George Institute for Global Health

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

INTRODUCTION: Systematic reviews provide a rigorous synthesis of the best available evidence regarding a certain question. Where high-quality evidence is lacking, systematic reviewers may choose to rely on case series studies to provide information in relation to their question. However, to date there has been limited guidance on how to incorporate case series studies within systematic reviews assessing the effectiveness of an intervention, particularly with reference to assessing the methodological quality or risk of bias of these studies. METHODS: An international working group was formed to review the methodological literature regarding case series as a form of evidence for inclusion in systematic reviews. The group then developed a critical appraisal tool based on the epidemiological literature relating to bias within these studies. This was then piloted, reviewed, and approved by JBI's international Scientific Committee. RESULTS: The JBI critical appraisal tool for case series studies includes 10 questions addressing the internal validity and risk of bias of case series designs, particularly confounding, selection, and information bias, in addition to the importance of clear reporting. CONCLUSION: In certain situations, case series designs may represent the best available evidence to inform clinical practice. The JBI critical appraisal tool for case series offers systematic reviewers an approved method to assess the methodological quality of these studies.

Novel Coronavirus disease (COVID-19) is a newly discovered contagious disease caused by severe acute respiratory syndrome (SARS)–coronavirus (CoV)-2 virus, primarily manifesting as an acute respiratory illness with interstitial and alveolar pneumonia, but it can affect multiple organs such as the kidney, heart, digestive tract, blood, and nervous system.1Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. https://doi.org/10.1001/jama.2020.1585. Accessed March 2, 2020.Google Scholar The rapidly spreading outbreak, which first emerged in Wuhan, Hubei Province, China, in December 2019, has since been declared a global pandemic. As of March 16, 2020, 167,511 cases of COVID-19 have been reported worldwide in 151 countries (and a cruise ship), with 6606 deaths.2World Health OrganizationCoronavirus disease (COVID-2019) situation reports.https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reportsDate accessed: March 16, 2020Google Scholar In recent days, the number of cases has risen rapidly in South Korea, Japan, Europe, and the United States. SARS-CoV-2 has been identified as a bat-origin CoV. The full-length genome sequence of the COVID-19 virus shows a close relationship with the bat SARS-like coronavirus strain BatCov RaTG13 belonging to the Betacoronavirus genus.3World Health OrganizationReport of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19).https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdfDate accessed: March 2, 2020Google Scholar Previous coronavirus infections, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-Co-V), have infected more than 10,000 people in the past 2 decades, with mortality rates of 10% and 37%, respectively.4World Health OrganizationSummary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003.https://www.who.int/csr/sars/country/table2004_04_21/en/Date accessed: January 27, 2020Google Scholar,5World Health OrganizationMiddle East respiratory syndrome coronavirus (MERS-CoV). November 2019.http://www.who.int/emergencies/mers-cov/en/Date accessed: February 27, 2020Google Scholar COVID-19 is more contagious than these illnesses, spreads by human-to-human transmission via droplets, fecal, or direct contact, and has an incubation period estimated at 1 to 14 days (usually 3 to 7 days). Infection has been reported in all ages, including children. The majority of infections are mild, presenting with a flu-like illness. The common clinical presentations of COVID-19 are fever (98%), cough (76%), and myalgia and fatigue (18% each),6Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.The Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar with accompanying leucopenia (25%) and lymphopenia (63%). Symptoms of upper respiratory infection with rhinorrhea and productive cough are uncommon, except in children. About 16% to 20% cases have been classified as severe or critical. Of the 41 patients described by Huang et al.,6Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.The Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar all had pneumonia with abnormalities on computerized tomographic examination of the chest (bilateral lobular and subsegmental areas of consolidation), and 32% required care from the intensive care unit. Higher plasma cytokine levels (interleukin [IL]-2, IL-7, IL-10, granulocyte-colony stimulating factor, interferon-inducing protein-10, monocyte chemoattractant protein 1, macrophage inflammatory protein-1a, tumor necrosis factor α) were present in patients requiring intensive care unit admission. Limited reports suggest that severe complications are uncommon in children.7Center for Disease Control and PreventionFrequently asked questions and answers: Coronavirus Disease-2019 (COVID-19) and children.https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/children-faq.htmlDate accessed: March 2, 2020Google Scholar The diagnosis is mainly based on epidemiological factors (history of contact), clinical manifestations, and laboratory examination (hemogram, chest computed tomography, and virological examination).8Ling L. Taisheng L. The National Health Commission of PRC Guideline for diagnosis and treatment of novel coronavirus disease (version 6).Natl Med J China. 