Reporting and interpretation of SF-36 outcomes in randomised trials: systematic review

Objective To determine how often health surveys and quality of life evaluations reach different conclusions from those of primary efficacy outcomes and whether discordant results make a difference in the interpretation of trial findings

Do systematic reviews on pediatric topics need special methodological considerations?

Abstract Background Systematic reviews are key tools to enable decision making by healthcare providers and policymakers. Despite the availability of the evidence based Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA-2009 and PRISMA-P 2015) statements that were developed to improve the transparency and quality of reporting of systematic reviews, uncertainty on how to deal with pediatric-specific methodological challenges of systematic reviews impairs decision-making in child health. In this paper, we identify methodological challenges specific to the design, conduct and reporting of pediatric systematic reviews, and propose a process to address these challenges. Discussion One fundamental decision at the outset of a systematic review is whether to focus on a pediatric population only, or to include both adult and pediatric populations. Both from the policy and patient care point of view, the appropriateness of interventions and comparators administered to pre-defined pediatric age subgroup is critical. Decisions need to be based on the biological plausibility of differences in treatment effects across the developmental trajectory in children. Synthesis of evidence from different trials is often impaired by the use of outcomes and measurement instruments that differ between trials and are neither relevant nor validated in the pediatric population. Other issues specific to pediatric systematic reviews include lack of pediatric-sensitive search strategies and inconsistent choices of pediatric age subgroups in meta-analyses. In addition to these methodological issues generic to all pediatric systematic reviews, special considerations are required for reviews of health care interventions’ safety and efficacy in neonatology, global health, comparative effectiveness interventions and individual participant data meta-analyses. To date, there is no standard approach available to overcome this problem. We propose to develop a consensus-based checklist of essential items which researchers should consider when they are planning (PRISMA-PC-Protocol for Children) or reporting (PRISMA-C-reporting for Children) a pediatric systematic review. Summary Available guidelines including PRISMA do not cover the complexity associated with the conduct and reporting of systematic reviews in the pediatric population; they require additional and modified standards for reporting items. Such guidance will facilitate the translation of knowledge from the literature to bedside care and policy, thereby enhancing delivery of care and improving child health outcomes

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

Robustness of reported postacute health outcomes in children with SARS-CoV-2 infection: a systematic review

Objective: To systematically assess the robustness of reported postacute SARS-CoV-2 infection health outcomes in children. Methods: A search on PubMed and Web of Science was conducted to identify studies published up to 22 January 2022 that reported on postacute SARS-CoV-2 infection health outcomes in children (&lt;18 years) with follow-up of ≥2 months since detection of infection or ≥1 month since recovery from acute illness. We assessed the consideration of confounding bias and causality, as well as the risk of bias. Results: 21 studies including 81 896 children reported up to 97 symptoms with follow-up periods of 2.0-11.5 months. Fifteen studies had no control group. The reported proportion of children with post-COVID syndrome was between 0% and 66.5% in children with SARS-CoV-2 infection (n=16 986) and between 2.0% and 53.3% in children without SARS-CoV-2 infection (n=64 910). Only two studies made a clear causal interpretation of an association between SARS-CoV-2 infection and the main outcome of € post-COVID syndrome' and provided recommendations regarding prevention measures. The robustness of all 21 studies was seriously limited due to an overall critical risk of bias. Conclusions: The robustness of reported postacute SARS-CoV-2 infection health outcomes in children is seriously limited, at least in all the published articles we could identify. None of the studies provided evidence with reasonable certainty on whether SARS-CoV-2 infection has an impact on postacute health outcomes, let alone to what extent. Children and their families urgently need much more reliable and methodologically robust evidence to address their concerns and improve care.</p

Robustness of reported postacute health outcomes in children with SARS-CoV-2 infection : a systematic review

