methods. We will present specific characteristics of the clinical trials from 2007 and 2017 in tabular and graphical forms. We will report the difference in the proportion of P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. Clustering around P values of significance, if observed, will be reported. Discussion This review will present the difference in the proportion of trials that reported on P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. The implications for future clinical research will be discussed and this research work will be published in a peer-reviewed journal. This review has the potential to help inform the need for a change in the methodological approach from the null hypothesis significance test to Bayesian methods. Systematic review registration Open Science Framework https://osf.io/aj2df

Abstract Purpose To inform recommendations by the Canadian Task Force on Preventive Health Care on screening in primary care for the prevention and early detection of cervical cancer by systematically reviewing evidence of (a) effectiveness; (b) test accuracy; (c) individuals’ values and preferences; and (d) strategies aimed at improving screening rates. Methods De novo reviews will be conducted to evaluate effectiveness and to assess values and preferences. For test accuracy and strategies to improve screening rates, we will integrate studies from existing systematic reviews with search updates to the present. Two Cochrane reviews will provide evidence of adverse pregnancy outcomes from the conservative management of cervical intraepithelial neoplasia. We will search Medline, Embase, and Cochrane Central (except for individuals’ values and preferences, where Medline, Scopus, and EconLit will be searched) via peer-reviewed search strategies and the reference lists of included studies and reviews. We will search ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. Two reviewers will screen potentially eligible studies and agree on those to include. Data will be extracted by one reviewer with verification by another. Two reviewers will independently assess risk of bias and reach consensus. Where possible and suitable, we will pool studies via meta-analysis. We will compare accuracy data per outcome and per comparison using the Rutter and Gatsonis hierarchical summary receiver operating characteristic model and report relative sensitivities and specificities. Findings on values and preferences will be synthesized using a narrative synthesis approach and thematic analysis, depending on study designs. Two reviewers will appraise the certainty of evidence for all outcomes using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and come to consensus. Discussion The publication of guidance on screening in primary care for the prevention and early detection of cervical cancer by the Task Force in 2013 focused on cytology. Since 2013, new studies using human papillomavirus tests for cervical screening have been published that will improve our understanding of screening in primary care settings. This review will inform updated recommendations based on currently available studies and address key evidence gaps noted in our previous review.

Abstract Background An estimated 20–30% of community-dwelling Canadian adults aged 65 years or older experience one or more falls each year. Fall-related injuries are a leading cause of hospitalization and can lead to functional independence. Many fall prevention interventions, often based on modifiable risk factors, have been studied. Apart from the magnitude of the benefits and harms from different interventions, the preferences of older adults for different interventions as well as the relative importance they place on the different potential outcomes may influence recommendations by guideline panels. These reviews on benefits and harms of interventions, and on patient values and preferences, will inform the Canadian Task Force on Preventive Health Care to develop recommendations on fall prevention for primary care providers. Methods To review the benefits and harms of fall prevention interventions, we will update a previous systematic review of randomized controlled trials with adaptations to modify the classification of interventions and narrow the scope to community-dwelling older adults and primary-care relevant interventions. Four databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Ageline), reference lists, trial registries, and relevant websites will be searched, using limits for randomized trials and date (2016 onwards). We will classify interventions according to the Prevention of Falls Network Europe (ProFANE) Group’s taxonomy. Outcomes include fallers, falls, injurious falls, fractures, hip fractures, institutionalization, health-related quality of life, functional status, and intervention-related adverse effects. For studies not included in the previous review, screening, study selection, data extraction on outcomes, and risk of bias assessments will be independently undertaken by two reviewers with consensus used for final decisions. Where quantitative analysis is suitable, network or pairwise meta-analysis will be conducted using a frequentist approach in Stata. Assessment of the transitivity and coherence of the network meta-analyses will be undertaken. For the reviews on patient preferences and outcome valuation (relative importance of outcomes), we will perform de novo reviews with searches in three databases (MEDLINE, PsycInfo, and CINAHL) and reference lists for cross-sectional, longitudinal quantitative, or qualitative studies published from 2000. Selection, data extraction, and risk of bias assessments suitable for each study design will be performed in duplicate. The analysis will be guided by a narrative synthesis approach, which may include meta-analysis for health-state utilities. We will use the CINeMa approach to a rate the certainty of the evidence for outcomes on intervention effects analyzed using network meta-analysis and the GRADE approach for all other outcomes. Discussion We will describe the flow of literature and characteristics of all studies and present results of all analyses and summary of finding tables. We will compare our findings to others and discuss the limitations of the reviews and the available literature. Systematic review registration This protocol has not been registered.

