Each day, more than 100 firearm deaths occur in the United States.¹ In 2021, there were 48 953 fatalities from firearms, the highest number of firearm deaths recorded since the Centers for Disease Control and Prevention (CDC) began tracking injury fatalities in 1981.² Previous study findings suggested a recent increase in overall firearm-related mortality rates, and firearms are now the leading cause death in youths aged 1 to 19 years, accounting for 20% of adolescent deaths.^3-7

Low plasma arginine bioavailability has been implicated in endothelial dysfunction and immune dysregulation. The role of arginine in COVID-19 is unknown, but could contribute to cellular damage if low. Our objective was to determine arginine bioavailability in adults and children with COVID-19 vs. healthy controls. We hypothesized that arginine bioavailability would be low in patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We conducted a prospective observational study of three patient cohorts; arginine bioavailability was determined in asymptomatic healthy controls, adults hospitalized with COVID-19, and hospitalized children/adolescents <21 y old with COVID-19, MIS-C, or asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified on admission screen. Mean patient plasma amino acids were compared to controls using the Student’s t test. Arginine-to-ornithine ratio, a biomarker of arginase activity, and global arginine bioavailability ratio (GABR, arginine/[ornithine+citrulline]) were assessed in all three groups. A total of 80 patients were included (28 controls, 32 adults with COVID-19, and 20 pediatric patients with COVID-19/MIS-C). Mean plasma arginine and arginine bioavailability ratios were lower among adult and pediatric patients with COVID-19/MIS-C compared to controls. There was no difference between arginine bioavailability in children with COVID-19 vs. MIS-C. Adults and children with COVID-19 and MIS-C in our cohort had low arginine bioavailability compared to healthy adult controls. This may contribute to immune dysregulation and endothelial dysfunction in COVID-19. Low arginine-to-ornithine ratio in patients with COVID-19 or MIS-C suggests an elevation of arginase activity. Further study is merited to explore the role of arginine dysregulation in COVID-19.

Rare diseases affect as many as 60 million people in the United States and Europe. However, most rare diseases lack effective therapies and are in critical need of clinical research. Our objective was to determine the frequency of noncompletion and nonpublication of trials studying rare diseases. We conducted a cross-sectional analysis of randomized clinical trials studying rare diseases as defined by the Genetic and Rare Disease Information Center database that were registered in ClinicalTrials.gov between January 1, 2010, and December 31, 2012, and completed or discontinued by December 31, 2014. Our main outcome measures were the frequency of trial noncompletion and, among completed studies, frequency of trial nonpublication at 2 and 4 years following trial completion. Reasons for discontinuation were extracted from the registry, and trial sponsors were contacted for additional information, as needed. Two independent investigators performed publication searches for each trial in PubMed, EMBASE, and GoogleScholar, allowing for a minimum of 45 months between trial completion and publication. When a publication could not be identified, trial sponsors were contacted to confirm publication status. The impact of funding source on trial noncompletion was assessed with multivariable logistic regression, and the effect on time to publication was examined with Cox proportional hazards regression. Control variables included intervention type, trial phase, masking, enrollment, and study population. We analyzed 659 rare disease trials accounting for 70,305 enrolled patients. Industry was the primary funder for 327 trials (49.6%) and academic institutions for 184 trials (27.9%). There were 79 trials (12.0%) focused on pediatric populations. A total of 199 trials (30.2%) were discontinued. Lack of patient accrual (n = 64, 32.1%) and informative termination (n = 41, 20.6%) were the most common reasons for trial noncompletion. Among completed trials, 306 (66.5%) remained unpublished at 2 years and 142 (31.5%) at 4 years. In multivariable analyses, industry-funded trials were less likely to be discontinued than trials funded by healthcare centers (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.34–4.39, P = 0.003). We found no significant association between funding source and time to publication. A total of 18,148 patients were enrolled in trials that were discontinued or unpublished 4 years after completion. A potential limitation of our study is that certain interventional trials for rare diseases may not have been registered in ClinicalTrials.gov, in particular Phase 0 and Phase I trials, which are not required to be registered. In this study, over half of clinical trials initiated for rare diseases were either discontinued or not published 4 years after completion, resulting in large numbers of patients with rare diseases exposed to interventions that did not lead to informative findings. Concerted efforts are needed to ensure that participation of patients in rare disease trials advances scientific knowledge and treatments for rare diseases.

Clinical trials provide the highest level of evidence for assessment of the safety, comparative effectiveness, and efficacy of medications and interventions that guide clinical care.¹ However, results from clinical trials that lack racial and ethnic minority participants may not be generalizable to all populations that may benefit from trial results.^2,3 Race is a social construct reflecting the “impact of unequal social experiences on health,”^4,p872 and ethnicity refers to social groupings based on culture and language.^4,5 The National Institutes of Health and the US Food and Drug Administration mandate the planned inclusion of participants from multiple racial and ethnic groups when applying for support.^6,7

Introduction Authorship parasitism (ie, no authors affiliated with the country in which the study took place) occurs frequently in research conducted in low-income and middle-income countries, despite published recommendations defining authorship criteria. The objective was to compare characteristics of articles exhibiting authorship parasitism in sub-Saharan Africa to articles with author representation from sub-Saharan African countries. Methods A bibliometric review of articles indexed in PubMed published from January 2014 through December 2018 reporting research conducted in sub-Saharan Africa was performed. Author affiliations were assigned to countries based on regular expression algorithms. Choropleth maps and network diagrams were created to determine where authorship parasitism occurred, and multivariable logistic regression was used to determine associated factors. Results Of 32 061 articles, 14.8% (n=4754) demonstrated authorship parasitism, which was most common among studies from Somalia (n=175/233, 75.1%) and Sao Tome and Principe (n=20/28, 71.4%). Authors affiliated with USA and UK institutions were most commonly involved in articles exhibiting authorship parasitism. Authorship parasitism was more common in articles: published in North American journals (adjusted OR (aOR) 1.26, 95% CI 1.07 to 1.50) than in sub-Saharan African journals, reporting work from multiple sub-Saharan African countries (aOR 8.41, 95% CI 7.30 to 9.68) compared with work from upper-middle income sub-Saharan African countries, with 10 authors, and was less common in articles published in French (aOR 0.60, 95% CI 0.41 to 0.85) than English. Conclusions Authorship parasitism was common in articles reporting research conducted in sub-Saharan Africa. There were reliable predictors of authorship parasitism. Investigators and institutions in high-income countries, as well as funding agencies and journals should promote research from sub-Saharan Africa, including its publication, in a collaborative and equitable manner.