Estimating disparities in breast cancer screening programs towards mortality, case fatality, and DALYs across BRICS-plus.

BACKGROUND: Numerous studies over the past four decades have revealed that breast cancer screening (BCS) significantly reduces breast cancer (BC) mortality. However, in BRICS-plus countries, the association between BCS and BC case fatality and disability are unknown. This study examines the association of different BCS approaches with age-standardized mortality, case-fatality, and disability-adjusted life years (DALYs) rates, as well as with other biological and sociodemographic risk variables, across BRICS-plus from a national and economic perspective. METHODS: In this ecological study applying mixed-effect multilevel regression models, a country-specific dataset was analyzed by combining data from the Global Burden of Disease study 2019 on female age-standardized BC mortality, incidence, and DALYs rates with information on national/regional BCS availability (against no such program or only a pilot program) and BCS type (only self-breast examination (SBE) and/or clinical breast examination (CBE) [SBE/CBE] versus SBE/CBE with mammographic screening availability [MM and/or SBE/CBE] versus SBE/CBE/mammographic with digital mammography and/or ultrasound (US) [DMM/US and/or previous tests] in BRICS-plus countries. RESULTS: Compared to self/clinical breast examinations (SBE/CBE) across BRICS-plus, more complex BCS program availability was the most significant predictor of decreased mortality [MM and/or SBE/CBE: - 2.64, p < 0.001; DMM/US and/or previous tests: - 1.40, p < 0.001]. In the BRICS-plus, CVD presence, high BMI, second-hand smoke, and active smoking all contributed to an increase in BC mortality and DALY rate. High-income and middle-income regions in BRICS-plus had significantly lower age-standardized BC mortality, case-fatality, and DALYs rates than low-income regions when nationwide BC screening programs were implemented. CONCLUSIONS: The availability of mammography (digital or traditional) and BCS is associated with breast cancer burden in BRICS-plus countries, with regional variations. In light of high-quality evidence from previous causal studies, these findings further support the preventive role of mammography screening for BCS at the national level. Intervening on BCS related risk factors may further reduce the disease burden associated with BC.

The cost of implementing measles campaign in Nigeria: comparing the stand-alone and the integrated strategy.

BACKGROUND: Effective integration, one of the seven strategic priorities of the Immunization Agenda 2030, can contribute to increasing vaccination coverage and efficiency. The objective of the study is to measure and compare input costs of "non-selective" measles vaccination campaign as a stand-alone strategy and when integrated with another vaccination campaign. METHODS: We conducted a cost-minimization study using a matched design and data from five states of Nigeria. We carried-out our analysis in 3 states that integrated measles vaccination with Meningitis A and the 2 states that implemented a stand-alone measles campaign. The operational costs (e.g., costs of personnel, training, supervision etc.) were extracted from the budgeted costs, the financial and technical reports. We further used the results of the coverage surveys to demonstrate that the strategies have similar health outputs. RESULTS: The analysis of the impact on campaign budget (currency year: 2019) estimated that savings were up to 420,000 United States Dollar (USD) with the integrated strategies; Over 200 USD per 1,000 children in the target population for measles vaccination (0.2 USD per children) was saved in the studied states. The savings on the coverage survey components were accrued by lower costs in the integration of trainings, and through reduced field work and quality assurance measures costs. CONCLUSIONS: Integration translated to greater value in improving access and efficiency, as through sharing of costs, more life-saving interventions are made accessible to the communities. Important considerations for integration are resource needs, micro-planning adjustments, and health systems delivery platforms.

Sex disparities in the effect of statins on lipid parameters: The PharmLines Initiative.

