Cardiac myosin-specific autoimmune T cells contribute to immune-checkpoint-inhibitor-associated myocarditis

Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear. Here, we show the development of myocarditis in A/J mice induced by anti-PD-1 monoclonal antibody (mAb) administration alone without tumor cell inoculation, immunization, or viral infection. Mice with myocarditis have increased cardiac infiltration, elevated cardiac troponin levels, and arrhythmia. Anti-PD-1 mAb treatment also causes irAEs in other organs. Autoimmune T cells recognizing cardiac myosin are activated and increased in mice with myocarditis. Notably, cardiac myosin-specific T cells are present in naive mice, showing a phenotype of antigen-experienced T cells. Collectively, we establish a clinically relevant mouse model for ICI-associated myocarditis and find a contribution of cardiac myosin-specific T cells to ICI-associated myocarditis development and pathogenesi

Designing a Study to Investigate Older Novice Drivers

DTNH2217D00031/693JJ920F000207Drivers 15 to 20 years old\u2014many of whom were novice drivers\u2014represented 8.5 percent of drivers involved in fatal crashes but only 5.1 percent of all licensed drivers in 2020. Graduated driver licensing (GDL) laws are the most effective behavioral countermeasure for young drivers. However, although an increasing proportion of young people are delaying licensure until 18 or older, few States currently apply the full GDL program to 18- to 20-year-old novice drivers, and little is known about the safety and driving habits of this group. In this project the research team developed a hypothetical naturalistic driving study to investigate research questions about the safety and driving exposure of younger (15.5 to 16.5 years old) and older (18 to 20 years old) novice drivers in the first year of unsupervised (independent) driving

Comparison of alternative risk adjustment measures for predictive modeling: high risk patient case finding using Taiwan's National Health Insurance claims

<p>Abstract</p> <p>Background</p> <p>Predictive modeling presents an opportunity to contain the expansion of medical expenditures by focusing on very few people. Evaluation of how risk adjustment models perform in predictive modeling in Taiwan or Asia has been rare. The aims of this study were to evaluate the performance of different risk adjustment models (the ACG risk adjustment system and prior expenditures) in predictive modeling, using Taiwan's National Health Insurance (NHI) claims data, and to compare characteristics of potentially high-expenditure subjects identified through different models.</p> <p>Methods</p> <p>A random sample of NHI enrollees continuously enrolled in 2002 and 2003 (n = 164,562) was selected. Health status measures and total expenditures derived from 2002 NHI claims data were used to predict the possibility of becoming 2003 top users. Statistics-based indicators (C-statistics, sensitivity, & Predictive Positive Value) and characteristics of identified top groups by different models (expenditures and prevalence of manageable diseases) were presented.</p> <p>Results</p> <p>Both diagnosis-based and prior expenditures models performed much better than the demographic model. Diagnosis-based models were better in identifying top users with manageable diseases; prior expenditures models were better in statistics-based indicators and identifying people with higher average expenditures. Prior expenditures status could correctly identify more actual top users than diagnosis-based or demographic models. The proportions of actual top users that could be identified by diagnosis-based models alone were much lower than that identified by prior expenditures status.</p> <p>Conclusions</p> <p>Predicted top users identified by different models have different characteristics and there is little agreement between modes regarding which groups would be potentially top users; therefore, which model to use should depend on the purpose of predictive modeling. Prior expenditures are a more powerful tool than diagnosis-based risk adjusters in terms of correctly identifying more actual high expenditures users. There is still much room left for improvement of diagnosis-based models in predictive modeling.</p

Consolidated standards of reporting trials of social and psychological interventions: CONSORT-SPI

