This Viewpoint explores potential justifications underlying the US Food and Drug Administration (FDA)’s rejection of methylenedioxymethamphetamine (MDMA) as a treatment for posttraumatic stress disorder, including lack of blinding and issues around the integrity of relevant clinical trials.
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Longitudinal study of adolescent stress, critical consciousness and resilience trajectories in the context of structural racism: the RISE Baltimore study protocol
Introduction
Systemic racism exposes Black and Latinx adolescents to a range of traumatic stressors that increase the risk for long-term emotional and behavioural health (EBH) problems. Researchers have theorised that critical consciousness (CC)—awareness of societal inequities and engagement in action to promote social justice—may serve as a protective factor that promotes youth well-being. There are few rigorous longitudinal research studies, however, that examine the development of CC among adolescents, the association over time of CC with EBH and the potential of CC to protect against harmful effects of race-related stress. This longitudinal study, Resilience in a Stressful Era (RISE), addresses these gaps using a mixed methods approach with Black, Latinx and White adolescents in Baltimore.
Methods and analysis
We plan to enrol up to 650 Black, Latinx and White adolescents ages 14–19 who reside in Baltimore, Maryland. The recruitment will include outreach through youth-serving organisations, community events, youth networks, social media, snowball sampling and re-contacting adolescents who participated in a prior study (R01HD090022; PI: Mendelson). Participants will complete online questionnaires assessing exposure to pandemic- and race-related stress, CC and EBH twice per year over 4 years as they transition into early adulthood. Using an explanatory sequential mixed methods approach, in-depth interviews exploring the development and impact of CC will be conducted with a subset of participants selected based on their CC scores and, separately, their caregivers. A Youth Advisory Board comprised of adolescents who are representative of our target study population will be developed to provide input on the study and its implementation. Growth mixture modelling and latent variable modelling will be used to analyse quantitative data. Themes identified through qualitative analyses will expand the understanding of quantitative findings.
Ethics and dissemination
All study procedures were approved by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board. Findings will be disseminated through publications in peer-reviewed journals and presentations at academic conferences. We will also communicate research findings with study participants and disseminate findings to the Baltimore community, such as developing briefs for the Baltimore City Health Department and/or hosting a town hall meeting for Baltimore families.
Stress, sonno e rumore influenzano il microbiota intestinale
Non solo alimentazione e farmaci, lo studio di Campus Bio-Medico
Robot-assisted versus video-assisted thoracoscopic thymectomy for stage I-II thymic epithelial tumour: a protocol for the first multicentre, randomised controlled clinical trial
Background
Minimally invasive approaches, including video-assisted thoracoscopic thymectomy (VATT) and robot-assisted thoracoscopic thymectomy (RATT), have emerged as alternatives to median sternotomy for resectable thymic epithelial tumours (TETs). However, their comparative clinical efficacy remains inconclusive due to limited prospective evidence. This phase II randomised controlled trial aims to provide the first direct comparative analysis of perioperative outcomes between RATT and VATT in stage I–II TETs.
Methods and analysis
This phase II clinical trial is a prospective, multicentre, randomised controlled study. A total of 100 patients with stage I–II TETs will be recruited and randomly allocated into two groups: RATT and VATT groups, with a 1:1 ratio. Follow-up visits will be scheduled at 1 month, 3 months and 6 months postsurgery, and semiannual visits will continue until November 2027, including the record of tumour recurrence, metastasis, survival outcomes and overall long-term effects. The primary endpoint is total postoperative thoracic drainage. Secondary outcomes encompass intraoperative factors like R0 resection rate, operative time, postoperative drainage duration, hospital stay length, conversion rates, levels of stress markers, pain scores, quality of life assessments, perioperative complication rates, mortality rates and 3-year disease-free and overall survival rates.
Ethics and dissemination
The study protocol is approved by the ethics committees of Zhongshan Hospital, Fudan University (No. B2024-365), and will be conducted under the guidance of the Helsinki Declaration. All data and findings will be disseminated and published through peer review.
Trial registration number
NCT06654830.
