Tag: statistics

Biometrics. 2026 Apr 9;82(2):ujag081. doi: 10.1093/biomtc/ujag081.

ABSTRACT

A dynamic treatment regime is a sequence of medical decisions that adapts to the evolving clinical status of a patient over time. To facilitate personalized care, it is crucial to assess the probability of each available treatment option being optimal for a specific patient, while also identifying the key prognostic factors that determine the optimal sequence of treatments. This task has become increasingly challenging due to the growing number of individual prognostic factors typically available. In response to these challenges, we propose a Bayesian model for optimizing dynamic treatment regimes that addresses the uncertainty in identifying optimal decision sequences and incorporates dimensionality reduction to manage high-dimensional individual covariates. The first task is achieved through a suitable augmentation of the model to handle counterfactual variables. For the second, we introduce a novel class of spike-and-slab priors for the multi-stage selection of significant factors, to favor the sharing of information across stages. The effectiveness of the proposed approach is demonstrated through an extensive simulation study and illustrated using clinical trial data on severe acute arterial hypertension.

PMID:42166188 | DOI:10.1093/biomtc/ujag081

Biometrics. 2026 Apr 9;82(2):ujag088. doi: 10.1093/biomtc/ujag088.

ABSTRACT

Multistate models offer an appealing framework for studying the onset and progression of chronic diseases in large cohort studies. Such studies often involve the collection and storage of biospecimens at an initial assessment, and intermittent observation of the disease process at future assessment times. We consider the design of two-phase biomarker studies in such settings where budgetary constraints prohibit assaying all biospecimens. A subsample of individuals is instead chosen to have their biospecimens assayed to facilitate examination of the association between a biomarker of interest and the disease process. Analyses based on likelihood, conditional likelihood, and estimating functions are considered, with the efficiency gains from various subsampling strategies investigated. Pseudo-score residual-dependent sampling strategies are shown to yield highly efficient maximum likelihood estimates of biomarker effects on disease progression. This sampling strategy along with competing methods are empirically studied and applied to a motivating study of the relationship between the HLA-B27 marker and joint damage in patients with psoriatic arthritis.

PMID:42166187 | DOI:10.1093/biomtc/ujag088

Biometrics. 2026 Apr 9;82(2):ujag053. doi: 10.1093/biomtc/ujag053.

ABSTRACT

As standards of care advance, patients are living longer and once-fatal diseases are becoming manageable. Clinical trials increasingly focus on reducing disease burden, which can be quantified by the timing and occurrence of multiple non-fatal clinical events. Most existing methods for the analysis of multiple event-time data require stringent modeling assumptions that can be difficult to verify empirically, leading to treatment efficacy estimates that forego interpretability when the underlying assumptions are not met. Moreover, many methods do not appropriately account for informative terminal events, such as premature treatment discontinuation or death, which prevent the occurrence of subsequent events. To address these limitations, we derive and validate estimation and inference procedures for the area under the mean cumulative function (AUMCF), an extension of the restricted mean survival time to the multiple event-time setting. The AUMCF is clinically interpretable, properly accounts for terminal competing risks, and can be estimated nonparametrically. To enable covariate adjustment, we also develop an augmentation estimator that provides efficiency at least equaling, and often exceeding, the unadjusted estimator. The utility and interpretability of the AUMCF are illustrated with extensive simulation studies and through an analysis of multiple heart-failure-related endpoints using data from the Beta-Blocker Evaluation of Survival Trial. Our open-source R package MCC makes conducting AUMCF analyses straightforward and accessible.

PMID:42166186 | DOI:10.1093/biomtc/ujag053

JAMA Netw Open. 2026 May 1;9(5):e2614557. doi: 10.1001/jamanetworkopen.2026.14557.

NO ABSTRACT

PMID:42166161 | DOI:10.1001/jamanetworkopen.2026.14557

JAMA Netw Open. 2026 May 1;9(5):e2614061. doi: 10.1001/jamanetworkopen.2026.14061.

ABSTRACT

IMPORTANCE: Understanding approaches to managing treatment-related adverse events (AEs) in immunotherapy and tyrosine kinase inhibitor-based treatments in a clinical setting is critical for reaching optimal patient outcomes.

OBJECTIVE: To investigate the management of AEs in community practices during first-line axitinib plus pembrolizumab therapy for advanced renal cell carcinoma (aRCC).

