Tag: pubmed

JAMA Pediatr. 2026 Aug 3. doi: 10.1001/jamapediatrics.2026.2470. Online ahead of print.

ABSTRACT

IMPORTANCE: Puberty is a critical window for bone mass acquisition, determining lifelong fracture risk. Gonadotropin-releasing hormone agonist (GnRHa)-based pubertal suppression followed by gender-affirming hormone therapy (GAHT) is increasingly used in transgender and gender-diverse (TGD) adolescents, raising concerns about peak bone mass.

OBJECTIVES: To quantify changes in bone mineral density (BMD), bone mineral apparent density (BMAD), and z scores in TGD adolescents undergoing GnRHa with or without GAHT, and to identify predictors of skeletal outcomes.

DATA SOURCES: PubMed, Scopus, Web of Science, and Cochrane Library, from inception through September 2025.

STUDY SELECTION: Longitudinal cohorts assessing BMD, BMAD, or z scores at the lumbar spine, total hip, or femoral neck in TGD adolescents treated with GnRHa with or without GAHT. Ten studies met the inclusion criteria.

DATA EXTRACTION AND SYNTHESIS: Data were extracted in duplicate; study quality was assessed using the Newcastle-Ottawa Scale. Random-effects models pooled mean changes across baseline (time 0 [T0]), after GnRHa (T1), and after GAHT (T2), stratified by skeletal site and sex assigned at birth. Metaregressions examined body mass index, age, Tanner stage, and treatment duration.

MAIN OUTCOMES AND MEASURES: Dual-energy x-ray absorptiometry-derived BMD, BMAD, and z scores.

RESULTS: Ten cohorts comprising 751 adolescents (427 assigned female at birth [AFAB]; 324 assigned male at birth [AMAB]) were included. Lumbar spine z scores declined during GnRHa (AFAB: z-score change, -0.97 [95% CI, -1.09 to -0.85]; AMAB: z-score change, -0.73 [95% CI, -0.93 to -0.53]) despite stable BMD. z Scores used sex-assigned-at-birth normative references. After GAHT, BMD increased (AFAB: BMD mean difference, 0.09 g/cm2 [95% CI, 0.07-0.10 g/cm2]; AMAB: BMD mean difference, 0.13 g/cm2 [95% CI, 0.10-0.16 g/cm2]), with partial z-score recovery; values remained below baseline at T2 (AFAB: z-score change, -0.51 [95% CI, -0.69 to -0.34]; AMAB: z-score change, -0.52 [95% CI, -0.82 to -0.21]) but were not consistently statistically different across skeletal sites. Recovery at the total hip and femoral neck was smaller and more heterogeneous. Higher body mass index, shorter GnRHa duration, and longer GAHT exposure were associated with more favorable outcomes.

CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found that pubertal suppression followed by GAHT was associated with transient z-score reductions and subsequent BMD increases. At T2, z scores remained numerically below baseline but were not consistently statistically different, suggesting an uncertain rather than demonstrated persistent deficit. Timely GAHT initiation is recommended.

PMID:42545689 | DOI:10.1001/jamapediatrics.2026.2470

JAMA. 2026 Aug 3. doi: 10.1001/jama.2026.9350. Online ahead of print.

ABSTRACT

IMPORTANCE: In a phase 2 randomized clinical trial, high-dose vitamin D3 added to standard treatment improved progression-free survival (PFS) compared with standard-dose vitamin D3 in patients with metastatic colorectal cancer (mCRC).

OBJECTIVE: To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with previously untreated mCRC.

DESIGN, SETTING, AND PARTICIPANTS: Double-blind phase 3 randomized clinical trial enrolling 455 patients with previously untreated mCRC, conducted in the US through the National Clinical Trials Network from October 2019 to December 2022 (database freeze: July 15, 2024).

INTERVENTIONS: mFOLFOX6 (modified FOLFOX6 [5-fluorouracil, leucovorin, oxaliplatin]) or FOLFIRI (5-fluorouracil, leucovorin, irinotecan) plus bevacizumab every 2 weeks with either high-dose vitamin D3 (8000 IU daily × 14 days as loading dose followed by 4000 IU daily) or standard-dose vitamin D3 (400 IU daily) until disease progression, intolerable toxicity, or withdrawal of consent.

