NISAN - the National Institute for Stroke and Applied Neurosciences
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Institute Director: Professor Valery Feigin
Deputy Director: Associate Professor Alice Theadom
The National Institute for Stroke and Applied Neurosciences (NISAN) conducts epidemiological studies and clinical trials to improve health and outcomes in people with major neurological disorders. Current research programmes focus on:
- Stroke
- Traumatic brain injury
- Neuromuscular disorders
- Neuroepidemiology
- Public health
- Neurorehabilitation
- Neuropsychology
- Biostatistics
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- ItemGlobal and Regional Burden of First-ever Ischaemic and Haemorrhagic Stroke During 1990-2010: Findings From the Global Burden of Disease Study 2010(Elsevier (Open), 2013-11) Krishnamurthi, RV; Feigin, VL; Forouzanfar, MH; Mensah, GA; Connor, M; Bennett, DA; Moran, AE; Sacco, RL; Anderson, LM; Truelsen, T; O'Donnell, M; Venketasubramanian, N; Barker-Collo, S; Lawes, CM; Wang, W; Shinohara, Y; Witt, E; Ezzati, M; Naghavi, M; Murray, C; The Lancet Global Health. Volume 1, Issue 5, November 2013, Pages e259–e281; GBD Stroke Experts GroupBackground The burden of ischaemic and haemorrhagic stroke varies between regions and over time. With differences in prognosis, revalence of risk factors, and treatment strategies, knowledge of stroke pathological type is important fortargeted region-specific health-care planning for stroke and could inform priorities for type-specific prevention strategies. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010. Methods We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR) to calculate regional and country-specific estimates for ischaemic and haemorrhagic stroke incidence, mortality, mortality-to-incidence ratio, and disability-adjusted life years (DALYs) lost, by age group (aged <75 years, ≥75 years, and in total) and country income level (high-income and low-income and middle-income) for 1990, 2005, and 2010. Findings We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). Worldwide, the burden of ischaemic and haemorrhagic stroke increased significantly between 1990 and 2010 in terms of the absolute number of people with incident ischaemic and haemorrhagic stroke (37% and 47% increase, respectively), number of deaths (21% and 20% increase), and DALYs lost (18% and 14% increase). In the past two decades in high-income countries, incidence of ischaemic stroke reduced significantly by 13% (95% CI 6–18), mortality by 37% (19–39), DALYs lost by 34% (16–36), and mortality-to-incidence ratios by 21% (10–27). For haemorrhagic stroke, incidence reduced significantly by 19% (1–15), mortality by 38% (32–43), DALYs lost by 39% (32–44), and mortality-to-incidence ratios by 27% (19–35). By contrast, in low-income and middle-income countries, we noted a significant increase of 22% (5–30) in incidence of haemorrhagic stroke and a 6% (–7 to 18) non-significant increase in the incidence of ischaemic stroke. Mortality rates for ischaemic stroke fell by 14% (9–19), DALYs lost by 17% (–11 to 21%), and mortality-to-incidence ratios by 16% (–12 to 22). For haemorrhagic stroke in low-income and middle-income countries, mortality rates reduced by 23% (–18 to 25%), DALYs lost by 25% (–21 to 28), and mortalityto-incidence ratios by 36% (–34 to 28). Interpretation Although age-standardised mortality rates for ischaemic and haemorrhagic stroke have decreased in the past two decades, the absolute number of people who have these stroke types annually, and the number with related deaths and DALYs lost, is increasing, with most of the burden in low-income and middle-income countries. Further study is needed in these countries to identify which subgroups of the population are at greatest risk and who could be targeted for preventive efforts.
