Search tips
Search criteria

Results 1-25 (1451053)

Clipboard (0)

Related Articles

1.  Estimating health-adjusted life expectancy conditional on risk factors: results for smoking and obesity 
Smoking and obesity are risk factors causing a large burden of disease. To help formulate and prioritize among smoking and obesity prevention activities, estimations of health-adjusted life expectancy (HALE) for cohorts that differ solely in their lifestyle (e.g. smoking vs. non smoking) can provide valuable information. Furthermore, in combination with estimates of life expectancy (LE), it can be tested whether prevention of obesity and smoking results in compression of morbidity.
Using a dynamic population model that calculates the incidence of chronic disease conditional on epidemiological risk factors, we estimated LE and HALE at age 20 for a cohort of smokers with a normal weight (BMI < 25), a cohort of non-smoking obese people (BMI>30) and a cohort of 'healthy living' people (i.e. non smoking with a BMI < 25). Health state valuations for the different cohorts were calculated using the estimated disease prevalence rates in combination with data from the Dutch Burden of Disease study. Health state valuations are multiplied with life years to estimate HALE. Absolute compression of morbidity is defined as a reduction in unhealthy life expectancy (LE-HALE) and relative compression as a reduction in the proportion of life lived in good health (LE-HALE)/LE.
Estimates of HALE are highest for a 'healthy living' cohort (54.8 years for men and 55.4 years for women at age 20). Differences in HALE compared to 'healthy living' men at age 20 are 7.8 and 4.6 for respectively smoking and obese men. Differences in HALE compared to 'healthy living' women at age 20 are 6.0 and 4.5 for respectively smoking and obese women. Unhealthy life expectancy is about equal for all cohorts, meaning that successful prevention would not result in absolute compression of morbidity. Sensitivity analyses demonstrate that although estimates of LE and HALE are sensitive to changes in disease epidemiology, differences in LE and HALE between the different cohorts are fairly robust. In most cases, elimination of smoking or obesity does not result in absolute compression of morbidity but slightly increases the part of life lived in good health.
Differences in HALE between smoking, obese and 'healthy living' cohorts are substantial and similar to differences in LE. However, our results do not indicate that substantial compression of morbidity is to be expected as a result of successful smoking or obesity prevention.
PMCID: PMC1636666  PMID: 17083719
2.  Adjusting for dependent comorbidity in the calculation of healthy life expectancy 
Healthy life expectancy – sometimes called health-adjusted life expectancy (HALE) – is a form of health expectancy indicator that extends measures of life expectancy to account for the distribution of health states in the population. The World Health Organization has estimated healthy life expectancy for 192 WHO Member States using information from health interview surveys and from the Global Burden of Disease Study. The latter estimates loss of health by cause, age and sex for populations. Summation of prevalent years lived with disability (PYLD) across all causes would result in overestimation of the severity of the population average health state because of comorbidity between conditions. Earlier HALE calculations made adjustments for independent comorbidity in adding PYLD across causes. This paper presents a method for adjusting for dependent comorbidity using available empirical data.
Data from five large national health surveys were analysed by age and sex to estimate "dependent comorbidity" factors for pairs of conditions. These factors were defined as the ratio of the prevalence of people with both conditions to the product of the two total prevalences for each of the conditions. The resulting dependent comorbidity factors were used for all Member States to adjust for dependent comorbidity in summation of PYLD across all causes and in the calculation of HALE. A sensitivity analysis was also carried out for order effects in the proposed calculation method.
There was surprising consistency in the dependent comorbidity factors across the five surveys. The improved estimation of dependent comorbidity resulted in reductions in total PYLD per capita ranging from a few per cent in younger adult ages to around 8% in the oldest age group (80 years and over) in developed countries and up to 15% in the oldest age group in the least developed countries. The effect of the dependent comorbidity adjustment on estimated healthy life expectancies is small for some regions (high income countries, Eastern Europe, Western Pacific) and ranges from an increase of 0.5 to 1.5 years for countries in Latin America, South East Asia and Sub-Saharan Africa.
The available evidence suggests that dependent comorbidity is important, and that adjustment for it makes a significant difference to resulting HALE estimates for some regions of the world. Given the data limitations, we recommend a normative adjustment based on the available evidence, and applied consistently across all countries.
PMCID: PMC1484491  PMID: 16620383
3.  Impact of diabetes mellitus on life expectancy and health-adjusted life expectancy in Canada 
The objectives of this study were to estimate life expectancy (LE) and health-adjusted life expectancy (HALE) for Canadians with and without diabetes and to evaluate the impact of diabetes on population health using administrative and survey data.
Mortality data from the Canadian Chronic Disease Surveillance System (2004 to 2006) and Health Utilities Index data from the Canadian Community Health Survey (2000 to 2005) were used. Life table analysis was applied to calculate LE, HALE, and their confidence intervals using the Chiang and the adapted Sullivan methods.
LE and HALE were significantly lower among people with diabetes than for people without the disease. LE and HALE for females without diabetes were 85.0 and 73.3 years, respectively (males: 80.2 and 70.9 years). Diabetes was associated with a loss of LE and HALE of 6.0 years and 5.8 years, respectively, for females, and 5.0 years and 5.3 years, respectively, for males, living with diabetes at 55 years of age. The overall gains in LE and HALE after the hypothetical elimination of prevalent diagnosed diabetes cases in the population were 1.4 years and 1.2 years, respectively, for females, and 1.3 years for both LE and HALE for males.
The results of the study confirm that diabetes is an important disease burden in Canada impacting the female and male populations differently. The methods can be used to calculate LE and HALE for other chronic conditions, providing useful information for public health researchers and policymakers.
PMCID: PMC3787852  PMID: 22531113
Life expectancy; Health-adjusted life expectancy; Diabetes mellitus; Health utilities index; Summary measure of population health
4.  Comparing life expectancy and health-adjusted life expectancy by body mass index category in adult Canadians: a descriptive study 
While many studies have examined differences between body mass index (BMI) categories in terms of mortality risk and health-related quality of life (HRQL), little is known about the effect of body weight on health expectancy. We examined life expectancy (LE), health-adjusted life expectancy (HALE), and proportion of LE spent in nonoptimal (or poor) health by BMI category for the Canadian adult population (age ≥ 20).
Respondents to the National Population Health Survey (NPHS) were followed for mortality outcomes from 1994 to 2009. Our study population at baseline (n=12,478) was 20 to 100 years old with an average age of 47. LE was produced by building abridged life tables by sex and BMI category using data from the NPHS and the Canadian Chronic Disease Surveillance System. HALE was estimated using the Health Utilities Index from the Canadian Community Health Survey as a measure of HRQL. The contribution of HRQL to loss of healthy life years for each BMI category was also assessed using two methods: by calculating differences between LE and HALE proportional to LE and by using a decomposition technique to separate out mortality and HRQL contributions to loss of HALE.
At age 20, for both sexes, LE is significantly lower in the underweight and obesity class 2+ categories, but significantly higher in the overweight category when compared to normal weight (obesity class 1 was nonsignificant). HALE at age 20 follows these same associations and is significantly lower for class 1 obesity in women. Proportion of life spent in nonoptimal health and decomposition of HALE demonstrate progressively higher losses of healthy life associated with lowered HRQL for BMI categories in excess of normal weight.
Although being in the overweight category for adults may be associated with a gain in life expectancy as compared to normal weight adults, overweight individuals also experience a higher proportion of these years of life in poorer health. Due to the descriptive nature of this study, further research is needed to explore the causal mechanisms which explain these results, including the important differences we observed between sexes and within obesity subcategories.
PMCID: PMC3842774  PMID: 24252500
Overweight; Obesity; Underweight; Body mass index; Life expectancy; Health expectancy; Mortality; Health-related quality of life
5.  Self-rated health as a tool for estimating health-adjusted life expectancy among patients newly diagnosed with localized prostate cancer: A preliminary study 
Localized prostate cancer (LPC) patients are faced with numerous treatment options, including observation or watchful waiting. The choice of treatment largely depends on their baseline health-adjusted life expectancy (HALE). By consensus, physicians recommend treatment if the patient’s HALE is ten or more years. However, the estimation of HALE is difficult. Although subjective by nature, self-rated health (SRH) is a robust predictor of mortality. We studied the usefulness of SRH in estimating HALE in patients who are considering treatment for LPC.
A total of 144 LPC patients from a large urology private practice in Norfolk, Virginia, were surveyed before they had chosen a treatment option.
HALE determined by SRH correlated well with objective health measures, and was higher than age-based life expectancy by an average of 2 years. The observed difference in life expectancy due to SRH adjustment was higher among patients with a better socioeconomic and health profile.
SRH is an easy-to-use indicator of HALE in LPC patients. A table for HALE estimation by age and SRH is provided for men aged 70-80 years. Additional research with larger samples and prospective study designs are needed before the SRH method can be used in primary care and urology settings.
PMCID: PMC3066264  PMID: 21132389
Localized Prostate Cancer; Life Expectancy; Self-rated Health; Urology
6.  Using linked data to calculate summary measures of population health: Health-adjusted life expectancy of people with Diabetes Mellitus 
To estimate the health-adjusted life expectancy (HALE) from diabetes mellitus (DM) using a population health survey linked to a population-based DM registry.
The 1996/97 Ontario Health Survey (N = 35,517) was linked to the Ontario Diabetes Database (N = 487,576). The Health Utilities Index (HUI3) was used to estimate health-related quality of life. HALE was estimated using an adapted Sullivan method.
Life expectancy at birth of people with DM was 64.7 and 70.7 years for men and women – 12.8 and 12.2 years less than for men and women without DM. The HUI3 was lower for physician-diagnosed DM compared to self-reported DM (0.799 versus 0.872). HALE at birth was 58.3 and 62.8 years for men and women – 11.9 and 10.7 years less than that of men and women without DM.
The linked data approach demonstrates that DM is an important cause of disease burden. This approach reduces assumptions when estimating the prevalence and severity of disability from DM compared to methods that rely on self-reported disease status or indirect assessment of disability severity.
PMCID: PMC406424  PMID: 15038828
7.  Health-Adjusted Life Expectancy among Canadian Adults with and without Hypertension 
Hypertension can lead to cardiovascular diseases and other chronic conditions. While the impact of hypertension on premature death and life expectancy has been published, the impact on health-adjusted life expectancy has not, and constitutes the research objective of this study. Health-adjusted life expectancy (HALE) is the number of expected years of life equivalent to years lived in full health. Data were obtained from the Canadian Chronic Disease Surveillance System (mortality data 2004–2006) and the Canadian Community Health Survey (Health Utilities Index data 2000–2005) for people with and without hypertension. Life table analysis was applied to calculate life expectancy and health-adjusted life expectancy and their confidence intervals. Our results show that for Canadians 20 years of age, without hypertension, life expectancy is 65.4 years and 61.0 years, for females and males, respectively. HALE is 55.0 years and 52.8 years for the two sexes at age 20; and 24.7 years and 22.9 years at age 55. For Canadians with hypertension, HALE is only 48.9 years and 47.1 years for the two sexes at age 20; and 22.7 years and 20.2 years at age 55. Hypertension is associated with a significant loss in health-adjusted life expectancy compared to life expectancy.
PMCID: PMC3123912  PMID: 21738858
8.  Measuring the Population Burden of Injuries—Implications for Global and National Estimates: A Multi-centre Prospective UK Longitudinal Study 
PLoS Medicine  2011;8(12):e1001140.
Ronan Lyons and colleagues compared the population burden of injuries using different approaches from the UK Burden of Injury and Global Burden of Disease studies and find that the absolute UK burden of injury is higher than previously estimated.
Current methods of measuring the population burden of injuries rely on many assumptions and limited data available to the global burden of diseases (GBD) studies. The aim of this study was to compare the population burden of injuries using different approaches from the UK Burden of Injury (UKBOI) and GBD studies.
Methods and Findings
The UKBOI was a prospective cohort of 1,517 injured individuals that collected patient-reported outcomes. Extrapolated outcome data were combined with multiple sources of morbidity and mortality data to derive population metrics of the burden of injury in the UK. Participants were injured patients recruited from hospitals in four UK cities and towns: Swansea, Nottingham, Bristol, and Guildford, between September 2005 and April 2007. Patient-reported changes in quality of life using the EQ-5D at baseline, 1, 4, and 12 months after injury provided disability weights used to calculate the years lived with disability (YLDs) component of disability adjusted life years (DALYs). DALYs were calculated for the UK and extrapolated to global estimates using both UKBOI and GBD disability weights. Estimated numbers (and rates per 100,000) for UK population extrapolations were 750,999 (1,240) for hospital admissions, 7,982,947 (13,339) for emergency department (ED) attendances, and 22,185 (36.8) for injury-related deaths in 2005. Nonadmitted ED-treated injuries accounted for 67% of YLDs. Estimates for UK DALYs amounted to 1,771,486 (82% due to YLDs), compared with 669,822 (52% due to YLDs) using the GBD approach. Extrapolating patient-derived disability weights to GBD estimates would increase injury-related DALYs 2.6-fold.
The use of disability weights derived from patient experiences combined with additional morbidity data on ED-treated patients and inpatients suggests that the absolute burden of injury is higher than previously estimated. These findings have substantial implications for improving measurement of the national and global burden of injury.
Please see later in the article for the Editors' Summary
Editors' Summary
Injuries—resulting from traffic collisions, drowning, poisoning, falls or burns, and violence from assault, self-inflicted violence, or acts of war—kill more than 5 million people worldwide every year and cause harm to millions more. Injuries account for at least 9% of global mortality and are a threat to health in every country of the world. Furthermore, for every death-related injury, dozens of injured people are admitted to hospitals, hundreds visit emergency rooms, and thousands go to see their doctors by appointment. A large proportion of people surviving their injuries will be left with temporary or permanent disabilities.
The Global Burden of Diseases, Injuries and Risk Factors (GBD) Studies are instrumental in quantifying the burden of injuries placed on society and are essential for the public health response, priority setting, and policy development. Central to the GBD methodology is the concept of Disability Adjusted Life years (DALYs), and a combination of premature mortality, referred to as years of life lost and years lived with disability. However, rather than evidence and measurements, the GBD Study used panel studies and expert opinion to estimate weights and durations of disability. Therefore, although the GBD has been a major development, it may have underestimated the population burden.
Why Was This Study Done?
Accurate measurement of the burden of injuries is essential to ensure adequate policy responses to prevention and treatment. In this study, the researchers aimed to overcome the limitations of previous studies and for the first time, measured the population burden of injuries in the UK using a combination of disability and morbidity metrics, including years of life lost, and years lived with disabilities.
What Did the Researchers Do and Find?
The researchers recruited patients aged over 5 years with a wide range of injuries (including fractures and dislocations, lacerations, bruises and abrasions, sprains, burns and scalds, and head, eye, thorax, and abdominal injuries) from hospitals in four English cities—Swansea, Nottingham, Bristol, and Guildford—between September 2005 and April 2007. The researchers collected data on injury-related mortality, hospital admissions, and attendances to emergency rooms. They also invited patients (or their proxy, if participants were young children) to complete a self-administered questionnaire at recruitment and at 1, 4, and 12 months postinjury to allow data collection on injury characteristics, use of health and social services, time off work, and recovery from injury, in addition to sociodemographic and economic and occupational characteristics. The researchers also used standardized tools to measure health-related quality of life and work problems. Then, the researchers used these patient-reported changes to calculate DALYs for the UK and then extrapolated these results to calculate global estimates.
In the four study sites, a total of 1,517 injured people (median age of 37.4 years and 53.9% male) participated in the study. The researchers found that the vast majority of injuries were unintentional and that the home was the most frequent location of injury. Using the data and information collected from the questionnaires, the researchers extrapolated their results and found that in 2005, there were an estimated 750,999 injury-related hospital admissions, 7,982,947 emergency room attendances, and 22,185 injury-related deaths, translating to a rate per 100,000 of 1,240, 13,339, and 36.8, respectively. The researchers estimated UK DALYs related to injury to be 1,771,486 compared with 669,822 using the GBD approach. Furthermore, the researchers found that extrapolating patient-derived disability weights to GBD estimates would increase injury-related DALYs 2.6-fold.
What Do These Findings Mean?
The findings of this study suggest that, when using data and information derived from patient experiences, combined with additional morbidity data on patients treated in emergency rooms and those, admitted to hospital, the absolute burden of injury is higher than previously estimated. While this study was carried out in the UK the principal findings are relevant to other countries. However, measurement of the population burden of injuries requires access to high quality data, which may be difficult in less affluent countries, and these data rely on access to health facilities, which is often restricted in resource-limited settings. Despite these concerns, these findings have substantial implications for improving measurements of the national and global burden of injury.
