Tag: statistics

Pulm Ther. 2026 Feb 28. doi: 10.1007/s41030-026-00353-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Small airways disease (SAD) is increasingly recognized as a relevant trait in severe asthma, but its influence on outcomes with biologic therapies remains uncertain. We assessed the prevalence of SAD and its association with real-world treatment response in a severe asthma cohort. We hypothesized that baseline SAD, particularly when identified by oscillometry, would be associated with non-response to biologic therapy over 12 months.

METHODS: This single-center, retrospective cohort included adult severe asthma outpatients initiating biologic therapy. At enrolment, participants underwent clinical and biomarker evaluation, complete lung function testing (spirometry/plethysmography), and the Forced Oscillation Technique. SAD was defined by the coexistence of ≥ 1 oscillometry abnormality and ≥ 1 spirometry/plethysmography abnormality. “Non-responders” were defined as patients experiencing ≥ 2 exacerbations during 12-month follow-up. Multivariable logistic regression was used to identify independent predictors of response, adjusting for biologic therapy and key confounders (including BMI).

RESULTS: The analytic sample comprised 156 patients (aged 55 ± 18 years, 91 females) treated with omalizumab (n = 60), benralizumab (n = 23), mepolizumab (n = 32), or dupilumab (n = 41). After 12 months, 24/156 patients (15%) were classified as non-responders. At baseline, SAD was present in 69/156 patients (44%) and was more prevalent in non-responders than in responders (75% vs. 40%, p < 0.01). Non-responders showed worse spirometric indices (FEV₁% and FEV₁/VC) and more abnormal oscillometry (lower X5exp and higher ΔXrs, R5exp, and R5-R19). In multivariable models adjusted for biologic and key confounders, baseline oscillometry abnormalities were independently associated with a reduced odds of response (adjusted OR 0.08, 95% CI 0.02-0.37; p = 0.001).

CONCLUSIONS: In a real-world severe asthma cohort, baseline SAD, particularly when identified by oscillometry, was associated with subsequent non-response to biologic therapy, suggesting potential value for risk stratification.

PMID:41762423 | DOI:10.1007/s41030-026-00353-2

J Prev (2022). 2026 Feb 28. doi: 10.1007/s10935-026-00900-2. Online ahead of print.

ABSTRACT

To develop effective health policies and prevention strategies for reducing lung cancer mortality, it is essential to understand its associations with contextual factors, yet prior studies have produced inconsistent results suggesting the associations might vary over space. Very few studies have explicitly examined gender-specific spatial variations in the associations and investigated how the spatial patterns are shaped by community socioeconomic characteristics. This study aimed to examine spatial variations and gender differences in associations of lung cancer mortality rate with contextual environmental, socioeconomic, and health factors in response to the varying socioeconomic characteristics across 159 counties in Georgia, USA for 2019-2023. Following a cross-sectional ecological study design based on county-level aggregated data, this study linked three environmental, fifteen socioeconomic, and fourteen health factors to lung cancer mortality rates for males and females, and conducted various statistical and spatial analyses including Geographically Weighted Regression (GWR) to explore the spatially varying associations of lung cancer mortality rate with those contextual factors. As an explanatory local spatial statistical technique, GWR revealed that the associations varied across space and gender, with significant links observed in fewer counties than nonsignificant ones. No significant spatial autocorrelation was detected in the residuals from the GWR models of lung cancer mortality rate for either males or females (I=-0.121, p = 0.064 for males; I=-0.110, p = 0.098 for females). Key findings include: (1) radon was a more consistent factor associated with elevated lung cancer mortality rates than PM_2.5 and ozone, particularly for males in urban and suburban areas, while air pollutants were significant only in some rural counties; (2) higher socioeconomic and household vulnerabilities increased risks for both genders in rural counties, whereas higher minority populations and greater housing density were linked to lower risks, especially for males in northern urban/suburban counties; (3) prevalences of chronic diseases and smoking were significant factors associated with elevated lung cancer mortality rate for both genders, with chronic diseases showing more spatially consistent effects among females, while annual checkup was a stronger factor associated with reduced lung cancer mortality rate for females, especially in less socioeconomically vulnerable urban/suburban counties; and (4) health factors had the strongest and most spatially consistent effects on mortality rate, followed by socioeconomic and then environmental factors. These findings suggest that effective lung cancer control requires public health policies and preventive measures to be locally tailored, gender-sensitive, emphasizing chronic disease management, smoking cessation, regular preventive care, and socioeconomic development.

