Tag: nevin manimala

Stat Med. 2026 Mar;45(6-7):e70505. doi: 10.1002/sim.70505.

ABSTRACT

Improving patients’ quality of life (QoL) is one of the primary goals of palliative care clinical trials. However, a significant challenge in this area is the “truncation by death problem,” where QoL data cannot be observed after a patient dies, potentially introducing bias into statistical analyses. Understanding the impact of truncation by death when estimating the association between QoL and exposure or treatment is essential, especially when a relatively large proportion of subjects die during a study. To address this issue, we propose a Bayesian joint modeling framework that considers dependencies at both the individual and cluster levels while examining longitudinal QoL trajectories and survival outcomes simultaneously. This approach builds on existing joint modeling methods by incorporating cluster-level random effects. We model QoL on a retrospective scale relative to the time of death, while linking survival via both the subject and cluster-level random effects. The longitudinal sub-model also allows for flexible, non-linear QoL trajectories, which are modeled using penalized regression splines. For the survival sub-model, we use a proportional hazards frailty model with a Weibull baseline hazard. The model is estimated using a Bayesian framework, implemented via Markov Chain Monte Carlo (MCMC) sampling. To evaluate the performance of our method, we conducted a comprehensive simulation study including scenarios with different numbers of clusters. We also show results from applying this novel methodology to data from the Reducing End of Life Symptoms with Touch (REST) study.

PMID:41853920 | DOI:10.1002/sim.70505

Stat Med. 2026 Mar;45(6-7):e70492. doi: 10.1002/sim.70492.

ABSTRACT

Basket trials are an efficient approach to simultaneously evaluate a single therapy across multiple diseases where patients share a common molecular target. Bayesian hierarchical models (BHMs) are widely used to estimate the treatment effects while accounting for heterogeneity between patient subgroups within a basket trial. However, the use of analysis of covariance (ANCOVA) with treatment-by-covariate interaction terms, in this context of patient heterogeneity and small samples, has been largely unexplored, despite the widespread use of ANCOVA for improving estimation precision in traditional settings from a frequentist perspective. In this paper, we propose two covariate-adjusted BHMs that incorporate ANCOVA into the data model to enhance the estimation precision in basket trials, wherein borrowing of information is permitted across subgroups to a certain extent. Specifically, both ANCOVA without treatment-by-covariate interaction terms and ANCOVA with interaction terms are explored in the analysis of basket trials. We perform a simulation study to demonstrate the advantages of covariate-adjusted BHMs compared to unadjusted BHMs, as well as frequentist ANCOVA models. The BHMs are then retrospectively applied to the analysis of the MAJIC study, a randomized controlled basket trial involving two subtypes of blood cancer.

PMID:41853914 | DOI:10.1002/sim.70492

Cytometry B Clin Cytom. 2026 Mar 19. doi: 10.1002/cyto.b.70023. Online ahead of print.

ABSTRACT

Systemic mastocytosis (SM) is a clonal mast cell (MC) disorder characterized by aberrant immunophenotypes, including expression of CD25, CD2, and occasionally CD30. CD123, the α-subunit of the interleukin-3 receptor, is a therapeutic target in hematologic malignancies and has been reported to be expressed on neoplastic MCs by immunohistochemistry (IHC) with prognostic implications. This study aims to characterize CD123 expression in SM by flow cytometry. We retrospectively analyzed 142 bone marrow samples from 79 SM patients (81 diagnostic samples) and 25 controls with normal MC immunophenotype. Flow cytometry was performed using a clinically validated 9-color mast cell tube which included CD123. Data collected included SM subtype, clinical and laboratory features, MC burden, and marker expression. Statistical analyses were performed in R. CD123 was expressed on MCs in 91% of SM cases (ISM 92%, SM-AHN 94%, SSM 100%, ASM 100%, MCL 50%). Median percentage of MCs positive for CD123 was 53.9% (IQR 8.1-83.4). Compared to prior IHC data (overall 64% positivity), flow cytometry demonstrated more cases with CD123 expression by MCs. No significant correlations were observed between CD123 expression and serum tryptase, KIT D816V allele burden, or MC burden. CD123 is frequently expressed on neoplastic MCs in SM by flow cytometry, across all subtypes. These findings support further investigation of CD123 as a therapeutic target and warrant correlation with IHC and clinical outcomes in larger cohorts.

