Primary Composite Outcome Research Articles

Clinical effectiveness of oral antivirals for non-hospitalized adult COVID-19 patients aged 18–60 years

ABSTRACT Objective To investigate the effectiveness of oral antiviral agents – nirmatrelvir – ritonavir or molnupiravir in non-hospitalized COVID-19 patients aged <60 years. Methods This retrospective cohort study analyzed data of patients aged 18–60 years diagnosed with COVID-19 between 1 January 2022, and 30 June 2023. Propensity score matching was used to balance the demographic and clinical characteristics of patients receiving oral antivirals (nirmatrelvir – ritonavir or molnupiravir) and untreated controls. The primary outcome was a composite of all-cause emergency department visits, hospitalizations, or mortality within 30 days. The secondary outcomes included each individual component of the primary composite outcome. Results Two matched cohorts (antiviral group and control group) comprising 52,585 patients with balanced baseline characteristics were created using propensity score-matching. During follow-up period, the antiviral group demonstrated a lower risk of the primary outcome than the control group (hazard ratio [HR] 0.772, 95% confidence interval [CI] 0.736–0.808, p < 0.001). The antiviral group also exhibited a reduced risk of individual secondary outcomes, including emergency department visits (HR 0.780, 95% CI, 0.738–0.825), hospitalization (HR 0.755, 95% CI, 0.715–0.840), and mortality (HR 0.297, 95% CI, 0.147–0.600). Conclusion Oral antiviral agents were associated with lower risks of all-cause emergency department visits, hospitalizations, and mortality in non-hospitalized COVID-19 patients aged <60 years.

Osteoprotegerin, Osteopontin, and Osteocalcin Are Associated With Cardiovascular Events in Type 2 Diabetes: Insights From EXSCEL.

To evaluate the association of four bone metabolism biomarkers (osteoprotegerin, osteopontin, sclerostin, and osteocalcin) with cardiovascular events in people with type 2 diabetes (T2D). The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) was a randomized clinical trial evaluating the cardiovascular (CV) safety and efficacy of once-weekly exenatide for patients with T2D. Candidate biomarker data were selected from proteomic profiling performed at baseline and 12 months after randomization samples by SomaScan assay in 5,473 trial participants. The primary composite outcome was the first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke (major cardiovascular events [MACE]). Cox proportional hazards models controlling for confounders were used for time-to-event analyses to calculate hazard ratios (HRs) with 95% CI for a 1 SD increase in the biomarker concentrations. The primary outcome occurred in 813 participants (14.9%). Higher levels of osteoprotegerin (HR 1.11; 95% CI 1.03-1.20; P = 0.0047) and osteopontin (HR 1.10; 95% CI 1.02-1.18; P = 0.0095) were associated with an increased risk of MACE. The addition of osteoprotegerin and osteopontin to a clinical predictive model containing traditional CV risk factors provided minimal incremental value for MACE prediction (C-index 0.629 vs. 0.638; likelihood ratio test P < 0.001). Osteocalcin and sclerostin were not associated with MACE. Osteocalcin had a nonlinear association with all-cause death and with CV death. Higher levels of osteoprotegerin and osteopontin are associated with an increased risk of CV events in people with T2D, supporting the hypothesis that pathways involved in bone metabolism play a role in CV disease.

Implications of Tricuspid Regurgitation Severity in Patients Undergoing Mitral Transcatheter Edge-to-Edge Repair.

