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Introduction: In 2021, breast cancer affected 75,619 women in Denmark. Approximately 50% of breast cancers are considered human epidermal growth factor receptor 2 (HER2)-low. The DESTINY-Breast04 (DB-04) trial led to European Medicines Agency (EMA) approval of trastuzumab deruxtecan (T-DXd) as a treatment for patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. Moreover, the Danish Breast Cancer Group guidelines recently included T-DXd as a treatment for HER2-low metastatic breast cancer. This economic evaluation aims to estimate the cost-effectiveness of T-DXd for the approved EMA indication in Denmark., Methods: A three-state-progression-free, post-progression, and death-partitioned survival model was developed to estimate the cost-effectiveness of T-DXd versus treatment of physician's choice over a lifetime horizon following the Danish Medicines Council guidelines. Clinical data were gathered from the DB-04 trial, and cost and resource use data were sourced from the literature. Sensitivity and scenario analysis were conducted to explore uncertainty., Results: T-DXd led to 0.78 incremental quality-adjusted life years (QALYs) gained and incurred DKK 621,325 in incremental costs compared to the treatment of physician's choice. This resulted in an incremental cost-effectiveness ratio of DKK 795,181 per QALY gained, which falls below the willingness-to-pay threshold. Sensitivity and scenario analyses showed the robustness of the deterministic result, with T-DXd remaining cost-effective., Conclusion: Our study demonstrates that T-DXd is a cost-effective treatment for patients with HER2-low unresectable or metastatic breast cancer who have received prior chemotherapy in Denmark., Competing Interests: Declarations Conflict of Interest Jeroen Hendrikus Jacobus Paulissen, Alexander Victor van Schoonhoven, and Arjan Jacobus Postma are paid employees of Asc Academics; Emma Olin and Zacharie Mbanya are paid employees of AstraZeneca; Kyle John Dunton is a paid employee of Daiichi Sankyo International; Marinus van Hulst reports no financial interests; Maarten Jacobus Postma is advisor to Asc Academics. Roel Donald Freriks was an employee of Asc Academics at the time the research was conducted. He is currently employed by IQVIA. Asc Academics received consulting fees paid from Daiichi Sankyo International and AstraZeneca. Maarten Jacobus Postma is a non-remunerated member of the UK’s Joint Committee of Vaccination and Immunization, other authors report no non-financial interests. Ethical Approval This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors., (© 2024. The Author(s).)

Objectives: Trastuzumab deruxtecan (T-DXd) was recently recommended by the Committee for Medicinal Products for Human Use as a treatment for adult patients with unresectable or metastatic HER2-positive breast cancer, who had received a prior anti-HER2-based regimen. In our study, we evaluated the cost-effectiveness of T-DXd compared with ado-trastuzumab emtansine (T-DM1) for this indication in Finland., Methods: A three-state partitioned survival analysis model was developed with a payer's perspective. Time to event data from the DESTINY-Breast03 (DB-03) trial were extrapolated over a lifetime horizon either directly-for progression-free survival and time to treatment discontinuation-or using an alternative approach utilizing long-term T-DM1 survival data and DB-03 data-for overall survival. Discount rates of 3% were applied for costs and effects. Inputs were sourced from the Medicinal Products Database from Kela, Helsinki University Hospital service price list, Finnish Medicines Agency assessments, clinical experts, and DB-03. Sensitivity analyses were performed to characterize and demonstrate parameter uncertainties in the model., Results: Total quality-adjusted life years (QALYs) and life years (LYs) gained for T-DXd compared with T-DM1 were 1.93 and 2.56, respectively. Incremental costs for T-DXd compared with T-DM1 were €106,800, resulting in an ICER of €55,360 per QALY gained and an ICER of €41,775 per LY gained. One-way sensitivity analysis showed the hazard ratio of T-DXd vs T-DM1 for OS was the most influential parameter. The probabilistic sensitivity analysis showed similar results to the base case., Conclusions: T-DXd is cost-effective based on surrogate WTP thresholds of €72,000 and €139,000 per QALY., (© 2023. The Author(s).)

Background: Following clinical research of potential coronavirus disease 2019 (COVID-19) treatments, numerous decision-analytic models have been developed. Due to pandemic circumstances, clinical evidence was limited and modelling choices were made under great uncertainty. This study aimed to analyse key methodological characteristics of model-based economic evaluations of COVID-19 drug treatments, and specifically focused on modelling choices which pertain to disease severity levels during hospitalisation, model structure, sources of effectiveness and quality of life and long-term sequelae., Methods: We conducted a systematic literature review and searched key databases (including MEDLINE, EMBASE, Web of Science, Scopus) for original articles on model-based full economic evaluations of COVID-19 drug treatments. Studies focussing on vaccines, diagnostic techniques and non-pharmaceutical interventions were excluded. The search was last rerun on 22 July 2023. Results were narratively synthesised in tabular form. Several aspects were categorised into rubrics to enable comparison across studies., Results: Of the 1047 records identified, 27 were included, and 23 studies (85.2%) differentiated patients by disease severity in the hospitalisation phase. Patients were differentiated by type of respiratory support, level of care management, a combination of both or symptoms. A Markov model was applied in 16 studies (59.3%), whether or not preceded by a decision tree or an epidemiological model. Most cost-utility analyses lacked the incorporation of COVID-19-specific health utility values. Of ten studies with a lifetime horizon, seven adjusted general population estimates to account for long-term sequelae (i.e. mortality, quality of life and costs), lasting for 1 year, 5 years, or a patient's lifetime. The most often reported parameter influencing the outcome of the analysis was related to treatment effectiveness., Conclusion: The results illustrate the variety in modelling approaches of COVID-19 drug treatments and address the need for a more standardized approach in model-based economic evaluations of infectious diseases such as COVID-19., Trial Registry: Protocol registered in PROSPERO under CRD42023407646., (© 2024. The Author(s).)

Background: The treatment of chronic hepatitis C virus (HCV) infection using directly acting antivirals was recently adopted in the treatment guidelines of Zimbabwe. The objectives of this study were to design a simplified model of HCV care and estimate the cost of screening and treatment of hepatitis C infection at a tertiary hospital in Zimbabwe., Methods: We developed a model of care for HCV using WHO 2018 guidelines for the treatment of HCV infection and expert opinion. We then performed a micro-costing to estimate the costs of implementing the model of care from the healthcare sector perspective. Deterministic and probabilistic sensitivity analyses were performed to explore the impact of uncertainty in input parameters on the estimated total cost of care., Results: The total cost of screening and treatment was estimated to be US$2448 (SD=$290) per patient over a 12-week treatment duration using sofosbuvir/velpatasvir. The cost of directly acting antivirals contributed 57.5% to the total cost of care. The second largest cost driver was the cost of diagnosis, US$819, contributing 34.6% to the total cost of care., Conclusion: Screening and treatment of HCV-infected individuals using directly acting antivirals at a tertiary hospital in Zimbabwe may require substantial financial resources.

