Multivariate Cox Proportional Hazards Model Research Articles

Relationship between 3-dimensional aortic geometry and the risk of new-onset heart failure

Abstract Introduction Aortic geometric assessments to date have typically involved cross-sectional imaging of discrete aortic segments. However, the complex 3D geometry of the thoracic aorta, and its relationship to the risk of cardiovascular disease has not been assessed in large studies. Methods We segmented the thoracic aorta in SSFP axial MRI images from 49,282 UK Biobank participants using a deep convolutional neural network (U-Net). We then computed geometric measurements (centerline length, arch height, arch width, arch height-width ratio, arch unfolding index [inverse of tortuosity], curvature and mean, minimum and maximum diameters) in the overall thoracic aorta as well as in 6 subsegments. We quantified their relationship to the risk of cardiomyopathy and heart failure (HF) using multivariable Cox-proportional hazards models. All hazard ratios are standardized. Centerline length was allometrically indexed to body height. Results In models adjusted for age, sex, BMI kg/m2, low-density lipoprotein mg/dl, high-density lipoprotein mg/dl, triglycerides mg/dl, systolic blood pressure and diastolic blood pressure, the curvature of the aorta (HR=0.63; 95% CI=0.39, 0.99; P<0.05), particularly the aortic arch (HR=0.54; 95% CI= 0.35, 0.87; P<0.05) was strongly related to a lower risk of incident cardiomyopathy. A higher arch unfolding index (HR=1.46; 95% CI=1.03, 2.07; P<0.05), higher width-to-height ratio (HR=1.10; 95% CI= 1.02, 1.19; P<0.05) and lower aorta tortuosity (HR=1.20; 95% CI= 1.09, 1.32; P<0.05) were all associated with a higher risk of cardiomyopathy. This aortic geometric pattern was also associated with a greater risk of a new HF diagnosis (arch unfolding [HR=1.23; 95% CI= 1.07, 1.42; P<0.05], width to heigh ratio [HR=1.06; 95% CI= 1.01, 1.11; P0.05]). Conclusion We demonstrate that 3-D thoracic aortic geometric indices are strongly associated with incident cardiomyopathy and HF, independent of classic risk factors. This is likely related to abnormal afterload and ventricular-arterial interactions since adverse geometric remodeling affects left ventricular pulsatile load.Cardiomyopathy & Heart Failure Hazards

Heart failure burden among adults with congenital heart disease

Abstract Background Adult congenital heart disease (ACHD) is associated with high rates of healthcare utilization and mortality. Data on Heart failure (HF) burden among ACHD patients are limited. Purpose To study the association between HF and healthcare utilization and mortality among ACHD patients in the community. Methods The retrospective cohort study comprised 11,653≥ 18 year old ACHD patients insured by two large Israeli healthcare providers between January 2007 and December 2011. We used multivariable Cox proportional hazard and negative binomial models to study the associations of HF with mortality and healthcare utilization, respectively. Inverse treatment probability weighting accounted for drug indication. Results ACHD-HF patients (N=908; 7.8%) were older (median: 69 vs. 45 years), more likely men (53% vs. 45%), with complex congenital heart disease (14% vs. 4%), and higher comorbidity rates than ACHD patients without HF. HF was associated with higher healthcare utilization. Compared to patients without HF, ACHD-HF patients had higher adjusted relative rates (RR) of primary care (1.26, 95% confidence interval [CI]: 1.17-1.3), and cardiology clinic visits (1.9, 95% CI: 1.7-2.0), higher hospitalization rates (RR=2.0, 95% CI: 1.7-2.1), and higher risk of death (mortality hazard ratio [HR]: 1.9, 95% CI: 1.5-20.) over the study period. Among ACHD-HF patients, Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and diuretics were associated with a lower mortality risk (treated vs. untreated HR=0.56, 95% CI: 0.48-0.65; HR=0.7, 95% CI: 0.6-0.8; HR=0.84, 95% CI: 0.73-0.97; respectively). Conclusions HF presents a major burden on ACHD patients and health care systems. Drugs recommended to the general HF patient population are also associated with lower risk of hospitalization and mortality in ACHD patients. Clinical trials are needed to establish the benefit of HF pharmacotherapy in ACHD patients.Age adjusted ACHD patient survival by HF

