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Active Travel Mode and Incident Dementia and Brain Structure

JAMA Netw Open. 2025 Jun 2;8(6):e2514316. doi: 10.1001/jamanetworkopen.2025.14316.

ABSTRACT

IMPORTANCE: Active travel modes, such as walking and cycling, are feasible and readily embraced forms of physical activity, but their association with dementia risk and brain structure remains unclear.

OBJECTIVES: To investigate the long-term association between travel modes and dementia risk and brain structural metrics and to evaluate whether genetic predisposition could modify the association between travel modes and dementia risk.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included data collected from the UK Biobank from March 13, 2006, to October 1, 2010. Data were analyzed from March to October 2024.

EXPOSURES: Travel modes assessed using the question “In the last 4 weeks, which forms of transport have you used most often to get about (not including any journeys to and from work)?” and categorized into 4 groups: nonactive, walking, mixed-walking, and cycling and mixed-cycling mode.

MAIN OUTCOMES AND MEASURES: The incidence of all-cause dementia (including young-onset dementia [YOD] and late-onset dementia [LOD]) was the primary outcome, and dementia subtypes, such as Alzheimer disease (AD) and brain structure, were the secondary outcomes; all were identified through hospital records and death registers. Brain structure was measured by a magnetic resonance imaging scan. Travel mode and risk of incident dementia were assessed using Cox proportional hazards regression models with hazard ratios and 95% CIs.

RESULTS: The study encompassed 479 723 participants (mean [SD] age, 56.5 [8.1] years; 260 730 females [54.4%]), including 271 690 in the YOD analyses and 334 939 in the LOD analyses. Over a median follow-up of 13.1 years (IQR, 12.8-13.5 years), 8845 cases of dementia (1.8%) and 3956 cases of AD (0.8%) were recorded. Compared with a nonactive travel mode, multivariable-adjusted hazard ratios for cycling and mixed-cycling were 0.81 (95% CI, 0.73-0.91) for all-cause dementia, 0.78 (95% CI, 0.66-0.92) for AD, 0.60 (95% CI, 0.38-0.95) for YOD, and 0.83 (95% CI, 0.75-0.93) for LOD. A significant interaction between travel mode and genetic susceptibility in the all-cause dementia analysis (P = .02 for interaction) and the LOD analysis (P = .04 for interaction) was observed; specifically, for the cycling and mixed-cycling groups, the risks of all-cause dementia and LOD were lower among those without apolipoprotein E ε4 (APOE ε4) carrier status (all-cause dementia: hazard ratio [HR], 0.74 [95% CI, 0.63-0.87]; LOD: HR, 0.75 [95% CI, 0.63-0.89]) compared with those with APOE ε4 carrier status (all-cause dementia: HR, 0.88 [95% CI, 0.76-1.02]; LOD: HR, 0.91 [95% CI, 0.78-1.05]). The cycling and mixed-cycling mode was significantly associated with a higher hippocampal volume (β, 0.05 [95% CI, 0.02-0.08]). Genetic risk significantly modified the association with all-cause dementia (P = .02 for interaction) and LOD (P = .04 for interaction). Specifically, for the cycling and mixed-cycling groups, the risk of all-cause dementia was lower among those without APOE ε4 (HR, 0.74 [95% CI, 0.63-0.87]) compared with those with APOE ε4 (HR, 0.88 [95% CI, 0.76-1.02]). Similarly, the risk of LOD was lower among those without APOE ε4 (HR, 0.75 [95% CI, 0.63-0.89]) compared with those with APOE ε4 (HR, 0.91 [95% CI, 0.78-1.05]).

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest an association between active travel mode and incident dementia and brain structure. The cycling and mixed-cycling mode was associated with a reduced risk of all-cause dementia, including YOD, LOD, and AD, as well as an increased hippocampal volume, suggesting a promising approach for maintaining brain health.

PMID:40489111 | DOI:10.1001/jamanetworkopen.2025.14316

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Generating Timely Estimates of Overdose Deaths for the US Using Urine Drug Test Data

JAMA Netw Open. 2025 Jun 2;8(6):e2514402. doi: 10.1001/jamanetworkopen.2025.14402.

