Cox Proportional Hazards Model Research Articles

Relative Benefit of Dual Versus Single Antiplatelet Therapy Among Patients With Atrial Fibrillation on Oral Anticoagulation According to Time After ACS and PCI: Insights From the AUGUSTUS Trial.

In the AUGUSTUS trial (An Open-Label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs Vitamin K Antagonist and Aspirin vs Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), the combination of dual antiplatelet therapy plus oral anticoagulation increased the risk of bleeding without reducing ischemic events compared with a P2Y12 inhibitor plus oral anticoagulation among patients with atrial fibrillation and acute coronary syndrome or elective percutaneous coronary intervention. However, AUGUSTUS enrolled patients up to 14 days after acute coronary syndrome or percutaneous coronary intervention, and there may be a benefit to dual antiplatelet therapy plus oral anticoagulation early after an ischemic event. In this secondary analysis of AUGUSTUS, we divided patients into groups based on whether they were enrolled <6 days (early) or ≥6 days (later) after their index acute coronary syndrome or percutaneous coronary intervention, and tested the interaction between time from the index event to enrollment and randomized treatment (apixaban versus vitamin K antagonist and aspirin versus placebo) on 30-day and 6-month clinical outcomes using Cox proportional hazards models. Among 4605 patients enrolled in AUGUSTUS with data available on time from the index event to enrollment, the median time from the index event to enrollment was 6 (range, 0-14) days. There were no significant interactions between time from the index event and aspirin versus placebo on clinical outcomes at 30 days or 6 months, though patients with time from the index event <6 days had a nominally significant reduction in death or ischemic events at 30 days with aspirin (hazard ratio, 0.55 [95% CI, 0.30-0.99]), whereas patients with time from the index event ≥6 days did not (hazard ratio, 0.88 [95% CI, 0.54-1.43]; interaction P=0.23). There were no significant interactions between time from the index event and apixaban versus vitamin K antagonist on clinical outcomes. Among patients with atrial fibrillation with acute coronary syndrome or undergoing percutaneous coronary intervention, there was no difference in the relative benefit of apixaban versus vitamin K antagonist or aspirin versus placebo when patients were enrolled early versus later after their index event. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

Risk of Discontinuance in Contraceptive Uptake Among Kenya Women: A Survival Analysis Using the Cox Proportional Hazard Model

A problem of equal importance is the substantial challenge posed by the discontinuance of contraceptive use in family planning programs, particularly for developing countries such as Kenya. Investigating the determinants of contraceptive discontinuation using demographic factors can provide insights to enhance the efficacy of family planning. Using data from the Performance Monitoring for Action (PMA) survey, this study examined the demographic and contraceptive method-related covariates associated with the risk of discontinuation of contraception among Kenyan women. The study employed Cox proportional hazards models to analyze sampled data of Kenyan women from the PMA survey. Two separate models were used: a standard model which included demographic characteristics with a baseline contraceptive variable (Ever use contraceptive) and an extended model showing how specific contraceptive methods impact the likelihood of the risk of discontinuing contraception. Older age (Coefficient of -0.268 with a hazard ratio of 0.765) was associated with a decreased risk of contraceptive discontinuation. At the same time, women with higher educational levels (Coefficient of 0.015, with a hazard ratio of 1.015) were related to an elevated hazard and were more likely to discontinue their current method of contraception. The extended model showed that subcutaneous injectable contraceptives (Coefficient of -2.040 with a hazard ratio of 0.130) and male condoms (Coefficient of -1.137 with a hazard ratio of 0.321) were conditionally related to a significantly decreased hazard of discontinuation. The results highlight the importance of contraception choice and the significance of age and education in maintaining continuous contraception. To support Kenyan women in maintaining continuous contraception in achieving their reproductive health goals comprehensive education on emergency contraception and the provision of long-acting reversible contraceptives should be provided by health and family planning organizations. There is a call for a longitudinal study to offer an understanding of the dynamic behavior of contraception over time and the need for time-varying analyses to capture the evolving nature of contraception and its discontinuation.

Development and validation of the competing risk nomogram and risk classification system for predicting cancer-specific mortality in patients with cervical adenosquamous carcinoma treated via radical hysterectomy.

