Category: Statistics

Dermatol Ther (Heidelb). 2025 Sep 4. doi: 10.1007/s13555-025-01503-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Atopic dermatitis (AD) is a chronic, highly pruritic, relapsing inflammatory disease associated with high quality-of-life burden. Topical 1.5% ruxolitinib cream is a selective Janus kinase (JAK)1/JAK2 inhibitor that is well tolerated and effective in improving itch and lesion clearance in patients ≥ 12 years old. This analysis estimates comparative efficacy for 1.5% ruxolitinib cream relative to systemic therapies for treatment of patients ≥ 12 years with AD.

METHODS: A systematic literature review (SLR) identified randomized controlled trials evaluating 1.5% ruxolitinib cream, oral JAK inhibitors, monoclonal antibodies, phosphodiesterase 4 inhibitors, and systemic immunosuppressants. A feasibility assessment evaluated whether indirect treatment comparison (ITC) was appropriate and determined appropriate ITC methods. This network meta-analysis (NMA) assessed the comparative efficacy of 1.5% ruxolitinib cream against systemic therapies in a “systemic-eligible moderate AD” subgroup defined as ≥ 12 years old and eligible for topical and systemic therapies (Investigator’s Global Assessment [IGA] = 3, Eczema Area and Severity Index [EASI] ≥ 16, and body surface area ≥ 10%); an ITC with the full study populations was not feasible. A frequentist framework using a penalized likelihood NMA included outcomes of IGA 0/1 with at least a 2-point improvement from baseline, EASI-75, and Itch Numerical Rating Scale 4 (NRS4).

RESULTS: The SLR identified 25 studies, of which 12 reported outcomes for the relevant subgroup for four interventions: 1.5% ruxolitinib cream, dupilumab 300 mg, upadacitinib (15 mg, 30 mg), and abrocitinib (100 mg, 200 mg), which were compared against placebo or placebo + topical corticosteroids. There were no statistically significant differences between active comparators for IGA 0/1, EASI-75, and Itch NRS4, although point estimates numerically favored 1.5% ruxolitinib cream for IGA 0/1 and EASI‑75.

CONCLUSION: For patients with moderate AD who are eligible for systemic therapies, 1.5% ruxolitinib cream might provide disease control comparable to systemic treatments, such as dupilumab, regarding IGA 0/1, EASI-75, and Itch NRS4.

PMID:40906354 | DOI:10.1007/s13555-025-01503-1

Dermatol Ther (Heidelb). 2025 Sep 4. doi: 10.1007/s13555-025-01505-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Interleukin-1 receptor-associated kinase 4 (IRAK4) is expressed in various immune cells and regulates proinflammatory cytokine production. Its inhibition represents a novel, promising therapeutic option in the treatment of atopic dermatitis (AD). Zabedosertib (BAY1834845) is a potent, selective IRAK4 inhibitor that suppresses markers of local and systemic immune responses. This study aimed to evaluate the efficacy and safety of zabedosertib in adults with moderate-to-severe AD.

METHODS: DAMASK was a randomized, double-blind, 12-week, placebo-controlled, phase 2a, proof-of-concept study. Patients were randomized 2:1 to receive oral zabedosertib 120 mg twice daily or placebo. The primary efficacy endpoint was a composite of 75% reduction from baseline on the Eczema Area and Severity Index (EASI-75), no discontinuation of study medication for lack of efficacy, no rescue medication during the 4 weeks before Day 84, and no initiation of systemic AD treatment. Other efficacy assessments included validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD), Peak Pruritus numerical rating scale score, and affected body surface area (BSA); for safety, it included frequency and severity of treatment-emergent adverse events (TEAEs).

RESULTS: Of 77 randomized patients, 69 were included in the primary efficacy analysis (zabedosertib, n = 47; placebo, n = 22); 55 patients completed treatment. At Week 12, there was no significant difference between zabedosertib and placebo in the primary efficacy endpoint (32.3% vs. 37.4%) or percentage change in EASI from baseline (- 44.6% vs. – 55.9%). There were also no significant differences between zabedosertib and placebo at Week 12 in vIGA-AD response (15.9% vs. 28.5%), Peak Pruritus response (16.4% vs. 25.0%), percentage change in Peak Pruritus (- 20.7% vs. – 27.3%), or percentage change in BSA affected by AD (- 13.3% vs. – 20.3%). No severe or serious TEAEs were reported throughout the study.

