Importance:The age-adjusted D-dimer cutoff (age × 10 µg/L in patients 50 years or older), safely increases the diagnostic yield of D-dimer in patients with suspected pulmonary embolism but has not been validated in patients with suspected leg deep vein thrombosis (DVT). Objective:To prospectively validate whether using an age-adjusted D-dimer cutoff allows clinicians to safely rule out DVT. Design, Setting, and Patients:Multicenter, multinational prospective management outcome study conducted in 27 centers in Belgium, Canada, France, and Switzerland between January 2015 and October 2022 (last follow-up visit, January 30, 2023) and including outpatients presenting to the emergency department with suspected DVT. Interventions:Patients were assessed by a sequential diagnostic strategy based on the assessment of clinical pretest probability by the Wells score, a highly sensitive D-dimer test, and leg compression ultrasonography. Patients in whom DVT was ruled out were followed up for a 3-month period. Main Outcome and Measure:The primary outcome was the rate of adjudicated symptomatic venous thromboembolic events during follow-up in patients in whom DVT was ruled out based on a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff. Results:A total of 3205 patients were included. Median age was 59 years, and 1737 (54%) were female. DVT prevalence was 14%. Among the 2169 patients with a non-high or unlikely clinical probability, 531 (24.5% [95% CI, 22.7%-26.4%]) had a D-dimer level less than 500 µg/L, and 161 additional patients (7.4% [95% CI, 6.4%-8.6%]) had a D-dimer level between 500 µg/L and their age-adjusted cutoff. No failures were identified in patients with a D-dimer level 500 µg/L or greater but below the age-adjusted cutoff (0% [95% CI, 0%-2.3%]). Among patients 75 years or older, using the age-adjusted cutoff instead of the 500-µg/L cutoff increased the proportion of negative D-dimer from 33 of 379 (8.7% [95% CI, 6.3%-12.0%]) to 99 of 379 (26.1% [95% CI, 22.0%-30.8%]), without any false-negative test results. Conclusions and Relevance:The age-adjusted D-dimer cutoff may safely rule out DVT and was associated with a larger number of patients in whom DVT could be effectively ruled out. Trial Registration:ClinicalTrials.gov Identifier: NCT02384135.
Background. There is paucity of information on the role of cytomegalovirus (CMV) infection as a cause of stillbirths or childhood deaths in low- and middle-income countries (LMICs). We investigated attribution of CMV disease in the causal pathway to stillbirths and deaths in children <5 years of age in 7 LMICs participating in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. Methods. We analyzed stillbirths and decedents enrolled between December 2016 and July 2023. Deaths were investigated using postmortem minimally invasive tissue sampling with histopathology and molecular diagnostic investigations of tissues and body fluids, along with review of clinical records. Multidisciplinary expert panels reviewed findings and reported on the causal pathway to death. Results. CMV was detected in 19.5% (1140/5841) of all evaluated deaths, including 5.0% (111/2204), 6.2% (139/2229), 41.2% (107/260), 68.1% (323/474), and 68.2% (460/674) of stillbirths, neonates (deaths <28 days postnatal), early infants (28 to <90 days), late infants (90 to <365 days), and children (12 to <60 months), respectively. CMV disease was attributed in the causal pathway to death in 0.9% (20/2204) of stillbirths, 0.8% (17/2229) of neonates, 13.1% (34/260) of early infants, 9.7% (46/474) of late infants, and 3.3% (22/674) of children. Decedents with CMV disease, compared with those without CMV disease in the causal pathway, were more likely to have severe microcephaly (38.2% vs 21.1%; adjusted odds ratio [aOR], 2.2 [95% confidence interval {CI}, 1.3-3.6]) and to have human immunodeficiency virus (HIV) (36.9% vs 6.2%; aOR, 10.9 [95% CI, 6.5-18.5]). Conclusions. CMV disease is an important contributor to deaths during infancy and childhood and is often associated with severe microcephaly and HIV infection. Improving management of CMV in children with HIV and a vaccine to prevent CMV are needed interventions.
