Assessment of transparency indicators across the biomedical literature: How open is open?

Recent concerns about the reproducibility of science have led to several calls for more open and transparent research practices and for the monitoring of potential improvements over time. However, with tens of thousands of new biomedical articles published per week, manually mapping and monitoring changes in transparency is unrealistic. We present an open-source, automated approach to identify 5 indicators of transparency (data sharing, code sharing, conflicts of interest disclosures, funding disclosures, and protocol registration) and apply it across the entire open access biomedical literature of 2.75 million articles on PubMed Central (PMC). Our results indicate remarkable improvements in some (e.g., conflict of interest [COI] disclosures and funding disclosures), but not other (e.g., protocol registration and code sharing) areas of transparency over time, and map transparency across fields of science, countries, journals, and publishers. This work has enabled the creation of a large, integrated, and openly available database to expedite further efforts to monitor, understand, and promote transparency and reproducibility in science.

Transparency in Infectious Disease Research: Meta-research Survey of Specialty Journals.

BACKGROUND: Infectious diseases carry large global burdens and have implications for society at large. Therefore, reproducible, transparent research is extremely important. METHODS: We evaluated transparency indicators (code and data sharing, registration, and conflict and funding disclosures) in the 5340 PubMed Central Open Access articles published in 2019 or 2021 in the 9 most cited specialty journals in infectious diseases using the text-mining R package, rtransparent. RESULTS: A total of 5340 articles were evaluated (1860 published in 2019 and 3480 in 2021 [of which 1828 were on coronavirus disease 2019, or COVID-19]). Text mining identified code sharing in 98 (2%) articles, data sharing in 498 (9%), registration in 446 (8%), conflict of interest disclosures in 4209 (79%), and funding disclosures in 4866 (91%). There were substantial differences across the 9 journals: 1%-9% for code sharing, 5%-25% for data sharing, 1%-31% for registration, 7%-100% for conflicts of interest, and 65%-100% for funding disclosures. Validation-corrected imputed estimates were 3%, 11%, 8%, 79%, and 92%, respectively. There were no major differences between articles published in 2019 and non-COVID-19 articles in 2021. In 2021, non-COVID-19 articles had more data sharing (12%) than COVID-19 articles (4%). CONCLUSIONS: Data sharing, code sharing, and registration are very uncommon in infectious disease specialty journals. Increased transparency is required.

Age-stratified infection fatality rate of COVID-19 in the non-elderly population.

The largest burden of COVID-19 is carried by the elderly, and persons living in nursing homes are particularly vulnerable. However, 94% of the global population is younger than 70 years and 86% is younger than 60 years. The objective of this study was to accurately estimate the infection fatality rate (IFR) of COVID-19 among non-elderly people in the absence of vaccination or prior infection. In systematic searches in SeroTracker and PubMed (protocol: https://osf.io/xvupr), we identified 40 eligible national seroprevalence studies covering 38 countries with pre-vaccination seroprevalence data. For 29 countries (24 high-income, 5 others), publicly available age-stratified COVID-19 death data and age-stratified seroprevalence information were available and were included in the primary analysis. The IFRs had a median of 0.034% (interquartile range (IQR) 0.013-0.056%) for the 0-59 years old population, and 0.095% (IQR 0.036-0.119%) for the 0-69 years old. The median IFR was 0.0003% at 0-19 years, 0.002% at 20-29 years, 0.011% at 30-39 years, 0.035% at 40-49 years, 0.123% at 50-59 years, and 0.506% at 60-69 years. IFR increases approximately 4 times every 10 years. Including data from another 9 countries with imputed age distribution of COVID-19 deaths yielded median IFR of 0.025-0.032% for 0-59 years and 0.063-0.082% for 0-69 years. Meta-regression analyses also suggested global IFR of 0.03% and 0.07%, respectively in these age groups. The current analysis suggests a much lower pre-vaccination IFR in non-elderly populations than previously suggested. Large differences did exist between countries and may reflect differences in comorbidities and other factors. These estimates provide a baseline from which to fathom further IFR declines with the widespread use of vaccination, prior infections, and evolution of new variants.