Objectives: Systematic priority setting is necessary for achieving high-quality healthcare using limited resources in low- and middle-income countries. Health technology assessment (HTA) is a tool that can be used for systematic priority setting. The objective of this study was to conduct a stakeholder and situational analysis of HTA in Zimbabwe., Methods: We identified and analyzed stakeholders using the International Decision Support Initiative checklist. The identified stakeholders were invited to an HTA workshop convened at the University of Zimbabwe. We used an existing HTA situational analysis questionnaire to ask for participants' views on the need, demand, and supply of HTA. A follow-up survey was done among representatives of stakeholder organizations that failed to attend the workshop. We reviewed two health policy documents relevant to the HTA. Qualitative data from the survey and document review were analyzed using thematic analysis., Results: Forty-eight organizations were identified as stakeholders for HTA in Zimbabwe. A total of 41 respondents from these stakeholder organizations participated in the survey. Respondents highlighted that the HTA was needed for transparent decision making. The demand for HTA-related evidence was high except for the health economic and ethics dimensions, perhaps reflecting a lack of awareness. Ministry of Health was listed as a major supplier of HTA data., Conclusions: There is no formal HTA agency in the Zimbabwe healthcare system. Various institutions make decisions on prioritization, procurement, and coverage of health services. The activities undertaken by these organizations provide context for the institutionalization of HTA in Zimbabwe.

Introduction: The global measles incidence has decreased from 145 to 49 cases per 1 million population from 2000 to 2018, but evaluating the economic benefits of a second measles-containing vaccine (MCV2) is crucial. This study reviewed the evidence and quality of economic evaluation studies to guide MCV2 introduction., Methods: The systematic review of model-based economic evaluation studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search yielded 2231 articles, with 876 duplicates removed and 1355 articles screened, with nine studies included for final analysis., Results: Six studies reported a positive benefit-cost ratio with one resulting in net savings of $11.6 billion, and two studies estimated a 2-dose MMR vaccination program would save $119.24 to prevent one measles case, and a second dose could prevent 9,200 cases at 18 months, saving $548.19 per case. The most sensitive variables were the discount rate and vaccination administration cost., Conclusions: Two MCV doses or a second opportunity with an additional dose of MCV were highly cost-beneficial and resulted in substantial cost savings compared to a single routine vaccine. But further research using high-quality model-based health economic evaluation studies of MCV2 should be made available to decision-makers., Prospero Registration: CRD42020200669.

Aims: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guidelines to prevent strokes. Cost-effectiveness analyses of different screening programmes for AF are difficult to compare because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programmes in the Netherlands., Methods and Results: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the ARISTOTLE, RE-LY, and ROCKET AF trials combined with Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed. The maximum number of newly detected AF patients in the Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of >3000 strokes prevented using single-time point AF screening. Compared with no screening, screening 100 000 people provided a gain in QALYs ranging from 984 to 8727 and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. The probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥75 years visiting the geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥65 years visiting the GPs office had the highest impact on strokes prevented., Conclusion: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: This study aimed to evaluate the adherence to protocols for the use of reversal agents in direct oral anticoagulant (DOAC) users in Dutch hospitals., Methods: A retrospective cohort study was conducted in seven hospitals in the Netherlands. Treatment protocols for bleeding and (urgent) procedures in patients on DOAC were collected from each hospital. All patient data on the use of reversal agents were retrospectively collected from September 2021 to April 2022 and compared to the protocols. The degree of per-protocol adherence (compliance score) was categorized into four levels as follows: poor (<45%), moderate (45-79%), high (80-89%), and full (> 90%) adherence rates., Results: A total of 290 patients were included in our study. In patients with bleeding under DOAC, the protocol adherence for prothrombin complex concentrate (PCC) was "moderate" (61%). In the remaining cases (39%), non-adherence was mainly caused by underdosing (68%), overdosing (12%), and a lack of indication (14%). Furthermore, idarucizumab was administered for bleeding with "full" adherence (96%). For andexanet alfa, adherence to the hospital bleeding protocol was "moderate" (67%), with a lack of indication being the only reason for non-adherence. In case of reversal for an urgent procedure, the protocol adherence for PCC was "low" (45%), with underdosing, a lack of indication, and missing lab data being the main reasons for non-adherence. Missing lab data on dabigatran plasma concentration before reversal was the main reason for "low" adherence (26%) in idarucizumab. The adherence for andexanet alfa was also "low" (0%)., Conclusion: In case of reversal for bleeding under DOAC, overall adherence to the protocol was "moderate"; however, in patients needing an urgent procedure, it was "low." The major reasons for non-adherence were underdosing, off-label use, and a lack of specific lab testing. The results of this study can assist in improving the implementation of hospital protocols.

Background: Peak anti-Xa activity of low-molecular-weight heparin nadroparin is measured 3 to 5 hours after subcutaneous injection. In critically ill patients, physiological changes and medical therapies may result in peak activities before or after this interval, possibly impacting dosing., Objectives: The primary objective was to determine the percentage of critically ill patients with adequately estimated peak activities drawn 3 to 5 hours after subcutaneous administration of a therapeutic dose of nadroparin. Adequate was defined as a peak activity of ≥80% of the actual peak anti-Xa activity. If ≥80% of patients had adequately estimated peak activities in the 3- to 5-hour interval, measurement in this interval was regarded as acceptable. The secondary objective was to determine the pharmacokinetic profile of nadroparin., Methods: In this single-center, prospective study, we evaluated anti-Xa activities in patients admitted to a general intensive care unit. After ≥4 equal doses of nadroparin, anti-Xa activity was measured according to a 12- to 24-hour sampling scheme., Results: In 25 patients, anti-Xa activities drawn between 3 and 5 hours after administration ranged 80% to 100% of the actual peak activity. Compared to the threshold level of an adequate estimation in at least 20 patients (≥80%), measuring anti-Xa activities in the 3- to 5-hour interval is an acceptable method (1-tailed binomial test; P  < .02). We found a large interindividual variability for nadroparin exposure (mean ± SD area-under-the-curve 0-12h , 10.3 ± 4.8 IU·h/mL) and delayed elimination (t 1/2 range, 4.0-120.9 hours) despite adequate renal function., Conclusion: In critically ill patients, measuring anti-Xa activity in a 3- to 5-hour interval after subcutaneous injection of therapeutic nadroparin is an acceptable method to estimate the actual peak anti-Xa activity., (© 2023 The Authors.)

Objective: We aimed to assess the cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands., Methods: A Markov model was used to evaluate the health effects and costs of lung cancer screening from the healthcare perspective. The effects and costs of ten screening scenarios with different start and stop ages of screening were examined across a lifetime horizon in a cohort of 100,000 smokers and ex- smokers 50 years and older., Results: The incremental cost-effectiveness ratios (ICERs) of screening smokers and ex-smokers aged 50-60 years, 50-70 years, and 50 years and older are below the cost-effectiveness threshold of € 20,000 per quality adjusted life year (QALY) gained. Screening 50-60-year-old smokers and ex-smokers was the most cost-effective scenario with an ICER of € 14,094 per QALY gained. However, screening smokers and ex-smokers 50 years and older yielded the highest QALYs and resulted in an ICER of € 16,594 per QALY, which is below the threshold of € 20,000 per QALY. All screening scenarios compared to no screening resulted in CERs between the € 14,000 and € 16,000 per QALY gained. The efficiency frontier showed that screening smokers and ex-smokers in the age groups 70 years and older, 60-70 years, 60 years and older are excluded by extended dominance by no screening, screening smokers and ex-smokers aged 50-60 years and 50-70 years., Conclusion: This study showed that lung cancer screening is cost-effective in the Netherlands., (© 2022. The Author(s).)

