Tag: statistics

Dermatol Ther (Heidelb). 2025 Nov 15. doi: 10.1007/s13555-025-01592-y. Online ahead of print.

ABSTRACT

INTRODUCTION: A matching-adjusted indirect comparison (MAIC) was performed comparing the efficacy of delgocitinib and dupilumab in patients with atopic hand eczema (AHE), one aetiological subtype of chronic hand eczema (CHE).

METHODS: DELTA 1/2 were phase 3 trials in which adults with moderate to severe CHE received delgocitinib cream 20 mg/g or cream vehicle twice daily for 16 weeks. LIBERTY-AD-HAFT was a phase 3 trial in which patients with moderate to severe AD with hand or foot involvement received subcutaneous dupilumab or placebo every 2 weeks for 16 weeks. An anchored MAIC was conducted using individual patient data (IPD) from DELTA 1/2 and aggregate published data from LIBERTY-AD-HAFT, with vehicle and placebo as the common anchor. IPD from patients with AHE as the primary subtype in DELTA 1/2 were weighted to match age, race, sex and baseline Hand Eczema Severity Index (HECSI) score in LIBERTY-AD-HAFT.

RESULTS: LIBERTY-AD-HAFT included 133 patients (dupilumab, n = 67, placebo, n = 66) while DELTA 1/2 included 345 patients with AHE; the effective sample size after weighted matching was 201 (delgocitinib, n = 128, cream vehicle, n = 73). Anchor-adjusted odds ratios comparing delgocitinib versus dupilumab at week 16 were 1.1 (95% CI: 0.3, 3.4; p = 0.890) for Investigator’s Global Assessment for Chronic Hand Eczema / Hand and Foot Investigator’s Global Assessment score 0/1, 1.2 (95% CI: 0.4, 3.2; p = 0.773) for HECSI 75 and 1.3 (95% CI: 0.4, 4.9; p = 0.661) for HECSI 90 while response difference for HECSI percent improvement was 11.7% (95% CI: -9.2%, 32.7%; p = 0.273).

CONCLUSIONS: Topical delgocitinib and dupilumab in patients with AHE had comparable efficacy, with all results being numerically in favour of delgocitinib, although not statistically significant.

CLINICAL TRIAL REGISTRATION: NCT04871711, NCT04872101, NCT04417894.

PMID:41240207 | DOI:10.1007/s13555-025-01592-y

Mycopathologia. 2025 Nov 15;190(6):117. doi: 10.1007/s11046-025-01023-8.

ABSTRACT

INTRODUCTION: Cryptococcosis is a systemic mycosis prevalent in immunosuppressed individuals, particularly those with HIV/AIDS. Immune recovery achieved through antiretroviral therapy (ART) is crucial for controlling opportunistic infections in AIDS. Given clinical observations and evidence suggesting Cryptococcus spp. accelerates HIV replication in vitro, we hypothesized that cryptococcosis may hinder immune recovery in severely immunosuppressed AIDS patients.

OBJECTIVE: To investigate the association between cryptococcosis and immune recovery in AIDS patients with severe immunosuppression (CD4 + T-cells ≤ 200 cells/mm³) after starting ART.

METHODS: From 230 consecutive patients, those followed for > 100 days were included in a matched cohort study: 21 with cryptococcosis and 67 without, matched by CD4 + T-cells range at a 3:1 ratio. Immune recovery was defined as achieving a CD4 + T-cells count ≥ 350 cells/mm³. Statistical analyses included chi-square, Fisher’s exact, Mann-Whitney U tests, multivariate logistic regression, and Kaplan-Meier curves analyzed with Log Rank. A p-value < 0.05 was significant.

RESULTS: Immune recovery rates were lower in the cryptococcosis group (19.0 vs. 38.8%, p = 0.096). Multivariate analysis revealed that younger age (< 40 years), undetectable HIV viral load, and longer follow-up were independently associated with immune recovery. Patients with cryptococcosis had a 3.61-fold increased odds of immune recovery failure (95% CI 0.90-14.53; p = 0.071), approaching statistical significance.

CONCLUSION: These findings suggest that cryptococcosis may impair immune recovery in AIDS patients with severe immunosuppression. Further studies with larger cohorts are needed to confirm these results.

