Category: Statistics

Nephrol Dial Transplant. 2026 Aug 17:gfag176. doi: 10.1093/ndt/gfag176. Online ahead of print.

ABSTRACT

In both clinical research and study design, the definition of outcomes for chronic kidney disease (CKD) is changing. New molecules available for testing in humans, and the fact that kidney diseases are best treated earlier in their course, make the duration of studies requiring ‘hard endpoints’ longer than is feasible for registration purposes and funding agencies. Improved mathematical modelling and statistical analyses, and the availability of electronic medical records and registries have also impacted nephrology clinical research. Thus, eGFR slopes have been promoted as surrogate endpoints for kidney failure, competing-risk methods have exposed the limitations of standard survival analysis in high-mortality CKD and dialysis populations, and pragmatic, registry-based trials enroll patients who resemble those seen in daily practice. This review suggests that eGFR slopes, time to kidney failure, and competing risk factors must be considered in their totality, so that CKD and cardiovascular (CV) evidence can be understood in clinical practice by patients and clinicians. We propose that eGFR slopes may provide a clinically intuitive summary of ‘kidney time’, showing how, under appropriate conditions, chronic slope differences may be translated into approximate ‘years of dialysis delayed’ at the population level. We frame competing risks as a clinical, not only statistical, issue, and we examine how pragmatic CKD trials can and should integrate slope-based endpoints and competing-risk analyses into their design and reporting. To advance nephrology research, we must embrace these changes in study design and methodology to ensure that clinicians and patients understand them, and thus are more prepared to implement trial results.

PMID:42606392 | DOI:10.1093/ndt/gfag176

Clin Rehabil. 2026 Aug 17:2692155261467649. doi: 10.1177/02692155261467649. Online ahead of print.

ABSTRACT

ObjectivePrognostication may help guide mobility rehabilitation planning and goal setting post-stroke. This systematic review aimed to examine the prognostic capacity of early neuroimaging and neurophysiological biomarkers of mobility outcomes up to 24 months post-stroke.Data sourcesMEDLINE/EMBASE was searched from inception to May 2026. Cohort studies that reported neuroimaging or neurophysiological biomarkers measured <14 days post-stroke and mobility outcome(s) assessed >14 days but ≤24 months post-stroke were included.Review methodsBiomarker analyses were classified by statistical analysis approach (association, discrimination/classification, validation). Magnitude of relevant statistical measures was the primary indicator of prognostic capacity. Risk of bias was assessed using the Quality in Prognostic Studies tool.ResultsTwenty-six reports from 23 independent study samples (n = 2678 participants) were included. Biomarkers were measured a median of 9.3 days post-stroke, and outcomes were assessed between 1 and 24 months. One hundred and nine biomarker analyses were identified (84 neuroimaging, 25 neurophysiological). Most analyses were association (88%), and few were discrimination/classification (10%) and validation (2%). Structural and functional corticospinal tract integrity metrics were frequently investigated, but findings were mostly small or non-significant. Lesion location and size findings were also commonly examined, but findings were inconsistent. Common methodological limitations included small sample sizes, moderate to high risk of bias, poor magnitude reporting and heterogeneous outcomes and follow-up timepoints.ConclusionCurrent evidence is insufficient to support the use of early neuroimaging and neurophysiological biomarkers for post-stroke mobility prognostication. International collaboration using harmonised methodologies, standardised statistical reporting and consistent outcome measures and timepoints is needed to generate meaningful prognostic information to guide rehabilitation.RegistrationCRD42022350771.

PMID:42606361 | DOI:10.1177/02692155261467649

Work. 2026 Aug 17:10519815261476659. doi: 10.1177/10519815261476659. Online ahead of print.

ABSTRACT

BackgroundEmotional exhaustion is a central component of burnout and is highly prevalent among police officers due to the emotionally demanding nature of policing work. Psychosocial safety climate (PSC), as an organizational resource, may influence emotional exhaustion directly and through emotional regulation strategies such as surface acting.ObjectiveThis study aimed to examine the relationship between psychosocial safety climate, surface acting, and emotional exhaustion among police officers, and to investigate whether surface acting mediates the association between PSC and emotional exhaustion.MethodsPolice officers from police stations in Guangxi, China, completed anonymous online questionnaires. The study employed the Psychosocial Safety Climate Scale (PSC-12), the Emotional Labor Scale, and the Emotional Exhaustion Scale. Data were analyzed using IBM SPSS Statistics 27.0 and regression-based mediation analysis.ResultsA more positive psychosocial safety climate was significantly associated with lower emotional exhaustion and lower levels of surface acting. Surface acting was positively associated with emotional exhaustion. Mediation analysis indicated that surface acting partially mediated the relationship between psychosocial safety climate and emotional exhaustion.ConclusionsThe findings suggest that psychosocial safety climate may be associated with emotional exhaustion both directly and indirectly through surface acting. Strengthening organizational support and fostering psychologically safe work environments may help reduce emotional strain among police officers.

