Category: Statistics

JAMA Netw Open. 2026 May 1;9(5):e266147. doi: 10.1001/jamanetworkopen.2026.6147.

ABSTRACT

IMPORTANCE: The US has higher mortality rates than other high-income countries (HICs). However, a comprehensive analysis of excess US deaths encompassing all leading causes of death over the past 2 decades is currently lacking.

OBJECTIVE: To investigate causes of death responsible for excess US mortality compared with other HICs and how the causes of death involved in this US mortality disadvantage have changed over time.

DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional study included mortality data from the World Health Organization Mortality Database spanning 1999 to 2022 for the US and 17 other HICs. Data were analyzed from September 2023 to December 2025.

EXPOSURES: Residing in the US vs another of the included HICs.

MAIN OUTCOME AND MEASURES: The main outcome was excess US mortality in each year due to specific causes of death. Differences between the US and other HICs were quantified for each cause of death as (1) excess US deaths (ie, absolute difference between observed deaths and deaths expected if US death rates equaled the rates of other HICs); (2) years of life lost (YLL) resulting from excess US deaths; and (3) mortality rate ratios (ie, ratios of observed to expected age-standardized death rates).

RESULTS: A total of 63 547 318 deaths occurred in the US from 1999 to 2022 (50.4% among males; mean [SD] age at death, 73.2 [18.5] years). In this period, 12 675 646 excess US deaths occurred, increasing from 346 166 in 1999 to 905 159 in 2022. Circulatory diseases were the leading cause of excess US deaths every year except 2010, increasing after 2001 for ages 45 to 64 years and after 2009 for ages 65 years or older. Together, circulatory and metabolic diseases accounted for 52% of excess US deaths in 2022. Excess US deaths due to drug poisonings, alcohol, and suicide increased from -5762 in 1999 to 131 151 in 2022; together, these 3 causes accounted for 24% of the increase in excess US deaths overall and most of the increase in excess US deaths for individuals aged 0 to 44 years. In 2022, deaths from drug poisonings were 7.48 times higher in the US than in other HICs. In 2020 and 2021, 19% and 23% of excess US deaths, respectively, were attributed to COVID-19, but excess US deaths from other causes also increased.

CONCLUSIONS AND RELEVANCE: In this repeated cross-sectional study of cross-national mortality, the US had substantially higher death rates than other HICs between 1999 and 2022, despite having similar access to advanced medical technology. Many of these excess US deaths could likely be avoided by adopting health and social policies that have benefited other HICs. These descriptive findings should be interpreted in light of uncertainty arising from differences in death coding, data completeness, and other aspects of data comparability across countries.

PMID:42101842 | DOI:10.1001/jamanetworkopen.2026.6147

JAMA Netw Open. 2026 May 1;9(5):e2611418. doi: 10.1001/jamanetworkopen.2026.11418.

ABSTRACT

IMPORTANCE: Smoking cessation interventions could ultimately offer greater impact to the extent that they are brief, concrete, and face valid (to the individuals presenting and receiving the intervention), which would then make these interventions scalable across a broad spectrum of adults who smoke (AWS). Medication sampling is one potential strategy to meet that need.

OBJECTIVE: To determine outcomes of varenicline sampling in a fully powered randomized clinical trial (RCT), conducted from February 2021 to April 2025.

DESIGN, SETTING, AND PARTICIPANTS: This decentralized RCT included non-treatment seeking AWS with varying levels of motivation to quit who were recruited throughout South Carolina.

INTERVENTION: Participants were randomized to receive a 4-week sample of varenicline, nicotine replacement therapy (NRT; active control), or quitline referral (inactive control) in a 2:1:1 ratio. Accompanying 4-week medication supply, intervention messaging in both sampling groups emphasized naturalistic use, ie, a participant-driven experience with self-determined uptake, use, and goals for use.

MAIN OUTCOMES AND MEASURES: The primary outcome was self-reported 7-day point prevalence abstinence (PPA) at 6-month follow-up. Secondary outcomes included carbon monoxide (CO)-verified abstinence, floating abstinence (any 7-day period of not smoking throughout follow-up), quit attempts, and smoking reduction.

RESULTS: The study sample included 651 AWS (mean [SD] age, 52 [11] years; 431 (66%) female), with 161 randomized to the no-sampling control, 172 randomized to NRT, and 318 randomized to varenicline. Compared with the no-sampling control, AWS receiving varenicline samples had higher rates of self-reported PPA at month 6 (16 of 161 [10%] vs 53 of 318 [17%]; P = .048), floating abstinence throughout follow-up (33 [20%] vs 108 [34%]; P = .003); and greater incidence of 50% or greater reduction in cigarettes per day (CPD) by 6 months (31 [19%] vs 106 [33%]; P = .002); however, rates of CO-verified abstinence at 6 months were not significantly different. Varenicline sampling was superior to NRT sampling for 6-month self-reported abstinence (53 [17%] vs 14 of 172 [8%]; P = .01); floating abstinence through 6 months (108 [34%] vs 43 [25%]; P = .04); and incidence of 50% or greater reduction in CPD at week 8 (111 [35%] vs 38 [22%]; P = .005) but not at 6 months.

CONCLUSIONS AND RELEVANCE: In this RCT of 651 AWS, varenicline sampling was efficacious, with potentially superior outcomes compared with NRT. Results provide additional evidence in support of medication sampling as a pragmatic option to engage AWS in cessation, worth further evaluation within an applied settings.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04525755.

PMID:42101840 | DOI:10.1001/jamanetworkopen.2026.11418

JAMA Netw Open. 2026 May 1;9(5):e2611700. doi: 10.1001/jamanetworkopen.2026.11700.

ABSTRACT

IMPORTANCE: The ultimate goal of residency education is to train physicians to deliver high-quality patient care. However, residents rarely receive data-driven feedback because resident-level quality measures are lacking.

OBJECTIVE: To develop and evaluate resident-sensitive quality measures (RSQMs) using electronic health record data to inform graduate medical education.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used call schedules linking senior internal medicine residents to patient admissions during overnight internal medicine call shifts at 5 teaching hospitals in Canada from July 1, 2010, through December 31, 2019. Using clinical practice guidelines, 7 RSQMs related to pneumonia or general care for all internal medicine admissions were developed. To support interpretation, a care variation framework was applied that categorized measures as low value (not recommended), discretionary (context dependent), or evidence based (recommended) to enable comparisons between observed and expected variation. The data were analyzed between March 1, 2024, and February 23, 2026.

MAIN OUTCOMES AND MEASURES: The low-value care RSQM measured potentially inappropriate red cell transfusions (all admissions). Discretionary RSQMs measured use of antibiotics, imaging, or blood work for either pneumonia or all admissions. The evidence-based care RSQM measured ordering of first-line antibiotics for pneumonia. Resident-level variation was assessed using descriptive statistics, including the median proportion of eligible admissions with each RSQM performed and interquartile range.

RESULTS: The cohort included 132 291 patient admissions (median [IQR] age, 70 [55-83] years; 50.6% male) linked to 793 residents. Residents had a median (IQR) of 187 (89-228) admissions, including a median (IQR) of 18 (10-24) admissions for pneumonia. Potentially inappropriate red cell transfusions occurred in a low proportion of encounters, with little variation (median, 0%; IQR, 0%-0%). Discretionary measures, including use of second-line antibiotics, advanced imaging, chest computed tomography, and serum protein electrophoresis, varied across residents. For pneumonia admissions (n = 13 470), the RSQM for first-line antibiotic use in pneumonia was sensitive to the time windows for included orders, ranging from 22% (3027 admissions) to 76% (10 205 admissions), depending on the cutoffs applied.

CONCLUSIONS AND RELEVANCE: This cohort study outlined an approach to developing and evaluating RSQMs using readily available electronic health record data to evaluate internal medicine residents’ quality of care. Although the RSQMs showed potential, their use for inpatient internal medicine may be more appropriate at the program level due to unresolved concerns regarding attribution and statistical reliability.

PMID:42101838 | DOI:10.1001/jamanetworkopen.2026.11700

JAMA Netw Open. 2026 May 1;9(5):e2611711. doi: 10.1001/jamanetworkopen.2026.11711.

ABSTRACT

IMPORTANCE: Urine drug testing (UDT) is commonly used in substance use disorder (SUD) treatment. However, there is little evidence to guide optimal use of UDT and growing concern that some UDT may represent low-value care.

OBJECTIVE: To determine whether a statewide policy limiting Medicaid reimbursement for UDT is associated with testing frequency, expenditures, and clinical outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional study was performed among Louisiana Medicaid beneficiaries between July 1, 2017, and February 29, 2020. Data were analyzed from November 1, 2024, to November 30, 2025. For each outcome, best-fit lines for pre-enactment trends were constructed and used to estimate postenactment trends, which were then compared with observed trends. The 3-way interaction of time by intervention period by outcome was analyzed to assess changes for each UDT utilization outcome compared with a matched control procedure (colonoscopy). Concomitant trends in overdose encounters and prescription of medications for opioid use disorder (MOUD) were also assessed.

