Tag: statistics

JMIR Med Inform. 2026 May 7;14:e97580. doi: 10.2196/97580.

ABSTRACT

[This corrects the article DOI: 10.2196/68182.].

PMID:42096260 | DOI:10.2196/97580

JAMA. 2026 May 7. doi: 10.1001/jama.2026.5164. Online ahead of print.

ABSTRACT

IMPORTANCE: Despite high recanalization rates with endovascular thrombectomy for acute ischemic stroke due to large vessel occlusion, functional outcomes remain suboptimal. The benefit of adjunctive intra-arterial thrombolysis after successful thrombectomy is uncertain.

OBJECTIVE: To assess whether adjunctive intra-arterial alteplase after successful thrombectomy improves functional outcomes and cerebral reperfusion.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label trial with blinded outcome assessment conducted at 14 stroke centers in Spain from December 11, 2023, through November 26, 2025. A total of 440 patients with acute ischemic stroke due to large vessel occlusion treated with thrombectomy within 24 hours and achieving an expanded Treatment in Cerebral Ischemia score of 2b50 to 3 were randomized.

INTERVENTIONS: Thrombectomy plus intra-arterial alteplase (0.225 mg/kg; maximum dose, 20 mg/kg) infused over 15 minutes (n = 221) or thrombectomy alone (n = 219).

MAIN OUTCOMES AND MEASURES: The primary outcome was an excellent functional outcome at 90 days, which was defined as a modified Rankin Scale score of 0 or 1. There were 6 secondary outcomes, including residual hypoperfusion on follow-up computed tomography perfusion. The safety outcomes included symptomatic intracranial hemorrhage and death.

RESULTS: Of 3786 patients treated with thrombectomy, 2776 (73%) fulfilled angiographic criteria and 440 (12%) were randomized. There were 433 patients who were treated as randomized (median age, 76 [IQR, 75-78] years; 51% female). At 90 days, 57.5% of patients (123/214) in the thrombectomy plus intra-arterial alteplase group had a modified Rankin Scale score of 0 or 1 vs 42.5% of patients (93/219) in the thrombectomy alone group (adjusted risk difference, 15.0% [95% CI, 5.7% to 24.3%]; P = .002). Of 6 secondary outcomes, 4 showed no significant between-group differences. Residual hypoperfusion occurred in 28.6% (55/192) of patients in the thrombectomy plus intra-arterial alteplase group vs 50.5% (96/190) of patients in the thrombectomy alone group (adjusted risk difference, -22.0% [95% CI, -31.5% to -12.4%]; P < .001) and symptomatic intracranial hemorrhage occurred in 1.4% (3/214) vs 0.5% (1/219), respectively (adjusted odds ratio, 3.10 [95% CI, 0.32 to 30.0]; P = .33). Mortality at 90 days was 12.1% (26/214) in the thrombectomy plus intra-arterial alteplase group vs 6.4% (14/219) in the thrombectomy alone group (adjusted risk difference, 5.9% [95% CI, 0.5% to 11.3%]; P = .03).

CONCLUSIONS AND RELEVANCE: Among patients with acute ischemic stroke and successful thrombectomy, adjunctive intra-arterial alteplase increased the proportion achieving excellent functional outcome at 90 days without a significant increase in symptomatic intracranial hemorrhage. Higher mortality in the thrombectomy plus intra-arterial alteplase group warrants further study.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05797792.

PMID:42096239 | DOI:10.1001/jama.2026.5164

JAMA Oncol. 2026 May 7. doi: 10.1001/jamaoncol.2026.1080. Online ahead of print.

ABSTRACT

IMPORTANCE: Metastatic non-small cell lung cancer (mNSCLC) has very high mortality rates, and comprises approximately half of new cases of lung cancer; however, highly effective and better tolerated treatments have become available in recent decades. Nevertheless, population-level treatment of mNSCLC is poorly characterized in the era of rapid treatment advances.

OBJECTIVE: To characterize treatment rates, trends, and factors associated with treatment of mNSCLC.

DESIGN, SETTING, AND PARTICIPANTS: This population-based study used linked Surveillance Epidemiology and End Results (SEER) and Medicare claims data and the analysis included patients 65 years and older diagnosed with mNSCLC from January 2006 to December 2021. Data were analyzed from October 2025 to February 2026.

