Category: Statistics

Kidney Int. 2026 Mar 20:S0085-2538(26)00217-6. doi: 10.1016/j.kint.2026.02.023. Online ahead of print.

ABSTRACT

INTRODUCTION: Diabetic kidney disease (DKD) is a significant complication of diabetes, and an unmet need remains for new therapeutic options. Here, we investigated the efficacy and safety of monlunabant, a second-generation cannabinoid receptor 1 inverse agonist, in individuals with DKD.

METHODS: This phase 2, randomized, double-blind, placebo-controlled, multicenter study, enrolled adults with DKD. Participants were randomized (1:1:1) to receive oral tablets of monlunabant 10 mg or 25 mg, or placebo once daily for 16 weeks. The primary endpoint was the change in urine albumin-to-creatinine ratio (UACR) from baseline to week 16. Secondary endpoints included changes in urine protein-to-creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR).

RESULTS: In total, 254 participants formed the full analysis set (85, 86, and 83 in the 10 mg, 25 mg, and placebo groups, respectively). At week 16, the estimated geometric least squares mean ratios to baseline for UACR were 0.58, 0.51, and 0.71 in the 10 mg, 25 mg, and placebo groups, respectively. Monlunabant 25 mg did not show statistically significant differences compared to placebo (estimated treatment ratio [ETR] 0.72, 95% confidence interval (0.46 to 1.14)). Therefore, formal testing was not performed for 10 mg compared to placebo (ETR 0.82 (0.53 to 1.27)). Secondary endpoints showed similar trends, with no differences in UPCR or eGFR, when compared to placebo. The most frequently reported adverse events were mild to moderate gastrointestinal disorders, driven by nausea, vomiting, and diarrhea. Participant withdrawals increased with monlunabant dose.

CONCLUSIONS: Our study failed to establish proof of concept of monlunabant in DKD, as the effect on UACR at week 16 was not significantly different from placebo. However, greater than anticipated variability and a large placebo response affect interpretation.

PMID:41866124 | DOI:10.1016/j.kint.2026.02.023

J Vasc Surg Venous Lymphat Disord. 2026 Mar 20:102490. doi: 10.1016/j.jvsv.2026.102490. Online ahead of print.

ABSTRACT

OBJECTIVES: Endovenous radiofrequency ablation (RFA) and cyanoacrylate ablation (CA) are widely used for the treatment of chronic great saphenous vein (GSV) insufficiency. Compared with traditional surgery, both modalities have demonstrated well-recognized therapeutic benefits. However, controversy remains regarding the optimal choice between RFA and CA. The aim of this study was to conduct a systematic review and meta-analysis to compare the early and mid-term clinical outcomes of RFA versus CA.

METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. Comprehensive searches were conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies. Randomized controlled trials, cohort studies, and case-control studies evaluating RFA and CA for the treatment of GSV incompetence were included. The primary outcomes were GSV occlusion rate and venous clinical severity score (VCSS). Secondary outcomes included skin pigmentation, phlebitis, deep vein thrombosis (DVT), ecchymosis, and procedure-related phlebitis. Data extraction and quality assessment were independently performed by two reviewers. Statistical analyses were conducted using Review Manager 5.3.

RESULTS: A total of 21 studies were included, encompassing 7,844 patients and 9,677 limbs. In terms of efficacy, there were no significant differences between CA and RFA in GSV occlusion rate or VCSS. Regarding safety, pooled data showed that CA was associated with a lower incidence of ecchymosis (5.96% vs. 10.97%; P = 0.01) and paresthesia (1.24% vs. 2.97%; P = 0.04). No significant differences were observed between the two groups in the incidence of phlebitis, DVT, or pigmentation. In addition, the procedure time was significantly shorter in the CA group than in the RFA group (P < 0.001).

CONCLUSIONS: For the treatment of incompetent saphenous veins, CA provides comparable efficacy to RFA. However, CA is associated with lower rates of skin pigmentation and ecchymosis, as well as a shorter procedure time.

PMID:41866115 | DOI:10.1016/j.jvsv.2026.102490

J Vasc Surg. 2026 Mar 20:S0741-5214(26)00652-X. doi: 10.1016/j.jvs.2026.03.435. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate longitudinal changes in quality of life (QoL) and health status (HS) in patients with an abdominal aortic aneurysm (AAA) undergoing endovascular aneurysm repair (EVAR).

METHODS: This prospective international multicenter cohort study included patients undergoing elective infrarenal EVAR in 21 institutions. QoL (WHOQOL-BREF questionnaire) and HS (SF-12 questionnaire) were assessed preoperatively and postoperatively at 6 and 12 months. Preset minimal clinically important difference (MCID)-thresholds defined meaningful changes in QoL or HS for each patient. Linear mixed models evaluated longitudinal changes for whole cohort.

RESULTS: In total, 151 patients were included (mean age 74.4 ±6.6 years). At 12 months, MCID-based individual-patient analysis demonstrated that QoL domains were higher in 14-31% and lower in 21-45% and that HS summary scores were higher in 26-29% and lower in 38%. In linear mixed models, environmental QoL was significantly lower at 6 and 12 months (mean difference -0.45 [95%CI -0.05; -0.84, p=0.021] and -0.44 [95%CI -0.05; -0.84, p=0.024]) and social QoL at 12 months (mean difference -0.62 [95%CI -0.11; -1.12, p=0.010]) compared to baseline, whereas no significant differences were observed in HS.

CONCLUSIONS: QoL measures (WHOQOL-BREF) indicated significant differences in social and environmental QoL domains after EVAR when compared to baseline, while HS measures (SF-12) did not reflect statistically significant changes. This suggests that QoL and HS capture different concepts of patient wellbeing after EVAR and that HS measures alone may not reflect what patients value. MCID-based individual-analysis demonstrated substantial heterogeneity in QoL and HS trajectories. These findings may support shared decision-making by informing patients about expected postoperative trajectories. Long term evaluations that incorporate frailty and multimorbidity are warranted.

PMID:41866090 | DOI:10.1016/j.jvs.2026.03.435

Orthop Traumatol Surg Res. 2026 Mar 20:104687. doi: 10.1016/j.otsr.2026.104687. Online ahead of print.

ABSTRACT

INTRODUCTION: Knee arthroplasty is associated with a variable risk of blood transfusion depending on the surgical technique, with a higher risk for total knee arthroplasty (TKA) than for unicompartmental knee arthroplasty (UKA). Although the safety of single-stage bilateral procedures has now been established, the risk of transfusion for single-stage bilateral TKA is high at approximately 20% whereas the risk of transfusion for bilateral UKA is only 2%. Although this difference appears to be significant, to date there is no study comparing transfusion rates between the two procedures when performed as single stage surgeries. Reducing transfusion risk would support the use of unicompartmental knee arthroplasty, since transfusion is a known risk factor for postoperative complications, especially infections. The objective of this study was to compare blood loss and transfusion rate between these two techniques and to identify risk factors.

MATERIALS AND METHODS: A multicenter retrospective study was conducted in four French centers including 277 patients who underwent single-stage bilateral knee arthroplasty between January 2021 and December 2023: 149 bilateral TKA procedures and 128 bilateral UKA procedures. The parameters analyzed included preoperative hemoglobin, hemoglobin levels at postoperative day 1 (D1) and day 3 (D3), blood loss volume, number of transfused red blood cell units, use of a pneumatic tourniquet or suction drain, early complications, and patient satisfaction. Statistical comparisons were performed using Student’s t-test and the chi-square test, with a significance threshold set at p < 0.05.