Background: In Ethiopia, cervical cancer is the second most common cancer among women of the reproductive age group. Since 2018, the quadrivalent human papillomavirus (4vHPV) vaccine targeting four HPV types (6/11/16/18) has been introduced in the national immunization program in Ethiopia. Currently, however, a nonavalent HPV (9vHPV) vaccine which provides broader protection against nine HPV types (6/11/16/18/31/33/45/52/58) is available for global use. Our study, therefore, aims to estimate the cost-effectiveness of 9vHPV vaccine compared to the current HPV vaccination program in Ethiopia., Method: A static Markov cohort model was used to simulate the progression of HPV infection to cervical cancer for a cohort of 12-years-old girls (N = 100,000) in Ethiopia. The model ran up to the age of 100 years, with a cycle length of 1 year. One-way and probabilistic sensitivity analyses were used to explore the robustness of the model and uncertainties around the parameters included in the model. Cost-effectiveness thresholds of one and three times gross domestic product (GDP) per quality-adjusted life-year (QALY) gained were considered., Results: At a price of US$ 6.9, the incremental cost-effectiveness ratio (ICER) per QALY gained for the 9vHPV vaccine was US$ 454 compared to the 4vHPV vaccine, which is less than one times GDP per capita of Ethiopia. The ICER was most sensitive to the change in the discount rate of QALYs. Compared to 4vHPV vaccine, for 9vHPV vaccine to remain very cost-effective and cost-effective, its price per dose should not exceed US$ 8.4 and US$ 15, respectively, at a threshold of one and three times GDP per capita., Conclusion: Compared to the 4vHPV vaccine, the 9vHPV vaccine is a cost-effective option in Ethiopia, given that its price per dose does not exceed US$15., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MJP reports grants and personal fees from Merck Sharp & Dohme, GlaxoSmithKline, Pfizer, Boehringer Ingelheim, Novavax, Bristol-Myers Squibb, AstraZeneca, Sanofi, IQVIA, and Seqirus; personal fees from Quintiles, Novartis, and Pharmerit; grants from Bayer, BioMerieux, WHO, the EU, the FIND project, Antilope, DIKTI, LPDP, and Budi; acts as an advisor to Asc Academics; and holds stocks in Ingress Health and PAG. AW and MvH declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: This study aims to quantify socioeconomic inequalities-and the factors contributing to these inequalities-in measles vaccine uptake among children aged 12 to 23 months in Ethiopia between 2005 and 2016., Methods: Inequalities in measles vaccine uptake were investigated based on data from the Ethiopian Demographic and Health Surveys conducted in 2005, 2011, and 2016. Concentration curves and concentration indices were used to measure the degree of inequality, and decomposition analysis was used to identify factors contributing to these inequalities., Results: The overall level of national measles vaccine uptake in Ethiopia exhibited an increasing trend between 2005 and 2016. As indicated by the concentration index of measles vaccine uptake, however, which was estimated at 0.202 (P < .01) in 2005, 0.226 (P < .01) in 2011, and 0.223 (P < .01) in 2016, measles vaccine uptake became consistently more concentrated among children from more affluent households. The dominance test of the concentration curve further confirmed the persistence of inequalities in measles vaccine uptake over time. Various factors-including maternal educational level, antenatal care use, institutional delivery, and exposure to media-were identified as the most important contributors to the inequalities., Conclusions: Although the national measles vaccine uptake showed improvement between 2005 and 2016, socioeconomic inequalities in the uptake persisted over time. Efforts to improve the national immunization coverage should be accompanied by appropriate measures to address the inequalities., (Copyright © 2021. Published by Elsevier Inc.)

Very few low-income countries have developed national plans to achieve the viral hepatitis elimination targets set in the World Health Organization (WHO) strategy. We reviewed the policy environment, strategies and challenges on the fight against viral hepatitis in Zimbabwe. The review focussed on the Ministry of Health and Child Care (MoHCC) policy documents, strategic plans and reports. We performed key informant interviews to enhance evidence generated from the document review. Twelve documents were reviewed and interviews with 10 key informants were completed. The MoHCC established a technical working group to work towards elimination of viral hepatitis. The technical working group drafted a strategic plan for elimination of viral hepatitis; however, it is still awaiting implementation. Key strategies that are working well include screening of donated blood for transfusion, safe injection practices and hepatitis B virus (HBV) three-dose vaccination. Current challenges in the drive towards elimination of viral hepatitis include poor to non-existent surveillance systems, lack of epidemiological data, absence of the HBV vaccine birth dose and lack of systematic screening and treatment services for viral hepatitis. In conclusion, despite political will demonstrated towards achieving viral hepatitis elimination, substantial investment and work are required to implement the strategic plan and realize significant success., (© 2021 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Acute intoxication with a vitamin K antagonist may cause serious coagulopathy. We report the accidental ingestion of a high dose of acenocoumarol in a young child. Two intravenous administrations of 5 mg of vitamin K, in combination with fast and repeated administration of activated charcoal and sodium sulfate, were sufficient to prevent coagulopathy and related symptoms, despite a confirmed elevated blood acenocoumarol concentration (260 µg/L)., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: For the non-vitamin-K oral anticoagulants, data on bleeding when used for 42 days as thromboprophylaxis after total knee arthroplasty (TKA) are scarce. This pilot study assessed feasibility of a multicentre randomised clinical trial to evaluate major and clinically relevant non-major bleeding during 42-day use of dabigatran, nadroparin and rivaroxaban after TKA., Patients and Methods: In 70 weeks, between July 2012 and November 2013, 198 TKA patients were screened for eligibility in the Martini Hospital (Groningen, the Netherlands). Patients were randomly assigned to dabigatran (n=45), nadroparin (n=45) or rivaroxaban (n=48). The primary outcome was the combined endpoint of major bleeding and clinically relevant non-major bleeding. Secondary endpoints of this study were the occurrence of clinical venous thromboembolism (VTE) (pulmonary embolism or deep venous thrombosis), compliance, duration of hospital stay, rehospitalisation, adverse events and Knee Injury and Osteoarthritis Outcome Score (KOOS)., Results: The primary outcome was observed in 33.3% (95% CI 20.0% to 49.0%), 24.4% (95% CI 12.9% to 39.5%) and 27.1% (95% CI 15.3% to 41.8%) of patients who received dabigatran, nadroparin or rivaroxaban, respectively (p=0.67). Major bleeding was found in two patients who received nadroparin (p=0.21). Clinically relevant non-major bleeding was observed in 33.3% (95% CI 20.0% to 49.0%), 22.2% (95% CI 11.2% to 37.1%) and 27.1% (95% CI 15.3% to 41.8%) for dabigatran, nadroparin and rivaroxaban, respectively (p=0.51). Wound haematoma was the most observed bleeding event. VTE was found in one patient who received dabigatran (p=0.65). The presurgery and postsurgery KOOS qQuestionnaires were available for 32 (71%), 35 (77%) and 35 (73%) patients for dabigatran, nadroparin and rivaroxaban, respectively. KOOS was highly variable, and no significant difference between treatment groups in mean improvement was observed., Conclusions: A multicentre clinical trial may be feasible. However, investments will be substantial. No differences in major and clinically relevant non-major bleeding events were found between dabigatran, nadroparin and rivaroxaban during 42 days after TKA. KOOS may not be suitable to detect functional loss due to bleeding., Trial Registration Number: NCT01431456., Competing Interests: Competing interests: MvH reports grants from Bayer and personal fees from Boehringer Ingelheim during the conduct of the study. Other authors have nothing to report., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

In Ethiopia, full vaccination coverage among children aged 12-23 months has improved in recent decades. This study aimed to investigate drivers of the improvement in the vaccination coverage. The Oaxaca-Blinder decomposition technique was applied to identify the drivers using data from Ethiopian Demographic and Health Survey conducted in 2000 and 2016. The vaccination coverage rose from 14.3% in 2000 to 38.5% in 2016. The decomposition analysis showed that most of the rise in vaccination coverage (73.7%) resulted from the change in the effect of explanatory variables over time and other unmeasured characteristics. Muslim religion had a counteracting effect on the observed increase in vaccination coverage. The remaining 26.3% of the increase was attributed to the change in the composition of the explanatory variables between 2000 and 2016, with maternal educational level and maternal health care utilization as significant contributors. The findings highlight the need for further improvements in maternal health care utilization and educational status to maintain the momentum towards universal coverage of childhood vaccination. Targeted intervention among Muslim-dominated communities is also needed to improve the current situation. Besides which, future studies need to be conducted to identify additional potential modifiable factors.