- ItemPrevalence of Muscular Dystrophies: A Systematic Literature Review(Karger, 2014) Theadom, A; Rodrigues, M; Roxburgh, R; Balalla, S; Higgins, C; Bhattacharjee, R; Jones, K; Krishnamurthi, R; Feigin, VBackground: Determining the prevalence of neuromuscular disorders for the general population is important to identify the scope of burden on society and enable comparisons with other health conditions. This systematic review aims to identify and collate the findings of studies published between 1960 and 2013 on the prevalence of all types of muscular dystrophies. Summary: Relevant articles were identified through electronic database searches and manual searches of reference lists. There were 38 articles from across 19 countries that met the inclusion criteria. The total combined prevalence for all muscular dystrophies for studies classified as having a low risk of bias ranged between 19.8 and 25.1 per 100,000 person-years. Myotonic dystrophy (0.5-18.1 per 100,000), Duchenne muscular dystrophy (1.7-4.2) and facioscapulohumeral muscular dystrophy (3.2-4.6 per 100,000) were found to be the most common types of disorder. There was wide variation in study methodology, case ascertainment, and verification procedures and populations studied, all of which may contribute to the wide prevalence range, in addition to the likely variation in prevalence by country. Key Messages: Greater consistency in the conduct and reporting of neuroepidemiological studies is urgently needed to enable comparisons to be made between studies, countries, and over time.
- ItemThe Global Burden of Ischemic Stroke: Findings of the GBD 2010 Study(Elsevier, 2014) Bennett, DA; Krishnamurthi, RV; Barker-Collo, S; Forouzanfar, MH; Naghavi, M; Connor, M; Lawes, CMM; Moran, AE; Anderson, LM; Roth, GA; Mensah, GA; Ezzati, M; Murray, CJL; Feigin, VLBackground and objectives: To summarize the findings of The Global Burden of Diseases, Injuries, and Risk Factors (GBD 2010) Study for ischaemic stroke (IS) and report the impact of tobacco smoking on IS burden in specific countries. Methods: The GBD 2010 searched multiple databases to identify relevant studies published between 1990 and 2010. The GBD 2010 analytical tools were used to calculate region-specific IS incidence, mortality, mortality to incidence (MI) ratio and disability-adjusted life years (DALYs) lost, including 95% uncertainty intervals (UI). Findings: In 2010, there were approximately 11,569,000 incident IS events (63% in low- and middleincome countries [LMIC]), approximately 2,835,000 deaths from IS (57% in LMIC), and approximately 39,389,000 DALYs lost due to IS (64% in LMIC).From 1990-2010, there was a significant increase in global IS burden in terms of absolute number of people with incident IS (37% increase), deaths from IS (21% increase) and DALYs lost due to IS (18% increase). Age-standardised IS incidence, DALYs lost, mortality, and MI ratios in HIC declined by about 13% (95% UI 6-18%), 34% (95% UI 16-36%), and 37% (95% UI 19-39%), 21% (95% UI 10-27%), respectively. However, in LMIC there was a modest 6% increase in the age-standardised incidence of IS (95% UI -7%; 18%) despite modest reductions in mortality rates, DALYs lost, and MI ratios. There was considerable variability among country-specific estimates within broad GBD regions. China, Russia and India were ranked highest in both 1990 and 2010 for IS deaths attributable to tobacco consumption. Conclusions: Although age-standardized IS mortality rates have declined over the last two decades, the absolute global burden of IS is increasing, with the bulk of DALYs lost in LMIC. Tobacco consumption is an important modifiable risk factor for IS and in both 1990 and 2010 the top ranked countries for IS deaths that could be attributed to tobacco consumption were China, Russia and India. Tobacco control policies that target both smoking initiation and smoking cessation can play an important role in the prevention of IS. In China, Russia and India, even modest reductions in the number of current smokers could see millions of lives saved due to prevention of IS alone.