EXPOSURES: Sociodemographic variables, comorbidity burden, histologic type, referral to subspecialist, enrollment in Medicare Part D, and biomarker testing.

MAIN OUTCOMES: The primary outcome was receipt of systemic treatment. Statistical analyses included summary statistics and a competing risk proportional hazards model for receipt of systemic treatment.

RESULTS: Of 254 611 patients with mNSCLC, the cohort median (IQR) age was 73 (68-80) years, with 133 635 (52.5%) male individuals; a total of 9512 (3.7%) were Asian, 26 546 (10.4%) were Black, 4553 (1.8%) were Hispanic, 205 381 (80.7%) were White, and 8619 (3.4%) were another or unknown race. A total of 119 197 patients (46.8%) ever received systemic treatment. Of the 100 367 (39.8%) who died within 90 days of diagnosis, 13.2% were treated compared with 69% of those surviving more than 90 days. The treated proportion increased only slightly between 2006 and 2021. In a competing risk model, referral to oncology specialists was associated with treatment (hazard ratio [HR], 2.5; 95% CI, 2.41-2.67; P < .001) which corresponded to a 30.3% greater cumulative incidence of treatment at 180 days (CIF180) compared with those without a referral. Similarly, those with biomarker testing had a 17.8% greater CIF180, whereas those older than 80 years had a 15.4% lower CIF180 compared to those aged 65 to 69 years. Patients with NSCLC not otherwise specified histologic findings had a 12.8% lower CIF180 compared with those with adenocarcinoma histologic findings. Other factors associated with significant but smaller differences in receipt of treatment included comorbidity burden, marital status, Medicare Part C or Part D coverage, rurality, and race and ethnicity.

CONCLUSIONS AND RELEVANCE: In this cohort study of older adults with mNSCLC, despite advances in therapy in recent decades, almost half of patients never received systemic therapy, and the proportion treated only minimally improved over time. Approximately one-fifth of those with the most favorable clinical profiles did not receive systemic therapy.

PMID:42096214 | DOI:10.1001/jamaoncol.2026.1080

JAMA Netw Open. 2026 May 1;9(5):e2611251. doi: 10.1001/jamanetworkopen.2026.11251.

ABSTRACT

IMPORTANCE: Public health emergency waivers enacted during the COVID-19 pandemic dramatically expanded telemedicine use. Expiration of these waivers would limit access to this convenient care option for older adults, but it is unknown how expiration would affect patients’ burden of care, quantified as health care contact days (days receiving in-person care).

OBJECTIVE: To measure the extent to which telemedicine days experienced by older adults enrolled in traditional Medicare may supplement in-person health care contact days and to estimate how telemedicine waiver expiration could increase the number of health care contact days.

DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional study of the 2022 Medicare Current Beneficiary Survey examining a nationally representative sample of community-dwelling adults aged 65 years or older enrolled in traditional Medicare. Data analysis was performed from March 2025 to March 2026.

MAIN OUTCOMES AND MEASURES: The primary outcomes were total telemedicine days (days with any telemedicine service) and additional health care contact days if telemedicine waivers expired (telemedicine days converted to in-person contact days, assuming 100% substitution). Multivariable logistic and Poisson regressions evaluated associations between patient characteristics and the probability and rate of additional health care contact days.

RESULTS: Among 5151 community-dwelling older adults (weighted number, 27 321 585 individuals; mean [SD] age, 74.6 [7.0] years; 2496 female individuals [52.4%]), 1294 (weighted 22.7%) used telemedicine. Telemedicine use varied widely (median [IQR], 1 [1-3] telemedicine day; maximum, 91 days), with 10.5% of telemedicine users (135 respondents) accounting for 50% of all telemedicine days. If telemedicine waivers expired and all affected telemedicine services were substituted with in-person services, 74.1% of older adults (951 respondents) using telemedicine would experience at least 1 additional health care contact day, totaling 8 772 118 additional contact days. Having more chronic conditions (adjusted odds ratio for >10 conditions, 8.42; 95% CI, 5.44-13.00) and difficulty getting places (adjusted odds ratio, 1.29; 95% CI, 1.10-1.53) were associated with higher odds of additional contact days.

CONCLUSIONS AND RELEVANCE: This cross-sectional study of older adults enrolled in traditional Medicare found that most older adults using telemedicine would experience additional health care contact days if telemedicine waivers expired and all affected telemedicine services were substituted with in-person services. The resulting burden would fall disproportionately on adults with multiple chronic conditions and difficulty getting places, potentially exacerbating access barriers for patients most in need of care.

PMID:42096202 | DOI:10.1001/jamanetworkopen.2026.11251

JAMA Netw Open. 2026 May 1;9(5):e2611335. doi: 10.1001/jamanetworkopen.2026.11335.

ABSTRACT

IMPORTANCE: Blood-based neural biomarkers linked to aging may provide insights into the biological end point of the human lifespan. However, the key biomarker associated with cognition and mortality in centenarians remains unclear.

OBJECTIVE: To investigate the associations between 3 neural biomarkers-amyloid-β42 and amyloid-β40 ratio (Aβ42/40), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL)-and both cognitive function and all-cause mortality in centenarians.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included Japanese centenarians aged 100 years or older who were enrolled between September 2000 and January 2021. Participants underwent baseline cognitive assessments and blood sampling and were followed up for 17 years for mortality. Data analysis was performed in February 2026.

EXPOSURES: Baseline plasma levels of Aβ42/40, p-tau181, and NfL measured using ultrasensitive immunoassays.

MAIN OUTCOMES AND MEASURES: Cognitive function at baseline, measured using the Mini-Mental State Examination (MMSE), and all-cause mortality.

RESULTS: Of 495 participants (398 [80.4%] women; mean [SD] age 104.1 [3.0] years), 419 completed a cognitive assessment (mean [SD] MMSE, 14.9 [6.9]). During 17 years of follow-up, 466 participants (95.5%) died. Lower Aβ42/40 (β = 0.99; 95% CI, 0.46 to 1.52) and higher NfL levels (β = -0.92; 95% CI, -1.62 to -0.23) were significantly associated with lower MMSE scores after adjusting for confounders. Higher NfL levels were also associated with increased mortality (hazard ratio, 1.36; 95% CI, 1.17 to 1.57), showing the greatest point estimate among the biomarkers, all of which were standardized and statistically significant (change in Akaike Information Criterion, likelihood ratio test, χ2 = 30.16; P < .001). Aβ42/40 and p-tau181 were not statistically significant after full adjustment.

CONCLUSIONS AND RELEVANCE: In this cohort study of centenarians, higher plasma NfL levels were associated with lower cognitive function and increased all-cause mortality, whereas Aβ42/40 and p-tau181 showed no associations. These findings suggest that plasma NfL was associated with neurodegeneration in extreme aging. Further studies are needed to confirm its clinical utility before routine implementation.

PMID:42096201 | DOI:10.1001/jamanetworkopen.2026.11335

JAMA Netw Open. 2026 May 1;9(5):e2611440. doi: 10.1001/jamanetworkopen.2026.11440.

ABSTRACT

IMPORTANCE: There is conflicting evidence for associations between maternal SARS-CoV-2 infection and neonatal congenital anomalies. Population-based studies evaluating confirmed maternal infection during pregnancy and at specific gestational time periods are needed.

OBJECTIVE: To evaluate associations between laboratory-confirmed maternal SARS-CoV-2 infection in pregnancy and neonatal congenital anomalies, overall during pregnancy and by specific trimester of exposure.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, matched cohort study of live births with maternal SARS-CoV-2 infection in pregnancy matched 1:4 to live births without maternal infection in Ontario, Canada, was conducted from December 14, 2020, to December 31, 2021. Matching was performed on maternal age, delivery date, gestational age at birth, neonatal sex, and prepregnancy diabetes. Analyses were conducted from May to August 2025.

EXPOSURE: Maternal SARS-CoV-2 infection in pregnancy confirmed by positive real-time polymerase chain reaction (RT-PCR) test. Pregnancies with no positive RT-PCR test were considered SARS-CoV-2 negative.

MAIN OUTCOMES AND MEASURES: The primary outcome was any neonatal congenital anomaly. The secondary outcome was any neonatal cardiac anomaly. Crude incidence rates of congenital anomalies per 1000 live births by maternal SARS-CoV-2 infection status with 95% CI were determined with a Poisson distribution for the study sample overall, and by each trimester of exposure.

