Genetic risk factors for drug-induced long QT syndrome: findings from a large real-world case-control study.

Aim: Drug-induced long QT syndrome (diLQTS), an adverse effect of many drugs, can lead to sudden cardiac death. Candidate genetic variants in cardiac ion channels have been associated with diLQTS, but several limitations of previous studies hamper clinical utility. Materials & methods: Thus, the purpose of this study was to assess the associations of KCNE1-D85N, KCNE2-I57T and SCN5A-G615E with diLQTS in a large observational case-control study (6,083 self-reported white patients treated with 27 different high-risk QT-prolonging medications; 12.0% with diLQTS). Results: KCNE1-D85N significantly associated with diLQTS (adjusted odds ratio: 2.24 [95% CI: 1.35-3.58]; p = 0.001). Given low minor allele frequencies, the study had insufficient power to analyze KCNE2-I57T and SCN5A-G615E. Conclusion: KCNE1-D85N is a risk factor for diLQTS that should be considered in future clinical practice guidelines.

Some medications can lead to a condition called drug-induced long QT syndrome (diLQTS), which can be a serious abnormal heart rhythm in some patients. In our research, we explored three specific changes in DNA related to the electrical function of the heart (KCNE1-D85N, KCNE2-I57T, SCN5A-G615E) and their link to diLQTS. Our study revealed a connection between KCNE1-D85N and diLQTS. This study emphasized the importance of including KCNE1-D85N in the medical guidelines to help identify patients at risk of diLQTS. We were unable to identify the connection of KCNE2-I57T and SCN5A-G615E with diLQTS, due to a low number of carriers in the study.

Comprehension and usefulness of Spanish language health information about depression treatment.

US Latine adults who prefer the Spanish language for healthcare encounter communication have high risk of health disparitiesm in part from low organizational health literacy, mental health stigma and discrimination. Latine organizational health literacy includes the provision of culturally responsive, language concordant health information, which supports good comprehension and could mitigate some health disparities. We conducted a pilot study to assess commonly provided patient health information handouts about depression treatment and antidepressant consumer medication information sheets. Thirty Latine adults with a Spanish language preference and a history of depression and antidepressant use participated in one phone interview. Descriptive statistics and thematic analysis were used to assess comprehension and usefulness of selected sections extracted verbatim from these documents. Overall, 83% (n = 25) participants reported that all sections were easy to understand and 97% (n = 29) said that they were useful. Yet, responses to open-ended questions for 53% (n = 16) of revealed 'confusing' terminology in at least one section, and 10% (n = 3) expressed concerns about or misunderstood an idiomatic phrase as reinforcing stigma. The organizational health literacy-based issues identified in this and previous studies require that government and health service organizations make necessary and timely revisions to address them.

Health-system specialty pharmacist intervention types, acceptance, and associated actions for patients with multiple sclerosis.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Health-system specialty pharmacy (HSSP) pharmacists play an integral role in the care of patients with multiple sclerosis (PwMS) by facilitating medication access, providing counseling, improving adherence, and decreasing provider workload. However, current literature detailing pharmacist interventions and their acceptance rates in this population is limited. The purpose of this study was to identify the types and acceptance rate of clinical interventions completed by pharmacists for PwMS. METHODS: To evaluate the acceptance rate of HSSP pharmacist interventions, we conducted a retrospective, multicenter, observational, descriptive study for the period from October 2019 to August 2022. Intervention types were categorized into reasons for intervention, recommendations from the pharmacists, and their acceptance rates. RESULTS: For 225 patients enrolled in HSSP services, 449 interventions were completed with an average of 2.0 interventions per patient. Most interventions identified were associated with medication adherence (28.7%), medication regimen (27.6%), adverse drug reaction (ADR) (20.7%), and laboratory values (15.1%). The average adherence, defined by the proportion of days covered, was 94%. The most common recommendations were to continue therapy (14.9%), schedule laboratory tests (12.7%), and follow up with providers (11.8%). Recommendations had an acceptance rate of 85.3%, with 3.8% of recommendations declined and 10.9% requiring follow-up with providers. CONCLUSION: P Pharmacists impact patient outcomes through the completion of clinical interventions that improve adherence, identify medication regimen problems, manage ADRs, and coordinate proper laboratory testing. Pharmacist recommendations were most often accepted for interventions related to medication regimen and ADRs. Proper identification and management of medication regimen concerns, as well as tolerability of medications, can positively impact adherence and improve overall patient outcomes.

