Tag: pubmed

JAMA Dermatol. 2026 Jan 28. doi: 10.1001/jamadermatol.2025.5662. Online ahead of print.

ABSTRACT

IMPORTANCE: Currently, there are no treatments approved by the US Food and Drug Administration for juvenile localized scleroderma (JLS), a rare disease. While methotrexate (MTX) is regularly used as a first-line therapy, emerging data from case series and applications in systemic sclerosis suggest that mycophenolate mofetil (MMF) may be clinically comparable, with potential benefits in tolerability and adherence.

OBJECTIVE: To compare clinical outcomes of patients with JLS treated with MTX and MMF using standardized clinical outcome measures.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of patients with clinician-diagnosed JLS who were enrolled in the National Registry of Childhood Onset Scleroderma was conducted at UPMC Children’s Hospital of Pittsburgh. Data were from January 2010 to January 2023 and first analyzed in April 2023. All patients were evaluated and followed up by the same physician. Patients were included if they had disease onset before age 18 years and a localized scleroderma diagnosis and enrollment in the National Registry of Childhood Onset Scleroderma before age 21 years. Patients were required to be receiving MTX monotherapy, MMF monotherapy, or combination therapy (CT) of the 2 for their localized scleroderma.

EXPOSURES: Patients were treated with MTX, MMF, or CT as prescribed by the examining physician.

MAIN OUTCOMES AND MEASURES: This study measured comparative medication treatment response through associations with disease activity, as measured using the Localized Scleroderma Cutaneous Assessment Tool.

RESULTS: Of 114 patients, 77 (67.5%) were female, and the median (IQR) age at onset was 8.3 (5.4-11.2) years. The MTX, MMF, and CT groups included 68 (59.6%), 28 (24.6%), and 18 patients (15.8%), respectively. There were no significant differences in baseline demographic characteristics, disease subtype, or disease severity between groups, but patients in the MMF group had longer disease duration. Mixed-effects modeling showed statistically significant decreases in activity across all groups (β = -0.14; 95% CI, -0.62 to 0.33). A Kaplan-Meier analysis showed no significant difference in disease flare rate over the follow-up interval (hazard ratio, 0.85; 95% CI, 0.51-1.33). However, patients treated with MTX compared with those treated with MMF had significantly higher rates of fatigue (47% vs. 11%, P = .001) and nausea (60% vs. 7%; P = .001).

CONCLUSIONS AND RELEVANCE: The study results suggest that MMF demonstrated a similar response to treatment as MTX in reducing disease activity in JLS, with comparable flare rates and improved tolerability. These initial findings support MMF as a potential candidate for first-line treatment of JLS. Prospective, randomized, noninferiority trials are warranted to confirm these results and guide future treatment recommendations.

PMID:41604178 | DOI:10.1001/jamadermatol.2025.5662

JAMA Dermatol. 2026 Jan 28. doi: 10.1001/jamadermatol.2025.5700. Online ahead of print.

ABSTRACT

IMPORTANCE: Cutaneous squamous cell carcinoma (cSCC), cSCC in situ (CIS), and keratoacanthoma (KA) pose growing public health challenges, due to their associated morbidity, health care burden and costs. However, many countries lack systematic registration of these extremely frequent keratinocyte neoplasms.

OBJECTIVE: To estimate incidence rates and trends of first-time, histologically confirmed cSCC, CIS, and KA in Denmark (2005-2023) by sex, age, and anatomical site.

DESIGN, SETTING, AND PARTICIPANTS: A nationwide, population-based study using data from the Danish Pathology Registry and Cancer Registry was conducted, including individuals 20 years or older receiving a first-time diagnosis of cSCC, CIS, or KA from January 1, 2005 to December 31, 2023. Data analyses were conducted from January to July 2025.

MAIN OUTCOMES AND MEASURES: Age-standardized incidence rates (ASIRs) as well as age-specific incidence rates per 100 000 person-years with corresponding estimated annual percentage changes (EAPCs) and 95% CIs were calculated.

