Category: Statistics

Clin Res Hepatol Gastroenterol. 2026 Apr 2:102822. doi: 10.1016/j.clinre.2026.102822. Online ahead of print.

ABSTRACT

BACKGROUND: In individuals with normal body weight, altered fat distribution contributes to metabolic dysfunction and hepatic steatosis. We hypothesized that the weight-adjusted waist index (WWI), an indicator of abdominal fat accumulation, is associated with lean MASLD.

METHODS: We analyzed lean adults from 2017-March 2020 pre-pandemic (N = 824). MASLD was defined using controlled attenuation parameter (CAP) from vibration-controlled transient elastography together with metabolic criteria. Four machine learning models (XGB, GBM, LASSO, SVM) were trained to prioritize candidate predictors from anthropometric and metabolic indices. The top consensus predictor was then evaluated in an independent cohort (NHANES August 2021-August 2023, N = 782) using survey-weighted logistic regression, subgroup analyses, and smooth curve fitting to assess potential non-linearity.

RESULTS: Across models, WWI ranked as the most important feature for discriminating lean MASLD and exceeded established indices such as the lipid accumulation product (LAP) and cardiometabolic index (CMI) in global importance metrics. The XGB model achieved the highest discrimination (AUC = 0.756). In the validation cohort, MASLD prevalence increased across WWI quartiles (7.5% to 44.0%). As a continuous variable, WWI was associated with MASLD after full adjustment (OR = 3.08, 95% CI: 1.53-6.21). However, quartile-based associations were attenuated and not statistically significant in the fully adjusted model. A modest trend across quartiles remained. Subgroup analyses demonstrated generally consistent associations across demographic and clinical strata. The dose-response analysis suggested a non-linear relationship, with MASLD risk increasing more steeply beyond a WWI of approximately 11 cm/√kg.

CONCLUSIONS: Among lean adults, WWI is independently associated with MASLD and may capture central-adiposity-related risk not reflected by BMI alone. WWI could serve as a simple complementary anthropometric marker for risk stratification in normal-weight populations, pending prospective validation.

PMID:41935737 | DOI:10.1016/j.clinre.2026.102822

Free Radic Biol Med. 2026 Apr 2:S0891-5849(26)00270-4. doi: 10.1016/j.freeradbiomed.2026.03.073. Online ahead of print.

ABSTRACT

BACKGROUND: Personalized antioxidant supplementation is promoted to optimize redox balance and inflammation profile.

OBJECTIVE: To quantify the short-term effects of vitamin C supplementation on redox and inflammatory outcome measures and explore the potential for supplement response heterogeneity in participants with vitamin C inadequacy through aggregated sets of multi-cycle n-of-1 trials.

METHODS: Eight healthy young males (age 25.56 ± 3.15 years, body mass 68.24 ± 9.70 kg) completed four supplementation (vitamin C 1g) and four placebo trials administered on repeated occasions in randomized sequences following a 1-month run-in period. Vitamin C, F₂-isoprostanes, interleukin-6, and tumor necrosis factor-α were assessed as primary outcomes. Separate within-participant linear mixed-effects modelling and meta-analytic models estimated replicate-averaged treatment effects and person-by-treatment response variation to vitamin C supplementation.

RESULTS: Supplementation resulted in a statistically significant increase in plasma vitamin C of 20.6 μmol/L (95% confidence interval [CI]: 16.8 to 24.5). This mean treatment effect was lower than our selected clinically important threshold of 23 μmol/L. Vitamin C supplementation reduced F₂-isoprostanes by 25.9 pg/mL (CI: 22.2 to 29.6 pg/mL), interleukin-6 by 1.2 pg/mL (CI: 0.7 to 1.7 pg/mL), and tumor necrosis factor-α by 0.5 pg/mL (CI: 0.2 to 0.9 pg/mL). The participant-by-treatment variance component from linear mixed-effects modelling was not statistically significant for all outcomes (P>0.05), agreeing with the small τ-statistics for all outcomes. Shrinkage-adjusted estimates also showed strong shrinkage toward the mean, indicating that the observed response variation mainly reflected random within-person cycle-to-cycle variability rather than true inter-individual variability.

CONCLUSIONS: Replicate-averaged treatment effects of vitamin C supplementation on our study outcomes were statistically significant, but heterogenous treatment effects were not detected between participants with baseline inadequacy. Cycle-to-cycle within-participant variation was larger than the observed inter-individual variability for each primary outcome response, suggesting that, if clinically relevant, “average treatment” may suffice for people prone to vitamin C inadequacy.