EXPOSURE: Statewide policy limiting Medicaid reimbursement for UDT enacted in July 2019. Colonoscopy rates were used as a temporal comparison procedure.

MAIN OUTCOMES AND MEASURES: Outcomes included rates of monthly UDT (total, presumptive, and definitive) and expenditures per 1000 beneficiaries for 24 months before and 7 months after policy enactment.

RESULTS: The sample included a total of 900 678 unique Medicaid-eligible beneficiaries, 536 841 (59.6%) of whom were female and 606 012 (67.3%) were younger than 40 years. Following policy enactment, the monthly rate of change for total UDT utilization decreased from 0.67 (95% CI, 0.48- 0.85) to -1.03 (95% CI, -1.65 to -0.40) tests per month per 1000 beneficiaries (difference, -1.70 [95% CI, -2.34 to -1.06] tests per month per 1000 beneficiaries); presumptive UDT decreased from 0.42 (95% CI, 0.30-0.53) to -0.63 (95% CI, -0.92 to -0.35) tests per month per 1000 beneficiaries (difference, -1.05 [95% CI, -1.36 to -0.74] tests per month per 1000 beneficiaries); and definitive UDT decreased from 0.25 (95% CI, 0.17-0.34) to -0.39 (95% CI, -0.97 to 0.18) tests per month per 1000 beneficiaries (difference, -0.65 [95% CI, -1.23 to -0.07] tests per month per 1000 beneficiaries). These decreases were all statistically significant compared with colonoscopy (all P < .05). UDT expenditures also significantly decreased, totaling an estimated $14.8 million in savings during the 7-month postenactment period. The policy change was not associated with reduced MOUD receipt or increased overdose encounters.

CONCLUSION AND RELEVANCE: In this cross-sectional study, a state policy limiting reimbursement for UDT was associated with significant reductions in UDT utilization and expenditures. Future research and policymaking should investigate ways to optimize UDT for patient health while reducing low-value care.

PMID:42101837 | DOI:10.1001/jamanetworkopen.2026.11711

Rev Sci Instrum. 2026 May 1;97(5):055208. doi: 10.1063/5.0314932.

ABSTRACT

Soft x-ray angle-resolved photoemission spectroscopy (SX-ARPES) is one of the most powerful spectroscopic techniques to visualize the three-dimensional bulk electronic structure in reciprocal lattice space. Compared with ARPES employing low-energy photon sources, the time burden imposed by a lower photoelectron yield, stemming from the photoionization cross-section, has been a persistent technical challenge. To address this challenge, we have developed a noise-reduction system by using the deep prior-based approach and integrated it into the micro-focused SX-ARPES (μSX-ARPES) system at BL25SU in SPring-8. The implemented system effectively eliminates instrumental artifacts, such as grid and spike structures typical of ARPES data acquired using the voltage Fixed mode, within ∼30 s. We demonstrate, through the μSX-ARPES measurements on a single crystal of CeRu2Si2, that data with sufficient statistical accuracy can be obtained in ∼40 s. In addition, we present the potential of high signal-to-noise ratio ARPES measurement, achieving an energy resolution of 51.6 meV at an excitation energy of 708 eV in μSX-ARPES measurements on polycrystalline gold. Our developed system successfully reduces the time burden in SX-ARPES and paves the way for advancements in lower photoelectron yield measurements, such as those requiring higher energy resolution and three-dimensional nonequilibrium measurements.

PMID:42101827 | DOI:10.1063/5.0314932

Environ Sci Pollut Res Int. 2026 May 8. doi: 10.1007/s11356-026-37788-8. Online ahead of print.