RESULTS: A total of 109 787 histologically confirmed cases were identified in 95 352 unique individuals (55 891 male individuals [50.9%], 53 896 female individuals [49.1%]) 20 years or older in Denmark, receiving a first-time diagnosis of cSCC (n = 54 563), CIS (n = 31 712), or KA (n = 23 512). From 2005 to 2023, cSCC ASIRs increased (EAPC for male individuals, 2.6%; EAPC for female individuals, 3.1%), reaching 131.6 and 77.7 per 100 000 person-years in male individuals and female individuals, respectively. CIS increased markedly (EAPC, for male individuals, 6.4%; EAPC for female individuals, 5.8%), and KA declined. Stratified analyses showed distinct sex-specific anatomic patterns. Predilection sites for cSCC and CIS were the face, scalp, and neck, with particular predominance among male individuals. Female individuals exhibited higher ASIRs on the lower limbs compared with male individuals (male vs female individuals: cSCC, 7.63 vs 12.32 per 100 000; CIS, 6.21 vs 12.63 per 100 000; KA, 3.47 vs 7.20 per 100 000, respectively). KA primarily affected the extremities. Female individuals aged 40 to 59 years showed higher incidence rates than male individuals across all keratinocyte neoplasms (male vs female individuals: cSCC, 131.6 vs. 77.7 per 100 000; CIS, 89.4 vs. 78.6 per 100 000; KA 28.6 vs. 27.6 per 100 000, respectively). Trends among individuals younger than 50 years with cSCC and KA were stable.

CONCLUSIONS AND RELEVANCE: In this nationwide cohort study presenting the most comprehensive dataset of incident cSCC, CIS, and KA, with 109 787 histologically confirmed patient cases, covering nearly 2 decades and spanning across all Danish health care sectors, incidence of cSCC and CIS continued to rise, consequently affecting more people, and sex differences diminished. Stabilizing trends in individuals younger than 50 years may indicate early prevention effects. Findings of this study have the potential to influence future surveillance activities and clinical care through attention to sex, age, and anatomical site.

PMID:41604163 | DOI:10.1001/jamadermatol.2025.5700

JAMA Netw Open. 2026 Jan 2;9(1):e2555952. doi: 10.1001/jamanetworkopen.2025.55952.

ABSTRACT

IMPORTANCE: Patients with diabetes and a history of major adverse limb events (MALEs) are at an increased risk of cardiovascular and limb-related complications; however, effective glucose-lowering therapies for secondary prevention in this population are limited.

OBJECTIVE: To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with reduced risk of MALEs and major adverse cardiovascular events (MACE) compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetes and prior MALEs.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, nationwide cohort study used data from the Taiwan National Health Insurance Research Database from October 2012 to December 2023. Patients with diabetes and a history of MALE who initiated GLP-1 RAs or DPP-4 inhibitors were included. MALEs were defined as chronic limb-threatening ischemia, lower limb revascularization, or nontraumatic minor and major amputation.

EXPOSURES: Initiation of GLP-1 RAs (liraglutide, dulaglutide, or semaglutide) vs DPP-4 inhibitors.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of lower limb revascularization and nontraumatic major and minor amputation. The secondary outcomes were MACEs (cardiovascular death, ischemic stroke, and myocardial infarction), all-cause mortality, and progression to long-term dialysis. A new-user, active-comparator design with inverse probability of treatment weighting was employed.

RESULTS: Among 17 288 patients (mean [SD] age, 70.7 [12.0] years; 10 010 male [57.9%]), 1583 initiated GLP-1 RAs and 15 705 initiated DPP-4 inhibitors. After weighting, the use of GLP-1 RAs was associated with a lower risk of MALEs (subdistribution hazard ratio [SHR], 0.90; 95% CI, 0.83-0.97), primarily due to a marked reduction in amputation (SHR, 0.86; 95% CI, 0.75-0.98). GLP-1 RAs were also associated with reduced risks of MACEs (HR, 0.62; 95% CI, 0.58-0.65), cardiovascular death (HR, 0.57; 95% CI, 0.53-0.61), all-cause mortality (HR 0.63; 95% CI, 0.60-0.66), and progression to dialysis (SHR, 0.61; 95% CI, 0.54-0.70).

CONCLUSIONS AND RELEVANCE: In this nationwide cohort study of patients with diabetes and prior MALEs, treatment with GLP-1 RAs was associated with significantly lower risks of recurrent limb events, cardiovascular events, all-cause mortality, and kidney disease progression compared with DPP-4 inhibitors. These findings support the preferential use of GLP-1 RAs for secondary prevention in this high-risk population.

PMID:41604151 | DOI:10.1001/jamanetworkopen.2025.55952

JAMA Netw Open. 2026 Jan 2;9(1):e2556012. doi: 10.1001/jamanetworkopen.2025.56012.

