Assessment of Usefulness of Randomized Control Trials in Child Health Research Published in 2007 and 2017.

OBJECTIVE: To examine how clinical usefulness in pediatric research with randomized controlled trials (RCTs) has changed over a 10-year period via a research usefulness tool composed of unique clinical usefulness criteria. STUDY DESIGN: We leveraged a pre-existing sample of child health RCTs published in 2007, used by our team in a previous study. Using the same methods, a research librarian executed a literature search in the Cochrane Central Register of Controlled Trials for the 2017 cohort. We included the first 300 eligible citations from the randomly ordered list for each year, creating two cohorts of 300 publications each, 1 in 2007 and 1 in 2017. Each publication was analyzed and data regarding primary and secondary outcomes, as well as 11 unique criteria of clinical usefulness, were extracted. Each publication was then graded using a tool created by our research team. After quality review, statistical analysis was then performed. RESULTS: Six hundred pediatric RCT publications were included in this review. The mean score increased from 6.07 in 2007 to 9.20 in 2017 (P < .001). Usefulness factors that saw the largest increase in reporting were context placement, funding statements, and conflict of interest statements, while patient centeredness, value for money, and raw data availability remained infrequently reported. CONCLUSION: Our results demonstrate that clinical usefulness of pediatric research improved over this 10-year period, but there are still areas that need a great deal of improvement in order to maximize clinical usefulness and reduce research waste.

Systematic Review of Antimicrobial Lock Solutions for Prevention of Bacteremia in Pediatric Patients With Intestinal Failure.

OBJECTIVES: The goal of this systematic review was to determine whether antimicrobial lock (AML) solutions prevent catheter-related bloodstream infections (CRBSI) in children with intestinal failure (IF). METHODS: Electronic databases were searched: Ovid MEDLINE (1946-), Ovid Embase (1974-), Wiley Cochrane Library (inception-), and Web of Science Core Collection via Clarivate Analytics (1900-). Randomized and nonrandomized trials, case or cohort studies that studied any AML solution, and used comparator groups were included if they studied children with IF. A meta-analysis compared the rates of CRBSI with AML solutions versus controls, and a Boucher analysis was used to indirectly compare AML solutions. RESULTS: Twenty-eight studies met eligibility criteria (1 open label and 27 observational studies). Quality was good (N = 13), fair (N = 9), and poor (N = 6). All but 4 studied ethanol and taurolidine. Of 15 ethanol studies, 11 reported a decrease and 3 reported a trend toward a decreased incidence of CRBSI compared to controls; 1 reported no difference. Of 9 taurolidine studies, 7 reported a decrease and 2 a trend toward decreased CRBSI rates. There was a decrease in CRBSI with ethanol versus control ( P = 0.008) and with taurolidine-citrate versus control ( P < 0.0005). Using Bucher indirect comparison of the pooled estimates from ethanol versus control to taurolidine versus control, the estimated difference was -0.99 (-4.125, 2.27; P = 0.55). CONCLUSIONS: There were no randomized trials and over half of the 28 included studies were fair or poor quality. All but 1 reported at least a trend toward reduction in CRBSI. AML solutions appear to prevent CRBSI.

