Category: Statistics

JAMA Netw Open. 2025 Feb 3;8(2):e2460785. doi: 10.1001/jamanetworkopen.2024.60785.

ABSTRACT

IMPORTANCE: Prostate cancer (PCa) remains a leading cause of cancer-related death among men in the US.

OBJECTIVE: To evaluate the association of healthy lifestyle and dietary behaviors with survival after a nonmetastatic PCa diagnosis in a multiethnic population.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted among men aged 45 to 75 years enrolled between 1993 and 1996 in the Multiethnic Cohort study. Participants with nonmetastatic PCa completed a questionnaire after diagnosis (2003-2008) and were followed up until death or loss to follow-up. Data were analyzed from January 10, 2023, to May 20, 2024.

EXPOSURES: Lifestyle and dietary patterns were assessed after diagnosis using 3 PCa behavior scores and 13 dietary indices (4 prioritized scores: the Healthy Eating Index-2015, Healthful Plant-Based Diet Index, Dietary Inflammatory Index, and Empirical Dietary Index for Hyperinsulinemia).

MAIN OUTCOMES AND MEASURES: Cox proportional hazards models were used to evaluate multivariable-adjusted associations of each PCa behavior score with all-cause, cardiovascular disease (CVD), and PCa-specific mortality.

RESULTS: A total of 2603 men with nonmetastatic PCa (mean [SD] age, 69.6 [7.1] years) were followed up, and 1346 deaths were documented, including 356 (24.6%) from CVD and 197 (14.6%) from PCa. The median (IQR) follow-up was 10.9 (IQR, 6.8-12.7) years from questionnaire return and 14.5 (IQR, 11.8-18.0) years from diagnosis. The 2021 PCa Behavior Score was associated with reduced risks of all-cause (hazard ratio [HR] per point, 0.69; 95% CI, 0.63-0.77) and CVD-related (HR, 0.67; 95% CI, 0.56-0.79) mortality. This score was also associated with a lower risk of PCa-specific mortality among African American men (HR, 0.46; 95% CI, 0.24-0.88) but not in the other racial and ethnic groups. Comparing quintile 5 (highest score) with 1 (lowest score), the Empirical Dietary Index for Hyperinsulinemia was positively associated with all-cause (HR, 1.37; 95% CI, 1.02-1.84) and CVD-related (HR, 1.96; 95% CI, 1.15-3.33) mortality, whereas the Healthful Plant-Based Diet Index was associated with a reduced risk of all-cause (HR, 0.75; 95% CI, 0.58-0.97); findings for CVD-related mortality were not statistically significant (HR, 0.67; 95% CI, 0.44-1.03). No associations were found between lifestyle or dietary patterns and PCa mortality.

CONCLUSIONS AND RELEVANCE: In this multiethnic cohort of patients with nonmetastatic PCa, healthier lifestyles were associated with improved overall survival but not with PCa-specific survival. Given the predominance of non-PCa-specific deaths, these findings support the need for health behavior counseling to treat comorbidities in men with PCa.

PMID:40009382 | DOI:10.1001/jamanetworkopen.2024.60785

JAMA Netw Open. 2025 Feb 3;8(2):e2461639. doi: 10.1001/jamanetworkopen.2024.61639.

ABSTRACT

IMPORTANCE: Subgroup definitions for possible deescalation of neoadjuvant cancer treatment are urgently needed in clinical practice.

OBJECTIVE: To investigate the effect of BRCA1 and/or BRCA2 tumor pathogenic variants (tPVs) by comparing 2 deescalated neoadjuvant regimens (nab-paclitaxel plus either carboplatin or gemcitabine) on pathologic complete response (pCR), invasive disease-free survival (IDFS), and overall survival (OS) of patients with early-stage triple-negative breast cancer (TNBC).

DESIGN, SETTING, AND PARTICIPANTS: This was a preplanned secondary analysis of a phase 2 prospective randomized clinical trial (ADAPT-TN) conducted by the West German Study Group (WSG) at 45 sites in Germany between June 2013 and February 2015. The trial enrolled patients with noninflammatory early-stage TNBC (clinical tumor size ≥1 cm; estrogen receptor and progesterone receptor expression <1%; and ERBB2 negative). DNA samples from pretreatment biopsies were obtained. Genetic analysis was performed between January 2018 and March 2020. Final data analyses took place in September 2023.