PMID:41853900 | DOI:10.1002/cyto.b.70023

Scand J Surg. 2026 Mar 19:14574969261431953. doi: 10.1177/14574969261431953. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: ERAS protocols are widely used in colorectal surgery, yet their impact on outcomes in diverticular disease (DD) is unclear. The primary aim of this study was to compare postoperative complication rates after left-sided colon resections for either DD or left-sided colonic cancer within an ERAS pathway, the secondary aim was to assess ERAS protocol compliance.

METHODS: This retrospective multicenter cohort study used data from the Swedish ERAS® Interactive Audit System (EIAS) from 2010 to 2020. All participating centers consecutively register elective colorectal procedures in patients aged ⩾ 18 years. We included all adult patients undergoing elective left-sided colonic or sigmoid resection at participating centers, where all procedures are mandatorily registered within a standardized ERAS pathway, with no additional exclusions. ERAS protocol compliance (pre- and intraoperative items), postoperative symptoms, and postoperative complications were assessed according to ERAS® guidelines and compared between diagnostic groups. Associations between variables and outcomes were evaluated using logistic regression.

RESULTS: A total of 3774 patients were included (879 with DD and 2895 with cancer). Patients in the DD group were younger and had fewer comorbidities. ERAS compliance was similar between groups (86.3% for DD vs 86.7% for cancer). In multivariable analysis, there was no statistically significant difference in severe complications (Clavien-Dindo grade III-IV) between the DD and cancer groups (11.8% vs 13.1%; OR = 0.97, 95% CI = 0.87-1.09). However, DD was associated with a higher rate of overall complications (39.2% vs 36.5%; OR = 1.27, 95% CI = 1.07-1.52), particularly infectious complications (17.0% vs 12.1%; OR = 1.55, 95% CI = 1.23-1.97), including intra-abdominal abscesses (3.5% vs 2.3%; OR = 1.62, 95% CI = 1.01-2.60). In addition, DD patients were more likely to experience postoperative pain that delayed hospital discharge (5.2% vs 2.4%, OR = 1.78, 95% CI = 1.17-2.70).

CONCLUSIONS: Despite similar adherence to the ERAS protocol, surgery for DD was associated with a higher overall rate of postoperative complications and similar rates of severe complications as surgery for colonic cancer. The considerable risk of complications should be carefully considered when counseling patients with DD for elective surgery.

PMID:41853898 | DOI:10.1177/14574969261431953

Stat Med. 2026 Mar;45(6-7):e70497. doi: 10.1002/sim.70497.

ABSTRACT

High-dimensional omics data often exhibit complex yet organized dependencies, characterized by intelligent network properties like high modularity, small-worldness characteristics, and scale-free topology. However, integrating these structured interdependencies between omics variables into multivariate regression models presents challenges. The primary difficulty lies in accurately specifying and estimating dependency parameters that capture these network patterns within regression frameworks. Common covariance estimation methods may not preserve these network properties and can also be computationally intensive. To address these challenges, we propose a novel multivariate regression model that incorporates an interconnected community structure, reflecting the organized relationships among omics outcome variables. Our approach includes efficient estimation algorithms, featuring closed-form regression estimators and likelihood-based dependence estimators. We also establish the asymptotic properties of estimators to ensure theoretical robustness and hypothesis testing. Extensive simulations demonstrate the enhanced accuracy and sensitivity of our method, as evidenced through benchmarking against existing regression models. We applied our approach to a dataset to assess the associations between 249 metabolomic biomarkers, measured using nuclear magnetic resonance spectroscopy, and alcohol intake among 3984 participants. Results indicate that light alcohol consumption is positively associated with high-density lipoprotein cholesterol (HDL, i.e., the good cholesterol), high-density lipoprotein particles, and Apolipoproteins A1, indicators linked to cardiovascular health.

PMID:41853895 | DOI:10.1002/sim.70497

Pediatr Pulmonol. 2026 Mar;61(3):e71568. doi: 10.1002/ppul.71568.

ABSTRACT

INTRODUCTION: Pulmonary hemorrhage (PHem) is a severe and often fatal condition in neonates, particularly affecting preterm and very low birth weight infants. It is associated with significant morbidity and mortality, yet distinctions between early- and late-onset PHem and their respective risk factors remain unclear. This study aimed to evaluate clinical characteristics, risk factors, management strategies, and outcomes of neonates with PHem, with a focus on early versus late onset.