Screening for Gestational Diabetes: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Gestational diabetes is associated with several poor health outcomes. Objective: To update the 2012 review on screening for gestational diabetes to inform the US Preventive Services Task Force. Data Sources: MEDLINE, EMBASE, and CINAHL (2010 to May 2020), ClinicalTrials.gov, reference lists; surveillance through June 2021. Study Selection: English-language intervention studies for screening and treatment; observational studies on screening; prospective studies on screening test accuracy. Data Extraction and Synthesis: Dual review of titles/abstracts, full-text articles, and study quality. Single-reviewer data abstraction with verification. Random-effects meta-analysis or bivariate analysis (accuracy). Main Outcomes and Measures: Pregnancy, fetal/neonatal, and long-term health outcomes; harms of screening; accuracy. Results: A total of 76 studies were included (18 randomized clinical trials [RCTs] [n = 31 241], 2 nonrandomized intervention studies [n = 190], 56 observational studies [n = 261 678]). Direct evidence on benefits of screening vs no screening was limited to 4 observational studies with inconsistent findings and methodological limitations. Screening was not significantly associated with serious or long-term harm. In 5 RCTs (n = 25 772), 1-step (International Association of Diabetes and Pregnancy Study Group) vs 2-step (Carpenter and Coustan) screening was significantly associated with increased likelihood of gestational diabetes (11.5% vs 4.9%) but no improved health outcomes. At or after 24 weeks of gestation, oral glucose challenge tests with 140- and 135-mg/dL cutoffs had sensitivities of 82% and 93%, respectively, and specificities of 82% and 79%, respectively, against Carpenter and Coustan criteria, and a test with a 140-mg/dL cutoff had sensitivity of 85% and specificity of 81% against the National Diabetes Group Data criteria. Fasting plasma glucose tests with cutoffs of 85 and 90 mg/dL had sensitivities of 88% and 81% and specificities of 73% and 82%, respectively, against Carpenter and Coustan criteria. Based on 8 RCTs and 1 nonrandomized study (n = 3982), treatment was significantly associated with decreased risk of primary cesarean deliveries (relative risk [RR], 0.70 [95% CI, 0.54-0.91]; absolute risk difference [ARD], 5.3%), shoulder dystocia (RR, 0.42 [95% CI, 0.23-0.77]; ARD, 1.3%), macrosomia (RR, 0.53 [95% CI, 0.41-0.68]; ARD, 8.9%), large for gestational age (RR, 0.56 [95% CI, 0.47-0.66]; ARD, 8.4%), birth injuries (odds ratio, 0.33 [95% CI, 0.11-0.99]; ARD, 0.2%), and neonatal intensive care unit admissions (RR, 0.73 [95% CI, 0.53-0.99]; ARD, 2.0%). The association with reduction in preterm deliveries was not significant (RR, 0.75 [95% CI, 0.56-1.01]). Conclusions and Relevance: Direct evidence on screening vs no screening remains limited. One- vs 2-step screening was not significantly associated with improved health outcomes. At or after 24 weeks of gestation, treatment of gestational diabetes was significantly associated with improved health outcomes.

Association between supportive interventions and healthcare utilization and outcomes in patients on long-term prescribed opioid therapy presenting to acute healthcare settings: a systematic review and meta-analysis.

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".

A randomized trial of iPad distraction to reduce children's pain and distress during intravenous cannulation in the paediatric emergency department.

OBJECTIVES: We compared the addition of iPad distraction to standard care, versus standard care alone, to manage the pain and distress of intravenous (IV) cannulation. METHODS: Eighty-five children aged 6 to 11 years requiring IV cannulation (without child life services present) were recruited for a randomized controlled trial from a paediatric emergency department. Primary outcomes were self-reported pain (Faces Pain Scale-Revised [FPS-R]) and distress (Observational Scale of Behavioral Distress-Revised [OSBD-R]), analyzed with two-sample t-tests, Mann-Whitney U-tests, and regression analysis. RESULTS: Forty-two children received iPad distraction and 43 standard care; forty (95%) and 35 (81%) received topical anesthesia, respectively (P=0.09). There was no significant difference in procedural pain using an iPad (median [interquartile range]: 2.0 [0.0, 6.0]) in addition to standard care (2.0 [2.0, 6.0]) (P=0.35). There was no significant change from baseline behavioural distress using an iPad (mean ± SD: 0.53 ± 1.19) in addition to standard care (0.43 ± 1.56) (P=0.44). Less total behavioural distress was associated with having prior emergency department visits (odds ratio [95% confidence interval]: -1.90 [-3.37, -0.43]) or being discharged home (-1.78 [-3.04, -0.52]); prior hospitalization was associated with greater distress (1.29 [0.09, 2.49]). Significantly more parents wished to have the same approach in the future in the iPad arm (41 of 41, 100%) compared to standard care (36 of 42, 86%) (P=0.03). CONCLUSIONS: iPad distraction during IV cannulation in school-aged children was not associated with less pain or distress than standard care alone. The effects of iPad distraction may have been blunted by topical anesthetic cream usage. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT02326623.