Infectious Diseases-Related Hospitalizations During Oral Polio Vaccine (OPV) and Non-OPV Immunization Periods: An Empirical Evaluation of all Hospital Discharges in California (1985-2010).

BACKGROUND: Live attenuated vaccines such as oral polio vaccine (OPV) can stimulate innate immunity and may have off-target protective effects on other pathogens. We aimed to address this hypothesis by examining changes in infectious diseases (ID)-related hospitalizations in all hospital discharges in California during OPV (1985-1996) and non-OPV immunization periods (2000-2010). METHODS: We searched the Office of Statewide Health Planning and Development database for all hospital discharges with any ID-related discharge diagnosis code during 1985-2010. We compared the proportion of ID-related hospitalizations (with at least 1 ID-related discharge diagnosis) among total hospitalizations during OPV immunization (1985-1996) versus non-OPV immunization (2000-2010) periods. RESULTS: There were 19 281 039 ID-related hospitalizations (8 464 037 with an ID-related discharge diagnosis as the principal discharge diagnosis for the hospitalization) among 98 117 475 hospitalizations in 1985-2010; 9 520 810 ID hospitalizations/43 456 484 total hospitalizations in 2000-2010 versus 7 526 957/43 472 796 in 1985-1996. The risk ratio for ID-related hospitalizations in 2000-2010 versus 1985-1996 was 1.27 (95% confidence interval [CI], 1.26-1.27) for all diagnoses and 1.15 (95% CI: 1.15-1.16) for principal diagnoses. Increases also existed in the proportion of lower respiratory and gastrointestinal infections. DISCUSSION: The proportion of ID-related hospitalizations was lower in the OPV immunization period compared to the period after OPV was discontinued. When focused only on hospitalizations with ID as the principal discharge diagnosis, the signal remained significant but was smaller. These findings require replication in additional studies.

Change in age distribution of COVID-19 deaths with the introduction of COVID-19 vaccination.

OBJECTIVES: Most countries initially deployed COVID-19 vaccines preferentially in elderly populations. We aimed to evaluate whether population-level vaccine effectiveness is heralded by an increase in the relative proportion of deaths among non-elderly populations that were less covered by vaccination programs. ELIGIBLE DATA: We collected data from 40 countries on age-stratified COVID-19 deaths during the vaccination period (1/14/2021-5/31/2021) and two control periods (entire pre-vaccination period and excluding the first wave). MAIN OUTCOME MEASURES: We meta-analyzed the proportion of deaths in different age groups in vaccination versus control periods in (1) countries with low vaccination rates; (2) countries with age-independent vaccination policies; and (3) countries with standard age-dependent vaccination policies. RESULTS: Countries that prioritized vaccination among older people saw an increasing share of deaths among 0-69 year old people in the vaccination versus the two control periods (summary proportion ratio 1.32 [95 CI% 1.24-1.41] and 1.35 [95 CI% 1.26-1.44)]. No such change was seen on average in countries with age-independent vaccination policies (1.05 [95 CI% 0.78-1.41 and 0.97 [95 CI% 0.95-1.00], respectively) and limited vaccination (0.93 [95 CI% 0.85-1.01] and 0.95 [95 CI% 0.87-1.03], respectively). Proportion ratios were associated with the difference of vaccination rates in elderly versus non-elderly people. No significant changes occurred in the share of deaths in age 0-49 among all 0-69 deaths in the vaccination versus pre-vaccination periods. CONCLUSIONS: The substantial shift in the age distribution of COVID-19 deaths in countries that rapidly implemented vaccination predominantly among elderly provides evidence for the population level-effectiveness of COVID-19 vaccination and a favorable evolution of the pandemic towards endemicity with fewer elderly deaths.

Late Diagnosis of Congenital Toxoplasmosis with Macrocephaly in Dizygotic Twins after Incidental Detection of Leukocoria: A Case Report.

Untreated congenital toxoplasmosis remains an important cause of neurologic and ocular disease worldwide. However, congenitally infected infants may not have signs and symptoms their physicians recognize, leading to delayed diagnosis and missed opportunities for treatment. We describe a pair of twins diagnosed with congenital toxoplasmosis at 11 months of age following incidental detection of leukocoria in one twin.

