Cost-effectiveness of infant pneumococcal vaccination in the Netherlands

Objectives: The Dutch National Immunization Program offers the 10-valent pneumococcal conjugate vaccine (PCV10). Also licensed for use in the infant population is the 13-valent PCV (PCV13). To update cost-effectiveness (CE) estimates of PCV13 over PCV10, using current epidemiological and economic data. Methods: We modeled vaccinating a birth cohort with either PCV10 or PCV13 (3+1 dose schedule), and calculated costs and effects linked to resulting disease. We modeled invasive pneumococcal disease (IPD), non-invasive pneumonia and acute otitis media, and considered death and lifetime impairments after IPD. We calculated direct effects in the vaccinated cohort and indirect effects -herd immunity for the vaccine-type (VT) serotypes and replacement for the non-VT serotypes- in the rest of the population. Since no price is available, we use a price difference of € 11 per dose and vary this price difference in sensitivity analyses. Epidemiological and economic data are taken as current as possible. A set of scenarios explore different assumptions, including different sets of epidemiological data, assumptions on vaccine efficacy and indirect effects. Results: Taking only direct effects into account PCV13 cannot be considered cost-effective, unless the price difference is much lower than € 11 per dose. In three scenarios, PCV10 dominates PCV13; in the other scenarios the ICER is between € 89000 and € 153000 per QALY gained. If indirect effects are also taken into account, the ICER of PCV13 compared to PCV10 is below € 20,000 per QALY for all scenarios. Scenarios do not have a large impact on the policy decision, unless we assume extra efficacy of PCV10 against non-typeable Haemophilus influenzae. Conclusions: Replacing PCV10 with PCV13 is not likely to be cost-effective in preventing invasive pneumococcal disease in young children. Taking potential benefits in elderly into account, PCV13 is likely cost-effective. The CE of PCV13 was highly sensitive for indirect effects our analysis

Substrate induction and glucose repression of maltose utilization by Streptomyces coelicolor A3(2) is controlled by malR, a member of the lacI-galR family of regulatory genes

malR of Strepomyces coelicolor A3(2) encodes a homologue of the Lacl/Galr family of repressor proteins, and is divergently transcribed from the malEFG gene cluster, which encodes components of an ATP-dependent transport system that is required for maltose utilization. Transcription of malE was induced by maltose and repressed by glucose. Disruption or deletion of malR resulted in constitutive, glucose-insensitive malE transcription at a level markedly above that observed in the parental malR+ strain, and overproduction of MalR prevented growth on maltose as carbon source. Consequently, MalR plays a crucial role in both substrate induction and glucose repression of maltose utilization. MalR is expressed from a single promoter with transcription initiating at the first G of the predicted GTG translataion start codon

PIN22 Cost-Effectiveness of Hepatitis a Vaccination in Indonesia

Objectives: This study aims to assess the cost-effectiveness of hepatitis A vaccination in Indonesia, including an explicit comparison between one-dose and twodose vaccines. Methods: An age-structured cohort model based on a decision tree was developed for the 2012 Indonesia birth cohort. Using the model, we made a comparison on the use of two-dose and one-dose vaccines. The model involves a 70-year time horizon with 1-month cycles for children less than 2 years old and annually thereafter. Monte Carlo simulations were used to examine the economic acceptability and affordability of the hepatitis A vaccination. Results: With the vaccine price of US$4.49 per dose, the implementation of the hepatitis A vaccine from the societal perspective would yield incremental-cost-effectiveness-ratios (ICERs) at US$ 9,194 and US$4,577 for the two-dose and one-dose vaccine schedules, respectively. Considering the 2012 gross-domestic-product (GDP) per capita in Indonesia of US$ 3,557, the results indicate that hepatitis A vaccination would be a cost-effective intervention, both for the two-dose and one-dose vaccine schedules. Vaccination would be 100% affordable at budgets of US$89,918,000 and US$ 46,778,000 for the implementation of the two-dose and one-dose vaccine schedules, respectively. Conclusions: The implementation of hepatitis A vaccination in Indonesia would be a cost-effective health intervention under the market vaccine prices. Given the budget limitations, the use of a one-dose-vaccine schedule would be more realistic to be applied than a two-dose schedule. The discount rate, vaccine price, vaccine efficacy and mortality rate were the most influential parameters impacting the ICERs

Indirect treatment comparison and economic evaluation of novel oral anticoagulants for the prevention of stroke in patients with atrial fibrillation in the Netherlands

Objectives: Management with vitamin K antagonists (VKAs) has been an effective and cost-effective strategy for stroke prevention in atrial fibrillation (AF) but is associated with shortcomings. Novel oral anticoagulants (NOACs) were developed with the aims of no monitoring requirement and improved effectiveness and safety profiles. Economic evaluations require the comparison of all relevant options. However, there are no randomized controlled trials (RCTs) directly comparing these agents. In such cases, indirect treatment comparison (ITC) can be used to synthesize indirect comparative evidence. Through ITC-based evidence synthesis the cost-effectiveness of all available NOACs for stroke prevention in AF patients may be evaluated. Methods: ITC models were based on RCTs data comparing dabigratran, rivaroxaban, or apixaban with VKA treatment. Relative effectiveness was estimated for stroke/systemic embolism, intracranial hemorrhage, myocardial infarction, extracranial hemorrhage, and minor bleeding. A Markov model was developed using ITC-synthesized evidence with VKA as the baseline. Health utilities were collected from international sources whereas costs and mortality data were extracted from Dutch sources. Univariate and probabilistic sensitivity analyses (PSA) were conducted on the base-case incremental cost-effectiveness ratio (ICER). Results: The ICERs for dabigatran, apixaban, and rivaroxaban compared to VKA were € 12,146/QALY, € 12,488/QALY, and € 24,124/QALY, respectively. Sensitivity analysis using the upper and lower limits of the 95% confidence interval for absolute stroke risk with VKA treatment resulted in ICERs that varied drastically from dominance for VKA to being dominated by all NOACs. This is likely due to the large uncertainty observed between the baseline risk profiles of the VKA arms in the three RCTs. The options with the highest probabilities of cost-effectiveness in PSA were VKA at thresholds under € 13,000/QALY and dabigatran or apixaban at thresholds above this mark. Conclusions: Dabigatran and apixaban were shown to be cost-effective options for AF patients in The Netherlands. However, these results were strongly influenced by uncertainty around stroke risk with VKA treatment

