Search

Background: From 2006 to 2014, alcohol-related visits to the emergency department (ED) increased by 76% in the United States, highlighting the need for improved ED-driven interventions addressing alcohol use disorder (AUD). Naltrexone is an FDA-approved medication for AUD shown to decrease craving and self-administration of alcohol. While oral naltrexone and extended-release naltrexone have been long utilized in primary care and inpatient hospital settings, the use of naltrexone in the ED is limited., Methods: This study implemented and analyzed a multifaceted intervention regarding ED naltrexone prescribing at a large safety net, academic, urban hospital. A baseline assessment of preintervention conditions and perspectives on naltrexone prescribing was conducted through a chart review and standardized interviews with ED providers, respectively. The interview results guided design of interventions that addressed identified barriers. These included provider education, prescribing aids, and zero-cost naltrexone tablets supplied by the ED pharmacy to patients upon discharge., Results: Between September 1, 2019, and August 31, 2020, of 753 unique patients who had a primary diagnosis or chief complaint containing the word "alcohol," only five (0.66%) were prescribed naltrexone. ED providers identified lack of training regarding naltrexone, lack of a prescribing protocol, and limited patient and provider education materials as barriers to prescribing naltrexone. Following the intervention, among 278 eligible patients, 11 oral naltrexone prescriptions were written (3.96%) between April 13, 2021, and August 1, 2021. This represents a sixfold increase over the preintervention period., Conclusions: An intervention to increase ED oral naltrexone prescriptions for AUD was successfully implemented, addressing lack of provider education, lack of prescribing resources, and patient barriers to accessing prescribed medications. Longer-term follow-up is needed to assess the efficacy and sustainability of these interventions. Nevertheless, ED clinicians are well positioned to initiate naltrexone prescriptions for patients presenting with AUD., (© 2024 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Aims: Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be due to mutations in the genes encoding β-myosin heavy chain (MYH7) or cardiac myosin-binding protein C (MYBPC3). The aim of the present study was to determine the prevalence and spectrum of mutations in both genes in German HCM and DCM patients and to establish novel genotype-to-phenotype correlations., Methods and Results: Coding exons and intron flanks of the two genes MYH7 and MYBPC3 of 236 patients with HCM and 652 patients with DCM were sequenced by conventional and array-based means. Clinical records were established following standard protocols. Mutations were detected in 41 and 11% of the patients with HCM and DCM, respectively. Differences were observed in the frequency of splice site and frame-shift mutations in the gene MYBPC3, which occurred more frequently (P< 0.02, P< 0.001, respectively) in HCM than in DCM, suggesting that cardiac myosin-binding protein C haploinsufficiency predisposes to hypertrophy rather than to dilation. Additional novel genotype-to-phenotype correlations were found in HCM, among these a link between MYBPC3 mutations and a particularly large thickness of the interventricular septum (P= 0.04 vs. carriers of a mutation in MYH7). Interestingly, this correlation and a link between MYH7 mutations and a higher degree of mitral valve regurgitation held true for both HCM and DCM, indicating that the gene affected by a mutation may determine the magnitude of structural and functional alterations in both HCM and DCM., Conclusion: A large clinical-genetic study has unravelled novel genotype-to-phenotype correlations in HCM and DCM which warrant future investigation of both the underlying mechanisms and the prognostic use.

Mitochondrial transcription factors mtTFA, mtTFB1 and mtTFB2 are required for the replication of mitochondrial DNA (mtDNA), regulating the number of mtDNA copies. Mice with a mtTFA deletion showed a reduced number of mtDNA copies, a reduction in respiratory chain activity, and a characteristic dilated cardiomyopathy. DNA variants in these genes could be involved in the risk for cardiac hypertrophy (HCM). We determined the variation in the TFAM, TFB1M, and TFB2M genes (using SSCA, DHPLC, and direct sequencing) in a total of 200 HCM-patients from Spain and Germany, and in 250 healthy controls. We found several common polymorphisms that defined haplotype blocks in these genes, with frequencies that did not differ between patients and controls. We also found four novel variants in patients which were absent in the controls: -91 C > A (5'-UTR) and Ala105 > Thr in TFAM, and Thr211 > Ala and Arg256 > Lys in TFB1M. The three missense changes were in highly conserved amino acids, and could be involved in HCM-risk. In conclusion, common variants in the mitochondrial transcription factors were not associated with the risk for HCM. However, rare DNA variants (putative mutations) could be involved in the pathogenesis of HCM in a reduced number of cases.

Background: One-third of cases of dilated cardiomyopathy (DCM) is of familial aetiology. Several genes have been reported to cause the autosomal dominant form of DCM., Aims: To analyze the lamin A/C gene (LMNA) in 31 unrelated patients with DCM and conduction system disease (CSD)., Methods: Patients and family members underwent physical examination, ECG/Holter-ECG, echocardiography, and selective coronary angiography. Genetic analysis of all coding exons of LMNA was performed using PCR and sequencing., Results: Three different LMNA mutations (Arg377His, c.1397delA, c.424&#95;425ins21nt) were identified in three families with autosomal dominant disease comprised of 39 individuals. 21 individuals were mutation carriers, of whom 12 were symptomatic. We observed a progressive and age-dependent form of DCM with CSD and arrhythmias. First, the patients developed a moderate left ventricular dilatation without symptoms. Later, systolic function declined progressively and the patients became symptomatic resulting in a high mortality due to sudden death and heart failure., Conclusions: Genetic screening leads to the identification of symptomatic and asymptomatic mutant carriers. The latter at a young age should be regarded as "presymptomatic" because of the age-dependent disease manifestation. New guidelines are required for the management of these individuals.