DESIGN, SETTING, AND PARTICIPANTS: This study comprised a cross-sectional electronic physician survey and a multisite, retrospective cohort study of the medical records of US patients with aRCC who initiated first-line axitinib-pembrolizumab between April 22, 2019, and January 31, 2024. Data were analyzed from September 18 to December 20, 2024.

EXPOSURE: First-line axitinib-pembrolizumab therapy.

MAIN OUTCOMES AND MEASURES: Main outcomes included patient characteristics, treatment patterns, AEs, and physician perspectives on management of AEs. End points were summarized using descriptive statistics as well as the Kaplan Meier method for time-to-event outcomes.

RESULTS: A total of 300 patients with aRCC who received first-line axitinib-pembrolizumab therapy (mean [SD] age, 66.0 [9.3] years; 183 [61.0%] male) and 25 physicians (mean [SD] time in practice, 14.6 [7.3] years) were included. The median follow-up was 12.3 (IQR, 8.1-21.6) months. Most patients (285 [95.0%]) started treatment with axitinib at a dose of 5 mg twice daily. Overall, 43 patients (14.3%) required at least 1 dose reduction of axitinib, 41 (13.7%) required at least 1 interruption of axitinib, and 18 (6.0%) required at least 1 interruption of pembrolizumab. AEs were the most common reason for reductions and interruptions. For patients who discontinued axitinib (n = 141) and/or pembrolizumab (n = 146), the most common reason was disease progression (111 of 141 [78.7%] for axitinib and 110 of 146 [75.3%] for pembrolizumab); 11 of 141 (7.8%) discontinued axitinib and 14 of 146 (9.6%) discontinued pembrolizumab due to AEs. All participating physicians were medical oncologists and 22 (88.0%) practiced in community settings. Sixteen physicians (64.0%) had access to multispecialty consultation for managing AEs. Nineteen physicians (76.0%) indicated that overall survival was the top factor in their selection of first-line axitinib-pembrolizumab therapy (6 [24.0%] selected safety profile as one of the top 3 factors). Patient comorbidities (16 of 21 [76.2%]) and performance status (15 of 21 [71.4%]) were important factors when considering treatment modification vs discontinuation.

CONCLUSIONS AND RELEVANCE: In this cohort study including patients with aRCC who received first-line axitinib-pembrolizumab therapy and physicians with experience treating aRCC, few patients permanently discontinued treatment due to AEs, and physicians reported balancing treatment effectiveness, safety, and patient-level factors when managing treatment-related AEs. Future work is warranted to evaluate the effects of AE management on clinical outcomes.

PMID:42166160 | DOI:10.1001/jamanetworkopen.2026.14061

JAMA Netw Open. 2026 May 1;9(5):e2614107. doi: 10.1001/jamanetworkopen.2026.14107.

ABSTRACT

IMPORTANCE: Phototherapy is widely used in the care of preterm newborns to prevent brain damage resulting from hyperbilirubinemia. However, concerns regarding its safety have been raised.

OBJECTIVE: To determine the associations between phototherapy and neonatal mortality or morbidity.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study from the Swedish Neonatal Quality Register included preterm newborns (gestational age, 22-31 weeks) admitted for care between November 2015 and December 2024, and followed up to hospital discharge. Deaths before 7 days of age, major congenital anomalies, or newborns without data on phototherapy were excluded.

EXPOSURES: Duration of phototherapy categorized as 0 to 3, 4 to 5, and 6 to 7 days. Peak bilirubin levels in the first week were categorized as less than 25th, 25th to 50th, 51st to 75th, and greater than 75th percentiles.

MAIN OUTCOMES AND MEASURES: The primary outcome was late neonatal mortality (LNM) on postnatal days 8 to 27 with a composite of severe neonatal morbidity as secondary outcome: intraventricular hemorrhage (IVH) grade 3 to 4; treated patent ductus arteriosus; necrotizing enterocolitis stage IIa or higher; severe bronchopulmonary dysplasia (BPD); or retinopathy of prematurity. Adjusted odds ratios (aORs) were calculated and adjusted for multiple pregnancy, preeclampsia, cesarean delivery, newborn sex, gestational age, Apgar score less than 4 at 5 minutes, and being small for gestational age or large for gestational age.