PMID:41762417 | DOI:10.1007/s10935-026-00900-2

Adv Ther. 2026 Feb 28. doi: 10.1007/s12325-026-03522-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Olutasidenib and ivosidenib are isocitrate dehydrogenase 1 (IDH1) inhibitors approved for relapsed/refractory (R/R) IDH1 mutant (IDH1m) acute myeloid leukemia (AML).

METHODS: A matching-adjusted indirect comparison estimated relative treatment effects using registrational Phase I/II data for olutasidenib (Study 2102-HEM-101; individual patient data) and ivosidenib (Study AG120-C-001; study-level data) since a head-to-head trial is unlikely. Weights were estimated using a logistic propensity score model adjusted for pre-defined covariates identified from a literature review, validated by clinical experts. Eight covariates were determined to be the most important prognostic factors/effect modifiers for the target population as reported in the Food and Drug Administration labels: number of prior systemic therapies, age, prior hematopoietic stem cell transplantation, AML type, relapse type, cytogenetic risk, Eastern Cooperative Oncology Group performance status, and IDH1 mutation.

RESULTS: Olutasidenib versus ivosidenib adjusted rates of complete remission (CR; odds ratio [OR] 1.12, 95% confidence interval [CI] 0.61-2.08), CR plus CR with partial hematologic recovery (CR + CRh; OR 0.83, 95% CI 0.46-1.50), and median CR duration (difference in medians 11.18 months, 95% CI – 4.30 to 22.72) were not significantly different. Median CR + CRh duration was significantly longer for olutasidenib (difference in medians 9.84 months, 95% CI 3.24-22.28), accompanied by a numerical non-significant trend in overall survival that should be considered exploratory (hazard ratio 0.75, 95% CI 0.53-1.07).

CONCLUSION: While not confirmatory, these findings may be clinically relevant in the context of this difficult-to-treat R/R IDH1m AML population.

PMID:41762374 | DOI:10.1007/s12325-026-03522-6

Adv Ther. 2026 Feb 28. doi: 10.1007/s12325-026-03520-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Psoriasis is a chronic inflammatory disease often accompanied by musculoskeletal symptoms and psoriatic arthritis (PsA). Early identification of PsA remains challenging, underscoring the need for interdisciplinary care between dermatology and rheumatology. To evaluate the diagnostic and therapeutic impact of an interdisciplinary dermatology-rheumatology board (IDRB) for patients with psoriasis, we initiated a non-randomized, prospective bicentric study.

METHODS: A total of 182 patients with psoriasis were enrolled at baseline (V0), of whom 111 completed the 12-month follow-up (V2). Forty-seven (25.8%) patients participated in the IDRB, and 135 (74.2%) patients received standard dermatological care. Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS-A/D), pain, systemic inflammation, psoriatic arthritis (PsA) diagnosis, and systemic therapy courses were analyzed. Group differences and changes over time were assessed using non-parametric and parametric tests, and predictors of therapy modification were explored using univariate logistic regression.

RESULTS: Over 12 months, patients in the IDRB group showed statistically significant improvements in PASI, DLQI, and HADS-A (all p ≤ 0.05). Among participants without PsA at baseline and with complete PsA documentation at follow-up, new PsA diagnoses occurred more often in the IDRB cohort (31%) than in standard care (9.8%) (Fisher’s exact p = 0.0295; χ² p = 0.0360; OR = 4.14). In univariate analyses, higher baseline PASI, DLQI, and HADS-A values were each associated with subsequent therapy modification. Within the IDRB group, biologic treatments shifted over time toward IL-17- and IL-23-targeted agents, indicating a move toward more streamlined and targeted systemic therapy patterns compared with standard care.

CONCLUSION: An IDRB may contribute to more structured PsA assessment and to more informed therapeutic decisions in patients with psoriasis. Integrating objective clinical measures together with patient-reported burden appears crucial for guiding treatment modification and optimizing outcomes. Given the non-randomized, self-selected design, these findings should be interpreted as associations.

TRIAL REGISTRATION: DRKS-Deutsches Register Klinischer Studien listing: DRKS00037907.

PMID:41762372 | DOI:10.1007/s12325-026-03520-8

Lifetime Data Anal. 2026 Feb 28;32(2):17. doi: 10.1007/s10985-026-09695-0.

