Category: Statistics

JAMA Netw Open. 2026 Jul 1;9(7):e2623006. doi: 10.1001/jamanetworkopen.2026.23006.

ABSTRACT

IMPORTANCE: Early vision screening plays a critical role in detecting and treating vision loss-related conditions in children. Despite this, few studies have examined pediatric vision screening rates alongside vision health outcomes using large primary care electronic health record (EHR) datasets.

OBJECTIVE: To measure annual rates of vision screening at well-child care (WCC) visits and the prevalence of vision loss-related conditions among children aged 3 to 17 years, focusing on American Indian or Alaska Native children.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used patient-level EHR data from a large Minnesota-based health system and included children aged 3 to 17 years with at least 1 WCC visit between January 1, 2018, and December 31, 2023. Analyses were conducted between January 2024 and April 2025.

EXPOSURES: Patient age, self-identified race and ethnicity, and insurance type. Race and ethnicity categories included American Indian or Alaska Native, Asian, Black or African American, Hispanic or Latino, Native Hawaiian or Pacific Islander, White, and other (those who selected “some other race” as an option).

MAIN OUTCOMES AND MEASURES: Primary outcomes were (1) annual vision screening rates during WCC visits and (2) the prevalence of 9 vision loss-related conditions identified using diagnostic codes in the EHR. Two-proportion Z tests were used to test for statistical significance between children who identified as American Indian or Alaska Native and those who did not (ie, those who identified as any other race or ethnicity category).

RESULTS: Overall, 209 775 children (mean [SD] age, 10.8 [4.6] years; 103 605 [49.4%] female) were evaluated, with 1358 children self-identifying as American Indian or Alaska Native (0.6%) and 203 197 (96.9%) identifying as any other race or ethnicity category. The annual vision screening rate at WCC visits was 88.7% (95% CI, 88.6%-88.8%), with small differences by race and ethnicity and insurance type and larger differences by age. Rates were lowest among those aged 3 to 5 years. Screening rates did not differ significantly between children who identified as American Indian or Alaska Native compared with those who did not; however, American Indian or Alaska Native children had a higher prevalence of amblyopia (5.2% [95% CI, 3.8%-6.5%] vs 3.7% [95% CI, 3.6%-3.8%]) and several refractive error conditions, including astigmatism (17.4% [95% CI, 15.3%-19.7%] vs 12.5% [95% CI, 12.3%-12.6%]), hyperopia (13.3% [95% CI, 11.2%-15.3%] vs 10.7% [95% CI, 10.6%-10.9%]), and myopia (11.1% [95% CI, 9.3%-12.9%] vs 8.3% [95% CI, 8.1%-8.4%]).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of children aged 3 to 17 years, American Indian or Alaska Native children experienced a higher burden of vision loss-related conditions despite comparable screening rates; across all race and ethnicity groups, screening rates were lowest among young children. These findings highlight opportunities to strengthen early vision screening and to better understand factors associated with observed inequities in pediatric vision health.

PMID:42440316 | DOI:10.1001/jamanetworkopen.2026.23006

JAMA Netw Open. 2026 Jul 1;9(7):e2623042. doi: 10.1001/jamanetworkopen.2026.23042.

ABSTRACT

IMPORTANCE: During the COVID-19 pandemic, the major burden of morbidity and mortality was in older age groups. While within-household transmission is well documented, the wider role of social networks for transmission to the older population is less well understood.

OBJECTIVE: To estimate whether children’s birthdays were associated with grandparents’ SARS-CoV-2 infection risk.

DESIGN, SETTING, AND PARTICIPANTS: This nationwide, register-based cohort study included grandparents residing in Denmark with 1 to 5 grandchildren aged 0 to 15 years during the period between February 19, 2020, and February 28, 2022. The timing of birthdays of grandchildren was used as a natural experiment to examine whether birthday-related opportunity for family gatherings was associated with the risk of SARS-CoV-2 infection in grandparents. Family structures were mapped at the individual level. Data were analyzed from June 2024 to December 2026.

EXPOSURES: Birthdays of grandchildren turning 1 to 16 years. A birthday risk window, the period when positive test results could be ascribed to a celebration, was defined as the 7-day time window from 2 to 8 days after the grandchild’s birthday.