Diagnostic Test Accuracy of Commercial Tests for Detection of Shiga Toxin-Producing Escherichia coli: A Systematic Review and Meta-Analysis.

BACKGROUND: Rapid detection of Shiga toxin-producing Escherichia coli (STEC) enables appropriate monitoring and treatment. We synthesized available evidence to compare the performance of enzyme immunoassay (EIA) and PCR tests for the detection of STEC. METHODS: We searched published and gray literature for studies of STEC EIA and/or PCR diagnostic test accuracy relative to reference standards including at least one nucleic acid amplification test. Two reviewers independently screened studies, extracted data, and assessed quality with the second version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Bivariate random effects models were used to meta-analyze the clinical sensitivity and specificity of commercial EIA and PCR STEC diagnostic tests, and summary receiver operator characteristic curves were constructed. We evaluated the certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We identified 43 articles reflecting 25 260 specimens. Meta-analysis of EIA and PCR accuracy included 25 and 22 articles, respectively. STEC EIA pooled sensitivity and specificity were 0.681 (95% CI, 0.571-0.773; very low certainty of evidence) and 1.00 (95% CI, 0.998-1.00; moderate certainty of evidence), respectively. STEC PCR pooled sensitivity and specificity were 1.00 (95% CI, 0.904-1.00; low certainty of evidence) and 0.999 (95% CI, 0.997-0.999; low certainty of evidence), respectively. Certainty of evidence was downgraded because of high risk of bias. CONCLUSIONS: PCR tests to identify the presence of STEC are more sensitive than EIA tests, with no meaningful loss of specificity. However, given the low certainty of evidence, our results may overestimate the difference in performance.

Systematic review with meta-analysis: Nutritional screening and assessment tools in cirrhosis.

BACKGROUND & AIMS: Disease-related malnutrition is common in cirrhosis. Multiple studies have evaluated nutritional screening tools (NSTs, rapid bedside tests targeting who needs assessment) and nutritional assessment tools (NATs, used in diagnosing malnutrition) as predictors of clinical outcome in this population. We performed a systematic review and meta-analysis of this literature with the aim of summarising the varying definitions of malnutrition across studies, the available evidence for NSTs and the ability of NSTs and NATs to predict clinical outcomes in cirrhosis. METHODS: The primary outcome measures were pre- and post-transplant mortality with a range of secondary outcomes. Inclusion: cirrhosis over age 16. Exclusion: >25% with hepatocellular carcinoma, primarily laboratory test-based NATs or lack of screening, assessment or outcome criteria. RESULTS: Eight thousand eight hundred fifty patients were included across 47 studies. Only 3 studies assessed NSTs. Thirty-two definitions for malnutrition were utilised across studies. NATs predicted pre-transplant mortality in 69% of cases that were assessed with a risk ratio (RR) of 2.38 (95% CI 1.96-2.89). NATs were prognostic for post-transplant mortality only 28% of the times they were assessed, with a RR of 3.04 (95% CI 1.51-6.12). CONCLUSIONS: The cirrhosis literature includes limited data on nutrition screening and multiple definitions for what constitutes malnutrition using NATs. Despite this discordance, it is clear that malnutrition is a valuable predictor of pre-transplant mortality almost regardless of how it is defined. We require clinical and research consensus around the definition of malnutrition and the accepted processes and cut-points for nutrition screening and assessment in cirrhosis.

The impact of occupational activities during pregnancy on pregnancy outcomes: a systematic review and metaanalysis.

OBJECTIVE: Data: An increasing number of studies suggest that exposure to physically demanding work during pregnancy could be associated with increased risks of adverse pregnancy outcomes, but the results remain conflicted and inconclusive. The purpose of this study was to examine the influence of occupational activities during pregnancy on maternal and fetal health outcomes. STUDY: Studies of all designs (except case studies and reviews) that contained information on the relevant population (women who engaged in paid work during pregnancy), occupational exposures (heavy lifting, prolonged standing, prolonged walking, prolonged bending, and heavy physical workload), comparator (no exposure to the listed physical work demands), and outcomes (preterm birth, low birthweight, small for gestational age, miscarriage, gestational hypertension, preeclampsia, gestational diabetes mellitus, stillbirth, and intrauterine growth restriction) were included. STUDY APPRAISAL AND SYNTHESIS METHODS: Five electronic databases and 3 gray literature sources were searched up to March 15, 2019. RESULTS: Eighty observational studies (N=853,149) were included. Low-to-very low certainty evidence revealed that lifting objects ≥11 kg was associated with an increased odds ratio of miscarriage (odds ratio, 1.31; 95% confidence interval, 1.08-1.58; I2=79%), and preeclampsia (odds ratio, 1.35; 95% confidence interval, 1.07-1.71; I2=0%). Lifting objects for a combined weight of ≥100 kg per day was associated with an increased odds of preterm delivery (odds ratio, 1.31; 95% confidence interval, 1.11-1.56; I2=0%) and having a low birthweight neonate (odds ratio, 2.08; 95% confidence interval, 1.06-4.11; I2=73%). Prolonged standing was associated with increased odds of preterm delivery (odds ratio, 1.11; 95% confidence interval, 1.02-1.22; I2=30%) and having a small-for-gestational-age neonate (odds ratio, 1.17; 95% confidence interval, 1.01-1.35; I2=41%). A heavy physical workload was associated with increased odds of preterm delivery (odds ratio, 1.23; 95% confidence interval, 1.07-1.41; I2=32%) and having a low birthweight neonate (odds ratio, 1.79; 95% confidence interval, 1.11-2.87; I2=87%). All other associations were not statistically significant. Dose-response analysis showed women stand for >2.5 hours per day (vs no standing) had a 10% increase in the odds of having a preterm delivery. CONCLUSION: Physically demanding work during pregnancy is associated with an increased risk of adverse pregnancy outcomes.

Brain natriuretic peptide to predict successful liberation from mechanical ventilation in critically ill patients: a systematic review and meta-analysis.

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).

Determining the optimal time for liberation from renal replacement therapy in critically ill patients: a systematic review and meta-analysis (DOnE RRT).

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.

Intravenous immunoglobulin for presumed viral myocarditis in children and adults.

BACKGROUND: This is an update of a previous review. Case reports and case series have described dramatic responses to intravenous immunoglobulin (IVIG) in people with presumed viral myocarditis, and its administration has become commonplace. OBJECTIVES: The primary objective of this review was to compare event-free (death, requirement for a cardiac transplant, or placement of a left ventricular assist device) or overall (death) survival of adults and children with presumed viral myocarditis treated with IVIG versus those who did not receive IVIG. A secondary objective was to determine if a group of patients with presumed viral myocarditis could be identified (on the basis of age, duration of symptoms, acuity of onset of symptoms, cardiac function at presentation, virological results, or the presence or absence of histological evidence of acute myocarditis on cardiac biopsy in patients in whom a biopsy was performed) who would be the most likely to benefit from IVIG. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, DARE, CINAHL, Web of Science Core Collection, and LILACS in July 2019, and two trial registries in November 2019. We contacted authors of trials and checked reference lists of relevant papers. We applied no language restrictions. SELECTION CRITERIA: We included studies if (1) participants had a clinical diagnosis of acute myocarditis with a left ventricular ejection fraction (LVEF) ≤ 0.45, left ventricular end-diastolic diameter (LVEDD) > 2 standard deviations (SDs) above the norm, or a left ventricular shortening fraction (LVSF) > 2 SDs below the mean, with duration of cardiac symptoms < 6 months; (2) participants had no evidence of non-infectious or bacterial cardiac disease; and (3) participants were randomly assigned to receive at least 1 g/kg of IVIG versus no IVIG or placebo. We excluded studies if (1) participants had received immunosuppression before outcome assessment; or (2) onset of myocarditis was reported to have occurred < 6 months postpartum. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and extracted data. We assessed risk of bias with the Cochrane 'Risk of bias' tool. We conducted meta-analysis for two outcomes (overall survival and improvement in LVEF) with two adult trials. Other meta-analyses were not possible because only three relevant trials were included, and researchers analysed markedly different populations and used different outcome measures. MAIN RESULTS: In this update we added two trials to the two previously included trials. A quasi-randomised trial was previously included due to a paucity of evidence from randomised trials; however, with the addition of two new randomised trials, it was removed from this update. For two adult trials, the overall risk of bias was unclear with very low-certainty evidence for all outcomes. The first trial studied 62 adults with recent-onset dilated cardiomyopathy randomly assigned to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The effect on event-free survival between groups was uncertain (risk ratio (RR) of any event 1.76, 95% confidence interval (CI) 0.48 to 6.40). The second trial studied 41 adults with acute myocarditis randomised to either high-dose IVIG (1 to 2 g/kg over two days) or no treatment. The IVIG group reported greater survival time after 60 days (no raw data, P < 0.01), but the evidence is uncertain. We pooled the reported number of deaths in both trials, with no evidence of a difference between groups (RR 0.91, 95% CI 0.23 to 3.62, I2 = 31%, very low-certainty evidence). The evidence on the effect of IVIG treatment on LVEF (pooled mean difference (MD) -0.01, 95% CI -0.06 to 0.05) after 12 months and an unknown time frame is uncertain. The results for functional capacity, assessed by peak oxygen consumption at 12 months, were uncertain (MD -0.80, 95% CI -4.57 to 2.97). The results for infusion-related side effects were also uncertain due to a very large CI (RR 20.29, 95% CI 1.25 to 329.93). Lastly, there was uncertain evidence addressing failure to attain complete recovery (RR 0.46, 95% CI 0.19 to 1.14).  Evidence for improvement in LVEDD, left ventricular shortening fraction, and hospitalisation status in adults was not reported.  In the single included paediatric trial, the overall risk of bias was low with very low-certainty evidence for all outcomes. The trial included 86 children in Egypt presenting with acute myocarditis. Children were randomly assigned to 1 g/kg IVIG daily for two consecutive days or placebo followed by echocardiography one and six months post randomisation for recording of LVEDD and LVSF. The evidence for overall survival after six months was uncertain (risk of death RR 0.48, 95% CI 0.20 to 1.15). The evidence was also uncertain for improvement in LVEDD and LVSF after six months (LVEDD MD -4.00, 95% CI -9.52 to 1.52; LVSF no raw data).  Evidence for improvement in LVEF, functional capacity, side effects, complete recovery, and hospitalisation status in children was not reported.  AUTHORS' CONCLUSIONS: Evidence from two trials of very low certainty and with unclear risk of bias provides contradictory evidence on the use of IVIG in the treatment of adults with presumed viral myocarditis. One trial reported that use of IVIG results in longer survival time after 60 days, whilst the other trial found that IVIG does not provide an appreciable benefit. The evidence of a difference in event-free or overall survival, LVEDD, or LVSF is of very low certainty in a single paediatric trial with a low risk of bias. Until higher-quality studies with low risk of bias and larger sample sizes have demonstrated benefit in a particular group of patients, the evidence for treatment with IVIG for presumed viral myocarditis is uncertain. Further studies of the pathophysiology of myocarditis would lead to improved diagnostic criteria, which would facilitate future research.

The impact of occupational shift work and working hours during pregnancy on health outcomes: a systematic review and meta-analysis.