Respective impact of bleeding and ischemic complications of mortality after percutaneous coronary interventions: substudy from the FRANCE-PCI registry

Abstract Background Patients undergoing percutaneous coronary interventions (PCI) remain at high risk of both bleeding and ischemic events, both burdened with high morbimortality. The respective impact of both type of complications in contemporary PCI, however, remains unclear. Purpose To evaluate and compare the respective impact of ischemic and bleeding complications on mortality after PCI Methods The FRANCE PCI is an ongoing registry of consecutive French patients undergoing PCI and monitored for one year thereafter. Patients presenting with complications after the index PCI were categorized as ischemic complications in case of stent thrombosis, myocardial infarction, stroke or unplanned revascularization, as hemorrhagic complications in case of bleeding BARC ≥3 or as ischemic and hemorrhagic when both types of events occurred in the same patients. The impact of ischemic and hemorrhagic complications on mortality was evaluated separately for the index hospitalization and the 12-months follow-up after hospital discharge, using multivariate logistic model and Cox proportional hazards model, respectively. The multivariate Cox model was developed using complications as time-dependent variables and estimating the hazard ratios (HRs) over 3 periods of time (0 to 8 weeks, 8 to 24 weeks, and 24 to 52 weeks). Consequently, the proportional hazard assumption, tested using the Schoenfeld test, was met for each period. Multiple imputations were performed for missing data on covariates. Results A total of 54,599 patients, with a median age of 69 [60.0-78.0] years, 75.0% male, underwent PCI in 30 centers between 2014 and 2020, in an elective setting for 47% of the cases. During the index hospitalization, an ischemic and hemorrhagic complications occurred in 610 (1.1% 95%CI 1.0-1.2) and 531 (1.0% 95%CI 0.9-1.1) patients, respectively, while the mortality rate was 2.1% 95%CI 2.0-2.2. The association between ischemic, hemorrhagic and ischemic and hemorrhagic events with mortality was aOR 8.4 95%CI 6.4-10.9, aOR 10.3 95%CI 8.1-13.2 and aOR 13.2 95%CI 7.0-24.7, respectively. Among the 51,738 patients alive and not lost-to-follow-up after discharge, an ischemic and hemorrhagic complications occurred in 2,727 (5.3% 95%CI 5.1-5.5) and 1,022 (2.0% 95%CI 1.9-2.1) patients, respectively, while the mortality incidence was 3.8% 95%CI 3.6-4.0. The associations between ischemic, hemorrhagic and ischemic and hemorrhagic events with mortality according to the periods of time are detailed in Table 1 and Figure 1. Conclusion Both ischemic and hemorrhagic complications after PCI are associated with increased risk of mortality. The risk is particularly increased during the early period after the index PCI and diminishes over time, albeit faster after ischemic complications alone, compared to hemorrhagic events alone or the association of ischemic and hemorrhagic complications.

Long-term outcomes and operators' experience in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

Primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) is typically performed by experienced operators. Therefore, the safety of pPCI for STEMI performed by less experienced operators with the support of experienced operators remains unknown. We aimed to investigate the long-term outcomes of pPCI for STEMI performed by less experienced operators with the support of experienced operators. In total, 775 STEMI patients were enrolled and divided into groups according to operator experience in PCI: less experienced (n = 384) and experienced (n = 391) operator groups. Experienced operators were defined as those who had performed > 50 elective PCI procedures per year as the first operator or instructional assistant, whereas less experienced operators were defined as others. When less experienced operators performed the pPCI, experienced operators supported them. The primary endpoint was any cardiovascular event, defined as a composite of cardiovascular death, nonfatal myocardial infarction, and unplanned hospitalization for heart failure. In the propensity score-matched analysis, 324 patients were included in each group. The cumulative incidence of the primary endpoint over a median of 5years in the less experienced operator group was similar to that in the experienced operator group (15% vs. 18%, P = 0.209). In the multivariate Cox proportional hazards model, there was no excess risk for patients operated upon by less experienced operators for the primary endpoint (adjusted hazard ratio, 0.85; 95% confidence interval, 0.58-1.25; P = 0.417). pPCI for STEMI by less experienced operators did not increase the risk of in-hospital mortality or 5-year long-term cardiovascular events if supported by experienced operators.

Effect of Physical Function on Access to Repeat Kidney Transplantation.

