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1.  Adjusting for dependent comorbidity in the calculation of healthy life expectancy 
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1478-7954-4-4
PMCID: PMC1484491  PMID: 16620383
2.  Estimating health-adjusted life expectancy conditional on risk factors: results for smoking and obesity 
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1478-7954-4-14
PMCID: PMC1636666  PMID: 17083719
3.  Self-rated health as a tool for estimating health-adjusted life expectancy among patients newly diagnosed with localized prostate cancer: A preliminary study 
Purpose
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.
Methods
A total of 144 LPC patients from a large urology private practice in Norfolk, Virginia, were surveyed before they had chosen a treatment option.
Results
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.
Conclusions
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.
doi:10.1007/s11136-010-9805-3
PMCID: PMC3066264  PMID: 21132389
Localized Prostate Cancer; Life Expectancy; Self-rated Health; Urology
4.  Using linked data to calculate summary measures of population health: Health-adjusted life expectancy of people with Diabetes Mellitus 
Objectives
To estimate the health-adjusted life expectancy (HALE) from diabetes mellitus (DM) using a population health survey linked to a population-based DM registry.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1478-7954-2-4
PMCID: PMC406424  PMID: 15038828
5.  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 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1478-7954-9-10
PMCID: PMC3096905  PMID: 21513572
6.  The burden of disease and injury in Iran 2003 
Background
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
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.
Results
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.
Conclusion
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.
doi:10.1186/1478-7954-7-9
PMCID: PMC2711041  PMID: 19527516
7.  Global patterns of healthy life expectancy in the year 2002 
BMC Public Health  2004;4:66.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1471-2458-4-66
PMCID: PMC547900  PMID: 15619327
8.  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.
doi:10.4061/2011/612968
PMCID: PMC3123912  PMID: 21738858
9.  Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis 
Neurology  2010;74(13):1041-1047.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
GLOSSARY
= Expanded Disability Status Scale;
= hazard ratio;
= multiple sclerosis;
= North American Research Committee on Multiple Sclerosis;
= Patient Determined Disease Steps.
doi:10.1212/WNL.0b013e3181d6b125
PMCID: PMC2848107  PMID: 20350978
10.  Burden of disease due to cancer in Spain 
BMC Public Health  2009;9:42.
Background
Burden of disease is a joint measure of mortality and morbidity which makes it easier to compare health problems in which these two components enjoy different degrees of relative importance. The objective of this study is ascertaining the burden of disease due to cancer in Spain via the calculation of disability-adjusted life years (DALYs).
Methods
DALYs are the sum of years of life lost due to premature mortality and years lost due to disability. World Health Organization methodology and the following sources of data were used: the Mortality Register and Princeton Model Life Table for Years of life lost due to premature mortality and population, incidence estimates (Spanish tumour registries and fitting of generalized linear mixed models), duration (from data of survival in Spain from the EUROCARE-3 study and fitting of Weibull distribution function) and disability (weights published in the literature) for Years lost due to disability.
Results
There were 828,997 DALYs due to cancer (20.5 DALYs/1,000 population), 61% in men. Of the total, 51% corresponded to lung, colorectal, breast, stomach and prostate cancers. Mortality (84% of DALYs) predominated over disability. Subjects aged under 20 years accounted for 1.6% and those aged over 70 years accounted for 30.1% of DALYs.
Conclusion
Lung, colorectal and breast cancers are responsible for the highest number of DALYs in Spain. Even if the burden of disease due to cancer is predominantly caused by mortality, some cancers have a significant weight of disability. Information on 2000 burden of disease due to cancer can be useful to assess how it has evolved over time and the impact of medical advances on it in terms of mortality and disability.
doi:10.1186/1471-2458-9-42
PMCID: PMC2642814  PMID: 19183440
11.  Valuation of health states in the U.S. study to establish disability weights: lessons from the literature 
The metric of disability-adjusted life years (DALYs) has become the global standard of measuring burden of disease. DALYs are comprised of years of life lost due to premature mortality and years of healthy life lost due to living with disability. In order to calculate the second part of the DALY equation, disease specific disability weights have to be established, i.e., measures for the decline of health associated with these disease states, which vary between 0 for perfect health and 1 for death. Although these disability weights are key for estimating DALYs, there have not been many comprehensive studies with empirical determinations of them. This article describes a systematic review on the state of the art with respect to empirically determining disability weights. Based on this review, a multi-method approach is outlined, which has also been implemented in a U.S. study to measure burden of disease. This approach involves the use of psychometric methodology as well as economic trade-off methods for determining the value of health states. It is conceptualized as a disaggregated approach, where the disability weight of any health state can be calculated if the attributes of this health state are known. The U.S. study received the collaboration of experts from more than 20 institutes of the National Institutes of Health and of the Centers for Disease Control and Prevention. First results will be available by the end of this year.
