Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation

The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Efforts to quantify the global burden of enteric fever are valuable for understanding the health lost and the large-scale spatial distribution of the disease. We present the estimates of typhoid and paratyphoid fever burden from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, and the approach taken to produce them. METHODS: For this systematic analysis we broke down the relative contributions of typhoid and paratyphoid fevers by country, year, and age, and analysed trends in incidence and mortality. We modelled the combined incidence of typhoid and paratyphoid fevers and split these total cases proportionally between typhoid and paratyphoid fevers using aetiological proportion models. We estimated deaths using vital registration data for countries with sufficiently high data completeness and using a natural history approach for other locations. We also estimated disability-adjusted life-years (DALYs) for typhoid and paratyphoid fevers. FINDINGS: Globally, 14·3 million (95% uncertainty interval [UI] 12·5-16·3) cases of typhoid and paratyphoid fevers occurred in 2017, a 44·6% (42·2-47·0) decline from 25·9 million (22·0-29·9) in 1990. Age-standardised incidence rates declined by 54·9% (53·4-56·5), from 439·2 (376·7-507·7) per 100 000 person-years in 1990, to 197·8 (172·0-226·2) per 100 000 person-years in 2017. In 2017, Salmonella enterica serotype Typhi caused 76·3% (71·8-80·5) of cases of enteric fever. We estimated a global case fatality of 0·95% (0·54-1·53) in 2017, with higher case fatality estimates among children and older adults, and among those living in lower-income countries. We therefore estimated 135·9 thousand (76·9-218·9) deaths from typhoid and paratyphoid fever globally in 2017, a 41·0% (33·6-48·3) decline from 230·5 thousand (131·2-372·6) in 1990. Overall, typhoid and paratyphoid fevers were responsible for 9·8 million (5·6-15·8) DALYs in 2017, down 43·0% (35·5-50·6) from 17·2 million (9·9-27·8) DALYs in 1990. INTERPRETATION: Despite notable progress, typhoid and paratyphoid fevers remain major causes of disability and death, with billions of people likely to be exposed to the pathogens. Although improvements in water and sanitation remain essential, increased vaccine use (including with typhoid conjugate vaccines that are effective in infants and young children and protective for longer periods) and improved data and surveillance to inform vaccine rollout are likely to drive the greatest improvements in the global burden of the disease. FUNDING: Bill & Melinda Gates Foundation

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016

Summary Background Stroke is a leading cause of mortality and disability worldwide and the economic costs of treatment and post-stroke care are substantial. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic, comparable method of quantifying health loss by disease, age, sex, year, and location to provide information to health systems and policy makers on more than 300 causes of disease and injury, including stroke. The results presented here are the estimates of burden due to overall stroke and ischaemic and haemorrhagic stroke from GBD 2016. Methods We report estimates and corresponding uncertainty intervals (UIs), from 1990 to 2016, for incidence, prevalence, deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). DALYs were generated by summing YLLs and YLDs. Cause-specific mortality was estimated using an ensemble modelling process with vital registration and verbal autopsy data as inputs. Non-fatal estimates were generated using Bayesian meta-regression incorporating data from registries, scientific literature, administrative records, and surveys. The Socio-demographic Index (SDI), a summary indicator generated using educational attainment, lagged distributed income, and total fertility rate, was used to group countries into quintiles. Findings In 2016, there were 5·5 million (95% UI 5·3 to 5·7) deaths and 116·4 million (111·4 to 121·4) DALYs due to stroke. The global age-standardised mortality rate decreased by 36·2% (–39·3 to –33·6) from 1990 to 2016, with decreases in all SDI quintiles. Over the same period, the global age-standardised DALY rate declined by 34·2% (–37·2 to –31·5), also with decreases in all SDI quintiles. There were 13·7 million (12·7 to 14·7) new stroke cases in 2016. Global age-standardised incidence declined by 8·1% (–10·7 to –5·5) from 1990 to 2016 and decreased in all SDI quintiles except the middle SDI group. There were 80·1 million (74·1 to 86·3) prevalent cases of stroke globally in 2016; 41·1 million (38·0 to 44·3) in women and 39·0 million (36·1 to 42·1) in men. Interpretation Although age-standardised mortality rates have decreased sharply from 1990 to 2016, the decrease in age-standardised incidence has been less steep, indicating that the burden of stroke is likely to remain high. Planned updates to future GBD iterations include generating separate estimates for subarachnoid haemorrhage and intracerebral haemorrhage, generating estimates of transient ischaemic attack, and including atrial fibrillation as a risk factor

Association of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma

Purpose: Inflammatory genes and microRNAs have roles in colon carcinogenesis; therefore, they may provide useful biomarkers for colon cancer. This study examines the potential clinical utility of an inflammatory gene expression signature as a prognostic biomarker for colon cancer in addition to previously examined miR-21 expression. Experimental Design: Quantitative reverse transcriptase-PCR. was used to measure the expression of 23 inflammatory genes in colon adenocarcinomas and adjacent noncancerous tissues from 196 patients. These data were used to develop models for cancer-specific mortality on a training cohort (n = 57), and this model was tested in both a test (n = 56) and a validation (n = 83) cohort. Expression data for miR-21 were available for these patients and were compared and combined with inflammatory gene expression. Results: PRG1, IL-10, CD68, IL-23a, and IL-12a expression in noncancerous tissue, and PRG1, ANXA1, IL-23a, IL-17a, FOXP3, and HLA-DRA expression in tumor tissues were associated with poor prognosis based on Cox regression (|Z-score| >1.5) and were used to generate the inflammatory risk score (IRS). IRS was associated with cancer-specific mortality in the training, test (P = 0.01), and validation (P = 0.02) cohorts. This association was strong for stage II cases (P = 0.002). Expression of miR-21 was associated with IL-6, IL-8, IL-10, IL-12a, and NOS2a, providing evidence that the function of this micro-RNA and these inflammatory genes are linked. Both IRS and miR-21 expression were independently associated with cancer-specific mortality, including stage II patients alone. Conclusion: IRS and miR-21 expression are independent predictors of colon cancer prognosis and may provide a clinically useful tool to identify high-risk patients. © 2009 American Association for Cancer Research.link_to_OA_fulltex

Dengue in Adults Admitted to a Referral Hospital in Hanoi, Vietnam

Knowledge of adult dengue virus (DENV) infection from Hanoi, Vietnam, is limited. In 2008, we prospectively studied 143 (77 male) confirmed (nonstructural 1 antigen enzyme-linked immunosorbent assay [ELISA], DENV polymerase chain reaction, paired serology) adult dengue patients of median age 23.5 (range 16-72) years. They were admitted to the National Hospital for Tropical Diseases, Hanoi, on median illness day (D) 5 (range 1-8). By D8, 141 (98.6%) were afebrile. Platelet counts and hematocrit (median, interquartile range [IQR]) nadired and peaked on D5 and D4, respectively: 40,000/μL (10,000-109,000/μL), 43.4% (34.9-49.7%). Four (2.8%) patients had severe dengue: 1) D10 shock (N = 1) and 2) aspartate aminotransferase (AST) ≥ 1,000 IU/L (N = 3, D5 and D7). Of 143 patients, 118 (82.5%) had ≥ 1 warning sign (World Health Organization [WHO] 2009 criteria): mucosal bleeding 66/143 (46.1%), soft tissue edema 54/143 (37.7%), and ultrasound detected plasma leakage (pleural effusions/ascites) 30/129 (23.25%). 138 (96.5%) patients received intravenous (IV) fluids: 3 L (IQR: 0.5-8.5 L). Most patients had non-severe dengue with warning signs. High rates of edema and plasma leakage may be explained partly by liberal use of IV fluids. Studies are needed on optimizing fluid management in non-severe adult dengue