Background: The long-term success rate of kidney transplantation is disappointing, with repeat transplantation necessary for more than half of recipients. When a repeat kidney transplantation is needed, patients are often elderly and suffer from underlying advanced kidney disease, comorbidities, and adverse effects of immunosuppressants, leading to physical function limitations. Limited physical function is known to hinder access to an initial kidney transplantation, but there is no information about its impact on repeat transplantations. Objective: This study aimed to determine the effect of physical function on access to wait-listing for repeat transplantation. Methods: Data from the national registry was utilized to analyze 28,884 kidney transplant recipients. Physical function was assessed with Karnofsky scores, and patients were categorized into three strata: total assistance, some assistance, and no assistance. Logistic regression and multivariate Cox proportional hazard models were used to assess the impact of physical function on waiting list access and duration until wait-listing, respectively. Results: Patients with greater physical independence were more likely to be wait-listed for repeat kidney transplantation. Highly sensitized patients, those with diabetes, Black patients, and elderly individuals had a lower likelihood of access to wait-listing after kidney failure. Interestingly, those with limited physical function, provided they remained in the work-up process, experienced a relatively shorter duration to wait-listing after graft failure.Conclusions: These findings highlight the need to promote and support physical function throughout the kidney transplant journey to improve access to repeat transplantation and subsequent patient outcomes.

Persistent proteinuria is associated with the occurrence of cardiovascular disease: a nationwide population-based cohort study

Proteinuria is an important risk factor for cardiovascular disease (CVD) and acts as a surrogate marker of renal damage. This study aimed to determine the association between changes in proteinuria and the occurrence of CVD. In our study, 1,708,712 participants who consecutively underwent national health examinations from 2003−2004 (first period) to 2005−2006 (second period) were included. They were classified into four groups based on the presence of proteinuria at the two consecutive health examinations: (1) normal (0 → 0), (2) proteinuria-improved (participants who had improved proteinuria (+ 1 → 0, + 2 → ≤ +1 [0 or + 1], ≥ +3 → ≤ +2 [0, + 1 or + 2]), (3) proteinuria-progressed (0 → ≥ +1, + 1 → ≥ +2, + 2 → ≥ +3), and (4) proteinuria-persistent (+ 1 → +1, + 2 → +2, ≥ +3 → ≥ +3). We used a multivariate Cox proportional hazards model to assess the occurrence of CVD according to changes of presence and severity of proteinuria. During a median of 14.2 years of follow-up, 143,041 participants (event rate, 8.37%) with composite CVD were observed. Compared with the normal group, the risk of incident risk of CVD was increased according to the severity of proteinuria in each of the persistent, progressed, and improved groups (p for trend < 0.001). In a pairwise comparison, the risk of composite CVD in the improved (hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.27–1.37), progressed (HR: 1.49, 95% CI: 1.44–1.54), and persistent groups (HR: 1.78, 95% CI: 1.64–1.94) were higher than that of the normal group. Furthermore, the improved group had a relatively lower risk of composite CVD compared to the persistent group (HR: 0.75, 95% CI: 0.69–0.83, p < 0.001). The incidence risk of composite CVD was associated with changes of presence and severity of proteinuria. Persistent proteinuria may be associated with increased risk of CVD, even compared with improved or progressed proteinuria status.

Association between the triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular diseases in people living with human immunodeficiency virus: Evidence from a retrospectively cohort study 2005-2022.

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored. We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People's Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects. At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for non-linear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Prognostic Value of Systemic Inflammation, Nutritional Status and Sarcopenia in Patients With Amyotrophic Lateral Sclerosis.