Disruption of cTnT-Mediated Sarcomere–Mitochondrial Communication Results in Dilated Cardiomyopathy
Circulation, Ahead of Print. BACKGROUND:Dilated cardiomyopathy (DCM) is substantially influenced by genetic factors. Sarcomere function is intricately associated with other organelles, particularly the reciprocal regulation between sarcomeres and mitochondria. Mitochondrial stress dysregulation is linked to DCM progression, yet mechanisms remain unclear. In this study, we investigated the effects of cTnT (cardiac troponin T) dysregulation on sarcomere–mitochondrial communication in DCM.METHODS:Induced pluripotent stem cells (iPSCs) derived from a DCM family cohort were used in this study, and CRISPR-Cas9 genome editing was used to rectify theTNNT2(c.A553G) sequence variation in iPSCs. A knock-in mouse model harboring the (p.K192E) sequence variation, equivalent to the human cTnT (p.K185E) sequence variation, was subsequently established. The pathological phenotypes were analyzed in iPSC-derived cardiomyocytes, iPSC-derived cardiac organoids, and mice. RNA sequencing, metabolite profiling, and coimmunoprecipitation mass spectrometry were used to elucidate the molecular mechanisms.RESULTS:Through whole exome sequencing, we identified a novel pathogenic variant in cTnT (p.K185E) as the causal sequence variation in a familial DCM cohort. In iPSC-derived cardiomyocytes from patients with DCM, we observed sarcomere disarray and mitochondrial fragmentation accompanied by severe mitochondrial dysfunction. The diminished interaction between cTnT (p.K185E) and 14-3-3 proteins resulted in the dissociation of 14-3-3 proteins from sarcomeric structures. The free 14-3-3 proteins aberrantly engaged in the RAS/RAF1 signaling axis, driving aberrant p44/42 kinase activation that culminated in the phosphorylation of mitochondrial fission regulators DRP1 (dynamin-related protein 1) and MFF (mitochondrial fission factor). These observations were replicated in iPSC-derived cardiac organoids. The knock-in mice bearing the orthologous cTnT sequence variation faithfully recapitulated the hallmark features of human DCM, including cardiac dysfunction, ventricular dilatation, sarcomeric disarray, and mitochondrial fragmentation. Mdivi-1, a mitochondrial fission inhibitor, alleviated DCM phenotypes in vivo.CONCLUSIONS:Our findings delineate a novel pathogenic mechanism underlying DCM, demonstrating that cTnT (p.K185E) sequence variation disrupts sarcomere–mitochondrial communication by weakening the interaction between cTnT and 14-3-3 proteins, thereby accelerating mitochondrial fragmentation through excessive activation of the 14-3-3 protein–mediated RAS/RAF1-p44/42-DRP1/MFF signaling axis. Therefore, therapeutic targeting of 14-3-3 proteins and p44/42 kinase activity may represent a promising strategy for DCM and other cardiac diseases associated with aberrant mitochondrial dynamics.
Online child sexual abuse: a convergent parallel mixed-method exploration among Bangladeshi youth
Objectives
This study aimed to explore the experience of online sexual abuse among school-going Bangladeshi youth.
Design
A convergent parallel mixed-method study. The quantitative strand employed a self-administered questionnaire survey conducted in classroom settings, while the qualitative strand used in-depth interviews guided by semistructured protocols. Data from both strands were analysed separately and then merged.
Participants and settings
Grade 9–10 students from four randomly selected schools in both an urban and a rural area of Bangladesh participated in the study. A total of 456 students participated in the quantitative survey, and 16 were subsequently interviewed for qualitative data.
Outcome measures
The frequency of online sexual abuse along with its contributing factors and patterns, including victim’s characteristics, perpetrator’s identity, potential avenue of abuse, knowledge and psychosocial consequences.
Results
About 88% of the participants reported using the Internet, and nearly 53% reported being victims of online sexual abuse at some point in their lives. The occurrence of common sexual abuses included online grooming (53%), cyberflashing (38%), sexting (35%), sexual solicitation (18%) and sextortion (12%) among Internet users. The odds of being sexually abused online were higher among urban children (OR=2.04, 95% CI 1.21–3.45), who spent more hours daily on the Internet (OR=1.09, 95% CI 1.01–1.18), who visited more social media (OR=1.42, 95% CI 1.27–1.59) and who used more Internet devices (OR=1.93, 95% CI 1.25–2.98). Many participants were aware of these incidents but did not know how to respond to online sexual abuse. Social media, chat groups and video games were described as primary avenues for abuse, while unemployed male young adults and partners in love affairs were identified as the possible perpetrators. Psychosocial consequences such as anxiety, depression, helplessness, stress, distrust, lack of concentration, social isolation, self-hate and suicidal attempts were reported by the victims. Encountering online sexual abuse also manifested in academic underperformance.
