Stillbirth is a devastating and often avoidable adverse pregnancy outcome. Monitoring stillbirth levels and trends-in a comprehensive manner that leaves no one uncounted-is imperative for continuing progress in pregnancy loss reduction. This analysis, completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, methodically accounted for different stillbirth definitions with the aim of comprehensively estimating all stillbirths at 20 weeks or longer for 204 countries and territories from 1990 to 2021.

The optimal timing of anticoagulation for patients with acute ischaemic stoke with atrial fibrillation is uncertain. We investigated the efficacy and safety of early compared with delayed initiation of direct oral anticoagulants (DOACs) in patients with acute ischaemic stroke associated with atrial fibrillation.

High-dose haemodiafiltration has been shown, in a randomised clinical trial, to result in a 23% lower risk of mortality for patients with kidney failure when compared with conventional high-flux haemodialysis. Nevertheless, whether treatment effects differ across subgroups, whether a dose-response relationship with convection volume exists, and the effects on cause-specific mortality remain unclear. The aim of this individual patient data meta-analysis was to compare the effects of haemodiafiltration and standard haemodialysis on all-cause and cause-specific mortality.

Most individuals use medication during pregnancy. However, decision making on antenatal pharmacotherapy presents considerable ethical and scientific challenges. Amid a sociocultural paradigm prioritising the elimination of fetal risks, available evidence and guidance are limited, and current decision making on antenatal drugs mostly proceeds in an ad-hoc and, often, biased manner. This approach might undermine the health of both mother and child. The need for a systematic approach towards antenatal drug decisions is becoming even more pressing with the growing knowledge of pregnancy-induced changes in drug disposition and effects. With this new complexity, pregnancy-specific doses might be necessary, potentially altering the balance between maternal and fetal benefits and risks. In this Viewpoint, we argue that ethical principles and a pregnant individual's values must be integrated alongside existing evidence when making decisions on antenatal drug use and dosing. We use the example of sertraline to outline practical strategies for achieving this goal. This approach is urgently needed to foster better-informed and balanced decisions on antenatal pharmacotherapy.

Steatotic liver disease is the overarching term for conditions characterised by abnormal lipid accumulation in the liver (liver or hepatic steatosis). Steatotic liver disease encompasses what was previously termed non-alcoholic fatty liver disease (NAFLD), which is now called metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, steatotic liver disease includes alcohol-related liver disease (ALD) and MetALD, the new classification for the overlap between MASLD and ALD, and rare causes of liver steatosis. Cirrhosis is globally the 11th leading cause of death, and steatotic liver disease has become the leading cause of cirrhosis in the EU and USA. Steatotic liver disease affects around 30% of the global population and is mainly driven by obesity, type 2 diabetes, and alcohol intake, but only a minor proportion with steatotic liver disease progress to cirrhosis. The presence and progression of liver fibrosis led by hepatic inflammation is the main predictor of liver-related death across the entire spectrum of steatotic liver diseases. A combination of recent advancements of widely available biomarkers for early detection of liver fibrosis together with considerable advancements in therapeutic interventions offer the possibility to reduce morbidity and mortality in patients with steatotic liver disease. This Seminar covers the recent reclassification of steatotic liver disease and how it reflects clinical practice and prognosis. For early detection of liver fibrosis, we propose a collaborative diagnostic framework between primary care and liver specialists. Lastly, we discuss current best practices for managing steatotic liver disease, we explore therapeutic targets across the spectrum of steatotic liver diseases, and we review the pipeline of drugs in development for MASLD.

In low-income and middle-income countries, individuals with major depressive disorder often do not receive screening and treatment. We assessed effectiveness and cost-effectiveness of an integrated care model for treating major depressive disorder in Malawi, accounting for two sets of positive externalities: household benefits and improvements in comorbidities.

Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires. We aimed to investigate whether a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with an FFR-based strategy.

Despite the initial hope inspired by the 2015 Paris Agreement, the world is now dangerously close to breaching its target of limiting global multiyear mean heating to 1·5°C. Annual mean surface temperature reached a record high of 1·45°C above the pre-industrial baseline in 2023, and new temperature highs were recorded throughout 2024. The resulting climatic extremes are increasingly claiming lives and livelihoods worldwide. The Lancet Countdown: tracking progress on health and climate change was established the same year the Paris Agreement entered into force, to monitor the health impacts and opportunities of the world’s response to this landmark agreement. Supported through strategic core funding from Wellcome, the collaboration brings together over 300 multidisciplinary researchers and health professionals from around the world to take stock annually of the evolving links between health and climate change at global, regional, and national levels. The 2024 report of the Lancet Countdown, building on the expertise of 122 leading researchers from UN agencies and academic institutions worldwide, reveals the most concerning findings yet in the collaboration’s 8 years of monitoring.

Persistent non-plateauing adverse event rates in patients who underwent percutaneous coronary intervention (PCI) remain a challenge. A bioadaptor is a novel implant that addresses this issue by restoring the haemodynamic modulation of the artery, allowing cyclic pulsatility, vasomotion, and adaptative remodelling, by unlocking and providing dynamic support to the artery. We aimed to assess outcomes with the device versus a contemporary drug-eluting stent (DES) in a representative PCI population.

Biological monoclonal antibody drugs inhibit overactive cytokine signalling that drives chronic inflammatory disease in different organ systems. In the last 10 years, interleukin (IL)-23 inhibitors have attained an important position in the treatment of psoriatic skin and joint disease as well as inflammatory bowel diseases. Addressing an upstream pathological mechanism shared between these disorders, this drug class has high efficacy rates and a durable response that extends dosing intervals up to 3 months. Pooled clinical trial data show objective disease improvement for more than 70% of patients with psoriasis and up to 50% of patients with inflammatory bowel disease. The first antibody inhibitor for IL-23A targeted a p40 subunit shared with IL-12. Subsequently, even greater improvement was established for inhibitors of the p19 protein unique to IL-23A. IL-23 p19 inhibitors elicit clinical response in both bio-naive and bio-exposed patients and show superiority to tumour necrosis factor α inhibitors in plaque psoriasis. Reported differences in efficacy between p19 inhibitors suggest that individual drug action might be modulated by antibody affinity. Although long-term safety data are accumulating, rates of serious adverse events and infections for interleukin (IL)-23 inhibitors are similar to the rates for placebo across approved indications.

Tranexamic acid is a recommended treatment for women with a clinical diagnosis of postpartum haemorrhage, but whether it can prevent bleeding is unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis of randomised controlled trials to assess the effects of tranexamic acid in women giving birth.

Tranexamic acid, given within 3 h of birth, reduces bleeding deaths in women with postpartum haemorrhage. We examined whether giving tranexamic acid shortly after birth can prevent postpartum haemorrhage in women with moderate or severe anaemia.

Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years.

Single-pill combinations (SPCs) of three low-dose antihypertensive drugs can improve hypertension control but are not widely available. A key issue for any combination product is the contribution of each component to efficacy and tolerability. This trial compared a new triple SPC called GMRx2, containing telmisartan, amlodipine, and indapamide, with dual combinations of components for efficacy and safety.

Monkeypox virus clade I is endemic in several central African countries and characterised by an increase in disease severity and mortality. Since October, 2023, a large-scale mpox outbreak has emerged in DR Congo, and in March, 2024, the first individuals with mpox were reported outside the endemic areas in Republic of the Congo. We aimed to provide insight into the epidemic by sequencing samples obtained from individuals with mpox in Republic of the Congo.

Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer.

Global health 2050 (GH2050), a new report from the Lancet Commission on Investing in Health, finds that dramatic improvements in human welfare are achievable by mid-century with focused health investments. By 2050, countries that choose to do so can halve their probability of premature death (PPD)—the probability of dying before age 70—from their pre-pandemic level in 2019. We call this goal “50 by 50”: a 50% reduction in PPD by 2050. The interventions for achieving “50 by 50” will also reduce morbidity and disability at all ages. Historical experience and continued scientific advance indicate that this is a feasible aspiration. Eight of the 30 most populous countries reduced their PPD over the last decade at a rate that would halve PPD before 2050, including countries as diverse as Bangladesh, Iran, Tanzania, and Turkey. These focused gains can be achieved relatively early on the pathway to full universal health coverage (UHC). The path to achieving “50 by 50” runs through control of a remarkably narrow set of just 15 conditions. For currently high mortality countries, eight infectious diseases and maternal conditions are the highest priority. Seven clusters of noncommunicable diseases and injuries are important everywhere and addressing them will prove central to achieving “50 by 50” in most countries with lower initial levels of mortality. Focused attention to health system strengthening (HSS) for primary care and first level hospitals will generate capacity to better tackle the 15 priority conditions and will be a critical step on the way to improving capacity to address all the conditions in a UHC package. Packaging interventions into 19 modules (e.g., a childhood immunization module, a module on cardiovascular disease prevention and low-cost, widely available treatment) will address the 15 priority conditions. Adopting this focused approach also invests in key areas of HSS and addresses major morbidities, such as psychiatric illness, not already covered by mortality-reducing interventions. Value for money can be assessed through a two-step process: technical cost effectiveness to assess how best to achieve module-specific goals (e.g., reduction in child mortality, reduction in cardiovascular mortality) and political evaluation of trade-offs in investing in expanding module coverage. In many countries seeking reform, standard budgetary mechanisms have failed to successfully reorient systems toward priority interventions that improve health. This mechanism of blanket budget transfers from ministries of finance to ministries of health has not been fit to support such reorientation. The Commission concluded that this problem could be addressed by directing a substantial and increasing fraction of budget transfers to making available and affordable the specific drugs, vaccines, diagnostics, and other commodities that are currently available for control of the 15 priority conditions. Drug availability and affordability will typically require four complementary components: (i) redirecting general budget transfers to line item transfers (subsidies) for specific priority drugs; (ii) centralized procurement by government (or perhaps internationally); (iii) procurement in sufficient volumes to ensure availability when needed; and (iv) use and strengthening of existing supply chains, public and private. Of the many intersectoral policies that governments can adopt to help achieve “50 by 50,” tobacco control is by far the most important, given the number of deaths caused by tobacco and the established and improving capacity of governments to implement tobacco policy. A high level of tobacco taxation is essential, and valuable in the short to medium term for public finance, and should be accompanied by a package of other effective tobacco control policies. Background research conducted for the Commission points to exceptionally high ongoing levels of mortality risk from pandemics. Country performance against COVID-19 varied greatly, although eventual vaccine availability attenuated, but far from eliminated, this variability by the end of COVID-19’s emergency phase. National implementation of public health fundamentals—early action, isolation of infected individuals, quarantining of those exposed, and social and financial support for people isolating or quarantining—accounted for much of the success of the best-performing nations, such as Japan. In the next pandemic, these fundamentals will help to avert mortality while waiting for vaccine development and deployment. The conclusions above are primarily aimed at national governments. Our final conclusion is aimed at the development assistance community. We conclude that such assistance should focus on two broad purposes. The first is to provide direct financial and technical support to countries with the least resources—to help develop health systems to better control diseases. The second is to finance global public goods, including strengthening data systems; reducing the development and spread of antimicrobial resistance; preventing and responding to pandemics; fostering global health leadership and advocacy; identifying and spreading best practices; and developing and deploying new health technologies. For both purposes, focusing efforts on the 15 priority conditions would best contribute to “50 by 50.” A decade ago, there were no malaria vaccines and the only available tuberculosis vaccine had low efficacy. Today, two partially successful malaria vaccines have been approved and three promising tuberculosis vaccine candidates are in late stage trials. These successes exemplify the enormous value in funding development of new medicines, vaccines, diagnostics, and operational research against the 15 priority conditions. The prize of “50 by 50,” with an interim milestone of “30 by 2035” (a 30% reduction in PPD by 2035), remains a prize within reach. The most efficient route is to focus resources against a narrow set of conditions and scale up financing to develop and deploy new health technologies. Our economic analyses have shown that the value of achievable mortality declines remains high and indeed is often a substantial fraction of the value of gains in gross domestic product. Today, the case is better than ever for the value of investing in health for reducing mortality and morbidity, alleviating poverty, growing economies, and improving human welfare.

Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival.

Postnatal depression necessitates timely and effective interventions to mitigate adverse maternal and child outcomes in the short term and over the life course. British south Asian women with depression are often underserved and undertreated due to stigma, language barriers, and cultural barriers. This trial aimed to test the clinical efficacy of a culturally adapted, group cognitive behavioural therapy (CBT)-based intervention, the Positive Health Programme (PHP), delivered by non-specialist health workers for postnatal depression in British south Asian women.

WHO currently recommends a single dose of typhoid conjugate vaccine (TCV) in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials. Given the decay of immunogenicity, the protection beyond 2 years is unknown. We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination.