Nevin Manimala

Epidemiology. 2026 Mar 2. doi: 10.1097/EDE.0000000000001967. Online ahead of print.

ABSTRACT

Air quality regulations and programs are vital for protecting the public from harms caused by air pollution. To support these actions, numerous epidemiological studies have sought to identify the pollutants most responsible for adverse outcomes. These studies often used statistical adjustments for co-pollutants in outcome regression models, a practice also commonly applied to assess interactions between co-pollutants. Here, we highlight possible pitfalls of multi-pollutant analyses. Indiscriminate co-pollutant adjustment can induce noncausal associations through collider adjustment, distorting effect estimates for individual air pollutants. We describe the underlying mechanisms and provide empirical evidence on how such bias may realistically influence the relationships between air pollution and health outcomes from a well-characterized Canadian national cohort alongside a simulation study. Additionally, we discuss strategies to mitigate the impact of this bias. Given the widespread interest in multi-pollutant approaches among the scientific and policy communities, greater caution is needed when conducting and interpreting research on multiple pollutants.

PMID:41790994 | DOI:10.1097/EDE.0000000000001967

J Urol. 2026 Mar 6:101097JU0000000000005027. doi: 10.1097/JU.0000000000005027. Online ahead of print.

ABSTRACT

PURPOSE: We sought to review our experience with the postoperative use of ureteral stents with and without extraction strings in a large series of pediatric patients following robotic pyeloplasty (RALP).

MATERIALS AND METHODS: All RALP at our institution from 2012-present were retrospectively reviewed. Patients with <60 days of follow-up, preoperative nephrostomy tubes, and redo pyeloplasty were excluded. Statistical analysis was performed.

RESULTS: A total of 245 patients underwent RALP: 179 (73%) patients had ureteral stents with extraction strings (SWES) and 66 (27%) had internalized stents. Groups were similar with regards to demographics and perioperative characteristics, except for longer operative times in the internalized stent group (p=0.01).No statistically significant difference in postoperative complications (OR 0.77, 95% CI 0.35-1.68, p=0.5) and urinary tract infections (OR 0.72, 95% CI 0.24-2.20, p=0.6) were observed between SWES compared to internalized stents. No difference in Clavien-Dindo Grade 3 complications were seen between groups (OR 1.78, 95% CI 0.49-6.41, p=0.4). Subgroup analysis did not reveal increased risk for postoperative complications or UTI with female gender, prior UTI history, or circumcision status (p≥0.16). Non-use of antibiotic prophylaxis was associated with increased risk of postoperative UTI in the SWES group (p=0.02). Of patients with SWES, 21 (12%) required stent removal in the office setting, 3 (1.7%) required removal in the operating room under anesthesia, and 153 (86%) were able to remove at home.

CONCLUSIONS: Ureteral stents with extraction strings were not associated with an increased risk of postoperative UTI or complications in our series.

PMID:41790987 | DOI:10.1097/JU.0000000000005027

Lupus. 2026 Mar 6:9612033261432154. doi: 10.1177/09612033261432154. Online ahead of print.

ABSTRACT

ObjectiveType I interferons (IFN) drive systemic lupus erythematosus (SLE) pathogenesis. Some patients develop neutralizing IFN autoantibodies (anti-IFN ab), which theoretically could modify disease activity. We aimed to determine the prevalence of anti-IFN ab in patients with SLE, identify the age and when during the disease course of anti-IFN ab emerge, and assess their association with organ damage.MethodsThis cross-sectional study included 173 SLE patients from the Lund Lupus Cohort. Samples taken at routine outpatient visits were analyzed for anti-IFN ab using ELISA, and positive samples were tested for IFN neutralizing capacity with a gene-reporter assay. Longitudinal samples were analyzed to determine the time-point and age of first positive sample. Demographic and clinical data were obtained from research registries.ResultsEighteen (10.4%) patients were positive for anti-IFN ab by ELISA. Among these, antibodies from nine patients (5.2%) displayed IFN neutralizing capacity. No statistically significant differences were detected between patients positive for neutralizing antibodies and antibody-negative patients with respect to demography, organ damage or ACR classification criteria. The group with neutralizing antibodies were slightly older (median age 59 vs 45 years, p = .14) and had a higher proportion of renal involvement (67% vs 33%, p = .088). Longitudinal analysis of samples from patients with neutralizing anti-IFN ab revealed two age-related patterns: late-onset (≥65 years, n = 4), including one patient positive at diagnosis at age 69, and early-onset (≤40 years, n = 5), with antibodies present at or soon after diagnosis in four cases. Organ damage did not differ between patients with or without neutralizing antibodies (p = .65). At the latest follow-up (2-38 years after anti-IFN ab detection), three of nine patients remained free of organ damage.ConclusionsApproximately 5% of SLE patients have neutralizing anti-IFN antibodies, which may present early in disease or develop later in life. While late-onset antibodies may reflect age-related changes in immune regulation and early-onset antibodies could potentially modulate IFN-driven mechanisms, our data do not support a protective effect against organ damage.