Prognostically meaningful tricuspid regurgitation (TR) is not well-defined in the mitral transcatheter edge-to-edge repair arena. We aimed to explore the prevalence, correlates, and consequences of TR grades and postprocedural trends in this setting. A single-center registry of isolated, first-time interventions was retrospectively assessed for pre-, intra-, and postprocedural aspects up to 1 year, of them the primary composite outcome of all-cause deaths or heart failure (HF) hospitalizations, all according to TR severity at baseline and at 1 month following mitral transcatheter edge-to-edge repair. Overall, 1287 individuals (60.3% men, age 78 [interquartile range, 69-85] years, 52.9% with functional mitral regurgitation) were included. Below-moderate, moderate, and above-moderate TR affected 48.4%, 29.5%, and 22.1% of patients, respectively. Increasing TR severity was accompanied by higher rates of functional, severe mitral regurgitation, greater comorbidity, and more advanced heart failure. Although not affecting technical and echocardiographic procedural success, moderate-and-above TR degrees were associated with higher incidence of mortality, heart failure admissions, and functional class III to IV postprocedure, with moderate-to-severe and greater TR independently conferring increased risk for the various outcomes (primary end point; HR, 1.36 [95% CI, 1.21-1.80]; P=0.027). One-month postprocedural TR severity directly correlated with, and was mostly similar to or worse than, its baseline counterpart. Rather than the change between the two, moderate-and-above grade at 1 month, observed in 37.1% of eligible cases, emerged as predictive of the primary outcome's risk. Among patients undergoing mitral transcatheter edge-to-edge repair, above-moderate TR at baseline and the closely related moderate-and-above TR at 1 month postprocedure are highly prevalent and signal a suboptimal course.

Real-life use of the PEXIVAS reduced-dose glucocorticoid regimen in granulomatosis with polyangiitis and microscopic polyangiitis

BackgroundThe PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect...

The relationship between HBV antigens deposition in kidneys and renal prognosis in IgA nephropathy patients infected with HBV

Background Hepatitis B virus (HBV) is a risk factor for the progression of immunoglobulin A (IgA) nephropathy. The effect of HBV antigens deposition in kidneys and treatment influencing HBV deposition requires further investigation. Methods We analyzed 198 patients with IgAN, including 99 patients with HBV infection and 99 propensity score-matched patients without HBV infection. The primary outcome was a composite of 30% decrease in eGFR from the baseline, kidney failure and all-cause mortality. A Cox proportional hazard model was used to assess the impact of both HBV positive in the serum and HBV antigens deposition in the kidneys on renal outcomes. Results Among 198 individuals, 27 primary composite outcome events were observed, of which 20 (20%) in the HBV positive group and seven (7%) were in the HBV-negative group. The former had a 2.72-fold increased risk of primary outcome events (adjusted hazard ratio: 2.22; 95% confidence interval: 0.89–5.53). HBV antigens deposition in kidneys increased the risk significantly after adjusting for confounders at the latest follow-up (adjusted hazard ratio: 7.49; 95% confidence interval: 1.00–56.04). Antiviral treatment did not influence the deposition of HBV antigens. Conclusions HBV antigen deposition in the kidneys, compared with no deposition in the kidneys, was associated with a 7.49-fold increased risk of renal prognosis in patients with IgA nephropathy.

Colchicine in Acute Myocardial Infarction.

Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events. In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed. A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P = 0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups. Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization). (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).

Prognosis of apparent treatment-resistant hypertension and poor adherence: a nationwide cohort study.

Large-scale studies of the prognosis of resistant hypertension in Asian populations are limited, and the impact of poor adherence on clinical prognosis in patients with apparent treatment-resistant hypertension has not been studied. A nationwide cohort analysis was done utilizing the National Health Insurance Service database in Korea, covering patients who participated in health examinations from 2013 to 2018. A total of 935,002 patients were classified into apparent treatment-resistant (N = 69,372) or nonresistant (N = 865,630) hypertension based on blood pressure control and antihypertensive medication use. Medication adherence was assessed using the proportion of days covered. The primary composite outcome included all-cause mortality, myocardial infarction, stroke, and heart failure. Other outcomes were the development of atrial fibrillation and progression to end-stage renal disease (ESRD). The median follow-up duration was 6.0 (interquartile range [IQR], 4.1-7.0) years. Patients with apparent treatment-resistant hypertension were at a higher risk for the primary composite outcome than those with nonresistant hypertension (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.29-1.35). The incidence rates of ESRD were notably higher in the resistant hypertension group (HR, 3.02; 95% CI, 2.85-3.20). Among participants with resistant hypertension, 3852 (5.7%), 11,667 (17.3%), and 51,879 (77%) had poor, suboptimal, and optimal adherence, respectively. Poor medication adherence in apparent treatment-resistant hypertension was associated with a higher risk of the primary composite outcome compared to optimal adherence (HR, 1.49; 95% CI, 1.36-1.63). Apparent treatment-resistant hypertension is associated with significant cardiovascular risks in the Korean population. Poor adherence to antihypertensive medication significantly elevates the risk of adverse clinical outcomes in patients with apparent treatment-resistant hypertension, underscoring the need for stringent management of these patients.

A Proteomics-Based Approach for Prediction of Different Cardiovascular Diseases and Dementia.

Many studies have explored whether individual plasma protein biomarkers improve cardiovascular disease risk prediction. We sought to investigate the use of a plasma proteomics-based approach in predicting different cardiovascular outcomes. Among 51 859 UK Biobank participants (mean age, 56.7 years; 45.5% male) without cardiovascular disease and with proteomics measurements, we examined the primary composite outcome of fatal and nonfatal coronary heart disease, stroke, or heart failure (major adverse cardiovascular events), as well as additional secondary cardiovascular outcomes. An exposome-wide association study was conducted using relative protein concentrations, adjusted for a range of classic, demographic, and lifestyle risk factors. A prediction model using only age, sex, and protein markers (protein model) was developed using a least absolute shrinkage and selection operator-regularized approach (derivation: 80% of cohort) and validated using split-sample testing (20% of cohort). Their performance was assessed by comparing calibration, net reclassification index, and c statistic with the PREVENT (Predicting Risk of CVD Events) risk score. Over a median 13.6 years of follow-up, 4857 participants experienced first major adverse cardiovascular events. After adjustment, the proteins most strongly associated with major adverse cardiovascular events included NT-proBNP (N-terminal pro B-type natriuretic peptide; hazard ratio [HR], 1.68 per SD increase), proADM (pro-adrenomedullin; HR, 1.60), GDF-15 (growth differentiation factor-15; HR, 1.47), WFDC2 (WAP four-disulfide core domain protein 2; HR, 1.46), and IGFBP4 (insulin-like growth factor-binding protein 4; HR, 1.41). In total, 222 separate proteins were predictors of all outcomes of interest in the protein model, and 86 were selected for the primary outcome specifically. In the validation cohort, compared with the PREVENT risk factor model, the protein model improved calibration, net reclassification (net reclassification index +0.09), and c statistic for major adverse cardiovascular events (+0.051). The protein model also improved the prediction of other outcomes, including ASCVD (c statistic +0.035), myocardial infarction (+0.023), stroke (+0.024), aortic stenosis (+0.015), heart failure (+0.060), abdominal aortic aneurysm (+0.024), and dementia (+0.068). Measurement of targeted protein biomarkers produced superior prediction of aggregated and disaggregated cardiovascular events. This study represents an important proof of concept for the application of targeted proteomics in predicting a range of cardiovascular outcomes.

Should we restrict food intake during labor? A randomized controlled trial.

To evaluate whether consuming food during labor influences its outcomes. This randomized controlled study included healthy, laboring patients at 37-41weeks of gestation. After epidural anesthesia, patients were randomized into groups of eating at will versus drinking clear fluids only. The primary composite outcome included unplanned cesarean delivery, the need for general anesthesia, asphyxia, postpartum fever, and prolonged postpartum admission (more than 5days). Secondary outcomes included the need for oxytocin, length of the second stage of labor, postpartum analgesia requirements, and early maternal and neonatal outcomes. Sample size analysis indicated that 126 patients needed to be randomized to detect a statistically significance difference between the groups. A total of 129 patients were randomized: 58 to the fluids-only group and 71 to the food group. The groups had similar basic characteristics. The composite outcome of complications attributed to eating during labor and delivery was comparable between groups. Labor progression and the need for oxytocin augmentation were similar in both groups. The groups had comparable fetal heart rate tracings, modes of delivery, maternal and neonatal outcomes, and complications. None of the patients in the study experienced aspiration or an indication for general anesthesia. While our data suggest that eating during labor does not adversely affect labor progression or outcomes, we recommend a cautious approach, allowing patients autonomy while considering individual risk factors. The study has been registered in the primary clinical trial registry on 02/12/2023. ISRCTN trial number ISRCTN11794106, registration number 44513. https://www.isrctn.com/ISRCTN11794106 .

A causal model for predicting the impact of pharmacotherapy on colorectal surgery outcomes.

Evidence-based principles in enhanced recovery programs (ERPs) demonstrate substantial improvement in patient outcomes. Determining which latent variables predict composite outcomes could refine ERP pharmacotherapy recommendations. Using R, pharmacotherapy data were modeled from an existing dataset of adult elective colorectal surgery patients. Primary composite outcome was absence of surgical site infection, venous thromboembolism, postoperative nausea and vomiting, and other in-hospital postoperative complications (POCs). Secondary composite outcome included no postdischarge POCs, hospital length of stay ≤3days, and no readmission at 7- or 30-days. Variables with greater odds of predicting both positive primary and secondary composite outcomes included prehospital oral iron and oral antibiotic use, postoperative sugammadex and neostigmine use, postoperative morphine milligram equivalents (MME)≤50, and IV fluid stop by postoperative day 2. Preoperative scopolamine patch (OR=0.29 and CI=-0.19-0.77) and perioperative gabapentin (OR=0.46 and CI=0.06-0.83) had lesser odds for both primary and secondary composite outcomes. Ketamine nonanesthetic bolus, ondansetron IV use, and in-hospital enoxaparin use had paradoxical lesser primary but greater odds for secondary composite outcomes. Prehospital oral laxative use (OR=0.61 and CI=0.18-1.04) and postoperative dual IV antibiotics (OR=0.52 and CI=0.10-0.94) had lesser odds for primary, but not secondary, outcome. To improve the odds for positive composite outcomes, oral iron and antibiotics, sugammadex and neostigmine, lower MME, and early IV fluid cessation could be considered essential core items, whereas postoperative dual IV antibiotics and epidural anesthesia might be avoided. Additional research needs to clarify the impacts of in-hospital enoxaparin, ketamine nonanesthetic bolus, and ondansetron use on composite patient outcomes.

Abstract 4132351: Soluble Urokinase Plasminogen Activator Receptor Levels Predict Incident Cardio-Kidney-Metabolic Disease Risk

Introduction: Given the rising global incidence of cardio-kidney-metabolic (CKM) syndrome, there is an urgent need for novel risk prediction strategies for CKM disease. Hypothesis: As soluble urokinase plasminogen activator receptor (suPAR) levels have been associated with the development of cardio-kidney disease, we hypothesized that elevated suPAR levels would predict incident CKM disease risk. Methods: A total of 25,596 UK Biobank participants without CKM disease at enrollment were analyzed for the association of suPAR levels and incident CKM disease. CKM disease was defined as the first occurrence of CVD (heart failure, atrial fibrillation/flutter, coronary heart disease, stroke, and peripheral artery disease), chronic kidney disease (CKD), or metabolic disease (type 2 diabetes mellitus and obesity). Incident CVD, CKD, and metabolic disease were also analyzed separately as secondary outcomes. Kaplan-Meier analysis was performed to visualize the association between suPAR levels and the primary composite CKM outcome. Competing-risk regression, while accounting for competing non-CKM disease death, was performed to examine the association between suPAR levels and the primary composite CKM outcome. Models were adjusted for demographics, traditional risk factors, and CRP levels. Results: The mean age was 56.0 (SD 8.3) years, 44% were male, and 94% were White. suPAR levels were associated with a significantly higher rate of composite CKM events (P&lt;0.001) (Figure 1). During a median follow-up of 13.5 [IQR 1.7] years, 5,012 (20.0%) composite CKM events, 3,599 (8.3%) incident CVD events, 863 (3.4%) incident CKD events, and 1,397 (4.7%) incident metabolic disease events occurred. suPAR levels (per SD) significantly predicted the primary composite CKM outcome (sHR 1.23, 95% CI 1.19-1.27) after adjustment. suPAR levels (per SD) also significantly predicted incident CVD (sHR 1.24, 95% CI 1.19-1.29), incident CKD (sHR 1.41, 95% CI 1.30-1.53), and incident metabolic disease (sHR 1.17, 95% CI 1.10-1.24) after adjustment. Conclusion(s): In this large, longitudinal cohort study of UKB participants, plasma suPAR levels were a significant predictor of CKM disease risk, independent of demographics, traditional risk factors, and CRP levels.

Abstract 4127562: Age, Adiposity-Related Anthropometrics, and Clinical Outcomes in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: A Participant-Level Pooled Analysis of Randomized Trials

Background: Age has been shown to modify the population-level association between body mass index (BMI) and mortality. However, whether age modifies the association between adiposity-related anthropometrics and adverse outcomes in heart failure (HF) populations has not been systematically explored. Methods: In this participant-level pooled analysis of five international, multicenter, randomized-controlled trials enrolling adults with HF and either mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), the association between age and adiposity-related anthropometrics (BMI, waist circumference [WC], and waist-to-height ratio [WHtR]) and the primary composite outcome of time-to-first HF hospitalization or cardiovascular (CV) death was evaluated using multivariable adjusted Cox proportional hazards models (stratified by treatment and trial) and restricted cubic splines. Results: Among 21,606 participants in the analysis (mean age, 71±9 years; 49% female; 83% White; mean BMI, 30±6 kg/m 2 ), 5,350 (25%) were aged &lt;65 years, 8,273 (38%) were aged 65-74 years, and 7,983 (37%) were aged ≥75 years at baseline. Older individuals were more likely to be female, have lower BMI and WC, and higher left ventricular ejection fraction. Overall, BMI, WC, and WHtR were steeply and non-linearly associated with the primary outcome ( Figure ). Age, as either a categorical or continuous variable, significantly modified the covariate-adjusted association between all anthropometrics and the primary composite outcome ( P ≤0.001 for all) ( Figure ). A J-shaped relationship, characterized by higher incidence of the primary outcome with lower anthropometric values, was observed only for BMI and was substantially attenuated among younger adults. Irrespective of the anthropometric used, increasing adiposity was most steeply associated with primary events among adults aged &lt;65 years. Conclusions: In this pooled analysis of HFmrEF/HFpEF trials, age was a powerful modifier of the relationship between excess adiposity and HF hospitalization or CV death. An “obesity-survival paradox” – observed only for BMI – was not apparent in younger participants, who exhibited the steepest increase in the rate of clinical events with higher adiposity.

Abstract 4134637: Impact of Glucagon-Like Peptide-1 Agonists on Cardiovascular Outcomes in Chronic Kidney Disease Stage 5: A Propensity Score-Matched Analysis

Background: Patients with chronic kidney disease stage 5 (CKD-5) face heightened risks of cardiovascular (CV) complications and mortality. Glucagon-like peptide-1 agonists (GLP-1a), primarily used in type 2 diabetes, are being investigated for potential CV benefits in this population. This study aims to evaluate the impact of GLP-1a treatment on CV outcomes and survival among CKD-5 patients. Methods: This retrospective cohort study utilized data of adult patients diagnosed with CKD-5 between January 2014 and August 2023 from the TriNetX global research network. A propensity score matching analysis of those treated with GLP-1a for at least six months versus those never exposed to GLP-1a therapy was conducted. Results: Our analysis showed significantly reduced odds for the composite primary outcome of acute myocardial infarction (AMI), stroke, and mortality (OR = 0.66, 95% CI: 0.57-0.78, p&lt;0.001), and other CV outcomes such as cardiac arrest, hypertensive crisis, and hypertensive urgency, among the GLP-1a cohort compared with the non-GLP-1a cohort. Kaplan-Meier survival analysis revealed a significantly higher five-year incidence-free probability for the composite primary outcome (63.5% vs. 50.5%, p&lt;0.001) and for other CV outcomes such as hypertensive events, AMI, cardiac arrest, and hemorrhagic stroke for the GLP-1a cohort. Conclusion: The study suggests that GLP-1a therapy in CKD 5 patients may confer certain CV benefits. Further investigations are warranted to elucidate the underlying mechanisms and confirm the therapeutic efficacy of GLP-1a in this patient population.

Abstract 4127681: Neutrophil-lymphocyte ratio as a marker of cardiovascular outcomes in patients with chronic coronary syndrome

Background: Inflammation is one of the pathophysiological processes involved in the genesis and progression of atherosclerosis and has been increasingly used as a therapeutic target in recent years. The neutrophil-lymphocyte ratio (NLR) is a promptly accessible inflammatory biomarker strongly associated with prognosis in the acute coronary setting. However, there are few data in patients with chronic coronary syndrome (CCS). Objective: Analyze the association between NLR and cardiovascular outcomes in patients with CCS. Methods: Patients with CCS, defined as a previous revascularization procedure (surgical or percutaneous), previous myocardial infarction (MI) or stenosis &gt; 50% in at least one epicardial coronary artery, were included and followed up on an outpatient basis. The NLR was calculated using the baseline blood count. The main outcome was the composite of death, non-fatal myocardial infarction and non-fatal stroke. Results: The study population consisted of 975 patients, with a median age of 65 years and 30% were women. Previous MI was present in 61%, 30% had undergone previous revascularization surgery and 46% had percutaneous coronary intervention. Diabetes was prevalent in 59% and hypertension in 95%. The median NLR was 2.15 (IQR 1.25 - 2.87). Patients with NLR ≥ 2.15, when compared to those with NLR &lt; 2.15, presented more left ventricular (LV) dysfunction (58% vs. 55%; p=0.003) and lower LDL-C serum levels (81 vs. 88 mg/dL; p=0.004). There was no association between NLR and coronary anatomical severity. NLR correlated with age, LDL-C and LV function (p &lt; 0.05 for all). During follow-up, 152 events of the composite primary outcome were registered, with an estimated 3-year incidence of 15.6% in the overall population – higher within patients with NLR ≥ 2.15 when compared to NLR &lt; 2.15 (20% x 14%, p = 0.002), as shown in the figure. In the multivariate analysis, the 3rd quartile of NLR had a 31% higher risk than the 1st quartile (p &lt; 0.05). Conclusion: In this study, the NLR, an easily available inflammatory biomarker, independently correlates with cardiovascular outcomes in a population with CCS.

The Association of Echocardiographically Measured Donor Left Ventricular Massand 1-Year Outcomes After HeartTransplantation.

Donor-recipient heart size matching is crucial in heart transplantation; however, the often-used predicted heart mass (PHM) ratio may be inaccurate in the setting of obesity. In this study, the authors sought to investigate the association between echocardiographically measured donor left ventricular mass (LVM) for heart size matching and the risk of the primary 1-year composite outcome of death or retransplantation. The Donor Heart Study was a prospective, multicenter, observational cohort study that collected echocardiograms from brain-dead donors. The measured LVM ratio (donor measured LVM/recipient predicted LVM) was defined as the exposure variable, and the association with the primary outcome was analyzed with Cox proportional hazard modeling. Secondary analyses evaluated the association of the PHM and predicted LVM (donor predicted LVM/recipient predicted LVM) ratios with the primary outcome. In 2,015 heart transplants, the measured LVM ratio demonstrated that undersized matches (<0.80) had a 47% higher risk (adjusted HR [aHR]: 1.47; 95%CI: 1.01-2.15) and oversized (>1.20) matches had a 58% increased risk (aHR: 1.58; 95%CI: 1.05-2.37) of the 1-year composite outcome compared with ideally matched transplants. However, the PHM and predicted LVM ratios were not associated with the primary outcome. Nonlinear modeling demonstrated a U-shaped relationship between the measured LVM ratio and composite outcome. The measured LVM ratio had superior predictive power for poor post-transplantation outcomes in obese recipients. Measuring donor LVM with the use of echocardiography may provide a more accurate method for donor-recipient heart size matching that could improve heart transplant outcomes, especially in obese recipients.

Associations of SGLT2i with Cardiorenal Outcomes Among Diabetics with Prostate Cancer on Hormone Therapy.

Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM), and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer. Patients ≥ 18years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new-onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over 2years from HT initiation. After propensity score matching, 2155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (OR 0.539, 95% CI 0.446-0.651; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations, and all-cause mortality. Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal, and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer.

Combined spinal-epidural vs. dural puncture epidural techniques for labour analgesia: a randomised controlled trial.

The dural puncture epidural technique is a modification of the combined spinal-epidural technique. Data comparing the two techniques are limited. We performed this randomised study to compare the quality of labour analgesia following initiation of analgesia with the dural puncture epidural vs. the combined spinal-epidural technique. Term parturients requesting labour epidural analgesia were allocated randomly to receive either dural puncture epidural or combined spinal-epidural. Analgesia was initiated with 2 mg intrathecal bupivacaine and 10 μg fentanyl in parturients allocated to the combined spinal-epidural group and with 20 ml ropivacaine 0.1% with 2 μg.ml-1 fentanyl in parturients allocated to the dural puncture epidural group. Analgesia was maintained using patient-controlled epidural analgesia with programmed intermittent epidural boluses. The primary outcome of the study was the quality of labour analgesia, which was defined by a composite of five components: asymmetric block after 30 min of initiation (difference in sensory level of more than two dermatomes); epidural top-up interventions; catheter adjustment; catheter replacement; and failed conversion to neuraxial anaesthesia for caesarean delivery, requiring general anaesthesia or replacement of the neuraxial block. One hundred parturients were included in the analysis (48 combined spinal-epidural, 52 dural puncture epidural). There were no significant differences between the two groups in the primary composite outcome of quality of analgesia (33% in the combined spinal-epidural group vs. 25% in the dural puncture epidural group), risk ratio (95%CI) 0.75 (0.40-1.39); p = 0.486. Median (IQR [range]) pain scores at 15 min were significantly lower in patients allocated to the combined spinal-epidural group compared with the dural puncture epidural group (0 (0-1[0-8]) vs. 1 (0-4 [0-10]); p = 0.018). There were no significant differences in the quality of labour analgesia following initiation of a combined spinal-epidural compared with a dural puncture epidural technique.

Safety of Simultaneous vs Sequential mRNA COVID-19 and Inactivated Influenza Vaccines

