Tag: pubmed

JAMA Netw Open. 2026 Jan 2;9(1):e2553803. doi: 10.1001/jamanetworkopen.2025.53803.

NO ABSTRACT

PMID:41533381 | DOI:10.1001/jamanetworkopen.2025.53803

JAMA Netw Open. 2026 Jan 2;9(1):e2551807. doi: 10.1001/jamanetworkopen.2025.51807.

ABSTRACT

IMPORTANCE: More than 30 million people in the US take prescribed benzodiazepines, which, when taken long-term, carry risks of falls, cognitive decline, and dependence. A previous trial showed that a patient-focused self-management intervention (Eliminating Medications Through Patient Ownership of End Results; EMPOWER) can reduce long-term benzodiazepine dependence use and the risks that accompany it.

OBJECTIVE: To replicate the finding of the EMPOWER trial after converting the intervention from printed materials to electronic format.

DESIGN, SETTING, AND PARTICIPANTS: This 2-arm, individually randomized clinical trial with a 6-month follow-up was conducted at US Veterans Health Administration primary care clinics in 2 Veterans Affairs health care systems. Participants included 161 primary care patients taking benzodiazepines for 3 or more months and having access to a smartphone, tablet, or desktop computer. Recruitment occurred from June 1, 2022, to January 31, 2024.

INTERVENTION: Participants were randomized to either the electronically delivered EMPOWER (EMPOWER-ED) protocol or asked to continue to follow clinician recommendations regarding their benzodiazepine use (treatment as usual).

MAIN OUTCOMES AND MEASURES: Preregistered primary outcomes were complete benzodiazepine cessation and at least 25% dose reduction at 6-month follow-up, assessed using pharmacy data. Secondary outcomes were self-reported anxiety symptoms, sleep quality, and overall health and quality of life. Analysis was performed on an intent-to-treat basis.

RESULTS: The 161 participants had a mean (SD) age of 61.9 (13.7) years and were mostly male (134 [83.2%]). Individuals assigned to the EMPOWER-ED group had a significantly greater likelihood of complete benzodiazepine cessation (odds ratio [OR], 5.31 [95% CI, 1.12-25.12]). There was no likelihood of at least a 25% dose reduction in the EMPOWER-ED group relative to the control group (OR, 2.51 [95% CI, 0.91-6.90]). No statistically significant difference was found between the 2 groups for the secondary outcomes.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found a large effect of a low-cost, self-administered electronic intervention for reducing benzodiazepine use among long-term users. Findings from this replicated clinical trial are encouraging given the prevalence of benzodiazepine dependence and the constraints on clinician time available to address it. Dissemination of this intervention-which is in the public domain-by health care and public health systems seems warranted.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04572750.

PMID:41533380 | DOI:10.1001/jamanetworkopen.2025.51807

JAMA Netw Open. 2026 Jan 2;9(1):e2552518. doi: 10.1001/jamanetworkopen.2025.52518.

ABSTRACT

IMPORTANCE: Lyme disease (LD) is the most common vector-borne illness in the US. Given the increasing prevalence and expanding geographic bounds of LD, in-depth, up-to-date understanding of costs associated with an LD diagnosis, including patient out-of-pocket (OOP) costs, is needed.

OBJECTIVE: To assess health care costs in a broad US population diagnosed with LD, overall and stratified by localized disease vs disseminated disease.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study identified patients from Optum’s deidentified Market Clarity Data (Optum Market Clarity) between December 2, 2014, and January 30, 2023 (study period), with an LD diagnosis between January 1, 2016, and December 31, 2022 (identification period), having at least 14 months of continuous health plan enrollment. Optum Market Clarity is an integrated, multisource medical claims, pharmacy claims, and electronic health records data set. Outpatients had a claim with an LD diagnosis plus relevant antibiotics within 30 days, and inpatients had a claim with LD as the primary diagnosis or as a secondary diagnosis with an LD-associated condition as the primary diagnosis. Data were analyzed from February 27, 2023, to October 20, 2025.

EXPOSURE: The main exposure was LD diagnosis. Case patients were classified as having disseminated, localized, or indeterminate LD based on diagnosis codes for LD and LD-associated conditions, inpatient vs outpatient services, or antibiotic treatment type.

MAIN OUTCOMES AND MEASURES: Health care costs (reported in US dollars) for LD cases overall and stratified by localized disease vs disseminated disease were assessed 4 ways: (1) LD-specific costs per episode, (2) all-cause 6-month baseline vs follow-up costs for case patients with LD, (3) all-cause 6-month follow-up costs for case patients with LD compared with the control group, and (4) multivariable case-control analysis. Costs are reported as estimated direct (standardized) costs and patient OOP costs. Wald 95% CIs were used for means of cost measures.

