tbuckley/cabot-search huggingface dataset:
High-Deductible Health Plans and Receipt of Guideline-Concordant Care for Adults With Chronic Illness
Authors: Risha Gidwani, Veronica Yank, Steven M. Asch, Lane Burgette, Aaron Kofner, Alex Peltz, Zachary Wagner
Journal: JAMA Network Open (2025)

Importance High-deductible health plans (HDHPs) are a common insurance mechanism. Objective To evaluate whether HDHPs are meeting the medical needs of persons with chronical illness. Design, Setting, and Participants This longitudinal cohort study used 2016 to 2019 national administrative and claims data from MarketScan. Cohort members were adults aged 18 to 64 years with asthma, diabetes, hypertension, coronary artery disease, heart failure, or major depressive disorder. The treatment group was persons newly enrolling in an HDHP; the control group was persons continuously enrolled in non-HDHPs. Data were analyzed from October 2022 to April 2024, with revisions conducted between December and January 2025. Exposure New enrollment in an HDHP was instrumented by firms changing the plan choice options to promote HDHP enrollment (ie, restricted-choice firms). Analyses used difference-in-differences models combined with this instrumental variable. Entropy balancing was used to address residual confounding. Main Outcomes and Measures Use of annual recommended medical care, which was abstracted from disease-specific evidence-based clinical practice guidelines and included clinic visits, prescription drugs, laboratory tests, and an overall measure that combined all 3. Results were pooled across disease type to improve policy relevance of findings; disease-specific analyses were also conducted. Hypotheses were formulated prior to data collection. Results The cohort consisted of 343 137 adults (182 532 [53.20%] female; 149 760 [43.64%] aged 55-64 years [before entropy balancing]). Groups exhibited covariate balance after entropy balancing. Restricted-choice enrollment into an HDHP was associated with reduced use of recommended medical care, with persons in HDHPs reducing their use of recommended clinic visits by 3.1 (95% CI, −4.9 to −1.2) percentage points ( P &amp;amp;lt; .001), their use of recommended prescription drugs by 9.0 (95% CI, −11.8 to −6.2) percentage points ( P &amp;amp;lt; .001), and their use of recommended annual laboratory testing by 5.7 (95% CI, −8.2 to −3.2) percentage points ( P &amp;amp;lt; .001). Overall, HDHP enrollees were 4.7 (95% CI, −6.2 to −3.3) percentage points less likely to receive recommended medical care compared with non-HDHP enrollees ( P &amp;amp;lt; .001). Conclusions and Relevance This longitudinal cohort study of 343 137 adults with chronic illness found HDHP enrollment was associated with reduced receipt of recommended medical care across a variety of conditions. These results have important implications for recently proposed federal legislation that proposes to exempt chronic illness management from HDHP deductibles.
Pavements to Longevity: The Influence of Neighborhood Walkability on Mortality in Taiwan
Authors: Yiqian Zeng, Gavin Rudge, Tsung Yu, Weiyi Chen, Ka Chun Chong, Yu Huang, G. Neil Thomas, Xiang Qian Lao
Journal: Environmental Health Perspectives (2025)

There is limited information on the association between walkability and health in Asian countries. Our study aims to investigate the association between neighborhood walkability and mortality in Taiwanese adults. We selected 457,874 participants (≥18 years old) from Taiwan who joined a standard medical examination program between 1998 and 2016, and followed them until 31 July 2021. Three walkability measures were estimated within a walking distance of 640m of participant's addresses: points of interest (POI), transit stations, and impedance (restrictions to walking due to absence of intersections and physical barriers). Walkability measures were applied as continuous and categorical (tertiles) variables in data analyses. Mortality data was obtained from the National Death Registry maintained by the Ministry of Health and Welfare in Taiwan. A time-varying Cox regression model was used to investigate the association of neighborhood walkability with deaths from natural causes and specific causes. This study identified 24,744 deaths over a median follow up of 16.9 years. Compared with participants living with the first tertile for numbers of POI and transit stations, those living with higher numbers of POI and transit stations were associated with a lower risk of natural-cause mortality, with hazard ratios (HRs) (95% confidence intervals (CIs)) of 0.97 (0.94, 1.00) and 0.93 (0.90, 0.96) for second and third tertiles of numbers of POI, and 0.99 (0.96, 1.02) and 0.94 (0.92, 0.98) for second and third tertiles of numbers of transit station, respectively. Each unit increase in POI and transit stations were associated with a 3% [HR (95% CI): 0.97 (0.96, 0.99)] and 2% [HR (95% CI): 0.98 (0.97, 0.99)] reduced risk of natural-cause mortality, respectively. In addition, compared with living in areas with the first tertile of impedance, living with the third tertile of impedance was associated a higher risk of natural-cause mortality, with HRs (95%CI) of 1.01 (1.00, 1.03). One unit increase in impedance was associated with a 1% [HR (95% CI): 1.01 (1.00, 1.03)] increased risk of natural-cause mortality. We also found significantly inverse associations between three walkability measures with deaths from cardiovascular diseases, and between POI and death from chronic respiratory diseases. Our findings indicate that a higher level of neighborhood walkability was associated with a lower risk of mortality. Our data suggests it is important to take into account neighborhood walkability in urban planning and health guideline development. https://doi.org/10.1289/EHP15209.