MAIN OUTCOMES AND MEASURES: The primary outcome was a positive result on a SARS-CoV-2 test (by polymerase chain reaction or antigen testing) recorded in the national surveillance system. Hazard ratios comparing the hazard of having positive test result for SARS-CoV-2 (outcome) in grandparents in birthday-windows vs grandparents who at the same moment were in nonbirthday periods, were estimated using Cox proportional hazards regression with birthdays as time-varying covariates.

RESULTS: Among 1 106 493 grandparents (median [IQR] age, 67 [60-73] years; 54% female), grandparents had 9.9% (95% CI, 7.9%-12.0%) higher hazard of SARS-CoV-2 infection during birthday risk windows. The hazard varied over time and by variant and was not seen during the period when Alpha dominated. The risk was greater for birthdays of preschool-aged grandchildren (adjusted hazard ratio, 1.15; 95% CI, 1.12-1.18) than during birthdays of school-aged grandchildren (adjusted hazard ratio, 1.07; 95% CI, 1.04-1.09).

CONCLUSIONS AND RELEVANCE: This cohort study of grandparents found that grandchild birthdays, despite official advice not to gather during part of the pandemic, were associated with increased SARS-CoV-2 infection risk among grandparents during much of the pandemic, with magnitude of risk varying over time and by viral variant. These results emphasize the role of culturally important events in intergenerational transmission dynamics, supporting future targeted risk mitigation around small family events.

PMID:42440315 | DOI:10.1001/jamanetworkopen.2026.23042

JAMA Netw Open. 2026 Jul 1;9(7):e2623260. doi: 10.1001/jamanetworkopen.2026.23260.

ABSTRACT

IMPORTANCE: Tenecteplase is an alternative to alteplase for intravenous thrombolysis in acute ischemic stroke given its simplified administration and comparable safety and efficacy. However, its impact on workflow metrics that may affect clinical outcomes, such as door-to-needle and door-in-door-out times, has not been well-characterized.

OBJECTIVE: To compare door-to-needle and door-in-door-out times between tenecteplase-treated and alteplase-treated patients with acute ischemic stroke in US hospitals.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the American Heart Association’s Get With The Guidelines-Stroke registry between July 1, 2020, and June 30, 2022. The analysis included adult patients with ischemic stroke who received intravenous thrombolysis. Data analysis was conducted from August to November 2023.

EXPOSURE: Tenecteplase or alteplase treatment in a consecutive series of patients with ischemic stroke.

MAIN OUTCOMES AND MEASURES: Primary outcomes were door-to-needle time among patients who arrived directly to the reporting hospital and door-in-door-out time among those transferred after thrombolytic administration. Secondary outcomes were door-to-puncture and other endovascular workflow metrics among patients treated with thrombectomy after thrombolysis. Generalized linear mixed models were used to assess the association between thrombolytic treatment and workflow time intervals outcomes.

RESULTS: Of 133 228 thrombolysis-treated patients (mean [SD] age, 68.3 [14.8] years; 64 173 female [48.2%]; median [IQR] National Institutes of Health Stroke Scale score, 7 [3-14]), 13 988 (10.5%) received tenecteplase, and 119 240 (89.5%) received alteplase. The mean (SD) door-to-needle time was significantly shorter with tenecteplase vs alteplase (47.0 [26.8] vs 52.7 [28.0] minutes; adjusted mean difference, -3.13 minutes; 95% CI, -3.84 to -2.42 minutes). Door-to-needle time 30 minutes or less occurred more frequently with tenecteplase than with alteplase (2955 of 9893 patients [29.9%] vs 14 781 of 72 539 patients [20.4%]; adjusted odds ratio [aOR], 1.34; 95% CI, 1.25 to 1.44), as did door-to-needle time 45 minutes or less (5766 of 9893 patients [58.3%] vs 35 238 of 72 539 patients [48.6%]; aOR, 1.24; 95% CI, 1.17 to 1.32) and 60 minutes or less (7670 of 9893 patients [77.5%] vs 51 282 of 72 539 patients [70.7%]; aOR, 1.25; 95% CI, 1.17 to 1.33). Among transferred patients likely eligible for mechanical thrombectomy, mean (SD) door-in-door-out times were shorter for tenecteplase vs alteplase (108.3 [31.6] vs 114.1 [32.0] minutes; adjusted mean difference, -5.94 minutes; 95% CI, -9.10 to -2.77 minutes). Among patients receiving thrombectomy, shorter times were observed in the tenecteplase group for door-to-arterial puncture, door-to-device deployment, and door-to-reperfusion. Hospitals that transitioned to tenecteplase during the study period had faster door-to-needle time times after vs before the switch (mean [SD], 51.1 [12.1] vs 52.7 [10.8] minutes; adjusted mean difference, -1.52 minutes; 95% CI, -2.88 to -0.15 minutes).

