Tag: statistics

Neurology. 2026 Jul 28;107(2):e218280. doi: 10.1212/WNL.0000000000218280. Epub 2026 Jul 1.

ABSTRACT

BACKGROUND AND OBJECTIVES: Genetics represent a nonmodifiable risk factor for Alzheimer disease (AD), with 60%-80% heritability. Midlife hypertension is a modifiable risk factor for both dementia and death. Our primary objective was to determine how genetic risk for AD modifies the association between hypertension and dementia.

METHODS: The Atherosclerosis Risk in Communities Study is an ongoing community-based prospective cohort study of 4 US centers. We analyzed White and Black participants free of dementia at age 55 years with genotypes and blood pressure measured at visit 1 (1987-1989). Three genetic risk groups (low, medium, high) were defined based on tertiles of a race-specific AD polygenic risk score. Dementia was ascertained through cognitive testing, informant interviews, hospitalization, codes and death records. Death was ascertained through the National Death Index. We examined the association of midlife hypertension with incident dementia within 3 genetic risk groups using Cox proportional-hazards and cumulative incidence function estimations. We used age 55 years as the time origin, with left truncation to allow entry at ages older than 55 years; age on December 31, 2022, was the administrative censoring date.

RESULTS: Among 8,931 White and 2,666 Black participants, the median follow up time was 26.6 and 23.8 years, the mean age was 54.0/53.5 years, and 53.0%/62.5% were female, respectively. After adjusting for demographics, midlife hypertension was significantly associated with dementia incidence across all genetic risk groups among White participants (low risk hazard ratio [HR] 1.29; 95% CI 1.07-1.55, medium risk HR 1.34; 95% CI 1.13-1.58, high risk HR 1.19; 95% CI 1.03-1.38) and among Black participants at high genetic risk (HR 1.31; 95% CI 1.04-1.66). Associations for low and medium genetic risk Black participants were consistent but not statistically significant. There were no significant differences in association of hypertension with dementia by AD genetic risk group. Individuals with hypertension had a 0%-2% higher probability of developing dementia by age 80 and a 6%-13% lower probability of dementia-free survival to age 80 years vs those without hypertension, across race and genetic risk groups.

DISCUSSION: Genetic risk for AD does not modify the association between hypertension and dementia. These data support the fact that all individuals with hypertension are likely to benefit from antihypertensive treatment.

PMID:42385118 | DOI:10.1212/WNL.0000000000218280

Neurology. 2026 Jul 28;107(2):e218226. doi: 10.1212/WNL.0000000000218226. Epub 2026 Jul 1.

ABSTRACT

BACKGROUND AND OBJECTIVES: Putamen dopamine depletion characterizes Parkinson disease (PD). Intraneuronal processes determining dopamine stores have not been systematically examined. This study explored relative contributions of dopamine synthesis, storage, and metabolism to control-PD differences.

METHODS: We updated an intramural tabulation from 2002 to 2024 of postmortem putamen tissue contents of reactants, including the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), from patients with PD and controls. Based on computational models applying first-order kinetics and equilibrium equations, we then compared estimated rates of dopamine synthesis through tyrosine hydroxylase (TH), L-aromatic-amino-acid decarboxylase, vesicular active uptake and passive leakage, exocytotic release and reuptake, and other intraneuronal processes. Results from the modeling were compared with those from in vivo ¹⁸F-DOPA PET.

RESULTS: Postmortem data were analyzed from 13 patients with PD (median age 77 years, range 73-85 years) and 20 controls (median age 77 years, range 35-91 years). There was approximately a 98% decrease in putamen tissue dopamine in PD, and the concentration ratio of DOPAL/dopamine (DA) was approximately 9 times that of control. Applying the simplest kinetic model, vesicular sequestration was estimated to be decreased by 98.5% (0.073 vs 4.91 nmol/minute). Approximately 3-fold greater in vivo “washout” of putamen ¹⁸F-DOPA-derived radioactivity compared with controls also indicated attenuated vesicular storage in PD. According to the complete model, control-PD differences in intraneuronal reaction rates were in descending order of vesicular uptake ≈ vesicular leakage > exocytotic release ≈ neuronal reuptake > L-aromatic-amino-acid decarboxylase activity ≈ TH activity > other reactions.

DISCUSSION: Convergent quantitative evidence points to a substantial vesicular storage defect in residual dopaminergic terminals in PD. This finding challenges the sufficiency of nigrostriatal dopaminergic denervation alone to account for the biochemical phenotype of PD and highlights vesicular dopamine handling as a critical determinant of putamen dopamine deficiency. The reaction rate estimates were drawn from published point values rather than fitted to an experimental data set, and so conventional goodness-of-fit regression statistics were not conducted. Because of the assumption of steady-state conditions for calculating reaction rates based on equilibrium equations, the model does not address the dynamics of disease pathogenesis over years but does provide a platform for further extension to disease progression.

BRIEF SUMMARY: We estimated rates of reactions involved with the synthesis, storage, release, reuptake, and metabolism of dopamine in the putamen in PD and found that the main intraneuronal functional abnormality separating PD from controls was attenuated vesicular sequestration, implicating decreased vesicular uptake through the vesicular monoamine transporter and increased vesicular leakiness as key determinants of putamen dopamine deficiency in PD.

PMID:42385115 | DOI:10.1212/WNL.0000000000218226

JCO Precis Oncol. 2026 Jul;10(7):e2600045. doi: 10.1200/PO-26-00045. Epub 2026 Jul 1.

ABSTRACT

PURPOSE: Intermediate-risk neuroblastoma patients older than 18 months, with non-MYCN amplified, International Neuroblastoma Risk Group Staging System localized, unresectable or International Neuroblastoma Staging System stage 3 tumors, and unfavorable histology have inferior outcomes compared with other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup.

METHODS: We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms and gene expression in a subset, and correlated results with patient survival.

RESULTS: Among 98 tumors, 9/98 (9.2%) had oncogene amplifications (CDK4/MDM2/TERT coamplification (n = 1), CDK4/MDM2 coamplification (n = 4), CDK4 (n = 2), TERT (n = 1), and MYC (n = 1)), while 63/98 (64.3%) had typical segmental chromosomal aberrations (tSCAs). Patients with tumors with oncogene amplification had the worst 5-year event-free survival (EFS; 0%; P < .0001 log-rank test) and 5-year overall survival (OS; 44.4% [95% CI, 21.4 to 92.3]; P < .01 log-rank test). Patients with tumors harboring tSCAs had inferior EFS compared with those with numerical chromosomal aberrations only (51.7% [95% CI, 40.6 to 65.8] v 93.3% [95% CI, 81.5 to 100]; P < .01). Patients with p53 pathway tumor alterations (n = 10) had worse EFS than those without (0% v 61.1% [95% CI, 50.3 to 74.3]; P < .0001, log-rank test) and worse OS (26.7% [95% CI, 8.9 to 80.3] v 80.9% [95% CI, 71.8 to 91.3]; P < .001 log-rank test). Multivariable analysis identified tSCAs as an independent prognostic variable for EFS and oncogene amplification or p53 pathway abnormalities as independent prognostic variables for EFS and OS.

CONCLUSION: Oncogene amplification and/or p53 pathway abnormalities and/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.

PMID:42385103 | DOI:10.1200/PO-26-00045

JCO Clin Cancer Inform. 2026 Jul;10(3):e2500208. doi: 10.1200/CCI-25-00208. Epub 2026 Jul 1.

ABSTRACT

PURPOSE: Recurrent cancers are not captured in a standardized way by US tumor registries, making it difficult to conduct research on risk factors for cancer recurrence. We developed rule-based algorithms to be used with electronic health data to identify recurrent cases of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

METHODS: Incident DLBCL and FL cases (2000-2018) were identified in tumor registry data at two health plan study sites. We captured pharmacy and procedure codes to indicate first-line treatment initiation. Recurrent cases were defined as those who completed first-line treatment followed by ≥6 months with no treatment-related codes, but who later restarted treatment. The baseline algorithm was built using a claims-based database from Fallon Health (FH; Massachusetts) and tested using electronic health records and claims data at Henry Ford Health (Michigan). Results were validated by chart review at Henry Ford, and measures of validity calculated overall and by subtype. The algorithm was subsequently revised to reduce the false-positive rate.

RESULTS: FH identified 137 DLBCL and 88 FL eligible cases; 42 patients met the baseline algorithm-defined criteria for recurrent disease. Henry Ford identified 246 DLBCL and 146 FL cases. The baseline algorithm identified 115 recurrent cases with a 54% false-positive rate; the revised algorithm (R2D-non-Hodgkin lymphoma [NHL]) identified 60 recurrent cases, with a 10% false-positive rate. Following chart review, the R2D-NHL algorithm had a sensitivity of 74%, specificity of 90%, negative predictive value of 83%, and positive predictive value of 83%. Measures varied slightly between subtypes.