Abstract Background Long-term prescription of opioids by healthcare professionals has been linked to poor individual patient outcomes and high resource utilization. Supportive strategies in this population regarding acute healthcare settings may have substantial impact. Methods We performed a systematic review and meta-analysis of primary studies. The studies were included according to the following criteria: 1) age 18 and older; 2) long-term prescribed opioid therapy; 3) acute healthcare setting presentation from a complication of opioid therapy; 4) evaluating a supportive strategy; 5) comparing the effectiveness of different interventions; 6) addressing patient or healthcare related outcomes. We performed a qualitative analysis of supportive strategies identified. We pooled patient and system related outcome data for each supportive strategy. Results A total of 5664 studies were screened and 19 studies were included. A total of 9 broad categories of supportive strategies were identified. Meta-analysis was performed for the “supports for patients in pain” supportive strategy on two system-related outcomes using a ratio of means. The number of emergency department (ED) visits were significantly reduced for cohort studies (n = 6, 0.36, 95% CI [0.20–0.62], I2 = 87%) and randomized controlled trials (RCTs) (n = 3, 0.71, 95% CI [0.61–0.82], I2 = 0%). The number of opioid prescriptions at ED discharge was significantly reduced for RCTs (n = 3, 0.34, 95% CI [0.14–0.82], I2 = 78%). Conclusion For patients presenting to acute healthcare settings with complications related to long-term opioid therapy, the intervention with the most robust data is “supports for patients in pain”.

Abstract Background We evaluated the benefits and risks of using the Abstrackr machine learning (ML) tool to semi-automate title-abstract screening and explored whether Abstrackr’s predictions varied by review or study-level characteristics. Methods For a convenience sample of 16 reviews for which adequate data were available to address our objectives (11 systematic reviews and 5 rapid reviews), we screened a 200-record training set in Abstrackr and downloaded the relevance (relevant or irrelevant) of the remaining records, as predicted by the tool. We retrospectively simulated the liberal-accelerated screening approach. We estimated the time savings and proportion missed compared with dual independent screening. For reviews with pairwise meta-analyses, we evaluated changes to the pooled effects after removing the missed studies. We explored whether the tool’s predictions varied by review and study-level characteristics. Results Using the ML-assisted liberal-accelerated approach, we wrongly excluded 0 to 3 (0 to 14%) records that were included in the final reports, but saved a median (IQR) 26 (9, 42) h of screening time. One missed study was included in eight pairwise meta-analyses in one systematic review. The pooled effect for just one of those meta-analyses changed considerably (from MD (95% CI) − 1.53 (− 2.92, − 0.15) to − 1.17 (− 2.70, 0.36)). Of 802 records in the final reports, 87% were correctly predicted as relevant. The correctness of the predictions did not differ by review (systematic or rapid, P = 0.37) or intervention type (simple or complex, P = 0.47). The predictions were more often correct in reviews with multiple (89%) vs. single (83%) research questions (P = 0.01), or that included only trials (95%) vs. multiple designs (86%) (P = 0.003). At the study level, trials (91%), mixed methods (100%), and qualitative (93%) studies were more often correctly predicted as relevant compared with observational studies (79%) or reviews (83%) (P = 0.0006). Studies at high or unclear (88%) vs. low risk of bias (80%) (P = 0.039), and those published more recently (mean (SD) 2008 (7) vs. 2006 (10), P = 0.02) were more often correctly predicted as relevant. Conclusion Our screening approach saved time and may be suitable in conditions where the limited risk of missing relevant records is acceptable. Several of our findings are paradoxical and require further study to fully understand the tasks to which ML-assisted screening is best suited. The findings should be interpreted in light of the fact that the protocol was prepared for the funder, but not published a priori. Because we used a convenience sample, the findings may be prone to selection bias. The results may not be generalizable to other samples of reviews, ML tools, or screening approaches. The small number of missed studies across reviews with pairwise meta-analyses hindered strong conclusions about the effect of missed studies on the results and conclusions of systematic reviews.

Abstract Background Acute liver failure is a rare syndrome with significant morbidity and mortality, particularly in absence of transplantation as a rescue therapy. An important mechanism contributing to mortality is hyperammonemia which drives cerebral edema and raised intracranial pressure. Multiple therapies for managing hyperammonemia have been trialed. Continuous renal replacement therapy is effective in treating hyperammonemia in other disease states (notably inborn errors of metabolism). Its efficacy in acute liver failure has been suggested but further investigation is required to prove this. The objective of this systematic review will be to determine the efficacy of continuous renal replacement therapy in patients with acute liver failure and its effect on mortality and transplant-free survival. Methods MEDLINE, EMBASE, Web of Science, and Cochrane Database will be searched. Identified studies will include all patients with acute liver failure in a critical care unit treated with continuous renal replacement therapy. Primary outcome will be effectiveness of ammonia clearance and mortality. Patients treated with any other modality of ammonia lowering therapy (such as plasma exchange or Molecular Adsorbent Recirculating System) will be excluded. Narrative synthesis of the identified studies will occur and if clinical homogeneity is identified, data will be pooled for meta-analysis using a DerSimonian-Laird random effects model. Discussion We present a protocol for a systematic review seeking to establish a link between transplant-free survival in acute liver failure and the use of continuous renal replacement therapy. Given the anticipated paucity of literature on this subject, both narrative and quantitative syntheses are planned. Systematic review registration (PROSPERO) CRD42019122520 , registered April 16, 2019.

