Tag: statistics

JAMA Health Forum. 2025 Jul 3;6(7):e251930. doi: 10.1001/jamahealthforum.2025.1930.

ABSTRACT

IMPORTANCE: Independent evaluations of Bundled Payments for Care Improvement Advanced (BPCI-A) have focused on hospitals and have not assessed the performance of physicians in participating physician group practices (PGPs). However, PGPs are accountable for a larger proportion of surgical procedures, including for lower-extremity joint replacement, in the BPCI-A model than are hospitals.

OBJECTIVE: To evaluate the association of treatment by BPCI-A-participating physicians and hospitals with health care spending, quality, and utilization for joint replacement procedures compared to nonparticipants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Medicare claims of beneficiaries receiving lower-extremity joint replacement between April 2016 and September 2019 and data on BPCI-A-participating PGPs and hospitals to assess spending, quality, and utilization. Differences-in-differences methods adjusting for patient and market characteristics (aDID) were used with matched comparison groups of nonparticipating physicians and hospitals. Data analysis was performed from January 2023 to January 2025.

EXPOSURES: Lower-extremity joint replacement by a physician in a PGP or hospital that began BPCI-A participation in October 2018.

MAIN OUTCOMES AND MEASURES: Ninety-day total episode spending for joint replacement. Secondary outcomes were postacute care utilization, mortality, hospital readmissions, and joint replacement complications.

RESULTS: The matched cohort included 846 529 Medicare beneficiaries (mean [SD] age, 73.7 [8.3] years; 63.8% female) who obtained a joint replacement in April 2016 to September 2019, of whom 281 189 were treated by 2820 physicians in BPCI-A-participating PGPs, and 69 107 by 174 BPCI-A-participating hospitals. An additional 28 309 beneficiaries were treated by physicians and hospitals both participating in BPCI-A. The remaining 467 924 were treated by 4671 nonparticipating physicians and 432 nonparticipating hospitals. Before BPCI-A participation, total unadjusted baseline episode spending was $26 483 for participating physicians and $29 854 for participating hospitals. Treatments by BPCI-A participating physicians and hospitals were each associated with differentially lower total spending (physician aDID, -$855; 95% CI, -$1074 to -$636; hospital aDID, -$613; 95% CI, -$1039 to -$187). Treatment by a BPCI-A-participating physician or hospital was associated with differentially lower institutional postacute care utilization. Physician participation was associated with a differential increase in outpatient visits 7 days postdischarge (aDID, 2.9 percentage points; 95% CI, 2.0 to 3.8), while hospital participation was not associated with a change in outpatient visits. Differential changes in mortality, readmissions, and complications were not observed for either participant type.

CONCLUSIONS AND RELEVANCE: This cohort study found that participation in BPCI-A for joint replacement was associated with differentially lower total spending for both physicians and hospitals. Given that physicians in PGPs accounted for 73% of all the joint replacement episodes, these findings highlight the importance of facilitating alignment between hospitals and physicians in future bundled-payment models, including those that allow only hospitals.

PMID:40711779 | DOI:10.1001/jamahealthforum.2025.1930

JAMA Health Forum. 2025 Jul 3;6(7):e252223. doi: 10.1001/jamahealthforum.2025.2223.

ABSTRACT

IMPORTANCE: Estimating global lives and life-years saved is important to put into perspective the benefits of COVID-19 vaccination. Prior studies have focused mainly on the pre-Omicron period or only on specific regions, and lack crucial life-year calculations and often depend on strong modeling assumptions with unaccounted uncertainty.

OBJECTIVE: To calculate the lives and life-years saved by COVID-19 vaccination worldwide from the onset of the vaccination campaigns and until October 1, 2024.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study considered different strata of the worldwide population according to age, community-dwelling and long-term care residence status, pre-Omicron and Omicron periods, and vaccination before and after a SARS-CoV-2 infection.

EXPOSURES: Any COVID-19 vaccination in any schedule and number of doses.

MAIN OUTCOME MEASURE: Death.

RESULTS: In the main analysis, more than 2.5 million deaths were averted (1 death averted per 5400 vaccine doses administered). Eighty-two percent were among people vaccinated before any infection, 57% were during the Omicron period, and 90% pertained to people 60 years or older. Sensitivity analyses suggested 1.4 to 4.0 million lives were saved. Some sensitivity analyses showed a preponderance of the benefit during the pre-Omicron period. An estimated 14.8 million life-years were saved (1 life-year saved per 900 vaccine doses administered). The sensitivity range was 7.4 to 23.6 million life-years. Most life-years saved (76%) were among people 60 years or older, but long-term care residents contributed only 2% of the total. Children and adolescents (0.01% of lives saved and 0.1% of life-years saved) and young adults aged 20 through 29 years (0.07% of lives saved and 0.3% of life-years saved) had very small contributions to the total benefit.

CONCLUSIONS AND RELEVANCE: Estimates in this study are substantially more conservative than previous calculations focusing mostly on the first year of vaccination, but they still clearly demonstrate a major overall benefit from COVID-19 vaccination during the years 2020-2024. Most benefits in lives and life-years saved was secured for a portion of older persons, a minority of the global population.

PMID:40711778 | DOI:10.1001/jamahealthforum.2025.2223

DNA Cell Biol. 2025 Jul 21. doi: 10.1177/10445498251361047. Online ahead of print.

ABSTRACT

Tail fat weight is a key economic trait in fat-tailed sheep; reducing tail fat deposition is of significant importance for improving the economic efficiency of sheep farming. In this article, we measured the live weight before slaughter, tail fat weight, and carcass weight of Hu male sheep at 6 months of age and performed the descriptive statistical analysis. The results indicated the coefficient of variation of tail fat-related-traits ranged from 25% to 50%. Simultaneously, we selected IGFBP3 and TUSC5 as candidate genes based on their close association with fat deposition. Target regions were amplified using gene-specific primers in PCR, followed by Sanger sequencing of PCR products to identify genetic variants. Polymorphisms were subsequently validated using the KASPar genotyping assay. Finally, quantitative reverse transcription PCR (qRT-PCR) was performed to determine the expression levels of IGFBP3 and TUSC5. Our findings revealed a missense mutation (g.83695349 C>T) in exon 1 of the IGFBP3 gene and a synonymous mutation (g.41771645 C>T) in exon 2 of the TUSC5 gene. Association analysis showed that these mutations were significantly correlated (p < 0.05) with tail fat weight traits. Moreover, the tail fat weight of the mutant genotypes (CT and TT) was significantly reduced compared with that of the CC genotype, suggesting that the gene may exert a negative regulatory effect on this trait, thereby leading to the reduction of tail fat weight. Furthermore, the genotype combinations showed a significant relationship with tail fat traits. Moreover, qRT-PCR results showed that TUSC5 and IGFBP3 genes were expressed in all experimental tissues of Hu sheep, and the highest expression was observed in tail fat compared with other tissues (heart, liver, spleen, lung, kidney, rumen, duodenum, muscle, and lymph). Notably, their expression levels were significantly lower in the large-tail fat group than in the small-tail fat group. Overall, these results will provide novel candidate variation for reducing tail fat deposition in sheep breeding practice.

PMID:40711772 | DOI:10.1177/10445498251361047

Pharm Stat. 2025 Sep-Oct;24(5):e70027. doi: 10.1002/pst.70027.

ABSTRACT

A major emphasis in personalized medicine is to optimally treat subgroups of patients who may benefit from certain therapeutic agents. One relevant study design is the targeted design, in which patients have consented for their specimens to be obtained at baseline and the specimens are sent to a laboratory for assessing the biomarker status prior to randomization. Here, only biomarker-positive patients will be randomized to either an experimental or the standard of care arms. Many biomarkers, however, are derived from patient tissue specimens, which are heterogeneous leading to variability in the biomarker levels and status. This heterogeneity would have an adverse impact on the power of an enriched biomarker clinical trial. In this article, we show the adverse effect of using the uncorrected sample size and overcome this challenge by presenting an approach to adjust for misclassification for the targeted design. Specifically, we propose a sample size formula that adjusts for misclassification and apply it in the design of two phase III clinical trials in renal and prostate cancer.

PMID:40711765 | DOI:10.1002/pst.70027

Ann Med. 2025 Dec;57(1):2534094. doi: 10.1080/07853890.2025.2534094. Epub 2025 Jul 25.

ABSTRACT

BACKGROUND: Interhospital transfer (IHT) for pulmonary embolism (PE) is increasingly performed to improve access to advanced reperfusion therapies, but it is unclear if IHT times influence overall outcomes. We studied the association between transfer times and outcomes of patients with acute PE requiring IHT.

METHODS: 139 patients with acute PE undergoing IHT to the Mount Sinai Health System between September 2021 and June 2023 were retrospectively studied. Primary outcomes were 30-day mortality and 30-day major bleeding. ‘Door to IHT’ time was defined as the time from diagnosis of acute PE to the time patient physically arrived in the receiving hospital. Patients were divided into groups based on quartiles of ‘door to IHT’ time; those within the first and fourth quartiles of ‘door to IHT’ time were compared using propensity score-weighted analyses. The propensity score was calculated from six variables: age, sex, BMI [Body Mass Index], PESI [PE Severity Index] score, ESC [European Society of Cardiology] risk class and presence of a central PE. Multivariable regression models were fitted within the propensity score-matched sample to assess the association of ‘door to IHT’ time with primary outcomes.

RESULTS: Median age of included patients was 61 years and 76 (54.7%) were women. Median PESI score was 88 points. Median ‘door to IHT’ time was 10.8 (IQR: 7.3-19.4) hours. Rates of 30-day mortality and 30-day major bleeding were 7.2% and 2.2%. Within propensity score-weighted analyses, no significant associations were found between ‘door to IHT’ time and any of the primary outcomes (30-day mortality or 30-day major bleeding).

CONCLUSION: In this retrospective study of patients with acute PE undergoing IHT, differences in ‘door to IHT’ time were not significantly associated with 30-day mortality or 30-day major bleeding. This suggests that delays in IHT do not adversely influence outcomes of patients with acute PE undergoing IHT.

PMID:40711763 | DOI:10.1080/07853890.2025.2534094

Strabismus. 2025 Jul 25:1-10. doi: 10.1080/09273972.2025.2537361. Online ahead of print.

ABSTRACT

Background: Amblyopia is a neurodevelopmental disorder of vision with various treatment modalities available for treatment. This study was conducted to compare visual outcomes and stereoacuity in sequential and simultaneous refractive correction and patching in treatment of amblyopia. Materials and methods: A prospective randomized interventional study was conducted in age group 3-14 years with unilateral mild-to-moderate amblyopia in two groups (total 70 patients, 35 each) over a period of 1 year. Group A patients underwent simultaneous treatment and Group B patients underwent sequential treatment. Follow-up data for distant and near best corrected visual acuity (BCVA) and stereopsis was taken at baseline, 1 week, 6 weeks, 9 weeks and 12 weeks. Results: At final follow-up, the mean distant BCVA in amblyopic eye was 0.35LogMAReq (SD – 0.14) and 0.33LogMAReq (SD – 0.15) in Group A and Group B, respectively, with no statistically significant difference between both groups (p = .58). At final follow-up, there was a significant improvement in mean near BCVA in amblyopic eye in both the groups (p, Group A < .01, Group B < .01) with no statistically significant difference between the two groups (p = .93). The mean stereoacuity at final follow-up was 512.3 arc secs and 165.74 arc secs in Group A and Group B, respectively. The median (IQR) stereoacuity at final follow-up was 200 (300) and 100 (137) for Group A and Group B, respectively. The difference between the two groups was statistically significant (p = .01) at 9 weeks and (p < .01) at 12 weeks. For intergroup comparison, while the difference in stereoacuity was not statistically different comparing anisometropia amblyopia subtype (p = .95), there was a statistically significant difference in stereoacuity at final follow-up for strabismic amblyopia (p = .04), with Group B having better stereoacuity. Conclusion: It is concluded that there is no significant difference between simultaneous and sequential group for BCVA, however sequential group yields better stereopsis as compared to simultaneous group.