PMID:41240188 | DOI:10.1007/s11046-025-01023-8

Eur J Pediatr. 2025 Nov 15;184(12):765. doi: 10.1007/s00431-025-06627-2.

ABSTRACT

The current gold standard for neonatal hyperbilirubinemia is phototherapy. However, phototherapy for a longer duration has side effects like fluid imbalance and diarrhea. Probiotics and synbiotics are used as adjuncts to reduce the duration of phototherapy. Three electronic databases, namely PubMed, clinicalTrials.gov, and the Cochrane Library, cover the period from inception up to May 2025. Neonates with hyperbilirubinemia treated with probiotics/synbiotics in addition to phototherapy were included. Review Manager (5.4.1) was used for data analysis. Subgrouping based on gestational age and probiotic and synbiotic strains was done. The risk of bias was assessed using the Cochrane RoB2 tool. A total of 17 RCTs involving 2017 neonates were included. Our analysis revealed that neonates who received probiotic/synbiotic supplementation along with phototherapy showed statistically significant reductions in duration of hospitalization (MD, – 0.35; 95% CI, – 0.49 to – 0.20) and phototherapy (MD, – 13.10; 95% CI, – 19.19 to – 7.01). Moreover, neonates in the probiotic/synbiotic group demonstrated significant reductions in serum bilirubin levels at 24 h (MD, – 1.45; 95% CI, – 2.19 to – 0.72) and a borderline difference between the two groups at 72 h (MD, – 0.54; 95% CI, – 1.07 to – 0.02). In contrast, discharge bilirubin favored phototherapy alone (MD, 0.22; 95% CI, 0.19 to 0.26).

CONCLUSION: Probiotics/synbiotics, in combination with phototherapy, may reduce the duration of phototherapy, hospitalization, and serum bilirubin levels at 24 and 72 h; however, the findings are heterogeneous, and the results for discharge bilirubin are inconsistent. This emphasizes the need for further population- and strain-specific multicenter RCTs.

WHAT IS KNOWN: • Probiotics/Synbiotics combined with phototherapy may shorten phototherapy duration and hospitalization, but subgroup effects, strain-specific efficacy, and the impact on bilirubin at specific time points remain unclear due to variable study quality and mixed populations.

WHAT IS NEW: • This meta-analysis provides a more refined and clinically meaningful evaluation by focusing specifically on live-strain probiotics/synbiotics, prespecified subgroups (term vs preterm), and standardized outcomes (24h, 72h bilirubin, discharge bilirubin). • We identified a consistent reduction in hospitalization and phototherapy duration, but importantly found that bilirubin at discharge was lower in the phototherapyonly group, a novel finding likely influenced by study design differences (including blinding status).

PMID:41240173 | DOI:10.1007/s00431-025-06627-2

J Clin Immunol. 2025 Nov 15;45(1):161. doi: 10.1007/s10875-025-01962-3.

ABSTRACT

X-linked agammaglobulinemia (XLA) is caused by loss-of-function variants in Bruton’s tyrosine kinase, leading to absence of circulating B lymphocytes and inability to produce antibodies. Despite the fear that patients with XLA would be at high risk for severe infection when the novel virus SARS-CoV-2 emerged in the society with low pre-existing immunity, most patients with XLA did not suffer from severe disease. However, some patients were critically affected. Factors associated with hospitalization in patients with XLA remain poorly described. Thus, we designed a study to determine risk factors associated with hospitalization due to Covid-19 in patients with XLA. Data was collected from 17 sites in Europe and the US, comprising n = 81 patients, with hospitalization due to SARS-CoV-2 infection in 14 patients. Nearly 17% of patients with XLA required hospitalization due to Covid-19, but only 3 patients had ventilatory support. After correcting for the effect of the date of infection during the early pandemic, univariate and multiple logistic regression analysis showed that preexisting bronchiectasis and lower IgG serum trough levels (< 8 g/L) before infection were associated with an increased risk for hospitalization, with a high rate of superinfection. The lack of vaccination seemed to contribute to this risk, and ambulatory patients had higher amounts of CD4⁺ T cells before infection compared to hospitalized patients. Thus, our data suggests a need for IgG trough levels above 8 g/L, especially in patients with bronchiectasis, to protect patients with XLA during viral infections such as Covid-19 and reduce morbidity due to superinfections.

