Leprosy, also known as Hansen's disease, is a curable granulomatous condition caused by Mycobacterium leprae or Mycobacterium lepromatosis, disproportionately affecting impoverished communities across the globe. The bacteria's tropism for dermal histiocytes, endothelial cells, and Schwann cells causes neuronal and dermal damage that often results in disability, permanent disfigurement, stigma, and social exclusion. Despite important achievements in the understanding of the disease, its elimination has been hampered by the scarcity of sensitive diagnostic tools, suboptimal integration and implementation of coordinated and financially stable preventive interventions, persistent stigmatisation, and failure to efficiently and sustainably address the socioeconomic and demographic factors associated with an increased risk of leprosy. In this Seminar, we provide an update on key public health and clinical aspects of the disease.

GLP-1 receptor agonists were initially developed to treat type 2 diabetes and have had a transformative effect on its therapy, and are highly effective for glycaemic control, with the added benefit of bodyweight reduction and a low risk of causing hypoglycaemia. GLP-1 receptor agonists reduce risks for major adverse cardiovascular events (eg, non-fatal myocardial infarction, stroke, and cardiovascular death), and the risk of admission to or treatment within hospital for heart failure. These drugs reduce albuminuria and slow the decline in estimated glomerular filtration rate over time, therefore delaying or preventing kidney failure. Furthermore, GLP-1 receptor agonists (eg, liraglutide and semaglutide) and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor co-agonist tirzepatide have been approved for treatment of obesity, with clinical trials establishing benefits for various obesity-related conditions: prevention of type 2 diabetes; risk for major adverse cardiovascular events; heart failure, especially with preserved ejection fraction; regression of steatosis and prevention of fibrosis in steatotic liver disease; and symptomatic improvements in obstructive sleep apnoea and knee osteoarthritis. Current developments include the exploration of novel indications (eg, neurodegenerative diseases and substance use disorders) with suggestive evidence of efficacy, and the development of small-molecule GLP-1 receptor agonists for oral treatment to improve convenience. Dual (ie, GLP-1-glucagon and GLP-1-amylin) and triple (ie, GIP-GLP-1-glucagon) receptor agonists activating multiple receptors promise greater efficacy than mono-agonists, especially for weight loss. However, some clinical development programmes have a high burden of adverse gastrointestinal events, and dose-escalation regimens should be optimised to reach acceptable tolerability.

Tetanus, although preventable by a highly effective vaccine, continues to cause 30 000-50 000 deaths annually. Global mortality has fallen substantially since the 1980s due to widespread vaccination efforts, yet adult disease persists, especially among those with weakened immune response, diabetes, and people who inject drugs. Diagnosis is still clinical, and management combines wound debridement, antibiotics, and antitoxin. However, key questions about prevention, diagnosis, and management remain unanswered. Recent trials suggest human and equine antitoxin perform equally, but shortages and high costs persist. Autonomic instability, once thought a late stage complication, is now defined early in the disease course, affecting the prognosis. Due to patients being in intensive care, complications such as nosocomial infections can increase the burden of the disease, reinforcing that vaccination, surveillance, equitable access, and new therapy options are vital.

The effects of small, realistic changes in physical activity and sedentary behaviour on population-level mortality are unclear. We aimed to estimate the proportion of deaths preventable by 5-min and 10-min incremental increases in moderate-to-vigorous intensity physical activity (MVPA) and 30-min and 60-min reductions in daily sedentary time.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a monogenic disease of adulthood characterised by treatment-refractory systemic inflammation and progressive bone marrow failure. VEXAS syndrome is caused by acquired mutations in the UBA1 gene that are restricted to haematopoietic cells. Men aged 50 years or older are particularly susceptible to VEXAS syndrome, with prevalence estimates of approximately one in 4000 men. Perturbation of UBA1, the master enzyme of cellular ubiquitination, promotes myeloid-driven inflammation that is difficult to control with medications other than glucocorticoids. Cytokine-directed therapies (ie, IL-6 and JAK inhibitors) might temporise symptoms and allow glucocorticoid reduction. Hypomethylating agents (ie, azacytidine) can induce clinical and molecular remission in some patients, but are associated with substantial toxicities. Haematopoietic cell transplant might be effective treatment in patients who are suitable candidates. The discovery of VEXAS syndrome highlights the potential role of somatic mutations in complex inflammatory diseases.

