A Blueprint for Multi-use Disease Modeling in Health Economics: Results from Two Expert-Panel Consultations.

BACKGROUND: The current use of health economic decision models in HTA is mostly confined to single use cases, which may be inefficient and result in little consistency over different treatment comparisons, and consequently inconsistent health policy decisions, for the same disorder. Multi-use disease models (MUDMs) (other terms: generic models, whole disease models, disease models) may offer a solution. However, much is uncertain about their definition and application. The current research aimed to develop a blueprint for the application of MUDMs. METHODS: We elicited expert opinion using a two-round modified Delphi process. The panel consisted of experts and stakeholders in health economic modelling from various professional backgrounds. The first questionnaire concerned definition, terminology, potential applications, issues and recommendations for MUDMs and was based on an exploratory scoping review. In the second round, the panel members were asked to reconsider their input, based on feedback regarding first-round results, and to score issues and recommendations for priority. Finally, adding input from external advisors and policy makers in a structured way, an overview of issues and challenges was developed during two team consensus meetings. RESULTS: In total, 54 respondents contributed to the panel results. The term 'multi-use disease models' was proposed and agreed upon, and a definition was provided. The panel prioritized 10 potential applications (with comparing alternative policies and supporting resource allocation decisions as the top 2), while 20 issues (with model transparency and stakeholders' roles as the top 2) were identified as challenges. Opinions on potential features concerning operationalization of multi-use models were given, with 11 of these subsequently receiving high priority scores (regular updates and revalidation after updates were the top 2). CONCLUSIONS: MUDMs would improve on current decision support regarding cost-effectiveness information. Given feasibility challenges, this would be most relevant for diseases with multiple treatments, large burden of disease and requiring more complex models. The current overview offers policy makers a starting point to organize the development, use, and maintenance of MUDMs and to support choices concerning which diseases and policy decisions they will be helpful for.

Human Biomonitoring Guidance Values for Deoxynivalenol Derived under the European Human Biomonitoring Initiative (HBM4EU).

The mycotoxin deoxynivalenol (DON) was one of the priority substances in the European Joint Human Biomonitoring Initiative (HBM4EU) project. In this study, to better interpret the actual internal exposure of DON in the general population and safeguard public health, human biomonitoring guidance values of DON for the general population (HBM-GVGenPop) were derived. The HBM-GVGenPop of DON was based on either the total DON (DON and its glucuronides) or DON's main metabolite (DON-15-GlcA) levels in 24-h urine samples, resulting in a HBM-GVGenPop of 0.023 µg/mL for the total DON or a HBM-GVGenPop of 0.020 µg/mL for DON-15-GlcA. The use of 24-h urine samples is recommended based on the fact that DON and its metabolites have a short elimination half-life (T1/2), and 95% of the cumulative amount was excreted within 12 h after DON intake. The T1/2 for DON, DON-15-GlcA, and total DON were estimated to be 2.55 h, 2.95 h, and 2.95 h, respectively. Therefore, a 24-h urine sample reflects almost all of the DON exposure from the previous day, and this type of sample was considered for the derivation of a HBM-GVGenPop for DON.

Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol.

Toxicokinetic modelling provides a powerful tool in relating internal human exposure (i.e., assessed through urinary biomarker levels) to external exposure. Chemical specific toxicokinetic models are available; however, this specificity prevents their application to similar contaminants or to other routes of exposure. For this reason, we investigated whether a generic physiological-based kinetic (PBK) model might be a suitable alternative for a biokinetic model of deoxynivalenol (DON). IndusChemFate (ICF) was selected as a generic PBK model, which could be fit for purpose. Being suited for simulating multiple routes of exposure, ICF has particularly been used to relate the inhalation and dermal exposure of industrial chemicals to their urinary excretion. For the first time, the ICF model was adapted as a generic model for the human biomonitoring of mycotoxins, thereby extending its applicability domain. For this purpose, chemical-specific data for DON and its metabolites were collected directly from the literature (distribution and metabolism) or indirectly (absorption and excretion) by fitting the ICF model to previously described urinary excretion data. The obtained results indicate that this generic model can be used to model the urinary excretion of DON and its glucuronidated metabolites following dietary exposure to DON. Additionally, the present study establishes the basis for further development of the model to include an inhalation exposure route alongside the oral exposure route.