RESULTS: Preoperative hemoglobin levels were slightly higher in the UKA group (14.5 g/dL vs 14.2 g/dL; p = 0.038). The mean hemoglobin decrease at D3 was significantly greater in the TKA group (4.8 g/dL vs 2.1 g/dL; p < 0.0001), as was blood loss volume (1.2 L vs 0.5 L; p < 0.0001). The transfusion rate was 20% in the TKA group versus 0% in the UKA group (p < 0.0001). The use of a suction drain was associated with significantly higher blood loss in both groups. No association was found between transfusion risk and age or ASA score. The rate of early complications was 6% in the TKA group and 1.6% in the UKA group, with no statistical difference. Patient satisfaction exceeded 94% in both groups. In multivariate analysis, lower preoperative hemoglobin level (OR ≈ 0.52, p = 0.011) and use of a suction drain (OR ≈ 11.3, p < 0.001) were independently associated with an increased risk of transfusion.

CONCLUSION: Single-stage bilateral total knee arthroplasty is associated with significantly greater blood loss and transfusion risk than bilateral unicompartmental knee arthroplasty. These results support the value of unicompartmental arthroplasty in reducing perioperative morbidity in the treatment of disabling knee osteoarthritis. However, patient-related factors appear to play a decisive role in bleeding risk, and additional studies will need to exclude these factors to clarify the influence of the surgical technique.

LEVEL OF EVIDENCE: III; Retrospective comparative study.

PMID:41866078 | DOI:10.1016/j.otsr.2026.104687

Hosp Pediatr. 2026 Mar 23:e2025008748. doi: 10.1542/hpeds.2025-008748. Online ahead of print.

ABSTRACT

OBJECTIVE: Prenatal substance exposure is associated with harm to newborns and their families. Clinicians must report in utero controlled substance exposure to Child Protective Services (CPS). Studies have found that clinicians disproportionately order toxicology tests for Black infants, particularly in the absence of standardized policies for drug testing, which may lead to disproportionate downstream harm for Black families. The aim of this single-center quality improvement (QI) study is to eliminate racial inequity in drug testing for potentially substance-exposed newborns.

METHODS: The QI team identified lack of standardized policy and clinician education as key drivers and implemented a QI change from December 2022 to July 2024, which included a policy to standardize indications for meconium drug testing linked to an order set and QI dashboard. Descriptive statistics regarding testing rates and indications for testing stratified by race and ethnicity were performed before and after QI interventions.

RESULTS: A total of 10 637 individuals were included in the study population. The rate of testing increased from 5.2% pre-policy to 9.9% post-policy for Black newborns (relative risk [RR] 1.89, 95% CI: 1.27-2.81, P = .002). The rate of testing for white newborns was stable (3.2% to 3.7%, RR 1.14, 95% CI: 0.90-1.45, P = .27). Reasons for testing varied by race; being late to prenatal care accounted for 19.4% of all tests performed for Black newborns compared with 7.1% of all tests for white newborns. Testing for isolated marijuana use increased from 4.5% to 7.2% for Black newborns and remained stable, from 2.6% for 2.7%, for white newborns.

CONCLUSIONS: Implementing a standardized policy and order set widened the inequity between Black and white newborns and increased testing rates for all newborns. Ongoing QI efforts include reevaluation of our approach to postnatal drug testing for prenatal cannabis exposure.

PMID:41866040 | DOI:10.1542/hpeds.2025-008748

Adv Sci (Weinh). 2026 Mar 22:e12369. doi: 10.1002/advs.202512369. Online ahead of print.

