Tag: statistics

JAMA Cardiol. 2025 Mar 5. doi: 10.1001/jamacardio.2025.0025. Online ahead of print.

ABSTRACT

IMPORTANCE: Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) have a spectrum of risk, and the effect of therapies may vary by risk.

OBJECTIVES: To validate the Prognostic Models for Mortality and Morbidity in HFpEF (PREDICT-HFpEF) in the phase 3 randomized clinical trial Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) and to evaluate the effect of finerenone, compared with placebo, across the spectrum of risk in these patients.

DESIGN, SETTING, AND PARTICIPANTS: The FINEARTS-HF trial was conducted across 653 sites in 37 countries. Participants were adults 40 years and older with symptomatic HF and left ventricular EF of 40% or greater randomized between September 2020 and January 2023.

INTERVENTION: Finerenone (titrated to 20 mg or 40 mg) or placebo.

MAIN OUTCOMES AND MEASURES: The 3 PREDICT-HFpEF risk scores for the composite outcome of cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death, respectively, were calculated. Predicted risk was compared with observed outcomes. Model performance was assessed using the Harrell C statistic. The rates of the predicted outcomes (plus the composite of cardiovascular death and worsening HF events, which was the primary end point in the trial) were examined according to quintiles of risk score, as was the effect of finerenone according to risk quintiles.

RESULTS: A total of 6001 patients (mean [SD] age, 72 [9.6] years; 3269 male [54.5%]) were randomized in the FINEARTS-HF trial. The C statistics for cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death at 2 years were 0.71 (95% CI, 0.69-0.72), 0.68 (95% CI, 0.66-0.71), and 0.69 (95% CI, 0.67-0.71), respectively. The risk of the composite outcomes was approximately 8- to 10-fold higher in those in the highest compared with the lowest risk quintile. The relative risk reduction with finerenone compared with placebo was consistent across the spectrum of risk for all outcomes examined (eg, interaction P value for primary outcome = .24).

CONCLUSIONS AND RELEVANCE: Results of the FINEARTS-HF randomized clinical trial demonstrate that the PREDICT-HFpEF models performed well in terms of calibration and discrimination. Baseline risk did not modify the benefit of finerenone.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

PMID:40042880 | DOI:10.1001/jamacardio.2025.0025

Eur J Prev Cardiol. 2025 Mar 5:zwaf117. doi: 10.1093/eurjpc/zwaf117. Online ahead of print.

ABSTRACT

AIMS: The role of adult HDL-C in atherosclerotic cardiovascular disease (ASCVD) faces challenges from Mendelian randomisations and drug trials. However, the association between childhood HDL-C and its changes and adult ASCVD remains undefined. This study aimed to determine this association.

METHODS: Participants: Children in the International Childhood Cardiovascular Cohort (i3C) Consortium with childhood HDL-C and adult ASCVD follow-up. Age- and sex-standardized HDL-C z-scores were calculated for childhood (3-19 years), early childhood (3-11 years), and adolescence (12-19 years); Low HDL-C defined as <1.03mmol/L; Participants classified as consistently normal, low-to-normal, normal-to-low, and consistently low based on HDL-C status at early childhood and adolescence. ASCVD events: Identified using self-reports adjudicated by medical records or death registries. Analysis: Cox proportional hazards models quantified the associations between childhood HDL-C and adult ASCVD.

RESULTS: The study included 38,589 participants (49.7% males, mean age in 2016: 46.4 years) with 779 ASCVD and 784 imputed ASCVD events. After adjusting for sex, cohort, age and HDL-C measurement year, higher HDL-C z-scores in childhood, early childhood and adolescence were associated with lower adult ASCVD risk (HRs: 0.81-0.82), with the lowest risk at HDL-C >1.50mmol/L. Normal-to-low (HR 1.38, 95%CI 1.04-1.82) and consistently low (HR 1.94, 95%CI 1.45-2.63) childhood HDL-C increased adult ASCVD risk compared to consistently normal HDL-C. Adjusting for BMI and triglycerides weakened these associations.