Objective: We aimed to assess the cost-effectiveness of hepatitis C virus (HCV) screening strategies among recently arrived migrants in the Netherlands., Methods: A Markov model was used to estimate the health effects and costs of HCV screening from the healthcare perspective. A cohort of 50,000 recently arrived migrants was used. In this cohort, three HCV screening strategies were evaluated: (i) no screening, (ii) screening of migrants from HCV-endemic countries and (iii) screening of all migrants., Results: Strategy (ii) screening of migrants from HCV-endemic countries compared to strategy (i) no screening, yielded an incremental cost-effectiveness ratio (ICER) of €971 per quality-adjusted life-years (QALYs) gained. Strategy (iii) screening of all migrants compared with strategy (ii) screening of migrants from HCV-endemic countries yielded an ICER of €1005 per QALY gained. The budget impact of strategy (ii) screening of migrants from HCV-endemic countries and strategy (iii) screening of all migrants was €13,752,039 and €20,786,683, respectively., Conclusion: HCV screening is cost-effective. However, the budget impact may have a strong influence on decision making., Competing Interests: The authors declare no conflict of interest.

A previous study in Ethiopia reported significant variation in rotavirus vaccine uptake across socioeconomic strata. This study aims to quantify socioeconomic inequality of rotavirus vaccine uptake in Ethiopia and to identify the contributing factors for the inequality. The concentration curve (CC) and the Erreygers Normalized Concentration Index (ECI) were used to assess the socioeconomic related inequality in rotavirus vaccine uptake using data from the 2016 Ethiopian Demographic and Health Survey. Decomposition analysis was conducted to identify the drivers of inequalities. The CC for rotavirus vaccine uptake lay below the line of equality and the ECI was 0.270 ( p < 0.001) indicating that uptake of rotavirus vaccine in Ethiopia was significantly concentrated among children from families with better socioeconomic status. The decomposition analysis showed that underlining inequalities in maternal health care services utilization, including antenatal care use (18.4%) and institutional delivery (8.1%), exposure to media (12.8%), and maternal educational level (9.7%) were responsible for the majority of observed inequalities in the uptake of rotavirus vaccine. The findings suggested that there is significant socioeconomic inequality in rotavirus vaccine uptake in Ethiopia. Multi-sectoral actions are required to reduce the inequalities, inclusive increasing maternal health care services, and educational attainments among economically disadvantaged mothers., Competing Interests: Postma reports grants and honoraria from various pharmaceutical companies, including those developing, producing and marketing rotavirus vaccine.

Objective: Critically ill patients admitted to the intensive care unit (ICU) often develop atrial fibrillation (AF), with an incidence of around 5%. Stroke prevention in AF is well described in clinical guidelines. The extent to which stroke prevention is prescribed to ICU patients with AF is unknown. We aimed to determine the incidence of new-onset AF and describe stroke prevention strategies initiated on the ICU of our teaching hospital. Also, we compared mortality in patients with new-onset AF to critically ill patients with previously diagnosed AF and patients without any AF., Methods: This study was a retrospective cohort study including all admissions to the ICU of the Martini Hospital (Groningen, The Netherlands) in the period 2011 to 2016. Survival analyses were performed using these real-world data., Results: In total, 3334 patients were admitted to the ICU, of whom 213 patients (6.4%) developed new-onset AF. 583 patients (17.5%) had a previous AF diagnosis, the other patients were in sinus rhythm. In-hospital mortality and 1-year mortality after hospital discharge were significantly higher for new-onset AF patients compared with patients with no history of AF or previously diagnosed AF. At hospital discharge, only 56.3% of the new-onset AF-patients eligible for stroke prevention received an anticoagulant. Anticoagulation was not dependent on CHA 2 DS 2 -VASc score or other patient characteristics. An effect of anticoagulative status on mortality was not significant., Conclusion: AF is associated with increased mortality in critically ill patients admitted to the ICU. More guidance is needed to optimise anticoagulant treatment in critically ill new-onset AF patients., Competing Interests: Competing interests: MJ is an employee of Sanofi. The work presented here is not related to this employment and presents a personal opinion in the context of PhD research. RGT reports grants and personal fees from Boehringer Ingelheim, personal fees from Bayer and personal fees from Pfizer/Bristol Meyer Squibb all outside the submitted work. MJP reports grants and personal fees from various pharmaceutical industries all outside the submitted work. MJP holds stocks in Ingress Health and Pharmacoeconomics Advice Groningen (PAG Ltd)., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Randomized clinical trials (RCTs) and real-world data (RWD) in patients with atrial fibrillation have shown that-compared to vitamin K antagonists (VKAs)-non-VKA oral anticoagulants (NOACs) are at least as effective in the prevention of ischaemic stroke, while decreasing the risk of bleeding., Objective: We aim to evaluate the cost-effectiveness of the NOAC apixaban versus other NOACs (dabigatran, edoxaban and rivaroxaban) and VKA, for stroke prevention in patients with atrial fibrillation by including the available data both from RCT and real-world analyses of all NOACs into one integrative previously published model., Methods: The model was updated to the current Dutch healthcare situation. The incremental cost-effectiveness ratio was calculated using either efficacy/effectiveness and safety data derived from a network meta-analysis (NMA) synthesizing NOAC RCTs or RWD. We conducted a systematic literature search to identify eligible publication to best inform the RWD-based analysis. Additional sensitivity and scenario analyses were conducted to test the robustness of the outcomes., Results: In the NMA-based analysis, apixaban appeared to be cost-effective compared to VKA (€3,506 per quality adjusted life-year) and dominant (cost-saving and more effective) over dabigatran 110 mg, dabigatran 150 mg, edoxaban and rivaroxaban. In the RWD-based analysis, apixaban was dominant over all other anticoagulants. In the scenario analysis apixaban appeared to be not cost-effective compared to dabigatran 150 mg, when using equal event-unrelated treatment discontinuation rates for each drug. In all other scenarios apixaban is cost-effective or cost-saving compared to VKA and other NOACs., Conclusion: Based on RCTs as well as RWD, we conclude that apixaban is generally cost-effective or even cost-saving (less costly and more effective) compared to VKA and other NOACs in the overall population of patients with atrial fibrillation., Competing Interests: Maarten J. Postma has received grants and honoraria from all companies developing, producing, and marketing non-vitamin K oral anticoagulants (NOACs)—Boehringer Ingelheim, Pfizer, Bayer, Daiichi-Sankyo and Bristol-Myers Squibb—both in relation to NOACs and related to other topics. He has also received grants and honoraria from other companies fully unrelated to the subject matter of this paper, namely GSK, Astra Zeneca, Biomarin, MSD, Merck, Sanofi, and Novartis. In addition, he is adviser to the consultancy company Asc Academics and holds stock in Ingress Health. Marinus van Hulst has no current competing interests. However, in the past he received travel grants and speaker honoraria from Bayer, and consulted for Boehringer Ingelheim. Robert G. Tieleman has received research grants and personal fees from Boehringer Ingelheim, Pfizer, Bayer, and Bristol-Myers Squibb. Menno V. Huisman has obtained grants from ZonMW Dutch Healthcare Fund as well as grants and personal fees from Boehringer-Ingelheim, Pfizer-BMS, Bayer Health Care, Aspen, and Daiichi-Sankyo outside the submitted work. Harrie Rila and Jelena Stevanovic are employees of Bristol-Myers Squibb without ownership of stock in Bristol-Myers Squibb Company. They were involved with the start of the research but did not influence the results and discussion. Lisa A. de Jong and Jessie Groeneveld have no conflicts of interest with relation to the subject. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Over three-quarters of deaths from cardiovascular disease and diabetes occur in low- and middle-income countries, which include many African countries. Global studies showed that the prevalence of the cardiac arrhythmia atrial fibrillation (AF) appeared to be lower in Africa. A systematic search of PubMed and African Journals Online was conducted to determine the prevalence of AF and associated stroke risk factors in Africa and to quantify the need for screening. The publications search yielded a total of 840 articles of which 41 were included. AF was often not identified as the disease of primary interest with its own risks. Data on prevalence in the general population was scarce. The prevalence of stroke risk factors showed a large variation between studies, as well as within clustered subpopulations. AF in Africa is under-reported in published reports. The study types and populations are highly heterogeneous, making it difficult to draw a definitive conclusion on AF prevalence., (Copyright © 2019 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)

