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
Multicenter StudyCombining loop with thiazide diuretics in patients discharged home after a heart failure decompensation: Association with 30-day outcomes.
To investigate the association of the addition of thiazide diuretic on top of loop diuretic and standard of care with short-term outcomes of patients discharged after surviving an acute heart failure (AHF) episode. ⋯ The combination of thiazide and loop diuretics was not associated with changes in risk of death, hospitalization or a combination of both.
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Eur. J. Intern. Med. · Sep 2024
Multicenter StudyDirect oral anticoagulant-associated bleeding complications in patients with gastrointestinal cancer and venous thromboembolism.
Direct oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer. ⋯ URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816.