CLINICAL TRIAL REGISTRY: Open Science Framework (osf.io/e567r).

ETHICS: ERC-009/2024; #83059/2024.

PMID:41935704 | DOI:10.1016/j.freeradbiomed.2026.03.073

Am J Obstet Gynecol MFM. 2026 Apr 2:101959. doi: 10.1016/j.ajogmf.2026.101959. Online ahead of print.

ABSTRACT

BACKGROUND: The postpartum period is a critical window to address maternal health inequities. Black, Hispanic, Indigenous, and rural populations experience disproportionately high rates of postpartum morbidity and postpartum hospital use (PHU), defined as readmissions or emergency department visits after delivery. Delivery hospitalizations provide an opportunity for early identification of individuals at high risk of PHU, who may benefit from targeted interventions to prevent adverse outcomes. We previously developed a 30-day PHU prediction model using New York City (NYC) birth data (2016-2018), which achieved an area under the receiver operating curve (AUC) of 0.69. However, its performance in obstetric populations outside of a dense urban setting has not been examined.

STUDY DESIGN: We aimed to evaluate the accuracy of our PHU prediction model in South Carolina (SC) and Florida (FL), states with diverse populations, including substantial rural representation, and in a different US geographic region than the NYC development sample. We additionally examined model performance in subgroups defined by race/ethnicity, Medicaid insurance, and rural residence.

METHODS: We performed a retrospective cohort study of linked birth certificate and hospital discharge data from 2016-2019 births in SC (n=183,836) and FL (n=696,963). We ascertained 21 predictors consistent with the NYC model, excluding two variables (prenatal depression, Apgar) unavailable in the new states. PHU was defined as ≥1 inpatient or ED encounter within 30 days postpartum. Model performance was assessed using calibration (intercept, slope) and discrimination (AUC). We first applied the original NYC model coefficients to generate PHU predicted probabilities among SC and FL births. We then tested a series of stepwise model updating strategies: recalibrating intercepts, re-estimating predictor coefficients, and incorporating additional contextual indicators of hospital access – residential rurality and driving distance to the nearest delivery hospital – hypothesized to be relevant in settings with larger rural populations.

RESULTS: Cumulative 30-day PHU incidence was 7.4% in SC and 7.2% in FL; rates were higher among Black individuals, Medicaid-insured individuals, and rural residents. Applying the original NYC model coefficients achieved an AUC of 0.68 [95% CI 0.67-0.68] and 0.69 [95% CI 0.68-0.69] among SC and FL births, respectively, but generated overestimated and extreme risk predictions compared with observed risk. Updating model intercepts corrected calibration, and additionally re-estimating coefficients resulted in an AUC of 0.69 [95% CI 0.68-0.69) in SC and 0.70 [95% CI 0.70-0.71] in FL. Inclusion of hospital distance and rurality did not meaningfully change calibration or discrimination. Model discrimination was slightly lower when subset to Black, Medicaid-insured, and rural residents, but AUC increased within each group after re-estimating predictor coefficients.

CONCLUSION: A PHU prediction model developed in an urban NYC cohort demonstrated similarly moderate discrimination in SC and FL as in the original NYC sample but overestimated absolute risk in these new settings. Modest model updating, including recalibration of intercepts and re-estimation of coefficients, yielded well-calibrated models without requiring new predictors. Hospital access measures did not substantially improve prediction. These findings demonstrate that an existing prediction model for postpartum acute care use can be adapted for use in geographically and socio-demographically diverse populations. Geographic validation and model updating are important steps in deploying predictive tools to reduce persistent gaps in maternal health outcomes.

PMID:41935688 | DOI:10.1016/j.ajogmf.2026.101959

J Allergy Clin Immunol. 2026 Apr 2:S0091-6749(26)00222-8. doi: 10.1016/j.jaci.2026.03.017. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma has heterogeneous risk factors, subtypes, and treatments. It is often unclear how to stratify this heterogeneity in scientific studies and clinical care. Genetics could explain root causes of this clinical heterogeneity, called endotypes, but prior studies have used models that are not designed for complex diseases like asthma.

OBJECTIVE: We aimed to find genetic effects that partly explain different asthma endotypes.

METHODS: We used recent powerful and robust statistical models of context-specific genetic effects in complex traits. We identified genetic subtypes by clustering clinical asthma features in a case/control cohort, GALA II. We replicated the genetic endotypes in UK Biobank with gene-context interaction tests.