CONCLUSION: We developed a rule-based algorithm that can be applied to electronic health data for population-based research requiring the identification of recurrence for two common but dissimilar NHL subtypes.

PMID:42385099 | DOI:10.1200/CCI-25-00208

JCO Glob Oncol. 2026 Jul;12(7):e2500352. doi: 10.1200/GO-25-00352. Epub 2026 Jul 1.

ABSTRACT

PURPOSE: The number of cancer survivors from low- and middle-income countries is rising, but most research has been conducted in high-income countries. Although studies have characterized the detection and treatment of cervical cancer in Botswana, survivorship care is a severely understudied area. We assessed short- and long-term survivorship visit adherence and factors associated with adherence in patients treated for cervical cancer in Botswana.

METHODS: Between 2015 and 2022, females with cervical cancer were prospectively enrolled in an observational cohort study. Based on recommendations in the Botswana National Cervical Cancer Guidelines, adherence was defined as completion of a clinical visit biannually (every 6 months) during short-term survivorship care (0-2 years after treatment) and annually for long-term survivorship care (3-5 years after treatment). Generalized estimating equations (adjusted odds ratio [aOR]) were used to evaluate factors associated with short- and long-term adherence.

RESULTS: This cohort included 857 females treated with definitive- or curative-intent surgery- or radiation-based treatment, with a median age of 47.7 years (IQR, 41.6-58.2 years) and 68.6% living with HIV. On multivariable analysis of short-term care (n = 772), patients who traveled ≥100 km to the treatment facility (aOR, 0.35; P < .001), had advanced-stage (III and IV) cervical cancer (aOR, 0.69; P = .007), and were undergoing care during the COVID-19 pandemic (aOR, 0.72; P = .005) were less likely to be adherent. Results were similar for long-term care.

CONCLUSION: Adherence to recommended survivorship visits in Botswana is suboptimal. Strategies to help survivors, particularly those living farther away from treatment facilities and with advanced disease, are needed to improve adherence and reduce cervical cancer mortality.

PMID:42385095 | DOI:10.1200/GO-25-00352

FASEB J. 2026 Jul 15;40(13):e72094. doi: 10.1096/fj.202505048R.

ABSTRACT

Asthma is one of the most common chronic respiratory diseases affecting both children and adults worldwide. Its pathogenesis is driven by complex interactions between genetic susceptibility and environmental exposures. Investigating gene-environment (G × E) interactions holds significant potential to elucidate the regulatory genetic architecture underlying individual responses to environmental risk factors in childhood asthma. In this review, we systematically summarize the environmental exposure factors during prenatal and postnatal periods and analyze their independent effects on the risk of childhood asthma. Secondly, we explore the role of G × E interactions in asthma from three perspectives: statistical interaction, mechanistic interaction, and epigenetic-mediated interaction. Finally, we evaluate current treatment and intervention strategies, distinguish established recommendations for the general population from emerging and exploratory methods, and point out existing limitations. Our analysis reinforces that investigating G × E interactions is a robust approach for uncovering the molecular mechanisms underlying childhood asthma. Despite substantial technical challenges and unresolved questions regarding generalizability and heterogeneity, such investigative strategies are expected to enhance our understanding of asthma endotypes and the development of more effective, precision-based preventive and therapeutic interventions.

PMID:42384431 | DOI:10.1096/fj.202505048R

JAMA Surg. 2026 Jul 1. doi: 10.1001/jamasurg.2026.2340. Online ahead of print.

ABSTRACT

IMPORTANCE: The NRG Oncology research organization and NSABP B-35 randomized clinical trial prospectively collected margin width data on postmenopausal women with hormone receptor (HR)-positive ductal carcinoma in situ (DCIS) who underwent lumpectomy, whole-breast irradiation (WBI), and randomly assigned adjuvant anastrozole or tamoxifen therapy. This permitted analysis of outcomes per margin width.

OBJECTIVE: To analyze the effect of margin width on ipsilateral breast tumor recurrence (IBTR).

DESIGN, SETTING, AND PARTICIPANTS: NSABP B-35 was a phase 3, double-blind, randomized clinical trial in which patients were randomized to either 5 years of tamoxifen or anastrozole. Postmenopausal women with HR-positive DCIS and tumor-free margins were eligible. Enrollment was from January 6, 2003, to June 15, 2006, in academic and community hospital members of the NSABP. Study data were analyzed from July 2024 to April 2025.

INTERVENTIONS: There were no specific interventions based on lumpectomy margin width.

