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1.  Medical Tourism: A Cost or Benefit to the NHS? 
PLoS ONE  2013;8(10):e70406.
‘Medical Tourism’ – the phenomenon of people travelling abroad to access medical treatment - has received increasing attention in academic and popular media. This paper reports findings from a study examining effect of inbound and outbound medical tourism on the UK NHS, by estimating volume of medical tourism and associated costs and benefits. A mixed methods study it includes analysis of the UK International Passenger Survey (IPS); interviews with 77 returning UK medical tourists, 63 policymakers, NHS managers and medical tourism industry actors policymakers, and a review of published literature. These informed costing of three types of treatments for which patients commonly travel abroad: fertility treatment, cosmetic and bariatric surgery. Costing of inbound tourism relied on data obtained through 28 Freedom-of-Information requests to NHS Foundation Trusts. Findings demonstrate that contrary to some popular media reports, far from being a net importer of patients, the UK is now a clear net exporter of medical travellers. In 2010, an estimated 63,000 UK residents travelled for treatment, while around 52,000 patients sought treatment in the UK. Inbound medical tourists treated as private patients within NHS facilities may be especially profitable when compared to UK private patients, yielding close to a quarter of revenue from only 7% of volume in the data examined. Costs arise where patients travel abroad and return with complications. Analysis also indicates possible savings especially in future health care and social costs averted. These are likely to be specific to procedures and conditions treated. UK medical tourism is a growing phenomenon that presents risks and opportunities to the NHS. To fully understand its implications and guide policy on issues such as NHS global activities and patient safety will require investment in further research and monitoring. Results point to likely impact of medical tourism in other universal public health systems.
doi:10.1371/journal.pone.0070406
PMCID: PMC3812100  PMID: 24204556
2.  DYNAMO-HIA–A Dynamic Modeling Tool for Generic Health Impact Assessments 
PLoS ONE  2012;7(5):e33317.
Background
Currently, no standard tool is publicly available that allows researchers or policy-makers to quantify the impact of policies using epidemiological evidence within the causal framework of Health Impact Assessment (HIA). A standard tool should comply with three technical criteria (real-life population, dynamic projection, explicit risk-factor states) and three usability criteria (modest data requirements, rich model output, generally accessible) to be useful in the applied setting of HIA. With DYNAMO-HIA (Dynamic Modeling for Health Impact Assessment), we introduce such a generic software tool specifically designed to facilitate quantification in the assessment of the health impacts of policies.
Methods and Results
DYNAMO-HIA quantifies the impact of user-specified risk-factor changes on multiple diseases and in turn on overall population health, comparing one reference scenario with one or more intervention scenarios. The Markov-based modeling approach allows for explicit risk-factor states and simulation of a real-life population. A built-in parameter estimation module ensures that only standard population-level epidemiological evidence is required, i.e. data on incidence, prevalence, relative risks, and mortality. DYNAMO-HIA provides a rich output of summary measures – e.g. life expectancy and disease-free life expectancy – and detailed data – e.g. prevalences and mortality/survival rates – by age, sex, and risk-factor status over time. DYNAMO-HIA is controlled via a graphical user interface and is publicly available from the internet, ensuring general accessibility. We illustrate the use of DYNAMO-HIA with two example applications: a policy causing an overall increase in alcohol consumption and quantifying the disease-burden of smoking.
Conclusion
By combining modest data needs with general accessibility and user friendliness within the causal framework of HIA, DYNAMO-HIA is a potential standard tool for health impact assessment based on epidemiologic evidence.
doi:10.1371/journal.pone.0033317
PMCID: PMC3349723  PMID: 22590491
3.  Targeted versus universal prevention. a resource allocation model to prioritize cardiovascular prevention 
Background
Diabetes mellitus brings an increased risk for cardiovascular complications and patients profit from prevention. This prevention also suits the general population. The question arises what is a better strategy: target the general population or diabetes patients.
Methods
A mathematical programming model was developed to calculate optimal allocations for the Dutch population of the following interventions: smoking cessation support, diet and exercise to reduce overweight, statins, and medication to reduce blood pressure. Outcomes were total lifetime health care costs and QALYs. Budget sizes were varied and the division of resources between the general population and diabetes patients was assessed.
Results
Full implementation of all interventions resulted in a gain of 560,000 QALY at a cost of €640 per capita, about €12,900 per QALY on average. The large majority of these QALY gains could be obtained at incremental costs below €20,000 per QALY. Low or high budgets (below €9 or above €100 per capita) were predominantly spent in the general population. Moderate budgets were mostly spent in diabetes patients.
Conclusions
Major health gains can be realized efficiently by offering prevention to both the general and the diabetic population. However, a priori setting a specific distribution of resources is suboptimal. Resource allocation models allow accounting for capacity constraints and program size in addition to efficiency.
doi:10.1186/1478-7547-9-14
PMCID: PMC3200148  PMID: 21974836
4.  Cost-Effectiveness of Total Hip and Knee Replacements for the Australian Population with Osteoarthritis: Discrete-Event Simulation Model 
PLoS ONE  2011;6(9):e25403.
Background
Osteoarthritis constitutes a major musculoskeletal burden for the aged Australians. Hip and knee replacement surgeries are effective interventions once all conservative therapies to manage the symptoms have been exhausted. This study aims to evaluate the cost-effectiveness of hip and knee replacements in Australia. To our best knowledge, the study is the first attempt to account for the dual nature of hip and knee osteoarthritis in modelling the severities of right and left joints separately.