Cost-Effectiveness of SGLT2 Inhibitors in a Real-World Population: A MICADO Model-Based Analysis Using Routine Data from a GP Registry.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to reduce the risk of cardiovascular complications, which largely drive diabetes' health and economic burdens. Trial results indicated that SGLT2i are cost effective. However, these findings may not be generalizable to the real-world target population. This study aims to evaluate the cost effectiveness of SGLT2i in a routine care type 2 diabetes population that meets Dutch reimbursement criteria using the MICADO model. METHODS: Individuals from the Hoorn Diabetes Care System cohort (N = 15,392) were filtered to satisfy trial inclusion criteria (including EMPA-REG, CANVAS, and DECLARE-TIMI58) or satisfy the current Dutch reimbursement criteria for SGLT2i. We validated a health economic model (MICADO) by comparing simulated and observed outcomes regarding the relative risks of events in the intervention and comparator arm from three trials, and used the validated model to evaluate the long-term health outcomes using the filtered cohorts' baseline characteristics and treatment effects from trials and a review of observational studies. The incremental cost-effectiveness ratio (ICER) of SGLT2i, compared with care-as-usual, was assessed from a third-party payer perspective, measured in euros (2021 price level), using a discount rate of 4% for costs and 1.5% for effects. RESULTS: From Dutch individuals with diabetes in routine care, 15.8% qualify for the current Dutch reimbursement criteria for SGLT2i. Their characteristics were significantly different (lower HbA1c, higher age, and generally more preexisting complications) than trial populations. After validating the MICADO model, we found that lifetime ICERs of SGLT2i, when compared with usual care, were favorable (< €20,000/QALY) for all filtered cohorts, resulting in an ICER of €5440/QALY using trial-based treatment effect estimates in reimbursed population. Several pragmatic scenarios were tested, the ICERs remained favorable. CONCLUSIONS: Although the Dutch reimbursement indications led to a target group that deviates from trial populations, SGLT2i are likely to be cost effective when compared with usual care.

A congener-specific modelling approach for the transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans and dioxin-like polychlorinated biphenyls from feed to eggs of laying hens.

Calibration of a kinetic model for the transfer of PCDD/Fs and dl-PCBs from feed to the hen's body and eggs was thus far restricted to the total TEQ concentration, i.e. the summed concentrations of PCDD/Fs and dl-PCBs expressed in terms of equivalents of 2,3,7,8-TCDD. However, this approach may lead to over- or underestimation of the transfer if the mixture contains congeners with kinetic characteristics which differ considerably from those used in such a model. This paper extends a previous transfer model of PCDD/Fs and dl-PCBs from feed to egg yolk fat and abdominal fat of high production laying hens, based on the total TEQ approach, to the level of individual congeners. Both modelling approaches are compared and the new approach is presented as a webtool application. This congener-specific approach enabled the calibration of 25 of the 29 relevant PCDD/F and dl-PCB congeners with respect to their individual transfer characteristics to body fat and egg yolk fat and their clearance from the body. Limitations of the available experimental data prevented the calibration of 1,2,3,4,6,7,8-HpCDD, OCDD, OCDF and PCB 123. The fraction transferred to egg yolk fat after long-term daily intake of contaminated feed was found to be at least 0.78 for 2,3,7,8-TCDD, 0.75 for PeCDD, 0.42-0.61 for HxCDDs, 0.70 for 2,3,7,8-TCDF, 0.71 for PeCDF, 0.54-0.60 for HxCDFs, 0.18-0.24 for HpCDFs and 0.89-1.00 for dl-PCBs. Various experimental and feed incident mixtures were used to compare the total TEQ- model with the congener-specific approach. An overestimation of the transfer by the total TEQ method was shown in particular for mixtures with a substantial contribution of hexa-, hepta- and octa-PCDD/Fs to the total TEQ level.

Integrating in vitro chemical transplacental passage into a generic PBK model: A QIVIVE approach.