In this study, we established and validated a competing risk nomogram for predicting the cumulative incidence of cervical adenosquamous carcinoma (ASC)-specific death in patients undergoing radical hysterectomy. Patients diagnosed with ASC between 2010 and 2019 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence function (CIF) for various variables influencing ASC-specific mortality was computed. A Fine-Gray competing risk model was used to identify independent predictors, formulating a competing risk nomogram. A multivariate Cox proportional hazards model was also applied for comparative analysis. The performance of the nomogram was assessed using metrics such as the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A corresponding risk classification system was constructed based on nomogram-derived scores. Factors such as advanced age, racial background (Black race), higher tumor grade, increased tumor size, advanced TNM stage, and receipt of radiotherapy without chemotherapy were found to be positively associated with elevated ASC-specific mortality. Additionally, age, T stage, M stage, and chemotherapy were identified as independent predictors correlated with ASC-specific mortality. The established nomogram exhibited accurate discriminatory capabilities and superior net benefits compared to the traditional TNM staging system. Additionally, the high-risk group consistently demonstrated higher probabilities of ASC-specific death in both the training and validation sets. The developed nomogram proficiently quantified the incidence of ASC-specific death in patients subjected to radical hysterectomy for ASC. This tool could help clinicians in formulating personalized treatment strategies and devising follow-up protocols.

Association of COVID-19 With Risk of Posttransplant Diabetes Mellitus.

Posttransplant diabetes mellitus (PTDM) is an important complication for solid organ transplant recipients (SOTRs). COVID-19 has been associated with an increased risk of incident diabetes in the general population. However, the association between COVID-19 and new-onset PTDM has not been explored. Using the National COVID Cohort Collaborative Enclave, we conducted a cohort study of adults without diabetes receiving a solid organ transplant (heart, lung, kidney, or liver) in the United States between April 1, 2020, and March 31, 2023, with and without a first diagnosis of COVID-19 (COVID+ versus COVID-) within 180 d of SOT. We propensity score matched a single COVID+ SOTR with a COVID- SOTR who was diabetes free at the same point posttransplant. Within this matched cohort, we used multivariable Cox proportional hazards models to examine the adjusted risk of PTDM associated with COVID+. Among 1342 COVID+ SOTRs matched to 1342 COVID- SOTRs, the crude rate of newly diagnosed PTDM in the 2 y post-COVID was 17% in those with versus 13% in those without COVID-19 (P = 0.007). COVID-19 was significantly associated with new PTDM (adjusted hazard ratio, 1.37; 95% confidence interval, 1.12-1.68 at 2 y). Similar to other viral infections, COVID-19 is associated with an increased risk of PTDM in SOTRs.

Colonoscopy is associated with lower colorectal cancer occurrence and mortality in the older population: A population-based cohort study.

We aimed to evaluate the association between colonoscopy (CS) and colorectal cancer (CRC) occurrence and related mortality in an older population. This retrospective, nationwide, population-based cohort study used data of adults aged ≥40 years from the Health Insurance Review and Assessment Service database. After excluding CS within 6 months of CRC diagnosis during enrollment, CRC occurrence and related mortality were compared between CS and non-CS groups using a time-dependent Cox proportional hazard model. Sub-group analysis was conducted among four age groups: young, middle age, old, and very old. Results Among 748,989 individuals followed for 9.64±0.99 years, the CS group had a 65% lower CRC occurrence (adjusted hazard ratio [HRa]: 0.35, 95% confidence interval [95%CI]: 0.32-0.38) and 76% lower CRC-related mortality (HRa: 0.24, 95%CI: 0.18-0.31) after 5 years than the non-CS group. CS was associated with the most significant reduction in CRC occurrence in the middle age group (HRa: 0.32, 95%CI: 0.29-0.35) and CRC-related mortality in the young age group (HRa: 0.04, 95%CI: 0.01-0.33); the very old age group had the least reduction in both CRC occurrence and CRC-related mortality (HRa: 0.44, 95%CI: 0.33-0.59 and HRa: 0.28, 95%CI: 0.15-0.53, respectively). Conclusion We found a significant association between colonoscopy and reduction in CRC occurrence and CRC-related mortality in adults aged ≥ 40 years after 5 years of follow-up; however, these associations were weaker in the very old group. Research is needed on the association between colonoscopy and older age.