ABSTRACT

IMPORTANCE: Provisional estimates of fatal drug overdoses in the US are lagging by 6 months. Efforts to estimate the overdose burden for this 6-month lag window require up-to-date data, such as real-time urine drug test (UDT) data, capable of identifying sudden changes in the overdose trajectory, such as the increase in overdose deaths experienced at the beginning of the COVID-19 pandemic.

OBJECTIVE: To evaluate the utility of using aggregated UDT data to estimate national-level drug overdose deaths for the 6-month lag window in which overdose data are unavailable.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included 3 135 748 urine samples submitted for UDT by Millennium Health from patients aged 18 years or older in substance use disorder treatment health care facilities across the US between January 1, 2015, and January 31, 2025. Urine drug test results were aggregated to generate monthly positivity rates and mean creatinine-normalized levels of fentanyl and methamphetamine (among the sample testing positive for fentanyl). Monthly, national drug overdose mortality counts were obtained from the Centers for Disease Control and Prevention.

EXPOSURES: Urine drug testing.

MAIN OUTCOMES AND MEASURES: Drug overdose death totals were estimated for every 6-month period from January to June 2019 through August 2024 to January 2025 by training generalized linear models with a negative binomial distribution on the preceding 4 years of data and using monthly UDT data to generate overdose estimates for the 6-month lag window of interest. Mean absolute error (MAE), mean absolute percentage error (MAPE), and root mean squared error (RMSE) were calculated by comparing projected monthly estimates with observed overdose death totals.

RESULTS: A total of 3 135 748 UDT specimens (57.2% from men; mean [SD] age, 38.1 [12.4] years) were included in this study. From 2019 to August 2024, 537 104 people died of an overdose in the US, with a substantial increase in early 2020 at the onset of the COVID-19 pandemic. The UDT modeling strategy (MAPE, 7.1%; MAE, 540.9 deaths per month; RMSE, 659.4) outperformed the baseline autoregressive integrated moving average model (MAPE, 9.0%; MAE, 704.9 deaths per month; RMSE, 1075.8) across all metrics. Furthermore, the model detected the sudden increase in overdose deaths at the start of the COVID-19 pandemic.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, findings suggested that aggregated UDT data may be used to estimate up-to-date overdose death trends. Model implementation can be improved by introducing additional exposure variables, such as those related to drug seizures and syndromic surveillance.

PMID:40489110 | DOI:10.1001/jamanetworkopen.2025.14402

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Long-Term Coronary Microvascular and Cardiac Dysfunction After Severe COVID-19 Hospitalization

JAMA Netw Open. 2025 Jun 2;8(6):e2514411. doi: 10.1001/jamanetworkopen.2025.14411.

ABSTRACT

IMPORTANCE: COVID-19 can lead to long-term cardiopulmonary symptoms and is associated with coronary microvascular dysfunction (CMD). However, long-term data on CMD after severe COVID-19 are lacking.

OBJECTIVE: To investigate long-term left ventricular function and the presence of CMD after severe COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study was conducted among patients at a single center from the prospective Follow-Up of Patients With Severe COVID-19 (UppCov) study, with follow-up multiparametric perfusion cardiovascular magnetic resonance (CMR) at 10 months after discharge from November 2020 to February 2021. Patients previously hospitalized due to severe COVID-19 (ventilatory support, oxygen flow ≥5 L/min, or both) with or without cardiac involvement (troponin t > 14 ng/L, pulmonary artery pressure >34 mm Hg, or both) were compared with historical sex- and age-matched volunteers without symptomatic ischemic heart disease. Standard contraindications to adenosine CMR were applied. Data were analyzed between March 2023 and March 2025.

EXPOSURE: Hospitalization due to severe COVID-19.

MAIN MEASURES AND OUTCOMES: Comprehensive CMR included native T1, native T2, extracellular volume, adenosine stress and rest perfusion mapping, gadolinium enhancement, and cine imaging. Comorbidities, medications, symptoms at follow-up, and details regarding hospitalization were obtained from patient records.