PMID:41240154 | DOI:10.1007/s10875-025-01962-3

Biogerontology. 2025 Nov 15;27(1):2. doi: 10.1007/s10522-025-10354-4.

ABSTRACT

While immune system involvement in aging is increasingly recognized, causal relationships between specific immune cell populations and biological aging indicators remain unclear. We aimed to identify immune targets influencing aging trajectories to inform future immunomodulatory interventions. We conducted two-sample Mendelian randomization (MR) analysis using immunophenotype GWAS data (3,757 Sardinian participants) and aging phenotype statistics (PhenoAgeAccel: n = 107,460; BioAgeAccel: n = 98,446). Analysis employed IVW methodology with sensitivity analyses including weighted median estimation, MR-Egger regression, MR-PRESSO, and Cochran’s Q statistic. Significance was determined using False Discovery Rate (FDR) correction (P_FDR < 0.05). After FDR correction, seventeen immune cell phenotypes showed significant associations with PhenoAgeAccel: two cDCs, one monocyte subtype, ten myeloid cells, three TBNK cells, and one Treg population. Key findings included protective effects of FSC-A on granulocyte (β = -0.24, 95% CI:-0.37 to -0.10, P_FDR = 1.81 × 10^-2) and risk associations of CD14⁺ CD16^– monocyte (β = 0.41, 95% CI:0.24-0.58, P_FDR = 6.84 × 10^-4). Among TBNK cells, CD8⁺ T cell (β = 0.32, 95% CI: 0.16-0.47, P_FDR = 6.44 × 10^-3) and CD28^– CD8⁺ T cell (β = 0.40, 95% CI: 0.23-0.58, P_FDR = 8.14 × 10^-4) emerged as risk factors. For BioAgeAccel, four phenotypes showed suggestive relationships, with Unswitched Memory B Cell showing the strongest protective effect (β = – 0.32, 95% CI:-0.52 to-0.12, p = 1.75 × 10^-3). Our study revealed causal relationships between specific immune cell phenotypes and biological aging acceleration, identifying potential therapeutic targets for age-modulation and suggesting immune signatures as crucial regulators in aging-related processes.

PMID:41240153 | DOI:10.1007/s10522-025-10354-4

Environ Monit Assess. 2025 Nov 15;197(12):1340. doi: 10.1007/s10661-025-14779-9.

ABSTRACT

Groundwater potential mapping is essential for sustainable water resource management, particularly in tropical lateritic terrains where communities depend heavily on groundwater for domestic and agricultural needs. This study delineates groundwater potential zones (GWPZs) in the Ithikkara River Basin, South Kerala, India, through an integrated geospatial and machine learning framework that combines self-organizing maps (SOM), K-means clustering, and random forest (RF) feature importance analysis. Eight hydro-environmental parameters-land use/land cover (LULC), geomorphology, geology, slope, relative relief, lineament density, drainage density, and mean depth to water table (MDTW)-were normalized and processed in a GIS environment. SOM was trained and optimally clustered into five groundwater potential classes, as supported by a Davies-Bouldin Index (DBI). The clusters were reclassified into very low, low, moderate, high, and very high groundwater potential. RF analysis identified LULC, geomorphology, and geology as the dominant controls on groundwater occurrence. Validation using observed well yield and water table depth confirmed strong agreement, with high-potential zones coinciding with high-yield wells and shallow aquifers in the southwestern and central alluvial-fractured zones. The results provide practical insights for groundwater exploration, artificial recharge planning, and sustainable extraction in hydrogeologically complex terrains of the Western Ghats. Beyond regional applications, the proposed methodology is scalable and interpretable, offering a transferable framework for groundwater potential mapping in other tropical river basins. Future research should incorporate long-term hydroclimatic variability, socio-economic drivers, and climate change projections to further strengthen sustainable groundwater management strategies.

PMID:41240127 | DOI:10.1007/s10661-025-14779-9

Lasers Med Sci. 2025 Nov 15;40(1):481. doi: 10.1007/s10103-025-04730-2.