PMID:40711760 | DOI:10.1080/09273972.2025.2537361

J Mater Chem B. 2025 Jul 25. doi: 10.1039/d5tb01157d. Online ahead of print.

ABSTRACT

Surgical precision in tumor resection critically relies on real-time intraoperative imaging, yet conventional probes face limitations in specificity and spatiotemporal control. Here, we present a tumor microenvironment (TME)-activated near-infrared (NIR) fluorescent nanoprobe (DNS-DYE/PEG-NI) that integrates dual responsiveness to hypoxia and glutathione (GSH) for submillimeter-level surgical navigation. The system comprises a GSH-activatable NIR fluorophore (λ_ex/em = 679/730 nm) quenched by 2,4-dinitrobenzenesulfonyl (DNS) moieties and hypoxia-sensitive amphiphilic PEG-NI micelles. Upon tumor accumulation via the enhanced permeability and retention (EPR) effect, a hypoxic TME triggers micelle disassembly through nitroimidazole (NI) reduction, releasing DNS-DYE. Subsequent GSH cleavage restores fluorescence via intramolecular charge transfer (ICT) recovery, achieving a 12.3-fold tumor-to-normal tissue signal ratio and >90% reduction in off-target activation compared to non-responsive controls. Systematic validation demonstrates: (1) dose-dependent fluorescence recovery (35-fold intensity increase at 10 mM GSH); (2) hypoxia-driven micelle destabilization (800% hydrodynamic diameter expansion); (3) sustained colloidal stability (12.9% size variation over 15 days); and (4) low cytotoxicity (cell viability >90% at 125 μg mL^-1). In vivo studies reveal precise tumor delineation within 12 h post-injection, enabling real-time resection of submillimeter lesions. By coupling TME-specific activation with prolonged tumor retention, this dual-responsive nanoprobe advances fluorescence-guided surgery toward precision oncology, reducing positive margin rates from 70% to <5% in preclinical models.

PMID:40711756 | DOI:10.1039/d5tb01157d

Ann Nucl Med. 2025 Jul 25. doi: 10.1007/s12149-025-02069-w. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the prognostic value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in patients with mucosal melanoma of the head and neck (MMHN) treated with carbon ion radiotherapy (CIRT).

METHODS: This single-center retrospective study included patients with MMHN who underwent CIRT and FDG-PET/CT. Correlations between pre-treatment FDG-PET/CT-derived parameters, including the maximum standardized uptake variable (SUVmax), metabolic tumor volume (MTV) with a 50% threshold, total lesion glycolysis (TLG), bone marrow/liver SUVmax and mean standardized uptake variable (SUVmean) ratios, and spleen/liver SUVmax and SUVmean ratios (SLRmax, SLRmean), with clinical parameters and prognosis were statistically analyzed.

RESULTS: A total of 32 patients with MMHN were enrolled (median age, 72.5 years). The tumor stages were distributed as follows: T3, 17 patients; T4a, 14 patients; T4b, one patient. The median total observation period was 22.6 months, the median overall survival (OS) was 21.6 months, and the median progression-free survival (PFS) was 11.5 months. Thirteen patients (40.6%) died, 10 (31.3%) experienced local recurrence, and 19 (59.4%) had distant metastases during the observation period. The 1 and 3-year survival rates were 78.1% and 62.5%, respectively. FDG-PET/CT showed pronounced positive uptake for all tumors (median SUVmax: 13.8, range 2.7-33.0). SLRmax was high in patients with negative programmed death-ligand 1 expression in the tumor (p = 0.05). PFS was shorter in patients with a high MTV (p = 0.018). In the multivariate analysis, MTV was an independent prognostic factor for PFS (hazard ratio, 2.60; 95% confidence interval, 1.065-6.345; p = 0.036). MTV and TLG were not predictive of OS in the univariate analysis.