PMID:42606332 | DOI:10.1177/10519815261476659

Work. 2026 Aug 17:10519815261476681. doi: 10.1177/10519815261476681. Online ahead of print.

ABSTRACT

BackgroundManaging an affiliated private hospital through various hospital groups in Thailand may increase job stress among health workers and support staff.ObjectivesTo determine the prevalence and identify the factors affecting job stress among 2242 health workers and support staff in an affiliated private hospital in Thailand.MethodsThis cross-sectional analytical study included, via convenience sampling, health workers and support staff who worked at seven hospitals of an affiliated private hospital located in the Bangkok Metropolitan Region (BMR) and the Eastern Economic Corridor (EEC) of Thailand. Online-based questionnaires about personal and working factors and the Thai version of the job content questionnaires (Thai-JCQ) were used as research instruments. Descriptive statistics were used to explain personal and working factors and determine the prevalence of job stress. Multiple logistic regressions were used to identify the factors affecting job stress among health workers and support staff.ResultsAbout 16.01% of the participants experienced job stress. The results of multiple logistic regressions showed that gender, age, educational level, sufficiency of income, hospital location, working hours per week, shift work, physical job demand, social support, and hazards at work were the factors affecting job stress among health workers and support staff.ConclusionRelevant private hospital groups may utilize the findings of this study to develop a sustainable system of job stress management for health workers and support staff by emphasizing the significance of personal and working factors.

PMID:42606331 | DOI:10.1177/10519815261476681

Invest Ophthalmol Vis Sci. 2026 Aug 3;67(10):40. doi: 10.1167/iovs.67.10.40.

ABSTRACT

PURPOSE: To identify risk loci for hereditary corneal dystrophy and improve a polygenic prediction model for Fuchs endothelial corneal dystrophy (FECD).

METHODS: We conducted a meta-analysis of 7316 Europeans with hereditary corneal dystrophy (including FECD and related conditions) and 1,588,467 controls from the UK Biobank, All of Us, FinnGen, and Million Veteran Program (MVP), assessing phenotype validity via genetic correlation. Polygenic risk scores (PRS) were derived using SBayesRC and validated in two independent European FECD cohorts. A genome-wide association study of African ancestry from MVP (455 cases and 121,154 controls) was used to develop African PRS. TCF4 CTG18.1 short tandem repeat (STR) lengths were inferred in All of Us to model STR expansion and PRS.

RESULTS: We identified 24 risk loci associated with corneal dystrophy, including 12 loci not previously reported in FECD studies. The optimized PRS achieved strong performance in two European FECD validation cohorts (area under the curve [AUC] = 0.83; 95% confidence interval, 0.82-0.84; DeLong’s P = 7.04 × 10-19), with individuals in the top decile showing 14‑fold and 19‑fold elevated risk. In All of Us, STR expansion (>40 repeats) was the key predictor of FECD risk (AUC = 0.89; odds ratio [OR] = 54), with minimal incremental value from PRS. STR expansion remained the primary risk driver across ancestries, whereas PRS provided modest independent predictive value for broader corneal dystrophy phenotypes in European and admixed American groups. Among individuals without large STR expansions, PRS was the only significant contributor in Europeans (OR = 1.37), whereas analyses of FECD non‑expansion carriers were underpowered.

CONCLUSIONS: These findings refine the genetic architecture of hereditary corneal dystrophy, improve risk prediction for FECD, and support a tiered strategy integrating STR expansion with PRS.

PMID:42606190 | DOI:10.1167/iovs.67.10.40

J Nurs Manag. 2026;2026(1):e4994782. doi: 10.1155/jonm/4994782.

ABSTRACT

BACKGROUND: The transition into the workplace exposes newly graduated nurses to significant stressors and challenges that enhance their vulnerability to burnout. However, evidence on the level of burnout and its related factors in newly graduated nurses remains limited.

OBJECTIVES: To determine the prevalence and severity of burnout among newly graduated nurses, identify its associated factors, and examine differences across geographic regions and before versus during the COVID-19 pandemic.

METHODS: A systematic search of PubMed, CINAHL, MEDLINE, Web of Science, Japan Medical Abstracts Society, and China National Knowledge Infrastructure databases was performed from inception to July 2024. Pooled mean scores for three subscales of the 22-item Maslach Burnout Inventory were calculated using R software (Version 4.4.1) to assess burnout levels. Publication bias tests, sensitivity analyses, and subgroup analyses were performed. Burnout prevalence and associated factors were summarized using narrative synthesis.

