G.A. de Wit

Statin treatment for primary prevention of vascular disease: whom to treat? Cost-effectiveness analysis

Objective To assess the cost-effectiveness of low dose statins for primary prevention of vascular disease, incorporating current prices, non-adherence (reduced clinical efficacy while maintaining healthcare costs), and the results of the recently published JUPITER trial. Design Cost-effectiveness analysis using a Markov model. Sensitivity analyses and Monte Carlo simulation evaluated the robustness of the results. Setting Primary care in The Netherlands. Participants Hypothetical populations of men and women aged 45 to 75 years without a history of vascular disease at different levels of risk for vascular disease (myocardial infarction and stroke) over 10 years. Interventions Low dose statin treatment daily versus no treatment for 10 years. Main outcome measures Number of fatal and nonfatal vascular events prevented, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios over 10 years. Results Over a 10-year period, statin treatment cost €35 000 (£30 000,

Costs of gastroenteritis in The Netherlands.

49 000) per QALY gained for men aged 55 years with a 10-year vascular risk of 10%. The incremental cost-effectiveness ratio improved as risk for vascular disease increased. The cost per QALY ranged from approximately €5000 to €125 000 when the 10-year vascular risk for men aged 55 years was varied from 25% to 5%. The incremental cost-effectiveness ratio slightly decreased with age after the level of vascular risk was specified. Results were sensitive to the costs of statin treatment, statin effectiveness, non-adherence, disutility of taking medication daily, and the time horizon of the model. Conclusions In daily practice, statin treatment seemed not to be cost-effective for primary prevention in populations at low risk of vascular disease, despite low costs of generic drug pills. Adherence to statin treatment needs to be improved to enhance the cost-effectiveness of the use of statins for primary prevention.

Disease burden in The Netherlands due to infections with Shiga toxin-producing Escherichia coli O157

: In order to target the most important cost components of gastroenteritis in The Netherlands and to indicate which change of policy yields the largest decrease in costs, the cost of illness of gastroenteritis and the number of Disability Adjusted Life Years (DALYs) in the Dutch population in 1999 were determined. The costs of gastroenteritis were estimated using data mainly from a community-based cohort study. For calculating DALYs, data on the number of deaths due to gastroenteritis were used from Statistics Netherlands. On average, the costs for gastroenteritis were 77 Euro (euros) per case. For all patients in The Netherlands, the costs were estimated at 345 million euros (ranging between 252 and 531 million euros). Indirect costs made up 82% of this total. An estimate of costs for patients with campylobacter, salmonella or norovirus infections was, in total, 10-17% of the costs of gastroenteritis. Gastroenteritis was associated with a loss of approximately 67,000 DALYs.

Vaccination against hepatitis B in low endemic countries

Surveys carried out between 1990 and 2000 indicated that the incidence of STEC O157-associated gastroenteritis in The Netherlands was 1250 cases/year (median), of which 180 visited a general practitioner, 40 are reported and 0.6 are fatal, mainly in the elderly. There are approximately 20 cases of STEC O157-associated haemolytic-uraemic syndrome (HUS) per year, mainly in children. There are 2.5 HUS patients per year who develop end-stage renal disease (ESRD). There are an estimated 2 HUS-related and 0.5 ESRD-related fatalities per year. The mean disease burden associated with STEC O157 in the Dutch population is 116 (90% confidence interval 85-160) Disability Adjusted Life Years (DALYs) per year. Mortality due to HUS (58 DALYs), and ESRD (21 DALYs) and dialysis due to ESRD (21 DALYs) constitute the main determinants of disease burden. Sensitivity analysis indicates that uncertainty associated with model assumptions did not have a major effect on these estimates.

Internet based vascular risk factor management for patients with clinically manifest vascular disease: randomised controlled trial

A mathematical model that takes transmission by sexual contact and vertical transmission into account was employed to describe the transmission dynamics of hepatitis B virus (HBV) and vaccination against it. The model is an extension of a model by Williams et al. (Epidemiol Infect 1996: 116; 71-89) in that it takes immigration of hepatitis B carriers from countries with higher prevalence into account. Model parameters were estimated from data from The Netherlands where available. The main results were that, given the estimates for the parameters describing sexual behaviour in The Netherlands, the basic reproduction number R0 is smaller than 1 in the heterosexual population. As a consequence, the immigration of carriers into the population largely determines the prevalence of HBV carriage and therefore limits the possible success of universal vaccination. Taking into account the prevalence of hepatitis B carriage among immigrants and an age-dependent probability of becoming a carrier after infection, we estimate that a fraction of between 5 and 10% of carrier states could be prevented by universal vaccination.

