Category: Statistics

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

Pediatr Cardiol. 2026 Jul 9. doi: 10.1007/s00246-026-04343-8. Online ahead of print.

ABSTRACT

Recommendations for infective endocarditis (IE) prophylaxis have narrowed substantially over the past two decades. Current guidance from the American Heart Association and the European Society of Cardiology is largely derived from adult populations and may not account for the unique anatomic substrates and lifelong device exposure encountered in pediatric and congenital heart disease (CHD) patients with cardiac implantable electronic devices (CIEDs). To evaluate contemporary practice patterns regarding IE prophylaxis among clinicians caring for pediatric and CHD patients with CIEDs and to describe clinician-reported experience with device-associated IE. A cross-sectional, web-based survey was distributed to members of the Pediatric and Congenital Electrophysiology Society (PACES). The survey was sent to approximately 200 members, with 67 responses received (34%). Survey questions addressed prophylaxis practices for dental, gastrointestinal, genitourinary, and respiratory procedures. Respondents were also asked to report prior clinical experience with IE in patients with CIEDs. Responses were analyzed using descriptive statistics. Sixty-seven clinicians completed the survey. Substantial variation in prophylaxis practices was observed across clinical scenarios. Most respondents reported practice patterns consistent with guideline recommendations for CIED patients with structurally normal hearts. However, nearly all respondents (92%) reported recommending long-term antibiotic prophylaxis for CIED patients with complex or high-risk repaired congenital heart disease. Respondents collectively reported experience with 35 cases of CIED-associated IE, of which 34 involved transvenous lead systems, with the majority occurring more than six months after device implantation. Most reported cases of IE were not associated with a preceding invasive procedure. Practice patterns for IE prophylaxis in pediatric and congenital patients with CIEDs vary considerably among clinicians. These findings highlight uncertainty regarding the applicability of adult-derived IE prophylaxis guidelines to pediatric and congenital populations and underscore the need for studies to better define IE risk and guide pediatric-specific recommendations.

PMID:42423984 | DOI:10.1007/s00246-026-04343-8

Pediatr Cardiol. 2026 Jul 9. doi: 10.1007/s00246-026-04344-7. Online ahead of print.

ABSTRACT

Heart transplant (HT) rejection surveillance is rapidly evolving with evidence supporting use of donor-derived cellfree DNA (ddcfDNA) with its high negative predictive value and use of cardiac magnetic resonance (CMR). Both modalities are imperfect in diagnosing biopsy proven rejection, however, combining them may improve diagnostic power. Our study goal is to characterize multiparametric CMR trends between pediatric HT patients (PHT) with high versus low ddcfDNA. Single center retrospective study of PHT who had clinically indicated multiparametric CMR (biventricular volumes and ejection fraction (EF), T2 mapping, T1 mapping with extracellular volume fraction (ECV) and ddcfDNA within 30 days; corresponding EMB was not always performed as per institutional clinical protocol. Demographics and CMR variables were compared between ddcfDNA of ≥ 0.16% (high group) and < 0.16% (low group). 68 PHT (14 high group, 54 low group) were included. The high group was significantly older, with longer time between CMR and HT, had longer time between CMR and ddcfDNA, had more frequent CMR indication of clinical concern and had history of CAV or moderate severe rejection. No statistical difference in CMR derived ventricular volumes or function was noted between groups. There were significant differences in multiparametric mapping with high ddcfDNA group showing higher global T1 (1086 [1050, 1118] vs. 1029 [1002, 1075] ms; p = 0.01), peak segmental T1 (1163 [1140, 1220] vs. 1121 [1056, 1175] ms; p = 0.04), global T2 (52 [50, 55] vs. 48 [46, 51] ms; p = 0.008), and peak segmental T2 (58 [54, 60] vs. 53 [51, 59] ms; p = 0.04) compared to the low ddcfDNA group respectively. Multiparametric CMR suggests graft structure differences between high and low ddcfDNA PHT. Studies on larger cohorts with wider ddcfDNA ranges can help understand the combined role of CMR and ddcfDNA in improving surveillance.

PMID:42423982 | DOI:10.1007/s00246-026-04344-7

J Comput Assist Tomogr. 2026 Jul 9. doi: 10.1097/RCT.0000000000001907. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the frequency, anatomic distribution, and potential mechanisms of postmortem gas formation identified on postmortem computed tomography (PMCT) in infants and young children, with emphasis on the association between postmortem gas and perimortem cardiopulmonary resuscitation (CPR).

METHODS: This retrospective study included 63 pediatric decedents (age range: birth to 25 mo) who underwent PMCT as part of medicolegal investigations, followed by autopsy. Two radiologists independently reviewed PMCT images, reports, and autopsy findings to determine the presence, location, and likely cause of postmortem gas. The presence of CPR was established based on documented history, autopsy findings, and imaging indicators. Descriptive statistics were used to characterize the cohort, and Fisher exact and t tests were applied for group comparisons with statistical significance set at P<0.05.

RESULTS: Postmortem gas was detected in 56 of 63 cases (89%). Among 61 cases with known CPR status, 57 had received CPR, and 4 had not. Gas was significantly more frequent in those with CPR (89%, 51/57) than in those without (25%, 1/4; P=0.008). The most commonly affected regions were the heart (64%) and liver (61%). Gas in the heart, liver, or brain was associated with a longer mean interval between death and imaging (7.4 vs. 3.9 h), although this difference did not reach statistical significance (P=0.06). Gas formation was observed as early as 0.5 hours postmortem.

CONCLUSIONS: PMCT frequently demonstrates postmortem gas in pediatric deaths, most notably in cases with prior CPR. The distribution pattern-favoring the heart and liver-and early appearance within hours of death suggest a major contribution from resuscitation-related mechanisms rather than decomposition only. Recognition of these CPR-related imaging patterns is essential for distinguishing physiological postintervention findings from decomposition or pathologic processes and may improve the forensic interpretive value of PMCT in pediatric death investigations.

PMID:42423975 | DOI:10.1097/RCT.0000000000001907

Int Urol Nephrol. 2026 Jul 9. doi: 10.1007/s11255-026-05264-4. Online ahead of print.

ABSTRACT

BACKGROUND: Sclerostin, an osteocyte-derived Wnt/β-catenin inhibitor, increases with declining kidney function and is implicated in chronic kidney disease-mineral and bone disorder (CKD-MBD). Whether circulating sclerostin reflects disease-specific activity in biopsy-proven glomerulonephritis (GN), independent of renal function and demographic confounders, remains unclear.

METHODS: In a single-centre cross-sectional case-control study, 49 adults with biopsy-proven GN and 30 healthy controls were enrolled. Serum sclerostin was measured by enzyme-linked immunosorbent assay (ELISA). Its associations with kidney function (estimated glomerular filtration rate, eGFR), proteinuria and routine biochemical parameters were examined using non-parametric tests and multivariable linear regression adjusted for age, sex and eGFR. To address baseline differences between groups and to test whether kidney function explained the observed associations, we additionally performed a propensity-score-weighted sensitivity analysis and a mediation-style statistical decomposition, with correction for multiple comparisons.

RESULTS: GN patients were older, more often male and had lower eGFR than controls. Serum sclerostin was higher in GN patients than in controls in the unadjusted comparison (median 10.86 vs 7.14 ng/mL, p < 0.001). However, this difference progressively weakened after accounting for age and sex, and was no longer statistically significant once kidney function (eGFR) was taken into account. The propensity-score-weighted sensitivity analysis showed the same pattern. Within the GN group, higher sclerostin was strongly associated with lower kidney function, and this relationship persisted in adjusted models. The apparent link between sclerostin and proteinuria was likewise explained mainly by kidney function: about three-quarters of the crude association was accounted for by the eGFR pathway (indirect effect 0.71; 95% confidence interval [95% CI] 0.16 to 1.54). Sclerostin was not robustly associated with the inflammatory markers C-reactive protein or ferritin, and an isolated inverse association with fibrinogen was regarded as exploratory because fibrinogen was measured in only 13 patients.

CONCLUSIONS: In biopsy-proven GN, elevated circulating sclerostin primarily reflects differences in kidney function, age and sex rather than GN-specific activity; within the limits of a healthy-control rather than CKD-control comparison, the data do not support serum sclerostin as an independent biomarker of glomerular disease activity. Prospective studies with non-GN CKD comparators and a complete CKD-MBD panel are needed.

PMID:42423954 | DOI:10.1007/s11255-026-05264-4

Adv Ther. 2026 Jul 9. doi: 10.1007/s12325-026-03679-0. Online ahead of print.

ABSTRACT

INTRODUCTION: This study evaluated the real-world utilization, effectiveness, occurrence of adverse events (AEs), and healthcare costs in patients treated with next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI), alectinib, brigatinib, and lorlatinib, among ALK TKI-naïve patients with ALK rearrangement-positive metastatic non-small cell lung cancer (ALK + mNSCLC) in the US.

METHODS: This retrospective, observational cohort study used Veradigm electronic health records linked with Komodo closed claims. Eligible patients were adults with ALK + mNSCLC diagnosis who received their first ALK TKI (alectinib, brigatinib, or lorlatinib) between 5/22/2020 (US FDA approval of first-line brigatinib) and 12/31/2024. Descriptive analyses included baseline patient demographics, clinical characteristics, occurrence of AEs, and treatment patterns. Unweighted Cox proportional hazards models and propensity score-weighted Cox proportional hazards models were conducted to compare real-world treatment effectiveness [real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), real-world progression-free survival (rwPFS), real-world overall survival (rwOS)], and all-cause healthcare utilization and costs across ALK TKIs.

RESULTS: A total of 481 patients (alectinib: 391; brigatinib: 32; lorlatinib: 58) were included. Mean age ranged from 58.5 to 63.7 years across the three treatment groups; more than half of the patients were female (less than half male), White, or covered by commercial insurance. In the unweighted and weighted analyses, there were no statistically significant differences in rwTTD, rwTTNT, rwPFS, or rwOS between treatment groups. Mean weighted all-cause healthcare costs per-patient-per-month during the index TKI treatment duration were not significantly different across cohorts (alectinib: US$20,873; brigatinib: $25,693; lorlatinib: $24,984).

CONCLUSION: This study found no statistically significant differences in real-world clinical effectiveness and total all-cause healthcare costs between alectinib, brigatinib, or lorlatinib for ALK TKI-naïve patients with ALK + mNSCLC. Future studies with larger sample sizes and longer follow-up time are needed to confirm these findings.

PMID:42423952 | DOI:10.1007/s12325-026-03679-0