ABSTRACT

Despite growing evidence that the visual system pools sensory data into a summary statistical representation, the underlying neural mechanisms remain unclear. We characterized the neural coding of summary statistics at the single-cell and population levels using calcium signals imaged in primary visual cortex (V1) and posterior parietal cortex (PPC) while head-fixed mice passively viewed or classified eight mean motion directions of randomly moving dots into two categories. A small portion of neurons in both areas showed global mean motion direction selectivity beyond what would be expected from the simple summation of responses to individual dot motions. Although this selectivity was variable across stimulus variability and trials, population activity robustly encoded global mean motion direction, even though most neurons were not significantly tuned. The V1 population-level mean motion representation was dependent on stimulus variance and systematically biased toward the category center during the motion categorization task. These, along with the observed population-level neural coding of stimulus variance, suggest that multivariate V1 activity is well suited to processing summary statistics. The redundant summary statistical encodings in both V1 and PPC suggest that such information accumulates across the visual hierarchy, which may allow PPC to bind multiple levels of summary statistical representations into task-oriented category signals.

PMID:41865416 | DOI:10.1002/advs.202512369

Cell Rep. 2026 Mar 20;45(4):117136. doi: 10.1016/j.celrep.2026.117136. Online ahead of print.

ABSTRACT

IL-4 can have significant therapeutic benefit in many injury settings, but its mechanism of action is unclear. Using a model of carbon tetrachloride (CCl₄)-mediated acute liver injury, we find that exogenous IL-4 causes a dramatic shift from recruited Ly6C^hi monocytes to an abundance of monocyte-derived macrophages (MoMFs) within the injured tissue that is accompanied by reduced indices of hepatic damage and enhanced hepatic regeneration. Rather than altering the recruitment or differentiation of monocytes, treatment with IL-4 triggers monocyte apoptosis alongside proliferation of MoMFs. Single-cell RNA sequencing reveals injury and cell-type-specific responses to IL-4 treatment across hepatic myeloid lineages and a largely pro-reparative gene signature in the expanded pool of MoMFs. IL-4 treatment fails to enhance hepatic repair when the accrual of MoMFs is limited using Ccr2-deficient monocytopenic mice. Together, these data reveal a pathway through which therapeutic IL-4 alters the composition, number, and function of injury-associated myeloid cells to resolve liver injury.

PMID:41865375 | DOI:10.1016/j.celrep.2026.117136

Clin Transl Oncol. 2026 Mar 22. doi: 10.1007/s12094-026-04311-x. Online ahead of print.

ABSTRACT

AIM: Four-dimensional computed tomography (4D-CT) is the gold standard for radiotherapy planning in non-small cell lung cancer (NSCLC), yet its use in radiomics remains underexplored. This study proposes a reproducible, scalable methodology for assessing radiomic feature (RF) stability in 4D-CT and evaluates whether image filtering identifies additional stable RFs compared to unfiltered images.

METHODS: Early-stage NSCLC patients treated with SBRT with 4D-CT were included. Gross tumor volumes (GTVs) were re-segmented on all available phases. RFs were extracted using PyRadiomics. Features with near-zero variance in > 85% of patients were excluded. RF stability was evaluated using two complementary approaches: (i) coefficient of variation (COV), quantifying the magnitude of inter-phase variability, and (ii) repeated-measures modeling, assessing the presence of a statistically significant association between RF values and respiratory phase. RFs with COV < 5% and 5-10% were considered highly stable and stable, respectively. Repeated-measures analyses were performed separately for expiratory (0-40%) and inspiratory (50-90%) phases.

RESULTS: Seventy patients met the inclusion criteria. 1892 RFs were analyzable. Based on COV, about 21% (397/1892) of RFs were highly stable, and 18% (338/1892) were stable, while the remaining showed intermediate or high variability. The largest proportion of highly stable RFs derived from lbp-3D (25%) and log-sigma (12%) filtered images. Repeated measures analysis showed that only a limited subset of RFs had a statistically-significant dependence on respiratory phase, with 1747 and 1744 RFs remaining time-independent across expiratory and inspiratory phases, respectively.