Cardiomyopathy-Associated Gene Variants in Atrial Fibrillation
Authors: Leonoor F. J. M. Wijdeveld, Ezimamaka Ajufo, Saketh P. Challa, Joel T. Rämö, Xin Wang, Shinwan Kany, Jennifer L. Halford, Lu-Chen Weng, Seung Hoan Choi, Krishna G. Aragam, J. Peter van Tintelen, Bianca J. J. M. Brundel, Sean J. Jurgens, Patrick T. Ellinor
Journal: JAMA Cardiology (2025)

Importance Patients with atrial fibrillation (AF), a common morbid arrhythmia, are more likely to carry rare genetic variants associated with inherited cardiomyopathies. Prior studies on rare pathogenic variants in AF relied on small, hospital referral populations, and knowledge on clinical outcomes remains limited. Objective To evaluate the prevalence and prognostic implications of cardiomyopathy-associated pathogenic or likely pathogenic (CMP-PLP) genetic variants in patients with AF. Design, Setting, and Participants In 2 prospective cohort studies, the prevalence of CMP-PLP variants was assessed in the population of patients with AF and early-onset AF. The association between carrying a CMP-PLP variant and the risk of incident cardiomyopathy or heart failure (CMP/HF) after AF diagnosis was evaluated. Finally, the joint contributions of CMP-PLP variants, clinical risk, and polygenic risk were assessed. Included in this study were 2 large longitudinal cohort studies, the UK Biobank (UKB) (data 2006-2023) and the All of Us Research Program (AllofUs) (2018-2022). The UKB and AllofUs cohorts, respectively, contained 393 768 and 193 232 unrelated genotyped participants. Exposures CMP-PLP variants. Main Outcomes and Measures Prevalence of CMP-PLP variants and risk of incident CMP/HF after AF diagnosis. Results In the UKB cohort, 32 281 participants (8%) had AF (mean [SD] age, 62 [6] years; 20 459 male [63.4%]). In the AllofUs cohort, 11 901 participants (6%) had AF (mean [SD] age, 67 [12] years; 6576 male [55.3%]). Compared with the biobank populations, CMP-PLP variants were twice as prevalent in patients with AF (UKB, 2.04%; 95% CI, 1.89%-2.20%; AllofUs, 2.52%; 95% CI, 2.25%-2.82%) and 5 times as prevalent in AF with onset before age 45 years (UKB, 4.99%; 95% CI, 3.07%-7.91%; AllofUs, 4.66%; 3.40%-6.32%). Cumulative incidence of CMP/HF was high in patients with AF (18%) compared with patients without AF (3%). Still, among patients with AF without prior CMP/HF (UKB, 20 226; AllofUs, 8330), carrying a CMP-PLP variant was associated with 1.6-fold risk of incident CMP/HF (meta-analysis, 95% CI, 1.32-1.90). Finally, CMP-PLP variants, a polygenic score, and clinical risk factors were independent estimators of CMP/HF. Conclusions and Relevance Results of this cohort study suggest that the prevalence of CMP-PLP variants was substantial in patients with early-onset AF. Patients with AF carrying a CMP-PLP variant had an associated increased risk of future CMP/HF, independent of clinical and polygenic risk. These results indicate that genetic testing in patients with AF may identify individuals at higher risk for developing CMP/HF.
