94 million people are blind or visually impaired globally, and cataract is the most common cause of blindness worldwide. However, most cases of blindness are avoidable. Cataract is associated with decreased quality of life and reduced life expectancy. Most cases of cataract occur after birth and share ageing and oxidative stress as primary causes, although several non-modifiable and modifiable risk factors can accelerate cataract formation. In most patients, phacoemulsification with intraocular lens implantation is the preferred treatment and is highly cost-effective. There has been an increase in the use of comprehensive cataract surgical services, including diagnoses, treatment referrals, and rehabilitation. However, global inequity in surgical service quality is still a limitation. Implementation of preoperative risk assessment, risk reduction strategies, and new surgical technologies have made cataract surgery possible at an earlier stage of cataract severity with the expectation of good refractive outcomes. The main challenge is making the service that is currently available to some patients accessible to all by use of universal health coverage.

Randomised controlled trials, including the National Lung Screening Trial (NLST) and the NELSON trial, have shown reduced mortality with lung cancer screening with low-dose CT compared with chest radiography or no screening. Although research has provided clarity on key issues of lung cancer screening, uncertainty remains about aspects that might be critical to optimise clinical effectiveness and cost-effectiveness. This Review brings together current evidence on lung cancer screening, including an overview of clinical trials, considerations regarding the identification of individuals who benefit from lung cancer screening, management of screen-detected findings, smoking cessation interventions, cost-effectiveness, the role of artificial intelligence and biomarkers, and current challenges, solutions, and opportunities surrounding the implementation of lung cancer screening programmes from an international perspective. Further research into risk models for patient selection, personalised screening intervals, novel biomarkers, integrated cardiovascular disease and chronic obstructive pulmonary disease assessments, smoking cessation interventions, and artificial intelligence for lung nodule detection and risk stratification are key opportunities to increase the efficiency of lung cancer screening and ensure equity of access.

Depression is common, costly, debilitating, and associated with increased risk of suicide. It is one of the leading global public health problems. Although existing available pharmacological treatments can be effective, their onset of action can take up to 6 weeks, side-effects are common, and recovery can require treatment with multiple different agents. Although psychosocial interventions might also be recommended, more effective treatments than those currently available are needed for people with moderate or severe depression. In the past 10 years, treatment trials have developed and tested many new targeted interventions. In this Review, we assess novel and emerging biological treatments for major depressive disorder, evaluate their putative brain and body mechanisms, and highlight how close each might be to clinical use.

Louis Pasteur has long been heralded as one of the fathers of microbiology and immunology. Less known is Pasteur's vision on infection prevention and control (IPC) that drove current infection control, public health, and much of modern medicine and surgery. In this Review, we revisited Pasteur's pioneering works to assess progress and challenges in the process and technological innovation of IPC. We focused on Pasteur's far-sighted conceptualisation of the hospital as a reservoir of microorganisms and amplifier of transmission, aseptic technique in surgery, public health education, interdisciplinary working, and the protection of health services and patients. Examples from across the globe help inform future thinking for IPC innovation, adoption, scale up and sustained use.

The education of health professionals substantially changed before, during, and after the COVID-19 pandemic. A 2010 Lancet Commission examined the 100-year history of health-professional education, beginning with the 1910 Flexner report. Since the publication of the Lancet Commission, several transformative developments have happened, including in competency-based education, interprofessional education, and the large-scale application of information technology to education. Although the COVID-19 pandemic did not initiate these developments, it increased their implementation, and they are likely to have a long-term effect on health-professional education. They converge with other societal changes, such as globalisation of health care and increasing concerns of health disparities across the world, that were exacerbated by the pandemic. In this Health Policy, we list institutional and instructional reforms to assess what has happened to health-professional education since the publication of the Lancet Commission and how the COVID-19 pandemic altered the education process.

Racism, xenophobia, and discrimination are key determinants of health and equity and must be addressed for improved health outcomes. We conclude that far broader, deeper, transformative action is needed compared with current measures to tackle adverse effects of racism on health. To challenge the structural drivers of racism and xenophobia, anti-racist action and other wider measures that target determinants should implement an intersectional approach to effectively address the causes and consequences of racism within a population. Structurally, legal instruments and human rights law provide a robust framework to challenge the pervasive drivers of disadvantage linked to caste, ethnicity, Indigeneity, migratory status, race, religion, and skin colour. Actions need to consider the historical, economic, and political contexts in which the effects of racism, xenophobia, and discrimination affect health. We propose several specific actions: a commission that explores how we action the approaches laid out in this paper; building a conversation and a series of events with international multilateral agency stakeholders to raise the issue and profile of racism, xenophobia, and discrimination within health; and using our multiple platforms to build coalitions, expand knowledge, highlight inequities, and advocate for change across the world.

Intersectionality is a useful tool to address health inequalities, by helping us understand and respond to the individual and group effects of converging systems of power. Intersectionality rejects the notion of inequalities being the result of single, distinct factors, and instead focuses on the relationships between overlapping processes that create inequities. In this Series paper, we use an intersectional approach to highlight the intersections of racism, xenophobia, and discrimination with other systems of oppression, how this affects health, and what can be done about it. We present five case studies from different global locations that outline different dimensions of discrimination based on caste, ethnicity and migration status, Indigeneity, religion, and skin colour. Although experiences are diverse, the case studies show commonalities in how discrimination operates to affect health and wellbeing: how historical factors and coloniality shape contemporary experiences of race and racism; how racism leads to separation and hierarchies across shifting lines of identity and privilege; how racism and discrimination are institutionalised at a systems level and are embedded in laws, regulations, practices, and health systems; how discrimination, minoritisation, and exclusion are racialised processes, influenced by visible factors and tacit knowledge; and how racism is a form of structural violence. These insights allow us to begin to articulate starting points for justice-based action that addresses root causes, engages beyond the health sector, and encourages transnational solidarity.

Despite being globally pervasive, racism, xenophobia, and discrimination are not universally recognised determinants of health. We challenge widespread beliefs related to the inevitability of increased mortality and morbidity associated with particular ethnicities and minoritised groups. In refuting that racial categories have a genetic basis and acknowledging that socioeconomic factors offer incomplete explanations in understanding these health disparities, we examine the pathways by which discrimination based on caste, ethnicity, Indigeneity, migratory status, race, religion, and skin colour affect health. Discrimination based on these categories, although having many unique historical and cultural contexts, operates in the same way, with overlapping pathways and health effects. We synthesise how such discrimination affects health systems, spatial determination, and communities, and how these processes manifest at the individual level, across the life course, and intergenerationally. We explore how individuals respond to and internalise these complex mechanisms psychologically, behaviourally, and physiologically. The evidence shows that racism, xenophobia, and discrimination affect a range of health outcomes across all ages around the world, and remain embedded within the universal challenges we face, from COVID-19 to the climate emergency.

This Series shows how racism, xenophobia, discrimination, and the structures that support them are detrimental to health. In this first Series paper, we describe the conceptual model used throughout the Series and the underlying principles and definitions. We explore concepts of epistemic injustice, biological experimentation, and misconceptions about race using a historical lens. We focus on the core structural factors of separation and hierarchical power that permeate society and result in the negative health consequences we see. We are at a crucial moment in history, as populist leaders pushing the politics of hate have become more powerful in several countries. These leaders exploit racism, xenophobia, and other forms of discrimination to divide and control populations, with immediate and long-term consequences for both individual and population health. The COVID-19 pandemic and transnational racial justice movements have brought renewed attention to persisting structural racial injustice.

Indigenous Brazilian peoples have faced an unparalleled increase in the rate of cardiovascular diseases following rapid nutritional transition to more urban diets. We aimed to conduct a systematic review and meta-analysis to evaluate the association between urbanisation (including data from Amazon rainforest deforestation) and cardiometabolic risk factors and outcomes.

Existing evidence on the effects of race and ethnicity on pregnancy outcomes is restricted to individual studies done within specific countries and health systems. We aimed to assess the impact of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries, and to ascertain whether the magnitude of disparities, if any, varied across geographical regions.

Congenital adrenal hyperplasia is a group of autosomal recessive disorders leading to multiple complex hormonal imbalances caused by various enzyme deficiencies in the adrenal steroidogenic pathway. The most common type of congenital adrenal hyperplasia is due to steroid 21-hydroxylase (21-OHase, henceforth 21OH) deficiency. The rare, classic (severe) form caused by 21OH deficiency is characterised by life-threatening adrenal crises and is the most common cause of atypical genitalia in neonates with 46,XX karyotype. After the introduction of life-saving hormone replacement therapy in the 1950s and neonatal screening programmes in many countries, nowadays neonatal survival rates in patients with congenital adrenal hyperplasia are high. However, disease-related mortality is increased and therapeutic management remains challenging, with multiple long-term complications related to treatment and disease affecting growth and development, metabolic and cardiovascular health, and fertility. Non-classic (mild) forms of congenital adrenal hyperplasia caused by 21OH deficiency are more common than the classic ones; they are detected clinically and primarily identified in female patients with hirsutism or impaired fertility. Novel treatment approaches are emerging with the aim of mimicking physiological circadian cortisol rhythm or to reduce adrenal hyperandrogenism independent of the suppressive effect of glucocorticoids.

Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy.

Systemic sclerosis, also known as scleroderma, is a rare and complex autoimmune connective-tissue disease. Once considered an untreatable and unpredictable condition, research advancements have improved our understanding of its disease pathogenesis and clinical phenotypes and expanded our treatment armamentarium. Early and accurate diagnosis is essential, while ongoing efforts to risk stratify patients have a central role in predicting both organ involvement and disease progression. A holistic approach is required when choosing the optimal therapeutic strategy, balancing the side-effect profile with efficacy and tailoring the treatment according to the goals of care of the patient. This Seminar reviews the multiple clinical dimensions of systemic sclerosis, beginning at a precursor very early stage of disease, with a focus on timely early detection of organ involvement. This Seminar also summarises management considerations according to the pathological hallmarks of systemic sclerosis (eg, inflammation, fibrosis, and vasculopathy) and highlights unmet needs and opportunities for future research and discovery.

Although it is a rare disease, the number of available therapeutic options for treating pulmonary arterial hypertension has increased since the late 1990s, with multiple drugs developed that are shown to be effective in phase 3 randomised controlled trials. Despite considerable advancements in pulmonary arterial hypertension treatment, prognosis remains poor. Existing therapies target pulmonary endothelial dysfunction with vasodilation and anti-proliferative effects. Novel therapies that target proliferative vascular remodelling and affect important outcomes are urgently needed. There is need for additional innovations in clinical trial design so that all emerging candidate therapies can be rigorously studied. Pulmonary arterial hypertension trial design has shifted from short-term submaximal exercise capacity as a primary endpoint, to larger clinical event-driven trial outcomes. Event-driven pulmonary arterial hypertension trials could face feasibility and efficiency issues in the future because increasing sample sizes and longer follow-up durations are needed, which would be problematic in such a rare disease. Enrichment strategies, innovative and alternative trial designs, and novel trial endpoints are potential solutions that could improve the efficiency of future pulmonary arterial hypertension trials while maintaining robustness and clinically meaningful evidence.

Around the world, populations are ageing at a faster pace than in the past and this demographic transition will have impacts on all aspects of societies. In May 2020, the UN General Assembly declared 2021–2030 the Decade of Healthy Ageing, highlighting the importance for policymakers across the world to focus policy on improving the lives of older people, both today and in the future. While rapid population ageing poses challenges, China’s rapid economic growth over the last forty years has created space for policy to assist older persons and families in their efforts to improve health and well-being at older ages. As China is home to 1/5 of the world’s older people, China is often held up as an example for other middle-income countries. This Commission Report aims to help readers to understand the process of healthy ageing in China as a means of drawing lessons from the China experience. In addition, with the purpose of informing the ongoing policy dialogue within China, the Commission Report highlights the policy challenges on the horizon and draws lessons from international experience.

When the history of the COVID-19 pandemic is written, the failure of many states to live up to their human rights obligations should be a central narrative. The pandemic began with Wuhan officials in China suppressing information, silencing whistleblowers, and violating the freedom of expression and the right to health. Since then, COVID-19's effects have been profoundly unequal, both nationally and globally. These inequalities have emphatically highlighted how far countries are from meeting the supreme human rights command of non-discrimination, from achieving the highest attainable standard of health that is equally the right of all people everywhere, and from taking the human rights obligation of international assistance and cooperation seriously. We propose embedding human rights and equity within a transformed global health architecture as the necessary response to COVID-19's rights violations. This means vastly more funding from high-income countries to support low-income and middle-income countries in rights-based recoveries, plus implementing measures to ensure equitable distribution of COVID-19 medical technologies. We also emphasise structured approaches to funding and equitable distribution going forward, which includes embedding human rights into a new pandemic treaty. Above all, new legal instruments and mechanisms, from a right to health treaty to a fund for civil society right to health advocacy, are required so that the narratives of future health emergencies-and people's daily lives-are ones of equality and human rights.