2020; 100: E001Google Scholar Of note, there are recent cases without any travel history or apparent contact with infected individuals. Several COVID-19 nucleic acid detection assays have been developed, both in-house and commercial. They use fluorescence polymerase chain reaction and probe anchoring polymerization techniques. Gene sequencing has also been used. The World Health Organization has appointed referral laboratories in different countries.9World Health OrganizationSpecimen referral for 2019nCoV - operational details of referral laboratories.https://www.who.int/docs/default-source/coronaviruse/who-appointed-2019-ncov-referral-laboratories-7-february-2020.pdf?sfvrsn=c3fa3ec3_4Date accessed: March 2, 2020Google Scholar A serological test has been developed and allowed detection of a cluster of cases in Singapore.10Normile D. Singapore claims first use of antibody test to track coronavirus infections.https://www.sciencemag.org/news/2020/02/singapore-claims-first-use-antibody-test-track-coronavirus-infectionsDate accessed: March 2, 2020Google Scholar More sensitive and convenient detection methods continue to be developed. In previous reports of SARS and MERS-CoV infections, acute kidney injury (AKI) developed in 5% to 15% cases and carried a high (60%–90%) mortality rate. Early reports suggested a lower incidence (3%–9%) of AKI in those with COVID-19 infection.1Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. https://doi.org/10.1001/jama.2020.1585. Accessed March 2, 2020.Google Scholar,11Chen N. Zhou M. Dong X. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14520) Google Scholar, 12Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of 2019 novel coronavirus infection in China [e-pub ahead of print]. N Engl J Med. https://doi.org/10.1056/NEJMoa2002032. Accessed March 2, 2020.Google Scholar, 13Cheng Y, Luo R, Wang K, et al. Kidney impairment is associated with in-hospital death of COVID-19 patients [e-pub ahead of print]. medRxiv 2020.02.18.20023242. https://doi.org/10.1101/2020.02.18.20023242. Accessed March 2, 2020.Google Scholar Recent reports, however, have shown higher frequency of renal abnormalities. A study of 59 patients with COVID-19 found that 34% of patients developed massive albuminuria on the first day of admission, and 63% developed proteinuria during their stay in hospital.14Li Z. Wu M. Guo J. et al.Caution on kidney dysfunctions of 2019-nCoV patients. medRxiv 2020.02.08.20021212.Date accessed: March 2, 2020Google Scholar Blood urea nitrogen was elevated in 27% overall and in two-thirds of patients who died. Computed tomography scan of the kidneys showed reduced density, suggestive of inflammation and edema. Cheng et al.13Cheng Y, Luo R, Wang K, et al. Kidney impairment is associated with in-hospital death of COVID-19 patients [e-pub ahead of print]. medRxiv 2020.02.18.20023242. https://doi.org/10.1101/2020.02.18.20023242. Accessed March 2, 2020.Google Scholar recently reported that amongst 710 consecutive hospitalized patients with COVID-19, 44% had proteinuria and hematuria and 26.7% had hematuria on admission. The prevalence of elevated serum creatinine and blood urea nitrogen was 15.5% and 14.1%, respectively. AKI was an independent risk factor for patients’ in-hospital mortality.13Cheng Y, Luo R, Wang K, et al. Kidney impairment is associated with in-hospital death of COVID-19 patients [e-pub ahead of print]. medRxiv 2020.02.18.20023242. https://doi.org/10.1101/2020.02.18.20023242. Accessed March 2, 2020.Google Scholar,14Li Z. Wu M. Guo J. et al.Caution on kidney dysfunctions of 2019-nCoV patients. medRxiv 2020.02.08.20021212.Date accessed: March 2, 2020Google Scholar The exact mechanism of kidney involvement is unclear: postulated mechanisms include sepsis leading to cytokine storm syndrome or direct cellular injury due to the virus. Angiotensin-converting enzyme and dipeptidyl peptidase-4, both expressed on renal tubular cells, were identified as binding partners for SARS-CoV and MERS-CoV, respectively.15Li W. Moore M.J. Vasilieva N. et al.Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.Nature. 2003; 426: 450-454Crossref PubMed Scopus (4580) Google Scholar,16Raj V.S. Mou H. Smits S.L. et al.Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC.Nature. 2013; 495: 251-254Crossref PubMed Scopus (1588) Google Scholar Viral RNA has been identified in kidney tissue and urine in both infections.17Peiri J.S.M. Chu C.M. Cheng V.C.C. et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study.Lancet. 2003; 361: 1767-1772Abstract Full Text Full Text PDF PubMed Scopus (1998) Google Scholar,18Ding Y. He L. Zhang Q. et al.Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways.J Pathol. 2004; 203: 622-630Crossref PubMed Scopus (841) Google Scholar Recently, Zhong’s lab in Guangzhou successfully isolated SARS-CoV-2 from the urine sample of an infected patient, suggesting the kidney as the target of this novel coronavirus.19The team of Zhong Nanshan responded that the isolation of SARS-CoV-2 from urine remind us to pay more attention to the cleaning of individuals and families.Guangzhou Daily. Published February 22, 2020; Google Scholar The current treatment of COVID-19 with AKI includes general and supportive management and kidney replacement therapy. There is no effective antiviral therapy available at present. All patients with confirmed COVID-19 need to be quarantined. An N95 fit-tested respirator and protective clothes and equipment are essential. Early admission to intensive care units in designated hospitals is recommended for severely ill patients. Supportive care, namely bed rest, nutritional and fluid support, and maintenance of blood pressure and oxygenation are important measures, as for all critically ill patients. Other measures include prevention and treatment of complications by providing organ support, maintaining hemodynamic stability, and preventing secondary infection. There is no specific effective antiviral drug for COVID-19 at present. The guidelines of the Chinese National Health Commission recommend aerosolized inhalation of interferon α and lopinavir/ritonavir. The specific therapeutic value and safety of lopinavir/ritonavir in patients with COVID-19 are under investigation (ChiCTR2000029308).20Expert Team of Chinese Society of NephrologyExpert consensus on diagnosis and treatment of 2019 novel coronavirus (2019 - nCoV) infection with acute kidney injury.Chin J Nephrol. 