Journal of internal medicine
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Osteoarthritis (OA) is a chronic joint disease caused by disruption of joint homeostasis by a variety of systemic and biomechanical factors. The disease is characterized by degradation of cartilage and other joint tissues, and low-grade inflammation which may result in pain, reduced function, and disability. The disease appears to have ancient origins, with findings of OA recognized in fossilized bones from birdlike dinosaurs living some 130 million years ago. ⋯ Current development of drug candidates, aimed to restore joint homeostasis, is mainly targeting either inhibition of catabolic factors or stimulation of anabolic factors. However, there is yet no breakthrough in stage III clinical trials. Earlier diagnosis, better knowledge of endotypes-for example, by new insights into soluble biomarkers, and compositional imaging-and more careful selection of patients into clinical trials are possible tools to aid development of future therapies.
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Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over liver safety. This study aimed to determine the association between cannabidiol use, liver enzyme elevation, and drug-induced liver injury (DILI). ⋯ Cannabidiol-associated liver enzyme elevations and DILI meet the criteria of common adverse drug events. Clinicians are encouraged to screen for cannabidiol use and monitor liver function in patients at increased risk.
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Emerging research suggests that exposures occurring years before conception are important determinants of the health of future offspring and subsequent generations. Environmental exposures of both the father and mother, or exposure to disease processes such as obesity or infections, may influence germline cells and thereby cause a cascade of health outcomes in multiple subsequent generations. There is now increasing evidence that respiratory health is influenced by parental exposures that occur long before conception. ⋯ The results are strengthened by mechanistic research from animal models and (scarce) human studies that have identified molecular mechanisms that can explain the epidemiological findings, suggesting transfer of epigenetic signals through germline cells, with susceptibility windows in utero (both male and female line) and prepuberty (male line). The concept that our lifestyles and behaviours may influence the health of our future children represents a new paradigm. This raises concerns for future health in decades to come with respect to harmful exposures but may also open for radical rethinking of preventive strategies that may improve health in multiple generations, reverse the imprint of our parents and forefathers, and underpin strategies that can break the vicious circle of propagation of health inequalities across generations.
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Sodium-glucose transport inhibitors (SGLT2i) are effective in heart failure (HF) with ejection fraction (EF) <40% (referred to as HF with reduced EF - HFrEF) and left ventricular EF (LVEF) >40%. Current evidence suggests that SGLT2i should be initiated across a large spectrum of EFs and renal function in patients with HF and with and without diabetes. We reviewed the benefits of SGLT2i in the entire spectrum of HF and provided some clues that may guide physicians in their strategy of initiating and maintaining SGLT2i (with or without SGLT1i effect) therapy. ⋯ SGLT2i appear to be effective and well-tolerated drugs in the majority of clinical HF scenarios, regardless of LVEF, estimated glomerular filtration rate, diabetic status or the level of the acuteness of the clinical setting. Therefore, most patients with HF should be treated with SGLT2i. However, in the face of the therapeutic inertia that has been observed in HF over the past decades, the actual implementation of SGLT2i in routine practice remains the most significant challenge.
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Alcohol use is a major cause of disability and death globally. These negative consequences disproportionately affect people who develop alcohol addiction, a chronic relapsing condition characterized by increased motivation to use alcohol, choice of alcohol over healthy, natural rewards, and continued use despite negative consequences. Available pharmacotherapies for alcohol addiction are few, have effect sizes in need of improvement, and remain infrequently prescribed. ⋯ Two mechanisms in this category, antagonism at corticotropin-releasing factor type 1, and neurokinin 1/substance P receptors, have been subject to initial evaluation in humans. A third, kappa-opioid receptor antagonism, has been evaluated in nicotine addiction and could soon be tested for alcohol. This paper discusses findings with these mechanisms to date, and their prospects as future targets for novel medications.