Viral bronchiolitis is the most common cause of admission to hospital for infants in high-income countries. Respiratory syncytial virus accounts for 60-80% of bronchiolitis presentations. Bronchiolitis is diagnosed clinically without the need for viral testing. Management recommendations, based predominantly on high-quality evidence, advise clinicians to support hydration and oxygenation only. Evidence suggests no benefit with use of glucocorticoids or bronchodilators, with further evidence required to support use of hypertonic saline in bronchiolitis. Evidence is scarce in the intensive care unit. Evidence suggests use of high-flow therapy in bronchiolitis is limited to rescue therapy after failure of standard subnasal oxygen only in infants who are hypoxic and does not decrease rates of intensive care unit admission or intubation. Despite systematic reviews and international clinical practice guidelines promoting supportive rather than interventional therapy, universal de-implementation of interventional care in bronchiolitis has not occurred and remains a major challenge.

Complex post-traumatic stress disorder (complex PTSD) is a severe mental disorder that emerges in response to traumatic life events. Complex PTSD is characterised by three core post-traumatic symptom clusters, along with chronic and pervasive disturbances in emotion regulation, identity, and relationships. Complex PTSD has been adopted as a new diagnosis in the ICD-11. Individuals with complex PTSD typically have sustained or multiple exposures to trauma, such as childhood abuse and domestic or community violence. The disorder has a 1-8% population prevalence and up to 50% prevalence in mental health facilities. Progress in diagnostics, assessment, and differentiation from post-traumatic stress disorder and borderline personality disorder is reported, along with assessment and treatment of children and adolescents. Studies recommend multicomponent therapies starting with a focus on safety, psychoeducation, and patient-provider collaboration, and treatment components that include self-regulatory strategies and trauma-focused interventions.

Estimates of the effectiveness of water, sanitation, and hygiene (WASH) interventions that provide high levels of service on childhood diarrhoea are scarce. We aimed to provide up-to-date estimates on the burden of disease attributable to WASH and on the effects of different types of WASH interventions on childhood diarrhoea in low-income and middle-income countries (LMICs).

The goal of this Series paper is to show how road safety has evolved as a global public health issue over the past two decades and to discuss the political and economic dynamics that led to this change. Specifically, the key stakeholders, influences, networks, issue framing, actor power, and synergistic interactions that have contributed to how road safety has evolved as a global public health issue will be discussed. In doing so, we capture the important chronology of events and discuss a set of challenges that highlight the complexity of road safety. We posit that the global road safety community needs to re-evaluate its role and strategy for the next decade and focus more on implementation and country action to achieve reductions in road traffic injuries. We call for an open and inclusive process to ensure that such a reflection occurs before the end of the current decade.

Global road mortality is a leading cause of death in many low-income and middle-income countries. Data to support priority setting under current resource constraints are urgently needed to achieve Sustainable Development Goal (SDG) 3.6. This Series paper estimates the potential number of lives saved if each country implemented interventions to address risk factors for road injuries. We did a systematic review of all available evidence-based, preventive interventions for mortality reduction that targeted the four main risk factors for road injuries (ie, speeding, drink driving, helmet use, and use of seatbelt or child restraint). We used literature review variables and considered three key country-level variables (gross domestic product per capita, population density, and government effectiveness) to generate country-specific estimates on the potential annual attributable number of lives that would be saved by interventions focusing on these four risk factors in 185 countries. Our results suggest that the implementation of evidence-based road safety interventions that target the four main road safety risk factors could prevent between 25% and 40% of all fatal road injuries worldwide. Interventions addressing speed could save about 347 258 lives globally per year, and at least 16 304 lives would be saved through drink driving interventions. The implementation of seatbelt interventions could save about 121 083 lives, and 51 698 lives could be saved by helmet interventions. We identify country-specific estimates of the potential number of lives saved that would be attributable to these interventions. Our results show the potential effectiveness of the implementation and scaling of these interventions. This paper presents key evidence for priority setting on road safety interventions and shows a path for reaching SDG 3.6.

Over 90% of the annual 1·35 million worldwide deaths due to road traffic injuries (RTIs) occur in low-income and middle-income countries (LMICs). For this Series paper, our aim was two-fold. Firstly, to review evidence on effective interventions for victims of RTIs; and secondly, to estimate the potential number of lives saved by effective trauma care systems and clinical interventions in LMICs. We reviewed all the literature on trauma-related health systems and clinical interventions published during the past 20 years using MEDLINE, Embase, and Web of Science. We included studies in which mortality was the primary outcome and excluded studies in which trauma other than RTIs was the predominant injury. We used data from the Global Status Report on Road Safety 2018 and a Monte Carlo simulation technique to estimate the potential annual attributable number of lives saved in LMICs. Of the 1921 studies identified for our review of the literature, 62 (3·2%) met the inclusion criteria. Only 28 (1·5%) had data to calculate relative risk. We found that more than 200 000 lives per year can be saved globally with the implementation of a complete trauma system with 100% coverage in LMICs. Partial system improvements such as establishing trauma centres (>145 000 lives saved) and instituting and improving trauma teams (>115 000) were also effective. Emergency medical services had a wide range of effects on mortality, from increasing mortality to saving lives (>200 000 excess deaths to >200 000 lives saved per year). For clinical interventions, damage control resuscitation (>60 000 lives saved per year) and institution of interventional radiology (>50 000 lives saved per year) were the most effective interventions. On the basis of the scarce evidence available, a few key interventions have been identified to provide guidance to policy makers and clinicians on evidence-based interventions that can reduce deaths due to RTIs in LMICs. We also highlight important gaps in knowledge on the effects of other interventions.

Excessive opioid prescribing after surgery has contributed to the current opioid crisis; however, the value of prescribing opioids at surgical discharge remains uncertain. We aimed to estimate the extent to which opioid prescribing after discharge affects self-reported pain intensity and adverse events in comparison with an opioid-free analgesic regimen.

Coeliac disease is an autoimmune disorder that primarily affects the small intestine, and is caused by the ingestion of gluten in genetically susceptible individuals. Prevalence in the general population ranges from 0·5% to 2%, with an average of about 1%. The development of the coeliac enteropathy depends on a complex immune response to gluten proteins, including both adaptive and innate mechanisms. Clinical presentation of coeliac disease is highly variable and includes classical and non-classical gastrointestinal symptoms, extraintestinal manifestations, and subclinical cases. The disease is associated with a risk of complications, such as osteoporosis and intestinal lymphoma. Diagnosis of coeliac disease requires a positive serology (IgA anti-transglutaminase 2 and anti-endomysial antibodies) and villous atrophy on small-intestinal biopsy. Treatment involves a gluten-free diet; however, owing to the high psychosocial burden of such a diet, research into alternative pharmacological treatments is currently very active.

Thalassaemia is a diverse group of genetic disorders with a worldwide distribution affecting globin chain synthesis. The pathogenesis of thalassaemia lies in the unbalanced globin chain production, leading to ineffective erythropoiesis, increased haemolysis, and deranged iron homoeostasis. The clinical phenotype shows heterogeneity, ranging from close to normal without complications to severe requiring lifelong transfusion support. Conservative treatment with transfusion and iron chelation has transformed the natural history of thalassaemia major into a chronic disease with a prolonged life expectancy, albeit with co-morbidities and substantial disease burden. Curative therapy with allogeneic haematopoietic stem cell transplantation is advocated for suitable patients. The understanding of the pathogenesis of the disease is guiding therapeutic advances. Novel agents have shown efficacy in improving anaemia and transfusion burden, and initial results from gene therapy approaches are promising. Despite scientific developments, worldwide inequality in the access of health resources is a major concern, because most patients live in underserved areas.

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development.

The UN has declared universal health coverage an urgent global goal. Efforts to achieve this goal have been supported by rigorous research on the scientific, technical, and administrative aspects of health systems design. Yet a substantial portion of the world's population does not have access to essential health services. There is growing recognition that achieving universal health coverage is a political challenge. However, fundamental concepts from the political science discipline are often overlooked in the health literature. This Series paper draws on political science research to highlight the ways in which politics can facilitate, or stymie, policy reform. Specifically, we present a framework of analysis that explores how interests, ideas, and institutions shape universal health coverage. We then examine key considerations relating to the implementation of relevant policies. This Series paper shows that a political understanding of universal health coverage is needed to achieve health for all.

Over the past two decades, global health diplomacy, foreign policy for health, and global health policy have changed substantially. Diplomacy is a constitutive part of the system of global health governance. COVID-19 hit the world when multilateral cooperation was subject to major challenges, and global health has since become integral to geopolitics. The importance of global health diplomacy, especially at WHO, in keeping countries jointly committed to improving health for everyone, has once again been shown. Through a systematic review, this Series paper explores how international relations concepts and theories have been applied to better understand the role of power in shaping positions, negotiations, and outcomes in global health diplomacy. We apply an international relations perspective to reflect on the effect that those concepts and theories have had on global health diplomacy over the past two decades. This Series paper argues that a more central role of international relations concepts and theories in analysing global health diplomacy would help develop a more nuanced understanding of global health policy making. However, the world has changed to an extent that was not envisioned in academic discourse. This shift calls for new international relations concepts and theories to inform global health diplomacy.

Health issues vary in the amount of attention and resources they receive from global health organisations and national governments. How issues are framed could shape differences in levels of priority. We reviewed scholarship on global health policy making to examine the role of framing in shaping global health priorities. The review provides evidence of the influence of three framing processes-securitisation, moralisation, and technification. Securitisation refers to an issue's framing as an existential threat, moralisation as an ethical imperative, and technification as a wise investment that science can solve. These framing processes concern more than how issues are portrayed publicly. They are socio-political processes, characterised by contestation among actors in civil society, government, international organisations, foundations, and research institutions. These actors deploy various forms of power to advance particular frames as a means of securing attention and resources for the issues that concern them. The ascription of an issue as a security concern, an ethical imperative, or a wise investment is historically contingent: it is not inevitable that any given issue will be framed in one or more of these ways. A health issue's inherent characteristics-such as the lethality of a pathogen that causes it-also shape these ascriptions, but do not fully determine them. Although commonly facing resistance, global health elites often determine which frames prevail, raising questions about the legitimacy of priority-setting processes. We draw on the review to offer ideas on how to make these processes fairer than they are at present, including a call for democratic representation even as necessary space is preserved for elite expertise.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity, mortality, and health-care use worldwide. COPD is caused by exposure to inhaled noxious particles, notably tobacco smoke and pollutants. However, the broad range of factors that increase the risk of development and progression of COPD throughout the life course are increasingly being recognised. Innovations in omics and imaging techniques have provided greater insight into disease pathobiology, which might result in advances in COPD prevention, diagnosis, and treatment. Although few novel treatments have been approved for COPD in the past 5 years, advances have been made in targeting existing therapies to specific subpopulations using new biomarker-based strategies. Additionally, COVID-19 has undeniably affected individuals with COPD, who are not only at higher risk for severe disease manifestations than healthy individuals but also negatively affected by interruptions in health-care delivery and social isolation. This Seminar reviews COPD with an emphasis on recent advances in epidemiology, pathophysiology, imaging, diagnosis, and treatment.

Suicide and self-harm are major health and societal issues worldwide, but the greatest burden of both behaviours occurs in low-income and middle-income countries. Although rates of suicide are higher in male than in female individuals, self-harm is more common in female individuals. Rather than having a single cause, suicide and self-harm are the result of a complex interplay of several factors that occur throughout the life course, and vary by gender, age, ethnicity, and geography. Several clinical and public health interventions show promise, although our understanding of their effectiveness has largely originated from high-income countries. Attempting to predict suicide is unlikely to be helpful. Intervention and prevention must include both a clinical and community focus, and every health professional has a crucial part to play.

Despite health gains over the past 30 years, children and adolescents are not reaching their health potential in many low-income and middle-income countries (LMICs). In addition to health systems, social systems, such as schools, communities, families, and digital platforms, can be used to promote health. We did a targeted literature review of how well health and social systems are meeting the needs of children in LMICs using the framework of The Lancet Global Health Commission on high-quality health systems and we reviewed evidence for structural reforms in health and social sectors. We found that quality of services for children is substandard across both health and social systems. Health systems have deficits in care competence (eg, diagnosis and management), system competence (eg, timeliness, continuity, and referral), user experience (eg, respect and usability), service provision for common and serious conditions (eg, cancer, trauma, and mental health), and service offerings for adolescents. Education and social services for child health are limited by low funding and poor coordination with other sectors. Structural reforms are more likely to improve service quality substantially and at scale than are micro-level efforts. Promising approaches include governing for quality (eg, leadership, expert management, and learning systems), redesigning service delivery to maximise outcomes, and empowering families to better care for children and to demand quality care from health and social systems. Additional research is needed on health needs across the life course, health system performance for children and families, and large-scale evaluation of promising health and social programmes.

Progress has been made globally in improving the coverage of key maternal, newborn, and early childhood interventions in low-income and middle-income countries, which has contributed to a decrease in child mortality and morbidity. However, inequities remain, and many children and adolescents are still not covered by life-saving and nurturing care interventions, despite their relatively low costs and high cost-effectiveness. This Series paper builds on a large body of work from the past two decades on evidence-based interventions and packages of care for survival, strategies for delivery, and platforms to reach the most vulnerable. We review the current evidence base on the effectiveness of a variety of essential and emerging interventions that can be delivered from before conception until age 20 years to help children and adolescents not only survive into adulthood, but also to grow and develop optimally, support their wellbeing, and help them reach their full developmental potential. Although scaling up evidence-based interventions in children younger than 5 years might have the greatest effect on reducing child mortality rates, we highlight interventions and evidence gaps for school-age children (5-9 years) and the transition from childhood to adolescence (10-19 years), including interventions to support mental health and positive development, and address unintentional injuries, neglected tropical diseases, and non-communicable diseases.

The survival and nutrition of children and, to a lesser extent, adolescents have improved substantially in the past two decades. Improvements have been linked to the delivery of effective biomedical, behavioural, and environmental interventions; however, large disparities exist between and within countries. Using data from 95 national surveys in low-income and middle-income countries (LMICs), we analyse how strongly the health, nutrition, and cognitive development of children and adolescents are related to early-life poverty. Additionally, using data from six large, long-running birth cohorts in LMICs, we show how early-life poverty can have a lasting effect on health and human capital throughout the life course. We emphasise the importance of implementing multisectoral anti-poverty policies and programmes to complement specific health and nutrition interventions delivered at an individual level, particularly at a time when COVID-19 continues to disrupt economic, health, and educational gains achieved in the recent past.

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5-19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood.