Background: Recent approval and adoption of pangenotypic direct acting antivirals (DAAs) necessitated a revision of the 2015 World Health Organization guidelines for the management of persons with hepatitis C virus (HCV) infection. Methods: We searched MEDLINE, EMBASE, CENTRAL, and relevant conference proceedings to identify randomized and non-randomized trials, as well as prospective observational studies of DAAs. The proportions of persons with events were pooled for sustained virological response at 12 weeks post-treatment (SVR12), discontinuations due to adverse events (DAEs), serious adverse events (SAEs), and all-cause mortality. Analyses were stratified by HCV genotype and antiviral treatment experience, with subgroup analyses based on presence of cirrhosis and HIV-HCV coinfection. Findings: The evidence base consisted of 238 publications describing 142 studies. In the overall analysis, which included all persons irrespective of treatment experience or comorbidities, the pooled proportion achieving SVR12 exceeded 0.94 for all pangenotypic regimens across genotypes 1, 2, and 4. Some heterogeneity may have led to lower SVR rates in persons with genotype 3 infection. High SVR12 (>0.90) was observed in persons with genotype 1 infection with cirrhosis, though evidence varied and was limited for genotypes 2À4. Evidence was sparse for persons with HIVÀHCV coinfection. All regimens were associated with small proportions of persons with DAEs, SAEs, or all-cause mortality. Interpretation: Based on this and other supporting evidence, the WHO issued updated guidelines with a conditional recommendation, based on moderate quality evidence, for the use of pangenotypic DAA regimens for persons with chronic HCV infection aged 18 years and older (July 2018). Funding: This study was funded by the World Health Organization.

BackgroundEvidence from epidemiological and animal studies support the concept of programming fetal, neonatal, and adult health in response to in utero exposures such as maternal obesity and lifestyle variables. Excess gestational weight gain (GWG), maternal physical activity, and sub-optimal and excess nutrition during pregnancy may program the offspring’s risk of obesity. Maternal intake of dairy foods rich in high-quality proteins, calcium, and vitamin D may influence later bone health status. Current clinical practice guidelines for managing GWG are not founded on randomized trials and lack specific “active intervention ingredients.” The Be Healthy in Pregnancy (BHIP) study is a randomized controlled trial (RCT) designed to test the effectiveness of a novel structured and monitored Nutrition + Exercise intervention in pregnant women of all pre-pregnancy weight categories (except extreme obesity), delivered through prenatal care in community settings (rather than in hospital settings), on the likelihood of women achieving recommended GWG and a benefit to bone status of offspring and mother at birth and six months postpartum.MethodsThe BHIP study is a two-site RCT that will recruit up to 242 participants aged > 18 years at 12–17 weeks of gestation. After baseline measures, participants are randomized to either a structured and monitored Nutrition + Exercise (intervention) or usual care (control) program for the duration of their pregnancy. The primary outcome of the study is the percent of women who achieve GWG within the Institute of Medicine (IOM) guidelines. The secondary outcomes include: (1) maternal bone status via blood bone biomarkers during pregnancy; (2) infant bone status in cord blood; (3) mother and infant bone status measured by dual-energy absorptiometry scanning (DXA scan) at six months postpartum; (4) other measures including maternal blood pressure, blood glucose and lipid profiles, % body fat, and postpartum weight retention; and (5) infant weight z-scores and fat mass at six months of age.DiscussionIf effective, this RCT will generate high-quality evidence to refine the nutrition guidelines during pregnancy to improve the likelihood of women achieving recommended GWG. It will also demonstrate the importance of early nutrition on bone health in the offspring.Trial registrationClinicalTrials.gov, NCT01689961 Registered on 21 September 2012.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-3065-x) contains supplementary material, which is available to authorized users.

Background Dietary recommendations and policies should be guided by rigorous systematic reviews. Reviews that are of poor methodological quality may be ineffective or misleading. Most of the evidence in nutrition comes from nonrandomized studies of nutritional exposures (usually referred to as nutritional epidemiology studies), but to date methodological evaluations of the quality of systematic reviews of such studies have been sparse and inconsistent. Objectives We aimed to investigate the quality of recently published systematic reviews and meta-analyses of nutritional epidemiology studies and to propose guidance addressing major limitations. Methods We searched MEDLINE (January 2018–August 2019), EMBASE (January 2018–August 2019), and the Cochrane Database of Systematic Reviews (January 2018–February 2019) for systematic reviews of nutritional epidemiology studies. We included a random sample of 150 reviews. Results Most reviews were published by authors from Asia (n = 49; 32.7%) or Europe (n = 43; 28.7%) and investigated foods or beverages (n = 60; 40.0%) and cancer morbidity and mortality (n = 54; 36%). Reviews often had important limitations: less than one-quarter (n = 30; 20.0%) reported preregistration of a protocol and almost one-third (n = 42; 28.0%) did not report a replicable search strategy. Suboptimal practices and errors in the synthesis of results were common: one-quarter of meta-analyses (n = 30; 26.1%) selected the meta-analytic model based on statistical indicators of heterogeneity and almost half of meta-analyses (n = 50; 43.5%) did not consider dose–response associations even when it was appropriate to do so. Only 16 (10.7%) reviews used an established system to evaluate the certainty of evidence. Conclusions Systematic reviews of nutritional epidemiology studies often have serious limitations. Authors can improve future reviews by involving statisticians, methodologists, and researchers with substantive knowledge in the specific area of nutrition being studied and using a rigorous and transparent system to evaluate the certainty of evidence.

Background Observational studies provide important information about the effects of exposures that cannot be easily studied in clinical trials, such as nutritional exposures, but are subject to confounding. Investigators adjust for confounders by entering them as covariates in analytic models. Objective The aim of this study was to evaluate the reporting and credibility of methods for selection of covariates in nutritional epidemiology studies. Methods We sampled 150 nutritional epidemiology studies published in 2007/2008 and 2017/2018 from the top 5 high-impact nutrition and medical journals and extracted information on methods for selection of covariates. Results Most studies did not report selecting covariates a priori (94.0%) or criteria for selection of covariates (63.3%). There was general inconsistency in choice of covariates, even among studies investigating similar questions. One-third of studies did not acknowledge potential for residual confounding in their discussion. Conclusion Studies often do not report methods for selection of covariates, follow available guidance for selection of covariates, nor discuss potential for residual confounding.