RESULTS: Asthma-associated SNPs, polygenic scores, and genome-wide heritability revealed subtype-specific genetic endotypes correlated with type 2 inflammation (T2), allergy, and neuroticism. We validated the T2 associations with molecular data including nasal RNA-seq. In UK Biobank, we replicated these endotypes and found they interact with several polygenic scores and drug-relevant genes.

CONCLUSION: Our results show how context-specific genetic effects can unravel biomedically meaningful endotypes of complex disease and suggest novel precision treatment strategies.

PMID:41935671 | DOI:10.1016/j.jaci.2026.03.017

J Ethnopharmacol. 2026 Apr 2:121622. doi: 10.1016/j.jep.2026.121622. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum (P. multiflorum) is the dried root tuber of P. multiflorum Thunb., a perennial herbaceous plant belonging to the Polygonaceae family. Traditionally, it is believed to possess effects such as nourishing blood, replenishing yin, and moistening the intestines to relieve constipation. Research indicates that the processing procedure significantly alters the chemical composition, pharmacological activity, and hepatotoxicity of substances; however, the underlying mechanisms responsible for attenuating toxicity and enhancing efficacy remain to be clarified. Traditional experience suggests that with an increase in the number of processing cycles (e.g., nine-time processing), their properties shift from purgative to tonic, yet a systematic comparison of the specific differences among samples subjected to varying processing cycles is still lacking.

AIM OF THE STUDY: Based on the central hypothesis that processing alters the chemical composition profile of P. multiflorum and thereby synergistically regulates its toxicity and efficacy, this study established the fingerprint profiles of samples subjected to different processing cycles (0, 3, 6, and 9 times). It systematically compared the hepatotoxicity and efficacy differences between the raw product and its processed products, and focused on identifying the key bioactive components and potential mechanisms responsible for the distinct toxicity and efficacy between the raw product and the nine-steamed-nine-dried product (9x-P. multiflorum) using spectrum-effect relationship analysis.

MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was first employed to establish the chemical fingerprints of the raw P. multiflorum and its processed products after 3, 6, and 9 cycles of steaming with black bean juice (three-steamed-three-dried product, 3x-P. multiflorum; six-steamed-six-dried product, 6x-P. multiflorum; 9x-P. multiflorum), to characterize the dynamic changes in chemical constituents during processing. Zebrafish models of liver injury, intestinal peristalsis, anemia, and immunosuppression were used to systematically compare the hepatotoxicity and efficacy of samples with different processing cycles, with a focus on the toxicity-efficacy shift between raw P. multiflorum (0 cycles) and 9x-P. multiflorum. Hematoxylin and eosin (H&E) staining was performed to observe histopathological changes and evaluate liver injury. Each group contained 10 zebrafish larvae, and data were statistically analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test. Furthermore, a spectrum-effect relationship model was constructed using grey relational analysis (GRA) combined with the entropy weight method (EWM), to correlate common chemical constituents with hepatotoxicity and efficacy indicators. Finally, network pharmacology and molecular docking were integrated to systematically predict and verify the targets and molecular mechanisms of the screened potential active components, especially those that differed significantly between raw P. multiflorum and 9x-P. multiflorum.

RESULTS: Compared with the control group, raw P. multiflorum significantly decreased the liver area-to-lateral body area ratio (LA/BA) by 29% and increased hepatocyte apoptosis by 72.5%, indicating marked hepatotoxicity. H&E staining revealed hepatocyte swelling, vacuolar degeneration, and focal necrosis. In contrast, 9x-P. multiflorum caused no significant increase in apoptosis and increased the LA/BA by 15.5%. Raw P. multiflorum exerted a strong pro-peristaltic effect, reducing the mean gastrointestinal fluorescence intensity (GI FI) by 31.2%, whereas 9x-P. multiflorum decreased it by only 5.7%. For tonic effects, 9x-P. multiflorum increased red blood cell staining intensity by 203% and macrophage count by 82.5%, which was significantly superior to raw P. multiflorum. Spectrum-effect analysis showed that Peak 5 (emodin-8-O-glucoside, EmG), Peak 7 (emodin, Emo), Peak 6 (physcion-8-O-β-D-glucoside, PhG), and Peak 8 (physcion, Phys) were closely correlated with hepatotoxicity and purgative activity. Peak 4 (2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside, TSG) and Peak 7 (Emo) exhibited stronger correlations with tonic effects. Activity validation confirmed that Emo, Phys, and their glucosides showed varying degrees of hepatotoxicity; Emo and Phys displayed significant purgative effects; while TSG and Emo exerted obvious blood-tonifying activity, verifying the reliability of the spectrum-effect analysis. Network pharmacology identified 28 common targets associated with P. multiflorum-induced liver injury, and protein-protein interaction (PPI) network analysis recognized Estrogen Receptor 1 (ESR1) as a hub target. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed significant enrichment in the PI3K-Akt, mitogen-activated protein kinase (MAPK), and estrogen signaling pathways. Molecular docking confirmed that EmG binds strongly to core targets including ESR1 and epidermal growth factor receptor (EGFR) (binding energy < -7.0 kcal/mol).