CONCLUSIONS: Zabedosertib was safe and well tolerated in adults with moderate-to-severe AD but showed no evidence of efficacy in reducing disease severity or pruritus in this placebo-controlled study.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05656911.

PMID:40906353 | DOI:10.1007/s13555-025-01505-z

J Nephrol. 2025 Sep 4. doi: 10.1007/s40620-025-02380-9. Online ahead of print.

ABSTRACT

BACKGROUND: Kidney function decline is associated with cardiovascular disease and various other morbidities. Previous studies regarding polygenic risk scores of estimated glomerular filtration rate (eGFR) change were generally based on individuals of European ancestry and not validated on populations of East Asian ancestry.

METHODS: We conducted a genome-wide association study for eGFR slope among 26,755 non-diabetic individuals from the Taiwan Biobank. We developed an eGFR slope polygenic risk score and validated its prediction power on chronic kidney disease (CKD) in another sample with 58,777 non-diabetic individuals.

RESULTS: Eight candidate loci associated with eGFR slope (P-value ranging from 1.56 × 10^-6 to 8.73 × 10^-6) located in the SLC9A9, SLC26A8, DEPTOR, OBP2B, PRMT8, C19orf44 genes and an intergenic locus between MTMR12-ZFR genes were identified and a polygenic risk score for eGFR slope was constructed. The polygenic risk score was validated externally to be significantly associated with CKD in another set of individuals (P-value = 0.0182; odds ratio = 0.753; 95% confidence interval: 0.5936-0.9504).

CONCLUSIONS: We constructed a genome-wide polygenic risk score for eGFR decline and externally validated its use in predicting CKD in another Taiwan population. Our eGFR slope polygenic risk score might be useful for clinical CKD risk assessment in future, especially for East Asians.

PMID:40906351 | DOI:10.1007/s40620-025-02380-9

Clin Rheumatol. 2025 Sep 4. doi: 10.1007/s10067-025-07670-y. Online ahead of print.

ABSTRACT

OBJECTIVES: This study compared the incidence and time-to-event outcomes of ocular extraintestinal manifestations (O-EIMs) and EIMs among patients with human leukocyte antigen (HLA)-B27-associated diseases receiving different classes of immunotherapy.

METHODS: A retrospective cohort study was conducted using aggregated electronic health records from the TriNetX network between January 1, 2014, and December 31, 2024. Patients with HLA-B27-associated diseases were included if they were newly prescribed tumor necrosis factor (TNF), janus kinase (JAK), or interleukin (IL) inhibitors on or after their initial diagnosis. The cumulative incidence of O-EIMs and EIMs was calculated per 100 person-years. Kaplan-Meier estimates were used to graph time-to-event outcomes using R Studio (version 4.4.1).

RESULTS: We identified 22,287 patients [mean age 47.2 (16.8) years; 13,132 (58.9) % women]. The cumulative incidence of anterior uveitis from the index date was 0.11 cases per 100 person-years. According to first medication prescribed, the incidence of anterior uveitis was lowest in patients prescribed IL inhibitors, followed by JAK and TNF inhibitors (0.07%, 0.10%, and 0.20%, cases per 100 person-years respectively). Time-to-event analysis showed a higher likelihood of anterior uveitis with initial TNF inhibitor use, although the difference was not statistically significant. Regarding EIMs, incident sacroiliitis was highest with TNF (0.91%), followed by JAK (0.72%) and IL (0.37%). Psoriatic dermatitis incidence was highest with JAK inhibitors (2.85%), compared to TNF (2.19%) and IL (2.17%).

CONCLUSION: In this cohort study of patients with HLA-B27-associated diseases, the lack of statistical significance indicates similar effectiveness across immunotherapy classes in preventing O-EIMs and EIMs. Key Points • Large-scale comparative study assessing time-to-incident O-EIMs and EIMs in patients with HLA-B27-associated diseases treated with TNF, JAK, or IL inhibitor therapies using real-world data from the TriNetX network. • Low overall incidence of O-EIMs and EIMs was observed across all immunotherapy classes, with no statistically significant difference in time-to-event outcomes, indicating similar effectiveness in preventing these manifestations.