Aims: Bridging anticoagulation in atrial fibrillation (AF) patients who need to interrupt vitamin K antagonists for procedures is a clinical dilemma. Currently, guidelines recommend clinicians to take the stroke and bleeding risk into consideration, but no clear thresholds are advised. To aid clinical decision making, we aimed to develop a model in which periprocedural bridging therapy is compared with withholding anticoagulation in AF patients, for several bleeding and stroke risk groups., Methods and Results: A model was developed to simulate both a bridge and a non-bridge cohort, using simulated international normalized ratio (INR) values for patients on warfarin, acenocoumarol, and phenprocoumon. For both clinical strategies, stroke and bleeding risks were included and outcomes were stratified by CHA2DS2-VASc or CHADS2 and HAS-BLED groups. Quality-adjusted life expectancy was the main outcome considered. Our analyses show bridging to only be beneficial for patients with HAS-BLED scores equal or lower to 2 and with CHA2DS2-VASc scores of 6 or higher. For patients using acenocoumarol bridging may be beneficial starting at a CHA2DS2-VASc score of 7. Post-procedural time to therapeutic INR has a significant influence on the results: no significant benefit of bridging was found for patients reaching therapeutic INR values within 5 days., Conclusion: When deciding whether to bridge anticoagulation, clinicians should consider the patient's individual stroke and bleeding risk, while also considering the patient's post-procedural INR management. In practice, only a small subset of patients is expected to benefit from bridging anticoagulation treatment., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: The increasing number of available, often expensive, medicines asks for continuous assessment of rational prescribing. We aimed to develop a simple and robust data infrastructure in order to monitor hospital medicine utilisation in real time., Methods: Within a collaboration (Santeon) of large teaching hospitals in the Netherlands, we set up a process for extraction, transformation, anonymisation and load of individual medicine prescription data and major clinical outcomes from different hospital information systems into a central database. Quarterly reports were constructed to monitor and validate the quality of the uploaded data., Results: A central database has been developed that includes data from all patients from 2010 onwards and is refreshed on a weekly basis by an automated process. Beginning in 2017, the database holds data from almost 800 000 patients with prescriptions. All hospitals provide at least 18 mandatory data items per patient. Provided data include, among others, individual prescriptions, diagnosis data, and hospitalisation and survival data. The database is currently used to benchmark the level of biosimilar prescribing and to assess the impact of novel systemic treatments on survival rates in metastatic cancers., Conclusion: We showed that it is feasible for a group of hospitals to construct their own database that can serve as a tool to benchmark the positioning of medicines and to start with monitoring their impact on clinical outcomes., Competing Interests: Competing interests: None declared.

Background: Electrical cardioversion (ECV) is a procedure in which a direct current electric shock is used to quickly and effectively restore the normal sinus rhythm. Appropriate anticoagulation reduces the risk of embolic events during and after ECV. The aim of this study was to estimate the cost-effectiveness of rivaroxaban compared with vitamin K oral antagonists (VKAs) in patients with atrial fibrillation undergoing elective ECV in the Netherlands., Methods and Results: A static transmission model over a 1-year time horizon was developed to compare rivaroxaban with VKAs in terms of clinical outcomes, health effects (quality-adjusted life years; QALYs), and costs. Cost-effectiveness was assessed from a societal and health care payer perspective at a willingness-to-pay level of €20,000 per QALY gained. The use of rivaroxaban as an anticoagulant in patients with atrial fibrillation scheduled for ECV would lead to a health gain of 0.23 QALYs per patient and would cost €1.83 per patient from the societal perspective, resulting in an incremental cost-effectiveness ratio of €7.92 per QALY gained. The probability of rivaroxaban being cost-saving compared with VKAs was 49.6% from this perspective. From the health care payer perspective, the incremental cost would be €509 per patient with a health gain of 0.23 QALYs per patient, resulting in an incremental cost-effectiveness ratio of €2198 per QALY gained., Conclusions: The use of rivaroxaban in elective ECV is a cost-effective alternative to the use of VKAs. Rivaroxaban has a 50% probability of being cost-saving compared with VKAs and would increase a patient's quality of life when non-health care costs such as productivity loss and informal care costs are taken into account.

Background: Atrial fibrillation (AF) causes a significant health and economic burden to the Dutch society. Dabigatran was proven to have at least similar efficacy and a similar or better safety profile when compared to vitamin K antagonists (VKAs) in preventing arterial thromboembolism in patients with AF., Objective: To evaluate the cost-effectiveness and monetary benefit of dabigatran vs VKAs in Dutch patients with non-valvular AF. Value-based pricing considerations and corresponding negotiations on dabigatran will be explicitly considered., Methods: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the RE-LY trial and Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed., Results: Dabigatran was cost saving compared to VKAs. A total of 4,552 QALYs were gained, and €13,892,288 was saved in a cohort of 10,000 AF patients. The economic value of dabigatran was strongly related to the costs of VKA control that are averted. Notably, dabigatran was cost saving compared to VKAs if annual costs of VKA control exceeded €159 per person, or dabigatran costs were below €2.81 per day., Conclusion: Dabigatran was cost saving compared to VKAs for the prevention of atrial thromboembolism in patients with non-valvular AF in the Netherlands. This result appeared robust in the sensitivity analysis. Furthermore, volume based reduction of the price in the Netherlands will further increase the monetary benefits of dabigatran.

