Adarsh Raja

Background: Heart Failure (HF) and Diabetes Mellitus (DM) often coexist, and each condition independently increases the likelihood of developing the other. While there has been concern regarding the increasing burden of disease for both conditions individually over the last decade, a comprehensive examination of mortality trends and demographic and regional disparities needs to be thoroughly explored in the United States (US). Methods: This study analyzed death certificates from the CDC WONDER database, focusing on mortality caused by the co-occurrence of HF and DM in adults aged 75 and older from 1999 to 2020. Age-adjusted mortality rates (AAMRs) and annual percent changes (APCs) were computed and categorized by year, gender, race, census region, state, and metropolitan status. Results: A total of 663,016 deaths were reported in patients with coexisting HF and DM. Overall, AAMR increased from 154.1 to 186.1 per 100,000 population between 1999 and 2020, with a notable significant increase from 2018 to 2020 (APC: 11.30). Older men had consistently higher AAMRs than older women (185 vs. 135.4). Furthermore, we found that AAMRs were highest among non-Hispanic (NH) American Indian or Alaskan natives and lowest in NH Asian or Pacific Islanders (214.4 vs. 104.1). Similarly, AAMRs were highest in the Midwestern region and among those dwelling in non-metropolitan areas. Conclusions: Mortality from HF and DM has risen significantly in recent years, especially among older men, NH American Indian or Alaska Natives, and those in non-metropolitan areas. Urgent policies need to be developed to address these disparities and promote equitable healthcare access.

Introduction: Non-alcoholic fatty liver disease (NAFLD), spanning from non-alcoholic steatohepatitis (NASH) to liver fibrosis, poses a global health challenge amid rising obesity and metabolic syndrome rates. Effective pharmacological treatments for NASH and liver fibrosis are limited. Objective: This study systematically reviews and meta-analyzes the safety and efficacy of resmetirom, a selective thyroid hormone receptor-β agonist, in NASH and liver fibrosis treatment. By analyzing data from clinical trials, we aim to offer evidence-based recommendations for resmetirom’s use in managing these conditions and identify avenues for future research. Methods: Electronic databases (PubMed, Scopus, Science Direct, Google Scholar, ClinicalTrials.gov, and Cochrane CENTRAL) were systematically searched, supplemented by manual screening of relevant sources. Only English-language randomized controlled trials were included. Data extraction, risk of bias assessment, pooled analyses, and meta-regression were performed. Results: Three randomized controlled trials involving 2231 participants were analyzed. Resmetirom demonstrated significant reductions in hepatic fat fraction [standardized mean difference (SMD) −4.61, 95% CI −6.77 to −2.44, P < 0.0001], NASH resolution without worsening fibrosis [risk ratio (RR) 2.51, 95% CI 1.74–3.64, P = 0.00001), and liver fibrosis improvement (RR 2.31, 95% CI 1.20–4.44, P = 0.01). Secondary outcomes showed significant improvements in lipid profiles, liver enzymes, and NASH biomarkers with resmetirom treatment. Meta-regression revealed associations between covariates and primary outcomes. Conclusion: Resmetirom exhibits promising efficacy in reducing hepatic fat, improving NASH resolution, and ameliorating liver fibrosis with a favorable safety profile. Further research is warranted to validate findings and optimize therapeutic strategies for NASH and liver fibrosis management.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) are prevalent cardiovascular disorders that frequently co-occur, exacerbating each other's effects and resulting in adverse clinical outcomes. Despite the well-established association between these conditions, there is a paucity of research examining AF/atrial flutter (AFL) as direct contributors to HF-related mortality across various demographics and regions within the United States. OBJECTIVE: This study aims to investigate the patterns of AF/AFL-related HF mortality in the U.S. from 1999 to 2024, stratified by age, gender, race/ethnicity, urban-rural classification, and geographic region. METHODS: A retrospective analysis was conducted utilizing data from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. Mortality data were extracted from death certificates that identified AF/AFL related HF as a primary or contributing cause of death (ICD-10 codes I11.0, I13.0, I13.2, I48 and I50). Age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated, and annual percentage changes (APC) were assessed using Joinpoint regression. RESULTS: Between 1999 and 2024, 1,307,809 deaths in the United States were attributed to atrial fibrillation/flutter-related heart failure (AF/AFL-HF). The age-adjusted mortality rate (AAMR) rose significantly from 8.2 to 24.3 per 100,000 population. Males consistently exhibited higher AAMRs than females (15.7 vs. 12.3 per 100,000, respectively). Racial disparities were evident, with non-Hispanic Whites having the highest cumulative AAMR (15.1), and non-Hispanic Asians/Pacific Islanders the lowest (5.7). Geographic differences were also prominent: Oregon recorded the highest state-level AAMR (25.5), while Hawaii had the lowest (8.8). Regionally, the West (15.3) and Midwest (14.9) had the highest cumulative AAMRs. Place-of-death trends showed a shift toward home deaths, which became the most common location by 2024. Although AAMRs increased sharply from 2010 to 2021 across most subgroups, rates stabilized between 2021 and 2024. CONCLUSION: AF/AFL-related heart failure mortality has increased substantially over the past 26 years in the U.S. with marked disparities by sex, race/ethnicity, region, and urbanization. While recent years have seen a plateau in mortality rates, the continued burden-especially among vulnerable populations underscores the need for equitable, targeted public health interventions and improved access to cardiovascular care.

BACKGROUND & AIMS: Chronic migraine poses a global health burden, particularly affecting young women, and has substantial societal implications. This study aimed to assess the efficacy of Greater Occipital Nerve Block (GONB) in individuals with chronic migraine, focusing on the impact of local anesthetics compared with placebo. METHODS: A meta-analysis and systematic review were conducted following the PRISMA principles and Cochrane Collaboration methods. Eligible studies included case-control, cohort, and randomized control trials in adults with chronic migraine, adhering to the International Classification of Headache Disorders, third edition (ICHD3). Primary efficacy outcomes included headache frequency, duration, and intensity along with safety assessments. RESULTS: Literature searches across multiple databases yielded eight studies for qualitative analysis, with five included in the final quantitative analysis. A remarkable reduction in headache intensity and frequency during the first and second months of treatment with GONB using local anesthetics compared to placebo has been reported. The incidence of adverse events did not differ significantly between the intervention and placebo groups. CONCLUSION: The analysis emphasized the safety and efficacy of GONB, albeit with a cautious interpretation due to the limited number of studies and relatively small sample size. This study advocates for further research exploring various drugs, frequencies, and treatment plans to enhance the robustness and applicability of GONB for chronic migraine management.

Introduction: Major depressive disorder (MDD), postpartum depression (PPD), and insomnia are neuropsychological conditions in which zuranolone is used to improve symptoms and prognosis of the disorder. This meta-analysis aimed to determine the efficacy of zuranolone in comparison to other drugs used for treating these conditions. Methods: This meta-analysis included patients aged between 18 and 75 years who were diagnosed with major depressive disorder and postpartum depression with or without insomnia and were administered zuranolone for treatment. Only randomized controlled trials (RCTs) were included, and animal studies were excluded. The databases used were PubMed, Scopus, Cochrane, and Clinicaltrials.gov, with MeSH terms and relevant keywords for (Zuranolone) and (Depression). The Cochrane risk of bias tool was used for quality assessment. Results: The meta-analysis included eight RCTs that analyzed data from 2031 patients. The meta-analysis revealed statistically significant changes in the Hamilton Depression Rating Scale (HAM-D), Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and treatment-emergent adverse effects (TEAE) scores in the PPD subgroup. HAM-D and TEAEs scores were also significant in the MDD subgroup, but the changes in the MADRS, HAM-A, and Bech-6 scores were insignificant. Serious adverse events were insignificant in all subgroups. Conclusion: Meta-analysis found a significant improvement in depressive symptoms with zuranolone treatment, especially on day 15. This suggests that zuranolone is a promising therapeutic option for patients with MDD and PPD with or without insomnia. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459554, identifier CRD42023459554.