RESULTS: Forty-five studies involving 18,203 newly graduated nurses were included. The reported rates of high-level burnout ranged widely from 1.0% to 78.3%. The pooled mean scores were 28.39 (95% CI: 26.17-30.61) for Emotional Exhaustion, 11.48 (95% CI: 9.40-13.55) for Depersonalization, and 24.99 (95% CI: 21.22-28.76) for Personal Accomplishment. Subgroup analyses showed that newly graduated nurses in Asia had higher depersonalization (12.48 vs. 8.24) and lower personal accomplishment scores (22.34 vs. 32.99) than non-Asian counterparts (both p < 0.01). Factors associated with burnout included personal traits and competencies (such as coping strategies and psychological capital), work-related factors (such as work environment and workplace bullying and incivility), and other factors such as social support; however, evidence regarding sociodemographic factors was mixed.

CONCLUSIONS: Newly graduated nurses experienced severe burnout, especially in Asia. Factors related to burnout among newly graduated nurses are multifaceted, highlighting the need for nursing managers to prioritize targeted strategies to facilitate their transition to professional roles. Structured orientation, effective preceptorship, supportive work environments, and accessible psychological support may help reduce burnout among newly graduated nurses.

PMID:42606181 | DOI:10.1155/jonm/4994782

Arthritis Care Res (Hoboken). 2026 Aug 17. doi: 10.1002/acr.80141. Online ahead of print.

ABSTRACT

OBJECTIVES: Hand synovitis affects over 20% middle-aged and older adults. Although the roles of synovitis in hand pain and osteoarthritis are well established, its relationship with serious outcomes such as mortality remains uncertain. We investigate the association between hand synovitis and all-cause mortality.

METHODS: In the population-based Xiangya Osteoarthritis (XO) Study, participants underwent bilateral hand ultrasound at baseline to assess synovitis (grades 0-3; ≥2 defined as positive). Mortality data were obtained from local registries. Cox proportional hazards models were employed to examine the association between hand synovitis and all-cause mortality, adjusting for age, age squared, sex, body mass index, educational level, alcohol consumption, smoking status, hand injury, physical activity level, radiographic hand osteoarthritis status, hypertension, hyperlipidemia, and the age-adjusted Charlson Comorbidity Index.

RESULTS: Among 3,552 participants (mean age 64.4 ± 9.3 years, 57.9% women), 393 deaths occurred over a mean follow-up of 5.72 years. Ultrasound-detected hand synovitis was significantly associated with higher all-cause mortality (adjusted hazard ratio [aHR]=1.26, 95% confidence interval [CI]: 1.01-1.58). Compared with no synovitis, bilateral involvement conferred a higher mortality than unilateral involvement (aHRs: 1.42 [1.03-1.96] versus 1.20 [0.93-1.54]). Mortality risk also increased with the number of affected joints (aHRs: 1.19 [0.91-1.57] for one joint; 1.35 [1.02-1.80] for > 1 joint; P for trend < 0.05). In the exploratory analyses, the strongest association was observed for distal interphalangeal joint synovitis (aHR: 1.82 [1.14-2.91]).

CONCLUSION: Hand synovitis, especially when bilateral or polyarticular, may serve as a marker of increased all-cause mortality risk, though future studies are needed to confirm and investigate this further. Ultrasound assessment offers a non-invasive and accessible approach to identify this potential biomarker for mortality risk.

PMID:42606178 | DOI:10.1002/acr.80141

Clin Pharmacol Ther. 2026 Aug 17. doi: 10.1002/cpt.70442. Online ahead of print.

ABSTRACT

Host metabolic changes in response to drug treatment may shape individual pharmacological outcomes. This study aims to identify serum metabolomics signatures potentially associated with individual responses to enzalutamide treatment in metastatic castrate-resistant prostate cancer (mCRPC) patients. Targeted metabolomic profiles in serum collected from 18 mCRPC patients treated with 160 mg/day of enzalutamide were measured at baseline, after 3 months of treatment, and until disease progression by a validated liquid chromatography tandem mass spectrometry analytical platform. The difference in the serum metabolomic profiles during enzalutamide treatment between good and poor responders was investigated by both multivariate and univariate statistical analysis. Primary mouse hepatocytes and Caco-2 cell models were employed to gain mechanistic insights into the most relevant changes detected. Enzalutamide induced a significant and sustained increase in several amino acids, with taurine displaying the most significant change. The in vitro data suggest that enzalutamide-induced elevation of systemic taurine results from both increased intestinal absorption and decreased hepatic extraction. Finally, serum metabolomic changes observed after 3 months of treatment were found to be significantly associated with the pharmacological response. This hypothesis-generating study reveals that enzalutamide significantly alters the host serum metabolome, inducing changes that correlate with therapeutic response over time. These results highlight the importance of host-drug metabolic interactions during androgen receptor inhibitor treatment and, although further validation is required, they support the hypothesis that metabolic profiling could eventually aid in the personalized management of enzalutamide therapy.

PMID:42606154 | DOI:10.1002/cpt.70442

J Pediatr Orthop. 2026 Aug 17. doi: 10.1097/BPO.0000000000003442. Online ahead of print.

ABSTRACT

BACKGROUND: Cast saw burns (CSBs) are a preventable, iatrogenic complication that may occur during bivalving or removal of fiberglass casts. Children undergoing fracture reduction with the use of procedural sedation, typically in the emergency department (ED), are at heightened risk for CSBs because they cannot provide real-time pain feedback during cast saw use. While prior investigations have examined the effects of cast material, cast thickness, and water dip temperature, the comparative thermal performance of commercially available cast padding products during cast bivalving has not been systematically evaluated. This study used thermal probes to compare measured temperatures beneath 2 widely used cast padding products, Webril (Kendall/Cardinal Health) and Specialist (BSN Medical), during a standardized cast application, molding, and bivalving protocol.

METHODS: A custom upper-extremity model was instrumented with 2 calibrated thermocouples (labeled “near” and “far”). Twenty experimental runs were performed, 10 each per padding product, with bivalving performed separately for near and far probes (N=40 total). Temperatures were recorded at 3 time points: baseline (before the application of any materials), prebivalve (immediately after fiberglass application ), and at maximum temperature during bivalving with an oscillating cast saw. The primary outcome was the change in temperature from prebivalve to maximum bivalve temperature (ΔT) measured by near and far probes. Secondary outcome included maximum temperatures relative to established burn injury thresholds.

RESULTS: The mean ΔT during bivalving was 13.2±13.0°C for Specialist padding and 13.0±6.9°C for Webril padding (P=0.95). The mean absolute maximum temperature was 40.8±13.2°C for Specialist and 39.5±6.8°C for Webril. In the Specialist group, 6/10 runs exceeded the 44°C adult burn threshold on at least one probe, compared with 4/10 runs in the Webril group. Linear mixed-effects analysis with Kenward-Roger degrees of freedom revealed a significant material×probe interaction during bivalving (P=0.020): at the near probe, Specialist peak temperatures averaged 8.5°C higher than Webril (P=0.041), whereas the 2 materials did not differ significantly at the far probe (P=0.146).

CONCLUSION: Maximum temperatures exceeded clinically relevant burn thresholds in both cast padding groups, supporting the high-risk thermal environment at cast mold sites during bivalving. While Webril had some protective effect, neither commercially available cast-padding product provided consistently sufficient or statistically superior thermal protection.

LEVELS OF EVIDENCE: Not applicable (biomechanical study).

PMID:42606122 | DOI:10.1097/BPO.0000000000003442

Otolaryngol Head Neck Surg. 2026 Aug 17. doi: 10.1002/ohn.70403. Online ahead of print.

ABSTRACT

OBJECTIVE: Injection laryngoplasty is a standard-of-care intervention for unilateral vocal fold paralysis (UVFP), offering minimally invasive medialization with limited durability. We evaluated a regenerative injectable approach integrating an immunotolerant scaffold-forming collagen (Oligomer) with autologous motor-endplate expressing (MEE) cells to support long-term augmentation and neuromuscular recovery.

STUDY DESIGN: Porcine UVFP model.

SETTING: Translational research laboratory.

METHODS: Twelve Yucatan minipigs underwent right recurrent laryngeal nerve transection. Autologous muscle progenitor cells were isolated, differentiated, and induced into MEEs. Approximately 1 month after denervation, Saline, Oligomer, or MEE+Oligomer was injected into the paralyzed vocal fold. Outcomes were assessed through 6 months using videolaryngoscopy and acoustic vocalization analysis. Neuromuscular function was evaluated at baseline and 6 months using laryngeal electromyography (L-EMG) and laryngeal adductor pressure (LAP). Larynges were also harvested for volumetric ultrasound, histology, and gene expression analyses.

RESULTS: All injections were well tolerated, with no evidence of foreign body response. Oligomer and MEE+Oligomer produced persistent augmentation, with MEE+Oligomer demonstrating laryngeal adductor muscle volumes statistically similar to contralateral controls at 6 months. Both treatments improved vocalization outcomes, and MEE+Oligomer was associated with greater neuromuscular function, as indicated by improved stimulated vocal fold adduction, L-EMG activity, and LAP responses. Histological analysis demonstrated identifiable scaffold integration with preservation of muscle morphology.

CONCLUSION: In a porcine UVFP model, scaffold-forming Oligomer provided persistent, immunotolerant augmentation with sustained voice improvement. MEE incorporation supported enhanced neuromuscular function consistent with improved reinnervation. This regenerative injection laryngoplasty strategy integrates structural and biological mechanisms to address both mechanical and physiological deficits following UVFP.

PMID:42606116 | DOI:10.1002/ohn.70403