Aims: Atrial fibrillation (AF) is the most common arrhythmia and prevalence increases with age. Patients with AF have a high risk of stroke, and screening for AF is recommended in all people aged 65 years or older to identify patients eligible for stroke prevention. A handheld, single-lead electrocardiogram (ECG) device can be used for systematic screening in the population at risk. The objective of this study is to estimate the cost-effectiveness of screening for AF in primary care with the MyDiagnostick® during seasonal influenza vaccination in the Netherlands., Methods and Results: Lifetime costs and effects of a single screening session for AF detection were assessed from a societal perspective with a decision analytic model consisting of a straightforward decision tree and a joining Markov model. The decision model simulated all patients aged 65 years and over attending the seasonal influenza vaccination in the Netherlands. Event probabilities were derived from clinical trials. Sensitivity analyses were performed to assess the impact of important model assumptions as well as determining the relative effect of individual parameters. Screening for AF with the MyDiagnostick® in all patients older than 65 years that attend seasonal influenza vaccination in the Netherlands would decrease the overall costs by €764 and increase the quality-adjusted life-years (QALYs) by 0.27 years per patient. Early detection of AF would prevent strokes and leads to beneficial health effects with subsequent cost savings. This screening method would have an estimated probability of 99.8% for being cost-effective at a conservative willingness-to-pay of €20 000/QALY., Conclusion: Screening for AF in primary care with a handheld, single-lead ECG during seasonal influenza vaccination is very likely to be cost saving for identifying new cases of AF in the Dutch population aged 65 years and over. Active screening for AF with a single-lead, handheld ECG device during seasonal influenza vaccination could be implemented in primary care., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: The aim of this study was to assess the cost effectiveness of introducing individual-donation nucleic acid testing (ID-NAT), in addition to serologic tests, compared with the exclusive use of serologic tests for the identification of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) I and II among blood donors in Zimbabwe., Study Design and Methods: The costs, health consequences, and cost effectiveness of adding ID-NAT to serologic tests, compared with serologic testing alone, were estimated from a health care perspective using a decision-analytic model., Results: The introduction of ID-NAT in addition to serologic tests would lower the risk of HBV, HCV, and HIV transmission to 46.9, 0.3, and 2.7 per 100,000 donations, respectively. ID-NAT would prevent an estimated 25, 6, and 9 HBV, HCV, and HIV transfusion-transmitted infections per 100,000 donations, respectively. The introduction of this intervention would result in an estimated 212 quality-adjusted life-years (QALYs) gained. The incremental cost-effectiveness ratio is estimated at US$17,774/QALY, a value far more than three times the gross national income per capita for Zimbabwe., Conclusion: Although the introduction of NAT could further improve the safety of the blood supply, current evidence suggests that it cannot be considered cost effective. Reducing the test costs for NAT through efficient donor recruitment, negotiating the price of reagents, and the efficient use of technology will improve cost effectiveness., (© 2016 AABB.)

Background: Various models for estimating the residual risk (RR) of transmission of infections by blood transfusion have been published mainly based on data from high-income countries. However, to obtain the data required for such an assessment remains challenging for most developing settings. The National Blood Service Zimbabwe (NBSZ) adapted a published incidence-window period (IWP) model, which has less demanding data requirements. In this study we assess the impact of various definitions of blood donor subpopulations and models on RR estimates. We compared the outcomes of two published models and an adapted NBSZ model., Study Design and Methods: The Schreiber IWP model (Model 1), an amended version (Model 2), and an adapted NBSZ model (Model 3) were applied. Variably the three models include prevalence, incidence, preseroconversion intervals, mean lifetime risk, and person-years at risk. Annual mean RR estimates and 95% confidence intervals for each of the three models for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) were determined using NBSZ blood donor data from 2002 through 2011., Results: The annual mean RR estimates for Models 1 through 3 were 1 in 6542, 5805, and 6418, respectively for HIV; 1 in 1978, 2027, and 1628 for HBV; and 1 in 9588, 15,126, and 7750, for HCV., Conclusions: The adapted NBSZ model provided comparable results to the published methods and these highlight the high occurrence of HBV in Zimbabwe. The adapted NBSZ model could be used as an alternative to estimate RRs when in settings where two repeat donations are not available., (© 2016 AABB.)

Background: The EUFRAT (European Up-Front Risk Assessment Tool) was developed as an online risk assessment tool ( http://eufrattool.ecdc.europa.eu ) to help decision-makers assess the transmission risk of emerging infectious diseases (EID) through blood transfusion. The aim of this study is to extend the methodology developed in the EUFRAT project to quantify the transfusion transmission (TT) risk from travelling donors., Methods: A generic model for estimating the TT risk from a group of travelling donors that visited an EID risk area was developed. In addition, the new model distinguishes projected future transmissions from those that have already occurred. As an illustration the model was applied to the outbreaks of chikungunya in Italy in 2007 and Q fever in the Netherlands in 2007-2009., Results: Formulas for calculating the travelling donors' TT risk were derived. For the chikungunya outbreak in Italy an early intervention (at the end of week 7 after the start of the outbreak, so after only 19% of all cases) would have been required to prevent only 41% of all expected transmissions at that time. For Q fever, in which the transmission of chronic Q fever is considered, even at the end of the third annual outbreak's peak 47% of all (chronic) Q fever transmissions could still be prevented., Conclusions: The updated model allows estimation of the infection transmission risk from travelling donors. In combination with the distinction between past and future transmissions, these estimates provide valuable information to support decisions concerning communication with the public and/or the implementation of safety interventions.

Background: There is lack of published data on the costs of blood and blood transfusion in sub-Saharan Africa. This study aimed to assess the unit costs of producing blood in Zimbabwe using an activity-based costing (ABC) method., Study Design and Methods: A management accounting approach, based on the ABC method, was used to develop a cost model for blood. The production of blood was broken down into recruitment, collection, testing, processing, and storage plus distribution. Data for the year 2013 were collected retrospectively from budgets, financial and expenditure reports, databases, and interviews with transfusion personnel and managers. All direct and indirect costs, in 2013 US$, were allocated, accordingly, to the activities of blood acquisition., Results: The total cost of producing safe blood in Zimbabwe for the year 2013 was US$8.6 million. Variable costs accounted for 51.2% of the total cost of production. The unit production costs for red blood cells (RBCs) were US$15.94 for recruitment, US$34.62 for collection, US$17.88 for testing, US$11.49 for processing, and US$3.06 for storage plus distribution. The overall cost of production of one unit of whole blood was US$118.42 and RBCs was US$130.94 constituting 12.4 and 13.7% of the country's annual GDP per capita., Conclusions: The high unit cost of producing blood relative to the annual GDP per capita demonstrates that acquiring safe blood is a burden on the health care sector in Zimbabwe. Introducing additional safety measures, such as nucleic acid amplification testing and pathogen reduction technology, although desirable, will further increase this burden., (© 2015 AABB.)

Background: There are limited published data on the characteristics of blood transfusion recipients in sub-Saharan Africa. This study describes the demographic characteristics of blood transfusion recipients and patterns of blood and blood component use in Zimbabwe., Materials and Methods: Data on the characteristics of the blood transfusion recipients (age, sex, blood group), blood components received (type, quantity), discharge diagnoses and outcomes following transfusion (discharge status, duration of stay in hospital), were retrospectively collected from four major hospitals for the period from January 1, 2012 to December 31, 2012. Diagnoses were grouped into broad categories according to the disease headings of the International Classification of Diseases (ICD-10). Surgical procedures were grouped into broad categories according to organ system using ICD-9., Results: Most of the 1,793 transfusion recipients studied were female (63.2%) and in the reproductive age group, i.e. 15-49 years (65.3%). The median age of the recipients was 33 years (range, 0-93). The majority of these recipients (n=1,642; 91.6%) received a red blood cell transfusion. The majority of the patients were diagnosed with conditions related to pregnancy and childbirth (22.3%), and diseases of blood and blood-forming organs (17.7%). The median time spent in hospital was 8 days (range, 0-214) and in-hospital mortality was 15.4%., Discussion: Our sample of blood transfusion recipients were fairly young and most of them received red blood cell transfusions. The majority of patients in the reproductive age group received blood transfusions for pregnancy and childbirth-related diagnoses.