ABSTRACT

Low-energy semiconductor percutaneous laser disc decompression (LS-PLDD) is a minimally invasive technique that employs laser energy to treat lumbar disc herniation (LDH). To date, no clinical studies have evaluated its efficacy in adolescent patients. This study aimed to assess the safety and effectiveness of LS-PLDD compared with percutaneous endoscopic lumbar discectomy (PELD) in the management of adolescent LDH. Collected data on 30 adolescent LDH patients who underwent LS-PLDD, and 60 adolescent LDH patients who underwent PELD, matched for age and sex. Lumbar ODI scores and back pain VAS scores were recorded preoperatively and at 1 week, 1 month, 3 months, and 6 months postoperatively to evaluate clinical outcomes in the two groups. In addition, lumbar MRI scans obtained preoperatively and at 3 months postoperatively were compared to assess disc changes. The preoperative back VAS scores were (7.0 ± 0.91) and (7 ± 0.8) in the LS-PLDD group and PELD group respectively, with no significant statistical difference (P = 0.779). The VAS scores of both groups had improvement after surgery. At the last follow-up, the VAS scores of both groups were (2.0 ± 1.3) and (1.0 ± 0.8) respectively ( P < 0.01). The VAS scores of patients in PELD group improved most significantly in the first week after surgery and then gradually stabilized, while that in LS-PLDD group improved more gradually during 6 months after surgery. The preoperative ODI scores of the LS-PLDD group and PELD group were (71.1 ± 7.9)% and (68.0 ± 7.3)% (P = 0.061), at the last follow-up, the ODI scores were (28.0 ± 13.1)% and (19.0 ± 8.4)% (P < 0.01). The preoperative canal cross-sectional areas in the LS-PLDD group and PELD group were (1373.0 ± 376.6) and (1457 ± 415.9) respectively, with no significant difference between the two groups (P = 0.157), at the last follow-up, the canal cross-sectional area of the surgical segments were (1373 ± 476.6) and (1457 ± 579.1) (P = 0.227)respectively. This study shows that low energy semiconductor laser LS-PLDD is a safe and effective treatment method for adolescent LDH. It can achieve sustained retraction of the herniated disc and retain the intact structure of the disc.

PMID:41240123 | DOI:10.1007/s10103-025-04730-2

Clin Oral Investig. 2025 Nov 15;29(12):570. doi: 10.1007/s00784-025-06638-1.

ABSTRACT

OBJECTIVES: Obesity is a risk factor for periodontal disease and is associated with socioeconomic status (SES). However, it remains unclear whether SES modifies the relationship between obesity and periodontal disease. This study investigated the influence of SES on the association between obesity and periodontal disease.

MATERIALS AND METHODS: We used multilevel Poisson regression, after adjusting for potential confounding factors including population-level SES, to analyze the body mass index (BMI) and periodontal parameters of 962 participants (mean age 58.3 years; SD: 13.8).

RESULTS: A significant association was observed between obesity and the proportion of teeth with probing pocket depth (PPD) ≥ 4 mm (ratio of means [RM]: 1.25, 95% confidence interval [CI]: 1.14, 1.37; p < 0.001), whereas the high-income group exhibited a significantly lower proportion of teeth with PPD ≥ 4 mm (RM: 0.84, 95% CI: 0.71, 0.998; p = 0.047). Interaction analysis also revealed a significant interaction between obesity and the high-income group regarding the proportion of teeth with PPD ≥ 4 mm (p = 0.020). The subgroup analysis demonstrated that the RM of obesity for the proportion of teeth with PPD ≥ 4 mm was higher in females than in males.

CONCLUSIONS: Income-related inequalities are associated with the relationship between obesity and periodontal disease. Among obese adults, those with low- and middle-income levels may have a higher risk of periodontal disease than those with high income.

CLINICAL RELEVANCE: Comprehensive care and oral health education may be enhanced for obese individuals in low-income populations to mitigate their elevated risk of periodontal disease.

PMID:41240121 | DOI:10.1007/s00784-025-06638-1

Eur J Pediatr. 2025 Nov 15;184(12):763. doi: 10.1007/s00431-025-06568-w.