ABSTRACT

IMPORTANCE: The associations of adverse childhood experiences (ACEs) and adverse adulthood experiences (AAEs) with incident dementia and stroke in the Chinese population are not well understood.

OBJECTIVES: To investigate the associations of ACEs and AAEs with dementia and stroke incidence, and to examine whether depression mediates these associations.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study utilized data from the China Health and Retirement Longitudinal Study (June 2015 to December 2020). Participants aged 45 years and older with complete adverse experience data were included and were followed up for a mean (SD) of 4.89 (0.48) years for dementia and 4.84 (0.57) years for stroke. Statistical analysis was performed from August 20, 2025, to November 23, 2025.

EXPOSURES: ACEs and AAEs were assessed through a structured questionnaire, with cumulative scores calculated for both categories.

MAIN OUTCOMES AND MEASURES: Dementia was identified using a standardized cognitive battery and activities of daily living scale, while stroke was determined through self-reported physician diagnosis. Depression was evaluated using the 10-item Centre for Epidemiologic Studies Depression Scale. Cox proportional hazards regression analysis was used to explore the association of ACEs and AAEs with the risk of new-onset dementia and stroke, with results presented as hazard ratios (HRs) with 95% CIs.

RESULTS: Among 11 601 participants (mean [SD] age, 59.18 [9.41] years; 5569 male [48.0%]), 9145 (78.8%) were exposed to at least 1 ACE indicator, 4241 (36.6%) to at least 1 AAE indicator, and 3531 (30.4%) to both ACE and AAE markers. Both ACEs (HR, 1.11; 95% CI, 1.05-1.18) and AAEs (HR, 1.23; 95% CI, 1.14-1.33) were significantly associated with higher hazards of dementia during follow-up, whereas only AAEs were associated with higher hazards of stroke (HR, 1.19; 95% CI, 1.12-1.26). Latent class analysis identified a high-risk ACEs subgroup associated with incident stroke (HR, 1.33; 95% CI, 1.08-1.65). In the joint effects analyses, participants in the high-risk groups for both ACEs and AAEs exhibited higher hazards of dementia (HR, 3.28; 95% CI, 1.54-7.02) and stroke (HR, 2.50; 95% CI, 1.24-5.30). Depression mediated 34.3% of the association of ACEs with dementia (β = 0.10; 95% CI, 0.04-0.17), 20.9% of the association of AAEs with dementia (β = 0.22; 95% CI, 0.13-0.30), and 17.5% of the association of AAEs with stroke (β = 0.18; 95% CI, 0.11-0.24).

CONCLUSIONS AND RELEVANCE: In this cohort study, exposure to adverse experiences throughout life was associated with increased risks of dementia and stroke, with depression mediating these associations. These findings highlight the importance of implementing life-course interventions that address both psychological trauma and mental health to reduce the burden of neurovascular diseases.

PMID:41604149 | DOI:10.1001/jamanetworkopen.2025.56012

J Health Psychol. 2026 Jan 28:13591053251414005. doi: 10.1177/13591053251414005. Online ahead of print.

ABSTRACT

Open label placebos (OLPs) refer to the non-deceptive administration of inert treatment. This pre-registered study (AsPrediced#139837) explored the role of expectations and tailored health feedback on the OLP effect using an automated online procedure. Healthy participants (N = 293) were randomised to a 10-day course of OLP pills with veridical feedback (OLP-Feedback: N = 92), without feedback (OLP-Standard: N = 105), or to a no-treatment control (NTC: N = 96). Participants were informed the pills were inert but may enhance wellbeing. Wellbeing was assessed at baseline, day-5 and day-10. Feedback was delivered on day-5 and day-10 via interactive graphs and descriptive statistics. OLP-treatment significantly improved wellbeing (negative emotions and sleep quality), while feedback did not significantly enhance this effect. Expectations for improvement were significantly elevated among OLP-treated participants across the 10-day study. However, at the individual level, expectations only mediated OLP outcomes once treatment experience had been acquired. Results reconcile inconsistencies in the literature regarding mechanisms.

PMID:41604142 | DOI:10.1177/13591053251414005

Ther Drug Monit. 2026 Jan 28. doi: 10.1097/FTD.0000000000001399. Online ahead of print.