MAIN OUTCOMES AND MEASURES: The primary end point was PFS assessed by the unstratified log-rank test. Secondary end points included objective response rate, overall survival, and toxicity. Prespecified subgroup analyses of PFS were performed according to known prognostic factors.

RESULTS: Among 455 randomized patients (median age, 59 years; 181 [40%] female) with median follow-up 20 months, the median PFS for high-dose vitamin D3 (n = 228) was 11.8 months (95% CI, 10.3-13.3) vs 10.3 months (95% CI, 9.4-12.2) for standard-dose vitamin D3 (n = 227) (1-sided log-rank P = .25). There were no significant differences in objective response rate between high-dose and standard-dose vitamin D3 (51% [95% CI, 44%-58%] vs 44% [95% CI, 37%-50%], respectively; P = .12), or in overall survival (median, 25.6 vs 27.0 months; 1-sided log-rank P = .66). There were no clinically meaningful differences in the most common grade 3 or greater adverse events between the high- and standard-dose groups, including neutropenia (n = 67 [32%] vs n = 62 [30%]) and hypertension (n = 42 [20%] vs n = 49 [23%]) or in incidence of vitamin D-associated toxicities.

CONCLUSIONS AND RELEVANCE: Among patients with previously untreated mCRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy plus bevacizumab did not improve PFS.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04094688.

PMID:42545685 | DOI:10.1001/jama.2026.9350

Int Health. 2026 Aug 3:ihag077. doi: 10.1093/inthealth/ihag077. Online ahead of print.

ABSTRACT

OBJECTIVES: Smoking is a major cause of preventable morbidity and mortality worldwide. Despite global tobacco control efforts, smoking prevalence remains high in many regions. This study aimed to determine the prevalence of smoking and its associated factors in the Kurdistan Region of Iraq.

METHODS: A community-based, cross-sectional study was conducted in 2025, consisting of 1132 individuals aged ≥18 years selected through multistage random sampling from 12 districts of Duhok City. Data were collected using a structured questionnaire and anthropometric measurements. Descriptive statistics and logistic regression analyses were performed to identify factors associated with smoking.

RESULTS: The mean age of participants was 37.5 ± 14.8 years. The overall prevalence of smoking was 33.6%, with a marked gender disparity (50.9% in men vs 5.7% in women). In univariate analysis, smoking was significantly associated with gender, education, marital status, employment status, physical activity, hypertension, waist circumference, and body mass index. Multivariate logistic regression showed that gender, education level, and employment status remained independently associated with smoking.

CONCLUSIONS: Smoking prevalence in the Kurdistan Region of Iraq is alarmingly high, particularly among men, individuals with lower education, and employed adults. These findings highlight the urgent need for strengthened tobacco control policies and targeted public health interventions in the region.

PMID:42545682 | DOI:10.1093/inthealth/ihag077

J Endocrinol Invest. 2026 Aug 3. doi: 10.1007/s40618-026-02999-w. Online ahead of print.

ABSTRACT

BACKGROUND: Pediatric obstructive sleep apnea (OSA) is an independent factor associated with cardiometabolic disease in obese youth. While chronic intermittent hypoxia alters metabolic homeostasis, evaluating this “hypoxic burden” through fasting biomarkers frequently yields inconsistent results in pediatric cohorts. We investigated whether OSA is associated with early dynamic glycemic dysfunction independent of obesity severity and evaluated the diagnostic utility of morning serum lactate.

METHODS: This retrospective cross-sectional study evaluated 53 obese adolescents (mean age 13.5 ± 1.7 years) undergoing diagnostic overnight polysomnography in a hospital setting. Participants were stratified into Mild OSA (AHI ≤ 5; n = 35) and Moderate-to-Severe OSA (AHI > 5; n = 18) cohorts. Due to the non-normal distribution of glycemic data, we performed an Analysis of Covariance (ANCOVA) using log10-transformed 2-hour OGTT glucose levels while adjusting for age. Morning serum lactate and standard metabolic indices were evaluated using non-parametric tests.

RESULTS: The Moderate-to-Severe OSA cohort demonstrated significantly elevated 2-hour OGTT glucose levels compared to the Mild OSA cohort (Median: 100 [IQR: 95-135] vs. 98 [IQR: 90-108] mg/dL; p = 0.048, Cohen’s d = 0.609). After adjusting for age as a covariate using log10-transformed data, the difference remained statistically significant (adjusted mean difference [log10]: 0.042, 95% CI [0.001 to 0.083]; p = 0.049). Morning serum lactate indicated a marginal trend toward elevation in the Moderate-to-Severe group (Median: 14.5 [IQR: 12-18] vs. 12.0 [IQR: 10-14] mg/dL; p = 0.068, Cohen’s d = 0.343). Fasting glucose and insulin levels remained comparable between groups.

CONCLUSION: Dynamic glucose dysregulation is independently associated with OSA severity in obese adolescents. The OGTT may unmask early metabolic impairment that remains hidden in fasting states.

PMID:42545670 | DOI:10.1007/s40618-026-02999-w

Eur J Health Econ. 2026 Aug 3. doi: 10.1007/s10198-026-01979-4. Online ahead of print.

ABSTRACT

PURPOSE: Maintaining or improving the health-related quality of life (QoL) of lung cancer patients is essential throughout treatment. To support shared decision-making and improve patient-physician communication, patients’ preferences should be understood and considered in clinical decision-making; however, existing research indicates notable discrepancies between patient and physician priorities. This study therefore aims to elicit and compare their preferences regarding QoL dimensions in lung cancer care in Germany.

METHODS: Based on systematic literature reviews as well as qualitative analysis, two discrete choice experiments (DCEs) were applied to elicit the preferences of patients and treating physicians. In the DCE scenarios, both groups chose between alternative QoL profiles reflecting different health states during lung cancer treatment. Data were analyzed using multinomial logit models.

RESULTS: The final DCEs comprised five common attributes – activities of daily living, shortness of breath, anxiety, social life, and emotional impairment – and one group-specific attribute: financial difficulties in the patient DCE and severity of pain in the physician DCE. Overall, 162 patients (mean age: 60.39 years, SD 10.05) and 154 referring physicians (mean age: 51.26 years, SD 11.28) participated. All model coefficients were statistically significant (p < 0.001). Patients prioritized “Shortness of breath” (28.0%; level range of 1.417) and “Activities of daily living” (23.8%; level range of 1.207), while “Emotional impairment” (6.4%; level range of 0.323) ranked lowest. In contrast, treating physicians emphasized ”Shortness of breath” (26.0%; level range of 1.114) and “Severity of pain” (22.5%; level range of 0.962); again, “Emotional impairment” ranked lowest (4.8%; level range of 0.207).

CONCLUSIONS: Overall, patients and treating physicians showed broad agreement regarding the importance of several central QoL dimensions, particularly shortness of breath and activities of daily living. At the same time, differences in the weighting of selected attributes suggest that individual QoL priorities should be addressed explicitly in patient-physician communication.

PMID:42545648 | DOI:10.1007/s10198-026-01979-4

Lifetime Data Anal. 2026 Aug 3;32(3):46. doi: 10.1007/s10985-026-09725-x.

ABSTRACT

Dynamic prediction of future clinical outcomes based on longitudinally measured predictors plays a crucial role in disease management and patient counseling, particularly when conventional static models are inadequate. Joint modeling of longitudinal and time-to-event data provides a useful framework for addressing this challenge. In this paper, we present a comprehensive development of the recently proposed backward joint model (BJM; Shen and Li, 2021), which factorizes the likelihood into the distribution of time-to-event data and the conditional distribution of longitudinal data given the event time. This structure facilitates computation and is well-suited for multivariate longitudinal data. We introduce several novel developments to the BJM, including the extrapolation and two-part specifications, as well as the incorporation of competing risks. We also address an important yet underexplored problem in the literature: predicting future longitudinal trajectories conditional on predicted event times. Additionally, we explore the connection between BJM and existing joint modeling approaches. All these extensions preserve the computational advantages of the basic BJM formulation, including one-dimensional numerical integration, convex optimization via the EM algorithm, and a quick procedure for consistent estimation using standard software. We evaluate the method’s performance through simulation studies and illustrate its utility in a chronic kidney disease application.

PMID:42545639 | DOI:10.1007/s10985-026-09725-x

J Autism Dev Disord. 2026 Aug 3. doi: 10.1007/s10803-026-07469-z. Online ahead of print.

ABSTRACT

PURPOSE: Children with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) may be especially sensitive to early screen exposure due to sensory and emotional vulnerabilities. This study examined whether early screen time differentially affects behavioral trajectories in ASD, ADHD, and neurotypical children.

METHODS: Using data from the Longitudinal Study of Australian Children, linear mixed-effects models assessed outcomes. Screen time before age 2 was categorized as ≥ 14 vs. <14 h/week. Hyperactivity and emotional problems were measured at ages 4, 6, and 8, with ASD and ADHD diagnoses tested as moderators.

RESULTS: ASD was linked to higher baseline hyperactivity and emotional problems and steeper increases in both outcomes over time. ADHD was associated with higher baseline hyperactivity and steeper symptom growth in hyperactivity and emotional problems over time. Greater early screen time was associated with steeper increases in emotional problems scores across all subgroups. However, no significant interaction between screen time, age, and diagnosis was found, indicating that screen exposure did not disproportionately worsen trajectories in ASD or ADHD compared to neurotypical peers.

CONCLUSION: Early screen exposure is associated with a statistically significant but small increase in emotional problem scores but does not uniquely amplify risks in ASD or ADHD. While both conditions independently show steeper behavioral symptom growth, these patterns are not exacerbated by screen time. Findings support universal, rather than disorder-specific, screen time guidelines.

PMID:42545633 | DOI:10.1007/s10803-026-07469-z

Clin Transl Oncol. 2026 Aug 3. doi: 10.1007/s12094-026-04530-2. Online ahead of print.

ABSTRACT

CONTEXT: Delirium is a frequent neuropsychiatric syndrome in patients with advanced cancer, particularly in acute palliative care settings, where its prevalence, reversibility, and prognostic implications remain incompletely characterized.

OBJECTIVES: To determine the prevalence of delirium in acute palliative care units (PCUs), identify associated clinical factors, evaluate reversibility, and assess its impact on overall survival (OS) in patients with advanced cancer.

METHODS: A prospective, longitudinal, observational study was conducted in acute PCUs at two tertiary hospitals. Adult patients with advanced cancer were assessed at admission and every 5 ± 2 days. Delirium was diagnosed according to DSM-5 criteria using the Memorial Delirium Assessment Scale (MDAS; cutoff ≥ 7). Univariate analyses were performed to explore associations with clinical variables. Overall survival was analyzed using Kaplan-Meier methods and Cox regression.

RESULTS: Among 355 eligible admissions, delirium occurred in 28% of patients, with 82% identified at admission. The hypoactive subtype was predominant, and reversibility was observed in 16%. Advanced age and poor functional status were significant predisposing factors, while infection, insomnia, fever, dehydration, immobility, and hypoglycemia were associated conditions. Median OS was significantly shorter in patients with delirium (24.5 95%CI 15-43 vs. 52 days, 95%CI 47-63). In unadjusted analyses, delirium was associated with increased mortality (HR = 1.51; 95%CI 1.19-1.92; p < 0.001). However, this association did not remain statistically significant after multivariable adjustment (adjusted HR = 1.28; 95%CI 0.98-1.66; p = 0.068).

CONCLUSIONS: Delirium affected one in four patients admitted to acute PCUs, showed limited reversibility, and was associated with reduced survival. These findings highlight delirium as a frequent and clinically meaningful syndrome and underscore the importance of systematic screening and early, proactive management in acute palliative care.