ABSTRACT: Real-world evidence on a potential statin effect modification by sex is inconclusive, especially for the primary prevention of cardiovascular disease (CVD). We aimed to quantify the differences in the effect of statins on lipid parameters between men and women.The PharmLines Initiative linked the Lifelines Cohort Study and the IADB.nl prescription database. This database covers a representative population from the Netherlands. We selected participants aged ≥40 years at the index date: the date of the first prescription of any statin monotherapy in the study period 2006 to 2017. Multivariate regression modeling was used to compare the difference of the mean percentage change of lipid parameters (% mean difference [MD]) from baseline to follow-up measurement between the sexes.Out of 5366 statin users from approximately 50,000 participants available in the final linked database, 685 were statin initiators. At baseline, women had significantly higher levels of mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) than men (all P values <.01). At follow-up, women had a significantly higher mean percentage change of HDL-C compared to men (adjusted % MD 5.59, 95% confidence interval [CI] 2.42-8.75, P < .01). There was no significant sex difference in other parameters, nor in the proportion of men and women who achieved LDL-C ≤2.5 mmol/L.Statins appear to have a greater effect on increasing HDL-C levels in women than men while showing similar effect on other lipid parameters in both sexes. Men should not be treated differently than women.

Interview-based cross-sectional needs assessment to advance the implementation of an effective antibiotic stewardship program in Indonesian hospitals.

Antibiotic resistance has become a global health issue, negatively affecting the quality and safety of patient care, and increasing medical expenses, notably in Indonesia. Antibiotic stewardship programs (ASPs) aim to reduce resistance rates and their implementation in hospitals, has a high priority worldwide. We aimed to monitor the progress in the organizational implementation of ASPs in Indonesian hospitals by an Antimicrobial Resistance Control Program (ARCP) team and to identify possible hurdles. We conducted a cross-sectional study with structured interviews based on a checklist designed to assess the achievement of structural indicators at the organizational level in four private and three public hospitals in four regions (Surabaya, Sidoarjo, Mojokerto, Bangil) in East Java, Indonesia. The organizational structure of public hospitals scored better than that of private hospitals. Only three of the seven hospitals had an ARCP team. The most important deficiency of support appeared to be insufficient funding allocation for information technology development and lacking availability and/or adherence to antibiotic use guidelines. The studied hospitals are, in principle, prepared to adequately implement ASPs, but with various degrees of eagerness. The hospital managements have to construct a strategic plan and to set clear priorities to overcome the shortcomings.

Pharmacy-based predictors of non-adherence, non-persistence and reinitiation of antihypertensive drugs among patients on oral diabetes drugs in the Netherlands.

BACKGROUND: Adherence to antihypertensive drugs in patients with diabetes is important. To support adherence, attention should be paid to the dynamic process of implementation, persistence and reinitiation of these drugs. We assessed non-adherence, non-persistence and reinitiation patterns for antihypertensive drugs in patients on oral diabetes drugs and identified pharmacy-based predictors of these processes. METHODS: We conducted a cohort study in patients on oral diabetes drugs who initiated antihypertensive drugs between 1995-2015, as registered in the IADB.nl pharmacy database. Non-adherence was defined as a medication possession ratio < 80% and non-persistence as a gap > 180 days. We defined reinitiation as the dispensing of an antihypertensive drug within one year following discontinuation. We provide descriptive statistics for different time periods and applied logistic and Cox regressions to assess associations with sociodemographic and drug-related factors. RESULTS: Of 6,669 initiators, non-adherence rates in persistent patients decreased from 11.0% in the first year to 8.5% and 7.7% in the second and third years, respectively. Non-persistence rates decreased from 18.0% in the first year to 3.7% and 2.9% in the second and third years, respectively. Of the 1,201 patients who discontinued in the first year, 22.0% reinitiated treatment within one year. Non-adherence and non-persistence rates were lower in the more recent time period. Predictors of non-adherence were secondary prevention (OR: 1.45; 95% CI: 1.10-1.93) and diuretics as initial drug class (OR: 1.37; 95% CI: 1.08-1.74). Predictors of non-persistence were female gender (HR: 1.18; 95% CI: 1.05-1.32), older age (HR: 1.33; 95% CI: 1.08-1.63) and diuretics, beta-blocking agents or calcium channel blockers as initial drug class. Longer duration of persistence was a predictor of reinitiation. CONCLUSIONS: Adherence to antihypertensive drugs in patients on oral diabetes drugs has improved over time. The first year after initiation is the most crucial with regard to non-adherence and non-persistence, and the risk groups are different for both processes. Early non-persistence is a risk factor for not reinitiating treatment.