This collection involves data from a project to develop Consolidated Standards of Reporting Trials of Social and Psychological Interventions: CONSORT-SPI. Namely, two phases of the project involved the collection of new data: an online Delphi process and a consensus meeting. The online Delphi process aimed to develop and refine a prioritised list of reporting items to consider for a new guideline for social and psychological intervention trials. A secondary objective was to engage a wide group of stakeholders internationally at an early stage in the CONSORT-SPI project. Delphi participants were identified using a multistep, iterative approach and met pre-specified eligibility criteria as researchers, practitioners, policy-makers, journal editors, researcher funders, and/or representatives of intervention service users. Participants were asked to rate concepts, identified from the review of reporting standards in the last chapter, for importance in a guideline for reporting social and psychological intervention trials. In Round 1, participants ranked the degree of importance of 77 proposed guideline items on a scale of 1 to 10, with higher scores indicating higher importance for social and psychological intervention trials. In Round 2, participants ranked whether remaining items not reaching consensus in Round 1 should be included or excluded in a set of minimum reporting standards for these trials. In both rounds, participants had the opportunity to comment on proposed items and nominate items that may be missing from the surveys. The median, inter-percentile range, and counts of rankings for each item—in addition to participants’ comments—were used to measure consensus. The purpose of the consensus meeting was to discuss and select items for the CONSORT-SPI checklist. A group of 31 researchers, journal editors, and funders met in March 2014 to extend the CONSORT 2010 Statement to RCTs of social and psychological interventions. A three-day consensus development conference was held to discuss preliminary research on social and psychological intervention RCTs, vote on items for the CONSORT-SPI reporting standards checklist, and discuss a dissemination and implementation plan for the CONSORT-SPI guidelines. In addition to the data, the related resources provided include links to the project website and related project manuscripts. This project will develop and disseminate a guideline for reporting experiments of psychological, social, and environmental interventions. To coordinate and publicise the initiative, Steering Group of experts in core social science disciplines has been assembled. With their guidance, we will first conduct an international Delphi process with researchers, journal editors, and other stakeholders to generate a list of important reporting standards to consider for inclusion in the guideline. Results from two reviews we have conducted indicate that publications often omit information that would allow readers to assess internal validity (eg blinding and level of randomisation). Such reports may overestimate intervention effects by as much as 30 per cent. Secondly, reports should include more information relevant to the external validity of experiments (eg participant selection, intervention implementation). We will then host a consensus meeting to finalise the list of minimal reporting standards for inclusion in the guideline.The outputs from this project will help authors write clear reports, create a framework for reviewers to assess publications, expedite funding evaluations, provide a pedagogical tool for understanding these experiments, and help consumers evaluate study validity and applicability. In these ways, the guideline will facilitate efficient and effective transfer of research evidence into real-world use.</p

Capturing the COVID-19 Crisis through Public Health and Social Measures Data Science

In response to COVID-19, governments worldwide are implementing public health and social measures (PHSM) that substantially impact many areas beyond public health. The new field of PHSM data science collects, structures, and disseminates data on PHSM; here, we report the main achievements, challenges, and focus areas of this novel field of research

Treatment outcomes among children younger than five years living with HIV in rural Zambia, 2008–2018: a cohort study

Abstract Background HIV testing and treatment guidelines for children in sub-Saharan Africa have evolved over time, such that children are now treated at younger ages. The objective of this study was to describe the treatment experience for immunologic, virologic, and growth outcomes among HIV-infected Zambian children younger than 5 years of age from 2008 to 2018. Methods Participants enrolled in a clinical cohort study in Macha, Zambia and initiating antiretroviral treatment before 5 years of age between 2008 and 2015 were included in the analysis and followed up to the end of 2018. Outcomes, including growth, CD4+ T-cell percentage, viral suppression, and mortality, were evaluated among all children using longitudinal and survival analyses. Comparisons by age at treatment initiation

Treatment outcomes among children younger than five years living with HIV in rural Zambia, 2008–2018: a cohort study

Abstract Background HIV testing and treatment guidelines for children in sub-Saharan Africa have evolved over time, such that children are now treated at younger ages. The objective of this study was to describe the treatment experience for immunologic, virologic, and growth outcomes among HIV-infected Zambian children younger than 5 years of age from 2008 to 2018. Methods Participants enrolled in a clinical cohort study in Macha, Zambia and initiating antiretroviral treatment before 5 years of age between 2008 and 2015 were included in the analysis and followed up to the end of 2018. Outcomes, including growth, CD4+ T-cell percentage, viral suppression, and mortality, were evaluated among all children using longitudinal and survival analyses. Comparisons by age at treatment initiation