Abstract Background Predicting successful liberation from mechanical ventilation (MV) in critically ill patients is challenging. Brain natriuretic peptide (BNP) has been proposed to help guide decision-making for readiness to liberate from MV following a spontaneous breathing trial (SBT). Methods We performed a systematic review and meta-analysis of randomized and prospective observational studies that measured BNP levels at the time of SBT in patients receiving MV. The primary endpoint was successful liberation from MV (absence of reintubation or non-invasive ventilation at 48 h). Statistical analyses included bi-variate and Moses-Littenberg models and DerSimonian-Laird pooling of areas under ROC curve (AUROC). Results A total of 731 articles were screened. Eighteen adult and 2 pediatric studies were fulfilled pre-specified eligibility. The measure of the relative variation of BNP during SBT (ΔBNP%) after exclusion of SBT failure by clinical criteria in adults yielded a sensitivity and specificity of 0.889 [0.831–0.929] and 0.828 [0.730–0.896] for successful liberation from MV, respectively, with a pooled AUROC of 0.92 [0.88–0.97]. The pooled AUROC for any method of analysis for absolute variation of BNP (ΔBNP), pre-SBT BNP, and post-SBT BNP were 0.89 [0.83–0.95], 0.77 [0.63–0.91], and 0.85 [0.80–0.90], respectively. Conclusion The relative change in BNP during a SBT has potential value as an incremental tool after successful SBT to predict successful liberation from MV in adults. There is insufficient data to support the use of BNP in children or as an alternate test to clinical indices of SBT, or the use of ΔBNP, BNP-pre, and BNP-post as an alternate or incremental test. Trial registration PROSPERO CRD42018087474 (6 February 2018)

Abstract Introduction Renal replacement therapy (RRT) is associated with high mortality and costs; however, no clinical guidelines currently provide specific recommendations for clinicians on when and how to stop RRT in recovering patients. Our objective was to systematically review the current evidence for clinical and biochemical parameters that can be used to predict successful discontinuation of RRT. Methods A systematic review and meta-analysis were performed with a peer-reviewed search strategy combining the themes of renal replacement therapy (IHD, CRRT, SLED), predictors of successful discontinuation or weaning (defined as an extended period of time free from further RRT), and patient outcomes. Major databases were searched and citations were screened using predefined criteria. Studied parameters were reported and, where possible, data was analyzed in the pooled analysis. Results Our search yielded 23 studies describing 16 variables for predicting the successful discontinuation of RRT. All studies were observational in nature. None were externally validated. Fourteen studies described conventional biochemical criteria used as surrogates of glomerular filtration rate (serum urea, serum creatinine, creatinine clearance, urine urea excretion, urine creatinine excretion). Thirteen studies described physiologic parameters such as urine output before and after cessation of RRT, and 13 studies reported on newer kidney biomarkers, such as serum cystatin C and serum neutrophil gelatinase-associated lipocalin (NGAL). Six studies reported sensitivity and specificity characteristics of multivariate models. Urine output prior to discontinuation of RRT was the most-studied variable, with nine studies reporting. Pooled analysis found a sensitivity of 66.2% (95% CI, 53.6–76.9%) and specificity of 73.6% (95% CI, 67.5–79.0%) for urine output to predict successful RRT discontinuation. Due to heterogeneity in the thresholds of urine output used across the studies, an optimal threshold value could not be determined. Conclusions Numerous variables have been described to predict successful discontinuation of RRT; however, available studies are limited by study design, variable heterogeneity, and lack of prospective validation. Urine output prior to discontinuation of RRT was the most commonly described and robust predictor. Further research should focus on the determination and validation of urine output thresholds, and the evaluation of additional clinical and biochemical parameters in multivariate models to enhance predictive accuracy.