Concordance assessment of self-reported medication use in the Netherlands three-generation Lifelines Cohort study with the pharmacy database iaDB.nl: The PharmLines initiative.

BACKGROUND: While self-reported data are commonly used as a source of medication use for pharmaco-epidemiological studies, such information is prone to forms of bias. Several previous studies showed that various factors like age, type of drug and data collection method may influence accuracy. We aimed to assess the concordance of the self-reported medication use that was documented at entry to the Lifelines Cohort Study, a three-generation follow-up study in the Netherlands that started in 2006 and included over 167,000 participants. MATERIALS AND METHODS: As part of the PharmLines Initiative, we collected medication data from the Lifelines participants encoded according to the Anatomical Therapeutic Chemical (ATC) coding scheme and linked the data via Statistics Netherlands to the widely used and representative pharmacy prescription database of the University of Groningen, IADB.nl. Analyses were conducted at second level of ATC coding for all recorded medications as well as a top list of most used medications at drug-specific fifth level. Cohen's kappa statistics were used to measure the concordance for all participants according to sex and age. RESULTS: The level of concordance between the two data sources largely differed according to the therapeutic class. Medication used for the cardiovascular system and diabetes, thyroid therapy, bisphosphonates and anti-thrombotic drugs showed a very good agreement (κ>0.75). Medication as needed or prone to stigmatization bias showed a moderate agreement (κ=0.41-0.60), whereas medications used for short periods of time showed a fair agreement (κ=0.0-0.4). Concordance was similar for males and females, but younger adults tended to have lower concordance rates than older adults. CONCLUSION: The self-reported method was valid for capturing prevalent chronic medication use at one moment in time, but invalid for medication used for short periods of time. There is no effect of sex on the agreement, and more studies are needed on the influence of age. Future pharmaco-epidemiological studies should preferably combine the two data sources to achieve the highest accuracy of drug exposure rates.

The potential economic value of influenza vaccination for healthcare workers in The Netherlands.

BACKGROUND: Despite the clinical evidence, influenza vaccination coverage of healthcare workers remains low. To assess the health economic value of implementing an influenza immunization program among healthcare workers (HCW) in University Medical Centers (UMCs) in the Netherlands, a cost-benefit model was developed using a societal perspective. METHODS/PATIENTS: The model was based on a trial performed among all UMCs in the Netherlands that included both hospital staff and patients admitted to the pediatrics and internal medicine departments. The model structure and parameters estimates were based on the trial and complemented with literature research, and the impact of uncertainty explored with sensitivity analyses. RESULTS: In a base-case scenario without vaccine coverage, influenza-related annual costs were estimated at € 410 815 for an average UMC with 8000 HCWs and an average occupancy during the influenza period of 6000 hospitalized patients. Of these costs, 82% attributed to the HCWs and 18% were patient-related. With a vaccination coverage of 15.47%, the societal program's savings were € 2861 which corresponds to a saving of € 270.53 per extended hospitalization. Univariate sensitivity analyses show that the results are most sensitive to changes in the model parameters vaccine effectiveness in reducing influenza-like illness (ILI) and the vaccination-related costs. CONCLUSION: In addition to the decreased burden of patient morbidity among hospitalized patients, the effects of the hospital immunization program slightly outweigh the economic investments. These outcomes may support healthcare policymakers' recommendations about the influenza vaccination program for healthcare workers.

Impact and cost-effectiveness of different vaccination strategies to reduce the burden of pneumococcal disease among elderly in the Netherlands.