Prognostic significance of fibrinogen levels in sepsis-associated acute kidney injury: unveiling a nonlinear relationship and clinical implications

BackgroundFibrinogen plays a pivotal role in the inflammatory cascade and is intricately linked to the pathogenesis of sepsis. Nevertheless, its significance as a prognostic marker for sepsis-associated acute kidney injury (SA-AKI) remains uncertain. This study aimed to investigate the association between fibrinogen levels and 28-day mortality with sepsis-associated acute kidney injury.MethodThe fibrinogen levels of patients admitted to the intensive care unit of Beth Israel Deaconess Medical Center between 2008 and 2019 were retrospectively assessed, and those diagnosed with SA-AKI were divided into low, middle and high fibrinogen level groups according to tertiles. Multivariate Cox proportional hazards model was used to assess the 28-day mortality risk of the SA-AKI patients.ResultsA total of 3,479 patients with SA-AKI were included in the study. Fibrinogen demonstrated an independent association with 28-day mortality, yielding a hazard ratio (HR) of 0.961 (95% confidence interval [CI]: 0.923-0.999, P = 0.0471). Notably, a non-linear relationship between fibrinogen levels and 28-day mortality was observed, with the threshold observed at approximately 1.6 g/l. The effect sizes and corresponding CIs below and above this threshold were 0.509 (0.367, 0.707) and 1.011 (0.961, 1.064), respectively. Specifically, the risk of mortality among SA-AKI patients decreased by 49.1% for every 1 g/l increment in fibrinogen, provided that fibrinogen levels were less than 1.6 g/l.ConclusionIn patients with SA-AKI, a non-linear relationship was identified between fibrinogen levels and 28-day mortality. Particularly, when their fibrinogen levels were less than 1.6 g/l, a concomitant decrease in 28-day mortality was observed as fibrinogen levels increased.

Prognosis of patients with wild-type transthyretin cardiac amyloidosis and non-sustained ventricular tachycardia.

Little is known regarding the prevalence and prognostic implications of non-sustained ventricular tachycardia (NSVT) in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA). We aimed to investigate the prevalence of NSVT in patients with ATTRwr-CA, and the association of NSVT with sustained ventricular arrhythmias (VA) and all-cause mortality. In a cohort of ATTRwt-CA patients from 2011 to 2022 without prior sustained VA, we ascertained the presence and characteristics of NSVT during clinically indicated ambulatory Holter monitoring. Patients were stratified based on the presence of NSVT at baseline. The primary and secondary endpoints of sustained VA and all-cause mortality, respectively, were assessed during follow-up. The cohort included 217 patients with ATTRwt-CA (95% males, median age 75 years; median NYHA class 2). Baseline Holter monitoring demonstrated NSVT in 116 (53%) patients. During a median follow-up of 27 months (IQR 16-45) after the index Holter monitor, 11 (5.1%) patients reached the primary endpoint of sustained VA (incidence 1.8 per 100 person-years, all monomorphic VT), and 46 (21%) patients died. In univariable Cox proportional hazard model, NYHA class 3 or 4 heart failure (p = .048), the presence of NSVT (p = .04), the duration of longest NSVT run (p = .029), and the percentage of ventricular ectopy (p < .001) were associated with the primary outcome. When adjusting for age and NYHA class 3 or 4 heart failure, the presence of NSVT remained associated with the primary outcome (p = .03). All-cause mortality was not significantly different between patients with and without NSVT. A cutoff for ventricular ectopy burden of 0.5%, the median for all patients in this study, was associated with increased risk in sustained VA (log-rank p = .004) and mortality (log-rank p = .02). NSVT is highly prevalent among ATTRwt-CA patients undergoing clinically indicated Holter monitoring and may confer an increased risk of incident sustained VA.

Association between self-reported weight loss and new long-term care insurance certifications: A 9-year Japanese older adult cohort study.

This cohort study aimed to assess weight loss associated with new long-term care insurance (LTCI) certifications over a 9-year period, accounting for the competing risk of death. We analyzed data from 3749 Japanese individuals aged ≥65 years in Kami Town, Hyogo Prefecture, Japan. Weight loss was assessed using the Kihon Checklist during the baseline survey. Data regarding LTCI certifications were collected until March 2022. Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) of 9-year LTCI certification because of weight loss, adjusted for confounding factors. To exclude the effect of competing risks, Fine-Gray regression was used to estimate subdistribution HRs. Subgroup analyses were carried out after the examination of potential interactions between subjective cognitive function, body mass index categories and weight loss. The incidence rate of new LTCI certifications was 5.16 per 100 person-years overall - broken down into 7.02 for those with weight loss and 4.97 for those without. The adjusted HR for weight loss to new LTCI certifications was 1.35 (95% CI 1.15-1.59). Considering mortality as a competing risk, the adjusted subdistribution HR was 1.37 (95% CI 1.16-1.61). Conversely, no interaction was observed between weight loss and subjective cognitive function or body mass index categories. Excluding the effect of mortality, weight loss was identified as a risk factor for new LTCI certifications. However, no interaction was observed between weight loss and subjective cognitive function or body mass index categories. Geriatr Gerontol Int 2024; ••: ••-••.

Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Results of Polish multicenter observational study.

Patients with head and neck squamous cell carcinoma (HNSCC) who have progressed following primary treatment (PT) have a poor prognosis. In this group, nivolumab has been demonstrated to significantly improve outcomes. This study presents the efficacy of nivolumab in Polish patients with recurrent and/or metastatic (R/M) HNSCC using real-world data. The analyzed group consisted of 324 adult patients with R/M HNSCC following platinum-based therapy. Patients were divided into 3 groups based on the time from completion of PT to nivolumab initiation (tPT-N): within 6 months (refractory), between 6 and 24 months (sensitive, tPT-N ≤24), and beyond 24 months (sensitive, tPT-N >24). Survival analysis and the Cox proportional hazards model were performed to evaluate how various risk factors affect patient outcomes. The 1-year and 2-year overall survival (OS) was 19.1%, 6.1%, 30.7%, 9.4%, and 45.7%, 29.1% in refractory, sensitive tPT-N ≤24, sensitive tPT-N >24 patients, respectively and was higher for both sensitivity groups vs. refractory (p = .004) and for sensitive tPT-N >24 versus refractory and sensitive tPT-N ≤24 (p <.001). Patients with nasopharyngeal cancer had OS significantly higher than patients with other primary tumor localization. The multivariate Cox analysis showed a significant favorable effect of tPT-N >24 (HR = 0.53, p = .001) and nasopharyngeal cancer on OS (HR = 0.20, p = .008). Conversely, female sex was identified as an unfavorable factor for OS (HR = 1.48, p = .020). In our study, we established that the benefit of nivolumab increases with the increasing tPT-N. The probability of death is significantly lower in male patients and patients with nasopharyngeal cancer regardless of tPT-N.

Breastfeeding, genetic susceptibility, and the risk of asthma and allergic diseases in children and adolescents: a retrospective national population-based cohort study.

Asthma and allergic diseases (such as allergic rhinitis) are multifactorial chronic respiratory diseases, and have many common pathogenic mechanisms. This study aimed to assess the joint effects of breastfeeding and genetic susceptibility on asthma, allergic disease in children and adolescents and sought to examine whether the effect of breastfeeding was consistent under distinct levels of genetic risk. A total of 351,931 UK Biobank participants were analyzed. Firstly, Cox proportional hazards model was used to evaluate the relation between breastfeeding and asthma, allergic disease and their comorbidity. Next, we incorporated the polygenic risk score as an additional covariate into the model. Then, we explored the role of breastfeeding at each stage of asthma and allergic disease through a multi-state model. Meanwhile, several sensitivity analyses were conducted to evaluate the robustness of our results. Finally, we calculated the attributable protection and population attributable protection of breastfeeding. Breastfeeding was related to a reduced risk of occurring asthma (adjusted hazard ratio [HR] = 0.89, 95% confidence interval [CI] 0.86 ~ 0.93), allergic disease (HR = 0.89, 95%CI 0.87 ~ 0.91) and comorbidity (HR = 0.89, 95%CI 0.83 ~ 0.94). The effect of breastfeeding was almost unchanged after considering PRS and did not substantially differ across distinct genetic risk levels. Breastfeeding showed a stronger risk-decreased impact on individuals who developed from allergic rhinitis to comorbidity (HR = 0.83, 95%CI 0.73 ~ 0.93). Further, the influence of breastfeeding was robust against covariates considered and the confounding influence of adolescent smoking. Finally, due to breastfeeding, 12.0%, 13.0% or 13.0% of the exposed population would not suffer from asthma, allergic diseases and the comorbidity, while 7.1%, 7.6% or 7.6% of the general population would not suffer from these diseases. This study provided supportive evidence for the risk-reduced effect of breastfeeding on asthma, allergic diseases, and the comorbidity in children and adolescents, and further revealed that such an influence was consistent across distinct genetic risk levels.

Elevated risk of end-stage kidney disease in stroke patients: A population-based observational study.

Estimating the incidence of end-stage kidney disease (ESKD) in stroke survivors is important to assess and predict clinical course, improve post-stroke quality of life, and ultimately reduce health burden. Our objective was to assess the risk of ESKD in patients compared to a matched stroke-free control cohort. A nationwide retrospective cohort study was conducted in 315,326 stroke subjects and 390,781 matched stroke-free control subjects. Health examination results and claims data were collected from the Korean National Health Insurance Service during 2010-2018. Cox proportional hazard models were used to assess the risk of ESKD in the stroke cohort. During a mean follow-up period of 4.3 years, the incidence of ESKD was 1.83 per 100,000 person-years in the stroke cohort versus 0.57 per 100,000 person-years in the control cohort. The stroke cohort exhibited a significantly higher risk of developing ESKD compared to the matched control, with an adjusted hazard ratio (aHR) of 1.79 (95% confidence interval (CI) = 1.67-1.93). Stroke survivors were associated with a higher risk of developing ESKD, regardless of the severity of disability (aHRs of 1.93, 95% CI = 1.69-2.21 for severe disability; 1.71, 95% CI = 1.41-2.07 for mild disability; and 1.78, 95% CI = 1.65-1.92 for no disability), compared to the matching control cohort. The elevated risk was observed in both hemorrhagic stroke (aHR = 1.96, 95% CI = 1.73-2.23) and ischemic stroke (aHR = 1.75, 95% CI = 1.62-1.89). This study demonstrates that stroke patients have a significantly higher risk of incident ESKD. This highlights the need for heightened clinical awareness and improved monitoring of kidney function in this population.

Association of improvement and worsening of depressive symptoms with arthritis

PurposeThe longitudinal association between changes in depressive symptoms (improvement/worsening) and arthritis is unclear.MethodsStudy data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) 2011–2018. The 10-item Center for Epidemiological Studies Depression Scale (CES-D-10) was used to examine participant depressive symptoms and data on self-reported history of arthritis were collected. Depressive symptoms improving is defined as depression at baseline and no depression at follow-up. Similarly, depressive symptoms worsening is defined as no depression at baseline and depression at follow-up. Cox proportional hazards models were used to evaluate the effects of improvement or deterioration in depressive symptoms on arthritis. Participants with missing data on depression and arthritis, having arthritis in 2011 CHARLS and lost to follow-up was excluded.ResultsA total of 8556 participants free of arthritis were included from 2011 to 2018. After adjustment for confounders, depressive symptoms were associated with a 54% increased risk of developing arthritis. Each 1-point increase in CES-D-10 score was associated with a 4% higher risk of arthritis. Participants with depressive symptoms at baseline but improved symptoms (without depressive symptoms) at follow-up had a 25% lower rate of arthritis, and a 1-point reduction in CES-D-10 score during 8 years of follow-up was associated with a 5% lower risk of developing arthritis. Participants with no depressive symptoms at baseline but depression at follow-up had a 66% higher rate of arthritis, and a 1-point increase in CES-D-10 score during 8 years of follow-up was associated with a 5% higher risk of arthritis.ConclusionsImprovement in depressive symptoms was associated with lower risk of arthritis and worsening of depression was associated with higher risk of arthritis. These findings suggest that the relationship between depression and arthritis is complex.

Negative Impact of Systemic Therapy on Survival in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Low-Grade Metastatic Appendiceal Adenocarcinoma.

Despite studies demonstrating that patients with peritoneal metastases from low-grade appendiceal adenocarcinoma (AA) do not respond well to systemic chemotherapy (SC), patients frequently undergo combination of SC with cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) regardless of grade. A nationwide retrospective analysis using the National Cancer Database evaluated patients with AA with peritoneal metastasis from 2016 to 2021. Cox proportional hazards model was used to evaluate the impact of SC in addition to CRS/HIPEC on overall survival (OS) stratified by tumor grade. A total of 1,449 patients were included: 481 low-grade, 428 intermediate-grade, and 540 high-grade tumors. Clinical variables, such as age, sex, and comorbidity index, were similar across tumor grades. Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy without SC was utilized in 65.73% of low-grade cases compared with 41.01% in intermediate-grade and 11.11% in high-grade cases. Systemic chemotherapy was utilized alone in 17.74% and with CRS/HIPEC in 16.53% of low-grade cases. In adjusted survival analysis, addition of SC to CRS/HIPEC was associated with worse OS for patients with low-grade AA (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.18-6.50) but not for intermediate (HR 1.65, 95% CI 0.82-3.35) and high-grade tumors (HR 1.18, 95% CI 0.67-2.45). The addition of time to definitive surgery variable nullified the negative impact of adding SC to CRS/HIPEC in low-grade AA (HR 1.76, 95% CI 0.68-4.53). Negative OS impact of SC may be mediated by delays in effective surgical/intraoperative therapy. If CRS/HIPEC is planned for patients with metastatic low-grade AA, avoiding SC may facilitate earlier surgical intervention and improve survival.