Conclusion
Urgent multisectoral measures are needed to address online sexual abuse to safeguard children’s right to be protected on online platforms.
Support measures and demand among healthcare workers during the COVID-19 pandemic: a survey in high-workload provinces of China, 2023
Objectives
To assess the demands for support measures of healthcare workers (HCWs) in China’s high-workload provinces during the COVID-19 pandemic and identify specific needs to make evidence-based recommendations.
Design
Prospective cross-sectional study.
Setting
Conducted in three Chinese provinces characterised by their significant healthcare demands during the pandemic.
Participants
The study comprised 683 HCWs, including doctors, nurses, resident physicians and hospital administrators. The sample was predominantly female (68.1%), with the majority aged between 25 and 34 years. Participants were recruited through convenience and snowball sampling methods, with a focus on individuals working in high-intensity clinical environments.
Results
Hierarchical analysis was performed to assess the layered impact of support measures across different roles and genders. Substantial gender disparity was observed, with female staff reporting significantly reduced access to material support (p
Household food security and its influence on psychological well-being: a cross-sectional study among adults in slums in Bangladesh
Background
Rapid urbanisation and the dense population of Bangladesh foster the growth of slum settlements, where poverty and food insecurity are magnified by economic instability and inflationary pressures, adversely affecting psychological health.
Objectives
This study aimed to assess household food security and its influence on psychological well-being among adults living in urban slums of Bangladesh.
Methods
A cross-sectional study using convenient sampling was conducted among 300 adults in slums in Dhaka, Bangladesh, using a semistructured questionnaire to collect data on sociodemographics, food security and mental health status. Multivariable logistic regression analyses were conducted to observe the influence of food insecurity on mental health status, controlling for other covariates.
Results
The majority of the participants experienced food insecurity, with 38.0% expressing severe food insecurity. High levels of psychological distress were observed, including stress (54.7%), anxiety (63.3%) and depression (73.3%). Older adults (aOR 4.5, 95% CI 1.3 to 15.5) and females (aOR 4.1, 95% CI 2.0 to 8.4) had higher odds of experiencing anxiety. Single individuals were more prone to experience depression, while homemakers exhibited elevated levels of both depression and anxiety. Furthermore, moderate to severe food insecurity was significantly associated with higher odds of depression (aOR 2.8, 95% CI 1.2 to 6.7) and anxiety (aOR 8.2, 95% CI 3.3 to 20.3) compared with no or mild food insecurity.
Conclusions
This study highlights the pervasive influence of household food insecurity on urban slum dwellers’ psychological well-being. Addressing vulnerabilities tied to age, marital status and occupation is crucial for alleviating mental health burdens.
An adaptive multiarm randomised trial of biomedical and psychosocial interventions to improve convalescence following severe acute malnutrition in sub-Saharan Africa: Co-SAM trial protocol
Introduction
Children discharged from hospital following management of complicated severe acute malnutrition (SAM) have a high risk of mortality, readmission and failed nutritional recovery. Current management approaches fail to sufficiently promote convalescence after inpatient nutritional rehabilitation. Novel interventions during the post-discharge period could enhance convalescence to help children survive and thrive.