CONCLUSIONS: Childhood and adolescent HDL-C were prospectively and inversely associated with adult ASCVD, suggesting that low HDL-C could be a risk maker of adult ASCVD. Future replications, mechanistic studies and Mendelian randomisations on childhood HDL-C may clarify its causal effects on adult ASCVD.

PMID:40042879 | DOI:10.1093/eurjpc/zwaf117

Am J Respir Cell Mol Biol. 2025 Mar 5. doi: 10.1165/rcmb.2024-0282LE. Online ahead of print.

NO ABSTRACT

PMID:40042866 | DOI:10.1165/rcmb.2024-0282LE

JAMA Dermatol. 2025 Mar 5. doi: 10.1001/jamadermatol.2025.0055. Online ahead of print.

ABSTRACT

IMPORTANCE: The uncertainties about the real-world effectiveness of adalimumab biosimilars limit their widespread adoption for psoriasis.

OBJECTIVE: To compare the effectiveness of adalimumab biosimilars Amjevita and Imraldi with Humira for psoriasis.

DESIGN, SETTING, AND PARTICIPANTS: An emulation of 2 targeted pragmatic clinical trials was conducted using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a prospective pharmacovigilance registry tracking individuals receiving biologic and conventional systemic treatments for psoriasis in the UK and the Republic of Ireland. Data from patients with psoriasis using adalimumab registered to BADBIR were included. Data were collected from September 2007 to January 2023, and data were analyzed from January to September 2023.

EXPOSURES: The effectiveness of initiating Amjevita and Imraldi were compared with initiating Humira among adalimumab-naive patients, and the effectiveness of switching from Humira to either Amjevita or Imraldi were compared with continuing Humira among patients who had been using Humira consistently for more than 2 years.

MAIN OUTCOMES AND MEASURES: The study outcomes were absolute Psoriasis Area and Severity Index (PASI) score of 2 or less and PASI score of 4 or less at 12 months after the index date. Inverse propensity treatment weighting was used to analyze receiving either biosimilars or Humira to account for confounding. Multiple imputations were used to account for missing PASI data at 12 months and inverse probability of censoring weighting to account for censorship due to deviation from the treatments under investigation. Logistic regression models were fitted to compare the outcomes between study cohorts.

RESULTS: Of 11 400 included patients, 6924 (60.7%) were male, and the mean (SD) age was 45.3 (12.5) years. A total of 6133 patients were identified in the new user analysis (5416 starting Humira, 382 starting Amjevita, and 335 starting Imraldi) and 5267 patients in the switcher analysis (3808 continuing Humira, 847 switching to Amjevita, and 612 switching to Imraldi). Amjevita and Imraldi new users had no significantly different probability of achieving a PASI score of 2 or less (Amjevita: adjusted odds ratio [aOR], 0.98; 95% CI, 0.78-1.25; Imraldi: aOR, 0.83; 95% CI, 0.64-1.07) and a PASI score of 4 or less (Amjevita: aOR, 1.07; 95% CI, 0.84-1.37; Imraldi: aOR, 0.91; 95% CI, 0.69-1.20) compared with Humira new users. Patients who switched to Amjevita and Imraldi also had no statistically significant differences in achieving a PASI score of 2 or less (Amjevita: aOR, 1.19; 95% CI, 0.94-1.51; Imraldi: aOR, 0.92; 95% CI, 0.72-1.18) and a PASI score of 4 or less (Amjevita: aOR, 1.32; 95% CI, 0.96-1.84; Imraldi: aOR, 1.00; 95% CI, 0.70-1.41) compared with those who continued Humira.

CONCLUSIONS AND RELEVANCE: In this study, Amjevita and Imraldi were as effective as Humira for both new starters and patients switching to biosimilars from Humira.