PFAS and menopause onset: Is it just a matter of reverse causation? Cross-sectional and longitudinal analyses in highly exposed women in the Veneto Region

IntroductionSeveral cross-sectional studies have linked perfluoroalkyl substances (PFAS) to prevalence of menopause. These findings might be influenced by reverse causation mechanism, making longitudinal studies more suitable. However, existing longitudinal studies are limited and present conflicting results. AimThis study investigates the association between PFAS and both prevalence and incidence of menopause, using longitudinal designs to limit the impact of reverse causation. MethodsA surveillance program on a PFAS highly exposed population in the Veneto region started in 2017 with two rounds of screening, on average 3.8 years apart. Women who participated in the first screening (n = 11,046) were included in the cross-sectional analysis. Multivariate logistic regression models were used to estimate the Odds Ratios (ORs) of menopause associated with exposure to different PFAS. For incidence analysis a retrospective-prospective design used PFOA concentrations reconstructed to 2013 (n = 8536), and a prospective design involved women participating in both screenings (n = 1709), evaluating their baseline concentrations of PFOA, PFOS, and PFHxS. Cox proportional hazards models with age as the timescale were used to estimate Hazard Ratios (HRs), adjusting for sociodemographic and lifestyle factors. ResultsIncreased menopause prevalence was associated with higher ln-concentrations of PFOA, PFOS, and PFHxS, with ORs of 1.31 (CI: 1.25–1.38), 1.51 (CI: 1.38–1.66), and 1.42 (CI: 1.34–1.51), respectively. The retrospective-prospective study showed increased risk of menopause in higher PFOA reconstructed quartiles, with HRs of 1.01 (CI: 0.87–1.18), 1.17 (CI: 1.02–1.37), and 1.07 (CI: 0.93–1.23) for the second, third and fourth quartiles. The prospective longitudinal study found no association between PFAS and menopause onset. ConclusionsOur results showed a strong cross-sectional association between PFAS exposure and menopause, a weak positive association in the retrospective-prospective study, and no association in the prospective study. This suggests that cross-sectional associations may largely result from reverse causality due to early menopause on reducing PFAS excretion.

Recovery time and its predictors of severe acute malnutrition among under five children admitted at the therapeutic feeding center of Hiwot Fana comprehensive specialized hospital, eastern Ethiopia, 2024: a semi-parametric model

BackgroundEarly recovery is a performance indicator of quality care for children under five admitted due to severe acute malnutrition (SAM) at therapeutic feeding centers. Despite the available interventions to tackle such nutritional problems, there is limited information on the time to recovery and its predictors among children with severe acute malnutrition in Ethiopia, more particularly in the study setting.ObjectiveThe study aimed to assess the time to recovery from severe acute malnutrition and its predictors among children aged 6–59 months admitted to the therapeutic feeding center (TFC) of Hiwot Fana Comprehensive Specialized Hospital (HFCSH), eastern Ethiopia, from 1st September 2019 to 1st March 012024.MethodsA retrospective cohort study was conducted at the therapeutic feeding center of HFCSH among a randomly selected sample of 349 patients with severe acute malnutrition who were undergoing therapeutic feeding. Data were collected using a data abstraction tool and then stored in Epi-data version 4.6 and STATA version 17.0 statistical software. Descriptive statistics, Kaplan–Meier (KM) plots, median survival times, the log-rank test, and the Cox proportional hazards regression model were used to report the findings of this study. After performing the Cox proportional hazards regression, the model goodness of fit and assumptions were checked. Finally, the association between independent variables and the time to recovery in days was assessed using the multivariable Cox proportional hazards model, and the variables with a p-value &amp;lt;0.05 were considered statistically significant.ResultsThe median survival time to recovery among the patients with severe acute malnutrition was 17 days [95% confidence interval (CI): 16–18]. The incidence density recovery rate was 5.7 (95%CI, 4.9–6.6) per 100 person-days of observation. Factors that affected the time to recovery included residing in rural areas [adjusted hazard ratio (AHR) = 2.072; 95%CI = 1.336–3.215], being vaccinated according to age (AHR = 1.848; 95%CI = 1.162–2.939), and lack of analgesic administration (AHR = 0.685; 95%CI = 0.472–0.995).ConclusionThe median survival time to recovery in this study was found to be optimal. Residency, vaccination status of the child, and analgesic administration were the determinant factors. Paying attention to vaccination coverage, fever management, and pain management as part of the protocol helps reduce the length of hospital stay by facilitating recovery rates among severely malnourished children under five in Ethiopia.

