The Access to COVID-19 Tools Accelerator (ACT-A) is a multistakeholder initiative quickly constructed in the early months of the COVID-19 pandemic to respond to a catastrophic breakdown in global cooperation. ACT-A is now the largest international effort to achieve equitable access to COVID-19 health technologies, and its governance is a matter of broad public importance. We traced the evolution of ACT-A's governance through publicly available documents and analysed it against three principles embedded in the founding mission statement of ACT-A: participation, transparency, and accountability. We found three challenges to realising these principles. First, the roles of the various organisations in ACT-A decision making are unclear, obscuring who might be accountable to whom and for what. Second, the absence of a clearly defined decision making body; ACT-A instead has multiple centres of legally binding decision making and uneven arrangements for information transparency, inhibiting meaningful participation. Third, the nearly indiscernible role of governments in ACT-A, raising key questions about political legitimacy and channels for public accountability. With global public health and billions in public funding at stake, short-term improvements to governance arrangements can and should now be made. Efforts to strengthen pandemic preparedness for the future require attention to ethical, legitimate arrangements for governance.

Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs.

Adolescence is a pivotal point in the life course, characterised by transformative physical, cognitive, and emotional growth, an openness to change, and a drive to reshape the social environment. It offers unique opportunities to adopt changes in diet and physical activity that can persist into later life. Yet pre-existing nutritional problems, including micronutrient deficiencies, food insecurity, and poor-quality diets, persist at the same time as adolescents face the rapid emergence of an obesity epidemic. Adolescent growth and nutrition has been largely overlooked in intervention and policy research. Most intervention studies have emphasised micronutrient supplementation, with few taking into account the multiple drivers of adolescent diets. This Series paper highlights that effective interventions and policies will need to cut across sectors; be supported by multifaceted and multilevel policy; and extend across education, health, food systems, social protection, and digital media. Better data standardisation and systems will be essential in coordinating and monitoring these responses. In a context of shifts in planetary ecosystems and commercial drivers, resilient food systems will need to both ensure access to healthy and affordable foods and provide the infrastructure and incentives for continuing physical activity. Intergenerational partnerships with young people will be essential in bringing about transformative change and ensuring that food policies reflect their needs and aspirations.

Dietary intake during adolescence sets the foundation for a healthy life, but adolescents are diverse in their dietary patterns and in factors that influence food choice. More evidence to understand the key diet-related issues and the meaning and context of food choices for adolescents is needed to increase the potential for impactful actions. The aim of this second Series paper is to elevate the importance given to adolescent dietary intake and food choice, bringing a developmental perspective to inform policy and programmatic actions to improve diets. We describe patterns of dietary intake, then draw on existing literature to map how food choice can be influenced by unique features of adolescent development. Pooled qualitative data is then combined with evidence from the literature to explore ways in which adolescent development can interact with sociocultural context and the food environment to influence food choice. Irrespective of context, adolescents have a lot to say about why they eat what they eat, and insights into factors that might motivate them to change. Adolescents must be active partners in shaping local and global actions that support healthy eating patterns. Efforts to improve food environments and ultimately adolescent food choice should harness widely shared adolescent values beyond nutrition or health.

During adolescence, growth and development are transformative and have profound consequences on an individual's health in later life, as well as the health of any potential children. The current generation of adolescents is growing up at a time of unprecedented change in food environments, whereby nutritional problems of micronutrient deficiency and food insecurity persist, and overweight and obesity are burgeoning. In a context of pervasive policy neglect, research on nutrition during adolescence specifically has been underinvested, compared with such research in other age groups, which has inhibited the development of adolescent-responsive nutritional policies. One consequence has been the absence of an integrated perspective on adolescent growth and development, and the role that nutrition plays. Through late childhood and early adolescence, nutrition has a formative role in the timing and pattern of puberty, with consequences for adult height, muscle, and fat mass accrual, as well as risk of non-communicable diseases in later life. Nutritional effects in adolescent development extend beyond musculoskeletal growth, to cardiorespiratory fitness, neurodevelopment, and immunity. High rates of early adolescent pregnancy in many countries continue to jeopardise the growth and nutrition of female adolescents, with consequences that extend to the next generation. Adolescence is a nutrition-sensitive phase for growth, in which the benefits of good nutrition extend to many other physiological systems.

The optimal revascularisation strategy for patients with left main coronary artery disease is uncertain. We therefore aimed to evaluate long-term outcomes for patients treated with percutaneous coronary intervention (PCI) with drug-eluting stents versus coronary artery bypass grafting (CABG).

Since the first case of COVID-19 was identified in the USA in January, 2020, over 46 million people in the country have tested positive for SARS-CoV-2 infection. Several COVID-19 vaccines have received emergency use authorisations from the US Food and Drug Administration, with the Pfizer-BioNTech vaccine receiving full approval on Aug 23, 2021. When paired with masking, physical distancing, and ventilation, COVID-19 vaccines are the best intervention to sustainably control the pandemic. However, surveys have consistently found that a sizeable minority of US residents do not plan to get a COVID-19 vaccine. The most severe consequence of an inadequate uptake of COVID-19 vaccines has been sustained community transmission (including of the delta [B.1.617.2] variant, a surge of which began in July, 2021). Exacerbating the direct impact of the virus, a low uptake of COVID-19 vaccines will prolong the social and economic repercussions of the pandemic on families and communities, especially low-income and minority ethnic groups, into 2022, or even longer. The scale and challenges of the COVID-19 vaccination campaign are unprecedented. Therefore, through a series of recommendations, we present a coordinated, evidence-based education, communication, and behavioural intervention strategy that is likely to improve the success of COVID-19 vaccine programmes across the USA.

Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis.

Type 1 diabetes is on the rise globally; however, the burden of mortality remains disproportionate in low-income and middle-income countries (LMICs). As 2021 marks 100 years since the discovery of insulin, we revisit progress, global burden of type 1 diabetes trends, and understanding of the pathogenesis and management practices related to the disease. Despite much progress, inequities in access and availability of insulin formulations persist and are reflected in differences in survival and morbidity patterns related to the disease. Some of these inequities have also been exacerbated by health-system challenges during the COVID-19 pandemic. There is a clear opportunity to improve access to insulin and related essential technologies for improved management of type 1 diabetes in LMICs, especially as a part of universal health coverage. These improvements will require concerted action and investments in human resources, community engagement, and education for the timely diagnosis and management of type 1 diabetes, as well as adequate health-care financing. Further research in LMICs, especially those in Africa, is needed to improve our understanding of the burden, risk factors, and implementation strategies for managing type 1 diabetes.

Understanding the spread of SARS-CoV-2, how and when evidence emerged, and the timing of local, national, regional, and global responses is essential to establish how an outbreak became a pandemic and to prepare for future health threats. With that aim, the Independent Panel for Pandemic Preparedness and Response has developed a chronology of events, actions, and recommendations, from December, 2019, when the first cases of COVID-19 were identified in China, to the end of March, 2020, by which time the outbreak had spread extensively worldwide and had been characterised as a pandemic. Datapoints are based on two literature reviews, WHO documents and correspondence, submissions to the Panel, and an expert verification process. The retrospective analysis of the chronology shows a dedicated initial response by WHO and some national governments, but also aspects of the response that could have been quicker, including outbreak notifications under the International Health Regulations (IHR), presumption and confirmation of human-to-human transmission of SARS-CoV-2, declaration of a Public Health Emergency of International Concern, and, most importantly, the public health response of many national governments. The chronology also shows that some countries, largely those with previous experience with similar outbreaks, reacted quickly, even ahead of WHO alerts, and were more successful in initially containing the virus. Mapping actions against IHR obligations, the chronology shows where efficiency and accountability could be improved at local, national, and international levels to more quickly alert and contain health threats in the future. In particular, these improvements include necessary reforms to international law and governance for pandemic preparedness and response, including the IHR and a potential framework convention on pandemic preparedness and response.

40 years ago, Italy saw the birth of a national, universal health-care system (Servizio Sanitario Nazionale [SSN]), which provides a full range of health-care services with a free choice of providers. The SSN is consistently rated within the Organisation for Economic Co-operation and Development among the highest countries for life expectancy and among the lowest in health-care spending as a proportion of gross domestic product. Italy appears to be in an envious position. However, a rapidly ageing population, increasing prevalence of chronic diseases, rising demand, and the COVID-19 pandemic have exposed weaknesses in the system. These weaknesses are linked to the often tumultuous history of the nation and the health-care system, in which innovation and initiative often lead to spiralling costs and difficulties, followed by austere cost-containment measures. We describe how the tenuous balance of centralised versus regional control has shifted over time to create not one, but 20 different health systems, exacerbating differences in access to care across regions. We explore how Italy can rise to the challenges ahead, providing recommendations for systemic change, with emphasis on data-driven planning, prevention, and research; integrated care and technology; and investments in personnel. The evolution of the SSN is characterised by an ongoing struggle to balance centralisation and decentralisation in a health-care system, a dilemma faced by many nations. If in times of emergency, planning, coordination, and control by the central government can guarantee uniformity of provider behaviour and access to care, during non-emergency times, we believe that a balance can be found provided that autonomy is paired with accountability in achieving certain objectives, and that the central government develops the skills and, therefore, the legitimacy, to formulate health policies of a national nature. These processes would provide local governments with the strategic means to develop local plans and programmes, and the knowledge and tools to coordinate local initiatives for eventual transfer to the larger system.

Borderline personality disorder (BPD) is a mental disorder with a high burden on patients, family members, and health-care systems. The condition was previously regarded as untreatable, but progress in understanding and management has resulted in earlier diagnosis and better treatment outcomes. A coherent syndrome of BPD typically onsets during adolescence (after age 12 years). BPD is often preceded by or co-develops with symptoms of internalising disorders (depression and anxiety), externalising disorders (conduct problems, hyperactivity, and substance use), or both. BPD is associated with various poor outcomes, including low occupational and educational attainment, lack of long-term relationships, increased partner conflict, sexual risk-taking, low levels of social support, low life satisfaction, and increased service use. Psychotherapy is the main treatment for BPD; drug treatment is only indicated for comorbid conditions that require medication, or during a crisis if psychosocial interventions are insufficient. Awareness of BPD by non-specialists, as well as specialists, is key to appropriate early intervention.

The Lancet Countdown is an international collaboration that independently monitors the health consequences of a changing climate. Publishing updated, new, and improved indicators each year, the Lancet Countdown represents the consensus of leading researchers from 43 academic institutions and UN agencies. The 44 indicators of this report expose an unabated rise in the health impacts of climate change and the current health consequences of the delayed and inconsistent response of countries around the globe—providing a clear imperative for accelerated action that puts the health of people and planet above all else. The 2021 report coincides with the UN Framework Convention on Climate Change 26th Conference of the Parties (COP26), at which countries are facing pressure to realise the ambition of the Paris Agreement to keep the global average temperature rise to 1·5°C and to mobilise the financial resources required for all countries to have an effective climate response. These negotiations unfold in the context of the COVID-19 pandemic—a global health crisis that has claimed millions of lives, affected livelihoods and communities around the globe, and exposed deep fissures and inequities in the world’s capacity to cope with, and respond to, health emergencies. Yet, in its response to both crises, the world is faced with an unprecedented opportunity to ensure a healthy future for all.

Disease-related malnutrition in adult patients who have been admitted to hospital is a syndrome associated with substantially increased morbidity, disability, short-term and long-term mortality, impaired recovery from illness, and cost of care. There is uncertainty regarding optimal diagnostic criteria, definitions for malnutrition, and how to identify patients who would benefit from nutritional intervention. Malnutrition has become the focus of research aimed at translating current knowledge of its pathophysiology into improved diagnosis and treatment. Researchers are particularly interested in developing nutritional interventions that reverse the negative effects of disease-related malnutrition in the hospital setting. High-quality randomised trials have provided evidence that nutritional therapy can reduce morbidity and other complications associated with malnutrition in some patients. Screening of patients for risk of malnutrition at hospital admission, followed by nutritional assessment and individualised nutritional interventions for malnourished patients, should become part of routine clinical care and multimodal treatment in hospitals worldwide.

Before 2020, mental disorders were leading causes of the global health-related burden, with depressive and anxiety disorders being leading contributors to this burden. The emergence of the COVID-19 pandemic has created an environment where many determinants of poor mental health are exacerbated. The need for up-to-date information on the mental health impacts of COVID-19 in a way that informs health system responses is imperative. In this study, we aimed to quantify the impact of the COVID-19 pandemic on the prevalence and burden of major depressive disorder and anxiety disorders globally in 2020.