RESULTS: The study included 37 patients with COVID-19 (mean age, 56 years [95% CI, 53 to 61 years]; 28 male [75.7%]) and 22 healthy volunteers (mean age, 51 years [95% CI, 45 to 57 years]; 12 male [54.4%]). Patients with COVID-19 compared with healthy patients demonstrated reduced mean stress perfusion (2.80 mL/min/g [95% CI, 2.53 to 3.07 mL/min/g] vs 3.43 mL/min/g [95% CI, 3.13 to 3.74 mL/min/g]; P = .003), impaired mean global longitudinal strain (-17% [95% CI, -18% to -16%] vs -19% [-20% to -18%]; P = .003), and impaired mean global circumferential strain (-16% [95% CI, -17% to -15%] vs -19% [-20% to -18%]; P = .001). There were no differences in stress perfusion or myocardial perfusion reserve in the COVID-19 group between patients with vs without cardiovascular risk factors or cardiac symptoms.

CONCLUSIONS AND RELEVANCE: In this study, patients with COVID-19 exhibited long-term reduced stress perfusion indicating CMD, along with declined left ventricular function by global longitudinal strain and global circumferential strain. Lack of variation in stress perfusion between patients with and without cardiovascular risk factors may suggest CMD due to severe COVID-19, warranting further investigation to elucidate mechanisms and guide potential therapies.

PMID:40489109 | DOI:10.1001/jamanetworkopen.2025.14411

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Efficacy and safety of low-dose prasugrel as dual antiplatelet therapy in patients with ischemic heart disease: a systematic review and network meta-analysis of randomized controlled trials

Cardiovasc Interv Ther. 2025 Jun 9. doi: 10.1007/s12928-025-01129-2. Online ahead of print.

ABSTRACT

Low-dose prasugrel could provide a better balance between adverse ischemic and bleeding events compared to other P2Y12 receptor inhibitors as part of dual antiplatelet therapy (DAPT) for patients with ischemic heart disease. This study evaluated these risks of adverse events associated with low-dose prasugrel and other P2Y12 receptor inhibitors. A network meta-analysis was conducted, searching for randomized controlled trials (RCTs) comparing clopidogrel (75 mg), low-dose (3.75 mg) and standard-dose (10 mg or 5 mg) prasugrel, or ticagrelor (180 mg). The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, or stroke. The secondary endpoint was major bleeding, cardiovascular death, myocardial infarction, and stroke. Across 13 RCTs, neither low-dose prasugrel, standard-dose prasugrel, nor ticagrelor showed a statistically significant difference in MACE compared to clopidogrel [risk ratio (RR): 0.73, 95% confidence interval (CI) 0.49-1.09; RR: 0.86, 95% CI 0.68-1.09; RR: 1.02, 95% CI 0.62-1.67, respectively]. However, the standard dose of prasugrel was associated with a significantly higher risk of bleeding events compared to clopidogrel (RR, 0.72; 95% CI 0.35-1.49; RR, 1.26; 95% CI 1.01-1.58; RR, 1.26; 95% CI 0.82-1.96). The surface under the cumulative ranking curves was highest for low-dose prasugrel for both MACE and bleeding events (17.3 and 64.6 for clopidogrel, 84.5 and 84.9 for low-dose prasugrel, 62.0 and 11.8 for standard-dose prasugrel, and 36.2 and 38.7 for ticagrelor, respectively). Low-dose prasugrel may be a viable option in addition to standard P2Y12 receptor inhibitors.

PMID:40489021 | DOI:10.1007/s12928-025-01129-2

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Comparative accuracy of two commercial AI algorithms for musculoskeletal trauma detection in emergency radiographs

Emerg Radiol. 2025 Jun 9. doi: 10.1007/s10140-025-02353-2. Online ahead of print.

ABSTRACT

PURPOSE: Missed fractures are the primary cause of interpretation errors in emergency radiology, and artificial intelligence has recently shown great promise in radiograph interpretation. This study compared the diagnostic performance of two AI algorithms, BoneView and RBfracture, in detecting traumatic abnormalities (fractures and dislocations) in MSK radiographs.

METHODS: AI algorithms analyzed 998 radiographs (585 normal, 413 abnormal), against the consensus of two MSK specialists. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and interobserver agreement (Cohen’s Kappa) were calculated. 95% confidence intervals (CI) assessed robustness, and McNemar’s tests compared sensitivity and specificity between the AI algorithms.

