The state of health in the European Union (EU-27) in 2019: a systematic analysis for the Global Burden of Disease study 2019.

BACKGROUND: The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010. METHODS: We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE). RESULTS: In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for "HIV/AIDS and sexually transmitted diseases" and "transport injuries" (each -19%). "Diabetes and kidney diseases" showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, "mental disorders" showed an increasing age-standardised YLL rate (14.5%). CONCLUSIONS: There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease.

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.

Albuminuria as a risk factor for mild cognitive impairment and dementia-what is the evidence?

Kidney dysfunction can profoundly influence many organ systems, and recent evidence suggests a potential role for increased albuminuria in the development of mild cognitive impairment (MCI) or dementia. Epidemiological studies conducted in different populations have demonstrated that the presence of increased albuminuria is associated with a higher relative risk of MCI or dementia both in cross-sectional analyses and in studies with long-term follow-up. The underlying pathophysiological mechanisms of albuminuria's effect are as yet insufficiently studied, with several important knowledge gaps still present in a complex relationship with other MCI and dementia risk factors. Both the kidney and the brain have microvascular similarities that make them sensitive to endothelial dysfunction involving different mechanisms, including oxidative stress and inflammation. The exact substrate of MCI and dementia is still under investigation, however available experimental data indicate that elevated albuminuria and low glomerular filtration rate are associated with significant neuroanatomical declines in hippocampal function and grey matter volume. Thus, albuminuria may be critical in the development of cognitive impairment and its progression to dementia. In this review, we summarize the available evidence on albuminuria's link to MCI and dementia, point to existing gaps in our knowledge and suggest actions to overcome them. The major question of whether interventions that target increased albuminuria could prevent cognitive decline remains unanswered. Our recommendations for future research are aimed at helping to plan clinical trials and to solve the complex conundrum outlined in this review, with the ultimate goal of improving the lives of patients with chronic kidney disease.

A comparison of metrics and performance characteristics of different search strategies for article retrieval for a systematic review of the global epidemiology of kidney and urinary diseases.

BACKGROUND: Conducting a systematic review requires a comprehensive bibliographic search. Comparing different search strategies is essential for choosing those that cover all useful data sources. Our aim was to develop search strategies for article retrieval for a systematic review of the global epidemiology of kidney and urinary diseases, and evaluate their metrics and performance characteristics that could be useful for other systematic epidemiologic reviews. METHODS: We described the methodological framework and analysed approaches applied in the previously conducted systematic review intended to obtain published data for global estimates of the kidney and urinary disease burden. We used several search strategies in PubMed and EMBASE, and compared several metrics: number needed to retrieve (NNR), number of extracted data rows, number of covered countries, and when appropriate, sensitivity, specificity, precision, and accuracy. RESULTS: The initial search obtained 29,460 records from PubMed, and 4247 from EMBASE. After the revision, the full text of 381 and 14 articles respectively was obtained for data extraction (the percentage of useful records is 1.3% for PubMed, 0.3% for EMBASE). For PubMed we developed two search strategies and compared them with a 'gold standard' formed by merging their results: free word search strategy (FreeWoSS) was based on the search for keywords in all fields, and subject headings based search strategy (SuHeSS) used only MeSH-mapped conditions and countries names. SuHeSS excluded almost 15% of useful articles and data rows extracted from them, but had a lower NNR of 40 and higher specificity. FreeWoSS had better sensitivity and was able to cover the vast majority of articles and extracted data rows, but had a higher NNR of 65. CONCLUSIONS: The sensitive FreeWoSS strategy provides more data for modelling, while the more specific SuHeSS strategy could be used when resources are limited. EMBASE has limited value for our systematic review.

Global Cardiovascular and Renal Outcomes of Reduced GFR.

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.

Maintenance Dialysis throughout the World in Years 1990 and 2010.

Rapidly rising global rates of chronic diseases portend a consequent rise in ESRD. Despite this, kidney disease is not included in the list of noncommunicable diseases (NCDs) targeted by the United Nations for 25% reduction by year 2025. In an effort to accurately report the trajectory and pattern of global growth of maintenance dialysis, we present the change in prevalence and incidence from 1990 to 2010. Data were extracted from the Global Burden of Disease 2010 epidemiologic database. The results are on the basis of an analysis of data from worldwide national and regional renal disease registries and detailed systematic literature review for years 1980-2010. Incidence and prevalence estimates of provision of maintenance dialysis from this database were updated using a negative binomial Bayesian meta-regression tool for 187 countries. Results indicate substantial growth in utilization of maintenance dialysis in almost all world regions. Changes in population structure, changes in aging, and the worldwide increase in diabetes mellitus and hypertension explain a significant portion, but not all, of the increase because increased dialysis provision also accounts for a portion of the rise. These findings argue for the importance of inclusion of kidney disease among NCD targets for reducing premature death throughout the world.

Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.

BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.

BACKGROUND: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). METHODS: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. FINDINGS: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350,000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. INTERPRETATION: Rates of YLDs per 100,000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. FUNDING: Bill & Melinda Gates Foundation.

Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.

BACKGROUND: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS: Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results. FUNDING: Bill & Melinda Gates Foundation.

Burden of Acute Kidney Injury among Adult Hospital Patients in the Italian Lombardy Region: A 20-Year Real-World Data Analysis.

BACKGROUND: Acute kidney injury (AKI) is a frequent condition, with persistent shortage of large-scale epidemiological studies. We analyzed the population-wide healthcare system of the Italian Lombardy region over the 2000-2019 period, and evaluated AKI incidence, mortality, and related healthcare resource utilization and cost in all citizens 40 years and older. METHODS: The retrospective cohort analysis of an administrative claims database that routinely collects information about healthcare provision in a high-income region with 10 million citizens. Over 20 years, AKI was identified in 84,384 hospital discharge records by the International Classification of Diseases 9th Revision codes (mean age 77.4 ± 11.6 years, 52.5% were males). RESULTS: From 2000 to 2019, the AKI rates per 100,000 population changed from 32.9 to 90.5 for incidence, from 4.7 to 11.9 for mortality, and from 32.3 to 44.1 for years of life lost (YLLs), respectively. In-hospital mortality changed slightly (14.2% and 13.2%, respectively), while 30-day mortality decreased from 21.5% to 17.4%, respectively. Incidence rates increased with age and were higher in males, and varied almost four-fold between provinces. The median hospitalization cost was €4,014 (IQR: 3,652; 4,134), and the annual cost of treatment risen from €5.2 million in 2000 to €22.9 million in 2019. Hemodialysis was administered in 7.4% of hospitalizations. Over the total study period the cumulative AKI burden accounted for 11,420 in-hospital deaths, 63,370.8 YLLs, and €329 million of direct cost. CONCLUSIONS: This real-world analysis demonstrates the high burden of AKI with prominent geographical differences that require further implementation of preventive and diagnostic actions.

Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study.

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients. DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials). PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021. MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys. TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.

Willingness to share contacts in case of COVID-19 positivity-predictors of collaboration resistance in a nation-wide Italian survey.

BACKGROUND: The unwillingness to share contacts is one of the least explored aspects of the COVID-19 pandemic. Here we report the factors associated with resistance to collaborate on contact tracing, based on the results of a nation-wide survey conducted in Italy in January-March 2021. METHODS AND FINDINGS: The repeated cross-sectional on-line survey was conducted among 7,513 respondents (mean age 45.7, 50.4% women) selected to represent the Italian adult population 18-70 years old. Two groups were defined based on the direct question response expressing (1) unwillingness or (2) willingness to share the names of individuals with whom respondents had contact. We selected 70% of participants (training data set) to produce several multivariable binomial generalized linear models and estimated the proportion of variation explained by the model by McFadden R2, and the model's discriminatory ability by the index of concordance. Then, we have validated the regression models using the remaining 30% of respondents (testing data set), and identified the best performing model by removing the variables based on their impact on the Akaike information criterion and then evaluating the model predictive accuracy. We also performed a sensitivity analysis using principal component analysis. Overall, 5.5% of the respondents indicated that in case of positive SARS-CoV-2 test they would not share contacts. Of note, this percentage varied from 0.8% to 46.5% depending on the answers to other survey questions. From the 139 questions included in the multivariable analysis, the initial model proposed 20 independent factors that were reduced to the 6 factors with only modest changes in the model performance. The 6-variables model demonstrated good performance in the training (c-index 0.85 and McFadden R2 criteria 0.25) and in the testing data set (93.3% accuracy, AUC 0.78, sensitivity 30.4% and specificity 97.4%). The most influential factors related to unwillingness to share contacts were the lack of intention to perform the test in case of contact with a COVID-19 positive individual (OR 5.60, 95% CI 4.14 to 7.58, in a fully adjusted multivariable analysis), disagreement that the government should be allowed to force people into self-isolation (OR 1.79, 95% CI 1.12 to 2.84), disagreement with the national vaccination schedule (OR 2.63, 95% CI 1.86 to 3.69), not following to the preventive anti-COVID measures (OR 3.23, 95% CI 1.85 to 5.59), the absence of people in the immediate social environment who have been infected with COVID-19 (1.66, 95% CI 1.24 to 2.21), as well as difficulties in finding or understanding the information about the infection or related recommendations. A limitation of this study is the under-representation of persons not participating in internet-based surveys and some vulnerable groups like homeless people, persons with disabilities or migrants. CONCLUSIONS: Our analysis revealed several groups that expressed unwillingness to collaborate on contact tracing. The identified patterns may play a principal role not only in the COVID-19 epidemic but also be important for possible future public health threats, and appropriate interventions for their correction should be developed and ready for the implementation.

Fighting the unbearable lightness of neglecting kidney health: the decade of the kidney.

A brief comprehensive overview is provided of the elements constituting the burden of kidney disease [chronic kidney disease (CKD) and acute kidney injury]. This publication can be used for advocacy, emphasizing the importance and urgency of reducing this heavy and rapidly growing burden. Kidney diseases contribute to significant physical limitations, loss of quality of life, emotional and cognitive disorders, social isolation and premature death. CKD affects close to 100 million Europeans, with 300 million being at risk, and is projected to become the fifth cause of worldwide death by 2040. Kidney disease also imposes financial burdens, given the costs of accessing healthcare and inability to work. The extrapolated annual cost of all CKD is at least as high as that for cancer or diabetes. In addition, dialysis treatment of kidney diseases imposes environmental burdens by necessitating high energy and water consumption and producing plastic waste. Acute kidney injury is associated with further increases in global morbidity, mortality and economic burden. Yet investment in research for treatment of kidney disease lags behind that of other diseases. This publication is a call for European investment in research for kidney health. The innovations generated should mirror the successful European Union actions against cancer over the last 30 years. It is also a plea to nephrology professionals, patients and their families, caregivers and kidney health advocacy organizations to draw, during the Decade of the Kidney (2020-30), the attention of authorities to realize changes in understanding, research and treatment of kidney disease.

Long-Term Outcomes of Kidney Transplants from Older/Marginal Donors: A Cohort Study.

INTRODUCTION: To safely expand the donor pool, we introduced a strategy of biopsy-guided selection and allocation to single or dual transplantation of kidneys from donors >60 years old or with hypertension, diabetes, and/or proteinuria (older/marginal donors). Here, we evaluated the long-term performance of this approach in everyday clinical practice. METHODS: In this single-center cohort study, we compared outcomes of 98 patients who received one or two biopsy-evaluated grafts from older/marginal donors ("recipients") and 198 patients who received nonhistologically assessed single graft from ideal donors ("reference-recipients") from October 2004 to December 2015 at the Bergamo Transplant Center (Italy). RESULTS: Older/marginal donors and their recipients were 27.9 and 19.3 years older than ideal donors and their reference-recipients, respectively. KDPI/KDRI and donor serum creatinine were higher and cold ischemia time longer in the recipient group. During a median follow-up of 51.9 (interquartile range 23.1-88.6) months, 11.2% of recipients died, 7.1% lost their graft, and 16.3% had biopsy-proven acute rejection (BPAR) versus 3.5, 7.6, and 17.7%, respectively, of reference-recipients. Overall death-censored graft failure (rate ratio 0.78 [95% CI 0.33-2.08]), 5-year death-censored graft survival (94.3% [87.8-100.0] vs. 94.2% [90.5-98.0]), BPAR incidence (rate ratio 0.87 [0.49-1.62]), and yearly measured glomerular filtration rate decline (1.18 ± 3.27 vs. 0.68 ± 2.42 mL/min/1.73 m2, p = 0.37) were similar between recipients and reference-recipients, respectively. CONCLUSIONS: Biopsy-guided selection and allocation of kidneys from older/marginal donors can safely increase transplant activity in clinical practice without affecting long-term outcomes. This may help manage the growing gap between organ demand and supply without affecting long-term recipient and graft outcomes.

Trends in cardiovascular diseases burden and vascular risk factors in Italy: The Global Burden of Disease study 1990-2017.

AIMS: An exhaustive and updated estimation of cardiovascular disease burden and vascular risk factors is still lacking in European countries. This study aims to fill this gap assessing the global Italian cardiovascular disease burden and its changes from 1990 to 2017 and comparing the Italian situation with European countries. METHODS: All accessible data sources from the 2017 Global Burden of Disease study were used to estimate the cardiovascular disease prevalence, mortality and disability-adjusted life years and cardiovascular disease attributable risk factors burden in Italy from 1990 to 2017. Furthermore, we compared the cardiovascular disease burden within the 28 European Union countries. RESULTS: Since 1990, we observed a significant decrease of cardiovascular disease burden, particularly in the age-standardised prevalence (-12.7%), mortality rate (-53.8%), and disability-adjusted life years rate (-55.5%). Similar improvements were observed in the majority of European countries. However, we found an increase in all-ages prevalence of cardiovascular diseases from 5.75 m to 7.49 m Italian residents. Cardiovascular diseases still remain the first cause of death (34.8% of total mortality). More than 80% of the cardiovascular disease burden could be attributed to known modifiable risk factors such as high systolic blood pressure, dietary risks, high low density lipoprotein cholesterol, and impaired kidney function. CONCLUSIONS: Our study shows a decline in cardiovascular mortality and disability-adjusted life years, which reflects the success in reducing disability, premature death and early incidence of cardiovascular diseases. However, the burden of cardiovascular diseases is still high. An approach that includes the cooperation and coordination of all stakeholders of the Italian National Health System is required to further reduce this burden.

R Open Source Programming Code for Calculation of the Kidney Donor Profile Index and Kidney Donor Risk Index.

BACKGROUND: The Kidney Donor Profile Index (KDPI) and Kidney Donor Risk Index (KDRI) were developed by the United States Organ Procurement and Transplantation Network (OPTN). They may influence the clinical decision whether to accept or discard a donor kidney, but still there are debates about KDPI/KDRI applicability and its consequences. To further evaluate these indexes in different populations, more data should be analyzed, and a universally applicable program code would facilitate it. Currently, KDPI/KDRI calculation could be readily done only on the OPTN website that is convenient for a single donor, but not suitable for processing data sets with many records. SUMMARY: A universally applicable program algorithm in widely used R language for calculating KDPI and KDRI was developed according to donor factors and coefficients described in the OPTN guide. KEY MESSAGES: The open R code permits to calculate KDPI/KDRI either for a single donor or for an unlimited number of records in large data sets. The presented software code would save substantial time to research groups all over the world and help to clarify the KDPI/KDRI role in global settings.

Disparities in Chronic Kidney Disease Prevalence among Males and Females in 195 Countries: Analysis of the Global Burden of Disease 2016 Study.

BACKGROUND: Chronic kidney disease (CKD) imposes a substantial burden on health care systems. There are some especially vulnerable groups with a high CKD burden, one of which is women. We performed an analysis of gender disparities in the prevalence of all CKD stages and renal replacement therapy (defined as impaired kidney function [IKF]) in 195 countries. METHODS: We used estimates produced by the Global Burden of Disease (GBD) Study 2016 revision using a Bayesian-regression analytic tool, DisMoD-MR 2.1. Data on gross domestic product based on purchasing power parity per capita (GDP PPP) was obtained via the World Bank International Comparison Program database. To estimate gender disparities, we calculated the male:female all-age prevalence rate ratio for each IKF condition. RESULTS: In 2016, the global number of individuals with IKF reached 752.7 million, including 417.0 million females and 335.7 million males. The most prevalent form of IKF in both groups was albuminuria with preserved glomerular filtration rate. Geospatial analysis shows a very heterogeneous distribution of the male:female ratio for all IKF conditions, with the most prominent contrast found in kidney transplant patients. The median male:female ratio varies substantially according to GDP PPP quintiles; however, countries with different economic states could have similar male:female ratios. A strong correlation of GDP PPP with dialysis-to-transplant ratio was found. CONCLUSIONS: The GBD study highlights the prominent gender disparities in CKD prevalence among 195 countries. The nature of these disparities, however, is complex and must be interpreted cautiously taking into account all possible circumstances.

Hemodialysis practice patterns in the Russia Dialysis Outcomes and Practice Patterns Study (DOPPS), with international comparisons.

INTRODUCTION: There is little comparable information about hemodialysis (HD) practices in low- and middle income countries, including Russia. Evaluation of HD in Russia and its international comparisons could highlight factors providing opportunities for improvement. METHODS: We examined treatment patterns for 481 prevalent HD patients in 20 Russian facilities, and compared them to contemporary data for 8512 patients from 311 facilities in seven European countries, Japan, and North America. Data were collected according to the uniform methodology of the Dialysis Outcomes and Practice Patterns Study, phase 5. FINDINGS: Compared to other regions, Russian patients were younger (mean age 53.4 years), had a lower percent of males (52.5%), higher arteriovenous fistula use (89.7%), and longer treatment time (mean: 252 minutes, SD: 37 minutes). Mean single pool Kt/V was 1.49 (SD 0.58). Prescription of dialysate calcium 3.5 mEq/L and aluminum-based phosphate binders were high (15.2% and 17.6% of patients, respectively), while intravenous vitamin D and cinacalcet were low (3.3% and 2.2%, respectively). The percents with parathyroid hormone >600 pg/mL (30.9%) and serum phosphate >1.78 mmol/L (37.7%) were high. Use of erythropoetin stimulating agents (78%) was lower, but hemoglobin, ferritin, and transferrin saturation were generally comparable to North America and Europe. DISCUSSION: These detailed data for hemodialysis in Russia demonstrate that many practice patterns contrasted sharply to those in Europe, Japan, and North America, while other features were similar. Our analysis revealed several positive and some less favorable treatment patterns in Russia that represent opportunities for improving patient care and outcomes.