Methodology/Principal Findings
We developed a discrete-event simulation model that follows up the individuals with osteoarthritis over their lifetimes. The model defines separate attributes for right and left joints and accounts for several repeat replacements. The Australian population with osteoarthritis who were 40 years of age or older in 2003 were followed up until extinct. Intervention effects were modelled by means of disability-adjusted life-years (DALYs) averted. Both hip and knee replacements are highly cost effective (AUD 5,000 per DALY and AUD 12,000 per DALY respectively) under an AUD 50,000/DALY threshold level. The exclusion of cost offsets, and inclusion of future unrelated health care costs in extended years of life, did not change the findings that the interventions are cost-effective (AUD 17,000 per DALY and AUD 26,000 per DALY respectively). However, there was a substantial difference between hip and knee replacements where surgeries administered for hips were more cost-effective than for knees.
Conclusions/Significance
Both hip and knee replacements are cost-effective interventions to improve the quality of life of people with osteoarthritis. It was also shown that the dual nature of hip and knee OA should be taken into account to provide more accurate estimation on the cost-effectiveness of hip and knee replacements.
doi:10.1371/journal.pone.0025403
PMCID: PMC3179521  PMID: 21966520
5.  Self-Rated Health as a Predictor of Disability Retirement – The Contribution of Ill-Health and Working Conditions 
PLoS ONE  2011;6(9):e25004.
Objective
Self-rated health is a generic health indicator predicting mortality, many diseases, and need for care. We examined self-rated health as a predictor of subsequent disability retirement, and ill-health and working conditions as potential explanations for the association.
Methods
Self-rated health and the covariates were obtained from the Helsinki Health Study baseline mail surveys in 2000–2002 conducted among municipal employees aged 40–60 years (n = 6525). Data for disability retirement events (n = 625) along with diagnoses were linked from the Finnish Centre for Pensions, with a follow-up by the end of 2010. Hazard ratios (HR) and their 95% confidence intervals (CI) were calculated using competing risks models.
Results
Less than good self-rated health predicted disability retirement due to all causes among both women (HR = 4.60, 95% CI = 3.84–5.51) and men (HR = 3.83, 95% CI = 2.64–5.56), as well as due to musculoskeletal diseases (HR = 5.17, 95% CI = 4.02–6.66) and mental disorders (HR = 4.80, 95% CI = 3.50–6.59) among women and men pooled. Ill-health and physical working conditions partly explained the found associations, which nevertheless remained after the adjustments. Among the measures of ill-health limiting long-standing illness explained the association most in all-cause disability retirement and disability retirements due to musculoskeletal diseases, whereas common mental disorders explained the association most in disability retirements due to mental health disorders. Among working conditions physical work load and hazardous exposures at work explained the association most, although much less than ill-health.
Conclusions
Self-rated health is a strong predictor of disability retirement. This can be partly explained by ill-health and working conditions. Poor self-rated health provides a useful marker for increased risk of work disability and subsequent disability retirement.
doi:10.1371/journal.pone.0025004
PMCID: PMC3176797  PMID: 21949830
6.  Co-occurrence of diabetes, myocardial infarction, stroke, and cancer: quantifying age patterns in the Dutch population using health survey data 
Background
The high prevalence of chronic diseases in Western countries implies that the presence of multiple chronic diseases within one person is common. Especially at older ages, when the likelihood of having a chronic disease increases, the co-occurrence of distinct diseases will be encountered more frequently. The aim of this study was to estimate the age-specific prevalence of multimorbidity in the general population. In particular, we investigate to what extent specific pairs of diseases cluster within people and how this deviates from what is to be expected under the assumption of the independent occurrence of diseases (i.e., sheer coincidence).
Methods
We used data from a Dutch health survey to estimate the prevalence of pairs of chronic diseases specified by age. Diseases we focused on were diabetes, myocardial infarction, stroke, and cancer. Multinomial P-splines were fitted to the data to model the relation between age and disease status (single versus two diseases). To assess to what extent co-occurrence cannot be explained by independent occurrence, we estimated observed/expected co-occurrence ratios using predictions of the fitted regression models.
Results
Prevalence increased with age for all disease pairs. For all disease pairs, prevalence at most ages was much higher than is to be expected on the basis of coincidence. Observed/expected ratios of disease combinations decreased with age.
Conclusion
Common chronic diseases co-occur in one individual more frequently than is due to chance. In monitoring the occurrence of diseases among the population at large, such multimorbidity is insufficiently taken into account.
doi:10.1186/1478-7954-9-51
PMCID: PMC3175448  PMID: 21884614
multimorbidity; comorbidity; diabetes; cancer; cardiovascular disease; stroke; P-splines
7.  Cost-Effectiveness of Opportunistic Screening and Minimal Contact Psychotherapy to Prevent Depression in Primary Care Patients 
PLoS ONE  2011;6(8):e22884.
Background
Depression causes a large burden of disease worldwide. Effective prevention has the potential to reduce that burden considerably. This study aimed to investigate the cost-effectiveness of minimal contact psychotherapy, based on Lewinsohn's ‘Coping with depression’ course, targeted at opportunistically screened individuals with sub-threshold depression.
Methods and Results
Using a Markov model, future health effects and costs of an intervention scenario and a current practice scenario were estimated. The time horizon was five years. Incremental cost-effectiveness ratios were expressed in euro per Disability Adjusted Life Year (DALY) averted. Probabilistic sensitivity analysis was employed to study the effect of uncertainty in the model parameters. From the health care perspective the incremental cost-effectiveness ratio was € 1,400 per DALY, and from the societal perspective the intervention was cost-saving. Although the estimated incremental costs and effects were surrounded with large uncertainty, given a willingness to pay of € 20,000 per DALY, the probability that the intervention is cost-effective was around 80%.
Conclusion
This modelling study showed that opportunistic screening in primary care for sub-threshold depression in combination with minimal contact psychotherapy may be cost-effective in the prevention of major depression.
doi:10.1371/journal.pone.0022884
PMCID: PMC3154255  PMID: 21853053
8.  Entrepreneurs, Chance, and the Deterministic Concentration of Wealth 
PLoS ONE  2011;6(7):e20728.
In many economies, wealth is strikingly concentrated. Entrepreneurs–individuals with ownership in for-profit enterprises–comprise a large portion of the wealthiest individuals, and their behavior may help explain patterns in the national distribution of wealth. Entrepreneurs are less diversified and more heavily invested in their own companies than is commonly assumed in economic models. We present an intentionally simplified individual-based model of wealth generation among entrepreneurs to assess the role of chance and determinism in the distribution of wealth. We demonstrate that chance alone, combined with the deterministic effects of compounding returns, can lead to unlimited concentration of wealth, such that the percentage of all wealth owned by a few entrepreneurs eventually approaches 100%. Specifically, concentration of wealth results when the rate of return on investment varies by entrepreneur and by time. This result is robust to inclusion of realities such as differing skill among entrepreneurs. The most likely overall growth rate of the economy decreases as businesses become less diverse, suggesting that high concentrations of wealth may adversely affect a country's economic growth. We show that a tax on large inherited fortunes, applied to a small portion of the most fortunate in the population, can efficiently arrest the concentration of wealth at intermediate levels.
doi:10.1371/journal.pone.0020728
PMCID: PMC3140971  PMID: 21814540
9.  Decomposing cross-country differences in quality adjusted life expectancy: the impact of value sets 
Background
The validity, reliability and cross-country comparability of summary measures of population health (SMPH) have been persistently debated. In this debate, the measurement and valuation of nonfatal health outcomes have been defined as key issues. Our goal was to quantify and decompose international differences in health expectancy based on health-related quality of life (HRQoL). We focused on the impact of value set choice on cross-country variation.
Methods
We calculated Quality Adjusted Life Expectancy (QALE) at age 20 for 15 countries in which EQ-5D population surveys had been conducted. We applied the Sullivan approach to combine the EQ-5D based HRQoL data with life tables from the Human Mortality Database. Mean HRQoL by country-gender-age was estimated using a parametric model. We used nonparametric bootstrap techniques to compute confidence intervals. QALE was then compared across the six country-specific time trade-off value sets that were available. Finally, three counterfactual estimates were generated in order to assess the contribution of mortality, health states and health-state values to cross-country differences in QALE.
Results
QALE at age 20 ranged from 33 years in Armenia to almost 61 years in Japan, using the UK value set. The value sets of the other five countries generated different estimates, up to seven years higher. The relative impact of choosing a different value set differed across country-gender strata between 2% and 20%. In 50% of the country-gender strata the ranking changed by two or more positions across value sets. The decomposition demonstrated a varying impact of health states, health-state values, and mortality on QALE differences across countries.
Conclusions
The choice of the value set in SMPH may seriously affect cross-country comparisons of health expectancy, even across populations of similar levels of wealth and education. In our opinion, it is essential to get more insight into the drivers of differences in health-state values across populations. This will enhance the usefulness of health-expectancy measures.
doi:10.1186/1478-7954-9-17
PMCID: PMC3146826  PMID: 21699675
10.  Estimating and comparing incidence and prevalence of chronic diseases by combining GP registry data: the role of uncertainty 
BMC Public Health  2011;11:163.
Background
Estimates of disease incidence and prevalence are core indicators of public health. The manner in which these indicators stand out against each other provide guidance as to which diseases are most common and what health problems deserve priority. Our aim was to investigate how routinely collected data from different general practitioner registration networks (GPRNs) can be combined to estimate incidence and prevalence of chronic diseases and to explore the role of uncertainty when comparing diseases.
Methods
Incidence and prevalence counts, specified by gender and age, of 18 chronic diseases from 5 GPRNs in the Netherlands from the year 2007 were used as input. Generalized linear mixed models were fitted with the GPRN identifier acting as random intercept, and age and gender as explanatory variables. Using predictions of the regression models we estimated the incidence and prevalence for 18 chronic diseases and calculated a stochastic ranking of diseases in terms of incidence and prevalence per 1,000.
Results
Incidence was highest for coronary heart disease and prevalence was highest for diabetes if we looked at the point estimates. The between GPRN variance in general was higher for incidence than for prevalence. Since uncertainty intervals were wide for some diseases and overlapped, the ranking of diseases was subject to uncertainty. For incidence shifts in rank of up to twelve positions were observed. For prevalence, most diseases shifted maximally three or four places in rank.
Conclusion
Estimates of incidence and prevalence can be obtained by combining data from GPRNs. Uncertainty in the estimates of absolute figures may lead to different rankings of diseases and, hence, should be taken into consideration when comparing disease incidences and prevalences.
doi:10.1186/1471-2458-11-163
PMCID: PMC3064641  PMID: 21406092
incidence; prevalence; Monte Carlo simulation; uncertainty
11.  Cost-Effectiveness of Lifestyle Modification in Diabetic Patients 
Diabetes Care  2009;32(8):1453-1458.
OBJECTIVE
To explore the potential long-term health and economic consequences of lifestyle interventions for diabetic patients.