RESULTS: BoneView demonstrated a sensitivity of 0.893 (95% CI: 0.860-0.920), specificity of 0.885 (95% CI: 0.857-0.909), PPV of 0.846, NPV of 0.922, and accuracy of 0.889. RBfracture demonstrated a sensitivity of 0.872 (95% CI: 0.836-0.901), specificity of 0.892 (95% CI: 0.865-0.915), PPV of 0.851, NPV of 0.908, and accuracy of 0.884. No statistically significant differences were found in sensitivity (p = 0.151) or specificity (p = 0.708). Kappa was 0.81 (95% CI: 0.77-0.84), indicating almost perfect agreement between the two AI algorithms. Performance was similar in adults and children. Both AI algorithms struggled more with subtle abnormalities, which constituted 66% and 70% of false negatives but only 20% and 18% of true positives for the two AI algorithms, respectively (p < 0.001).

CONCLUSIONS: BoneView and RBfracture exhibited high diagnostic performance and almost perfect agreement, with consistent results across adults and children, highlighting the potential of AI in emergency radiograph interpretation.

PMID:40489014 | DOI:10.1007/s10140-025-02353-2

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User Engagement with A Multimodal Conversational Agent for Self-Care and Chronic Disease Management: A Retrospective Analysis

J Med Syst. 2025 Jun 9;49(1):76. doi: 10.1007/s10916-025-02202-2.

ABSTRACT

INTRODUCTION: Understanding user engagement with conversational agents is key to their sustainable use in mobile health and improving patient outcomes. This retrospective study analyzed interactions with a multimodal conversational agent in the Albert Health app to identify usage patterns and barriers to long-term engagement in self-care and chronic disease management.

METHODS: We retrospectively analyzed interactions from 24,537 users of a Turkish-language mobile health app (between January 1, 2022, and December 31, 2023). Interactions with the app’s multimodal conversational agent (voice and text) were categorized by demographics, interaction type, and engagement mode. Descriptive statistics summarized patterns, while Mann-Whitney U, Chi-square, and logistic regression identified group differences and predictors of sustainable engagement.

RESULTS: Most users were female (56%) and aged 30-45 (44%). The majority (92%) used general health programs, with only 8% in disease-specific ones. Common interaction types included health information (32%), small talk (20%), and clinical parameter logging (16%; e.g., blood pressure). Voice use was frequent in fallback (80%; unclear/ out-of-scope input), small talk (64%), and medication tasks (53%), while screen input was more common for clinical logging (61%) and health queries (59%). Engagement peaked in the first week and declined after 10 days. Sustainable engagement was associated with disease-specific program use (OR = 0.67, 95%CI: 0.60-0.74, p < 0.001), greater voice interaction (OR = 1.005, 95%CI: 1.004-1.006, p < 0.001), and a balanced mix of clinical and non-clinical use (OR = 1.56, 95%CI: 1.43-1.70, p < 0.05).

CONCLUSIONS: This study highlights user preferences for voice interaction and health information access when using a multimodal conversational agent. The high rate of single-session users (58%) points to barriers to sustainable engagement, emphasizing the need for better user experience strategies.

PMID:40488988 | DOI:10.1007/s10916-025-02202-2

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Bayesian Meta-Analysis: A Practical Introduction

Pharmacoeconomics. 2025 Jun 9. doi: 10.1007/s40273-025-01510-2. Online ahead of print.

NO ABSTRACT

PMID:40488987 | DOI:10.1007/s40273-025-01510-2

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Comparative analysis of cardiac dysfunction in non-functioning adrenal adenomas, primary aldosteronism, and essential hypertension

J Endocrinol Invest. 2025 Jun 9. doi: 10.1007/s40618-025-02594-5. Online ahead of print.

ABSTRACT

BACKGROUND: Speckle tracking echocardiography (STE) provides a quantitative assessment of left ventricular systolic performance, including myocardial motion and deformation. Global longitudinal strain (GLS) is a reliable and sensitive indicator of systolic function, with clinical and prognostic value in various settings, including secondary hypertension. There is limited data on GLS evaluation in patients with non-functioning adrenal adenomas (NF), despite emerging evidence suggesting its association with subclinical cardiovascular dysfunction. Investigating the cardiac impact of NF is essential for understanding its role in early cardiac remodeling compared to primary aldosteronism (PA) and essential hypertension (EH).

OBJECTIVE: To retrospectively evaluate the utility of GLS in detecting early cardiac dysfunction in patients with NF, PA, and EH without adrenal adenoma or hyperplasia.

METHODS: This retrospective study included 33 patients with NF, 33 with PA, and 33 with EH, matched by gender and age. Speckle tracking echocardiography was used to assess the GLS of the left ventricle. Data analysis was conducted using IBM SPSS Statistics version 29.0, with a significance threshold set at P < 0.050.

RESULTS: The GLS in NF patients (-20.63 ± 3.10%) was significantly lower than in EH patients (-22.17 ± 3.03%) but higher than in PA patients (-18.55 ± 2.45%), despite NF patients having the lowest prevalence of hypertension and systolic blood pressure. GLS was significantly correlated with cortisol levels, impaired glucose tolerance, and ARR across all patient groups, highlighting the complex interplay between metabolic and hormonal factors in cardiac dysfunction.

CONCLUSION: Cardiac function impairment in NF patients lies between that observed in EH and PA patients, suggesting a nuanced impact of non-functioning adrenal adenomas on cardiac health.

PMID:40488985 | DOI:10.1007/s40618-025-02594-5

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Fertility and parturition parameters in beef type heifers

Trop Anim Health Prod. 2025 Jun 9;57(5):250. doi: 10.1007/s11250-025-04505-5.

ABSTRACT

This study compared fertility and parturition parameters in Limousin (L) and Charolais (C) heifers to identify the breed most suitable for beef production. A total of 234 L and 76 C Hungarian-origin heifers, aged 9-11 months, were managed under standardized housing and feeding conditions at Dogan Farm. Parturitions were categorized based on the time of day (day: 07:00-19:00; night) and season (cold, cool, hot). Statistical analyses were conducted using ANOVA and Chi-square tests Results showed that C heifers required significantly more inseminations to conceive (C: 3.39 ± 0.22, L: 2.32 ± 0.10, P < 0.0001), indicating lower reproductive efficiency. Additionally, C calves were significantly heavier at birth than L calves (C: 46.1 ± 0.8 kg, L: 40.2 ± 0.3 kg, P < 0.0001), with male calves being generally heavier than females (M: 43.7 ± 0.5 kg, F: 39.5 ± 0.3 kg, P < 0.0001). The incidence of dystocia was higher in C heifers (63.16%) compared to L heifers (41.88%), while L heifers experienced greater parturition ease (58.12% vs. 36.84%; X2 = 10.4244, P < 0.0054).

PMID:40488966 | DOI:10.1007/s11250-025-04505-5

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Prevalence of ocular allergy among adults in Trinidad and Tobago: A cross-sectional study

Int Ophthalmol. 2025 Jun 9;45(1):235. doi: 10.1007/s10792-025-03613-3.

ABSTRACT

BACKGROUND: Ocular allergy (OA) is a significant public health concern, but its prevalence remains underreported due to underdiagnosis. This study aims to determine the prevalence of OA among adults in Trinidad and Tobago.

METHOD: A descriptive cross-sectional study was conducted using an online questionnaire to assess OA prevalence. Sociodemographic, environmental, and systemic characteristics of participants were also evaluated. Data was analyzed using SPSS with both descriptive and inferential statistical techniques, including bi-variable and multivariable logistic regression.

RESULTS: A total of 591 participants completed the survey with majority (73.6%) as female and aged 18-24 years (50.1%). The overall prevalence of OA was 41.6% (95% CI, 37.2-45.0), with seasonal OA being the most common (80.1%). OA symptoms were most prevalent in spring (62.1%), with light sensitivity reported by 57.7% of participants. Bi-variable analysis identified asthma, allergic rhinitis, pollen allergy, and exposure to environmental factors such as cigarettes and air conditioning as associated with OA. Multivariable analysis confirmed these associations, with significant p-values for asthma (0.017), allergic rhinitis (0.035), pollen allergy (< 0.001), mite allergy (0.038), cigarettes (0.006), air conditioning (< 0.001), and OA awareness (< 0.001).

CONCLUSION: There is a high prevalence of OA among adults in Trinidad and Tobago, with systemic and environmental allergens playing a significant role. Interventions to reduce exposure to allergens, such as using indoor air filters and managing allergic conditions, could help mitigate OA prevalence. Regular assessment of patients with allergic rhinitis and asthma for OA is recommended.

PMID:40488956 | DOI:10.1007/s10792-025-03613-3