Cost-effectiveness of rotavirus immunization in vietnam: Exploring impacts of herd immunity and patterns of breastfeedingof

OBJECTIVES: : Rotavirus is the most common cause of severe diarrhoea worldwide. This study was designed to evaluate the cost-effectiveness of rotavirus immunization in Vietnam taking into account herd immunity and patterns of breastfeeding. The affordability of implementing universal rotavirus immunization was assessed based on both GAVI-subsidized and market vaccine prices for the next 5 years from the perspective of the Vietnamese health care system. METHODS: An age-structured birth cohort model for Vietnam was developed to compare two strategies of no vaccination and universal rotavirus vaccination in 2011. A lifetime time horizon was used with monthly time cycles for those under one year and annually thereafter. The analysis was performed under three breastfeeding scenarios: 1) 100% exclusive breastfeeding for children under 6 months; 2) 100% partial breastfeeding, and 3) 100% no breastfeeding. Herd immunity was explored in all scenarios. Monte Carlo simulations were used to examine the acceptability and affordability of the immunization strategy. RESULTS: Rotavirus immunization would effectively reduce severe cases of rotavirus during the first 5 years of life. Herd immunity makes rotavirus vaccination a cost-saving strategy under the GAVI-subsidized vaccine price in the case of partial breastfeeding and a cost-effective strategy in all breastfeeding scenarios under the market vaccine price. Affordability results showed that at the GAVI-subsidized vaccine price, rotavirus vaccination is affordable. CONCLUSIONS: This is the first study in developing countries considering herd immunity under rotavirus vaccination. If the indirect effect were considered, vaccination would become a cost-saving strategy. Given the high mortality rate of diarrhea in children under-five-years of age, our findings show rotavirus immunization to be an effective and “must-do” prevention strategy. Vaccination, however, only becomes affordable if Vietnam receives GAVI's financial support. In the next five years, Vietnam will need financial support from international organizations to implement rotavirus vaccination

Costs of ownership of ready-to-administer pre-filled sterilized syringes in a Dutch hospital:A cost minimization analysis

Objectives: Preparation errors occur frequently during conventional multiple step preparation of parenteral drugs at the bedside, causing potential adverse drug events (ADEs), which can be a burden to the patient and involves high costs for the national healthcare system. The use of ready-to-administer (RTA) pre-filled sterilized syringes (PFSS) produced by the hospital pharmacy can prevent a significant part of preparation errors and reduces the risk of bacteremia due to contamination of the intravenous fluid. This research aims to compare the total cost of the conventional preparation methods (CPM) with the PFSS method. Methods: In the analysis, costs related to the preparation of the drugs, bacteremia due to contamination, ADEs as a result of medication errors and wastage of syringes were taken into account. Annual costs in a general Dutch hospital were consistently calculated. Three scenarios were investigated: (i) all preparations CPM (864.246 administrations per year); (ii) all preparations as PFSS; and (iii) 200.000 PFSS and the remaining part CPM (reflecting a transition state as currently present). Deterministic and probabilistic analyses are performed. Results: The first scenario shows higher annual costs at € 10.862.609 compared to the second scenario. The current situation (third scenario) already shows savings of € 2.420.545 compared to the old situation (first scenario). Sensitivity analyses revealed that cost savings of PFSS were mainly the result of decreased risks of medication errors and contamination of intravenous fluids. Extrapolating these results nationwide indicates potential savings over € 300 million if only PFSS were used Conclusions: The use of PFSS prepared at the hospital pharmacy yielded cost-savings compared to conventional preparation at the bedside in the Dutch hospital

Synthesis and cellular penetration properties of new phosphonium based cationic amphiphilic peptides

A new category of phosphonium based cationic amphiphilic peptides has been developed and evaluated as potential antimicrobial peptides and cell penetrating peptides. The required building blocks were conveniently accessible from cysteine and could be applied in a solid phase peptide synthesis protocol for incorporation into peptide sequences. Evaluation of the antimicrobial properties and cellular toxicity of these phosphonium based peptides showed that these “soft” cationic side-chain containing peptides have poor antimicrobial properties and most of them were virtually non toxic (on HEK cells tested at 256 and 512 μM) and non-haemolytic (on horse erythrocytes tested at 512 μM), hinting at an interesting potential application as cell penetrating peptides. This possibility was evaluated using fluorescent peptide derivatives and showed that these phosphonium based peptide derivatives were capable of entering HEK cells and depending on the sequence confined to specific cellular areas