Limited randomized clinical trial data exist on the safety of simultaneous administration of COVID-19 and influenza vaccines. To compare the reactogenicity, safety, and changes in health-related quality of life (HRQOL) after simultaneous vs sequential receipt of messenger RNA (mRNA) COVID-19 vaccine and quadrivalent inactivated influenza vaccine (IIV4). This randomized, placebo-controlled clinical trial was conducted between October 8, 2021, and June 14, 2023, at 3 US sites. Participants were nonpregnant persons aged 5 years or older with the intention of receiving both influenza and mRNA COVID-19 vaccines. Intramuscular administration in opposite arms of either IIV4 or saline placebo simultaneously with mRNA COVID-19 vaccine at visit 1. Those who received placebo at visit 1 received IIV4 and those who received IIV4 at visit 1 received placebo 1 to 2 weeks later at visit 2. The primary composite reactogenicity outcome was the proportion of participants with fever, chills, myalgia, and/or arthralgia of moderate or greater severity within 7 days after vaccination visits 1 and/or 2, using a 10% noninferiority margin. Secondary outcomes were solicited reactogenicity events and unsolicited adverse events (AEs) for 7 days after each visit separately and HRQOL after visit 1, assessed by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index. Serious AEs (SAEs) and AEs of special interest (AESIs) were assessed for 121 days. Outcomes were compared between groups. A total of 335 persons (mean [SD] age, 33.4 [15.1] years) were randomized (169 to the simultaneous group and 166 to the sequential group); 211 (63.0%) were female, and 255 (76.1%) received bivalent BNT162b2 mRNA COVID-19 vaccine. The proportion with the primary composite reactogenicity outcome in the simultaneous group (25.6% [n = 43]) was noninferior to the proportion in the sequential group (31.3% [n = 52]) (site-adjusted difference, -5.6 percentage points [pp]; 95% CI, -15.2 to 4.0 pp). Respective proportions in each group were similar after each visit separately (visit 1, 40 [23.8%] vs 47 [28.3%]; visit 2, 5 [3.0%] vs 9 [5.4%]). No significant group differences in participants with AEs (21 [12.4%] vs 16 [9.6%]), SAEs (1 [0.6%] vs 1 [0.6%]), and AESIs (19 [11.2%] vs 9 [5.4%]) were observed in the simultaneous vs sequential groups, respectively. Among participants with severe reactogenicity, the mean (SD) EQ-5D-5L Index score decreased from 0.92 (0.08) to 0.92 (0.09) prevaccination to 0.81 (0.09) to 0.82 (0.12) postvaccination. In this randomized clinical trial assessing simultaneous vs sequential administration of mRNA COVID-19 and IIV4 vaccines, reactogenicity was comparable in both groups. These findings support the option of simultaneous administration of these vaccines. ClinicalTrials.gov Identifier: NCT05028361.

Evaluating the effectiveness of the Smart About Meds (SAM) mobile application among patients discharged from hospital: protocol of a randomised controlled trial

IntroductionAlmost half of patients discharged from hospital are readmitted or return to the emergency department (ED) within 90 days. Non-adherence to medication changes made during hospitalisation and the use of...

Long-Term Impacts of Complete Revascularization on Clinical Outcomes in Patients with Coronary Chronic Total Occlusion

The impact of complete revascularization (CR), achieved through the recanalization of coronary chronic total occlusions (CTOs), on long-term patient outcomes remains uncertain.To evaluate this in patients who achieved CR after CTO-PCI with those who did not due to deferred CTO-PCI, the Asan Medical Center Registry was reviewed to identify coronary artery disease (CAD) patients with CTOs treated between January 2003 and December 2018. Patients were included with single-vessel disease with CTO and with multivessel disease who had undergone revascularization for non-CTO lesions. These subjects were divided into those who achieved CR with CTO-PCI and those who did not due to deferred CTO-PCI. Their outcomes were compared following 1:1 propensity score matching. Of the 2,746 enrolled CAD patients with CTOs, 1,837 achieved CR with CTO-PCI and 909 did not. Propensity score matching yielded 653 patient pairs. The CR-achieving group had a significantly lower 10-year risk of the primary composite outcome of death, myocardial infarction, stroke, or repeat revascularization (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.46–0.72; P < 0.001), as well as significantly lower risks of death (HR: 0.66; 95% CI: 0.51–0.87; P = 0.003) and repeat revascularization (HR: 0.67; 95% CI: 0.48–0.95; P = 0.023). CR was beneficial in all subgroups, including patients with major cardiovascular risk factors such as older age, hypertension, diabetes, and advanced CAD. Compared with incomplete revascularization, CR may significantly reduce the 10-year incidence of major adverse cardiac events in patients with CTO.