Prolonged grief disorder is a mental health disorder recently included in diagnostic manuals worldwide. This Review presents published research evidence in strong support for the current conceptualisation of prolonged grief disorder: a diagnosable mental health condition with core symptoms of yearning, preoccupation, or both, which is associated with symptoms of emotional pain, identity disturbances, loss of meaning and purpose, and functional impairment. The public and academic discourse surrounding prolonged grief disorder has catalysed researchers to produce methodologically rigorous research evidence in support of this much-needed diagnosis. A coherent syndrome of prolonged grief disorder has a typical onset of 6 to 12 months after the death of a close person. Prolonged grief disorder is associated with various poor outcomes, including negative health outcomes (eg, high blood pressure), increased rates of suicidality, low life satisfaction, and increased service use. Psychotherapy is the main treatment for prolonged grief disorder. Theoretical models of the cause and maintenance of prolonged grief disorder are presently being refined through the rapidly increasing empirical literature. Awareness of prolonged grief disorder by general health practitioners, as well as mental health specialists, is key to appropriate early intervention.

Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent.

PEPFAR (President's Emergency Plan for AIDS Relief), a landmark US foreign health policy, is recognised for saving 26 million lives from HIV. PEPFAR investments have also had life-saving impacts for children across sub-Saharan Africa through childhood HIV prevention, care, and treatment, ensuring 7·8 million babies were born HIV-free, supporting 13 million orphaned and vulnerable children, and protecting 10·3 million girls from sexual abuse. In this Health Policy, we review data from UNAIDS, UNICEF, World Bank, Violence Against Children Surveys, SPECTRUM model data, and Population-based HIV Impact Assessments; synthesise PEPFAR reports; conduct in-depth interviews; search PubMed for programme effectiveness evidence; and review economic reports. PEPFAR support is associated with substantial collateral benefits for the USA and Africa, including a four-fold increase in export of US goods to Africa, and US$71·6 billion in total goods trade between the USA and Africa in 2024. PEPFAR-supported countries in Africa are committed to ownership of HIV responses by 2030-overall, PEPFAR-supported countries in sub-Saharan Africa have progressively increased their co-financing of their health systems through domestic government and private expenditure from $13·7 billion per year in 2004 to $42·6 billion per year in 2021. The feasibility of a 5-year transition to country-led sustainability is supported by evidence of innovative cost-saving models of delivery, including through faith-based and community-based organisations, and high return-on-investment for PEPFAR programmes. There are also collateral benefits of PEPFAR for US and Africa national security and health security, for example, reducing forced migration and increasing capacity to control emerging transborder infectious disease threats. Risks in sub-Saharan Africa remain acute: one in five girls (younger than 18 years) experience rape or sexual assault; one in ten children (younger than 18 years) are orphaned; and a child (younger than 15 years) is estimated to die from AIDS every 7 min. Without continued PEPFAR programmes, models predict that by 2030, an additional 1 million children will become infected with HIV, 0·5 million additional children will die of AIDS, and 2·8 million children will additionally become orphaned by AIDS. There is now an opportunity for a transformational partnership between the USA and Africa, to accelerate domestic government co-financing, private-sector investments, and charitable foundations. A 5-year progressive runway of transition can occur through continued authorisation of PEPFAR programmes, which can lead to the end of AIDS for children and families, an historic achievement.

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.

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.

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.

Tuberculosis is a leading cause of death globally. Given the airborne transmission of tuberculosis, anybody can be infected, but people in high-incidence settings are more exposed. Risk of progression to disease is higher in the first years after infection, and in people with undernourishment, immunosuppression, or who smoke, drink alcohol, or have diabetes. Although cough, fever, and weight loss are hallmark symptoms, people with tuberculosis can be asymptomatic, so a high index of suspicion is required. Prompt diagnosis can be made by sputum examination (ideally with rapid molecular tests), but chest radiography can be helpful. Most people with disease can be treated with regimens of 6 months or less; longer regimens may be necessary for those with drug resistance. Central to successful treatment is comprehensive, person-centred care including addressing key determinants, such as undernourishment, smoking, and alcohol use, and optimising management of comorbidities, such as diabetes and HIV. Care should continue after treatment ends, as long-term sequelae are common. Prevention relies mostly on treatment with rifamycin-based regimens; current vaccines have limited efficacy. Ongoing research on shorter and safer regimens for infection and disease treatment, and simpler and more accurate diagnostic methods will be key for tuberculosis elimination.

Haemophilia A and B are congenital X-linked bleeding disorders resulting from deficiencies in clotting factors VIII (haemophilia A) and IX (haemophilia B). Patients with severe deficiency, defined as having less than 1% of normal plasma factor activivity, often have spontaneous bleeding within the first few years of life. Those with moderate and mild deficiencies typically present with post-traumatic or post-surgical bleeding later in life. A high index of suspicion and measurement of factor activity in plasma facilitates early diagnosis. In the 21st century, therapeutic advances and comprehensive care have substantially improved both mortality and morbidity associated with these conditions. Management strategies for haemophilia include on-demand treatment for bleeding episodes and all surgeries and regular treatment (ie, prophylaxis) aimed at reducing bleeds, morbidity, and mortality, thereby enhancing quality of life. Treatment options include factor replacement therapy, non-replacement therapies that increase thrombin generation, and gene therapies that facilitate in vivo clotting factor synthesis. The therapies differ in their use for prophylaxis and on-demand treatment, the mode and frequency of administration, duration of treatment effect, degree of haemostatic protection, and side-effects. Monitoring the effectiveness of these prophylactic therapies involves assessing annual bleeding rates and joint damage. Personalised management strategies, which align treatment with individual goals (eg, playing competitive sports), initiated at diagnosis and maintained throughout the lifespan, are crucial for optimal outcomes. These strategies are facilitated by a multidisciplinary team and supported by clinician-led education for both clinicians and patients.

Schistosomiasis is a neglected tropical disease caused by infection with blood flukes of the genus Schistosoma. Widely distributed in the Middle East, southeast Asia, Latin America, and (mostly) sub-Saharan Africa, schistosomiasis is acquired upon skin penetration of infective larvae released by freshwater snails. Acute infection might present with self-limiting hypersensitivity reactions (known as Katayama fever). Chronic infection typically leads to two main clinical patterns: intestinal or urogenital schistosomiasis, depending on the infecting species. Impairment of other body sites (eg, the CNS or respiratory tract) can occur. The intestinal form is characterised by abdominal pain and diarrhoea, with or without blood; complications are hepatic fibrosis, portal hypertension, splenomegaly, and variceal bleeding. The urogenital form is characterised by dysuria and haematuria; complications are renal failure and squamous-cell carcinoma of the bladder. Conventional diagnosis is based on egg detection in faeces or urine, although sensitivity might be low. Praziquantel is the first-line treatment, and it is also provided in preventive chemotherapy campaigns by mass drug administration to afflicted communities.

Atopic dermatitis is the most common chronic inflammatory skin disease globally. Key features include an eczematous eruption accompanied by intense itch, which can have an enormous negative effect on patients' quality of life, especially in those with moderate-to-severe disease. Atopic dermatitis is part of a spectrum of atopic conditions that can also include several non-cutaneous organs such as respiratory (eg, allergic rhinitis and asthma) and gastrointestinal (eg, food allergy) systems. For decades, long-term disease control and maintenance were particularly challenging given that treatment options were limited to broad topical and systemic immunosuppressive agents. However, better insights into the pathophysiology of this condition over the past decade have led to the development and approval of safe and efficacious novel targeted treatment approaches. The updated pathophysiological understanding and the evolving therapeutic landscape of atopic dermatitis are discussed in this Seminar.

Some of the physiological changes that occur in pregnancy manifest in the liver. These alterations might exacerbate or improve some pre-existent liver diseases, while many conditions remain unaffected. Some hepatic manifestations during pregnancy are secondary to disorders unique to pregnancy. Due to improved management of chronic conditions and assisted conception methods, pregnancies in people with cirrhosis or after liver transplantation are increasingly common. With pregnancy also becoming more common in older people and with the rising prevalence of comorbidities, such as obesity, diabetes, and metabolic syndrome, hypertensive disorders of pregnancy and gestational diabetes are increasing in prevalance. Thus, a broad range of specialists might encounter liver abnormalities in pregnancy, necessitating an understanding of how the liver changes during pregnancy and the importance of multi-disciplinary input to mitigate maternal-fetal risks. From a global health perspective, pregnancy also offers a unique opportunity to influence disease management and initiate interventions that might influence the life course of pregnant people and their families. In this Review, we describe the challenges of diagnosing, risk stratifying, and managing liver disease in pregnancy, and explore factors that might affect future maternal health.

Hidradenitis suppurativa is a chronic inflammatory disease characterised by painful, deep-seated nodules, abscesses, and draining tunnels in the skin of axillary, inguinal, genitoanal, or inframammary areas. In recent years, the body of knowledge in hidradenitis suppurativa has advanced greatly. This disorder typically starts in the second or third decade of life. The average worldwide prevalence is 1% but varies geographically. Hidradenitis suppurativa has a profound negative effect on patients' quality of life and on the gross value added to society. Comorbidities (eg, metabolic syndrome, inflammatory arthritis, and inflammatory bowel disease) frequently accompany skin alterations, because of systemic inflammation. Pathogenesis of hidradenitis suppurativa is complex and includes innate immune mechanisms (eg, macrophages, neutrophils, IL-1β, tumour necrosis factor [TNF], and granulocyte colony-stimulating factor), T-cell mechanisms (eg, IL-17 and IFN-γ), and B-cell mechanisms (eg, associated with dermal tertiary lymphatic structures and autoantibodies). Chronic inflammation leads to irreversible skin damage with tunnel formation and morbid scarring. Current treatment includes drug therapy (for the initial, purely inflammatory phase), combined drug and surgical therapy (for the destructive phase), or surgery alone (for the burnout phase). The first systemic therapies approved for hidradenitis suppurativa targeting TNF (adalimumab) and IL-17 (secukinumab and bimekizumab) have expanded drug therapy options for moderate-to-severe disease, which were previously mainly restricted to oral antibiotics. Moreover, there is a robust pipeline of immunomodulatory drugs in various stages of development for hidradenitis suppurativa. Aims of management should include early intervention to prevent irreversible skin damage, adequate control of symptoms including pain, and mitigation of extra-cutaneous comorbidities, all requiring early diagnosis and an interdisciplinary, holistic and personalised approach.