PMID:40042863 | DOI:10.1001/jamadermatol.2025.0055

Brief Funct Genomics. 2025 Jan 15;24:elaf001. doi: 10.1093/bfgp/elaf001.

ABSTRACT

Molecular epidemiology of Foot-and-mouth disease (FMD) is crucial to implement its control strategies including vaccination and containment, which primarily deals with knowing serotype, topotype, and lineage of the virus. The existing approaches including serotyping are biological in nature, which are time-consuming and risky due to live virus handling. Thus, novel computational tools are highly required for large-scale molecular epidemiology of the FMD virus. This study reported a comprehensive computational tool for FMD molecular epidemiology. Ten learning algorithms were initially evaluated on cross-validated and ten independent secondary datasets for serotype prediction using sequence-based features through accuracy, sensitivity and 14 other metrics. Next, best performing algorithms, with higher serotype predictive accuracies, were evaluated for topotype and lineage prediction using cross-validation. These algorithms are implemented in the computational tool. Then, performance of the developed approach was assessed on five independent secondary datasets, never seen before, and primary experimental data. Our cross-validated and independent evaluation of learning algorithms for serotype prediction revealed that support vector machine, random forest, XGBoost, and AdaBoost algorithms outperformed others. Then, these four algorithms were evaluated for topotype and lineage prediction, which achieved accuracy ≥96% and precision ≥95% on cross-validated data. These algorithms are implemented in the web-server (https://nifmd-bbf.icar.gov.in/MolEpidPred), which allows rapid molecular epidemiology of FMD virus. The independent validation of the MolEpidPred observed accuracies ≥98%, ≥90%, and ≥ 80% for serotype, topotype, and lineage prediction, respectively. On wet-lab data, the MolEpidPred tool provided results in fewer seconds and achieved accuracies of 100%, 100%, and 96% for serotype, topotype, and lineage prediction, respectively, when benchmarked with phylogenetic analysis. MolEpidPred tool provides an innovative platform for large-scale molecular epidemiology of FMD virus, which is crucial for tracking FMD virus infection and implementing control program.

PMID:40042853 | DOI:10.1093/bfgp/elaf001

JAMA Netw Open. 2025 Mar 3;8(3):e250024. doi: 10.1001/jamanetworkopen.2025.0024.

ABSTRACT

IMPORTANCE: Although mother’s own milk (MOM) is associated with reduced risk of neonatal complications of prematurity and improved neurodevelopmental outcomes, to our knowledge, there have been no large US studies reporting rates of MOM feeding initiation and sustained MOM feedings by gestational age (GA).

OBJECTIVE: To compare rates of MOM feeding initiation and continuation at 12 weeks for infants by GA.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study used state-level surveillance data for maternal characteristics and behaviors before and after pregnancy. Participants were women who gave birth from January 1 through December 31, 2021, in 36 US jurisdictions (33 states, the District of Columbia, New York City, and Puerto Rico) and completed the Pregnancy Risk Assessment Monitoring System (PRAMS) questionnaire. Data were analyzed from July 2023 to April 2024.

EXPOSURE: Infant GA, including early preterm (EPT; ≤27 weeks’ gestation), moderately preterm (MPT; 28-33 weeks’ gestation), late preterm (LPT; 34-36 weeks’ gestation), and early term to postterm (≥37 weeks’ gestation).

MAIN OUTCOMES AND MEASURES: MOM feeding initiation and continuation at 12 weeks after delivery. Weighted multivariable binary logistic regression models were used to test the association between MOM feeding initiation and continued provision at 12 weeks after delivery by infant GA.

RESULTS: Among 29 098 births, there were 0.4% EPT, 1.8% MPT, 6.7% LPT, and 91.1% early-term to postterm infants. Unadjusted MOM feeding initiation was highest for EPT infants (89.7% [95% CI, 85.0%-94.7%]) and lowest for LPT infants (81.8% [95% CI, 79.5%-84.1%]). For infants that initially received MOM, 71.6% (95% CI, 70.7%-72.6%) of early-term to postterm infants still received MOM at 12 weeks followed by 63.1% (95% CI, 52.9%-73.2%) of EPT infants, 61.2% (95% CI, 58.0%-64.3%) of LPT infants, and 58.6% (95% CI, 53.4%-63.8%) of MPT infants. After adjusting for maternal characteristics, LPT infants were 4.4 (95% CI, -6.7 to -2.1) percentage points less likely to initiate MOM feedings and those who received any MOM were 6.7 (95% CI, -9.9 to -3.5) percentage points less likely to receive MOM at 12 weeks compared with early-term to postterm infants. There were no differences in adjusted initiation or continuation rates among EPT (3.1 [95% CI, -1.4 to 7.5] percentage points for initiation and -0.0 [95% CI, -8.6 to 8.6] percentage points for continuation) or MPT (2.4 [95% CI, -0.5 to 5.3] percentage points for initiation and -3.3 [95% CI, -8.0 to 1.5] percentage points for continuation) infants compared with early-term to postterm infants.

CONCLUSIONS AND RELEVANCE: This cross-sectional study found that MOM feeding initiation and continuation rates at 12 weeks after birth for LPT infants were substantially lower than rates for infants with other GAs. Research is needed to pinpoint barriers to MOM feeding initiation and continuation in this vulnerable population of infants.

PMID:40042846 | DOI:10.1001/jamanetworkopen.2025.0024

JAMA Netw Open. 2025 Mar 3;8(3):e250089. doi: 10.1001/jamanetworkopen.2025.0089.

ABSTRACT

IMPORTANCE: An important public health goal is to increase tobacco cessation, but there is limited research on associations of vaping with tobacco cessation.

OBJECTIVE: To estimate the association of vaping with long-term tobacco cessation among US cigarette smokers who used electronic nicotine delivery systems (ENDS; ie, e-cigarettes) in 2017.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a nationally representative sample of US cigarette smokers from the Population Assessment of Tobacco and Health cohort at wave 4 (2017) with follow-up at wave 6 (2021). Data were analyzed from June 2023 to June 2024.

EXPOSURE: Wave 4 ENDS use: daily, nondaily, or no use.

MAIN OUTCOMES AND MEASURES: The primary outcomes were 12 or more months’ abstinence from cigarette smoking and 12 or more months’ abstinence from both cigarette and ENDS use, ascertained at wave 6. Propensity score matching was used to control confounding on 14 potential confounders, including interest in quitting, income, age, education, nondaily smoking, and presence of a smoke-free home.

RESULTS: A total of 6013 smokers were included in the sample (3634 aged ≥35 years [weighted percentage, 65.2%]; 3182 female [weighted percentage, 46.5%]). Among smokers who vaped daily (228 individuals), an estimated 20.9% (95% CI, 15.0% to 26.8%) were abstinent from cigarette smoking at follow-up, compared with 14.3% abstinence (95% CI, 13.0% to 15.5%) among smokers who did not vape (5070 individuals) and 12.6% abstinence (95% CI, 9.8% to 15.4%) among smokers who vaped nondaily (715 individuals). Compared with similar propensity score-matched smokers who did not vape, smoking cessation was 4.1 percentage points lower among those who vaped daily (95% CI, -11.9 to 3.6 percentage points; P = .30), a nonsignificant difference. Smoking cessation was 5.3 percentage points lower among those who vaped nondaily (95% CI, -9.1 to -1.5 percentage points; P = .01) compared with similar propensity score-matched controls. Considering abstinence from both smoking and vaping, compared with matched controls, smokers who vaped daily had lower abstinence at follow-up by 14.7 percentage points (95% CI, -20.2 to -9.2 percentage points; P < .001), and those who vaped nondaily had lower abstinence by 7.2 percentage points (95% CI, -10.7 to -3.8 percentage points; P < .001).