Methods and analysis
The Co-SAM trial is an adaptive, multicountry, phase III, individually randomised clinical trial, based on the principles that (i) interacting biological and social factors drive multimorbidity in children with SAM, and (ii) both medical and psychosocial interventions may therefore ameliorate underlying causal pathways to reduce morbidity and mortality and improve recovery. Children aged 6–59 months with complicated SAM, who have stabilised and started the transition to ready-to-use therapeutic food (RUTF), will be enrolled and randomised to one of five trial arms (standard-of-care alone; antimicrobials; reformulated RUTF; psychosocial support; or a combination of all strategies). Standard-of-care, which is provided in all trial arms, includes RUTF until nutritional recovery (defined as weight-for-height Z-score >–2, mid-upper arm circumference >12.5 cm and oedema-free since the last study visit), and other management recommended in WHO guidelines. The 12-week antimicrobial package provides daily co-formulated rifampicin and isoniazid (with pyridoxine) and 3 days of azithromycin monthly. The reformulated RUTF, which incorporates medium-chain triglycerides and hydrolysed protein to increase nutrient bioavailability and reduce metabolic stress, is provided at the same dose and duration as standard RUTF. The 12-week psychosocial package includes caregiver problem-solving therapy, educational modules, peer support groups and child play. The combined arm includes all interventions. Children start their intervention package prior to hospital discharge, with follow-up data collection in study clinics at 2, 4, 6, 8, 12 and 24 weeks. The primary composite outcome is death, hospitalisation or failed nutritional recovery within 24 weeks post-randomisation. An interim analysis will allow unpromising arms to be dropped, while the final analysis will be conducted when 1266 children have completed the study. Embedded process evaluation and laboratory substudies will explore the mechanisms of action of the interventions.
Ethics and dissemination
The trial has been approved by ethics committees in Zimbabwe, Zambia, Kenya and UK. Dissemination will be via community advisory boards in each country; Ministries of Health; and dialogue with policymakers including UNICEF.
Trial registration number
Clinicaltrials.gov: NCT05994742; Pan African Clinical Trials Registry: PACTR202311478928378.
Cost-effectiveness of massed versus spaced trauma-focused treatment as first-line treatment for post-traumatic stress disorder in adults with multiple trauma exposure: protocol for a single-blind non-inferiority randomised controlled trial
Introduction
Post-traumatic stress disorder (PTSD) is a serious disorder that burdens individuals and society. The current standard of first-line treatment for PTSD is spaced trauma-focused treatment (S-TFT), involving weekly sessions. While effective, S-TFT may take relatively long to complete, especially in patients exposed to multiple potentially traumatic events (PTEs). Massed trauma-focused treatment (M-TFT), involving increased session frequency, potentially results in faster symptom reduction and restoration of quality of life, as well as in a reduction of societal costs. However, M-TFT is not recommended as first-line treatment. This paper describes the research protocol of a single-blind, multicentre randomised controlled trial (RCT) aimed at investigating: (1) the clinical and cost-effectiveness of M-TFT versus S-TFT in employed, multiply traumatised patients who seek first-line treatment for PTSD and (2) predictive and moderating factors related to treatment response.
Methods and analysis
186 participants are recruited from five centres and will be included if they are ≥18 years old, meet criteria for a Diagnostic and Statistical Manual of Mental Disorders Fifth Edition PTSD diagnosis based on ≥two PTEs, seek treatment for the first time and are employed. Patients with specified comorbid disorders and insufficient Dutch language proficiency are excluded. Participants are randomised to 800 min of either M-TFT or S-TFT. M-TFT consists of two once-weekly preparatory sessions, 10 twice-daily sessions of prolonged exposure, eye movement desensitisation and reprocessing therapy for 2 weeks and two once-weekly closing sessions. S-TFT consists of weekly sessions of one of five evidence-based treatment interventions. Outcomes are assessed at baseline and at 7 weeks, 17 weeks, 6 months and 9 months after baseline. Primary outcomes are clinical effectiveness in terms of PTSD symptom severity and cost-effectiveness based on quality of life measures and societal costs. Data will be analysed with linear mixed models.
Ethics and dissemination
This study protocol was approved by the Medical Ethics Review Board of the Amsterdam University Medical Center (NL86057.018.24). Participants will provide informed consent before enrolment in the trial. Results will be published in peer-reviewed journals and will be released to clinicians, patient groups and the general community.
Trial registration number
This protocol is registered at Overview of Medical Research in the Netherlands (OMON; trial register number 56960) and ClinicalTrials.gov (NCT06700590).
Assessment of the prevalence of stress, anxiety and depression in healthcare workers providing services related to communicable diseases in primary-level health units in Maputo city, Mozambique: an observational cross-sectional study protocol
Introduction
Mental health is essential for well-being and critical to the quality of care delivered by healthcare professionals. Health workers face increased risks of mental health disorders due to long hours, high emotional and physical demands, and exposure to communicable diseases, which exacerbate stress and anxiety levels. Evidence from low-income countries, including Mozambique, is scarce, yet health professionals in these regions frequently deal with the dual burden of communicable diseases and resource constraints. This study addresses a critical evidence gap by focusing on the mental health of healthcare professionals in Mozambique who are frequently exposed to psychological stress while managing communicable diseases. It aims to assess the prevalence of stress, anxiety and depression among healthcare workers providing services related to communicable diseases in primary-level health units (PHUs) in Maputo City, Mozambique. The study also seeks to identify personal and professional factors associated with these mental health disorders.