CONCLUSIONS: FDG-PET/CT showed a strong positive uptake for MMHN. FDG-PET/CT-derived imaging parameters may be significant prognostic biomarkers for predicting tumor progression in patients with MMHN.

PMID:40711750 | DOI:10.1007/s12149-025-02069-w

Aging Clin Exp Res. 2025 Jul 25;37(1):232. doi: 10.1007/s40520-025-03138-w.

ABSTRACT

BACKGROUND: Some observational studies have indicated that osteoarthritis (OA) is a fall risk factor. However, the causal relationship between OA and falls remains unclear.

METHODS: We conducted a two-step Mendelian randomization (MR) to investigate the causal relationships between OA, paracetamol use, and the risk of falls and to estimate the mediating effect of paracetamol use. Publicly accessible data for hip OA, knee OA, paracetamol use, and falling risk were sourced from Genome-Wide Association Studies (GWAS).

RESULT: In the forward MR analysis, the Inverse Variance Weighted (IVW) method indicated that a genetic predisposition to hip OA was significantly associated with an increased risk of falls (OR: 1.053, 95% CI: 1.014 to 1.094, P = 0.007). Consistent directions of effect were observed across other MR analysis methods. The mediated proportion of paracetamol use on the relationship between hip OA and falling risk was 21.70% (β = 0.0113, 95% CI: 5.73-37.8%, P = 0.0078). No causal relationship was observed between knee OA and falling risk, nor between knee OA and the use of paracetamol. In the reversed MR analysis, the IVW method showed that a genetic predisposition to falls may not increase the risk of developing hip and knee OA.

CONCLUSION: These results provide genetic evidence for a causal effect of hip OA on fall risk, partially mediated by paracetamol, and underscore the importance of fall prevention education and cautious paracetamol use for patients with hip OA.

PMID:40711723 | DOI:10.1007/s40520-025-03138-w

Ophthalmol Ther. 2025 Jul 25. doi: 10.1007/s40123-025-01194-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Ocular redness is common, can affect quality of life, and can be relieved by short-term use of topical adrenergic receptor (AR) agonists. Brimonidine tartrate ophthalmic solution 0.025% (LUMIFY^® 0.025%) is the first α2-AR-selective agonist approved for ocular redness. The preservative benzalkonium chloride (BAK) maintains ophthalmic solution sterility, reducing the risk of ocular infections, but may cause symptoms of ocular surface disease (OSD) in some patients. A BAK-free formulation of LUMIFY 0.025% (BTOS-PF 0.025%) could offer a solution for BAK-sensitive patients.

METHODS: This randomized, active-controlled, multicenter study aimed to establish non-inferior efficacy of BTOS-PF 0.025% to LUMIFY 0.025% and compare safety. Randomized participants received either formulation instilled as a single drop four times daily, for 4 weeks. The primary endpoint was investigator-assessed ocular redness at 5, 15, 30, 60, 90, 120, 180, and 240 min post-instillation at visit 1 (day 1). Eight hierarchical secondary endpoints included additional post-instillation timepoints at visit 1 and visits 2 and 3 (days 14 and 28), and participant-assessed redness.

RESULTS: BTOS-PF 0.025% was statistically non-inferior to LUMIFY 0.025% for ocular redness reduction across the eight timepoints at visit 1. Efficacy for both formulations was seen as early as 1 min and up to 8 h post-instillation. BTOS-PF 0.025% performed similarly to LUMIFY 0.025% after 14 and 28 days, rebound redness rates were low and similar, and total clearance of ocular redness and participant-evaluated redness were similar. The safety profile of both formulations was similar, with no severe or serious ocular events.

CONCLUSIONS: BTOS-PF 0.025% was non-inferior to LUMIFY 0.025% in reducing ocular redness in adults, was well-tolerated, and offers an alternative topical solution, without loss of efficacy or compromised safety, for patients who prefer a preservative-free formulation or are at increased risk of OSD.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05360784. Date of registration: 29 April 2022.

PMID:40711722 | DOI:10.1007/s40123-025-01194-z