Motor signs and incident dementia with Lewy bodies in older adults with mild cognitive impairment.

Motor signs may herald incident dementia and allow the earlier detection of high-risk individuals and the timely implementation of preventive interventions. The current study was performed to investigate the prognostic properties of motor signs with respect to incident dementia with Lewy bodies (DLB) in older adults with mild cognitive impairment (MCI). Emphasis was placed on sex differences. The specificity of these associations was explored. We analyzed data from the National Alzheimer's Coordinating Center Uniform Data Set. Participants 55 + years old with a diagnosis of MCI were included in the analysis. Those with Parkinson's disease (PD) or other parkinsonian disorders at baseline and those with PD dementia at follow-up were excluded. UPDRS III was used to assess the presence or absence of motor signs in nine domains: hypophonia; masked facies; resting tremor; action/postural tremor; rigidity; bradykinesia; impaired chair rise; impaired posture/gait; postural instability. Αdjusted Cox proportional hazards models featuring sex by motor sign interactions were estimated. Throughout the average follow-up of 3.7 ± 3.1 years, among 4623 individuals with MCI, 2211 progressed to dementia (66 of whom converted to DLB). Masked facies [HR = 4.21 (1.74-10.18)], resting tremor [HR = 4.71 (1.44-15.40)], and bradykinesia [HR = 3.43 (1.82-6.45)] exclusively increased the risk of DLB. The HR of DLB was approximately 15 times greater in women compared to men with masked facies. Impaired posture-gait (approximately 10 times) and resting tremor (approximately 8.5 times) exhibited a similar trend (prominent risk-conferring properties in women compared to men) but failed to achieve statistical significance. Rigidity and hypophonia elevated the risk of other dementia entities, as well. The remaining motor features were not related to incident dementia of any type. Specific motor signs may herald DLB among individuals with MCI. Different associations may exist between masked facies, impaired posture-gait, resting tremor, and incident DLB in men versus women.

Brisk walking pace offsets venous thromboembolism risk equivalent to established monogenic mutations.

Mendelian mutations in F2 and F5 genes are known risk factors for venous thromboembolism (VTE). This study aimed to explore the association between walking pace and VTE, compare its risk with Mendelian mutations, and identify if blood biomarkers mediate this effect. We followed 445,261 UK Biobank participants free of VTE at baseline. Walking pace was self-reported, and carrier status for F2 and F5 gene mutations was determined by rs1799963 and rs6025 genotypes. We used a Cox proportional hazard model to estimate walking pace's effect on VTE risk, bidirectional Mendelian randomization (MR) analysis to assess causality, and mediation analysis to explore blood biomarkers. Over a median follow-up of 12.8 years, 11,155 incident VTE cases were identified. The 10-year incidence rates for brisk and slow walking paces were 1.32% and 3.90%, respectively. For F5 carriers, the rates were 1.70% (brisk pace) and 3.62% (slow pace). Brisk walking pace reduced VTE risk in F5 carriers (2.65%) compared to non-carriers with a slow pace (3.66%). MR analysis confirmed a causal relationship from walking pace to VTE risk. Mediation analysis revealed that serum albumin and cystatin C mediated 8.7% to 11.7% of the effect of brisk walking pace on VTE risk. A slow walking pace is causally associated with increased VTE risk. A brisk walking pace mitigates VTE risk, particularly in individuals with F5 gene mutations, and this effect is partially mediated by serum albumin and cystatin C.

Sex Differences in Long-Term Cardiovascular Outcomes and Mortality After COVID-19 Hospitalization During Alpha, Delta and Omicron Waves

