tbuckley/cabot-search huggingface dataset:
Use of gabapentinoid treatment and the risk of self-harm: population based self-controlled case series study
Authors: Andrew S C Yuen, Boqing Chen, Adrienne Y L Chan, Joseph F Hayes, David P J Osborn, Frank M C Besag, Wallis C Y Lau, Ian C K Wong, Li Wei, Kenneth K C Man
Journal: BMJ (2025)

To estimate the effect of gabapentinoid treatment on self-harm. A population based self-controlled case series study. UK Clinical Practice Research Datalink Aurum database linked to the Hospital Episode Statistics and Office for National Statistics databases. 10 002 adults (aged ≥18 years), with gabapentinoid prescriptions, who had an incident event of self-harm between 1 January 2000 and 31 December 2020. Individual censoring occurred on the date of epilepsy, substance misuse, or cancer diagnosis. Crude incidence rates of self-harm in different risk periods: 90 days before gabapentinoid treatment, gabapentinoid treatment period, 14 days after treatment periods, and reference periods were calculated. Conditional Poisson regression derived the incidence rate ratio and 95% confidence intervals (CIs) to evaluate the risk of self-harm in different risk periods, compared with reference period for each individual. 1 503 597 individuals received gabapentinoid prescriptions and 10 002 individuals were included in the analysis. The incidence rate of self-harm per 100 person years was 16.79 (95% CI 16.65 to 16.92) in the 90 days before treatment period, 9.66 (9.62 to 9.70) in the treatment period, 29.60 (29.09 to 30.11) in the 14 days after treatment period, and 6.75 (6.74 to 6.77) in the reference period. The results yielded an increased risk of self-harm during the 90 day period before treatment, with an adjusted incidence rate ratio of 1.69 (95% CI 1.55 to 1.85). The spline based analysis showed that the risk of self-harm declined gradually around the time of treatment initiation and returned to reference level during the treatment period (adjusted incidence rate ratio 1.06 (0.98 to 1.13)). Adjusted incidence rate ratio for self-harm increased within 14 days after treatment cessation (3.02 (2.53 to 3.60)). The findings remained consistent throughout a series of subgroups and sensitivity analyses. The association between gabapentinoids and risk of self-harm seems to be multifaceted: an elevated risk of self-harm is present before initiation of gabapentinoid treatment, which persists during the initial phase of the treatment period, and rises again shortly after treatment discontinuation. These findings do not support a direct effect of gabapentinoid treatment on self-harm but underscore the necessity for close patient monitoring of self-harm throughout the gabapentinoid treatment journey.
Identification of soluble biomarkers that associate with distinct manifestations of long COVID
Authors: Yu Gao, Curtis Cai, Sarah Adamo, Elsa Biteus, Habiba Kamal, Lena Dager, Kelly L Miners, Sian Llewellyn-Lacey, Kristin Ladell, Pragati S Amratia, Kirsten Bentley, Simon Kollnberger, Jinghua Wu, Mily Akhirunnesa, Samantha A Jones, Per Julin, Christer Lidman, Richard J Stanton, Paul A Goepfert, Michael J Peluso, Steven G Deeks, Helen E Davies, Soo Aleman, Marcus Buggert, David A Price
Journal: Nature Immunology (2025)
Systematic evaluation of patient-reported outcomes in clinical trials of digital health in cardiovascular diseases
Authors: Qianying Wang, Xiqian Huo, Jianlan Cui, Jie Li, Xueke Bai, Chaoqun Wu, Qian Zhang, Dianjianyi Sun, Jie Zhao
Journal: npj Digital Medicine (2025)

The integration of patient-reported outcomes (PROs) in digital health (DH) trials for cardiovascular diseases (CVDs) remains unknown. We searched ClinicalTrials.gov for randomized trials that tested DH interventions in CVDs from 2004 to 2024. The search identified 8037 trials, with 673 eligible trials included in the analysis. Among these, 321 trials (48%) incorporated PROs. The number of DH trials and the use of PROs have shown a significant upward trend. Phone-based interventions predominated (38%), mostly targeting hypertension (38%) and heart failure (27%). Behavioral interventions showed higher prevalence of PROs' usage (1.24 [1.04-1.48]), while trials for diagnostic or screening purpose (0.39 [0.20-0.77]) utilized PROs less frequently. Only 15% of trials reported results on ClinicalTrials.gov, while 58% were published in PubMed after completion. Despite DH trial expansion, PRO integration remains insufficient, especially in trials where clinical and patient perspectives are important in informing treatment decisions. Timely results dissemination is critical to improving transparency.
Net Benefit of Anticoagulation in Subclinical Device-Detected Atrial Fibrillation
Authors: Aleksi K. Winstén, Ville Langén, K. E. Juhani Airaksinen, Konsta Teppo
Journal: JAMA Network Open (2025)