RESEARCH DESIGN AND METHODS
A literature search was performed to identify interventions for diabetic patients in which lifestyle issues were addressed. We selected recent (2003–2008), randomized controlled trials with a minimum follow-up of 12 months. The long-term outcomes for these interventions, if implemented in the Dutch diabetic population, were simulated with a computer-based model. Costs and effects were discounted at, respectively, 4 and 1.5% annually. A lifelong time horizon was applied. Probabilistic sensitivity analyses were performed, taking account of variability in intervention costs and (long-term) treatment effects.
RESULTS
Seven trials with 147–5,145 participants met our predefined criteria. All interventions improved cardiovascular risk factors at ≥1 year follow-up and were projected to reduce cardiovascular morbidity over lifetime. The interventions resulted in an average gain of 0.01–0.14 quality-adjusted life-years (QALYs) per participant. Health benefits were generally achieved at reasonable costs (≤€50,000/QALY). A self-management education program (X-PERT) and physical activity counseling achieved the best results with ≥0.10 QALYs gained and ≥99% probability to be very cost-effective (≤€20,000/QALY).
CONCLUSIONS
Implementation of lifestyle interventions would probably yield important health benefits at reasonable costs. However, essential evidence for long-term maintenance of health benefits was limited. Future research should be focused on long-term effectiveness and multiple treatment strategies should be compared to determine incremental costs and benefits of one over the other.
doi:10.2337/dc09-0363
PMCID: PMC2713648  PMID: 19435958
12.  Cost-Effectiveness of an Opportunistic Screening Programme and Brief Intervention for Excessive Alcohol Use in Primary Care 
PLoS ONE  2009;4(5):e5696.
Background
Effective prevention of excessive alcohol use has the potential to reduce the public burden of disease considerably. We investigated the cost-effectiveness of Screening and Brief Intervention (SBI) for excessive alcohol use in primary care in the Netherlands, which is targeted at early detection and treatment of ‘at-risk’ drinkers.
Methodology and Results
We compared a SBI scenario (opportunistic screening and brief intervention for ‘at-risk’ drinkers) in general practices with the current practice scenario (no SBI) in the Netherlands. We used the RIVM Chronic Disease Model (CDM) to extrapolate from decreased alcohol consumption to effects on health care costs and Quality Adjusted Life Years (QALYs) gained. Probabilistic sensitivity analysis was employed to study the effect of uncertainty in the model parameters. In total, 56,000 QALYs were gained at an additional cost of €298,000,000 due to providing alcohol SBI in the target population, resulting in a cost-effectiveness ratio of €5,400 per QALY gained.
Conclusion
Prevention of excessive alcohol use by implementing SBI for excessive alcohol use in primary care settings appears to be cost-effective.
doi:10.1371/journal.pone.0005696
PMCID: PMC2682644  PMID: 19479081
13.  Mortality Risk among Children Admitted in a Large-Scale Nutritional Program in Niger, 2006 
PLoS ONE  2009;4(1):e4313.
Background
In 2006, the Médecins sans Frontières nutritional program in the region of Maradi (Niger) included 68,001 children 6–59 months of age with either moderate or severe malnutrition, according to the NCHS reference (weight-for-height<80% of the NCHS median, and/or mid-upper arm circumference<110 mm for children taller than 65 cm and/or presence of bipedal edema). Our objective was to identify baseline risk factors for death among children diagnosed with severe malnutrition using the newly introduced WHO growth standards. As the release of WHO growth standards changed the definition of severe malnutrition, which now includes many children formerly identified as moderately malnourished with the NCHS reference, studying this new category of children is crucial.
Methodology
Program monitoring data were collected from the medical records of all children admitted in the program. Data included age, sex, height, weight, MUAC, clinical signs on admission including edema, and type of discharge (recovery, death, and default/loss to follow up). Additional data included results of a malaria rapid diagnostic test due to Plasmodium falciparum (Paracheck®) and whether the child was a resident of the region of Maradi or came from bordering Nigeria to seek treatment. Multivariate logistic regression was performed on a subset of 27,687 children meeting the new WHO growth standards criteria for severe malnutrition (weight-for-height<−3 Z score, mid-upper arm circumference<110 mm for children taller than 65 cm or presence of bipedal edema). We explored two different models: one with only basic anthropometric data and a second model that included perfunctory clinical signs.
Principal Findings
In the first model including only weight, height, sex and presence of edema, the risk factors retained were the weight/height1.84 ratio (OR: 5,774; 95% CI: [2,284; 14,594]) and presence of edema (7.51 [5.12; 11.0]). A second model, taking into account supplementary data from perfunctory clinical examination, identified other risk factors for death: apathy (9.71 [6.92; 13.6]), pallor (2.25 [1.25; 4.05]), anorexia (1.89 [1.35; 2.66]), fever>38.5°C (1.83 [1.25; 2.69]), and age below 1 year (1.42 [1.01; 1.99]).
Conclusions
Although clinicians will continue to perform screening using clinical signs and anthropometry, these risk indicators may provide additional criteria for the assessment of absolute and relative risk of death. Better appraisal of the child's risk of death may help orientate the child towards either hospitalization or ambulatory care. As the transition from the NCHS growth reference to the WHO standards will increase the number of children classified as severely malnourished, further studies should explore means to identify children at highest risk of death within this group using simple and standardized indicators.
doi:10.1371/journal.pone.0004313
PMCID: PMC2629565  PMID: 19177169
14.  The cost-effectiveness of increasing alcohol taxes: a modelling study 
BMC Medicine  2008;6:36.
Background
Excessive alcohol use increases risks of chronic diseases such as coronary heart disease and several types of cancer, with associated losses of quality of life and life-years. Alcohol taxes can be considered as a public health instrument as they are known to be able to decrease alcohol consumption. In this paper, we estimate the cost-effectiveness of an alcohol tax increase for the entire Dutch population from a health-care perspective focusing on health benefits and health-care costs in alcohol users.