BACKGROUND: Streptococcus pneumoniae causes morbidity and mortality among all ages in The Netherlands. To reduce this burden, infants in The Netherlands receive the 10-valent pneumococcal conjugated vaccine (PCV10), but older persons are not targeted. We assessed the impact and cost-effectiveness of vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) or 13-valent PCV (PCV13) among all those aged 60, 65 or 70 and/or in combination with replacing PCV10 with PCV13 in the infant vaccination programme. METHODS: A static cost-effectiveness model was parameterized including projected trends for invasive pneumococcal disease (IPD) and hospitalised community acquired pneumonia (CAP). The different strategies were evaluated using vaccine list prices and a 10-year time horizon. Incremental cost-effectiveness ratios (ICER) were calculated with the current strategy (infant vaccination program with PCV10) as reference. RESULTS: Compared to the reference, the largest impact on pneumococcal disease burden was projected with a combined use of PCV13 among infants and PPV23 at 60, 65 and 70 years, preventing 1,635 cases of IPD and 914 cases of CAP. The most cost-effective strategy was vaccinating with PPV23 at 70 years only with similar low ICERs at age 60 and 65. The impact of the use of PCV13 among infants depends strongly on the projected herd-immunity effect on serotype 19A. Vaccinating elderly with either PCV13 or PPV23 was dominated by PPV23 in all investigated scenarios, mainly due to the lower price of PPV23. CONCLUSION: Under the current assumptions, the best value for money is the use of PPV23 for elderly, with a single dose or at five year increment between age 60 to age 70.

Influenza Vaccine Research funded by the European Commission FP7-Health-2013-Innovation-1 project.

Due to influenza viruses continuously displaying antigenic variation, current seasonal influenza vaccines must be updated annually to include the latest predicted strains. Despite all the efforts put into vaccine strain selection, vaccine production, testing, and administration, the protective efficacy of seasonal influenza vaccines is greatly reduced when predicted vaccine strains antigenically mismatch with the actual circulating strains. Moreover, preparing for a pandemic outbreak is a challenge, because it is unpredictable which strain will cause the next pandemic. The European Commission has funded five consortia on influenza vaccine development under the Seventh Framework Programme for Research and Technological Development (FP7) in 2013. The call of the EU aimed at developing broadly protective influenza vaccines. Here we review the scientific strategies used by the different consortia with respect to antigen selection, vaccine delivery system, and formulation. The issues related to the development of novel influenza vaccines are discussed.

Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH) is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at school often leads to reduced compliance, sub-optimal treatment, and therefore economic loss. Replacement of IR-MPH with a single-dose extended release (ER-MPH) formulation may improve drug response and economic efficiency. OBJECTIVE: To evaluate the cost-effectiveness from a societal perspective of a switch from IR-MPH to ER-MPH in patients who are sub-optimally treated. METHODS: A daily Markov-cycle model covering a time-span of 10 years was developed including four different health states: (1) optimal response, (2) sub-optimal response, (3) discontinued treatment, and (4) natural remission. ER-MPH options included methylphenidate osmotic release oral system (MPH-OROS) and Equasym XL/Medikinet CR. Both direct costs and indirect costs were included in the analysis, and effects were expressed as quality-adjusted life years (QALYs). Univariate, multivariate as well as probabilistic sensitivity analysis were conducted and the main outcomes were incremental cost-effectiveness ratios. RESULTS: Switching sub-optimally treated patients from IR-MPH to MPH-OROS or Equasym XL/Medikinet CR led to per-patient cost-savings of €4200 and €5400, respectively, over a 10-year treatment span. Sensitivity analysis with plausible variations of input parameters resulted in cost-savings in the vast majority of estimations. CONCLUSIONS: This study lends economic support to switching patients with ADHD with suboptimal response to short-acting IR-MPH to long-acting ER-MPH regimens.

Effects and cost-effectiveness of pharmacogenetic screening for CYP2D6 among older adults starting therapy with nortriptyline or venlafaxine: study protocol for a pragmatic randomized controlled trial (CYSCEtrial).