PMID:41790986 | DOI:10.1177/09612033261432154

Biometrics. 2026 Jan 6;82(1):ujag040. doi: 10.1093/biomtc/ujag040.

ABSTRACT

Analyzing multiple outcome variables via regional quantile regression in high-dimensional settings poses significant statistical and computational challenges. In this paper, we propose a new framework that models multivariate quantile varying coefficients using principal component functions, enforcing a low-rank structure on the coefficient matrix to achieve parsimony and interpretability. Our approach augments this representation with a KNN-fused LASSO penalty to capture shared dynamic patterns and identify latent clusters within the principal components. Through comprehensive simulation studies, we demonstrate that our method consistently provides accurate estimates and robust performance under various high-dimensional scenarios. We further illustrate its practical utility with two real-world health datasets, where our approach uncovers complex, quantile-specific associations between predictors and multiple correlated outcomes across a time index.

PMID:41790491 | DOI:10.1093/biomtc/ujag040

JAMA Netw Open. 2026 Mar 2;9(3):e260888. doi: 10.1001/jamanetworkopen.2026.0888.

ABSTRACT

IMPORTANCE: Older adults undergoing major surgery often face increased risks of functional decline, cognitive impairment, and loss of independence. While shared decision-making (SDM) is recommended, there are no standardized guidelines defining its key components for this population.

OBJECTIVE: To identify valid and feasible components of surgical SDM tailored to older adults.

EVIDENCE REVIEW: This qualitative consensus study used a 2-round modified Delphi process with the RAND/UCLA Appropriateness Method between June 1 and September 9, 2023. Forty-one candidate SDM components were developed from existing frameworks and stakeholder input and were rated for validity and feasibility on a scale of 1.0 to 9.0. Ratings were collected via REDCap. Components meeting a median score of 7.0 or greater with statistical agreement were considered valid and/or feasible. Data were analyzed from June 12, 2023, to January 1, 2024.

FINDINGS: The 11 panelists included 8 clinicians (from the fields of surgery, geriatrics, palliative care, ethics, and social work) and 3 patient representatives. Seven panelists (63.6%) were female. Clinicians practiced in an urban, academic setting with a mean clinical experience of 13.8 (range, 1-35) years; the mean patient age was 67.6 (range, 52-84) years. In round 1, all 41 candidate components were rated valid; 33 (80.5%) were rated feasible and 8 (19.5%) were rated as having uncertain feasibility. After panel discussion and revisions, round 2 concluded that 39 components (95.1%) were feasible, while 2 (4.9%) were rated as unfeasible and removed. Four new components were added and rated valid and feasible for a total of 43 components. Barriers to implementation included knowledge and/or skills (55 of 164 [33.5%]), time (43 of 164 [26.2%]), and cultural factors (30 of 164 [18.3%]). Specific challenges involved assessing cognitive function and decisional capacity and counseling on long-term functional outcomes after surgery.

CONCLUSIONS AND RELEVANCE: Through a structured consensus process, 43 components were identified as valid and feasible for surgical SDM with older adults. These components provide a framework to guide preoperative communication, inform quality measurement, and support the development of interventions to improve SDM. Addressing barriers such as time, knowledge, and cultural constraints will be essential for implementation.

PMID:41790475 | DOI:10.1001/jamanetworkopen.2026.0888

JAMA Netw Open. 2026 Mar 2;9(3):e260277. doi: 10.1001/jamanetworkopen.2026.0277.

ABSTRACT

IMPORTANCE: The language used to describe health equity efforts has become increasingly contested. Understanding how language influences public attitudes is essential to effectively communicate equity-focused concepts across ideological groups.

OBJECTIVE: To assess the association of language and framing with public receptiveness to health equity concepts, including alignment of definitions with shared values, reactions to common terms, and preferences for public health framing statements.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional online survey of 1000 US adults was conducted between April 9 and April 25, 2025, using an international public opinion research firm that recruited from a nonprobability-based online panel with matching and weighting to national benchmarks. Participants were stratified by age, sex, race and ethnicity, self-reported political ideology, and geographic region to approximate national demographics.

