A systematic review and meta-analysis of the efficacy and safety of Mavacamten therapy in international cohort of 524 patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.

Trazodone-induced parkinsonism in a middle-aged male: A case report.

Introduction: Trazodone is an antidepressant agent approved for treating major depressive disorders and is also prescribed for insomnia due to its sedative effect. In a few cases, trazodone was associated with parkinsonism. Herein, we describe a case of parkinsonism after a brief exposure to a moderate dose of trazodone. Objective: To describe a case of a patient with trazodone-induced parkinsonism in which the diagnosis was suspected after the exclusion of other common and serious causes. Methods: A case report of trazodone-induced parkinsonism. Clinical Case: A 58-year-old male with sleeping problems was prescribed trazodone 50 mg daily at bedtime. The subject doubled the dosage without medical advice a week later. After 14 days of trazodone treatment, he started to experience difficulty in moving his upper limbs and recurrent falling. Neuroimaging, electrodiagnostic studies, and laboratory exams were unremarkable. Trazodone was discontinued, and the patient fully recovered. Noteworthy, the patient developed a recurrence of the motor symptoms with trazodone-rechallenge. Conclusion: Our case showed reversibly induced parkinsonism after a short intake of a moderate dose of trazodone which was prescribed for insomnia. The patient had a complete recovery after trazodone withdrawal. Noteworthy, the symptoms recurred upon trazodone-rechallenge.

Three Cases of Myoclonus Secondary to Ciprofloxacin: "Ciproclonus".

OBJECTIVES: Ciprofloxacin is a fluoroquinolone that is used for bacterial infections involving different systems. In some cases, ciprofloxacin was reported to induce myoclonus. METHODS: We performed a chart review of 3 patients with myoclonus secondary to ciprofloxacin and reviewed the literature for similar cases. Written consent for publication was obtained from each patient, and their identities were concealed for ethical reasons. RESULTS: We describe 3 cases of myoclonus secondary to ciprofloxacin, 2 males and a female aged 61, 26, and 48 years, respectively. The myoclonus appeared within 3 days of ciprofloxacin intake. In all 3 cases, ciprofloxacin was prescribed for urinary tract infection. Electroencephalogram and neuroimaging studies were normal and possible causes were excluded. Thus, ciprofloxacin was believed to be the underlying cause and hence it was withdrawn. The patients had complete recovery on follow-up. CONCLUSIONS: Although ciprofloxacin is widely prescribed for different infections, only 13 cases were reported to develop myoclonus secondary to ciprofloxacin. The mean age of patients was 62 years. Fifty-four percent of cases were males. Cessation of ciprofloxacin was the most common management course. All individuals fully recovered after ciprofloxacin withdrawal. The mechanism of ciprofloxacin-induced myoclonus is probably associated with γ-aminobutyric acid and glutamate pathways.

Unravelling COVID-19 vaccination attributes worldwide: an extensive review regarding uptake, hesitancy, and future implication.

Since the declaration of the coronavirus disease 2019 pandemic, all efforts were directed towards limiting the transfer of the disease and preventing severe disease forms from occurring. In this regard, numerous vaccines were quickly developed to limit the associated morbidity and mortality of the disease and to reduce the burden on healthcare systems worldwide. However, to date, vaccine hesitancy remains a major limitation to vaccine distribution, with varying degrees in different countries. Therefore, the authors conducted this literature review to highlight the magnitude of this issue throughout the globe and summarize some of its major causes (i.e. governmental, healthcare system-related, population-related, and vaccine-related) and contributing factors (i.e. knowledge/awareness, social media, etc.). In addition, the authors highlighted some of the main motivating factors that can minimize the burden of vaccine hesitancy at the population, governmental, and worldwide levels. These include structural (i.e. government, country), extrinsic (i.e. family, friends), intrinsic (i.e. self-perception), and other factors (financial and nonfinancial). Finally, the authors proposed some implications for future research to ease the vaccination process and hopefully, put an end to this problem.