ABSTRACT

Dyeing with natural dyes offers an eco-friendly and sustainable alternative to synthetic colorants, aligning with the increasing demand for environmentally responsible textile processing. This study investigates the aesthetic and functional enhancement of wool yarns dyed with Spartium junceum flower extract, employing a comprehensive mordanting strategy including single metal salts (Cr, Cu, Ni, Co, Zn), binary metal combinations, biomordants (oak hull, sumac fruit, eucalyptus leaves, gallnut, ascorbic, and gallic acids), and metal-biomordant hybrids, yielding 52 formulations in total. Colorimetric evaluation (K/S, L*, a*, b*, C*, h°) showed that Cr(III)- and Cu(II)-based systems markedly increased color strength and shade depth compared with unmordanted and biomordant-only samples, while hybrid systems such as Cr/GA, Cr/EU, Cu/GA, Cu/AA, and Zn/Cr produced the deepest, most saturated yellow-orange shades at reduced metal dosages. Fastness testing confirmed good-very good wash and rub fastness and substantially improved light fastness (6-7 and 7) for the best-performing hybrids, further supported by very low ΔE* values. Functional assessment revealed that selected metal-biomordant systems dramatically enhanced UV protection, increasing UPF from “Poor/Good” for raw and unmordanted yarns to “Excellent” levels, with several hybrids exhibiting UPF values well above 100. The same systems also showed strongly increased antioxidant activity in the DPPH assay relative to unmordanted controls. Principal Component Analysis (PCA) revealed that PC1 and PC2 together explained 73.78% of the total variance, confirming the multivariate interdependence between color depth, UV shielding, and radical scavenging. Box plots and radar charts further emphasized Cr-GA and Cu-AA as high-performance mordant systems with balanced functional and aesthetic profiles. A composite performance index was used to rank formulations, identifying 11 top-performing systems with scores exceeding 0.63. This study illustrates how bio-metal mordanting, coupled with multivariate analysis, can be leveraged to design natural textiles with high multifunctionality. Finally, a machine learning (i.e., random forest) model was used to predict colorimetric attributes, and the satisfactory performance of the model was noted, implying the potential of using machine learning in prediction of similar process parameters.

PMID:42101801 | DOI:10.1007/s11356-026-37788-8

Health Econ Rev. 2026 May 8. doi: 10.1186/s13561-026-00779-z. Online ahead of print.

ABSTRACT

BACKGROUND: As China’s population aging rapidly, long-term care insurance (LTCI) has emerged as a critical policy instrument to address the care needs of older adults. While previous studies have examined the effects of LTCI on service utilization, less is known about its effect on assistive device utilization-a key component in supporting functional independence and reducing caregiver burden. This study examines the association between LTCI benefit design and assistive device use among older adults in China.

METHODS: We use cross-sectional data from 1,460 older adults residing in elderly care institutions located in non-pilot areas, general LTCI pilot areas (covering care services only), and special LTCI pilot areas (covering both care services and assistive devices). Logistic regression models were used to estimate the associations between LTCI benefit types and assistive device use. Robustness checks were conducted using propensity score matching (PSM), and subgroup analyses were performed by age, education, and household registration.

RESULTS: General LTCI programs that cover care service only were significantly associated with a lower probability of assistive device use, consistent with a potential substitution effect in which subsidized formal care services may replace the need for assistive devices. In contrast, LTCI programs that explicitly include assistive device benefits were associated with a higher probability of assistive device use. These associations were more pronounced among the oldest-old, individuals with urban household registration, and those with lower education levels. Additional analyses indicate that the observed associations are primarily driven by mobility-related devices, whereas estimates for ADL-related devices and total device counts are not statistically significant.

CONCLUSION: The findings suggest that the design of LTCI benefit packages may influence older adults’ care choices and technology adoption. While causal interpretation remains limited, the results highlight the potential role of benefit design in shaping the balance between formal care services and assistive technology use. Expanding assistive device coverage and improving accessibility may help support functional independence among older adults in ageing societies, particularly in underserved rural regions.

PMID:42101796 | DOI:10.1186/s13561-026-00779-z

Target Oncol. 2026 May 8. doi: 10.1007/s11523-026-01221-4. Online ahead of print.

ABSTRACT

BACKGROUND: Adjuvant anti-PD-1 therapy improves outcomes in resected stage IIB/IIC melanoma at high risk of recurrence; however, no randomized head-to-head trial has directly compared pembrolizumab with nivolumab.

OBJECTIVE: The objective was to compare the efficacy of pembrolizumab and nivolumab as adjuvant therapies in resected stage IIB/IIC melanoma using an indirect treatment comparison (ITC).

PATIENTS AND METHODS: An anchored Bucher ITC was performed linking the results of KEYNOTE-716 and the CheckMate-76K trials. Primary analyses used the most recent follow-up hazard ratios (HRs), with secondary analyses based on the original trial publications.

RESULTS: The ITC showed no statistically significant differences between pembrolizumab and nivolumab for recurrence-free survival (RFS; HR 0.97, 95% confidence intervals (CI) 0.69-1.35) or distant metastasis-free survival (DMFS; HR 0.81, 95% CI 0.54-1.21). Subgroup analyses for RFS were also nonsignificant: stage IIB HR 0.97, 95% CI 0.62-1.50; stage IIC HR 1.00, 95% CI 0.61-1.65; age < 65 years HR 1.20, 95% CI 0.76-1.89; and age ≥ 65 years HR 0.77, 95% CI 0.47-1.25. Secondary analyses based on the original trial publications yielded nonsignificant estimates that numerically favored nivolumab, with RFS HR 1.48 (95% CI 0.98-2.23) and DMFS HR 1.26 (95% CI 0.74-2.13).

CONCLUSIONS: This ITC demonstrated no statistically significant differences between pembrolizumab and nivolumab for RFS or DMFS in resected stage IIB/IIC melanoma, with consistently null findings across subgroup analyses. Longer follow-up attenuated earlier numerical trends, with effect estimates converging toward unity.

PMID:42101794 | DOI:10.1007/s11523-026-01221-4

World J Microbiol Biotechnol. 2026 May 8;42(6):267. doi: 10.1007/s11274-026-05002-z.

ABSTRACT

The safety of live probiotics remains debated due to concerns regarding their viability and functional efficacy under harsh in vivo and in vitro conditions. Inflammatory bowel disease (IBD) is a complex disease stemming from various factors. It has been reported that probiotics shows anti-inflammatory function. This study evaluated the immunomodulatory and anti-inflammatory properties of heat-killed Lactobacillus strains (a form of postbiotics). Because viable Loigolactobacillus coryniformis NA-3 exhibited lower in vitro viability than Lactiplantibacillus plantarum NA, we first evaluated the phagocytic activity and TLR2-mediated immunoregulatory effects of heat-killed L. coryniformis NA-3 in RAW 264.7 cells, and conducted a preliminary comparative assessment of both live and heat-killed L. coryniformis NA-3 in murine models. We further investigated two distinct heat-killed strains: L. coryniformis NA-3 and Lactiplantibacillus plantarum NA. Heat-killed L. coryniformis NA-3 induced TLR2-dependent immunomodulatory effects in vitro and showed effects comparable to those of its live counterpart in vivo under the conditions tested. Both heat-killed strains were associated with changes in inflammatory markers, including decreased levels of pro-inflammatory cytokines (IL-6, TNF-α) and increased levels of anti-inflammatory mediators (IL-4, IL-10, TGF-β) in mice. In addition, they were associated with alterations in antioxidant parameters, including changes in SOD, GSH-Px, GR, NQO1, HO-1, Nrf2, and MDA levels, as well as increased expression of the tight junction proteins claudin-1 and occluding. Observations from this study are consistent with the potential involvement of the TLR2/NF-κB p65 signaling pathway. These findings highlight the potential of heat-killed probiotics as safe and effective alternatives to live strains in immune regulation and anti-inflammation.

PMID:42101791 | DOI:10.1007/s11274-026-05002-z

Jpn J Ophthalmol. 2026 May 8. doi: 10.1007/s10384-026-01362-z. Online ahead of print.

ABSTRACT

PURPOSE: To compare physician-assessed and patient-reported outcomes quantified with the Japanese Ocular Surface Disease Index (J-OSDI) following the treatment of bacterial blepharitis and to evaluate the utility of the J-OSDI.

STUDY DESIGN: Multicenter prospective observational study.

METHODS: Physicians assessed symptoms and findings, calculating clinical total scores at baseline (T0), 7 (T1) and 14 (T2) days post-treatment with 1% azithromycin ophthalmic solution, and 1 month after discontinuation (T3). Patients self-reported symptoms using the J-OSDI at these times. The J-OSDI score trends and differences in temporal changes between the J-OSDI and clinical total scores were analyzed by use of a linear mixed-effects model.

RESULTS: Forty-six eyes (46 patients; mean age, 71.8 years) were studied. The J-OSDI scores decreased significantly post-treatment for all the patients, with similar trends for both anterior and posterior blepharitis. For all the patients, the slope difference between the J-OSDI and clinical total scores was not significant in the T0-T1 period (P = .219), meaning that the J-OSDI scores reflected the clinical results, whereas it was significant in the T1-T2 (P = .004) and T2-T3 (P <.001) periods. The within-subject correlation between the 2 scores was 0.525 (95% CI 0.401-0.631). For anterior blepharitis, the slope differences were significant across all the periods, but for posterior blepharitis, no significant differences were observed in the T0-T1 or T1-T2 (P = .205, 0.06, respectively) periods, although significant differences were noted in the T2-T3 period (P = .018).

CONCLUSION: The J-OSDI trajectory often diverges from physician-rated changes. Whilst the J-OSDI does not assess treatment response in anterior blepharitis, it may be partially reflective of improvement in posterior blepharitis.

PMID:42101788 | DOI:10.1007/s10384-026-01362-z