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
Artificial intelligence in scientific medical writing: Legitimate and deceptive uses and ethical concerns.
The debate surrounding the integration of artificial intelligence (AI) into scientific writing has already attracted significant interest in medical and life sciences. While AI can undoubtedly expedite the process of manuscript creation and correction, it raises several criticisms. The crossover between AI and health sciences is relatively recent, but the use of AI tools among physicians and other scientists who work in the life sciences is growing very fast. ⋯ Even more impressively, they can learn and adapt as they engage with a growing volume of human language input. They all share neural networks as background mathematical models and differ from old chatbots for their use of a specific network architecture called transformer model [1]. Some of them exceed 100 terabytes (TB) (e.g., Bloom, LaMDA) or even 500 TB (e.g., Megatron-Turing NLG) of text data, the 4.0 version of ChatGPT (GPT-4) was trained with nearly 45 TB, but stays updated by the internet connection and may integrate with different plugins that enhance its functionality, making it multimodal.