OCT vs Angiography for Guidance of Percutaneous Coronary Intervention of Calcified Lesions
Authors: Nicolas Amabile, Gregoire Rangé, Quentin Landolff, Erwan Bressollette, Nicolas Meneveau, Benoit Lattuca, Sebastien Levesque, Ziad Boueri, Julien Adjedj, Frederic Casassus, Ayoub Belfekih, Aurelie Veugeois, Géraud Souteyrand, Benjamin Honton
Journal: JAMA Cardiology (2025)

Importance The use of intravascular imaging for calcified plaque characterization and preparation has been advocated over conventional methods to improve percutaneous coronary intervention (PCI) outcomes, but this approach has never been evaluated. Objective To determine if optical coherence tomography (OCT) is superior to angiography for calcified lesions PCI guidance. Design, Setting, and Participants The CALIPSO (Calcified Lesion Intervention Planning Steered by OCT) trial was a prospective, multicenter, open-label, randomized clinical trial that included patients with stable moderate to severe calcified coronary lesions on coronary angiography scheduled for PCI. The trial was conducted at 12 sites in France between December 2021 and June 2023, and data were analyzed from December 2023 to April 2024. Intervention After diagnostic coronary angiography, eligible patients were randomly assigned in a 1:1 ratio to receive OCT-guided PCI or angiography-guided PCI. In the OCT group, the procedures were guided by OCT analysis and predefined standardized management algorithms. Patients from both arms had control post-PCI OCT analysis after procedure completion for primary end point measurement. Main Outcomes and Measures The primary end point was the minimal stent area (MSA) measured by OCT in both groups. Secondary key safety end points included periprocedural myocardial infarction, radiation dose, contrast medium volume, and procedure duration. Results A total of 143 patients were randomized, and 134 were included in the final analysis (65 in the OCT group and 69 in the angiography group). Median (IQR) patient age was 73.0 (66.0-78.0) years, and 25 patients (18.7%) were female. The baseline characteristics of the groups were comparable, but the use of intravascular lithotripsy was more frequent in the OCT arm (30 patients [46%] vs 8 patients [12%]; P &amp;amp;lt; .001). The final median (IQR) MSA was larger in the OCT group than in the angiography group (6.5 [5.5-8.1] mm 2 vs 5.0 [4.1-6.1] mm 2 ; P &amp;amp;lt; .001). There was no difference in periprocedural complications incidence, contrast medium volume, or procedure duration between groups. Conclusions and Relevance The CALIPSO randomized clinical trial showed that OCT guidance associated with predefined algorithmic management achieved better stent implantation results than angiography guidance in patients with calcified lesions PCI, without any additional safety concern. Trial Registration ClinicalTrials.gov Identifier: NCT05301218
Improving the Reporting of Trials Evaluating Organ-Support Therapies Using Multistate Modeling
Authors: David Hajage, Stéphane Gaudry, Alain Combes, Virginie Lemiale, Matthieu Schmidt, Jérôme Lambert
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Managing critically ill patients in the ICU often involves organ-support therapies (OST), such as mechanical ventilation, extracorporeal membrane oxygenation, renal replacement therapy, and various pharmacologic strategies. Clinical trials in this context pursue diverse goals-including improving survival, reducing OST use, facilitating weaning, or comparing timing of OST initiation-which leads to substantial heterogeneity in OST-related endpoints. One commonly used outcome, the number of OST-free days (OFD), has been criticized for its composite nature, which can obscure important clinical differences between patients with similar OFD values. Variability in how weaning success is defined, how intercurrent OST-free periods are handled, and how death is incorporated further complicates comparisons across trials. To illustrate how multistate modeling can offer an intuitive framework for analyzing randomized clinical trials involving OSTs, and how this approach allows to better describe and compare patient conditions during the entire follow-up. We describe the core principles of multistate modeling, including its assumptions (like the Markov assumption), advantages, and limitations. We then present two recent randomized controlled trials evaluating OSTs and identify the main statistical challenges encountered in their analysis. Using a multistate modeling approach, we re-analyzed both trials to characterize and compare patient trajectories over time. The multistate framework enabled clearer insight into how interventions impact the timing of transitions between clinical states, providing a richer and more clinically relevant understanding of treatment effects. Multistate modeling can substantially inform the interpretation and primary analysis of a clinical trial evaluating an organ-support therapy.