EXPOSURES: The survey included 3 modules: (1) random assignment to a definition of health equity or health equality with values-alignment questions; (2) evaluative reactions to 10 common health equity terms; and (3) preferences for 4 pairs of equivalent public health statements differing only in framing.

MAIN OUTCOMES AND MEASURES: Primary outcomes included participant ratings of values alignment (including personal values and values core to national identity, the latter of which were termed American values in the survey), evaluative reactions to equity-related terms (negative to nonnegative), and framing preferences across ideology groups. Descriptive statistics assessed values alignment, reactions to terms, and framing preferences.

RESULTS: Among 1000 US adults (weighted number, 513.2 [51.3%] female; 105.8 [10.6%] very liberal, 164.0 [16.4%] liberal, 344.0 [34.4%] moderate, 205.9 [20.6%] conservative, 98.7 [9.9%] very conservative, and 81.5 [8.2%] not sure), respondents represented a broad range of ages, racial and ethnic backgrounds, and educational attainment. Respondents assigned to the health equity definition reported higher alignment with personal values (42.9%-87.4% across groups) than those assigned to health equality (28.5%-79.0% across groups), with endorsement of either concept increasing progressively from very conservative to very liberal respondents (P < .001 in both cases). When assessing perceived core American values, health equity (47.0% [95% CI, 33.1%-60.8%]) was more frequently endorsed than health equality (21.1% [95% CI, 9.6%-32.5%]) among those identifying as very conservative. Four terms-accessible health care, health care investment, population health, and community health-were broadly well received (<10% negative responses in most groups), whereas the terms marginalized communities and inclusive health elicited more divergent reactions across ideologies (P < .01 in both cases). Collectivist (our health vs your health) and affirming (start, support, and increase) framings were consistently preferred across groups.

CONCLUSIONS AND RELEVANCE: In this national online survey of 1000 US adults, respondents showed both ideological differences and areas of convergence in responses to health equity language and framing. These findings suggest that strategic use of broadly resonant terms and collective, affirming framings may foster understanding of and support for health initiatives across political ideologies.

PMID:41790470 | DOI:10.1001/jamanetworkopen.2026.0277

JAMA Netw Open. 2026 Mar 2;9(3):e260853. doi: 10.1001/jamanetworkopen.2026.0853.

ABSTRACT

IMPORTANCE: Alzheimer disease (AD) pathology may begin decades before symptoms. Genetic factors, such as APOE ε4 carrier status and polygenic risk scores (PRS), influence AD risk, but their roles in cognitive decline among Asian populations remain unclear.

OBJECTIVE: To evaluate whether APOE ε4 carrier status and a non-APOE polygenic risk score (PRS_ADnapoe) are associated with age-related cognitive decline in community-dwelling older adults in Taiwan.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from 2 assessment waves of the Healthy Aging Longitudinal Study in Taiwan, spanning 2009 to 2019. Participants were aged 55 years and older and had both genetic data and Mini-Mental State Examination (MMSE) scores. Data analyses were conducted from August to December 2025.

EXPOSURES: APOE ε4 carrier status (noncarrier, heterozygote, homozygote) and PRS_ADnapoe score, derived from genome-wide association summary statistics excluding APOE variants.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in MMSE scores, which were assessed cross-sectionally and longitudinally, modeled with mixed-effects regression accounting for age-related effects and covariates including sex, education, smoking, and population structure.

RESULTS: Among 4392 participants (mean [SD] age, 68.2 [7.8] years; 2359 [53.7%] women), 723 (16.5%) were APOE ε4 heterozygotes and 33 (0.8%) were APOE ε4 homozygotes. Over a mean (SD) follow-up of 6.3 (0.9) years, the mean (SD) annual MMSE decline was -0.2 (0.5). APOE ε4 carriage was associated with a significantly steeper quadratic age-associated decline in MMSE scores compared with noncarriers (estimate, -0.005; SE, 0.001; P = .001). This association was strongest among homozygotes (estimate, -0.017; SE, 0.008; P = .03), with MMSE trajectories diverging after approximately age 70 years. In contrast, PRS_ADnapoe scores were not associated with MMSE decline. Sensitivity analyses restricted to participants with 2-wave data and adjusted with inverse probability of censoring weighting confirmed these findings.