CONCLUSIONS: This study verified the central hypothesis: raw P. multiflorum exhibits prominent hepatotoxicity and purgative effects, whereas processing with black bean juice achieves detoxification and enhances blood-tonifying and immune-enhancing efficacy. Emo, Phys, and their glycosides are the main material basis for hepatotoxicity and purgation, while TSG and Emo mediate the tonic effects. Network pharmacology and molecular docking further revealed that conjugated anthraquinones may synergistically disrupt liver-protective pathways via multiple targets such as ESR1 and EGFR. Processing reduces conjugated anthraquinone content and rewires the regulatory targets from a toxicity network toward a tonic network. These findings provide modern scientific evidence for the traditional Chinese medicine (TCM) theory that “raw P. multiflorum purges while processed P. multiflorum tonifies”, and demonstrate the value of integrating spectrum-effect-toxicity correlation with network pharmacology in the mechanistic study of Chinese herbal medicine processing.

PMID:41935648 | DOI:10.1016/j.jep.2026.121622

Int J Infect Dis. 2026 Apr 2:108672. doi: 10.1016/j.ijid.2026.108672. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare secondary SARS-CoV-2 transmission detected through RT-PCR screening in childcare and school-aged settings during the Omicron wave.

METHODS: We analyzed Okinawa School PCR Project events from January 1 to March 11, 2022, in which secondary cases were ascertained through school-based RT-PCR screening conducted after the last exposure. Index cases were classified as child/student or teacher/staff. Secondary cases were defined as RT-PCR-confirmed infections detected through school-based screening. We estimated the proportion of events with ≥1 secondary case and the mean number of secondary cases per event (R_event).

RESULTS: Among 897 events with known index case role, 73.1% detected no secondary cases. In nurseries/kindergartens, secondary cases were detected in 32.3% of teacher/staff-index events (R_event 0.62; 95% CI 0.53-0.72), compared with 12.8% in elementary and secondary schools (R_event 0.15; 95% CI 0.06-0.33). No secondary infections were detected after teacher/staff-index events in junior high (n=11) or high schools (n=6).

CONCLUSIONS: Childcare worker-index events in nurseries and kindergartens generated secondary cases in ≈30% of events, whereas teacher/staff-index events in elementary and secondary schools infrequently generated secondary cases under mitigation measures. Prioritizing screening and prevention resources toward childcare workers may improve efficiency when diagnostic capacity is constrained.

PMID:41935615 | DOI:10.1016/j.ijid.2026.108672

Hip Int. 2026 Apr 4:11207000261426459. doi: 10.1177/11207000261426459. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine factors associated with lag screw slide following fixation of intertrochanteric hip fractures with 1 type of cephalomedullary nail.

METHODS: Retrospective review of patients operatively treated for intertrochanteric hip fractures (OTA/AO 31A1 and 31A2) with a single cephalomedullary nail (CMN) at a single academic medical centre between November 2014 and November 2023. CMN lag screw was placed in “dynamic” mode to allow for controlled collapse, or screw “slide.” Screw slide was defined as the difference in lateral prominence of the lag screw at latest follow up compared to its initial position. Patients were grouped based on the amount of screw slide (<5 mm, 5-15 mm, >15 mm) and correlation analysis was performed.

RESULTS: 614 intertrochanteric hip fracture patients were identified (mean age 80.76 years; 72.3% female) with mean 6.2 months follow-up. Mean amount of slide was 3.77 ± 4.79 mm. 66.3% of patients had <5 mm of slide, while 31.3% had 5-15 mm and 2.4% had >15 mm. Univariate analysis demonstrated that slide >15 mm was associated with increased patient BMI (p = <0.001), use of some anti-osteoporotic medications (p = 0.021) and more than 5 mm of immediate postoperative prominence (p = 0.016). Although not statistically significant, patients with >15 mm of slide were only taking vitamin D and calcium whereas those with <15 mm slide more often took bisphosphonates, denosumab and teriparatide (p = 0.163). Multivariate regression demonstrated that only BMI (OR 1.14, 95% CI, 1.04-1.24; p = 0.002) was associated with >15 mm screw slide.