Background: Haemovigilance hinges on a systematically structured reporting system, which unfortunately does not always exist in resource-limited settings. We determined the incidence and pattern of transfusion-related adverse events reported to the National Blood Service Zimbabwe., Materials and Methods: A retrospective review of the transfusion-event records of the National Blood Service Zimbabwe was conducted covering the period from 1 January 1999 to 31 December 2011. All transfusion-related event reports received during the period were analysed., Results: A total of 308 transfusion adverse events (0.046%) were reported for 670,625 blood components distributed. The majority (61.6%) of the patients who experienced an adverse event were female. The median age was 36 years (range, 1-89 years). The majority (68.8%) of the adverse events were acute transfusion reactions consisting of febrile non-haemolytic transfusion reactions (58.5%), minor allergies (31.6%), haemolytic reactions (5.2%), severe allergic reactions (2.4%), anaphylaxis (1.4%) and hypotension (0.9%). Two-thirds (66.6%) of the adverse events occurred following administration of whole blood, although only 10.6% of the blood was distributed as whole blood. Packed cells, which accounted for 75% of blood components distributed, were associated with 20.1% of the events., Discussion: The incidence of suspected transfusion adverse events was generally lower than the incidences reported globally in countries with well-established haemovigilance systems. The administration of whole blood was disproportionately associated with transfusion adverse events. The pattern of the transfusion adverse events reported here highlights the probable differences in practice between different settings. Under-reporting of transfusion events is rife in passive reporting systems.

Background: National Blood Service Zimbabwe human immunodeficiency virus (HIV) risk management strategy includes screening and discarding of first-time donations, which are collected in blood packs without an anticoagulant (dry pack). To evaluate the impact of discarding first-time donations on blood safety the HIV prevalence, incidence, and residual risk in first-time and repeat donations (wet packs) were compared., Study Design and Methods: Donor data from 2002 to 2010 were retrieved from a centralized national electronic donor database and retrospectively analyzed. Chi-square test was used to compare HIV prevalence with relative risk (RR), and the RR point estimates and 95% confidence interval (CI) are reported. Trend analysis was done using Cochran-Armitage trend test. HIV residual risk estimates were determined using published residual risk estimation models., Results: Over the 9 years the overall HIV prevalence estimates are 1.29% (n = 116,058) and 0.42% (n = 434,695) for first-time and repeat donations, respectively. The overall RR was 3.1 (95% CI, 2.9-3.3; p < 0.0001). The overall mean residual transmission risk of HIV window phase donations in first-time was 1:7384 (range, 1:11,308-1:5356) and in repeat donors it was 1:5496 (range, 1:9943-1:3347)., Conclusion: The significantly high HIV prevalence estimates recorded in first-time over repeat donations is indicative of the effectiveness of the HIV risk management strategy. However, comparable residual transmission risk estimates in first-time and repeat donors point to the need to further review the risk management strategies. Given the potential wastage of valuable resources, future studies should focus on the cost-effectiveness and utility of screening and discarding first-time donations., (© 2013 American Association of Blood Banks.)

Objectives: To perform a cost-effectiveness analysis and to identify the cost-effectiveness affordability levels for a newborn universal vaccination program against hepatitis B virus (HBV) in Vietnam., Methods: By using a Markov model, we simulated a Vietnamese birth cohort using 1,639,000 newborns in 2002 and estimated the incremental cost-effectiveness ratios for quality-adjusted life-year gained following universal newborn HBV vaccination. Two types of analyses were performed, including and excluding expenditures on the treatment of chronic hepatitis B and its complications. We used Monte Carlo simulations to examine cost-effectiveness acceptability and affordability from the payer's perspective and constructed a cost-effectiveness affordability curve to assess the costs and health effects of the program., Results: In the base-case analysis, newborn universal HBV vaccination reduced the carrier rate by 58% at a cost of US $42 per carrier averted. From the payer's perspective, incremental cost-effectiveness ratio per quality-adjusted life-year gained was US $3.77, much lower than the 2002 per-capita gross domestic product of US $440. Vaccination could potentially be affordable starting at a US $2.1 million budget. At the cost-effectiveness threshold of US $3.77 per quality-adjusted life-year and an annual budget of US $5.9 million, the probability that vaccination will be both cost-effective and affordable was 21%., Conclusions: Universal newborn HBV vaccination is highly cost-effective in Vietnam. In low-income, high-endemic countries, where funds are limited and the economic results are uncertain, our findings on the cost-effectiveness affordability options may assist decision makers in proper health investments., (Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objectives: Dabigatran etexilate is a new oral direct thrombin inhibitor for prophylaxis of venous thromboembolism (VTE) in patients who have elective surgery for total hip replacement (THR) or total knee replacement (TKR). Among the advantages of dabigatran etexilate over subcutaneous prophylaxis with Low Molecular Weight Heparin (LMWH) are reduced resource uses for (i) teaching patients to self-inject; (ii) home-care visits for subcutaneous administration; and (iii) absence of heparin-induced thrombocytopenia (HIT). Based on the demonstrated non-inferiority, the aim of this study was to conduct a cost-minimization analysis of oral dabigatran etexilate vs subcutaneous low-molecular weight heparin (LMWH) and fondaparinux from the Dutch healthcare perspective., Methods: A retrospective cohort study was conducted to measure resource use associated with subcutaneous prophylaxis. Results of this study were used in the model to elucidate specific advantages of dabigatran etexilate, next to reduced needs for self-inject teaching and lack of Heparin-Induced Thrombocytopenia. Drug and other resource utilization data were combined with local unit costs. Probabilistic sensitivity analysis was performed to account for uncertainty around relevant parameters included., Results: Home-care visits for subcutaneous administration problems were needed in 9.9% (95% CI=6.4-13.4) and 9.6% (95% CI=5.8-13.4) of THR and TKR patients, respectively. Based on costs for 1000 patients treated with dabigatran etexilate vs LMWHs, per patient cost-savings with dabigatran etexilate were estimated at €30.68 (95% CI=2.01-65.52) and €23.19 (95% CI=0.69-48.48) for THR and TKR, respectively. The probability that dabigatran etexilate would be cost-saving was estimated at 98.3% and 97.9% for THR and TKR, respectively. These cost-savings were even higher when including fondaparinux in the analysis, with per patient cost-savings of €69.87 (43.42-106.10) and €18.33 (1.63-41.26) for THR and TKR, respectively. Separate calculations for dabigatran etexilate vs nadroparin and dalteparin in THR resulted in probabilities of achieving cost-savings with dabigatran etexilate of 36.2% and 100%, respectively. For TKR these probabilities were estimated at 54.3% and 100%, respectively., Conclusions: Thromboprophylaxis with dabigatran etexilate is cost-saving in patients undergoing THR and TKR from the Dutch healthcare perspective, compared to subcutaneous LMWHs.