Methods
The chronic disease model of the National Institute for Public Health and the Environment was used to extrapolate from decreased alcohol consumption due to tax increases to effects on health-care costs, life-years gained and quality-adjusted life-years gained, A Dutch scenario in which tax increases for beer are planned, and a Swedish scenario representing one of the highest alcohol taxes in Europe, were compared with current practice in the Netherlands. To estimate cost-effectiveness ratios, yearly differences in model outcomes between intervention and current practice scenarios were discounted and added over the time horizon of 100 years to find net present values for incremental life-years gained, quality-adjusted life-years gained, and health-care costs.
Results
In the Swedish scenario, many more quality-adjusted life-years were gained than in the Dutch scenario, but both scenarios had almost equal incremental cost-effectiveness ratios: €5100 per quality-adjusted life-year and €5300 per quality-adjusted life-year, respectively.
Conclusion
Focusing on health-care costs and health consequences for drinkers, an alcohol tax increase is a cost-effective policy instrument.
doi:10.1186/1741-7015-6-36
PMCID: PMC2637894  PMID: 19040717
15.  Lifetime Medical Costs of Obesity: Prevention No Cure for Increasing Health Expenditure 
PLoS Medicine  2008;5(2):e29.
Background
Obesity is a major cause of morbidity and mortality and is associated with high medical expenditures. It has been suggested that obesity prevention could result in cost savings. The objective of this study was to estimate the annual and lifetime medical costs attributable to obesity, to compare those to similar costs attributable to smoking, and to discuss the implications for prevention.
Methods and Findings
With a simulation model, lifetime health-care costs were estimated for a cohort of obese people aged 20 y at baseline. To assess the impact of obesity, comparisons were made with similar cohorts of smokers and “healthy-living” persons (defined as nonsmokers with a body mass index between 18.5 and 25). Except for relative risk values, all input parameters of the simulation model were based on data from The Netherlands. In sensitivity analyses the effects of epidemiologic parameters and cost definitions were assessed. Until age 56 y, annual health expenditure was highest for obese people. At older ages, smokers incurred higher costs. Because of differences in life expectancy, however, lifetime health expenditure was highest among healthy-living people and lowest for smokers. Obese individuals held an intermediate position. Alternative values of epidemiologic parameters and cost definitions did not alter these conclusions.
Conclusions
Although effective obesity prevention leads to a decrease in costs of obesity-related diseases, this decrease is offset by cost increases due to diseases unrelated to obesity in life-years gained. Obesity prevention may be an important and cost-effective way of improving public health, but it is not a cure for increasing health expenditures.
Using a simulation model, Pieter van Baal and colleagues conclude that obesity prevention leads to a decrease in costs of obesity-related diseases, but this is offset by cost increases due to diseases unrelated to obesity in life-years gained.
Editors' Summary
Background.
Since the mid 1970s, the proportion of people who are obese (people who have an unhealthy amount of body fat) has increased sharply in many countries. One-third of all US adults, for example, are now classified as obese, and recent forecasts suggest that by 2025 half of US adults will be obese. A person is overweight if their body mass index (BMI, calculated by dividing their weight in kilograms by their height in meters squared) is between 25 and 30, and obese if BMI is greater than 30. Compared to people with a healthy weight (a BMI between 18.5 and 25), overweight and obese individuals have an increased risk of developing many diseases, such as diabetes, coronary heart disease and stroke, and tend to die younger. People become unhealthily fat by consuming food and drink that contains more energy than they need for their daily activities. In these circumstances, the body converts the excess energy into fat for use at a later date. Obesity can be prevented, therefore, by having a healthy diet and exercising regularly.
Why Was This Study Done?
Because obesity causes so much illness and premature death, many governments have public-health policies that aim to prevent obesity. Clearly, the improvement in health associated with the prevention of obesity is a worthwhile goal in itself but the prevention of obesity might also reduce national spending on medical care. It would do this, the argument goes, by reducing the amount of money spent on treating the diseases for which obesity is a risk factor. However, some experts have suggested that these short-term savings might be offset by spending on treating the diseases that would occur during the extra lifespan experienced by non-obese individuals. In this study, therefore, the researchers have used a computer model to calculate yearly and lifetime medical costs associated with obesity in The Netherlands.
What Did the Researchers Do and Find?
The researchers used their model to estimate the number of surviving individuals and the occurrence of various diseases for three hypothetical groups of men and women, examining data from the age of 20 until the time when the model predicted that everyone had died. The “obese” group consisted of never-smoking people with a BMI of more than 30; the “healthy-living” group consisted of never-smoking people with a healthy weight; the “smoking” group consisted of lifetime smokers with a healthy weight. Data from the Netherlands on the costs of illness were fed into the model to calculate the yearly and lifetime health-care costs of all three groups. The model predicted that until the age of 56, yearly health costs were highest for obese people and lowest for healthy-living people. At older ages, the highest yearly costs were incurred by the smoking group. However, because of differences in life expectancy (life expectancy at age 20 was 5 years less for the obese group, and 8 years less for the smoking group, compared to the healthy-living group), total lifetime health spending was greatest for the healthy-living people, lowest for the smokers, and intermediate for the obese people.
What Do These Findings Mean?