Ivarmacitinib for Moderate to Severe Atopic Dermatitis in Adults and Adolescents
Authors: Yan Zhao, Melinda Gooderham, Bin Yang, Jiyuan Wu, Liming Wu, Wei Jing Loo, Darryl Toth, Maxwell Sauder, Jingyi Li, Aijun Chen, Xiaohua Tao, Jianyun Lu, Zhiqiang Song, Jiande Han, Hongyi Li, Yijing Li, Lihong Xu, Jianzhong Zhang
Journal: JAMA Dermatology (2025)

Importance Ivarmacitinib, a selective oral Janus kinase 1 (JAK1) inhibitor, has demonstrated efficacy for treating adults with moderate to severe atopic dermatitis (AD) in a phase 2 trial. Objective To evaluate the efficacy and adverse events of ivarmacitinib in adolescents and adults with moderate to severe AD. Design, Setting, and Participants This multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial included patients aged 12 to 75 years with moderate to severe AD. Patients were enrolled from 53 sites in Canada and China from April 2021 to April 2022. Data were analyzed from July 11 to September 27, 2023. Interventions Patients were randomized (1:1:1) to receive once-daily 4- or 8-mg ivarmacitinib or placebo for 16 weeks. Main Outcomes and Measures Co-primary end points were the proportions of patients achieving an Investigator Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-grade improvement from baseline and an Eczema Area and Severity Index score improvement of 75% (EASI-75) at week 16. Results Of 336 randomized patients (mean [SD] age, 31.1 [15.4] years; 213 [63.4%] male; 286 [85.1%] Asian), 113 received 4-mg ivarmacitinib, 112 received 8-mg ivarmacitinib, and 111 received placebo. At week 16, significantly more patients in the 4-mg ivarmacitinib group (41 of 113 [36.3%]; 95% CI, 27.5%-45.9%; P &amp;amp;lt; .001) and the 8-mg ivarmacitinib group (47 of 112 [42.0%]; 95% CI, 32.7%-51.7%; P &amp;amp;lt; .001) achieved an IGA score of 0 or 1 with at least a 2-grade improvement compared to the placebo group (10 of 111 [9.0%]; 95% CI, 4.4%-15.9%). EASI-75 responses were also significantly higher in the ivarmacitinib groups: 61 patients (54.0%; 95% CI, 44.4%-63.4%; P &amp;amp;lt; .001) in the 4-mg group, and 74 (66.1%; 95% CI, 56.5%-74.8%; P &amp;amp;lt; .001) in 8-mg group compared to 24 patients (21.6%; 95% CI, 14.4%-30.4%) in the placebo group. Treatment-emergent adverse events were reported by 78 patients (69.0%) in the 4-mg group, 74 (66.1%) in the 8-mg group, and 72 (64.9%) in the placebo group. Serious treatment-emergent adverse events occurred in 3 patients (2.7%) in the 4-mg group, 2 (1.8%) in the 8-mg group, and 3 (2.7%) in the placebo group. Conclusions and Relevance This phase 3 randomized clinical trial determined that once-daily ivarmacitinib demonstrated significant efficacy and a favorable risk-benefit profile for treating moderate to severe AD in adults and adolescents. These results support the potential of ivarmacitinib as a new therapeutic option. Trial Registration ClinicalTrials.gov Identifier: NCT04875169
NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging
Authors: Sabina Chubanava, Iuliia Karavaeva, Amy M Ehrlich, Roger M Justicia, Astrid L Basse, Ivan Kulik, Emilie Dalbram, Danial Ahwazi, Samuel R Heaselgrave, Kajetan Trošt, Ben Stocks, Ondřej Hodek, Raissa N Rodrigues, Jesper F Havelund, Farina L Schlabs, Steen Larsen, Caio Y Yonamine, Carlos Henriquez-Olguín, Daniela Giustarini, Ranieri Rossi, Zachary Gerhart-Hines, Thomas Moritz, Juleen R Zierath, Kei Sakamoto, Thomas E Jensen, Nils J Færgeman, Gareth G Lavery, Atul S Deshmukh, Jonas T Treebak
Journal: Cell Metabolism (2025)

Nicotinamide adenine dinucleotide (NAD) is a ubiquitous electron carrier essential for energy metabolism and post-translational modification of numerous regulatory proteins. Dysregulations of NAD metabolism are widely regarded as detrimental to health, with NAD depletion commonly implicated in aging. However, the extent to which cellular NAD concentration can decline without adverse consequences remains unclear. To investigate this, we generated a mouse model in which nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ biosynthesis was disrupted in adult skeletal muscle. The intervention resulted in an 85% reduction in muscle NAD+ abundance while maintaining tissue integrity and functionality, as demonstrated by preserved muscle morphology, contractility, and exercise tolerance. This absence of functional impairments was further supported by intact mitochondrial respiratory capacity and unaltered muscle transcriptomic and proteomic profiles. Furthermore, lifelong NAD depletion did not accelerate muscle aging or impair whole-body metabolism. Collectively, these findings suggest that NAD depletion does not contribute to age-related decline in skeletal muscle function.
Cost-effectiveness of Lynch syndrome screening in colorectal cancer: universal germline vs sequential screening
Authors: Satoko Ito, Rosa M Xicola, Manraj Sra, Kunal C Potnis, Vinit Singh, Peter Gershkovich, Edward Stites, Joanna Gibson, Harlan M Krumholz, Xavier Llor, George Goshua
Journal: Clinical Gastroenterology and Hepatology (2025)
An Expert Consensus Delphi Panel in MetALD: Opportunities and Challenges in Clinical Practice
Authors: Luis Antonio Diaz, Veeral Ajmera, Juan Pablo Arab, Daniel Q Huang, Cynthia Hsu, Brian P Lee, Alexandre Louvet, Maja Thiele, Federica Tavaglione, Monica Tincopa, Elisa Pose, Leon A Adams, William Alazawi, Marco Arrese, Ramon Bataller, Ajay Duseja, Suthat Liangpunsakul, Michael R Lucey, Philippe Mathurin, Jessica Mellinger, Atsushi Nakajima, Vlad Ratziu, Nancy Reau, Mary E Rinella, Mark Thursz, Vincent Wai-Sun Wong, Patrick S Kamath, Rohit Loomba
Journal: Clinical Gastroenterology and Hepatology (2025)
Detection of Barrett’s Esophagus Prior to Development of Esophageal and Esophagogastric Junction Adenocarcinoma
Authors: Michelle Russin, Matthew Harbrecht, Ankit Mishra, Dhiraj Peddu, Matthew Kubina, Joy W Chang, Jennifer A Burns, Maria E Arasim, Joel H Rubenstein
Journal: Clinical Gastroenterology and Hepatology (2025)
Urachal actinomycosis mimicking a urachal adenocarcinoma: case report and systematic review
Authors: Camilo Medina, Valentina Garcia, Andrés Gutiérrez, Juan Ignacio Caicedo, Camilo Torres, Sebastian Peña, César Alejandro Diaz, Carolina Barrera, Juan Carlos López, Mauricio Palau
Journal: The Lancet Infectious Diseases (2025)
A joint learning approach for automated diagnosis of keratinocyte carcinoma using optical attenuation coefficients
Authors: Lei Zhang, Xiaoran Li, Wen Chen, Yuanjie Gu, Hao Wu, Zhong Lu, Biqin Dong
Journal: npj Digital Medicine (2025)

Keratinocyte carcinoma, such as Actinic Keratosis (AK) and Basal Cell Carcinoma (BCC), share similar clinical presentations but differ significantly in prognosis and treatment, highlighting the importance of effective screening. Optical coherence tomography (OCT) shows promise for diagnosing AK and BCC using signal intensity and skin layer thickness, but variability due to skin characteristics and system settings underscores the need for a standardized diagnostic method. Here, we propose an automated diagnostic method using the optical attenuation coefficient (OAC) and a joint learning strategy to classify AK, BCC, and normal skin. OAC images extracted from OCT data revealed notable disparities between normal and cancerous tissues. By incorporating probability distribution function (PDF) information alongside OAC images, the model achieved an accuracy of over 80% and approaching 100% by utilizing 3D OAC data to enhance robustness. This approach highlights the potential of OAC-based analysis for automated, intelligent diagnosis of early-stage non-melanoma skin cancers.
LV Structure and Function in HFrEF With and Without Peak-Flow-Triggered Adaptive Servo-Ventilation-Treated Sleep-Disordered Breathing
Authors: Shoichiro Yatsu, Anna Woo, Christian M Horvath, Tomoyuki Tobushi, Alexander G Logan, John S Floras, George Tomlinson, T Douglas Bradley
Journal: JACC Heart Failure (2025)
The p.Asn271Ile Variant in the TNNT2 Gene Is Associated With Low-Risk Late-Onset Hypertrophic Cardiomyopathy
Authors: José M Larrañaga-Moreira, Juan P Ochoa, Rosalía Peteiro-Debén, Esteban Martín-Álvarez, Tomás Ripoll-Vera, Jorge Álvarez-Rubio, María L Peña-Peña, Helena Llamas-Gómez, Adrián Fernández, María Gallego-Delgado, Ana I Rodríguez-Serrano, Carles Díez-López, Perry M Elliott, Julián Palomino-Doza, Rebeca Lorca, Javier Limeres, Olga Azevedo, Esther Zorio, Ernesto Martín-Dorado, Irene Méndez-Fernández, Raúl Franco-Gutiérrez, Fernando de Frutos, Aida Escudero, Luis Ruiz-Guerrero, Alejandro Rodríguez-Vilela, Andrea Mazzanti, William J McKenna, Roberto Barriales-Villa
Journal: JACC Heart Failure (2025)