BACKGROUND: Nortriptyline and venlafaxine are commonly used antidepressants for treatment of depression in older patients. Both drugs are metabolized by the polymorphic cytochrome P450-2D6 (CYP2D6) enzyme and guidelines for dose adaptations based on the CYP2D6 genotype have been developed. The CYP2D6 Screening Among Elderly (CYSCE) trial is designed to address the potential health and economic value of genotyping for CYP2D6 in optimizing dose-finding of nortriptyline and venlafaxine. METHODS/DESIGN: In a pragmatic randomized controlled trial, patients diagnosed with a major depressive disorder according to the DSM-IV and aged 60 years or older will be recruited from psychiatric centers across the Netherlands. After CYP2D6 genotyping determined in peripheral blood obtained by finger-prick, patients will be grouped into poor, intermediate, extensive, or ultrarapid metabolizers. Patients with deviant genotype (that is poor, intermediate or ultrarapid genotype) will be randomly allocated to an intervention group in which the genotype and dosing advice is communicated to the treating physician, or to a control group in which patients receive care as usual. Additionally, an external reference group of patients with the extensive metabolizer genotype is included. Primary outcome in all groups is time needed to obtain an adequate blood level of the antidepressant drug. Secondary outcomes include adverse drug reactions measured by a shortened Antidepressant Side-Effects Checklist (ASEC), and cost-effectiveness of the screening. DISCUSSION: Results of this trial will guide policy-making with regard to pharmacogenetic screening prior to treatment with nortriptyline or venlafaxine among older patients with depression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01778907 ; registration date: 22 January 2013.

Cost-effectiveness of statins for primary prevention in patients newly diagnosed with type 2 diabetes in the Netherlands.

BACKGROUND: Statins are lipid-lowering drugs that reduce the risk of cardiovascular events in patients with diabetes. OBJECTIVES: The objective of this study was to determine whether statin treatment for primary prevention in newly diagnosed type 2 diabetes is cost-effective, taking nonadherence, baseline risk, and age into account. METHODS: A cost-effectiveness analysis was performed by using a Markov model with a time horizon of 10 years. The baseline 10-year cardiovascular risk was estimated in a Dutch population of primary prevention patients with newly diagnosed diabetes from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database, using the United Kingdom Prospective Diabetes Study risk engine. Statin adherence was measured as pill days covered in the IADB.nl pharmacy research database. Cost-effectiveness was measured in costs per quality-adjusted life-year (QALY) from the health care payers' perspective. RESULTS: For an average patient aged 60 years, the base case, statin treatment was highly cost-effective at €2245 per QALY. Favorable cost-effectiveness was robust in sensitivity analysis. Differences in age and 10-year cardiovascular risk showed large differences in cost-effectiveness from almost €100,000 per QALY to almost being cost saving. Treating all patients younger than 45 years at diabetes diagnosis was not cost-effective (weighted cost-effectiveness of almost €60,000 per QALY). CONCLUSIONS: Despite the nonadherence levels observed in actual practice, statin treatment is cost-effective for primary prevention in patients newly diagnosed with type 2 diabetes. Because of large differences in cost-effectiveness according to different risk and age groups, the efficiency of the treatment could be increased by targeting patients with relatively higher cardiovascular risk and higher ages.

Using spatial analysis to predict health care use at the local level: a case study of type 2 diabetes medication use and its association with demographic change and socioeconomic status.

Local health status and health care use may be negatively influenced by low local socio-economic profile, population decline and population ageing. To support the need for targeted local health care, we explored spatial patterns of type 2 diabetes mellitus (T2DM) drug use at local level and determined its association with local demographic, socio-economic and access to care variables. We assessed spatial variability in these associations. We estimated the five-year prevalence of T2DM drug use (2005-2009) in persons aged 45 years and older at four-digit postal code level using the University of Groningen pharmacy database IADB.nl. Statistics Netherlands supplied data on potential predictor variables. We assessed spatial clustering, correlations and estimated a multiple linear regression model and a geographically weighted regression (GWR) model. Prevalence of T2DM medicine use ranged from 2.0% to 25.4%. The regression model included the extent of population ageing, proportion of social welfare/benefits, proportion of low incomes and proportion of pensioners, all significant positive predictors of local T2DM drug use. The GWR model demonstrated considerable spatial variability in the association between T2DM drug use and above predictors and was more accurate. The findings demonstrate the added value of spatial analysis in predicting health care use at local level.

Prevalence and predictors of over-the-counter medication use among pregnant women: a cross-sectional study in the Netherlands.