Nutritional status, systemic inflammatory responses and muscle mass are associated with the prognosis of patients with amyotrophic lateral sclerosis (ALS). However, the optimal biomarker for predicting prognosis remains unclear. This study aimed to identify the optimal indicators of survival among the nutrition-based, inflammation-based and muscle mass-related markers for ALS patients. We enrolled ALS patients from January 2014 to December 2019. Experienced neurologists followed up with the participants until January 2022. This study included a total of 17 nutritional, systemic inflammatory or muscle mass-related indicators. Maximally selected rank statistics determined the cut-off points for these indicators. Kaplan-Meier estimation was used to assess survival. Uni- and multivariate Cox proportional hazards models were used to determine the effects of indicators on survival. Finally, time-dependent receiver operating characteristic (time-ROC) curves and the C-index were calculated to evaluate the predictive efficacy of different indicators. A total of 506 patients with ALS were enrolled in this study, including 288 males (56.9%) and 218 females (43.1%), with a mean age of 54.2 ± 10.5 years. Among these ALS patients, 334 cases (68.0%) either died or underwent tracheotomy. In univariate Cox proportional hazards regression, 11 indicators were significantly associated with ALS survival (p < 0.05). And systemic immune inflammation (SII), platelet-to-lymphocyte ratio (PLR), modified geriatric nutritional risk index (mGNRI), creatinine and sarcopenia index (SI, (creatinine/cystatin C) × 100) were determined as independent predictors (p < 0.05) in multivariate Cox proportional hazards regression. A higher SI predicted longer survival (hazard ratio, 0.59; 95% confidence interval [CI], 0.46-0.76; p < 0.001). The results of time-ROC and C-index analyses indicated that SI had the best predictive efficacy for ALS survival, with a C-index of 0.65 (95% CI, 0.54-0.75) for 1-year, 0.61 (95% CI, 0.57-0.65) for 3-year and 0.59 (95% CI, 0.55-0.62) for 5-year survival. Across different subgroups, SI had the highest C-index in men and women, limb onset and aged < 60 year ALS patients, compared with other indicators. However, cystatin C was the best indicator for predicting the survival of ALS patients with bulbar onset, whereas the prognostic nutritional index (PNI) was the best for those aged ≥60 years. The serum SI demonstrates superior prognostic ability compared to other inflammation-based, nutrition-based and muscle mass-related indicators for patients with ALS. Given its simplicity and availability, it is well suited for clinical use in evaluating the prognosis of ALS patients.

Influence of the Type of Antiretroviral Treatment on the Time to Reach High Pharmacotherapy Complexity in People Living With HIV.

The introduction of antiretroviral therapy (ARV) has significantly improved the survival of people living with HIV (PLWH), increasing the proportion of individuals over 50 years old. This aging trend poses challenges, such as the development of age-related comorbidities and a higher prevalence of polypharmacy. The pharmacotherapeutic complexity, assessed using the Medication Regimen Complexity Index (MRCI), is crucial for identifying and optimizing treatment, especially in elderly and polymedicated patients. The main objective was to assess the association between different ARV regimens and the time required to reach a high level of pharmacotherapeutic complexity in PLWH. A single-center observational analytical research study was conducted, including adult PLWH on active ARV from January 2010 to December 2021 with follow-up until December 2023. An analysis of the time to reach MRCI ≥11.25 was performed, followed by a Cox regression model to determine the influence of ARV on high MRCI. A total of 789 PLWH were included, median age of 52 years (interquartile range: 45-58). Overall, 195 patients had an MRCI value ≥11.25 with a mean time to reach it of 181.86 months (95% confidence interval [CI]: 176.24 to 187.49). Significant differences were observed in sex, advanced age, AIDS stage, presence of comorbidities, polypharmacy, and ARV-related variables. A multivariate Cox proportional hazards model showed an association between integrase inhibitor (INSTI)-containing regimens (hazard ratio [HR]: 1.83; 95% CI: 1.08 to 3.10) and non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (HR: 0.72; 95% CI: 0.52 to 0.98) with the time to reach high MRCI. In summary, NNRTI-based regimens were associated with a lower likelihood of developing high MRCI compared to INSTI-based regimens, which was associated with a higher likelihood. These conclusions are based on a profile of PLWH that included advanced age and a high prevalence of comorbidities and polypharmacy. Identifying high MRCI may help us implement pharmacotherapeutic optimization strategies to improve health outcomes.

Preoperative Factors Affecting Graft Survival After ABO-incompatible Adult Liver Transplantation.