As with all mathematical models such as this, the accuracy of these findings depend on how well the model reflects real life and the data fed into it. In this case, the model does not take into account varying degrees of obesity, which are likely to affect lifetime health-care costs, nor indirect costs of obesity such as reduced productivity. Nevertheless, these findings suggest that although effective obesity prevention reduces the costs of obesity-related diseases, this reduction is offset by the increased costs of diseases unrelated to obesity that occur during the extra years of life gained by slimming down.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/doi:10.1371/journal.pmed.0050029.
The MedlinePlus encyclopedia has a page on obesity (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on all aspects of obesity (in English and Spanish)
The UK National Health Service's health Web site (NHS Direct) provides information about obesity
The International Obesity Taskforce provides information about preventing obesity
The UK Foods Standards Agency, the United States Department of Agriculture, and Shaping America's Health all provide useful advice about healthy eating
The Netherlands National Institute for Public Health and the Environment (RIVM) Web site provides more information on the cost of illness and illness prevention in the Netherlands (in English and Dutch)
doi:10.1371/journal.pmed.0050029
PMCID: PMC2225430  PMID: 18254654
16.  Dynamic effects of smoking cessation on disease incidence, mortality and quality of life: The role of time since cessation 
Background
To support health policy makers in setting priorities, quantifying the potential effects of tobacco control on the burden of disease is useful. However, smoking is related to a variety of diseases and the dynamic effects of smoking cessation on the incidence of these diseases differ. Furthermore, many people who quit smoking relapse, most of them within a relatively short period.
Methods
In this paper, a method is presented for calculating the effects of smoking cessation interventions on disease incidence that allows to deal with relapse and the effect of time since quitting. A simulation model is described that links smoking to the incidence of 14 smoking related diseases. To demonstrate the model, health effects are estimated of two interventions in which part of current smokers in the Netherlands quits smoking.
To illustrate the advantages of the model its results are compared with those of two simpler versions of the model. In one version we assumed no relapse after quitting and equal incidence rates for all former smokers. In the second version, incidence rates depend on time since cessation, but we assumed still no relapse after quitting.
Results
Not taking into account time since smoking cessation on disease incidence rates results in biased estimates of the effects of interventions. The immediate public health effects are overestimated, since the health risk of quitters immediately drops to the mean level of all former smokers. However, the long-term public health effects are underestimated since after longer periods of time the effects of past smoking disappear and so surviving quitters start to resemble never smokers. On balance, total health gains of smoking cessation are underestimated if one does not account for the effect of time since cessation on disease incidence rates. Not taking into account relapse of quitters overestimates health gains substantially.
Conclusion
The results show that simulation models are sensitive to assumptions made in specifying the model. The model should be specified carefully in accordance with the questions it is supposed to answer. If the aim of the model is to estimate effects of smoking cessation interventions on mortality and morbidity, one should include relapse of quitters and dependency on time since cessation of incidence rates of smoking-related chronic diseases. A drawback of such models is that data requirements are extensive.
doi:10.1186/1478-7547-6-1
PMCID: PMC2267164  PMID: 18190684
17.  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
18.  Disability weights for comorbidity and their influence on Health-adjusted Life Expectancy 
Background
Comorbidity complicates estimations of health-adjusted life expectancy (HALE) using disease prevalences and disability weights from Burden of Disease studies. Usually, the exact amount of comorbidity is unknown and no disability weights are defined for comorbidity.
Methods
Using data of the Dutch national burden of disease study, the effects of different methods to adjust for comorbidity on HALE calculations are estimated. The default multiplicative adjustment method to define disability weights for comorbidity is compared to HALE estimates without adjustment for comorbidity and to HALE estimates in which the amount of disability in patients with multiple diseases is solely determined by the disease that leads to most disability (the maximum adjustment method). To estimate the amount of comorbidity, independence between diseases is assumed.
Results
Compared to the multiplicative adjustment method, the maximum adjustment method lowers HALE estimates by 1.2 years for males and 1.9 years for females. Compared to no adjustment, a multiplicative adjustment lowers HALE estimates by 1.0 years for males and 1.4 years for females.
Conclusion
The differences in HALE caused by the different adjustment methods demonstrate that adjusting for comorbidity in HALE calculations is an important topic that needs more attention. More empirical research is needed to develop a more general theory as to how comorbidity influences disability.
doi:10.1186/1478-7954-4-1
PMCID: PMC1523368  PMID: 16606448
19.  Extending Employment beyond the Pensionable Age: A Cohort Study of the Influence of Chronic Diseases, Health Risk Factors, and Working Conditions 
PLoS ONE  2014;9(2):e88695.
Background
In response to the economic consequences of ageing of the population, governments are seeking ways with which people might work into older age. We examined the association of working conditions and health with extended employment (defined as >6 months beyond the pensionable age) in a cohort of older, non-disabled employees who have reached old-age retirement.
Methods
A total of 4,677 Finnish employees who reached their old-age pensionable date between 2005 and 2011 (mean age 59.8 years in 2005, 73% women) had their survey responses before pensionable age linked to national health and pension registers, resulting in a prospective cohort study.
Results
In all, 832 participants (17.8%) extended their employment by more than 6 months beyond the pensionable date. After multivariable adjustment, the following factors were associated with extended employment: absence of diagnosed mental disorder (OR 1.25, 95% confidence interval = 1.01–1.54) and psychological distress (OR 1.68; 1.35–2.08) and of the work characteristics, high work time control (OR 2.31; 1.88–2.84). The projected probability of extended employment was 21.3% (19.5–23.1) among those free of psychiatric morbidity and with high work time control, while the corresponding probability was only 9.2% (7.4–11.4) among those with both psychiatric morbidity and poor work time control. The contribution of chronic somatic diseases was modest.