RESULTS: A total of 5049 live births with corresponding maternal SARS-CoV-2 infection in pregnancy (mean [SD] maternal age, 31.0 [4.9] years) were matched 1:4 to 20 196 live births without maternal infection (mean [SD] maternal age, 31.1 [4.7] years). Compared with patients without infection, those with infection were more likely to be immigrants and to have high levels of material deprivation and were less likely to receive COVID-19 vaccination and live in rural areas. The crude incidence rate of any congenital anomaly was 32.5 anomalies per 1000 live births (95% CI, 27.9-37.9 anomalies per 1000 live births) with maternal SARS-CoV-2 infection and 31.1 anomalies per 1000 live births (95% CI, 28.8-33.6 anomalies per 1000 live births) without maternal SARS-CoV-2 infection (unadjusted rate ratio, 1.04; 95% CI, 0.87-1.24; P = .65). Multivariable logistic regression adjusting for maternal socioeconomic variables and prepregnancy COVID-19 vaccination did not alter these findings. Infection separately by trimester was not statistically significantly associated with the outcome. There were no statistically significant associations between maternal SARS-CoV-2 infection and cardiac anomalies in pregnancy overall or by trimester.

CONCLUSIONS AND RELEVANCE: In this Ontario population-based study of 5049 live births with maternal SARS-CoV-2 infection matched to 20 196 live births without maternal infection, there was no association between laboratory-confirmed maternal SARS-CoV-2 infection and neonatal congenital anomalies in pregnancy overall, or by trimester of infection. These findings may provide reassurance to pregnant patients and their health care professionals, although further studies evaluating first trimester infection and risks of specific anomalies are warranted.

PMID:42096200 | DOI:10.1001/jamanetworkopen.2026.11440

JAMA Netw Open. 2026 May 1;9(5):e2611644. doi: 10.1001/jamanetworkopen.2026.11644.

ABSTRACT

IMPORTANCE: Attending anesthesiologists are not subject to work hour restrictions. Fatigue from long shifts may plausibly contribute to patient harm.

OBJECTIVE: To examine the association between anesthesiologist extended work periods and patient outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Multicenter Perioperative Outcomes Group registry from January 1, 2010, to August 30, 2020, representing all surgical procedures in patients 18 years or older from more than 50 hospitals across 18 US states. Data analyses were conducted from July 1 through November 30, 2025.

EXPOSURE: Anesthesiologist extended work periods, defined as 16 hours or more of continuous intraoperative work.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of in-hospital mortality or major complication. Secondary outcomes were individual components of the composite. A within-anesthesiologist approach was used to compare outcomes for patients treated by each anesthesiologist when in an extended work period vs not, adjusting for patient demographics, comorbidities, American Society of Anesthesiologists classification, emergency status, hour of surgery start, and surgery type.

RESULTS: The study cohort comprised 1 648 720 surgical procedures involving 1711 unique anesthesiologists across 36 institutions (patient mean [SD] age, 51.7 [17.8] years; 982 020 [59.6%] female). A total of 11 556 procedures (0.7%) involved anesthesiologists in an extended work period. Unadjusted incidence of the composite outcome was 12.3% (95% CI, 11.7%-12.9%) for extended work periods vs 12.0% (95% CI, 12.0%-12.1%) for standard work periods. Adjusted absolute risk difference in the composite outcome was 0.1% (95% CI, -0.4% to 0.5%; P = .82). Multiple sensitivity analyses resulted in statistical significance with point estimates of similar direction and magnitude. In-hospital mortality was higher for extended (1.3%; 95% CI, 1.1%-1.6%) vs standard (1.0%; 95% CI, 1.0%-1.0%) work periods, with a risk difference of 0.3 (95% CI, 0.1%-0.5%; P = .009). Other secondary outcomes had risk increases of similar magnitude.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the primary analysis did not identify a statistically significant difference in composite outcome, although the magnitude and precision of risk estimates across multiple sensitivity analyses suggested a small (<1.0%) increase in risk. Secondary analyses also suggested small absolute increases in outcomes, including in-hospital mortality. These findings raise the possibility that fatigue related to prolonged anesthesiologist work periods may have implications for patient safety.

PMID:42096198 | DOI:10.1001/jamanetworkopen.2026.11644

Expert Rev Anticancer Ther. 2026 May 7. doi: 10.1080/14737140.2026.2671251. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment options for non-small cell lung cancer (NSCLC) patients lacking actionable genetic alterations (non-AGA) remain limited, particularly after first-line (1 L) therapy. This study evaluated real-world treatment patterns and outcomes among second or later-line (2 L+) patients with non-AGA nonsquamous (NSQ) metastatic NSCLC (mNSCLC) at a Health Maintenance Organization in Israel.