Abstract Background To systematically review the literature on clinical interventions that influence vaginal birth after cesarean (VBAC) rates. Methods We searched Ovid Medline, Ovid Embase, Wiley Cochrane Library, CINAHL via EBSCOhost; and Ovid PsycINFO. Additional studies were identified by searching for clinical trial records, conference proceedings and dissertations. Limits were applied for language (English and French) and year of publication (1985 to present). Two reviewers independently screened comparative studies (randomized or non-randomized controlled trials, and observational designs) according to a priori eligibility criteria: women with prior cesarean sections; any clinical intervention or exposure intended to increase the VBAC rate; any comparator; and, outcomes reporting VBAC, uterine rupture and uterine dehiscence rates. One reviewer extracted data and a second reviewer verified for accuracy. Meta-analysis was conducted using Mantel-Haenszel (random effects model) relative risks (VBAC rate) and risk differences (uterine rupture and dehiscence). Two reviewers independently conducted methodological quality assessments using the Mixed Methods Appraisal Tool (MMAT). Results Twenty-nine studies (six trials and 23 cohorts) examined different clinical interventions affecting rates of vaginal deliveries among women with a prior cesarean delivery (CD). Methodological quality was good overall for the trials; however, concerns among the cohort studies regarding selection bias, comparability of groups and outcome measurement resulted in higher risk of bias. Interventions for labor induction, with or without cervical ripening, included pharmacologic (oxytocin, prostaglandins, misoprostol, mifepristone, epidural analgesia), non-pharmacologic (membrane sweep, amniotomy, balloon devices), and combined (pharmacologic and non-pharmacologic). Single studies with small sample sizes and event rates contributed to most comparisons, with no clear differences between groups on rates of VBAC, uterine rupture and uterine dehiscence. Conclusions This systematic review evaluated clinical interventions directed at increasing the rate of vaginal delivery among women with a prior CD and found low to very low certainty in the body of evidence for cervical ripening and/or labor induction techniques. There is insufficient high-quality evidence to inform optimal clinical interventions among women attempting a trial of labor after a prior CD.

Objectives Rapid review to determine the magnitude of association between potential risk factors and severity of COVID-19, to inform vaccine prioritisation in Canada.Setting Ovid MEDLINE(R) ALL, Epistemonikos COVID-19 in L·OVE Platform, McMaster COVID-19 Evidence Alerts and websites were searched to 15 June 2020. Eligible studies were conducted in high-income countries and used multivariate analyses.Participants After piloting, screening, data extraction and quality appraisal were performed by a single experienced reviewer. Of 3740 unique records identified, 34 were included that reported on median 596 (range 44–418 794) participants, aged 42–84 years. 19/34 (56%) were good quality.Outcomes Hospitalisation, intensive care unit admission, length of stay in hospital or intensive care unit, mechanical ventilation, severe disease, mortality.Results Authors synthesised findings narratively and appraised the certainty of the evidence for each risk factor–outcome association. There was low or moderate certainty evidence for a large (≥2-fold) magnitude of association between hospitalisation in people with COVID-19, and: obesity class III, heart failure, diabetes, chronic kidney disease, dementia, age >45 years, male gender, black race/ethnicity (vs non-Hispanic white), homelessness and low income. Age >60 and >70 years may be associated with large increases in mechanical ventilation and severe disease, respectively. For mortality, a large magnitude of association may exist with liver disease, Bangladeshi ethnicity (vs British white), age >45 years, age >80 years (vs 65–69 years) and male gender among 20–64 years (but not older). Associations with hospitalisation and mortality may be very large (≥5-fold) for those aged ≥60 years.Conclusions Increasing age (especially >60 years) may be the most important risk factor for severe outcomes. High-quality primary research accounting for multiple confounders is needed to better understand the magnitude of associations for severity of COVID-19 with several other factors.PROSPERO registration number CRD42020198001.

Abstract Purpose To inform recommendations by the Canadian Task Force on Preventive Health Care by systematically reviewing direct evidence on the effectiveness and acceptability of screening adults 40 years and older in primary care to reduce fragility fractures and related mortality and morbidity, and indirect evidence on the accuracy of fracture risk prediction tools. Evidence on the benefits and harms of pharmacological treatment will be reviewed, if needed to meaningfully influence the Task Force’s decision-making. Methods A modified update of an existing systematic review will evaluate screening effectiveness, the accuracy of screening tools, and treatment benefits. For treatment harms, we will integrate studies from existing systematic reviews. A de novo review on acceptability will be conducted. Peer-reviewed searches (Medline, Embase, Cochrane Library, PsycINFO [acceptability only]), grey literature, and hand searches of reviews and included studies will update the literature. Based on pre-specified criteria, we will screen studies for inclusion following a liberal-accelerated approach. Final inclusion will be based on consensus. Data extraction for study results will be performed independently by two reviewers while other data will be verified by a second reviewer; there may be some reliance on extracted data from the existing reviews. The risk of bias assessments reported in the existing reviews will be verified and for new studies will be performed independently. When appropriate, results will be pooled using either pairwise random effects meta-analysis (screening and treatment) or restricted maximum likelihood estimation with Hartun-Knapp-Sidnick-Jonkman correction (risk prediction model calibration). Subgroups of interest to explain heterogeneity are age, sex, and menopausal status. Two independent reviewers will rate the certainty of evidence using the GRADE approach, with consensus reached for each outcome rated as critical or important by the Task Force. Discussion Since the publication of other guidance in Canada, new trials have been published that are likely to improve understanding of screening in primary care settings to prevent fragility fractures. A systematic review is required to inform updated recommendations that align with the current evidence base.