PMID:40906344 | DOI:10.1007/s10067-025-07670-y

Sleep Breath. 2025 Sep 4;29(5):280. doi: 10.1007/s11325-025-03448-3.

ABSTRACT

PURPOSE: Armodafinil has been approved for treating excessive daytime sleepiness (EDS) in OSA patients who still experience EDS after adequately treated with CPAP. However, the effectiveness of armodafinil administration in OSA patients with suboptimal CPAP usage and persistent EDS remains unexplored.

METHOD: A 12-week prospective cohort study enrolled 33 moderate to severe OSA patients with suboptimal CPAP usage (2- < 4 h/night) who experienced EDS and were naïve to armodafinil. Patients received daily 150 mg of armodafinil and continued using CPAP. Efficacy and adverse events were evaluated.

RESULTS: A total of 30 patients with mean age of 45.10 ± 10.74 years and Epworth sleepiness scale (ESS) of 13.93 ± 3.16 completed the study; however, one participant completed only the 8-week follow-up. After 12 weeks, ESS was significantly decreased by 5.03 ± 4.22 (p < 0.001). Clinical global impression (CGI) rated by investigators and by participants was significantly decreased by 1.79 ± 0.72 (p < 0.001) and 1.93 ± 0.75 (p < 0.001); respectively. Pittsburgh sleep quality index (PSQI) was significantly decreased by 5.27 ± 2.93 (p < 0.001). The OSLER error index did not significantly improved (p = 0.61); however, a trend toward improvement was observed in patients with baseline psychomotor vigilance impairment (p = 0.17). While CPAP adherence showed no statistically significant change, there was a trend toward improvement from 2.99 ± 0.63 h/night at baseline to 3.47 ± 1.38 h/night (p = 0.09). No serious side effects were observed.

CONCLUSION: In moderate to severe OSA patients with suboptimal CPAP usage who still experience EDS, administering armodafinil over 12 weeks period significantly improved EDS and sleep quality subjectively without compromising CPAP adherence. Armodafinil demonstrated excellent tolerability with self-limiting side effects.

PMID:40906339 | DOI:10.1007/s11325-025-03448-3

Sleep Breath. 2025 Sep 4;29(5):281. doi: 10.1007/s11325-025-03455-4.

ABSTRACT

PURPOSE: The objectives of this study were to monitor transcutaneous and end-tidal partial pressures of CO₂ simultaneously during polysomnography, determine the advantages and disadvantages of each method, and identify relevant factors that can affect the results.

METHODS: This cross-sectional study enrolled 55 adults who underwent polysomnography at the Ajou University Hospital Sleep Center between February 2021 and September 2022. They were volunteers who spontaneously breathed room air. Polysomnography reports, including those of CO₂ monitoring, of all participants were reviewed and analyzed by sleep experts. Generalized Estimation Evaluation, Bon Ferroni Post Hoc and multivariable regression analysis were used for statistical analysis.

RESULTS: Throughout all sleep stages, the mean, highest, and lowest values of end-tidal and transcutaneous partial pressure of CO₂ showed significant differences. The mean transcutaneous partial pressure was higher than the mean end-tidal partial pressure by 2.53 mmHg. The apnea index, apnea-hypopnea index, and height were significant factors affecting the difference between the mean transcutaneous and end-tidal partial pressure of CO₂. As the obstructive sleep apnea grade increased, the mean end-tidal CO₂ partial pressure value decreased. Two patients had hypoventilation; one met the criteria based on the transcutaneous partial pressure of CO₂ and the other met those based on the end-tidal partial pressure of CO₂.

CONCLUSION: During diagnostic sleep studies, the application of both transcutaneous and end-tidal measurements is suggested for stable and accurate monitoring of partial pressure of CO₂ and complementary analysis.

PMID:40906334 | DOI:10.1007/s11325-025-03455-4

Cancer Causes Control. 2025 Sep 4. doi: 10.1007/s10552-025-02042-y. Online ahead of print.

ABSTRACT

BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and it is indicative of poor prognosis and progressive functional impairment. The role of the gut microbiome in the development of cachexia in colorectal cancer (CRC) patients has not been established.