doi:10.1002/mpr.300
PMCID: PMC3306052  PMID: 20191661
disability-adjusted life years (DALYs); burden of disease; disability weight; empirical assessment; psychometrics; trade-off methods
12.  Subjective assessments of comorbidity correlate with quality of life health outcomes: Initial validation of a comorbidity assessment instrument 
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1477-7525-3-51
PMCID: PMC1208932  PMID: 16137329
13.  Burden of disease resulting from chronic mountain sickness among young Chinese male immigrants in Tibet 
BMC Public Health  2012;12:401.
Background
In young Chinese men of the highland immigrant population, chronic mountain sickness (CMS) is a major public health problem. The aim of this study was to measure the disease burden of CMS in this population.
Methods
We used disability-adjusted life years (DALYs) to estimate the disease burden of CMS. Disability weights were derived using the person trade-off methodology. CMS diagnoses, symptom severity, and individual characteristics were obtained from surveys collected in Tibet in 2009 and 2010. The DALYs of individual patients and the DALYs/1,000 were calculated.
Results
Disability weights were obtained for 21 CMS health stages. The results of the analyses of the two surveys were consistent with each other. At different altitudes, the CMS rates ranged from 2.1-37.4%; the individual DALYs of patients ranged from 0.13-0.33, and the DALYs/1,000 ranged from 3.60-52.78. The age, highland service years, blood pressure, heart rate, smoking rate, and proportion of the sample working in engineering or construction were significantly higher in the CMS group than in the non-CMS group (p < 0.05). These variables were also positively associated with the individual DALYs (p < 0.05). Among the symptoms, headaches caused the largest proportion of DALYs.
Conclusion
The results show that CMS imposes a considerable burden on Chinese immigrants to Tibet. Immigrants with characteristics such as a higher residential altitude, more advanced age, longer highland service years, being a smoker, and working in engineering or construction were more likely to develop CMS and to increase the disease burden. Higher blood pressure and heart rate as a result of CMS were also positively associated with the disease burden. The authorities should pay attention to the highland disease burden and support the development and application of DALYs studies of CMS and other highland diseases.
doi:10.1186/1471-2458-12-401
PMCID: PMC3444415  PMID: 22672510
chronic mountain sickness; burden of disease; disability-adjusted life years; disability weight; immigrant; high altitude
14.  Pulmonary impairment after tuberculosis and its contribution to TB burden 
BMC Public Health  2010;10:259.
Background
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).
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1471-2458-10-259
PMCID: PMC2894771  PMID: 20482835
15.  Describing and Quantifying Asthma Comorbidty: A Population Study 
PLoS ONE  2012;7(5):e34967.
Background
Asthma comorbidity has been correlated with poor asthma control, increased health services use, and decreased quality of life. Managing it improves these outcomes. Little is known about the amount of different types of comorbidity associated with asthma and how they vary by age.
Methodology/Principal Findings
The authors conducted a population study using health administrative data on all individuals living in Ontario, Canada (population 12 million). Types of asthma comorbidity were quantified by comparing physician health care claims between individuals with and without asthma in each of 14 major disease categories; results were adjusted for demographic factors and other comorbidity and stratified by age. Compared to those without asthma, individuals with asthma had higher rates of comorbidity in most major disease categories. Most notably, they had about fifty percent or more physician health care claims for respiratory disease (other than asthma) in all age groups; psychiatric disorders in individuals age four and under and age 18 to 44; perinatal disorders in individuals 17 years and under, and metabolic and immunity, and hematologic disorders in children four years and under.
Conclusion/Significance
Asthma appears to be associated with significant rates of various types of comorbidity that vary according to age. These results can be used to develop strategies to recognize and address asthma comorbidity to improve the overall health of individuals with asthma.
doi:10.1371/journal.pone.0034967
PMCID: PMC3346768  PMID: 22586445
16.  The cost of obesity in Canada 
BACKGROUND: Almost one-third of adult Canadians are at increased risk of disability, disease and premature death because of being obese. In order to allocate limited health care resources rationally, it is necessary to elucidate the economic burden of obesity. OBJECTIVE: To estimate the direct costs related to the treatment of and research into obesity in Canada in 1997. METHODS: The prevalence of obesity (body mass index of 27 or greater) in Canada was determined using data from the National Population Health Survey, 1994-1995. Ten comorbidities of obesity were identified from the medical literature. A population attributable fraction (PAF) was calculated for each comorbidity with data from large cohort studies to determine the extent to which each comorbidity and its management costs were attributable to obesity. The direct cost of each comorbidity was determined using data from the Canadian Institute of Health Information (for direct expenditure categories) and from Health Canada (for the proportion of expenditure category attributable to the comorbidity). This prevalence-based approach identified the direct costs of hospital care, physician services, services of other health professionals, drugs, other health care and health research. For each comorbidity, the cost attributable to obesity was determined by multiplying the PAF by the total direct cost of the comorbidity. The overall impact of obesity was estimated as the sum of the PAF-weighted costs of treating the comorbidities. A sensitivity analysis was completed on both the estimated costs and the PAFs. RESULTS: The total direct cost of obesity in Canada in 1997 was estimated to be over $1.8 billion. This corresponded to 2.4% of the total health care expenditures for all diseases in Canada in 1997. The sensitivity analysis revealed that the total cost could be as high as $3.5 billion or as low as $829.4 million; this corresponded to 4.6% and 1.1% respectively of the total health care expenditures in 1997. When the contributions of the comorbidities to the total cost were considered, the 3 largest contributors were hypertension ($656.6 million), type 2 diabetes mellitus ($423.2 million) and coronary artery disease ($346.0 million). INTERPRETATION: A considerable proportion of health care dollars is devoted to the treatment and management of obesity-related comorbidities in Canada. Further research into the therapeutic benefits and cost-effectiveness of management strategies for obesity is required. It is anticipated that the prevention and treatment of obesity will have major positive effects on the overall cost of health care.
PMCID: PMC1230073  PMID: 10081464
17.  A comparison of cancer burden and research spending reveals discrepancies in the distribution of research funding 
BMC Public Health  2012;12:526.
Background
Ideally, the distribution of research funding for different types of cancer should be equitable with respect to the societal burden each type of cancer imposes. These burdens can be estimated in a variety of ways; “Years of Life Lost” (YLL) measures the severity of death in regard to the age it occurs, "Disability-Adjusted Life-Years" (DALY) estimates the effects of non-lethal disabilities incurred by disease and economic metrics focus on the losses to tax revenue, productivity or direct medical expenses. We compared research funding from the National Cancer Institute (NCI) to a variety of burden metrics for the most common types of cancer to identify mismatches between spending and societal burden.
Methods
Research funding levels were obtained from the NCI website and information for societal health and economic burdens were collected from government databases and published reports. We calculated the funding levels per unit burden for a wide range of different cancers and burden metrics and compared these values to identify discrepancies.
Results
Our analysis reveals a considerable mismatch between funding levels and burden. Some cancers are funded at levels far higher than their relative burden suggests (breast cancer, prostate cancer, and leukemia) while other cancers appear underfunded (bladder, esophageal, liver, oral, pancreatic, stomach, and uterine cancers).
Conclusions
These discrepancies indicate that an improved method of health care research funding allocation should be investigated to better match funding levels to societal burden.
doi:10.1186/1471-2458-12-526
PMCID: PMC3411479  PMID: 22800364
Cancer; Research funding; Years of life lost; YLL; Disability adjusted life years; DALY; Burden; Economic cost
18.  Disability Weight of Clonorchis sinensis Infection: Captured from Community Study and Model Simulation 
Background
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.
Conclusion/Significance
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.
doi:10.1371/journal.pntd.0001377
PMCID: PMC3236727  PMID: 22180791
19.  The Impact of Comorbidity of Mental and Physical Conditions on Role Disability in the US Adult Household Population 
Archives of general psychiatry  2007;64(10):1180-1188.
Context
There is limited information that accounts for comorbidity on the impact of role disability associated with a wide range of mental and physical disorders in population-based samples.
Objective
To estimate the comparative effects of common mental and physical conditions on role disability in the general population using a novel method that accounts for comorbidity.
Design
Direct interviews about physical and mental conditions during the past year.
Setting
The National Comorbidity Survey Replication, a nationally representative series of face-to-face interviews.
Patients
A nationally representative sample of adults living in households (N=5962 respondents, 18 years and older).
Main Outcome Measure
Disability in major life roles was assessed with the World Health Organization Disability Assessment Schedule. Simulations that allow for complex interactions among conditions were used to estimate the conditions’ effects on disability days, when respondents were completely unable to carry out their usual daily activities because of problems with mental or physical health, in the past 12 months.
Results
An estimated 53.4 % of US adults have 1 or more of the mental or physical conditions assessed in the survey. These respondents report an average 32.1 more role-disability days in the past year than demographically matched controls, equivalent to nearly 3.6 billion days of role disability in the population. Musculoskeletal disorders and major depression had the greatest effects on disability days. Mental conditions accounted for more than half as many disability days as all physical conditions at the population level. Associations of specific conditions with disability decreased substantially after controlling for comorbidity, suggesting that prior studies, which generally did not control for comorbidity, overestimated disease-specific effects.
Conclusion
The staggering amount of health-related disability associated with mental and physical conditions should be considered in establishing priorities for the allocation of health care and research resources.
doi:10.1001/archpsyc.64.10.1180
PMCID: PMC2248275  PMID: 17909130
20.  Health-related quality of life in adults reporting arthritis: analysis from the National Health Measurement Study 
Quality of Life Research  2011;20(7):1131-1140.
Background
Arthritis is the leading cause of disability in the United States. We assess the generic health-related quality-of-life (HRQOL) among a nationally representative sample of US adults with and without self-reported arthritis.
Methods
The NHMS, a cross-sectional survey of 3,844 adults (35–89 years) administered EuroQol-5D (EQ-5D), Health Utilities Index Mark 2 (HUI2) and 3 (HUI3), SF-36v2™, Quality of Well-being Scale self-administered form (QWB-SA), and the Health and Activities Limitations index (HALex) to each respondent via a telephone interview. Weighted multiple linear regression was used to generate age-gender-arthritis-stratified unadjusted HRQOL means and means adjusted for sociodemographic, socioeconomic covariates and comorbidities by arthritis–age category.
Results
The estimated population prevalence of self-reported arthritis was 31%. People with arthritis were more likely to be woman, older, of lower socioeconomic status, and had more self-reported comorbidities than were those not reporting arthritis. Adults with arthritis had lower HRQOL on six different indexes compared with adults without arthritis, with overall differences ranging from 0.03 (QWB-SA, age-group 65–74) to 0.17 (HUI3, age-group 35–44; all P-value < .05).
Conclusion
Arthritis in adults is associated with poorer HRQOL. We provide age-related reference values for six generic HRQOL measures in people with arthritis.
doi:10.1007/s11136-011-9849-z
PMCID: PMC3156343  PMID: 21298347
Health-Related Quality of Life; HRQOL; Arthritis; National Health Measurement Study; Self-reported arthritis; EQ-5D; SF-6D; HUI2; HUI3; HALex; QWB; QWB-SA
21.  Burden of Cancer in Serbia 
Croatian medical journal  2006;47(1):134-141.
Aim
To provide a comprehensive assessment of burden of selected cancers in Serbia.
Method
We calculated disability adjusted life years (DALY) – the sum of the years of life lost (YLL) from premature mortality and the years lived with disability (YLD) – for cancers of stomach, colon and rectum, lung, breast, and cervical cancer for central Serbia and Vojvodina, Serbia and Montenegro. The obtained values were compared with the corresponding values for European region as estimated by the World Health Organization. The study was conducted between October 2002 and September 2003. The cancer burden was estimated for the year 2000.
Results
Observed cancers were responsible for 133 689 DALYs (73 197 for men and 60 482 for women). There were significantly more losses because of premature death than disease disability (95.2% vs 4.8% in men P<0.001, and 93.2% vs 6.8% in females, P<0.001). The cancer burden was dominated by lung cancer in men and breast cancer in women. The cancer burden was very small before the age of 35.
Conclusion
DALYs per 1000 population were higher in Serbia than in theEuropean region for all observed cancers except for stomach cancer. The participation of a burden caused by disability in the total burden of selected cancers was lower in Serbia than in other European countries, with the greatest differences in colorectal, breast, and cervical cancers.
PMCID: PMC2080367  PMID: 16489706
22.  The burden of disease and injury in the United States 1996 
Background
Burden of disease studies have been implemented in many countries using the Disability-Adjusted Life Year (DALY) to assess major health problems. Important objectives of the study were to quantify intra-country differentials in health outcomes and to place the United States situation in the international context.
Methods
We applied methods developed for the Global Burden of Disease (GBD) to data specific to the United States to compute Disability-Adjusted Life Years. Estimates are provided by age and gender for the general population of the United States and for each of the four official race groups: White; Black; American Indian or Alaskan Native; and Asian or Pacific Islander. Several adjustments of GBD methods were made: the inclusion of race; a revised list of causes; and a revised algorithm to allocate cardiovascular disease garbage codes to ischaemic heart disease. We compared the results of this analysis to international estimates published by the World Health Organization for developed and developing regions of the world.
Results
In the mid-1990s the leading sources of premature death and disability in the United States, as measured by DALYs, were: cardiovascular conditions, breast and lung cancers, depression, osteoarthritis, diabetes mellitus, and alcohol use and abuse. In addition, motor vehicle-related injuries and the HIV epidemic exacted a substantial toll on the health status of the US population, particularly among racial minorities. The major sources of death and disability in these latter populations were more similar to patterns of burden in developing rather than developed countries.
Conclusion
Estimating DALYs specifically for the United States provides a comprehensive assessment of health problems for this country compared to what is available using mortality data alone.
doi:10.1186/1478-7954-4-11
PMCID: PMC1635736  PMID: 17049081
23.  Schistosomiasis, Soil-Transmitted Helminthiasis, and Sociodemographic Factors Influence Quality of Life of Adults in Côte d'Ivoire 
Background
Burden of disease estimates are widely used for priority setting in public health and disability-adjusted life years are a powerful “currency” nowadays. However, disability weights, which capture the disability incurred by a typical patient of a certain condition, are fundamental to such burden calculation and their determination remains a widely debated issue.
Methodology
A cross-sectional epidemiological survey was conducted in the recently established Taabo health demographic surveillance system (HDSS) in south-central Côte d'Ivoire, to provide new, population-based evidence on the disability caused by schistosomiasis and soil-transmitted helminthiasis. Parasitological results from stool, urine, and blood examinations were juxtaposed to quality of life (QoL) questionnaire results from 187 adults. A multivariable linear regression model with stepwise backward elimination was used to identify significant associations, considering also sociodemographic characteristics obtained from the Taabo HDSS database.
Principal Findings
Prevalences for hookworm, Plasmodium spp., Trichuris trichiura, Schistosoma haematobium and Schistosoma mansoni were 39.0%, 18.2%, 2.7%, 2.1% and 2.1%, respectively. S. mansoni and T. trichiura infections of any intensity reduced the participants' self-rated QoL by 16 points (95% confidence interval (CI): 4–29 points) and 13 points (95% CI: 1–24 points), respectively, on a scale from 0 (worst QoL) to 100 points (best QoL). The only other statistically significant effect was a 1-point (95% CI: 0.1–2 points) increase on the QoL scale per one unit increase in a calculated wealth index.
Conclusions/Significance
We found consistent and significant results on the negative effects of schistosomiasis and soil-transmitted helminthiasis on adults' self-rated QoL, also when taking sociodemographic characteristics into account. Our results warrant further investigation on the disability incurred by helmintic infections and the usefulness of generic QoL questionnaires in this endeavor.
Author Summary
In public health, "burden" estimates should capture the human suffering caused by certain health states, and the estimates are often used for priority setting. However, such "burden" estimates need to assess not only the number of affected people by certain conditions, but also the disability incurred by the average patient, and the determination of the degree of disability remains a widely debated issue. In order to provide new, population-based evidence on the disability caused by infections with parasitic worms, we administered a quality of life (QoL) questionnaire to 187 adults in rural Côte d'Ivoire and concurrently examined them for parasitic worm infections. We also considered sociodemographic characteristics in our analysis. In comparison with their non-infected counterparts, infected people reported a 13–16 points lower QoL on a scale from 0 (worst QoL) to 100 points (best QoL). At the same time, a one unit increase in a calculated wealth index revealed a 1-point increase in the participants' QoL. The results are consistent and warrant further investigation on the disability induced by parasitic worm infections and the usefulness of QoL questionnaires in this endeavor.
doi:10.1371/journal.pntd.0001855
PMCID: PMC3464303  PMID: 23056662
24.  A Cost-effectiveness Analysis of Laparoscopic Gastric Bypass, Adjustable Gastric Banding and Non-Surgical Weight Loss Interventions 
Setting
Laparoscopic adjustable gastric banding (LAGB) and Laparoscopic Roux-en-Y gastric bypass (LRYGB) are the two most commonly performed bariatric procedures. While both procedures likely reduce healthcare expenditures related to the resolution of comorbid conditions, they have different rates of perioperative risks and differential rates of associated weight loss.
Objective
We designed a model to evaluate the incremental cost-effectiveness (ICER) of these procedures compared to non-operative weight loss interventions and to each other.
Methods
Deterministic, payer-perspective model comparing the lifetime expected costs and outcomes of LAGB, LRYGB and non-surgical treatment. The major endpoints were survival, health related quality of life and weight loss. Life expectancy and lifetime medical costs were calculated across age, sex and body mass index (BMI) strata using previously published data.
Results
For both men and women LRYGB and LAGB were cost-effective at less than $25,000/QALY even when evaluating the full range of baseline BMI and estimates of adverse outcomes, weight loss and costs. For base-case scenarios in men (age 35, BMI 40) the ICER was $11,604 per QALY for LAGB, compared to $18,543 per QALY for LRYGB. For base-case scenarios in women (age 35, BMI 40) the ICER was $8,878 per QALY for LAGB, compared to $14,680 per QALY for LRYGB.
Conclusions
Modeled cost-effectiveness analysis showed that both operative interventions for morbid obesity, LAGB and RYGB, were cost-effective at less than $25,000, and LAGB was more cost-effective than RYGB for all the base-case scenarios.
doi:10.1016/j.soard.2007.09.009
PMCID: PMC2706260  PMID: 18069075
Laparoscopic adjustable gastric banding; Laparoscopic Roux-en-Y gastric bypass; Cost effectiveness analyses; Quality-adjusted life-years
25.  Comorbidity and Sex-Related Differences in Mortality in Oxygen-Dependent Chronic Obstructive Pulmonary Disease 
PLoS ONE  2012;7(4):e35806.
Background
It is not known why survival differs between men and women in oxygen-dependent chronic obstructive pulmonary disease (COPD). The present study evaluates differences in comorbidity between men and women, and tests the hypothesis that comorbidity contributes to sex-related differences in mortality in oxygen-dependent COPD.
Methods
National prospective study of patients aged 50 years or older, starting long-term oxygen therapy (LTOT) for COPD in Sweden between 1992 and 2008. Comorbidities were obtained from the Swedish Hospital Discharge Register. Sex-related differences in comorbidity were estimated using logistic regression, adjusting for age, smoking status and year of inclusion. The effect of comorbidity on overall mortality and the interaction between comorbidity and sex were evaluated using Cox regression, adjusting for age, sex, PaO2 breathing air, FEV1, smoking history and year of inclusion.
Results
In total, 8,712 patients (55% women) were included and 6,729 patients died during the study period. No patient was lost to follow-up. Compared with women, men had significantly more arrhythmia, cancer, ischemic heart disease and renal failure, and less hypertension, mental disorders, osteoporosis and rheumatoid arthritis (P<0.05 for all odds ratios). Comorbidity was an independent predictor of mortality, and the effect was similar for the sexes. Women had lower mortality, which remained unchanged even after adjusting for comorbidity; hazard ratio 0.73 (95% confidence interval, 0.68–0.77; P<0.001).
Conclusions
Comorbidity is different in men and women, but does not explain the sex-related difference in mortality in oxygen-dependent COPD.
doi:10.1371/journal.pone.0035806
PMCID: PMC3338527  PMID: 22563405

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