CONCLUSIONS AND RELEVANCE: In this representative cohort study of US smokers who used ENDS, neither daily nor nondaily vaping was associated with increased smoking cessation, and each was associated with reduced tobacco abstinence, suggesting that careful adjustment of confounding is critical in studies of ENDS and smoking cessation.

PMID:40042845 | DOI:10.1001/jamanetworkopen.2025.0089

JAMA Netw Open. 2025 Mar 3;8(3):e250122. doi: 10.1001/jamanetworkopen.2025.0122.

ABSTRACT

IMPORTANCE: Improving mental health of young people is a major societal challenge, particularly among the high numbers of young people living in deprived urban areas.

OBJECTIVE: To identify factors associated with depression and anxiety among young people in deprived urban areas in South America.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study recruited adolescents (age 15-16 years) and young adults (age 20-24 years) from education and community settings in deprived areas in Bogotá, Colombia; Buenos Aires, Argentina; and Lima, Peru, between April 2021 and November 2022. Participants who met threshold criteria for self-reported depression or anxiety. Community controls who did not meet the criteria were identified.

EXPOSURES: Sociodemographic characteristics, stressful life events before and during the past year, substance use, social capital, sports and arts activities, social media engagement.

MAIN OUTCOMES AND MEASURES: Depression, assessed using the 8-item Patient Health Questionnaire (range, 0-24, with higher scores indicating greater symptom severity), and anxiety, assessed using the 7-item Generalized Anxiety Disorder questionnaire (range, 0-21, with higher scores indicating greater symptom severity), were defined by threshold scores higher than 9. Various factors were compared between groups with and without anxiety and depression in multivariable logistic regression, testing for interactions by age group.

RESULTS: Of 2402 analyzed participants, 1560 (64.9%) were female, 1080 (45.0%) were adolescents, and 1322 (55.0%) were young adults; 1437 (59.8%) met the criteria for depression and/or anxiety, and 965 (40.2%) were controls. In a multivariable model, female gender (OR, 1.99 [95% CI, 1.65-2.40), more than 2 stressful life events in the previous year (OR, 1.67 [95% CI, 1.40-2.01]), more than 7 stressful life events before the previous year (OR, 1.52 [95% CI, 1.27-1.81), lifetime consumption of sedatives (OR, 2.26 [95% CI, 1.65-3.14]), participating in arts activities in the past 30 days (OR, 1.22 [95% CI, 1.01-1.48]), and stronger engagement with social media (OR, 1.59 [95% CI, 1.34-1.89]) were independently associated with increased odds of depression and anxiety, while sports activities were associated with reduced odds (OR, 0.80 [95% CI, 0.67-0.96]). The odds of having depression and/or anxiety symptoms associated with lifetime use of sedatives were higher among adolescents (OR, 6.54 [95% CI, 3.33-14.27]) than among young adults (OR, 2.54 [95% CI, 1.79-3.66]) (P = .01 for interaction).

CONCLUSIONS AND RELEVANCE: In this case-control study, female gender, stressful life events, substance use, arts activities, and social media engagement were associated with greater odds of depression and anxiety, while sport activities were associated with lesser odds. The findings suggest that policies for improving mental health in deprived urban neighborhoods in South America and related research should consider similar factors associated with mental distress in adolescents and young adults.

PMID:40042842 | DOI:10.1001/jamanetworkopen.2025.0122

Ann Surg. 2025 Mar 5. doi: 10.1097/SLA.0000000000006687. Online ahead of print.

ABSTRACT

SUMMARY OF BACKGROUND DATA: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is typically managed like pancreatic intraepithelial neoplasia (PanIN)-derived pancreatic cancer. However, in IPMN-derived pancreatic cancer, the role of chemotherapy remains controversial, particularly in the neoadjuvant setting (NAT).