ABSTRACT

BACKGROUND: With the patchwork legalization of cannabis in the United States and the loopholes surrounding “legal” highs, the prevalence of Δ8-tetrahydrocannabinol (Δ8-THC) has been rising, requiring the development of methods to extract, differentiate, and detect it separately from Δ9-tetrahydrocannabinol (Δ9-THC) and its metabolites. The authors focused on developing a method to detect the primary metabolite Δ8-carboxy-tetrahydrocannabinol (Δ8-THC-COOH) separately from Δ9-carboxy-tetrahydrocannabinol (Δ9-THC-COOH) in urine, a commonly collected sample in human performance toxicology.

METHODS: Liquid-liquid extraction with hydrolysis was used to isolate and extract metabolites from forensic urine samples. After evaporation, the extract was flash-derivatized using an MTBSTFA:ACN (1:3) solution, followed by gas chromatography-mass spectrometry analysis. The results were tabulated and subjected to statistical analysis.

RESULTS: Forensic human performance urine specimens (n = 127) were analyzed for ∆8-THC-COOH, ∆9-THC-COOH, and 7-carboxy-cannabidiol (7-COOH-CBD) between January 2023 and January 2024. In total, 52 samples contained only ∆9-THC-COOH, 70 contained both ∆8-THC-COOH and ∆9-THC-COOH, 3 contained only ∆8-THC-COOH, and 5 contained both 7-COOH-CBD and ∆9-THC-COOH, with 3 of these containing all 3 metabolites. The area abundances of their respective chromatographic peaks was used to calculate the ∆8:∆9 metabolite ratio when both ∆8-THC-COOH and ∆9-THC-COOH were detected. Despite a higher mean ratio in driving under the influence cases (13.87 versus 8.53), the difference between the mean values was not statistically significant (independent-sample t test: t (68) = -0.670, p = 0.505).

CONCLUSIONS: This study and its methodology provide insight into the effective separation and analysis of the compounds of interest, and discuss the potential differentiation of ∆8-THC-dominant products from traditional cannabis, and underscore the prevalence of ∆8-THC and ∆8-THC-dominant products in the current market, while highlighting the need for further studies on this topic.

PMID:41604141 | DOI:10.1097/FTD.0000000000001399

Matern Child Health J. 2026 Jan 28. doi: 10.1007/s10995-026-04227-6. Online ahead of print.

ABSTRACT

OBJECTIVES: Military families experience lifestyle and circumstance-specific stressors that may impact their parental stress, family resilience, and emotional support for parenthood. These outcomes may influence parenting behaviors and mental health that have further implications on child development and growth. Research is needed to examine these outcomes among military families in the United States on a national scale due to the importance of potential intergenerational implications.

METHODS: This cross-sectional study used data from the 2021-2022 National Survey of Children’s Health to investigate the relationship between caregiver military status and outcomes of parental stress, family resilience, and emotional support for parenthood (n = 99,869). Bivariate analyses through chi-square tests were calculated to determine differences between outcomes from military caregivers and civilian caregivers with select covariates. Multivariable regression analyses were calculated to further explore the relationship between caregiver military status and emotional support for parenthood.

RESULTS: The prevalence of emotional support with parenthood was higher among military caregivers compared to civilian caregivers (82.8% vs. 75.0%, p < 0.0001); however, this difference was not statistically significant in adjusted analyses. No statistically significant differences were found between military families and civilian families in parenting stress and family resilience.

CONCLUSIONS: This study extended previous research that have focused on state or station specific outcomes in military families by examining these outcomes on a national scale. This study has important implications towards expanding research and interventions that reduce parenting stress and improve family resilience and emotional support for parenthood to ensure continued positive outcomes.

PMID:41604131 | DOI:10.1007/s10995-026-04227-6

J Autism Dev Disord. 2026 Jan 28. doi: 10.1007/s10803-025-07204-0. Online ahead of print.

ABSTRACT

PURPOSE: Social difficulties are fundamental aspects of autism spectrum disorder (ASD). However, behavioral issues such as attention difficulties, thought problems, externalizing behaviors, and internalizing behaviors can further hinder children’s ability to develop social skills. We aimed to explore how co-occurring behavioral challenges may intensify social difficulties in autistic children and adolescents by assessing whether a higher prevalence of behavioral problems is associated with poorer social functioning in real-world scenarios.

METHODS: We surveyed parents of 225 children diagnosed with ASD. Parents completed two questionnaires-the Child Behavior Checklist (CBCL) measuring psychiatric symptoms, and the Social Skills Improvement System (SSIS) assessing observable social abilities. We statistically analyzed the connection between behavioral scores and social scores.