RESULTS: A total of 70 531 case patients with LD were included. Their mean (SD) age was 44.8 (21.3) years; 51.3% were female. Estimated direct costs of LD were substantial across assessment methods, including episode cost (mean, $2227 [95% CI, $2111-$2342]), case patients as self-controls analysis (difference, $3304 [95% CI, $3117-$3491] in mean 6-month costs between baseline and follow-up), case-control analysis (difference, $4098 [95% CI, $3888-$4307] in mean 6-month follow-up costs), and multivariable-adjusted analysis (case-control difference, $5571 in projected mean 6-month follow-up costs; cost ratio, 1.96 [95% CI, 1.90-2.02]). OOP costs were available for 10 962 patients (15.5%) with LD. Mean OOP costs attributed to LD ranged from $188 to $399. Extrapolating to the US population in high-incidence states, annual costs of LD could range between $591 million and $1.05 billion (2022 dollars), with $411 to $771 million attributable to disseminated disease.

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, LD presented a large financial burden to the health care system and patients, especially for those with disseminated disease. These findings highlight the need for effective preventive measures to reduce costs for patients and the health care system.

PMID:41533379 | DOI:10.1001/jamanetworkopen.2025.52518

JAMA Netw Open. 2026 Jan 2;9(1):e2553965. doi: 10.1001/jamanetworkopen.2025.53965.

ABSTRACT

IMPORTANCE: Laboratory testing is necessary to distinguish blastomycosis, coccidioidomycosis, or histoplasmosis from other causes of community-acquired pneumonia (CAP). Robust data about testing for and diagnosis of these fungal diseases among patients with CAP throughout the US are lacking.

OBJECTIVE: To examine proportions and characteristics of (1) adult outpatients with CAP who underwent diagnostic testing for blastomycosis, coccidioidomycosis, or histoplasmosis; and (2) tested patients who received diagnoses of these diseases.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used 2017 to 2023 commercial health insurance claims data from the Merative MarketScan Commercial/Medicare Database. Adult outpatients with diagnosis codes for unspecified CAP were included.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who underwent fungal diagnostic testing. The secondary outcomes were the proportions of tested patients who received diagnoses of blastomycosis, coccidioidomycosis, or histoplasmosis. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) for characteristics independently associated with receiving a diagnosis of coccidioidomycosis or histoplasmosis.

RESULTS: Among 573 994 patients (318 152 female [55%]; median [IQR] age, 54 [41-63] years) with unspecified CAP, 25 822 (5%) underwent fungal diagnostic testing, which occurred a median (IQR) of 3 (1-6) health care visits after the initial CAP diagnosis. Among tested patients, 755 (3%) received a blastomycosis, coccidioidomycosis, or histoplasmosis diagnosis code. Rash (aOR, 3.24; 95% CI, 2.27-4.63), lymphadenopathy (aOR, 1.74; 95% CI, 1.15-2.63), myalgia (aOR, 1.66; 95% CI, 1.11-2.49), chest pain (aOR, 1.65; 95% CI, 1.35-2.02), and receipt of antibiotics from multiple classes (aOR, 1.40; 95% CI, 1.17-1.67) were independently associated with increased odds of receiving a coccidioidomycosis diagnosis. Autoimmune inflammatory disease (aOR, 3.00; 95% CI, 1.72-5.21), chest pain (aOR, 1.84; 95% CI, 1.20-2.82), and abnormal weight loss (aOR, 5.15; 95% CI, 2.71-9.79) were associated with increased odds of receiving a histoplasmosis diagnosis.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with unspecified CAP, testing rates for blastomycosis, coccidioidomycosis, and histoplasmosis were low in many locations. Increased awareness of these fungal infections may help increase timely testing for fungal diseases among patients with CAP, decrease health care utilization and inappropriate antibiotic use, and improve patient outcomes.

PMID:41533376 | DOI:10.1001/jamanetworkopen.2025.53965

JAMA Netw Open. 2026 Jan 2;9(1):e2553974. doi: 10.1001/jamanetworkopen.2025.53974.

ABSTRACT

IMPORTANCE: Burnout is highly prevalent among resident physicians, producing serious personal, professional, and system consequences. While work hour restrictions were implemented to improve patient safety and resident fatigue, the relationship between work hours with burnout and well-being remains unclear.

OBJECTIVE: To evaluate the association of work hours with burnout, stress, and self-perceived competency among residents in high-burnout specialties, and to explore potential demographic and well-being-related moderators.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included responses from a remote survey conducted from February to June 2024 as part of a randomized clinical trial evaluating a well-being intervention among resident physicians. Eligible participants were residents enrolled in high-burnout specialty residency programs (surgery, obstetrics-gynecology, family, internal, and emergency medicine) in the US.

EXPOSURE: Self-reported average weekly work hours and total hours worked in the past week.

MAIN OUTCOME AND MEASURES: Burnout, stress, and self-assessed Accreditation Council for Graduate Medical Education (ACGME) competency milestones, adjusting for demographics.

RESULTS: A total of 540 residents responded (356 cisgender women [66.8%]; 112 Asian [21.1%], 28 Black [5.3%], 355 White [67.0%]). The sample was predominantly in a medical specialty (56%). The mean (SD) number of average hours worked was 65.4 (11.3) and the mean (SD) number of hours worked in the last week was 60.1 (17.4). There was no significant association between burnout and average hours worked (β = 0.05 [95% CI, -0.05 to 0.15]; P = .34) or hours worked last week (β = 0.06 [95% CI, -0.03 to 0.15]; P = .21). However, stress was positively associated with average hours worked (β = 0.17 [95% CI, 0.07 to 0.26]; P = .001) and hours worked last week (β = 0.27 [95% CI, 0.18 to 0.36]; P < .001). Self-assessed ACGME competency milestones were also positively associated with average hours worked (β = 0.14 [95% CI, 0.07 to 0.21]; P < .001) and hours worked last week (β = 0.08 [95% CI, 0.01 to 0.15]; P = .02). Despite exploring a large set of candidate moderators, very few moderators were identified and none survived P value adjustment.

CONCLUSION AND RELEVANCE: In this cross-sectional nationwide study of resident physicians in high-burnout specialties, longer work hours were associated with higher stress and self-perceived competency, but not with burnout. This suggests that work hours alone may not explain high burnout levels in residency; a more comprehensive approach beyond work hour restrictions is needed to support resident well-being in training.

PMID:41533375 | DOI:10.1001/jamanetworkopen.2025.53974

JAMA Dermatol. 2026 Jan 14. doi: 10.1001/jamadermatol.2025.5295. Online ahead of print.

ABSTRACT

IMPORTANCE: ICP-332 is a tyrosine kinase 2 inhibitor currently under investigation for the treatment of atopic dermatitis (AD).

OBJECTIVE: To evaluate the safety and efficacy of ICP-332 for moderate to severe AD.

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, phase 2 randomized clinical trial was conducted between February 6 and November 7, 2023, across 19 centers in China. Individuals aged 18 to 75 years who had diagnosis of AD for 1 year or longer and a history of contraindication or inadequate response to topical therapies were included.

INTERVENTION: Participants were randomized 1:1:1 to receive ICP-332 at 80 mg or 120 mg, or placebo orally once daily for 4 weeks. Study participants and personnel were blinded to group assignment.

MAIN OUTCOMES AND MEASURES: The primary outcome was safety. The key efficacy outcome was the percentage change from baseline in Eczema Area and Severity Index (EASI) at week 4. Other outcomes included percentages of patients achieving EASI-75 (a ≥75% improvement in EASI) and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or more points improvement.

RESULTS: This study included 75 patients (mean [SD] age, 37.3 [18.0] years in the ICP-332 groups and 44.5 [17.4] years in the placebo group; 21 women [28%] and 54 men [72%]). Among the 74 patients included in the safety set, 17 of 25 (68%) in the placebo group, 19 of 25 (76%) in the 80-mg ICP-332 group, and 18 of 24 (75%) in the 120-mg ICP-332 group experienced treatment-emergent adverse events, with all events being mild or moderate. The most common adverse event was decreased blood fibrinogen (1 of 25 [4%] in the placebo group, 6 of 25 [44%] in the 80-mg ICP-332 group, and 5 of 24 [21%] in the 120-mg ICP-332 group). Percentage reductions in EASI at week 4 were -78.2% (95% CI, -89.8% to -66.6%) in the 80-mg ICP-332 group, -72.5% (95% CI, -84.3% to -60.7%) in the 120-mg ICP-332 group, and -16.7% (95% CI, -28.7% to -4.6%) for those receiving placebo. Mean differences vs placebo for percentage reductions from baseline at week 4 in EASI were -61.6% (95% CI, -78.4% to -44.7%; P < .001) and -55.8% (95% CI, -72.8% to -38.9%; P < .001) for 80-mg ICP-332 and 120-mg ICP-332, respectively. There was a statistically significant higher EASI-75 response rate with both ICP-332 doses (64.0% for each; difference vs placebo, 56.0%; 95% CI, 34.4%-77.6%; P < .001) than with placebo and a greater percentage of Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and improvement of 2 or more points at week 4 in the 80-mg ICP-332 group vs placebo (36.0%; difference vs placebo, 32.0%; 95% CI, 11.7%-52.3%; P = .005).

CONCLUSIONS AND RELEVANCE: In this phase 2 randomized clinical trial, ICP-332 demonstrated a favorable safety profile and encouraging efficacy, supporting further development for AD.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05702268.

PMID:41533373 | DOI:10.1001/jamadermatol.2025.5295

JAMA Psychiatry. 2026 Jan 14. doi: 10.1001/jamapsychiatry.2025.4106. Online ahead of print.

ABSTRACT

IMPORTANCE: Grief-focused cognitive behavioral therapies (GF-CBTs) are found effective in treating prolonged grief disorder (PGD), but the relative efficacy of different delivery formats is unknown. While evidence for individual GF-CBT (GF-CBT individual) is well established, evidence for group GF-CBT (GF-CBT group) is scarce. However, the group format holds possible advantages in a bereavement context.

OBJECTIVE: To examine whether GF-CBT group is noninferior to GF-CBT individual in reducing PGD symptoms in older adults.

DESIGN, SETTING, AND PARTICIPANTS: Enrollment and data collection for this noninferiority randomized clinical trial took place from April 2021 to May 2025. Participants were randomized 1:1 to GF-CBT group and GF-CBT individual and followed up with until 6 months posttreatment. Recruitment and treatment were done in a naturalistic clinical practice. Participants included older bereaved adults (65 years or older) with clinically relevant levels of PGD, posttraumatic stress disorder (PTSD), depression, and/or anxiety based on established cutoffs on self-report questionnaires. These data were analyzed from June 2025 through August 2025.

INTERVENTIONS: GF-CBT group and GF-CBT individual consisted of 12 weekly sessions (duration: 2 hours vs 1 hour), including the same intervention techniques in the same order (exposure, cognitive restructuring, and behavioral activation).

MAIN OUTCOMES AND MEASURES: Outcomes were measured at pretreatment, posttreatment, 3-month follow-up, and 6-month follow-up as the primary end point. The primary outcome was PGD symptoms measured with the Prolonged Grief-13 questionnaire. Secondary outcomes included symptoms of PTSD, depression, anxiety, loneliness, social support, functional impairment, quality of life, and well-being.

RESULTS: Participants (N = 113; mean [SD] age, 71.58 [5.86] years; 92 female [81.4%], 20 male [17.7%], and 1 person [.09%] had missing information on gender) were randomized to GF-CBT group (n = 56) or GF-CBT individual (n = 57). Mixed linear models on the intention-to-treat sample showed that both formats yielded statistically significant large reductions in PGD symptoms over time (GF-CBT group: d = 1.74; GF-CBT individual: d = 1.46). GF-CBT group was noninferior compared with GF-CBT individual (d = 0.09; 95% CI, -0.06 to 0.25) at 6-month follow-up. The noninferiority of GF-CBT group was evidenced for all secondary outcomes. Dropout rates were 23% (GF-CBT group) vs 19% (GF-CBT individual).

CONCLUSIONS AND RELEVANCE: In this study, GF-CBT group was noninferior to GF-CBT individual at 6-month follow-up in reducing PGD symptoms, but also symptoms of PTSD, depression, and anxiety. Both formats had large effects on symptoms over time and appear to be relevant treatment formats for older adults with symptoms of PGD and other disorders post loss.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04694807.

PMID:41533372 | DOI:10.1001/jamapsychiatry.2025.4106

Int J Environ Health Res. 2026 Jan 14:1-9. doi: 10.1080/09603123.2026.2614976. Online ahead of print.

ABSTRACT

CVS prevalence was found to be 76.9%. Females had higher odds of CVS (OR = 1.834, p = 0.028). Each one-unit increase in screen time was associated with higher odds of CVS (OR = 1.340, p = 0.030). Each one-unit increase in screen distance was associated with higher odds of CVS (OR = 2.153, p = 0.004). Each one-unit increase in room illumination was associated with lower odds of CVS (OR = 0.555, p = 0.015). Those who used at least one protective measure had lower odds of CVS (OR = 0.403, p = 0.006). There was no statistically significant relationship between CVS and academic year, screen brightness, or posture.

These findings highlight the need for spreading awareness and promoting targeted interventions to improve eye health.

PMID:41533339 | DOI:10.1080/09603123.2026.2614976

Am J Physiol Cell Physiol. 2026 Jan 14. doi: 10.1152/ajpcell.00845.2025. Online ahead of print.

ABSTRACT

Prostate cancer progression and metastasis is a complex step that is controlled by various molecular and cellular mechanisms. Here, the process of osteomimicry has a vital role in the context of bone metastasis. Osteomimicry phenomenon refers to the ability of cancer cells to acquire bone-like properties, thus enabling them to adapt to and survive in their bone microenvironment. This phenomenon promotes cancer cell and bone microenvironment interactions and contributes directly to tumor survival, growth, and the development of bone metastatic lesions. In this review we discuss the role of different osteomimicry factors in prostate cancer progression and metastasis, highlighting their involvement in each stage of the metastatic cascade. Key factors involved in osteomimicry – such as bone matrix proteins, signaling pathways, and transcriptional regulators – play important roles throughout the various stages of cancer progression. These include the initial development of the tumor, its local invasion into surrounding tissues, entry into the bloodstream (intravasation), spread to other more distant areas (extravasation), and ultimately, colonization and growth in the bone. Gaining a better understanding of how these factors are regulated, interact, and function can shed light on new treatment strategies aimed at targeting osteomimicry to slow down or prevent the progression of prostate cancer and its spread to the bones.

PMID:41533336 | DOI:10.1152/ajpcell.00845.2025

Tissue Eng Regen Med. 2026 Jan 14. doi: 10.1007/s13770-025-00782-1. Online ahead of print.

ABSTRACT

BACKGROUND: Alzheimer’s disease (AD) presents significant unmet medical needs with no effective therapeutic options. Current pharmacological treatments provide only symptomatic relief and do not prevent the ongoing neurodegeneration. Cell therapies using mesenchymal stem cells (MSCs) are being widely investigated for its potential in treating AD but remain unverified. This review aimed to evaluate therapeutic effects of MSCs on AD patients through a review of clinical trial literatures.

METHODS: Publications and registered clinical trials from January 2011 to June 2025 were collected from the international databases (ClinicalTrials.gov, PubMed, Web of Science, SCOPUS) using the keywords of “Alzheimer’s disease”, “mesenchymal stem cells”, and “clinical trials”. After initial screening and sorting, 17 clinical trials and 4 related papers were finally selected for in-depth analysis.

RESULTS: The 17 clinical trials were mostly early stages with 4 phase 1 (23.5%), 9 phases 1/2 (52.9%), 3 phase 2 (17.7%), and 1 pilot phase (5.9%). The source of MSCs included allogeneic umbilical cord blood (UCB) in 5 trials (29.4%), autologous adipose tissue in 4 (23.5%), allogeneic umbilical cord (UC) in 3 (17.6%), allogeneic bone marrow (BM) in 3 (17.6%), allogeneic placenta in 1 (5.9%) and 1 unknown (5.9%). Administration routes were primarily intravenous (IV) infusion in 12 trials (70.6%), intracerebroventricular (ICV) infusion via Ommaya reservoir in 3 (17.6%), and stereotactic brain injection (SBI) in 2 (11.8%). Among the 17 clinical trials, outcome data of 7 trials have been reported in 4 clinical papers and 1 clinical results posted in ClincalTrials.gov: 4 trials using UCB MSCs (NEUROSTEM-AD) in 2 papers, 2 trials using BM MSCs (Lomecel-B) in 2 papers and 1 trial using adipose MSCs (AstroStem) in ClinicalTrials.gov. All 5 reports using different cell types, administration routes or dosages claimed the safety of MSCs administration. As for the therapeutic efficacy, 2 reports using Lomecel-B reported meaningful improvement in AD pathophysiology or cognitive functions, while the other 3 reports using NEUROSTEM-AD or AstroStem failed to show statistically significant efficacy.

CONCLUSION: The analysis of 17 clinical trials and 5 relevant clinical outcomes showed that MSCs therapy if feasible and generally safe in AD patients. There are indications of potential therapeutic benefits such as improved cognitive function or quality of life measures in some AD patients. However, its therapeutic efficacy has not been proven definitely due to small size of subjects, variations in dosage, MSCs source, and administration scheme (route, timing, and frequency). Larger subject sizes and well-controlled trials are needed to provide more conclusive evidence.

PMID:41533329 | DOI:10.1007/s13770-025-00782-1