European journal of internal medicine
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Eur. J. Intern. Med. · Sep 2024
Randomized Controlled Trial Multicenter StudyLow-dose ondansetron: A candidate prospective precision medicine to treat alcohol use disorder endophenotypes.
Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise in reducing alcohol consumption among affected individuals while minimizing adverse effects. ⋯ In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04's adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure.
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Eur. J. Intern. Med. · Sep 2024
Randomized Controlled TrialSafety and compliance of long-term low-dose ondansetron in alcohol use disorder treatment.
The increasing prevalence of alcohol use disorder (AUD) and the parallel surge in alcohol-associated liver disease (ALD) emphasize the urgent need for comprehensive alcohol management strategies. Low-dose ondansetron (AD04, a 5-HT3 antagonist) was shown recently to be a promising treatment for AUD with a specific genotypic profile (5-marker). The liver safety of AD04 has never been evaluated in subjects with AUD. The aim of the present study was to assess the liver safety profile of AD04 compared with placebo in subjects with AUD. ⋯ Low-dose AD04 has the potential to be a safe treatment option for subjects with AUD and ALD, indicating the need for an RCT for this specific cohort. Such a trial would pave the way for the design of a precision treatment for combined AUD with ALD.
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Eur. J. Intern. Med. · Sep 2024
ReviewEast meets West: Bringing the ESH 2023 hypertension guidelines into Asia.
Hypertension remains a major problem worldwide, especially across the Asia-Pacific region, which reports high prevalence rates and slow improvements in treatment rate and blood pressure (BP) control rate. Asian patients with hypertension may also vary with regard to phenotype and the epidemiology of the complications of hypertension, especially when compared with Western patients. ⋯ This narrative review aims to provide a critical comparison between the recently published European Society of Hypertension (ESH) 2023 guidelines and existing local guidelines in select Asian countries, offer expert opinion on how to fill gaps in the ESH 2023 guidelines for hypertension in the Asian context, and examine the need for harmonisation of hypertension guidelines worldwide. This review focuses on the definition and diagnosis of hypertension, the treatment thresholds and targets, and recommendations on the use of pharmacotherapy.
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Eur. J. Intern. Med. · Sep 2024
Meta AnalysisEfficacy and safety of rituximab induction therapy and effect of rituximab maintenance for IgG4-related disease: a systematic review and meta-analysis.
Previous studies have reported that rituximab (RTX) therapy might be beneficial in reducing relapse rates in patients with IgG4-related disease (IgG4-RD). Therefore, we aimed to systematically assess the efficacy and safety of RTX induction treatment and the effect of RTX maintenance in patients with IgG4-RD. ⋯ RTX induction therapy appears to have satisfactory efficacy in the induction of remission in IgG4-RD. In addition, prophylactic RTX maintenance therapy after induction may be beneficial in preventing relapse of IgG4-RD.