RESULTS: The results showed that more severe behavioral issues on the CBCL tied to weaker social skills overall on the SSIS. Among all behavioral domains, attention problems showed the strongest negative associations with total social skills and all subdomains. Thought problems also demonstrated significant negative association with several aspects of social functioning. Externalizing behaviors and internalizing behaviors were also negatively associated with social skills, though their effects were less pronounced than those of attention and thought problems.

CONCLUSION: Our findings provide real-world evidence that common co-occurring behavioral problems especially attention problems and thought problems showed strong negative associations with social skill difficulties in autistic children and adolescents. Screening for and adjusting conditions like attention problems, thought problems, and disruptive behaviors may be an important piece of helping autistic children build social competence.

PMID:41604128 | DOI:10.1007/s10803-025-07204-0

J Prev (2022). 2026 Jan 28. doi: 10.1007/s10935-026-00898-7. Online ahead of print.

ABSTRACT

Substance use and high-risk sexual behaviors remain pressing public health challenges among U.S. adolescents, with tobacco, alcohol, and marijuana being the most used substances. While previous research has shown an association between substance use and risky sexual behavior, there is limited data on how these associations vary based on demographic modifiers such as race, sex, and sexual identity among sexually active adolescents. This study explores the association between current substance use (cigarettes, e-cigarettes, alcohol, and marijuana) and high-risk sexual behaviors (having multiple sexual partners and lack of condom use), examining how these associations vary by race, sex, and sexual identity. The 2023 Youth Risk Behavior Survey (YRBS) data was analyzed for 5420 adolescents attending U.S. public and private high schools. Multiple Logistic regression was used to examine associations, and interaction effects for race, sex, and sexual identity were introduced to the model to determine variations in associations. Overall adjusted analyses revealed current use of cigarette, e-cigarette, and alcohol was associated with higher likelihood of having multiple (2 or more) sexual partners in the past 3 months. Additionally, current marijuana use was associated with a higher likelihood of not using a condom during last sexual intercourse. A statistically significant interaction was observed only for the association between current marijuana use and condomless sex during last sexual intercourse (p = 0.010). Stratified analyses indicated that this association varied by sexual identity and was stronger among heterosexual students compared to Lesbian, Gay, Bisexual, Queer, and other (LGBQ+) students. Results confirm the link between substance use and high-risk sexual behavior among youth, reinforcing our need for increased programming around substance use prevention and sexual health education. Heterosexual youth may be at increased risk for high-risk sexual behavior associated with their marijuana use, calling for tailored interventions that target the unique needs of this demographic subgroup.

PMID:41604127 | DOI:10.1007/s10935-026-00898-7

J Prev (2022). 2026 Jan 28. doi: 10.1007/s10935-026-00899-6. Online ahead of print.

ABSTRACT

The burden that multimorbidity places on people, families, and society as a whole has made it a global public health concern. While physical activity (PA) is supported by the World Health Organization (WHO) as a crucial approach for avoiding chronic diseases, there is minimal data to support its link with multimorbidity, especially among populations of middle-aged and elderly in China. Derived from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2018, a cross-sectional data was employed in this study. To analyze the linear connection between multimorbidity and PA, Restricted Cubic Spline (RCS) and Binary logistic regression were applied. The heterogeneity of this association across other groups was investigated using subgroup and interaction analysis. Three sensitivity analyses validated the results’ robustness. Among 19,453 participants, 25.24% of middle-aged and older individuals actively engaged in moderate vigorous PA, 58.40% often participated in vigorous PA, and the prevalence of multimorbidity was 40.18%. After adjusting for all confounding factors, compared with low-intensity PA, moderate vigorous PA (OR = 0.889, 95% CI: 0.810-0.976) and vigorous PA (OR = 0.731, 95% CI: 0.673-0.794) demonstrated a significantly attenuated risk of multimorbidity. Multimorbidity and PA did not significantly correlate linearly, according to the RCS result. Age, residence, social activities and drinking were found to have substantial modifying effects on the relationship between PA and multimorbidity, according to the subgroup and interaction analyses. The outcomes of this research underline the the association between physical activity and a reduced risk of multimorbidity. This suggests that under the premise of ensuring safety, higher levels of physical activity among middle-aged and older adults may be linked to later onset of chronic disease.

PMID:41604126 | DOI:10.1007/s10935-026-00899-6