OBJECTIVE: To evaluate the role of neoadjuvant chemotherapy in IPMN-derived pancreatic cancer.

METHODS: Patients with IPMN-derived pancreatic cancer treated with either upfront surgery (US) or NAT were identified from eight international centers (2000-2023). Clinicopathologic data were compared. Date of first treatment was used for Kaplan-Meier and log-rank tests to compare overall (OS) and recurrence free survival (RFS). Multivariable Cox-regression was performed in patients that underwent NAT.

RESULTS: In 1,019 patients, 76 (7%) underwent NAT. Patients who received NAT had higher baseline CA19-9 levels (P<0.001). Of these 76 patients, 27 (36%), 20 (26%), and 29 (38%) had resectable, borderline resectable, or locally advanced pancreatic cancer at diagnosis, respectively. Advanced resectability stage was significantly more common in the NAT patients as compared to those who underwent US (P<0.001). OS for US patients was 38.0 months (95%CI: 33.7.1-44.3), which was not statistically different than those that received NAT [27.5 mo (95%CI: 23.1-46.7), P=0.121]. This was also valid for patients with resectable disease [US: 38.1 mo vs. NAT: 35.6 mo, P=0.920)]. Complete or marked pathological treatment response (P=0.046) and serological CA19-9 normalization after NAT (P=0.017) were associated with improved survival. On Cox-regression for OS, N2 disease [HR: 4.15 (95%CI: 1.71-10.10)], elevated CA19-9 [HR: 2.02 (95%CI:1.06-3.85)] and R1 margin [HR: 2.36 (95%CI:1.20-4.61)] was independently associated with OS after NAT, while resectability status was not.

CONCLUSION: After NAT and resection, advanced resectability stage was not associated with worse OS indicating the value of this approach for borderline resectable and locally advanced IPMN-derived pancreatic cancer. The benefit of NAT in resectable disease is unclear and may require an individualized approach. Biological treatment effect can be assessed with CA19-9 and confirmed by pathologic response.

PMID:40042799 | DOI:10.1097/SLA.0000000000006687

Discov Oncol. 2025 Mar 5;16(1):266. doi: 10.1007/s12672-025-02023-2.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally, and infection with the hepatitis B virus (HBV) is one of the major risk factors for the development of HCC. However, the definitive causal relationship between HBV infection and liver cancer has not been clearly established. In this study, we employed Mendelian randomization (MR) to estimate the causal effect of HBV infection on hepatocellular carcinoma by using genetic variations as instrumental variables.

METHODS: We obtained summary statistics from genome-wide association studies (GWAS) related to hepatocellular carcinoma and hepatitis B. We conducted Mendelian randomization analysis, using genetic variants associated with HBV infection as instrumental variables to estimate the risk of liver cancer. In our MR analysis, we employed the inverse variance weighted (IVW) method and performed sensitivity analyses and robustness assessments using MR Egger regression and the weighted median method.

RESULTS: Our MR analysis revealed a significant causal association, indicating that HBV infection leads to liver cancer (IVW odds ratio = 2.233, 95% confidence interval = 1.844-2.703, P < 0.001). Sensitivity analyses using MR Egger regression and the weighted median method confirmed the causal effect, with no evidence of horizontal pleiotropy. Similar results were observed across different MR methods, supporting a strong causal association between HBV and liver cancer risk. Specifically, we observed a causal effect of CD25 on the IgD-CD38- B cell subset (β = 1.15, 95% CI 1.07-1.24, P = 3.0 × 10^- 4). Additionally, five immune phenotypes were significantly associated with HCC risk: HLA DR + + monocytes.

CONCLUSION: This MR study demonstrates a causal relationship between HBV infection and liver cancer risk, highlighting HBV as a potential causal factor in the development of hepatocellular carcinoma.

PMID:40042791 | DOI:10.1007/s12672-025-02023-2