Abstract Introduction Opioids are routinely used to treat a variety of chronic conditions associated with pain. However, they are a class of medications with a significant potential for adverse health effects, with and without misuse. Opioid misuse, as defined as inappropriate use of appropriately prescribed opioids, is becoming more well-recognized publicly but does not have clear treatment options. Opioid misuse has been linked to variety of poor outcomes and its consequences have a significant impact on healthcare resource utilization. The evidence on harm reduction strategies to mitigate adverse events prompting presentation to acute care settings for patients presenting with long-term opioid use is sparse. Methods and analysis We will perform a systematic review and meta-analysis to catalog effective harm reduction strategies and identify the most effective ones to reduce avoidable healthcare utilization in patients on long-term opioid therapy who present to acute health care settings with complications attributed to opioid misuse. A search strategy will be developed and executed by an information specialist; electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Library) and additional sources will be searched. Search themes will include opioids, chronic drug use, and acute healthcare settings. Citation screening, selection, quality assessment, and data abstraction will be performed in duplicate. A comprehensive inventory of harm reduction strategies will be developed. Data will be collected on patient-related outcomes associated with each identified harm reduction strategy. When sufficiently homogeneous data on interventions, population, and outcomes is available, it will be pooled for aggregate analysis. Evaluation of the methodological quality of individual studies and of the quality of the body of evidence will be performed. Our primary objective will be to identify harm reduction strategies that have been shown to result in clinically relevant and statistically significant improvements in patient outcomes and/or decreased healthcare utilization. Discussion This study will better characterize harm reduction strategies for patients on long-term prescribed opioids presenting to acute healthcare settings. It will also add new knowledge and generate greater understanding of key knowledge gaps of the long-term prescribed opioid use and its impact on healthcare utilization. Systematic review registration CRD42018088962.

Abstract Background An electronic frailty index (eFI) has been developed and validated in the UK; it uses data from primary care electronic medical records (EMR) for effective frailty case-finding in primary care. This project examined the convergent validity of the eFI from Canadian primary care EMR data with a validated frailty index based on comprehensive geriatric assessment (FI-CGA), in order to understand its potential use in the Canadian context. Methods A cross-sectional validation study, using data from an integrated primary care research program for seniors living with frailty in Edmonton, AB. Eighty-five patients 65 years of age and older from six primary care physicians’ practices were recruited. Patients were excluded if they were under 65 years of age, did not provide consent to participate in the program, or were living in a long term care facility at the time of enrolment. We used scatter plots to assess linearity and Pearson correlation coefficients to examine correlations. Results Results indicate a strong statistically significant correlation between the eFI and FI-CGA (r = 0.72, 95% CI 0.60–0.81, p

Abstract Background Chlamydia trachomatis and Neisseria gonorrhoeae are the most commonly reported sexually transmitted infections in Canada. Existing national guidance on screening for these infections was not based on a systematic review, and recommendations as well as implementation considerations (e.g., population groups, testing and case management) should be explicit and reflect the quality of evidence. The aim of this systematic review is to synthesize research on screening for these infections in sexually active individuals within primary care. We will also review evidence on how people weigh the relative importance of the potential outcomes from screening, rated as most important by the Canadian Task Force on Preventive Health Care (CTFPHC) with input from patients and stakeholders. Methods We have developed a peer-reviewed strategy to comprehensively search MEDLINE, Embase, Cochrane Library, CINAHL, and PsycINFO for English and French literature published 1996 onwards. We will also search trial registries and conference proceedings, and mine references lists. Screening, study selection, risk of bias assessments, and quality of findings across studies (for each outcome) will be independently undertaken by two reviewers with consensus for final decisions. Data extraction will be conducted by one reviewer and checked by another for accuracy and completeness. The CTFPHC and content experts will provide input for decisions on study design (i.e., when and whether to include uncontrolled studies for screening effectiveness) and for interpretation of the findings. Discussion The results section of the review will include a description of all studies, results of all analyses, including planned subgroup and sensitivity analyses, and evidence profiles and summary of findings tables incorporating assessment based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods to communicate our confidence in the estimates of effect. We will compare our findings to others and discuss limitations of the review and available literature. The findings will be used by the CTFPHC—supplemented by consultations with patients and stakeholders and from other sources on issues of feasibility, acceptability, costs/resources, and equity―to inform recommendations on screening to support primary health care providers in delivering preventive care. Systematic review registration International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42018100733.