With the increasing application of cell culture models as primary tools for predicting chemical safety, the quantitative extrapolation of the effective dose from in vitro to in vivo (QIVIVE) is of increasing importance. For developmental toxicity this requires scaling the in vitro observed dose-response characteristics to in vivo fetal exposure, while integrating maternal in vivo kinetics during pregnancy, in particular transplacental transfer. Here the transfer of substances across the placental barrier, has been studied using the in vitro BeWo cell assay and six embryotoxic compounds of different kinetic complexity. The BeWo assay results were incorporated in an existing generic Physiologically Based Kinetic (PBK) model which for this purpose was extended with rat pregnancy. Finally, as a "proof of principle", the BeWo PBK model was used to perform a QIVIVE based on developmental toxicity as observed in various different in vitro toxicity assays. The BeWo results illustrated different transport profiles of the chemicals across the BeWo monolayer, allocating the substances into two distinct groups: the 'quickly-transported' and the 'slowly-transported'. BeWo PBK exposure simulations during gestation were compared to experimentally measured maternal blood and fetal concentrations and a reverse dosimetry approach was applied to translate in vitro observed embryotoxicity into equivalent in vivo dose-response curves. This approach allowed for a direct comparison of the in vitro dose-response characteristics as observed in the Whole Embryo Culture (WEC), and the Embryonic Stem Cell test (cardiac:ESTc and neural:ESTn) with in vivo rat developmental toxicity data. Overall, the in vitro to in vivo comparisons suggest a promising future for the application of such QIVIVE methodologies for screening and prioritization purposes of developmental toxicants. Nevertheless, the clear need for further improvements is acknowledged for a wider application of the approach in chemical safety assessment.

Modelling the Renal Excretion of the Mycotoxin Deoxynivalenol in Humans in an Everyday Situation.

The dietary exposure to the mycotoxin deoxynivalenol (DON) can be assessed by human biomonitoring (HBM). Here, we assessed the relation between dietary DON intake and the excretion of its major metabolite DON-15-glucuronide (DON15GlcA) through time, in an everyday situation. For 49 volunteers from the EuroMix biomonitoring study, the intake of DON from each meal was calculated and the excretion of DON and its metabolites was analyzed for each urine void collected separately throughout a 24-h period. The relation between DON and DON15GlcA was analyzed with a statistical model to assess the residence time and the excreted fraction of ingested DON as DON15GlcA (fabs_excr). Fabs_excr was treated as a random effect variable to address its heterogeneity in the population. The estimated time in which 97.5% of the ingested DON was excreted as DON15GlcA was 12.1 h, the elimination half-life was 4.0 h. Based on the estimated fabs_excr, the mean reversed dosimetry factor (RDF) of DON15GlcA was 2.28. This RDF can be used to calculate the amount of total DON intake in an everyday situation, based on the excreted amount of DON15GlcA. We show that urine samples collected over 24 h are the optimal design to study DON exposure by HBM.

Lifetime cost-effectiveness and equity impacts of the Healthy Primary School of the Future initiative.

BACKGROUND: This study estimated the lifetime cost-effectiveness and equity impacts associated with two lifestyle interventions in the Dutch primary school setting (targeting 4-12 year olds). METHODS: The Healthy Primary School of the Future (HPSF; a healthy school lunch and structured physical activity) and the Physical Activity School (PAS; structured physical activity) were compared to the regular Dutch curriculum (N = 1676). An adolescence model, calculating weight development, and the RIVM Chronic Disease Model, calculating overweight-related chronic diseases, were linked to estimate the lifetime impact on chronic diseases, quality adjusted life years (QALYs), healthcare, and productivity costs. Cost-effectiveness was expressed as the additional costs/QALY gained and we used €20,000 as threshold. Scenario analyses accounted for alternative effect maintenance scenarios and equity analyses examined cost-effectiveness in different socioeconomic status (SES) groups. RESULTS: HPSF resulted in a lifetime costs of €773 (societal perspective) and a lifetime QALY gain of 0.039 per child versus control schools. HPSF led to lower costs and more QALYs as compared to PAS. From a societal perspective, HPSF had a cost/QALY gained of €19,734 versus control schools, 50% probability of being cost-effective, and beneficial equity impact (0.02 QALYs gained/child for low versus high SES). The cost-effectiveness threshold was surpassed when intervention effects decayed over time. CONCLUSIONS: HPSF may be a cost-effective and equitable strategy for combatting the lifetime burden of unhealthy lifestyles. The win-win situation will, however, only be realised if the intervention effect is sustained into adulthood for all SES groups. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02800616 ). Registered 15 June 2016 - Retrospectively registered.

