Effect on Mortality of Higher Versus Lower β-Blocker (Metoprolol Succinate or Carvedilol) Dose in Patients With Heart Failure

This study aimed to compare the effect of β-blocker dose and heart rate (HR) on mortality in patients with heart failure with reduced ejection fraction (HFrEF). The Veteran Affairs databases were queried to identify all patients diagnosed with HFrEF based on International Classification of Diseases Ninth Revision codes from 2007 to 2015 and β-blocker (carvedilol or metoprolol succinate) use. 36,168 patients on low dose β blocker were then matched with 36,168 patients on high dose β-blocker using propensity score matching. The impact of β-blocker dose and HR was assessed on overall mortality using Cox proportional hazard model. After dividing average HR into separate quartiles and adjusting for patient characteristics, high β-blocker dose was associated with lower overall mortality as compared with a low dose of β blocker (hazard ratio 0.75, 95% confidence interval 0.73 to 0.77, p <0.01) independent of the HR achieved. The results held for all 4 quartiles of average HR. A higher β-blocker dose or a lower HR were independently and jointly associated with lower mortality for all quartiles of HR. In conclusion, higher dose of β-blocker therapy and a lower achieved HR were independently associated with a reduction in mortality in HFrEF patients

How the Arts Benefit the Whole Child

This literature review draws on insights from scholars and arts advocates, it delves into the significance of incorporating artistic practices in schools and advocates for including arts education in public schools. This literature review utilizes studies, peer-reviewed research papers, and governmental recommendations based on current research. Art has a highly transformative power. It benefits the development of complex thought processes and offers insights into children\u27s abilities. By integrating art into education, educators can address the evolving challenges of early childhood education and cultivate environments where students can be engaged by enthusiastic, trained teachers and get excited about learning. Art prepares students for the future world of work and nurtures their social responsibility and resilience, empowering them to navigate life\u27s complexities with confidence and adaptability. Ultimately, by embracing the arts in education, educators can foster intellectually curious, socially adept, emotionally resilient, and physically safe children. Through engaging students in art-making experiences, schools can create environments that stimulate growth and prepare children for the multifaceted challenges of tomorrow

Methods for Prenatal Sex Determination and Their Importance in Understanding and Prevention of Gender-Related Birth Defects

Various hormones, chemicals, and teratogenic agents exhibit gender-related effects in utero as well as postnatally. Among such gender-specific teratogens are endocrine disruptors, especially phthalates that affect male gonads, diabetes-induced oxidative stress with more deleterious effects on male offspring, procarbazine-induced cleft palate affecting more male fetal rats compared to females, and VPA-induced autism-like behavior that affects differently males than females. Hence, there are many needs for the accurate determination of genetic gender. In newborn animals, the morphological methods that exist for sex determination (i.e., anogenital distance) are generally inaccurate. Hence, an accurate and simple method for the prenatal and early postnatal assessment of the genetic sex, prior to reliable evaluation from the external genitalia, is of utmost importance. Indeed, several methods have been developed for accurate assessment of genetic sex, which are discussed in this chapter. Findings from studies in our laboratory have shown that the method described by McFarlan et al. for the assessment of genetic sex in adult mice by PCR of Sly/Xlr genes can be reliably used for the genetic sex determination of any tissue, including embryos and fetuses, with an accuracy of about 100%

Impact of changes in conventional risk factors induced by once-weekly GLP-1 receptor agonist exenatide on cardiovascular outcomes: an EXSCEL post hoc analysis

Background: The objective of this study was to examine the degree to which conventional cardiovascular (CV) risk factor changes induced by once-weekly exenatide (EQW) might explain the placebo-controlled differences in CV outcomes observed in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). Methods: We entered participant-level risk factor values over time into a validated type 2 diabetes–specific clinical outcomes model to estimate event rates, and compared simulated with observed relative risk changes in EXSCEL. We performed simulations for each participant to minimize uncertainty and to optimize confidence interval precision around risk point estimates. Six outcomes were examined: major adverse CV event (MACE), all-cause mortality (ACM), CV death, fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and hospitalization for heart failure (hHF). We also performed a mediation analysis using Cox regression models to evaluate potential key mediators for ACM. Results: Model simulations explained only modest proportions of the observed relative risk reductions for MACE (29%), ACM (15%), CV death (18%), and stroke (29%), but greater proportions for hHF (67%) and MI (200%). Mediation analysis suggested that baseline-to-6 or 12-month changes in HbA1c, blood pressure, heart rate, low-density lipoprotein cholesterol, triglycerides, and weight did not mediate the EQW effect on ACM. Conclusions: These model simulations explain only a modest proportion of the impact of observed EQW-induced changes in conventional CV risk factors on EXSCEL outcomes, apart from hHF and MI. Up to 1-year changes in conventional risk factors did not mediate the observed ACM risk reduction

Neuromodulation interventions in the management of heart failure

Despite remarkable improvements in the management of heart failure (HF), HF remains one of the most rapidly growing cardiovascular condition resulting in a substantial burden on healthcare systems worldwide. In clinical practice, however, a relevant proportion of patients are treated with suboptimal combinations and doses lower than those recommended in the current guidelines. Against this background, it remains important to identify new targets and investigate additional therapeutic options to alleviate symptoms and potentially improve prognosis in HF. Therefore, non-pharmacological interventions targeting autonomic imbalance in HF have been evaluated. This paper aims to review the physiology, available clinical data, and potential therapeutic role of device-based neuromodulation in HF

ScoEHR: generating synthetic electronic health records using continuous-time diffusion models

Global access to statistically and clinically representative patient health data holds potential for advancing disease research, enhancing patient care, and accelerating drug development. However, acquisition of health data such as electronic health records (EHRs) comes with challenges characterised by high costs, time constraints, and concerns related to patient privacy. An approach to tackling these challenges is by using synthetic data. In this paper we introduce ScoEHR, a novel deep learning method for generating synthetic EHRs, which combines an autoencoder with a continuous-time diffusion model. ScoEHR is shown to outperform three baseline synthetic EHR generation frameworks (medGAN, medWGAN, and medBGAN) on two publicly available datasets, MIMIC-III and the Yale New Haven Health System Emergency Department dataset, based on four widely accepted metrics of data utility. Additionally, a blind clinician evaluation was carried out to assess the qualitative realism of the synthetic data generated by ScoEHR. In this evaluation, a patient’s data was labeled as ‘unrealistic’ if at least one clinician found it to be unrealistic. This evaluation showed that existing real EHR data and ScoEHR generated synthetic data were scored as equally realistic. Our code is available at https://github.com/aanaseer/ ScoEHR

Rising mortality rates linked to type-2 diabetes and obesity in the United States: An observational analysis from 1999 to 2022.

BACKGROUND: The prevalence of type 2 diabetes (T2D) and obesity are increasing in the United States. However, population-level data for mortality trends due to T2D and obesity are limited. This study aims to assess these death trends among adults in the United States categorized by sex, race, and geographical location. METHODS: We queried the CDC-WONDER database for multiple cause of death data of adults aged ≥25 years. The crude mortality rates (CMR), age-adjusted mortality rates (AAMRs), annual percent change (APC), and the average APC (AAPC) along with a 95% confidence interval (CI) were analyzed. RESULTS: From 1999 to 2022, a total of 88,597 T2DM and obesity-related deaths were recorded in the United States. The AAMR consistently increased from 1999 to 2017 (APC: 7.64; 95% CI: 1.91-9.96), followed by a marked rise from 2017 to 2022 (APC: 20.13; 95% CI: 12.88-38.57). The AAMR was approximately 3.58 times higher during the COVID-19 pandemic compared to the period from 1999 to 2019. The AAMR for males was consistently greater than that for females. The highest AAMR was observed in non-Hispanic (NH) Blacks or African Americans, followed by NH White, Hispanic or Latino, and other NH populations. Rural areas (AAMR: 1.86, 95% CI: 1.83-1.89) exhibited a greater AAMR than urban regions 1.26 (95% CI: 1.25-1.27). CONCLUSIONS: Our results indicate a substantial increasing trend of T2D and obesity-related deaths in the United States especially during the COVID-19 pandemic

Editorial: Neuromodulation in COVID-19: From basic research to clinical applications

RECEIVED 20 January 2023; ACCEPTED 08 February 2023; PUBLISHED 16 February 2023Unidad Docente de Biodiversidad, Ecología y EvoluciónFac. de Óptica y OptometríaTRUEpu

Cardiovascular Efficacy and Safety of Finerenone: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, has emerged as a novel therapeutic option for the management of patients with diabetes, chronic kidney disease, or heart failure. We seek to summarize the evidence on the drugs effectiveness regarding cardiovascular (CV) outcomes. METHODS: We conducted a literature search of Pubmed, Cochrane CENTRAL, Embase, and ClinicalTrials.gov from inception to September 2024. Trials exploring the effects of finerenone on CV outcomes were extracted and analyzed. The results of pooled analyses were presented as risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of eight trials, incorporating 21 200 patients, were included. The pooled analysis demonstrated a significant reduction in all-cause death (RR 0.92, 95% CI: 0.85-0.99), major adverse CV events (RR 0.85, 95% CI: 0.81-0.90), heart failure-related hospitalizations or unplanned hospital visits (RR 0.82, 95% CI: 0.76-0.87) with finerenone administration compared to control. Finerenone use was associated with a trend of reduced risk of CV death without reaching statistical significance (RR 0.90, 95% CI: 0.81-1.00). The risk of myocardial infarction (RR 0.91, 95% CI: 0.74-1.12), adverse events (RR 0.96, 95% CI: 0.89-1.03), adverse events leading to discontinuation (RR 1.06, 95% CI: 0.96-1.17) remained comparable across both groups. However, an increased risk of hyperkalemia (RR 2.07, 95% CI: 1.88-2.27) was observed with finerenone therapy compared to the control group. CONCLUSION: Finerenone administration was associated with improved CV outcomes in the CV-renmetabolic conditions compared to the control group