Additional Information
Please access these websites via the online version of this summary at
The World Health Organization website provides detailed information about injuries and also details the work of the Global Burden of Disease Study
The Global Burden of Injury's website is a portal to websites run by groups conducting ongoing research into the measurement of global injury metrics
PMCID: PMC3232198  PMID: 22162954
9.  Comparing population health in the United States and Canada 
The objective of the paper is to compare population health in the United States (US) and Canada. Although the two countries are very similar in many ways, there are potentially important differences in the levels of social and economic inequality and the organization and financing of and access to health care in the two countries.
Data are from the Joint Canada/United States Survey of Health 2002/03. The Health Utilities Index Mark 3 (HUI3) was used to measure overall health-related quality of life (HRQL). Mean HUI3 scores were compared, adjusting for major determinants of health, including body mass index, smoking, education, gender, race, and income. In addition, estimates of life expectancy were compared. Finally, mean HUI3 scores by age and gender and Canadian and US life tables were used to estimate health-adjusted life expectancy (HALE).
Life expectancy in Canada is higher than in the US. For those < 40 years, there were no differences in HRQL between the US and Canada. For the 40+ group, HRQL appears to be higher in Canada. The results comparing the white-only population in both countries were very similar. For a 19-year-old, HALE was 52.0 years in Canada and 49.3 in the US.
The population of Canada appears to be substantially healthier than the US population with respect to life expectancy, HRQL, and HALE. Factors that account for the difference may include access to health care over the full life span (universal health insurance) and lower levels of social and economic inequality, especially among the elderly.
PMCID: PMC2873793  PMID: 20429875
10.  The societal gain of medical development and innovation in gastroenterology 
Gastroenterology has over the past 30 years evolved very rapidly. The societal benefits to which this has led are incompletely determined, yet form a mandate to determine the need for future innovations and further development of the field. A more thorough understanding of societal benefits may help to determine future goals and improve decision making.
The objective of this article is to determine the societal gains of medical innovations in the field of gastroenterology in the past and future, using peptic ulcer disease as an example of past innovation and the implementation of colorectal cancer screening as an illustration of future gains.
Literature searches were performed for data on peptic ulcer and colorectal cancer epidemiology, treatment outcomes, and costs. National and governmental databases in the Netherlands were searched to obtain the input for calculations of quality-adjusted life years (QALYs), health-adjusted life expectancy (HALE), and the corresponding societal benefit.
Since 1980 the improvements in peptic ulcer treatment have had a limited impact on life expectancy, rising from 83.6 years to 83.7 years, but have led to a yearly gain of 46,000 QALYs, caused by improved quality of life. These developments in the field of peptic ulcer translated into a yearly gain of 1.8 billion to 7.8 billion euros in 2008 compared with the 1980s.
Mortality due to colorectal cancer is high, with 21.6 deaths per 100,000 per year in the Netherlands (European Standardized Rate (ESR)). The future implementation of a nationwide call-recall colorectal cancer screening by means of biennial fecal immunochemical testing (FIT) is expected to result in a 50%–80% mortality reduction and thus a gain of an estimated 35,000 life years per year, corresponding to 26,000 QALYs per year. The effects of the implementation of FIT screening can be translated to a future societal gain of 1.0 billion to 4.4 billion euro.
The innovations and developments in the field of gastroenterology have led to significant societal gains in the past three decades. This process will continue in the near future as a result of further developments. These calculations provide a template for calculations on the need for specialist training as well as research and implementation of new developments in our field.
PMCID: PMC4040771  PMID: 24917981
Peptic ulcer; colon cancer; screening; societal gain; quality of life
11.  Global patterns of healthy life expectancy in the year 2002 
BMC Public Health  2004;4:66.
Healthy life expectancy – sometimes called health-adjusted life expectancy (HALE) – is a form of health expectancy indicator that extends measures of life expectancy to account for the distribution of health states in the population. The World Health Organization reports on healthy life expectancy for 192 WHO Member States. This paper describes variation in average levels of population health across these countries and by sex for the year 2002.
Mortality was analysed for 192 countries and disability from 135 causes assessed for 17 regions of the world. Health surveys in 61 countries were analyzed using new methods to improve the comparability of self-report data.
Healthy life expectancy at birth ranged from 40 years for males in Africa to over 70 years for females in developed countries in 2002. The equivalent "lost" healthy years ranged from 15% of total life expectancy at birth in Africa to 8–9% in developed countries.
People living in poor countries not only face lower life expectancies than those in richer countries but also live a higher proportion of their lives in poor health.
PMCID: PMC547900  PMID: 15619327
12.  Subjective assessments of comorbidity correlate with quality of life health outcomes: Initial validation of a comorbidity assessment instrument 
Interventions to improve care for persons with chronic medical conditions often use quality of life (QOL) outcomes. These outcomes may be affected by coexisting (comorbid) chronic conditions as well as the index condition of interest. A subjective measure of comorbidity that incorporates an assessment of disease severity may be particularly useful for assessing comorbidity for these investigations.
A survey including a list of 25 common chronic conditions was administered to a population of HMO members age 65 or older. Disease burden (comorbidity) was defined as the number of self-identified comorbid conditions weighted by the degree (from 1 to 5) to which each interfered with their daily activities. We calculated sensitivities and specificities relative to chart review for each condition. We correlated self-reported disease burden, relative to two other well-known comorbidity measures (the Charlson Comorbidity Index and the RxRisk score) and chart review, with our primary and secondary QOL outcomes of interest: general health status, physical functioning, depression screen and self-efficacy.
156 respondents reported an average of 5.9 chronic conditions. Median sensitivity and specificity relative to chart review were 75% and 92% respectively. QOL outcomes correlated most strongly with disease burden, followed by number of conditions by chart review, the Charlson Comorbidity Index and the RxRisk score.
Self-report appears to provide a reasonable estimate of comorbidity. For certain QOL assessments, self-reported disease burden may provide a more accurate estimate of comorbidity than existing measures that use different methodologies, and that were originally validated against other outcomes. Investigators adjusting for comorbidity in studies using QOL outcomes may wish to consider using subjective comorbidity measures that incorporate disease severity.
PMCID: PMC1208932  PMID: 16137329
13.  The effect of comorbidity on health-related quality of life for injury patients in the first year following injury: comparison of three comorbidity adjustment approaches 
Three approaches exist to deal with the impact of comorbidity in burden of disease studies - the maximum limit approach, the additive approach, and the multiplicative approach. The aim of this study was to compare the three comorbidity approaches in patients with temporary injury consequences as well as comorbid chronic conditions with nontrivial health impacts.
Disability weights were assessed using data from the EQ-5D instrument developed by the EuroQol Group and derived from a postal survey among 2,295 injury patients at 2.5 and 9 months after being treated at an emergency department. We compared the observed and predicted EQ-5D disability weights in comorbid cases using data from injury patients with and without comorbidity who were restored from their injuries at 9 months follow-up. The predicted disability weights were calculated using the maximum limit approach, additive approach, and multiplicative approach. The intraclass correlation coefficient (ICC) was used to test whether the values of the observed disability weights and the three model-predicted disability weights were correlated.
The EQ-5D disability weight of injury patients increased significantly with the number of comorbid diseases. The ICCs of the additive, multiplicative, and maximum limit models were 0.817, 0.778, and 0.674, respectively. Although the 95% confidence intervals of the ICCs of the three models overlap, the maximum limit model seems to fit less well than the additive and multiplicative models. For mild to moderate chronic disease (disability weight below 0.21), the association between predicted and observed disability weights was low.
Comorbidity has a high impact on disability measured with EQ-5D. Ignoring the effect of comorbidity restricts the use of the burden of disease concept in multimorbid populations. Gains from health care or interventions may be easily overestimated if a substantial number of patients suffer from additional conditions. The results of this study found that in accounting for comorbidity effects, all three models showed a strong association between the predicted and observed morbid disability weight, though the maximum limit model seems to fit less well than the additive and multiplicative models. The three models do not fit well in the case of mild to moderate pre-existing disease.
PMCID: PMC3096905  PMID: 21513572
14.  The burden of disease and injury in Iran 2003 
The objective of this study was to estimate the burden of disease and injury in Iran for the year 2003, using Disability-Adjusted Life Years (DALYs) at the national level and for six selected provinces.
Methods developed by the World Health Organization for National Burden of Disease (NBD) studies were applied to estimate disease and injury incidence for the calculation of Years of Life Lost due to premature mortality (YLL), Years Lived with Disability (YLD), and DALYs. The following adjustments of the NBD methodology were made in this study: a revised list with 213 disease and injury causes, development of new and more specific disease modeling templates for cancers and injuries, and adjustment for dependent comorbidity. We compared the results with World Health Organization (WHO) estimates for Eastern Mediterranean Region, sub-region B in 2002.