Conclusions
In the present study, good mental health in combination with the opportunity to control work time seem to be key factors in extended employment into older age. In addition, high work time control might promote work life participation irrespective of employees' somatic disease status.
doi:10.1371/journal.pone.0088695
PMCID: PMC3929527  PMID: 24586372
20.  Cost-Effectiveness of Preventive Interventions to Reduce Alcohol Consumption in Denmark 
PLoS ONE  2014;9(2):e88041.
Introduction
Excessive alcohol consumption increases the risk of many diseases and injuries, and the Global Burden of Disease 2010 study estimated that 6% of the burden of disease in Denmark is due to alcohol consumption. Alcohol consumption thus places a considerable economic burden on society.
Methods
We analysed the cost-effectiveness of six interventions aimed at preventing alcohol abuse in the adult Danish population: 30% increased taxation, increased minimum legal drinking age, advertisement bans, limited hours of retail sales, and brief and longer individual interventions. Potential health effects were evaluated as changes in incidence, prevalence and mortality of alcohol-related diseases and injuries. Net costs were calculated as the sum of intervention costs and cost offsets related to treatment of alcohol-related outcomes, based on health care costs from Danish national registers. Cost-effectiveness was evaluated by calculating incremental cost-effectiveness ratios (ICERs) for each intervention. We also created an intervention pathway to determine the optimal sequence of interventions and their combined effects.
Results
Three of the analysed interventions (advertising bans, limited hours of retail sales and taxation) were cost-saving, and the remaining three interventions were all cost-effective. Net costs varied from € -17 million per year for advertisement ban to € 8 million for longer individual intervention. Effectiveness varied from 115 disability-adjusted life years (DALY) per year for minimum legal drinking age to 2,900 DALY for advertisement ban. The total annual effect if all interventions were implemented would be 7,300 DALY, with a net cost of € -30 million.
Conclusion
Our results show that interventions targeting the whole population were more effective than individual-focused interventions. A ban on alcohol advertising, limited hours of retail sale and increased taxation had the highest probability of being cost-saving and should thus be first priority for implementation.
doi:10.1371/journal.pone.0088041
PMCID: PMC3914889  PMID: 24505370
21.  Cost-Effectiveness Analysis of Tdap in the Prevention of Pertussis in the Elderly 
PLoS ONE  2013;8(9):e67260.
Objectives
Health benefits and costs of combined reduced-antigen-content tetanus, diphtheria, and pertussis (Tdap) immunization among adults ≥65 years have not been evaluated. In February 2012, the Advisory Committee on Immunization Practices (ACIP) recommended expanding Tdap vaccination (one single dose) to include adults ≥65 years not previously vaccinated with Tdap. Our study estimated the health and economic outcomes of one-time replacement of the decennial tetanus and diphtheria (Td) booster with Tdap in the 10% of individuals aged 65 years assumed eligible each year compared with a baseline scenario of continued Td vaccination.
Methods
We constructed a model evaluating the cost-effectiveness of vaccinating a cohort of adults aged 65 with Tdap, by calculating pertussis cases averted due to direct vaccine effects only. Results are presented from societal and payer perspectives for a range of pertussis incidences (25–200 cases per 100,000), due to the uncertainty in estimating true annual incidence. Cases averted were accrued throughout the patient 's lifetime, and a probability tree used to estimate the clinical outcomes and costs (US$ 2010) for each case. Quality-adjusted life-years (QALYs) lost to acute disease were calculated by multiplying cases of mild/moderate/severe pertussis by the associated health-state disutility; QALY losses due to death and long-term sequelae were also considered. Incremental costs and QALYs were summed over the cohort to derive incremental cost-effectiveness ratios. Scenario analyses evaluated the effect of alternative plausible parameter estimates on results.
Results
At incidence levels of 25, 100, 200 cases/100,000, vaccinating adults aged 65 years costs an additional $336,000, $63,000 and $17,000/QALY gained, respectively. Vaccination has a cost-effectiveness ratio less than $50,000/QALY if pertussis incidence is >116 cases/100,000 from societal and payer perspectives. Results were robust to scenario analyses.
Conclusions
Tdap immunization of adults aged 65 years according to current ACIP recommendations is a cost-effective health-care intervention at plausible incidence assumptions.
doi:10.1371/journal.pone.0067260
PMCID: PMC3760878  PMID: 24019859
22.  Health-Related Financial Catastrophe, Inequality and Chronic Illness in Bangladesh 
PLoS ONE  2013;8(2):e56873.
Background
Bangladesh has a high proportion of households incurring catastrophic health expenditure, and very limited risk sharing mechanisms. Identifying determinants of out-of-pocket (OOP) payments and catastrophic health expenditure may reveal opportunities to reduce costs and protect households from financial risk.
Objective
This study investigates the determinants of high healthcare expenditure and healthcare- related financial catastrophe.
Methods
A cross-sectional household survey was conducted in Rajshahi city, Bangladesh, in 2011. Catastrophic health expenditure was estimated separately based on capacity to pay and proportion of non-food expenditure. Determinants of OOP payments and financial catastrophe were estimated using double hurdle and Poisson regression models respectively.
Results
On average households spent 11% of their total budgets on health, half the residents spent 7% of the monthly per capita consumption expenditure for one illness, and nearly 9% of households faced financial catastrophe. The poorest households spent less on health but had a four times higher risk of catastrophe than the richest households. The risk of financial catastrophe and the level of OOP payments were higher for users of inpatient, outpatient public and private facilities respectively compared to using self-medication or traditional healers. Other determinants of OOP payments and catastrophic expenses were economic status, presence of chronic illness in the household, and illness among children and adults.
