Global Burden of Disease Cancer Collaboration IMPORTANCE Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. OBJECTIVE To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. EVIDENCE REVIEW We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. FINDINGS In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs). CONCLUSIONS AND RELEVANCE The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equ...

Background Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019.Methods 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10-14 and 50-54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed agespecific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. FindingsThe global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66-2•79) in 2000 to 2•31 (2•17-2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5-137•8) in 2000 to a peak of 139•6 million (133•0-146•9) in 2016. Global livebirths then declined to 135•3 million (127•2-144•1) in 2019. Of the 204 countries and territories included in...

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.

Cerebral ischemia is caused by arterial occlusion due to a thrombus or an embolus. Such occlusion induces multiple and concomitant pathophysiological processes that involve bioenergetic failure, acidosis, loss of cell homeostasis, excitotoxicity, and disruption of the blood-brain barrier. All of these mechanisms contribute to neuronal death, mainly via apoptosis or necrosis. The immune system is involved in this process in the early phases after brain injury, which contributes to potential enlargement of the infarct size and involves the penumbra area. Whereas inflammation and the immune system both exert deleterious effects, they also contribute to brain protection by stimulating a preconditioning status and to the concomitant repair of the injured parenchyma. This review describes the main phases of the inflammatory process occurring after arterial cerebral occlusion, with an emphasis on the role of single mediators.

This meta-analysis suggests that some prehospital scoring systems including cortical signs showed better accuracy to predict stroke due to LVO. However, the assessment of these signs could be difficult to investigate by paramedics and personnel of Emergency Medical Services, and for this reason, further prospective evaluations are needed.

Background and Purpose Substantial uncertainty exists on the benefit of organizational paradigms in stroke networks. Here we systematically reviewed and meta-analyzed data from studies comparing functional outcome between the mothership (MS) and the drip and ship (DS) models.Methods The meta-analysis protocol was registered international prospective register of systematic reviews (PROSPERO) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, and Cochrane Central databases were searched for randomized-controlled clinical trials (RCTs), retrospective and prospective studies comparing MS versus DS. Primary endpoints were functional independence at 90 days (modified Rankin Scale <3) and successful recanalization (Thrombolysis in Cerebral Infarction Scale [TICI] >2a); secondary endpoints were 3-month mortality and symptomatic intracranial haemorrhage (sICH). Odds ratios for endpoints were pooled using the random effects model and were compared between the two organizational models.Results Overall, 18 studies (n=7,017) were included in quantitative synthesis. MS paradigm was superior to DS model for functional independence (odds ratio, 1.34; 95% confidence interval, 1.16 to 1.55; I2=30%). Meta-regression analysis revealed association between onset-to-needle time and good functional outcome, with longer onset-to-needle time being detrimental. Similar rates of recanalization, sICH and mortality at 90 days were documented between MS and DS.Conclusions Patients with acute ischemic stroke eligible for reperfusion strategies might benefit more from MS paradigm as compared to DS. RCTs are needed to further refine best management taking into account logistics, facilities and resources.

Objective To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy. Methods We retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg. Results Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19–55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1–10 days). No adverse events related to IVIg were observed. Conclusions Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.

To evaluate in the setting of a stroke unit ward the usefulness of a prolonged (>6 h) video-EEG recording (PVEEG) in identifying non-convulsive status epilepticus (NCSE) in patients with an acute ischemic stroke. Predictors of NCSE were also evaluated. Patients with an acute ischemic stroke, referred to our unit, were included in this prospective observational study. A PVEEG recording was implemented after stroke in all patients during the first week: (a) promptly in those exhibiting a clear or suspected epileptic manifestation; (b) at any time during the routine activity in the remaining patients. After the first week, a standard EEG/PVEEG recording was hooked up only in presence of an evident or suspected epileptic manifestation or as control of a previous epileptic episode. NCSE was identified in 32 of the 889 patients (3.6 %) included in the study. It occurred early (within the first week) in 20/32 (62.5 %) patients and late in the remaining 12. Diagnosis was made on the basis of a specific clinical suspect (n = 19, 59.4 %) or without any suspect (n = 13, 40.6 %). In a multivariate analysis, a significant association of NCSE was observed with NIHSS score, infarct size and large atherothrombotic etiology. NCSE is not a rare event after an acute ischemic stroke and a delayed diagnosis could worsen patient prognosis. Since NCSE can be difficult to be diagnosed only on clinical grounds, implementation of a prompt PVEEG should be kept available in a stroke unit whenever a patient develop signs, although subtle, consistent with NCSE.