Objectives: This systematic review (SR) highlights principles for nutrient clinical trials and explore the diverse physiological functions of vitamin D beyond its traditional role in the musculoskeletal system related to clinical study designs. Background: Thousands of published research articles have investigated the benefits of vitamin D (a nutrient example taken in this SR) beyond the musculoskeletal system, including the immune, pulmonary, and cardiovascular systems; pregnancy; autoimmune disorders; and cancer. They illustrated vitamin D's molecular mechanisms, interactions, and genomic and nongenomic actions. Methods: This SR was designed to identify shortcomings in clinical study designs, statistical methods, and data interpretation that led to inconsistent findings in vitamin D-related publications. SR also highlights examples and insights into avoiding study design errors in future clinical studies, including randomized controlled clinical trials (RCTs). The SR adheres to the latest PRISMA statement, guidelines, and the PICOS process. Results: Inappropriate or flawed study designs were frequent in clinical trials. Major failures discussed here include too short clinical study duration, inadequate or infrequent doses, insufficient statistical power, failure to measure baseline and achieved levels, and recruiting vitamin D-sufficient participants. These design errors have led to misleading interpretations. Thus, conclusions from such studies should not be generalized or used in guidelines, recommendations, or policymaking. Conclusion: Adequately powered epidemiological studies and RCTs with sufficient vitamin D and duration in individuals with vitamin D deficiency reported favorable clinical outcomes, enriching the literature, enabling to understand its physiology and mechanisms. Proper study designs with rigorous methodologies and cautious interpretation of outcomes are crucial in advancing the nutrient field. The principles discussed apply not only to vitamin D, but also other micro-nutrients and nutraceutical research. Adhering to them enhances the credibility and reliability of clinical trials, SRs, and meta-analysis outcomes. The study emphasizes the importance of focused, hypothesis-driven, well-designed, statistically powered RCTs to explore the diverse benefits of nutrients, conducted in index nutrient deficient participants, and avoidance of study design errors. Findings from such studies should be incorporated into clinical practice, policymaking, and public health guidelines, improving the health of the nation and reducing healthcare costs.

The complications and symptoms of hypoparathyroidism remain incompletely defined. Measuring serum parathyroid hormone (PTH) and calcium levels early after total thyroidectomy may predict the development of chronic hypoparathyroidism. The study aimed (i) to identify symptoms and complications associated with chronic hypoparathyroidism and determine the prevalence of those symptoms and complications (Part I), and (ii) to examine the utility of early postoperative measurements of PTH and calcium in predicting chronic hypoparathyroidism (Part II). We searched Medline, Medline In-Process, EMBASE, and Cochrane CENTRAL to identify complications and symptoms associated with chronic hypoparathyroidism. We used two predefined criteria (at least three studies reported the complication and symptom and had statistically significantly greater pooled relative estimates). To estimate prevalence, we used the median and interquartile range (IQR) of the studies reporting complications and symptoms. For testing the predictive values of early postoperative measurements of PTH and calcium, we used a bivariate model to perform diagnostic test meta-analysis. In Part I, the 93 eligible studies enrolled a total of 18,973 patients and reported on 170 complications and symptoms. We identified nine most common complications or symptoms probably associated with chronic hypoparathyroidism. The complications or symptoms and the prevalence are as follows: nephrocalcinosis/nephrolithiasis (median prevalence among all studies 15%), renal insufficiency (12%), cataract (17%), seizures (11%), arrhythmia (7%), ischemic heart disease (7%), depression (9%), infection (11%), and all-cause mortality (6%). In Part II, 18 studies with 4325 patients proved eligible. For PTH measurement, regarding the posttest probability, PTH values above 10 pg/mL 12-24 hours postsurgery virtually exclude chronic hypoparathyroidism irrespective of pretest probability (100%). When PTH values are below 10 pg/mL, posttest probabilities range from 3% to 64%. Nine complications and symptoms are probably associated with chronic hypoparathyroidism. A PTH value above a threshold of 10 pg/mL 12-24 hours after total thyroidectomy is a strong predictor that the patients will not develop chronic hypoparathyroidism. Patients with PTH values below the threshold need careful monitoring as some will develop chronic hypoparathyroidism. (c) 2022 American Society for Bone and Mineral Research (ASBMR).

The efficacy and safety of parathyroid hormone (PTH) therapy for managing long-term hypoparathyroidism is being evaluated in ongoing clinical trials. We undertook a systematic review and meta-analysis of currently available randomized controlled trials to investigate the benefits and harms of PTH therapy and conventional therapy in the management of patients with chronic hypoparathyroidism. To identify eligible studies, published in English, we searched Embase, PubMed, and Cochrane CENTRAL from inception to May 2022. Two reviewers independently extracted data and assessed the risk of bias. We defined patients' important outcomes and used grading of recommendations, assessment, development, and evaluation (GRADE) to provide the structure for quantifying absolute effects and rating the quality of evidence. Seven randomized trials of 12 publications that enrolled a total of 386 patients proved eligible. The follow-up duration ranged from 1 to 36 months. Compared with conventional therapy, PTH therapy probably achieves a small improvement in physical health-related quality of life (mean difference [MD] 3.4, 95% confidence interval [CI] 1.5-5.3, minimally important difference 3.0, moderate certainty). PTH therapy results in more patients reaching 50% or greater reduction in the dose of active vitamin D and calcium (relative risk [RR] = 6.5, 95% CI 2.5-16.4, 385 more per 1000 patients, high certainty). PTH therapy may increase hypercalcemia (RR =2.4, 95% CI 1.2-5.04, low certainty). The findings may support the use of PTH therapy in patients with chronic hypoparathyroidism. Because of limitations of short duration and small sample size, evidence from randomized trials is limited regarding important benefits of PTH therapy compared with conventional therapy. Establishing such benefits will require further studies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Objective: To describe and record the evolution of EBM in China. Study Design and Setting: We conducted the study following the general methodology of oral history. The interviews were done at Lanzhou University, between 18th and 22 nd April 2019 using pre-defined questions. All interviews were videorecorded. Two investigators extracted and analyzed the information from the interviews independently. Results: One international expert and ten Chinese experts participated in the interviews. After the introduction of EBM in China in the mid-1990s, more than 20 EBM centres have been established. According to the interviewees, Gordon Guyatt, David Sackett and lain Chalmers are the international experts who played the most important role in the development of EBM in China. China has contributed to EBM on the international level by conducting systematic reviews, developing reporting checklists, and introducing the principles of EBM into Traditional Medicine. The Chinese Cochrane Centre and the EBM Centre of Lanzhou University were ranked the top two EBM Centres in China by the interviewees. Conclusion: EBM has been developing in China for nearly a quarter of a century. Many achievements have been reached, however, EBM is still facing many challenges in China, including shortages of funding support and personnel, as well as limited local high-quality evidence. (C) 2021 Elsevier Inc. All rights reserved.

Objective: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect. Study design: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect. Results: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled < 50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-center trial were associated with increased odds of finding a statistically significant effect. Conclusions: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-center trial status in designing, evaluating, and interpreting the results of RCTs. (C) 2021 Elsevier Inc. All rights reserved.

Introduction: In 2001, 50%-55% of French-speaking minority communities did not have access to health services in French in Canada. Although Canada is officially a bilingual country, reports indicate that many healthcare services offered in French in Anglophone provinces are insufficient or substandard, leading to healthcare discrepancies among Canada's minority Francophone communities. Objectives: The primary aim of this scoping systematic review was to identify existing gaps in HIV-care delivery to Francophone minorities living with HIV in Canada. Study design: Scoping systematic review. Data sources: Search for studies published between 1990 and November 2019 reporting on health and healthcare in Francophone populations in Canada. Nine databases were searched, including Medline, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, the National Health Service Economic Development Database, Global Health, PsychInfo, PubMed, Scopus and Web of Science. Study selection: English or French language studies that include data on French-speaking people with HIV in an Anglophone majority Canadian province. Results: The literature search resulted in 294 studies. A total of 230 studies were excluded after duplicates were removed. The full texts of 43 potentially relevant papers were retrieved for evaluation and data extraction. Forty-one studies were further excluded based on failure to meet the inclusion criteria leaving two qualitative studies that met our inclusion criteria. These two studies reported on barriers on access to specialised care by Francophone and highlighted difficulties experienced by healthcare professionals in providing quality healthcare to Francophone patients in Ontario and Manitoba. Conclusion: The findings of this scoping systematic review highlight the need for more HIV research on linguistic minority communities and should inform health policymaking and HIV/AIDS community organisations in providing HIV care to Francophone immigrants and Canadians.

Extant literature illustrates a substantive impact on human health because of climate change. Despite this, discussions of the ethical and policymaking role of US health care's response to this problem are underdeveloped within peer-reviewed literature indexed in core medical databases. We conducted a systematic literature review in August 2017 at Vanderbilt University Medical Center of the following medical, business and policy databases to examine the state of inquiry on this topic: PubMed, CINAHL, PsychINFO, JAMA Network, Health Affairs, Business Source Complete, Greylit.org, LexisNexis Academic, Proquest Dissertations and Theses Global. An initial sample of n = 4434 rendered n = 75 articles precisely addressing this question following a two-tiered systematic examination of content. US medical professionals were most concerned by the health impacts of air pollution and respiratory complications, extreme weather events, and rising infectious/vector-borne diseases. They were least concerned by rising rates of migration and stresses to sanitation systems. Medical professionals took a broadly proactive stance to the issue, highlighting the need to implement education and advocacy strategies. Politics was the least pertinent motivation for climate change-related recommendations. Furthermore, partnerships between health care and public agencies were identified as holding the greatest potential for meaningful change. Mitigation approaches were slightly more common than adaptation approaches. We conclude that, while the enthusiasm of the medical community is commendable, efforts to address climate change in US health care are overly fractured, and lack the necessary expertise for efficaciousness.

Objective: To determine the association between subjective social status (SSS), or the individual's perception of his or her position in the social hierarchy, and the odds of coronary artery disease (CAD), hypertension, diabetes, obesity and dyslipidaemia. Study design: Systematic review and meta-analysis. Methods: We searched PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, SocINDEX, Web of Science and reference lists of all included studies up to October 2014, with a verification search in July 2015. Inclusion criteria were original studies in adults that reported odds, risk or hazard ratios of at least one outcome of interest (CAD, hypertension, diabetes, obesity or dyslipidaemia), comparing 'lower' versus 'higher' SSS groups, where SSS is measured on a self-anchoring ladder. ORs were pooled using a random-effects model. Results: 10 studies were included in the systematic review; 9 of these were included in the meta-analysis. In analyses unadjusted for objective socioeconomic status (SES) measures such as income, education or occupation, the pooled OR comparing the bottom versus the top of the SSS ladder was 1.82 (95% CI 1.10 to 2.99) for CAD, 1.88 (95% CI 1.27 to 2.79) for hypertension, 1.90 (95% CI 1.25 to 2.87) for diabetes, 3.68 (95% CI 2.03 to 6.64) for dyslipidaemia and 1.57 (95% CI 0.95 to 2.59) for obesity. These associations were attenuated when adjusting for objective SES measures, with the only statistically significant association remaining for dyslipidaemia (OR 2.10, 95% CI 1.09 to 4.06), though all ORs remained greater than 1. Conclusions: Lower SSS is associated with significantly increased odds of CAD, hypertension, diabetes and dyslipidaemia, with a trend towards increased odds of obesity. These trends are consistently present, though the effects attenuated when adjusting for SES, suggesting that perception of one's own status on a social hierarchy has health effects above and beyond one's actual income, occupation and education.

Background: Despite high-quality evidence being essential for planning and delivering eye health programmes, evidence on what works is relatively scarce. To address this need, we developed eye health Evidence Gap Maps (EGMs) with the first one focusing on cataract. These maps summarise, critically appraise and present evidence in a user-friendly format. This paper presents experiences of developing the cataract gap map and discusses the challenges and benefits of the process. Methods: Following a comprehensive search of relevant databases, we sifted and extracted data from all relevant reviews on cataract. Critical appraisal was conducted by two reviewers independently using Supported the Use of Research Evidence checklist and a summary quality assessment was shared with the authors for comments. Results: A total of 52 reviews were included in the map. The majority of the reviews addressed quality of clinical care (20) and types of treatment (18). Overall, 30 reviews provided strong evidence in response to the research question, 14 reviews showed weak or no evidence and in 14 reviews the results were inconclusive. 14 reviews were regarded as high quality, 12 were medium quality and 26 were graded as low quality. To verify the validity of the Supporting the Use for Research Evidence (SURE) checklist, studies were also appraised using the Scottish Intercollegiate Guidelines Network (SIGN) tool. Based on the κ statistics test, results showed excellent agreement between the two checklists (K=0.79). Discussion: EGMs support policy makers and programme managers to make informed decisions and enable researchers to prioritise future work based on the most evident gaps on knowledge.

Objective To examine whether significant differences exist between the self-reported prevalence of atopic disorders in the open population compared with physician diagnosed prevalence of atopic disorders in general practice. Methods Medline (OvidSP), PubMed Publisher, EMBASE, Google Scholar and the Cochrane Controlled Clinical Trials Register databases were systematically reviewed for articles providing data on the prevalence of asthma, allergic rhinitis and eczema in a GP setting. Studies were only included when they had a cross-sectional or cohort design and included more than 100 children (aged 0-18 years) in a general practice setting. All ISAAC studies (i.e. the open population) that geographically matched a study selected from the first search, were also included. A quality assessment was conducted. The primary outcome measures were prevalence of eczema, asthma and allergic rhinitis in children aged 0-18 years. Results The overall quality of the included studies was good. The annual and lifetime prevalences of the atopic disorders varied greatly in both general practice and the open population. On average, the prevalence of atopic disorders was higher in the open population. Conclusion There are significant differences between the self-reported prevalence of atopic disorders in the open population compared with physician diagnosed prevalence of atopic disorders in general practice. Data obtained in the open population cannot simply be extrapolated to the general practice setting. This should be taken into account when considering a research topic or requirements for policy development. GPs should be aware of the possible misclassification of allergic disorders in their practice.