Conclusion
Households that received inpatient or outpatient private care experienced the highest burden of health expenditure. The poorest members of the community also face large, often catastrophic expenses. Chronic illness management is crucial to reducing the total burden of disease in a household and its associated increased risk of level of OOP payments and catastrophic expenses. Households can only be protected from these situations by reducing the health system's dependency on OOP payments and providing more financial risk protection.
doi:10.1371/journal.pone.0056873
PMCID: PMC3581555  PMID: 23451102
23.  Are the Healthy Behaviors of US High-Deductible Health Plan Enrollees Driven by People Who Chose These Plans? Smoking as a Case Study 
PLoS ONE  2013;8(2):e56154.
Purpose
To determine whether negative associations between enrollment in a high-deductible health plan (HDHP) and one exemplar unhealthy behavior – daily smoking – are found only among people who chose these plans.
Design
Cross-sectional analysis of nationally-representative data.
Setting
United States from 2007 to 2008.
Subjects
6,941 privately insured non-elderly adult participants in the 2007 Health Tracking Household Survey.
Measures
Self-reported smoking status.
Analysis
We classified subjects as HDHP or traditional health plan enrollees with employer-sponsored insurance (ESI) and no choice of plans, ESI with a choice of plans, or coverage through the non-group market. We used multivariate logistic regression to measure associations between HDHP enrollment and daily smoking within each of the 3 coverage source groups while controlling for potential confounders.
Results
HDHP enrollment was associated with lower odds of smoking among individuals with ESI and a choice of plans (AOR 0.55, 95% CI 0.33–0.90) and those with non-group coverage (AOR 0.64, 95% CI 0.34–1.22), though the latter association was not statistically significant. HDHP enrollment was not associated with lower odds of smoking among individuals with ESI and no choice of plans (AOR 1.04, 95% CI 0.69–1.56).
Conclusions
HDHP enrollment is associated with lower odds of smoking only among individuals who chose to enroll in an HDHP. Lower rates of unhealthy behaviors among HDHP enrollees may be a reflection of individuals who choose these plans.
doi:10.1371/journal.pone.0056154
PMCID: PMC3572017  PMID: 23418528
24.  Cost-effectiveness of counseling and pedometer use to increase physical activity in the Netherlands: a modeling study 
Background
Counseling in combination with pedometer use has proven to be effective in increasing physical activity and improving health outcomes. We investigated the cost-effectiveness of this intervention targeted at one million insufficiently active adults who visit their general practitioner in the Netherlands.
Methods
We used the RIVM chronic disease model to estimate the long-term effects of increased physical activity on the future health care costs and quality adjusted life years (QALY) gained, from a health care perspective.
Results
The intervention resulted in almost 6000 people shifting to more favorable physical-activity levels, and in 5100 life years and 6100 QALYs gained, at an additional total cost of EUR 67.6 million. The incremental cost-effectiveness ratio (ICER) was EUR 13,200 per life year gained and EUR 11,100 per QALY gained. The intervention has a probability of 0.66 to be cost-effective if a QALY gained is valued at the Dutch informal threshold for cost-effectiveness of preventive intervention of EUR 20,000. A sensitivity analysis showed substantial uncertainty of ICER values.
Conclusion
Counseling in combination with pedometer use aiming to increase physical activity may be a cost-effective intervention. However, the intervention only yields relatively small health benefits in the Netherlands.
doi:10.1186/1478-7547-10-13
PMCID: PMC3495195  PMID: 23006466
Economic evaluation; Prevention; Modeling; Counseling; Pedometer use; Physical activity; Primary care
25.  Adaptive Pacing, Cognitive Behaviour Therapy, Graded Exercise, and Specialist Medical Care for Chronic Fatigue Syndrome: A Cost-Effectiveness Analysis 
PLoS ONE  2012;7(8):e40808.
Background
The PACE trial compared the effectiveness of adding adaptive pacing therapy (APT), cognitive behaviour therapy (CBT), or graded exercise therapy (GET), to specialist medical care (SMC) for patients with chronic fatigue syndrome. This paper reports the relative cost-effectiveness of these treatments in terms of quality adjusted life years (QALYs) and improvements in fatigue and physical function.
Methods
Resource use was measured and costs calculated. Healthcare and societal costs (healthcare plus lost production and unpaid informal care) were combined with QALYs gained, and changes in fatigue and disability; incremental cost-effectiveness ratios (ICERs) were computed.
Results
SMC patients had significantly lower healthcare costs than those receiving APT, CBT and GET. If society is willing to value a QALY at £30,000 there is a 62.7% likelihood that CBT is the most cost-effective therapy, a 26.8% likelihood that GET is most cost effective, 2.6% that APT is most cost-effective and 7.9% that SMC alone is most cost-effective. Compared to SMC alone, the incremental healthcare cost per QALY was £18,374 for CBT, £23,615 for GET and £55,235 for APT. From a societal perspective CBT has a 59.5% likelihood of being the most cost-effective, GET 34.8%, APT 0.2% and SMC alone 5.5%. CBT and GET dominated SMC, while APT had a cost per QALY of £127,047. ICERs using reductions in fatigue and disability as outcomes largely mirrored these findings.
Conclusions
Comparing the four treatments using a health care perspective, CBT had the greatest probability of being the most cost-effective followed by GET. APT had a lower probability of being the most cost-effective option than SMC alone. The relative cost-effectiveness was even greater from a societal perspective as additional cost savings due to reduced need for informal care were likely.
doi:10.1371/journal.pone.0040808
PMCID: PMC3411573  PMID: 22870204

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