Biosimilar perceptions among autoimmune prescribers and pharmacists in health system specialty pharmacy.

BACKGROUND: By the end of 2023, 10 self-administered biosimilars indicated for autoimmune conditions are expected to launch in the United States, resulting in alternative treatment options for patients and a potential for cost savings. However, studies about perception and knowledge of self-administered biosimilars among health system prescribers and health system specialty pharmacists are limited. OBJECTIVE: To assesses knowledge and perceptions of biosimilars among autoimmune prescribers and health system specialty pharmacists across the United States. METHODS: An anonymous, cross-sectional self-administered online questionnaire was conducted among prescribers and health system specialty pharmacists practicing in the specialties of rheumatology, dermatology, and gastroenterology across the United States. The survey was available from January 2023 to February 2023. RESULTS: 31 prescribers and 44 pharmacists completed the questionnaire. Only 16.0% of prescribers and 13.4% of pharmacists reported being "very prepared" to have conversations with patients about biosimilar options. 43% of prescribers indicated they would prescribe a biosimilar to biologic naive patients. However, 13.3% of prescribers would be willing to prescribe a biosimilar to patients successfully established on biologic therapy. Among pharmacists, 68.1% were comfortable recommending a biosimilar substitution to a biologic naive patient, but only 18.1% would recommend a biosimilar substitution to an existing patient successfully established on a biologic therapy. Less than half of prescribers (48.0%) and pharmacists (42.0%) understood regulations of interchangeability and substitution. CONCLUSIONS: Our study highlights several knowledge gaps and hesitancies that exist among health system specialty prescribers and pharmacists regarding biosimilar products. Education efforts are needed to overcome the lack of biosimilar adoption, which will increase affordability of therapy for patients and health care savings.

The genetics of drug-induced QT prolongation: evaluating the evidence for pharmacodynamic variants.

Drug-induced long QT syndrome (diLQTS) is an adverse effect of many commonly prescribed drugs, and it can increase the risk for lethal ventricular arrhythmias. Genetic variants in pharmacodynamic genes have been associated with diLQTS, but the strength of the evidence for each of those variants has not yet been evaluated. Therefore, the purpose of this review was to evaluate the strength of the evidence for pharmacodynamic genetic variants associated with diLQTS using a novel, semiquantitative scoring system modified from the approach used for congenital LQTS. KCNE1-D85N and KCNE2-T8A had definitive and strong evidence for diLQTS, respectively. The high level of evidence for these variants supports current consideration as risk factors for patients that will be prescribed a QT-prolonging drug.

Cinnamaldehyde inhibits L-type calcium channels in mouse ventricular cardiomyocytes and vascular smooth muscle cells.

Cinnamaldehyde (CA), a major component of cinnamon, is known to have important actions in the cardiovascular system, including vasorelaxation and decrease in blood pressure. Although CA-induced activation of the chemosensory cation channel TRPA1 seems to be involved in these phenomena, it has been shown that genetic ablation of Trpa1 is insufficient to abolish CA effects. Here, we confirm that CA relaxes rat aortic rings and report that it has negative inotropic and chronotropic effects on isolated mouse hearts. Considering the major role of L-type Ca(2+) channels in the control of the vascular tone and cardiac contraction, we used whole-cell patch-clamp to test whether CA affects L-type Ca(2+) currents in mouse ventricular cardiomyocytes (VCM, with Ca(2+) as charge carrier) and in mesenteric artery smooth muscle cells (VSMC, with Ba(2+) as charge carrier). We found that CA inhibited L-type currents in both cell types in a concentration-dependent manner, with little voltage-dependent effects. However, CA was more potent in VCM than in VSMC and caused opposite effects on the rate of inactivation. We found these divergences to be at least in part due to the use of different charge carriers. We conclude that CA inhibits L-type Ca(2+) channels and that this effect may contribute to its vasorelaxing action. Importantly, our results demonstrate that TRPA1 is not a specific target of CA and indicate that the inhibition of voltage-gated Ca(2+) channels should be taken into account when using CA to probe the pathophysiological roles of TRPA1.