Reducing Piperacillin and Tazobactam Use for Pediatric Perforated Appendicitis.

BACKGROUND: Although perforated appendicitis is associated with infectious complications, the choice of antibiotic therapy is controversial. We assess the effectiveness and safety of an intervention to reduce piperacillin and tazobactam (PT) use for pediatric acute perforated appendicitis. METHODS: This is a single-center, retrospective cohort study of children 18 y of age or younger who underwent primary appendectomy for perforated appendicitis between January 01, 2016 and June 30, 2019. An intervention to decrease PT use was implemented: the first phase was provider education (April 19, 2017) and the second phase was modification of electronic antibiotic orders to default to ceftriaxone and metronidazole (July 06, 2017). Preintervention and postintervention PT exposure, use of PT ≥ half of intravenous antibiotic days, and clinical outcomes were compared. RESULTS: Forty children before and 109 after intervention were included and had similar baseline characteristics. PT exposure was 31 of 40 (78%) and 20 of 109 (18%) (P < 0.001), and use ≥ half of intravenous antibiotic days was 31 of 40 (78%) and 14 of 109 (13%) (P < 0.001), in the preintervention and postintervention groups, respectively. There was no significant difference in mean duration of antibiotic therapy (10.8 versus 9.8 d), mean length of stay (6.2 versus 6.5 d), rate of surgical site infection (10% versus 11%), or rate of 30-d readmission and emergency department visit (20% versus 20%) between the preintervention and postintervention periods, respectively. CONCLUSIONS: Provider education and modification of electronic antibiotic orders safely reduced the use of PT for pediatric perforated appendicitis.

Second versus first wave of COVID-19 deaths: Shifts in age distribution and in nursing home fatalities.

OBJECTIVE: To examine whether the age distribution of COVID-19 deaths and the share of deaths in nursing homes changed in the second versus the first pandemic wave. ELIGIBLE DATA: We considered all countries that had at least 4000 COVID-19 deaths occurring as of January 14, 2021, at least 200 COVID-19 deaths occurring in each of the two epidemic wave periods; and which had sufficiently detailed information available on the age distribution of these deaths. We also considered countries with data available on COVID-19 deaths of nursing home residents for the two waves. MAIN OUTCOME MEASURES: Change in the second wave versus the first wave in the proportion of COVID-19 deaths occurring in people <50 years ("young deaths") among all COVID-19 deaths and among COVID-19 deaths in people <70 years old; and change in the proportion of COVID-19 deaths in nursing home residents among all COVID-19 deaths. RESULTS: Data on age distribution were available for 14 eligible countries. Individuals <50 years old had small absolute difference in their share of the total COVID-19 deaths in the two waves across 13 high-income countries (absolute differences 0.0-0.4%). Their proportion was higher in Ukraine, but it decreased markedly in the second wave. The proportion of young deaths was lower in the second versus the first wave (summary prevalence ratio 0.81, 95% CI 0.71-0.92) with large between-country heterogeneity. The proportion of young deaths among deaths <70 years did not differ significantly across the two waves (summary prevalence ratio 0.96, 95% CI 0.86-1.06). Eligible data on nursing home COVID-19 deaths were available for 11 countries. The share of COVID-19 deaths that were accounted by nursing home residents decreased in the second wave significantly and substantially in 8 countries (prevalence ratio estimates: 0.36 to 0.78), remained the same in Denmark and Norway and markedly increased in Australia. CONCLUSIONS: In the examined countries, age distribution of COVID-19 deaths has been fairly similar in the second versus the first wave, but the contribution of COVID-19 deaths in nursing home residents to total fatalities has decreased in most countries in the second wave.

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 <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 <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 <65 and no underlying diseases. MAIN OUTCOME MEASURES: Proportion of COVID-19 deaths in people <65 years old; relative mortality rate of COVID-19 death in people <65 versus ≥65 years old; absolute risk of COVID-19 death in people <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 <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 <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 <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 <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 <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 <65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people <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.

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.

Do systematic reviews on pediatric topics need special methodological considerations?

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. 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.

Effect of long-term antibiotic use on weight in adolescents with acne.