Importance The role of anticoagulation for stroke prevention in patients with device-detected atrial high-rate episodes, also known as subclinical atrial fibrillation (AF), is a subject of equipoise. Objective To assess the net benefit of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with device-detected subclinical AF. Design, Setting, and Participants Decision analytical model run with 10 000 patients with anticoagulation and 10 000 patients without anticoagulation in a clinical scenario of deciding whether to start NOACs for stroke prevention in patients with subclinical AF. A Markov decision model was conducted on October 1, 2024, to estimate net outcomes of NOACs. The patients had stroke risk and bleeding risks similar to those of patients in randomized trials of anticoagulation in subclinical AF. Exposure Anticoagulation was modeled to decrease the risk of ischemic stroke by 32% and increase the risk of major bleeding by 62%. In probabilistic sensitivity analyses, the 95% CIs for treatment effect sizes were also considered. Main Outcomes and Measures The main outcome measure for overall net benefit was the cumulative quality-adjusted life-years (QALYs) during the simulation. The model considered the number and severity of ischemic strokes, hemorrhagic strokes, other intracranial bleeds, and extracranial bleeds, as well as the number of deaths during a 10-year simulation. Results When comparing the 2 cohorts of 10 000 patients (mean age, 77 years; 3700 [37%] women), those receiving NOAC therapy had 233 fewer ischemic strokes (21.7%), 55 fewer deaths (1.1%), and 453 more major bleeding events (37.3%) over a 10-year simulation period. Per patient, these differences translated to approximately 1 additional quality-adjusted week of life (0.024 QALYs) with NOAC treatment during the 10-year simulation. When the 95% CIs of treatment effect sizes were considered in probabilistic sensitivity analysis, there was a 65.8% probability that NOAC treatment leads to more QALYs than withholding treatment. Conclusions and Relevance In this analytical model study, initiating NOACs in patients with device-detected subclinical AF was associated with a minimal increase in QALYs. However, the benefits were uncertain, and the effect size of the overall net benefit does not appear to be clinically meaningful.
Emergency Department Triage Accuracy and Delays in Care for High-Risk Conditions
Authors: Dana R. Sax, E. Margaret Warton, Dustin G. Mark, Mary E. Reed
Journal: JAMA Network Open (2025)

Importance Emergency department (ED) triage may impact timeliness of care for high-risk conditions. Objective To determine the association of ED undertriage with delays in care for patients with subarachnoid hemorrhage (SAH), aortic dissection (AD), and ST-elevation myocardial infarction (STEMI). Design, Setting, and Participants This retrospective cohort study included adult ED patients diagnosed with SAH, AD, or STEMI from January 1, 2016, to December 31, 2020, from a multicenter, community-based health care delivery system. Data analysis were completed in March 2023 to October 2024. Exposure Undertriage vs correct triage, defined by operational measures of mistriage. Main Outcomes and Measures Using a lognormal distribution, the outcomes of interest for patients with SAH and AD were adjusted median time to noncontrast computed tomography (CT) (head CT for patients with SAH, chest CT for patients with AD), antihypertensive medication orders (SAH), and β-blocker orders (AD), and ED length of stay (LOS). For patients with STEMI, outcomes of interest were adjusted median time to electrocardiogram (ECG) and troponin orders. Results A total of 5929 patients (median [IQR] age, 63.0 [54.0 to 73.0] years; 3876 [65.4%] male) were identified, including 915 with SAH, 480 with AD, and 4534 with STEMI. There were 1129 Asian patients (19.0%), 553 Black patients (9.3%), 889 Hispanic patients (15.0%), and 2906 non-Hispanic White patients (49.0%). Overall, 2175 patients (36.7%) were undertriaged. For patients with SAH, the lognormal estimate for delay in time to head CT was 0.2 (95% CI, 0.0-0.3), or a delay of 2.4 minutes, and for antihypertensive orders, the lognormal estimate was 4.8 (95% CI, 3.6-5.9), or a delay of 33.3 minutes; the lognormal estimate for ED LOS was 0.1 (95% CI, 0.0-0.1), or 7.7 minutes longer. For patients with AD, the lognormal estimate for delays were 0.2 (95% CI, 0.0-0.4), or 8.9 minutes, for chest CT and 0.5 (95% CI, 0.2-0.7), or 17.6 minutes, for β-blocker orders, and ED LOS was 0.2 (95% CI, 0.1-0.3), or 64 minutes longer. For patients with STEMI, differences in time to ECG and troponin orders were not statistically significant, at less than 1 minute, comparing correctly and undertriaged patients. Conclusions and Relevance In this cohort study of patients diagnosed with SAH, AD, or STEMI, ED undertriage was associated with small but significant delays in key diagnostic and therapeutic orders for patients with SAH and AD but not for patients with STEMI.
State-Level Tax Policy, Cancer Screening, and Mortality Rates in the US
Authors: Odysseas P. Chatzipanagiotou, Mujtaba Khalil, Usama Waqar, Selamawit Woldesenbet, Giovanni Catalano, Timothy M. Pawlik
Journal: JAMA Network Open (2025)

Importance The Healthy People 2030 initiative has set national cancer screening targets for breast, colon, and cervical cancers, as well as aims for reducing cancer mortality. State-level tax policy is an underappreciated social determinant of health that may improve cancer screening and mortality rates. Objective To define the association of tax revenue and tax progressivity with state-level cancer screening and mortality. Design, Setting, and Participants This ecologic, population-based, cross-sectional study assessed cancer screening (2020 and 2022) and mortality rates (1999-2021) in the US relative to state-level tax revenue (1997-2019) and tax progressivity (2002, 2009, 2012, 2014, and 2018) with a 2-year lag. The study included 50 states through 23 years with state-years used as the unit of analysis. Cancer screening rates were derived from the Centers for Disease Control and Prevention (CDC) Population Level Analysis and Community Estimates database. State-level cancer-related death and population counts were derived from the CDC Wide-Ranging Online Data for Epidemiologic Research database. Data analysis occurred from September to January 2024. Exposure State-level tax policy was proxied by tax revenue per capita and the Suits index of tax progressivity, with progressive taxation equaling lower tax burden for more disadvantaged populations. Main Outcomes and Measures Outcomes included screening rates for colon, breast, and cervical cancer, as well as mortality rates for all malignant neoplasms and malignant neoplasms with guideline-recommended screening. Multivariable models were adjusted for tax-related, socioeconomic, and demographic variables. Results In total, 1150 state-years were included in the analysis. Median (IQR) tax revenue per capita was $4432 ($3862-$5210), and the median (IQR) number of cancer-related deaths was 8341 (3150-13 585) across all state-years. Of note, each $1000 increase in tax revenue per capita was associated with a 1.61% (95% CI, 0.50%-2.73%) increase in colorectal cancer screening, 2.17% (95% CI, 1.39%-2.96%) increase in breast cancer screening, and 0.72% (95% CI, 0.34%-1.10%) increase in cervical cancer screening rate. For malignant neoplasms with guideline-recommended screening, each $1000 increase in tax revenue per capita was associated with a decreased cancer mortality rate among White (adjusted incidence rate ratio, 0.95, 95% CI, 0.93-0.98), but not racial and ethnic minority (adjusted incidence rate ratio, 0.99, 95% CI, 0.97-1.02) populations. Conclusions and Relevance In this cross-sectional study, tax policy was associated with increased state-level cancer screening rates, as well as decreased cancer mortality rates, which mostly benefited White populations, suggesting that state-level policies may contribute to bridging ongoing cancer care gaps.
Medicare Parity and Outpatient Mental Health Service Use and Costs Among Beneficiaries With Depression
Authors: Sonia M. Tetlow, Victoria L. Phillips, Jason M. Hockenberry
Journal: JAMA Network Open (2025)

Importance Less than half of the US population with any mental health condition receives services. Cost is the most commonly cited barrier to treatment. Objective To examine whether service use and out-of-pocket expenditures among Medicare beneficiaries with depression changed after Medicare implemented equal cost-sharing for outpatient mental health and medical services (Medicare parity). Design, Setting, and Participants This economic evaluation used a single-group, interrupted time series design and examined data from the Medical Expenditure Panel Survey Household Component from 2008 to 2019. The sample included Medicare beneficiaries aged 65 years or older with depression. Data were analyzed from June 2, 2023, to June 17, 2024. Exposure Under the Medicare Improvements for Patients and Providers Act of 2008, beneficiary cost-sharing for outpatient mental health services decreased from 50% prior to 2010 to 20% in 2014, creating parity with equivalent medical care. Main Outcomes and Measures The primary outcomes were outpatient mental health service use, as assessed by mean use, proportion of beneficiaries with any use, and intensity of use (ie, mean use among users), and out-of-pocket expenditures. Results The analysis included 5831 Medicare beneficiaries. Using the Medical Expenditure Panel Survey person-level survey weights, this number corresponded to a nationally representative sample of 72 436 656 beneficiaries (median [IQR] age, 72 [68-79] years; 64.2%-72.2% female per study year). After Medicare parity, mean use of outpatient mental health services among beneficiaries with depression increased by 0.54 visits per year (95% CI, 0.31-0.76 visits per year), and proportion of use increased by 6.61% per year (95% CI, 2.23%-10.99% per year). Intensity of use decreased at parity by a factor of 0.90 (95% CI, 0.82-1.00) and increased after parity by a multiple of 1.07 per year (95% CI, 1.04-1.10 per year). Mean out-of-pocket expenditures for these services increased after parity by $12.25 per year (95% CI, $2.42-$22.08 per year). Sensitivity analysis using the 2016 US Preventive Services Task Force recommendation for routine adult depression screening indicated that the proportion of use increased 28.26% (95% CI, 24.33%-32.19%) once the recommendation was issued. Conclusions and Relevance In this economic evaluation of Medicare parity, implementation of Medicare parity coupled with routine adult depression screening was associated with significant increases in outpatient mental health service use among Medicare beneficiaries with depression. These findings suggest that parity policies alone may not be sufficient to effectively address multiple barriers to mental health care but in tandem with physician screening, diagnosis, and referral practices, may increase the accessibility of mental health services.
Medicaid Unwinding and Changes in Buprenorphine Dispensing
Authors: Joanne Constantin, Genevieve M. Kenney, Kosali Simon, Kao-Ping Chua
Journal: JAMA Network Open (2025)

Importance After the Medicaid continuous enrollment provision ended on March 31, 2023, millions of Medicaid patients were disenrolled, a process called “Medicaid unwinding.” Whether this process was associated with changes in dispensing of buprenorphine, a medication for opioid use disorder preventing opioid overdose deaths, is unknown. Objective To evaluate changes in buprenorphine dispensing during Medicaid unwinding. Design, Setting, and Participants This cross-sectional study used difference-in-differences analysis to assess data from the IQVIA Longitudinal Prescription Database, capturing 92% of US retail prescriptions. Treatment and comparison states were those in the top vs bottom quartile of the percentage change in adult Medicaid enrollment between the month before the state resumed Medicaid eligibility determinations and December 31, 2023. Analyses included Medicaid-insured adults with active buprenorphine prescriptions in quarter 1 from 2017 to 2023. Exposure State-level change in adult Medicaid enrollment. The preexposure period was from July 1, 2017, to December 31, 2022, and the postexposure period was from July 1 to December 31, 2023 (quarters 3 and 4). Main Outcomes and Measures Four outcomes assessed buprenorphine dispensing in quarters 3 and 4 from 2017 to 2023: the number of days with active buprenorphine prescriptions, no active prescriptions, 1 or more active prescriptions paid with private insurance, and 1 or more active cash-pay prescriptions. Linear and logistic regression models compared changes in outcomes over time among treatment and comparison states. Results Analyses included 754 675 person-years from 569 069 patients (mean [SD] age, 39.2 [9.6] years; 386 719 men [51.2%]). Among adults in treatment states, the number of days with active buprenorphine prescriptions in quarters 3 and 4 decreased by 3.9 days (95% CI, −6.7 to −1.1 days) more compared with adults in comparison states. Adults in treatment states also had an increase of 1.8 percentage points (95% CI, 0.6-3.0 percentage points) in the probability of having no days with active prescriptions, an increase of 1.9 percentage points (95% CI, 0.4-3.4 percentage points) in the probability of having 1 or more active prescriptions paid with private insurance, and an increase of 0.9 percentage points (95% CI, 0.1-1.7 percentage points) in the probability of having 1 or more active cash-pay prescriptions. Conclusions and Relevance In this cross-sectional study using difference-in-differences analysis, Medicaid patients in states with the highest vs lowest magnitude of Medicaid disenrollment through December 2023 were more likely to decrease or discontinue buprenorphine use and more likely to transition to private insurance or cash to pay for prescriptions. Findings suggest that Medicaid unwinding was associated with disruptions in buprenorphine therapy, raising concerns about the potential for increased opioid-related morbidity and mortality among patients in this population.
Distinct type I and II interferon responses direct cortical and medullary thymic epithelial cell development
Authors: Abdulvasey Mohammed, Wenqing Wang, Martin Arreola, Benjamin D. Solomon, Priscila F. Slepicka, Kelsea M. Hubka, Hanh Dan Nguyen, Zihao Zheng, Michael G. Chavez, Christine Y. Yeh, Doo Kyung Kim, Michael R. Ma, Elisabeth Martin, Li Li, Anca M. Pasca, Virginia D. Winn, Casey A. Gifford, Veronika R. Kedlian, Jong-Eun Park, Purvesh Khatri, Georg A. Hollander, Maria Grazia Roncarolo, Vittorio Sebastiano, Sarah A. Teichmann, Andrew J. Gentles, Katja G. Weinacht
Journal: Science Immunology (2025)