Do background levels of the pesticide pirimiphosmethyl in plant-based aquafeeds affect food safety of farmed Atlantic salmon?

The substitution of fish oil and fishmeal with plant-based ingredients in commercial aquafeeds for Atlantic salmon, may introduce novel contaminants that have not previously been associated with farmed fish. The organophosphate pesticide pirimiphos-methyl (PM) is one of the novel contaminants that is most prevalent in commercial salmon feed. In this study, the feed-to-fillet transfer of dietary PM and its main metabolites was investigated in Atlantic salmon fillet. Based on the experimental determined PM and metabolite uptake, metabolisation, and elimination kinetics, a physiologically based toxicokinetic (PBTK) compartmental model was developed. Fish fed PM had a relatively low (~4%) PM retention and two main metabolites (2-DAMP and Desethyl-PM) were identified in liver, muscle, kidney and bile. The absence of more metabolised forms of 2-DAMP and Desethyl-PM in Atlantic salmon indicates different metabolism in cold-water fish compared to previous studies on ruminants. The model was used to simulate the long term (>1.5 years) feed-to-fillet transfer of PM + metabolite in Atlantic salmon under realistic farming conditions including seasonal fluctuations in feed intake, growth, and fat deposition in muscle tissue. The model predictions show that with the constant presence of the highest observed PM concentration in commercial salmon feed, fillet PM+ metabolite levels were approximately 5 nmol kg-1, with highest levels for the metabolite 2-DAMP. No EU maximum residue levels (MRL) for PM and its main metabolites exist in seafood to date, but the predicted levels were lower than the MRL for PM in swine of 32.7 nmol kg-1.

The Relationship Between Internal and External Dose: Some General Results Based on a Generic Compartmental Model.

Statements on how the internal-to-external-dose (IED) relationship looks like are often based on qualitative toxicokinetic arguments. For example, the recently proposed kinetically derived maximum dose (KMD) states that the IED relationship must have an inflection point, due to saturation of underlying processes like metabolism or absorption. However, such statements lack a solid quantitative foundation. Therefore, we derived expressions for the IED relationship for a number of scenarios based on a generic compartmental model involving saturation. The scenarios included repeated or single dose, and saturable metabolism or saturable absorption. For some of these scenarios, an explicit expression for the IED relationship can be derived, for others only implicit expressions can be established, which need to be evaluated numerically. The results show that saturable processes will lead to an IED relationship that is nonlinear over the whole dose range, ie, it can be approximated by a linear relationship at the lower end, whereas the approximation will become gradually poorer with increasing doses. The finding that saturation does not lead to an inflection point in the IED relationship, as assumed in the KMD, implies that the KMD is not a valid approach for selecting the top dose in toxicological studies. An additional use of our results is that the derived explicit expressions of the IED relationship can be fitted to IED data, and, possibly, for extrapolation outside the observed dose range.

Biomonitoring of Deoxynivalenol and Deoxynivalenol-3-glucoside in Human Volunteers: Renal Excretion Profiles.

Biomarkers for the determination of the dietary exposure to deoxynivalenol (DON) have been proposed in the past but so far no quantification of their use in humans has been carried out. Following a human intervention study with two mycotoxins, namely DON and deoxynivalenol-3-glucoside (DON3G), the renal excretion of these compounds, including their phase II metabolites, was analysed. The purpose was to develop biokinetic models that can be used to determine: (1) the preferred (set of) urinary biomarker(s), (2) the preferred urinary collection period, and (3) a method to estimate the dietary exposure to these mycotoxins. Twenty adult volunteers were restricted in consuming cereals and cereal-based foods for 4 days. At day 3, a single dose of 1 µg/kg body weight of DON or DON3G was orally administered to 16 volunteers; 4 volunteers served as control. All individual urine discharges were collected during 24 h after administration. The metabolism and renal excretion could be described by a biokinetic model using three physiological compartments (gastrointestinal tract, liver, and kidneys). Kinetic analysis revealed a complete recovery of the renal excretion of total DON (mainly DON and its glucuronides) within 24 h after administration of DON or DON3G. The so-called 'reverse dosimetry' factor was used to determine the preferred (set of) biomarker(s) and to estimate the dietary intake of the parent compounds in the future. The fact that DON3G was absorbed and mainly excreted as DON and its glucuronides confirms that DON3G (as well as other modified forms) should be taken into account in the exposure and risk assessment of this group of mycotoxins.