To systematically assess the robustness of reported postacute SARS-CoV-2 infection health outcomes in children. A search on PubMed and Web of Science was conducted to identify studies published up to 22 January 2022 that reported on postacute SARS-CoV-2 infection health outcomes in children (<18 years) with follow-up of ≥2 months since detection of infection or ≥1 month since recovery from acute illness. We assessed the consideration of confounding bias and causality, as well as the risk of bias. 21 studies including 81 896 children reported up to 97 symptoms with follow-up periods of 2.0–11.5 months. Fifteen studies had no control group. The reported proportion of children with post-COVID syndrome was between 0% and 66.5% in children with SARS-CoV-2 infection (n=16 986) and between 2.0% and 53.3% in children without SARS-CoV-2 infection (n=64 910). Only two studies made a clear causal interpretation of an association between SARS-CoV-2 infection and the main outcome of ‘post-COVID syndrome’ and provided recommendations regarding prevention measures. The robustness of all 21 studies was seriously limited due to an overall critical risk of bias. The robustness of reported postacute SARS-CoV-2 infection health outcomes in children is seriously limited, at least in all the published articles we could identify. None of the studies provided evidence with reasonable certainty on whether SARS-CoV-2 infection has an impact on postacute health outcomes, let alone to what extent. Children and their families urgently need much more reliable and methodologically robust evidence to address their concerns and improve care

International ranking systems for universities and institutions: a critical appraisal

<p>Abstract</p> <p>Background</p> <p>Ranking of universities and institutions has attracted wide attention recently. Several systems have been proposed that attempt to rank academic institutions worldwide.</p> <p>Methods</p> <p>We review the two most publicly visible ranking systems, the Shanghai Jiao Tong University 'Academic Ranking of World Universities' and the Times Higher Education Supplement 'World University Rankings' and also briefly review other ranking systems that use different criteria. We assess the construct validity for educational and research excellence and the measurement validity of each of the proposed ranking criteria, and try to identify generic challenges in international ranking of universities and institutions.</p> <p>Results</p> <p>None of the reviewed criteria for international ranking seems to have very good construct validity for both educational and research excellence, and most don't have very good construct validity even for just one of these two aspects of excellence. Measurement error for many items is also considerable or is not possible to determine due to lack of publication of the relevant data and methodology details. The concordance between the 2006 rankings by Shanghai and Times is modest at best, with only 133 universities shared in their top 200 lists. The examination of the existing international ranking systems suggests that generic challenges include adjustment for institutional size, definition of institutions, implications of average measurements of excellence versus measurements of extremes, adjustments for scientific field, time frame of measurement and allocation of credit for excellence.</p> <p>Conclusion</p> <p>Naïve lists of international institutional rankings that do not address these fundamental challenges with transparent methods are misleading and should be abandoned. We make some suggestions on how focused and standardized evaluations of excellence could be improved and placed in proper context.</p

Reporting of conflicts of interest in guidelines of preventive and therapeutic interventions

BACKGROUND: Guidelines published in major medical journals are very influential in determining clinical practice. It would be essential to evaluate whether conflicts of interests are disclosed in these publications. We evaluated the reporting of conflicts of interest and the factors that may affect such disclosure in a sample of 191 guidelines on therapeutic and/or preventive measures published in 6 major clinical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, New England Journal of Medicine, Pediatrics) in 1979, 1984, 1989, 1994 and 1999. RESULTS: Only 7 guidelines (3.7%) mentioned conflicts of interest and all were published in 1999 (17.5% (7/40) of guidelines published in 1999 alone). Reporting of conflicts of interest differed significantly by journal (p=0.026), availability of disclosure policy by the journal (p=0.043), source of funding (p < 0.001) and number of authors (p=0.004). In the entire database of 191 guidelines, a mere 18 authors disclosed a total of 24 potential conflicts of interest and most pertained to minor issues. CONCLUSIONS: Despite some recent improvement, reporting of conflicts of interest in clinical guidelines published in influential journals is largely neglected

Point-of-care testing for <i>Toxoplasma gondii</i> IgG/IgM using <i>Toxoplasma</i> ICT IgG-IgM test with sera from the United States and implications for developing countries

Background: Congenital toxoplasmosis is a serious but preventable and treatable disease. Gestational screening facilitates early detection and treatment of primary acquisition. Thus, fetal infection can be promptly diagnosed and treated and outcomes can be improved. Methods: We tested 180 sera with the Toxoplasma ICT IgG-IgM point-of-care (POC) test. Sera were from 116 chronically infected persons (48 serotype II; 14 serotype I-III; 25 serotype I-IIIa; 28 serotype Atypical, haplogroup 12; 1 not typed). These represent strains of parasites infecting mothers of congenitally infected children in the U.S. 51 seronegative samples and 13 samples from recently infected persons known to be IgG/IgM positive within the prior 2.7 months also were tested. Interpretation was confirmed by two blinded observers. A comparison of costs for POC vs. commercial laboratory testing methods was performed. Results: We found that this new Toxoplasma ICT IgG-IgM POC test was highly sensitive (100%) and specific (100%) for distinguishing IgG/IgM-positive from negative sera. Use of such reliable POC tests can be cost-saving and benefit patients. Conclusions: Our work demonstrates that the Toxoplasma ICT IgG-IgM test can function reliably as a point-of-care test to diagnose Toxoplasma gondii infection in the U.S. This provides an opportunity to improve maternal-fetal care by using approaches, diagnostic tools, and medicines already available. This infection has serious, lifelong consequences for infected persons and their families. From the present study, it appears a simple, low-cost POC test is now available to help prevent morbidity/disability, decrease cost, and make gestational screening feasible. It also offers new options for improved prenatal care in low- and middle-income countries.</p

The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days

Background: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Methods: Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases. A survey was conducted of all trials to assess their recruitment status up to July 6, 2020. Results: Most of the 689 trials (overall target sample size 396,366) were small (median sample size 120; interquartile range [IQR] 60-300) but randomized (75.8%; n=522) and were often conducted in China (51.1%; n=352) or the USA (11%; n=76). 525 trials (76.2%) planned to include 155,571 hospitalized patients, and 25 (3.6%) planned to include 96,821 health-care workers. Treatments were evaluated in 607 trials (88.1%), frequently antivirals (n=144) or antimalarials (n=112); 78 trials (11.3%) focused on prevention, including 14 vaccine trials. No trial investigated social distancing. Interventions tested in 11 trials with >5,000 participants were also tested in 169 smaller trials (median sample size 273; IQR 90-700). Hydroxychloroquine alone was investigated in 110 trials. While 414 trials (60.0%) expected completion in 2020, only 35 trials (4.1%; 3,071 participants) were completed by July 6. Of 112 trials with detailed recruitment information, 55 had recruited <20% of the targeted sample; 27 between 20-50%; and 30 over 50% (median 14.8% [IQR 2.0-62.0%]). Conclusions: The size and speed of the COVID-19 clinical trials agenda is unprecedented. However, most trials were small investigating a small fraction of treatment options. The feasibility of this research agenda is questionable, and many trials may end in futility, wasting research resources. Much better coordination is needed to respond to global health threats

Building Programs to Eradicate Toxoplasmosis Part I: Introduction and Overview

Purpose of Review Review building of programs to eliminate Toxoplasma infections. Recent Findings Morbidity and mortality from toxoplasmosis led to programs in USA, Panama, and Colombia to facilitate understanding, treatment, prevention, and regional resources, incorporating student work. Summary Studies foundational for building recent, regional approaches/programs are reviewed. Introduction provides an overview/review of programs in Panamá, the United States, and other countries. High prevalence/risk of exposure led to laws mandating testing in gestation, reporting, and development of broad-based teaching materials about Toxoplasma. These were tested for efficacy as learning tools for high-school students, pregnant women, medical students, physicians, scientists, public health officials and general public. Digitized, free, smart phone application effectively taught pregnant women about toxoplasmosis prevention. Perinatal infection care programs, identifying true regional risk factors, and point-of-care gestational screening facilitate prevention and care. When implemented fully across all demographics, such programs present opportunities to save lives, sight, and cognition with considerable spillover benefits for individuals and societies