ABSTRACT

Prognostic scores such as the Pediatric Index of Mortality (PIM-3) are widely used to estimate mortality risk in PICUs, yet their performance in low- and middle-income countries (LMICs) remains uncertain. We aimed to evaluate the predictive performance of PIM-3 in a Moroccan PICU; associations with ICU length of stay (LOS) and duration of mechanical ventilation (MV) were secondary exploratory outcomes. We conducted a prospective cohort study in the Mother-Child PICU at Hassan II University Hospital (Fez, Morocco) from June 1 to September 30, 2024, including all children aged 1 month to 16 years. PIM-3 variables were collected at admission. The primary focus was model performance: discrimination (AUROC, AUPRC), calibration (Hosmer-Lemeshow), and standardized mortality ratio (SMR). Univariable and multivariable regressions were used for the secondary exploratory analyses (mortality correlates, LOS, and MV duration). Among 122 patients, observed mortality was 28.7%, exceeding PIM-3 predictions (SMR = 7.7; p < 0.001). PIM-3 showed good discrimination (AUROC = 0.86; AUPRC = 0.65) but poor calibration. In secondary exploratory analyses, higher PIM-3 scores, lower GCS, multiple organ failures, and need for MV were associated with mortality. MV increased ICU stay duration and organ failures prolonged ventilation duration.

CONCLUSION: In this Moroccan PICU, PIM-3 showed good discrimination but poor calibration and thus underestimated mortality. These findings support considering local recalibration in future work, and exploration of machine-learning-based adaptation for LMIC settings. Clinical trial number: Not applicable.

WHAT IS KNOWN: • PIM-3 is widely used to estimate PICU mortality risk. It was developed and calibrated largely in high-resource settings. • External validations often show good discrimination but variable calibration, with under- or over-estimation in LMICs due to differences in case-mix, care processes, and resources.

WHAT IS NEW: • In a prospective Moroccan PICU cohort (n=122), PIM-3 showed good discrimination (AUROC 0.86; AUPRC 0.65) but markedly underestimated mortality (SMR 7.7). • Higher PIM-3 risk, lower Glasgow Coma Scale, multiple organ failures, and mechanical ventilation were associated with death, underscoring the need for local recalibration and exploration of machine learning-based adaptations for LMICs.

PMID:41240119 | DOI:10.1007/s00431-025-06568-w

World J Urol. 2025 Nov 15;43(1):699. doi: 10.1007/s00345-025-06078-2.

ABSTRACT

PURPOSE: To provide the first randomized study assessing the impact of an Enhanced Recovery after Surgery (ERAS) program on the outcomes of robot-assisted radical prostatectomy (RARP).

METHODS: 129 consecutive patients affected by prostate cancer were randomly assigned to standard-of-care (SoC, 61 patients) or ERAS perioperative protocol (68 patients) during hospitalization for RARP. The differences between the SoC and the ERAS groups were based on preoperative fasting, premedication, anesthesia, analgesia, hydration, and nutrition. The primary endpoint of the study was to compare the length of postoperative hospitalization after RARP surgery between the two groups. Secondary endpoints were the time to autonomous mobilization, the rate of postoperative comorbidities, and patients’ quality of life (QoL) as assessed by a validated questionnaire. The trial was registered on 21/12/2021 on ClinicalTrials.gov (NCT05172986).

RESULTS: Time to autonomous mobilization after surgery was significantly shorter in the ERAS group than in the SoC group (11.9 ± 5.7 h for ERAS and 17.2 ± 5.0 h for SoC, p < 0.001). However, there was no statistically significant difference in the length of postoperative hospitalization (43.1 ± 10.4 vs. 43.7 ± 18.1 h for the SoC and ERAS group, respectively, p = 0.81), time to oral nutrition, complication rate within 30 days from surgery, and QoL domains.

CONCLUSION: Prehabilitation, surgical expertise, and optimized SoC may limit further benefits from ERAS in contemporary RARP. When these three conditions were satisfied, ERAS did not further reduce the length of postoperative hospitalization, time to oral nutrition, postoperative complications, and the impact of surgery on the main domains of the patient’s QoL.

PMID:41240114 | DOI:10.1007/s00345-025-06078-2