An understanding of the causes of postpartum haemorrhage is needed to provide appropriate treatment and services. Knowledge of the risk factors for postpartum haemorrhage can help address modifiable risk factors. We did a systematic review and meta-analysis to identify and quantify the various causes and risk factors for postpartum haemorrhage.

Pancreatic cancer is frequently a lethal disease with an aggressive tumour biology often presenting with non-specific symptoms. Median survival is approximately 4 months with a 5-year survival of 13%. Surveillance is recommended in individuals with familial pancreatic cancer, specific mutations, and high-risk intraductal papillary mucinous neoplasm, as they are at high risk of developing pancreatic cancer. Chemotherapy combined with surgical resection remains the cornerstone of treatment. However, only a small subset of patients are candidates for surgery. Multi-agent chemotherapy has improved survival in the palliative setting for patients with metastatic disease, as (neo)adjuvant and induction therapy have in patients with borderline resectable and locally advanced pancreatic. Given that pancreatic cancer is predicted to become the second leading cause of cancer-related death by 2030, novel therapies are urgently needed.

Transcatheter aortic valve implantation (TAVI) is a guideline-directed treatment for severe aortic stenosis and degenerated aortic bioprostheses. When new transcatheter heart valve (THV) platforms for TAVI are launched, they should be compared with best-in-practice contemporary THVs for their short-term and long-term performance. The COMPARE-TAVI 1 trial was designed to provide a head-to-head comparison of the SAPIEN 3 or SAPIEN 3 Ultra THVs and the Myval or Myval Octacor THVs.

Coronary artery disease has long been understood through the paradigm of epicardial coronary artery obstruction, causing myocardial ischaemia (a mismatch between myocardial blood supply and demand). However, this model, which focuses on diagnosing and managing coronary artery disease based on ischaemia and cardiovascular events, is flawed. By the time ischaemia manifests, it is often too late for optimal intervention, limiting the effectiveness of treatment options. Despite decades of medical advances, coronary artery disease continues to be a leading cause of morbidity and mortality globally, highlighting the inadequacy of this traditional ischaemic-centric approach. The central limitation of current approaches is the focus on the temporary solutions of restoring myocardial blood flow after obstruction, rather than tackling the underlying disease. Coronary artery disease, caused by atherosclerosis, often results in myocardial infarction through mechanisms that emerge earlier in the progression of disease. The focus of medical care has predominantly been on the recognition of symptoms and treatment of acute events, missing opportunities for early detection and prevention of disease. Billions of dollars in health-care funding continue to be spent on identifying and managing coronary ischaemia; yet, the dominant mechanisms for myocardial infarction are atherosclerotic plaque rupture or erosion and, to a lesser extent, erupted calcified nodules that can emerge at a much earlier stage of the disease. This Commission advocates for a shift in the conceptual framework of coronary artery disease. We suggest reclassifying the condition as atherosclerotic coronary artery disease (ACAD), moving away from the traditional emphasis on ischaemia and acute cardiac events towards a more systematic understanding of atherosclerosis. This reframing will enable the identification and management of the disease much earlier in its course, potentially saving millions of lives worldwide. Risk of ACAD develops over a lifetime, beginning in utero, progressing through childhood and adolescence, and continuing into older age. The early stages of disease, which involve the formation of atherosclerotic plaques, are often undetected. A major shift is needed from acute event-centred care to strategies focused on early diagnosis, prevention, and management of atherosclerosis. In this new framework, ACAD should be recognised across all stages, from the earliest signs of atheroma formation to the advanced stages of disease. Our goals should not just to be to manage symptoms and events but to prevent the disease from developing in the first place and, where possible, reverse its course.

Mixed dyslipidaemia, characterised by elevated concentrations of circulating triglycerides and LDL cholesterol (LDL-C), is associated with an increased risk of atherosclerotic cardiovascular disease. Solbinsiran, a GalNAc-conjugated small interfering RNA targeting hepatic angiopoietin-like protein 3 (ANGPTL3), reduced triglycerides and LDL-C concentrations in a phase 1 study. This study aimed to assess the durability and efficacy of solbinsiran in reducing concentrations of atherogenic lipoproteins in adults with mixed dyslipidaemia.

The optimal strategy for long-term antiplatelet maintenance for patients who underwent percutaneous coronary intervention (PCI) remains uncertain. This study aimed to compare the efficacy and safety of clopidogrel versus aspirin monotherapy in patients who completed a standard duration of dual antiplatelet therapy (DAPT) following PCI with drug-eluting stents.

Long-term outcomes following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) might be changing because of improved techniques and better medical therapy. This final prespecified analysis of the Fractional Flow Reserve (FFR) versus Angiography for Multivessel Evaluation (FAME) 3 trial aimed to reassess their comparative effectiveness at 5 years.

Revascularisation decisions based on angiography-derived fractional flow reserve (FFR) or optimisation of stent implantation with intravascular ultrasound yield superior clinical outcomes compared with percutaneous coronary intervention (PCI) guided by angiography alone. However, the differences in outcomes when a single approach is used for both purposes remain unclear. We aimed to assess the non-inferiority of angiography-derived FFR versus intravascular ultrasound guidance in terms of clinical outcomes at 12 months in patients with angiographically significant stenosis.

Coronary artery calcification is common among patients undergoing percutaneous coronary intervention (PCI), and severe coronary artery lesion calcification is associated with increased procedural complexity, stent under-expansion, and high rates of intraprocedural complications and out-of-hospital adverse events. Whether calcium ablation before stent implantation can mitigate these adverse events is not currently established. We aimed to prospectively compare orbital atherectomy with a balloon angioplasty-based strategy before stent implantation for the treatment of severely calcified coronary lesions.

Peripheral artery disease is a highly morbid type of atherosclerotic vascular disease involving the legs and is estimated to affect over 230 million individuals globally. Few therapies improve functional capacity and health-related quality of life in people with lower limb peripheral artery disease. We aimed to evaluate whether semaglutide improves function as measured by walking ability as well as symptoms, quality of life, and outcomes in people with peripheral artery disease and type 2 diabetes.

Chikungunya disease is a growing global public health concern. Vimkunya (previously chikungunya virus virus-like particle vaccine, previously PXVX0317) is a single-dose, pre-filled syringe for intramuscular injection. Here, we report safety, tolerability, and immunogenicity data for Vimkunya versus placebo in healthy adolescents and adults aged 12-64 years, and evaluate lot-to-lot consistency.

Colonoscopy and the faecal immunochemical test are accepted strategies for colorectal cancer screening in the average-risk population (ie, people aged ≥50 years without personal or family history of colorectal cancer). In this trial, we aimed to compare whether invitation to screening with faecal immunochemical test was non-inferior to colonoscopy in a screening programme.

Adults older than 65 years are at increased risk for atypical presentations of chikungunya disease, as well as for severe outcomes including death.

Ageing is a scientifically fascinating and complex biological occurrence characterised by morphological and functional changes due to accumulated molecular and cellular damage impairing tissue and organ function. Ageing is often accompanied by cognitive decline but is also the biggest known risk factor for Alzheimer's disease, the most common form of dementia. Emerging evidence suggests that sedentary and unhealthy lifestyles accelerate brain ageing, while regular physical activity, high cardiorespiratory fitness (CRF), or a combination of both, can mitigate cognitive impairment and reduce dementia risk. The purpose of this Review is to explore the neuroprotective mechanisms of endurance exercise and highlight the importance of CRF in promoting healthy brain ageing. Key findings show how CRF mediates the neuroprotective effects of exercise via mechanisms such as improved cerebral blood flow, reduced inflammation, and enhanced neuroplasticity. We summarise evidence supporting the integration of endurance exercise that enhances CRF into public health initiatives as a preventive measure against age-related cognitive decline. Additionally, we address important challenges such as lack of long-term studies with harmonised study designs across preclinical and clinical settings, employing carefully controlled and repeatable exercise protocols, and outline directions for future research.

Overactive bladder is a common problem affecting women worldwide, with a negative effect on their social and professional lives. Before considering invasive treatments, guidelines recommend urodynamics to identify detrusor overactivity. However, the clinical-effectiveness and cost-effectiveness of urodynamics has never been robustly assessed in this cohort of women. We aimed to compare the clinical-effectiveness and cost-effectiveness of urodynamics plus comprehensive clinical assessment (CCA) versus CCA only in the management of women with refractory overactive bladder symptoms.

Almost 40 years ago, the discovery of the vasoactive neuropeptide calcitonin gene-related peptide (CGRP) and its role in migraine pathophysiology ushered in a new era in migraine treatment. Since 2018, monoclonal antibodies (mAbs) targeting the CGRP pathway are available for migraine prevention. The approval of these drugs marks a pioneering development, as they are the first pharmacological agents specifically tailored for migraine prevention. Introduction of these agents contrasts the historical reliance on traditional preventive medications initially formulated for other indications and later repurposed for migraine therapy. Although the emergence of evidence on the efficacy and safety of CGRP-targeted mAbs has raised the bar for treatment success in migraine, their efficacy in other headache entities, such as cluster headache, is low to moderate. Small-molecule CGRP receptor antagonists called gepants have also been proven to be effective both as acute and preventive migraine treatments. Furthermore, these agents have bridged the traditional categories of acute and preventive treatment strategies. Short-term prevention and treatment during the prodromal phase of migraine represent emerging strategies enabling clinicians to develop treatment approaches designed to meet changing patient needs; however, these strategies still require more formal evidence. Although solid data have been gathered, further research concerning the efficacy and long-term safety of drugs targeting the CGRP pathway and robust pharmacoeconomic evaluations are needed. Finally, randomised withdrawal and switching studies would facilitate the formulation of evidence-based guidance for the discontinuation of and switching between drugs targeting the CGRP pathway.

Despite a substantial reduction in the use of solid fuels for cooking worldwide, exposure to household air pollution (HAP) remains a leading global risk factor, contributing considerably to the burden of disease. We present a comprehensive analysis of spatial patterns and temporal trends in exposure and attributable disease from 1990 to 2021, featuring substantial methodological updates compared with previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study, including improved exposure estimations accounting for specific fuel types.

Human African trypanosomiasis or sleeping sickness is caused by infection with Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense parasites, which are transmitted by tsetse flies in sub-Saharan Africa. Control of human African trypanosomiasis is based on case detection, treatment, and vector control. In the past decade, simple rapid diagnostic tests were introduced for gambiense human African trypanosomiasis, facilitating screening in primary health-care facilities. A new oral drug, fexinidazole, became the first-line treatment for gambiense human African trypanosomiasis without severe meningo-encephalitic disease, as well as for rhodesiense human African trypanosomiasis. Medical interventions, in some areas combined with tiny target-based vector control, have substantially reduced human African trypanosomiasis incidence, despite temporary disruptions to health-care systems. The elimination of human African trypanosomiasis as a public health problem has been achieved, and elimination of gambiense human African trypanosomiasis transmission is now targeted for 2030. Improved diagnostics and drugs, continued involvement of populations at risk of disease, health staff, national authorities, and partners and donors all contribute to achieve this goal.

Uptake of colorectal cancer screening is suboptimal. The TEMPO trial evaluated the impact of two evidence-based, theory-informed, and co-designed behavioural interventions on uptake of faecal immunochemical test (FIT) colorectal screening.

Invasive meningococcal disease is a devastating public health problem for the African meningitis belt. We assessed the safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, Y, W, and X (NmCV-5) relative to a licensed, quadrivalent meningococcal conjugate vaccine (MenACWY-TT) when co-administered with routine childhood vaccines at ages 9 months and 15 months.