Category: Statistics

JMIR Form Res. 2026 Jul 9;10:e78916. doi: 10.2196/78916.

ABSTRACT

BACKGROUND: Out-of-pocket (OOP) costs pose a significant barrier to participating in cancer clinical trials (CCTs). Financial reimbursement programs (FRPs) that reduce the burden of OOP costs can support participation in CCTs if the information is readily available to participants at the time of enrollment. Prior studies have shown the importance and impact of FRPs, but despite improvements, significant barriers still remain.

OBJECTIVE: This study was designed to explore the feasibility and acceptability of automated texts designed to offer, screen, and enroll CCT participants in an FRP for OOP travel and lodging-related clinical trial costs.

METHODS: This study used a mixed methods approach. Eligible participants were those who consented to participate in a breast, leukemia, or chimeric antigen receptor T cell (CAR-T) trial at the Abramson Cancer Center of the University of Pennsylvania, a National Cancer Institute comprehensive cancer center. Quantitative data were collected through engagement metrics, including text response rates and enrollment rates, as well as patient-reported satisfaction scores. Qualitative data were derived from semistructured interviews. Program enrollment rates were used to determine feasibility, whereas the engagement metrics were used to measure the acceptability of the program. Semistructured interviews were conducted with a subsample of patients who responded to at least one of the FRP texts and agreed to be interviewed to determine the barriers to and facilitators of enrolling in the Improving Patient Access to Cancer Clinical Trials (IMPACT) program via text, perceived advantages and disadvantages of the text messaging program compared to a phone call, and overall feedback on the acceptability of the automated text messaging program.

RESULTS: Quantitative data, including engagement with texts, FRP eligibility screening, and enrollment rates, were collected from all participants who successfully received a text (n=51), and qualitative data were collected from a subsample of participants who agreed to participate in a semistructured interview (n=28) about the text-based program. Participants’ mean age was 58 (SD 12) years, approximately 65% (n=33) of participants were female, 21% (n=11) of participants were Black, and 4% (n=2) of participants were Hispanic or Latino. There was high engagement with texts (n=49, 96.1%) and a high screening rate for FRP eligibility (n=33, 64.7%). Of those who successfully screened, 26 (51%) screened via text. We also saw high overall FRP enrollment rates of those who completed the texts (n=16 of 24 eligible, 66.7%) and high satisfaction (Net Promoter Score=51). The text-based platform streamlined the enrollment process, allowing one-third of patients to complete enrollment independently, without assistance from the FRP coordinator. Reported facilitators for completion of the text conversation included support from the coordinator and introduction of the FRP by CCT teams. Barriers were a lack of communication from CCT teams, patient skepticism about the legitimacy of the texts, and limited program information via text.

CONCLUSIONS: Despite the small sample size and single study site, these findings suggest that automated text messaging can be an effective, low-cost, and scalable strategy to increase awareness and streamline enrollment in FRPs.

PMID:42424491 | DOI:10.2196/78916

Science. 2026 Jul 9;393(6807):eaeb9506. doi: 10.1126/science.aeb9506. Epub 2026 Jul 9.

ABSTRACT

From medicine to marketing to social sciences, the promise of tailoring interventions to individuals is undeniable. However, practical applications force weighing personalization’s potential benefits with its possible increased cost and fragility. We introduce a statistical hypothesis test that evaluates, given historical data, evidence that a personalized intervention policy’s performance will surpass deploying the best single intervention. The test maintains strict Type I error control while achieving asymptotic normality with the minimal possible variance under specified conditions. Results on diverse datasets from job training, depression treatment, education, and recommendation systems demonstrate the test’s versatility and its superior performance over alternatives. This test can support decision-makers throughout the intervention sciences by providing a simple and powerful quantification of the potential benefits of personalization.

PMID:42424443 | DOI:10.1126/science.aeb9506

Cancer. 2026 Jul 15;132(14):e70500. doi: 10.1002/cncr.70500.

ABSTRACT

BACKGROUND: Genomic complexity and small case numbers make statistically robust assessment of mutational patterns in osteosarcoma difficult. The authors analyzed a large cohort of targeted next-generation sequencing data from osteosarcoma cases from young patients submitted for clinical testing to Foundation Medicine.

