Asthma is a disease of reversible airflow obstruction characterised clinically by wheezing, shortness of breath, and coughing. Increases in airway type 2 cytokine activity, including interleukin-4 (IL-4), IL-5, and IL-13, are now established biological mechanisms in asthma. Inhaled corticosteroids have been the foundation for asthma treatment, in a large part because they decrease airway type 2 inflammation. However, inhaled or systemic corticosteroids are ineffective treatments in many patients with asthma and few treatment options exist for patients with steroid resistant asthma. Although mechanisms for corticosteroid refractory asthma are likely to be numerous, the development of a new class of biologic agents that target airway type 2 inflammation has provided a new model for treating some patients with corticosteroid refractory asthma. The objective of this Therapeutic paper is to summarise the new type 2 therapeutics, with an emphasis on the biological rationale and clinical efficacy of this new class of asthma therapeutics.

Attention-deficit hyperactivity disorder (ADHD), like other psychiatric disorders, represents an evolving construct that has been refined and developed over the past several decades in response to research into its clinical nature and structure. The clinical presentation and course of the disorder have been extensively characterised. Efficacious medication-based treatments are available and widely used, often alongside complementary psychosocial approaches. However, their effectiveness has been questioned because they might not address the broader clinical needs of many individuals with ADHD, especially over the longer term. Non-pharmacological approaches to treatment have proven less effective than previously thought, whereas scientific and clinical studies are starting to fundamentally challenge current conceptions of the causes of ADHD in ways that might have the potential to alter clinical approaches in the future. In view of this, we first provide an account of the diagnosis, epidemiology, and treatment of ADHD from the perspective of both the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the eleventh edition of the International Classification of Diseases. Second, we review the progress in our understanding of the causes and pathophysiology of ADHD on the basis of science over the past decade or so. Finally, using these discoveries, we explore some of the key challenges to both the current models and the treatment of ADHD, and the ways in which these findings can promote new perspectives.

Malnutrition has historically been researched and addressed within two distinct silos, focusing either on undernutrition, food insecurity, and micronutrient deficiencies, or on overweight, obesity, and dietary excess. However, through rapid global nutrition transition, an increasing proportion of individuals are exposed to different forms of malnutrition during the life course and have the double burden of malnutrition (DBM) directly. Long-lasting effects of malnutrition in early life can be attributed to interconnected biological pathways, involving imbalance of the gut microbiome, inflammation, metabolic dysregulation, and impaired insulin signalling. Life-course exposure to early undernutrition followed by later overweight increases the risk of non-communicable disease, by imposing a high metabolic load on a depleted capacity for homoeostasis, and in women increases the risk of childbirth complications. These life-course trajectories are shaped both by societal driving factors-ie, rapidly changing diets, norms of eating, and physical activity patterns-and by broader ecological factors such as pathogen burden and extrinsic mortality risk. Mitigation of the DBM will require major societal shifts regarding nutrition and public health, to implement comprehensive change that is sustained over decades, and scaled up into the entire global food system.

Actions to address different forms of malnutrition are typically managed by separate communities, policies, programmes, governance structures, and funding streams. By contrast, double-duty actions, which aim to simultaneously tackle both undernutrition and problems of overweight, obesity, and diet-related non-communicable diseases (DR-NCDs) have been proposed as a way to effectively address malnutrition in all its forms in a more holisitic way. This Series paper identifies ten double-duty actions that have strong potential to reduce the risk of both undernutrition, obesity, and DR-NCDs. It does so by summarising evidence on common drivers of different forms of malnutrition; documenting examples of unintended harm caused by some undernutrition-focused programmes on obesity and DR-NCDs; and highlighting examples of double-duty actions to tackle multiple forms of malnutrition. We find that undernutrition, obesity, and DR-NCDs are intrinsically linked through early-life nutrition, diet diversity, food environments, and socioeconomic factors. Some evidence shows that programmes focused on undernutrition have raised risks of poor quality diets, obesity, and DR-NCDs, especially in countries undergoing a rapid nutrition transition. This Series paper builds on this evidence to develop a framework to guide the design of double-duty approaches and strategies, and defines the first steps needed to deliver them. With a clear package of double-duty actions now identified, there is an urgent need to move forward with double-duty actions to address malnutrition in all its forms.