BACKGROUD: An increasing number of original studies suggest that exposure to shift work and long working hours during pregnancy could be associated with the risk of adverse pregnancy outcomes, but the results remain conflicting and inconclusive. OBJECTIVE: To examine the influences of shift work and longer working hours during pregnancy on maternal and fetal health outcomes. DATA SOURCES: Five electronic databases and 3 gray literature sources were searched up to March 15, 2019. METHODS OF STUDY SELECTION: Studies of all designs (except case studies and reviews) were included, which contained information on the relevant population (women who engaged in paid work during pregnancy); exposure (rotating shift work [shifts change according to a set schedule], fixed night shift [typical working period is between 11:00 pm and 11:00 am] or longer working hours [>40 hours per week]);comparator (fixed day shift [typical working period is between 8:00 am and 6:00 pm] or standard working hours [≤40 hours per week]); and outcomes (preterm delivery, low birthweight [birthweight <2500 g], small for gestational age, miscarriage, gestational hypertension, preeclampsia, intrauterine growth restriction, stillbirth, and gestational diabetes mellitus). TABULATION, INTEGRATION, AND RESULTS: From 3305 unique citations, 62 observational studies (196,989 women) were included. "Low" to "very low" certainty evidence from these studies revealed that working rotating shifts was associated with an increased odds of preterm delivery (odds ratio, 1.13; 95% confidence interval, 1.00-1.28, I2 = 31%), an infant small for gestational age (odds ratio, 1.18, 95% confidence interval, 1.01-1.38, I2 = 0%), preeclampsia (odds ratio, 1.75, 95% confidence interval, 1.01-3.01, I2 = 75%), and gestational hypertension (odds ratio, 1.19, 95% confidence interval, 1.10-1.29, I2 = 0%), compared to those who worked a fixed day shift. Working fixed night shifts was associated with an increased odds of preterm delivery (odds ratio, 1.21; 95% confidence interval, 1.03-1.42; I2 = 36%) and miscarriage (odds ratio, 1.23; 95% confidence interval, 1.03-1.47; I2 = 37%). Compared with standard hours, working longer hours was associated with an increased odds of miscarriage (odds ratio, 1.38; 95% confidence interval, 1.08-1.77; I2 = 73%), preterm delivery (odds ratio, 1.21; 95% confidence interval, 1.11-1.33; I2 = 30%), an infant of low birthweight (odds ratio, 1.43; 95% confidence interval, 1.11-1.84; I2 = 0%), or an infant small for gestational age (odds ratio, 1.16, 95% confidence interval, 1.00-1.36, I2 = 57%). Dose-response analysis showed that women working more than 55.5 hours (vs 40 hours) per week had a 10% increase in the odds of having a preterm delivery. CONCLUSION: Pregnant women who work rotating shifts, fixed night shifts, or longer hours have an increased risk of adverse pregnancy outcomes.

Evaluating the effectiveness of systemic corticosteroids to mitigate relapse in children assessed and treated for acute asthma: A network meta-analysis.

OBJECTIVE: The objective of this systematic review was to explore the effectiveness of various systemic corticosteroid (SCS) regimens to mitigate relapse in children with asthma discharged from an acute care setting. DATA SOURCES: Medline, EMBASE, Global Health, International Pharmaceutical Abstracts, EMB ALL, CINAHL, SCOPUS, Proquest Dissertations and Theses Global, and LILACS were searched using controlled vocabulary and key words. Additional citations were searched via clinical trial registries, Google Scholar, bibliographies, a SCOPUS forward search of a sentinel paper, and hand searching conference abstracts. STUDY SELECTION: No limitations based on language, publication status, or year of publication were applied. Two independent reviewers searched to identify randomized controlled trials comparing the effectiveness of SCS regimens to prevent relapse in children following treatment for acute asthma. RESULTS: Fifteen studies were included. In 3 studies comparing SCS to placebo, asthma relapse was significantly reduced (RR = 0.10; 95% CI: 0.01, 0.77; I2 = 0%). A network analysis identified a significant reduction in relapse in children treated with intramuscular corticosteroids (OR = 0.038; 95% CrI: 0.001, 0.397), short-course oral prednisone (OR = 0.054; 95% CrI: 0.002, 0.451), and oral dexamethasone (OR = 0.071; 95% CrI: 0.002, 0.733) compared to placebo. CONCLUSION: This review found evidence that SCS reduces relapse in children following treatment for acute asthma, albeit based on a limited number of studies. Additional studies are required to assess the differential effect of SCS doses and treatment duration to prevent relapse in children following discharge for acute asthma.

