Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This phase 3 study aimed to assess the efficacy and safety of efsitora compared with insulin degludec (degludec) in adults with type 1 diabetes.

The search for safe and efficacious products to prevent severe respiratory syncytial virus (RSV) disease in young infants has lasted more than 60 years. In high-income and middle-income countries, two new products have been authorised: an RSV monoclonal antibody for administration to infants (nirsevimab) and an RSV prefusion F maternal vaccine (RSVpreF [Pfizer, Puurs, Belgium]) for administration to pregnant people. These products are not yet available in low-income and lower-middle-income countries, where most RSV deaths occur. Other papers in this Series describe the acute burden of RSV disease in young children, the effects of RSV infection in early childhood on long-term lung health, and the burden of RSV disease and disease prevention products in older adults. In this Series paper, we briefly review the efficacy, effectiveness, and safety of nirsevimab and RSVpreF maternal vaccine for protection of infants. We then explore potential regulatory, policy, and implementation pathways and provide case studies of intervention uptake in Spain and Argentina, and considerations for use in Kenya. We also explore the health economic evidence to inform product introduction decisions. With sufficient political will and affordable pricing, RSV disease prevention in infants can become a global reality.

The global burden of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children is high. The RSV prevention strategies approved in 2023 will be essential to lowering the global disease burden. In this Series paper, we describe clinical presentation, burden of disease, hospital management, emerging therapies, and targeted prevention focusing on developments and groundbreaking publications for RSV. We conducted a systematic search for literature published in the past 15 years and used a non-systematic approach to analyse the results, prioritising important papers and the most recent reviews per subtopic. Annually, 33 million episodes of RSV LRTI occur in children younger than 5 years, resulting in 3·6 million hospitalisations and 118 200 deaths. RSV LRTI is a clinical diagnosis but a clinical case definition and universal clinical tool to predict severe disease are non-existent. The advent of molecular point-of-care testing allows rapid and accurate confirmation of RSV infection and could reduce antibiotic use. There is no evidence-based treatment of RSV, only supportive care. Despite widespread use, evidence for high-flow nasal cannula (HFNC) therapy is insufficient and increased paediatric intensive care admissions and intubation indicate the need to remove HFNC therapy from standard care. RSV is now a vaccine-preventable disease in young children with a market-approved long-acting monoclonal antibody and a maternal vaccine targeting the RSV prefusion protein. To have a high impact on life-threatening RSV infection, infants at high risk, especially in low-income and middle-income countries, should be prioritised as an interim strategy towards universal immunisation. The implementation of RSV preventive strategies will clarify the full burden of RSV infection. Vaccine probe studies can address existing knowledge gaps including the effect of RSV prevention on transmission dynamics, antibiotic misuse, the respiratory microbiome composition, and long-term sequalae.

The optimum number of units of blood and the associated number of blood donors required to meet a given population's needs remain undetermined globally. Typically, a whole blood donation rate of ten donations per 1000 population, at a minimum, is necessary to meet a country's blood needs. This rate is attributed to a WHO recommendation that 1% of a given country's population should donate blood to ensure a blood supply that is sufficient to meet clinical needs. This often cited metric was first referenced in a 1971 WHO report, yet neither supporting data or references were provided, suggesting that it was flawed at its founding. Regardless, this metric does not provide an accurate or contemporary determination of blood needs, which has ramifications for health service provision and planning, particularly in low-income and lower-middle-income countries. Modelling studies that account for geographical variability in disease burden, health-care infrastructure, and transfusion practices are needed to accurately estimate blood needs. A paucity of data to inform modelling remains a major obstacle in this regard. We discuss the history of the global blood donation index and highlight some factors that should be considered to better understand contemporary blood needs.

Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1.

Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year.

The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions.

Percutaneous active mechanical circulatory support (MCS) devices are being increasingly used in the treatment of acute myocardial infarction-related cardiogenic shock (AMICS) despite conflicting evidence regarding their effect on mortality. We aimed to ascertain the effect of early routine active percutaneous MCS versus control treatment on 6-month all-cause mortality in patients with AMICS.

Mineralocorticoid receptor antagonists (MRAs) reduce hospitalisations and death in patients with heart failure and reduced ejection fraction (HFrEF), but the benefit in patients with heart failure and mildly reduced ejection fraction (HFmrEF) or heart failure and preserved ejection fraction (HFpEF) is unclear. We evaluated the effect of MRAs in four trials that enrolled patients with heart failure across the range of ejection fraction.

Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation.

Heart failure with mildly reduced or preserved ejection fraction (hereafter referred to as HFpEF) is the most common type of heart failure and is associated with a high risk of hospitalisation and death, especially in patients with overweight, obesity, or type 2 diabetes. In the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide improved heart failure-related symptoms and physical limitations in participants with HFpEF. Whether semaglutide also reduces clinical heart failure events in this group remains to be established.

Hospitals, patients, and health-care workers are legally protected by international humanitarian law and the Geneva Convention. However, since Oct 7, 2023, the health-care system in the Gaza Strip, occupied Palestinian territory, has been under unprecedented direct military attacks by Israel, with support for patients proving to be challenging for the remaining health-care workers. Peer-to-peer telemedicine holds promise for assisting surgeons in high-risk, low-resource environments, but might be of reduced utility in extremely austere settings.

Medical abortion after 12 gestational weeks often requires a stay in hospital. We hypothesised that administering the first misoprostol dose at home could increase day-care procedures as compared with overnight care procedures, shorten inpatient stays, and improve patient satisfaction.

Adiposity can be measured using BMI (which is based on weight and height) as well as indices of abdominal adiposity. We examined the association between BMI and waist-to-height ratio (WHtR) within and across populations of different world regions and quantified how well these two metrics discriminate between people with and without hypertension.

Primary biliary cholangitis is a chronic, autoimmune, cholestatic disease that mainly affects women aged 40-70 years. Recent epidemiological studies have shown an increasing incidence worldwide despite geographical heterogeneity and a decrease in the female-to-male ratio of those the disease affects. Similar to other autoimmune diseases, primary biliary cholangitis occurs in genetically predisposed individuals upon exposure to environmental triggers, specifically xenobiotics, smoking, and the gut microbiome. Notably, the diversity of the intestinal microbiome is diminished in individuals with primary biliary cholangitis. The intricate interplay among immune cells, cytokines, chemokines, and biliary epithelial cells is postulated as the underlying pathogenic mechanism involved in the development and progression of primary biliary cholangitis, and extensive research has been dedicated to comprehending these complex interactions. Following the official approval of obeticholic acid as second-line treatment for patients with an incomplete response or intolerance to ursodeoxycholic acid, clinical trials have indicated that peroxisome proliferator activator receptor agonists are promising additional second-line drugs. Future dual or triple drug regimens might reach a new treatment goal of normalisation of alkaline phosphatase levels, rather than a decrease to less than 1·67 times the upper limit of normal levels, and potentially improve long-term outcomes. Improvement of health-related quality of life with better recognition and care of subjective symptoms, such as pruritus and fatigue, is also an important treatment goal. Promising clinical investigations are underway to alleviate these symptoms. Efforts to facilitate better access to medical care and dissemination of current knowledge should enable diagnosis at an earlier stage of primary biliary cholangitis and ensure access to treatments based on risk stratification for all patients.

Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure.

Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza.

The optimal antiviral drug for treatment of severe influenza remains unclear. To support updated WHO influenza clinical guidelines, this systematic review and network meta-analysis evaluated antivirals for treatment of patients with severe influenza.

X-linked hypophosphataemia is a genetic disease caused by defects in the phosphate regulating endopeptidase homolog X-linked (PHEX) gene and is characterised by X-linked dominant inheritance. The main consequence of PHEX deficiency is increased production of the phosphaturic hormone fibroblast growth factor 23 (FGF23) in osteoblasts and osteocytes. Chronic exposure to circulating FGF23 is responsible for renal phosphate wasting and decreased synthesis of calcitriol, which decreases intestinal phosphate absorption. These mechanisms result in lifelong hypophosphataemia, impaired growth plate and bone matrix mineralisation, and diverse manifestations in affected children and adults, including some debilitating morbidities and possibly increased mortality. Important progress has been made in disease knowledge and management over the past decade; in particular, targeting FGF23 is a therapeutic approach that has substantially improved outcomes. However, patients affected by this complex disease need lifelong care and innovative treatment strategies, such as gene repair of PHEX, are necessary to further limit the disease burden.

Obesity has increased in prevalence worldwide and WHO has declared it a global epidemic. Population-level preventive interventions have been insufficient to slow down this trajectory. Obesity is a complex, heterogeneous, chronic, and progressive disease, which substantially affects health, quality of life, and mortality. Lifestyle and behavioural interventions are key components of obesity management; however, when used alone, they provide substantial and durable response in a minority of people. Bariatric (metabolic) surgery remains the most effective and durable treatment, with proven benefits beyond weight loss, including for cardiovascular and renal health, and decreased rates of obesity-related cancers and mortality. Considerable progress has been made in the development of pharmacological agents that approach the weight loss efficacy of metabolic surgery, and relevant outcome data related to these agents' use are accumulating. However, all treatment approaches to obesity have been vastly underutilised.