MAIN OUTCOMES AND MEASURES: Lumpectomy margin width data were prospectively collected within 3 months of randomization. A pathology form classified margins as positive (ink on tumor), close (<1 mm), or negative (≥1 mm). For the negative margin subgroup, closest margin width was stated separately. Thus, an ancillary analysis using 1-mm and 2-mm margin width partitions was performed.

RESULTS: A total of 3104 postmenopausal women (mean [SD] age, 61 [7.8] years) were enrolled in NSABP B-35. In an ancillary analysis, 2707 patients were included in the 1-mm margin width partition group, and 2546 patients were included in the 2-mm margin width partition group. IBTR was the most common first event, occurring in 90 of 2707 patients (3.3%): 24 of 502 patients (4.8%) with a margin width less than 1 mm and 66 of 2205 patients (3.0%) with a margin width greater than or equal to 1 mm. Ten-year unadjusted cumulative incidence of IBTR events was 5.6% vs 4.0% for margins less than 1 mm vs margins greater than or equal to 1 mm (P = .04). Using 2 mm as the discriminant threshold for margin width, 39 of 879 patients (4.4%) with margins less than 2 mm and 49 of 1667 patients (2.9%) with margins greater than or equal to 2 mm experienced an IBTR first. Ten-year unadjusted cumulative incidence of IBTR events with margins less than or equal to 2 mm was 5.3% vs 3.8% for those with margins greater than 2 mm (P = .05). In models adjusting for other patient and tumor factors, margin width was not a significant predictor of IBTR risk (2-mm threshold hazard ratio, 1.33; 95% CI, 0.86-2.06).

CONCLUSIONS AND RELEVANCE: Results of this ancillary analysis of the NSABP B-35 trial show that absolute differences in IBTR rates using margin width groupings of less than 1 mm or greater than or equal to 1 mm and margin width groupings of less than 2 mm or greater than or equal to 2 mm in postmenopausal women with HR-positive DCIS receiving lumpectomy, WBI, and adjuvant endocrine therapy were small. Omission of reexcision lumpectomies based on margin widths of less than 1 mm or less than 2 mm can be reconsidered in appropriate patients.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00053898.

PMID:42384406 | DOI:10.1001/jamasurg.2026.2340

JAMA Surg. 2026 Jul 1. doi: 10.1001/jamasurg.2026.2355. Online ahead of print.

ABSTRACT

IMPORTANCE: The operating room (OR) is the most resource-intensive setting in the hospital, making accurate OR financial metrics essential for value-based initiatives and cost-effectiveness analyses. However, prior estimates of OR time have been rendered likely obsolete by the COVID-19 pandemic, sustained inflation, and hospital consolidation, and conflation of 3 financial parameters-costs, charges, and revenue-has led to misapplication of these estimates.

OBJECTIVES: To estimate the cost of 1 minute of OR time in California hospitals, assess trends over time by hospital ownership and teaching status, and provide benchmarks for OR charges and revenue.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cross-sectional study examined California Hospital Annual Disclosure Reports for fiscal years (FYs) 2014 to 2022 from short-term general and specialty care hospitals in California. Data were analyzed from January 24 to March 13, 2026.

MAIN OUTCOMES AND MEASURES: The primary outcome was mean costs, charges, and revenue per minute of OR time, stratified by hospital ownership and teaching status. Costs were further divided into direct and indirect components. Descriptive statistics summarized hospital characteristics and financial measures.

RESULTS: The study included 278 hospitals that provided California Hospital Annual Disclosure Reports for FY 2022. Of these, 164 (59.0%) were not-for-profit hospitals, 75 (27.0%) were for-profit hospitals, and 39 (14.0%) were government owned hospitals; 34 (12.2%) were teaching hospitals. The mean (SD) cost of OR time across all hospitals was $57.71/min ($24.09/min), representing a 54% increase from FY 2014 with an annual increase of 5.24% (95% CI, 4.63%-5.82%). Direct costs accounted for 56.6% of total costs ($32.56 of $57.53), with wages and benefits comprising approximately two-thirds of direct costs. The mean (SD) charge was $295.09/min ($148.23/min) and the mean (SD) revenue was $66.31/min ($31.30/min). Government-owned hospitals had the lowest charges, highest costs, and intermediate revenues, illustrating that these 3 measures are not interchangeable.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the mean cost of OR time in California hospitals was $57.71/min in FY 2022, establishing an updated benchmark for surgical cost analyses. Additionally, benchmarks were established for OR revenue ($66/min) and charges ($295/min). Appropriate use of the different financial metrics along with accurate values is essential for valid cost-effectiveness analyses and value-based surgical care initiatives.