Although ABO-incompatible liver transplantation (ABOi LT) has undergone remarkable progress, the prognostic factors are poorly understood. This study aimed to elucidate the preoperative factors affecting graft survival after ABOi LT. Patients who underwent ABOi LT between January 2012 and December 2020 at a single institution in South Korea were retrospectively reviewed. A total of 146 recipients, including 34 patients with graft loss, were analyzed. In the multivariate Cox proportional hazard model, recipient age (≥55 y; hazard ratio, 2.47; 95% confidence interval, 1.18-5.19; P = 0.017) and donor ABO type (donor A, hazard ratio, 3.12; 95% confidence interval, 1.33-7.33; P = 0.009) were significantly associated with an increased risk of graft loss. The most common cause of graft loss was recipient death due to bacterial infection (15/34, 44.1%). Both recipient age and donor ABO type were associated with an increased risk of recipient death due to bacterial infections. The incidence of complications after ABOi LT, including antibody-mediated rejection and diffuse intrahepatic biliary stricture, did not differ according to recipient age or donor ABO type. These findings suggest that recipient age and donor ABO type should be considered when preparing for ABOi LT. Careful monitoring and care after transplantation are required for recipients with preoperative risk factors.

Time to recovery from necrotizing enterocolitis and its predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar, Ethiopia: A retrospective follow up study, 2022.

Necrotizing enterocolitis is one of the most common, life-threatening, gastrointestinal disorders in neonates. The recovery time for neonates with NEC varies depending on disease severity, prompt diagnosis, and effective treatment. Therefore, this study was intended to assess the time to recover from necrotizing enterocolitis and its' predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar City, Ethiopia. An institution-based retrospective follow-up study design was employed. A sample of 361 medical records of neonates with necrotizing enterocolitis was selected using systematic random sampling. Diagnosis of NEC in this study required clinical, laboratory and radiographic findings. The survival function was described using Kaplan Meier survival curve and log-rank test. Bivariate and multivariate Cox-proportional hazard (Cox-PH) regression models were used for analysis. The median recovery time from necrotizing enterocolitis for neonates in the neonatal intensive care unit was 12 days. The multivariable Cox-PH model showed that neonates classified as Stage III NEC (AHR: 0.42, 95% CI = 0.23-0.77) and those exposed to perinatal asphyxia (AHR: 0.51, 95% CI: 0.35-0.74) had a negative impact on NEC recovery time. However, neonates with a birth weight of 1500-2499gm (AHR: 1.65, 95% CI: 1.05-2.58) and a platelet count greater than 150,000 (AHR: 1.75, 95% CI: 1.24-2.48) had a positive effect on NEC recovery time. The recovery time for neonates in the neonatal intensive care unit with necrotizing enterocolitis was longer. Comorbidities and advanced stage of NEC were associated with prolonged recovery time from NEC. However, neonates with better platelet count and birth weight greater than 1500mg had shorter recovery time from NEC.

Undetected Cribriform and Intraductal Prostate Cancer at biopsy is associated with adverse outcomes.

Intraductal carcinoma (IDC) and cribriform pattern (Crib) of prostate cancer are increasingly recognized as independent prognosticators of poor outcome, both in prostate biopsies and radical prostatectomy (RP) specimens. The aim of our project is to assess the impact of false negative biopsies for these two characteristics on oncological outcomes. Patients who underwent RP between January 2015 and December 2022 were included in the study. Predictors of Biochemical Failure were examined using a multivariate Cox proportional hazards model. Among the 836 patients who underwent RP, 233 (27.9%) had Crib, and 125 (15.0%) had IDC on prostate biopsy, with 71 (8.5%) patients having both IDC and Crib. Concerning IDC/Crib status at biopsy, 217 (26%) patients had a false-negative biopsy, 332 (39.7%) had a true-negative biopsy, 256 (30.6%) showed a true-positive biopsy, and 24 (3.7%) exhibited a false-positive biopsy, with respect to either pattern. When comparing false-negative, false-positive, true-negative and true-positive biopsies for IDC/Crib, we found that patients with a false-negative biopsy for IDC/Crib versus those with a true-negative biopsy for IDC/Crib disclosed a rate of advanced pathological stage (≥pT3) which was twice that of patients with a true-negative biopsy for IDC/Crib: 56.8% versus 28.1%, respectively (p < 0.001). On multivariate Cox analysis, log PSA before RP (hazard ratio [HR] 2.07, 95% CI 1.53-2.82; p < 0.001), a higher percentage of positive cores at biopsy ( ≥ 33%) (HR 1.68, 95% CI 1.07-2.63; p = 0.024), and false negative biopsy for IDC/Crib (HR 2.14, 95% CI 1.41-3.25; p < 0.001), were each significantly associated with an increased risk of BCR. A false-negative biopsy for IDC/Crib is independently associated with higher risk of BCR and advanced pathological stage compared to a true negative biopsy.

Association of blood count–derived immunoinflammatory makers and risk of epilepsy: A prospective cohort of 497,291 participants

ObjectiveTo explore the longitudinal association between blood count-derived immunoinflammatory markers and the risk of epilepsy in a large population cohort. MethodsWe used data from the UK Biobank (UKB) to investigate the association between pre-diagnostic peripheral immunoinflammatory cells and their derived ratios, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and the risk of epilepsy. This was a longitudinal cohort study in which multivariate Cox proportional hazards models and a series of sensitivity and subgroup analyses were performed to explore the nature of these associations. ResultsWe examined these associations in a prospective UKB cohort of 497,291 participants. During a median follow-up of 12.43 years, 2,715 participants developed epilepsy. After adjusting for all covariates, the results showed that higher monocyte counts and some blood count-derived immunoinflammatory metrics (monocyte counts, hazard ratio [HR]=1.093, 95 % confidence interval [CI] 1.052–1.136, P<0.001; NLR, HR=1.062, 95 % CI 1.022–1.103, P=0.002; PLR, HR=1.096, 95 % CI 1.055–1.139, P<0.001; SII, HR=1.041, 95 % CI 1.003–1.082, P=0.036) were associated with an increased risk of epilepsy. Conversely, we found that higher lymphocyte counts and LMR were negatively associated with the risk of epilepsy (lymphocyte count, HR=0.889, 95 % CI 0.856–0.923, P < 0.001; LMR, HR=0.85, 95 % CI 0.82–0.881, P < 0.001). ConclusionsMonocyte count, NLR, PLR, and SII increased the risk of epilepsy, whereas lymphocyte count and LMR decreased it. Further studies will help translate these findings into clinical practice or targeted treatments.

Frailty, age, and treatment effect of surgical coronary revascularization in ischemic cardiomyopathy: a post hoc analysis of the STICHES trial.

Frailty is common among older patients with heart failure (HF). The efficacy of coronary artery bypass grafting (CABG) on the risk of mortality amongfrailpatients with ischemic cardiomyopathy and HF is uncertain, and whether frailty burden modifies the treatment benefits of CABG among these patients is unknown. We performed a post hoc analysis of the STICHES trial, a randomized trial of CABG with medical therapy vs medical therapy alone among participants with ischemic cardiomyopathy with ejection fraction ≤ 35%. Baseline frailty was assessed through a Rockwood Frailty Index (FI), and based on FI cut-offs from prior HF studies, participants with FI ≥ 0.311 were classified as more frail, and those with FI < 0.311 were classified as less frail. A multivariable Cox proportional hazard model with multiplicative interaction terms was constructed to evaluate whether frailty status modified the treatment effect of CABG on mortalityin the overall trial cohort and among those < 60 vs ≥ 60 years of age. Of 1187 participants (12.4% female, 2.6% Black, median FI = 0.33 [IQR 0.27-0.39]), 678 were characterized as more frail. Frailty burden did not modify the efficacy of CABG on the risk of all-cause death in the overall cohort (Pint CABG × frailty = 0.2). In age stratified analysis,Baseline frailty status did not modify the treatment effect of CABG on the risk of all-cause mortality among younger (< 60years, Pint CABG × frailty = 0.2) as well as older participants (≥60years, Pint CABG × frailty = 0.6). In this post hoc analysis of the STICHES trial, baseline frailty status did not modify the efficacy of CABG in the overall cohort as well asamong younger or older participants. Frailty alone should not be used as a criterion to determine the utilization of CABG among patients with ischemic cardiomyopathy.

An assessment of cancer centre level designation and guideline adherent care in those with rectal cancer: A population based retrospective cohort study

BackgroundInstitutions providing care to individuals with cancer are organized based on available resources and treatments offered. It is presumed that increasing levels of care will result in improved quality of care and outcomes. The objective is to determine whether Cancer Level Designation is associated with guideline adherent care and/or survival. MethodsThis is a retrospective study of individuals within the Ontario Rectal Cancer Cohort, a population-level database including all adults undergoing surgical resection for rectal cancer between 2010 – 2019 were included in Ontario, Canada. The primary exposure was Cancer Centre Level Designation as defined by Cancer Care Ontario (i.e., Level 1/2 = regional cancer center; Level 3 = affiliate cancer center; Level 4 = satellite cancer center). The primary outcomes were guideline adherent care and survival. Associations were determined using one-way analysis of variances and a multivariable Cox proportional hazards model. Results12,399 patients were included with 54 % from a Level 1/2 centre, 33 % from a Level 3 centre and 13 % from a Level 4+ centre. All assessed aspects of guideline adherent care were associated with cancer centre level designation. Unadjusted 5-year overall survival was associated with cancer centre level designation (Level 1/2 79.5 % vs. Level 3 79.1 % vs. Level 4/non-designated 75.4 %, P = 0.003). Adjusted Cox Proportional Hazard Analysis for overall survival found the following: Level 4/5 HR 1.11 (95 %CI 0.99 – 1.25); Level 3 HR 1.01 (95 % CI 0.93 – 1.11); Level 1/2 1 [Referent group]. ConclusionsIncreasing Cancer Centre Level Designation was associated with higher likelihood of receiving the appropriate investigations and treatments in those with rectal cancer and may also be associated with survival. Policy SummaryFuture work should consider the centralization of complex rectal cancer care as well as quality improvement initiatives aimed at enhancing guideline adherent care across all centres managing rectal cancer.

Quality of care for secondary cardiovascular disease prevention in 2009–2017: population-wide cohort study of antiplatelet therapy use in Scotland

BackgroundAntiplatelet therapy (APT) can substantially reduce the risk of further vascular events in individuals with established atherosclerotic cardiovascular disease (ASCVD). However, knowledge regarding the extent and determinants of APT use...

Serum Autotaxin Levels Predict Liver-Related Events in Patients With Primary Biliary Cholangitis: A Long-Term Multicenter Observational Study.

A straightforward, reliable, and noninvasive method for predicting the development of liver-related events (LRE) in primary biliary cholangitis (PBC) has not been attained thus far. This study investigated whether serum autotaxin (ATX) could predict LRE in patients with PBC. This retrospective multicenter investigation included 190 biopsy-proven untreated patients with PBC. All subjects were followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, esophagogastric varices, ascites, and hepatic encephalopathy, was investigated in relation with ATX levels at the time of liver biopsy. During the median follow-up period of 9.7 years, LRE were observed in 22 patients (11.6%). The area under the receiver operating characteristic curve and cutoff value of serum ATX for predicting LRE were 0.80 and 1.086 mg/L, respectively. Patients with serum ATX ≥1.086 had a significantly higher cumulative incidence of LRE compared with patients with ATX < 1.086 (33.3% vs 3.6%, P < 0.00001). Notably, the predictive capability of ATX for LRE in patients with PBC surpassed that of FIB-4, ALBI, APRI, and Mac-2-binding protein glycan isomer. A multivariate Cox proportional hazards model revealed ATX as an independent associated factor for LRE (hazard ratio 6.24, 95% confidence interval 1.87-20.80, P = 0.003) along with Nakanuma stage (hazard ratio 2.75, 95% confidence interval 1.52-4.99, P < 0.001). These results were closely replicated in a serologically diagnosed PBC validation cohort (n = 32). Serum ATX levels may serve as a predictive marker for LRE in patients with PBC.

Effect of oral health on functional disability and mortality in older adults in Japan: a cohort study

