CONCORD is a global public health programme for long-term surveillance of population-based cancer survival. The first three cycles of this programme focused primarily on adults. In CONCORD-4, for the first time, we also included all cancers in children. The WHO Global Initiative for Childhood Cancer (GICC), published in 2018, set a target for 5-year survival for all childhood cancers combined, worldwide, to reach 60% by 2030. We designed the protocol for CONCORD-4 to assess progress towards this target in as many countries as possible.

Current therapies for osteoarthritis have limitations. LEVI-04 is a p75 neurotrophin receptor (p75NTR) fusion protein that inhibits neurotrophin-3. We assessed the efficacy and safety of LEVI-04 in individuals with knee osteoarthritis.

The clinical benefits of intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiation therapy (IMRT) for patients with oropharyngeal squamous cell carcinoma remain uncertain with respect to treatment-related effects on physical function and quality of life. We aimed to compare late functional, patient-reported, disease control, and survival outcomes between IMPT and IMRT.

Evidence, including animal, clinical, and real-world studies in individuals with type 2 diabetes and/or obesity, suggests reduced risk of dementia and Alzheimer's disease after GLP-1 receptor agonist exposure. The evoke and evoke+ trials aimed to investigate the efficacy and safety of oral semaglutide in individuals with early Alzheimer's disease.

Video-assisted thoracoscopic surgery (VATS) is currently the most common approach for pulmonary lobectomy in early-stage lung cancer. Reported advantages include less pain, fewer complications, faster recovery, and improved postoperative quality of life. The widespread adoption of VATS lobectomy is principally based on non-oncological benefits. Its oncological equivalence to open surgery remains assumed as no single trial has been powered for survival. To address this important question, we sought to conduct an individual patient data meta-analysis of eligible randomised trials.

Increased fluid intake is universally recommended to decrease the risk of recurrent urinary stones; however, adherence is challenging. The effectiveness of interventions to maintain high fluid intake has not been well studied. We sought to determine whether a multicomponent behavioural intervention programme to promote high fluid intake reduces symptomatic stone recurrence, compared with a control.

In sub-Saharan Africa, the burden of diabetes and hypertension is high, alongside a high prevalence of HIV. Whether these conditions can be managed in an integrated way in the community is unknown. We aim to compare integrated community-based care with integrated facility-based care for people with HIV, diabetes, and hypertension in Tanzania and Uganda.

Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive neoplasm that affects otherwise healthy adults. There are few systemic treatment options, highlighting an unmet need. We report the results of part 1 of the MANEUVER trial, which aimed to evaluate the efficacy and safety of pimicotinib, a highly selective, potent, colony-stimulating factor-1 receptor inhibitor, in patients with TGCT.

Aldosterone dysregulation is an important contributor in the pathogenesis of hard-to-control hypertension. We aimed to assess the effect of baxdrostat, a selective aldosterone synthase inhibitor, on ambulatory blood pressure in patients with resistant hypertension.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic kidney disease, resulting in substantial morbidity and mortality globally. Advances in molecular genetics and deep-phenotype imaging techniques have refined existing diagnostic and prognostic tools. The strong evidence-base for tolvaptan as a disease-modifying treatment supports its early use in groups at high risk of kidney failure. Screening and management of potentially serious complications including cyst infection, intracranial aneurysms, and polycystic liver disease are important components of a comprehensive care plan. This Review focuses on current approaches to diagnosis, risk assessment, treatment, and specific aspects of clinical management in ADPKD. An updated understanding of the genetic basis of disease, pathobiology with respect to potential therapeutic targets, and promising therapies now in clinical trials are summarised. We propose a holistic patient-centred care pathway that emphasises shared decision-making with a multidisciplinary clinical team to address the individual needs of patients throughout their lifelong journey.

Adding hormone therapy to definitive radiotherapy in localised prostate cancer improves overall survival, but whether it similarly improves overall survival in the context of postoperative radiotherapy (PORT) after radical prostatectomy is unclear. Herein, we report an individual patient data (IPD) meta-analysis of randomised trials aimed at quantifying the benefit of adding hormonal therapy to PORT.

Antipsychotic drugs are the established treatment for acute schizophrenia but differ in receptor-binding profiles. In 2024, a new-in-class muscarinic receptor agonist (xanomeline-trospium) was licenced, acting upstream of antidopaminergic agents, and providing hope to decrease the adverse effects burden of antipsychotics. We aimed to compare the efficacy and tolerability of antipsychotics by performing network meta-analysis of randomised controlled trials (RCTs).

The Management of Myelomeningocele Study (MOMS) trial established the benefit of in-utero repair of myelomeningocele, with a decreased need for ventriculoperitoneal shunt placement. However, although there was some improvement of motor function, over half of the patients were unable to ambulate independently. Live placenta-derived mesenchymal stem cells (PMSCs) seeded on an extracellular matrix have shown promise in rescuing neurological function in the fetal ovine model of myelomeningocele. We aimed to evaluate the safety of this novel, living, stem cell product to augment the prenatal repair of myelomeningocele.

Single-tablet regimens (STRs) revolutionised HIV-1 treatment, improving adherence and clinical outcomes; however, many people cannot take these due to resistance, contraindications, or drug-drug interactions, instead relying on complex multi-tablet regimens. Novel STRs are therefore needed. We aimed to evaluate the efficacy and safety of a novel STR, bictegravir-lenacapavir, in people with HIV-1.

Adult obesity has been linked to specific infections, but evidence across the full spectrum of infectious diseases remains scarce. In this multicohort study with impact modelling, we examined the association between this preventable risk factor and the incidence, hospitalisations, and mortality of 925 bacterial, viral, parasitic, and fungal infectious diseases, and estimated their global and regional attributable impact.

Statin product labels (eg, Summaries of Product Characteristics [SmPCs]) list certain adverse outcomes as potential treatment-related effects based mainly on non-randomised and non-blinded studies, which might be subject to bias. We aimed to assess the evidence for such undesirable effects more reliably through a meta-analysis of individual participant data from large double-blind trials of statin therapy.

Accurate assessment of mortality, bleeding, and atherothrombotic risk in patients with cancer and acute coronary syndrome could inform novel personalised treatment strategies, but no standardised tools for this purpose exist. We aimed to develop and validate a clinically applicable risk score for mortality, bleeding, and ischaemic events in patients with cancer and acute coronary syndrome.