The double burden of malnutrition (DBM), defined as the simultaneous manifestation of both undernutrition and overweight and obesity, affects most low-income and middle-income countries (LMICs). This Series paper describes the dynamics of the DBM in LMICs and how it differs by socioeconomic level. This Series paper shows that the DBM has increased in the poorest LMICs, mainly due to overweight and obesity increases. Indonesia is the largest country with a severe DBM, but many other Asian and sub-Saharan African countries also face this problem. We also discuss that overweight increases are mainly due to very rapid changes in the food system, particularly the availability of cheap ultra-processed food and beverages in LMICs, and major reductions in physical activity at work, transportation, home, and even leisure due to introductions of activity-saving technologies. Understanding that the lowest income LMICs face severe levels of the DBM and that the major direct cause is rapid increases in overweight allows identifying selected crucial drivers and possible options for addressing the DBM at all levels.

Observations from many countries indicate that multiple forms of malnutrition might coexist in a country, a household, and an individual. In this Series, the double burden of malnutrition (DBM) encompasses undernutrition in the form of stunting, and overweight and obesity. Health effects of the DBM include those associated with both undernutrition, such as impaired childhood development and greater susceptibility to infectious diseases, and overweight, especially in terms of increased risk of added visceral fat and increased risk of non-communicable diseases. These health effects have not been translated into economic costs for individuals and economies in the form of lost wages and productivity, as well as higher medical expenses. We summarise the existing approaches to modelling the economic effects of malnutrition and point out the weaknesses of these approaches for measuring economic losses from the DBM. Where population needs suggest that nutrition interventions take into account the DBM, economic evaluation can guide the choice of so-called double-duty interventions as an alternative to separate programming for stunting and overweight. We address the evidence gap with an economic analysis of the costs and benefits of an illustrative double-duty intervention that addresses both stunting and overweight in children aged 4 years and older by providing school meals with improved quality of diet. We assess the plausibility of our method and discuss how improved data and models can generate better estimates. Double-duty interventions could save money and be more efficient than single-duty interventions.

This final report of the Lancet Commission into liver disease in the UK stresses the continuing increase in burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions which are worsening in deprived areas. Only with comprehensive food and alcohol strategies based on fiscal and regulatory measures (including a minimum unit price for alcohol, the alcohol duty escalator, and an extension of the sugar levy on food content) can the disease burden be curtailed. Following introduction of minimum unit pricing in Scotland, alcohol sales fell by 3%, with the greatest effect on heavy drinkers of low-cost alcohol products. We also discuss the major contribution of obesity and alcohol to the ten most common cancers as well as measures outlined by the departing Chief Medical Officer to combat rising levels of obesity-the highest of any country in the west. Mortality of severely ill patients with liver disease in district general hospitals is unacceptably high, indicating the need to develop a masterplan for improving hospital care. We propose a plan based around specialist hospital centres that are linked to district general hospitals by operational delivery networks. This plan has received strong backing from the British Association for Study of the Liver and British Society of Gastroenterology, but is held up at NHS England. The value of so-called day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and, in particular, schemes to allow general practitioners to refer patients directly for elastography assessment. New funding arrangements for general practitioners will be required if these proposals are to be taken up more widely around the country. Understanding of the harm to health from lifestyle causes among the general population is low, with a poor knowledge of alcohol consumption and dietary guidelines. The Lancet Commission has serious doubts about whether the initiatives described in the Prevention Green Paper, with the onus placed on the individual based on the use of information technology and the latest in behavioural science, will be effective. We call for greater coordination between official and non-official bodies that have highlighted the unacceptable disease burden from liver disease in England in order to present a single, strong voice to the higher echelons of government.

Muscular dystrophies are primary diseases of muscle due to mutations in more than 40 genes, which result in dystrophic changes on muscle biopsy. Now that most of the genes responsible for these conditions have been identified, it is possible to accurately diagnose them and implement subtype-specific anticipatory care, as complications such as cardiac and respiratory muscle involvement vary greatly. This development and advances in the field of supportive medicine have changed the standard of care, with an overall improvement in the clinical course, survival, and quality of life of affected individuals. The improved understanding of the pathogenesis of these diseases is being used for the development of novel therapies. In the most common form, Duchenne muscular dystrophy, a few personalised therapies have recently achieved conditional approval and many more are at advanced stages of clinical development. In this Seminar, we concentrate on clinical manifestations, molecular pathogenesis, diagnostic strategy, and therapeutic developments for this group of conditions.

Corruption is embedded in health systems. Throughout my life-as a researcher, public health worker, and a Minister of Health-I have been able to see entrenched dishonesty and fraud. But despite being one of the most important barriers to implementing universal health coverage around the world, corruption is rarely openly discussed. In this Lecture, I outline the magnitude of the problem of corruption, how it started, and what is happening now. I also outline people's fears around the topic, what is needed to address corruption, and the responsibilities of the academic and research communities in all countries, irrespective of their level of economic development. Policy makers, researchers, and funders need to think about corruption as an important area of research in the same way we think about diseases. If we are really aiming to achieve the Sustainable Development Goals and ensure healthy lives for all, corruption in global health must no longer be an open secret.

Acute kidney injury (AKI) is defined by a rapid increase in serum creatinine, decrease in urine output, or both. AKI occurs in approximately 10-15% of patients admitted to hospital, while its incidence in intensive care has been reported in more than 50% of patients. Kidney dysfunction or damage can occur over a longer period or follow AKI in a continuum with acute and chronic kidney disease. Biomarkers of kidney injury or stress are new tools for risk assessment and could possibly guide therapy. AKI is not a single disease but rather a loose collection of syndromes as diverse as sepsis, cardiorenal syndrome, and urinary tract obstruction. The approach to a patient with AKI depends on the clinical context and can also vary by resource availability. Although the effectiveness of several widely applied treatments is still controversial, evidence for several interventions, especially when used together, has increased over the past decade.

The Lancet Countdown is an international, multidisciplinary collaboration, dedicated to monitoring the evolving health profile of climate change, and providing an independent assessment of the delivery of commitments made by governments worldwide under the Paris Agreement. The 2019 report presents an annual update of 41 indicators across five key domains: climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. The report represents the findings and consensus of 35 leading academic institutions and UN agencies from every continent. Each year, the methods and data that underpin the Lancet Countdown’s indicators are further developed and improved, with updates described at each stage of this report. The collaboration draws on the world-class expertise of climate scientists; ecologists; mathematicians; engineers; energy, food, and transport experts; economists; social and political scientists; public health professionals; and doctors, to generate the quality and diversity of data required. The science of climate change describes a range of possible futures, which are largely dependent on the degree of action or inaction in the face of a warming world. The policies implemented will have far-reaching effects in determining these eventualities, with the indicators tracked here monitoring both the present-day effects of climate change, as well as the worldwide response. Understanding these decisions as a choice between one of two pathways—one that continues with the business as usual response and one that redirects to a future that remains “well below 2°C”—helps to bring the importance of recognising the effects of climate change and the necessary response to the forefront. Evidence provided by the Intergovernmental Panel on Climate Change, the International Energy Agency, and the US National Aeronautics and Space Administration clarifies the degree and magnitude of climate change experienced today and contextualises these two pathways.

The Global Kidney Exchange (GKE) programme seeks to facilitate kidney transplants by matching donor-recipient pairs across high-income, medium-income, and low-income countries. The GKE programme pays the medical expenses of people in medium-income and low-income countries, thus enabling them to receive a kidney transplantation they otherwise could not afford. In doing so, the programme increases the global donor pool, and so benefits people in high-income countries by improving their chances of finding a donor match. Nevertheless, the GKE has been accused of being a form of organ trafficking, exploiting the poor, and involving coercion and commodification of donors. We refute these claims, arguing that the GKE promotes global justice and reduces the potential for people in need of kidneys in low-income and medium-income countries to be exploited. Misguided objections should not be allowed to prevent the GKE from realising its potential to reduce suffering and save the lives of rich and poor patients alike.

Migraine is one of the most prevalent and disabling diseases worldwide, but until recently, few migraine-specific therapies had been developed. Extensive basic and clinical scientific investigation has provided strong evidence that the neuropeptide calcitonin gene-related peptide (CGRP) has a key role in migraine. This evidence led to the development of small molecule CGRP receptor antagonists and monoclonal antibodies targeting either CGRP or its receptor. Clinical trials investigating these therapies have consistently shown statistically significant efficacy for either the acute or preventive treatment of migraine. No serious safety or tolerability issues have been identified in the trials of the monoclonal antibody therapies. Although the appropriate place of these new migraine-specific therapies relative to other available acute and preventive treatments remains to be determined, a growing body of evidence shows that therapeutic approaches targeting CGRP have the potential to transform the clinical management of migraine.

The rapid emergence since the mid-2000s of a large and diverse range of substances originally designed as legal alternatives to more established illicit drugs (pragmatically clustered and termed new psychoactive substances; [NPS]) has challenged traditional approaches to drug monitoring, surveillance, control, and public health responses. In this section of the Series, we describe the emergence of NPS and consider opportunities for strengthening the detection, identification, and responses to future substances of concern. First, we explore the definitional complexity of the term NPS. Second, we describe the origins and drivers surrounding NPS, including motivations for use. Third, we summarise evidence on NPS availability, use, and associated harms. Finally, we use NPS as a case example to explore challenges and opportunities for future drug monitoring, surveillance, control, and public health responses. We posit that the current means of responding to emerging substances might no longer be fit for purpose in a world in which different substances can be rapidly introduced, and where people who use drugs can change preferences on the basis of market availability.