MATERIALS AND METHODS: In this retrospective cross-sectional study, medical records of neonates diagnosed with PHem in a tertiary NICU between January 2014 and December 2020 were analyzed. Early PHem was defined as onset within the first 7 days of life, and late PHem as onset thereafter. Collected data included antenatal, perinatal, and postnatal variables, surfactant and PDA management, and clinical outcomes. Statistical analyses included univariate and multivariate logistic regression to identify risk factors for early PHem and mortality.

RESULTS: A total of 80 neonates with PHem were included (mean gestational age 27.7 ± 3.6 weeks; mean birth weight 1092 ± 587 g). Early PHem accounted for 83.7% (n = 67) and late PHem for 16.3% (n = 13) of cases. Infants with early PHem had significantly higher mean airway pressure (MAP) at 12 h (p = 0.044) and a greater need for post-PHem surfactant therapy (p = 0.044). Conversely, late PHem was associated with higher rates of sepsis (p = 0.009), coagulopathy (p = 0.019), and hemodynamically significant PDA (92.3% vs. 47.8%, p = 0.008). Duration of mechanical ventilation (p < 0.001) and oxygen therapy (p = 0.002) were longer in the late PHem group. Overall mortality was 82.5%, with no statistically significant difference between early and late PHem (80.6% vs. 92.3%, p = 0.446).

CONCLUSION: PHem remains a significant cause of neonatal morbidity and mortality. Early and late PHem represent distinct clinical entities with different risk profiles, their management and long-term outcomes are similar. Despite these differences, mortality remains high in both groups. Identification of key risk factors, especially delivery room resuscitation, may guide preventive strategies and optimize neonatal care.

PMID:41853879 | DOI:10.1002/ppul.71568

J Cosmet Dermatol. 2026 Mar;25(3):e70792. doi: 10.1111/jocd.70792.

ABSTRACT

BACKGROUND: Acne vulgaris is one of the most prevalent disorders affecting 9%-10% of the global population, representing as papules, pustules, and comedones, with a pathogenesis involving increased sebum production, C. acnes colonization, and inflammation. Conventional treatments like retinoids and antibiotics often cause side effects, thus diverting attention toward probiotics as an alternative therapy. Lactobacillus probiotics, having their immunomodulatory, anti-inflammatory, and antimicrobial properties, are useful in managing acne by reducing inflammation and oxidative stress with proved safety profile and the potential to reduce antibiotic reliance. This systematic review and meta-analysis evaluate the efficacy of Lactobacillus-based probiotics compared to placebo and benzoyl peroxide in reducing inflammatory lesions, non-inflammatory lesions, and total acne lesion counts. The findings aim to clarify their therapeutic role and provide evidence on their effectiveness and safety.

OBJECTIVES: This systematic review and meta-analysis investigated the effectiveness of oral and topical Lactobacillus-based probiotics or postbiotics, compared with placebo or benzoyl peroxide, in patients with acne vulgaris.

METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted, including studies evaluating oral or topical Lactobacillus-based probiotic or postbiotic interventions in patients with acne vulgaris. Primary outcomes were changes in inflammatory lesion counts, while secondary outcomes included non-inflammatory and total lesion counts, skin hydration, and sebum concentration. All analyses were performed using random-effects models with 95% confidence intervals (CI), and heterogeneity was quantified using the I² statistic.

RESULTS: A total of five RCTs involving 332 participants were included. The pooled mean difference for non-inflammatory lesions was -1.39 (95% CI -5.10 to 2.32, p = 0.46), for inflammatory lesions was -0.08 (95% CI -1.28 to 1.11, p = 0.89), and for total lesion counts was -9.07 (95% CI -20.71 to 2.57, p = 0.13). These results concluded that there was no significant reduction in lesion counts with Lactobacillus-based probiotics as compared to placebo or benzoyl peroxide. Heterogeneity was moderate to low across studies.

CONCLUSION: This meta-analysis indicates that Lactobacillus-based probiotics do not provide significant clinical benefits in reducing inflammatory lesions, non-inflammatory lesions, and total acne lesion counts in Acne vulgaris patients compared to placebo or benzoyl peroxide.