Randomised controlled trials have commonly excluded women who are pregnant, lactating, or of reproductive potential. When there is clinical equipoise, the exclusion of these women raises concerns regarding the principles of autonomy, beneficence, and justice. This exclusion also shifts evidence generation from the monitored setting of randomised controlled trials to clinical settings, where data can take several years to accrue. Here, we highlight key health, ethical, scientific, and regulatory considerations surrounding the inclusion of women who are pregnant, lactating, or of reproductive potential in clinical trials to guide further discussions. We offer recommendations for a judicious approach to inclusivity, highlighting regulatory, sponsor, and clinical trial design considerations. We highlight the need for patient engagement and interdisciplinary discourse throughout the research lifecycle.

Prostate cancer poses a substantial clinical challenge and accounts for a large proportion of cancer-related deaths worldwide. The therapeutic landscape has undergone a large transformation in the past 5 years, resulting in improved patient outcomes. In this Seminar, we review the pathology, diagnostic strategies, and treatments for prostate cancer. Active surveillance is the preferred treatment option for patients with indolent prostate cancer. For those requiring treatment, local therapies provide effective cancer control. Systemic treatment is essential for advanced and metastatic cases, and a wide range of therapies are now available, including androgen deprivation therapy, chemotherapy, and emerging targeted agents such as lutetium-177-labelled prostate-specific membrane antigen radioligand therapy and PARP inhibitors. Considering toxicity profiles alongside patient preferences is important to facilitating shared decision making. Further research is needed to establish the most effective sequence and combination of treatments for metastatic prostate cancer.

Monitoring the behaviour of transnational corporations is an important public health priority given the many ways corporate actors negatively affect health. Such effects can be mitigated by defining standards of corporate behaviour and implementing regulations to prohibit and sanction harmful behaviour. However, in the past two decades, market signals and corporate scorecards are increasingly being used to incentivise corporate actors to behave in a socially responsible manner. Two examples of relevance to global health are the Access to Medicine Index and the Access to Nutrition Initiative's Global Index. However, this Viewpoint argues that these indices are flawed and could have the perverse effect of reinforcing the power and dominance of the biggest pharmaceutical and food companies, and undermining broader public interest efforts to hold such companies accountable and improve equitable access to healthy foods, medicines, and vaccines.

Violence against women and against children are human rights violations with lasting harms to survivors and societies at large. Intimate partner violence (IPV) and sexual violence against children (SVAC) are two major forms of such abuse. Despite their wide-reaching effects on individual and community health, these risk factors have not been adequately prioritised as key drivers of global health burden. Comprehensive x§and reliable estimates of the comparative health burden of IPV and SVAC are urgently needed to inform investments in prevention and support for survivors at both national and global levels.

Heart failure is a complex clinical syndrome affecting around 70 million individuals globally. It has a prevalence of 2% in Europe and North America and approximately 1% in Asia and South America. Accurate diagnosis relies on the presence of typical signs and symptoms, elevated natriuretic peptide concentrations, and evidence of cardiac structural or functional abnormalities using cardiac imaging techniques. Approximately half of all heart failure cases are attributed to reduced left ventricular systolic function-classified as heart failure with reduced ejection fraction (HFrEF). Current guideline-directed medical therapy has markedly improved survival and quality of life for patients with HFrEF. Contemporary management emphasises early initiation and rapid uptitration of four foundational drug classes-renin-angiotensin system inhibitors or angiotensin receptor-neprilysin inhibitors, β blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors-alongside diuretics for the symptom relief of volume overload. Despite advances in management, heart failure remains a leading cause of cardiovascular morbidity and mortality, partly due to absence of implementation of, and poor adherence to, medications. Future directions to improve outcomes include the integration of personalised medicine approaches, multiomic profiling, and innovative clinical trial designs to address residual risk and identify novel therapeutic targets. This Seminar provides an overview of the current diagnostic and pharmacological management of patients with HFrEF, highlighting the progress and outlining the challenges that remain.

Coronary artery disease is one of the leading causes of morbidity and mortality worldwide. Although it can present with an acute coronary syndrome, it is often characterised by long periods of stability, known as chronic coronary artery disease. This Review presents a comprehensive overview of the diagnosis of the disease, with a focus on cardiac imaging. We discuss various cardiac imaging modalities, including CT coronary angiography, stress echocardiogram, stress single-photon emission CT, PET, and stress cardiac magnetic resonance. We also compare the roles of anatomical (eg, CT coronary angiography) versus functional (eg, stress echocardiogram) tests and examine the potential utility of artificial intelligence in more detail.

Globally, the prevalence of chronic kidney disease is estimated to be approximately 850 million cases, with approximately 4 million individuals needing kidney replacement therapy for kidney failure. By 2050, chronic kidney disease is projected to become the fifth leading underlying cause of death worldwide. Despite its numerous causes, chronic kidney disease can be screened for, diagnosed, and staged with simple laboratory tests. Individuals with chronic kidney disease are at increased risk of kidney failure and many other health implications. Risk of premature cardiovascular disease is particularly noteworthy, as most patients with chronic kidney disease develop a disability or die from cardiovascular disease before ever progressing to kidney failure. Since 2019, large randomised trials have identified several effective treatments that both slow progressive kidney function decline and reduce cardiovascular risk, greatly expanding available treatments for chronic kidney disease. The wide range of complications associated with chronic kidney disease means that patients encounter many different specialties. Active engagement in chronic kidney disease identification and timely initiation of cost-effective interventions by all clinicians could now substantially reduce the global burden of complications of chronic kidney disease and kidney failure.

Climate change inflicts substantial economic damage on developing African nations, threatening progress towards the UN Sustainable Development Goals. There are synergies between actions needed to tackle climate change and other ongoing development priorities for Africa, including infectious disease control, facilitating clean energy access, reducing air pollution, tackling malnutrition and food insecurity, and providing universal health coverage. Action to protect human health against climate change needs to be integrated into all systems that are responsible for delivering essential services and implementing policies across all sectors that underpin the attainment of key development priorities for Africa. These systems include the Sustainable Development Goals and the African Union's 2063 Agenda for building The Africa We Want, and the ongoing negotiations and work programmes in the UN Framework Convention on Climate Change. Adequate stocktaking of and access to robust data and scientific evidence is needed to support this effort and guide priorities for policies that protect and promote health and for monitoring progress over time. In response to this need, the Lancet Countdown is launching a new initiative to bring together a transdisciplinary research collaboration to help build regional capacity, strengthen existing networks, generate evidence, and mobilise data across numerous domains at the climate change and health nexus in Africa.

Dietary patterns high in ultra-processed foods (UPFs) have been associated with poor diet quality and health outcomes, and are displacing healthier dietary patterns-meals and dishes prepared with fresh and minimally processed foods-in most parts of the world. In the second paper of this Series, we propose a set of government policies aimed at halting and reversing the rise of UPFs worldwide. To date, policies have mainly focused on reducing consumption of foods high in added fats, sugar, and sodium, many of which are UPFs. However, we propose that these efforts be strengthened and expanded to address a broader set of food system drivers influencing the production, marketing, and consumption of UPFs. This Series paper addresses four food policy domains that correspond to the key dimensions of food system drivers of UPF production, marketing, and consumption: UPF products, UPF food environments, UPF manufacturers, fast-food corporations, and supermarket corporations retailers, and food supply chains. For each domain, we explore policy options and focus on large-scale food system measures that target areas in greatest need of change, and their potential impacts. We also examine policies to protect, incentivise, and support dietary patterns based on fresh and minimally processed foods, particularly for lower income households. Which policy actions governments decide to prioritise will depend on each country's level of UPF consumption, along with many other issues unique to each country. We emphasise the importance of advancing this agenda in all countries, irrespective of their development status, to promote healthier diets among populations.