CONCLUSIONS AND RELEVANCE: In this analysis of a large nationwide registry, tenecteplase was associated with faster door-to-needle and door-in-door-out times than alteplase. These workflow advantages provide support for broader use of tenecteplase for stroke thrombolysis.

PMID:42440314 | DOI:10.1001/jamanetworkopen.2026.23260

JAMA Intern Med. 2026 Jul 13. doi: 10.1001/jamainternmed.2026.2928. Online ahead of print.

NO ABSTRACT

PMID:42440299 | DOI:10.1001/jamainternmed.2026.2928

J Am Med Inform Assoc. 2026 Jul 13:ocag119. doi: 10.1093/jamia/ocag119. Online ahead of print.

ABSTRACT

BACKGROUND: Distributed Research Networks (DRNs) offer significant opportunities for collaborative multi-site research and have significantly advanced healthcare research based on clinical observational data. However, generating high-quality real-world evidence using fit-for-use data from multi-site studies faces important challenges, including biases associated with various types of heterogeneity within and across sites and data sharing difficulties. Over the last 10 years, Privacy-Preserving Distributed Algorithms (PDA) have been developed and utilized in numerous national and international real-world studies spanning diverse domains, from comparative effectiveness research, target trial emulation, to healthcare delivery, policy evaluation, and system performance assessment. Despite these advances, there remains a lack of comprehensive and clear guiding principles for generating high-quality real-world evidence through collaborative studies leveraging the methods under PDA.

OBJECTIVE: The paper aims to establish 10 principles of best practice for conducting high-quality multi-site studies using PDA. These principles cover all phases of research, including study preparation, protocol development, analysis, and final reporting.

DISCUSSION: The 10 principles for conducting a PDA study outline a principled, efficient, and transparent framework for employing distributed learning algorithms within DRNs to generate reliable and reproducible real-world evidence.

PMID:42440280 | DOI:10.1093/jamia/ocag119

Cochrane Database Syst Rev. 2026 Jul 13;7:CD013562. doi: 10.1002/14651858.CD013562.pub2.

ABSTRACT

RATIONALE: After inadequate response to first-line biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drug (DMARD) therapy in adults with rheumatoid arthritis, there are numerous alternative DMARD options, and current understanding of their comparative benefits and harms is limited.

OBJECTIVES: The aim of this living systematic review and network meta-analysis was to compare the benefits and harms of DMARDs after failure of biologic or targeted synthetic DMARDs in adults with rheumatoid arthritis.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and the WHO ICTRP) from inception until 28 November 2025, with no restrictions on language or date of publication.

ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) of adults aged 18 years or older diagnosed with rheumatoid arthritis according to 1958, 1987, or 2010 classification criteria who previously demonstrated inadequate response to a b/ts DMARD. Eligible interventions included conventional synthetic DMARDs (methotrexate, antimalarials, sulfasalazine, leflunomide, ciclosporin, and azathioprine), biologic DMARDs (adalimumab, certolizumab, etanercept, golimumab, infliximab, abatacept, rituximab, tocilizumab, sarilumab, and anakinra), and targeted synthetic DMARDs (tofacitinib, baricitinib, and upadacitinib).

OUTCOMES: Our critical outcomes were American College of Rheumatology 50% (ACR50) response, withdrawals due to adverse events, radiographic progression, Disease Activity Score 28 (DAS28) remission, pain as measured by visual analogue scale, function as measured by the Health Assessment Questionnaire (HAQ), and serious adverse events. Important outcomes included ACR20, ACR70, serious infections, fatigue, and quality of life.

RISK OF BIAS: We used Cochrane’s RoB 1 tool to assess risk of bias in the included studies.

SYNTHESIS METHODS: We first screened the records using an approach that combined machine learning and crowdsourcing to identify probable RCTs. We then reviewed the records identified as RCTs for eligibility and simultaneously classified them to the appropriate Population, Intervention, Comparator, and Outcome (PICO) question(s). Two review authors then extracted relevant data from the included studies in duplicate and independently, with any disagreements resolved by a third review author. A Bayesian random-effects network meta-analysis was conducted using a semi-informative prior probability distribution. We assessed the certainty of evidence for each outcome using the GRADE approach.