Background and Objectives: Health economics provides a standardised methodology for valid comparisons of interventions in different fields of health care. This review discusses the health economic evaluations of strategies to enhance blood product safety in sub-Saharan Africa., Methods: We reviewed health economic methodology with special reference to cost-effectiveness analysis. We searched the literature for cost-effectiveness in blood product safety in sub-Saharan Africa., Result: HIV-antibody screening in different settings in sub-Saharan Africa showed health gains and saved costs. Except for adding HIV-p24 screening, adding other tests such as nucleic acid amplification testing (NAT) to HIV-antibody screening displayed incremental cost-effectiveness ratios greater than the WHO/World Bank specified threshold for cost-effectiveness. The addition of HIV-p24 in combination with HCV antibody/antigen screening and multiplex (HBV, HCV and HIV) NAT in pools of 24 may also be cost-effective options for Ghana., Conclusions: From a health economic viewpoint, HIV-antibody screening should always be implemented in sub-Saharan Africa. The addition of HIV-p24 antigen screening, in combination with HCV antibody/antigen screening and multiplex (HBV, HCV and HIV) NAT in pools of 24 may be feasible options for Ghana. Suggestions for future health economic evaluations of blood transfusion safety interventions in sub-Saharan Africa are: mis-transfusion, laboratory quality and donor management., (Copyright 2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.)

Background: The goal of our research was to actively involve decision makers in the economic assessment of screening strategies in their region. This study attempted to accomplish this by providing an easy-to-use Web interface at http://www.bloodsafety.info that allows decision makers to adapt this model to local conditions., Study Design and Methods: The cost-effectiveness was compared of 1) adding antigen screening to antibody screening for hepatitis C virus (HCV) and human immunodeficiency virus (HIV); 2) adding nucleic acid amplification testing (NAT) on hepatitis B virus (HBV), HCV, and HIV in minipool (pool of 6 [MP6] and 24 [MP24]) to antibody screening and hepatitis B surface antigen (HBsAg) screening; and 3) individual-donation NAT on HBV, HCV, and HIV to antibody screening and HBsAg screening for Ghana, Thailand, and the Netherlands., Results: The combination of HCV antibody-antigen combination (combo) and HIV combo added to antibody screening in Ghana and Thailand was cost-effective according to the WHO criteria. MP24-NAT screening in Ghana was also cost-effective. MP24-NAT on HBV, HCV, and HIV was not cost-effective compared to the other screening strategies evaluated for the Netherlands. Large regional differences in cost-effectiveness were found for Thailand., Conclusion: The young transfusion recipient population of Ghana in combination with a high risk of viral transmission yields better cost-effectiveness for additional tests. The advanced age of the transfused population of the Netherlands and a small risk of viral transmission gives poor cost-effectiveness for more sensitive screening techniques. It was demonstrated that a global health economic model combined with a Web interface can provide easy access to risk assessment and cost-effectiveness analysis.

Economic evaluations, in particular cost-effectiveness, are important determinants for policy makers and stakeholders involved in decision-making for health interventions. Up until now, most evaluations of cost-effectiveness of hepatitis B vaccination have been performed in developed countries. Appropriate health-economic studies on this topic specifically targeted at the developing world are essential in order to justify adding another vaccine into the existing Expanded Program on Immunization in these countries. We present a systematic review of economic evaluations of vaccination against HBV for developing and less-developed countries. Vaccine price, the discount rate, incidence and prevalence of HBV infection were found to be major drivers of cost-effectiveness. Data accuracy and reliability were also major issues, with major potentials for improvement in studies of these countries. The choice between monovalent or combination vaccines (diphteria, tetanus and polio-hepatitis B) poses new challenges to cost-effectiveness analysis. It is concluded that for many developing countries implementation of universal immunization against HBV to reduce the level of endemicity of hepatitis B is an appropriate strategy, and probably cost effective in many settings. Given their limited financial resources, developing countries should properly plan how to achieve this. Further country-specific economic evaluations and related gathering of high-quality data must be conducted in developing countries in order to raise both public awareness of the effectiveness and economic attractiveness of universal immunization against HBV.

Objectives: Areas with high HIV-incidence rates compared to the developed world may benefit from additional testing in blood banks and may show more favorable cost-effectiveness ratios. We evaluated the cost-effectiveness of adding p24 antigen, mini pool nucleic acid amplification testing (MP-NAT), or individual donation NAT (ID-NAT) to the HIV-antibody screening at the Korle Bu Teaching Hospital (Accra, Ghana), where currently only HIV-antibody screening is undertaken., Methods: The residual risk of HIV transmission was derived from blood donations to the blood bank of the Korle Bu Teaching Hospital in 2004. Remaining life expectancies of patients receiving blood transfusion were estimated using the World Health Organization life expectancies. Cost-effectiveness ratios for adding the tests to HIV-antibody screening only were determined using a decision tree model and a Markov model for HIV., Results: The prevalence of HIV was estimated at 1.51% in 18,714 donations during 2004. The incremental cost per disability-adjusted life-year (DALY) averted was US$1237 for p24 antigen, US$3142 for MP-NAT and US$7695 compared to the next least expensive strategy. HIV-antibody screening itself was cost-saving compared to no screening at all, gaining US$73.85 and averting 0.86 DALY per transfused patient. Up to a willingness-to-pay of US$2736 per DALY averted, HIV-antibody screening without additional testing was the most cost-effective strategy. Over a willingness-to-pay of US$11,828 per DALY averted, ID-NAT was significantly more cost-effective than the other strategies., Conclusions: Adding p24 antigen, MP-NAT, or ID-NAT to the current antibody screening cannot be regarded as a cost-effective health-care intervention for Ghana.

Introduction: beta-Blockers are known to worsen FEV(1) and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment., Objective: To determine the effects of beta-blockers on AHR (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)]), FEV(1), and response to formoterol in patients with COPD., Design: A double-blind, placebo-controlled, randomized, cross-over study., Setting: An ambulatory, hospital outpatient clinic of pulmonary diseases., Patients: Patients with mild-to-moderate irreversible COPD and AHR., Intervention: Fifteen patients received propranolol (80 mg), metoprolol (100 mg), celiprolol (200 mg), or placebo for 4 days, followed by a washout period >/= 3 days. On day 4 of treatment, FEV(1) and PC(20) were assessed. Immediately hereafter, formoterol (12 microg) was administered and FEV(1) was measured for up to 30 min., Results: PC(20) was significantly lower (p < 0.01) with propranolol and metoprolol treatment (geometric means, 2.06 mg/mL and 2.02 mg/mL, respectively) than with placebo (3.16 mg/mL) or celiprolol (3.41 mg/mL). FEV(1) deteriorated only after propranolol treatment (2.08 +/- 0.31 L) [mean +/- SD] compared with placebo (2.24 +/- 0.37 L). The fast bronchodilating effect of formoterol was hampered by propranolol (mean increase in FEV(1) at 3 min, 6.7 +/- 8.9%) but was unaffected by the other beta-blockers (16.9 +/- 9.8%, 22 +/- 11.6%, and 16.9 +/- 9.0% for placebo, metoprolol, and celiprolol, respectively)., Conclusions: Pulmonary effects did not occur by celiprolol. Only propranolol reduced FEV(1) and the bronchodilating effect of formoterol. Both metoprolol and propranolol increased AHR. Thus, different classes of beta-blockers have different pulmonary effects. The anticipated beneficial cardiovascular effects of a beta-blocker must be weighted against the putative detrimental pulmonary effects, ie, effect on FEV(1), AHR, and response to additional beta(2)-agonists.