We estimated that in the year 2003, there were 21,572 DALYs due to all diseases and injuries per 100,000 Iranian people of all ages and both sexes. From this total number of DALYs, 62% were due to disability premature deaths (YLD) and 38% were due to premature deaths (YLL); 58% were due to noncommunicable diseases, 28% – to injuries, and 14% – to communicable, maternal, perinatal, and nutritional conditions. Fifty-three percent of the total number of 14.349 million DALYs in Iran were in males, with 36.5% of the total due to intentional and unintentional injuries, 15% due to mental and behavioral disorders, and 10% due to circulatory system diseases; and 47% of DALYs were in females, with 18% of the total due to mental and behavioral disorders, 18% due to intentional and unintentional injuries, and 12% due to circulatory system diseases. The disease and injury causes leading to the highest number of DALYs in males were road traffic accidents (1.071 million), natural disasters (548 thousand), opioid use (510 thousand), and ischemic heart disease (434 thousand). The leading causes of DALYs in females were ischemic heart disease (438 thousand), major depressive disorder (420 thousand), natural disasters (419 thousand), and road traffic accidents (235 thousand). The burden of disease at the province level showed marked variability. DALY estimates by Iran's NBD study were higher than those for EMR-B by WHO.
The health and disease profile in Iran has made the transition from the dominance of communicable diseases to that of noncommunicable diseases and road traffic injuries. NBD results are to be used in health program planning, research, and resource allocation and generation policies and practices.
PMCID: PMC2711041  PMID: 19527516
15.  Disability Weight of Clonorchis sinensis Infection: Captured from Community Study and Model Simulation 
Clonorchiasis is among the most neglected tropical diseases. It is caused by ingesting raw or undercooked fish or shrimp containing the larval of Clonorchis sinensis and mainly endemic in Southeast Asia including China, Korea and Vietnam. The global estimations for population at risk and infected are 601 million and 35 million, respectively. However, it is still not listed among the Global Burden of Disease (GBD) and no disability weight is available for it. Disability weight reflects the average degree of loss of life value due to certain chronic disease condition and ranges between 0 (complete health) and 1 (death). It is crucial parameter for calculating the morbidity part of any disease burden in terms of disability-adjusted life years (DALYs).
Methodology/Principal Findings
According to the probability and disability weight of single sequelae caused by C. sinensis infection, the overall disability weight could be captured through Monte Carlo simulation. The probability of single sequelae was gained from one community investigation, while the corresponding disability weight was searched from the literatures in evidence-based approach. The overall disability weights of the male and female were 0.101 and 0.050, respectively. The overall disability weights of the age group of 5–14, 15–29, 30–44, 45–59 and 60+ were 0.022, 0.052, 0.072, 0.094 and 0.118, respectively. There was some evidence showing that the disability weight and geometric mean of eggs per gram of feces (GMEPG) fitted a logarithmic equation.
The overall disability weights of C. sinensis infection are differential in different sex and age groups. The disability weight captured here may be referred for estimating the disease burden of C. sinensis infection.
Author Summary
Clonorchiasis is caused by eating incompletely cooked fishery product which carries the larval of Clonorchis sinensis. Millions of people are estimated to suffer in Southeast Asia. However, it is still among the most neglected tropical diseases due to the lack of clear evaluation, of which no disease burden available is one important reason. Our study is the first attempt to estimate the disability of C. sinensis infection, which reflects the average loss of life value due to some conditions and is crucial for calculating disease burden in terms of disability-adjusted life years (DALYs). After obtaining the probability and disability of single sequelae caused by C. sinensis infection through community investigation and literatures reviewing respectively, the overall disability was captured through model simulation. It was showed the overall disability of the male was higher than that of the female, positive correlation occurred between disability and infection intensity, and gallstone took the major attributable proportion. Thus, C. sinensis infection can cause apparent disability. The disability captured here may promote the further studies and benefit the final estimation of disease burden, which will promote health awareness and implementation of intervention.
PMCID: PMC3236727  PMID: 22180791
16.  Bariatric Surgery 
Executive Summary
To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of bariatric surgery.
Obesity is defined as a body mass index (BMI) of at last 30 kg/m2.1 Morbid obesity is defined as a BMI of at least 40 kg/m2 or at least 35 kg/m2 with comorbid conditions. Comorbid conditions associated with obesity include diabetes, hypertension, dyslipidemias, obstructive sleep apnea, weight-related arthropathies, and stress urinary incontinence. It is also associated with depression, and cancers of the breast, uterus, prostate, and colon, and is an independent risk factor for cardiovascular disease.
Obesity is also associated with higher all-cause mortality at any age, even after adjusting for potential confounding factors like smoking. A person with a BMI of 30 kg/m2 has about a 50% higher risk of dying than does someone with a healthy BMI. The risk more than doubles at a BMI of 35 kg/m2. An expert estimated that about 160,000 people are morbidly obese in Ontario. In the United States, the prevalence of morbid obesity is 4.7% (1999–2000).
In Ontario, the 2004 Chief Medical Officer of Health Report said that in 2003, almost one-half of Ontario adults were overweight (BMI 25–29.9 kg/m2) or obese (BMI ≥ 30 kg/m2). About 57% of Ontario men and 42% of Ontario women were overweight or obese. The proportion of the population that was overweight or obese increased gradually from 44% in 1990 to 49% in 2000, and it appears to have stabilized at 49% in 2003. The report also noted that the tendency to be overweight and obese increases with age up to 64 years. BMI should be used cautiously for people aged 65 years and older, because the “normal” range may begin at slightly above 18.5 kg/m2 and extend into the “overweight” range.
The Chief Medical Officer of Health cautioned that these data may underestimate the true extent of the problem, because they were based on self reports, and people tend to over-report their height and under-report their weight. The actual number of Ontario adults who are overweight or obese may be higher.
Diet, exercise, and behavioural therapy are used to help people lose weight. The goals of behavioural therapy are to identify, monitor, and alter behaviour that does not help weight loss. Techniques include self-monitoring of eating habits and physical activity, stress management, stimulus control, problem solving, cognitive restructuring, contingency management, and identifying and using social support. Relapse, when people resume old, unhealthy behaviour and then regain the weight, can be problematic.
Drugs (including gastrointestinal lipase inhibitors, serotonin norepinephrine reuptake inhibitors, and appetite suppressants) may be used if behavioural interventions fail. However, estimates of efficacy may be confounded by high rates of noncompliance, in part owing to the side effects of the drugs. In addition, the drugs have not been approved for indefinite use, despite the chronic nature of obesity.
The Technology
Morbidly obese people may be eligible for bariatric surgery. Bariatric surgery for morbid obesity is considered an intervention of last resort for patients who have attempted first-line forms of medical management, such as diet, increased physical activity, behavioural modification, and drugs.
There are various bariatric surgical procedures and several different variations for each of these procedures. The surgical interventions can be divided into 2 general types: malabsorptive (bypassing parts of the gastrointestinal tract to limit the absorption of food), and restrictive (decreasing the size of the stomach so that the patient is satiated with less food). All of these may be performed as either open surgery or laparoscopically. An example of a malabsorptive technique is Roux-en-Y gastric bypass (RYGB). Examples of restrictive techniques are vertical banded gastroplasty (VBG) and adjustable gastric banding (AGB).
The Ontario Health Insurance Plan (OHIP) Schedule of Benefits for Physician Services includes fee code “S120 gastric bypass or partition, for morbid obesity” as an insured service. The term gastric bypass is a general term that encompasses a variety of surgical methods, all of which involve reconfiguring the digestive system. The term gastric bypass does not include AGB. The number of gastric bypass procedures funded and done in Ontario, and funded as actual out-of-country approvals,2 is shown below.
Number of Gastric Bypass Procedures by Fiscal Year: Ontario and Actual Out-of-Country (OOC) Approvals
Data from Provider Services, MOHLTC
Courtesy of Provider Services, Ministry of Health and Long Term Care
Review Strategy
The Medical Advisory Secretariat reviewed the literature to assess the effectiveness, safety, and cost-effectiveness of bariatric surgery to treat morbid obesity. It used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. The interventions of interest were bariatric surgery and, for the controls, either optimal conventional management or another type of bariatric procedure. The outcomes of interest were improvement in comorbid conditions (e.g., diabetes, hypertension); short- and long-term weight loss; quality of life; adverse effects; and economic analysis data. The databases yielded 15 international health technology assessments or systematic reviews on bariatric surgery.
Subsequently, the Medical Advisory Secretariat searched MEDLINE and EMBASE from April 2004 to December 2004, after the search cut-off date of April, 2004, for the most recent systematic reviews on bariatric surgery. Ten studies met the inclusion criteria. One of those 10 was the Swedish Obese Subjects study, which started as a registry and intervention study, and then published findings on people who had been enrolled for at least 2 years or at least 10 years. In addition to the literature review of economic analysis data, the Medical Advisory Secretariat also did an Ontario-based economic analysis.
Summary of Findings
Bariatric surgery generally is effective for sustained weight loss of about 16% for people with BMIs of at least 40 kg/m2 or at least 35 kg/m2 with comorbid conditions (including diabetes, high lipid levels, and hypertension). It also is effective at resolving the associated comorbid conditions. This conclusion is largely based on level 3a evidence from the prospectively designed Swedish Obese Subjects study, which recently published 10-year outcomes for patients who had bariatric surgery compared with patients who received nonsurgical treatment. (1)
Regarding specific procedures, there is evidence that malabsorptive techniques are better than other banding techniques for weight loss and resolution of comorbid illnesses. However, there are no published prospective, long-term, direct comparisons of these techniques available.
Surgery for morbid obesity is considered an intervention of last resort for patients who have attempted first-line forms of medical management, such as diet, increased physical activity, behavioural modification, and drugs. In the absence of direct comparisons of active nonsurgical intervention via caloric restriction with bariatric techniques, the following observations are made:
A recent systematic review examining the efficacy of major commercial and organized self-help weight loss programs in the United States concluded that the evidence to support the use of such programs was suboptimal, except for one trial on Weight Watchers. Furthermore, the programs were associated with high costs, attrition rates, and probability of regaining at least 50% of the lost weight in 1 to 2 years. (2)
A recent randomized controlled trial reported 1-year outcomes comparing weight loss and metabolic changes in severely obese patients assigned to either a low-carbohydrate diet or a conventional weight loss diet. At 1 year, weight loss was similar for patients in each group (mean, 2–5 kg). There was a favourable effect on triglyceride levels and glycemic control in the low-carbohydrate diet group. (3)
A decision-analysis model showed bariatric surgery results in increased life expectancy in morbidly obese patients when compared to diet and exercise. (4)
A cost-effectiveness model showed bariatric surgery is cost-effective relative to nonsurgical management. (5)
Extrapolating from 2003 data from the United States, Ontario would likely need to do 3,500 bariatric surgeries per year. It currently does 508 per year, including out-of-country surgeries.
PMCID: PMC3382415  PMID: 23074460
17.  Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis 
Neurology  2010;74(13):1041-1047.
Vascular comorbidity adversely influences health outcomes in several chronic conditions. Vascular comorbidities are common in multiple sclerosis (MS), but their impact on disease severity is unknown. Vascular comorbidities may contribute to the poorly understood heterogeneity in MS disease severity. Treatment of vascular comorbidities may represent an avenue for treating MS.
A total of 8,983 patients with MS enrolled in the North American Research Committee on Multiple Sclerosis Registry participated in this cohort study. Time from symptom onset or diagnosis until ambulatory disability was compared for patients with or without vascular comorbidities to determine their impact on MS severity. Multivariable proportional hazards models were adjusted for sex, race, age at symptom onset, year of symptom onset, socioeconomic status, and region of residence.
Participants reporting one or more vascular comorbidities at diagnosis had an increased risk of ambulatory disability, and risk increased with the number of vascular conditions reported (hazard ratio [HR]/condition for early gait disability 1.51; 95% confidence interval [CI] 1.41–1.61). Vascular comorbidity at any time during the disease course also increased the risk of ambulatory disability (adjusted HR for unilateral walking assistance 1.54; 95% CI 1.44–1.65). The median time between diagnosis and need for ambulatory assistance was 18.8 years in patients without and 12.8 years in patients with vascular comorbidities.
Vascular comorbidity, whether present at symptom onset, diagnosis, or later in the disease course, is associated with a substantially increased risk of disability progression in multiple sclerosis. The impact of treating vascular comorbidities on disease progression deserves investigation.
= Expanded Disability Status Scale;
= hazard ratio;
= multiple sclerosis;
= North American Research Committee on Multiple Sclerosis;
= Patient Determined Disease Steps.
PMCID: PMC2848107  PMID: 20350978
18.  Optimal Management of High-Risk T1G3 Bladder Cancer: A Decision Analysis 
PLoS Medicine  2007;4(9):e284.
Controversy exists about the most appropriate treatment for high-risk superficial (stage T1; grade G3) bladder cancer. Immediate cystectomy offers the best chance for survival but may be associated with an impaired quality of life compared with conservative therapy. We estimated life expectancy (LE) and quality-adjusted life expectancy (QALE) for both of these treatments for men and women of different ages and comorbidity levels.
Methods and Findings
We evaluated two treatment strategies for high-risk, T1G3 bladder cancer using a decision-analytic Markov model: (1) Immediate cystectomy with neobladder creation versus (2) conservative management with intravesical bacillus Calmette-Guérin (BCG) and delayed cystectomy in individuals with resistant or progressive disease. Probabilities and utilities were derived from published literature where available, and otherwise from expert opinion. Extensive sensitivity analyses were conducted to identify variables most likely to influence the decision. Structural sensitivity analyses modifying the base case definition and the triggers for cystectomy in the conservative therapy arm were also explored. Probabilistic sensitivity analysis was used to assess the joint uncertainty of all variables simultaneously and the uncertainty in the base case results. External validation of model outputs was performed by comparing model-predicted survival rates with independent published literature. The mean LE of a 60-y-old male was 14.3 y for immediate cystectomy and 13.6 y with conservative management. With the addition of utilities, the immediate cystectomy strategy yielded a mean QALE of 12.32 y and remained preferred over conservative therapy by 0.35 y. Worsening patient comorbidity diminished the benefit of early cystectomy but altered the LE-based preferred treatment only for patients over age 70 y and the QALE-based preferred treatment for patients over age 65 y. Sensitivity analyses revealed that patients over the age of 70 y or those strongly averse to loss of sexual function, gastrointestinal dysfunction, or life without a bladder have a higher QALE with conservative therapy. The results of structural or probabilistic sensitivity analyses did not change the preferred treatment option. Model-predicted overall and disease-specific survival rates were similar to those reported in published studies, suggesting external validity.
Our model is, to our knowledge, the first of its kind in bladder cancer, and demonstrated that younger patients with high-risk T1G3 bladder had a higher LE and QALE with immediate cystectomy. The decision to pursue immediate cystectomy versus conservative therapy should be based on discussions that consider patient age, comorbid status, and an individual's preference for particular postcystectomy health states. Patients over the age of 70 y or those who place high value on sexual function, gastrointestinal function, or bladder preservation may benefit from a more conservative initial therapeutic approach.
Using a Markov model, Shabbir Alibhai and colleagues develop a decision analysis comparing cystectomy with conservative treatment for high-risk superficial bladder cancer depending on patient age, comorbid conditions, and preferences.
Editors' Summary
Every year, about 67,000 people in the US develop bladder cancer. Like all cancers, bladder cancer arises when a single cell begins to grow faster than normal, loses its characteristic shape, and moves into surrounding tissues. Most bladder cancers develop from cells that line the bladder (“transitional” cells) and most are detected before they spread out of this lining. These superficial or T1 stage cancers can be removed by transurethral resection of bladder tumor (TURBT). The urologist (a specialist who treats urinary tract problems) passes a small telescope into the bladder through the urethra (the tube through which urine leaves the body) and removes the tumor. If the tumor cells look normal under a microscope (so-called normal histology), the cancer is unlikely to return; if they have lost their normal appearance, the tumor is given a “G3” histological grade, which indicates a high risk of recurrence.
Why Was This Study Done?
The best treatment for T1G3 bladder cancer remains controversial. Some urologists recommend immediate radical cystectomy— surgical removal of the bladder, the urethra, and other nearby organs. This treatment often provides a complete cure but can cause serious short-term health problems and affects long-term quality of life. Patients often develop sexual dysfunction or intestinal (gut) problems and sometimes find it hard to live with a reconstructed bladder. The other recommended treatment is immunotherapy with bacillus Calmette-Guérin (BCG, bacteria that are also used to vaccinate against tuberculosis). Long-term survival is not always as good with this conservative treatment but it is less likely than surgery to cause short-term illness or to reduce quality of life. In this study, the researchers have used decision analysis (a systematic evaluation of the important factors affecting a decision) to determine whether immediate cystectomy or conservative therapy is the optimal treatment for patients with T1G3 bladder cancer. Decision analysis allowed the researchers to account for quality-of-life factors while comparing the health benefits of each treatment for T1G3 bladder cancer.
What Did the Researchers Do and Find?
Using a decision analysis model called a Markov model, the researchers calculated the months of life gained, and the quality of life expected to result, from each of the two treatments. To estimate the life expectancy (LE) associated with each treatment, the researchers incorporated the published probabilities of various outcomes of each treatment into their model. To estimate quality-adjusted life expectancy (QALE, the number of years of good quality life), they incorporated “utilities,” measures of relative satisfaction with outcomes. (A utility of 1 represents perfect health; death is assigned a value of 0, and outcomes considered less than ideal, but better than death, fall in between). For a sexually potent 60-year-old man with bladder cancer but no other illnesses, the average LE predicted by the model was nearly eight months longer with immediate cystectomy than with conservative treatment (both LEs predicted by this model matched those seen in clinical trials); the average QALE with cystectomy was 4.2 months longer than with conservative treatment. Having additional diseases decreased the benefit of immediate cystectomy but the treatment still gave a longer LE until the patient reached 70 years old, when conservative treatment became better. For QALE, this change in optimal treatment appeared at age 65. Finally, conservative treatment gave a higher QALE than immediate cystectomy for patients concerned about preserving sexual function or averse to living with intestinal problems or a reconstructed bladder.
What Do These Findings Mean?
As with all mathematical models, these results depend on the assumptions included in the model. In particular, because published probability and utility values are not available for some of the possible outcomes of the two treatments, the LE and QALE calculations could be inaccurate. Also, assigning numerical ratings to life experiences is generally something of a simplification, which could affect the reliability of the QALE (but not the LE) results. Nevertheless, these findings provide useful guidance for urologists trying to balance the benefits of immediate cystectomy or conservative treatment against the potential short-term and long-term effects of these treatments on patients' quality of life. Specifically, the results indicate that decisions on treatment for T1G3 bladder cancer should be based on a consideration of the patient's age and any coexisting disease coupled with detailed discussions with the patient about their attitudes regarding the possible health-related effects of cystectomy.
Additional Information.
Please access these Web sites via the online version of this summary at
MedlinePlus encyclopedia page on bladder cancer (in English and Spanish)
Information for patients and professionals from the US National Cancer Institute on bladder cancer (in English and Spanish)
Information for patients on bladder cancer from the UK charity Cancerbackup
Online course on Decision Analysis in Health Care from George Mason University
PMCID: PMC1989749  PMID: 17896857
19.  Burden of Depressive Disorders by Country, Sex, Age, and Year: Findings from the Global Burden of Disease Study 2010 
PLoS Medicine  2013;10(11):e1001547.
In this paper, Ferrari and colleagues analyzed the burden of depressive disorders in GBD 2010 and identified depressive disorders as a leading cause of burden. The authors present severity proportions; burden by country, region, age, sex, and year; as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease.
Please see later in the article for the Editors' Summary
Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD) 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease.
Methods and Findings
Burden was calculated for major depressive disorder (MDD) and dysthymia. A systematic review of epidemiological data was conducted. The data were pooled using a Bayesian meta-regression. Disability weights from population survey data quantified the severity of health loss from depressive disorders. These weights were used to calculate years lived with disability (YLDs) and disability adjusted life years (DALYs). Separate DALYs were estimated for suicide and ischemic heart disease attributable to depressive disorders.
Depressive disorders were the second leading cause of YLDs in 2010. MDD accounted for 8.2% (5.9%–10.8%) of global YLDs and dysthymia for 1.4% (0.9%–2.0%). Depressive disorders were a leading cause of DALYs even though no mortality was attributed to them as the underlying cause. MDD accounted for 2.5% (1.9%–3.2%) of global DALYs and dysthymia for 0.5% (0.3%–0.6%). There was more regional variation in burden for MDD than for dysthymia; with higher estimates in females, and adults of working age. Whilst burden increased by 37.5% between 1990 and 2010, this was due to population growth and ageing. MDD explained 16 million suicide DALYs and almost 4 million ischemic heart disease DALYs. This attributable burden would increase the overall burden of depressive disorders from 3.0% (2.2%–3.8%) to 3.8% (3.0%–4.7%) of global DALYs.
GBD 2010 identified depressive disorders as a leading cause of burden. MDD was also a contributor of burden allocated to suicide and ischemic heart disease. These findings emphasize the importance of including depressive disorders as a public-health priority and implementing cost-effective interventions to reduce its burden.
Please see later in the article for the Editors' Summary
Editors' Summary
Depressive disorders are common mental disorders that occur in people of all ages across all world regions. Depression—an overwhelming feeling of sadness and hopelessness that can last for months or years—can make people feel that life is no longer worth living. People affected by depression lose interest in the activities they used to enjoy and can also be affected by physical symptoms such as disturbed sleep. Major depressive disorder (MDD, also known as clinical depression) is an episodic disorder with a chronic (long-term) outcome and increased risk of death. It involves at least one major depressive episode in which the affected individual experiences a depressed mood almost all day, every day for at least 2 weeks. Dysthymia is a milder, chronic form of depression that lasts for at least 2 years. People with dysthymia are often described as constantly unhappy. Both these subtypes of depression (and others such as that experienced in bipolar disorder) can be treated with antidepressant drugs and with talking therapies.
Why Was This Study Done?
Depressive disorders were a leading cause of disease burden in the 1990 and 2000 Global Burden of Disease (GBD) studies, collaborative scientific efforts that quantify the health loss attributable to diseases and injuries in terms of disability adjusted life years (DALYs; one DALY represents the loss of a healthy year of life). DALYs are calculated by adding together the years of life lived with a disability (YLD, a measure that includes a disability weight factor reflecting disease severity) and the years of life lost because of disorder-specific premature death. The GBD initiative aims to provide data that can be used to improve public-health policy. Thus, knowing that depressive disorders are a leading cause of disease burden worldwide has helped to prioritize depressive disorders in global public-health agendas. Here, the researchers analyze the burden of MDD and dysthymia in GBD 2010 by country, region, age, and sex, and calculate the burden of suicide and ischemic heart disease attributable to depressive disorders (depression is a risk factor for suicide and ischemic heart disease). GBD 2010 is broader in scope than previous GBD studies and quantifies the direct burden of 291 diseases and injuries and the burden attributable to 67 risk factors across 187 countries.
What Did the Researchers Do and Find?
The researchers collected data on the prevalence, incidence, remission rates, and duration of MDD and dysthymia and on the excess deaths caused by these disorders from published articles. They pooled these data using a statistical method called Bayesian meta-regression and calculated YLDs for MDD and dysthymia using disability weights collected in population surveys. MDD accounted for 8.2% of global YLDs in 2010, making it the second leading cause of YLDs. Dysthymia accounted for 1.4% of global YLDs. MDD and dysthymia were also leading causes of DALYs, accounting for 2.5% and 0.5% of global DALYs, respectively. The regional variation in the burden was greater for MDD than for dysthymia, the burden of depressive disorders was higher in women than men, the largest proportion of YLDs from depressive disorders occurred among adults of working age, and the global burden of depressive disorders increased by 37.5% between 1990 and 2010 because of population growth and ageing. Finally, MDD explained an additional 16 million DALYs and 4 million DALYs when it was considered as a risk factor for suicide and ischemic heart disease, respectively. This “attributable” burden increased the overall burden of depressive disorders to 3.8% of global DALYs.
What Do These Findings Mean?
These findings update and extend the information available from GBD 1990 and 2000 on the global burden of depressive disorders. They confirm that depressive disorders are a leading direct cause of the global disease burden and show that MDD also contributes to the burden allocated to suicide and ischemic heart disease. The estimates of the global burden of depressive disorders reported in GBD 2010 are likely to be more accurate than those in previous GBD studies but are limited by factors such as the sparseness of data on depressive disorders from developing countries and the validity of the disability weights used to calculate YLDs. Even so, these findings reinforce the importance of treating depressive disorders as a public-health priority and of implementing cost-effective interventions to reduce their ubiquitous burden.
Additional Information
Please access these websites via the online version of this summary at
The US National Institute of Mental Health provides information on all aspects of depression
The UK National Health Service Choices website also provides detailed information about depression and includes personal stories about depression
More personal stories about depression are available from
MedlinePlus provides links to other resources about depression (in English and Spanish)
The World Health Organization provides information on depression and on the global burden of disease (in several languages)
Information about the Global Burden of Disease initiative is available
beyondblue provides many resources on depression
The Queensland Centre for Mental Health Research provides information on epidemiology and the global burden of disease specifically for mental disorders
PMCID: PMC3818162  PMID: 24223526
20.  Protein localization as a principal feature of the etiology and comorbidity of genetic diseases 
Proteins localized within the same subcellular compartment tend to be functionally associated. This study shows that subcellular localization and network distance between disease-associated proteins provide complementary information explaining patterns of disease comorbidity.
A positive correlation was found between subcellular localization of disease-associated protein pairs and measures of comorbidity.A higher comorbidity tendency was found for disease-associated protein pairs that are positioned within a shorter distance in the protein interaction network.The integration of subcellular localization information with protein interaction network sheds light onto the potential molecular connections underlying comorbidity patterns and will help to understand the mechanisms of human disease.
It was shown that the emergence of phenotypically similar diseases are triggered as a result of molecular connections between disease-causing genes (Oti and Brunner, 2007; Zaghloul and Katsanis, 2010). From a genetics, perspective diseases are associated with certain genes (Goh et al, 2007; Feldman et al, 2008), whereas from a proteomics perspective phenotypically similar diseases are connected via biological modules such as protein–protein interactions (PPIs) or molecular pathways (Lage et al, 2007; Jiang et al, 2008; Wu et al, 2008; Linghu et al, 2009; Suthram et al, 2010). These molecular connections between diseases were observed on the population level as well: diseases connected through molecular connections such as shared genes, PPIs, and metabolic pathways tend to show elevated comorbidity (Rzhetsky et al, 2007; Lee et al, 2008; Zhernakova et al, 2009; Park et al, 2009a, 2009b). While these findings constitute a step toward improving our understanding of the mechanism of disease progression, there are still many more molecule-level connections between disease pairs that need to be explored in order to establish a firmer comorbidity association.
Subcellular localization provides spatial information of proteins in the cell; proteins target subcellular localizations to interact with appropriate partners and form functional complexes in signaling pathways and metabolic processes (Au et al, 2007). Abnormal protein localizations are known to lead to the loss of functional effects in diseases (Luheshi et al, 2008; Laurila and Vihinen, 2009). For example, mis-localizations of nuclear/cytoplasmic transport have been detected in many types of carcinoma cells (Kau et al, 2004). A proper identification of protein subcellular localization can hence be useful in discovering disease-associated proteins (Giallourakis et al, 2005; Calvo and Mootha, 2010). With this understanding, we postulate that disease-associated proteins connected by subcellular localizations could also explain the phenotypic similarities between diseases. Furthermore, such connections may also couple to disease progressions that contribute to multiple disease manifestation, that is, comorbidity.
Protein subcellular localization has been extensively studied through various methods to determine a variety of protein functions. To the best of our knowledge, the connection between diseases and subcellular localizations are yet to be studied systematically. To resolve this we constructed, for the first time, a human Disease-associated Protein and subcellular Localization (DPL) matrix (top panel in Box 1). Our DPL matrix provides the ‘cellular localization map of diseases' that represents the spatial index of diseases in the cell. We found that each disease shows unique characteristics of subcellular localization profile in the DPL matrix. We were interested in determining whether subsets of 1284 human diseases exhibit distinct enrichment profiles across subcellular localizations. We calculated pairwise correlations and performed a hierarchical clustering of the enrichments of the 1284 diseases across 10 different subcellular localizations.
Our DPL matrix revealed that 778 diseases (∼62%, P=1.40 × 10−3) are enriched in a single localization and 273 diseases (∼21%, P=3.45 × 10−3) are enriched in dual localizations. In the DPL matrix, certain disease-associated proteins are likely to be found in membrane-bounded organelles such as mitochondria, lysosome, and peroxisome, indicating that the mutations of proteins localized to these compartments are connected to the pathophysiological conditions of those organelles. Meanwhile, certain disease-associated proteins in the DPL matrix are enriched in dual localizations, such as extracellular/plasma membrane or endoplasmic reticulum/Golgi. Although these two pairs of subcellular localizations appear to be distinct compartments at first, they are functionally related compartments in close proximity during protein translocation process in the cell, and thus are likely to share interacting protein partners (Gandhi et al, 2006).
Comorbidity represents the co-occurrence of multiple diseases in the same individual (Lee et al, 2008; Hidalgo et al, 2009; Park et al, 2009a). Many comorbid disease pairs have been shown to share common genes in the human disease network. For example, Diabetes and Alzheimer's disease share a risk factor in angiotensin I converting enzyme, and frequently occur together in an individual. In such instances, comorbidity can be partially attributed to the disease connections on the molecular level. To explore the impact of protein subcellular localization on comorbidity, we hypothesized that certain disease pairs could also be connected via subcellular localization by the molecular connections between the disease-associated proteins (bottom panel in Box 1).
We found a positive correlation between subcellular localization similarity and relative risk (Figure 3B, Pearson's correlation coefficient between relative risk and subcellular localization similarity=0.81, P=2.96 × 10−5). The subcellular localization similarity represents the correlation of subcellular localization profiles between disease pairs. To our surprise, when we compared the relative risk of disease pairs linked via various molecular connections, we found that disease pairs connected by subcellular localization showed a near three-fold higher comorbidity tendency (with link distances equal to 2 or 3) when compared with random pairs (Figure 3E).
We then assessed quantitatively the impact of network distances and subcellular localizations on the comorbidity tendency of disease pairs. We expected the proteins associated with comorbid disease pairs to be located closely in the protein interaction network via fewer links compared with random disease pairs. Indeed, a higher comorbidity tendency was found when two disease-associated proteins were positioned within a shorter distance (gray plots in Figure 3F). Moreover, when subcellular localization information was combined with small network distances, the comorbidity tendency increased dramatically (orange plots in Figure 3F). It suggests that subcellular localization and close network distances, two conceptually distinct molecular connections, contributed synergistically to the comorbidity tendency.
Disease progression is not restricted to the mutation of disease-causing genes, but also affected by molecular connections in ‘disease modules,' resulting in comorbidity (Fraser, 2006; Lee et al, 2008). In this study, for the first time we applied subcellular localization information to elucidate the molecular connections between comorbid diseases. We believe that, based on our finding, our approach helps to define the boundaries of ‘disease modules.' Taken together, integration of diverse molecular connections should improve the molecular level understanding of hitherto unexplained comorbid disease pairs and help us in expanding the scope of our knowledge of the mechanism of human disease progression.
Proteins targeting the same subcellular localization tend to participate in mutual protein–protein interactions (PPIs) and are often functionally associated. Here, we investigated the relationship between disease-associated proteins and their subcellular localizations, based on the assumption that protein pairs associated with phenotypically similar diseases are more likely to be connected via subcellular localization. The spatial constraints from subcellular localization significantly strengthened the disease associations of the proteins connected by subcellular localizations. In particular, certain disease types were more prevalent in specific subcellular localizations. We analyzed the enrichment of disease phenotypes within subcellular localizations, and found that there exists a significant correlation between disease classes and subcellular localizations. Furthermore, we found that two diseases displayed high comorbidity when disease-associated proteins were connected via subcellular localization. We newly explained 7584 disease pairs by using the context of protein subcellular localization, which had not been identified using shared genes or PPIs only. Our result establishes a direct correlation between protein subcellular localization and disease association, and helps to understand the mechanism of human disease progression.
PMCID: PMC3130560  PMID: 21613983
cellular networks; comorbidity; human disease; subcellular localization
21.  Pulmonary impairment after tuberculosis and its contribution to TB burden 
BMC Public Health  2010;10:259.
The health impacts of pulmonary impairment after tuberculosis (TB) treatment have not been included in assessments of TB burden. Therefore, previous global and national TB burden estimates do not reflect the full consequences of surviving TB. We assessed the burden of TB including pulmonary impairment after tuberculosis in Tarrant County, Texas using Disability-adjusted Life Years (DALYs).
TB burden was calculated for all culture-confirmed TB patients treated at Tarrant County Public Health between January 2005 and December 2006 using identical methods and life tables as the Global Burden of Disease Study. Years of life-lost were calculated as the difference between life expectancy using standardized life tables and age-at-death from TB. Years lived-with-disability were calculated from age and gender-specific TB disease incidence using published disability weights. Non-fatal health impacts of TB were divided into years lived-with-disability-acute and years lived-with-disability-chronic. Years lived-with-disability-acute was defined as TB burden resulting from illness prior to completion of treatment including the burden from treatment-related side effects. Years lived-with-disability-chronic was defined as TB burden from disability resulting from pulmonary impairment after tuberculosis.
