Rafael Tabarés‐Seisdedos

BACKGROUND: Neurological disorders are now the leading source of disability globally, and ageing is increasing the burden of neurodegenerative disorders, including Parkinson's disease. We aimed to determine the global burden of Parkinson's disease between 1990 and 2016 to identify trends and to enable appropriate public health, medical, and scientific responses. METHODS: Through a systematic analysis of epidemiological studies, we estimated global, regional, and country-specific prevalence and years of life lived with disability for Parkinson's disease from 1990 to 2016. We estimated the proportion of mild, moderate, and severe Parkinson's disease on the basis of studies that used the Hoehn and Yahr scale and assigned disability weights to each level. We jointly modelled prevalence and excess mortality risk in a natural history model to derive estimates of deaths due to Parkinson's disease. Death counts were multiplied by values from the Global Burden of Disease study's standard life expectancy to compute years of life lost. Disability-adjusted life-years (DALYs) were computed as the sum of years lived with disability and years of life lost. We also analysed results based on the Socio-demographic Index, a compound measure of income per capita, education, and fertility. FINDINGS: In 2016, 6·1 million (95% uncertainty interval [UI] 5·0-7·3) individuals had Parkinson's disease globally, compared with 2·5 million (2·0-3·0) in 1990. This increase was not solely due to increasing numbers of older people, because age-standardised prevalence rates increased by 21·7% (95% UI 18·1-25·3) over the same period (compared with an increase of 74·3%, 95% UI 69·2-79·6, for crude prevalence rates). Parkinson's disease caused 3·2 million (95% UI 2·6-4·0) DALYs and 211 296 deaths (95% UI 167 771-265 160) in 2016. The male-to-female ratios of age-standardised prevalence rates were similar in 2016 (1·40, 95% UI 1·36-1·43) and 1990 (1·37, 1·34-1·40). From 1990 to 2016, age-standardised prevalence, DALY rates, and death rates increased for all global burden of disease regions except for southern Latin America, eastern Europe, and Oceania. In addition, age-standardised DALY rates generally increased across the Socio-demographic Index. INTERPRETATION: Over the past generation, the global burden of Parkinson's disease has more than doubled as a result of increasing numbers of older people, with potential contributions from longer disease duration and environmental factors. Demographic and potentially other factors are poised to increase the future burden of Parkinson's disease substantially. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Bone fractures are a global public health issue; however, to date, no comprehensive study of their incidence and burden has been done. We aimed to measure the global, regional, and national incidence, prevalence, and years lived with disability (YLDs) of fractures from 1990 to 2019. METHODS: Using the framework of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we compared numbers and age-standardised rates of global incidence, prevalence, and YLDs of fractures across the 21 GBD regions and 204 countries and territories, by age, sex, and year, from 1990 to 2019. We report estimates with 95% uncertainty intervals (UIs). FINDINGS: Globally, in 2019, there were 178 million (95% UI 162-196) new fractures (an increase of 33·4% [30·1-37·0] since 1990), 455 million (428-484) prevalent cases of acute or long-term symptoms of a fracture (an increase of 70·1% [67·5-72·5] since 1990), and 25·8 million (17·8-35·8) YLDs (an increase of 65·3% [62·4-68·0] since 1990). The age-standardised rates of fractures in 2019 were 2296·2 incident cases (2091·1-2529·5) per 100 000 population (a decrease of 9·6% [8·1-11·1] since 1990), 5614·3 prevalent cases (5286·1-5977·5) per 100 000 population (a decrease of 6·7% [5·7-7·6] since 1990), and 319·0 YLDs (220·1-442·5) per 100 000 population (a decrease of 8·4% [7·2-9·5] since 1990). Lower leg fractures of the patella, tibia or fibula, or ankle were the most common and burdensome fracture in 2019, with an age-standardised incidence rate of 419·9 cases (345·8-512·0) per 100 000 population and an age-standardised rate of YLDs of 190·4 (125·0-276·9) per 100 000 population. In 2019, age-specific rates of fracture incidence were highest in the oldest age groups, with, for instance, 15 381·5 incident cases (11 245·3-20 651·9) per 100 000 population in those aged 95 years and older. INTERPRETATION: The global age-standardised rates of incidence, prevalence, and YLDs for fractures decreased slightly from 1990 to 2019, but the absolute counts increased substantially. Older people have a particularly high risk of fractures, and more widespread injury-prevention efforts and access to screening and treatment of osteoporosis for older individuals should help to reduce the overall burden. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Seizures and their consequences contribute to the burden of epilepsy because they can cause health loss (premature mortality and residual disability). Data on the burden of epilepsy are needed for health-care planning and resource allocation. The aim of this study was to quantify health loss due to epilepsy by age, sex, year, and location using data from the Global Burden of Diseases, Injuries, and Risk Factors Study. METHODS: We assessed the burden of epilepsy in 195 countries and territories from 1990 to 2016. Burden was measured as deaths, prevalence, and disability-adjusted life-years (DALYs; a summary measure of health loss defined by the sum of years of life lost [YLLs] for premature mortality and years lived with disability), by age, sex, year, location, and Socio-demographic Index (SDI; a compound measure of income per capita, education, and fertility). Vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy largely came from population representative surveys. All estimates were calculated with 95% uncertainty intervals (UIs). FINDINGS: In 2016, there were 45·9 million (95% UI 39·9-54·6) patients with all-active epilepsy (both idiopathic and secondary epilepsy globally; age-standardised prevalence 621·5 per 100 000 population; 540·1-737·0). Of these patients, 24·0 million (20·4-27·7) had active idiopathic epilepsy (prevalence 326·7 per 100 000 population; 278·4-378·1). Prevalence of active epilepsy increased with age, with peaks at 5-9 years (374·8 [280·1-490·0]) and at older than 80 years of age (545·1 [444·2-652·0]). Age-standardised prevalence of active idiopathic epilepsy was 329·3 per 100 000 population (280·3-381·2) in men and 318·9 per 100 000 population (271·1-369·4) in women, and was similar among SDI quintiles. Global age-standardised mortality rates of idiopathic epilepsy were 1·74 per 100 000 population (1·64-1·87; 1·40 per 100 000 population [1·23-1·54] for women and 2·09 per 100 000 population [1·96-2·25] for men). Age-standardised DALYs were 182·6 per 100 000 population (149·0-223·5; 163·6 per 100 000 population [130·6-204·3] for women and 201·2 per 100 000 population [166·9-241·4] for men). The higher DALY rates in men were due to higher YLL rates compared with women. Between 1990 and 2016, there was a non-significant 6·0% (-4·0 to 16·7) change in the age-standardised prevalence of idiopathic epilepsy, but a significant decrease in age-standardised mortality rates (24·5% [10·8 to 31·8]) and age-standardised DALY rates (19·4% [9·0 to 27·6]). A third of the difference in age-standardised DALY rates between low and high SDI quintile countries was due to the greater severity of epilepsy in low-income settings, and two-thirds were due to a higher YLL rate in low SDI countries. INTERPRETATION: Despite the decrease in the disease burden from 1990 to 2016, epilepsy is still an important cause of disability and mortality. Standardised collection of data on epilepsy in population representative surveys will strengthen the estimates, particularly in countries for which we currently have no or sparse data and if additional data is collected on severity, causes, and treatment. Sizeable gains in reducing the burden of epilepsy might be expected from improved access to existing treatments in low-income countries and from the development of new effective drugs worldwide. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Brain and CNS cancers (collectively referred to as CNS cancers) are a source of mortality and morbidity for which diagnosis and treatment require extensive resource allocation and sophisticated diagnostic and therapeutic technology. Previous epidemiological studies are limited to specific geographical regions or time periods, making them difficult to compare on a global scale. In this analysis, we aimed to provide a comparable and comprehensive estimation of the global burden of brain cancer between 1990 and 2016. METHODS: We report means and 95% uncertainty intervals (UIs) for incidence, mortality, and disability-adjusted life-years (DALYs) estimates for CNS cancers (according to the International Classification of Diseases tenth revision: malignant neoplasm of meninges, malignant neoplasm of brain, and malignant neoplasm of spinal cord, cranial nerves, and other parts of CNS) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016. Data sources include vital registration and cancer registry data. Mortality was modelled using an ensemble model approach. Incidence was estimated by dividing the final mortality estimates by mortality to incidence ratios. DALYs were estimated by summing years of life lost and years lived with disability. Locations were grouped into quintiles based on the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. FINDINGS: In 2016, there were 330 000 (95% UI 299 000 to 349 000) incident cases of CNS cancer and 227 000 (205 000 to 241 000) deaths globally, and age-standardised incidence rates of CNS cancer increased globally by 17·3% (95% UI 11·4 to 26·9) between 1990 and 2016 (2016 age-standardised incidence rate 4·63 per 100 000 person-years [4·17 to 4·90]). The highest age-standardised incidence rate was in the highest quintile of SDI (6·91 [5·71 to 7·53]). Age-standardised incidence rates increased with each SDI quintile. East Asia was the region with the most incident cases of CNS cancer for both sexes in 2016 (108 000 [95% UI 98 000 to 122 000]), followed by western Europe (49 000 [37 000 to 54 000]), and south Asia (31 000 [29 000 to 37 000]). The top three countries with the highest number of incident cases were China, the USA, and India. CNS cancer was responsible for 7·7 million (95% UI 6·9 to 8·3) DALYs globally, a non-significant change in age-standardised DALY rate of -10·0% (-16·4 to 2·6) between 1990 and 2016. The age-standardised DALY rate decreased in the high SDI quintile (-10·0% [-27·1 to -0·1]) and high-middle SDI quintile (-10·5% [-18·4 to -1·4]) over time but increased in the low SDI quintile (22·5% [11·2 to 50·5]). INTERPRETATION: CNS cancer is responsible for substantial morbidity and mortality worldwide, and incidence increased between 1990 and 2016. Significant geographical and regional variation in the incidence of CNS cancer might be reflective of differences in diagnoses and reporting practices or unknown environmental and genetic risk factors. Future efforts are needed to analyse CNS cancer burden by subtype. FUNDING: Bill & Melinda Gates Foundation.

INTRODUCTION: Few studies have examined the clinical, neuropsychological and pharmacological factors involved in the functional outcome of bipolar disorder despite the gap between clinical and functional recovery. METHODS: A sample of 77 euthymic bipolar patients were included in the study. Using an a priori definition of low versus good functional outcome, based on the psychosocial items of the Global Assessment of Functioning (GAF, DSM-IV), and taking also into account their occupational adaptation, the patients were divided into two groups: good or low occupational functioning. Patients with high (n = 46) and low (n = 31) functioning were compared on several clinical, neuropsychological and pharmacological variables and the two patient groups were contrasted with healthy controls (n = 35) on cognitive performance. RESULTS: High- and low-functioning groups did not differ with respect to clinical variables. However, bipolar patients in general showed poorer cognitive performance than healthy controls. This was most evident in low-functioning patients and in particular on verbal memory and executive function measures. CONCLUSIONS: Low-functioning patients were cognitively more impaired than highly functioning patients on verbal recall and executive functions. The variable that best predicted psychosocial functioning in bipolar patients was verbal memory.