RESULTS: This study included a total of 4970 newborns. Median (IQR) gestational age was 29.1 (26.7-30.7) weeks, the median (IQR) birth weight was 1180 (860-1510) g, 2741 newborns (55.2%) were male, and 4746 newborns (95.5%) were treated with phototherapy. LNM occurred in 34 of 1995 newborns (1.7%) treated with phototherapy for 0 to 3 days, in 55 of 1921 newborns (2.9%) treated 4 to 5 days, and in 48 of 1054 newborns (4.6%) treated 6 to 7 days. Compared with 0 to 3 days of phototherapy, the aOR for LNM after 4 to 5 was 1.13 (95% CI, 0.71-1.78), and that for 6 to 7 days of treatment was 1.01 (95% CI, 0.62-1.65). Excluding newborns with IVH, hemolytic disease, or Apgar score below 4 at 5 minutes did not alter the results; neither did an evaluation of phototherapy duration and LNM stratified by peak bilirubin categories. Compared with 0 to 3 days, the aOR for composite morbidity after 4 to 5 days of phototherapy was 1.29 (95% CI, 1.04-1.59), and that for 6 to 7 days of phototherapy was 1.66 (95% CI, 1.31-2.09), which could be attributed to more prevalent IVH and severe BPD in newborns with longer treatment durations.

CONCLUSIONS AND RELEVANCE: In this cohort study of very preterm newborns, the duration of phototherapy for hyperbilirubinemia was not associated with neonatal mortality. Nevertheless, prolonged phototherapy in very preterm newborns should be avoided.

PMID:42166159 | DOI:10.1001/jamanetworkopen.2026.14107

Ital J Dermatol Venerol. 2026 May 21. doi: 10.23736/S2784-8671.26.08454-9. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by skin and organ fibrosis, with high prevalence of emotional distress and impaired quality of life (QoL). Autogenic training (AT), a relaxation method, was found to be effective for managing symptoms in chronic illnesses, including SSc.

METHODS: The current observational, longitudinal study aimed at evaluating the feasibility and the effects of a four-month AT program on dispositional traits, emotional regulation, coping strategies, and physical function perceptions in SSc patients.

RESULTS: This longitudinal observational study included 44 patients with confirmed SSc, from a dermatological research hospital. Participants underwent six therapist-guided AT sessions with daily self-practice. Outcomes were assessed pre- and post-intervention using the Systemic Sclerosis Questionnaire (SySQ), Emotion Regulation Questionnaire (ERQ), COPE-NVI, and Millon Clinical Multiaxial Inventory-III. Statistical analyses included paired t-tests and Cohen’s d for effect sizes. Significant improvements were observed in SySQ scores (P<0.001, d=0.919), reflecting better QoL; in emotional regulation (P<0.001, d=1.255); in approach-oriented coping (P=0.005, d=0.489). Patients with specific personality traits (e.g., melancholic) showed greater QoL gains, while others (e.g., avoidant) reported worsened perceptions.

CONCLUSIONS: AT enhanced QoL, emotional regulation, and coping in SSc patients, though outcomes varied by personality traits. Personalizing interventions may optimize benefits according to patient’s psychological profiles.

PMID:42166115 | DOI:10.23736/S2784-8671.26.08454-9

Spine Deform. 2026 May 21. doi: 10.1007/s43390-026-01433-8. Online ahead of print.

ABSTRACT

PURPOSE: While 3D radiographic parameters are increasingly used to assess adolescent idiopathic scoliosis (AIS), barriers to 3D imaging limit their routine use. 2D-to-3D prediction algorithms have been proposed as a substitute. This study sought to determine if a predicted 3D kyphosis, derived from 2D images, is a more robust predictor of FEV1 in patients with AIS than a traditional 2D analysis.

METHODS: A retrospective, cross-sectional review of 259 AIS patients with surgical-range thoracic curves (> 40°) was performed. We built two multivariate linear regression models to predict FEV1. Due to structural multicollinearity, the deformity measures were tested separately. Model A included Main Thoracic Cobb, BMI, and Age. Model B included Predicted 3D T5-T12 Kyphosis, BMI, and Age. The models were compared using the Akaike Information Criterion (AIC) and adjusted.

RESULTS: The cohort (87% female, mean age 15.7 ± 3.3 years) presented with severe deformities (mean Main Thoracic Cobb 68.4° ± 16.5°) and widespread restrictive impairment (71%). Multivariate Analysis revealed that Model A, (2D Main Thoracic Cobb) was statistically superior to Model B (Predicted 3D T5 – T12 Kyphosis) with a lower AIC (-292.5 vs. -265.9) and a higher adjusted R² (0.241 vs. 0.159). All factors were significant independent predictors.

