Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015:a systematic analysis for the Global Burden of Disease Study 2015

Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores.Findings We generated 9.3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17.2 billion, 95% uncertainty interval [UI] 15.4-19.2 billion) and diarrhoeal diseases (2.39 billion, 2.30-2.50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2.36 billion (2.35-2.37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20-30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo.Interpretation Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available. Copyright (C) The Author(s). Published by Elsevier Ltd.</p

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

2013 WSES guidelines for management of intra-abdominal infections

Peer reviewe

Donor-specific cell-free DNA as a biomarker in solid organ transplantation: A systematic review

Background There is increasing interest in the use of noninvasive biomarkers to reduce the risks posed by invasive biopsy for monitoring of solid organ transplants (SOTs). One such promising marker is the presence of donor-derived cell-free DNA (dd-cfDNA) in the urine or blood of transplant recipients. Methods We systematically reviewed the published literature investigating the use of cfDNA in monitoring of graft health after SOT. Electronic databases were searched for studies relating cfDNA fraction or levels to clinical outcomes, and data including measures of diagnostic test accuracy were extracted. Narrative analysis was performed. Results Ninety-five articles from 47 studies met the inclusion criteria (18 kidneys, 7 livers, 11 hearts, 1 kidney-pancreas, 5 lungs, and 5 multiorgans). The majority were retrospective and prospective cohort studies, with 19 reporting diagnostic test accuracy data. Multiple techniques for measuring dd-cfDNA were reported, including many not requiring a donor sample. dd-cfDNA falls rapidly within 2 weeks, with baseline levels varying by organ type. Levels are elevated in the presence of allograft injury, including acute rejection and infection, and return to baseline after successful treatment. Elevation of cfDNA levels is seen in advance of clinically apparent organ injury. Discriminatory power was greatest for higher grades of T cell–mediated and antibody-mediated acute rejection, with high negative predictive values. Conclusions Cell-free DNA is a promising biomarker for monitoring the health of SOTs. Future studies will need to define how it can be used in routine clinical practice and determine clinical benefit with routine prospective monitoring.</p

Donor-specific cell-free DNA as a biomarker in solid organ transplantation: A systematic review

Background There is increasing interest in the use of noninvasive biomarkers to reduce the risks posed by invasive biopsy for monitoring of solid organ transplants (SOTs). One such promising marker is the presence of donor-derived cell-free DNA (dd-cfDNA) in the urine or blood of transplant recipients. Methods We systematically reviewed the published literature investigating the use of cfDNA in monitoring of graft health after SOT. Electronic databases were searched for studies relating cfDNA fraction or levels to clinical outcomes, and data including measures of diagnostic test accuracy were extracted. Narrative analysis was performed. Results Ninety-five articles from 47 studies met the inclusion criteria (18 kidneys, 7 livers, 11 hearts, 1 kidney-pancreas, 5 lungs, and 5 multiorgans). The majority were retrospective and prospective cohort studies, with 19 reporting diagnostic test accuracy data. Multiple techniques for measuring dd-cfDNA were reported, including many not requiring a donor sample. dd-cfDNA falls rapidly within 2 weeks, with baseline levels varying by organ type. Levels are elevated in the presence of allograft injury, including acute rejection and infection, and return to baseline after successful treatment. Elevation of cfDNA levels is seen in advance of clinically apparent organ injury. Discriminatory power was greatest for higher grades of T cell–mediated and antibody-mediated acute rejection, with high negative predictive values. Conclusions Cell-free DNA is a promising biomarker for monitoring the health of SOTs. Future studies will need to define how it can be used in routine clinical practice and determine clinical benefit with routine prospective monitoring.</p

Reactive Oxygen Species

Reactive oxygen species (ROS) is a collective term given to a group of oxygen-containing intermediates, many of which react with biomolecules such as DNA, lipids, or proteins. ROS include (but are not limited to) hydrogen peroxide (H2O2), the superoxide radical anion (O2˙−), the hydroxyl radical (˙OH), and singlet oxygen (1O2). ROS sometimes have one or more unpaired electrons – as denoted by a superscript dot “˙”

Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis – a proteomics study

We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and urine replacement (UR). Proteins were extracted from 16 kidney biopsies with URC (n=8 donors after brain death (DBD), n=8 donors after circulatory death (DCD)) and three with UR (n=2 DBD, n=1 DCD), followed by quantitative analysis by mass spectrometry. Damage‐associated molecular patterns (DAMPs) were decreased in kidney tissue after six hours NMP with URC, suggesting reduced inflammation. Vasoconstriction was also attenuated in kidneys with URC as angiotensinogen levels were reduced. Strikingly, kidneys became metabolically active during NMP, which could be enhanced and prolonged by URC. For instance, mitochondrial succinate dehydrogenase enzyme levels as well as carbonic anhydrase were enhanced with URC, contributing to pH stabilisation. Levels of cytosolic and the mitochondrial phosphoenolpyruvate carboxykinase were elevated after 24 hours of NMP, more prevalent in DCD than DBD tissue. Key enzymes involved in glucose metabolism were also increased after twelve and 24 hours of NMP with URC, including mitochondrial malate dehydrogenase and glutamic‐oxaloacetic transaminase, predominantly in DCD tissue. We conclude that NMP with URC permits prolonged preservation and revitalises metabolism to possibly better cope with ischemia reperfusion injury in discarded kidneys

Measurement and meaning of markers of reactive species of oxygen, nitrogen and sulfur in healthy human subjects and patients with inflammatory joint disease.

Reactive species of oxygen, nitrogen and sulfur play cell signalling roles in human health, e.g. recent studies have shown that increased dietary nitrate, which is a source of RNS (reactive nitrogen species), lowers resting blood pressure and the oxygen cost of exercise. In such studies, plasma nitrite and nitrate are readily determined by chemiluminescence. At sites of inflammation, such as the joints of RA (rheumatoid arthritis) patients, the generation of ROS (reactive oxygen species) and RNS overwhelms antioxidant defences and one consequence is oxidative/nitrative damage to proteins. For example, in the inflamed joint, increased RNS-mediated protein damage has been detected in the form of a biomarker, 3-nitrotyrosine, by immunohistochemistry, Western blotting, ELISAs and MS. In addition to NO•, another cell-signalling gas produced in the inflamed joint is H2S (hydrogen sulfide), an RSS (reactive sulfur species). This gas is generated by inflammatory induction of H2S-synthesizing enzymes. Using zinc-trap spectrophotometry, we detected high (micromolar) concentrations of H2S in RA synovial fluid and levels correlated with clinical scores of inflammation and disease activity. What might be the consequences of the inflammatory generation of reactive species? Effects on inflammatory cell-signalling pathways certainly appear to be crucial, but in the current review we highlight the concept that ROS/RNS-mediated protein damage creates neoepitopes, resulting in autoantibody formation against proteins, e.g. type-II collagen and the complement component, C1q. These autoantibodies have been detected in inflammatory autoimmune diseases

Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion

Ischaemia and reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI), which contributes to high morbidity and mortality rates in a wide range of injuries as well as the development of chronic kidney disease. The cellular and molecular responses of the kidney to IRI are complex and not fully understood. Here, we used an integrated proteomic and metabolomic approach to investigate the effects of IRI on protein abundance and metabolite levels. Rat kidneys were subjected to 45 min of warm ischaemia followed by 4 h and 24 h reperfusion, with contralateral and separate healthy kidneys serving as controls. Kidney tissue proteomics after IRI revealed elevated proteins belonging to the acute phase response, coagulation and complement pathways, and fatty acid (FA) signalling. Metabolic changes were already evident after 4 h reperfusion and showed increased level of glycolysis, lipids and FAs, whilst mitochondrial function and ATP production was impaired after 24 h. This deficit was partially compensated for by the contralateral kidney. Such a metabolic balance counteracts for the developing energy deficit due to reduced mitochondrial function in the injured kidney