CONCLUSIONS AND RELEVANCE: In this cohort study of middle-aged and older adults in Taiwan, APOE ε4 carriage, particularly homozygosity, was associated with accelerated age-related cognitive decline detectable after age 70 years, whereas non-APOE polygenic risk was not associated with cognitive decline over the current follow-up. These results highlight the potential utility of early genetic risk awareness and support consideration of targeted preventive strategies for APOE ε4 carriers.

PMID:41790466 | DOI:10.1001/jamanetworkopen.2026.0853

Clin Cancer Res. 2026 Mar 6. doi: 10.1158/1078-0432.CCR-25-3726. Online ahead of print.

ABSTRACT

On May 5, 2021 and March 19, 2025, the Food and Drug Administration (FDA) granted accelerated and regular approval for pembrolizumab plus trastuzumab and platinum-based chemotherapy for unresectable or metastatic human epidermal growth factor receptor-2 (HER2) gastric or gastroesophageal junction carcinoma. Both approvals were based on KEYNOTE-811, a randomized, multiregional trial, comparing pembrolizumab plus trastuzumab and chemotherapy versus placebo plus trastuzumab and chemotherapy. Accelerated approval was granted based on overall response rate (ORR) in the first 264 patients randomized, showing a statistically significant improvement with pembrolizumab (74.4% vs. 51.9%, p= 0.00006). The final overall survival (OS) analysis demonstrated a clinically meaningful improvement, with a median OS of 20.0 months (95% CI 17.8, 22.1) and 16.8 months (95% CI 14.9, 18.7) in the pembrolizumab and placebo arms respectively (HR 0.80 [95% CI 0.67, 0.94]; p= 0.004). However, in exploratory subgroup analyses treatment benefit appeared to be driven by the PD-L1 CPS ≥1 population (85% of patients, with an OS HR of 0.79 [95% CI 0.66, 0.95]), whereas in the CPS <1 subgroup (15% of patients) treatment with pembrolizumab did not show improvement (HR 1.10, [95% CI 0.72-1.68]). These results are consistent with analysis of pembrolizumab and other immune checkpoint inhibitors across multiple clinical trials in patients with gastric cancer. KEYNOTE-811 utilized a “one-trial” approach allowing accelerated approval based on response rate with subsequent conversion to regular approval based on survival outcomes. KEYNOTE-811 also provided data for earlier access to therapies in a frontline metastatic setting, following FDA’s Project Frontrunner approach.

PMID:41790455 | DOI:10.1158/1078-0432.CCR-25-3726

JAMA Health Forum. 2026 Mar 6;7(3):e256935. doi: 10.1001/jamahealthforum.2025.6935.

NO ABSTRACT

PMID:41790454 | DOI:10.1001/jamahealthforum.2025.6935

Int J Pharm Pract. 2026 Mar 6:riag031. doi: 10.1093/ijpp/riag031. Online ahead of print.

ABSTRACT

OBJECTIVES: In several countries, pharmacists have gained prescribing authority to enhance the quality and accessibility of healthcare. Elsewhere, pharmacists initiate or modify prescriptions that are subsequently countersigned by a prescriber, potentially serving as a stepping stone toward formal prescribing legislation. This study aimed to investigate current prescription modifications by Dutch pharmacists and their views on introducing prescribing authority.

METHODS: A nationwide cross-sectional survey was conducted among pharmacists in the Netherlands via national professional networks in April and May 2024. The questionnaire assessed current prescription modification practices, pharmacists’ agreement regarding the introduction of formal prescribing authority, and their perceived needs and readiness for prescribing. Data were analysed using descriptive statistics.

KEY FINDINGS: Among the 476 respondents, most worked in community pharmacy (76.7%; n = 365), followed by inpatient hospital pharmacy (14.7%; n = 70). The two most common prescription modifications were adjusting or initiating prescriptions based on clinical decision rules (81.1%; n = 386), and performing therapeutic substitution during drug shortages or according to local formularies (79.6%; n = 379). Almost all respondents favoured formal prescribing authority for at least one prescription modification practice (98.1%; n = 467). Respondents most often indicated clear task division and agreements between physicians and pharmacists (93.9%, n = 447) as a need for implementation. Readiness to use prescribing authority was reported by 92.6% (n = 441) of the respondents.

CONCLUSIONS: The majority of pharmacists frequently initiate or modify prescriptions, and expressed both willingness and readiness to formalize these practices. These findings are valuable for policymakers considering the introduction of formal pharmacist prescribing authority.

PMID:41790438 | DOI:10.1093/ijpp/riag031