2020; 3https://doi.org/10.3760/cma.j.cn441217-20200222-00035Google Scholar Successful treatment with remdesivir has been reported in a patient with COVID-19; a clinical trial on the efficacy of remdesivir in patients with COVID-19 is currently underway in China (NCT0425266; NCT04257656) and is expected to be completed in April 2020. Chloroquine phosphate has been shown to have some efficacy against COVID-19–associated pneumonia in multicenter clinical trials conducted in China.21Gao J. Tian Z. Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies.Biosci Trends. 2020; 14: 72-73Crossref PubMed Google Scholar Continuous renal replacement therapy (CRRT) has been successfully applied in the treatment of SARS, MERS, and sepsis.22Chu K.H. Tsang W.K. Tang C.S. et al.Acute renal impairment in coronavirus-associated severe acute respiratory syndrome.Kidney Int. 2005; 67: 698-705Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar,23Arabi Y.M. Arifi A.A. Balkhy H.H. et al.Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection.Ann Intern Med. 2014; 160: 389-397Crossref PubMed Google Scholar High-volume hemofiltration in a dose of 6 l/h removed inflammatory cytokines (IL-6) and improved the Sequential Organ Failure Assessment scores at day 7 in patients with sepsis.24Ghani R.A. Zainudin S. Ctkong N. et al.Serum IL-6 and IL-1-ra with sequential organ failure assessment scores in septic patients receiving high-volume haemofiltration and continuous venovenous haemofiltration.Nephrology (Carlton). 2006; 11: 386-393Crossref PubMed Scopus (83) Google Scholar Therefore, CRRT may play a role in patients with COVID-19 and sepsis syndrome. The potential role of extracorporeal therapy techniques needs to be evaluated, however. In a retrospective study of patients with SARS-CoV and sepsis, steroids, at a mean daily dose of 105.3 ± 86.1 mg in 147 of 249 noncritical patients (59.0%), reduced mortality rate and shortened duration of hospitalization, whereas 121 of 152 critical patients (79.6%) received corticosteroids at a mean daily dose of 133.5 ± 102.3 mg, and 25 died.25Chen R.C. Tang X.P. Tan S.Y. et al.Treatment of severe acute respiratory syndrome with glucosteroids: the Guangzhou experience.Chest. 2006; 129: 1441-1452Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar A subsequent retrospective, observational study of 309 patients with MERS showed that those who received high-dose steroids were more likely to require mechanical ventilation, vasopressors, and renal replacement therapy (RRT).26Arabi Y.M. Mandourah Y. Al-Hameed F. et al.Corticosteroid therapy for critically ill patients with middle east respiratory syndrome.Am J Respir Crit Care Med. 2018; 197: 757-767Crossref PubMed Scopus (838) Google Scholar In a meta-analysis of corticosteroid use in patients with SARS, 4 studies provided conclusive evidence of harm (psychosis, diabetes, avascular necrosis, and delayed viral clearance).27Stockman L.J. Bellamy R. Garner P. SARS: systematic review of treatment effects.PLoS Med. 2006; 3: e343Crossref PubMed Scopus (986) Google Scholar Therefore, the use of steroids is controversial and not recommended by the World Health Organization because of potential inhibition of viral clearance and prolongation of the duration of viremia.28Russell C.D. Millar J.E. Baillie J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury.Lancet. 2020; 395: 473-475Abstract Full Text Full Text PDF PubMed Scopus (1542) Google Scholar Preliminary clinical studies in China have shown that early application of convalescent plasma in patients with COVID-19 could accelerate clinical recovery.6Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.The Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar Currently 2 trials, an open-label, nonrandomized clinical trial (NCT04264858) and a multicenter, randomized, and parallel-controlled trial (ChiCTR2000029757) on the efficacy of convalescent plasma in patients with COVID-19, are underway in China. Monoclonal antibody directed against the Ras-binding domain of the S protein of MERS-CoV has been found to have neutralizing activities in plaque assays in vitro.29Park B.K. Maharjan S. Lee S.I. et al.Generation and characterization of a monoclonal antibody against MERS-CoV targeting the spike protein using a synthetic peptide epitope-CpG-DNA-liposome complex.BMB Rep. 2019; 52: 397-402Crossref PubMed Scopus (20) Google Scholar A monoclonal antibody against COVID-19 has not yet been developed. Tocilizumab, a monoclonal antibody against the IL-6 receptor, has achieved encouraging preliminary clinical results. The safety and efficacy of tocilizumab in COVID-19 infection are undergoing evaluation by a multicenter randomized controlled trial (ChiCTR2000029765). Pregnant women, newborns, the elderly, and patients with comorbidities like diabetes mellitus, hypertension, and cardiovascular disease are susceptible to COVID-19 infection and are likely to have more severe illness often requiring care from an intensive care unit. The impact of COVID-19 on chronic kidney disease has not been reported.30Ma Y. Diao B. Lv X. et al.2019 novel coronavirus disease in hemodialysis (HD) patients: report from one HD center in Wuhan, China.https://www.medrxiv.org/content/10.1101/2020.02.24.20027201v2Date accessed: March 2, 2020Google Scholar COVID-19 infection presents a special threat to patients on dialysis. There are 7184 patients on hemodialysis (HD) in 61 treatment centers in Wuhan City. At a single HD center in Renmin Hospital, Wuhan University, 37 out of 230 patients on HD and 4 of 33 staff members developed COVID-19 infection between January 14 and February 17, 2020.30Ma Y. Diao B. Lv X. et al.2019 novel coronavirus disease in hemodialysis (HD) patients: report from one HD center in Wuhan, China.https://www.medrxiv.org/content/10.1101/2020.02.24.20027201v2Date accessed: March 2, 2020Google Scholar A total of 7 patients on HD died, of whom 6 had COVID-19 infection. However, the deaths were deemed to be due to cardiovascular causes and not directly to the COVID-19 infection. Patients on HD with COVID-19 had less lymphopenia, lower serum levels of inflammatory cytokines, and milder clinical disease than other patients with COVID-19 infection. COVID-19 infection presents particular challenges for patients on dialysis, in particular, those in in-center HD. Patients with uremia are particularly to infection and may in clinical and HD the risk of transmission of including to staff and patients and all The Chinese Society of Team of Chinese for prevention and of novel coronavirus infection in blood center from Chinese J Nephrol. 2020; Scholar and the Society of Guideline for during COVID-19 Society of accessed: March 16, 2020Google Scholar have recently developed guidelines for units during the COVID-19 A of these guidelines is provided team of and in clinical of COVID-19, of infection at prevention and guidelines from the and The of staff be and by on and cluster history of patient, their of the and at be and care and be and to all care as can be or including and be is recommended that staff members have at different to and be removed and with during be to the of their and the team in or their members suggestive of COVID-19 and of people at risk of of or the and be and accompanying be the Patients and during dialysis. They can such as to with or confirmed COVID-19 infection be to a isolation of the of the isolation is the Care is recommended for patients under the period of for contact with of patients continue HD at the HD center and not to and not and staff to and infection. the who need be for novel coronavirus the on patients with confirmed or novel coronavirus infection be carried out in a designated with for not be used. Patients and and or N95 patients who have fever be for novel coronavirus infection and be in the of the day infection is for and the and not be with other patients. and with other patients at the be The and of of be in patients not be in close treatment and areas have and to from the care all in direct patient care including isolation and or be equipment that may contact with patients or be to a newly confirmed or of novel coronavirus infection in centers is be carried out in close contact with these patients not be for other patients from confirmed or patients with novel coronavirus infection be as and members with patients on all the and to patients to and transmission of COVID-19, which include and of on who have a or to can have as in during the the members or of a patient on have been to a confirmed the be and in with the In COVID-19, a caused by a novel is a global human Kidney involvement to be in this and AKI is an independent of The impact of this infection in those with chronic kidney disease has not been of patients on who have been to have been in contact with COVID-19 be carried out to to risk to other patients and care of these patients. reports from and All the other declared no Angiotensin-converting enzyme 2 during kidney inflammatory implications to to COVID-19 kidney enzyme 2 is the receptor for severe acute respiratory syndrome coronavirus 2 target cells, it has a role by a to an PDF the COVID-19 in the are to the to the coronavirus disease 2019 (COVID-19) pandemic. 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BACKGROUND: One potential solution to limited healthcare access in low and middle income countries (LMIC) is task-shifting- the training of non-physician healthcare workers (NPHWs) to perform tasks traditionally undertaken by physicians. The aim of this paper is to conduct a systematic review of studies involving task-shifting for the management of non-communicable disease (NCD) in LMIC. METHODS: A search strategy with the following terms "task-shifting", "non-physician healthcare workers", "community healthcare worker", "hypertension", "diabetes", "cardiovascular disease", "mental health", "depression", "chronic obstructive pulmonary disease", "respiratory disease", "cancer" was conducted using Medline via Pubmed and the Cochrane library. Two reviewers independently reviewed the databases and extracted the data. FINDINGS: Our search generated 7176 articles of which 22 were included in the review. Seven studies were randomised controlled trials and 15 were observational studies. Tasks performed by NPHWs included screening for NCDs and providing primary health care. The majority of studies showed improved health outcomes when compared with usual healthcare, including reductions in blood pressure, increased uptake of medications and lower depression scores. Factors such as training of NPHWs, provision of algorithms and protocols for screening, treatment and drug titration were the main enablers of the task-shifting intervention. The main barriers identified were restrictions on prescribing medications and availability of medicines. Only two studies described cost-effective analyses, both of which demonstrated that task-shifting was cost-effective. CONCLUSIONS: Task-shifting from physicians to NPHWs, if accompanied by health system re-structuring is a potentially effective and affordable strategy for improving access to healthcare for NCDs. Since the majority of study designs reviewed were of inadequate quality, future research methods should include robust evaluations of such strategies.

Haemodialysis (HD) is the commonest form of kidney replacement therapy in the world, accounting for approximately 69% of all kidney replacement therapy and 89% of all dialysis. Over the last six decades since the inception of HD, dialysis technology and patient access to the therapy have advanced considerably, particularly in high-income countries. However, HD availability, accessibility, cost and outcomes vary widely across the world and, overall, the rates of impaired quality of life, morbidity and mortality are high. Cardiovascular disease affects more than two-thirds of people receiving HD, is the major cause of morbidity and accounts for almost 50% of mortality. In addition, patients on HD have high symptom loads and are often under considerable financial strain. Despite the many advances in HD technology and delivery systems that have been achieved since the treatment was first developed, poor outcomes among patients receiving HD remain a major public health concern. Understanding the epidemiology of HD outcomes, why they might vary across different populations and how they might be improved is therefore crucial, although this goal is hampered by the considerable heterogeneity in the monitoring and reporting of these outcomes across settings. This Review examines the epidemiology of haemodialysis outcomes — clinical, patient-reported and surrogate outcomes — across world regions and populations, including vulnerable individuals. The authors also discuss the current status of monitoring and reporting of haemodialysis outcomes and potential strategies for improvement.

Importance: Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health. Objective: To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from 1990 to 2015 to provide a framework for policy discussion. Evidence Review: Cause-specific mortality and nonfatal health outcomes were analyzed for 195 countries and territories by age group, sex, and year from 1990 to 2015 using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger. A composite indicator of income, education, and fertility was developed (Socio-demographic Index [SDI]) for each geographic unit and year, which evaluates the historical association between SDI and health loss. Findings: Global child and adolescent mortality decreased from 14.18 million (95% uncertainty interval [UI], 14.09 million to 14.28 million) deaths in 1990 to 7.26 million (95% UI, 7.14 million to 7.39 million) deaths in 2015, but progress has been unevenly distributed. Countries with a lower SDI had a larger proportion of mortality burden (75%) in 2015 than was the case in 1990 (61%). Most deaths in 2015 occurred in South Asia and sub-Saharan Africa. Global trends were driven by reductions in mortality owing to infectious, nutritional, and neonatal disorders, which in the aggregate led to a relative increase in the importance of noncommunicable diseases and injuries in explaining global disease burden. The absolute burden of disability in children and adolescents increased 4.3% (95% UI, 3.1%-5.6%) from 1990 to 2015, with much of the increase owing to population growth and improved survival for children and adolescents to older ages. Other than infectious conditions, many top causes of disability are associated with long-term sequelae of conditions present at birth (eg, neonatal disorders, congenital birth defects, and hemoglobinopathies) and complications of a variety of infections and nutritional deficiencies. Anemia, developmental intellectual disability, hearing loss, epilepsy, and vision loss are important contributors to childhood disability that can arise from multiple causes. Maternal and reproductive health remains a key cause of disease burden in adolescent females, especially in lower-SDI countries. In low-SDI countries, mortality is the primary driver of health loss for children and adolescents, whereas disability predominates in higher-SDI locations; the specific pattern of epidemiological transition varies across diseases and injuries. Conclusions and Relevance: Consistent international attention and investment have led to sustained improvements in causes of health loss among children and adolescents in many countries, although progress has been uneven. The persistence of infectious diseases in some countries, coupled with ongoing epidemiologic transition to injuries and noncommunicable diseases, require all countries to carefully evaluate and implement appropriate strategies to maximize the health of their children and adolescents and for the international community to carefully consider which elements of child and adolescent health should be monitored.

Introduction The burden of chronic kidney disease (CKD) is growing rapidly around the world. However, there is limited information on the overall regional prevalence of CKD, as well as the variations in national prevalence within Asia. We aimed to consolidate available data and quantify estimates of the CKD burden in this region. Methods We systematically searched MEDLINE, Embase and Google Scholar for observational studies and contacted national experts to estimate CKD prevalence in countries of Asia (Eastern, Southern and South Eastern Asia). CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 or the presence of proteinuria. For countries without reported data, we estimated CKD prevalence using agglomerative average-linkage hierarchical clustering, based on country-level risk factors and random effects meta-analysis within clusters. Published CKD prevalence data were obtained for 16 countries (of the 26 countries in the region) and estimates were made for 10 countries. Results There was substantial variation in overall and advanced (eGFR <30 mL/min/1.73 m 2 ) CKD prevalence (range: 7.0%–34.3% and 0.1%–17.0%, respectively). Up to an estimated 434.3 million (95% CI 350.2 to 519.7) adults have CKD in Asia, including up to 65.6 million (95% CI 42.2 to 94.9) who have advanced CKD. The greatest number of adults living with CKD were in China (up to 159.8 million, 95% CI 146.6 to 174.1) and India (up to 140.2 million, 95% CI 110.7 to 169.7), collectively having 69.1% of the total number of adults with CKD in the region. Conclusion The large number of people with CKD, and the substantial number with advanced CKD, show the need for urgent collaborative action in Asia to prevent and manage CKD and its complications.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

BACKGROUND: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).

Importance: The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain. Objective: To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline. Design, Setting, and Participants: An international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m2 after at least 3 months of optimized background care from 67 centers in Australia, Canada, China, India, and Malaysia between May 2012 and November 2019, with follow-up until June 2021. Interventions: Participants were randomized in a 1:1 ratio to receive oral methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or placebo (n = 126). After 262 participants were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group). Main Outcomes And Measures: The primary end point was a composite of 40% decline in eGFR, kidney failure (dialysis, transplant), or death due to kidney disease. There were 11 secondary outcomes, including kidney failure. Results: Among 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m2; mean proteinuria, 2.46 g/d), 493 (98%) completed the trial. Over a mean of 4.2 years of follow-up, the primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group compared with 106 (43.1%) in the placebo group (hazard ratio [HR], 0.53 [95% CI, 0.39-0.72]; P < .001; absolute annual event rate difference, -4.8% per year [95% CI, -8.0% to -1.6%]). The effect on the primary outcome was seen across each dose compared with the relevant participants in the placebo group recruited to each regimen (P for heterogeneity = .11): full-dose HR, 0.58 (95% CI, 0.41-0.81); reduced-dose HR, 0.27 (95% CI, 0.11-0.65). Of the 11 prespecified secondary end points, 9 showed significant differences in favor of the intervention, including kidney failure (50 [19.5%] vs 67 [27.2%]; HR, 0.59 [95% CI, 0.40-0.87]; P = .008; annual event rate difference, -2.9% per year [95% CI, -5.4% to -0.3%]). Serious adverse events were more frequent with methylprednisolone vs placebo (28 [10.9%] vs 7 [2.8%] patients with serious adverse events), primarily with full-dose therapy compared with its matching placebo (22 [16.2%] vs 4 [3.2%]). Conclusions and Relevance: Among patients with IgA nephropathy at high risk of progression, treatment with oral methylprednisolone for 6 to 9 months, compared with placebo, significantly reduced the risk of the composite outcome of kidney function decline, kidney failure, or death due to kidney disease. However, the incidence of serious adverse events was increased with oral methylprednisolone, mainly with high-dose therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01560052.

Importance: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. Objective: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Design, Setting, and Participants: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. Exposures: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). Main Outcomes and Measures: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. Results: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). Conclusions and Relevance: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

BACKGROUND: Research priority setting with stakeholders can help direct the limited resources for health research toward priority areas of need. Ensuring transparency of the priority setting process can strengthen legitimacy and credibility for influencing the research agenda. This study aims to develop a reporting guideline for priority setting of health research. METHODS: We searched electronic databases and relevant websites for sources (frameworks, guidelines, or models for conducting, appraising, reporting or evaluating health research priority setting, and reviews (including systematic reviews)), and primary studies of research priority setting to July 2019. We inductively developed a list of reporting items and piloted the preliminary guideline with a diverse range of 30 priority setting studies from the records retrieved. RESULTS: From 21,556 records, we included 26 sources for the candidate REPRISE framework and 455 primary research studies. The REporting guideline for PRIority SEtting of health research (REPRISE) has 31 reporting items that cover 10 domains: context and scope, governance and team, framework for priority setting, stakeholders/participants, identification and collection of priorities, prioritization of research topics, output, evaluation and feedback, translation and implementation, and funding and conflict of interest. Each reporting item includes a descriptor and examples. CONCLUSIONS: The REPRISE guideline can facilitate comprehensive reporting of studies of research priority setting. Improved transparency in research priority setting may strengthen the acceptability and implementation of the research priorities identified, so that efforts and funding are invested in generating evidence that is of importance to all stakeholders. TRIAL REGISTRATION: Not applicable.

BACKGROUND: Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs. METHODS AND FINDINGS: Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%-64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%-41%) with beta-blockers, and 32% (95% CI: 25%-39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%-7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%-10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified. CONCLUSIONS: The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors' Summary.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.

The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.

OBJECTIVE: To determine the global capacity (availability, accessibility, quality, and affordability) to deliver kidney replacement therapy (dialysis and transplantation) and conservative kidney management. DESIGN: International cross sectional survey. SETTING: International Society of Nephrology (ISN) survey of 182 countries from July to September 2018. PARTICIPANTS: Key stakeholders identified by ISN's national and regional leaders. MAIN OUTCOME MEASURES: Markers of national capacity to deliver core components of kidney replacement therapy and conservative kidney management. RESULTS: Responses were received from 160 (87.9%) of 182 countries, comprising 97.8% (7338.5 million of 7501.3 million) of the world's population. A wide variation was found in capacity and structures for kidney replacement therapy and conservative kidney management-namely, funding mechanisms, health workforce, service delivery, and available technologies. Information on the prevalence of treated end stage kidney disease was available in 91 (42%) of 218 countries worldwide. Estimates varied more than 800-fold from 4 to 3392 per million population. Rwanda was the only low income country to report data on the prevalence of treated disease; 5 (<10%) of 53 African countries reported these data. Of 159 countries, 102 (64%) provided public funding for kidney replacement therapy. Sixty eight (43%) of 159 countries charged no fees at the point of care delivery and 34 (21%) made some charge. Haemodialysis was reported as available in 156 (100%) of 156 countries, peritoneal dialysis in 119 (76%) of 156 countries, and kidney transplantation in 114 (74%) of 155 countries. Dialysis and kidney transplantation were available to more than 50% of patients in only 108 (70%) and 45 (29%) of 154 countries that offered these services, respectively. Conservative kidney management was available in 124 (81%) of 154 countries. Worldwide, the median number of nephrologists was 9.96 per million population, which varied with income level. CONCLUSIONS: These comprehensive data show the capacity of countries (including low income countries) to provide optimal care for patients with end stage kidney disease. They demonstrate substantial variability in the burden of such disease and capacity for kidney replacement therapy and conservative kidney management, which have implications for policy.

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.

Developmental disabilities, emotional disorders and disruptive behaviour disorders are the leading mental health-related causes of the global burden of disease in children aged below 10 years. This article aims to address the treatment gap for child mental disorders through synthesising three bodies of evidence: the global evidence base on the treatment of these priority disorders; the barriers to implementation of this knowledge; and the innovative approaches taken to address these barriers and improve access to care. Our focus is on low-resource settings, which are mostly found in low- and middle-income countries (LMIC). Despite the evidence base on the burden of child mental disorders and their long-term consequences, and the recent mental health Gap Action Programme guidelines which testify to the effectiveness of a range of pharmacological and psychosocial interventions for these disorders, the vast majority of children in LMIC do not have access to these interventions. We identify three major barriers for the implementation of efficacious treatments: the lack of evidence on delivery of the treatments, the low levels of detection of child mental disorders and the shortage of skilled child mental health professionals. The evidence based on implementation, although weak, supports the use of screening measures for detection of probable disorders, coupled with a second-stage diagnostic assessment and the use of non-specialist workers in community and school settings for the delivery of psychosocial interventions. The most viable strategy to address the treatment gap is through the empowerment of existing human resources who are most intimately concerned with child care, including parents, through innovative technologies, such as mobile health, with the necessary skills for the detection and treatment of child mental disorders.

BACKGROUND: Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017. METHODS: Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning. RESULTS: Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes. CONCLUSIONS: There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries.

INTRODUCTION: Coronavirus disease (COVID-19), affects 213 countries or territories globally. We received a request from National Health Systems Resource Centre, a public agency in India, to conduct rapid evidence synthesis (RES) on community health workers (CHWs) for COVID-19 prevention and control in 3 days. METHODS: We searched PubMed, websites of ministries (n=3), public agencies (n=6), multilateral institutions (n=3), COVID-19 resource aggregators (n=5) and preprints (n=1) (without language restrictions) for articles on CHWs in pandemics. Two reviewers screened the records independently with a third reviewer resolving disagreements. One reviewer extracted data with another reviewer cross-checking it. A framework on CHW performance in primary healthcare not specific to pandemic was used to guide data extraction and narrative analysis. RESULTS: We retrieved 211 records and finally included 36 articles. Most of the evidence was from low-and middle-income countries with well-established CHW programmes. Evidence from CHW programmes initiated during pandemics and for CHW involvement in pandemic response in high-income countries was scant. CHW roles and tasks change substantially during pandemics. Clear guidance, training for changed roles and definition of what constitutes essential activities (ie, those that must to be sustained) is required. Most common additional activities during pandemics were community awareness, engagement and sensitisation (including for countering stigma) and contact tracing. CHWs were reported to be involved in all aspects of contact tracing - this was reported to affect routine service delivery. CHWs have often been stigmatised or been socially ostracised during pandemics. Providing PPE, housing allowance, equal training opportunities, transportation allowance, improving salaries (paid on time and for a broad range of services) and awards in high-profile public events contributed to better recruitment and retention. We also created inventories of resources with guiding notes on guidelines for health workers (n=24), self-isolation in the community (n=10) and information, education and counselling materials on COVID-19 (n=16). CONCLUSIONS: CHWs play a critical role in pandemics. It is important to ensure role clarity, training, supportive supervision, as well as their work satisfaction, health and well-being. More implementation research on CHWs in pandemics is required.