CONCLUSION: The predicted 3D-based model was not superior, while a parsimonious 2D-based multivariate model including Main Thoracic Cobb, BMI, and Age explained a significantly larger proportion of the variance in FEV1. This specific 2D-to-3D prediction algorithm is an imperfect proxy and is not a valid substitute for true 3D imaging in predicting pulmonary risk.

PMID:42166107 | DOI:10.1007/s43390-026-01433-8

Updates Surg. 2026 May 21. doi: 10.1007/s13304-026-02675-x. Online ahead of print.

ABSTRACT

Laparoscopic sleeve gastrectomy (LSG) is currently the most commonly performed weight loss surgery. Omentopexy is believed to help reduce the risk of postoperative nausea and vomiting (PONV), bleeding, gastric leakage, and gastroesophageal reflux disease (GERD). In recent years, fibrin glue posterior fixation has emerged as an alternative method shown to reduce gastrointestinal symptoms after LSG surgery. However, the comparative evidence between these two fixed techniques is still limited. This study aims to compare the clinical efficacy of two gastric fixation methods, fibrin glue posterior fixation and Omentopexy, in LSG. This retrospective study included 649 patients who underwent LSG between 2022 and 2024, divided into two groups: fibrin glue posterior fixation (n = 331) and Omentopexy (n = 318). A 1:1 propensity score-matching (PSM) was performed to balance baseline characteristics between the groups. After matching, 480 patients were included (240 per group). There were no significant differences between the fibrin glue posterior fixation group and the Omentopexy group in operative time or intraoperative blood loss (P > 0.05). The incidence of PONV in the two groups was 6.6% (16/240) and 5.8% (14/240), respectively, with no statistically significant difference (P > 0.05). The incidence of postoperative bleeding was 0.8% (2/240), and there was no significant difference between the groups (P > 0.05). There was 1 case of gastric leakage (0.4%) in the fibrin glue posterior fixation group, and no gastric leakage was observed in the Omentopexy group, and the difference between the groups was not statistically significant (P > 0.05). Neither group experienced gastric torsion. The incidence of postoperative GERD was 5.8% (14/240) and 7.5% (18/240), respectively, with no statistically significant difference (P > 0.05). In addition, both groups of postoperative bleeding patients underwent reoperation, with a reoperation rate of 0.8% (2/240), and there was no significant difference between the groups (P > 0.05). This study demonstrates that there were no significant differences in short-term postoperative complications between fibrin glue posterior fixation and Omentopexy in LSG.

PMID:42166091 | DOI:10.1007/s13304-026-02675-x

Mamm Genome. 2026 May 21;37(1):71. doi: 10.1007/s00335-026-10245-0.

ABSTRACT

Osteosarcopenia-the concurrent presence of osteoporosis and sarcopenia-affects approximately 18.5% of older adults globally, yet its shared genetic basis remains poorly understood. We applied genomic structural equation modeling (Genomic SEM) to integrate genome-wide association study (GWAS) summary statistics across five phenotypes spanning the pathophysiological spectrum of osteosarcopenia: appendicular lean mass (ALM), bone mineral density (BMD), handgrip strength (HGS), walking pace, and fracture. Fine-mapping, transcriptome-wide association study (TWAS), pathway enrichment, cell-type enrichment, and spatial transcriptomic mapping were performed to functionally annotate the identified loci. A single-factor model (CFI = 0.976) captured the shared genetic liability, with HGS and ALM loading most strongly. A two-factor sensitivity analysis confirmed partial separability of muscle and bone dimensions, though the single common factor was retained for integrated downstream annotation. We identified 58,696 genome-wide significant single-nucleotide polymorphisms (SNPs) condensed into 1078 independent lead variants, including 29 novel loci. Fine-mapping prioritized 317 high-confidence causal variants, encompassing key genes including BMP6, ACAN, IHH, LRP5, and SOX5. TWAS and MAGMA converged on IGF1R, FOXO3, and IRS1 as dual susceptibility genes. Pathway analysis revealed significant enrichment in endochondral ossification and growth hormone/insulin-like growth factor-1 signaling. Cell-type enrichment localized genetic risk to mesenchymal stem cells and skeletal muscle satellite cells, while spatial mapping identified cartilage primordium as the most enriched developmental context. This study systematically elucidates the shared genetic architecture of osteosarcopenia, highlighting developmental, endocrine, and stem cell-related pathways as core mediators. These findings provide a theoretical foundation for precision geroscience and the development of dual-target therapeutic strategies.

PMID:42166073 | DOI:10.1007/s00335-026-10245-0