Clinical interventions that influence vaginal birth after cesarean delivery rates: Systematic Review & Meta-Analysis.

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.

A cross-sectional study examining convergent validity of a frailty index based on electronic medical records in a Canadian primary care program.

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 < 0.001). A simple linear regression showed good ability of the eFI scores to predict FI-CGA scores (F (1,83) = 89.06, p < .0001, R2 = 0.51). Both indices were also correlated with age, number of chronic conditions and number of medications. CONCLUSIONS: The study findings support the convergent validity of the eFI, which further justifies implementation of a case-finding tool that uses routinely collected primary care data in the Canadian context.

Correction to: A cross-sectional study examining convergent validity of a frailty index based on electronic medical records in a Canadian primary care program.

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

Opioid use disorder in primary care: PEER umbrella systematic review of systematic reviews.

OBJECTIVE: To summarize the best available evidence regarding various topics related to primary care management of opioid use disorder (OUD). DATA SOURCES: MEDLINE, Cochrane Library, Google, and the references of included studies and relevant guidelines. STUDY SELECTION: Published systematic reviews and newer randomized controlled trials from the past 5 to 10 years that investigated patient-oriented outcomes related to managing OUD in primary care, diagnosis, pharmacotherapies (including buprenorphine, methadone, and naltrexone), tapering strategies, psychosocial interventions, prescribing practices, and management of comorbidities. SYNTHESIS: From 8626 articles, 39 systematic reviews and an additional 26 randomized controlled trials were included. New meta-analyses were performed where possible. One cohort study suggests 1 case-finding tool might be reasonable to assist with diagnosis (positive likelihood ratio of 10.3). Meta-analysis demonstrated that retention in treatment improves when buprenorphine or methadone are used (64% to 73% vs 22% to 39% for control), when OUD is treated in primary care (86% vs 67% in specialty care, risk ratio [RR] of 1.25, 95% CI 1.07 to 1.47), and when counseling is added to pharmacotherapy (74% vs 62% for controls, RR = 1.20, 95% CI 1.06 to 1.36). Retention was also improved with naltrexone (33% vs 25% for controls, RR = 1.35, 95% CI 1.11 to 1.64) and reduced with medication-related contingency management (eg, loss of take-home doses as a punitive measure; 68% vs 77% for no contingency, RR = 0.86, 95% CI 0.76 to 0.99). CONCLUSION: There is reasonable evidence that patients with OUD should be managed in the primary care setting. Diagnostic criteria for OUD remain elusive, with 1 reasonable case-finding tool. Methadone and buprenorphine improve treatment retention, while medication-related contingency methods could worsen retention. Counseling is beneficial when added to pharmacotherapy.

The Conduct and Reporting of Child Health Research: An Analysis of Randomized Controlled Trials Published in 2012 and Evaluation of Change over 5 Years.

