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

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

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

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

Prepandemic cross-reactive humoral immunity to SARS-CoV-2 in Africa: Systematic review and meta-analysis

Objectives: To assess the evidence on the presence of antibodies cross-reactive with SARS-CoV-2 antigens in prepandemic samples from African populations. Methods: We performed a systematic review and meta-analysis of studies evaluating prepandemic African samples using pre-set assay-specific thresholds for SARS-CoV-2 seropositivity. Results: In total, 26 articles with 156 datasets were eligible, including 3437 positives among 29,923 measurements (11.5%) with large between-dataset heterogeneity. Positivity was similar for anti-nucleocapsid (14%) and anti-spike antibodies (11%), higher for anti-spike1 (23%), and lower for anti-receptor-binding domain antibodies (7%). Positivity was similar, on average, for immunoglobulin M and immunoglobulin G. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (14%, 95% confidence interval, 12-15% vs 2%, 95% confidence interval 1-2% in other datasets). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (14% and 12%, respectively), and not without high malaria burden (2% and 0%, respectively). Lower SARS-CoV-2 cross-reactivity was seen in settings of high HIV seroprevalence. More sparse individual-level data showed associations of higher SARS-CoV-2 cross-reactivity with Plasmodium parasitemia and lower SARS-CoV-2 cross-reactivity with HIV seropositivity. Conclusion: Prepandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity. At the country level, cross-reactivity tracks especially with malaria prevalence

Population-level COVID-19 Mortality Risk for Non-elderly Individuals Overall and for Non-elderly Individuals without Underlying Diseases in Pandemic Epicenters

Objective: To provide estimates of the relative rate of COVID-19 death in people \u3c 65 years old versus older individuals in the general population, the absolute risk of COVID-19 death at the population level during the first epidemic wave, and the proportion of COVID-19 deaths in non-elderly people without underlying diseases in epicenters of the pandemic. Eligible data: Cross-sectional survey of countries and US states with at least 800 COVID-19 deaths as of April 24, 2020 and with information on the number of deaths in people with age \u3c 65. Data were available for 14 countries (Belgium, Canada, France, Germany, India, Ireland, Italy, Mexico, Netherlands, Portugal, Spain, Sweden, Switzerland, UK) and 13 US states (California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, Pennsylvania). We also examined available data on COVID-19 deaths in people with age Main outcome measures: Proportion of COVID-19 deaths in people \u3c 65 years old; relative mortality rate of COVID-19 death in people \u3c 65 versus ≥ 65 years old; absolute risk of COVID-19 death in people \u3c 65 and in those ≥ 80 years old in the general population as of June 17, 2020; absolute COVID-19 mortality rate expressed as equivalent of mortality rate from driving a motor vehicle. Results: Individuals with age \u3c 65 account for 4.5–11.2% of all COVID-19 deaths in European countries and Canada, 8.3–22.7% in the US locations, and were the majority in India and Mexico. People \u3c 65 years old had 30- to 100-fold lower risk of COVID-19 death than those ≥ 65 years old in 11 European countries and Canada, 16- to 52-fold lower risk in US locations, and less than 10-fold in India and Mexico. The absolute risk of COVID-19 death as of June 17, 2020 for people \u3c 65 years old in high-income countries ranged from 10 (Germany) to 349 per million (New Jersey) and it was 5 per million in India and 96 per million in Mexico. The absolute risk of COVID-19 death for people ≥ 80 years old ranged from 0.6 (Florida) to 17.5 per thousand (Connecticut). The COVID-19 mortality rate in people \u3c 65 years old during the period of fatalities from the epidemic was equivalent to the mortality rate from driving between 4 and 82 miles per day for 13 countries and 5 states, and was higher (equivalent to the mortality rate from driving 106–483 miles per day) for 8 other states and the UK. People \u3c 65 years old without underlying predisposing conditions accounted for only 0.7–3.6% of all COVID-19 deaths in France, Italy, Netherlands, Sweden, Georgia, and New York City and 17.7% in Mexico. Conclusions: People \u3c 65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people \u3c 65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic

Acute Toxoplasma gondii Infection among Family Members in the United States

We investigated 32 families of persons with acute toxoplasmosis in which >1 other family member was tested for Toxoplasma gondii infection; 18 (56%) families had >1 additional family member with acute infection. Family members of persons with acute toxoplasmosis should be screened for infection, especially pregnant women and immunocompromised persons

Comparative effect sizes in randomised trials from less developed and more developed countries: a meta-epidemiological assessment

AbstractBackgroundMany trials are done in developing countries without a longstanding tradition in research. We compared treatment effects from randomised trials conducted in developed versus developing countries.MethodsWe used data from the Cochrane Database of Systematic Reviews to identify meta-analyses about mortality with at least one trial from a developing country and one from a developed country (WHO and International Monetary Fund classifications). Effect estimates of developed and developing countrieswere compared by calculating the relative relative risks (RRR) for each topic and the summary RRRs across all topics. Similar analyses were done for the respective primary outcomes.Findings139 mortality meta-analyses were eligible. 128 (92%) meta-analyses reported no significant differences between developed and developing countries. Differences were beyond chance in 11 (8%) cases showing more favourable effects in trials from developing countries. The summary RRR was 1·12 (95% CI 1·06–1·18, p<0·0001, I2=0%), suggesting significantly increased favourable effects in trials from developing countries. Results were similar for meta-analyses with significant effects for mortality (RRR 1·15, 95% CI 1·08–1·23, p<0·0001), meta-analyses with recent trials (1·14, 1·08–1·21, p<0·0001); and when excluding trials from developing countries that became developed (1·12, 1·06–1.18, p<0·0001). For the primary outcomes (n=127), 20 topics had significant differences in effects (more favourable in developing countries in 15 cases).InterpretationTrials from developing countries sometimes show significantly more favourable effects than trials in developed countries. On average, effects are more favourable in developing countries than in developed countries. These discrepancies show biases in reporting or study design and genuine differences in baseline risk or treatment implementation and should be considered when generalising evidence.FundingNone