ABSTRACT

Current methodological research on randomized controlled trial design has predominantly focused on studies with a single primary endpoint. However, many trials in practice involve multiple competing target events. The optimal designs for survival trials with competing target events have not been systematically addressed in the statistical literature. This paper fills this significant gap by developing design methodologies for randomized discrete-time-to-event trials with competing endpoints. We derive the Fisher information matrix for the general discrete-time survival model (DTSM) by transforming the original discrete-time survival data into proper multinomial responses. By introducing a cost-based generalized [Formula: see text]-optimal design criterion, we identify various types of optimal designs for estimating the treatment effects. Under the assumption of a parametric competing risks model for the underlying survival process, we demonstrate that the optimal treatment allocation scheme is critically influenced by the parameter values within this model. Our methodology is applied to the redesign of the SANAD trial, which examines withdrawal times from anti-epileptic drugs, thereby highlighting the advantages of our optimal design strategies. A key finding is that assigning subjects equally to the different groups in a two-arm DTSM trial with competing risks is generally a favorable choice, unless the hazard rates over the duration of the trial in both groups are low.

PMID:41762364 | DOI:10.1007/s10985-026-09695-0

Eur Radiol. 2026 Feb 28. doi: 10.1007/s00330-026-12442-6. Online ahead of print.

NO ABSTRACT

PMID:41762263 | DOI:10.1007/s00330-026-12442-6

Eur Radiol. 2026 Feb 28. doi: 10.1007/s00330-026-12382-1. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the prevalence of adrenal vein involvement in primary and metastatic adrenal lesions and to determine if morphological changes in tumor shape precede venous extension.

MATERIALS AND METHODS: This retrospective, single-center observational study evaluated 102 patients: 28 adrenal cortical carcinoma (ACC) patients, and 74 non-ACC cancer patients that presented adrenal metastasis (82 metastatic adrenal lesions). Two readers reviewed cross-sectional imaging to assess tumor size, laterality, venous invasion, and the presence of the “edge sign.” Surgical and histopathological confirmation was the reference standard for ACCs, while for metastases, sequential imaging or PET-CT results showing hypermetabolism were used in 70.7% of cases and histopathology in 29.3% of cases.

RESULTS: Of the 28 ACC patients, 82.1% were female, with balanced laterality. Metastases primarily originated from the lung (24.4%), colorectal (13.4%), and breast (12.2%) cancers and had a left-sided dominance (61.7%). Venous extension was present in 14.6% of metastases and 21.4% of ACCs, a non-significant difference (p = 0.40). The “edge sign” was more frequently observed in metastatic lesions than in ACCs, 26.8 × 17.8%, although this difference has not reached statistical significance (p = 0.34). In multivariate analysis, both mean size and the “edge sign” were independent predictors of adrenal and renal vein extension. Interobserver agreement was almost perfect for venous extension (κ = 0.9256) and substantial for the edge sign (κ = 0.7844).

CONCLUSION: Venous extension was less prevalent in metastatic adrenal lesions compared to ACCs. The edge sign may precede venous extension, especially in metastatic cases, indicating the nature of the lesion. These findings potentially may alter disease management, expediting the decision for surgery; however, prospective multicenter studies are needed to confirm their clinical impact.

KEY POINTS: Question What is the prevalence of venous extension in malignant adrenal lesions-whether primary or secondary-and how can early involvement be recognized on imaging? Finding Adrenal vein involvement occurred similarly in ACCs (21.4%) and metastases (14.6%). Early extension may be preceded by the adrenal edge sign in 25% of cases. Clinical relevance Adrenal vein involvement occurs in both primary and metastatic adrenal lesions, with a tendency to be more prevalent in adrenocortical carcinomas. The ‘edge sign’ may precede venous extension in malignant lesions, aiding both diagnosis and therapeutic planning.

PMID:41762262 | DOI:10.1007/s00330-026-12382-1

Eur Radiol. 2026 Feb 28. doi: 10.1007/s00330-026-12389-8. Online ahead of print.

ABSTRACT

OBJECTIVES: The selection of ultrasound (US) plane for evaluating the taller-than-wide (TTW) shape remains controversial. This study aimed to determine whether the diagnostic value of TTW criteria differs when used alone or in combination with other US features, and to identify the optimal TTW criterion across four major Thyroid Imaging Reporting and Data Systems (TIRADS: Chinese (C)-TIRADS, American College of Radiology (ACR)-TIRADS, European (EU)-TIRADS and Korean (K)-TIRADS).

MATERIALS AND METHODS: Preoperative US images of thyroid nodules were reviewed retrospectively. Four TTW criteria were defined as follows: transverse plane only (T-only), longitudinal plane only (L-only), both planes (Dual-plane), and either one or both planes (Single- or dual-plane). Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI) for malignancy prediction and fine-needle aspiration (FNA) guidance.

