Lancet
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Alcohol use disorders consist of disorders characterised by compulsive heavy alcohol use and loss of control over alcohol intake. Alcohol use disorders are some of the most prevalent mental disorders globally, especially in high-income and upper-middle-income countries; and are associated with high mortality and burden of disease, mainly due to medical consequences, such as liver cirrhosis or injury. ⋯ Primary health care should be responsible for most treatment, with routine screening for alcohol use, and the provision of a staggered treatment response, from brief advice to pharmacological treatment. Clinical interventions for these disorders should be embedded in a supportive environment, which can be bolstered by the creation of alcohol control policies aimed at reducing the overall level of consumption.
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Antibody-drug conjugates (ADCs) are immunoconjugates comprised of a monoclonal antibody tethered to a cytotoxic drug (known as the payload) via a chemical linker. The ADC is designed to selectively deliver the ultratoxic payload directly to the target cancer cells. ⋯ In this Therapeutics paper, we review recent clinical experience with the approved ADCs and other promising late-stage candidates on the horizon, following an overview of the biology and chemistry of ADCs and how the individual components of an ADC (antibody [or target], linker and conjugation chemistry, and cytotoxic payload) influence its activity. We briefly discuss opportunities for enhancing ADC efficacy, drug resistance, and future perspectives for this novel antibody-based molecular platform, which has great potential to make a paradigm shift in cancer chemotherapy.
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Review
Primary prevention of ischaemic heart disease: populations, individuals, and health professionals.
Ischaemic heart disease has a multifactorial aetiology and can be prevented from developing in populations primordially, and in individuals at high risk by primary prevention. The primordial approach focuses on social determinants of health in populations: political, economic, and social factors, principally unplanned urbanisation, illiteracy, poverty, and working and living conditions. Implementation of the UN Sustainable Development Goals can lead to major improvements in cardiovascular health, and adequate health-care financing and universal health care are important for achieving these goals. ⋯ At the individual level, identification of people at high multifactorial risk and guideline-driven management of hypertension, LDL cholesterol, and diabetes is required. Strategies to improve adherence to healthy lifestyles and drug therapies are essential and can be implemented at health system, health care, and patient levels with use of education, technology, and personalised approaches. Improving quality of medical education with a focus on ischaemic heart disease prevention for physicians, nurses, allied health workers, and the public is required.
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Atherosclerosis and its clinical manifestation as ischaemic heart disease remains a considerable health burden. Given that many factors contribute to ischaemic heart disease, a multifactorial approach to prevention is recommended, starting with lifestyle advice, smoking cessation, and control of known cardiovascular risk factors, such as blood pressure and lipids. Within the lipid profile, the principal target is lowering LDL cholesterol, firstly with lifestyle interventions and subsequently with pharmacological therapy. ⋯ Phase 3 trials have also been completed for bempedoic acid (targeting ATP-citrate lyase) and inclisiran (an interference RNA-based therapeutic targeting hepatic PCSK9 synthesis). In addition to LDL cholesterol, mendelian randomisation studies support a causal role for lipoprotein(a) and triglycerides in ischaemic heart disease. In this Series paper, we appraise currently available and emerging therapies for lowering LDL cholesterol, lipoprotein(a), and triglycerides for prevention of ischaemic heart disease.
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Family health history (FHH) is the most useful means of assessing risk for common chronic diseases. The odds ratio for risk of developing disease with a positive FHH is frequently greater than 2, and actions can be taken to mitigate risk by adhering to screening guidelines, genetic counselling, genetic risk testing, and other screening methods. Challenges to the routine acquisition of FHH include constraints on provider time to collect data and the difficulty in accessing risk calculators. ⋯ Software that allows integration of FHH with the electronic medical record and clinical decision support capabilities has provided solutions to many of these challenges. Patient facing, electronic medical record, and web-enabled FHH platforms have been developed, and can provide greater identification of risk compared with conventional FHH ascertainment in primary care. FHH, along with cascade screening, can be an important component of population health management approaches to overall reduction of risk.