Modelling the long-term feed-to-fillet transfer of leuco crystal violet and leuco malachite green in Atlantic salmon (Salmo salar).

Leuco crystal violet (LCV) and leuco malachite green (LMG) are the main metabolites of two dyes that are forbidden for use in food production, but can be present at low background concentration in novel Atlantic salmon feed ingredients such as processed animal proteins (animal by-product [ABP]). In this study, the potential transfer of dietary LCV or LMG to the fillet of farmed Atlantic salmon was investigated. The uptake and elimination rate kinetics were determined in seawater-adapted Atlantic salmon (initial weight 587 ± 148 g) fed two levels of either LCV- or LMG-enriched diets (~500 and 4000 µg kg-1, respectively) for 40 days, followed by a 90-day depuration period with feeding on control diets (<0.15 µg kg-1 LCV and LMG). A three-compartmental model was developed, based on a fillet fat, fillet muscle and a central body compartment comprising all other tissues. Model calibrations showed a good fit with measured values during overall uptake and elimination period; however, the model poorly predicted the short-term (days) peak measured values at the end of the exposure period. The model was used to simulate the long-term (>16 months) LCV and LMG feed-to-fillet transfer in Atlantic salmon under realistic farming conditions such as the seasonal fluctuations in feed intake, growth and fillet fat deposition. The model predictions gave highest expected LCV and LMG fillet concentrations of approximately 0.12 and 0.45 µg kg-1, depending on the dietary levels of ABP and background level of LCV and LMG contamination. These levels are under the reference point for action of 2 µg kg-1 for the sum of MG and LMG that EFSA assessed as adequate to protect public health. However, for LCV, the predicted highest levels exceed the analytical decision limit (CCα) of 0.15 µg kg-1 for the method used in this paper.

You Only Die Once: Accounting for Multi-Attributable Mortality Risks in Multi-Disease Models for Health-Economic Analyses.

Mortality rates in Markov models, as used in health economic studies, are often estimated from summary statistics that allow limited adjustment for confounders. If interventions are targeted at multiple diseases and/or risk factors, these mortality rates need to be combined in a single model. This requires them to be mutually adjusted to avoid 'double counting' of mortality. We present a mathematical modeling approach to describe the joint effect of mutually dependent risk factors and chronic diseases on mortality in a consistent manner. Most importantly, this approach explicitly allows the use of readily available external data sources. An additional advantage is that existing models can be smoothly expanded to encompass more diseases/risk factors. To illustrate the usefulness of this method and how it should be implemented, we present a health economic model that links risk factors for diseases to mortality from these diseases, and describe the causal chain running from these risk factors (e.g., obesity) through to the occurrence of disease (e.g., diabetes, CVD) and death. Our results suggest that these adjustment procedures may have a large impact on estimated mortality rates. An improper adjustment of the mortality rates could result in an underestimation of disease prevalence and, therefore, disease costs.

Projecting the COPD population and costs in England and Scotland: 2011 to 2030.

We aimed to estimate the prevalence, healthcare costs and number of deaths among people with chronic obstructive pulmonary disease (COPD) in England and Scotland 2011-2030. We adapted the Dutch COPD Model by using English and Scottish demographic, COPD incidence, COPD prevalence, smoking prevalence and mortality data to make projections. In England, the prevalence of COPD was estimated to be 1.79% (95% uncertainty interval 1.77-1.81) in 2011, increasing to 2.19% (1.85-2.33) by 2030. In Scotland, prevalence was 2.03% (1.96-2.10) in 2011 increasing to 2.20% (1.98-2.40) in 2030. These increases were driven by more women developing COPD. Annual direct healthcare costs of COPD in England were estimated to increase from £1.50 billon (1.18-2.50) in 2011 to £2.32 (1.85-3.08) billion in 2030. In Scotland, costs increased from £159 million (128-268) in 2011 to £207 (165-274) million in 2030. The deaths in England were estimated to increase from 99,200 (92,500-128,500) in 2011, to 129,400 (126,400-133,400) by 2030. In Scotland, in 2011 there were 9,700 (9,000-12,300) deaths and 13,900 (13,400-14,500) deaths in 2030. The number of people with COPD will increase substantially over the coming years in England and Scotland, particularly in females. Services need to adapt to this increasing demand.