METHODS: The osteosarcoma cohort included 653 patients: 109 pediatric (males, <13 years old; females, <12 years old), 246 adolescent (males, 13-17 years old; females, 12-17 years old), and 298 young adult (males and females, 18-40 years old). Sequencing from osteosarcoma cases was compared to a pan-cancer cohort comprising 37,947 patients ≤40 years old.

RESULTS: Genes commonly altered and significantly enriched (p < .0001) for alterations in osteosarcoma compared to other cancers were TP53 (55%), RB1 (22%), GID4 (26%), MYC (17%), and CCND3 (16%). Less commonly altered genes also significantly enriched (p < .0001) for alterations in osteosarcoma included AURKB (odds ratio [OR], 28.0), NCOR1 (OR, 8.2), and BCL2L2 (OR, 8.9). Fisher exact tests demonstrated mutual exclusivity between MDM2 amplification and TP53 inactivation and between RB1 inactivation and CDK4 amplification or CDKN2A/B deletion. Chi-square tests and binomial regression revealed statistically significant differences in genomic events by age, including frequent amplification of CDK4 and MDM2 in young adults and MYC, CCND3, and CCNE1 in pediatric and adolescent cases.

CONCLUSIONS: Novel findings from this statistically rigorous analysis of a large patient population include: identifying genes of interest in osteosarcoma that are more often altered when compared to other cancers; identifying MYC and CCND3 amplification as significantly more prevalent in osteosarcoma diagnosed in childhood; and proving mutual exclusivity and co-occurrence with statistical robustness.

PMID:42424099 | DOI:10.1002/cncr.70500

JAMA Netw Open. 2026 Jul 1;9(7):e2622239. doi: 10.1001/jamanetworkopen.2026.22239.

ABSTRACT

IMPORTANCE: Although P2Y purinergic receptor 12 (P2Y12) inhibitors are commonly used in patients with atherosclerotic cardiovascular disease, there are limited data on intracerebral hemorrhage (ICH) associated with use of P2Y12 inhibitors.

OBJECTIVE: To compare stroke severity, in-hospital mortality, and functional outcomes in ICH among patients receiving P2Y12 inhibitor monotherapy, dual antiplatelet therapy (DAPT) with P2Y12 inhibitor plus aspirin, aspirin monotherapy, or no antiplatelet therapy prior to ICH.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study obtained data from the nationwide Get With The Guidelines-Stroke registry, which contains data from participating hospitals. Participants were patients hospitalized with spontaneous ICH between January 2013 to December 2021. The analysis was completed in January 2025.

EXPOSURES: Antiplatelet therapy before ICH, defined as any use within 7 days prior to hospital arrival.

MAIN OUTCOMES AND MEASURES: The primary outcomes were severe stroke at presentation and in-hospital mortality. Severity was assessed using the National Institutes of Health Stroke Scale (NIHSS; range: 0-42, with higher scores indicating greater severity), with a score of 21 or higher indicating severe stroke. Secondary outcomes included in-hospital mortality or discharge to hospice, discharge to home, independent ambulation, and modified Rankin Scale (mRS) score at discharge. An mRS score of 0 to 2 at discharge indicated functional independence.

RESULTS: Of the 252 691 patients included (median [IQR] age, 67 [56-78] years; 134 684 males [53.3%]), 6355 (2.5%) were receiving P2Y12 inhibitor monotherapy, 10 607 (4.2%) were receiving DAPT, 63 299 (25.0%) were receiving aspirin monotherapy, and 172 430 (68.2%) were receiving no antiplatelet agents prior to ICH. Patients taking P2Y12 inhibitors were older and had higher prevalence of cardiovascular risk factors. Overall, 1701 patients (26.8%) receiving P2Y12 monotherapy and 2688 patients (25.3%) receiving DAPT experienced severe ICH (NIHSS score ≥21) compared with 12 952 patients (20.5%) who used aspirin monotherapy and 39 970 (23.2%) patients who received no antiplatelet (P < .001). In-hospital mortality rates were highest in patients using DAPT (24.0%), followed by patients receiving P2Y12 inhibitor monotherapy (23.8%), no antiplatelet (16.8%), and aspirin monotherapy (16.5%) (P < .001). After risk adjustment, patients with prior use of P2Y12 inhibitors were more likely to present with severe stroke (P2Y12 inhibitor monotherapy: adjusted odds ratio [AOR], 1.43 [95% CI, 1.34-1.52]; P < .001; DAPT: AOR, 1.40 [95% CI, 1.33-1.47]; P < .001) and more likely to die in the hospital (P2Y12 inhibitor monotherapy: AOR, 1.55 [95% CI, 1.46-1.66]; P < .001; DAPT: AOR, 1.61 [95% CI, 1.53-1.71]; P < .001) compared with those using aspirin monotherapy. Furthermore, these patients were less likely to be discharged to home, be able to ambulate independently, or have functional independence at discharge. In contrast, there were no statistically significant differences in in-hospital outcomes between aspirin monotherapy and no antiplatelet therapy groups.