Methods and analysis
This is an observational cross-sectional study targeting healthcare workers in PHUs who provide services related to communicable diseases in Maputo City. Using convenience sampling, 382 participants will be recruited, stratified by health unit type. This sample size was calculated manually using the formula by Wang and Ji (2020). Data will be collected through a questionnaire, including demographic and professional information and a validated tool (Depression, Anxiety and Stress Scale, DASS-21), using the Research Electronic Data Capture (REDCap) Software for secure data capture. Descriptive and inferential statistical analyses will be performed using IBM SPSS Statistics to estimate prevalence rates and explore associated factors.
Ethics and dissemination
The study was approved by the Interinstitutional Committee on Bioethics in Health of the Faculty of Medicine/Maputo Central Hospital (CIBS FM&HCM/117/2024). Written informed consent will be obtained, and participants experiencing significant discomfort will be referred for mental health support. Findings will be disseminated via academic theses, peer-reviewed publications, national conferences, and reports shared with the Ministry of Health to inform mental health interventions for healthcare workers.
Registration
This protocol is registered with the Interinstitutional Committee on Bioethics in Health of the Faculty of Medicine/Maputo Central Hospital (CIBS FM&HCM).
Augmentation of trauma-focused psychotherapy for post-traumatic stress disorder: a protocol for a systematic review and meta-analysis
Introduction
Despite the established status of trauma-focused psychotherapy (TFP) as a first-line treatment for post-traumatic stress disorder (PTSD), a substantial proportion of individuals do not achieve clinically significant improvement or discontinue treatment. Exploring augmentation strategies to enhance treatment outcomes is essential to reduce the overall burden PTSD puts on individuals and society. This protocol outlines a systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating the efficacy of non-pharmacological augmentation strategies in addition to TFP for PTSD treatment.
Methods and Analysis
We comprehensively searched PubMed, Embase, CENTRAL, PTSDpubs, PsycArticles, PsycINFO, PSYNDEX and CINAHL for RCTs without restrictions on publication dates or languages in October 2024. Study screening is currently ongoing. Additionally, we will perform forward and backward searches of the included studies and relevant reviews. Two reviewers will independently screen and select studies, extract data and assess the risk of bias. We will conduct a narrative review to qualitatively synthesise data and a meta-analysis to quantitatively compare the treatment efficacy of augmented TFP with TFP alone or TFP plus placebo. Primary outcomes will be both symptom severity and response rates. The secondary outcome will be dropout rates. We will explore sources of between-study heterogeneity and potential moderators through subgroup and meta-regression analyses. We will assess the overall quality of the included studies with the Grading of Recommendations Assessment, Development, and Evaluation system.
Ethics and dissemination
Ethical approval is not required. We intend to publish results in a peer-reviewed journal and provide materials and data through the Open Science Framework.
PROSPERO registration number
CRD42024549435.
Association between problematic social media use and psychological distress among college students: a cross-sectional study in China exploring the mediating role of eating disorders
Objectives
This study aimed to examine the mediating role of eating disorders in the association between problematic social media use (PSMU) and psychological distress, including anxiety, depression and stress, among Chinese college students. The primary hypothesis was that eating disorders would partially mediate the relationship between PSMU and psychological distress.
Design
A cross-sectional study.
Setting
Participants were recruited from a vocational college in Jiangxi, China.
Participants
A total of 454 college students aged 18 years or older participated in the study. The median age was 19 years (IQR=18, 20), and 73.4% were male. Participants were included if they were enrolled in college and able to provide informed consent. Students undergoing psychological treatment or taking psychiatric medications were excluded.
Primary outcome measures
PSMU was assessed using the Bergen Social Media Addiction Scale, psychological distress was assessed using the Depression Anxiety Stress Scales-21 and eating disorder symptoms were assessed using the SCOFF questionnaire.