This first paper in a three-part Lancet Series combines narrative and systematic reviews with original analyses and meta-analyses to assess three hypotheses concerning a dietary pattern based on ultra-processed foods. The first hypothesis-that this pattern is globally displacing long-established diets centred on whole foods and their culinary preparation as dishes and meals-is supported by decades of national food intake and purchase surveys, and recent global sales data. The second-that this pattern results in deterioration of diet quality, especially in relation to chronic disease prevention-is confirmed by national food intake surveys, large cohorts, and interventional studies showing gross nutrient imbalances; overeating driven by high energy density, hyper-palatability, soft texture, and disrupted food matrices; reduced intake of health-protective phytochemicals; and increased intake of toxic compounds, endocrine disruptors, and potentially harmful classes and mixtures of food additives. The third and final hypothesis-that this pattern increases the risk of multiple diet-related chronic diseases through various mechanisms-is substantiated by more than 100 prospective studies, meta-analyses, randomised controlled trials, and mechanistic studies, covering adverse outcomes across nearly all organ systems. The totality of the evidence supports the thesis that displacement of long-established dietary patterns by ultra-processed foods is a key driver of the escalating global burden of multiple diet-related chronic diseases. Two companion papers in this Series specify policy actions and wider public health strategies to promote, protect, and support diets based on fresh and minimally processed foods and prevent their displacement by ultra-processed foods.

The rise of ultra-processed foods (UPFs) in human diets is harming global public health. However, policy responses are still emerging-much like tobacco control efforts decades ago-indicating the need to understand root causes and accelerate global action. This paper, the third in a three-part Lancet Series, takes several steps to advance knowledge of these causes, and to inform a global public health response. First, we show that the UPF industry is a key driver of the problem, as its leading corporations and co-dependent actors have expanded and restructured food systems almost everywhere, in favour of ultra-processed diets. The higher profitability of UPFs compared with other types of food fuels this growth, by financially incentivising the ultra-processed business model over alternatives, and generating resources for continued expansion. Second, we highlight that the main barrier to advancing policy responses is the industry's corporate political activities, coordinated transnationally through a global network of front groups, multi-stakeholder initiatives, and research partners, to counter opposition and block regulation. These activities include direct lobbying, infiltrating government agencies, and litigation; promoting corporate-friendly governance models, forms of regulation, and civil societies; and framing debate, generating favourable evidence, and manufacturing scientific doubt. Third, we present strategies for reducing the UPF industry's power in food systems and for mobilising a global public health response. Reducing the UPF industry's power involves disrupting the ultra-processed business model and redistributing resources to other types of food producers; protecting food governance from corporate interference; and implementing robust conflict of interest safeguards in policy making, research, and professional practice. Mobilising a global response includes framing UPFs as a priority global health issue; building powerful global and country-level advocacy coalitions; generating legal, research, and communication capacities to empower advocacy and drive policy change; and ensuring a just transition to low-UPF diets. A coordinated, well resourced global response is essential-one that confronts corporate power, reclaims public policy space, and restructures food systems to prioritise health, equity, and sustainability over corporate profit.

Hyperemesis gravidarum describes nausea and vomiting in pregnancy severe enough to cause weight loss, dehydration, electrolyte imbalance, and nutritional deficiencies. The condition can render women so physically and mentally unwell that they are at increased risk of terminating a wanted pregnancy and experiencing suicidal ideation. Concerns regarding prescribing in pregnancy and inaccurate assumptions that the condition is self-limiting result in women being dismissed and having difficulty accessing appropriate care. Over the past decade, a wealth of literature has been published that gives new insights into the causes of hyperemesis gravidarum, the safety of antiemetic therapy, and short-term and long-term consequences for women with the condition and their children. This Review summarises the findings of this literature with the aim of informing decisions about the care of these women and future research priorities.

In patients presenting with acute coronary syndromes and multivessel coronary artery disease, the question of whether to undertake a strategy of complete revascularisation in cases in which percutaneous coronary intervention (PCI) is performed routinely on non-culprit lesions (in addition to the culprit lesion) or whether to restrict PCI only to the culprit lesion is a common dilemma. The Complete Revascularisation Trialists' Collaboration aimed to determine, based on the totality of data from randomised trials, the effect of a complete revascularisation strategy on major cardiovascular events and whether it reduces cardiovascular death.