Inappropriate non-vitamin K antagonist oral anticoagulants prescriptions: be cautious with dose reductions.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are prescribed to patients with atrial fibrillation (AF) to reduce the risk of stroke. Prescribing the correct dose warrants careful consideration of the prevailing dose criteria that differ per NOAC. Electronic systems are useful to intercept prescriptions that are incorrect based on simple 'primary' criteria, for example dosing frequency and drug-drug interactions with concomitant medication. However, these systems do not take into account patient characteristics such as age, renal function or weight, which are crucial elements to determine the NOAC dose. METHODS: Our goal was to determine the appropriateness of all prescriptions, as compared with the product labelling approved by the European Medicines Agency, to address common pitfalls in prescribing NOACs. AF patients with a first NOAC prescription between January 2012 and December 2016 were identified from our electronic hospital information system (Martini Hospital, Groningen, the Netherlands). RESULTS: The study included 3,231 AF patients who had started on an NOAC; 10.7% received an inappropriate dose and the appropriateness of the prescription could not be determined in 14.1%. Underdosing and overdosing occurred in 5.4% and 4.5% of all prescriptions, respectively. A reduced-dose NOAC was a predictor for incorrect prescribing (odds ratio: 2.70, 95% confidence interval: 2.13-3.41). Patient factors were identified that predicted incorrect prescriptions for dabigatran and apixaban. CONCLUSION: An incorrect prescription occurred more often in the reduced-dose NOAC group. Clinical parameters such as renal function are often unknown whilst these are essential to determine the right NOAC and dose.

An assessment of differences in costs and health benefits of serology and NAT screening of donations for blood transfusion in different Western countries.

BACKGROUND AND OBJECTIVES: The cost-utility of safety interventions is becoming increasingly important as a driver of implementation decisions. The aim of this study was to compare the cost-utility of different blood screening strategies in various settings, and to analyse the extent and cause of differences in health economic results. MATERIALS AND METHODS: For eight Western countries (Australia, Canada, Denmark, Finland, France, The Netherlands, UK and the United States of America), data were collected on donor and recipient populations, blood products, screening tests, and on patient treatment practices and costs. An existing ISBT web-tool model was used to assess the cost-utility of various strategies for HIV, HCV and HBV screening. RESULTS: The cost-utility ratio of serology screening for these eight countries ranges between -11 000 and 92 000 US$ per QALY, and for NAT between -12 000 and 113 000 US$ per QALY when compared to no screening. Combined serology and NAT ranges between 600 and 217 000 US$ per QALY. The incremental cost-utility of NAT after implementation of serology screening ranges from 2 231 000 to 15 778 000 US$ per QALY. CONCLUSION: There are substantial differences in costs per QALY between countries for various HIV, HBV and HCV screening strategies. These differences are primarily caused by costs of screening tests and infection rates in the donor population. Within each country, similar cost per QALY results for serology and NAT compared to no screening, coupled with evidence of limited value of serology and NAT together prompts the need for further discussion on the acceptability of parallel testing by serology and NAT.

Development of a web-based application and multicountry analysis framework for assessing interdicted infections and cost-utility of screening donated blood for HIV, HCV and HBV.

BACKGROUND AND OBJECTIVES: Most countries test donations for HIV, HCV and HBV using serology with or without nucleic acid testing (NAT). Cost-utility analyses provide information on the relative value of different screening options. The aim of this project was to develop an open access risk assessment and cost-utility analysis web-tool for assessing HIV, HCV and HBV screening options (http://www.isbtweb.org/working-parties/transfusion-transmitted-infectious-diseases/). An analysis for six countries (Brazil, Ghana, the Netherlands, South Africa, Thailand and USA) was conducted. MATERIALS AND METHODS: Four strategies; (1) antibody assays (Abs) for HIV and HCV + HBsAg, (2) antibody assays that include antigens for HIV and HCV (Combo) + HBsAg, (3) NAT in minipools of variable size (MP NAT) and (4) individual donation (ID) NAT can be evaluated using the tool. Country-specific data on donors, donation testing results, recipient outcomes and costs are entered using the online interface. Results obtained include the number infections interdicted using each screening options, and the (incremental and average) cost-utility of the options. RESULTS: In each of the six countries evaluated, the use of antibody assays is cost effective or even cost saving. NAT has varying cost-utility depending on the setting, and where adopted, the incremental cost-utility exceeds any previously defined or proposed threshold in each country. CONCLUSION: The web-tool allows an assessment of infectious units interdicted and value for money of different testing strategies. Regardless of gross national income (GNI) per capita, countries appear willing to dedicate healthcare resources to blood supply safety in excess of that for other sectors of health care.

Health-related quality of life in HIV/AIDS patients on antiretroviral therapy at a tertiary care facility in Zimbabwe.

Health-related quality of life (HRQoL) is a broad concept reflecting a patient's general subjective perception of the effect of an illness or intervention on physical, psychological and social aspects of their daily life. HRQoL among patients infected with HIV has become an important indicator of impact of disease and treatment outcomes. A cross-sectional survey was carried out at Chitungwiza Central Hospital, Zimbabwe, to assess HRQoL in patients with HIV/AIDS receiving antiretroviral therapy (ART), using two validated instruments. The HIV/AIDS-targeted quality of life (HAT-QoL) and EuroQoL Five-dimensions-Three-level (EQ-5D-3L) instruments were used to assess HRQoL. Internal consistency reliability and convergent validity of the two instruments were also evaluated. For construct validity, the relationships between HRQoL scores and socio-economic and HIV/AIDS-related characteristics were explored. The median scores for the HAT-QoL dimensions ranged from 33.3 (financial worries) to 100 (HIV mastery). A considerably low HAT-QoL dimension score of 50.0 was observed for sexual function. There were ceiling effects for all HAT-QoL dimension scores except for financial worries and disclosure worries. Floor effects were observed for financial worries and sexual function. The median of the EQ-5D-3L index and visual analogue scale (VAS) was 0.81 and 79.0, respectively. There were no floor or ceiling effects for both the EQ-5D-3L index and VAS. The overall scale Cronbach's alpha was 0.83 for HAT-Qol and 0.67 for EQ-5D-3L. HAT-QoL demonstrated good convergent validity with EQ-5D index (0.58) and VAS (0.40). A higher level of HRQoL was positively and significantly related to income, education and employment. The patients' self-reported HRQoL was generally satisfactory in all the HAT-QoL dimensions as well as the two components on the EQ-5D-3L instrument. The two instruments demonstrated good measurement properties in HIV/AIDS patients receiving ART and have potential for use, alongside biomarkers, in monitoring outcomes of interventions.

Screening for Atrial Fibrillation in Sub-Saharan Africa: A Health Economic Evaluation to Assess the Feasibility in Nigeria.

Background: Cardiovascular disease reflects a major burden of non-communicable disease in Sub-Saharan Africa (SSA). Early detection and treatment of atrial fibrillation (AF), as a preventive measure against stroke, is currently not in the scope of the World Health Organization recommendation to reduce cardiovascular disease. Objective: We hypothesized that screening for AF would be an important approach to determine the true AF prevalence in the general population in African countries and to identify asymptomatic AF patients at risk for stroke to optimize prevention. Methods: A decision analytic model was developed to study the health-economic impact of AF screening in Nigeria over a life-time horizon. The patient population explored in the model was a population of newly detected AF cases that would be diagnosed with a one-time systematic screening for AF with a single lead ECG device in community health centres across Nigeria. Conclusions: The health gain per newly detected AF patient (N = 31,687) was 0.41 QALY at a cost of $5,205 per patient with 100% NOAC use, leading to an ICER of $12,587 per QALY gained. The intervention was cost-effective with a 99.9% warfarin use with an ICER of $1,363 per QALY gained. The total cost of a single screening session was $7.3 million for the total screened population in Nigeria or $1.60 per patient screened. Screening for AF to detect AF patients in need for stroke prevention can be a cost-effective intervention in the Sub-Saharan region, depending on type of anticoagulant used and drug costs.

Predictors for total hospital and cardiology cost claims among patients with atrial fibrillation initiating dabigatran or acenocoumarol in The Netherlands.

AIMS: The prevalence of atrial fibrillation (AF) has increased over the past years due to aging of the population, and healthcare costs associated with AF reflect a significant financial burden. The aim of this study was to explore predictors for the real-world AF-related in-hospital costs in patients that recently initiated anticoagulation with acenocoumarol or dabigatran. METHODS: Predictors for claimed total hospital care costs and cardiology costs in AF patients were explored by using hospital financial claims data from propensity score matched patient groups in a large Dutch community hospital. This study analyzed the total dataset (n = 766) and carried out a secondary analysis for all matched pairs of anticoagulation naïve AF patients (n = 590) by ordinal regression. RESULTS: Dabigatran was a predictor for significantly lower cardiology and total hospital care costs (Odds Ratio [OR] = 0.43, 95% confidence interval (CI) = 0.33-0.57; and OR = 0.60, 95% CI = 0.46-0.79, respectively). Female gender was a predictor for lower total hospital care costs. Predictors for an increase in total hospital care costs were the occurrence of stroke or systemic embolism, major bleeding, and minor bleeding. The costs predictors were comparable when limiting the analysis to patients that were anticoagulation naïve. Age and CHA2DS2-VASc were not predictors for either cardiology or total hospital care costs in both analyses. CONCLUSION: Dabigatran treatment was as a predictor for lower cardiology costs and lower total hospital care costs in AF patients that initiated oral anticoagulation.

Cost-effectiveness of pathogen inactivation for platelet transfusions in the Netherlands.

The objective of this study is to estimate cost-effectiveness of pathogen inactivation for platelet transfusions in the Netherlands. We used decision tree analysis to evaluate the cost-effectiveness of the addition of pathogen inactivation of pooled platelets to standard procedures for platelet transfusion safety (such as, donor recruitment and screening). Data on transfusions were derived from the University Medical Centre Groningen (the Netherlands) for 1997. Characteristics of platelet recipients (patient group, age, gender and survival) and data/assumptions on viral and bacterial risks were linked to direct and indirect costs/benefits of pathogen inactivation. Post-transfusion survival was simulated with a Markov model. Standard methods for cost-effectiveness were used. Cost-effectiveness was expressed in net costs per life-year gained (LYG) and estimated in baseline- and sensitivity analysis. Sensitivity was analysed with respect to various assumptions including sepsis risk, reduction of the discard rate and discounting. Stochastic analysis to derive 90% simulation intervals (SIs) was performed on sepsis risk. Net costs per LYG for pathogen inactivation were estimated 554,000 euro in the baseline-weighted average over the three patient groups (90% SI: 354,000-1092,500 euro). Sensitivity analysis revealed that cost-effectiveness was insensitive to viral risks and indirect costing, but highly sensitive to the assumed excess transfusions required and discounting of LYG. Given relatively high net costs per LYG that are internationally accepted for blood transfusion safety interventions, our estimated cost-effectiveness figures for pathogen inactivation may reflect acceptable cost-effectiveness in this specific area. Two main assumptions of our model were that the pathogen inactivation was 100% effective in preventing transmission of the pathogens considered and was not associated with major and/or costly adverse reactions. Validation of several crucial parameters is required, in particular the Dutch risk for acquiring and dying of transfusion-related sepsis.

Cost-effectiveness of leucocyte-depleted erythrocyte transfusion in cardiac valve surgery.

Cost-effectiveness of leucodepleted erythrocytes (LD) over buffy-coat-depleted packed cells (PC) is estimated from the primary dataset of a recently reported randomized clinical trial involving valve surgery (+/-CABG) patients. Data on the patient level of 474 adult patients who were randomized double-blind to LD or PC were used in order to calculate the healthcare costs and longevity per patient. The incremental cost-effectiveness ratio (ICER) in net costs per life-year gained was established from the healthcare perspective. Bootstrapping and cost-effectiveness acceptability curves were used in order to determine the confidence interval (CI) of the ICER. The longevity of patients in the PC and LD group was 10.6 and 11.4 years, respectively. Relative to PC, LD yielded an estimated 0.8 (95% CI = -0.27 to 1.84) life-year in the baseline. Adjusted for age and sex differences, health gains for LD are 0.4 life-year gained (95% CI = -0.67 to 1.44). Healthcare costs per patient averaged 10163 US dollars per patient in the PC group and 9949 US dollars in the LD group. Average cost-savings were 214 US dollars (95% CI = -1536 to 1964) per patient. Acceptability curves constructed from bootstrap simulations showed a probability of being cost-saving of 59% for universal leucodepletion from the healthcare perspective. The probability of adopting leucodepletion regardless of the costs reaches 92.7%. LD in patients receiving four or more transfusions showed the highest cost-savings and health gains. Leucodepletion of erythrocytes is a cost-saving strategy in cardiac valve (+/-CABG) patients. However, probablistic analysis failed to show a significant difference with buffy-coat-depleted PC.

Pharmaco-economics of blood transfusion safety: review of the available evidence.

BACKGROUND AND OBJECTIVES: Pharmaco-economics provides a standardized methodology for valid comparisons of interventions in different fields of health care. The role of pharmaco-economics in the safety of blood and blood products has, however, been very limited to date. This review discusses the pharmaco-economic evaluations of strategies to enhance blood product safety that have been published in the scientific literature. MATERIALS AND METHODS: We reviewed pharmaco-economic methodology with special reference to cost-effectiveness analysis. We searched the literature for cost-effectiveness in blood product safety. RESULT: Net costs per quality adjusted life-year (QALY) gained varied from cost-saving for human immunodeficiency virus (HIV)- and hepatitis C virus (HCV) antibody screening and leucoreduction to several million US dollars per QALY gained for solvent-detergent treatment of plasma, nucleic acid amplification testing and HIV p24 antigen testing. CONCLUSIONS: To date the safety of blood transfusion has been largely determined by available technology, irrespective of pharmaco-economics. Net costs up to several million US dollars per QALY gained were found for interventions implemented.