Results
PSMU was significantly associated with higher levels of psychological distress (r=0.321, p
Stepped wedge cluster randomised controlled trial to assess the impact of a decision support tool for physical restraint use in intensive care units (ARBORea Study): a study protocol
Introduction
Intensive care units (ICUs) manage patients with or likely to have one or more life-threatening acute organ failures that might require the use of invasive supportive therapies. The use of physical restraint is frequent, with rates up to 50%, and usually initiated to maintain patient safety especially if the patient is agitated. Physical restraints have been associated with delirium, post-traumatic stress disorder and physical injuries while restricting patients’ individual freedom. Moreover, the incidence of invasive therapeutic devices’ self-removal by patients might not be decreased by physical restraint use. No recommendation is available concerning ICU patients and physical restraint management, despite being a daily practice. The main objective is to evaluate whether a strategy aimed at decreasing physical restraint use in ICU patients with that of a strategy based on routine and subjective caregivers’ decision is safe and efficient.
Methods and analysis
ARBORea is a multicentre randomised, stepped-wedge trial testing an innovative, dedicated web-based, multiprofessionally developed, experts validated, nursing management strategy in comparison with standard care. The primary outcome is physical restraint use rate (effectiveness) measured at least every 8 hours and incidents’ rate (tolerance) defined as the rate of incidents attributable to non-compliance, corresponding to the deterioration or self-removal of critical devices, a fall or self-aggressive or heteroaggressive behaviours. Planned enrolment is 4000 ICU adult participants at 20 French academic and non-academic centres. Safety and long-term outcomes will be evaluated.
Ethics and dissemination
Trial results will be reported according to the Consolidated Standards of Reporting Trials 2010 guidelines. Findings will be published in peer-reviewed journals and presented at local, national and international meetings and conferences to publicise and explain the research to clinicians, commissioners and service users. The trial is funded by the French Ministry of Health and has been approved by the French local ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-Mer 2, Toulouse, France with registration number: 2020-A02904-35).
Trial registration number
(ClinicalTrials.gov) NCT04957238 on 12 July 2021 before first inclusion in study.
Novel Perivascular Macrophage Mechanism to Promote Glymphatic Aβ Clearance After Stroke
Stroke, Ahead of Print. BACKGROUND:Parenchymal border macrophages (PBMs) reside at the interface between the central nervous system and the periphery. They are known to mediate the accessibility of the substances to the brain. However, no one has examined their role in poststroke Aβ (amyloid-β) clearance.METHODS:Permanent focal cerebral ischemia was induced in 8- to 10-week-old C57/Bl6 male mice by distal middle cerebral artery occlusion. The clodronate liposomes were administered into the cerebral spinal fluid at 7 days before stroke to deplete the PBM population. Sensorimotor and cognitive functions, glymphatic system, and Aβ accumulation were assessed for up to 34 days after stroke.RESULTS:The Aβ accumulated along brain blood vessels after stroke in both the ipsilateral and contralateral hemispheres. When PBMs were depleted, glymphatic drainage of Aβ was markedly reduced, and this was accompanied by deterioration of cognitive function, highlighting a critical role for PBMs in poststroke Aβ disposal. A possible mechanism relates to MANF (mesencephalic astrocyte-derived neurotrophic factor). MANF derived from PBMs suppressed astrocytic stress and maintained glymphatic drainage when supplemented into the cerebral spinal fluid. In the chronic phase of stroke, MANF production in PBMs was downregulated, and consequently, glymphatic impairments were exacerbated, which led to ongoing Aβ accumulation and cognitive decline.CONCLUSIONS:In summary, supplementation of MANF not only mitigates the adverse impacts of PBM depletion but also exerts therapeutic effects that improve glymphatic system function. We thus propose that this represents a promising strategy to prevent poststroke cognitive impairment.
Cardiac Arrest in Long-Distance Running
Millions of people participate in long-distance running, particularly marathons and half-marathons, annually. While the health benefits of regular exercise are well established, long-distance running can cause significant cardiovascular stress, potentially increasing the risk of cardiac arrest in individuals with underlying heart conditions. This concern is particularly notable as the number of middle-aged and elderly runners—a population at higher average cardiovascular risk than younger runners—continues to rise. Understanding the incidence, causes, and outcomes of cardiac arrest in long-distance runners is crucial for informing risk, identifying prevention strategies, and optimizing race-day medical preparedness.