Oral health has previously shown associations with functional disability and mortality. We aimed to explore the associations of various aspects of oral health status with functional disability and mortality using survival analysis, as well as the relative magnitudes of the impact of these aspects on outcomes. We obtained data for individuals aged 75years and older in Shimane, Japan, who had at least one oral health check-up between April 1, 2016, and March 31, 2022under Japan's long-life medical care system insurance system. Those with missing data or with functional disability at baseline were excluded. 13aspects of oral health status were assessed by dentists or dental hygienists as part of the check-up (using protocols provided by the JapanDental Association and the Japanese Ministry of Health, Labour and Welfare): number of remaining teeth, subjective masticatory performance, objective masticatory performance, periodontal tissue status, functional dysphagia, tongue mobility, articulation, oral hygiene, number of decayed teeth, inadaptation of dentures of the upper jaw and lower jaw (considered separately), oral mucosal disease, and dry mouth. Multivariate Cox proportional hazards models were used to analyse the associations between each aspect of oral health and functional disability and mortality, with fully adjusted models adjusting for sex, age, BMI, medical history, or a propensity score derived from these covariates. Population-attributable fractions (PAFs) were calculated to assess the differential impacts of these oral health status aspects on outcome occurrence. Of the 24 619individuals who had an oral health check-up during the study period, 21 881individuals wereincluded in the analysis of functional disability (9175 [41·93%] men, 12 706 [58·07%] women, mean age 78·31years [SD 2·88], mean follow-up 41·43months [20·80]), and 22 747individuals in the analysis of mortality (9722 [42·74%] men, 13 025 [57·26%] women, mean age 78·34years [2·89], mean follow-up 42·63months [20·58]). All 13aspects of oral health status showed significant associations with the occurrence of mortality, while functional disabilitywas associated with 11aspects (excluding oral mucosal disease and dry mouth) in the fully adjusted model. Based on PAFs, of all oral health aspects assessed, objective masticatory performance hadthegreatestimpact on both functional disability (PAF 23·10% [95% CI 20·42-25·69] for the lowest and 10·62% [8·18-12·99] for the second-lowest quartile of performance) and mortality (16·47% [13·44-19·40] and 8·90% [5·87-11·82]). Various aspects of oral health are associated with mortality and functional disability. Maintaining good oral health in older adults might help to reduce these outcomes. None.

Association of Ambient Air Pollution Exposure With Incident Glaucoma: 12-Year Evidence From the UK Biobank Cohort.

Glaucoma is the leading cause of irreversible blindness worldwide. Despite growing concerns about air quality and its impact on ocular health, there remains a knowledge gap regarding the long-term association between air pollution and glaucoma risk. This study investigates the relationship between exposure to ambient air pollution and incidence of glaucoma. In this prospective study, we used land use regression models to estimate levels of various air pollutants, including fine particulate matter (PM2.5), PM2.5 absorbance, PM2.5-10, PM10, nitrogen dioxide (NO2), and nitrogen oxides (NOx). Incidents of glaucoma were ascertained through routinely collected hospital admission records. Multivariate Cox proportional hazards models were used to examine the associations between air pollution exposure and glaucoma incidence, adjusting for potential confounding sociodemographic, physical, and lifestyle factors. Data from 481,113 participants were included. Over a median follow-up of 12.8 years, 9224 incident cases of glaucoma were identified. In the maximally adjusted model, per interquartile range increase in PM2.5 was associated with a 3% greater risk of developing glaucoma (hazard ratio [HR] = 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.048). Participants in the highest quartile had a 10% increased risk of developing glaucoma compared to those in the lowest quartile (HR = 1.10, 95% CI = 1.03 to 1.17, P = 0.005). Higher levels of exposure to ambient air pollutants, particularly PM2.5, are associated with an increased risk of developing glaucoma. These results highlight the potential public health impact of ambient air pollution on glaucoma risk and underscore the urgent need for further research into targeted environmental interventions in this domain.

Epidemiology and survival of primary intracranial malignant tumor patients with drop metastasis: a population-based analysis.

Drop metastasis significantly impacts the survival of patients with primary intracranial malignant tumors. Using the information of collaborative stage from the SEER database, we aim to analyze the epidemiology and prognosis of primary intracranial malignant tumor patients with drop metastasis. We analyzed the distribution of patients and the frequency according to the demography and clinical characteristics of patients with drop metastasis. We also analyzed the survival of these patients with drop metastasis. Multivariate Cox proportional hazards models were used to analyze possible prognostic indicators. A total of 56,839 cases with primary intracranial malignant tumors were ultimately included in this cohort study. A total of 792 cases were confirmed to have drop metastasis. The average rate of drop metastasis was 1.4%. Most of the patients with drop metastases were diagnosed before ten years old. The three most common primary intracranial malignant tumors with drop metastasis were glioblastoma, embryonal/primitive/medulloblastoma, and anaplastic astrocytoma. Embryonal/primitive/medulloblastoma had the highest drop metastasis rate, at 11.6%. Tumors located in the infratentorial space and ventricles had a higher rate of drop metastasis than tumors in other locations. The prognosis for patients with drop metastasis is poor. Routine complete treatment (surgery of the primary tumor plus chemoradiotherapy) can significantly improve overall survival. We conducted a population-based analysis of primary intracranial malignant tumor patients with drop metastasis. Our study can help clinicians acquire general information on the epidemiology and survival of primary intracranial malignant tumor patients with drop metastasis.