Introduction In December 2019, the first cases of COVID-19 associated with SARS-CoV-2 viral infection were described in Wuhan, Hubei Province, China. Since then, it has spread rapidly affecting 188 countries and was declared a pandemic by the WHO on 11 March 2020. Preliminary reports suggest up to 30% of patients require intensive care unit (ICU) admission and case fatality rate estimate is 2.3%–7.2%. The primary reason for ICU admission is hypoxaemic respiratory failure, while factors associated with ICU admission include increased age, presence of comorbidities and cytokine storm. Case series and retrospective trials initially assessed proposed treatments with randomised controlled trials now reporting early outcomes. We conduct a systematic review and meta-analysis to identify epidemiological factors, treatments and complications that predict mortality among critically ill patients with COVID-19.Methods and analysis Our comprehensive search strategy was developed in consultation with a research librarian. We will search electronic databases: Ovid Medline, Ovid Embase, Ovid Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Wiley Cochrane Library. The search strategy combines concepts from COVID-19, validated COVID-19 search filters and geographical locations of large outbreaks. Citation screening, selection, quality assessment and data abstraction will be performed in duplicate. Clinically homogenous epidemiological characteristics, interventions and complications will be pooled in statistical meta-analysis. Within the framework of a living systematic review, the search and data analysis will be updated every 6 months.Ethics and dissemination Our systematic review will synthesise literature on risk factors and interventions associated with mortality in critically ill patients with COVID-19. Results will be presented at national and international conferences and submitted for peer-reviewed publication. The pooled analysis can provide guidance to inform clinical guidelines for care of critically ill patients with COVID-19. Iterative updates will be made public through open access. Research ethics approval is not required.PROSPERO registration number CRD42020176672.

Abstract Background Evidence relating maternal history of abuse before pregnancy with pregnancy outcomes is controversial. This study aims to examine the association between maternal histories of abuse before pregnancy and the risk of preterm delivery and low birth weight. Methods We searched Subject Headings and keywords for exposure and the outcomes through MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Psycinfo, CINAHL, Scopus, PILOTS, ProQuest Dissertations & Theses Global and Web of Science Core Collection in April 2017. We selected original studies that reported associations between maternal histories of abuse of any type and either preterm delivery or low birth weight. Studies that included interventions during pregnancy to lower maternal stress but reported no control data were excluded. We utilized the Newcastle-Ottawa Quality Assessment Scales for observational studies to assess the risk of bias in the primary studies. Two independent reviewers performed the selection of pertinent studies, assessment of risk of bias, and data extraction. Unadjusted pooled odds ratios (OR) with 95% Confidence Interval (CI) were calculated for the two outcomes of preterm delivery and low birth weight in 16 included studies. Results Maternal history of abuse before pregnancy was significantly associated with preterm delivery (OR 1.28, 95% CI: 1.12–1.47) and low birth weight (OR 1.35, 95% CI: 1.14–1.59). A substantial level of heterogeneity was detected within the two groups of studies reporting preterm birth and low birth weight (I2 = 75% and 69% respectively). Subgroup analysis based on the specific time of abuse before pregnancy indicated that childhood abuse increases the risk of low birth weight by 57% (95% CI: 0.99–2.49). When the included studies were categorized based on study design, cohort studies showed the highest effect estimates on preterm delivery and low birth weight (OR: 1.69, 95%CI: 1.19–2.40, OR: 1.56, 95% CI: 1.06–2.3, respectively). Conclusions We recommend that more high quality research studies on this topic are necessary to strengthen the inference. At the practice level, we suggest more attention in detecting maternal history of abuse before pregnancy during antenatal visits and using this information to inform risk assessment for adverse pregnancy outcomes. Trial registration Registration number: PROSPERO (CRD42016033231).

Abstract Background Systematic reviews (SRs) of randomised controlled trials (RCTs) can provide the best evidence to inform decision-making, but their methodological and reporting quality varies. Tools exist to guide the critical appraisal of quality and risk of bias in SRs, but evaluations of their measurement properties are limited. We will investigate the interrater reliability (IRR), usability, and applicability of A MeaSurement Tool to Assess systematic Reviews (AMSTAR), AMSTAR 2, and Risk Of Bias In Systematic reviews (ROBIS) for SRs in the fields of biomedicine and public health. Methods An international team of researchers at three collaborating centres will undertake the study. We will use a random sample of 30 SRs of RCTs investigating therapeutic interventions indexed in MEDLINE in February 2014. Two reviewers at each centre will appraise the quality and risk of bias in each SR using AMSTAR, AMSTAR 2, and ROBIS. We will record the time to complete each assessment and for the two reviewers to reach consensus for each SR. We will extract the descriptive characteristics of each SR, the included studies, participants, interventions, and comparators. We will also extract the direction and strength of the results and conclusions for the primary outcome. We will summarise the descriptive characteristics of the SRs using means and standard deviations, or frequencies and proportions. To test for interrater reliability between reviewers and between the consensus agreements of reviewer pairs, we will use Gwet’s AC1 statistic. For comparability to previous evaluations, we will also calculate weighted Cohen’s kappa and Fleiss’ kappa statistics. To estimate usability, we will calculate the mean time to complete the appraisal and to reach consensus for each tool. To inform applications of the tools, we will test for statistical associations between quality scores and risk of bias judgments, and the results and conclusions of the SRs. Discussion Appraising the methodological and reporting quality of SRs is necessary to determine the trustworthiness of their conclusions. Which tool may be most reliably applied and how the appraisals should be used is uncertain; the usability of newly developed tools is unknown. This investigation of common (AMSTAR) and newly developed (AMSTAR 2, ROBIS) tools will provide empiric data to inform their application, interpretation, and refinement.