Long-term health outcomes and cost-effectiveness of a computer-tailored physical activity intervention among people aged over fifty: modelling the results of a randomized controlled trial.

BACKGROUND: Physical inactivity is a significant predictor of several chronic diseases, becoming more prevalent as people age. Since the aging population increases demands on healthcare budgets, effectively stimulating physical activity (PA) against acceptable costs is of major relevance. This study provides insight into long-term health outcomes and cost-effectiveness of a tailored PA intervention among adults aged over fifty. METHODS: Intervention participants (N = 1729) received tailored advice three times within four months, targeting the psychosocial determinants of PA. The intervention was delivered in different conditions (i.e. print-delivered versus Web-based, and with or without additional information on local PA opportunities). In a clustered RCT, the effects of the different intervention conditions were compared to each other and to a control group. Effects on weekly Metabolic Equivalents (MET)-hours of PA obtained one year after the intervention started were extrapolated to long-term outcomes (5-year, 10-year and lifetime horizons) in terms of health effects and quality-adjusted life years (QALYs) and its effect on healthcare costs, using a computer simulation model. Combining the model outcomes with intervention cost estimates, this study provides insight into the long-term cost-effectiveness of the intervention. Incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: For all extrapolated time horizons, the printed and the Web-based intervention resulted in decreased incidence numbers for diabetes, colon cancer, breast cancer, acute myocardial infarctions, and stroke and increased QALYs as a result of increased PA. Considering a societal Willingness-to-Pay of €20,000/QALY, on a lifetime horizon the printed (ICER = €7,500/QALY) as well as the Web-based interventions (ICER = €10,100/QALY) were cost-effective. On a 5-year time horizon, the Web-based intervention was preferred over the printed intervention. On a 10-year and lifetime horizon, the printed intervention was the preferred intervention condition, since the monetary savings of the Web-based intervention did no longer outweigh its lower effects. Adding environmental information resulted in a lower cost-effectiveness. CONCLUSION: A tailored PA intervention in a printed delivery mode, without environmental information, has the most potential for being cost-effective in adults aged over 50. TRIAL REGISTRATION: The current study was registered at the Dutch Trial Register (NTR2297; April 26th 2010).

Tobacco control policies specified according to socioeconomic status: health disparities and cost-effectiveness.

INTRODUCTION: Little is known about the cost-effectiveness of tobacco control policy for different socioeconomic status (SES) groups. We aimed to evaluate SES-specific cost-effectiveness ratios of policies with known favorable effect in low-SES groups: a tobacco tax increase and reimbursement of cessation support. METHODS: A computer model of the adult population specified by smoking behavior (never/current/former smoker), age, gender, and SES simulated policy scenarios reflecting the implementation of a €0.22 tobacco tax increase or full reimbursement of cessation support, which were compared. Relating differences in costs to quality-adjusted life years (QALYs) gained generated cost-effectiveness ratios for each SES group. RESULTS: In a cohort of 11 million people, the tobacco tax increase resulted in 27,000 additional quitters after 5 years, who were proportionally divided among the SES groups. Reimbursement led to 59,000 additional quitters, with relatively more quitters in higher-SES groups. The number of QALYs gained were 3,400-6,200 among the various SES groups for the tax increase and 6,300-14,000 for the reimbursement scenario. For both interventions, favorability of the cost-effectiveness ratios increased with SES: costs per QALY decreased from €6,100 to €4,500 for the tax increase and from €21,000 to €11,000 for reimbursement. CONCLUSIONS: The reimbursement policy produced the greatest overall health gain. Surprisingly, neither tax increase nor reimbursement reduced health disparities. Differences in use were too small to compensate for improved health gains per quitter among higher-SES groups. Both policies qualified as cost-effective overall, with more favorable cost-effectiveness ratios for high-SES than for low-SES groups.

Potential effect of salt reduction in processed foods on health.

BACKGROUND: Excessive salt intake has been associated with hypertension and increased cardiovascular disease morbidity and mortality. Reducing salt intake is considered an important public health strategy in the Netherlands. OBJECTIVE: The objective was to evaluate the health benefits of salt-reduction strategies related to processed foods for the Dutch population. DESIGN: Three salt-reduction scenarios were developed: 1) substitution of high-salt foods with low-salt foods, 2) a reduction in the sodium content of processed foods, and 3) adherence to the recommended maximum salt intake of 6 g/d. Health outcomes were obtained in 2 steps: after salt intake was modeled into blood pressure levels, the Chronic Disease Model was used to translate modeled blood pressures into incidences of cardiovascular diseases, disability-adjusted life years (DALYs), and life expectancies. Health outcomes of the scenarios were compared with health outcomes obtained with current salt intake. RESULTS: In total, 4.8% of acute myocardial infarction cases, 1.7% of congestive heart failure cases, and 5.8% of stroke cases might be prevented if salt intake meets the recommended maximum intake. The burden of disease might be reduced by 56,400 DALYs, and life expectancy might increase by 0.15 y for a 40-y-old individual. Substitution of foods with comparable low-salt alternatives would lead to slightly higher salt intake reductions and thus to more health gain. The estimates for sodium reduction in processed foods would be slightly lower. CONCLUSION: Substantial health benefits might be achieved when added salt is removed from processed foods and when consumers choose more low-salt food alternatives.

[Societal costs of asthma, COPD and respiratory allergy]. / Maatschappelijke kosten van astma, COPD en respiratoire allergie.

OBJECTIVE: To estimate the societal costs of asthma, COPD and respiratory allergy for the year 2007 and future healthcare costs for the period 2007-2032. DESIGN: Descriptive study. METHODS: Representative registries were used to estimate the healthcare costs of asthma, COPD and respiratory allergy for the year 2007. A simulation model for asthma and COPD and a demographic projection for respiratory allergy were used to determine future healthcare costs. Production losses due to sick leave and work incapacity were calculated using the friction-cost method. RESULTS: Total healthcare costs for asthma, COPD and respiratory allergy in 2007 were estimated at 287, 415 and 103 million euros respectively; on average 530, 1400 and 170 euros per patient with asthma, COPD and respiratory allergy. Average costs of sick leave for asthma were on average 1200 euros and for COPD 1900 euros per employee per year. The costs of work incapacity of an employee with COPD were 1200 euros. There is expected to be an increase in the number of patients from 443,000 in 2007 to 567,000 in 2032 for asthma and from 335,000 to 600,000 for COPD. The number of patients with a respiratory allergy are expected to remain approximately stable at 625,000 patients. The healthcare costs for respiratory allergy are expected to rise by 73%, those for asthma to double, and those for COPD to triple. CONCLUSION: Patients with asthma and COPD have high healthcare costs. Sick leave makes up a large part of the costs of asthma and COPD. In addition, the costs of work incapacity for employees with COPD are high. The number of patients with asthma and COPD will rise in the coming decades, as well as the healthcare costs for these diseases.

The DYNAMO-HIA model: an efficient implementation of a risk factor/chronic disease Markov model for use in Health Impact Assessment (HIA).

In Health Impact Assessment (HIA), or priority-setting for health policy, effects of risk factors (exposures) on health need to be modeled, such as with a Markov model, in which exposure influences mortality and disease incidence rates. Because many risk factors are related to a variety of chronic diseases, these Markov models potentially contain a large number of states (risk factor and disease combinations), providing a challenge both technically (keeping down execution time and memory use) and practically (estimating the model parameters and retaining transparency). To meet this challenge, we propose an approach that combines micro-simulation of the exposure information with macro-simulation of the diseases and survival. This approach allows users to simulate exposure in detail while avoiding the need for large simulated populations because of the relative rareness of chronic disease events. Further efficiency is gained by splitting the disease state space into smaller spaces, each of which contains a cluster of diseases that is independent of the other clusters. The challenge of feasible input data requirements is met by including parameter calculation routines, which use marginal population data to estimate the transitions between states. As an illustration, we present the recently developed model DYNAMO-HIA (DYNAMIC MODEL for Health Impact Assessment) that implements this approach.