Advances in genomics have redefined our understanding of thymic epithelial heterogeneity and architecture, yet signals driving thymic epithelial differentiation remain incompletely understood. Here, we elucidated pathways instructing human thymic epithelial cell development in the context of other anterior foregut–derived organs. Activation of interferon response gene regulatory networks distinguished epithelial cells of the thymus from those of other anterior foregut–derived organs. Thymic cortex and medulla epithelia displayed distinctive interferon-responsive signatures defined by lineage-specific chromatin accessibility. We explored the effects of type I and II interferons on thymic epithelial progenitor differentiation from induced pluripotent stem cells. Type II interferon was essential for expressing proteasome and antigen-presenting molecules, whereas type I or II interferons were essential for inducing different cytokines in thymic epithelial progenitor cells. Our findings suggest that interferons are critical to cortical and medullary thymic epithelial cell differentiation.
Increased risk of psychiatric disease in patients with prurigo nodularis
Authors: Salam Alfarsi, Andreas Recke, Evelyn Gaffal, Jan P Klein, Henner Zirpel, Khalaf Kridin, Diamant Thaci, Henning Olbrich, Katja Bieber, Ralf J Ludwig
Journal: British Journal of Dermatology (2025)

Prurigo nodularis (PN) is a chronic skin disorder. Emerging, though limited, evidence suggests an association between PN and psychiatric comorbidities. Furthermore, the temporal relationship between PN and the onset of psychiatric conditions remains unclear. To address these unresolved, clinically relevant questions, retrospective cohort studies were conducted. Here, PN patients exhibited significantly higher risks of suicidal ideations, depressive disorders, and schizophrenia compared to matched controls. The findings underscore the importance of integrating mental health screening and support into PN patient care.
Cell type–specific efferocytosis determines functional plasticity of alveolar macrophages
Authors: Julian Better, Mohammad Estiri, Michael Wetstein, Learta Pervizaj-Oruqaj, Christina Malainou, Victoria Ogungbemi-Alt, Maximiliano Ruben Ferrero, Martin Langelage, Irina Kuznetsova, Ana Ivonne Vazquez-Armendariz, Lucas Kimmig, Oleg Pak, Siavash Mansouri, Rajkumar Savai, Jochen Wilhelm, Ioannis Alexopoulos, Natascha Sommer, Susanne Herold, Ulrich Matt
Journal: Science Immunology (2025)

Resolution of lung injuries is vital to maintain gas exchange, but there is an increased risk of secondary bacterial infections during this stage. Alveolar macrophages (AMs) are crucial to clear bacteria and control the resolution of inflammation, but environmental cues that switch functional phenotypes of AMs remain incompletely understood. Here, we found that AMs lack the capacity to mount an effective immune response against bacteria during resolution of inflammation. Neutrophil (PMN)–derived myeloperoxidase (MPO) fueled canonical glutaminolysis via the mitochondrial membrane transporter uncoupling protein–2 (UCP2), resulting in decreased mtROS-dependent killing of bacteria and secretion of pro-inflammatory cytokines. MPO-enhanced UCP2 expression inhibited mitochondrial hyperpolarization and boosted efferocytosis irrespective of the presence of bacterial pathogens. Conversely, efferocytosis of other cell types resulted in a distinct anti-inflammatory AM phenotype while maintaining antibacterial phenotypic plasticity. Overall, our findings indicate that the uptake of apoptotic PMNs or MPO switches AMs to prioritize resolution of inflammation over antibacterial responses, a feature that is conserved in murine extrapulmonary macrophages and human AMs.