Abstract Background We wished to compare the nuisance parameters of pediatric vs. adult randomized-trials (RCTs) and determine if the latter can be used in sample size computations of the former. Methods In this meta-epidemiologic empirical evaluation we examined meta-analyses from the Cochrane Database of Systematic-Reviews, with at least one pediatric-RCT and at least one adult-RCT. Within each meta-analysis of binary efficacy-outcomes, we calculated the pooled-control-group event-rate (CER) across separately all pediatric and adult-trials, using random-effect models and subsequently calculated the control-group event-rate risk-ratio (CER-RR) of the pooled-pediatric-CERs vs. adult-CERs. Within each meta-analysis with continuous outcomes we calculated the pooled-control-group effect standard deviation (CE-SD) across separately all pediatric and adult-trials and subsequently calculated the CE-SD-ratio of the pooled-pediatric-CE-SDs vs. adult-CE-SDs. We then calculated across all meta-analyses the pooled-CER-RRs and pooled-CE-SD-ratios (primary endpoints) and the pooled-magnitude of effect-sizes of CER-RRs and CE-SD-ratios using REMs. A ratio

The risk of major adverse events associated with chronic kidney disease (CKD) could potentially be reduced with effective medical interventions. The impact of multifaceted interventions as compared with usual care in patients with nondiabetic CKD is unclear. We performed a systematic review to analyze the impact of multifaceted interventions on reducing the risk of major adverse events in this population. Methods: Systematic review and meta-analysis. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library databases for medical literature published up to November 2016. Published original studies and abstracts were reviewed that reported on adult patients in a community or specialty care setting, with 2 or more CKD risk factors, treated with a combination of more than 2 interventions. We included randomized controlled trials, observational studies, and systematic reviews. Studies focused on diabetic patients were excluded. The intervention was defined as a treatment with a combination of 2 or more interventions compared with the usual care. The outcomes were defined as a reduction in the risk of adverse clinical outcomes (renal replacement therapy, all-cause hospitalizations, all-cause and cardiovascular mortality, cardiovascular events) as primary outcomes. Secondary outcomes were optimal risk factor control (attaining guideline concordant blood pressure, reduction of proteinuria, smoking cessation). Results: Five of the 5846 unique citations from our initial literature search met our study criteria. All identified studies reported on patients with CKD and their management. In comparison with usual care, multifaceted interventions tended to reduce all-cause mortality (risk ratio: 0.81, 95% confidence interval: 0.63–1.03) and were associated with a lower risk of progression to kidney failure requiring dialysis (risk ratio: 0.57, 95% confidence interval: 0.35–0.94). Multifaceted interventions were not associated with reducing risk of all-cause hospitalizations (risk ratio: 0.93, 95% confidence interval: 0.71–1.23) or improved blood pressure control (mean difference: −0.48, range: −2.5 to 1.55 mm Hg). Discussion: Multifaceted interventions targeting multiple risk factors tended to reduce the risk of all-cause mortality and reduced the risk to progress to end-stage kidney failure in patients with CKD. There is a need for high-quality studies that can rigorously evaluate a set of interventions targeting multiple domains of CKD management in the population with nondiabetic CKD due to paucity of data in the current published literature.

Abstract Background Systematic reviews (SRs) are an important source of information about healthcare interventions. A key component of a well-conducted SR is a comprehensive literature search. There is limited evidence on the contribution of non-English reports, unpublished studies, and dissertations and their impact on results of meta-analyses. Methods Our sample included SRs from three Cochrane Review Groups: Acute Respiratory Infections (ARI), Infectious Diseases (ID), Developmental Psychosocial and Learning Problems (DPLP) (n = 129). Outcomes included: 1) proportion of reviews that searched for and included each study type; 2) proportion of relevant studies represented by each study type; and 3) impact on results and conclusions of the primary meta-analysis for each study type. Results Most SRs searched for non-English studies; however, these were included in only 12% of reviews and represented less than 5% of included studies. There was a change in results in only four reviews (total sample = 129); in two cases the change did not have an impact on the statistical or clinical significance of results. Most SRs searched for unpublished studies but the majority did not include these (only 6%) and they represented 2% of included studies. In most cases the impact of including unpublished studies was small; a substantial impact was observed in one case that relied solely on unpublished data. Few reviews in ARI (9%) and ID (3%) searched for dissertations compared to 65% in DPLP. Overall, dissertations were included in only nine SRs and represented less than 2% of included studies. In the majority of cases the change in results was negligible or small; in the case where a large change was noted, the estimate was more conservative without dissertations. Conclusions The majority of SRs searched for non-English and unpublished studies; however, these represented a small proportion of included studies and rarely impacted the results and conclusions of the review. Inclusion of these study types may have an impact in situations where there are few relevant studies, or where there are questionable vested interests in the published literature. We found substantial variation in whether SRs searched for dissertations; in most reviews that included dissertations, these had little impact on results.