METHODS: A retrospective cohort study used the Maccabi Healthcare Services database to identify 2 L+ adult patients with non-AGA NSQ mNSCLC between January 2017 and December 2020. Outcomes included progression-free survival (PFS), overall survival (OS), and time-to-next-treatment or death (TTNTD), analyzed using descriptive statistics and Kaplan-Meier methodology.

RESULTS: Among 176 2 L+ patients, median age was 67 years, 66.5% were male, 51.7% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and 30.7% received third-line therapy. Anti-programmed death-receptor/ligand 1 (anti-PD-[L]1) was the most common 2 L therapy (n = 74, 42.0%) following 1 L chemotherapy. Median overall TTNTD from 2 L initiation was 3.73 months (docetaxel: 1.78 months; anti-PD-[L]1 combination: 7.05 months). Median overall PFS was 2.56 months (docetaxel: 1.78 months; anti-PD-[L]1 combination: 9.48 months) and median overall OS was 5.51 months (docetaxel: 1.81 months; anti-PD-[L]1 combination: 9.48 months).

CONCLUSIONS: These findings highlight the high unmet need among 2 L+ non-AGA NSQ mNSCLC patients in Israel.

PMID:42096187 | DOI:10.1080/14737140.2026.2671251

Environ Sci Technol. 2026 May 7. doi: 10.1021/acs.est.5c15628. Online ahead of print.

ABSTRACT

Fine particulate matter (PM₂.₅) is a major environmental health risk in China, yet urban-rural disparities in health burden remain insufficiently characterized. Using the high-resolution PM₂.₅ concentration data, Global Burden of Disease estimates, and urban-rural stratified provincial health statistics, this study quantified PM₂.₅-attributable premature deaths in urban and rural areas from 2000 to 2019 and applied decomposition analysis to assess contributions of PM₂.₅ concentrations, population size, age structure, baseline mortality, and urban expansion. Although PM₂.₅ concentrations declined substantially after 2014, the health burden remained substantial and shifted from rural to urban populations. Population aging was the dominant driver, especially in rural areas, where it offset much of the benefit from air-quality improvement. Urban population growth further increased risks, whereas rural depopulation and urban expansion reduced rural burdens. Declining baseline mortality prevented premature deaths but disproportionately benefited urban residents due to healthcare access inequities. These urban-rural trends were consistent across different exposure-response models, underscoring the robustness of our findings. These findings highlight the need for differentiated environmental health policies that integrate demographic changes, regional disparities, and environmental justice, coordinated urban-rural air-quality management, and targeted health interventions for aging populations.

PMID:42096176 | DOI:10.1021/acs.est.5c15628

Int J Comput Assist Radiol Surg. 2026 May 7. doi: 10.1007/s11548-026-03686-0. Online ahead of print.

ABSTRACT

PURPOSE: Robotic-assisted surgery (RAS) generates vast amounts of video and robotic data, presenting opportunities for machine learning. Video-based models, in particular, that can temporally segment frames by ontological categories such as procedure type, phase, steps, actions, etc., are needed. Training separate models for each category neglects statistical dependencies between categories and can yield incompatible predictions. Training large multi-category models may help, but increases complexity while reducing model modularity and interpretability.

METHODS: We present a model fusion alternative: an effectively zero-free-parameter Bayesian model fusion technique. Incorporating the empirical conditional dependencies across categories and time, we combine predictions from multiple segmentation models into one joint Bayesian inference. The result is a Bayes’ optimal distribution over all categories evolving over time with accumulated evidence.

RESULTS: On a large test set of hundreds of surgical cases, of nearly eight million frames of annotated data, we found that fused predictions from the joint Bayesian model provide clear benefits over the individual models, correcting inconsistent and inaccurate predictions, and even forming accurate beliefs when evidence was absent.

CONCLUSION: The model we present is a lightweight, principled alternative to machine learning-based model fusion. A sufficiently complex model could be trained to produce the same results, but would effectively trade explainable predictions with minimal overheard for computational complexity and transparency. We end by discussing how the same approach can be used to encompass larger more sophisticated models within the same conceptual framework.

PMID:42096125 | DOI:10.1007/s11548-026-03686-0