CONCLUSIONS AND RELEVANCE: In this registry-based cohort study of patients with ICH not associated with anticoagulation, P2Y12 inhibitors, either as monotherapy or in combination with aspirin, were associated with more severe stroke, in-hospital death, worse clinical outcomes, and reduced functional recovery compared with aspirin monotherapy or no antiplatelet therapy.

PMID:42424082 | DOI:10.1001/jamanetworkopen.2026.22239

JAMA Netw Open. 2026 Jul 1;9(7):e2622676. doi: 10.1001/jamanetworkopen.2026.22676.

ABSTRACT

IMPORTANCE: Adolescent substance use remains a leading preventable cause of morbidity and mortality in the US. Evidence is limited on whether sustained availability of dedicated school-based health coursework is associated with lower substance use prevalence at scale.

OBJECTIVE: To estimate whether sustained availability of a dedicated high school health course was associated with lower student-reported past 30-day substance use prevalence.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included California public high schools that participated in the California Healthy Kids Survey and were linked to annual University of California Office of the President course lists. Participants included high school students in grades 9 and 11 who completed the California Healthy Kids Survey high school between the 2017 to 2018 school year and the 2023 to 2024 school year. Data were analyzed from January to February 2026.

EXPOSURE: School year availability of at least 1 standalone health course that was approved by the University of California Office of the President. Availability was defined as sustained when present for at least 2 consecutive school years.

MAIN OUTCOMES AND MEASURES: Seven binary indicators of any past-30-day substance use: alcohol use, binge drinking, cigarette smoking, drug use, marijuana use, prescription drug misuse, and vaping. Difference-in-differences with 2-way fixed effects and prespecified event-study analyses were used.

RESULTS: The analytic sample included 1 942 640 student survey responses from 915 public high schools across 345 districts and 3499 school years; mean (SD) grade was 10.1 (1.0), and 942 180 responses (48.5%) were from female students. Sustained availability of a dedicated health course was associated with lower school year prevalence of vaping (-1.36 [95% CI, -2.15 to -0.57] percentage points), marijuana use (-1.22 [95% CI, -1.95 to -0.49] percentage points), alcohol use (-1.11 [95% CI, -1.91 to -0.30] percentage points), and binge drinking (-0.70 [95% CI, -1.17 to -0.24] percentage points). Estimates for drug use, prescription drug misuse, and cigarette smoking were smaller and had 95% CIs that included 0.

CONCLUSIONS AND RELEVANCE: In this cohort study of California public high schools, sustained availability of a dedicated health course was associated with modestly lower prevalence in several common forms of adolescent substance use. These findings suggest that sustained, dedicated health coursework may be a scalable component of school-based substance use prevention.

PMID:42424079 | DOI:10.1001/jamanetworkopen.2026.22676

JAMA Oncol. 2026 Jul 9. doi: 10.1001/jamaoncol.2026.2204. Online ahead of print.

ABSTRACT

IMPORTANCE: In the TOPAZ-1 trial’s primary analysis, durvalumab plus gemcitabine and cisplatin (GemCis) showed statistically significant improved overall survival (OS) vs placebo plus GemCis with comparable safety between treatment groups in participants with advanced biliary tract cancer (aBTC). Durvalumab plus GemCis was recently established as the first-line standard of care among patients with aBTC.

OBJECTIVE: To evaluate 4-year OS and safety of durvalumab plus GemCis in participants with aBTC.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the global, double-blind, placebo-controlled, phase 3 TOPAZ-1 randomized clinical trial included participants 18 years and older with histologically confirmed unresectable, locally advanced, or metastatic biliary tract adenocarcinoma. In the TOPAZ-1 trial, patients were enrolled from April 2019 to December 2020 at 105 sites in 17 countries. Data cutoff was February 28, 2025.