EXPOSURE: Patients were randomized to 12 weeks of treatment with nab-paclitaxel plus either carboplatin or gemcitabine; omission of otherwise mandatory anthracycline-containing chemotherapy was allowed in the case of pCR. tPVs in 20 cancer-associated genes, including BRCA1 and BRCA2, were analyzed using a customized gene panel.

MAIN OUTCOMES AND MEASURES: The prevalence of BRCA1 and/or BRCA2 tPVs and their effect on pCR rate, IDFS, and OS were evaluated using logistic and Cox proportional hazards regression.

RESULTS: Of the 307 patients with DNA samples from pretreatment biopsies available, tumor next-generation sequencing analyses were successful for 266 patients. The 266 patients included in this analysis were female, with a median age of 51 years (range, 26-76 years). A total of 162 patients (60.9%) had a clinical tumor size of 2 cm or greater, and 70 (26.3%) had clinical node-positive disease. BRCA1 and/or BRCA2 tPVs were detected in 42 patients (15.8%). The highest pCR rate among patients with BRCA1 and/or BRCA2 tPVs was seen in the nab-paclitaxel plus carboplatin group (9 of 14 patients [64.3%]) compared with the nab-paclitaxel plus gemcitabine group (10 of 28 [35.7%]) (odds ratio, 3.24 [95% CI, 0.85-12.36]; P = .08); the highest numeric 5-year IDFS and OS rates (84.4% and 92.9%, respectively) were seen in the nab-paclitaxel plus carboplatin group.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of the WSG-ADAPT-TN randomized clinical trial on tPVs, deescalated nab-paclitaxel plus carboplatin was superior to nab-paclitaxel plus gemcitabine, particularly in patients with BRCA1 and/or BRCA2 tPVs. These findings suggest that BRCA1 and/or BRCA2 tPV status could be a candidate marker for a deescalation strategy in early-stage TNBC; however, prospective validation of survival outcomes in larger cohorts with differentiation between germline and somatic pathogenic variants is necessary.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01815242.

PMID:40009381 | DOI:10.1001/jamanetworkopen.2024.61639

JAMA Netw Open. 2025 Feb 3;8(2):e2461899. doi: 10.1001/jamanetworkopen.2024.61899.

ABSTRACT

IMPORTANCE: Black patients with metastatic breast cancer (mBC) have higher mortality rates than White patients despite advances in treatment.

OBJECTIVES: To examine whether Black patients with metastatic breast cancer have different genomic profiles compared with White patients and whether there are inequities in targeted treatment use between these groups.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study assessed adult patients with mBC who underwent genomic profiling at academic institutions in the US between January 1, 2015, and December 31, 2023. Data analysis was performed between July 2023 and July 2024. A validation cohort was also included.

EXPOSURES: Targeted treatment use.

MAIN OUTCOMES AND MEASURES: The main outcomes were differences in circulating tumor DNA profiles and use of phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors between Black and White patients with metastatic breast cancer.

RESULTS: The study sample included 1327 women with mBC (mean [SD] age, 58.0 [12.8] years; 140 Black and 1057 White). Black patients had a significantly higher rate of GATA3 single-nucleotide variants (odds ratio, 2.31; 95% CI, 1.17-4.54; P = .02) and CCND2 copy number variants (odds ratio, 4.63; 95% CI, 1.79-11.97; P = .002) on multivariate analysis. These differences were validated in a population-based evidence cohort of 27 224 patients. Black patients with PIK3CA single-nucleotide variants were significantly less likely to receive PI3K inhibitors than White patients (1 of 17 [5.9%] vs 45 of 156 [28.8%]; P = .04), whereas there was no difference in use of CDK4/6 and mTOR inhibitors, which do not require a targetable alteration. Black patients had a shorter overall survival from the time of circulating tumor DNA testing compared with White patients.

CONCLUSIONS AND RELEVANCE: This cohort study of patients with mBC found somatic differences, shorter overall survival, and targeted treatment disparities in PI3K inhibitor use in Black compared with White patients despite equal incidence of PIK3CA alterations. Researchers should consider these differences when designing future research and interventions to address the striking and persistent outcomes gap between Black and White patients with mBC.

PMID:40009379 | DOI:10.1001/jamanetworkopen.2024.61899

JAMA Netw Open. 2025 Feb 3;8(2):e2461940. doi: 10.1001/jamanetworkopen.2024.61940.

ABSTRACT

IMPORTANCE: Social media is an influential source of medical information, but little is known about how posts discuss medical tests that carry potential for overdiagnosis or overuse.

OBJECTIVE: To investigate how social media posts discuss 5 popular medical tests: full-body magnetic resonance imaging, the multicancer early detection test, and tests for antimullerian hormone, gut microbiome, and testosterone.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study assessed posts on Instagram and TikTok between April 30, 2015, and January 23, 2024, that discussed full-body magnetic resonance imaging, the multicancer early detection test, and tests for antimullerian hormone, gut microbiome, and testosterone. Using keywords on newly created accounts, posts were searched and screened until 100 posts for each test on each platform were identified (n = 1000). Posts were excluded if they did not discuss 1 of the 5 tests or were not in English or if the account holders had fewer than 1000 followers.

MAIN OUTCOMES AND MEASURES: The main outcome was information about benefits, harms, and overall tone discussed in the post. All outcomes were summarized descriptively. Logistic regression was used to assess whether the use of evidence or the account holder being a physician or having financial interests influenced how tests were discussed.

RESULTS: A total of 982 posts from account holders with a combined 194 200 000 followers were analyzed. Across all tests, benefits were mentioned in 855 posts (87.1%) and harms in 144 (14.7%), with 60 (6.1%) mentioning overdiagnosis or overuse. Overall, 823 posts (83.8%) had a promotional (vs neutral or negative) tone. Evidence was explicitly used in 63 posts (6.4%), personal anecdotes were used in 333 (33.9%), 498 posts (50.7%) encouraged viewers to take action and get the test, and 668 account holders (68.0%) had financial interests. Posts from physicians were more likely to mention harms (odds ratio, 4.49; 95% CI, 2.85-7.06) and less likely to have an overall promotional tone (odds ratio, 0.53; 95% CI, 0.35-0.80).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of social media posts about 5 popular medical tests, most posts were misleading or failed to mention important harms, including overdiagnosis or overuse. These data demonstrate a need for stronger regulation of misleading medical information on social media.

PMID:40009378 | DOI:10.1001/jamanetworkopen.2024.61940

JAMA Netw Open. 2025 Feb 3;8(2):e2461972. doi: 10.1001/jamanetworkopen.2024.61972.

ABSTRACT

IMPORTANCE: The emergency department (ED) is an important safety net for children experiencing mental and behavioral health crises and can serve as a navigational hub for families seeking support for these concerns.

OBJECTIVES: To evaluate the outcomes of a novel mental health care bundle on child well-being, satisfaction with care, and health system metrics.

DESIGN, SETTING, AND PARTICIPANTS: Nonrandomized trial of 2 pediatric EDs in Alberta, Canada. Children younger than 18 years with mental and behavioral health presentations were enrolled before implementation (preimplementation: January 2020 to January 2021), at implementation onset (run-in: February 2021 to June 2021), and during bundle delivery (implementation: July 2021 to June 2022).

INTERVENTION: The bundle involved risk stratification, standardized mental health assessments, and provision of an urgent follow-up appointment after the visit, if required.

MAIN OUTCOMES AND MEASURES: The primary outcome, child well-being 30 days after the ED visit, was assessed using the Stirling Children’s Wellbeing Scale (children aged <14 years) or Warwick-Edinburgh Mental Wellbeing Scale (children aged 14-17 years). Change in well-being between the preimplementation and implementation periods was examined using interrupted time-series analysis and multivariable modeling. Changes in health system metrics (hospitalization, ED length of stay [LOS], and revisits) and care satisfaction were also examined.

RESULTS: A total of 1412 patients (median [IQR] age, 13 [11-15] years), with 715 enrolled preimplementation (390 [54.5%] female; 55 [7.7%] First Nations, Inuit, or Métis; 46 [6.4%] South, Southcentral, or Southeast Asian; and 501 [70.1%] White) and 697 enrolled at implementation (357 [51.2%] female; 51 [7.3%] First Nations, Inuit, or Métis; 39 [5.6%] South, Southcentral, or Southeast Asian; and 511 [73.3%] White) were included in the analysis. There were no differences between study periods in well-being. Reduced well-being z scores were associated with mood disorder diagnosis (standardized mean difference, -0.14; 95% CI, -0.26 to -0.02) and nonbinary gender identity (standardized mean difference, -0.41; 95% CI, -0.62 to -0.19). The implementation period involved fewer hospitalizations (difference in hospitalizations, -6.9; 95% CI, -10.4 to -3.4) and longer ED LOS (1.1 hours; 95% CI, 0.7 to 1.4 hours). There were no differences between study periods in ED revisits or care satisfaction.

CONCLUSIONS AND RELEVANCE: In this study, the delivery of a care bundle was not associated with higher child well-being 30 days after an ED visit. Hospitalizations did decrease during bundle delivery, but ED LOS did not. These health system findings may have been affected by broader changes in patient volumes and flow processes that occurred during the COVID-19 pandemic, which took place as the study was conducted.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04292379.

PMID:40009377 | DOI:10.1001/jamanetworkopen.2024.61972

J Laparoendosc Adv Surg Tech A. 2025 Feb 26. doi: 10.1089/lap.2024.0382. Online ahead of print.

ABSTRACT

Introduction: Laparoscopic common bile duct exploration (LCBDE) is a well-established and effective minimally invasive surgical approach for managing choledocholithiasis. However, its safety in the elderly population is not well established. Therefore, this study compares surgery-related outcomes in elderly patients undergoing LCBDE. Methods: We systematically searched PubMed, Embase, and Cochrane Library for studies comparing elderly and young patients undergoing LCBDE. Binary outcomes were compared using odds ratios (ORs), with 95% confidence intervals (CIs). Heterogeneity was assessed with I² statistics. Statistical analysis was performed using Software R, version 4.3.3. Results: Twelve studies comprising 3791 patients were included, of whom 1411 patients (37%) were from the elderly group. Elderly patients were associated with an increase in mortality (OR: 3.42; 95% CI: 1.08-10.85; P = .04; I² = 0%), overall postoperative complications (OR: 1.60; 95% CI: 1.11-2.22; P = .01; I² = 52%), and pneumonia (OR: 4.37; 95% CI: 2.00-9.55; P < .01; I² = 0%) rates. However, there were no significant differences between groups in remnant stones (OR: 1.37; 95% CI: 0.70-2.68; P = .36; I² = 0%) and recurrent stones (OR: 1.37; 95% CI: 0.64-2.95; P = .42; I² = 0%) pancreatitis (OR: 0.98; 95% CI: 0.16-5.95; P = .98; I² = 0%) and bile leakage (OR: 1.24; 95% CI: 0.75-2.07; P = .40; I² = 0%). Conclusion: In this meta-analysis, elderly patients who underwent LCBDE experienced increased mortality, overall complications, and pneumonia rates compared with young patients. Furthermore, there were no significant differences between the groups in remnant and retained stones, pancreatitis, and bile leakage.

PMID:40009351 | DOI:10.1089/lap.2024.0382

Behav Res Methods. 2025 Feb 26;57(4):101. doi: 10.3758/s13428-024-02532-y.

ABSTRACT

Established strategies commonly used to address latent quadratic and interaction effects within structural equation models, such as the unconstrained product indicator (UPI) approach or the latent moderated structural equations (LMS) approach, tend to perform effectively in models featuring only a limited number of nonlinear effects. However, as the complexity of the model increases with a higher number of nonlinear terms, the feasibility of joint or one-step methods such as UPI and LMS progressively diminishes. In response to this challenge, this paper advocates the adoption of structural after measurement (SAM) approaches to overcome this limitation. In a SAM approach, estimation proceeds in two stages. In a first stage, we estimate the parameters related to the measurement part of the model, while in a second stage, we estimate the parameters related to the structural part of the model. In this paper, we discuss three SAM approaches already documented in the literature and introduce a novel method based on the local SAM approach. To illustrate the utility of these SAM approaches, we conduct a modest simulation study, demonstrating that SAM approaches for latent quadratic and interaction effects offer a practical and viable alternative to the well-established one-step approaches.

PMID:40009313 | DOI:10.3758/s13428-024-02532-y

Clin Rheumatol. 2025 Feb 26. doi: 10.1007/s10067-025-07379-y. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to investigate the differences between neuropsychiatric systemic lupus erythematosus (NPSLE) patients with and without white matter hyperintensity (WMH) on magnetic resonance imaging (MRI) and to identify factors independently associated with the development of WMH in NPSLE.

METHOD: A comparative analysis was conducted on 84 NPSLE patients hospitalized at Peking University People’s Hospital from 2015 to 2022 at the initial diagnosis of NPSLE. Patients were categorized based on the presence of WMH on brain MRI scans. Demographic data, clinical characteristics, and laboratory parameters were reviewed and statistically analyzed.

RESULTS: The study included 84 NPSLE patients, 50% exhibiting WMH (NPSLE-WMH +). At the initial diagnosis of NPSLE, the NPSLE-WMH + group showed significantly higher levels of antinuclear antibody (ANA) titer, anti-double-stranded DNA antibody (anti-dsDNA), anti-nucleosome antibody (ANuA), and lower serum C3 levels. The proportion of patients with reduced WBC, elevated anti-dsDNA, elevated ANuA, elevated anticardiolipin antibody (ACA), positive urinary protein (UPR), and positive ANA was higher in the NPSLE-WMH + group. Univariate and multivariate analyses revealed that positive UPR (p = 0.040), positive ANA (p = 0.025), elevated anti-dsDNA (0.047), and elevated ACA (p = 0.025) were potentially independent factors associated with WMH development in NPSLE patients.

CONCLUSIONS: This study provides novel insights into the clinical and laboratory differences between NPSLE patients with and without WMH, identifying specific independently associated factors for WMH development. These findings may contribute to a better understanding of this intricate disease. Key Points • Although WMH is one of the most frequently observed lesions on MRI in patients with NPSLE, previous literature has given limited attention to it. This study focuses on the differences between NPSLE patients with and without WMH, unveiling independently associated factors for developing WMH in this disease.

PMID:40009312 | DOI:10.1007/s10067-025-07379-y

Emerg Radiol. 2025 Feb 26. doi: 10.1007/s10140-025-02321-w. Online ahead of print.

ABSTRACT

PURPOSE: Vertigo and dizziness are common complaints at emergency departments (ED), often leading to computed tomography (CT) and CT angiography (CTA) studies, which when used non-selectively, have low clinical utility. The study assesses whether two quality improvement interventions (educational rounds and clinical decision making support tool) can better align CTA ordering rates with clinical practice guidelines in the ED workup of vertigo/dizziness at a large community hospital.

METHODS: CTA head and neck imaging rates were collected for patients presenting to the hospital’s ED with dizziness/vertigo as the chief complaint during 6-month pre- and post-intervention periods and compared rates using the Chi-Square Test. The interventions were joint ED/Diagnostic Imaging/Stroke Neurology rounds discussing CTA head/neck indications and dissemination of a clinical decision making support tool.

RESULTS: The absolute reduction was 5.79% (N = 4,230, p < 0.001) in CTA rates for patients presenting with dizziness/vertigo between the pre- and post-intervention periods. For vertigo, the absolute reduction was 12.27% (N = 402, p < 0.005). For dizziness, the absolute reduction was 5.17% (N = 3828, p < 0.001). Despite the global decrease in CTA studies, there was no statistically significant decrease in CTA rates for the patients who were diagnosed with cerebrovascular accident or transient ischemic attack in the ED, indicating that the interventions were effective in limiting to the targeted CTA studies.

CONCLUSIONS: This project was effective in improving patient safety and system efficiency, while providing a framework for low-burden, effective, practice-modifying quality improvement initiatives.

PMID:40009296 | DOI:10.1007/s10140-025-02321-w

Biomech Model Mechanobiol. 2025 Feb 26. doi: 10.1007/s10237-025-01931-0. Online ahead of print.

ABSTRACT

In this work, we present the derivation of a novel model for the myocardium that incorporates the underlying poroelastic nature of the material constituents as well as the electrical conductivity. The myocardium has a microstructure consisting of a poroelastic extracellular matrix with embedded poroelastic myocytes, i.e. a double poroelastic material. Due to the sharp length scale separation that exists between the microscale, where the individual myocytes are clearly resolved from the surrounding matrix, and the length of the entire heart muscle, we can apply the asymptotic homogenization technique. The novel PDE model accounts for the difference in the electric potentials, elastic properties as well as the differences in the hydraulic conductivities at different points in the microstructure. The differences in these properties are encoded in the coefficients and are to be computed by solving differential cell problems arising when applying the asymptotic homogenization technique. We present a numerical analysis of the obtained Biot’s modulus, Young’s moduli as well as shears and the effective electrical activity. By investigating the poroelastic and electrical nature of the myocardium in one model, we can understand how the differences in elastic displacements between the extracellular matrix and the myocytes affect mechanotransduction and the influence of disease.

PMID:40009273 | DOI:10.1007/s10237-025-01931-0