OBJECTIVES: For child health randomized controlled trials (RCTs) published in 2012, we aimed to describe design and reporting characteristics and evaluate changes since 2007; assess the association between trial design and registration and risk of bias (RoB); and assess the association between RoB and effect size. STUDY DESIGN: For 300 RCTs, we extracted design and reporting characteristics and assessed RoB. We assessed 5-year changes in design and reporting (based on 300 RCTs we had previously analyzed) using the Fisher exact test. We tested for associations between design and reporting characteristics and overall RoB and registration using the Fisher exact, Cochran-Armitage, Kruskal-Wallis, and Jonckheere-Terpstra tests. We pooled effect sizes and tested for differences by RoB using the χ2 test for subgroups in meta-analysis. RESULTS: The 2012 and 2007 RCTs differed with respect to many design and reporting characteristics. From 2007 to 2012, RoB did not change for random sequence generation and improved for allocation concealment (P < .001). Fewer 2012 RCTs were rated high overall RoB and more were rated unclear (P = .03). Only 7.3% of 2012 RCTs were rated low overall RoB. Trial registration doubled from 2007 to 2012 (23% to 46%) (P < .001) and was associated with lower RoB (P = .009). Effect size did not differ by RoB (P = .43) CONCLUSIONS: Random sequence generation and allocation concealment were not often reported, and selective reporting was prevalent. Measures to increase trialists' awareness and application of existing reporting guidance, and the prospective registration of RCTs is needed to improve the trustworthiness of findings from this field.

Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation.

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 < 1 indicates that pediatric trials have smaller nuisance parameters than adult trials. RESULTS: We analyzed 208 meta-analyses (135 for binary-outcomes, 73 for continuous-outcomes). For binary outcomes, pediatric-RCTs had on average 10% smaller CERs than adult-RCTs (summary-CE-RR: 0.90; 95% CI: 0.83, 0.98). For mortality outcomes the summary-CE-RR was 0.48 (95% CIs: 0.31, 0.74). For continuous outcomes, pediatric-RCTs had on average 26% smaller CE-SDs than adult-RCTs (summary-CE-SD-ratio: 0.74). CONCLUSIONS: Clinically relevant differences in nuisance parameters between pediatric and adult trials were detected. These differences have implications for design of future studies. Extrapolation of nuisance parameters for sample-sizes calculations from adult-trials to pediatric-trials should be cautiously done.

Glucocorticoids for croup in children.

BACKGROUND: Glucocorticoids are commonly used for croup in children. This is an update of a Cochrane Review published in 1999 and previously updated in 2004 and 2011. OBJECTIVES: To examine the effects of glucocorticoids for the treatment of croup in children aged 0 to 18 years. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 2, 2018), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 3 April 2018), and Embase (Ovid) (1996 to 3 April 2018, week 14), and the trials registers ClinicalTrials.gov (3 April 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 3 April 2018). We scanned the reference lists of relevant systematic reviews and of the included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated children aged 0 to 18 years with croup and measured the effects of glucocorticoids, alone or in combination, compared to placebo or another pharmacologic treatment. The studies needed to report at least one of our primary or secondary outcomes: change in croup score; return visits, (re)admissions or both; length of stay; patient improvement; use of additional treatments; and adverse events. DATA COLLECTION AND ANALYSIS: One author extracted data from each study and another verified the extraction. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed risk of bias for each study using the Cochrane 'Risk of bias' tool and the certainty of the body of evidence for the primary outcomes using the GRADE approach. MAIN RESULTS: We added five new RCTs with 330 children. This review now includes 43 RCTs with a total of 4565 children. We assessed most (98%) studies as at high or unclear risk of bias. Compared to placebo, glucocorticoids improved symptoms of croup at two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs; 426 children; moderate-certainty evidence), and the effect lasted for at least 24 hours (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs; 351 children; low-certainty evidence). Compared to placebo, glucocorticoids reduced the rate of return visits or (re)admissions or both (risk ratio 0.52, 95% CI 0.36 to 0.75; 10 RCTs; 1679 children; moderate-certainty evidence). Glucocorticoid treatment reduced the length of stay in hospital by about 15 hours (mean difference -14.90, 95% CI -23.58 to -6.22; 8 RCTs; 476 children). Serious adverse events were infrequent. Publication bias was not evident. Uncertainty remains with regard to the optimal type, dose, and mode of administration of glucocorticoids for reducing croup symptoms in children. AUTHORS' CONCLUSIONS: Glucocorticoids reduced symptoms of croup at two hours, shortened hospital stays, and reduced the rate of return visits to care. Our conclusions have changed, as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours.