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1. Spectrum of cerebral arteriopathies in children with arterial ischemic stroke.

Author

Rafay, Mubeen F, Shapiro, Kevin A, Surmava, Ann-Marie, deVeber, Gabrielle A, Kirton, Adam, Fullerton, Heather J, Amlie-Lefond, Catherine, Weschke, Bernhard, Dlamini, Nomazulu, Carpenter, Jessica L, Mackay, Mark T, Rivkin, Michael, Linds, Alexandra, and Bernard, Timothy J

Subjects
Neurosciences, Stroke, Clinical Research, Brain Disorders, Pediatric, Adolescent, Age of Onset, Aneurysm, Dissecting, Anticoagulants, Brain Ischemia, Cerebral Arterial Diseases, Cerebral Infarction, Child, Child, Preschool, Female, Fibrinolytic Agents, Global Health, Headache, Humans, Infant, Infant, Newborn, Intracranial Aneurysm, Male, Prospective Studies, Recurrence, Registries, Risk Factors, Treatment Outcome, Vasculitis, Central Nervous System, International Pediatric Stroke Study (IPSS) Group, Aortic Dissection, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features.MethodsWe report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min-p adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes.ResultsOf 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy-inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, p = 0.029) with headache (OR 1.55, p = 0.023), multiple infarctions (OR 2.05, p < 0.001), sickle cell anemia (OR 2.9, p = 0.007), and head/neck trauma (OR 1.93, p = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions.ConclusionSpecific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials.

Published
2020

2. Seizures and Outcome One Year After Neonatal and Childhood Cerebral Sinovenous Thrombosis

Author

Mineyko, Aleksandra, Kirton, Adam, Billinghurst, Lori, Tatishvili, Nana Nino, Wintermark, Max, deVeber, Gabrielle, Fox, Christine, Investigators, SIPS, Abdalla, Abdalla, Zafeiriou, Dimitrios, Friedman, Neil, Aprasidze, Tatia, Kolk, Anneli, Armstrong, Jennifer, Ichord, Rebecca, Amlie-Lefond, Kovacevic, Gordana, Chavez, Marta Hernandez, Mackay, Mark, Titomanlio, Luigi, Guilliams, Kristin, Elbers, Jorina, Fullerton, Heather, Benedict, Susan, Dowling, Michael, Jordan, Lori, and Pergami, Paola

Subjects
Paediatrics, Biomedical and Clinical Sciences, Neurosciences, Minority Health, Neurodegenerative, Brain Disorders, Cerebrovascular, Pediatric, Clinical Research, Stroke, Epilepsy, Prevention, Perinatal Period - Conditions Originating in Perinatal Period, Childhood Injury, Hematology, 2.1 Biological and endogenous factors, 4.2 Evaluation of markers and technologies, Neurological, Adolescent, Anticonvulsants, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Ischemic Stroke, Male, Outcome Assessment, Health Care, Seizures, Sinus Thrombosis, Intracranial, Pediatric stroke, Cerebral sinovenous thrombosis, Outcomes, SIPS Investigators, Paediatrics and Reproductive Medicine, Neurology & Neurosurgery
Abstract

BackgroundPediatric cerebral sinovenous thrombosis is a treatable cause of brain injury, acute symptomatic seizures, and remote epilepsy. Our objective was to prospectively study epilepsy and outcomes in neonates and children one year after cerebral sinovenous thrombosis diagnosis.MethodsPatients with cerebral sinovenous thrombosis were enrolled prospectively from 21 international sites through the Seizures in Pediatric Stroke Study. Clinical data, including acute symptomatic seizures and cerebral sinovenous thrombosis risk factors, were collected at diagnosis. A neuroradiologist who was unaware of the diagnosis reviewed acute imaging. At one year, outcomes including seizure recurrence, epilepsy diagnosis, antiepileptic drug use, and modified Engel score were collected. Outcomes were assessed using the modified Rankin score and the King's Outcome Scale for Childhood Head Injury.ResultsTwenty-four participants with cerebral sinovenous thrombosis were enrolled (67% male, 21% neonates). Headache was the most common presenting symptom in non-neonates (47%, nine of 19). Nine (37.5%) presented with acute symptomatic seizures. Six (25%; 95% confidence interval, 10% to 47%) developed epilepsy by one-year follow-up. No clinical predictors associated with epilepsy were identified. King's Outcome Scale for Childhood Head Injury and modified Rankin scores at one year were favorable in 71%. Half of the patients who developed epilepsy (three of six) did not have infarcts, hemorrhage, or seizures identified during the acute hospitalization.ConclusionOur study provides a prospective estimate that epilepsy occurs in approximately one-quarter of patients by one year after diagnosis of cerebral sinovenous thrombosis. Later epilepsy can develop in the absence of acute seizures or parenchymal injury associated with the acute presentation.

Published
2020

3. Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016

Author

Feigin, Valery L, Nguyen, Grant, Cercy, Kelly, Johnson, Catherine O, Alam, Tahiya, Parmar, Priyakumari G, Abajobir, Amanuel A, Abate, Kalkidan H, Abd-Allah, Foad, Abejie, Ayenew N, Abyu, Gebre Y, Ademi, Zanfina, Agarwal, Gina, Ahmed, Muktar B, Akinyemi, Rufus O, Al-Raddadi, Rajaa, Aminde, Leopold N, Amlie-Lefond, Catherine, Ansari, Hossein, Asayesh, Hamid, Asgedom, Solomon W, Atey, Tesfay M, Ayele, Henok T, Banach, Maciej, Banerjee, Amitava, Barac, Aleksandra, Barker-Collo, Suzanne L, Bärnighausen, Till, Barregard, Lars, Basu, Sanjay, Bedi, Neeraj, Behzadifar, Masoud, Béjot, Yannick, Bennett, Derrick A, Bensenor, Isabela M, Berhe, Derbew F, Boneya, Dube J, Brainin, Michael, Campos-Nonato, Ismael R, Caso, Valeria, Castañeda-Orjuela, Carlos A, Rivas, Jacquelin C, Catalá-López, Ferrán, Christensen, Hanne, Criqui, Michael H, Damasceno, Albertino, Dandona, Lalit, Dandona, Rakhi, Davletov, Kairat, de Courten, Barbora, deVeber, Gabrielle, Dokova, Klara, Edessa, Dumessa, Endres, Matthias, Faraon, Emerito JA, Farvid, Maryam S, Fischer, Florian, Foreman, Kyle, Forouzanfar, Mohammad H, Gall, Seana L, Gebrehiwot, Tsegaye T, Geleijnse, Johanna M, Gillum, Richard F, Giroud, Maurice, Goulart, Alessandra C, Gupta, Rahul, Gupta, Rajeev, Hachinski, Vladimir, Hamadeh, Randah R, Hankey, Graeme J, Hareri, Habtamu A, Havmoeller, Rasmus, Hay, Simon I, Hegazy, Mohamed I, Hibstu, Desalegn T, James, Spencer L, Jeemon, Panniyammakal, John, Denny, Jonas, Jost B, Jóźwiak, Jacek, Kalani, Rizwan, Kandel, Amit, Kasaeian, Amir, Kengne, Andre P, Khader, Yousef S, Khan, Abdur R, Khang, Young-Ho, Khubchandani, Jagdish, Kim, Daniel, Kim, Yun J, Kivimaki, Mika, Kokubo, Yoshihiro, Kolte, Dhaval, Kopec, Jacek A, Kosen, Soewarta, Kravchenko, Michael, Krishnamurthi, Rita, Kumar, G Anil, Lafranconi, Alessandra, and Lavados, Pablo M

Subjects
Aging, Brain Disorders, Stroke, Prevention, Aetiology, 2.4 Surveillance and distribution, Good Health and Well Being, Adult, Age Distribution, Aged, Aged, 80 and over, Cause of Death, Female, Global Burden of Disease, Global Health, Humans, Incidence, Male, Middle Aged, Risk, Sex Distribution, Socioeconomic Factors, GBD 2016 Lifetime Risk of Stroke Collaborators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThe lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases.MethodsWe used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate.ResultsThe estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation.ConclusionsIn 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).

Published
2018

4. Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016.

Author

GBD 2016 Lifetime Risk of Stroke Collaborators, Feigin, Valery L, Nguyen, Grant, Cercy, Kelly, Johnson, Catherine O, Alam, Tahiya, Parmar, Priyakumari G, Abajobir, Amanuel A, Abate, Kalkidan H, Abd-Allah, Foad, Abejie, Ayenew N, Abyu, Gebre Y, Ademi, Zanfina, Agarwal, Gina, Ahmed, Muktar B, Akinyemi, Rufus O, Al-Raddadi, Rajaa, Aminde, Leopold N, Amlie-Lefond, Catherine, Ansari, Hossein, Asayesh, Hamid, Asgedom, Solomon W, Atey, Tesfay M, Ayele, Henok T, Banach, Maciej, Banerjee, Amitava, Barac, Aleksandra, Barker-Collo, Suzanne L, Bärnighausen, Till, Barregard, Lars, Basu, Sanjay, Bedi, Neeraj, Behzadifar, Masoud, Béjot, Yannick, Bennett, Derrick A, Bensenor, Isabela M, Berhe, Derbew F, Boneya, Dube J, Brainin, Michael, Campos-Nonato, Ismael R, Caso, Valeria, Castañeda-Orjuela, Carlos A, Rivas, Jacquelin C, Catalá-López, Ferrán, Christensen, Hanne, Criqui, Michael H, Damasceno, Albertino, Dandona, Lalit, Dandona, Rakhi, Davletov, Kairat, de Courten, Barbora, deVeber, Gabrielle, Dokova, Klara, Edessa, Dumessa, Endres, Matthias, Faraon, Emerito JA, Farvid, Maryam S, Fischer, Florian, Foreman, Kyle, Forouzanfar, Mohammad H, Gall, Seana L, Gebrehiwot, Tsegaye T, Geleijnse, Johanna M, Gillum, Richard F, Giroud, Maurice, Goulart, Alessandra C, Gupta, Rahul, Gupta, Rajeev, Hachinski, Vladimir, Hamadeh, Randah R, Hankey, Graeme J, Hareri, Habtamu A, Havmoeller, Rasmus, Hay, Simon I, Hegazy, Mohamed I, Hibstu, Desalegn T, James, Spencer L, Jeemon, Panniyammakal, John, Denny, Jonas, Jost B, Jóźwiak, Jacek, Kalani, Rizwan, Kandel, Amit, Kasaeian, Amir, Kengne, Andre P, Khader, Yousef S, Khan, Abdur R, Khang, Young-Ho, Khubchandani, Jagdish, Kim, Daniel, Kim, Yun J, Kivimaki, Mika, Kokubo, Yoshihiro, Kolte, Dhaval, Kopec, Jacek A, Kosen, Soewarta, Kravchenko, Michael, Krishnamurthi, Rita, Kumar, G Anil, and Lafranconi, Alessandra

Subjects
GBD 2016 Lifetime Risk of Stroke Collaborators, Humans, Incidence, Cause of Death, Risk, Age Distribution, Sex Distribution, Socioeconomic Factors, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Stroke, Global Health, Global Burden of Disease, Brain Disorders, Aging, Prevention, 2.4 Surveillance and distribution, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundThe lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases.MethodsWe used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate.ResultsThe estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation.ConclusionsIn 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).

Published
2018

5. Focal Cerebral Arteriopathy of Childhood

Author

Fullerton, Heather J, Stence, Nicholas, Hills, Nancy K, Jiang, Bin, Amlie-Lefond, Catherine, Bernard, Timothy J, Friedman, Neil R, Ichord, Rebecca, Mackay, Mark T, Rafay, Mubeen F, Chabrier, Stéphane, Steinlin, Maja, Elkind, Mitchell SV, deVeber, Gabrielle A, and Wintermark, Max

Subjects
Allied Health and Rehabilitation Science, Biomedical and Clinical Sciences, Health Sciences, Pediatric, Brain Disorders, Stroke, Neurosciences, Adolescent, Anterior Cerebral Artery, Brain Infarction, Carotid Artery, Internal, Carotid Stenosis, Cerebral Angiography, Cerebral Arterial Diseases, Child, Child, Preschool, Computed Tomography Angiography, Disease Progression, Female, Humans, Infant, Magnetic Resonance Angiography, Male, Middle Cerebral Artery, Posterior Cerebral Artery, Severity of Illness Index, brain ischemia, cerebrovascular disorders, child, follow-up studies, humans, VIPS Investigators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Background and Purpose- Focal cerebral arteriopathy (FCA)-a common cause of arterial ischemic stroke in previously healthy children-often progresses over days to weeks, increasing the risk of recurrent stroke. We developed a novel severity scoring system designed to quantify FCA progression and correlate with clinical outcomes. Methods- The VIPS study (Vascular Effects of Infection in Pediatric Stroke) prospectively enrolled 355 children with arterial ischemic stroke (2010-2014), including 41 with centrally confirmed FCA. Two neuroradiologists independently reviewed FCA cerebrovascular imaging, assigning a graded severity score of zero (no involvement) to 4 (occlusion) to individual arterial segments. The FCA severity score (FCASS) was the unweighted sum. In an iterative process, we modeled scores derived from different combinations of arterial segments to identify the model that optimized correlation with clinical outcome, simplicity, and reliability. Results- The optimal FCASS summed scores from 5 arterial segments: supraclinoid internal carotid artery, A1, A2, M1, and M2. The median (interquartile range) baseline FCASS was 4 (2-6). Of 33 children with follow-up imaging, the maximum FCASS (at any time point) was 7 (5-9). Twenty-four (73%) had FCA progression on follow-up with their maximum FCASS at a median of 8 (5-35.5) days poststroke; their median FCASS increase was 4 (2.5-6). FCASS did not correlate with recurrent arterial ischemic stroke. Maximum (but not baseline) FCASS correlated with 1-year pediatric stroke outcome measures ( P=0.037). Conclusions- Our novel scoring system for FCA severity correlates with neurological outcomes in the VIPS cohort and provides a tool for FCA treatment trials under development.

Published
2018

6. Children with post-stroke epilepsy have poorer outcomes one year after stroke

Author

Fox, Christine K, Jordan, Lori C, Beslow, Lauren A, Armstrong, Jennifer, Mackay, Mark T, and deVeber, Gabrielle

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Neurosciences, Rehabilitation, Clinical Research, Epilepsy, Stroke, Neurodegenerative, Brain Disorders, Pediatric, Adolescent, Brain Ischemia, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Male, Prospective Studies, Risk Factors, Young Adult, Ischemic stroke, risk factors, seizures, pediatric, outcomes, neurology, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Background Epilepsy is a common complication of pediatric stroke. Aim In this study, we aim to measure the association between epilepsy and neurologic outcome after childhood arterial ischemic stroke. Methods Prospective cohort study of children (29 days-19 years) enrolled after an acute arterial ischemic stroke at 21 international pediatric stroke centers and followed to identify epilepsy. One year post-stroke, outcomes were scored using the examination-based Pediatric Stroke Outcome Measure (range = 0-10); higher values reflect greater disability. Ordinal logistic regression was used to measure the association of Pediatric Stroke Outcome Measure scores (categorized as 0-1, 1.5-3, 3.5-6, 6.5-10) with epilepsy. Results Investigators enrolled 86 children (median age = 6.1 years, interquartile range (IQR) = 1.4-12.2 years) with acute stroke. At 1 year, 18/80 (23%) remained on an anticonvulsant including 8/80 (10%) with epilepsy. Among the 70 with Pediatric Stroke Outcome Measure scored, the median was 0.5 (IQR = 0-1.5) for children without epilepsy ( n = 63), and 6 (IQR = 0.5-10) for children with epilepsy ( n = 7). In univariable analyses, poorer 1-year outcome was associated with middle cerebral artery stroke, cortical infarcts, hemorrhagic transformation, hospital disposition not to home, and epilepsy. In multivariable analysis, middle cerebral artery stroke (odds ratio (OR) = 4.9, 95% confidence intervals (CI) = 1.1-21.3) and epilepsy (OR = 24.1, CI = 1.5-380) remained associated with poorer outcome. Conclusions Children who developed epilepsy during the first year post-stroke had poorer neurologic outcomes than those without epilepsy.

Published
2018

7. Socioeconomic determinants of outcome after childhood arterial ischemic stroke

Author

Jordan, Lori C, Hills, Nancy K, Fox, Christine K, Ichord, Rebecca N, Pergami, Paola, deVeber, Gabrielle A, Fullerton, Heather J, and Lo, Warren

Subjects
Neurosciences, Clinical Research, Stroke, Brain Disorders, Pediatric, Physical Rehabilitation, Behavioral and Social Science, Rehabilitation, Adolescent, Brain Ischemia, Child, Child, Preschool, Female, Humans, Income, Infant, Male, Prospective Studies, Social Class, Socioeconomic Factors, Treatment Outcome, VIPS Investigators, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo determine whether lower socioeconomic status (SES) is associated with worse 1-year neurologic outcomes and reduced access to rehabilitation services in children with arterial ischemic stroke (AIS).MethodsFrom 2010 to 2014, the Vascular effects of Infection in Pediatric Stroke (VIPS) observational study prospectively enrolled and confirmed 355 children (age 29 days-18 years) with AIS at 37 international centers. SES markers measured via parental interview included annual household income (US dollars) at the time of enrollment, maternal education level, and rural/suburban/urban residence. Receipt of rehabilitation services was measured by parental report. Pediatric Stroke Outcome Measure scores were categorized as 0 to 1, 1.5 to 3, 3.5 to 6, and 6.5 to 10. Univariate and multivariable ordinal logistic regression models examined potential predictors of outcome.ResultsAt 12 ± 3 months after stroke, 320 children had documented outcome measurements, including 15 who had died. In univariate analysis, very low income (p = 0.004). In multivariable analysis, including adjustment for stroke etiology, this association persisted (OR 3.17, 95% CI 1.18-8.47, p = 0.02). Income did not correlate with receiving rehabilitation services at 1 year after stroke; however, quality and quantity of services were not assessed.ConclusionsIn a large, multinational, prospective cohort of children with AIS, low income was associated with worse neurologic outcomes compared to higher income levels. This difference was not explained by stroke type, neurologic comorbidities, or reported use of rehabilitation services. The root causes of this disparity are not clear and warrant further investigation.

Published
2018

8. Parvovirus B19 Infection in Children With Arterial Ischemic Stroke

Author

Fullerton, Heather J, Luna, Jorge M, Wintermark, Max, Hills, Nancy K, Tokarz, Rafal, Li, Ying, Glaser, Carol, DeVeber, Gabrielle A, Lipkin, W Ian, and Elkind, Mitchell SV

Subjects
Pediatric, Brain Disorders, Prevention, Stroke, Neurosciences, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, Infection, Adolescent, Brain Ischemia, Case-Control Studies, Child, Child, Preschool, Female, Humans, Infant, Male, Parvoviridae Infections, Parvovirus B19, Human, Pilot Projects, case-control studies, carotid artery, internal, heart diseases, middle cerebral artery, parvovirus B19, human, polymerase chain reaction. stroke, VIPS Investigators*, case–control studies, polymerase chain reaction, stroke, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and purposeCase-control studies suggest that acute infection transiently increases the risk of childhood arterial ischemic stroke. We hypothesized that an unbiased pathogen discovery approach utilizing MassTag-polymerase chain reaction would identify pathogens in the blood of childhood arterial ischemic stroke cases.MethodsThe multicenter international VIPS study (Vascular Effects of Infection in Pediatric Stroke) enrolled arterial ischemic stroke cases, and stroke-free controls, aged 29 days through 18 years. Parental interview included questions on recent infections. In this pilot study, we used MassTag-polymerase chain reaction to test the plasma of the first 161 cases and 34 controls enrolled for a panel of 28 common bacterial and viral pathogens.ResultsPathogen DNA was detected in no controls and 14 cases (8.7%): parvovirus B19 (n=10), herpesvirus 6 (n=2), adenovirus (n=1), and rhinovirus 6C (n=1). Parvovirus B19 infection was confirmed by serologies in all 10; infection was subclinical in 8. Four cases with parvovirus B19 had underlying congenital heart disease, whereas another 5 had a distinct arteriopathy involving a long-segment stenosis of the distal internal carotid and proximal middle cerebral arteries.ConclusionsUsing MassTag-polymerase chain reaction, we detected parvovirus B19-a virus known to infect erythrocytes and endothelial cells-in some cases of childhood arterial ischemic stroke. This approach can generate new, testable hypotheses about childhood stroke pathogenesis.

Published
2017

9. Prolonged or recurrent acute seizures after pediatric arterial ischemic stroke are associated with increasing epilepsy risk

Author

Fox, Christine K, Mackay, Mark T, Dowling, Michael M, Pergami, Paola, Titomanlio, Luigi, Deveber, Gabrielle, and Investigators, the SIPS

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Brain Disorders, Pediatric, Neurodegenerative, Clinical Research, Stroke, Epilepsy, Management of diseases and conditions, 7.3 Management and decision making, Adolescent, Age Factors, Brain Ischemia, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Male, Online Systems, Recurrence, Risk Factors, SIPS Investigators, Medical and Health Sciences, Pediatrics, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

AimTo determine epilepsy risk factors after pediatric stroke.MethodA cohort of children with arterial ischemic stroke (birth-18y) was enrolled at 21 centers and followed for 1 year. Acute seizures (≤7d after stroke) and active epilepsy (at least one unprovoked remote seizure plus maintenance anticonvulsant at 1y) were identified. Predictors were determined using logistic regression.ResultsAmong 114 patients (28 neonates and 86 children) enrolled, 26 neonates (93%) and 32 children (37%) had an acute seizure. Acute seizures lasted longer than 5 minutes in 23 patients (40%) and were frequently recurrent: 33 (57%) had 2 to 10 seizures and 11 (19%) had more than 10. Among 109 patients with 1-year follow-up, 11 (10%) had active epilepsy. For each year younger, active epilepsy was 20% more likely (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6-0.99, p=0.041). Prolonged or recurrent acute seizures also increased epilepsy risk. Each additional 10 minutes of the longest acute seizure increased epilepsy risk fivefold (OR 4.7, 95% CI 1.7-13). Patients with more than 10 acute seizures had a 30-fold increased epilepsy risk (OR 30, 95% CI 2.9-305).InterpretationPediatric stroke survivors, especially younger children, have a high risk of epilepsy 1 year after stroke. Prolonged or recurrent acute seizures increase epilepsy risk in a dose-dependent manner.

Published
2017

10. Inflammatory Biomarkers in Childhood Arterial Ischemic Stroke: Correlates of Stroke Cause and Recurrence.

Author

Fullerton, Heather J, deVeber, Gabrielle A, Hills, Nancy K, Dowling, Michael M, Fox, Christine K, Mackay, Mark T, Kirton, Adam, Yager, Jerome Y, Bernard, Timothy J, Hod, Eldad A, Wintermark, Max, Elkind, Mitchell SV, and VIPS Investigators

Subjects
VIPS Investigators, Humans, Brain Ischemia, Cerebral Arterial Diseases, Recurrence, Peroxidase, Tumor Necrosis Factor-alpha, C-Reactive Protein, Serum Amyloid A Protein, Risk Factors, Adolescent, Child, Child, Preschool, Female, Male, Stroke, Biomarkers, C-reactive protein, Cox proportional hazards models, biomarkers, inflammation, serum amyloid A protein, stroke, Prevention, Pediatric, Brain Disorders, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Background and purposeAmong children with arterial ischemic stroke (AIS), those with arteriopathy have the highest recurrence risk. We hypothesized that arteriopathy progression is an inflammatory process and that inflammatory biomarkers would predict recurrent AIS.MethodsIn an international study of childhood AIS, we selected cases classified into 1 of the 3 most common childhood AIS causes: definite arteriopathic (n=103), cardioembolic (n=55), or idiopathic (n=78). We measured serum concentrations of high-sensitivity C-reactive protein, serum amyloid A, myeloperoxidase, and tumor necrosis factor-α. We used linear regression to compare analyte concentrations across the subtypes and Cox proportional hazards models to determine predictors of recurrent AIS.ResultsMedian age at index stroke was 8.2 years (interquartile range, 3.6-14.3); serum samples were collected at median 5.5 days post stroke (interquartile range, 3-10 days). In adjusted models (including age, infarct volume, and time to sample collection) with idiopathic as the reference, the cardioembolic (but not arteriopathic) group had higher concentrations of high-sensitivity C-reactive protein and myeloperoxidase, whereas both cardioembolic and arteriopathic groups had higher serum amyloid A. In the arteriopathic (but not cardioembolic) group, higher high-sensitivity C-reactive protein and serum amyloid A predicted recurrent AIS. Children with progressive arteriopathies on follow-up imaging had higher recurrence rates, and a trend toward higher high-sensitivity C-reactive protein and serum amyloid A, compared with children with stable or improved arteriopathies.ConclusionsAmong children with AIS, specific inflammatory biomarkers correlate with cause and-in the arteriopathy group-risk of stroke recurrence. Interventions targeting inflammation should be considered for pediatric secondary stroke prevention trials.

Published
2016

11. Arterial Tortuosity

Author

Wei, Felix, Diedrich, Karl T, Fullerton, Heather J, deVeber, Gabrielle, Wintermark, Max, Hodge, Jacquie, Kirton, Adam, Dowling, MM, Benedict, SL, Bernard, TJ, Fox, CK, Friedman, NR, Lo, WD, Ichord, RN, Tan, MA, Mackay, MT, Hernandez, Chavez MI, Humphreys, P, Jordan, LC, Sultan, SM, Rivkin, MJ, Rafay, MF, Titomanlio, L, Kovacevic, GS, Yager, JY, Amlie-Lefond, C, Dlamini, N, Condie, J, Yeh, EA, Kneen, R, Bjornson, BH, Pergami, P, Zou, LP, Elbers, J, Abdalla, A, Chan, AK, Farooq, O, Lim, MJ, Carpenter, JL, Pavlakis, S, Wong, VCN, and Forsyth, R

Subjects
Allied Health and Rehabilitation Science, Biomedical and Clinical Sciences, Health Sciences, Stroke, Brain Disorders, Cardiovascular, Pediatric, Neurosciences, Adolescent, Arteries, Biomarkers, Brain Ischemia, Cerebral Arterial Diseases, Child, Child, Preschool, Comorbidity, Female, Humans, Infant, Joint Instability, Male, Meningitis, Moyamoya Disease, Myocardial Infarction, Prospective Studies, Skin Diseases, Genetic, Vascular Malformations, arterial tortuosity, child, dissection, magnetic resonance angiography, pediatric stroke, stroke, Vascular Effects of Infection in Pediatric Stroke (VIPS) Investigators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Background and purposeArteriopathy is the leading cause of childhood arterial ischemic stroke. Mechanisms are poorly understood but may include inherent abnormalities of arterial structure. Extracranial dissection is associated with connective tissue disorders in adult stroke. Focal cerebral arteriopathy is a common syndrome where pathophysiology is unknown but may include intracranial dissection or transient cerebral arteriopathy. We aimed to quantify cerebral arterial tortuosity in childhood arterial ischemic stroke, hypothesizing increased tortuosity in dissection.MethodsChildren (1 month to 18 years) with arterial ischemic stroke were recruited within the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with controls from the Calgary Pediatric Stroke Program. Objective, multi-investigator review defined diagnostic categories. A validated imaging software method calculated the mean arterial tortuosity of the major cerebral arteries using 3-dimensional time-of-flight magnetic resonance angiographic source images. Tortuosity of unaffected vessels was compared between children with dissection, transient cerebral arteriopathy, meningitis, moyamoya, cardioembolic strokes, and controls (ANOVA and post hoc Tukey). Trauma-related versus spontaneous dissection was compared (Student t test).ResultsOne hundred fifteen children were studied (median, 6.8 years; 43% women). Age and sex were similar across groups. Tortuosity means and variances were consistent with validation studies. Tortuosity in controls (1.346±0.074; n=15) was comparable with moyamoya (1.324±0.038; n=15; P=0.998), meningitis (1.348±0.052; n=11; P=0.989), and cardioembolic (1.379±0.056; n=27; P=0.190) cases. Tortuosity was higher in both extracranial dissection (1.404±0.084; n=22; P=0.021) and transient cerebral arteriopathy (1.390±0.040; n=27; P=0.001) children. Tortuosity was not different between traumatic versus spontaneous dissections (P=0.70).ConclusionsIn children with dissection and transient cerebral arteriopathy, cerebral arteries demonstrate increased tortuosity. Quantified arterial tortuosity may represent a clinically relevant imaging biomarker of vascular biology in pediatric stroke.

Published
2016

12. Arterial Tortuosity: An Imaging Biomarker of Childhood Stroke Pathogenesis?

Author

Wei, Felix, Diedrich, Karl T, Fullerton, Heather J, deVeber, Gabrielle, Wintermark, Max, Hodge, Jacquie, Kirton, Adam, and Vascular Effects of Infection in Pediatric Stroke (VIPS) Investigators

Subjects
Vascular Effects of Infection in Pediatric Stroke (VIPS) Investigators, Arteries, Humans, Joint Instability, Brain Ischemia, Moyamoya Disease, Cerebral Arterial Diseases, Meningitis, Myocardial Infarction, Skin Diseases, Genetic, Prospective Studies, Comorbidity, Adolescent, Child, Child, Preschool, Infant, Female, Male, Stroke, Vascular Malformations, Biomarkers, arterial tortuosity, child, dissection, magnetic resonance angiography, pediatric stroke, stroke, Skin Diseases, Genetic, Preschool, Clinical Sciences, Cardiorespiratory Medicine and Haematology, Neurosciences, Neurology & Neurosurgery
Abstract

Background and purposeArteriopathy is the leading cause of childhood arterial ischemic stroke. Mechanisms are poorly understood but may include inherent abnormalities of arterial structure. Extracranial dissection is associated with connective tissue disorders in adult stroke. Focal cerebral arteriopathy is a common syndrome where pathophysiology is unknown but may include intracranial dissection or transient cerebral arteriopathy. We aimed to quantify cerebral arterial tortuosity in childhood arterial ischemic stroke, hypothesizing increased tortuosity in dissection.MethodsChildren (1 month to 18 years) with arterial ischemic stroke were recruited within the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with controls from the Calgary Pediatric Stroke Program. Objective, multi-investigator review defined diagnostic categories. A validated imaging software method calculated the mean arterial tortuosity of the major cerebral arteries using 3-dimensional time-of-flight magnetic resonance angiographic source images. Tortuosity of unaffected vessels was compared between children with dissection, transient cerebral arteriopathy, meningitis, moyamoya, cardioembolic strokes, and controls (ANOVA and post hoc Tukey). Trauma-related versus spontaneous dissection was compared (Student t test).ResultsOne hundred fifteen children were studied (median, 6.8 years; 43% women). Age and sex were similar across groups. Tortuosity means and variances were consistent with validation studies. Tortuosity in controls (1.346±0.074; n=15) was comparable with moyamoya (1.324±0.038; n=15; P=0.998), meningitis (1.348±0.052; n=11; P=0.989), and cardioembolic (1.379±0.056; n=27; P=0.190) cases. Tortuosity was higher in both extracranial dissection (1.404±0.084; n=22; P=0.021) and transient cerebral arteriopathy (1.390±0.040; n=27; P=0.001) children. Tortuosity was not different between traumatic versus spontaneous dissections (P=0.70).ConclusionsIn children with dissection and transient cerebral arteriopathy, cerebral arteries demonstrate increased tortuosity. Quantified arterial tortuosity may represent a clinically relevant imaging biomarker of vascular biology in pediatric stroke.

Published
2016

13. Herpesvirus Infections and Childhood Arterial Ischemic Stroke

Author

Elkind, Mitchell SV, Hills, Nancy K, Glaser, Carol A, Lo, Warren D, Amlie-Lefond, Catherine, Dlamini, Nomazulu, Kneen, Rachel, Hod, Eldad A, Wintermark, Max, deVeber, Gabrielle A, and Fullerton, Heather J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Prevention, Brain Disorders, Stroke, Sexually Transmitted Infections, Infectious Diseases, Aetiology, 2.2 Factors relating to the physical environment, Infection, Adolescent, Brain Ischemia, Case-Control Studies, Child, Child, Preschool, Female, Herpesviridae Infections, Humans, Infant, Infant, Newborn, Internationality, Male, Prospective Studies, child, herpesviridae infections, infection, pediatrics, stroke, VIPS Investigators*, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundEpidemiological studies demonstrate that childhood infections, including varicella zoster virus, are associated with an increased risk of arterial ischemic stroke (AIS). Other herpesviruses have been linked to childhood AIS in case reports. We sought to determine whether herpesvirus infections, which are potentially treatable, increase the risk of childhood AIS.Methods and resultsWe enrolled 326 centrally confirmed cases of AIS and 115 stroke-free controls with trauma (29 days to 18 years of age) with acute blood samples (≤3 weeks after stroke/trauma); cases had convalescent samples (7-28 days later) when feasible. Samples were tested by commercial enzyme-linked immunosorbent assay kits for immunoglobulin M/immunoglobulin G antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus. An algorithm developed a priori classified serological evidence of past and acute herpesvirus infection as dichotomous variables. The median (quartiles) age was 7.7 (3.1-14.3) years for cases and 10.7 (6.9-13.2) years for controls (P=0.03). Serological evidence of past infection did not differ between cases and controls. However, serological evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socioeconomic status (odds ratio, 2.2; 95% confidence interval, 1.2-4.0; P=0.007). Among 187 cases with acute and convalescent blood samples, 85 (45%) showed evidence of acute herpesvirus infection; herpes simplex virus 1 was found most often. Most infections were asymptomatic.ConclusionsHerpesviruses may act as a trigger for childhood AIS, even if the infection is subclinical. Antivirals like acyclovir might have a role in the prevention of recurrent stroke if further studies confirm a causal relationship.

Published
2016

14. Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study.

Author

Wintermark, Max, Hills, Nancy, Dowling, Michael, Tan, Marilyn, Rafay, Mubeen, Elkind, Mitchell, Barkovich, A, deVeber, Gabrielle, and Fullerton, Heather

Subjects
child, pediatrics, risk factor, stroke, vaccination, Adolescent, Brain Ischemia, Cerebral Arterial Diseases, Child, Child, Preschool, Cohort Studies, Female, Follow-Up Studies, Humans, Infant, Internationality, Male, Prospective Studies, Recurrence, Risk Factors, Stroke
Abstract

BACKGROUND AND PURPOSE: Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era. METHODS: The Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review. RESULTS: Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12%-48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection. CONCLUSIONS: Children with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.

Published
2016

15. Risk of Recurrent Arterial Ischemic Stroke in Childhood

Author

Fullerton, Heather J, Wintermark, Max, Hills, Nancy K, Dowling, Michael M, Tan, Marilyn, Rafay, Mubeen F, Elkind, Mitchell SV, Barkovich, A James, deVeber, Gabrielle A, Plumb, Patricia A, Benedict, Susan L, Bernard, Timothy J, Fox, Christine K, Friedman, Neil R, Lo, Warren D, Ichord, Rebecca N, Mackay, Mark T, Kirton, Adam, Hernandez-Chavez, Marta I, Humphreys, Peter, Jordan, Lori C, Sultan, Sally, Rivkin, Michael J, Titomanlio, Luigi, Kovacevic, Gordana S, Yager, Jerome Y, Amlie-Lefond, Catherine, Dlamini, Nomazulu, Condie, John, Yeh, Ann, Kneen, Rachel, Bjornson, Bruce, Pergami, Paola, Zou, Li Ping, Elbers, Jorina M, Abdalla, Abdalla, Chan, Anthony K, Farooq, Osman, Lim, Mingming J, Carpenter, Jessica L, Pavlakis, Steven, Wong, Virginia C, and Forsyth, Robert

Subjects
Paediatrics, Biomedical and Clinical Sciences, Brain Disorders, Pediatric, Stroke, Prevention, Neurosciences, Atherosclerosis, Adolescent, Brain Ischemia, Cerebral Arterial Diseases, Child, Child, Preschool, Cohort Studies, Female, Follow-Up Studies, Humans, Infant, Internationality, Male, Prospective Studies, Recurrence, Risk Factors, child, pediatrics, risk factor, stroke, vaccination, VIPS Investigators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Background and purposePublished cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era.MethodsThe Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review.ResultsOf the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12%-48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection.ConclusionsChildren with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.

Published
2016

16. Infection, vaccination, and childhood arterial ischemic stroke

Author

Fullerton, Heather J, Hills, Nancy K, Elkind, Mitchell SV, Dowling, Michael M, Wintermark, Max, Glaser, Carol A, Tan, Marilyn, Rivkin, Michael J, Titomanlio, Luigi, Barkovich, A James, and deVeber, Gabrielle A

Subjects
Immunization, Neurosciences, Stroke, Clinical Research, Pediatric, Prevention, Vaccine Related, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Infection, Adolescent, Bacteremia, Brain Ischemia, Case-Control Studies, Child, Child, Preschool, Female, Fever, Gastroenteritis, Humans, Immunization Schedule, Infant, Infant, Newborn, Infections, Infectious Encephalitis, Influenza, Human, Logistic Models, Male, Meningitis, Multivariate Analysis, Nasal Decongestants, Odds Ratio, Otitis Media, Pneumonia, Prevalence, Prospective Studies, Respiratory Tract Infections, Risk Factors, Sepsis, United States, Vaccination, Vaccines, VIPS Investigators, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectivesMinor infection can trigger adult arterial ischemic stroke (AIS) and is common in childhood. We tested the hypotheses that infection transiently increases risk of AIS in children, regardless of stroke subtype, while vaccination against infection is protective.MethodsThe Vascular Effects of Infection in Pediatric Stroke study is an international case-control study that prospectively enrolled 355 centrally confirmed cases of AIS (29 days-18 years old) and 354 stroke-free controls. To determine prior exposure to infections and vaccines, we conducted parental interviews and chart review.ResultsMedian (interquartile range) age was 7.6 years for cases and 9.3 for controls (p = 0.44). Infection in the week prior to stroke, or interview date for controls, was reported in 18% of cases, vs 3% of controls, conferring a 6.3-fold increased risk of AIS (p < 0.0001); upper respiratory infections were most common. Prevalence of preceding infection was similar across stroke subtypes: arteriopathic, cardioembolic, and idiopathic. Use of vasoactive cold medications was similarly low in both groups. Children with some/few/no routine vaccinations were at higher stroke risk than those receiving all or most (odds ratio [OR] 7.3, p = 0.0002). In an age-adjusted multivariate logistic regression model, independent risk factors for AIS included infection in the prior week (OR 6.3, p < 0.0001), undervaccination (OR 8.2, p = 0.0004), black race (compared to white; OR 1.9, p = 0.009), and rural residence (compared to urban; OR 3.0, p = 0.0003).ConclusionsInfection may act as a trigger for childhood AIS, while routine vaccinations appear protective. Hence, efforts to reduce the spread of common infections might help prevent stroke in children.

Published
2015

17. Stroke Prevalence, Mortality and Disability-Adjusted Life Years in Children and Youth Aged 0-19 Years: Data from the Global and Regional Burden of Stroke 2013

Author

Krishnamurthi, Rita V, deVeber, Gabrielle, Feigin, Valery L, Barker-Collo, Suzanne, Fullerton, Heather, Mackay, Mark T, O'Callahan, Finbar, Lindsay, M Patrice, Kolk, Anneli, Lo, Warren, Shah, Priyanka, Linds, Alexandra, Jones, Kelly, Parmar, Priya, Taylor, Steve, Norrving, Bo, Mensah, George A, Moran, Andrew E, Naghavi, Mohsen, Forouzanfar, Mohammed H, Nguyen, Grant, Johnson, Catherine O, Vos, Theo, Murray, Christopher JL, and Roth, Gregory A

Subjects
Prevention, Brain Disorders, Neurosciences, Stroke, Emerging Infectious Diseases, Aetiology, 2.4 Surveillance and distribution, Good Health and Well Being, Adolescent, Adult, Child, Child, Preschool, Cost of Illness, Disabled Persons, Female, Global Health, Health Surveys, Humans, Incidence, Infant, Male, Prevalence, Quality-Adjusted Life Years, Young Adult, Childhood stroke, Stroke epidemiology, Deaths, Disability-adjusted life years, GBD 2013 Stroke Panel Experts Group, Public Health and Health Services, Epidemiology
Abstract

BackgroundThere is increasing recognition of stroke as an important contributor to childhood morbidity and mortality. Current estimates of global childhood stroke burden and its temporal trends are sparse. Accurate and up-to-date estimates of childhood stroke burden are important for planning research and the resulting evidence-based strategies for stroke prevention and management.ObjectivesTo estimate the prevalence, mortality and disability-adjusted life years (DALYs) for ischemic stroke (IS), hemorrhagic stroke (HS) and all stroke types combined globally from 1990 to 2013.MethodologyStroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease 2013 methods. All available data on stroke-related incidence, prevalence, excess mortality and deaths were collected. Statistical models and country-level covariates were employed to produce comprehensive and consistent estimates of prevalence and mortality. Stroke-specific disability weights were used to estimate years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013.ResultsIn 2013, there were 97,792 (95% UI 90,564-106,016) prevalent cases of childhood IS and 67,621 (95% UI 62,899-72,214) prevalent cases of childhood HS, reflecting an increase of approximately 35% in the absolute numbers of prevalent childhood strokes since 1990. There were 33,069 (95% UI 28,627-38,998) deaths and 2,615,118 (95% UI 2,265,801-3,090,822) DALYs due to childhood stroke in 2013 globally, reflecting an approximately 200% decrease in the absolute numbers of death and DALYs in childhood stroke since 1990. Between 1990 and 2013, there were significant increases in the global prevalence rates of childhood IS, as well as significant decreases in the global death rate and DALYs rate of all strokes in those of age 0-19 years. While prevalence rates for childhood IS and HS decreased significantly in developed countries, a decline was seen only in HS, with no change in prevalence rates of IS, in developing countries. The childhood stroke DALY rates in 2013 were 13.3 (95% UI 10.6-17.1) for IS and 92.7 (95% UI 80.5-109.7) for HS per 100,000. While the prevalence of childhood IS compared to childhood HS was similar globally, the death rate and DALY rate of HS was 6- to 7-fold higher than that of IS. In 2013, the prevalence rate of both childhood IS and HS was significantly higher in developed countries than in developing countries. Conversely, both death and DALY rates for all stroke types were significantly lower in developed countries than in developing countries in 2013. Men showed a trend toward higher childhood stroke death rates (1.5 (1.3-1.8) per 100,000) than women (1.1 (0.9-1.5) per 100,000) and higher childhood stroke DALY rates (120.1 (100.8-143.4) per 100,000) than women (90.9 (74.6-122.4) per 100,000) globally in 2013.ConclusionsGlobally, between 1990 and 2013, there was a significant increase in the absolute number of prevalent childhood strokes, while absolute numbers and rates of both deaths and DALYs declined significantly. The gap in childhood stroke burden between developed and developing countries is closing; however, in 2013, childhood stroke burden in terms of absolute numbers of prevalent strokes, deaths and DALYs remained much higher in developing countries. There is an urgent need to address these disparities with both global and country-level initiatives targeting prevention as well as improved access to acute and chronic stroke care.

Published
2015

18. Arteriopathy Diagnosis in Childhood Arterial Ischemic Stroke

Author

Wintermark, Max, Hills, Nancy K, deVeber, Gabrielle A, Barkovich, A James, Elkind, Mitchell SV, Sear, Katherine, Zhu, Guangming, Leiva-Salinas, Carlos, Hou, Qinghua, Dowling, Michael M, Bernard, Timothy J, Friedman, Neil R, Ichord, Rebecca N, Fullerton, Heather J, Benedict, SL, Fox, CK, Lo, WD, Tan, MA, Mackay, MT, Kirton, A, Chavez, MI Hernandez, Humphreys, P, Jordan, LC, Sultan, SM, Rivkin, MJ, Rafay, MF, Titomanlio, L, Kovacevic, GS, Yager, JY, Amlie-Lefond, C, Dlamini, N, Condie, J, Yeh, A, Kneen, R, Bjornson, BH, Pergami, P, Zou, LP, Elbers, J, Abdalla, A, Chan, AK, Farooq, O, Lim, MJ, Carpenter, JL, Pavlakis, S, Wong, VC, and Forsyth, R

Subjects
Neurosciences, Stroke, Clinical Research, Pediatric, Brain Disorders, Prevention, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Adolescent, Arteries, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging, Male, Vascular Diseases, cerebral arterial diseases, pediatrics, stroke, transient ischemic attack, VIPS Investigators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and purposeAlthough arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke.MethodsVascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step.ResultsCases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78).ConclusionsClinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

Published
2014

19. Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Author

Kassebaum, Nicholas J, Bertozzi-Villa, Amelia, Coggeshall, Megan S, Shackelford, Katya A, Steiner, Caitlyn, Heuton, Kyle R, Gonzalez-Medina, Diego, Barber, Ryan, Huynh, Chantal, Dicker, Daniel, Templin, Tara, Wolock, Timothy M, Ozgoren, Ayse Abbasoglu, Abd-Allah, Foad, Abera, Semaw Ferede, Abubakar, Ibrahim, Achoki, Tom, Adelekan, Ademola, Ademi, Zanfina, Adou, Arsène Kouablan, Adsuar, José C, Agardh, Emilie E, Akena, Dickens, Alasfoor, Deena, Alemu, Zewdie Aderaw, Alfonso-Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Al Kahbouri, Mazin J, Alla, François, Allen, Peter J, AlMazroa, Mohammad A, Alsharif, Ubai, Alvarez, Elena, Alvis-Guzmán, Nelson, Amankwaa, Adansi A, Amare, Azmeraw T, Amini, Hassan, Ammar, Walid, Antonio, Carl AT, Anwari, Palwasha, Arnlöv, Johan, Arsenijevic, Valentina S Arsic, Artaman, Ali, Asad, Majed Masoud, Asghar, Rana J, Assadi, Reza, Atkins, Lydia S, Badawi, Alaa, Balakrishnan, Kalpana, Basu, Arindam, Basu, Sanjay, Beardsley, Justin, Bedi, Neeraj, Bekele, Tolesa, Bell, Michelle L, Bernabe, Eduardo, Beyene, Tariku J, Bhutta, Zulfiqar, Bin Abdulhak, Aref, Blore, Jed D, Basara, Berrak Bora, Bose, Dipan, Breitborde, Nicholas, Cárdenas, Rosario, Castañeda-Orjuela, Carlos A, Castro, Ruben Estanislao, Catalá-López, Ferrán, Cavlin, Alanur, Chang, Jung-Chen, Che, Xuan, Christophi, Costas A, Chugh, Sumeet S, Cirillo, Massimo, Colquhoun, Samantha M, Cooper, Leslie Trumbull, Cooper, Cyrus, da Costa Leite, Iuri, Dandona, Lalit, Dandona, Rakhi, Davis, Adrian, Dayama, Anand, Degenhardt, Louisa, De Leo, Diego, del Pozo-Cruz, Borja, Deribe, Kebede, Dessalegn, Muluken, deVeber, Gabrielle A, Dharmaratne, Samath D, Dilmen, Uğur, Ding, Eric L, Dorrington, Rob E, Driscoll, Tim R, Ermakov, Sergei Petrovich, Esteghamati, Alireza, Faraon, Emerito Jose A, Farzadfar, Farshad, Felicio, Manuela Mendonca, Fereshtehnejad, Seyed-Mohammad, and de Lima, Graça Maria Ferreira

Subjects
2.4 Surveillance and distribution, Aetiology, Infection, Reproductive health and childbirth, Good Health and Well Being, Age Distribution, Cause of Death, Female, Global Health, HIV Infections, Humans, Maternal Mortality, Models, Statistical, Organizational Objectives, Pregnancy, Pregnancy Complications, Infectious, Risk Factors, Socioeconomic Factors, Time Factors, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThe fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.MethodsWe used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.Findings292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.InterpretationGlobal rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.FundingBill & Melinda Gates Foundation.

Published
2014

20. Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries : an analysis from the Global Burden of Disease Study 2016

Author

Fullman, Nancy, Barber, Ryan M, Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abdulkader, Rizwan Suliankatchi, Abdulle, Abdishakur M, Abera, Semaw Ferede, Aboyans, Victor, De Steur, Hans, Gupta, Vipin, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Srinivasan, Vinay, Nguyen, Quyen Le, Stanaway, Jeffrey D, Atre, Sachin R, Kim, Daniel, Criqui, Michael H, Aryal, Krishna Kumar, Ahmadieh, Hamid, Stein, Dan J, Steiner, Caitlyn, Steinke, Sabine, Stokes, Mark Andrew, Strub, Bryan, Aichour, Miloud Taki Eddine, Nguyen, Trang Huyen, Defo, Barthelemy Kuate, Sufiyan, Muawiyyah Babale, Dandona, Rakhi, Mantovani, Lorenzo G, Sunguya, Bruno F, Sur, Patrick J, Mazidi, Mohsen, Kimokoti, Ruth W, Swaminathan, Soumya, Sykes, Bryan L, Avila-Burgos, Leticia, Sylte, Dillon O, Nguyen, Grant, Schwebel, David C, Szoeke, Cassandra E I, Murthy, Gudlavalleti Venkata Satyanarayana, Tabarés-Seisdedos, Rafael, Hafezi-Nejad, Nima, Tadakamadla, Santosh Kumar, Degenhardt, Louisa, McAlinden, Colm, Tandon, Nikhil, Kinfu, Yohannes, Tao, Tianchan, Schwendicke, Falk, Tarekegn, Yihunie L, Giref, Ababi Zergaw, Ahmed, Muktar Beshir, Tavakkoli, Mohammad, Taveira, Nuno, Tegegne, Teketo Kassaw, Avokpaho, Euripide Frinel G Arthur, Terkawi, Abdullah Sulieman, Hailu, Gessessew Bugssa, Alla, François, Seedat, Soraya, Tessema, Gizachew Assefa, Thakur, JS, Alam, Khurshid, Rajsic, Sasa, Nguyen, Minh, Deiparine, Selina, Thankappan, Kavumpurathu Raman, Thrift, Amanda G, Tiruye, Tenaw Yimer, Tobe-Gai, Ruoyan, Martin, Randall V, Topor-Madry, Roman, Torre, Anna, McGaughey, Madeline, Tortajada, Miguel, Ram, Usha, Hamadeh, Randah Ribhi, Nichols, Emma, Awasthi, Ashish, Fürst, Thomas, Tran, Bach Xuan, Sepanlou, Sadaf G, Troeger, Christopher, Deribe, Kebede, Truelsen, Thomas, Tsoi, Derrick, Tuem, Kald Beshir, Ranabhat, Chhabi Lal, McGrath, John J, Tuzcu, Emin Murat, Majeed, Azeem, Tyrovolas, Stefanos, Servan-Mori, Edson E, Ukwaja, Kingsley N, Hammami, Mouhanad, Kisa, Adnan, Uneke, Chigozie Jesse, Updike, Rachel, Azzopardi, Peter, Rao, Puja C, Uthman, Olalekan A, Adetokunboh, Olatunji, McKee, Martin, Griswold, Max, Cárdenas, Rosario, van Boven, Job F M, Varughese, Santosh, Vasankari, Tommi, Venketasubramanian, Narayanaswamy, Vidavalur, Ramesh, Abu-Raddad, Laith J, Rawaf, Salman, Hankey, Graeme J, Violante, Francesco S, Altirkawi, Khalid A, Vladimirov, Sergey K, Vlassov, Vasiliy Victorovich, Ningrum, Dina Nur Anggraini, Mehata, Suresh, Vollset, Stein Emil, Bacha, Umar, deVeber, Gabrielle A, Vos, Theo, Antonio, Carl Abelardo T, Wadilo, Fiseha, Rafay, Anwar, Wakayo, Tolassa, Kissimova-Skarbek, Katarzyna A, Wallin, Mitchell T, Harb, Hilda L, Nomura, Marika, Wang, Yuan-Pang, Mehndiratta, Man Mohan, Weichenthal, Scott, Weiderpass, Elisabete, Khader, Yousef Saleh, Carrero, Juan Jesus, Weintraub, Robert G, Weiss, Daniel J, Werdecker, Andrea, Ding, Eric L, Badawi, Alaa, Kivimaki, Mika, Chitheer, Abdulaal A, Westerman, Ronny, Whiteford, Harvey A, Chang, Hsing-Yi, Shackelford, Katya Anne, Reidy, Patrick, Hareri, Habtamu Abera, Wijeratne, Tissa, Wiysonge, Charles Shey, Woldeyes, Belete Getahun, Wolfe, Charles D A, Woodbrook, Rachel, Xavier, Denis, Alvis-Guzman, Nelson, Xu, Gelin, Shaheen, Amira, Kokubo, Yoshihiro, Reiner, Robert C, Djalalinia, Shirin, Karema, Corine Kakizi, Yadgir, Simon, Balakrishnan, Kalpana, Hassanvand, Mohammad Sadegh, Yakob, Bereket, Yan, Lijing L, Yano, Yuichiro, Shahraz, Saeid, Nong, Vuong Minh, Yaseri, Mehdi, Musa, Kamarul Imran, Ye, Pengpeng, Yimam, Hassen Hamid, Kopec, Jacek A, Meier, Toni, Yip, Paul, Yonemoto, Naohiro, Do, Huyen Phuc, Shaikh, Masood Ali, Yoon, Seok-Jun, Butt, Zahid A, Norheim, Ole F, Geleto, Ayele, Yotebieng, Marcel, Bannick, Marlena S, Younis, Mustafa Z, Zaidi, Zoubida, Zaki, Maysaa El Sayed, Breitborde, Nicholas J K, Shamsipour, Mansour, Kosen, Soewarta, Zavala-Arciniega, Luis, Zhang, Xueying, Zipkin, Ben, Reinig, Nikolas, Noubiap, Jean Jacques N, Zodpey, Sanjay, Dokova, Klara, Havmoeller, Rasmus, Lim, Stephen S, Dargan, Paul I, Murray, Christopher J L, Barac, Aleksandra, Meles, Kidanu Gebremariam, Barker-Collo, Suzanne L, Koul, Parvaiz A, Reitsma, Marissa B, Bärnighausen, Till, Obermeyer, Carla Makhlouf, Barrero, Lope H, Basu, Sanjay, Martinez-Raga, Jose, Battle, Katherine E, Baune, Bernhard T, Beardsley, Justin, Hawley, Caitlin, Doku, David Teye, Memish, Ziad A, Goldberg, Ellen M, Bedi, Neeraj, Beghi, Ettore, Gishu, Melkamu Dedefo, Asayesh, Hamid, Koyanagi, Ai, Béjot, Yannick, Bell, Michelle L, Bennett, Derrick A, Bennett, James R, Bensenor, Isabela M, Berhane, Adugnaw, Cromwell, Elizabeth A, Berhe, Derbew Fikadu, Mendoza, Walter, Shamsizadeh, Morteza, Aichour, Amani Nidhal, Malekzadeh, Reza, Bernabé, Eduardo, Donkelaar, Aaron van, Kravchenko, Michael, Betsu, Balem Demtsu, Beuran, Mircea, Beyene, Addisu Shunu, Remuzzi, Giuseppe, Bhala, Neeraj, Ansari, Hossein, Bhansali, Anil, Bhatt, Samir, Mengesha, Melkamu Merid, Ogbo, Felix Akpojene, Bhutta, Zulfiqar A, Bicer, Burcu Kucuk, Hay, Simon I, Bidgoli, Hassan Haghparast, Furtado, Joao M, Renzaho, Andre M N, Kawakami, Norito, Bikbov, Boris, Dorsey, E Ray, Bilal, Arebu I, Birungi, Charles, Biryukov, Stan, Friedman, Joseph, Allebeck, Peter, Bizuayehu, Habtamu Mellie, Blosser, Christopher D, Boneya, Dube Jara, Shariful Islam, Sheikh Mohammed, Resnikoff, Serge, Bose, Dipan, He, Jiawei, Krohn, Kristopher J, Bou-Orm, Ibrahim R, Brauer, Michael, Driscoll, Tim R, Oh, In-Hwan, Dubey, Manisha, Mengistie, Mubarek Abera, Sharma, Jayendra, Afshin, Ashkan, Rezaei, Satar, Duncan, Bruce Bartholow, Ebel, Beth E, Ebrahimi, Hedyeh, El-Khatib, Ziad Ziad, Enayati, Ahmadali, Alam, Noore, Hendrie, Delia, Oladimeji, Olanrewaju, Khosravi, Ardeshir, Endries, Aman Yesuf, Ermakov, Sergey Petrovich, Khalil, Ibrahim A, Mensah, George A, Erskine, Holly E, Eshrati, Babak, Eskandarieh, Sharareh, Agrawal, Anurag, Esteghamati, Alireza, Estep, Kara, Gugnani, Harish Chander, Faraon, Emerito Jose Aquino, Olagunju, Andrew Toyin, Carter, Austin, Naghavi, Mohsen, Farinha, Carla Sofia e Sa, Henry, Nathaniel J, Mensink, Gert B M, Faro, André, Farzadfar, Farshad, Fazeli, Mir Sohail, Sharma, Rajesh, Feigin, Valery L, Feigl, Andrea B, Fereshtehnejad, Seyed-Mohammad, Olagunju, Tinuke Oluwasefunmi, Rios Blancas, Maria Jesus, Agrawal, Sutapa, Fernandes, João C, Kulikoff, Xie Rachel, Ferrari, Alize J, Kasaeian, Amir, She, Jun, Feyissa, Tesfaye Regassa, Heredia-Pi, Ileana Beatriz, Filip, Irina, Fischer, Florian, Fitzmaurice, Christina, Kamal, Ritul, Christensen, Hanne, Flaxman, Abraham D, Foigt, Nataliya, Foreman, Kyle J, Shi, Peilin, Frank, Tahvi, Kumar, G Anil, Mereta, Seid Tiku, Ahmad Kiadaliri, Aliasghar, Franklin, Richard C, Hoek, Hans W, Rivas, Jacqueline Castillo, Holmberg, Mollie, Olivares, Pedro R, Cahuana-Hurtado, Lucero, Shibuya, Kenji, Horita, Nobuyuki, Hosgood, H Dean, Hostiuc, Sorin, Aichour, Ibtihel, Hoy, Damian G, Chang, Jung-Chen, Kumar Lal, Dharmesh, Anwari, Palwasha, Hsairi, Mohamed, Htet, Aung Soe, Martins-Melo, Francisco Rogerlândio, Amare, Azmeraw T, Huang, John J, Huang, Hsiang, Huynh, Chantal, Cameron, Ewan, Iburg, Kim Moesgaard, Ikeda, Chad, Inoue, Manami, Roba, Kedir Teji, Gemechu, Bikila Lencha, Rahimi-Movaghar, Vafa, Irvine, Caleb Mackay Salpeter, Kutz, Michael J, Olsen, Helen E, Aiyar, Sneha, Jacobsen, Kathryn H, Jahanmehr, Nader, Jakovljevic, Mihajlo B, Jauregui, Alejandra, Javanbakht, Mehdi, Rojas-Rueda, David, Shields, Chloe, Campuzano, Julio Cesar, Jeemon, Panniyammakal, Meretoja, Tuomo J, Jha, Vivekanand, Malhotra, Rajesh, John, Denny, Kyu, Hmwe H, Johnson, Catherine O, Johnson, Sarah Charlotte, Akinyemi, Rufus Olusola, Majdzadeh, Reza, Gona, Philimon N, Jonas, Jost B, Jürisson, Mikk, Kabir, Zubair, Kadel, Rajendra, Meretoja, Atte, Olusanya, Bolajoko Olubukunola, Carabin, Hélène, Kahsay, Amaha, Lalloo, Ratilal, Shifa, Girma Temam, Lansingh, Van C, Rokni, Mohammad Bagher, Gakidou, Emmanuela, Larsson, Anders, Lazarus, Jeffrey Victor, Lee, Paul H, Casey, Daniel C, Alasfoor, Deena, Giussani, Giorgia, Mezgebe, Haftay Berhane, das Neves, José, Leigh, James, Leung, Janni, Crump, John A, Leung, Ricky, Levi, Miriam, Li, Yongmei, Garcia-Basteiro, Alberto L, Liben, Misgan Legesse, Linn, Shai, Liu, Patrick Y, Shiferaw, Mekonnen Sisay, Keiyoro, Peter Njenga, Liu, Shiwei, Micha, Renata, Roshandel, Gholamreza, Castañeda-Orjuela, Carlos A, Lodha, Rakesh, Alene, Kefyalew Addis, Looker, Katharine J, Lopez, Alan D, Lorkowski, Stefan, Asgedom, Solomon Weldegebreal, Gebrehiwot, Tsegaye Tewelde, Lotufo, Paulo A, Olusanya, Jacob Olusegun, Lozano, Rafael, Naheed, Aliya, Lucas, Timothy C D, Millear, Anoushka, Lunevicius, Raimundas, Mackay, Mark T, Castro, Ruben Estanislao, Khubchandani, Jagdish, Maddison, Emilie R, Magdy Abd El Razek, Hassan, Alizadeh-Navaei, Reza, Magdy Abd El Razek, Mohammed, Ong, Kanyin, Roth, Gregory A, Geleijnse, Johanna M, Majdan, Marek, Miller, Ted R, Allen, Christine, Shigematsu, Mika, Kassebaum, Nicholas J, Minnig, Shawn, Mirarefin, Mojde, Mirrakhimov, Erkin M, Gething, Peter W, Charlson, Fiona J, Al-Aly, Ziyad, Oren, Eyal, Misganaw, Awoke, Mishra, Shiva Raj, Gupta, Rajeev, Mitchell, Philip B, Mohammad, Karzan Abdulmuhsin, Mohammed, Kedir Endris, Akseer, Nadia, Mohammed, Shafiu, Mohan, Murali B V, Al-Raddadi, Rajaa, Alkerwi, Ala'a, Mokdad, Ali H, Ortiz, Alberto, Shin, Min-Jeong, Gibney, Katherine B, Mollenkopf, Sarah K, Chew, Adrienne, Monasta, Lorenzo, Montañez Hernandez, Julio Cesar, Montico, Marcella, Kastor, Anshul, Moradi-Lakeh, Maziar, Roy, Ambuj, Moraga, Paula, Rahman, Mohammad Hifz Ur, Morawska, Lidia, Owolabi, Mayowa O, Morrison, Shane D, Moses, Mark W, Gill, Paramjit Singh, Alsharif, Ubai, Mountjoy-Venning, Cliff, Abu-Rmeileh, Niveen M E, Mueller, Ulrich O, Rubagotti, Enrico, Shiri, Rahman, Katikireddi, Srinivasa Vittal, Muller, Kate, PA, Mahesh, Christopher, Devasahayam Jesudas, Malta, Deborah Carvalho, Pana, Adrian, Panda, Basant Kumar, Amini, Erfan, Kelbore, Sefonias Getachew, Glenn, Scott D, Cercy, Kelly, 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Milicevic, Milena M, Shoman, Haitham, Mapoma, Chabila C, Artaman, Al, Khang, Young-Ho, Sartorius, Benn, Adedeji, Isaac Akinkunmi, Satpathy, Maheswar, Nangia, Vinay, Sawhney, Monika, Saxena, Sonia, Saylan, Mete I, Shrime, Mark G, Schmidt, Maria Inês, Schneider, Ione J C, Marks, Guy B, Goryakin, Yevgeniy, Schneider, Matthew T, Frostad, Joseph J, Schöttker, Ben, Natarajan, Gopalakrishnan, Schutte, Aletta E, Davitoiu, Dragos V, Kieling, Christian, Rahman, Muhammad Aziz, Silberberg, Donald H, Silva, Diego Augusto Santos, Gupta, Tanush, Negoi, Ruxandra Irina, Martopullo, Ira, Assadi, Reza, Silva, João Pedro, Silveira, Dayane Gabriele Alves, Singh, Jasvinder A, Singh, Virendra, Kesavachandran, Chandrasekharan Nair, Sinha, Dhirendra Narain, Skiadaresi, Eirini, Kim, Jun Y, Slepak, Erica Leigh, Negoi, Ionut, de Courten, Barbora, Mathur, Manu Raj, Sligar, Amber, Bulto, Lemma Negesa Bulto, Smith, David L, Rahman, Mahfuzar, Smith, Alison, Atey, Tesfay Mehari, Smith, Mari, Sobaih, Badr H A, Sobngwi, Eugene, Nguyen, Cuong Tat, Kim, Yun Jin, Soljak, Michael, Karch, André, Soneji, Samir, Rai, Rajesh Kumar, Sorensen, Reed J D, Halk Sağlığı, Veritati - Repositório Institucional da Universidade Católica Portuguesa, Fullman, Nancy, Barber, Ryan M., Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M., Abd-Allah, Foad, Abdulle, Abdishakur M., Abera, Semaw Ferede, Aboyans, Victor, Abu-Raddad, Laith J., Abu-Rmeileh, Niveen M.E., Adedeji, Isaac Akinkunmi, Adetokunboh, Olatunji, Afshin, Ashkan, Agrawal, Anurag, Agrawal, Sutapa, Kiadaliri, Aliasghar Ahmad, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Aichour, Amani Nidhal, Aichour, Ibtihel, Aichour, Miloud Taki Eddine, Aiyar, Sneha, Akinyemi, Rufus Olusola, Akseer, Nadia, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore, Alasfoor, Deena, Alene, Kefyalew Addi, Alizadeh-Navaei, Reza, Alkerwi, Ala'a, Alla, Françoi, Allebeck, Peter, Allen, Christine, Al-Raddadi, Rajaa, Alsharif, Ubai, Altirkawi, Khalid A., Alvis-Guzman, Nelson, Amare, Azmeraw T., Amini, Erfan, Ammar, Walid, Antonio, Carl Abelardo T., Ansari, Hossein, Anwari, Palwasha, Arora, Megha, Artaman, Al, Aryal, Krishna Kumar, Asayesh, Hamid, Asgedom, Solomon Weldegebreal, Assadi, Reza, Atey, Tesfay Mehari, Atre, Sachin R., Avila-Burgos, Leticia, Arthur Avokpaho, Euripide Frinel G., Awasthi, Ashish, Azzopardi, Peter, Bacha, Umar, Badawi, Alaa, Balakrishnan, Kalpana, Bannick, Marlena S., Barac, Aleksandra, Barker-Collo, Suzanne L., Bärnighausen, Till, Barrero, Lope H., Basu, Sanjay, Battle, Katherine E., Baune, Bernhard T., Beardsley, Justin, Bedi, Neeraj, Beghi, Ettore, Béjot, Yannick, Bell, Michelle L., Bennett, Derrick A., Bennett, James R., Bensenor, Isabela M., Berhane, Adugnaw, Berhe, Derbew Fikadu, Bernabé, Eduardo, Betsu, Balem Demtsu, Beuran, Mircea, Beyene, Addisu Shunu, Bhala, Neeraj, Bhansali, Anil, Bhatt, Samir, Bhutta, Zulfiqar A., Bikbov, Bori, Bilal, Arebu I., Birungi, Charle, Biryukov, Stan, Bizuayehu, Habtamu Mellie, Blosser, Christopher D., Boneya, Dube Jara, Bose, Dipan, Bou-Orm, Ibrahim R., Brauer, Michael, Breitborde, Nicholas J.K., Brugha, Traolach S., Bulto, Lemma Negesa Bulto, Butt, Zahid A., Cahuana-Hurtado, Lucero, Cameron, Ewan, Campuzano, Julio Cesar, Carabin, Hélène, Cárdenas, Rosario, Carrero, Juan Jesu, Carter, Austin, Casey, Daniel C., Castañeda-Orjuela, Carlos A., Rivas, Jacqueline Castillo, Castro, Ruben Estanislao, Catalá-López, Ferrán, Cercy, Kelly, Chang, Hsing-Yi, Chang, Jung-Chen, Charlson, Fiona J., Chew, Adrienne, Chisumpa, Vesper Hichilombwe, Chitheer, Abdulaal A., Christensen, Hanne, Christopher, Devasahayam Jesuda, Cirillo, Massimo, Cooper, Cyru, Criqui, Michael H., Cromwell, Elizabeth A., Crump, John A., Dandona, Lalit, Dandona, Rakhi, Dargan, Paul I., Das Neves, José, Davitoiu, Dragos V., De Courten, Barbora, De Steur, Han, Degenhardt, Louisa, Deiparine, Selina, Deribe, Kebede, DeVeber, Gabrielle A., Ding, Eric L., Djalalinia, Shirin, Do, Huyen Phuc, Dokova, Klara, Doku, David 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Anil, Kutz, Michael J., Kyu, Hmwe H., Lal, Dharmesh Kumar, Lalloo, Ratilal, Lansingh, Van C., Larsson, Ander, Lazarus, Jeffrey Victor, Lee, Paul H., Leigh, Jame, Leung, Janni, Leung, Ricky, Levi, Miriam, Li, Yongmei, Liben, Misgan Legesse, Linn, Shai, Liu, Patrick Y., Liu, Shiwei, Lodha, Rakesh, Looker, Katharine J., Lopez, Alan D., Lorkowski, Stefan, Lotufo, Paulo A., Lozano, Rafael, Lucas, Timothy C.D., Lunevicius, Raimunda, Mackay, Mark T., Maddison, Emilie R., El Razek, Hassan Magdy Abd, El Razek, Mohammed Magdy Abd, Majdan, Marek, Majdzadeh, Reza, Majeed, Azeem, Malekzadeh, Reza, Malhotra, Rajesh, Malta, Deborah Carvalho, Mamun, Abdullah A., Manguerra, Helena, Mantovani, Lorenzo G., Manyazewal, Tsegahun, Mapoma, Chabila C., Marks, Guy B., Martin, Randall V., Martinez-Raga, Jose, Martins-Melo, Francisco Rogerlândio, Martopullo, Ira, Mathur, Manu Raj, Mazidi, Mohsen, McAlinden, Colm, McGaughey, Madeline, McGrath, John J., McKee, Martin, Mehata, Suresh, Mehndiratta, Man Mohan, Meier, Toni, Meles, Kidanu Gebremariam, Memish, Ziad A., Mendoza, Walter, Mengesha, Melkamu Merid, Mengistie, Mubarek Abera, Mensah, George A., Mensink, Gert B.M., Mereta, Seid Tiku, Meretoja, Atte, Meretoja, Tuomo J., Mezgebe, Haftay Berhane, Micha, Renata, Millear, Anoushka, Miller, Ted R., Minnig, Shawn, Mirarefin, Mojde, Mirrakhimov, Erkin M., Misganaw, Awoke, Mishra, Shiva Raj, Mitchell, Philip B., Mohammad, Karzan Abdulmuhsin, Mohammed, Kedir Endri, Mohammed, Shafiu, Mohan, Murali B.V., Mokdad, Ali H., Mollenkopf, Sarah K., Monasta, Lorenzo, Hernandez, Julio Cesar Montañez, Montico, Marcella, Moradi-Lakeh, Maziar, Moraga, Paula, Morawska, Lidia, Morrison, Shane D., Moses, Mark W., Mountjoy-Venning, Cliff, Mueller, Ulrich O., Muller, Kate, Murthy, Gudlavalleti Venkata Satyanarayana, Musa, Kamarul Imran, Naghavi, Mohsen, Naheed, Aliya, Naidoo, Kovin S., Nangia, Vinay, Natarajan, Gopalakrishnan, Negoi, Ionut, Negoi, Ruxandra Irina, Nguyen, Cuong Tat, Nguyen, Grant, Nguyen, Minh, Nguyen, Quyen Le, Nguyen, Trang Huyen, Nichols, Emma, Ningrum, Dina Nur Anggraini, Nomura, Marika, Nong, Vuong Minh, Norheim, Ole F., Noubiap, Jean Jacques N., Obermeyer, Carla Makhlouf, Ogbo, Felix Akpojene, Oh, In-Hwan, Oladimeji, Olanrewaju, Olagunju, Andrew Toyin, Olagunju, Tinuke Oluwasefunmi, Olivares, Pedro R., Olsen, Helen E., Olusanya, Bolajoko Olubukunola, Olusanya, Jacob Olusegun, Ong, Kanyin, Oren, Eyal, Ortiz, Alberto, Owolabi, Mayowa O., Mahesh, P.A., Pana, Adrian, Panda, Basant Kumar, Panda-Jonas, Songhomitra, Papachristou, Christina, Park, Eun-Kee, Patton, George C., Paulson, Katherine, Pereira, David M., Perico, David Norberto, Pesudovs, Konrad, Petzold, Max, Phillips, Michael Robert, Pigott, David M., Pillay, Julian David, Pinho, Christine, Piradov, Michael A., Pishgar, Farhad, Poulton, Richie G., Pourmalek, Farshad, Qorbani, Mostafa, Radfar, Amir, Rafay, Anwar, Rao, Puja C., Rahimi-Movaghar, Vafa, Rahman, Mahfuzar, Ur Rahman, Mohammad Hifz, Rahman, Muhammad Aziz, Rai, Rajesh Kumar, Rajsic, Sasa, Ram, Usha, Ranabhat, Chhabi Lal, Rawaf, Salman, Reidy, Patrick, Reiner, Robert C., Reinig, Nikola, Reitsma, Marissa B., Remuzzi, Giuseppe, Renzaho, Andre M.N., Resnikoff, Serge, Rezaei, Satar, Blancas, Maria Jesus Rio, Roba, Kedir Teji, Rojas-Rueda, David, Rokni, Mohammad Bagher, Roshandel, Gholamreza, Roth, Gregory A., Roy, Ambuj, Rubagotti, Enrico, Sadat, Nafi, Safdarian, Mahdi, Safi, Sare, Safiri, Saeid, Sagar, Rajesh, Salama, Joseph, Salomon, Joshua A., Samy, Abdallah M., Sanabria, Juan Ramon, Santomauro, Damian, Santos, Itamar S., Santos, João Vasco, Santric Milicevic, Milena M., Sartorius, Benn, Satpathy, Maheswar, Sawhney, Monika, Saxena, Sonia, Saylan, Mete I., Shirude, Shreya, Schmidt, Maria Inê, Schneider, Ione J.C., Schneider, Matthew T., Schöttker, Ben, Schutte, Aletta E., Schwebel, David C., Schwendicke, Falk, Seedat, Soraya, Sepanlou, Sadaf G., Servan-Mori, Edson E., Shackelford, Katya Anne, Shaheen, Amira, Shahraz, Saeid, Shaikh, Masood Ali, Shamsipour, Mansour, Shamsizadeh, Morteza, Islam, Sheikh Mohammed Shariful, Sharma, Jayendra, Sharma, Rajesh, She, Jun, Shi, Peilin, Shibuya, Kenji, Shields, Chloe, Shiferaw, Mekonnen Sisay, Shigematsu, Mika, Shin, Min-Jeong, Shiri, Rahman, Shirkoohi, Reza, Shishani, Kawkab, Shoman, Haitham, Shrime, Mark G., Silberberg, Donald H., Silva, Diego Augusto Santo, Silva, João Pedro, Silveira, Dayane Gabriele Alve, Singh, Jasvinder A., Singh, Virendra, Sinha, Dhirendra Narain, Skiadaresi, Eirini, Slepak, Erica Leigh, Sligar, Amber, Smith, Alison, Smith, David L., Smith, Mari, Sobaih, Badr H.A., Sobngwi, Eugene, Soljak, Michael, Soneji, Samir, Sorensen, Reed J.D., Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Srinivasan, Vinay, Stanaway, Jeffrey D., Stein, Dan J., Steiner, Caitlyn, Steinke, Sabine, Stokes, Mark Andrew, Strub, Bryan, Sufiyan, Muawiyyah Babale, Abdulkader, Rizwan Suliankatchi, Sunguya, Bruno F., Sur, Patrick J., Swaminathan, Soumya, Sykes, Bryan L., Sylte, Dillon O., Szoeke, Cassandra E.I., Tabarés-Seisdedos, Rafael, Tadakamadla, Santosh Kumar, Tandon, Nikhil, Tao, Tianchan, Tarekegn, Yihunie L., Tavakkoli, Mohammad, Taveira, Nuno, Tegegne, Teketo Kassaw, Shifa, Girma Temam, Terkawi, Abdullah Sulieman, Tessema, Gizachew Assefa, Thakur, J.S., Thankappan, Kavumpurathu Raman, Thrift, Amanda G., Tiruye, Tenaw Yimer, Tobe-Gai, Ruoyan, Topor-Madry, Roman, Torre, Anna, Tortajada, Miguel, Tran, Bach Xuan, Troeger, Christopher, Truelsen, Thoma, Tsoi, Derrick, Tuem, Kald Beshir, Tuzcu, Emin Murat, Tyrovolas, Stefano, Ukwaja, Kingsley N., Uneke, Chigozie Jesse, Updike, Rachel, Uthman, Olalekan A., Van Boven, Job F.M., Van Donkelaar, Aaron, Varughese, Santosh, Vasankari, Tommi, Venketasubramanian, Narayanaswamy, Vidavalur, Ramesh, Violante, Francesco S., Vladimirov, Sergey K., Vlassov, Vasiliy Victorovich, Vollset, Stein Emil, Vos, Theo, Wadilo, Fiseha, Wakayo, Tolassa, Wallin, Mitchell T., Wang, Yuan-Pang, Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G., Weiss, Daniel J., Werdecker, Andrea, Westerman, Ronny, Whiteford, Harvey A., Wijeratne, Tissa, Wiysonge, Charles Shey, Woldeyes, Belete Getahun, Wolfe, Charles D.A., Woodbrook, Rachel, Xavier, Deni, Xu, Gelin, Yadgir, Simon, Yakob, Bereket, Yan, Lijing L., Yano, Yuichiro, Yaseri, Mehdi, Ye, Pengpeng, Yimam, Hassen Hamid, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Yotebieng, Marcel, Younis, Mustafa Z., Zaidi, Zoubida, El Sayed Zaki, Maysaa, Zavala-Arciniega, Lui, Zhang, Xueying, Zipkin, Ben, Zodpey, Sanjay, Lim, Stephen S., Murray, Christopher J.L., Fullman, N, Barber, R, Abajobir, A, Abate, K, Abbafati, C, Abbas, K, Abd-Allah, F, Abdulle, A, Abera, S, Aboyans, V, Abu-Raddad, L, Abu-Rmeileh, N, Adedeji, I, Adetokunboh, O, Afshin, A, Agrawal, A, Agrawal, S, Kiadaliri, A, Ahmadieh, H, Ahmed, M, Aichour, A, Aichour, I, Aichour, M, Aiyar, S, Akinyemi, R, Akseer, N, Al-Aly, Z, Alam, K, Alam, N, Alasfoor, D, Alene, K, Alizadeh-Navaei, R, Alkerwi, A, Alla, F, Allebeck, P, Allen, 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Chitheer, A, Christensen, H, Christopher, D, Cirillo, M, Cooper, C, Criqui, M, Cromwell, E, Crump, J, Dandona, L, Dandona, R, Dargan, P, Das Neves, J, Davitoiu, D, De Courten, B, De Steur, H, Degenhardt, L, Deiparine, S, Deribe, K, Deveber, G, Ding, E, Djalalinia, S, Do, H, Dokova, K, Doku, D, Dorsey, E, Driscoll, T, Dubey, M, Duncan, B, Ebel, B, Ebrahimi, H, El-Khatib, Z, Enayati, A, Endries, A, Ermakov, S, Erskine, H, Eshrati, B, Eskandarieh, S, Esteghamati, A, Estep, K, Faraon, E, Sofia E Sa Farinha, C, Faro, A, Farzadfar, F, Fazeli, M, Feigin, V, Feigl, A, Fereshtehnejad, S, Fernandes, J, Ferrari, A, Feyissa, T, Filip, I, Fischer, F, Fitzmaurice, C, Flaxman, A, Foigt, N, Foreman, K, Frank, T, Franklin, R, Friedman, J, Frostad, J, Fürst, T, Furtado, J, Gakidou, E, Garcia-Basteiro, A, Gebrehiwot, T, Geleijnse, J, Geleto, A, Gemechu, B, Gething, P, Gibney, K, Gill, P, Gillum, R, Giref, A, Gishu, M, Giussani, G, Glenn, S, Godwin, W, Goldberg, E, Gona, P, Goodridge, A, Gopalani, S, Goryakin, Y, Griswold, M, Gugnani, H, Gupta, R, Gupta, T, Gupta, V, Hafezi-Nejad, N, Bidgoli, H, Hailu, G, Hamadeh, R, Hammami, M, Hankey, G, Harb, H, Hareri, H, Hassanvand, M, Havmoeller, R, Hawley, C, Hay, S, He, J, Hendrie, D, Henry, N, Heredia-Pi, I, Hoek, H, Holmberg, M, Horita, N, Hosgood, H, Hostiuc, S, Hoy, D, Hsairi, M, Htet, A, Huang, H, Huang, J, Huynh, C, Iburg, K, Ikeda, C, Inoue, M, Irvine, C, Jacobsen, K, Jahanmehr, N, Jakovljevic, M, Jauregui, A, Javanbakht, M, Jeemon, P, Jha, V, John, D, Johnson, C, Johnson, S, Jonas, J, Jürisson, M, Kabir, Z, Kadel, R, Kahsay, A, Kamal, R, Karch, A, Karema, C, Kasaeian, A, Kassebaum, N, Kastor, A, Katikireddi, S, Kawakami, N, Keiyoro, P, Kelbore, S, Kemmer, L, Kengne, A, Kesavachandran, C, Khader, Y, Khalil, I, Khan, E, Khang, Y, Khosravi, A, Khubchandani, J, Kieling, C, Kim, D, Kim, J, Kim, Y, Kimokoti, R, Kinfu, Y, Kisa, A, Kissimova-Skarbek, K, Kivimaki, M, Kokubo, Y, Kopec, J, Kosen, S, Koul, P, Koyanagi, A, Kravchenko, M, Krohn, K, Defo, B, Bicer, B, Kulikoff, X, Kumar, G, Kutz, M, Kyu, H, Lal, D, Lalloo, R, Lansingh, V, Larsson, A, Lazarus, J, Lee, P, Leigh, J, Leung, J, Leung, R, Levi, M, Li, Y, Liben, M, Linn, S, Liu, P, Liu, S, Lodha, R, Looker, K, Lopez, A, Lorkowski, S, Lotufo, P, Lozano, R, Lucas, T, Lunevicius, R, Mackay, M, Maddison, E, El Razek, H, El Razek, M, Majdan, M, Majdzadeh, R, Majeed, A, Malekzadeh, R, Malhotra, R, Malta, D, Mamun, A, Manguerra, H, Mantovani, L, Manyazewal, T, Mapoma, C, Marks, G, Martin, R, Martinez-Raga, J, Martins-Melo, F, Martopullo, I, Mathur, M, Mazidi, M, Mcalinden, C, Mcgaughey, M, Mcgrath, J, Mckee, M, Mehata, S, Mehndiratta, M, Meier, T, Meles, K, Memish, Z, Mendoza, W, Mengesha, M, Mengistie, M, Mensah, G, Mensink, G, Mereta, S, Meretoja, A, Meretoja, T, Mezgebe, H, Micha, R, Millear, A, Miller, T, Minnig, S, Mirarefin, M, Mirrakhimov, E, Misganaw, A, Mishra, S, Mitchell, P, Mohammad, K, Mohammed, K, Mohammed, S, Mohan, M, Mokdad, A, Mollenkopf, S, Monasta, L, Hernandez, J, Montico, M, Moradi-Lakeh, M, Moraga, P, Morawska, L, Morrison, S, Moses, M, Mountjoy-Venning, C, Mueller, U, Muller, K, Murthy, G, Musa, K, Naghavi, M, Naheed, A, Naidoo, K, Nangia, V, Natarajan, G, Negoi, I, Negoi, R, Nguyen, C, Nguyen, G, Nguyen, M, Nguyen, Q, Nguyen, T, Nichols, E, Ningrum, D, Nomura, M, Nong, V, Norheim, O, Noubiap, J, Obermeyer, C, Ogbo, F, Oh, I, Oladimeji, O, Olagunju, A, Olagunju, T, Olivares, P, Olsen, H, Olusanya, B, Olusanya, J, Ong, K, Oren, E, Ortiz, A, Owolabi, M, Mahesh, P, Pana, A, Panda, B, Panda-Jonas, S, Papachristou, C, Park, E, Patton, G, Paulson, K, Pereira, D, Perico, D, Pesudovs, K, Petzold, M, Phillips, M, Pigott, D, Pillay, J, Pinho, C, Piradov, M, Pishgar, F, Poulton, R, Pourmalek, F, Qorbani, M, Radfar, A, Rafay, A, Rao, P, Rahimi-Movaghar, V, Rahman, M, Ur Rahman, M, Rai, R, Rajsic, S, Ram, U, Ranabhat, C, Rawaf, S, Reidy, P, Reiner, R, Reinig, N, Reitsma, M, Remuzzi, G, Renzaho, A, Resnikoff, S, Rezaei, S, Blancas, M, Roba, K, Rojas-Rueda, D, Rokni, M, Roshandel, G, Roth, G, Roy, A, Rubagotti, E, Sadat, N, Safdarian, M, Safi, S, Safiri, S, Sagar, R, Salama, J, Salomon, J, Samy, A, Sanabria, J, Santomauro, D, Santos, I, Santos, J, Santric Milicevic, M, Sartorius, B, Satpathy, M, Sawhney, M, Saxena, S, Saylan, M, Shirude, S, Schmidt, M, Schneider, I, Schneider, M, Schöttker, B, Schutte, A, Schwebel, D, Schwendicke, F, Seedat, S, Sepanlou, S, Servan-Mori, E, Shackelford, K, Shaheen, A, Shahraz, S, Shaikh, M, Shamsipour, M, Shamsizadeh, M, Islam, S, Sharma, J, Sharma, R, She, J, Shi, P, Shibuya, K, Shields, C, Shiferaw, M, Shigematsu, M, Shin, M, Shiri, R, Shirkoohi, R, Shishani, K, Shoman, H, Shrime, M, Silberberg, D, Silva, D, Silva, J, Silveira, D, Singh, J, Singh, V, Sinha, D, Skiadaresi, E, Slepak, E, Sligar, A, Smith, A, Smith, D, Smith, M, Sobaih, B, Sobngwi, E, Soljak, M, Soneji, S, Sorensen, R, Sposato, L, Sreeramareddy, C, Srinivasan, V, Stanaway, J, Stein, D, Steiner, C, Steinke, S, Stokes, M, Strub, B, Sufiyan, M, Abdulkader, R, Sunguya, B, Sur, P, Swaminathan, S, Sykes, B, Sylte, D, Szoeke, C, Tabarés-Seisdedos, R, Tadakamadla, S, Tandon, N, Tao, T, Tarekegn, Y, Tavakkoli, M, Taveira, N, Tegegne, T, Shifa, G, Terkawi, A, Tessema, G, Thakur, J, Thankappan, K, Thrift, A, Tiruye, T, Tobe-Gai, R, Topor-Madry, R, Torre, A, Tortajada, M, Tran, B, Troeger, C, Truelsen, T, Tsoi, D, Tuem, K, Tuzcu, E, Tyrovolas, S, Ukwaja, K, Uneke, C, Updike, R, Uthman, O, Van Boven, J, Van Donkelaar, A, Varughese, S, Vasankari, T, Venketasubramanian, N, Vidavalur, R, Violante, F, Vladimirov, S, Vlassov, V, Vollset, S, Vos, T, Wadilo, F, Wakayo, T, Wallin, M, Wang, Y, Weichenthal, S, Weiderpass, E, Weintraub, R, Weiss, D, Werdecker, A, Westerman, R, Whiteford, H, Wijeratne, T, Wiysonge, C, Woldeyes, B, Wolfe, C, Woodbrook, R, Xavier, D, Xu, G, Yadgir, S, Yakob, B, Yan, L, Yano, Y, Yaseri, M, Ye, P, Yimam, H, Yip, P, Yonemoto, N, Yoon, S, Yotebieng, M, Younis, M, Zaidi, Z, El Sayed Zaki, M, Zavala-Arciniega, L, Zhang, X, Zipkin, B, Zodpey, S, Lim, S, and Murray, C

Subjects
Adult, Male, Adolescent, DEVELOPMENT ASSISTANCE, Global Health, projection indicators to 2030, CHINA, Global Burden of Disease, Health Statu, MEXICO, Noncommunicable Disease, Young Adult, SYSTEMS, Quality-Adjusted Life Year, General & Internal Medicine, Infant Mortality, Medicine and Health Sciences, Conservation of Natural Resource, gains and gaps for the health-related SDGs,annualized rates of change, projection indicators to 2030, Health Status Indicator, annualized rates of change, Child, Medicine (all), MORTALITY, Infant, Newborn, Infant, Child Abuse, Sexual, Middle Aged, PREPAID PRIVATE, CARE, COVERAGE, Sex Offense, Child, Preschool, Female, 40-PERCENT, GOVERNMENT, gains and gaps for the health-related SDGs, Human
Abstract

Background The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2.5th percentile estimated between 1990 and 2030, and 100 as the 97.5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. Findings Globally, the median health-related SDG index was 56.7 (IQR 31.9-66.8) in 2016 and country-level performance markedly varied, with Singapore (86.8, 95% uncertainty interval 84.6-88.9), Iceland (86.0, 84.1-87.6), and Sweden (85.6, 81.8-87.8) having the highest levels in 2016 and Afghanistan (10.9, 9.6-11.9), the Central African Republic (11.0, 8.8-13.8), and Somalia (11.3, 9.5-13.1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. Interpretation GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations. Copyright The Authors. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 4.0 license.

Published
2017

21. Focal Cerebral Arteriopathy of Childhood: Novel Severity Score and Natural History

Author

Fullerton, Heather J, Stence, Nicholas, Hills, Nancy K, Jiang, Bin, Amlie-Lefond, Catherine, Bernard, Timothy J, Friedman, Neil R, Ichord, Rebecca, Mackay, Mark T, Rafay, Mubeen F, Chabrier, Stéphane, Steinlin, Maja, Elkind, Mitchell SV, deVeber, Gabrielle A, Wintermark, Max, and VIPS Investigators

Subjects
Brain Infarction, Male, Middle Cerebral Artery, Anterior Cerebral Artery, Adolescent, Computed Tomography Angiography, Clinical Sciences, Cardiorespiratory Medicine and Haematology, Severity of Illness Index, VIPS Investigators, Humans, Carotid Stenosis, Child, Preschool, Pediatric, Posterior Cerebral Artery, Neurology & Neurosurgery, Neurosciences, Infant, cerebrovascular disorders, Internal, brain ischemia, follow-up studies, Brain Disorders, Cerebral Angiography, Stroke, Disease Progression, Female, Cerebral Arterial Diseases, Carotid Artery, Magnetic Resonance Angiography
Abstract

Background and Purpose- Focal cerebral arteriopathy (FCA)-a common cause of arterial ischemic stroke in previously healthy children-often progresses over days to weeks, increasing the risk of recurrent stroke. We developed a novel severity scoring system designed to quantify FCA progression and correlate with clinical outcomes. Methods- The VIPS study (Vascular Effects of Infection in Pediatric Stroke) prospectively enrolled 355 children with arterial ischemic stroke (2010-2014), including 41 with centrally confirmed FCA. Two neuroradiologists independently reviewed FCA cerebrovascular imaging, assigning a graded severity score of zero (no involvement) to 4 (occlusion) to individual arterial segments. The FCA severity score (FCASS) was the unweighted sum. In an iterative process, we modeled scores derived from different combinations of arterial segments to identify the model that optimized correlation with clinical outcome, simplicity, and reliability. Results- The optimal FCASS summed scores from 5 arterial segments: supraclinoid internal carotid artery, A1, A2, M1, and M2. The median (interquartile range) baseline FCASS was 4 (2-6). Of 33 children with follow-up imaging, the maximum FCASS (at any time point) was 7 (5-9). Twenty-four (73%) had FCA progression on follow-up with their maximum FCASS at a median of 8 (5-35.5) days poststroke; their median FCASS increase was 4 (2.5-6). FCASS did not correlate with recurrent arterial ischemic stroke. Maximum (but not baseline) FCASS correlated with 1-year pediatric stroke outcome measures ( P=0.037). Conclusions- Our novel scoring system for FCA severity correlates with neurological outcomes in the VIPS cohort and provides a tool for FCA treatment trials under development.

Published
2018

22. Neonatal, infant, and under-5 mortality and morbidity burden in the Eastern Mediterranean region: findings from the Global Burden of Disease 2015 study

Author

Mokdad, Ali H, Khalil, Ibrahim, Collison, Michael, El Bcheraoui, Charbel, Charara, Raghid, Moradi-Lakeh, Maziar, Afshin, Ashkan, Krohn, Kristopher J, Daoud, Farah, Chew, Adrienne, Kassebaum, Nicholas J, Colombara, Danny, Cornaby, Leslie, Ehrenkranz, Rebecca, Foreman, Kyle J, Fraser, Maya, Frostad, Joseph, Kemmer, Laura, Kulikoff, Xie Rachel, Kutz, Michael, Kyu, Hmwe H, Liu, Patrick, Mikesell, Joseph, Nguyen, Grant, Rao, Puja C, Silpakit, Naris, Sligar, Amber, Smith, Alison, Stanaway, Jeffrey D, Arnlov, Johan, Abate, Kalkidan Hassen, Kiadaliri, Aliasghar Ahmad, Alam, Khurshid, Alasfoor, Deena, Ali, Raghib, Alizadeh-Navaei, Reza, Alraddadi, Rajaa, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Anber, Nahla, Ansari, Hossein, Antonio, Carl Abelardo T, Anwari, Palwasha, Artaman, Al, Asayesh, Hamid, Asgedom, Solomon Weldegebreal, Azzopardi, Peter, Bacha, Umar, Barac, Aleksandra, Barker-Collo, Suzanne L, Bedi, Neeraj, Beghi, Ettore, Bennett, Derrick A, Bhutta, Zulfiqar A, Bisanzio, Donal, Castaneda-Orjuela, Carlos A, Estanislao Castro, Ruben, Danawi, Hadi, Deribe, Kebede, Deribew, Amare, Jarlais, Don C Des, deVeber, Gabrielle A, Dey, Subhojit, Dharmaratne, Samath D, Djalalinia, Shirin, Do, Huyen Phuc, Esteghamati, Alireza, Farvid, Maryam S, Fereshtehnejad, Seyed-Mohammad, Fischer, Florian, Gebrehiwot, Tsegaye Tewelde, Giussani, Giorgia, Gona, Philimon N, Hafezi-Nejad, Nima, Hamadeh, Randah Ribhi, Hamidi, Samer, Hoy, Damian G, Hu, Guoqing, John, Denny, Jonas, Jost B, Karimi, Seyed M, Kasaeian, Amir, Khader, Yousef Saleh, Khan, Ejaz Ahmad, Khan, Gulfaraz, Kim, Daniel, Kim, Yun Jin, Kinfu, Yohannes, Larson, Heidi J, Latif, Asma Abdul, Leasher, Janet L, Lunevicius, Raimundas, Abd El Razek, Hassan Magdy, Abd El Razek, Mohammed Magdy, Majeed, Azeem, Malekzadeh, Reza, Memish, Ziad A, Mendoza, Walter, Mezgebe, Haftay Berhane, Miller, Ted R, Monasta, Lorenzo, Nguyen, Quyen Le, Obermeyer, Carla Makhlouf, Ortiz, Alberto, Papachristou, Christina, Park, Eun-Kee, Pereira, Claudia C, Petzold, Max, Pereira, David M, Phillips, Michael Robert, Pourmalek, Farshad, Qorbani, Mostafa, Rafay, Anwar, Rahimi-Movaghar, Vafa, Rai, Rajesh Kumar, Rana, Saleem M, Rawaf, David Laith, Rawaf, Salman, Renzaho, Andre MN, Rezaei, Satar, Rezai, Mohammad Sadegh, Ronfani, Luca, Roshandel, Gholamreza, Ruhago, George Mugambage, Safdarian, Mahdi, Safiri, Saeid, Sahraian, Mohammad Ali, Salamati, Payman, Samy, Abdallah M, Sanabria, Juan Ramon, Sartorius, Benn, Schwebel, David C, Seedat, Soraya, Sepanlou, Sadaf G, Setegn, Tesfaye, Shaheen, Amira, Shaikh, Masood Ali, Shamsizadeh, Morteza, Shiri, Rahman, Skirbekk, Vegard, Sobaih, Badr HA, Sreeramareddy, Chandrashekhar T, Stathopoulou, Vasiliki, Abdulkader, Rizwan Suliankatchi, Tehrani-Banihashemi, Arash, Temsah, Mohamad-Hani, Thakur, Arabia JS, Thomson, Alan J, Tran, Bach Xuan, Truelsen, Thomas, Ukwaja, Kingsley Nnanna, Uthman, Olalekan A, Vasankari, Tommi, Vlassov, Vasiliy Victorovich, Weiderpass, Elisabete, Weintraub, Robert G, Werdecker, Andrea, Yaghoubi, Mohsen, Yaseri, Mehdi, Yonemoto, Naohiro, Younis, Mustafa Z, Yu, Chuanhua, Jumaan, Aisha O, Vos, Theo, Hay, Simon I, Naghavi, Mohsen, Wang, Haidong, Murray, Christopher JL, Reg, GBD 2015 Eastern Mediterranean, Department of Public Health, Clinicum, and University of Helsinki

Subjects
Male, PNEUMONIA, Pediatrics, Health (social science), Poison control, 030204 cardiovascular system & hematology, Infant mortality, Global Health, Global Burden of Disease, 0302 clinical medicine, Neonatal, Global health, LIFE EXPECTANCY, 030212 general & internal medicine, health care economics and organizations, Mediterranean Region, Child Health, Burden of disease, 3142 Public health care science, environmental and occupational health, 3. Good health, UPDATED SYSTEMATIC ANALYSIS, 1117 Public Health And Health Services, Child, Preschool, Female, Original Article, Public Health, CHILD-MORTALITY, INTERVENTIONS, COUNTRIES, Child mortality, medicine.medical_specialty, INTEGRATED APPROACH, Eastern Mediterranean Region, 03 medical and health sciences, Middle East, Neonatal mortality, Environmental health, Injury prevention, medicine, Humans, PROGRESS, Perinatal Mortality, METAANALYSIS, business.industry, Public Health, Environmental and Occupational Health, Infant, Newborn, Klinisk medicin, Infant, DIARRHEA, mortality, Eastern mediterranean, Life expectancy, Morbidity, Clinical Medicine, business
Abstract

Objectives Although substantial reductions in under-5 mortality have been observed during the past 35 years, progress in the Eastern Mediterranean Region (EMR) has been uneven. This paper provides an overview of child mortality and morbidity in the EMR based on the Global Burden of Disease (GBD) study. Methods We used GBD 2015 study results to explore under-5 mortality and morbidity in EMR countries. Results In 2015, 755,844 (95% uncertainty interval (UI) 712,064–801,565) children under 5 died in the EMR. In the early neonatal category, deaths in the EMR decreased by 22.4%, compared to 42.4% globally. The rate of years of life lost per 100,000 population under 5 decreased 54.38% from 177,537 (173,812–181,463) in 1990 to 80,985 (76,308–85,876) in 2015; the rate of years lived with disability decreased by 0.57% in the EMR compared to 9.97% globally. Conclusions Our findings call for accelerated action to decrease child morbidity and mortality in the EMR. Governments and organizations should coordinate efforts to address this burden. Political commitment is needed to ensure that child health receives the resources needed to end preventable deaths. Electronic supplementary material The online version of this article (doi:10.1007/s00038-017-0998-x) contains supplementary material, which is available to authorized users.

Published
2018

23. Mortality after pediatric arterial ischemic stroke

Author

Beslow, Lauren A., Dowling, Michael M., Hassanein, Sahar M.A., Lynch, John K., Zafeiriou, Dimitrios, Sun, Lisa R., Kopyta, Ilona, Titomanlio, Luigi, Kolk, Anneli, Chan, Anthony, Biller, Jose, Grabowski, Eric F., Abdalla, Abdalla A., Mackay, Mark T., DeVeber, Gabrielle, Ashwal, Steve, Ferriero, Donna, Fullerton, Heather, Ichord, Rebecca, Kirkham, Fenella, O'Callaghan, Finbar, Pavlakis, Steve, Sebire, Guillaume, Willan, Andrew, Kirton, Adam, Goldenberg, Neil, Saengpattrachai, Montri, Crosswell, Hal, Rivkin, Michael, Bjornson, Bruce, Tatishvili, Nana, Brankovic-Sreckovic, Vesna, Bernard, Timothy, Armstrong, Jennifer, Humphreys, Peter, Heyer, Geoffrey, Fryer, Robert, Yeh, Ann, Billinghurst, Lori, Khoury, Chaouki, Abraham, Lisa, Whelan, Harry, Nowak-Gottl, Ulrike, Wainwright, Mark, Condie, John, Carpenter, Jessica, Holzhauer, Susanne, Guang, Yang, Zou, Li Ping, Taylor, J. Michael, and Pediatrics

Subjects
Heart Defects, Congenital, Male, Pediatrics, medicine.medical_specialty, Multivariate analysis, Heart disease, Infarction, Disease, Brain Ischemia, Brain ischemia, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 030225 pediatrics, medicine, Humans, Hospital Mortality, Registries, Child, Stroke, business.industry, Infant, Newborn, Infant, Odds ratio, Hispanic or Latino, medicine.disease, Confidence interval, United States, Hospitalization, Child, Preschool, Pediatrics, Perinatology and Child Health, Multivariate Analysis, Female, business, 030217 neurology & neurosurgery
Abstract

OBJECTIVES: Cerebrovascular disease is among the top 10 causes of death in US children, but risk factors for mortality are poorly understood. Within an international registry, we identify predictors of in-hospital mortality after pediatric arterial ischemic stroke (AIS). METHODS: Neonates (0–28 days) and children (29 days– RESULTS: Fourteen of 915 neonates (1.5%) and 70 of 2273 children (3.1%) died during hospitalization. Of 48 cases with reported causes of death, 31 (64.6%) were stroke-related, with remaining deaths attributed to medical disease. In multivariable analysis, congenital heart disease (odds ratio [OR]: 3.88; 95% confidence interval [CI]: 1.23–12.29; P = .021), posterior plus anterior circulation stroke (OR: 5.36; 95% CI: 1.70–16.85; P = .004), and stroke presentation without seizures (OR: 3.95; 95% CI: 1.26–12.37; P = .019) were associated with in-hospital mortality for neonates. Hispanic ethnicity (OR: 3.12; 95% CI: 1.56–6.24; P = .001), congenital heart disease (OR: 3.14; 95% CI: 1.75–5.61; P < .001), and posterior plus anterior circulation stroke (OR: 2.71; 95% CI: 1.40–5.25; P = .003) were associated with in-hospital mortality for children. CONCLUSIONS: In-hospital mortality occurred in 2.6% of pediatric AIS cases. Most deaths were attributable to stroke. Risk factors for in-hospital mortality included congenital heart disease and posterior plus anterior circulation stroke. Presentation without seizures and Hispanic ethnicity were also associated with mortality for neonates and children, respectively. Awareness and study of risk factors for mortality represent opportunities to increase survival.

Published
2018

24. Herpesvirus Infections and Childhood Arterial Ischemic Stroke: Results of the VIPS Study

Author

Elkind, Mitchell SV, Hills, Nancy K, Glaser, Carol A, Lo, Warren D, Amlie-Lefond, Catherine, Dlamini, Nomazulu, Kneen, Rachel, Hod, Eldad A, Wintermark, Max, deVeber, Gabrielle A, Fullerton, Heather J, and VIPS Investigators

Subjects
Male, Internationality, Adolescent, pediatrics, viruses, Clinical Sciences, herpesviridae infections, Cardiorespiratory Medicine and Haematology, Brain Ischemia, 2.2 Factors relating to the physical environment, Humans, Prospective Studies, Aetiology, Preschool, child, Prevention, VIPS Investigators, Infant, Newborn, stroke, infection, Brain Disorders, Infectious Diseases, Cardiovascular System & Hematology, Case-Control Studies, Public Health and Health Services, Sexually Transmitted Infections, Female
Abstract

BackgroundEpidemiological studies demonstrate that childhood infections, including varicella zoster virus, are associated with an increased risk of arterial ischemic stroke (AIS). Other herpesviruses have been linked to childhood AIS in case reports. We sought to determine whether herpesvirus infections, which are potentially treatable, increase the risk of childhood AIS.Methods and resultsWe enrolled 326 centrally confirmed cases of AIS and 115 stroke-free controls with trauma (29 days to 18 years of age) with acute blood samples (≤3 weeks after stroke/trauma); cases had convalescent samples (7-28 days later) when feasible. Samples were tested by commercial enzyme-linked immunosorbent assay kits for immunoglobulin M/immunoglobulin G antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus. An algorithm developed a priori classified serological evidence of past and acute herpesvirus infection as dichotomous variables. The median (quartiles) age was 7.7 (3.1-14.3) years for cases and 10.7 (6.9-13.2) years for controls (P=0.03). Serological evidence of past infection did not differ between cases and controls. However, serological evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socioeconomic status (odds ratio, 2.2; 95% confidence interval, 1.2-4.0; P=0.007). Among 187 cases with acute and convalescent blood samples, 85 (45%) showed evidence of acute herpesvirus infection; herpes simplex virus 1 was found most often. Most infections were asymptomatic.ConclusionsHerpesviruses may act as a trigger for childhood AIS, even if the infection is subclinical. Antivirals like acyclovir might have a role in the prevention of recurrent stroke if further studies confirm a causal relationship.

Published
2016

25. Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study

Author

Fullerton, Heather J, Wintermark, Max, Hills, Nancy K, Dowling, Michael M, Tan, Marilyn, Rafay, Mubeen F, Elkind, Mitchell SV, Barkovich, A James, deVeber, Gabrielle A, and VIPS Investigators

Subjects
Male, Internationality, Adolescent, pediatrics, Clinical Sciences, Cardiorespiratory Medicine and Haematology, Brain Ischemia, Cohort Studies, VIPS Investigators, Recurrence, Risk Factors, Humans, Prospective Studies, Child, Preschool, Pediatric, Neurology & Neurosurgery, Prevention, Neurosciences, Infant, vaccination, Atherosclerosis, stroke, Brain Disorders, risk factor, Female, Cerebral Arterial Diseases, Follow-Up Studies
Abstract

Background and purposePublished cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era.MethodsThe Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review.ResultsOf the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12%-48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection.ConclusionsChildren with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.

Published
2016

26. Thrombolysis in Pediatric Stroke (TIPS) study

Author

Rivkin, Michael J, deVeber, Gabrielle, Ichord, Rebecca N, Kirton, Adam, Chan, Anthony, Hovinga, Collin A, Gill, Joan Cox, Szabo, Aniko, Hill, Michael D, Scholz, Kelley, and Amlie-Lefond, Catherine

Subjects
Male, Time Factors, Adolescent, Cardiology, Bayes Theorem, Severity of Illness Index, Article, Cohort Studies, Stroke, Treatment Outcome, Fibrinolytic Agents, Child, Preschool, Tissue Plasminogen Activator, Humans, Female, Thrombolytic Therapy, Child, Infusions, Intravenous
Published
2015

27. Arteriopathy diagnosis in childhood arterial ischemic stroke: results of the vascular effects of infection in pediatric stroke study

Author

Wintermark, Max, Hills, Nancy K, deVeber, Gabrielle A, Barkovich, A James, Elkind, Mitchell SV, Sear, Katherine, Zhu, Guangming, Leiva-Salinas, Carlos, Hou, Qinghua, Dowling, Michael M, Bernard, Timothy J, Friedman, Neil R, Ichord, Rebecca N, Fullerton, Heather J, and VIPS Investigators

Subjects
Male, Adolescent, pediatrics, Clinical Sciences, Cardiorespiratory Medicine and Haematology, VIPS Investigators, Clinical Research, Humans, Vascular Diseases, Child, Preschool, Pediatric, screening and diagnosis, Neurology & Neurosurgery, Prevention, Neurosciences, Infant, Arteries, Newborn, Magnetic Resonance Imaging, stroke, cerebral arterial diseases, Brain Disorders, Detection, transient ischemic attack, Female, 4.2 Evaluation of markers and technologies
Abstract

Background and purposeAlthough arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke.MethodsVascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step.ResultsCases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78).ConclusionsClinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

Published
2014

28. Inter-rater Reliability of the Pediatric NIH Stroke Scale (PedNIHSS) in a Multicenter Study

Author

Ichord, Rebecca N, Bastian, Rachel, Abraham, Lisa, Askalan, Rand, Benedict, Susan, Bernard, Timothy J, Beslow, Lauren, deVeber, Gabrielle, Dowling, Michael, Friedman, Neil, Fullerton, Heather, Jordan, Lori, Kan, Li, Kirton, Adam, Amlie-Lefond, Catherine, Licht, Daniel, Lo, Warren, McClure, Chalmer, Pavlakis, Steve, Smith, Sabrina E, Tan, Marilyn, Kasner, Scott, and Jawad, Abbas F

Subjects
Male, Observer Variation, Adolescent, Reproducibility of Results, Pilot Projects, Severity of Illness Index, Article, United States, Cohort Studies, Stroke, National Institutes of Health (U.S.), Child, Preschool, Humans, Female, Prospective Studies, Child
Abstract

Stroke is an important cause of death and disability among children. Clinical trials for childhood stroke require a valid and reliable acute clinical stroke scale. We evaluated interrater reliability (IRR) of a pediatric adaptation of the National Institutes of Health Stroke Scale.The pediatric adaptation of the National Institutes of Health Stroke Scale was developed by pediatric and adult stroke experts by modifying each item of the adult National Institutes of Health Stroke Scale for children, retaining all examination items and scoring ranges of the National Institutes of Health Stroke Scale. Children 2 to 18 years of age with acute arterial ischemic stroke were enrolled in a prospective cohort study from 15 North American sites from January 2007 to October 2009. Examiners were child neurologists certified in the adult National Institutes of Health Stroke Scale. Each subject was examined daily for 7 days or until discharge. A subset of patients at 3 sites was scored simultaneously and independently by 2 study neurologists.IRR testing was performed in 25 of 113 a median of 3 days (interquartile range, 2 to 4 days) after symptom onset. Patient demographics, total initial pediatric adaptation of the National Institutes of Health Stroke Scale scores, risk factors, and infarct characteristics in the IRR subset were similar to the non-IRR subset. The 2 raters' total scores were identical in 60% and within 1 point in 84%. IRR was excellent as measured by concordance correlation coefficient of 0.97 (95% CI, 0.94 to 0.99); intraclass correlation coefficient of 0.99 (95% CI, 0.97 to 0.99); precision measured by Pearson ρ of 0.97; and accuracy measured by the bias correction factor of 1.0.There was excellent IRR of the pediatric adaptation of the National Institutes of Health Stroke Scale in a multicenter prospective cohort performed by trained child neurologists.

Published
2011

29. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013

Author

Yong Zhao, Hadi Danawi, Bach Xuan Tran, Gene Bukhman, Vasiliki Stathopoulou, Taavi Tillmann, Nelson Alvis-Guzman, Yongmei Li, Jerry Puthenpurakal Abraham, Sudan Prasad Neupane, Jack Caravanos, Ben Schöttker, Rafael Lozano, Damian G Hoy, Yoshihiro Kokubo, Nicholas J K Breitborde, Sergey Soshnikov, Yukito Shinohara, Randall V. Martin, Michael Brainin, Fernando Perez-Ruiz, Yingfeng Zheng, Santosh Mishra, Julio Cesar Montañez Hernandez, Michael Phillips, Belinda J. Gabbe, Hebe N. Gouda, Ziad A. Memish, Rupert R A Bourne, Guoqing Hu, Emmanuel A. Ameh, Abigail McLain, Michelle L. Bell, Christopher Margono, Marissa Iannarone, Wilkister N. Moturi, Donald H. Silberberg, Carl Abelardo T. Antonio, Nataliya Foigt, Anand Dayama, Yanping Wang, Amanda J. Mason-Jones, Bolajoko O. Olusanya, Monica S. Vavilala, Katherine B Gibney, David Tanne, Sidibe S Kany Roseline, Marcella Montico, Abhishek Singh, Sarah Derrett, Alireza Esteghamati, Seok Jun Yoon, Corine Karema, Rakhi Dandona, David M. Pereira, Kazem Rahimi, Gitanjali M. Singh, Vivekanand Jha, John Hornberger, Anne M. Riederer, Kathryn H. Jacobsen, Andrea Pedroza, Lily Alexander, Fiona M. Blyth, Tommi Vasankari, Kyle J Foreman, Rana J. Asghar, Tilahun Nigatu Haregu, Yousef Khader, Rafael Alfonso-Cristancho, Suzanne Barker-Collo, Lydia S. Atkins, Simerjot K. Jassal, Mohammad Ali Sahraian, Peter Scarborough, Hans W. Hoek, E. Ray Dorsey, Muluken Dessalegn, David C. Schwebel, Gavin Shaddick, Thomas D. Fleming, Mohammad Tavakkoli, Dorairaj Prabhakaran, Mohammad H. Forouzanfar, Christopher C. Mapoma, Jost B. Jonas, Erin C Mullany, Gene F. Kwan, Johanna M. Geleijnse, Antonio Luiz Pinho Ribeiro, Roberto Tchio Talongwa, Tolesa Bekele, Jed D. Blore, Gunn Marit Aasvang, Philimon Gona, Miguel Angel Alegretti, Babak Eshrati, Mitsuru Mukaigawara, Richard F. Gillum, Odgerel Chimed-Ochir, Ubai Alsharif, Richard C. Franklin, Felix Masiye, Richard T. Burnett, Sanjay Krishnaswami, Martin McKee, John J Huang, Lucía Cuevas-Nasu, Wagner Marcenes, Walid Ammar, Knud Juel, Joseph R. Zunt, Martha M Téllez Rojo, Mamta Swaroop, Noela M Prasad, Azmeraw T. Amare, Tim Driscoll, Michael Kravchenko, Heresh Amini, Amir Sapkota, Theo Vos, Charlotte Watts, Dennis Odai Laryea, D. Alex Quistberg, Justin Beardsley, Cheng Huang, Adnan M. Durrani, Sarah V Thackway, Rita Van Dingenen, Manami Inoue, Martha Híjar, Honglei Chen, Amany H. Refaat, Yichong Li, Vineet K. Chadha, Wenzhi Wang, Louisa Degenhardt, Kingsley N. Ukwaja, Nayu Ikeda, James D. Wilkinson, Linh N Bui, Maria Hagströmer, Gonghuan Yang, Ann Kristin Knudsen, David J. Margolis, Soewarta Kosen, Hans Kromhout, Atsushi Goto, Man Mohan Mehndiratta, Thomas N. Williams, Michael Soljak, Yun Jin Kim, Hideaki Toyoshima, Jeyaraj D Pandian, Borja del Pozo-Cruz, Soufiane Boufous, Ivy Shiue, Anders Larsson, Guilherme V. Polanczyk, John Powles, Yara A. Halasa, Robin Room, Ratilal Lalloo, Carolina Batis Ruvalcaba, Panniyammakal Jeemon, Elisabete Weiderpass, Jürgen Rehm, Ejaz Ahmad Khan, Alicia Aleman, Zacharie Tsala Dimbuene, Elena Alvarez, Rachelle Buchbinder, Randah R. Hamadeh, Bryan Hubbell, Sadaf G. Sepanlou, Farhad Islami, Costas A. Christophi, Heidi Stöckl, Ismael R. Campos-Nonato, Nigel Bruce, Edward J Mills, Samuel A L Perry, Taavi Lai, Baffour Awuah, Mete Saylan, Karen J. Courville, Arindam Basu, Vanessa De la Cruz-Góngora, Teresita González de Cosío, Naohiro Yonemoto, Frida Namnyak Ngalesoni, Muluken Azage Yenesew, Atte Meretoja, Michael Brauer, Cyrus Cooper, Giorgia Giussani, Valentina S. Arsic Arsenijevic, Vasiliy Victorovich Vlassov, André Karch, Leilei Duan, Matthew M Coates, Omid Ameli, Gelin Xu, Matthias Endres, Ganesan Karthikeyan, Ione Jayce Ceola Schneider, Mohamed Hsairi, Palwasha Anwari, Mazin J. Al Khabouri, Dariush Mozaffarian, Juan R. Sanabria, Pablo M. Lavados, Sumeet S. Chugh, Johan Ärnlöv, Ivo Rakovac, Maurice Giroud, Haidong Kan, Ibrahim Abdelmageem Mohamed Ginawi, José Luis Texcalac-Sangrador, Luigi Naldi, Erica Leigh Slepak, Deena Alasfoor, James E. Saunders, Richard Matzopoulos, Talal Bakfalouni, Stein Emil Vollset, Andrea Werdecker, Lennert J. Veerman, Lorenzo Monasta, Henrica A. F. M. Jansen, Reyna A Gutiérrez, Brittany Wurtz, Luz Maria Sanchez, Lijing L. Yan, M. Patrice Lindsay, Michele Meltzer, Sanjay Basu, Steven van de Vijver, Alaa Badawi, Thomas Claßen, Young-Ho Khang, Brett M. Kissela, Jun Zhu, In-Hwan Oh, Fiona J Charlson, Maria Cecilia Bahit, Dinorah González-Castell, Rosario Cárdenas, Dan Poenaru, Sayed Saidul Alam, Mitchell T. Wallin, Harish Chander Gugnani, James Leigh, Ferrán Catalá-López, Lidia Morawska, Jim van Os, Stephanie J. London, Kaire Innos, Isabelle Romieu, Fiorella Cavalleri, Adrian Davis, Hwee Pin Phua, Chakib Nejjari, Héctor Gómez Dantés, Boris I. Pavlin, Karen Sliwa, Lynne Gaffikin, Constance D. Pond, Michael F. MacIntyre, Blake Thomson, Norberto Perico, Ronny Westerman, Samantha M. Colquhoun, Michael H. Criqui, Ana Maria Nogales Vasconcelos, Wubegzier Mekonnen, Bulat Idrisov, Ana Basto-Abreu, Andrew G. M. Bulloch, Jasvinder A. Singh, Vinod K. Paul, Emin Murat Tuzcu, Svetlana Popova, Hmwe H Kyu, Richard L. Guerrant, Mohammed I. Albittar, Srikanth Mangalam, Steven E. Lipshultz, Lela Sturua, Semaw Ferede Abera, Eduardo Bernabé, George D. Thurston, Bruno F. Sunguya, Tiffany Ku, Alejandra G. Contreras, Abdullah Sulieman Terkawi, Charles Atkinson, Ashkan Afshin, Heidi J. Larson, Abdullatif Husseini, Jose C. Adsuar, Reza Assadi, Ademola Lukman Adelekan, Joshua A. Salomon, Yousef M. Elshrek, Gokalp Kadri Yentur, Devina Nand, Narayanaswamy Venketasubramanian, Graça Maria Ferreira De Lima, Maheswar Satpathy, Fotis Topouzis, Traolach S. Brugha, Hywel C Williams, Coen H. Van Gool, Andrew H. Kemp, Awoke Misganaw, Amado D Quezada, Norito Kawakami, Bert Brunekreef, Peter Burney, Tati S. Warouw, Jongmin Lee, Inga Dora Sigfusdottir, Marcel Tanner, Solveig A. Cunningham, Benjamin O. Anderson, Tariku Jibat Beyene, Lars Barregard, Xia Wan, Giuseppe Remuzzi, Bernadette Thomas, Lilia S Pedraza, Massimo Cirillo, Alina Rodriguez, Ricky Leung, Farshad Pourmalek, K. Srinath Reddy, Charles D.A. Wolfe, Ulrich O Mueller, Neeraj Bedi, Al Artaman, Lucia Hernandez, Itamar S. Santos, C. Arden Pope, Norlinah Mohamed Ibrahim, Carlo Irwin A. Panelo, Selen Begüm Uzun, Miltiadis K. Tsilimbaris, Anwar Rafay, Daniel Dicker, Melvin Barrientos Marzan, Sajjad Ur Rahman, Mohammed O. Basulaiman, Edgar P. Simard, Mohammad T Mashal, Maysaa El Sayed Zaki, Shiwei Liu, Don C. Des Jarlais, Bo Norrving, Salvador Villalpando, Miia Kivipelto, Yang Liu, Carolina Maria Teixeira, Catalina Medina, Sudha Jayaraman, Josep Maria Haro, Diego De Leo, Angel J Paternina Caicedo, Abigail C. McKay, Eric L. Ding, Mukesh Dherani, Ljiljana Pejin Stokic, Vinay Nangia, Sukanta Saha, Juan Liang, Elisabeth Cardis, Zourkaleini Younoussi, José R Nogueira, Braden Te Ao, Vasco Manuel Pedro Machado, Lionel Racapé, Ting Wu Chuang, Shahab Khatibzadeh, E Filipa de Castro, Barthelemy Kuate Defo, Ulises Trujillo, Alan D. Lopez, Soraya Seedat, Lope H Barrero, Linhong Wang, Daniel Pope, Alexandra Brazinova, Faris Lami, Valentina Colistro, G Anil Kumar, Derek F J Fay, Haidong Wang, Hwashin H. Shin, Raimundas Lunevicius, Suzanne Polinder, Dietrich Plass, David Rojas-Rueda, Stephen S Lim, Tania G Sánchez-Pimienta, K.M. Venkat Narayan, Yuantao Hao, Jung-Chen Chang, Corina Benjet, Seyed-Mohammad Fereshtehnejad, Luciano A. Sposato, Stan Biryukov, Kunihiro Matsushita, Beth E. Ebel, Cleusa P. Ferri, Soumya Swaminathan, K. Ryan Wessells, Gustavo Velasquez-Melendez, Leslie T. Cooper, David O. Carpenter, Nancy Lopez, Bryan L. Sykes, Sandra Nolte, Murray B. Stein, Paul N. Jensen, Fabiola Mejía-Rodríguez, Xiaonong Zou, Bradford D. Gessner, Dhruv S. Kazi, Dragos Virgil Davitoiu, Alejandra Jáuregui, Pouria Heydarpour, Megan Bohensky, Harvey Whiteford, Berrak Bora Basara, Zhengming Chen, Gregory R. Wagner, Paul I. Dargan, Hermann Brenner, Nima Hafezi-Nejad, John Nelson Opio, Scott Weichenthal, Deborah Salvo, Jun She, Tea Lallukka, Carolyn C. Gotay, Stephen G. Waller, Christian Kieling, Shivanthi Balalla, Valery L. Feigin, Qing Lan, Matias Trillini, Adam D M Briggs, Sungroul Kim, Niveen M E Abu-Rmeileh, Renata Micha, Sergey Petrovich Ermakov, Ole Frithjof Norheim, Zulfiqar A Bhutta, Paul S. F. Yip, Grant Nguyen, Ralph L. Sacco, Biju Abraham, Ken Takahashi, Jixiang Ma, Peter A. Meaney, Ayse Abbasoglu Ozgoren, Kimberly Cooperrider, M Rifat Kose, Shams Eldin Ali Hassan Khalifa, Rasmus Havmoeller, Alize J. Ferrari, Kebede Deribe, Nadim E. Karam, George A. Mensah, Bongani M. Mayosi, Konrad Pesudovs, Joanna Moschandreas, Ziad Nahas, James Damsere-Derry, Nsanzimana Sabin, Tonatiuh Barrientos-Gutiérrez, Ying Jiang, Andre Pascal Kengne, Peter Allebeck, Jonas Minet Kinge, Shankuan Zhu, Guy B. Marks, Daniel C Casey, Marco A Avila, Anna Roca, Lalit Dandona, Ami R. Moore, Adansi A. Amankwaa, David Gunnell, Andre Keren, Yohannes Adama Melaku, Nhung T Nguyen, Anthony D. Woolf, Mayuree Rao, Peter J. Allen, Christina Papachristou, Karzan Abdulmuhsin Mohammad, Ravi Kumar Balu, Marie Ng, Marcello Tonelli, Maziar Moradi-Lakeh, Maigeng Zhou, Emmanuela Gakidou, Mohammed K. Ali, Amanda W Pain, Dan J. Stein, Kawkab Shishani, Fortuné Gbètoho Gankpé, Howard J. Hoffman, James Scott, Nadine Steckling, Samia Alhabib, Deborah Jarvis, Kara Estep, Arsène Kouablan Adou, Ricardo Orozco, Holly Hagan, K. C. Astha, Reza Malekzadeh, Klara Dokova, Aliya Naheed, Ernst J. Kuipers, Valeria Caso, Derrick A Bennett, Andrea B. Feigl, Uche S. Uchendu, Holly E. Erskine, Shireen Sindi, Arjun Lakshmana Balaji, Francesco Saverio Violante, Monika Sawhney, Alejandra Cantoral, Ketevan Goginashvili, Raghib Ali, Fan Jiang, Robert G. Weintraub, Homie Razavi, Myriam Tobollik, Howard Hu, Emerito Jose A. Faraon, Irma Khonelidze, Patricia M. Riccio, Eun-Kee Park, Julio Cesar Campuzano, Ibrahim Abubakar, Jürgen C Schmidt, Konstantinos Stroumpoulis, Aref A. Bin Abdulhak, Graeme J. Hankey, Natan M. Bornstein, Mouhanad Hammami, Lee Richardson, Rintaro Mori, Alanur Çavlin, Ruth W Kimokoti, Samir Soneji, Mark J. Nieuwenhuijsen, John Q. Wong, Joseph Frostad, Tom Achoki, Rahman Shiri, Ashish Bhalla, Kurt Straif, Simon I. Hay, Scott B. Patten, Kalpana Balakrishnan, Awoke Misganaw Temesgen, Chandrashekhar T Sreeramareddy, Ryan M Barber, Rosana E. Norman, JianLi Wang, Siyi Shangguan, Luke Nyakarahuka, Kovin Naidoo, Charles D. H. Parry, Mercedes Colomar, H. Ross Anderson, Carlos Magis-Rodriguez, Joan M. Nolla, Muhammad Imran Nisar, Karen Devries, Andrew L. Thorne-Lyman, Denis Nash, Marape Marape, Rajiv Chowdhury, Dima M. Qato, Luca Ronfani, Nobhojit Roy, Daniel Kim, Yuichiro Yano, Luke D. Knibbs, Margaret Robinson, Hilda L Harb, Rogelio Pérez-Padilla, Janet L Leasher, Jonathan L. Wright, Peter Brooks, Cristiana Abbafati, Belinda K Lloyd, Victor Aboyans, Nikhil Tandon, Charles R. Newton, Simón Barquera, Ted R. Miller, Kinnari S. Murthy, Habib Benzian, Glen Mola, Paulo A. Lotufo, Burcu Kucuk Bicer, Peggy Pei-Chia Chiang, Alexander Kraemer, Solomon Meseret Woldeyohannes, Saman Fahimi, Lesley Rushton, Kim Moesgaard Iburg, Vafa Rahimi-Movaghar, Logan Sandar, Bruce Neal, Teresa Shamah Levy, Karen M. Tabb, Jeffrey A. Towbin, Christopher J L Murray, Ramesh Sahathevan, Aaron Cohen, Chanda Kulkarni, Van C. Lansingh, François Alla, Tasara T. Mazorodze, Murugesan Raju, Saeid Shahraz, Uchechukwu K.A. Sampson, Rajeev Gupta, Neil Pearce, Mustafa Z. Younis, Veena S. Kulkarni, Francisco A García-Guerra, Amanda G. Thrift, Stefan Ma, Samaya Ismayilova, Evariste Gasana, Amitava Banerjee, Aslam Pervaiz, Emilie Agardh, Abraham D. Flaxman, Farshad Farzadfar, Peter W. Gething, Ileana Heredia-Pi, Boris Bikbov, Wanqing Chen, Saad B. Omer, Ruben Castro, Neeraj Bhala, Sara Sheikhbahaei, Hilton Lam, Urbano Fra Paleo, Lidia Sanchez-Riera, Alicia Elena Beatriz Lawrynowicz, Kristen Delwiche, Richard G. Ellenbogen, Max Petzold, Yuri Y Varakin, Guilherme Borges, Guohong Jiang, Francis Guillemin, Kyle R. Heuton, Yohannes Kinfu, Victoria F Bachman, Joseph A Wagner, Carlos A Castañeda-Orjuela, Leonardo Trasande, Abbas Ali Mahdi, Josef Coresh, Chuanhua Yu, Kenji Shibuya, Berrin Serdar, Laetitia Huiart, Xiaofeng Liang, Jean de Dieu Ngirabega, Takayoshi Ohkubo, Natalie Stephens, Francis Apolinary Mhimbira, Jefferson Traebert, Amiran Gamkrelidze, Kjetil Søreide, Samath D Dharmaratne, Robert P. Dellavalle, George Mugambage Ruhago, Lakshmi Vijayakumar, Joannie Lortet-Tieulent, Dipan Bose, Tania C Aburto, Saleem M Rana, Miriam Levi, Mohammad Taghi Hedayati, Rodolfo S Pagcatipunan, Ron T. Gansevoort, H. D. Hosgood, Michael Burch, Mohsen Naghavi, Vegard Skirbekk, Ayfer Pekericli, Walter Mendoza, Pengpeng Ye, Gabrielle deVeber, Ali H. Mokdad, David M. Broday, Koranteng Adofo, Zewdie Aderaw Alemu, Shifalika Goenka, Carrie Beth Peterson, Nicolas J. C. Stapelberg, Edson Serván-Mori, Anil Kaul, Foad Abd-Allah, Marek Majdan, Rahul Gupta, Giancarlo Logroscino, Kardiyoloji, Peterson, Carrie B., Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Wisconsin Division of Public Health, Laboratoire de psychologie sociale et de psychologie cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Erosion torrentielle neige et avalanches (UR ETGR (ETNA)), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), London South Bank University, Metropolitan Police Service, Hong Kong Baptist University (HKBU), Institut für Informatik [München/Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Insight Centre for Data Analytics [Galway] (INSIGHT), National University of Ireland [Galway] (NUI Galway), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institute, karolinska institute, Department of Molecular Biosciences, Department of Molecular Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Centro de Estudios Avanzados en Zonas Aridas (CEAZA), Ecole Polytechnique Fédérale de Lausanne (EPFL), Regional Genetic Service, St Mary's Hospital, Manchester, Laboratoire d'Ingénierie des Matériaux (LIM), Centre National de la Recherche Scientifique (CNRS), Computer Science Department [Bristol], University of Bristol [Bristol], Universität Mannheim [Mannheim], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) (SRI-B), Computational Science and Engineering Department [Daresbury] (STFC), Science & Technologie Facilities Council, Multimedia Research Center (MRC), University of Alberta, Division of Biostatistics (Biostat - MINNEAPOLIS), University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, University of Southampton, Imperial College London, Neurology Department, Ichilov Medical Center, Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Risk Assessment Sciences Institute, Utrecht University [Utrecht], Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Respiratory Epidemiology and Public Health, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], CIBER de Epidemiología y Salud Pública (CIBERESP), STAR laboratory, Stanford University [Stanford], Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Tennent Institute of Ophthalmology, National University of Singapore (NUS), Centre de Robotique (CAOR), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Multidisciplinary Nanotechnology Centre, Swansea University, Cyprus International Institute for the Environment and Public Health, Harvard School of Public Health, Genomics Research Center, Academia Sinica, Neuro Rehab Services LLP [New Delhi], Department of Signal Theory and Communications (TSC), Univ. Politec. de Catalunya, King‘s College London, Dept. Mat. Engn. De Ma, Sao Carlos, Fed. Univ. Sao Carlos UFSCar, RESPEC (RESPEC), RESPEC, Advanced Laboratories on Embedded Systems [Roma] (ALES), Department of Biology [Miami], University of Miami [Coral Gables], Health Care, Minister Of Labour-Ministry of Labor, Health and Social Affairs, Department of Nephrology, University Medical Center, University of Groningen, Division of Human Nutrition, Wageningen University and Research Centre [Wageningen] (WUR), Spatial Ecology and Epidemiology Group, University of Oxford [Oxford], College of Medicine, University of Hail, Saudi Arabia, Laboratory of Neurologic Diseases, Mario Negri Institute, Milan, Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], GEMMA — Environmental Engineering and Microbiology Research Group, Department of Hydraulic, Maritime and Environmental Engineering, Universitat Politècnica de Catalunya [Barcelona] (UPC), Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Institut National de Recherche et d'Analyse Physico-Chimique (INRAP), Institut National de Recherche et d'Analyse Physico-chimique (Ariana, Tunisie) (INRAP), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University-Shahid Beheshti University, Center for Applied Medical Research (CIMA), University of Tehran, Secretariat of the Pacific Community, Public Health Division, Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, George Washington University (GW), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universiteit Gent [Ghent], Washington State University (WSU), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, School of Computer Science - China University of Geosciences (China University of Geosciences (East Area)), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Fachbereich Physik [Berlin], Freie Universität Berlin, Div Cyclotron & Radiopharmaceut Sci (DRDO, INMAS), Univ New Delhi, School of Physics and Astronomy, University of St Andrews [Scotland], University of Cape Town, Department of Neuroscience, Department of Computer Science and Engineering [Daejeon] (Chungnam National University), Lawrence University, Gastroenterology & Hepatology, Tata Research Development and Design Center (TRDDC), TCS Innovation Labs, University of Helsinki, Google Inc [Mountain View], Research at Google, Swedish Defense Research Agency (FOI), Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Novartis Pharmaceutical Corporation, Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble [1985-2015] (OSUG [1985-2015]), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Department of Mechanical and Automation Engineering (CAD Laboratory), The Chinese University of Hong Kong [Hong Kong], Università degli studi di Bari, Department of Health and Human Services, National Institutes of Health [Bethesda] (NIH), Centre d'études et de recherche en informatique et communications (CEDRIC), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] (Heudiasyc), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), College of Information and Electrical Engineering [Beijing] (CIEE), China Agricultural University (CAU), Thales Research and Technology [Palaiseau], THALES, Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Centre d'économie de la Sorbonne (CES), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Paris School of Economics (PSE), École supérieure du professorat et de l'éducation - Académie de Grenoble [2013-2019] (ESPE Grenoble [2013-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Department of Mathematics, University of Iowa [Iowa City], College of Medicine, Alfaisal University, Saudi Ministry of Health, Institut national des recherches agricoles du Bénin, Centre de Recherches agricoles du Sud, Departments of Epidemiology and Nutrition, Unit of Human Nutrition, Agricultural University of Athens, Department of Animal Science, Pennsylvania State University (Penn State), Penn State System-Penn State System, University of Virginia, University of Virginia [Charlottesville], Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health - IRCCS ‘‘Burlo Garofolo', Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], American University of Beirut [Beyrouth] (AUB), Department of Chemistry, Scientific Computing Research Unit, Department of dermatology, Milano University-Azienda Ospedaleria Ospedali Riuniti di Bergamo, Mailman School of Public Health, Columbia University [New York], The Georges Institute for International Health, The University of Sydney, Department of epidemiology and Public Health, Faculty of Medicine, Département Optique (OPT), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona], Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Nutriments Lipidiques et Prévention des Maladies Métaboliques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université de la Méditerranée - Aix-Marseille 2, Department of Neurology Lunds University Hospital Lund, Unit of Functional Bionanomaterials, School of Biosciences, University of Birmingham [Birmingham], Electrical Engineering and Computer Science Department - Case Western Reserve University, Case Western Reserve University [Cleveland], World Health Organization, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Nordic School of Public Health, The James Hutton Institute, Horia Hulubei National Institute for Physics and Nuclear Engineering, Department of Pediatrics, University of Washington [Seattle], Institute of Public Health, Department of Physics, Clarendon Laboratory, Center for TeleInFrastruktur (CTIF), Aalborg University [Denmark] (AAU), Physikalisches Institut [Freiburg], Albert-Ludwigs-Universität Freiburg, Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Dept.of Computer Science, Indian Institute of Technology Madras (IIT Madras), Istituto Mario Negri Bergamo, Centro Ricerche e Trapianti Villa Camozzi, Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut geològic de Catalunya (IGC), Institut Geològic de Catalunya-IGC, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Politecnico di Milano [Milan] (POLIMI), Symantec, University of Oviedo, European Microsoft Innovation Center (EMIC), Microsoft Corporation [Redmond, Wash.], Technion - Israel Institute of Technology [Haifa], Laboratoire de Mécanique, Physique et Géosciences (LMPG), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU), Department of Physics, Cavendish Laboratory, University of Cambridge [UK] (CAM), Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Departments of Applied Physics [New Haven], Yale University [New Haven], Center for Mathematical Modeling (CMM), Department of Global Health and Development, London School of Hygiene and Tropical Medicine (LSHTM), University of Occupational and Environmental Health [Kitakyushu] (UEOH), Department of Computer Science and Engineering [New Delhi], Indian Institute of Technology Delhi (IIT Delhi), Institut de Recherche sur les Phénomènes Hors Equilibre (IRPHE), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), GlaxoSmithKline, Imperial College London-Clinical Imaging Center, Universidade Federal de Pernambuco [Recife] (UFPE), Maclean Building, Benson Lane, Crowmarsh Gifford, Centre for Ecology and Hydrology, Nanoscience Institute (NEST), Dipartimento di Fisica, Università di Pisa, Aristotle University of Thessaloniki, Laboratory Of Immune Cell Biology (LICB), JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC), Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] (LNCC / MCT), Occupational Health Unit, Bologna University Hospital-Sant'Orsola-Malpighi Polyclinic, Royal Institute of Technology [Stockholm] (KTH ), NICTA [Eveleigh], National ICT Australia [Sydney] (NICTA), Division of Solid Mechanics, Lund University [Lund], University of Calgary, BioWare Corp, Manchester Academic Health Sciences Centre, Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Ghent University [Belgium] (UGENT), Imaging Sciences and Biomedical Engineering Division [London], Guy's and St Thomas' Hospital [London]-King‘s College London, Children’s Hospital of Philadelphia (CHOP ), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Neurorestoration Group, Wolfson Centre for Age-related Diseases-King‘s College London, Electronic Navigation Research Institute (ENRI), Ministry of Land, Infrastructure, Transport and Tourism, Department of Computer Science [KAIST] (CS), Korea Advanced Institute of Science and Technology (KAIST), Centre for Undergraduate Studies, University of the Punjab, Siemens Corporate Research, Siemens AG [Munich], University of Massachusetts [Boston] (UMass Boston), University of Massachusetts System (UMASS), Department of Materials Science, Sichuan University [Chengdu] (SCU), Natl Engn Res Ctr Vegetables, Key Lab Biol & Genet Improvement Hort Crops N Chi, Beijing Acad Agr & Forestry Sci, University Hospital Puerta de Hierro, Madrid, Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Shahid Beheshti University of Medical Sciences, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), MOLTECH-ANJOU (MOLTECH-ANJOU), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH)-Universidad del Desarrollo, Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), École supérieure du professorat et de l'éducation - Académie de Grenoble (ESPE Grenoble), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), California Institute of Technology (CALTECH)-NASA, Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), King‘s College London-Wolfson Centre for Age-related Diseases, Sichuan University, Universitat de Barcelona, Interne Geneeskunde, Medische Sociologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Psychiatrie & Neuropsychologie, CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Mines-Télécom [Paris] (IMT)-Télécom Bretagne-Université européenne de Bretagne - European University of Brittany (UEB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), RS: MHeNs - R2 - Mental Health, Laboratoire de Physique des Solides ( LPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de psychologie sociale et de psychologie cognitive ( LAPSCO ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ), Erosion torrentielle neige et avalanches ( UR ETGR ), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture ( IRSTEA ), Hong Kong Baptist University ( HKBU ), Institut für Informatik [München/Munich] ( LMU ), Ludwig-Maximilians-Universität München, Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Insight Centre for Data Analytics (National University of Ireland Galway (NUIG)) ( INSIGHT ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Oslo ( UiO ) -University of Oslo ( UiO ), Centro de Estudios Avanzados en Zonas Aridas ( CEAZA ), Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Laboratoire d'Ingénierie des Matériaux ( LIM ), Centre National de la Recherche Scientifique ( CNRS ), Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) ( SRI-B ), Computational Science and Engineering Department [Daresbury] ( STFC ), Multimedia Research Center ( MRC ), University of Alberta [Edmonton], Division of Biostatistics ( Biostat - MINNEAPOLIS ), University of Minnesota [Minneapolis], University of Southampton [Southampton], Interactions, transferts, ruptures artistiques et culturels - EA 6301 ( InTRu ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), University Medical Center Utrecht, Biologie Fonctionnelle et Adaptative ( BFA ), Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), National University of Singapore ( NUS ), Centre de Robotique ( CAOR ), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University ( PSL ), Department of Signal Theory and Communications ( TSC ), RESPEC ( RESPEC ), Advanced Laboratories on Embedded Systems [Roma] ( ALES ), Wageningen University and Research Centre [Wageningen] ( WUR ), Universitat Politècnica de Catalunya [Barcelona] ( UPC ), Institut National de Recherche et d'Analyse Physico-Chimique ( INRAP ), Institut National de Recherche et d'Analyse Physico-chimique (INRAP-Tunisie), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) ( FEMTO-ST ), Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ), Tehran University, Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Washington State University ( WSU ), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Chimiques de Rennes ( ISCR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Ecole Nationale Supérieure de Chimie de Rennes-Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche en informatique de Toulouse ( IRIT ), Institut National Polytechnique [Toulouse] ( INP ) -Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Université Catholique de Louvain ( UCL ), Freie Universität Berlin [Berlin], Div Cyclotron & Radiopharmaceut Sci ( DRDO, INMAS ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Tata Research Development and Design Center ( TRDDC ), Laboratoire MOLTECH-Anjou [Angers] ( MOLTECH ANJOU ), Université d'Angers ( UA ) -Centre National de la Recherche Scientifique ( CNRS ), University of Helsinki [Helsinki], Swedish Defense Research Agency ( FOI ), Servicio de Neurologia ( SANTIAGO - Neurologie ), Universidad de Santiago de Chile [Santiago] ( USACH ) -Universidad del Desarrollo, Novartis Pharmaceutical Corp., East Hanover NJ 07936, USA, Laboratoire de glaciologie et géophysique de l'environnement ( LGGE ), Observatoire des Sciences de l'Univers de Grenoble ( OSUG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Mechanical and Automation Engineering ( CAD Laboratory ), National Institutes of Health ( NIH ), Centre d'étude et de recherche en informatique et communications ( CEDRIC ), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise ( ENSIIE ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] ( Heudiasyc ), Université de Technologie de Compiègne ( UTC ) -Centre National de la Recherche Scientifique ( CNRS ), College of Information and Electrical Engineering [Beijing] ( CIEE ), China Agricultural University ( CAU ), Queen Mary University of London ( QMUL ), Centre d'économie de la Sorbonne ( CES ), Université Panthéon-Sorbonne ( UP1 ) -Centre National de la Recherche Scientifique ( CNRS ), Paris School of Economics ( PSE ), École supérieure du professorat et de l'éducation - Académie de Grenoble ( ESPE Grenoble ), Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Université Grenoble Alpes ( UGA ), PennState University [Pennsylvania] ( PSU ), Jet Propulsion Laboratory ( JPL ), NASA-California Institute of Technology ( CALTECH ), American University of Beirut [Beyrouth], The University of Sydney [Sydney], Département Optique ( OPT ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Laboratoire des signaux et systèmes ( L2S ), Université Paris-Sud - Paris 11 ( UP11 ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Center for Research in Environmental Epidemiology ( CREAL ), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique ( INRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for TeleInFrastruktur ( CTIF ), Aalborg University [Denmark] ( AAU ), Savoirs, Textes, Langage (STL) - UMR 8163 ( STL ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Indian Institute of Technology Madras ( IIT Madras ), Universidade Estadual Paulista Júlio de Mesquita ( UNESP ), Laboratoire de Génie Informatique et Ingénierie de Production ( LGI2P ), IMT - Mines Alès Ecole Mines - Télécom ( IMT - MINES ALES ), Institut geològic de Catalunya ( IGC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physiologie et Génomique des Poissons ( LPGP ), Institut National de la Recherche Agronomique ( INRA ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Politecnico di Milano [Milan], European Microsoft Innovation Center ( EMIC ), Laboratoire de Mécanique, Physique et Géosciences ( LMPG ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ), University of Cambridge [UK] ( CAM ), Laboratoire de Probabilités et Modèles Aléatoires ( LPMA ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Center for Mathematical Modeling ( CMM ), Universidad de Santiago de Chile [Santiago] ( USACH ), London School of Hygiene and Tropical Medicine ( LSHTM ), University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Indian Institute of Technology Delhi ( IIT Delhi ), Institut de Recherche sur les Phénomènes Hors Equilibre ( IRPHE ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Universidade Federal de Pernambuco [Recife] ( UFPE ), Nanoscience Institute ( NEST ), Laboratory Of Immune Cell Biology ( LICB ), JRC Institute for Environment and Sustainability ( IES ), European Commission - Joint Research Centre [Ispra] ( JRC ), Bonn Universität [Bonn], Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] ( LNCC / MCT ), Royal Institute of Technology [Stockholm] ( KTH ), National ICT Australia [Sydney] ( NICTA ), Institut d'Histoire et de Philosophie des Sciences et des Techniques ( IHPST ), Université Panthéon-Sorbonne ( UP1 ) -Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Ghent University [Belgium] ( UGENT ), Children’s Hospital of Philadelphia ( CHOP ), Univeristy of Pennsylvania Medical School, Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique ( LHEEA ), École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Génie Civil et Mécanique ( GeM ), Université de Nantes ( UN ) -École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Medical College of Georgia, Electronic Navigation Research Institute ( ENRI ), Department of Computer Science [KAIST] ( CS ), Korea Advanced Institute of Science and Technology ( KAIST ), Laboratoire de l'Accélérateur Linéaire ( LAL ), University of Massachusetts [Boston] ( UMass Boston ), Forouzanfar, Mohammad H, Alexander, Lily, Anderson, H. Ro, Bachman, Victoria F, Biryukov, Stan, Brauer, Michael, Burnett, Richard, Casey, Daniel, Coates, Matthew M, Cohen, Aaron, Delwiche, Kristen, Estep, Kara, Frostad, Joseph J, Kc, Astha, Kyu, Hmwe H, Moradi Lakeh, Maziar, Ng, Marie, Slepak, Erica Leigh, Thomas, Bernadette A, Wagner, Joseph, Aasvang, Gunn Marit, Abbafati, Cristiana, Ozgoren, Ayse Abbasoglu, Abd Allah, Foad, Abera, Semaw F, Aboyans, Victor, Abraham, Biju, Abraham, Jerry Puthenpurakal, Abubakar, Ibrahim, Abu Rmeileh, Niveen M. E, Aburto, Tania C, Achoki, Tom, Adelekan, Ademola, Adofo, Koranteng, Adou, Arsène K, Adsuar, José C, Afshin, Ashkan, Agardh, Emilie E, Al Khabouri, Mazin J, Al Lami, Faris H, Alam, Sayed Saidul, Alasfoor, Deena, Albittar, Mohammed I, Alegretti, Miguel A, Aleman, Alicia V, Alemu, Zewdie A, Alfonso Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Ali, Mohammed K, Alla, Françoi, Allebeck, Peter, Allen, Peter J, Alsharif, Ubai, Alvarez, Elena, Alvis Guzman, Nelson, Amankwaa, Adansi A, Amare, Azmeraw T, Ameh, Emmanuel A, Ameli, Omid, Amini, Heresh, Ammar, Walid, Anderson, Benjamin O, Antonio, Carl Abelardo T, Anwari, Palwasha, Cunningham, Solveig Argeseanu, Arnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Al, Asghar, Rana J, Assadi, Reza, Atkins, Lydia S, Atkinson, Charle, Avila, Marco A, Awuah, Baffour, Badawi, Alaa, Bahit, Maria C, Bakfalouni, Talal, Balakrishnan, Kalpana, Balalla, Shivanthi, Balu, Ravi Kumar, Banerjee, Amitava, Barber, Ryan M, Barker Collo, Suzanne L, Barquera, Simon, Barregard, Lar, Barrero, Lope H, Barrientos Gutierrez, Tonatiuh, Basto Abreu, Ana C, Basu, Arindam, Basu, Sanjay, Basulaiman, Mohammed O, Ruvalcaba, Carolina Bati, Beardsley, Justin, Bedi, Neeraj, Bekele, Tolesa, Bell, Michelle L, Benjet, Corina, Bennett, Derrick A, Benzian, Habib, Bernabé, Eduardo, Beyene, Tariku J, Bhala, Neeraj, Bhalla, Ashish, Bhutta, Zulfiqar A, Bikbov, Bori, Abdulhak, Aref A. Bin, Blore, Jed D, Blyth, Fiona M, Bohensky, Megan A, Başara, Berrak Bora, Borges, Guilherme, Bornstein, Natan M, Bose, Dipan, Boufous, Soufiane, Bourne, Rupert R, Brainin, Michael, Brazinova, Alexandra, Breitborde, Nicholas J, Brenner, Hermann, Briggs, Adam D. M, Broday, David M, Brooks, Peter M, Bruce, Nigel G, Brugha, Traolach S, Brunekreef, Bert, Buchbinder, Rachelle, Bui, Linh N, Bukhman, Gene, Bulloch, Andrew G, Burch, Michael, Burney, Peter G. J, Campos Nonato, Ismael R, Campuzano, Julio C, Cantoral, Alejandra J, Caravanos, Jack, Cárdenas, Rosario, Cardis, Elisabeth, Carpenter, David O, Caso, Valeria, Castañeda Orjuela, Carlos A, Castro, Ruben E, Catalá López, Ferrán, Cavalleri, Fiorella, Çavlin, Alanur, Chadha, Vineet K, Chang, Jung Chen, Charlson, Fiona J, Chen, Honglei, Chen, Wanqing, Chen, Zhengming, Chiang, Peggy P, Chimed Ochir, Odgerel, Chowdhury, Rajiv, Christophi, Costas A, Chuang, Ting Wu, Chugh, Sumeet S, Cirillo, Massimo, Claßen, Thomas Kd, Colistro, Valentina, Colomar, Mercede, Colquhoun, Samantha M, Contreras, Alejandra G, Cooper, Cyru, Cooperrider, Kimberly, Cooper, Leslie T, Coresh, Josef, Courville, Karen J, Criqui, Michael H, Cuevas Nasu, Lucia, Damsere Derry, Jame, Danawi, Hadi, Dandona, Lalit, Dandona, Rakhi, Dargan, Paul I, Davis, Adrian, Davitoiu, Dragos V, Dayama, Anand, de Castro, E. Filipa, De la Cruz Góngora, Vanessa, De Leo, Diego, de Lima, Graça, Degenhardt, Louisa, Del Pozo Cruz, Borja, Dellavalle, Robert P, Deribe, Kebede, Derrett, Sarah, Jarlais, Don C. De, Dessalegn, Muluken, Deveber, Gabrielle A, Devries, Karen M, Dharmaratne, Samath D, Dherani, Mukesh K, Dicker, Daniel, Ding, Eric L, Dokova, Klara, Dorsey, E. Ray, Driscoll, Tim R, Duan, Leilei, Durrani, Adnan M, Ebel, Beth E, Ellenbogen, Richard G, Elshrek, Yousef M, Endres, Matthia, Ermakov, Sergey P, Erskine, Holly E, Eshrati, Babak, Esteghamati, Alireza, Fahimi, Saman, Faraon, Emerito Jose A, Farzadfar, Farshad, Fay, Derek F. J, Feigin, Valery L, Feigl, Andrea B, Fereshtehnejad, Seyed Mohammad, Ferrari, Alize J, Ferri, Cleusa P, Flaxman, Abraham D, Fleming, Thomas D, Foigt, Nataliya, Foreman, Kyle J, Paleo, Urbano Fra, Franklin, Richard C, Gabbe, Belinda, Gaffikin, Lynne, Gakidou, Emmanuela, Gamkrelidze, Amiran, Gankpé, Fortuné G, Gansevoort, Ron T, García Guerra, Francisco A, Gasana, Evariste, Geleijnse, Johanna M, Gessner, Bradford D, Gething, Pete, Gibney, Katherine B, Gillum, Richard F, Ginawi, Ibrahim A. M, Giroud, Maurice, Giussani, Giorgia, Goenka, Shifalika, Goginashvili, Ketevan, Dantes, Hector Gomez, Gona, Philimon, de Cosio, Teresita Gonzalez, González Castell, Dinorah, Gotay, Carolyn C, Goto, Atsushi, Gouda, Hebe N, Guerrant, Richard L, Gugnani, Harish C, Guillemin, Franci, Gunnell, David, Gupta, Rahul, Gupta, Rajeev, Gutiérrez, Reyna A, Hafezi Nejad, Nima, Hagan, Holly, Hagstromer, Maria, Halasa, Yara A, Hamadeh, Randah R, Hammami, Mouhanad, Hankey, Graeme J, Hao, Yuantao, Harb, Hilda L, Haregu, Tilahun Nigatu, Haro, Josep Maria, Havmoeller, Rasmu, Hay, Simon I, Hedayati, Mohammad T, Heredia Pi, Ileana B, Hernandez, Lucia, Heuton, Kyle R, Heydarpour, Pouria, Hijar, Martha, Hoek, Hans W, Hoffman, Howard J, Hornberger, John C, Hosgood, H. Dean, Hoy, Damian G, Hsairi, Mohamed, Hu, Guoqing, Hu, Howard, Huang, Cheng, Huang, John J, Hubbell, Bryan J, Huiart, Laetitia, Husseini, Abdullatif, Iannarone, Marissa L, Iburg, Kim M, Idrisov, Bulat T, Ikeda, Nayu, Innos, Kaire, Inoue, Manami, Islami, Farhad, Ismayilova, Samaya, Jacobsen, Kathryn H, Jansen, Henrica A, Jarvis, Deborah L, Jassal, Simerjot K, Jauregui, Alejandra, Jayaraman, Sudha, Jeemon, Panniyammakal, Jensen, Paul N, Jha, Vivekanand, Jiang, Fan, Jiang, Guohong, Jiang, Ying, Jonas, Jost B, Juel, Knud, Kan, Haidong, Roseline, Sidibe S. Kany, Karam, Nadim E, Karch, André, Karema, Corine K, Karthikeyan, Ganesan, Kaul, Anil, Kawakami, Norito, Kazi, Dhruv S, Kemp, Andrew H, Kengne, Andre P, Keren, Andre, Khader, Yousef S, Khalifa, Shams Eldin Ali Hassan, Khan, Ejaz A, Khang, Young Ho, Khatibzadeh, Shahab, Khonelidze, Irma, Kieling, Christian, Kim, Daniel, Kim, Sungroul, Kim, Yunjin, Kimokoti, Ruth W, Kinfu, Yohanne, Kinge, Jonas M, Kissela, Brett M, Kivipelto, Miia, Knibbs, Luke D, Knudsen, Ann Kristin, Kokubo, Yoshihiro, Kose, M. Rifat, Kosen, Soewarta, Kraemer, Alexander, Kravchenko, Michael, Krishnaswami, Sanjay, Kromhout, Han, Ku, Tiffany, Defo, Barthelemy Kuate, Bicer, Burcu Kucuk, Kuipers, Ernst J, Kulkarni, Chanda, Kulkarni, Veena S, Kumar, G. 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Ryan, Westerman, Ronny, Whiteford, Harvey A, Wilkinson, James D, Williams, Hywel C, Williams, Thomas N, Woldeyohannes, Solomon M, Wolfe, Charles D. A, Wong, John Q, Woolf, Anthony D, Wright, Jonathan L, Wurtz, Brittany, Xu, Gelin, Yan, Lijing L, Yang, Gonghuan, Yano, Yuichiro, Ye, Pengpeng, Yenesew, Muluken, Yentür, Gökalp K, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok Jun, Younis, Mustafa Z, Younoussi, Zourkaleini, Yu, Chuanhua, Zaki, Maysaa E, Zhao, Yong, Zheng, Yingfeng, Zhou, Maigeng, Zhu, Jun, Zhu, Shankuan, Zou, Xiaonong, Zunt, Joseph R, Lopez, Alan D, Vos, Theo, Murray, Christopher J., Cell biology, Epidemiology, Neurosciences, Health Technology Assessment (HTA), Public Health, General practice, Bachman, Victoria F., Coates, Matthew M., Frostad, Joseph J., Astha, K.C., Kyu, Hmwe H., Moradi-Lakeh, Maziar, Thomas, Bernadette A., Abbasoglu Ozgoren, Ayse, Abd-Allah, Foad, Abera, Semaw F., Puthenpurakal Abraham, Jerry, Abu-Rmeileh, Niveen M.E., Aburto, Tania C., Adou, Arsène K., Adsuar, José C., Agardh, Emilie E., Al Khabouri, Mazin J., Al Lami, Faris H., Albittar, Mohammed I., Alegretti, Miguel A., Aleman, Alicia V., Alemu, Zewdie A., Alfonso-Cristancho, Rafael, Ali, Mohammed K., Allen, Peter J., Alvis-Guzman, Nelson, Amankwaa, Adansi A., Amare, Azmeraw T., Ameh, Emmanuel A., Anderson, Benjamin O., Antonio, Carl Abelardo T., Argeseanu Cunningham, Solveig, Arsic Arsenijevic, Valentina S., Asghar, Rana J., Atkins, Lydia S., Avila, Marco A., Bahit, Maria C., Barber, Ryan M., Barker-Collo, Suzanne L., Barrero, Lope H., Barrientos-Gutierrez, Tonatiuh, Basto-Abreu, Ana C., Basulaiman, Mohammed O., Batis Ruvalcaba, Carolina, Bell, Michelle L., Bennett, Derrick A., Beyene, Tariku J., Bhutta, Zulfiqar A., Bin Abdulhak, Aref A., Blore, Jed D., Blyth, Fiona M., Bohensky, Megan A., Bora Başara, Berrak, Bornstein, Natan M., Bourne, Rupert R., Breitborde, Nicholas J., Briggs, Adam D.M., Broday, David M., Brooks, Peter M., Bruce, Nigel G., Brugha, Traolach S., Bui, Linh N., Bulloch, Andrew G., Burney, Peter G.J., Campos-Nonato, Ismael R., Campuzano, Julio C., Cantoral, Alejandra J., Carpenter, David O., Castañeda-Orjuela, Carlos A., Castro, Ruben E., Catalá-López, Ferrán, Chadha, Vineet K., Chang, Jung-Chen, Charlson, Fiona J., Chiang, Peggy P., Chimed-Ochir, Odgerel, Christophi, Costas A., Chuang, Ting-Wu, Chugh, Sumeet S., Claßen, Thomas K.D., Colquhoun, Samantha M., Contreras, Alejandra G., Cooper, Leslie T., Courville, Karen J., Criqui, Michael H., Cuevas-Nasu, Lucia, Damsere-Derry, Jame, Dargan, Paul I., Davitoiu, Dragos V., De Castro, E. 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Venkat, Neupane, Sudan P., Newton, Charles R., Ngalesoni, Frida N., Ngirabega, Jean De Dieu, Nguyen, Nhung T., Nieuwenhuijsen, Mark J., Nisar, Muhammad I., Nogueira, José R., Nolla, Joan M., Norheim, Ole F., Norman, Rosana E., Oh, In-Hwan, Olusanya, Bolajoko O., Omer, Saad B., Pagcatipunan, Rodolfo S., Pain, Amanda W., Pandian, Jeyaraj D., Panelo, Carlo Irwin A., Park, Eun-Kee, Parry, Charles D., Paternina Caicedo, Angel J., Patten, Scott B., Paul, Vinod K., Pavlin, Boris I., Pedraza, Lilia S., Pejin Stokic, Ljiljana, Pereira, David M., Perez-Padilla, Rogelio, Perez-Ruiz, Fernando, Perry, Samuel A.L., Phillips, Michael R., Polanczyk, Guilherme V., Pond, Constance D., Prasad, Noela M., Qato, Dima M., Quezada, Amado D., Quistberg, D. Alex A., Rahimi-Movaghar, Vafa, Ur Rahman, Sajjad, Rana, Saleem M., Refaat, Amany H., Ribeiro, Antonio L., Riccio, Patricia M., Rojas-Rueda, David, Ruhago, George M., Sacco, Ralph L., Salomon, Joshua A., Sampson, Uchechukwu K., Sanabria, Juan R., Sánchez-Pimienta, Tania G., Sanchez-Riera, Lidia, Santos, Itamar S., Saunders, James E., Saylan, Mete I., Schmidt, Jürgen C., Schneider, Ione J.C., Schwebel, David C., Scott, James G., Sepanlou, Sadaf G., Servan-Mori, Edson E., Shamah Levy, Teresa, Shin, Hwashin H., Sigfusdottir, Inga D., Silberberg, Donald H., Simard, Edgar P., Singh, Gitanjali M., Singh, Jasvinder A., Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Stapelberg, Nicolas J.C., Stein, Dan J., Stein, Murray B., Sunguya, Bruno F., Sykes, Bryan L., Tabb, Karen M., Talongwa, Roberto T., Te Ao, Braden J., Teixeira, Carolina M., Téllez Rojo, Martha M., Terkawi, Abdullah S., Texcalac-Sangrador, José Lui, Thackway, Sarah V., Thorne-Lyman, Andrew L., Thrift, Amanda G., Thurston, George D., Towbin, Jeffrey A., Tran, Bach X., Tsala Dimbuene, Zacharie, Uchendu, Uche S., Ukwaja, Kingsley N., Uzun, Selen B., Van De Vijver, Steven, Van Gool, Coen H., Van Os, Jim, Varakin, Yuri Y., Vasankari, Tommi J., Vasconcelos, Ana Maria N., Vavilala, Monica S., Veerman, Lennert J., Velasquez-Melendez, Gustavo, Venketasubramanian, N., Violante, Francesco S., Victorovich Vlassov, Vasiliy, Wagner, Gregory R., Waller, Stephen G., Wallin, Mitchell T., Warouw, Tati S., Watts, Charlotte H., Weintraub, Robert G., Whiteford, Harvey A., Wilkinson, James D., Williams, Hywel C., Williams, Thomas N., Woldeyohannes, Solomon M., Wolfe, Charles D.A., Wong, John Q., Woolf, Anthony D., Wright, Jonathan L., Yan, Lijing L., Yentür, Gökalp K., Yoon, Seok-Jun, Younis, Mustafa Z., Zaki, Maysaa E., Zunt, Joseph R., Lopez, Alan D., and Temesgen, A.M.

Subjects
Male, Fine particulate matter, Nutrition and Disease, MESH : Sanitation, Health Behavior, Diseases, MESH: Metabolic Diseases, MESH: Global Health, 030204 cardiovascular system & hematology, MESH: Risk Assessment, Global Health, MESH : Nutritional Status, MESH: Occupational Exposure, 0302 clinical medicine, Unsafe Sex, MESH: Risk Factors, Risk Factors, Voeding en Ziekte, Medicine, Air-pollution, MESH : Female, 030212 general & internal medicine, MESH : Risk Assessment, Sanitation, Wasting, 2. Zero hunger, Factors de risc en les malalties, Medicine (all), [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, MESH : Occupational Diseases, MESH: Nutritional Status, All-cause mortality, MESH : Risk Factors, humanities, Environmental Exposure, Female, Humans, Metabolic Diseases, Nutritional Status, Occupational Diseases, Occupational Exposure, Risk Assessment, Tobacco smoking, 3. Good health, Nutritional Statu, MESH : Occupational Exposure, MESH : Metabolic Diseases, Cohort, medicine.symptom, Risk assessment, Blood-pressure, Human, MESH: Occupational Diseases, Risk factors in diseases, Coronary-heart-disease, MESH : Male, MESH: Health Behavior, MESH: Environmental Exposure, Population health, Body-mass index, 03 medical and health sciences, Household cooking, Cardiovascular-disease, Environmental health, General & Internal Medicine, parasitic diseases, Life Science, MESH: Sanitation, Risk factor, MESH : Health Behavior, VLAG, GBD2013, MESH: Humans, business.industry, Risk Factor, Global Burden of Disease Study, 79 behavioural, environmental and occupational, and metabolic risks, Long-term exposure, MESH : Humans, CAUSE-SPECIFIC MORTALITY, MESH: Male, Metabolic Disease, Occupational Disease, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, MALE BRITISH DOCTORS, Years of potential life lost, Relative risk, Malalties, MESH : Global Health, OUTDOOR AIR-POLLUTION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Environmental Exposure, MESH: Female
Abstract

Summary Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation. Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the fi rst of a series of annual updates of the GBD. Risk factor quantifi cation, particularly of modifi able risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the fi rst level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular fi ltration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation.

Published
2015

30. Global, regional, and national levels and causes of maternal mortality during 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013

Author

Carl Abelardo T. Antonio, Rob E. Dorrington, Belinda K Lloyd, Elisabete Weiderpass, Kovin Naidoo, Leslie T. Cooper, Sandra Nolte, Eduardo A. Undurraga, Mohammad A. AlMazroa, R. Kumar, Xiaofeng Liang, Amanda J. Mason-Jones, Kazem Rahimi, Sanjay Basu, Vasiliy Victorovich Vlassov, André Karch, Dipan Bose, Vivekanand Jha, Adansi A. Amankwaa, Kaire Innos, Ione Jayce Ceola Schneider, Itamar S. Santos, Anwar Rafay, Bolajoko O. Olusanya, Tommi Vasankari, Nana Kwaku Mainoo, Saleem M Rana, Wagner Marcenes, Fortuné Gbètoho Gankpé, Rana J. Asghar, Lela Sturua, Nicholas J K Breitborde, Corine Karema, Charles R. Newton, Uche S. Uchendu, Jongmin Lee, Inga Dora Sigfusdottir, Harish Chander Gugnani, Kaushalendra Kumar, Reza Assadi, Ibrahim Abubakar, Konstantinos Stroumpoulis, Megan Coggeshall, Timothy M. Wolock, Ronny Westerman, Samath D Dharmaratne, Katya Anne Shackelford, Anders Larsson, Jeffrey A. Towbin, Jixiang Ma, Lynne Gaffikin, Konstantin Kazanjan, Mohammad Ali Sahraian, Mohammad H. Forouzanfar, Yichong Li, Felix Sayinzoga, Daniel Dicker, Philimon Gona, Maurice Giroud, Maysaa El Sayed Zaki, Shiwei Liu, Lorenzo Monasta, Chantal Huynh, Abdullatif Husseini, Ted R. Miller, Solomon Meseret Woldeyohannes, D. Alex Quistberg, Justin Beardsley, Majed Asad, Uʇur Dilmen, Alaa Badawi, Hsien-Ho Lin, Haidong Kan, Vinod K. Paul, Mitsuru Mukaigawara, James Leigh, Xiao Nong Zou, Sajjad Ur Rahman, Valentina Arsić Arsenijević, Gokalp Kadri Yentur, Man Mohan Mehndiratta, Murugesan Raju, Stephanie J. London, Kingsley N. Ukwaja, Young-Ho Khang, Knud Juel, Mohsen Naghavi, Rasmus Havmoeller, Gelin Xu, Semaw Ferede Abera, Devina Nand, Norito Kawakami, Neil Pearce, Elisabeth Barboza França, Ferrán Catalá-López, Ketevan Goginashvili, Vegard Skirbekk, Neeraj Bedi, Barthelemy Kuate Defo, Andrew H. Kemp, H. Dean Hosgood, Vafa Rahimi-Movaghar, Konrad Pesudovs, Linhong Wang, Xiao Rong Wang, Alan D. Lopez, Ademola Lukman Adelekan, Joshua A. Salomon, Walter Mendoza, Aref A. Bin Abdulhak, Ivy Shiue, G Anil Kumar, Yuichiro Yano, Luke D. Knibbs, Jung-Chen Chang, Yousef Khader, Caitlyn Steiner, Selen Begüm Uzun, Luciano A. Sposato, Gabrielle deVeber, Raghib Ali, Andre Pascal Kengne, Chakib Nejjari, Rafael Alfonso-Cristancho, Tania Georgina Sánchez Pimienta, Roberto Tchio Talongwa, Hilda L Harb, Ali H. Mokdad, Edward J Mills, Angel J Paternina Caicedo, Xiaohong Li, Luke Nyakarahuka, Diego De Leo, Rashmi Gupta, Robert G. Weintraub, Tim Driscoll, Sun Ha Jee, Carolina Maria Teixeira, Ole Frithjof Norheim, Zulfiqar A Bhutta, Hwashin Hyun Shin, Palwasha Anwari, Daniel Pope, Hassan Amini, Jae-Hyun Park, Saad B. Omer, Eric L. Ding, Narayanaswamy Venketasubramanian, Juan Liang, Tara Templin, Arindam Basu, Farshad Farzadfar, Yang Yang, Xuan Che, Scott Weichenthal, Jeyaraj D Pandian, David L. Tirschwell, Adrian Davis, Hilton Lam, Feng Tan, Stephen S Lim, Soewarta Kosen, Atsushi Goto, Ratilal Lalloo, Yanping Wang, Glen Mola, Paulo A. Lotufo, Dhruv S. Kazi, Jose C. Adsuar, Amany H Refaat, Ruben Castro, Gene F. Kwan, Johanna M. Geleijnse, Emerito Jose A. Faraon, Costas A. Christophi, Theo Vos, Sara Sheikhbahaei, Guilherme V. Polanczyk, Jed D. Blore, Azmeraw T. Amare, Kyle R. Heuton, Walid Ammar, Louisa Degenhardt, Andrew Vallely, Guohong Jiang, Ricky Leung, Jasvinder A. Singh, Zewdie Aderaw Alemu, A Artaman, Steven E. Lipshultz, Carlos A Castañeda-Orjuela, Seyed-Mohammad Fereshtehnejad, Sadaf G. Sepanlou, Mark J. Nieuwenhuijsen, John Q. Wong, Manami Inoue, Coen H. Van Gool, James D. Wilkinson, Ejaz Ahmad Khan, Yoshihiro Kokubo, Manuela Mendonca Felicio, Farshad Pourmalek, Boris I. Pavlin, Karen Sliwa, Robert G. Nelson, Tom Achoki, Edmond K. Kabagambe, Orish Ebere Orisakwe, Christopher J L Murray, In-Hwan Oh, Uchechukwu K.A. Sampson, Ulrich O Mueller, Austin E Schumacher, Edson Serván-Mori, Berrak Bora Basara, Simon I. Hay, Anil Kaul, Foad Abd-Allah, Takayoshi Ohkubo, Kim Yun Jin, Abdullah Sulieman Terkawi, Mall Leinsalu, Sergei Petrovich Ermakov, Marek Majdan, Ileana B. Heredia Pi, Christina Papachristou, Scott B. Patten, Rajeev Gupta, Kalpana Balakrishnan, Mustafa Z. Younis, Kenji Shibuya, Graça Maria Ferreira De Lima, Andrea P. Silva, Maziar Moradi-Lakeh, Anand Dayama, Eiman Jahangir, Stefan Ma, Karen M. Tabb, Nicholas J Kassebaum, Shams Eldin Ali Hassan Khalifa, Mazin J. Al Kahbouri, Nadim E. Karam, Jun Zhu, Chandrashekhar T Sreeramareddy, Dinorah González-Castell, Diego Gonzalez-Medina, Aliya Naheed, Ryan M Barber, Salvador Villalpando, Yang Liu, Chanda Kulkarni, Vinay Nangia, Haidong Wang, Yongmei Li, Rosario Cárdenas, Randah R. Hamadeh, Suzanne Polinder, Van C. Lansingh, François Alla, Max Petzold, Bryan L. Sykes, Ubai Alsharif, Chuanhua Yu, Francesco Saverio Violante, Monika Sawhney, Ayse Abbasoglu Ozgoren, Graeme J. Hankey, Mouhanad Hammami, Iuri da Costa Leite, Dickens Akena, Rintaro Mori, Alanur Çavlin, Maia Kereselidze, Jonathan de la Cruz Monis, Deena Alasfoor, Taavi Lai, Eric Y. Tenkorang, Cyrus Cooper, Sudan Prasad Neupane, Dan Poenaru, Veena S. Kulkarni, Naohiro Yonemoto, Elizabeth Glaser, Sergey Soshnikov, Ziad A. Memish, Paul N. Jensen, Fabiola Mejía-Rodríguez, Ana C. Garcia, Rakhi Dandona, Emilie Agardh, Katherine B Gibney, Vasco Manuel Pedro Machado, Michelle L. Bell, David M. Pereira, Muluemebet Abera Wordofa, Samantha M. Colquhoun, Elena Alvarez, Stephen G. Waller, Ketevan Gambashidze, Eduardo Bernabé, Rafael Lozano, Damian G Hoy, Miltiadis K. Tsilimbaris, Hebe N. Gouda, Muhammad Imran Nisar, Zanfina Ademi, Andrew L. Thorne-Lyman, Denis Nash, Dima M. Qato, Luca Ronfani, Nobhojit Roy, Donald H. Silberberg, Monica S. Vavilala, Lydia S. Atkins, Hans W. Hoek, Muluken Dessalegn, David C. Schwebel, Christopher C. Mapoma, Jost B. Jonas, Tolesa Bekele, Lalit Dandona, Borja del Pozo-Cruz, Sumeet S. Chugh, Johan Ärnlöv, Tariku Jibat Beyene, Melvin Barrientos Marzan, Ami R. Moore, Marie Ng, Maigeng Zhou, Samia Alhabib, Massimo Cirillo, Soraya Seedat, Paul S. F. Yip, Nima Hafezi-Nejad, Amelia Bertozzi-Villa, Kebede Deribe, John Nelson Opio, Peter J. Allen, Marina Shakh-Nazarova, Bach Xuan Tran, Arsène Kouablan Adou, Yingfeng Zheng, Julio Cesar Montañez Hernandez, Yong Zhao, Nelson Alvis-Guzman, Bulat Idrisov, Alireza Esteghamati, Seok Jun Yoon, Kathryn H. Jacobsen, Kassebaum, Nicholas J., Bertozzi-Villa, Amelia, Coggeshall, Megan S., Shackelford, Katya A., Steiner, Caitlyn, Heuton, Kyle R., Gonzalez-Medina, Diego, Barber, Ryan, Huynh, Chantal, Dicker, Daniel, Templin, Tara, Wolock, Timothy M., Ozgoren, Ayse Abbasoglu, Abd-Allah, Foad, Abera, Semaw Ferede, Abubakar, Ibrahim, Achoki, Tom, Adelekan, Ademola, Ademi, Zanfina, Adou, Arsène Kouablan, Adsuar, José C., Agardh, Emilie E., Akena, Dicken, Alasfoor, Deena, Alemu, Zewdie Aderaw, Alfonso-Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Al Kahbouri, Mazin J., Alla, Françoi, Allen, Peter J., Almazroa, Mohammad A., Alsharif, Ubai, Alvarez, Elena, Alvis-Guzmán, Nelson, Amankwaa, Adansi A., Amare, Azmeraw T., Amini, Hassan, Ammar, Walid, Antonio, Carl A.T., Anwari, Palwasha, Ärnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Ali, Asad, Majed Masoud, Asghar, Rana J., Assadi, Reza, Atkins, Lydia S., Badawi, Alaa, Balakrishnan, Kalpana, Basu, Arindam, Basu, Sanjay, Beardsley, Justin, Bedi, Neeraj, Bekele, Tolesa, Bell, Michelle L., Bernabe, Eduardo, Beyene, Tariku J., Bhutta, Zulfiqar, Abdulhak, Aref Bin, Blore, Jed D., Basara, Berrak Bora, Bose, Dipan, Breitborde, Nichola, Cárdenas, Rosario, Castañeda-Orjuela, Carlos A., Castro, Ruben Estanislao, Catalá-López, Ferrán, Cavlin, Alanur, Chang, Jung-Chen, Che, Xuan, Christophi, Costas A., Chugh, Sumeet S., Cirillo, Massimo, Colquhoun, Samantha M., Cooper, Leslie Trumbull, Cooper, Cyru, Da Costa Leite, Iuri, Dandona, Lalit, Dandona, Rakhi, Davis, Adrian, Dayama, Anand, Degenhardt, Louisa, De Leo, Diego, Del Pozo-Cruz, Borja, Deribe, Kebede, Dessalegn, Muluken, Deveber, Gabrielle A., Dharmaratne, Samath D., Dilmen, Uʇur, Ding, Eric L., Dorrington, Rob E., Driscoll, Tim R., Ermakov, Sergei Petrovich, Esteghamati, Alireza, Faraon, Emerito Jose A., Farzadfar, Farshad, Felicio, Manuela Mendonca, Fereshtehnejad, Seyed-Mohammad, De Lima, Graça Maria Ferreira, Forouzanfar, Mohammad H., França, Elisabeth B., Gaffikin, Lynne, Gambashidze, Ketevan, Gankpé, Fortuné Gbètoho, Garcia, Ana C., Geleijnse, Johanna M., Gibney, Katherine B., Giroud, Maurice, Glaser, Elizabeth L., Goginashvili, Ketevan, Gona, Philimon, González-Castell, Dinorah, Goto, Atsushi, Gouda, Hebe N., Gugnani, Harish Chander, Gupta, Rahul, Gupta, Rajeev, Hafezi-Nejad, Nima, Hamadeh, Randah Ribhi, Hammami, Mouhanad, Hankey, Graeme J., Harb, Hilda L., Havmoeller, Rasmu, Hay, Simon I., Pi, Ileana B. Heredia, Hoek, Hans W., Hosgood, H Dean, Hoy, Damian G., Husseini, Abdullatif, Idrisov, Bulat T., Innos, Kaire, Inoue, Manami, Jacobsen, Kathryn H., Jahangir, Eiman, Jee, Sun Ha, Jensen, Paul N., Jha, Vivekanand, Jiang, Guohong, Jonas, Jost B., Juel, Knud, Kabagambe, Edmond Kato, Kan, Haidong, Karam, Nadim E., Karch, André, Karema, Corine Kakizi, Kaul, Anil, Kawakami, Norito, Kazanjan, Konstantin, Kazi, Dhruv S., Kemp, Andrew H., Kengne, Andre Pascal, Kereselidze, Maia, Khader, Yousef Saleh, Khalifa, Shams Eldin Ali Hassan, Khan, Ejaz Ahmed, Khang, Young-Ho, Knibbs, Luke, Kokubo, Yoshihiro, Kosen, Soewarta, Defo, Barthelemy Kuate, Kulkarni, Chanda, Kulkarni, Veena S., Kumar, G. Anil, Kumar, Kaushalendra, Kumar, Ravi B., Kwan, Gene, Lai, Taavi, Lalloo, Ratilal, Lam, Hilton, Lansingh, Van C., Larsson, Ander, Lee, Jong-Tae, Leigh, Jame, Leinsalu, Mall, Leung, Ricky, Li, Xiaohong, Li, Yichong, Li, Yongmei, Liang, Juan, Liang, Xiaofeng, Lim, Stephen S., Lin, Hsien-Ho, Lipshultz, Steven E., Liu, Shiwei, Liu, Yang, Lloyd, Belinda K., London, Stephanie J., Lotufo, Paulo A., Ma, Jixiang, Ma, Stefan, Machado, Vasco Manuel Pedro, Mainoo, Nana Kwaku, Majdan, Marek, Mapoma, Christopher Chabila, Marcenes, Wagner, Marzan, Melvin Barriento, Mason-Jones, Amanda J., Mehndiratta, Man Mohan, Mejia-Rodriguez, Fabiola, Memish, Ziad A., Mendoza, Walter, Miller, Ted R., Mills, Edward J., Mokdad, Ali H., Mola, Glen Liddell, Monasta, Lorenzo, De La Cruz Monis, Jonathan, Hernandez, Julio Cesar Montañez, Moore, Ami R., Moradi-Lakeh, Maziar, Mori, Rintaro, Mueller, Ulrich O., Mukaigawara, Mitsuru, Naheed, Aliya, Naidoo, Kovin S., Nand, Devina, Nangia, Vinay, Nash, Deni, Nejjari, Chakib, Nelson, Robert G., Neupane, Sudan Prasad, Newton, Charles R., Ng, Marie, Nieuwenhuijsen, Mark J., Nisar, Muhammad Imran, Nolte, Sandra, Norheim, Ole F., Nyakarahuka, Luke, Oh, In-Hwan, Ohkubo, Takayoshi, Olusanya, Bolajoko O., Omer, Saad B., Opio, John Nelson, Orisakwe, Orish Ebere, Pandian, Jeyaraj D., Papachristou, Christina, Park, Jae-Hyun, Paternina Caicedo, Angel J., Patten, Scott B., Paul, Vinod K., Pavlin, Boris Igor, Pearce, Neil, Pereira, David M., Pesudovs, Konrad, Petzold, Max, Poenaru, Dan, Polanczyk, Guilherme V., Polinder, Suzanne, Pope, Dan, Pourmalek, Farshad, Qato, Dima, Quistberg, D. Alex, Rafay, Anwar, Rahimi, Kazem, Rahimi-Movaghar, Vafa, Ur Rahman, Sajjad, Raju, Murugesan, Rana, Saleem M., Refaat, Amany, Ronfani, Luca, Roy, Nobhojit, Pimienta, Tania Georgina Sánchez, Sahraian, Mohammad Ali, Salomon, Joshua A., Sampson, Uchechukwu, Santos, Itamar S., Sawhney, Monika, Sayinzoga, Felix, Schneider, Ione J.C., Schumacher, Austin, Schwebel, David C., Seedat, Soraya, Sepanlou, Sadaf G., Servan-Mori, Edson E., Shakh-Nazarova, Marina, Sheikhbahaei, Sara, Shibuya, Kenji, Shin, Hwashin Hyun, Shiue, Ivy, Sigfusdottir, Inga Dora, Silberberg, Donald H., Silva, Andrea P., Singh, Jasvinder A., Skirbekk, Vegard, Sliwa, Karen, Soshnikov, Sergey S., Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Stroumpoulis, Konstantino, Sturua, Lela, Sykes, Bryan L., Tabb, Karen M., Talongwa, Roberto Tchio, Tan, Feng, Teixeira, Carolina Maria, Tenkorang, Eric Yeboah, Terkawi, Abdullah Sulieman, Thorne-Lyman, Andrew L., Tirschwell, David L., Towbin, Jeffrey A., Tran, Bach X., Tsilimbaris, Miltiadi, Uchendu, Uche S., Ukwaja, Kingsley N., Undurraga, Eduardo A., Uzun, Selen Begüm, Vallely, Andrew J., Van Gool, Coen H., Vasankari, Tommi J., Vavilala, Monica S., Venketasubramanian, N., Villalpando, Salvador, Violante, Francesco S., Vlassov, Vasiliy Victorovich, Vos, Theo, Waller, Stephen, Wang, Haidong, Wang, Linhong, Wang, Xiao Rong, Wang, Yanping, Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G., Westerman, Ronny, Wilkinson, James D., Woldeyohannes, Solomon Meseret, Wong, John Q., Wordofa, Muluemebet Abera, Xu, Gelin, Yang, Yang C., Yano, Yuichiro, Yentur, Gokalp Kadri, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Younis, Mustafa Z., Yu, Chuanhua, Jin, Kim Yun, El Sayed Zaki, Maysaa, Zhao, Yong, Zheng, Yingfeng, Zhou, Maigeng, Zhu, Jun, Zou, Xiao Nong, Lopez, Alan D., Naghavi, Mohsen, Murray, Christopher J.L., Lozano, Rafael, Kassebaum, Nj, Bertozzi-Villa, A, Coggeshall, M, Shackelford, Ka, Steiner, C, Heuton, Kr, Gonzalez-Medina, D, Barber, R, Huynh, C, Dicker, D, Templin, T, Wolock, Tm, Ozgoren, Aa, Abd-Allah, F, Abera, Sf, Achoki, T, Adelekan, A, Ademi, Z, Adou, Ak, Adsuar, Jc, Agardh, Ee, Akena, D, Alasfoor, D, Alemu, Za, Alfonso-Cristancho, R, Alhabib, S, Ali, R, Al Kahbouri, Mj, Alla, F, Allen, Pj, Almazroa, Ma, Alsharif, U, Alvarez, E, Alvis-Guzmán, N, Amankwaa, Aa, Amare, At, Amini, H, Ammar, W, Antonio, Ca, Anwari, P, Arnlöv, J, Arsenijevic, V, Artaman, A, Asad, Mm, Asghar, Rj, Assadi, R, Atkins, L, Badawi, A, Balakrishnan, K, Basu, A, Basu, S, Beardsley, J, Bedi, N, Bekele, T, Bell, Ml, Bernabe, E, Beyene, Tj, Bhutta, Z, Bin Abdulhak, A, Blore, J, Basara, Bb, Bose, D, Breitborde, N, Cárdenas, R, Castañeda-Orjuela, Ca, Castro, Re, Catalá-López, F, Cavlin, A, Chang, Jc, Che, X, Christophi, Ca, Chugh, S, Cirillo, M, Colquhoun, Sm, Cooper, Lt, Cooper, C, da Costa Leite, I, Dandona, L, Dandona, R, Davis, A, Dayama, A, Degenhardt, L, De Leo, D, Del Pozo-Cruz, B, Deribe, K, Dessalegn, M, Deveber, Ga, Dharmaratne, Sd, Dilmen, U, Ding, El, Dorrington, Re, Driscoll, Tr, Ermakov, Sp, Esteghamati, A, Faraon, Ej, Farzadfar, F, Felicio, Mm, Fereshtehnejad, Sm, de Lima, Gm, Forouzanfar, Mh, França, Eb, Gaffikin, L, Gambashidze, K, Gankpé, Fg, Garcia, Ac, Geleijnse, Jm, Gibney, Kb, Giroud, M, Glaser, El, Goginashvili, K, Gona, P, González-Castell, D, Goto, A, Gouda, Hn, Gugnani, Hc, Gupta, R, Hafezi-Nejad, N, Hamadeh, Rr, Hammami, M, Hankey, Gj, Harb, Hl, Havmoeller, R, Hay, S, Pi, Ib, Hoek, Hw, Hosgood, Hd, Hoy, Dg, Husseini, A, Idrisov, Bt, Innos, K, Inoue, M, Jacobsen, Kh, Jahangir, E, Jee, Sh, Jensen, Pn, Jha, V, Jiang, G, Juel, K, Kabagambe, Ek, Kan, H, Karam, Ne, Karch, A, Karema, Ck, Kaul, A, Kawakami, N, Kazanjan, K, Kazi, D, Kemp, Ag, Kengne, Ap, Kereselidze, M, Khader, Y, Khalifa, Se, Khan, Ea, Khang, Yh, Knibbs, L, Kokubo, Y, Kosen, S, Defo, Bk, Kulkarni, C, Kulkarni, V, Kumar, Ga, Kumar, K, Kumar, Rb, Kwan, G, Lai, T, Lalloo, R, Lam, H, Lansingh, Vc, Larsson, A, Lee, Jt, Leigh, J, Leinsalu, M, Leung, R, Li, X, Li, Y, Liang, J, Liang, X, Lim, S, Lin, Hh, Lipshultz, Se, Liu, S, Liu, Y, Lloyd, Bk, London, Sj, Lotufo, Pa, Ma, J, Ma, S, Machado, Vm, Mainoo, Nk, Majdan, M, Mapoma, Cc, Marcenes, W, Marzan, Mb, Mason-Jones, Aj, Mehndiratta, Mm, Mejia-Rodriguez, F, Memish, Za, Mendoza, W, Miller, Tr, Mills, Ej, Mokdad, Ah, Mola, Gl, Monasta, L, de la Cruz Monis, J, Hernandez, Jc, Moore, Ar, Mori, R, Mueller, Uo, Mukaigawara, M, Naheed, A, Naidoo, K, Nand, D, Nangia, V, Nash, D, Nejjari, C, Nelson, Rg, Neupane, Sp, Newton, Cr, Ng, M, Nieuwenhuijsen, Mj, Nisar, Mi, Nolte, S, Norheim, Of, Nyakarahuka, L, Oh, Ih, Ohkubo, T, Olusanya, Bo, Omer, Sb, Opio, Jn, Orisakwe, Oe, Pandian, Jd, Papachristou, C, Park, Jh, Caicedo, Aj, Patten, Sb, Paul, Vk, Pavlin, Bi, Pearce, N, Pereira, Dm, Pesudovs, K, Petzold, M, Poenaru, D, Polanczyk, Gv, Polinder, S, Pope, D, Pourmalek, F, Qato, D, Quistberg, Da, Rafay, A, Rahimi, K, Rahimi-Movaghar, V, Ur Rahman, S, Raju, M, Rana, Sm, Refaat, A, Ronfani, L, Roy, N, Pimienta, Tg, Sahraian, Ma, Salomon, J, Sampson, U, Santos, I, Sawhney, M, Sayinzoga, F, Schneider, Ij, Schumacher, A, Schwebel, Dc, Seedat, S, Sepanlou, Sg, Servan-Mori, Ee, Shakh-Nazarova, M, Sheikhbahaei, S, Shibuya, K, Shin, Hh, Shiue, I, Sigfusdottir, Id, Silberberg, Dh, Silva, Ap, Singh, Ja, Skirbekk, V, Sliwa, K, Soshnikov, S, Sposato, La, Sreeramareddy, Ct, Stroumpoulis, K, Sturua, L, Sykes, Bl, Tabb, Km, Talongwa, Rt, Tan, F, Teixeira, Cm, Tenkorang, Ey, Terkawi, A, Thorne-Lyman, Al, Tirschwell, Dl, Towbin, Ja, Tran, Bx, Tsilimbaris, M, Uchendu, U, Ukwaja, Kn, Undurraga, Ea, Uzun, Sb, Vallely, Aj, van Gool, Ch, Vasankari, Tj, Vavilala, M, Venketasubramanian, N, Villalpando, S, Violante, F, Vlassov, Vv, Vos, T, Waller, S, Wang, H, Wang, L, Wang, Sx, Wang, Y, Weichenthal, S, Weiderpass, E, Weintraub, Rg, Westerman, R, Wilkinson, Jd, Woldeyohannes, Sm, Wong, Jq, Wordofa, Ma, Xu, G, Yang, Yc, Yano, Y, Yentur, Gk, Yip, P, Yonemoto, N, Yoon, Sj, Younis, Mz, Yu, C, Jin, Ky, El Sayed Zaki, M, Zhao, Y, Zheng, Y, Zhou, M, Zhu, J, Zou, Xn, Lopez, Ad, Naghavi, M, Murray, Cj, Lozano, R, Cell biology, Epidemiology, Public Health, Erasmus MC other, Cardiothoracic Surgery, and Pathology

Subjects
Pediatrics, Time Factors, Nutrition and Disease, hiv-infection, immunodeficiency virus-1 infection, peripartum cardiomyopathy, Poison control, HIV Infections, IMMUNODEFICIENCY VIRUS-1 INFECTION, Socioeconomic Factor, Global Health, 0302 clinical medicine, PERIPARTUM CARDIOMYOPATHY, pregnancy-related mortality, Risk Factors, Pregnancy, Voeding en Ziekte, Cause of Death, Global health, HIV Infection, 030212 general & internal medicine, Pregnancy Complications, Infectious, 10. No inequality, Cause of death, 030219 obstetrics & reproductive medicine, south-africa, Medicine (all), 1. No poverty, WOMEN, PREGNANCY-RELATED MORTALITY, health initiatives, General Medicine, SOUTH-AFRICA, 3. Good health, Maternal Mortality, World Health, CHILD SURVIVAL, Female, Maternal death, women, Human, medicine.medical_specialty, Time Factor, DEATHS, child survival, Article, adult mortality, 03 medical and health sciences, Age Distribution, HEALTH INITIATIVES, SDG 3 - Good Health and Well-being, HIV-INFECTION, ADULT MORTALITY, Injury prevention, medicine, Organizational Objectives, Organizational Objective, Humans, VLAG, Models, Statistical, business.industry, Risk Factor, medicine.disease, deaths, Standardized mortality ratio, Socioeconomic Factors, Relative risk, Pregnancy Complications, Infectiou, business, Demography
Abstract

BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.FUNDING: Bill & Melinda Gates Foundation.

Published
2016

31. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013

Author

Vos, T, Barber, Rm, Bell, B, Bertozzi Villa, A, Biryukov, S, Bolliger, I, Charlson, F, Davis, A, Degenhardt, L, Dicker, D, Duan, L, Erskine, H, Feigin, Vl, Ferrari, Aj, Fitzmaurice, C, Fleming, T, Graetz, N, Guinovart, C, Haagsma, J, Hansen, Gm, Hanson, Sw, Heuton, Kr, Higashi, H, Kassebaum, N, Kyu, H, Laurie, E, Liang, X, Lofgren, K, Lozano, R, Macintyre, Mf, Moradi Lakeh, M, Naghavi, M, Nguyen, G, Odell, S, Ortblad, K, Roberts, Da, Roth, Ga, Sandar, L, Serina, Pt, Stanaway, Jd, Steiner, C, Thomas, B, Vollset, Se, Whiteford, H, Wolock, Tm, Ye, P, Zhou, M, Ãvila, Ma, Aasvang, Gm, Abbafati, C, Abbasoglu, Ozgoren, A, Abd Allah, F, Abdel, Aziz, Abera, Sf, Aboyans, V, Abraham, Jp, Abraham, B, Abubakar, I, Abu Raddad, Lj, Abu Rmeileh, Nm, Aburto, Tc, Achoki, T, Ackerman, In, Adelekan, A, Ademi, Z, Adou, Ak, Adsuar, Jc, Arnlov, J, Agardh, Ee, Khabouri, Al, Alam, Ss, Alasfoor, D, Albittar, Mi, Alegretti, Ma, Aleman, Av, Alemu, Za, Alfonso Cristancho, R, Alhabib, S, Ali, R, Alla, F, Allebeck, P, Allen, Pj, Almazroa, Ma, Alsharif, U, Alvarez, E, Alvis, Guzman, Ameli, N, O, Amini, H, Ammar, W, Anderson, Bo, Anderson, Hr, Antonio, Ca, Anwari, P, Apfel, H, Arsenijevic, Vs, Artaman, A, Asghar, Rj, Assadi, R, Atkins, Ls, Atkinson, C, Badawi, A, Bahit, Mc, Bakfalouni, T, Balakrishnan, K, Balalla, S, Banerjee, A, Barker Collo, Sl, Barquera, S, Barregard, L, Barrero, Lh, Basu, S, Basu, A, Baxter, A, Beardsley, J, Bedi, N, Beghi, E, Bekele, T, Bell, Ml, Benjet, C, Bennett, Da, Bensenor, Im, Benzian, H, Bernabe, E, Beyene, Tj, Bhala, N, Bhalla, A, Bhutta, Z, Bienhoff, K, Bikbov, B, Bin, Abdulhak, Blore, Jd, Blyth, Fm, Bohensky, Ma, Bora, Basara, B, Borges, G, Bornstein, Nm, Bose, D, Boufous, S, Bourne, Rr, Boyers, Ln, Brainin, M, Brauer, M, Brayne, Ce, Brazinova, A, Breitborde, Nj, Brenner, H, Briggs, Ad, Brooks, Pm, Brown, J, Brugha, Ts, Buchbinder, R, Buckle, Gc, Bukhman, G, Bulloch, Ag, Burch, M, Burnett, R, Cardenas, R, Cabral, Nl, Campos, Nonato, Campuzano, Ir, Carapetis, Jc, Carpenter, Do, Caso, V, Castaneda Orjuela, Ca, Catala Lopez, F, Chadha, Vk, Chang, Jc, Chen, H, Chen, W, Chiang, Pp, Chimed Ochir, O, Chowdhury, R, Christensen, H, Christophi, Ca, Chugh, Ss, Cirillo, Massimo, Coggeshall, M, Cohen, A, Colistro, V, Colquhoun, Sm, Contreras, Ag, Cooper, Lt, Cooper, C, Cooperrider, K, Coresh, J, Cortinovis, M, Criqui, Mh, Crump, Ja, Cuevas Nasu, L, Dandona, R, Dandona, L, Dansereau, E, Dantes, Hg, Dargan, Pi, Davey, G, Davitoiu, Dv, Dayama, A, La, De, Cruz, Gongora, De, V, Vega, La, De, Sf, Leo, D, Del, Pozo, Cruz, Dellavalle, Rp, Deribe, K, Derrett, S, Des, Jarlais, Dessalegn, M, Deveber, Ga, Dharmaratne, Sd, Diaz Torne, C, Ding, El, Dokova, K, Dorsey, Er, Driscoll, Tr, Duber, H, Durrani, Am, Edmond, Km, Ellenbogen, Rg, Endres, M, Ermakov, Sp, Eshrati, B, Esteghamati, A, Estep, K, Fahimi, S, Farzadfar, F, Fay, Df, Felson, Dt, Fereshtehnejad, Sm, Fernandes, Jg, Ferri, Cp, Flaxman, A, Foigt, N, Foreman, Kj, Fowkes, Fg, Franklin, Rc, Furst, T, Futran, Nd, Gabbe, Bj, Gankpe, Fg, Garcia, Guerra, Geleijnse, Fa, Gessner, Bd, Gibney, Kb, Gillum, Rf, Ginawi, Ia, Giroud, M, Giussani, G, Goenka, S, Goginashvili, K, Gona, P, Gonzalez, De, Cosio, T, Gosselin, Ra, Gotay, Cc, Goto, A, Gouda, Hn, Guerrant, Rl, Gugnani, Hc, Gunnell, D, Gupta, R, Gutierrez, Ra, Hafezi Nejad, N, Hagan, H, Halasa, Y, Hamadeh, Rr, Hamavid, H, Hammami, M, Hankey, Gj, Hao, Y, Harb, Hl, Haro, Jm, Havmoeller, R, Hay, Rj, Hay, S, Hedayati, Mt, Heredia, Pi, Heydarpour, P, Hijar, M, Hoek, Hw, Hoffman, Hj, Hornberger, Jc, Hosgood, Hd, Hossain, M, Hotez, Pj, Hoy, Dg, Hsairi, M, Hu, H, Hu, G, Huang, Jj, Huang, C, Huiart, L, Husseini, A, Iannarone, M, Iburg, Km, Innos, K, Inoue, M, Jacobsen, Kh, Jassal, Sk, Jeemon, P, Jensen, Pn, Jha, V, Jiang, G, Jiang, Y, Jonas, Jb, Joseph, J, Juel, K, Kan, H, Karch, A, Karimkhani, C, Karthikeyan, G, Katz, R, Kaul, A, Kawakami, N, Kazi, Ds, Kemp, Ah, Kengne, Ap, Khader, Ys, Khalifa, Se, Khan, Ea, Khan, G, Khang, Yh, Khonelidze, I, Kieling, C, Kim, D, Kim, S, Kimokoti, Rw, Kinfu, Y, Kinge, Jm, Kissela, Bm, Kivipelto, M, Knibbs, L, Knudsen, Ak, Kokubo, Y, Kosen, S, Kramer, A, Kravchenko, M, Krishnamurthi, Rv, Krishnaswami, S, Kuate, Defo, Kucuk, B, Bicer, B, Kuipers, Ej, Kulkarni, Vs, Kumar, K, Kumar, Ga, Kwan, Gf, Lai, T, Lalloo, R, Lam, H, Lan, Q, Lansingh, Vc, Larson, H, Larsson, A, Lawrynowicz, Ae, Leasher, Jl, Lee, Jt, Leigh, J, Leung, R, Levi, M, Li, B, Li, Y, Liang, J, Lim, S, Lin, Hh, Lind, M, Lindsay, Mp, Lipshultz, Se, Liu, S, Lloyd, Bk, Lockett, Ohno, S, Logroscino, G, Looker, Kj, Lopez, Ad, Lopez Olmedo, N, Lortet Tieulent, J, Lotufo, Pa, Low, N, Lucas, Rm, Lunevicius, R, Lyons, Ra, Ma, J, Ma, S, Mackay, Mt, Majdan, M, Malekzadeh, R, Mapoma, Cc, Marcenes, W, March, Lm, Margono, C, Marks, Gb, Marzan, Mb, Masci, Jr, Mason Jones, Aj, Matzopoulos, Rg, Mayosi, Bm, Mazorodze, Tt, Mcgill, Nw, Mcgrath, Jj, Mckee, M, Mclain, A, Mcmahon, Bj, Meaney, Pa, Mehndiratta, Mm, Mejia Rodriguez, F, Mekonnen, W, Melaku, Ya, Meltzer, M, Memish, Za, Mensah, G, Meretoja, A, Mhimbira, Fa, Micha, R, Miller, Tr, Mills, Ej, Mitchell, Pb, Mock, Cn, Moffitt, Te, Mohamed, Ibrahim, N, Mohammad, Ka, Mokdad, Ah, Mola, Gl, Monasta, L, Montico, M, Montine, Tj, Moore, Ar, Moran, Ae, Morawska, L, Mori, R, Moschandreas, J, Moturi, Wn, Moyer, M, Mozaffarian, D, Mueller, Uo, Mukaigawara, M, Murdoch, Me, Murray, J, Murthy, Ks, Naghavi, P, Nahas, Z, Naheed, A, Naidoo, Ks, Naldi, L, Nand, D, Nangia, V, Narayan, Km, Nash, D, Nejjari, C, Neupane, Sp, Newman, Lm, Newton, Cr, Ng, M, Ngalesoni, Fn, Nhung, Nt, Nisar, Mi, Nolte, S, Norheim, Of, Norman, Re, Norrving, B, Nyakarahuka, L, Ih, Oh, Ohkubo, T, Omer, Sb, Opio, Jn, Ortiz, A, Pandian, Jd, Panelo, Ci, Papachristou, C, Park, Ek, Parry, Cd, Caicedo, Aj, Patten, Sb, Paul, Vk, Pavlin, Bi, Pearce, N, Pedraza, Ls, Pellegrini, Ca, Pereira, Dm, Perez Ruiz, Fp, Perico, N, Pervaiz, A, Pesudovs, K, Peterson, Cb, Petzold, M, Phillips, Mr, Phillips, D, Phillips, B, Piel, Fb, Plass, D, Poenaru, D, Polanczyk, Gv, Polinder, S, Pope, Ca, Popova, S, Poulton, Rg, Pourmalek, F, Prabhakaran, D, Prasad, Nm, Qato, D, Quistberg, Da, Rafay, A, Rahimi, K, Rahimi Movaghar, V, Rahman, Su, Raju, M, Rakovac, I, Rana, Sm, Razavi, H, Refaat, A, Rehm, J, Remuzzi, G, Resnikoff, S, Ribeiro, Al, Riccio, Pm, Richardson, L, Richardus, Jh, Riederer, Am, Robinson, M, Roca, A, Rodriguez, A, Rojas Rueda, D, Ronfani, L, Rothenbacher, D, Roy, N, Ruhago, Gm, Sabin, N, Sacco, Rl, Ksoreide, K, Saha, S, Sahathevan, R, Sahraian, Ma, Sampson, U, Sanabria, Jr, Sanchez Riera, L, Santos, Is, Satpathy, M, Saunders, Je, Sawhney, M, Saylan, Mi, Scarborough, P, Schoettker, B, Schneider, Ij, Schwebel, Dc, Scott, Jg, Seedat, S, Sepanlou, Sg, Serdar, B, Servan Mori, Ee, Shackelford, K, Shaheen, A, Shahraz, S, Shamah, Levy, T, Shangguan, S, She, J, Sheikhbahaei, S, Shepard, Ds, Shi, P, Shibuya, K, Shinohara, Y, Shiri, R, Shishani, K, Shiue, I, Shrime, Mg, Sigfusdottir, Id, Silberberg, Dh, Simard, Ep, Sindi, S, Singh, Ja, Singh, L, Skirbekk, V, Sliwa, K, Soljak, M, Soneji, S, Soshnikov, Ss, Speyer, P, Sposato, La, Sreeramareddy, Ct, Stoeckl, H, Stathopoulou, Vk, Steckling, N, Stein, Mb, Stein, Dj, Steiner, Tj, Stewart, A, Stork, E, Stovner, Lj, Stroumpoulis, K, Sturua, L, Sunguya, Bf, Swaroop, M, Sykes, Bl, Tabb, Km, Takahashi, K, Tan, F, Tandon, N, Tanne, D, Tanner, M, Tavakkoli, M, Taylor, Hr, Ao, Te, Temesgen, Am, Ten, Have, M, Tenkorang, Ey, Terkawi, As, Theadom, Am, Thomas, E, Thorne Lyman, Al, Thrift, Ag, Tleyjeh, Im, Tonelli, M, Topouzis, F, Towbin, Ja, Toyoshima, H, Traebert, J, Tran, Bx, Trasande, L, Trillini, M, Truelsen, T, Trujillo, U, Tsilimbaris, M, Tuzcu, Em, Ukwaja, Kn, Undurraga, Ea, Uzun, Sb, Van, Brakel, Van, Wh, Vijver, De, Van, S, Dingenen, R, Van, Gool, Varakin, Yy, Vasankari, Tj, Vavilala, Ms, Veerman, Lj, Velasquez, Melendez, G, Venketasubramanian, N, Vijayakumar, L, Villalpando, S, Violante, Fs, Vlassov, Vv, Waller, S, Wallin, Mt, Wan, X, Wang, L, Wang, J, Wang, Y, Warouw, Ts, Weichenthal, S, Weiderpass, E, Weintraub, Rg, Werdecker, A, Wessells, Kr, Westerman, R, Wilkinson, Jd, Williams, Hc, Williams, Tn, Woldeyohannes, Sm, Wolfe, Cd, Wong, Jq, Wong, H, Woolf, Ad, Wright, Jl, Wurtz, B, Xu, G, Yang, G, Yano, Y, Yenesew, Ma, Yentur, Gk, Yip, P, Yonemoto, N, Yoon, Sj, Younis, M, Yu, C, Kim, Ky, Zaki, Mel, Zhang, Y, Zhao, Z, Zhao, Y, Zhu, J, Zonies, D, Zunt, Jr, Salomon, Ja, Murray, C. J., Vos, T, Barber, Rm, Bell, B, Bertozzi-Villa, A, Biryukov, S, Bolliger, I, Charlson, F, Davis, A, Degenhardt, L, Dicker, D, Duan, L, Erskine, H, Feigin, Vl, Ferrari, Aj, Fitzmaurice, C, Fleming, T, Graetz, N, Guinovart, C, Haagsma, J, Hansen, Gm, Hanson, Sw, Heuton, Kr, Higashi, H, Kassebaum, N, Kyu, H, Laurie ELiang, X, Lofgren, K, Lozano, R, Macintyre, Mf, Moradi-Lakeh, M, Naghavi, M, Nguyen, G, Odell, S, Ortblad, K, Roberts, Da, Roth, Ga, Sandar, L, Serina, Pt, Stanaway, Jd, Steiner, C, Thomas, B, Vollset, Se, Whiteford, H, Wolock, Tm, Ye, P, Zhou, M, Ãvila, Ma, Aasvang, Gm, Abbafati, C, Abbasoglu Ozgoren, A, Abd-Allah, F, Abdel Aziz MI, Abera, Sf, Aboyans, V, Abraham, Jp, Abraham, B, Abubakar, I, Abu-Raddad, Lj, Abu-Rmeileh, Nm, Aburto, Tc, Achoki TAckerman IN, Adelekan, A, Ademi, Z, Adou, Ak, Adsuar, Jc, Arnlov, J, Agardh, Ee, Al Khabouri MJ, Alam, S, Alasfoor, D, Albittar, Mi, Alegretti MAAleman AV, Alemu, Za, Alfonso-Cristancho, R, Alhabib, S, Ali, R, Alla, F, Allebeck, P, Allen, Pj, Almazroa, Ma, Alsharif, U, Alvarez, E, Alvis-Guzman NAmeli, O, Amini, H, Ammar, W, Anderson, Bo, Anderson, Hr, Antonio, Ca, Anwari, P, Apfel, H, Arsenijevic, V, Artaman, A, Asghar, Rj, Assadi, R, Atkins, L, Atkinson, C, Badawi, A, Bahit, Mc, Bakfalouni, T, Balakrishnan, K, Balalla, S, Banerjee, A, Barker-Collo, Sl, Barquera, S, Barregard, L, Barrero LHBasu, S, Basu, A, Baxter, A, Beardsley, J, Bedi, N, Beghi, E, Bekele, T, Bell, Ml, Benjet, C, Bennett, Da, Bensenor, Im, Benzian, H, Bernabe, E, Beyene TJBhala, N, Bhalla, A, Bhutta, Z, Bienhoff, K, Bikbov, B, Bin Abdulhak, A, Blore, Jd, Blyth, Fm, Bohensky, Ma, Bora Basara, B, Borges, G, Bornstein, Nm, Bose, D, Boufous, S, Bourne, Rr, Boyers, Ln, Brainin, M, Brauer, M, Brayne, Ce, Brazinova, A, Breitborde, Nj, Brenner, H, Briggs, Ad, Brooks, Pm, Brown JBrugha TS, Buchbinder, R, Buckle, Gc, Bukhman, G, Bulloch, Ag, Burch, M, Burnett, R, Cardenas, R, Cabral, Nl, Campos Nonato IR, Campuzano JCCarapetis JR, Carpenter, Do, Caso, V, Castaneda-Orjuela, Ca, Catala-Lopez, F, Chadha, Vk, Chang, Jc, Chen, H, Chen, W, Chiang, Pp, Chimed-Ochir, O, Chowdhury, R, Christensen, H, Christophi, Ca, Chugh, S, Cirillo, M, Coggeshall, M, Cohen, A, Colistro, V, Colquhoun, Sm, Contreras, Ag, Cooper LTCooper, C, Cooperrider, K, Coresh, J, Cortinovis, M, Criqui, Mh, Crump, Ja, Cuevas-Nasu, L, Dandona, R, Dandona, L, Dansereau, E, Dantes, Hg, Dargan, Pi, Davey, G, Davitoiu, Dv, Dayama, A, De la Cruz-Gongora, V, de la Vega SF, De Leo, D, del Pozo-Cruz, B, Dellavalle, Rp, Deribe, K, Derrett, S, Des Jarlais DC, Dessalegn, M, Deveber, Ga, Dharmaratne, Sd, Diaz-Torne, C, Ding, El, Dokova, K, Dorsey, Er, Driscoll, Tr, Duber, H, Durrani, Am, Edmond, Km, Ellenbogen, Rg, Endres, M, Ermakov, Sp, Eshrati, B, Esteghamati, A, Estep, K, Fahimi, S, Farzadfar, F, Fay, Df, Felson, Dt, Fereshtehnejad SMFernandes JG, Ferri, Cp, Flaxman, A, Foigt, N, Foreman, Kj, Fowkes, Fg, Franklin, Rc, Furst, T, Futran, Nd, Gabbe, Bj, Gankpe, Fg, Garcia-Guerra FAGeleijnse JM, Gessner, Bd, Gibney, Kb, Gillum, Rf, Ginawi, Ia, Giroud, M, Giussani, G, Goenka, S, Goginashvili, K, Gona, P, Gonzalez de Cosio TGosselin RA, Gotay, Cc, Goto, A, Gouda, Hn, Guerrant, Rl, Gugnani, Hc, Gunnell, D, Gupta, R, Gutierrez, Ra, Hafezi-Nejad, N, Hagan HHalasa, Y, Hamadeh, Rr, Hamavid, H, Hammami, M, Hankey, Gj, Hao, Y, Harb, Hl, Haro, Jm, Havmoeller, R, Hay, Rj, Hay, S, Hedayati, Mt, Heredia Pi IB, Heydarpour, P, Hijar, M, Hoek, Hw, Hoffman, Hj, Hornberger, Jc, Hosgood, Hd, Hossain, M, Hotez, Pj, Hoy, Dg, Hsairi, M, Hu, H, Hu, G, Huang JJHuang, C, Huiart, L, Husseini, A, Iannarone, M, Iburg, Km, Innos, K, Inoue, M, Jacobsen, Kh, Jassal, Sk, Jeemon, P, Jensen, Pn, Jha, V, Jiang, G, Jiang YJonas JB, Joseph, J, Juel, K, Kan, H, Karch, A, Karimkhani, C, Karthikeyan, G, Katz, R, Kaul, A, Kawakami, N, Kazi, D, Kemp, Ah, Kengne, Ap, Khader, Y, Khalifa, Se, Khan, Ea, Khan, G, Khang, Yh, Khonelidze, I, Kieling, C, Kim, D, Kim, S, Kimokoti, Rw, Kinfu, Y, Kinge, Jm, Kissela, Bm, Kivipelto MKnibbs, L, Knudsen, Ak, Kokubo, Y, Kosen, S, Kramer, A, Kravchenko, M, Krishnamurthi, Rv, Krishnaswami, S, Kuate Defo, B, Kucuk Bicer, B, Kuipers EJKulkarni VS, Kumar, K, Kumar, Ga, Kwan, Gf, Lai, T, Lalloo, R, Lam, H, Lan, Q, Lansingh, Vc, Larson, H, Larsson, A, Lawrynowicz, Ae, Leasher, Jl, Lee, Jt, Leigh, J, Leung, R, Levi, M, Li, B, Li, Y, Liang, J, Lim, S, Lin, Hh, Lind, M, Lindsay, Mp, Lipshultz, Se, Liu, S, Lloyd, Bk, Lockett Ohno, S, Logroscino, G, Looker, Kj, Lopez, Ad, Lopez-Olmedo, N, Lortet-Tieulent, J, Lotufo, Pa, Low, N, Lucas, Rm, Lunevicius, R, Lyons, Ra, Ma, J, Ma, S, Mackay MTMajdan, M, Malekzadeh, R, Mapoma, Cc, Marcenes, W, March, Lm, Margono, C, Marks, Gb, Marzan, Mb, Masci, Jr, Mason-Jones, Aj, Matzopoulos RGMayosi BM, Mazorodze, Tt, Mcgill, Nw, Mcgrath, Jj, Mckee, M, Mclain, A, Mcmahon, Bj, Meaney, Pa, Mehndiratta, Mm, Mejia-Rodriguez, F, Mekonnen, W, Melaku, Ya, Meltzer, M, Memish, Za, Mensah, G, Meretoja, A, Mhimbira, Fa, Micha, R, Miller, Tr, Mills, Ej, Mitchell, Pb, Mock, Cn, Moffitt TEMohamed Ibrahim, N, Mohammad, Ka, Mokdad, Ah, Mola, Gl, Monasta, L, Montico, M, Montine, Tj, Moore, Ar, Moran, Ae, Morawska, L, Mori RMoschandreas, J, Moturi, Wn, Moyer, M, Mozaffarian, D, Mueller, Uo, Mukaigawara, M, Murdoch, Me, Murray, J, Murthy, K, Naghavi, P, Nahas ZNaheed, A, Naidoo, K, Naldi, L, Nand, D, Nangia, V, Narayan, Km, Nash, D, Nejjari, C, Neupane, Sp, Newman, Lm, Newton, Cr, Ng, M, Ngalesoni FNNhung NT, Nisar, Mi, Nolte, S, Norheim, Of, Norman, Re, Norrving, B, Nyakarahuka, L, Oh, Ih, Ohkubo, T, Omer, Sb, Opio, Jn, Ortiz, A, Pandian JDPanelo CI, Papachristou, C, Park, Ek, Parry, Cd, Caicedo, Aj, Patten, Sb, Paul, Vk, Pavlin, Bi, Pearce, N, Pedraza, L, Pellegrini, Ca, Pereira, Dm, Perez-Ruiz, Fp, Perico, N, Pervaiz, A, Pesudovs, K, Peterson, Cb, Petzold, M, Phillips, Mr, Phillips, D, Phillips, B, Piel, Fb, Plass, D, Poenaru, D, Polanczyk GVPolinder, S, Pope, Ca, Popova, S, Poulton, Rg, Pourmalek, F, Prabhakaran, 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Ryan, Westerman, Ronny, Wilkinson, James D., Williams, Hywel C., Williams, Thomas N., Woldeyohannes, Solomon M., Wolfe, Charles D.A., Wong, John Q., Wong, Haidong, Woolf, Anthony D., Wright, Jonathan L., Wurtz, Brittany, Xu, Gelin, Yang, Gonghuan, Yano, Yuichiro, Yenesew, Muluken A., Yentur, Gokalp K., Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Younis, Mustafa, Yu, Chuanhua, Kim, Kim Yun, Zaki, Maysaa El Sayed, Zhang, Yong, Zhao, Zheng, Zhao, Yong, Zhu, Jun, Zonies, David, Zunt, Joseph R., Salomon, Joshua A., Murray, Christopher J.L., Cell biology, Gastroenterology & Hepatology, Epidemiology, Health Technology Assessment (HTA), and Public Health

Subjects
Male, Gerontology, Nutrition and Disease, Epidemiology, years lived with disability, Global burden of disease, acute and chronic diseases, countries, Prevalence, Disease, Global Health, Medical and Health Sciences, Conduct disorder, Otitis-media, Cost of Illness, Residence Characteristics, Voeding en Ziekte, 80 and over, Global health, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, countries, Aetiology, Child, Aged, 80 and over, Medicine(all), education.field_of_study, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, Incidence, Mortality rate, Incidence (epidemiology), Pain Research, Neglected Diseases, Alcohol dependence, General Medicine, Middle Aged, Global burden of disease, Global Burden of Disease Study 2013 Collaborators, Mental Health, Infectious Diseases, Attention deficit/Hyperactivity disorder, Burden of Illness, Child, Preschool, Acute Disease, Female, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Adolescent, GBD 2013, Population, acute and chronic diseases, Young Adult, Mental-disorders, Age Distribution, Medicine, General & Internal, Weights, General & Internal Medicine, medicine, Humans, Life Science, Disabled Persons, Sex Distribution, Preschool, education, Developing Countries, VLAG, Aged, Science & Technology, business.industry, Developed Countries, Cutaneous Leishmaniasis, Infant, Newborn, Infant, Health outcomes, Newborn, medicine.disease, Comorbidity, Brain Disorders, years lived with disability, Good Health and Well Being, Disease, injury, incidence, prevalence, YLDs, GBD 2010, Chronic Disease, Wounds and Injuries, business, 2.4 Surveillance and distribution, Iron-deficiency, Demography
Abstract

Summary Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2·4 billion and 1·6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537·6 million in 1990 to 764·8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114·87 per 1000 people to 110·31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21·1% in 1990 to 31·2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries. Funding Bill & Melinda Gates Foundation. Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2·4 billion and 1·6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537·6 million in 1990 to 764·8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114·87 per 1000 people to 110·31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21·1% in 1990 to 31·2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries. Funding Bill & Melinda Gates Foundation.

Published
2015

32. The Global Burden of Cancer 2013

Author

Juan R. Sanabria, Janet L Leasher, Eun-Kee Park, Al Artaman, James Leigh, Braden Te Ao, Graham S Cooke, Alan D. Lopez, G Anil Kumar, Rakhi Dandona, Randah R. Hamadeh, Scott B. Patten, Chante Karimkhani, Vasiliy Victorovich Vlassov, Marcella Montico, Sara Sheikhbahaei, Taavi Tillmann, Jasvinder A. Singh, Gillian M. Hansen, Chandrashekhar T Sreeramareddy, Paul S. F. Yip, Yuichiro Yano, Coen H. Van Gool, Nima Hafezi-Nejad, Luke D. Knibbs, Max Petzold, Mark Green, Charles D.A. Wolfe, Ulrich O Mueller, Johanna M. Geleijnse, David C. Schwebel, Chuanhua Yu, Jost B. Jonas, Christine Allen, Paulo A. Lotufo, Robyn M. Lucas, Lalit Dandona, Matias Trillini, Christopher J L Murray, Subhojit Dey, Naohiro Yonemoto, Hannah Hamavid, W. S. Marcenes, Mohsen Naghavi, Mustafa Z. Younis, Babak Eshrati, Ronny Westerman, Roderick J Hay, Kedede Deribe, Lorenzo Monasta, Brian J. McMahon, Tommi J. Vasankari, Luigi Naldi, Denis Nash, Maziar Moradi-Lakeh, Kjetil Søreide, Gabrielle deVeber, Robert P. Dellavalle, Ferrán Catalá-López, Hans Krueger, Scott Weichenthal, Christina Fitzmaurice, Kinnari S. Murthy, Wubegzier Mekonnen, Yongmei Li, Joshua A. Salomon, Gulfaraz Khan, Kingsley N. Ukwaja, Edward J Mills, Theo Vos, Ismael Campos, Luca Ronfani, H. Dean Hosgood, Ami R. Moore, Reza Malekzadeh, Farshad Pourmalek, Rosario Cardenas, Nobhojit Roy, Daniel Kim, Diego De Leo, Francesco Saverio Violante, Semaw Ferede Abera, Alireza Esteghamati, Vafa Rahimi-Movaghar, Haidong Wang, Rafael Lozano, Ken Takahashi, Raimundas Lunevicius, Kathryn H. Jacobsen, David O. Carpenter, Edgar P. Simard, Benjamin C Cowie, Mark G. Shrime, Graeme J. Hankey, Raghib Ali, Michael F. MacIntyre, Robert G. Weintraub, Ali Mokdad, Maia Kereselidze, A. Werdecker, David M. Pereira, Itamar S. Santos, Dietrich Plass, David Rojas-Rueda, Carlos A Castañeda-Orjuela, Kenji Shibuya, Daniel Dicker, Carolyn C. Gotay, Mohammad H. Forouzanfar, Stein Emil Vollset, Tim Driscoll, George D. Thurston, Hywel C Williams, Seyed-Mohammad Fereshtehnejad, Bradford D. Gessner, Kim Yun Jin, Carl Abelardo T. Antonio, Nicholas J K Breitborde, Ivy Shiue, Rachel Woodbrook, Ubai Alsharif, Richard C. Franklin, Dhruv S. Kazi, Sandra Nolte, Azmeraw T. Amare, Marcello Tonelli, Sadaf G. Sepanlou, In-Hwan Oh, Yohannes Adama Melaku, Justin Beardsley, Jennifer H MacLachlan, Amanda W Pain, Fitzmaurice, Christina, Dicker, Daniel, Pain, Amanda, Hamavid, Hannah, Moradi-Lakeh, Maziar, Macintyre, Michael F, Allen, Christine, Hansen, Gillian, Woodbrook, Rachel, Wolfe, Charle, Hamadeh, Randah R, Moore, Ami, Werdecker, Andrea, Gessner, Bradford D, Te Ao, Braden, Mcmahon, Brian, Karimkhani, Chante, Yu, Chuanhua, Cooke, Graham S, Schwebel, David C, Carpenter, David O, Pereira, David M, Nash, Deni, Kazi, Dhruv S, De Leo, Diego, Plass, Dietrich, Ukwaja, Kingsley N, Thurston, George D, Yun Jin, Kim, Simard, Edgar P, Mills, Edward, Park, Eun-Kee, Catalá-López, Ferrán, Deveber, Gabrielle, Gotay, Carolyn, Khan, Gulfaraz, Hosgood, H Dean, Santos, Itamar S, Leasher, Janet L, Singh, Jasvinder, Leigh, Jame, Jonas, Jost B, Jonas, Jost, Sanabria, Juan, Beardsley, Justin, Jacobsen, Kathryn H, Takahashi, Ken, Franklin, Richard C, Ronfani, Luca, Montico, Marcella, Naldi, Luigi, Tonelli, Marcello, Geleijnse, Johanna, Petzold, Max, Shrime, Mark G, Younis, Mustafa, Yonemoto, Naohiro, Breitborde, Nichola, Yip, Paul, Pourmalek, Farshad, Lotufo, Paulo A, Esteghamati, Alireza, Hankey, Graeme J, Ali, Raghib, Lunevicius, Raimunda, Malekzadeh, Reza, Dellavalle, Robert, Weintraub, Robert, Lucas, Robyn, Hay, Roderick, Rojas-Rueda, David, Westerman, Ronny, Sepanlou, Sadaf G, Nolte, Sandra, Patten, Scott, Weichenthal, Scott, Abera, Semaw Ferede, Fereshtehnejad, Seyed-Mohammad, Shiue, Ivy, Driscoll, Tim, Vasankari, Tommi, Alsharif, Ubai, Rahimi-Movaghar, Vafa, Vlassov, Vasiliy V, Marcenes, W S, Mekonnen, Wubegzier, Melaku, Yohannes Adama, Yano, Yuichiro, Artaman, Al, Campos, Ismael, Maclachlan, Jennifer, Mueller, Ulrich, Kim, Daniel, Trillini, Matia, Eshrati, Babak, Williams, Hywel C, Shibuya, Kenji, Dandona, Rakhi, Murthy, Kinnari, Cowie, Benjamin, Amare, Azmeraw T, Antonio, Carl Abelardo, Castañeda-Orjuela, Carlo, van Gool, Coen H, Violante, Francesco, Oh, In-Hwan, Deribe, Kedede, Soreide, Kjetil, Knibbs, Luke, Kereselidze, Maia, Green, Mark, Cardenas, Rosario, Roy, Nobhojit, Tillmann, Taavi, Tillman, Taavi, Li, Yongmei, Krueger, Han, Monasta, Lorenzo, Dey, Subhojit, Sheikhbahaei, Sara, Hafezi-Nejad, Nima, Kumar, G Anil, Sreeramareddy, Chandrashekhar T, Dandona, Lalit, Wang, Haidong, Vollset, Stein Emil, Mokdad, Ali, Salomon, Joshua A, Lozano, Rafael, Vos, Theo, Forouzanfar, Mohammad, Lopez, Alan, Murray, Christopher, and Naghavi, Mohsen

Subjects
Gerontology, Male, Cancer Research, Time Factors, Nutrition and Disease, Sex Factor, Global Health, Disability Evaluation, Risk Factors, Voeding en Ziekte, Neoplasms, Epidemiology of cancer, Prevalence, Age Factor, Child, Aged, 80 and over, Mortality rate, Incidence, Age Factors, Middle Aged, Prognosis, Oncology, Child, Preschool, Female, Human, Adult, Adolescent, Time Factor, Prognosi, Young Adult, Sex Factors, Breast cancer, Age Distribution, Life Expectancy, medicine, Life Science, Humans, Disability-adjusted life year, Sex Distribution, VLAG, Aged, Cancer Death Rate, Cancer prevention, business.industry, Risk Factor, Cancer, medicine.disease, Years of potential life lost, Neoplasm, business, Demography
Abstract

Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. OBJECTIVE To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. EVIDENCE REVIEW The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. TheMI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated usingMI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. FINDINGS In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. CONCLUSIONS AND RELEVANCE Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.

Published
2015

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