The burden of Lyme borreliosis expressed in disability-adjusted life years

Objective To investigate whether an internet based, nurse led vascular risk factor management programme promoting self management on top of usual care is more effective than usual care alone in reducing vascular risk factors in patients with clinically manifest vascular disease. Design Prospective randomised controlled trial. Setting Multicentre trial in secondary and tertiary healthcare setting. Participants 330 patients with a recent clinical manifestation of atherosclerosis in the coronary, cerebral, or peripheral arteries and with at least two treatable risk factors not at goal. Intervention Personalised website with an overview and actual status of patients’ risk factors and mail communication via the website with a nurse practitioner for 12 months; the intervention combined self management support, monitoring of disease control, and drug treatment. Main outcome measures The primary endpoint was the relative change in Framingham heart risk score after 1 year. Secondary endpoints were absolute changes in the levels of risk factors and the differences between groups in the change in proportion of patients reaching treatment goals for each risk factor. Results Participants’ mean age was 59.9 (SD 8.4) years, and most patients (n=246; 75%) were male. After 1 year, the relative change in Framingham heart risk score of the intervention group compared with the usual care group was −14% (95% confidence interval −25% to −2%). At baseline, the Framingham heart risk score was higher in the intervention group than in the usual care group (16.1 (SD 10.6) v 14.0 (10.5)), so the outcome was adjusted for the separate variables of the Framingham heart risk score and for the baseline Framingham heart risk score. This produced a relative change of −12% (−22% to −3%) in Framingham heart risk score for the intervention group compared with the usual care group adjusted for the separate variables of the score and −8% (−18% to 2%) adjusted for the baseline score. Of the individual risk factors, a difference between groups was observed in low density lipoprotein cholesterol (−0.3, −0.5 to −0.1, mmol/L) and smoking (−7.7%, −14.9% to −0.4%). Some other risk factors tended to improve (body mass index, triglycerides, systolic blood pressure, renal function) or tended to worsen (glucose concentration, albuminuria). Conclusion An internet based, nurse led treatment programme on top of usual care for vascular risk factors had a small effect on lowering vascular risk and on lowering of some vascular risk factors in patients with vascular disease. Trial registration Clinical trials NCT00785031.

Cost-effectiveness of targeted screening for hepatitis C in The Netherlands.

BACKGROUND Lyme borreliosis (LB) is the most commonly reported tick-borne infection in Europe and North America. In the last 15 years a 3-fold increase was observed in general practitioner consultations for LB in the Netherlands. To support prioritization of prevention and control efforts for LB, we estimated its burden expressed in Disability-Adjusted Life Years (DALYs). METHODS We used available incidence estimates for three LB outcomes: (i) erythema migrans (EM), (ii) disseminated LB and (iii) Lyme-related persisting symptoms. To generate DALYs, disability weights and duration per outcome were derived using a patient questionnaire including health-related quality of life as measured by the EQ-5D. RESULTS We estimated the total LB burden for the Netherlands in 2010 at 10.55 DALYs per 100,000 population (95% CI: 8.80-12.43); i.e. 0.60 DALYs for EM, 0.86 DALYs for disseminated LB and 9.09 DALYs for Lyme-related persisting symptoms. Per patient this was 0.005 DALYs for EM, 0.113 for disseminated LB and 1.661 DALYs for a patient with Lyme-related persisting symptoms. In a sensitivity analysis the total LB burden ranged from 7.58 to 16.93 DALYs per 100,000 population. CONCLUSIONS LB causes a substantial disease burden in the Netherlands. The vast majority of this burden is caused by patients with Lyme-related persisting symptoms. EM and disseminated Lyme have a more modest impact. Further research should focus on the mechanisms that trigger development of these persisting symptoms that patients and their physicians attribute to LB.

Effectiveness and cost-effectiveness of 3-monthly versus 6-monthly monitoring of well-controlled type 2 diabetes patients: a pragmatic randomised controlled patient-preference equivalence trial in primary care (EFFIMODI study)

On account of the serious complications of hepatitis C virus (HCV) infection and the improved treatment possibilities, the need to improve HCV awareness and case-finding is increasingly recognized. To optimize a future national campaign with this objective, three pilot campaigns were executed in three regions in The Netherlands. One campaign was aimed at the general population, a second (similar) campaign was extended with a support programme for primary care and a third campaign was specifically aimed at hard-drug users. Data from the pilot campaigns were used to build a mathematical model to estimate the incremental cost-effectiveness ratio of the different campaigns. The campaign aimed at the general public without support for primary care did not improve case-finding and was therefore not cost-effective. The similar campaign accompanied by additional support for primary care and the campaign aimed at hard-drug users emerged as cost-effective interventions for identification of HCV carriers.

Selective decontamination of the digestive tract and selective oropharyngeal decontamination in intensive care unit patients: a cost-effectiveness analysis

To investigate effectiveness and cost‐effectiveness of 6‐monthly monitoring compared with 3‐monthly monitoring of well‐controlled type 2 diabetes patients in primary care.

Use of DALYs in economic analyses on interventions for infectious diseases: a systematic review

Objective To determine costs and effects of selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) as compared with standard care (ie, no SDD/SOD (SC)) from a healthcare perspective in Dutch Intensive Care Units (ICUs). Design A post hoc analysis of a previously performed cluster-randomised trial (NEJM 2009;360:20). Setting 13 Dutch ICUs. Participants Patients with ICU-stay of >48 h that received SDD (n=2045), SOD (n=1904) or SC (n=1990). Interventions SDD or SOD. Primary and secondary outcome measures Effects were based on hospital survival, expressed as crude Life Years Gained (cLYG). The incremental cost-effectiveness ratio (ICER) was calculated, with corresponding cost acceptability curves. Sensitivity analyses were performed for discount rates, costs of SDD, SOD and mechanical ventilation. Results Total costs per patient were €41 941 for SC (95% CI €40 184 to €43 698), €40 433 for SOD (95% CI €38 838 to €42 029) and €41 183 for SOD (95% CI €39 408 to €42 958). SOD and SDD resulted in crude LYG of +0.04 and +0.25, respectively, as compared with SC, implying that both SDD and SOD are dominant (ie, cheaper and more beneficial) over SC. In cost-effectiveness acceptability curves probabilities for cost-effectiveness, compared with standard care, ranged from 89% to 93% for SOD and from 63% to 72% for SDD, for acceptable costs for 1 LYG ranging from €0 to €20 000. Sensitivity analysis for mechanical ventilation and discount rates did not change interpretation. Yet, if costs of the topical component of SDD and SOD would increase 40-fold to €400/day and €40/day (maximum values based on free market prices in 2012), the estimated ICER as compared with SC for SDD would be €21 590 per LYG. SOD would remain cost-saving. Conclusions SDD and SOD were both effective and cost-saving in Dutch ICUs.