Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease ...analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability YLD and years of life lost YLL) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% 95% uncertainty interval 6·2–7·7 of global DALYs), tobacco smoking including second-hand smoke (6·3% 5·5–7·0), and household air pollution from solid fuels (4·3% 3·4–5·3). In 1990, the leading risks were childhood underweight (7·9% 6·8–9·4), household air pollution from solid fuels (HAP; 6·8% 5·5–8·0), and tobacco smoking including second-hand smoke (6·1% 5·4–6·8). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, Andean Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, most of Latin America, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.
Summary Background Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of ...Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. Methods We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. Findings In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45–54% since 1990; ischaemic heart disease and stroke YLLs increased by 17–28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. Interpretation Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. Funding Bill & Melinda Gates Foundation.
Summary Background Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of ...disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach. Methods We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO's most recent update of the Global Burden of Disease Study for 2004. Findings 13 902 individuals participated in household surveys and 16 328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh ( r =0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights ( r =0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously. Interpretation This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results. Funding Bill & Melinda Gates Foundation.
Summary Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease ...(GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.
Abstract Purpose Options for leveraging available telemedicine technologies, ranging from simple webcams and telephones to smartphone apps and medical-grade wearable sensors, are evolving faster than ...the culture of clinical research. Until recently, most clinical trials relied on paper-based processes and technology. This cost- and labor-intensive system, while slowly changing, remains an obstacle to new drug development. Alternatives that use existing tools and processes for collecting real-world data in home settings warrant closer examination. Methods The site-less clinical research organization (CRO) model, whereby pharmacists or other health care professionals provide useful and timely counseling for protocol compliance by regular phone and videoconferencing sessions, is a flexible approach to managing clinical trial participants directly from their homes. An expert panel, including clinical specialists in metabolic or neurodegenerative diseases, health information technology and CRO innovators, and the pharmaceutical industry, met in Dallas, Texas, December 2016, to discuss advancing avenues for site-less CRO and other remote clinical trial practices, taking into account investigator, sponsor, and regulatory perspectives. Findings Real-time “site-less” management of clinical trials can augment traditional research and development methods by providing data from a broader, more diverse group of patients in real-world practice settings. This methodology also helps to proactively identify safety profile and operational issues. Current use of site-less CRO practices constitutes an important bridge to alternative trial models, including “large simple trials” that strive to answer one or two questions using data derived from representative patient populations treated in typical clinical settings. Implications Site-less CROs offer a working example of how remote technologies and in-home monitoring methods can address shortcomings of conventional drug development. This model maximizes time and cost, as well as potentially earlier identification of adverse events. Coordinated communication among investigators, sponsors, regulators, and patients will be needed to develop standardized strategies for incorporating site-less CROs into current and future study design.
An Update on Parkinson's Disease: Improving Patient Outcomes Kremens, Daniel, MD, JD; Hauser, Robert A., MD, MBA; Dorsey, E. Ray, MD
The American journal of medicine,
2014, January 2014, 2014-Jan, 2014-01-00, 20140101, Volume:
127, Issue:
1
Journal Article
Peer reviewed
Open access
Abstract Neurologists are faced with many challenges in caring for patients with Parkinson's disease (PD). This chronic, long-term illness that affects at least one million people in the United ...States requires a coordinated healthcare partnership between the physician and the patient. The importance of early diagnosis is essential to delaying disease progression and early diagnosis and intervention may be aided by recent advances in biomarkers, genomics, and imaging. A misdiagnosis or late diagnosis will lead to deteriorating patient health. Additionally, physicians should incorporate current guidelines into their treatment strategies, and awareness of the reasoning behind these guidelines is critical for appropriate use. Physicians should be up to date on identifying the most appropriate therapies based on emerging science and disease staging, and should implement patient education into their practice. Due to limitations for currently available therapies, adjunctive therapies may lead to improved outcomes in patients with PD. The use of multiple therapies can improve myriad symptoms, more so than a monotherapy. Knowledge of these therapies is critical to achieving best outcomes in patients with PD. This webcast will discuss the current challenges with PD clinical practice, clinical features of PD, the impact of treatment, future treatments for PD and improving patient outcomes.
Abstract Objectives Because of several recent clinical and regulatory changes regarding attention deficit−hyperactivity disorder (ADHD) in the United States, we quantified changes in the diagnosis of ...ADHD and its pharmacologic treatment from 2000 through 2010. Methods We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of office-based providers, to examine aggregate trends among children and adolescents younger than 18 years of age. We also quantified how diagnosis and treatment patterns have evolved on the basis of patient and physician characteristics and the therapeutic classes used. Results From 2000 to 2010, the number of physician outpatient visits in which ADHD was diagnosed increased 66% from 6.2 million (95% confidence interval 5.5−6.9M) to 10.4 million visits (95% confidence interval 9.3−11.6 million). Of these visits, psychostimulants have remained the dominant treatment; they were used in 96% of treatment visits in 2000 and 87% of treatment visits in 2010. Atomoxetine use decreased from 15% of treatment visits upon product launch in 2003 to 6% of treatment visits by 2010. The use of potential substitute therapies—clonidine, guanfacine, and bupropion—remained relatively constant (between 5% and 9% of treatment visits) during most of the period examined. During this period, the management of ADHD shifted away from pediatricians and towards psychiatrists (from 24% to 36% of all visits) without large changes in illness severity or the proportion of ADHD treatment visits accounted for by males (73%–77%). Conclusions In 10 years, the ambulatory diagnosis of ADHD increased by two-thirds and is increasingly managed by psychiatrists. The effects of these changing treatment patterns on children’s health outcomes and their families are unknown.
Abstract Huntington disease is an autosomal-dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive ...decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins that result in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state, resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease.
Abstract Objective: The aim of this substudy was to determine the agreement between 2 approaches for measuring health care resource utilization (eg, number of hospital visits, number of primary care ...physician visits) in trial participants with Parkinson's disease (PD). Methods: A substudy of the 1-year multicenter futility trial of GPI-1485 and coenzyme Q10 (FS-TOO) was performed to assess health care resource utilization agreement by measuring participant utilization recall after 12 months versus measuring participant utilization recall at regular 3-month intervals. Trial participants were selected from patients in the National Institutes of Health—sponsored FS-TOO multicenter study. Persons aged ≥30 years with confirmed PD diagnosis within the previous 5 years were eligible for inclusion in the substudy. Participants were also required to have at least 2 of 3 cardinal manifestations of PD (tremor, rigidity, and bradykinesia). Participants were excluded from the study if they had presence of atypical Parkinson's syndromes due to drugs, metabolic identified neurogenetic disorders, encephalitis, or other degenerative diseases. Agreement was determined using Lin's concordance and Cohen's kappa statistics. Results: Between March and July of 2004, a total of 424 potential subjects were identified and evaluated for trial eligibility. Of these, 213 subjects (139 men, 74 women; mean SD age, 61.5 10.3 years) met entry criteria and were included in the study. Trial participants were randomized equally to 1 of 3 groups. The 3 groups had similar baseline characteristics in terms of demographic data (age, race, sex, employment status, and annual income), total Unified Parkinson Disease Rating Scale (UPDRS) score, and UPDRS subscores. In this substudy, 141 participants had a true baseline visit, indicating a clinical baseline date, and 182 participants completed the Baseline Resource Utilization Form within 3 months of the true baseline visit. The comparison of concordance between the summed information over 3-month recalls and the 12-month recall from baseline was derived from these 182 participants. The level of agreement between the 2 approaches was high, ranging from 64.4% to 95.1%. Where disagreement was identified, the more frequent measurement approach (every 3 months) led to higher estimates, ranging from 20.4% to 77.4%. Conclusion: The results of this trial indicate internal consistency with the self-reported measures of health care resource utilization, suggesting that these simple measures might provide reliable information about units of health care resource utilization in the context of clinical trials for PD.
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