CONCLUSION: Radiomic features extracted from 4D-CT images in early-stage NSCLC patients show heterogeneous stability across respiratory phases. Radiomic features extracted from 4D-CT images in early-stage NSCLC exhibit heterogeneous quantitative variability across respiratory phases. However, only a minority of features show statistically significant time dependence. The study provides a reproducible methodological framework to identify stable radiomic features from 4D-CT, enabling their more reliable use in lung cancer radiomic studies.

PMID:41865337 | DOI:10.1007/s12094-026-04311-x

World J Urol. 2026 Mar 22;44(1):254. doi: 10.1007/s00345-026-06291-7.

ABSTRACT

PURPOSE: Post-prostatectomy urinary incontinence (PPI) significantly impacts quality of life. While an artificial urinary sphincter is the standard surgical treatment for PPI, adjustable continence therapy balloons (ProACT) have emerged as a less invasive alternative over the past two decades. ProACT implantation is considered technically challenging and limited to three high-volume Dutch medical centers, yet little is known about the surgical learning curve. This study aims to assess the learning curve to inform training requirements for ProACT implantation.

METHODS: This retrospective single-center study included all ProACT implantations performed by one urologist at Erasmus University medical Center, Rotterdam. Surgery success was defined as postoperative use of a maximum of one ‘safety pad’, less than 10 mL urine loss or ≥ 95% subjective improvement of continence. Multivariable logistic regression assessed the learning curve.

RESULTS: A total of 108 surgeries between 2019 and 2024 were included, of which 15 were supervised by an experienced surgeon. No statistical relation was found between the progressive surgeon’s experience and surgical success (per 10 surgeries, OR 0.89, 95%CI: 0.75-1.07, p = 0.2). Preoperative incontinence (pads/day) was statistically significantly associated with surgical success (OR 0.65, 95%CI: 0.47-0.89, p = 0.009). The overall surgical success rate was 61%, with an additional 20% achieving > 50% continence improvement. Complication rate within six months was 21% of which six (5.6%) included explantations of the ProACT device.

CONCLUSION: ProACT implantation achieves consistent outcomes after brief supervised training, with no statistically significant learning curve. This supports a broader adoption of this technique by urologists treating PPI.

PMID:41865333 | DOI:10.1007/s00345-026-06291-7

Pharmacoeconomics. 2026 Mar 22. doi: 10.1007/s40273-026-01611-6. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is a major global cause of morbidity and mortality. Recent nephroprotective therapies have improved CKD management, yet their cost effectiveness across settings remains uncertain. This review systematically identified and compared cost-effectiveness studies of novel CKD treatments for both broad CKD populations and disease-specific subgroups.

METHODS: A systematic search was conducted in PubMed and the Cochrane Library using terms related to “chronic kidney disease,” “cost-effectiveness,” “cost-utility,” “health technology assessment,” “SGLT2 inhibitor,” and commercial and generic names of nephroprotective drugs approved since 2013. Eligible studies were full-length articles in English published between January 2015 and September 2025. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were extracted. All monetary values were standardized to 2025 US dollars.

RESULTS: The search yielded 172 records, of which 26 met inclusion criteria. A supplementary search identified ten additional studies, resulting in 36 evaluations. Most studies assessed sodium-glucose cotransporter 2 inhibitors or finerenone. Across evaluations, these therapies consistently improved outcomes, with QALY gains reported in all studies (0.012-1.44 QALYs gained). Most concluded that the interventions were cost effective compared with standard of care, and 13 reported cost-saving results. Only three studies reported an incremental cost-efffectiveness ratio above $100,000 per QALY threshold. Cost effectiveness was observed in both general CKD and CKD with diabetes mellitus, although estimates varied by country, time horizon, and analytic perspective.

CONCLUSIONS: Current evidence indicates that novel nephroprotective therapies for CKD are generally cost effective, and in some settings cost saving. These findings support their value in both general CKD and diabetic populations and highlight the importance of early treatment adoption to delay disease progression and reduce long-term healthcare costs.

PMID:41865332 | DOI:10.1007/s40273-026-01611-6