PMID:42545626 | DOI:10.1007/s12094-026-04530-2

Clin Transl Oncol. 2026 Aug 3. doi: 10.1007/s12094-026-04522-2. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate whether principal component analysis (PCA) of rectal and bladder dose-volume histograms (DVHs) identifies dose regions associated with late toxicity after prostate stereotactic body radiotherapy (SBRT).

METHODS/PATIENTS: This retrospective single-institution study included 106 patients with linked clinical and dosimetric data after prostate SBRT to 36.25 Gy in five fractions. PCA was applied separately to whole-organ and wall-based rectal and bladder DVHs. Associations with late grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) toxicity at 12 months were explored using Spearman correlation, ROC analysis and deliberately limited logistic regression. Toxicity was extracted retrospectively from institutional follow-up records scored according to CTCAE v5.0.

RESULTS: Among 84 patients with 12-month follow-up in the DVH-linked dosimetric cohort, grade ≥ 2 toxicity was uncommon, with 3 GI events (3.6%) and 2 GU events (2.4%). Intermediate-dose rectal metrics showed the strongest exploratory signal for late GI toxicity, particularly rectal V18.1 Gy (AUC 0.868, 95% CI 0.740-0.997) and V29 Gy (AUC 0.827). These estimates are based on very few events and should not be interpreted as validated predictive performance or as evidence of a new planning threshold. No bladder or bladder-wall metric showed clinically meaningful discrimination for GU toxicity.

CONCLUSIONS: Intermediate whole-rectum dose was associated with late GI toxicity in this low-event SBRT cohort, but the findings are exploratory and require validation. No isolated dosimetric predictor of late GU toxicity was identified.

PMID:42545625 | DOI:10.1007/s12094-026-04522-2

Acta Neurol Belg. 2026 Aug 3. doi: 10.1007/s13760-026-03155-0. Online ahead of print.

ABSTRACT

OBJECTIVE: The glymphatic system is vital for metabolic waste clearance, and its impairment has been implicated in various neurological disorders. We investigated the relationship between structural perivascular space (PVS) burden and the DTI-ALPS index (A non-invasive proxy reflecting perivascular diffusion characteristics) in healthy young adults, to evaluate their utility as complementary markers of subclinical perivascular alterations.

METHODS: Twenty-four healthy volunteers (mean age: 32.3 ± 6.2 years) underwent 3T MRI including 64-direction diffusion tensor imaging. The DTI-ALPS index was calculated via an automated ROI method with visual quality control. Participants with Pittsburgh Sleep Quality Index (PSQI) > 5 were excluded. PVS burden (count and score) was assessed in the basal ganglia and centrum semiovale according to STRIVE criteria. Inter-rater agreement between two blinded neuroradiologists was assessed using Cohen’s weighted kappa (κw). Group differences based on enlarged PVS (EPVS > 3 mm) were analyzed using Mann-Whitney U tests with effect size calculations.

RESULTS: Strong negative correlations were found between the DTI-ALPS index and total PVS score (ρ = -0.869) and total PVS count (ρ = -0.888) (p < 0.001). Participants with EPVS (n = 11) exhibited significantly lower DTI-ALPS indices (p < 0.001; rank-biserial correlation = 0.972). Regression analysis revealed PVS load independently explained 76.3% of DTI-ALPS variance (R² = 0.763) after controlling for age. Post-hoc power analysis confirmed adequate statistical power for all primary analyses (1 – β > 0.99) despite the modest sample size, owing to the large observed effect sizes.

CONCLUSION: In healthy young adults, increased PVS burden and the presence of EPVS are strongly associated with reduced DTI-ALPS index values. This robust structure-diffusion coupling may hypothetically reflect subclinical alterations in glymphatic clearance capacity, though causal functional interpretation requires direct validation. PVS analysis may serve as a complementary, non-invasive radiological marker for monitoring perivascular integrity at its subclinical stages.

PMID:42545619 | DOI:10.1007/s13760-026-03155-0