INTERVENTION: Participants received intravenous durvalumab, 1500 mg, or placebo plus gemcitabine, 1000 mg/m2, and cisplatin, 25 mg/m2, on days 1 and 8 every 3 weeks for up to 8 cycles, followed by durvalumab or placebo monotherapy every 4 weeks.

MAIN OUTCOMES AND MEASURES: OS, duration of treatment exposure, serious adverse events, and adverse events resulting in discontinuation were assessed approximately 48 months after the last participant was randomized.

RESULTS: Overall, 685 participants were randomized, with 341 receiving durvalumab plus GemCis (median [range] age, 64 [20-84] years; 172 [50.4%] female) and 344 receiving placebo plus GemCis (median [range] age, 64 [31-85] years; 168 [48.8%] female). Median (range) follow-up in censored participants was 56.9 (1.7-67.2) months for participants who received durvalumab plus GemCis and 50.7 (0.9-62.6) months for participants who received placebo plus GemCis. Median OS was 13.0 (95% CI, 11.6-14.1) months for durvalumab plus GemCis and 11.4 (95% CI, 10.1-12.5) months for placebo plus GemCis (hazard ratio, 0.75; 95% CI, 0.64-0.88); 48-month OS rate was 11.8% vs 4.3%, respectively. The rate of serious adverse events possibly related to treatment was similar between arms (52 of 338 participants [15.4%] in the durvalumab plus GemCis arm vs 59 of 342 participants [17.3%] in the placebo plus GemCis arm). In the durvalumab plus GemCis and placebo plus GemCis arms, 21 of 338 participants (6.2%) and 18 of 342 participants (5.3%), respectively, experienced adverse events leading to study drug discontinuation.

CONCLUSIONS AND RELEVANCE: In this post hoc analysis of the phase 3 TOPAZ-1 randomized clinical trial, durvalumab plus GemCis demonstrated long-term survival benefit and a clinically manageable safety profile, supporting its use as a first-line treatment for aBTC.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03875235.

PMID:42424063 | DOI:10.1001/jamaoncol.2026.2204

Nurse Educ. 2026 Jul 9. doi: 10.1097/NNE.0000000000002248. Online ahead of print.

ABSTRACT

BACKGROUND: Health care education increasingly requires nurses who are confident, entrepreneurial, and able to innovate.

PURPOSE: To examine the relationships among self-efficacy, entrepreneurship, and innovativeness among nursing students and to test whether entrepreneurship mediates the relationship between self-efficacy and innovativeness.

METHODS: This cross-sectional correlational study included 528 undergraduate nursing students from 4 academic years. Students completed Arabic versions of the General Self-Efficacy Scale, Entrepreneurship Measurement Instrument for Nursing Students, and Individual Innovativeness Scale.

RESULTS: Self-efficacy correlated positively with entrepreneurship and innovativeness, and entrepreneurship correlated positively with innovativeness. Path analysis showed that self-efficacy predicted entrepreneurship, and entrepreneurship predicted innovativeness, while the direct path from self-efficacy to innovativeness was not significant.

CONCLUSIONS: Entrepreneurship may act as a statistical pathway linking self-efficacy with innovativeness. Nursing curricula should combine confidence-building with entrepreneurial learning to support innovation.

PMID:42424032 | DOI:10.1097/NNE.0000000000002248

Int J Biometeorol. 2026 Jul 9;70(7):208. doi: 10.1007/s00484-026-03266-6.

ABSTRACT

This study assesses climatic and bioclimatic variability on Kolguev Island (Barents Sea) using meteorological observations from the Kolguev Severny station for 1941-2024 and expedition measurements conducted in June-July 2023 and 2025. Trends in air temperature, precipitation, frost-free and growing seasons were analyzed, while bioclimatic conditions were evaluated using the Universal Thermal Climate Index (UTCI). A statistically significant increase in air temperature was identified in all seasons, with a pronounced intensification after 2000. Mean annual temperature increased by 0.27 °C per decade during 1941-2024 and by 0.89 °C per decade during 2000-2024. The spring transition of air temperature across 0 °C shifted to earlier dates, while the autumn transition shifted later, resulting in an increase in the frost-free period from 146 days (1961-1990) to 157 days in the 1991-2020. The duration of the growing season increased by about one month, and the sum of positive temperatures rose by 117 °C. During the second decade of the 21st century, a tendency toward decreasing moisture availability on the island has also been observed. Bioclimatic conditions on Kolguev Island are dominated by cold stress of varying intensity according to the UTCI classification, ranging from extreme to slight cold stress. The frequency of extreme cold stress decreased from 18% of days in the 1970s to 9% in the 2010s, while the proportion of days without thermal stress in summer increased from 4% to 7%. Expedition observations showed prevailing strong and moderate cold stress conditions, although rapid changes from very strong to moderate cold stress may occur within hours due to weakening winds. The observed climatic changes contribute to Arctic “greening,” increasing vegetation productivity and potentially affecting tundra ecosystems, reindeer herding, and biodiversity.

PMID:42424024 | DOI:10.1007/s00484-026-03266-6

Indian Pediatr. 2026 Jul 9. doi: 10.1007/s13312-026-00377-6. Online ahead of print.

ABSTRACT

CONTEXT: There is a wide variation in the use of intrapleural fibrinolytic therapy (IPFT) in children with empyema. This necessitates an up-to-date evaluation of the evidence, to develop an evidence-based guideline recommendation.

OBJECTIVE: To evaluate the efficacy and safety of IPFT versus no IPFT in children with empyema.

EVIDENCE ACQUISITION: A systematic search for randomized controlled trials (RCTs) comparing IPFT versus no IPFT in children with empyema, was conducted in databases of published literature (PubMed, Embase, Cochrane Library, Scopus, Web of Science), grey literature, and four clinical trial registries. Multiple a priori outcomes reflecting efficacy and safety were evaluated. The Cochrane Risk-of-Bias 2 tool was used for quality assessment, and the certainty of evidence was evaluated using the GRADE approach.

RESULTS: The literature search identified 3,113 citations, and their step-wise screening identified three relevant RCTs. The pooled odds ratio for the critical outcome ‘failure of therapy’ was 0.15 (95% CI 0.04 – 0.50, I² = 50%) with fixed-effect model, and 0.14 (95% CI 0.02 – 1.12, I² = 50%) with the random-effects model. Serious adverse events were rare but comparable between the groups. Length of hospitalization was reported variably, but one RCT reported a shorter stay with IPFT. There were no data on long-term clinical outcomes, pulmonary function tests, or cost of therapy. The evidence certainty was ‘very low’.

CONCLUSION: The available evidence on IPFT as an initial modality for pediatric empyema is limited and of very low certainty. Although pooled estimates suggested a potential reduction in treatment failure with IPFT, the results were sensitive to the statistical model used.

PMID:42424022 | DOI:10.1007/s13312-026-00377-6

Calcif Tissue Int. 2026 Jul 9;117(1):111. doi: 10.1007/s00223-026-01569-9.

ABSTRACT

Osteoporosis and osteopenia are major health burdens among postmenopausal women. Potassium citrate, which is an alkaline salt that neutralizes the acid load in the diet is a preventive measure for bone loss. We conducted a systematic review and meta-analysis following PRISMA guidelines. We searched PubMed, Web of Science, Scopus, and Cochrane CENTRAL for randomized controlled trials examining potassium citrate supplementation effects on bone health outcomes in postmenopausal women. Random-effects models calculated mean differences with 95% confidence intervals. Trial sequential analysis assessed evidence sufficiency. Five RCTs involving 401 postmenopausal women were included. Potassium citrate significantly reduced urinary N-terminal telopeptide (NTX) at 1 month compared with placebo (MD = – 4.05 nmol BCE/mmol creatinine; 95% CI – 8.05 to – 0.05; p = 0.0474; I² = 0%). However, no significant effects were observed on serum C-terminal telopeptide (CTX) at 3 or 6 months, or on procollagen type 1 N-terminal propeptide (P1NP) at 3, 6, or 12 months. Potassium citrate significantly increased urinary potassium excretion at both 3 months and 6 months, while urinary calcium, serum calcium, parathyroid hormone, and urinary pH showed no statistically significant differences between groups. Trial sequential analysis indicated that the available evidence for P1NP at 3 and 6 months remains inconclusive, with the accrued sample size below the required information size. Potassium citrate supplementation showed a selective reduction in urinary NTX, suggesting a potential effect on bone resorption. However, no consistent significant effects were observed on other bone turnover markers, including CTX and P1NP, or on calcium-related biochemical outcomes. The clinical relevance of this finding remains uncertain, and further large, well-designed trials with longer follow-up are needed to clarify the role of potassium citrate in preventing postmenopausal bone loss.

PMID:42423994 | DOI:10.1007/s00223-026-01569-9