PMID:42384389 | DOI:10.1001/jamasurg.2026.2355

Acad Med. 2026 Jul 1:wvag209. doi: 10.1093/acamed/wvag209. Online ahead of print.

ABSTRACT

PURPOSE: Marital status has been associated with the well-being and career decisions of physicians; however, its role during residency remains underexplored, particularly in Japan. This study aimed to examine the association among marital status, psychological well-being, and intended specialty choice among postgraduate medical residents in Japan, with a focus on sex differences.

METHOD: The authors conducted a nationwide cross-sectional survey in January 2023 of postgraduate second-year residents in Japan immediately after the 2022 General Medicine In-training Examination (GM-ITE). Participants completed the survey and provided complete data on their marital status and outcome measures. The primary outcomes included depressive symptoms (assessed using the Patient Health Questionnaire-2), burnout symptoms, job satisfaction, and work-related stress (assessed using the Mini-Z 2.0) as well as gender role attitudes and intended specialty. The authors estimated adjusted prevalence ratios (PRs) using modified Poisson regression with generalized estimating equations.

RESULTS: Among 2,721 residents included in the analysis (mean age, 27.7 years; 879 [32.3%] female), 551 (20.2%) were married, of whom 282 (51.2%) had physician spouses. Depressive symptoms were most common among unmarried residents (613/2,170 [28.2%]) and least common among those married to physicians (50/282 [17.7%]; P < .001). In adjusted analyses, being married to a physician was associated with a reduced depressive symptoms prevalence (PR, 0.62; 95% confidence interval [CI], 0.48-0.81) and increased job satisfaction (PR, 1.09; 95% CI, 1.02-1.18). Marital status showed no statistically significant association with burnout symptoms or work-related stress, and no statistically significant specialty preferences differences were observed according to marital status. Female residents, particularly those married to physicians, were more likely to disagree with traditional gender roles than their male counterparts.

CONCLUSIONS: Among Japanese medical residents, marriage-particularly to another physician-was associated with fewer depressive symptoms and greater job satisfaction, whereas marital status was not associated with intended specialty choice.

PMID:42384362 | DOI:10.1093/acamed/wvag209

Eur Radiol Exp. 2026 Jul 1;10(1):104. doi: 10.1186/s41747-026-00759-2.

ABSTRACT

OBJECTIVE: To determine the optimal low-keV level using deep learning image reconstruction (DLIR) that maximizes lesion detectability, and to assess the potential for iodinated contrast media (ICM) reduction based on detectability improvements across varying patient body habitus.

MATERIALS AND METHODS: An abdominal phantom was scanned using a standard thoraco-abdomino-pelvic dual-energy computed tomography (DECT) protocol during the portal venous phase, with three rings inserted simulating different body habitus. Virtual monoenergetic images (VMI) were reconstructed from 40 to 70 keV in 10 keV increments using adaptive statistical iterative reconstruction-V (ASIR-V) 50% and high-strength DLIR (DLIR-H). Contrast enhancement was quantified, spatial resolution was evaluated with the task-based transfer function, and noise characteristics were analyzed using the noise power spectrum. Low-contrast lesion detectability (5-10 mm) was assessed using an anthropomorphic model observer.

RESULTS: Compared to ASIR-V, DLIR-H provided equivalent contrast, reduced image noise, and improved spatial resolution. All lesion sizes with DLIR-H were technically detectable under all conditions. The reconstruction at 40 keV demonstrated the highest detectability of hypovascular lesions under all conditions. However, a decrease in detectability was observed in the large phantom relative to the small and medium phantoms, resulting in a reduced theoretical potential for iodine dose reduction. The theoretical potential for iodine dose reduction using 40 keV with DLIR-H is at least 31.3% based on the phantom-based model.

CONCLUSION: Under phantom conditions, 40 keV with DLIR-H shows superior detectability of hypovascular lesions under all conditions, suggesting the theoretical possibility of reducing iodine load by up to 31.3%, based on modeled detectability performance.

RELEVANCE STATEMENT: Based on a phantom-derived model, the combination of 40-keV VMI reconstruction with DLIR-H suggests the potential for more than 30% ICM reduction in oncologic body CT, a finding that warrants confirmation in clinical studies.

KEY POINTS: Based on a phantom-derived model 40 keV VMI with DLIR-H achieved the highest detectability of hypovascular liver lesions. This approach enabled a 31.3% ICM volume reduction. Larger body habitus limits ICM volume reduction optimization margins.

PMID:42384360 | DOI:10.1186/s41747-026-00759-2