Background: Increased mortality and occurrence of cardiovascular (CV) outcomes during hospitalization and in short-term follow-up for moderate to severe SARS-CoV-2 infection have been associated with male sex, yet data regarding long-term outcomes by sex and COVID-19 variant (Alpha, Delta, and Omicron) are limited. Methods: This prospective study of 4882 patients examines potential differences by sex in the occurrence of primary combined cardiovascular outcomes (CV death, CV hospitalization, myocardial infarction (MI), stroke, pulmonary embolism) as well as secondary outcomes (CV death, cardiovascular hospitalizations, myocardial infarction, stroke, pulmonary embolism) at 18-month follow-up after urgent hospitalization for SARS-CoV-2-associated pneumonia, as well as evaluating for differences during the three COVID-19 waves. Survival rate was analyzed for the entire cohort by sex and SARS-CoV-2 variant and adjusted for age using the multiple Kaplan–Meier method. To compare survival in groups of men and women for each wave, the Gehan–Wilcoxon test was applied with significance p &lt; 0.05. Univariate Cox proportional hazards models were used to search for potential risk factors of CV death at 18-months follow-up separately for men and women in each COVID-19 wave. Results: Men had significantly higher 18-month CV mortality compared to women in the Delta wave (6.13% men vs. 3.62% women, p = 0.017). Although men had higher percentages of all other CV endpoints (excepting pulmonary embolism) at follow-up during the Delta wave, none were significant compared with women, except for the combined CV endpoint (16.87% men vs. 12.61% women, p = 0.017). No significant differences by sex in CV outcomes were seen during the Alpha and Omicron variants. Discrepancies in CV outcomes in demographical data and concomitant disease between the COVID-19 variants of concern existed. Conclusions: Higher male mortality and higher but non-significant incidences of CV outcomes occurred during the Delta wave of the COVID-19 pandemic, with the lowest incidence of CV outcomes observed during the Omicron variant.

Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol-Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis.

Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) levels are independently associated with atherosclerotic cardiovascular disease (ASCVD). However, the relationship between Lp(a) level, LDL-C level, and ASCVD risk at different thresholds is not well defined. A participant-level meta-analysis of 27 658 participants enrolled in 6 placebo-controlled statin trials was performed to assess the association of LDL-C and Lp(a) levels with risk of fatal or nonfatal coronary heart disease events, stroke, or any coronary or carotid revascularization (ASCVD). The multivariable-adjusted association between baseline Lp(a) level and ASCVD risk was modeled continuously using generalized additive models, and the association between baseline LDL-C level and ASCVD risk by baseline Lp(a) level by Cox proportional hazards models with random effects. The joint association between Lp(a) level and statin-achieved LDL-C level with ASCVD risk was evaluated using Cox proportional hazards models. Compared with an Lp(a) level of 5 mg/dL, increasing levels of Lp(a) were log-linearly associated with ASCVD risk in statin- and placebo-treated patients. Among statin-treated individuals, those with Lp(a) level >50 mg/dL (≈125 nmol/L) had increased risk across all quartiles of achieved LDL-C level and absolute change in LDL-C level. Even among those with the lowest quartile of achieved LDL-C level (3.1-77.0 mg/dL), those with Lp(a) level >50 mg/dL had greater ASCVD risk (hazard ratio, 1.38 [95% CI, 1.06-1.79]) than those with Lp(a) level ≤50 mg/dL. The greatest risk was observed with both Lp(a) level >50 mg/dL and LDL-C level in the fourth quartile (hazard ratio, 1.90 [95% CI, 1.46-2.48]). These findings demonstrate the independent and additive nature of Lp(a) and LDL-C levels for ASCVD risk, and that LDL-C lowering does not fully offset Lp(a)-mediated risk.

Are background breast parenchymal features on preoperative breast MRI associated with disease-free survival in patients with invasive breast cancer?

To evaluate whether breast parenchymal features of the contralateral breast on preoperative MRI are associated with primary breast cancer characteristics and disease-free survival (DFS) in women with invasive breast cancer. Women with newly diagnosed invasive breast cancer who underwent preoperative breast MRI followed by surgery were retrospectively evaluated. Background parenchymal enhancement (BPE) on dynamic contrast-enhanced MRI and background diffusion signal (BDS) on diffusion-weighted MRI of the contralateral breast were qualitatively assessed using a four-category scale: minimal, mild, moderate, or marked. Primary breast cancer characteristics were compared based on the degree of BPE or BDS. Cox proportional hazards models were used to evaluate the association between MRI parenchymal features and DFS after adjusting for clinicopathologic features. A total of 515 women (mean age, 54years) were included. Of whom, 46 (8.9%) patients who developed disease recurrence at a median follow-up of 60months were observed. A high level (moderate/marked) of BPE or BDS was associated with younger age (≤ 45) and premenopausal status (all P < 0.05) compared to a low level (minimal/mild), but it was not associated with primary cancer characteristics such as tumor stage, grade, or subtype. Multivariable Cox proportional hazards analysis demonstrated that larger tumor size (> 2cm) (hazard ratio [HR], 3.877; P < . 001), triple-negative subtype (HR, 2.440; P = .013), and axillary node metastasis (HR, 1.823; P = .049) were associated with worse DFS. No associations were observed between background parenchymal features and disease outcomes. MRI parenchymal features, including BPE and BDS, of the contralateral breast showed no associations with primary breast cancer characteristics or DFS in women with invasive breast cancer.