- ItemThe Global Burden of Mental, Neurological and Substance Use Disorders: An Analysis From the Global Burden of Disease Study 2010(PLOS, 2015) Whiteford, HA; Ferrari, AJ; Degenhardt, L; Feigin, V; Vos, TBackground The Global Burden of Disease Study 2010 (GBD 2010), estimated that a substantial proportion of the world’s disease burden came from mental, neurological and substance use disorders. In this paper, we used GBD 2010 data to investigate time, year, region and age specific trends in burden due to mental, neurological and substance use disorders. Method For each disorder, prevalence data were assembled from systematic literature reviews. DisMod-MR, a Bayesian meta-regression tool, was used to model prevalence by country, region, age, sex and year. Prevalence data were combined with disability weights derived from survey data to estimate years lived with disability (YLDs). Years lost to premature mortality (YLLs) were estimated by multiplying deaths occurring as a result of a given disorder by the reference standard life expectancy at the age death occurred. Disability-adjusted life years (DALYs) were computed as the sum of YLDs and YLLs. Results In 2010, mental, neurological and substance use disorders accounted for 10.4% of global DALYs, 2.3% of global YLLs and, 28.5% of global YLDs, making them the leading cause of YLDs. Mental disorders accounted for the largest proportion of DALYs (56.7%), followed by neurological disorders (28.6%) and substance use disorders (14.7%). DALYs peaked in early adulthood for mental and substance use disorders but were more consistent across age for neurological disorders. Females accounted for more DALYs in all mental and neurological disorders, except for mental disorders occurring in childhood, schizophrenia, substance use disorders, Parkinson’s disease and epilepsy where males accounted for more DALYs. Overall DALYs were highest in Eastern Europe/Central Asia and lowest in East Asia/the Pacific. Conclusion Mental, neurological and substance use disorders contribute to a significant proportion of disease burden. Health systems can respond by implementing established, cost effective interventions, or by supporting the research necessary to develop better prevention and treatment options.
- ItemAmbient Air Pollution Exposure Estimation for the Global Burden of Disease 2012(American Chemical Society (ACS), 2015) Brauer, M; Feigin, V; et alExposure to ambient air pollution is a major risk factor for global disease. Assessment of the impacts of air pollution on population health and evaluation of trends relative to other major risk factors requires regularly updated, accurate, spatially resolved exposure estimates. We combined satellite-based estimates, chemical transport model simulations, and ground measurements from 79 different countries to produce global estimates of annual average fine particle (PM2.5) and ozone concentrations at 0.1° × 0.1° spatial resolution for five-year intervals from 1990 to 2010 and the year 2013. These estimates were applied to assess population-weighted mean concentrations for 1990–2013 for each of 188 countries. In 2013, 87% of the world’s population lived in areas exceeding the World Health Organization Air Quality Guideline of 10 μg/m3 PM2.5 (annual average). Between 1990 and 2013, global population-weighted PM2.5 increased by 20.4% driven by trends in South Asia, Southeast Asia, and China. Decreases in population-weighted mean concentrations of PM2.5 were evident in most high income countries. Population-weighted mean concentrations of ozone increased globally by 8.9% from 1990–2013 with increases in most countries—except for modest decreases in North America, parts of Europe, and several countries in Southeast Asia.
- ItemMortality From Cardiovascular Diseases in Sub-saharan Africa, 1990-2013: A Systematic Analysis of Data From the Global Burden of Disease Study 2013(Clinics Cardive Publishing, 2015) Mensah, GA; Roth, GA; Sampson, UK; Moran, AE; Feigin, VL; Forouzanfar, MH; Naghavi, M; Murray, CJ; GBD 2013 Mortality and Causes of Death collaboratorsCardiovascular disease (CVD) has been the leading cause of death in developed countries for most of the last century. Most CVD deaths, however, occur in low- and middle-income, developing countries (LMICs) and there is great concern that CVD mortality and burden are rapidly increasing in LMICs as a result of population growth, ageing and health transitions. In sub-Saharan Africa (SSA), where all countries are part of the LMICs, the pattern, magnitude and trends in CVD deaths remain incompletely understood, which limits formulation of data-driven regional and national health policies.
- ItemDaytime Napping Associated With Increased Symptom Severity in Fibromyalgia Syndrome(BioMed Central Ltd., 2015) Theadom, A; Cropley, M; Kantermann, TBackground: Previous qualitative research has revealed that people with fibromyalgia use daytime napping as a coping strategy for managing symptoms against clinical advice. Yet there is no evidence to suggest whether daytime napping is beneficial or detrimental for people with fibromyalgia. The purpose of this study was to explore how people use daytime naps and to determine the links between daytime napping and symptom severity in fibromyalgia syndrome. Methods: A community based sample of 1044 adults who had been diagnosed with fibromyalgia syndrome by a clinician completed an online questionnaire. Associations between napping behavior, sleep quality and fibromyalgia symptoms were explored using Spearman correlations, with possible predictors of napping behaviour entered into a logistic regression model. Differences between participants who napped on a daily basis and those who napped less regularly, as well as nap duration were explored. Results: Daytime napping was significantly associated with increased pain, depression, anxiety, fatigue, memory difficulties and sleep problems. Sleep problems and fatigue explained the greatest amount of variance in napping behaviour, p < 0.010. Those who engaged in daytime naps for >30 minutes had higher memory difficulties (t = -3.45) and levels of depression (t = -2.50) than those who napped for shorter periods (<30mins) (p < 0.010). Conclusions: Frequent use and longer duration of daytime napping was linked with greater symptom severity in people with fibromyalgia. Given the common use of daytime napping in people with fibromyalgia evidence based guidelines on the use of daytime napping in people with chronic pain are urgently needed.
- ItemCollaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (Center-tbi): A Prospective Longitudinal Observational Study(Congress of Neurological Surgeons, 2015) Theadom, A; Maas, AIR; Menon, D; Steyerberg, EW; Citerio, G; Lecky, F; Manley, GT; Hill, S; Legrand, V; Sorgner, A; On behalf of the CENTER-TBI participants and, IBACKGROUND: Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE: To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS: This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients, presenting within 24 hours of injury, with a clinical diagnosis of TBI and an indication for computed tomography. Broader registry-level data collection in approximately 20 000 patients will assess generalizability. Cross sectional comprehensive outcome assessments, including quality of life and neuropsychological testing, will be performed at 6 months. Longitudinal assessments will continue up to 24 months post TBI in patient subsets. Advanced neuroimaging and genomic and biomarker data will be used to improve characterization, and analyses will include neuroinformatics approaches to address variations in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES: Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification, evidence to support treatment recommendations, and benchmarks for quality of care. Data and sample repositories will ensure opportunities for legacy research. DISCUSSION: Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient populations by exploiting differences in biology, care, and outcome to support optimal personalized patient management.
- ItemMethodology of the Stroke Self-management Rehabilitation Trial: An International, Multisite Pilot Trial(Elsevier, 2015) Jones, KM; Bhattacharjee, R; Krishnamurthi, R; Blanton, S; Theadom, A; Barker-Collo, S; Thrift, A; Parmar, P; Maujean, A; Ranta, A; Sanya, E; Feigin, VL; on behalf of the SMART Study GroupRationale Stroke is a major cause of long-term adult disability with many survivors living in the community relying on family members for on-going support. However, reports of inadequate understanding of rehabilitation techniques are common. A self-management DVD-based observational learning tool may help improve functional outcomes for survivors of stroke and reduce caregivers' burden. Aims This article describes the methodology of the stroke self-management rehabilitation trial. The overall aim of this pilot trial is to assess the feasibility and preliminary efficacy of a DVD-based intervention for improving functional outcomes of survivors of stroke 2 months postrandomization to inform the design of a full-scale randomized clinical trial. Design Recruitment of a minimum of 20 survivors of stroke and their informal caregivers (where available) in each of the participating centers will occur across multiple international sites. After baseline assessments, participants will be randomly assigned to an intervention or standard care group. The intervention comprises a structured DVD observation and practice schedule over 8 weeks. All participants will complete follow-up assessments. Study outcomes The outcome measures will include a global shift in the Rankin Scale scores and dichotomized scores, changes in quality of life, general health, depression, and caregiver burden at 2 months postrandomization. A qualitative analysis of the effects of the intervention will also be undertaken. Discussion The results of the pilot study will provide knowledge of whether observational learning techniques delivered via DVD can effectively improve recovery after stroke and reduce caregiver burden.
- ItemEpidemiology of Traumatic Brain Injury in Europe: A Living Systematic Review(Mary Ann Liebert, Inc., 2015) Brazinova, A; Rehorcikova, V; Taylor, MS; Buckova, V; Majdan, M; Psota, M; Peeters, W; Feigin, V; Theadom, A; Holkovic, L; Synnot, AThis systematic review provides a comprehensive, up-to-date summary of traumatic brain injury (TBI) epidemiology in Europe, describing incidence, mortality, age, and sex distribution, plus severity, mechanism of injury, and time trends. PubMed, CINAHL, EMBASE, and Web of Science were searched in January 2015 for observational, descriptive, English language studies reporting incidence, mortality, or case fatality of TBI in Europe. There were no limitations according to date, age, or TBI severity. Methodological quality was assessed using the Methodological Evaluation of Observational Research checklist. Data were presented narratively. Sixty-six studies were included in the review. Country-level data were provided in 22 studies, regional population or treatment center catchment area data were reported by 44 studies. Crude incidence rates varied widely. For all ages and TBI severities, crude incidence rates ranged from 47.3 per 100,000, to 694 per 100,000 population per year (country-level studies) and 83.3 per 100,000, to 849 per 100,000 population per year (regional-level studies). Crude mortality rates ranged from 9 to 28.10 per 100,000 population per year (country-level studies), and 3.3 to 24.4 per 100,000 population per year (regional-level studies.) The most common mechanisms of injury were traffic accidents and falls. Over time, the contribution of traffic accidents to total TBI events may be reducing. Case ascertainment and definitions of TBI are variable. Improved standardization would enable more accurate comparisons.
- ItemFrom Data to Action: Neuroepidemiology Informs Implementation Research for Global Stroke Prevention and Treatment(Karger, 2015) Mensah, GA; Sacco, RL; Vickrey, BG; Sampson, UKA; Waddy, S; Ovbiagel, B; Pandian, JD; Norrving, B; Feigin, VLAs a scientific field of study, neuroepidemiology encompasses more than just the descriptive study of the frequency, distribution, determinants and outcomes of neurologic diseases in populations. It also includes experimental aspects that span the full spectrum of clinical and population science research. As such, neuroepidemiology has a strong potential to inform implementation research for global stroke prevention and treatment. This review begins with an overview of the progress that has been made in descriptive and experimental neuroepidemiology over the past quarter century with emphasis on standards for evidence generation, critical appraisal of that evidence and impact on clinical and public health practice at the national, regional and global levels. Specific advances made in high-income countries as well as in low- and middle-income countries are presented. Gaps in implementation as well as evidence gaps in stroke research, stroke burden, clinical outcomes and disparities between developed and developing countries are then described. The continuing need for high quality neuroepidemiologic data in low- and middle-income countries is highlighted. Additionally, persisting disparities in stroke burden and care by sex, race, ethnicity, income and socioeconomic status are discussed. The crucial role that national stroke registries have played in neuroepidemiologic research is also addressed. Opportunities presented by new directions in comparative effectiveness and implementation research are discussed as avenues for turning neuroepidemiological insights into action to maximize health impact and to guide further biomedical research on neurological diseases.
- ItemMind and Body Therapy for Fibromyalgia(John Wiley & Sons, Inc., 2015-04-09) Theadom, A; Cropley, M; Smith, HE; Feigin, VL; McPherson, KMind-body interventions are based on the holistic principle that mind, body and behaviour are all interconnected. Mind-body interventions incorporate strategies that are thought to improve psychological and physical well-being, aim to allow patients to take an active role in their treatment, and promote people's ability to cope. Mind-body interventions are widely used by people with fibromyalgia to help manage their symptoms and improve well-being. Examples of mind-body therapies include psychological therapies, biofeedback, mindfulness, movement therapies and relaxation strategies.
- ItemGlobal, Regional, and National Comparative Risk Assessment of 79 Behavioural, Environmental and Occupational, and Metabolic Risks or Clusters of Risks, 1990-2015: A Systematic Analysis for the Global Burden of Disease Study 2015(Elsevier, 2016) Feigin, V; GBD 2015 Risk Factors CollaboratorsBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted causespecifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient defi ciencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading fi ve risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden.
- ItemGlobal, Regional, and National Incidence, Prevalence, and Years Lived With Disability for 310 Acute and Chronic Diseases and Injuries, 1990-2015: A Systematic Analysis for the Global Burden of Disease Study 2015(Elsevier, 2016) Feigin, V; GBD 2015 Disease and Injury Incidence and Prevalence CollaboratorsBackground Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores. Findings We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4–19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30–2·50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35–2·37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20–30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo. Interpretation Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available.
- ItemMeasuring the Health-related Sustainable Development Goals in 188 Countries: A Baseline Analysis From the Global Burden of Disease Study 2015(Elsevier, 2016) Feigin, V; GBD 2015 SDG CollaboratorsBackground In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). Methods We applied statistical methods to systematically compiled data to estimate the performance of 33 healthrelated SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. Findings In 2015, the median health-related SDG index was 59∙3 (95% uncertainty interval 56∙8–61∙8) and varied widely by country, ranging from 85∙5 (84∙2–86∙5) in Iceland to 20∙4 (15∙4–24∙9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r²=0∙88) and the MDG index (r²=0∙92), whereas the non-MDG index had a weaker relation with SDI (r²=0∙79). Between 2000 and 2015, the health-related SDG index improved by a median of 7∙9 (IQR 5∙0–10∙4), and gains on the MDG index (a median change of 10∙0 [6∙7–13∙1]) exceeded that of the non- MDG index (a median change of 5∙5 [2∙1–8∙9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. Interpretation GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be suffi cient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to eff ectively address the expanded scope of the health-related SDGs.
- ItemOptimising Qualitative Longitudinal Analysis: Insights From a Study of Traumatic Brain Injury Recovery and Adaptation(John Wiley & Sons, 2016) Fadyl, JK; Channon, A; Theadom, A; McPherson, KM; TBI Experiences Research GroupKnowledge about aspects that influence recovery and adaptation in the postacute phase of disabling health events is key to understanding how best to provide appropriate rehabilitation and health services. Qualitative longitudinal research makes it possible to look for patterns, key time points and critical moments that could be vital for interventions and supports. However, strategies that support robust data management and analysis for longitudinal qualitative research in health-care are not well documented in the literature. This article reviews three challenges encountered in a large longitudinal qualitative descriptive study about experiences of recovery and adaptation after traumatic brain injury in New Zealand, and the strategies and technologies used to address them. These were (i) tracking coding and analysis decisions during an extended analysis period; (ii) navigating interpretations over time and in response to new data; and (iii) exploiting data volume and complexity. Concept mapping during coding review, a considered combination of information technologies, employing both cross-sectional and narrative analysis, and an expectation that subanalyses would be required for key topics helped us manage the study in a way that facilitated useful and novel insights. These strategies could be applied in other qualitative longitudinal studies in healthcare inquiry to optimise data analysis and stimulate important insights.
- ItemIncidence of Transient Ischemic Attack in Auckland, New Zealand, in 2011 to 2012(American Heart Association, 2016) Barber, PA; Krishnamurthi, R; Parag, V; Anderson, NE; Ranta, A; Klifoyle, D; Wong, E; Green, G; Arroll, B; Bennett, DA; Witt, E; Rush, E; Suh, FM; Theadom, A; Rathnasabapathy, Y; Te Ao, B; Parmar, P; Feigin, V; for the ARCOS IV study groupBackground and Purpose—There have been few recent population-based studies reporting the incidence (first ever) and attack rates (incident and recurrent) of transient ischemic attack (TIA). Methods—The fourth Auckland Regional Community Stroke study (ARCOS IV) used multiple overlapping case ascertainment methods to identify all hospitalized and nonhospitalized cases of TIA that occurred in people ≥16 years of age usually resident in Auckland (population ≥16 years of age is 1.12 million), during the 12 months from March 1, 2011. All first-ever and recurrent new TIAs (any new TIA 28 days after the index event) during the study period were recorded. Results—There were 785 people with TIA (402 [51.2%] women, mean [SD] age 71.5 [13.8] years); 614 (78%) of European origin, 84 (11%) Māori/Pacific, and 75 (10%) Asian/Other. The annual incidence of TIA was 40 (95% confidence interval, 36–43), and attack rate was 63 (95% confidence interval, 59–68), per 100 000 people, age standardized to the World Health Organization world population. Approximately two thirds of people were known to be hypertensive or were being treated with blood pressure–lowering agents, half were taking antiplatelet agents and just under half were taking lipid-lowering therapy before the index TIA. Two hundred ten (27%) people were known to have atrial fibrillation at the time of the TIA, of whom only 61 (29%) were taking anticoagulant therapy, suggesting a failure to identify or treat atrial fibrillation. Conclusions—This study describes the burden of TIA in an era of aggressive primary and secondary vascular risk factor management. Education programs for medical practitioners and patients around the identification and management of atrial fibrillation are required.
- ItemReliable Individual Change in Post Concussive Symptoms in the Year Following Mild Traumatic Brain Injury: Data From the Longitudinal, Population-based Brain Injury Incidence and Outcomes New Zealand in the Community (Bionic) Study(JSciMed Central, 2016) Barker-Collo, S; Theadom, A; Jones, K; Ameratunga, S; Feigin, V; Starkey, N; Dudley, M; Kahan, MObjective: Post concussive syndromes (PCS) is common after mild-TBI, yet are not well studied on a population level. This study examined PCS symptoms, including reliable change over time in a population-based sample up to one year post-TBI. Methods: Prospective follow-up of 527 adults (≥16 years) with mild TBI (mTBI) and assessment data (Rivermead Post concussion Questionnaire; RPQ) at baseline, 1, 6, and/or 12-months post-TBI. Change in mean scores and clinically significant change across RPQ items for each person was calculated between assessment time points using a reliable change index (RCI). Results: While prevalence of all symptoms reduced over time, >30% of participants reported fatigue, slowed thinking, and forgetfulness 12-months postinjury. Using the RCI, <12% of individuals improved from baseline to 1-month, 50% from 1 to 6-months, and 4.2% from 6 to 12-months. Conclusions: Improvements in PCS post-mTBI were most obvious between 1 and 6-months, suggesting lengthy recovery trajectory. A third of patients experience residual cognitive problems 12-months following a mTBI, and while many individuals improve post-TBI, a large proportion remain stable or worsen.
- ItemGlobal, Regional, and National Life Expectancy, All-cause Mortality, and Cause-specific Mortality for 249 Causes of Death, 1980-2015: A Systematic Analysis for the Global Burden of Disease Study 2015(Elsevier, 2016) Feigin, V; GBD2015 Mortality and Causes of Death CollaboratorsBackground Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography–year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4–61·9) in 1980 to 71·8 years (71·5–72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7–17·4), to 62·6 years (56·5–70·2). Total deaths increased by 4·1% (2·6–5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8–18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6–16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9–14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1–44·6), malaria (43·1%, 34·7–51·8), neonatal preterm birth complications (29·8%, 24·8–34·9), and maternal disorders (29·1%, 19·3–37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000–183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000–532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
- ItemGlobal, Regional, and National Disability-adjusted Life Years (Dalys) for 315 Diseases and Injuries and Healthy Life Expectancy (Hale), 1990-2015: A Systematic Analysis for the Global Burden of Disease Study 2015(Elsevier, 2016) Feigin, V; GBD 2015 DALYs and HALE CollaboratorsBackground Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specifi c death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE diff ered from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes signifi cantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9–3·0) for men and 3·5 years (3·4–3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78–0·92) and 1·2 years (1·1–1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued eff orts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specifi c health performance and SDG progress. Countryspecifi c drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform fi nancial and research investments, prevention eff orts,