Monte Carlo molecular simulation of solution and surface-bound DNA hybridization of short oligomers at varying surface densities.

DNA microarrays utilize surface bound sequences to probe for target sequences in samples of interest, and density of surface coverage plays an important role in any duplex formation and subsequent detection. Here, Monte Carlo molecular simulations utilize a modified coarse-grained DNA model to calculate the impact of binding density and arrangement as well as temperature on duplex structure and hydrogen bonding patterns for two different undecamer sequences. Results indicate a modest, sequence-dependent increase in dissociation related to the proximity of neighboring duplexes but little impact on duplex structure or hydrogen bonding pattern.

The Public Health Status and Foresight report 2014: Four normative perspectives on a healthier Netherlands in 2040.

Policy-oriented foresight reports aim to inform and advise decision-makers. In value-laden areas such as public health and healthcare, deliberative scenario methods are clearly needed. For the sixth Dutch Public Health Status and Forecasts-report (PHSF-2014), a new approach of co-creation was developed aiming to incorporate different societal norms and values in the description of possible future developments. The major future trends in the Netherlands were used as a starting point for a deliberative dialogue with stakeholders to identify the most important societal challenges for public health and healthcare. Four societal challenges were identified: 1) To keep people healthy as long as possible and cure illness promptly, 2) To support vulnerable people and enable social participation, 3) To promote individual autonomy and freedom of choice, and 4) To keep health care affordable. Working with stakeholders, we expanded these societal challenges into four corresponding normative scenarios. In a survey the normative scenarios were found to be recognizable and sufficiently distinctive. We organized meetings with experts to explore how engagement and policy strategies in each scenario would affect the other three societal challenges. Possible synergies and trade-offs between the four scenarios were identified. Public health foresight based on a business-as-usual scenario and normative scenarios is clearly practicable. The process and the outcomes support and elucidate a wide range of strategic discussions in public health.

Good practice characteristics of diet and physical activity interventions and policies: an umbrella review.

BACKGROUND: This umbrella review aimed at eliciting good practice characteristics of interventions and policies aiming at healthy diet, increasing physical activity, and lowering sedentary behaviors. Applying the World Health Organization's framework, we sought for 3 types of characteristics, reflecting: (1) main intervention/policy characteristics, referring to the design, targets, and participants, (2) monitoring and evaluation processes, and (3) implementation issues. This investigation was undertaken by the DEDPIAC Knowledge Hub (the Knowledge Hub on the DEterminants of DIet and Physical ACtivity), which is an action of the European Union's joint programming initiative. METHODS: A systematic review of reviews and stakeholder documents was conducted. Data from 7 databases was analyzed (99 documents met inclusion criteria). Additionally, resources of 7 major stakeholders (e.g., World Health Organization) were systematically searched (10 documents met inclusion criteria). Overall, the review yielded 74 systematic reviews, 16 position review papers, and 19 stakeholders' documents. Across characteristics, 25% were supported by ≥ 4 systematic reviews. Further, 25% characteristics were supported by ≥ 3 stakeholders' documents. If identified characteristics were included in at least 4 systematic reviews or at least 3 stakeholders' documents, these good practice characteristics were classified as relevant. RESULTS: We derived a list of 149 potential good practice characteristics, of which 53 were classified as relevant. The main characteristics of intervention/policy (n = 18) fell into 6 categories: the use of theory, participants, target behavior, content development/management, multidimensionality, practitioners/settings. Monitoring and evaluation characteristics (n = 18) were grouped into 6 categories: costs/funding, outcomes, evaluation of effects, time/effect size, reach, the evaluation of participation and generalizability, active components/underlying processes. Implementation characteristics (n = 17) were grouped into eight categories: participation processes, training for practitioners, the use/integration of existing resources, feasibility, maintenance/sustainability, implementation partnerships, implementation consistency/adaptation processes, transferability. CONCLUSIONS: The use of the proposed list of 53 good practice characteristics may foster further development of health promotion sciences, as it would allow for identification of success vectors in the domains of main characteristics of interventions/policies, their implementation, evaluation and monitoring processes.

Value of information analysis from a societal perspective: a case study in prevention of major depression.

OBJECTIVES: Productivity losses usually have a considerable impact on cost-effectiveness estimates while their estimated values are often relatively uncertain. Therefore, parameters related to these indirect costs play a role in setting priorities for future research from a societal perspective. Until now, however, value of information analyses have usually applied a health care perspective for economic evaluations. Hence, the effect of productivity losses has rarely been investigated in such analyses. The aim of the current study therefore was to investigate the effects of including or excluding productivity costs in value of information analyses. METHODS: Expected value of information analysis (EVPI) was performed in cost-effectiveness evaluation of prevention from both societal and health care perspectives, to give us the opportunity to compare different perspectives. Priorities for future research were determined by partial EVPI. The program to prevent major depression in patients with subthreshold depression was opportunistic screening followed by minimal contact psychotherapy. RESULTS: The EVPI indicated that regardless of perspective, further research is potentially worthwhile. Partial EVPI results underlined the importance of productivity losses when a societal perspective was considered. Furthermore, priority setting for future research differed according to perspective. CONCLUSIONS: The results illustrated that advise for future research will differ for a health care versus a societal perspective and hence the value of information analysis should be adjusted to the perspective that is relevant for the decision makers involved. The outcomes underlined the need for carefully choosing the suitable perspective for the decision problem at hand.

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.

Worksite mental health interventions: a systematic review of economic evaluations.

OBJECTIVE: To give an overview of the evidence on the cost-effectiveness (CE) and financial return of worksite mental health interventions. METHODS: A systematic search was conducted in relevant databases. Included economic evaluations were classified into two groups based on type of intervention: (1) aimed at prevention or treatment of mental health problems among workers or (2) aimed at return to work (RTW) for workers sick-listed from mental health problems. The quality of the included economic evaluations was assessed using the Consensus Health Economic Criteria list (CHEC-list). RESULTS: Ten economic evaluations were included in this systematic review. All four economic evaluations on the prevention or treatment of mental health problems found a positive cost-benefit ratio, although three of these studies had low to moderate methodological quality. In five out of six economic evaluation studies on RTW interventions, no favourable CE or cost-benefit balance was found. One study of moderate methodological quality reported on a positive CE balance. CONCLUSIONS: Due to a limited number of economic evaluations on worksite mental health interventions of which a majority was lacking methodological quality or lacking evidence, only a tentative conclusion can be drawn from the results of this systematic review. Worksite interventions to prevent or treat mental health problems might be cost-effective, while those RTW interventions that included a full economic evaluation aimed at depressed employees do not seem to be cost-beneficial. More high-quality economic evaluation studies of effective worksite mental health interventions are needed to get more insight into the economic impact of worksite mental health interventions.

[Cost-effectiveness: euros per QALY is not enough]. / Kosteneffectiviteit: euro's per QALY is niet genoeg.

The number of economic evaluations being published in scientific literature each year is increasing exponentially. Cost-effectiveness seems to be playing an increasing role in decisions about reimbursement or the implementation of curative or preventive interventions. A cost-effectiveness ratio represents the fraction between the costs and effects that are associated with an intervention. What costs are included in the numerator of the fraction? What assumptions on effectiveness and reach are made to express the denominator? Various examples have shown that small differences in assumptions can have significant consequences for the cost-effectiveness ratio. This holds true for presumptions on the long-term effects of an intervention as well as the willingness to participate in an intervention. Such assumptions and choices can sometimes highly determine the outcome of a cost-effectiveness analysis. For this reason, caution in interpreting results of cost-effectiveness analyses is warranted.

The polypill in the primary prevention of cardiovascular disease: cost-effectiveness in the Dutch population.

Objectives The aim of the present study was to estimate the cost-effectiveness of the polypill in the primary prevention of cardiovascular disease. Design A health economic modelling study. Setting Primary healthcare in the Netherlands. Participants Simulated individuals from the general Dutch population, aged 45-75 years. Interventions Opportunistic screening followed by prescription of the polypill to eligible individuals. Eligibility was defined as having a minimum 10-year risk of cardiovascular death as assessed with the Systematic Coronary Risk Evaluation function of alternatively 5%, 7.5% or 10%. Different versions of the polypill were considered, depending on composition: (1) the Indian polycap, with three different types of blood pressure-lowering drugs, a statin and aspirin; (2) as (1) but without aspirin and (3) as (2) but with a double statin dose. In addition, a scenario of (targeted) separate antihypertensive and/or statin medication was simulated. Primary outcome measures Cases of acute myocardial infarction or stroke prevented, quality-adjusted life years (QALYs) gained and the costs per QALY gained. All interventions were compared with usual care. Results All scenarios were cost-effective with an incremental cost-effectiveness ratio between €7900 and 12 300 per QALY compared with usual care. Most health gains were achieved with the polypill without aspirin and containing a double dose of statins. With a 10-year risk of 7.5% as the threshold, this pill would prevent approximately 3.5% of all cardiovascular events. Conclusions Opportunistic screening based on global cardiovascular risk assessment followed by polypill prescription to those with increased risk offers a cost-effective strategy. Most health gain is achieved by the polypill without aspirin and a double statin dose.

Cost-effectiveness of opportunistic screening and minimal contact psychotherapy to prevent depression in primary care patients.

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.

Primary prevention of cardiovascular diseases: a cost study in family practices.

BACKGROUND: Considering the scarcity of health care resources and the high costs associated with cardiovascular diseases, we investigated the spending on cardiovascular primary preventive activities and the prescribing behaviour of primary preventive cardiovascular medication (PPCM) in Dutch family practices (FPs). METHODS: A mixed methods design was used, which consisted of a questionnaire (n = 80 FPs), video recordings of hypertension- or cholesterol-related general practitioner visits (n = 56), and the database of Netherlands Information Network of General Practice (n = 45 FPs; n = 157,137 patients). The questionnaire and video recordings were used to determine the average frequency and time spent on cardiovascular primary preventive activities per FP respectively. Taking into account the annual income and full time equivalents of general practitioners, health care assistants, and practice nurses as well as the practice costs, the total spending on cardiovascular primary preventive activities in Dutch FPs was calculated. The database of Netherlands Information Network of General Practice was used to determine the prescribing behaviour in Dutch FPs by conducting multilevel regression models and adjusting for patient and practice characteristics. RESULTS: Total expenditure on cardiovascular primary preventive activities in FPs in 2009 was €38.8 million (€2.35 per capita), of which 47% was spent on blood pressure measurements, 26% on cardiovascular risk profiling, and 11% on lifestyle counselling. Fifteen percent (€11 per capita) of all cardiovascular medication prescribed in FPs was a PPCM. FPs differed greatly on prescription of PPCM (odds ratio of 3.1). CONCLUSIONS: Total costs of cardiovascular primary preventive activities in FPs such as blood pressure measurements and lifestyle counselling are relatively low compared to the costs of PPCM. There is considerable heterogeneity in prescribing behaviour of PPCM between FPs. Further research is needed to determine whether such large differences in prescription rates are justified. Striving for an optimal use of cardiovascular primary preventive activities might lead to similar health outcomes, but may achieve important cost savings.

Cost-effectiveness research on preventive interventions: a survey of the publications in 2008.

BACKGROUND: In recent years the literature regarding the cost-effectiveness of disease prevention and health promotion has grown exponentially. Aim of this study is to investigate: (i) how many and what type of economic evaluations have been published in 2008, (ii) the diseases or health problems World Health Organization International Classification of Diseases 10 chapters the economic evaluations of preventive interventions focus on, in relation to the global burden of disease and (iii) the cost-effectiveness of these interventions. METHODS: Literature study of economic evaluations on preventive interventions in PubMed and Scopus. RESULTS: In 2008, 232 economic evaluations of preventive interventions have been published. Of these studies, 75% (n = 175) used costs per (Quality Adjusted) Life Year [(QA)LY] gained as outcome measure. Most economic evaluations focus on the prevention of infectious diseases (31.5%, n = 73) and cancers (21%, n = 49) Infectious diseases are responsible for the highest global burden of disease (19.8%), followed by mental and behavioural disorders (11.7%). Of the included economic evaluations, 80% remained below a threshold of €50 000 and 60% below €20 000 per (QA)LY. CONCLUSION: This study shows that many economic evaluations of preventive interventions use a generic outcome measure. This adds to the comparability of different studies on the cost-effectiveness of prevention. Although the focus of published economic evaluations in general corresponds well with those diseases that cause a large share of the world's burden of disease, mental and behavioural diseases and diseases of the respiratory system remain underrepresented. Finally, it appears that the vast majority of published economic evaluations of preventive measures show favourable cost-effectiveness levels.

The scope of costs in alcohol studies: Cost-of-illness studies differ from economic evaluations.

BACKGROUND: Alcohol abuse results in problems on various levels in society. In terms of health, alcohol abuse is not only an important risk factor for chronic disease, but it is also related to injuries. Social harms which can be related to drinking include interpersonal problems, work problems, violent and other crimes. The scope of societal costs related to alcohol abuse in principle should be the same for both economic evaluations and cost-of-illness studies. In general, economic evaluations report a small part of all societal costs. To determine the cost- effectiveness of an intervention it is necessary that all costs and benefits are included. The purpose of this study is to describe and quantify the difference in societal costs incorporated in economic evaluations and cost-of-illness studies on alcohol abuse. METHOD: To investigate the economic costs attributable to alcohol in cost-of-illness studies we used the results of a recent systematic review (June 2009). We performed a PubMed search to identify economic evaluations on alcohol interventions. Only economic evaluations in which two or more interventions were compared from a societal perspective were included. The proportion of health care costs and the proportion of societal costs were estimated in both type of studies. RESULTS: The proportion of healthcare costs in cost-of-illness studies was 17% and the proportion of societal costs 83%. In economic evaluations, the proportion of healthcare costs was 57%, and the proportion of societal costs was 43%. CONCLUSIONS: The costs included in economic evaluations performed from a societal perspective do not correspond with those included in cost-of-illness studies. Economic evaluations on alcohol abuse underreport true societal cost of alcohol abuse. When considering implementation of alcohol abuse interventions, policy makers should take into account that economic evaluations from the societal perspective might underestimate the total effects and costs of interventions.

[Screening for abdominal aortic aneurysm; effectivity and cost-effectiveness]. / Screening op aneurysma aortae abdominalis: effectiviteit en kosteneffectiviteit.

OBJECTIVE: To review the current literature concerning the effectivity and cost-effectiveness of screening for abdominal aortic aneurysm (AAA). DESIGN: Systematic review. METHOD: A review of literature of evaluations of effectivity via meta-analyses and economic evaluations. RESULTS: The short-term meta-analyses showed that screening for AAA leads to a significant reduction of AAA-related mortality. The average absolute risk reduction (ARR) was 0.12%. The long-term meta-analysis also showed a significant reduction of overall mortality. The ARR was in this case almost 1%. The five economic evaluations all resulted in cost-effectiveness ratios below euro 20,000 per quality-adjusted life year (QALY), a used threshold level in the Netherlands. CONCLUSION: Based on the available literature, screening for AAA has appeared to be both effective and cost-effective. However, the economic evaluations did not always take into account the peri- and post-operative mortality and morbidity. Economic evaluations are only useful if all possible outcomes are included in the model. Therefore a good model analysis should be made for the Dutch situation, after which a decision may be taken on a possible pilot study and the optimal design thereof.

Cost-effectiveness of an opportunistic screening programme and brief intervention for excessive alcohol use in primary care.

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 euros due to providing alcohol SBI in the target population, resulting in a cost-effectiveness ratio of 5,400 euros 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.

A literature review of assumptions on test characteristics and adherence in economic evaluations of colonoscopy and CT-colonography screening.

Colorectal cancer screening is an effective public health strategy for decreasing colorectal cancer mortality. Since many screening modalities exist, it needs to be determined what the most cost-effective strategy is. The aim of this review is to summarise the available cost-effectiveness evidence for colonoscopy versus CT-colonography screening, and to pay special attention to assumptions regarding test characteristics and adherence. A literature search resulted in twelve economic evaluations that could be included in the review. The incremental cost-effectiveness ratios of colonoscopy and CT-colonography versus no screening remained under 20,000 euro and 30,000 euro per life year gained, respectively. Although, both screening modalities were cost-effective according to most international thresholds, in most of the economic evaluations colonoscopy seemed more cost-effective than colonography screening. In many studies, model assumptions on major parameters (e.g. screening uptake) were more positive than real life data suggest. None of the models included indirect costs, which disproportionally favoured the relative cost-effectiveness of colonoscopy. For a good comparison of both screening methods, it is necessary that the assumptions used in economic evaluations are realistic, and include all costs.

The cost-effectiveness of increasing alcohol taxes: a modelling study.

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 euros per quality-adjusted life-year and 5300 euros 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.

Cost-effectiveness of a low-calorie diet and orlistat for obese persons: modeling long-term health gains through prevention of obesity-related chronic diseases.

OBJECTIVE: Our study estimated the cost-effectiveness of pharmacologic treatment of obesity in combination with a low-calorie diet in The Netherlands. METHODS: Costs and effects of a low-calorie diet-only intervention and of a low-calorie diet in combination with 1 year of orlistat were compared to no treatment. The RIVM Chronic Disease Model was used to project the differences in quality adjusted life years (QALYs) and lifetime health-care costs because of the effects of the interventions on body mass index (BMI) status. This was done by linking BMI status to the occurrence of obesity-related diseases and by relating quality of life to disease status. Probabilistic sensitivity analysis was employed to study the effect of uncertainty in the model parameters. In univariate sensitivity analysis, we assessed how sensitive the results were to several key assumptions. RESULTS: Incremental costs per QALY gained were Euro 17,900 for the low-calorie diet-only intervention compared to no intervention and Euro 58,800 for the low-calorie diet + orlistat compared to the low-calorie diet only. Assuming a direct relation between BMI and quality of life, these ratios decreased to Euro 6000 per QALY gained and Euro 24,100 per QALY gained. Costs per QALY gained were also sensitive to assumptions about long-term weight loss maintenance. CONCLUSIONS: Cost-effectiveness ratios of interventions aiming at weight reduction depend strongly on assumptions regarding the relation between BMI and quality of life. We recommend that a low-calorie diet should be the first option for policymakers in combating obesity.

Informed decision making in the context of prenatal screening.

OBJECTIVE: This study aimed to construct a measure of informed decision making that includes knowledge, deliberation, and value-consistency, and to assess the level of informed decision making about prenatal screening, and differences between test acceptors and test decliners. METHODS: Women attending one of 44 midwifery and gynaecology practices were asked to fill out postal questionnaires before and after the prenatal screening offer. The principal outcome was the level of informed decision making. For this purpose, knowledge about prenatal screening, deliberation about the pros and cons of the alternatives, test uptake, and attitude towards having a prenatal screening test were measured. RESULTS: Eighty-four percent of the participants were sufficiently knowledgeable about prenatal screening, 75% of the decisions were deliberate, and 82% were value-consistent. Fifty-one percent of the participants made an informed decision. Test acceptors made less informed decisions as compared to test decliners. This difference was mainly caused by the lower rate of deliberation in this group. CONCLUSION: It appears from this study that prenatal screening decisions are often not informed decisions. This is inconsistent with the main objective of offering screening, which is to enable people to make informed decisions. PRACTICE IMPLICATIONS: Decision makers should be encouraged during the counselling to deliberate about the various alternatives.

Are pregnant women making informed choices about prenatal screening?

PURPOSE: Prenatal screening should enable pregnant women to make informed choices. An informed decision is defined as being based on sufficient, relevant information and consistent with the decision maker's values. This study aims to assess to what extent pregnant women make informed choices about prenatal screening, and to assess the psychological effects of informed decision-making. METHODS: The study sample consisted of 1159 pregnant women who were offered the nuchal translucency measurement or the maternal serum screening test. Level of knowledge, value consistency, informed choice, decisional conflict, satisfaction with decision, and anxiety were measured using questionnaires. RESULTS: Of the participants, 83% were classified as having sufficient knowledge about prenatal screening, 82% made a value-consistent decision to accept or decline prenatal screening, and 68% made an informed decision. Informed choice was associated with more satisfaction with the decision, less decisional conflict (this applied only to test acceptors), but was not associated with less anxiety. CONCLUSION: Although the rate of informed choice is relatively high, substantial percentages of women making uninformed choices due to insufficient knowledge, value inconsistency, or both, were found. Informed choice appeared to be psychologically beneficial. The present study underlines the importance of achieving informed choice in the context of prenatal screening.