BACKGROUND: Over-the-counter-medication (OTC-medication) use during pregnancy can be potentially harmful for the fetus. To successfully counsel the patient it is important to know if the patient is at risk. In this study possible predictors for OTC-medication use were identified and a model was designed to predict OTC-medication use during pregnancy. METHODS: We performed a post-hoc analysis on data collected for a clustered clinical trial to study a screening strategy for Query fever. Pregnant women under supervision of a midwife were eligible for inclusion. These women filled out questionnaires during their pregnancy and post-partum. These questionnaires were used to determine the prevalence and to select possible predictors for OTC-medication use. These predictors were included in a prediction model using multivariate analysis. The discrimination and calibration of the model were assessed with Receiver Operating Characteristic analysis and the Hosmer and Lemeshow test. RESULTS: Of the 1348 women enrolling in the clustered clinical trial, we included 1246 women in this analysis. The prevalence of OTC-medication use was 12.5%. The predictors for OTC-medication use in our cohort were: nulliparity, use of prescription medication, the presence of a comorbidity, Body Mass Index between 26 and 30 kg/m2 and General Practitioner visits. These predictors were used to design a prediction model for OTC-medication use. The area under the Receiver Operating Characteristic-curve of the prediction model was 0.667 (95% CI 0.620-0.714 P<0.001) and the predictive probabilities ranged from 6.6% to 57.4%. The Hosmer and Lemeshow goodness-of-fit test indicated good calibration of the model (P = 0.640). CONCLUSION: It is possible to indicate women at risk for OTC-medication use during pregnancy, using five maternal characteristics that independently contribute to the prediction model. The predictors are easy to estimate and the model is easy to implement in daily practice.

Cost-effectiveness of vaccination against meningococcal B among Dutch infants: Crucial impact of changes in incidence.

OBJECTIVE: Recently, a vaccine with the capacity to protect against serogroup B meningococcal (MenB) disease received a positive opinion of the European Medicines Agency. Previously, such a vaccine was estimated to be cost-effective. However, since then, the MenB disease incidence has declined drastically in the Netherlands. Therefore, we re-assessed the potential incremental cost-effectiveness ratio (ICER) of vaccinating infants in the Netherlands with a MenB vaccine. RESULTS: Routine infant vaccination (2, 3, 4+11 mo) could prevent 39 cases of MenB disease in a single birth cohort, corresponding to a total gain of 133 quality-adjusted life years (QALYs). However, this strategy is unlikely to be cost-effective if the vaccine costs €40 per dose (€243,778 per QALY). At a disease incidence of 5.7 per 100,000 person-years or a vaccine price of €10 per dose including administration costs, the ICER becomes more acceptable and remains below a threshold of €50,000 per QALY. METHODS: A cohort of 185,000 Dutch newborns was followed in a Markov model to compare routine vaccination against MenB disease with no vaccination. The ICER was estimated for different disease incidences. The study was performed from a societal perspective. CONCLUSIONS: At the current low level of disease incidence, introduction of routine infant vaccination, following a 2, 3, 4+11 mo schedule, against MenB disease is unlikely cost-effective in the Netherlands. If the MenB disease incidence increases or the vaccine price is substantially lower than €40, routine infant vaccination has the potential to be cost-effective.

Cost-effectiveness of vaccination of the elderly against herpes zoster in The Netherlands.