Abstract Background One of the best sources for high quality information about healthcare interventions is a systematic review. A well-conducted systematic review includes a comprehensive literature search. There is limited empiric evidence to guide the extent of searching, in particular the number of electronic databases that should be searched. We conducted a cross-sectional quantitative analysis to examine the potential impact of selective database searching on results of meta-analyses. Methods Our sample included systematic reviews (SRs) with at least one meta-analysis from three Cochrane Review Groups: Acute Respiratory Infections (ARI), Infectious Diseases (ID), Developmental Psychosocial and Learning Problems (DPLP) (n = 129). Outcomes included: 1) proportion of relevant studies indexed in each of 10 databases; and 2) changes in results and statistical significance of primary meta-analysis for studies identified in Medline only and in Medline plus each of the other databases. Results Due to variation across topics, we present results by group (ARI n = 57, ID n = 38, DPLP n = 34). For ARI, identification of relevant studies was highest for Medline (85 %) and Embase (80 %). Restricting meta-analyses to trials that appeared in Medline + Embase yielded fewest changes in statistical significance: 53/55 meta-analyses showed no change. Point estimates changed in 12 cases; in 7 the change was less than 20 %. For ID, yield was highest for Medline (92 %), Embase (81 %), and BIOSIS (67 %). Restricting meta-analyses to trials that appeared in Medline + BIOSIS yielded fewest changes with 1 meta-analysis changing in statistical significance. Point estimates changed in 8 of 31 meta-analyses; change less than 20 % in all cases. For DPLP, identification of relevant studies was highest for Medline (75 %) and Embase (62 %). Restricting meta-analyses to trials that appeared in Medline + PsycINFO resulted in only one change in significance. Point estimates changed for 13 of 33 meta-analyses; less than 20 % in 9 cases. Conclusions Majority of relevant studies can be found within a limited number of databases. Results of meta-analyses based on the majority of studies did not differ in most cases. There were very few cases of changes in statistical significance. Effect estimates changed in a minority of meta-analyses but in most the change was small. Results did not change in a systematic manner (i.e., regularly over- or underestimating treatment effects), suggesting that selective searching may not introduce bias in terms of effect estimates.

Almost half a million breast reduction surgeries are performed internationally each year, yet it is unclear how this type of surgery impacts breastfeeding. This is particularly important given the benefits of breastfeeding.To determine if breast reduction surgery impacts breastfeeding success and whether different surgical techniques differentially impact breast feeding success.Databases were searched up to September 5, 2017. Studies were included if they reported the number of women successful at breastfeeding or lactation after breast reduction surgery, and if they reported either the total number of women who had children following breast reduction surgery, or the total number of women who attempted to breastfeed following surgery.Of 1,212 studies, 51 studies met the inclusion criteria; they were located worldwide and had 31 distinct breast reduction techniques. The percentage of breastfeeding success among studies was highly variable. However, when analyzed by the preservation of the column of parenchyma from the nipple areola complex to the chest wall (subareolar parenchyma), a clear pattern emerged. The median breastfeeding success was 4% (interquartile range (IQR) 0-38%) for techniques with no preservation, compared to 75% (IQR 37-100%) for techniques with partial preservation and 100% (IQR 75-100%) for techniques with full preservation.Techniques that preserve the column of subareolar parenchyma appear to have a greater likelihood of successful breastfeeding. The preservation of the column of subareolar parenchyma should be disclosed to women prior to surgery. Guidelines on the best breast reduction techniques to be used in women of child bearing years may be advantageous to ensure women have the greatest potential for successful breastfeeding after breast reduction surgery.

Following the publication of this article [1], the authors reported a typesetting error in the “Results” section.

To quantify bias related to specific methodological characteristics in child-relevant randomized controlled trials (RCTs).Meta-epidemiological study.We identified systematic reviews containing a meta-analysis with 10-40 RCTs that were relevant to child health in the Cochrane Database of Systematic Reviews.Two reviewers independently assessed RCTs using items in the Cochrane Risk of Bias tool and other study factors. We used meta-epidemiological methods to assess for differences in effect estimates between studies classified as high/unclear vs. low risk of bias.We included 287 RCTs from 17 meta-analyses. The proportion of studies at high/unclear risk of bias was: 79% sequence generation, 83% allocation concealment, 67% blinding of participants, 47% blinding of outcome assessment, 49% incomplete outcome data, 32% selective outcome reporting, 44% other sources of bias, 97% overall risk of bias, 56% funding, 35% baseline imbalance, 13% blocked randomization in unblinded trials, and 1% early stopping for benefit. We found no significant differences in effect estimates for studies that were high/unclear vs. low risk of bias for any of the risk of bias domains, overall risk of bias, or other study factors.We found no differences in effect estimates between studies based on risk of bias. A potential explanation is the number of trials included, in particular the small number of studies with low risk of bias. Until further evidence is available, reviewers should not exclude RCTs from systematic reviews and meta-analyses based solely on risk of bias particularly in the area of child health.