OBJECTIVES: Antibiotics increase weight in farm animals and may cause weight gain in humans. We used electronic health records from a large primary care organization to determine the effect of antibiotics on weight and BMI in healthy adolescents with acne. METHODS: We performed a retrospective cohort study of adolescents with acne prescribed ≥4 weeks of oral antibiotics with weight measurements within 18 months pre-antibiotics and 12 months post-antibiotics. We compared within-individual changes in weight-for-age Z-scores (WAZs) and BMI-for-age Z-scores (BMIZs). We used: (i) paired t-tests to analyse changes between the last pre-antibiotics versus the first post-antibiotic measurements; (ii) piecewise-constant-mixed models to capture changes between mean measurements pre- versus post-antibiotics; (iii) piecewise-linear-mixed models to capture changes in trajectory slopes pre- versus post-antibiotics; and (iv) χ(2) tests to compare proportions of adolescents with ≥0.2 Z-scores WAZ or BMIZ increase or decrease. RESULTS: Our cohort included 1012 adolescents with WAZs; 542 also had BMIZs. WAZs decreased post-antibiotics in all analyses [change between last WAZ pre-antibiotics versus first WAZ post-antibiotics = -0.041 Z-scores (P < 0.001); change between mean WAZ pre- versus post-antibiotics = -0.050 Z-scores (P < 0.001); change in WAZ trajectory slopes pre- versus post-antibiotics = -0.025 Z-scores/6 months (P = 0.002)]. More adolescents had a WAZ decrease post-antibiotics ≥0.2 Z-scores than an increase (26% versus 18%; P < 0.001). Trends were similar, though not statistically significant, for BMIZ changes. CONCLUSIONS: Contrary to original expectations, long-term antibiotic use in healthy adolescents with acne was not associated with weight gain. This finding, which was consistent across all analyses, does not support a weight-promoting effect of antibiotics in adolescents.

Clustering of Toxoplasma gondii Infections Within Families of Congenitally Infected Infants.

BACKGROUND: Family clusters and epidemics of toxoplasmosis in North, Central, and South America led us to determine whether fathers of congenitally infected infants in the National Collaborative Chicago-Based Congenital Toxoplasmosis Study (NCCCTS) have a high incidence of Toxoplasma gondii infection. METHODS: We analyzed serum samples collected from NCCCTS families between 1981 and 2013. Paternal serum samples were tested for T. gondii antibodies with immunoglobulin (Ig) G dye test and IgM enzyme-linked immunosorbent assay. Additional testing of paternal serum samples was performed with differential-agglutination and IgG avidity tests when T. gondii IgG and IgM results were positive and serum samples were collected by the 1-year visit of the congenitally infected child. Prevalence of paternal seropositivity and incidence of recent infection were calculated. We analyzed whether certain demographics, maternal parasite serotype, risk factors, or maternal/infant clinical manifestations were associated with paternal T. gondii infection status. RESULTS: Serologic testing revealed a high prevalence (29 of 81; 36%) of T. gondii infection in fathers, relative to the average seropositivity rate of 9.8% for boys and men aged 12-49 years in the United States between 1994 and 2004 (P < .001). Moreover, there was a higher-than-expected incidence of recent infections among fathers with serum samples collected by the 1-year visit of their child (6 of 45; 13%; P < .001). No demographic patterns or clinical manifestations in mothers or infants were associated with paternal infections, except for sandbox exposure. CONCLUSIONS: The high prevalence of chronic and incidence of recent T. gondii infections in fathers of congenitally infected children indicates that T. gondii infections cluster within families in North America. When a recently infected person is identified, family clustering and community risk factors should be investigated for appropriate clinical management.

Patient safety strategies targeted at diagnostic errors: a systematic review.