BACKGROUND: Each year a substantial number of Dutch elderly suffers from herpes zoster (HZ), caused by the reactivation of the varicella zoster virus (VZV). A potential complication of HZ is postherpetic neuralgia (PHN) which results in a prolonged loss of quality of life. A large randomized clinical trial, labelled the Shingles Prevention study (SPS), demonstrated that a live attenuated VZV vaccine can reduce the incidence of HZ and PHN. OBJECTIVE: We aimed to estimate the incremental cost-effectiveness ratio (ICER) of vaccination of the elderly against HZ versus no such vaccination in The Netherlands. METHODS: A cohort model was developed to compare the costs and effects in a vaccinated and a non-vaccinated age- and gender-stratified cohort of immune-competent elderly. Vaccination age was varied from 60 to 75 years. Data from published literature such as the SPS were used for transition probabilities. The study was performed from the societal as well as the health care payer's perspective and results were expressed in euros per quality-adjusted life year (QALY) gained. RESULTS: In the base case, we estimated that vaccination of a cohort of 100,000 60-year-olds would prevent 4136 cases of HZ, 305 cases of PHN resulting in a QALY-gain of 209. From the societal perspective, a total of €1.9 million was saved and the ICER was €35,555 per QALY gained when a vaccine price of €87 was used. Vaccination of women resulted in a lower ICER than vaccination of men (€33,258 vs. €40,984 per QALY gained). The vaccination age with the most favourable ICER was 70 years (€29,664 per QALY gained). Parameters with a major impact on the ICER were the vaccine price and HZ incidence rates. In addition, the model was sensitive to utility of mild pain, vaccine efficacy at the moment of uptake and the duration of protection induced by the vaccine. CONCLUSION: Vaccination against HZ might be cost-effective for ages ranging from 60 to 75 when a threshold of €50,000 per QALY gained would be used, at €20,000 per QALY this might not be the case. Additional information on the duration of vaccine-protection is needed to further optimize cost-effectiveness estimations.

Cost-effectiveness of rotavirus vaccination in the Netherlands; the results of a consensus model.

BACKGROUND: Each year rotavirus gastroenteritis results in thousands of paediatric hospitalisations and primary care visits in the Netherlands. While two vaccines against rotavirus are registered, routine immunisation of infants has not yet been implemented. Existing cost-effectiveness studies showed inconsistent results for these vaccines because of lack of consensus on the impact. We aimed to investigate which factors had a major impact on cost-effectiveness and were primarily responsible for the large differences in previously estimated cost-effectiveness ratios. METHODS: Based on updated data on health outcomes and cost estimates, we re-assessed the cost-effectiveness of routine paediatric rotavirus vaccination within the National Immunization Program for the Netherlands. Two consensus meetings were organised with national and international experts in the field to achieve consensus and resolve potential controversies. RESULTS: It was estimated that rotavirus vaccination in the Netherlands could avert 34,214 cases of rotavirus gastroenteritis in children aged less than 5 years. Notably, 2,779 hospitalisations were averted of which 315 were extensions of existing hospital stays due to nosocomial rotavirus infection. With a threshold varying from 20K € - 50K € per QALY and according to the base-case scenario, the full vaccination costs per child leading to cost-effectiveness was € 57.76 -€ 77.71. Results were sensitive to the inclusion of potential vaccine induced herd protection, QALY losses and number of deaths associated with rotavirus gastroenteritis. CONCLUSIONS: Our economic analysis indicates that inclusion of rotavirus vaccination in the Dutch National Immunization Program might be cost-effective depending on the cost of the vaccine and the impact of rotavirus gastroenteritis on children's quality of life.

Cost-effectiveness of a screening strategy for Q fever among pregnant women in risk areas: a clustered randomized controlled trial.

BACKGROUND: In The Netherlands the largest human Q fever outbreak ever reported in the literature is currently ongoing with more than 2300 notified cases in 2009. Pregnant women are particularly at risk as Q fever during pregnancy may cause maternal and obstetric complications. Since the majority of infected pregnant women are asymptomatic, a screening strategy might be of great value to reduce Q fever related complications. We designed a trial to assess the (cost-)effectiveness of a screening program for Q fever in pregnant women living in risks areas in The Netherlands. METHODS/DESIGN: We will conduct a clustered randomized controlled trial in which primary care midwife centres in Q fever risk areas are randomized to recruit pregnant women for either the control group or the intervention group. In both groups a blood sample is taken around 20 weeks postmenstrual age. In the intervention group, this sample is immediately analyzed by indirect immunofluorescence assay for detection of IgG and IgM antibodies using a sensitive cut-off level of 1:32. In case of an active Q fever infection, antibiotic treatment is recommended and serological follow up is performed. In the control group, serum is frozen for analysis after delivery. The primary endpoint is a maternal (chronic Q fever or reactivation) or obstetric complication (low birth weight, preterm delivery or fetal death) in Q fever positive women. Secondary aims pertain to the course of infection in pregnant women, diagnostic accuracy of laboratory tests used for screening, histo-pathological abnormalities of the placenta of Q fever positive women, side effects of therapy, and costs. The analysis will be according to the intention-to-screen principle, and cost-effectiveness analysis will be performed by comparing the direct and indirect costs between the intervention and control group. DISCUSSION: With this study we aim to provide insight into the balance of risks of undetected and detected Q fever during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov, protocol record NL30340.042.09.