RESULTS: Among 1125 nodules, 558 (49.6%) were benign and 567 (50.4%) were malignant. Using the TTW shape alone, Single- or dual-plane achieved the highest AUC for malignancy (0.813). Within TIRADS, Dual-plane demonstrated the highest AUCs in C-TIRADS (0.884) and EU-TIRADS (0.874) and improved reclassification, whereas in ACR-TIRADS and K-TIRADS, Dual-plane and Single- or dual-plane performed similarly and outperformed the T-only and L-only. For FNA guidance, the Dual-plane also showed improvements in C-TIRADS and ACR-TIRADS.

CONCLUSION: The optimal TTW US plane differs when applied alone versus when combined with other suspicious US features. Within the TIRADS, assessment of the TTW shape in both transverse and longitudinal planes achieves superior accuracy and contributes to improving malignancy diagnosis and FNA decision-making.

KEY POINTS: Question Which TTW criterion provides the best diagnostic performance for malignancy risk stratification and FNA guidance across the four major TIRADS? Findings Dual-plane TTW yielded the best performance in C-TIRADS and EU-TIRADS, and improved FNA guidance in C-TIRADS and ACR-TIRADS versus other TTW criteria. Clinical relevance The stricter criterion not only improves the malignancy diagnosis but also provides better guidance for biopsy, offering valuable evidence for refining future guideline recommendations and standardizing the evaluation of thyroid nodules.

PMID:41762261 | DOI:10.1007/s00330-026-12389-8

World J Urol. 2026 Feb 28;44(1):212. doi: 10.1007/s00345-026-06312-5.

ABSTRACT

PURPOSE: Despite well-defined standards for urethral stricture management, significant practice variations persist. This survey assessed guideline adherence among Turkish urologists.

METHODS: An online SurveyMonkey survey was sent to Turkish Urological Association members, open October 10-17, 2021, with two reminders. Data were centrally collected and analyzed using descriptive statistics.

RESULTS: Of 2,078 members, 222 (11%) responded, mostly aged 30-45 years. Retrograde urethrography (26%), uroflowmetry (90%), and cystourethroscopy (61%) were used for diagnosis, with academic urologists employing these more often (p < 0.05). Blind dilatation with metal bougies (47%) exceeded plastic dilators over guidewire (23%) or disposable catheters (26%). Material preference was unrelated to experience (p = 0.39), but non-metal methods were more common in academic centers (p = 0.04). For 1-2 cm primary bulbar strictures, 7% chose urethroplasty, while 72% preferred Direct Vision Internal Urethrotomy (DVIU) with dilatation. Academic urologists performed more urethroplasties (p = 0.01). In recurrent cases, 76.5% performed DVIU ≥ 4 times, and 79.3% recommended periodic post-DVIU dilatation.

CONCLUSIONS: Urologists’ approaches to urethral strictures often deviate from guidelines. Retrograde urethrography use is low, metal bougies dominate dilatation, and urethroplasty is underused, favoring repeated DVIU and dilatation. Academic urologists adhere more to guideline recommendations than non-academic peers.

PMID:41762243 | DOI:10.1007/s00345-026-06312-5

Diagnosis (Berl). 2026 Mar 2. doi: 10.1515/dx-2025-0152. Online ahead of print.

ABSTRACT

OBJECTIVES: Clinical prediction requires formalizing uncertainty into a statistical model. However, persistent confusion between prediction and inference, and between traditional (stepwise) and modern (penalized) development strategies, leads to unstable, poorly calibrated, and overfit models. A structured statistical framework is essential.

METHODS: This article is a structured, didactic tutorial that explains the core concepts of clinical prediction models. It covers the definition of a prediction model, the fundamental strategies for its construction, and the essential framework for its evaluation, illustrated through an applied example using real-world clinical data.

RESULTS: The tutorial illustrates model development using the GUSTO-I dataset (N = 40,830). Penalized methods (LASSO and Elastic Net) successfully identified clinical signals while eliminating engineered noise variables. The LASSO model (λ_1se) achieved excellent discrimination (AUC 0.818; 95 % CI: 0.803-0.832) and overall accuracy (Brier score 0.058). Calibration analysis revealed a slope of 1.28 and intercept of 0.63, identifying conservative bias and systematic risk underestimation inherent to λ_1se selection. Decision curve analysis confirmed significant clinical utility across relevant probability thresholds.

CONCLUSIONS: This guide equips clinicians with a rigorous methodological framework for the critical appraisal and interpretation of modern clinical prediction models.

PMID:41762231 | DOI:10.1515/dx-2025-0152