CONCLUSIONS: Excessive lag screw slide (>15 mm) was associated with higher patient BMI. Patients with higher BMIs should be monitored to identify excessive slide. Surgeons should attempt to keep the lag screw as close to the lateral cortex as possible. While the use of anti-osteoporotic therapy was associated with more slide, this was almost exclusively seen in patients only prescribed vitamin D and calcium.

PMID:41934208 | DOI:10.1177/11207000261426459

Womens Health (Lond). 2026 Jan-Dec;22:17455057261437261. doi: 10.1177/17455057261437261. Epub 2026 Apr 4.

ABSTRACT

BACKGROUND: Pregnancy and substance use disorders (SUD) for incarcerated individuals often overlap, but their management varies greatly between jails. A better understanding of pregnancy management across jails is needed to better guide policy and practice recommendations.

OBJECTIVES: To examine the current state of pregnancy management across North Carolina jails, including current practices, challenges, and gaps in pregnancy management in jails.

DESIGN: This is a qualitative analysis within a mixed-methods study assessing the scope of perinatal incarceration and the capacity of North Carolina jails to manage perinatal SUD.

METHODS: We conducted in-depth interviews with North Carolina jail staff using a semi-structured interview guide between October 2022 and September 2023. We used the ideal-type analysis approach to systematically compare pregnancy management and SUD management practices across facilities.

RESULTS: We completed 26 interviews with jail staff. Pregnancy management approaches were unevenly distributed across three ideal types: (1) exclusive use of internal prenatal care resources (n = 2), (2) exclusive use of external prenatal care resources (n = 16), and (3) hybrid use of both internal and external prenatal care resources (n = 8). Within ideal types, SUD management was highly variable.

CONCLUSION: The heavy reliance on external resources for prenatal and SUD care highlights the chronic underfunding and staffing challenges faced by these facilities. There is an urgent need for standardized policies governing prenatal care in jail facilities to help reduce disparities in care quality and ensure that all pregnant individuals receive adequate support, regardless of the jail’s resources. Alternatives to incarceration during pregnancy should be prioritized.

PMID:41934195 | DOI:10.1177/17455057261437261

Gynecol Endocrinol. 2026 Dec 31;42(1):2650027. doi: 10.1080/09513590.2026.2650027. Epub 2026 Apr 4.

ABSTRACT

OBJECTIVES: This retrospective study compares pregnancy outcomes in polycystic ovary syndrome (PCOS) patients across different controlled ovarian stimulation (COS) protocols-specifically GnRH antagonist and GnRH agonist cycles-combined with various frozen embryo transfer(FET) preparation methods, such as hormone replacement therapy (HRT) and ovulatory cycles. Despite the known variations in COS and FET protocols, the optimal combination for improving pregnancy outcomes in this population remains unclear.

METHODS: We analyzed the first FET cycles of 2510 patients with PCOS at our center between January 2017 and September 2024. Baseline characteristics and pregnancy outcomes were compared using the Kruskal‒Wallis test, the chi-square (χ²) statistic, the Bonferroni correction for multiple comparisons, and inverse probability of treatment weighting (IPTW) adjustment.

RESULTS: After IPTW adjustment, no significant differences were observed in live birth rates or other key reproductive outcomes among the four protocol combinations (all P > 0.05). Exploratory analyses revealed nonsignificant trends, suggesting two patterns: 1) GnRH agonist (vs. antagonist) COS protocols were associated with lower point estimates for the risks of preterm PROM and HDP; 2) ovulation (vs. HRT) cycles for FET preparation were similarly associated with lower point estimates for these risks.

CONCLUSIONS: For PCOS patients, live birth success is equivalent regardless of COS/FET protocol combination, supporting flexible treatment personalization. Clinical decision-making involves a critical trade-off: GnRH agonist protocols and ovulation FET cycles may be associated with a trend toward lower obstetric morbidity, potentially linked to the promotion of a more physiological ovulatory milieu. This balance between immediate iatrogenic risk and long-term pregnancy health warrants further study.

PMID:41934169 | DOI:10.1080/09513590.2026.2650027