Missed, delayed, or incorrect diagnosis can lead to inappropriate patient care, poor patient outcomes, and increased cost. This systematic review analyzed evaluations of interventions to prevent diagnostic errors. Searches used MEDLINE (1966 to October 2012), the Agency for Healthcare Research and Quality's Patient Safety Network, bibliographies, and prior systematic reviews. Studies that evaluated any intervention to decrease diagnostic errors in any clinical setting and with any study design were eligible, provided that they addressed a patient-related outcome. Two independent reviewers extracted study data and rated study quality. There were 109 studies that addressed 1 or more intervention categories: personnel changes (n = 6), educational interventions (n = 11), technique (n = 23), structured process changes (n = 27), technology-based systems interventions (n = 32), and review methods (n = 38). Of 14 randomized trials, which were rated as having mostly low to moderate risk of bias, 11 reported interventions that reduced diagnostic errors. Evidence seemed strongest for technology-based systems (for example, text message alerting) and specific techniques (for example, testing equipment adaptations). Studies provided no information on harms, cost, or contextual application of interventions. Overall, the review showed a growing field of diagnostic error research and categorized and identified promising interventions that warrant evaluation in large studies across diverse settings.

Acute Toxoplasma gondii infection among family members in the United States.

We investigated 32 families of persons with acute toxoplasmosis in which > or = 1 other family member was tested for Toxoplasma gondii infection; 18 (56%) families had > or = 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.

Concordance of effects of medical interventions on hospital admission and readmission rates with effects on mortality.

BACKGROUND: Many clinical trials examine a composite outcome of admission to hospital and death, or infer a relationship between hospital admission and survival benefit. This assumes concordance of the outcomes "hospital admission" and "death." However, whether the effects of a treatment on hospital admissions and readmissions correlate to its effect on serious outcomes such as death is unknown. We aimed to assess the correlation and concordance of effects of medical interventions on admission rates and mortality. METHODS: We searched the Cochrane Database of Systematic Reviews from its inception to January 2012 (issue 1, 2012) for systematic reviews of treatment comparisons that included meta-analyses for both admission and mortality outcomes. For each meta-analysis, we synthesized treatment effects on admissions and death, from respective randomized trials reporting those outcomes, using random-effects models. We then measured the concordance of directions of effect sizes and the correlation of summary estimates for the 2 outcomes. RESULTS: We identified 61 meta-analyses including 398 trials reporting mortality and 182 trials reporting admission rates; 125 trials reported both outcomes. In 27.9% of comparisons, the point estimates of treatment effects for the 2 outcomes were in opposite directions; in 8.2% of trials, the 95% confidence intervals did not overlap. We found no significant correlation between effect sizes for admission and death (Pearson r = 0.07, p = 0.6). Our results were similar when we limited our analysis to trials reporting both outcomes. INTERPRETATION: In this metaepidemiological study, admission and mortality outcomes did not correlate, and discordances occurred in about one-third of the treatment comparisons included in our analyses. Both outcomes convey useful information and should be reported separately, but extrapolating the benefits of admission to survival is unreliable and should be avoided.

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.

Differential COVID-19 infection rates in children, adults, and elderly: Systematic review and meta-analysis of 38 pre-vaccination national seroprevalence studies.

Background: Debate exists about whether extra protection of elderly and other vulnerable individuals is feasible in COVID-19. We aimed to assess the relative infection rates in the elderly vs the non-elderly and, secondarily, in children vs adults. Methods: We performed a systematic review and meta-analysis of seroprevalence studies conducted in the pre-vaccination era. We identified representative national studies without high risk of bias through SeroTracker and PubMed searches (last updated May 17, 2022). We noted seroprevalence estimates for children, non-elderly adults, and elderly adults, using cut-offs of 20 and 60 years (or as close to these ages, if they were unavailable) and compared them between different age groups. Results: We included 38 national seroprevalence studies from 36 different countries comprising 826 963 participants. Twenty-six of these studies also included pediatric populations and twenty-five were from high-income countries. The median ratio of seroprevalence in elderly vs non-elderly adults (or non-elderly in general, if pediatric and adult population data were not offered separately) was 0.90-0.95 in different analyses, with large variability across studies. In five studies (all in high-income countries), we observed significant protection of the elderly with a ratio of <0.40, with a median of 0.83 in high-income countries and 1.02 elsewhere. The median ratio of seroprevalence in children vs adults was 0.89 and only one study showed a significant ratio of <0.40. The main limitation of our study is the inaccuracies and biases in seroprevalence studies. Conclusions: Precision shielding of elderly community-dwelling populations before the availability of vaccines was indicated in some high-income countries, but most countries failed to achieve any substantial focused protection. Registration: Open Science Framework (available at: https://osf.io/xvupr).