METHODS: Pre-surgical stool samples from n = 103 stage I-III CRC patients in the ColoCare Study were analyzed using 16S rRNA gene sequencing (Illumina) to characterize fecal bacteria. We calculated estimates of alpha- and beta-diversity and a priori- and exploratory-selected bacterial relative abundance. Using Fearon criteria, cachexia onset at 6 months post-surgery was defined as > 5% weight loss over the past 6 months and/or body mass index (BMI) of < 20 kg/m² and weight loss of > 2%. Associations of microbial metrics with cachexia onset were estimated using multivariable logistic regression models.

RESULTS: Higher alpha-diversity was positively associated with cachexia onset, with stronger associations in females, patients < 65 years, those receiving adjuvant treatment, consuming high fiber, or with energy intake outside USDA recommendations (p < 0.05). Porphyromonas (OR = 0.51, 95% CI 0.26-0.89, p = 0.03) and Actinomyces (OR = 0.72, 95% CI 0.48-1.03, p = 0.08) were inversely associated with cachexia, although the association for Actinomyces did not reach statistical significance. Stratified analyses revealed a stronger inverse association between Porphyromonas and cachexia onset in males, patients with rectal or stage III tumors, those receiving neoadjuvant treatment, physically inactive individuals, and those consuming low fiber. However, these associations did not reach statistical significance (0.05 ≤ p < 0.10).

CONCLUSION: Higher gut microbial alpha-diversity and lower relative abundances of the genera Porphyromonas and Actinomyces in pre-surgery stool samples were associated with onset of cachexia in CRC patients six months post-surgery. This is the first study to explore a link between the gut microbiome and cachexia in CRC patients, providing novel insights into the biology of cachexia and potential clinical interventions.

PMID:40906320 | DOI:10.1007/s10552-025-02042-y

Aesthetic Plast Surg. 2025 Sep 4. doi: 10.1007/s00266-025-05189-w. Online ahead of print.

ABSTRACT

INTRODUCTION: This meta-analysis evaluates the impact of ethnicity-conscious rhinoplasty on patient satisfaction and complication rates. Traditional rhinoplasty techniques often overlook ethnic anatomical differences, leading to suboptimal aesthetic outcomes and higher revision rates. In contrast, individualised approaches aim to optimise both form and function by tailoring procedures to specific anatomical and cultural contexts.

METHODS: A systematic search of PubMed, PROSPERO, DynaMed, EMBASE, and the Cochrane Library was conducted in April 2025. Seventeen comparative clinical studies (2003-2023) were included in a PRISMA-compliant meta-analysis (PROSPERO ID: CRD420251045319). Primary outcomes were patient-reported satisfaction, complication rates, and revision frequency. Secondary analyses assessed effectiveness of specific surgical techniques across major ethnic groups: Hispanic/Mestizo, African-American, Middle Eastern, Indian-American, Asian, and Caucasian. Statistical analyses used RevMan 5.4 with random-effects modelling and I² for heterogeneity. Study quality was evaluated using the Newcastle-Ottawa scale and AHRQ criteria.

RESULTS: Ethnicity-conscious rhinoplasty was associated with significantly greater patient satisfaction (SMD = 0.68 [95% CI 0.63-0.73]; p < 0.001). The highest satisfaction was observed in multi-ethnic (SMD = 0.76), African-American (0.71), and Middle Eastern (0.63) groups. Indian (0.58) and Asian (0.55) patients also showed favourable outcomes, while Caucasian patients had the lowest satisfaction (0.21). Tailored approaches resulted in lower complication (8.7%) and revision (5.3%) rates compared to conventional methods (17.4% and 12.1%). Heterogeneity was minimal (I² = 0%), with no evidence of publication bias.

CONCLUSION: Ethnicity-conscious rhinoplasty enhances patient satisfaction and safety across diverse populations. These findings support the need for culturally and anatomically informed surgical planning in modern aesthetic practice.

LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:40906288 | DOI:10.1007/s00266-025-05189-w

Aesthetic Plast Surg. 2025 Sep 4. doi: 10.1007/s00266-025-05185-0. Online ahead of print.

ABSTRACT

BACKGROUND: No studies in Japan have investigated delayed-onset inflammatory nodules as an adverse event following hyaluronic acid (HA) injections. Our institution, located in a rural area with no nearby aesthetic clinics, allows for comprehensive follow-up of HA-treated patients. This study analyzed complications from 673 cases over 6 years, focusing on delayed-onset inflammatory nodules.