There were 224 TB cases in the time period, of these 177 were culture confirmed. These 177 subjects lost a total of 1189 DALYs. Of these 1189 DALYs 23% were from years of life-lost, 2% were from years lived-with-disability-acute and 75% were from years lived-with-disability-chronic.
Our findings demonstrate that the disease burden from TB is greater than previously estimated. Pulmonary impairment after tuberculosis was responsible for the majority of the burden. These data demonstrate that successful TB control efforts may reduce the health burden more than previously recognized.
PMCID: PMC2894771  PMID: 20482835
22.  Comorbidity and disease burden in the National Comorbidity Survey Replication (NCS-R) 
Depression and anxiety  2012;29(9):797-806.
Disease burden estimates rarely consider comorbidity. Using a recently developed methodology for integrating information about comorbidity into disease burden estimates, we examined the comparative burdens of 9 mental and 10 chronic physical disorders in the National Comorbidity Survey Replication (NCS-R).
Face-to-face interviews in a national household sample (n = 5,692) assessed associations of disorders with scores on a visual analog scale (VAS) of perceived health. Multiple regression analysis with interactions for comorbidity was used to estimate these associations. Simulation was used to estimate incremental disorder-specific effects adjusting for comorbidity.
74.9% of respondents reported one or more disorders. 73.8–98.2% of respondents with disorders reported having at least one other disorder. The best-fitting model to predict VAS scores included disorder main effects and interactions for number of disorders. Adjustment for comorbidity reduced individual-level disorder-specific burden estimates substantially, but with considerable between-disorder variation (.07–.69 ratios of disorder-specific estimates with and without adjustment for comorbidity). Four of the five most burdensome disorders at the individual level were mental disorders based on bivariate analyses (panic/agoraphobia, bipolar disorder, PTSD, major depression) but only two based on multivariate analyses, adjusting for comorbidity (panic/agoraphobia, major depression). Neurological disorders, chronic pain conditions, and diabetes were the other most burdensome individual-level disorders. Chronic pain conditions, cardiovascular disorders, arthritis, insomnia, and major depression were the most burdensome societal-level disorders.
Adjustments for comorbidity substantially influence estimates of disease burden, especially those of mental disorders, underlining the importance of including information about comorbidity in studies of mental disorders.
PMCID: PMC4005614  PMID: 22585578
bias; burden of illness; confounding factors; cost of illness; epidemiology; global burden of disease; health valuation; visual analog scale (VAS)
23.  Mortality and guideline-concordant care for older patients with schizophrenia: a retrospective longitudinal study 
BMC Medicine  2012;10:147.
Schizophrenia is associated with excess mortality and multimorbidity, which is possibly associated with difficulty in coordinating care for multiple mental and physical comorbidities. We analyzed the receipt by patients with schizophrenia of 11 types of guideline-concordant care and the association of such care with survival.
Guideline-concordant care over an 8-year period (financial years 2002 to 2009) was examined in a nationwide sample of 49,173 male veterans with schizophrenia, who were aged 50 years or older. Administrative databases from the electronic medical record system of the Veterans Health Administration (VA) provided comprehensive measures of patient demographics and medical information. Relying on the 2004 American Psychiatric Association guidelines, patterns in 11 types of care were identified and cluster-analyzed. Care types included cardiovascular, metabolic, weight management, nicotine dependence, infectious diseases, vision, and mental health counseling (individual, family, drugs/alcohol, psychiatric medication, and compensated work therapy). Survival analysis estimated association of care patterns with survival, adjusting for clinical and demographic covariates.
There was an average of four chronic diseases in addition to schizophrenia in the cohort, notably hypertension (43%) and dyslipidemia (29%). Three longitudinal trajectories (clusters) were identified: 'high-consistent' (averaging 5.4 types of care annually), 'moderate-consistent' (averaging 3.8), and 'poor-decreasing' (averaging 1.9). Most veterans were receiving cardiovascular care (67 to 76%), hepatic and renal function assays (79 to 84%), individual counseling (72 to 85%) and psychiatry consults (66 to 82%), with the proportion receiving care varying by cluster group. After adjustment for age, baseline comorbidity, and other covariates, there was a greater survival rate for those with poor-decreasing care compared with high-consistent care, and for high-consistent compared with moderate-consistent care.
Relatively low levels of guideline-concordant care were seen for older VA patients with schizophrenia, and trajectories of care over time were associated with survival in a non-intuitive pattern. The group with the lowest and decreasing levels of care was also the oldest, but nonetheless had the best age-adjusted and other covariate-adjusted survival rates, possibly because they were requiring less care relative to younger, sicker veterans, and thus their comorbidity burden was markedly lower. Notably, in the group with the sickest individuals (that is those with the highest comorbidity scores, who were very disabled), receiving guideline-concordant care was associated with improved survival in adjusted models compared with those patients receiving only moderate levels of care.
PMCID: PMC3523058  PMID: 23181341
schizophrenia; veterans; quality of health care; mortality; primary care; preventive care
24.  Comorbidity delays diagnosis and increases disability at diagnosis in MS 
Neurology  2009;72(2):117-124.
Comorbidity is common in the general population and is associated with adverse health outcomes. In multiple sclerosis (MS), it is unknown whether preexisting comorbidity affects the delay between initial symptom onset and diagnosis (“diagnostic delay”) or the severity of disability at MS diagnosis.
Using the North American Research Committee on Multiple Sclerosis Registry, we assessed the association between comorbidity and both the diagnostic delay and severity of disability at diagnosis. In 2006, we queried participants regarding physical and mental comorbidities, including date of diagnosis, smoking status, current height, and past and present weight. Using multivariate Cox regression, we compared the diagnostic delay between participants with and without comorbidity at diagnosis. We classified participants enrolled within 2 years of diagnosis (n = 2,375) as having mild, moderate, or severe disability using Patient Determined Disease Steps, and assessed the association of disability with comorbidity using polytomous logistic regression.
The study included 8,983 participants. After multivariable adjustment for demographic and clinical characteristics, the diagnostic delay increased if obesity, smoking, or physical or mental comorbidities were present. Among participants enrolled within 2 years of diagnosis, the adjusted odds of moderate as compared to mild disability at diagnosis increased in participants with vascular comorbidity (odds ratio [OR] 1.51, 95% CI 1.12–2.05) or obesity (OR 1.38, 95% CI 1.02–1.87). The odds of severe as compared with mild disability increased with musculoskeletal (OR 1.81, 95% CI 1.25–2.63) or mental (OR 1.62, 95% CI 1.23–2.14) comorbidity.
Both diagnostic delay and disability at diagnosis are influenced by comorbidity. The mechanisms underlying these associations deserve further investigation.
= body mass index;
= Expanded Disability Status Scale;
= multiple sclerosis;
= North American Research Committee on Multiple Sclerosis;
= National Institute of Neurological Disorders and Stroke;
= National Multiple Sclerosis Society;
= odds ratio;
= Patient Determined Disease Steps.
PMCID: PMC2677495  PMID: 18971448
25.  ‘Imi Hale – The Native Hawaiian Cancer Awareness, Research, and Training Network: Second-Year Status Report 
The purpose of this paper is to describe ‘Imi Hale, a program developed and managed by Native Hawaiians to increase cancer awareness and research capacity among Native Hawaiians. This US subgroup of indigenous people of the Hawaiian islands has disproportionately high rates of cancer mortality and low rates of participation in health and research careers.
As a community-based research project, ‘Imi Hale spent its first year gathering data from Native Hawaiians about their cancer awareness and research priorities. These findings guide ‘Imi Hale’s community and scientific advisors, a community-based Institutional Review Board, Na Liko Noelo (budding researchers), and staff in developing and carrying out projects that address these priority areas. Emphasis is placed on transferring skills and resources to Native Hawaiians through training, technical assistance, and mentorship. A biennial survey assesses the extent to which community-based participatory research principles are being followed.
Principal Findings
By the end of the second year, statewide and island-specific awareness plans were produced, and 9 funded awareness projects are supporting the development and dissemination of Hawaiian health education materials. Research accomplishments include the enrollment of 42 Native Hawaiian Na Liko Noelo (budding researchers), 22 of which are involved in 14 funded research projects. The biennial evaluation survey found that 92% of our advisors felt that ‘Imi Hale was promoting scientifically rigorous research that was culturally appropriate and respectful of Native Hawaiian beliefs, and 96% felt that ‘Imi Hale was following its own principles of community-based participatory research.
‘Imi Hale’s community-based approach to promoting cancer awareness will result in a sustainable infrastructure for reducing the cancer burden on Native Hawaiians.
PMCID: PMC2914229  PMID: 15352771

Results 1-25 (1451053)