[Influenza vaccination of hospital healthcare staff from the perspective of the employer: a positive balance]. / Influenzavaccinatie van ziekenhuismedewerkers vanuit werkgeversperspectief: batig saldo.

OBJECTIVE: To assess the annual productivity loss among hospital healthcare workers attributable to influenza and to estimate the costs and economic benefits of a vaccination programme from the perspective of the the employer. DESIGN: Cost-benefit analysis. METHODS: The percentage of work loss due to influenza was determined using monthly age and gender specific figures for productivity loss among healthcare workers of the University Medical Center Groningen (UMCG), the Netherlands over the period January 2006-June 2008. Influenza periods were determined on the basis of national surveillance data. The average increase in productivity loss in these periods was estimated by comparison with the periods outside influenza seasons. The direct costs of productivity loss from the perspective of the employer were estimated using the friction cost method. In the sensitivity analyses various modelling parameters were varied, such as the vaccination coverage. RESULTS: In the UMCG, with approximately 9,400 employees, the estimated annual costs associated with productivity loss due to influenza before the introduction of the yearly influenza vaccination program were € 675,242 or on average, € 72 per employee. The economic benefits of the current vaccination program with a vaccination coverage of 24% with a vaccine effectiveness of 71% were estimated at € 89,858 or € 10 per employee. The nett economic benefits of a vaccination program with a target vaccination coverage of 70% with a vaccine effectiveness of 71% were estimated at € 244,325 or € 26 per employee. CONCLUSION: This modelling study performed from the perspective of the employer showed that an annual influenza vaccination programme for hospital personnel can save costs.

Results of a cohort model analysis of the cost-effectiveness of routine immunization with 13-valent pneumococcal conjugate vaccine of those aged > or =65 years in the Netherlands.

BACKGROUND: Community-acquired pneumonia and invasive pneumococcal disease are common among older people (ie, those aged > or =65 years). A new 13-valent pneumococcal conjugate vaccine (PCV-13) is under study in the Netherlands. OBJECTIVE: The aim of this work was to model the cost-effectiveness of PCV-13 vaccination among those aged > or =65 years in the Netherlands, both in the total population and in those at increased risk for pneumonia, for various levels of efficacy (30%-90%) assumed. METHODS: Our previously published cost-effectiveness model was updated to include age-specific epidemiologic data and health-care utilization and costs for a hypothetical cohort of adults aged > or =65 years in the Netherlands. This cohort was followed twice-once as unvaccinated and once as vaccinated-over a time period of 5 years, with differences between both analyses reported. Outcome measures included costs, life-years gained (LYGs), quality-adjusted life-years, and incremental cost-effectiveness ratios (ICERs). All analyses were performed from a societal perspective. RESULTS: In the model, the ICER for vaccination remained below euro80,000/LYG, except when the vaccine was assumed to protect only against bacteremic pneumonia, with a relatively low effectiveness (40%) in combination with a high vaccine price (euro65), and indirect effects of serotype replacement would largely offset the direct effect of vaccination. For various assumptions, introduction of widespread PCV-13 vaccination (assuming a 60% efficacy against invasive and noninvasive disease because of vaccine serotypes, and a cost of euro50 per vaccinated person) was associated with the ICERs varying from cost-saving to euro50,676/LYG. CONCLUSIONS: In this model analysis of a hypothetical cohort in the Netherlands, vaccination with PCV-13 might be considered cost-effective, both for the total population and for the high-risk population aged > or =65 years, from a societal perspective, over a 5-year time horizon. The main limitation of this study was uncertainty regarding how great a proportion of pneumonia could be attributed to pneumococcal disease.