INCLUDED STUDIES: We included 19 unique studies (4779 participants) in the review, all of which were parallel-design RCTs. Eleven trials were placebo controlled; two trials had an inactive comparator arm; and six trials had an active comparator arm. The trials were performed in a well-established rheumatoid arthritis population, with the median baseline disease duration ranging from 6.4 to 14 years, median age of participants ranging from 49 to 58 years, and median baseline disease activity (DAS28) ranging from 4.87 to 6.79.

SYNTHESIS OF RESULTS: ACR50 response We found moderate-/high-certainty evidence that using a tumour necrosis factor (TNF) inhibitor not previously tried, interleukin-6 (IL-6) inhibitors, abatacept, rituximab, and Janus kinase (JAK) inhibitors was more effective than placebo: TNF inhibitor not previously tried (odds ratio (OR) 6.04, 95% credible interval (CrI) 2.49 to 16.3; high-certainty evidence), sarilumab (OR 3.11, 95% CrI 1.25 to 7.76; high-certainty evidence), tocilizumab 4 mg/kg intravenous (OR 5.31, 95% CrI 2.09 to 12.09; high-certainty evidence), tocilizumab 8 mg/kg intravenous (OR 10.03, 95% CrI 3.65 to 31.27; high-certainty evidence), subcutaneous abatacept (OR 4.31, 95% CrI 0.97 to 18.28; moderate-certainty evidence), intravenous abatacept (OR 4.57, 95% CrI 2.21 to 10.18; high-certainty evidence), rituximab (OR 5.50, 95% CrI 2.31 to 13.12; high-certainty evidence), upadacitinib (OR 3.93, 95% CrI 1.53 to 10.32; high-certainty evidence), tofacitinib (OR 3.93, 95% CrI 1.53 to 10.32; high-certainty evidence), baricitinib 2 mg (OR 2.00, 95% CrI 0.77 to 5.23; moderate-certainty evidence), baricitinib 4 mg (OR 2.79, 95% CrI 1.10 to 7.22; high-certainty evidence). With an assumed risk for placebo of 78 out of 1000 patients, the expected effects for the active drugs ranged from 143 (baricitinib 2 mg) to 455 (tocilizumab 8 mg/kg). Withdrawals due to adverse events For most interventions, there were sparse data with low-certainty evidence, except for TNF inhibitor not previously tried (risk ratio (RR) 0.32, 95% CrI 0.07 to 1.1; moderate-certainty evidence), which is probably less harmful than placebo, and sarilumab (RR 1.98, 95% CrI 0.57 to 7.19; moderate-certainty evidence), which is probably more harmful than placebo. Low-certainty evidence suggests that intravenous abatacept (RR 0.92, 95% CrI 0.34 to 2.79), upadacitinib (RR 0.41, 95% CrI 0.08 to 1.83), and baricitinib 2 mg (RR 0.93, 95% CrI 0.22 to 4.01) may be less harmful than placebo. Low-certainty evidence suggests that tocilizumab 4 mg/kg (RR 1.39, 95% CrI 0.39 to 5.28), tocilizumab 8 mg/kg (RR 1.49, 95% CrI 0.51 to 4.81), subcutaneous abatacept (RR 3.11, 95% CrI 0.05 to 249.6), rituximab (RR 2.38, 95% CrI 0.44 to 23.31), tofacitinib (RR 1.37, 95% CrI 0.35 to 5.58), and baricitinib 4 mg (RR 1.43, 95% CrI 0.38 to 5.81) may be more harmful than placebo. Data were insufficient to perform a network meta-analysis for radiographic progression. For DAS28 and the HAQ, there was mostly moderate-/high-certainty evidence of a benefit, with some exceptions for comparisons with indirect evidence only that was of low or very low certainty. For the other efficacy outcomes, data were sparse with wide credible intervals, and the certainty of evidence was typically low.

AUTHORS’ CONCLUSIONS: We found high-certainty evidence that nine therapies and moderate-certainty evidence that two therapies provide a clinically important benefit in improving disease activity compared to placebo for people with rheumatoid arthritis after failure of b/ts DMARD therapy. There was significant uncertainty surrounding treatment-related harms, with the evidence having been downgraded for serious or extremely serious imprecision. Pair-wise comparisons showed no significant differences among therapies, although the certainty of evidence was low. The lack of clarity regarding safety and comparative efficacy suggests that treatment decisions should be guided by individual patient characteristics and preferences.

