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

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 modeling study. SETTING: Primary health care in the Netherlands. PARTICIPANTS: Simulated individuals from the general Dutch population, aged 45-75 years of age. 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 SCORE 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; 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, 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 €7,900-12,300 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 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

Trivial, Critical and Near-critical Scaling Limits of Two-dimensional Percolation

It is natural to expect that there are only three possible types of scaling limits for the collection of all percolation interfaces in the plane: (1) a trivial one, consisting of no curves at all, (2) a critical one, in which all points of the plane are surrounded by arbitrarily large loops and every deterministic point is almost surely surrounded by a countably infinite family of nested loops with radii going to zero, and (3) an intermediate one, in which every deterministic point of the plane is almost surely surrounded by a largest loop and by a countably infinite family of nested loops with radii going to zero. We show how one can prove this using elementary arguments, with the help of known scaling relations for percolation. The trivial limit corresponds to subcritical and supercritical percolation, as well as to the case when the density p approaches the critical probability, p_c, sufficiently slowly as the lattice spacing is sent to zero. The second type corresponds to critical percolation and to a faster approach of p to p_c. The third, or near-critical, type of limit corresponds to an intermediate speed of approach of p to p_c. The fact that in the near-critical case a deterministic point is a.s. surrounded by a largest loop demonstrates the persistence of a macroscopic correlation length in the scaling limit and the absence of scale invariance.Comment: 15 pages, 3 figure

Haploid genetic screens identify SPRING/C12ORF49 as a determinant of SREBP signaling and cholesterol metabolism

The sterol-regulatory element binding proteins (SREBP) are central transcriptional regulators of lipid metabolism. Using haploid genetic screens we identify the SREBPRegulating Gene (SPRING/C12ORF49) as a determinant of the SREBP pathway. SPRING is a glycosylated Golgi-resident membrane protein and its ablation in Hap1 cells, Hepa1-6 hepatoma cells, and primary murine hepatocytes reduces SREBP signaling. In mice, Spring deletion is embryonic lethal yet silencing of hepatic Spring expression also attenuates the SREBP response. Mechanistically, attenuated SREBP signaling in SPRING(KO) cells results from reduced SREBP cleavage-activating protein (SCAP) and its mislocalization to the Golgi irrespective of the cellular sterol status. Consistent with limited functional SCAP in SPRING(KO) cells, reintroducing SCAP restores SREBP-dependent signaling and function. Moreover, in line with the role of SREBP in tumor growth, a wide range of tumor cell lines display dependency on SPRING expression. In conclusion, we identify SPRING as a previously unrecognized modulator of SREBP signaling

Not the Root of the Problem—Hair Cortisol and Cortisone Do Not Mediate the Effect of Child Maltreatment on Body Mass Index

Background: Experiencing maltreatment during childhood exerts substantial stress on the child and increases the risk for overweight and obesity later in life. The current study tests whether hair cortisol—a measure of chronic stress—and its metabolite cortisone mediate the relation between abuse and neglect on the one hand, and body mass index (BMI) on the other. Method: The sample consisted of 249 participants aged 8 to 87 years (M = 36.13, SD = 19.33). We collected data on child abuse and neglect using questionnaires, measured cortisol and cortisone concentrations in hair, and BMI. In a structural model, the effects of abuse and neglect on hair cortisol, hair cortisone, and BMI were tested, as well as the covariance between hair cortisol and BMI, and hair cortisone and BMI. Results: Within the sample, 23% were overweight but not obese and 14% were obese. Higher levels of experienced abuse were related to higher cortisone concentrations in hair (β = 0.24, p <.001) and higher B

Diminished liver microperfusion in Fontan patients:A biexponential DWI study

It has been demonstrated that hepatic apparent diffusion coefficients (ADC) are decreasing in patients with a Fontan circulation. It remains however unclear whether this is a true decrease of molecular diffusion, or rather reflects decreased microperfusion due to decreased portal blood flow. The purpose of this study was therefore to differentiate diffusion and microperfusion using intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) for different liver segments in patients with a Fontan circulation, compare to a control group, and relate with liver function, chronic hepatic congestion and hepatic disease. For that purpose, livers of 59 consecutively included patients with Fontan circulation (29 men; mean-age, 19.1 years) were examined (Oct 2012-Dec 2013) with 1.5T MRI and DWI (b = 0,50,100,250,500, 750,1500,1750 s/mm(2)). IVIM (D-slow,D-fast,f(fast)) and ADC were calculated for eight liver segments, compared to a control group (19 volunteers; 10 men; mean-age, 32.9 years), and correlated to follow-up duration, clinical variables, and laboratory measurements associated with liver function. The results demonstrated that microperfusion was reduced (p <0.001) in Fontan livers compared to controls with -38.1% for D-fast and -32.6% for f(fast). Molecular diffusion (D-slow) was similar between patients and controls, while ADC was significantly lower (-14.3%) in patients (p <0.001). ADC decreased significantly with follow-up duration after Fontan operation (r = -0.657). D-slow showed significant inverse correlations (r = -0.591) with follow-up duration whereas D-fast and f(fast) did not. From these results it was concluded that the decreasing ADC values in Fontan livers compared with controls reflect decreases in hepatic microperfusion rather than any change in molecular diffusion. However, with the time elapsed since the Fontan operation molecular diffusion and ADC decreased while microperfusion remained stable. This indicates that after Fontan operation initial blood flow effects on the liver are followed by intracellular changes preceding the formation of fibrosis and cirrhosis

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>Focusing on health-care costs and health consequences for drinkers, an alcohol tax increase is a cost-effective policy instrument.</p

Cost-Effectiveness of an Opportunistic Screening Programme and Brief Intervention for Excessive Alcohol Use in Primary Care

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.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.Prevention of excessive alcohol use by implementing SBI for excessive alcohol use in primary care settings appears to be cost-effective

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

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