In contrast to anger, a natural and often adaptive emotion, problematic anger is difficult to predict and regulate in a healthy manner. Emerging evidence from studies with military personnel and veterans indicates that problematic anger often leads to significant functional impairment and is linked to exposures to potentially psychologically traumatic events (PPTEs) and a range of mental health disorders. By virtue of their work, public safety personnel (PSP) are exposed to numerous PPTEs and may therefore be at a similarly elevated risk for problematic anger. The current study was designed to assess the prevalence of problematic anger and associations between problematic anger and mental health disorder symptoms among Canadian PSP, extending research with problematic anger among Canadian military personnel and Veterans. Serving correctional workers, firefighters, paramedics, municipal/provincial police, and Royal Canadian Mounted Police completed measures of problematic anger, mental health disorder symptoms, and sociodemographic characteristics via an online self-report survey. Descriptive statistics examined the prevalence of problematic anger and mental health disorder symptoms; bivariate correlations assessed for associations between problematic anger and mental health disorder symptoms; and linear and logistic regressions assessed for associations between problematic anger and mental health disorder symptoms and positive screens, respectively, controlling for sociodemographic covariates. Problematic anger was associated with every mental health outcome assessed and remained a strong predictor of positive screens after controlling for sociodemographic factors. These findings reinforce problematic anger as a common, clinically relevant mechanism linking PPTE exposure to mental health challenges across trauma‑exposed professions.
Background: Antibiotics are essential for treating infections; however, they disrupt the microbiome and key microbiome-dependent functions. Clinical evidence is mixed for probiotic supplementation following antibiotics due to product heterogeneity and inconsistencies in evaluating biological mechanisms that drive clinical consequences. Accordingly, this study investigates the effects of a multi-species synbiotic on gut microbiome composition and function, and gut barrier integrity, during and following antibiotics. Methods: In a randomized, placebo-controlled trial designed to assess proof-of-mechanism, healthy adult participants received a daily synbiotic (53.6 billion AFU multi-species probiotic and 400 mg Indian pomegranate extract; DS-01) or matching placebo for 91 days. All participants also received ciprofloxacin (500 mg orally twice daily) and metronidazole (500 mg orally three times daily) for the first 7 days. Samples were collected at baseline and Days 7, 14, 49, and 91. Endpoints included fecal microbiome composition, fecal acetate and butyrate levels, urinary Urolithin A (UroA), serum p-cresol sulfate (pCS), gut barrier integrity, and safety. Results: The multi-species synbiotic significantly increased the alpha-diversity of Bifidobacterium and Lactobacillus at all timepoints compared to placebo, including short-term (Day 7, p < 0.0001) and end-of-study (Day 91, p < 0.001). The multi-species synbiotic enhanced recovery of native beneficial microbes, including butyrate-producing species and a novel Oscillospiraceae species (UMGS1312 sp900550625, p < 0.001). Beneficial microbiome-dependent metabolites increased, including fecal butyrate (119%, p < 0.05), fecal acetate (62%, p < 0.01), and UroA (13,008%, p < 0.05), whereas detrimental metabolite pCS decreased (68%, p < 0.05) compared to placebo. Functionally, the multi-species synbiotic improved gut barrier integrity rapidly (Day 7; 305%, p < 0.05) and over the long-term (Day 91; 161%, p < 0.05) compared to placebo. Conclusions: During and after antibiotics, this multi-species synbiotic promotes recovery of gut microbiome diversity and native beneficial microbes, microbiome metabolite recovery, and gut barrier function, all of which underpin antibiotic-associated gastrointestinal symptoms.
Financial hardship is a significant but underexplored challenge for medical students from lower socioeconomic backgrounds. While the financial barriers to medical school admissions are well-documented, there is limited research on the nuanced financial struggles these students face after matriculation. Traditional qualitative data collection methods often limit students' disclosure of these sensitive experiences. To uncover deeper insights into the experiences of financially disadvantaged medical students, a thematic analysis was conducted in February 2024 using comments from Reddit (r/medicalschool) (from February 2019-2024), a platform that offers anonymous and candid discussions. Three researchers analyzed threads discussing financial burdens in medical training through an inductive coding process. From 9,590 comments across 144 threads, we identified four key themes: personal costs, institutional and systemic barriers, social isolation and peer comparisons, and career trade-offs and professional development. Students described extreme budgeting measures that often led to compromises on basic needs such as food and healthcare. The emotional toll of financial stress was evident in widespread mental health concerns, with many students feeling anxious and inadequate compared to their wealthier peers. Financial disparities also contributed to social isolation and envy, while the need to manage debt heavily shaped career decisions, with many prioritizing high-earning specialties or loan forgiveness opportunities. Interpreted through the complementary frameworks of Bourdieu and Freidson, the findings suggest that financial hardship operates not only as an individual challenge but as a pattern shaped by the institutional organization of medical training. The findings highlight the pervasive financial challenges faced by low-income medical students. Addressing these issues will require greater transparency around the hidden costs of medical education, more comprehensive financial support, and increased institutional empathy toward students' financial difficulties.