FUNDING: This work was supported by grants from the Canadian Institutes for Health Research (CIHR) [Funding Reference Numbers (FRN) 178375 and 180324] and the National Health and Medical Research Council (NHMRC) Cochrane Collaboration. This research was supported by Arthritis Society Canada (Doctoral Studentship TGP-23-0211).

REGISTRATION: This study was outlined in a Cochrane protocol (CD013562; DOI 10.1002/14651858.CD013562).

PMID:42440279 | DOI:10.1002/14651858.CD013562.pub2

Otol Neurotol. 2026 Aug 1;47(7):860-867. doi: 10.1097/MAO.0000000000004933. Epub 2026 May 1.

ABSTRACT

OBJECTIVE: To evaluate whether cochlear implantation reduces listening-related fatigue in children with unilateral hearing loss.

STUDY DESIGN: Prospective within-subjects crossover study.

SETTING: Three academic medical centers specializing in pediatric cochlear implantation.

METHODS: Fatigue was assessed using the Vanderbilt Fatigue Scale and PedsQL™ 3.0 Multidimensional Fatigue Scale. Parent- and child-reported versions were completed after consecutive days of baseline cochlear implant use and following a three-day discontinuation during a holiday break. Paired t-tests compared conditions (P <0.05). Univariable regressions examined associations with age, sex, and deafness duration. Intraclass correlation coefficients assessed parent-child agreement.

RESULTS: Of 69 eligible patients, 37 responded; 18 declined due to reluctance to discontinue CI use. Nineteen children (mean age 8.6 y, 26.3% male, mean deafness duration 3.4 y) completed the study. Parent-reported fatigue significantly worsened after implant non-use in mental (P=0.01) and physical domains (P=0.04) on the Vanderbilt scale, and in cognitive fatigue (P=0.03) on the PedsQL. Child-reported scores trended toward greater fatigue during non-use, though not statistically significant. Younger age and male sex were associated with higher fatigue in parent reports. Intraclass correlation coefficients indicated moderate to good parent-child agreement.

CONCLUSION: Cochlear implantation alleviates listening-related fatigue in children with unilateral hearing loss, particularly in cognitive and physical domains as perceived by parents. Fatigue represents a clinically meaningful, non-audiological outcome in candidacy assessment and postoperative evaluation.

PMID:42440270 | DOI:10.1097/MAO.0000000000004933

Cell Biochem Biophys. 2026 Jul 13. doi: 10.1007/s12013-026-02117-w. Online ahead of print.

ABSTRACT

This research aims to explore the human-like taste response of three bitter molecules (chloroquine, denatonium, and saccharin) on the human bronchi receptor T2R agonist using a statistical physics approach. By fitting the concentration-taste response curves, we estimate three model parameters (R_M, n, C_1/2) to assess the intermolecular interactions with T2R receptor sites. In addition, the transduction coefficient (α) of the three tasting molecules has been determined. This analysis provides valuable insights into the binding energy spectrum (AES) and establishes a common gustatory band for the bitter tastes, with adhesive energies distributed over a relatively wide range (2.5-22.5 kJ mol⁻¹). In addition, molecular docking simulations were conducted, revealing that denatonium exhibits stronger binding affinities (28.87 kJ/mol) with the T₂R₁₀ human taste receptor site compared to chloroquine (26.78 kJ/mol). Conversely, saccharin displayed a binding affinity of approximately 23.85 kJ/mol with the binding pocket of the T₂R₃₁ ion channel receptors. This three molecules undergoes theoretical analysis using the DFT/B3LYP/6-311 G(d, p) basis set to determine its frontier orbital features and stability. The type and strength of interactions were identified using the topological parameters of the “Atoms in Molecules” (AIM) method, NCI analysis was used to study intra- and intermolecular noncovalent interactions within a molecular system, as well as natural bond orbital (NBO) analysis. NBO analyses indicate that all three tasting molecules exhibits significant stability. NCI interaction analyses indicate that Van der Waals forces and steric effects are observed in the three tasting molecules. 3D shaded potential surface revealed a projection of LOL examination and the electron localization function (ELF) indicated that an area of electron depletion is observed in the three tasting molecules.