PMID:41853869 | DOI:10.1111/jocd.70792

Vet Radiol Ultrasound. 2026 Mar;67(2):e70156. doi: 10.1111/vru.70156.

ABSTRACT

Elastography is a promising technique for assessing tissue stiffness in the adrenal glands of dogs with hypercortisolism (HC). This study compared 30 dogs, 15 of which were healthy (control group) and 15 diagnosed with HC, confirmed by low-dose dexamethasone suppression test (n = 11) or ACTH stimulation test (n = 4) without prior treatment. Ultrasound measurements revealed a significant increase in the dimensions of the adrenal glands, especially in the left adrenal gland, with more frequent changes in the cranial pole (86.7%, p = 0.00003) and caudal pole (80%, p = 0.00005). Qualitative elastography indicated varied tissue stiffness patterns in sick dogs, with a predominance of mixed patterns (46.7%), whereas dogs in the control group showed uniform moderate stiffness. Semiquantitative analysis showed that the adrenal glands of sick dogs were significantly stiffer compared to the adjacent mesentery, with variations ranging from 33% to 80% stiffer. The Mann-Whitney test revealed statistically significant differences in adrenal stiffness between the groups (U = 4.500; Z = -4.621; p < 0.001). These findings suggest that elastography, combined with conventional ultrasonography, may be an effective complementary diagnostic tool in detecting adrenal changes in dogs with HC.

PMID:41853861 | DOI:10.1111/vru.70156

Circulation. 2026 Mar 19. doi: 10.1161/CIRCULATIONAHA.125.079023. Online ahead of print.

ABSTRACT

BACKGROUND: Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias.

METHODS: We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (≥50% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidence of new-onset atrial fibrillation.

RESULTS: Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points; P=0.0045). The responder rate was higher with memantine than with placebo (52.4% versus 23.1%; P<0.0001). Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points; P=0.0043) and was associated with a lower cumulative incidence of new-onset atrial fibrillation (4.8% versus 23.9%; P<0.0001). No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred.

CONCLUSIONS: In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile. These findings provide proof of concept for a novel, non-ion channel-based therapeutic strategy targeting the cardiac glutamatergic system.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06501638.

PMID:41853846 | DOI:10.1161/CIRCULATIONAHA.125.079023

Front Psychol. 2026 Mar 3;17:1773282. doi: 10.3389/fpsyg.2026.1773282. eCollection 2026.

ABSTRACT

BACKGROUND: There is no recommended measure of parent-infant interaction that is psychometrically robust, feasible (i.e., brief and simple to use) and validated for use from birth to 12 months for routine use in Perinatal Mental Health Services (PMHS). This study tested the cross-sectional construct validity of the global sensitivity scale and a sensitivity composite from the NICHD Parent-Infant Interaction scales in a clinical sample of parents and babies, and the inter-rater reliability of all the NICHD scales in a sub-sample of dyads with infants under 3 months of age.

METHODS: Secondary analysis using parent-infant interaction videos from a Randomized Controlled Trial in specialist PMHS in England were used. Participants were 275 dyads who completed baseline self-reports (parental mental health symptoms, parent-reported bonding) and parent-infant observation tasks where sensitivity was measured (free play, book sharing, clothing change). Parents with infants over 2 months of age (N = 180), also completed measures of child development. Non-parametric correlations and linear regression were conducted to assess construct validity and intra-class correlations were conducted to evaluate inter-rater reliability.

RESULTS: Amongst dyads with infants 0-3 months, inter-rater reliability was good for the global and composite sensitivity scale, but poor-to-moderate for the scales of parental intrusiveness, dyadic mutuality and the infant scales. In the full sample of dyads, there was a small but significant negative association between the global and composite sensitivity scales and parental mental health symptom severity, but this association was not statistically significant when sensitivity was observed in the free play alone. In terms of child development, greater sensitivity was only associated with fewer socio-emotional problems when it was observed during the clothing change task. There was a statistically significant negative association between observed sensitivity and bonding difficulties, and the strength of this association was greater for younger infants than older infants.

CONCLUSION: These findings contribute to the evidence base of the NICHD scales in a PMHS setting and suggest ways that the clinical utility of the NICHD scales could be improved for routine practice.

PMID:41853827 | PMC:PMC12992259 | DOI:10.3389/fpsyg.2026.1773282