METHODS: A retrospective review of medical records was conducted for patients treated with AbbVie-Allergan HA products between January 2018 and December 2023. Adverse events were categorized as acute complications or delayed-onset inflammatory nodules. Statistical analysis assessed product type, time to onset, patient history, and treatment approaches.

RESULTS: One acute allergic reaction and seven cases (1.07%) of delayed-onset inflammatory nodules were identified. Volbella was involved in 4 cases, Volift in 1 case, Voluma in 1 case, and Ultra Plus in 1 case. Statistical analysis revealed a significantly higher incidence with Volbella (p = 0.0484). The average onset was 144 days, with no seasonal pattern. Among affected patients, three had a history of non-HA-related allergies, and one had a preceding infection. Treatments included oral antibiotics (2 cases), oral antihistamines (5 cases), topical steroids (3 cases), hyaluronidase injections (4 cases), oral steroids (2 cases), and surgical intervention (1 case).

CONCLUSIONS: Delayed-onset inflammatory nodules occurred in approximately 1% of cases, with Volbella showing the highest incidence. Patients with allergies or prior infections may have an increased risk. Comprehensive informed consent should emphasize potential delayed complications to ensure patient understanding.

LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:40906285 | DOI:10.1007/s00266-025-05185-0

Knee Surg Sports Traumatol Arthrosc. 2025 Sep 4. doi: 10.1002/ksa.70052. Online ahead of print.

ABSTRACT

PURPOSE: To compare graft synovialization and tear rates between autograft and allograft anterior cruciate ligament (ACL) reconstruction based upon second-look arthroscopy (SLA), along with joint stability, subjective and objective clinical outcomes.

METHODS: A systematic search of PubMed, Embase and the Cochrane Library was conducted on 7 March 2025, to identify studies reporting graft synovial coverage and tear rates on SLA following primary ACL reconstruction. Meta-analyses were conducted using a random-effects model with logit transformation. Study weights were calculated via the inverse variance method. Heterogeneity was assessed using Cochran’s Q and the I² statistic. Forest plots were created to display individual and pooled estimates with 95% confidence intervals.

RESULTS: A total of 26 clinical studies comprising 2891 patients were included in this systematic review. Of these, 2164 patients underwent ACL reconstruction with autografts and 727 with allografts. SLA was performed in 2009 patients, including 1570 in the autograft group (78.1%) and 481 in the allograft group (23.9%). Good synovial coverage (>50% of the graft) was observed in 1303 autograft cases (83%) and 341 allograft cases (70.9%) (p < 0.001). Poor synovial coverage (<50%) was seen in 146 autografts (9.3%) and 93 allografts (19.3%) (p < 0.001). Torn grafts were found in 125 autografts (8%) and 25 allografts (10%) (n.s.). No significant differences in synovial coverage or graft tear rates were observed when comparing single bundle versus double bundle ACL reconstructions. Mean anterior tibial translation was significantly lower in the autograft group compared to the allograft group (1.23 ± 0.68 vs. 2.00 ± 0.38 mm; p < 0.001). No significant differences were noted in postoperative Lachman (n.s.) and pivot shift tests (n.s.), or in subjective outcomes based on Lysholm (p = 0.05) and Tegner scores (n.s.). However, significantly more patients in the autograft group achieved normal (A) or nearly normal (B) International Knee Documentation Committee (IKDC) objective scores (p = 0.02), whereas higher rates of abnormal or severely abnormal (grades C and D) IKDC scores were observed in the allograft group (p < 0.001). Remnant-preserving ACL reconstruction resulted in significantly better synovial coverage, fewer graft tears and improved knee stability compared to conventional ACL reconstruction (all p < 0.001), with no difference in cyclops lesion incidence (n.s.).

CONCLUSIONS: Autograft ACL reconstruction showed superior synovial coverage, lower retear and failure rates, reduced anterior tibial translation and better IKDC objective scores compared to allografts. Remnant-preserving techniques further enhanced synovial coverage, lowered graft tear rates and improved joint stability. No significant differences in synovial coverage, graft tears or failure rates were observed between single bundle and double bundle ACL reconstruction.

LEVEL OF EVIDENCE: Level IV, systematic review and meta-analysis.

PMID:40905314 | DOI:10.1002/ksa.70052