PMID:42440246 | DOI:10.1007/s12013-026-02117-w

Clin Rheumatol. 2026 Jul 13. doi: 10.1007/s10067-026-08131-w. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to describe the clinical characteristics of patients with progressive pulmonary fibrosis (PPF) in systemic sclerosis (SSc)-associated interstitial lung disease (ILD) and to explore factors associated with PPF.

METHODS: Medical records of patients with SSc who visited Seoul St. Mary’s Hospital between April 2015 and March 2025 were retrospectively reviewed. PPF in SSc-ILD was defined as a relative decline in predicted forced vital capacity (FVC) ≥ 10% within 24 months. Clinical characteristics and outcomes were compared using logistic regression and survival analyses.

RESULTS: Among 319 patients with SSc evaluated with thoracic CT, ILD was identified in 168 (52.7%). Of the 140 patients with SSc-ILD who had serial spirometry, 27 (19.3%) developed PPF. Patients with PPF exhibited digital gangrene (25.9% vs. 8.8%, P = 0.02), pulmonary hypertension (40.7% vs. 20.0%, P = 0.04), and mixed NSIP-UIP (11.1% vs. 1.8%, P = 0.049) more frequently than those without PPF. Treatment with methotrexate (37.0% vs. 15.0%, P = 0.01) and nintedanib (18.5% vs. 1.8%, P = 0.003) was also more prevalent. None of the variables remained statistically significant in the multivariable analysis, and overall survival did not differ between patients with and without PPF.

CONCLUSION: In patients with SSc-associated ILD, PPF was associated with prominent vascular manifestations and mixed NSIP-UIP. These findings underscore the heterogeneity of SSc-ILD and highlight the importance of close and longitudinal pulmonary function monitoring to identify disease progression. Key Points • ILD is common in systemic sclerosis, and a subset of patients with SSc-ILD develop PPF. • Patients with PPF more frequently exhibit vascular manifestations and distinct radiologic features, including mixed NSIP-UIP. • Regular longitudinal monitoring with pulmonary function tests is essential for early detection of disease progression in SSc-ILD.

PMID:42440242 | DOI:10.1007/s10067-026-08131-w

J Endocrinol Invest. 2026 Jul 13. doi: 10.1007/s40618-026-02984-3. Online ahead of print.

ABSTRACT

BACKGROUND: Testicular adrenal rest tumors (TARTs) are benign, hormonally responsive testicular lesions in male patients with congenital adrenal hyperplasia (CAH). TARTs represent a leading contributor to gonadal dysfunction and infertility in this population. This study aimed to investigate the clinical and genetic characteristics of TARTs and to identify clinical indicators that may facilitate their early detection.

METHODS: A retrospective cohort study included 38 male patients with biochemically and molecularly confirmed CAH who were followed at our pediatric endocrinology clinic between January 2019 and January 2025. Demographic characteristics, underlying enzymatic defects, CYP21A2 and CYP11B1 genotype, clinical phenotype, hormonal profiles-including adrenocorticotropic hormone (ACTH) and 17-hydroxyprogesterone (17-OHP) concentrations-pubertal status, skeletal maturation as assessed by bone age, and scrotal ultrasonographic findings were systematically retrieved from medical records and analyzed.

RESULTS: TARTs were identified in 14 of 38 patients, corresponding to a prevalence of 36.8%. Of the affected individuals, 12 (85.7%) harbored 21-hydroxylase deficiency and 2 (14.3%) had 11β-hydroxylase deficiency. No statistically significant differences were observed in ACTH or 17-OHP levels between patients with and without TART (p = 0.75 and p = 0.36, respectively). TARTs were significantly more prevalent among patients with the salt-wasting phenotype relative to other clinical forms (p = 0.002) and among pubertal compared with prepubertal patients (p = 0.016). Skeletal maturation, as reflected by bone age advancement, was significantly more pronounced in the TART-positive group (p = 0.012). Multivariable logistic regression analysis identified bone age advancement (OR = 1.76; 95% CI: 1.10-2.83; p = 0.019) and pubertal status (OR = 12.5; 95% CI: 1.7-91.6; p = 0.013) as factors independently associated with the presence of TART.

CONCLUSIONS: Bone age advancement was independently associated with the presence of TART and may represent a clinically useful marker associated with TART in male patients with CAH. These findings suggest that bone age assessment may complement isolated hormonal measurements and may help identify patients who could benefit from closer ultrasonographic surveillance. Early detection and timely therapeutic intervention remain important for preserving gonadal function and future fertility.

PMID:42440236 | DOI:10.1007/s40618-026-02984-3