Web interface-supported transmission risk assessment and cost-effectiveness analysis of postdonation screening:a global model applied to Ghana, Thailand, and the Netherlands

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

Tobramycin Clearance Is Best Described by Renal Function Estimates in Obese and Non-obese Individuals: Results of a Prospective Rich Sampling Pharmacokinetic Study

Purpose Tobramycin is an aminoglycoside antibiotic of which the 24 h exposure correlates with efficacy. Recently, we found that clearance of the aminoglycoside gentamicin correlates with total body weight (TBW). In this study, we investigate the full pharmacokinetic profile of tobramycin in obese and non-obese individuals with normal renal function. Methods Morbidly obese individuals (n = 20) undergoing bariatric surgery and non-obese healthy volunteers (n = 8), with TBW ranging 57–194 kg, received an IV dose of tobramycin with plasma concentrations measured over 24 h (n = 10 per individual). Statistical analysis, modelling and simulations were performed using NONMEM. Results In a two-compartment model, TBW was the best predictor for central volume of distribution (p< 0.001). For clearance, MDRD (de-indexed for body surface area) was identified as best covariate (p < 0.001), and was superior over TBW ((p < 0.05). Other renal function estimates (24 h urine GFR and de-indexed CKD-EPI) led to similar results as MDRD (all p < 0.001)). Conclusions In obese and non-obese individuals with normal renal function, renal function estimates such as MDRD were identified as best predictors f

A Prospective Clinical Study Characterizing the Influence of Morbid Obesity on the Pharmacokinetics of Gentamicin: Towards Individualized Dosing in Obese Patients

Background and Objective Gentamicin is an aminoglycoside antibiotic predominantly used in bloodstream infections. Although the prevalence of obesity is increasing dramatically, there is no consensus on how to adjust the dose in obese individuals. In this prospective clinical study, we study the pharmacokinetics of gentamicin in morbidly obese and non-obese individuals to develop a dosing algorithm that results in adequate drug exposure across body weights. Methods Morbidly obese subjects undergoing bariatric surgery and non-obese healthy volunteers received one intravenous dose of gentamicin (obese: 5 mg/kg based on lean body weight, non-obese: 5 mg/kg based on total body weight [TBW]) with subsequent 24-h sampling. All individuals had a normal renal function. Statistical analysis, modelling and Monte Carlo simulations were performed using R version 3.4.4 and NONMEM® version 7.3. Results A two-compartment model best described the data. TBW was the best predictor for both clearance [CL = 0.089 × (TBW/70)0.73] and central volume of distribution [Vc = 11.9 × (TBW/70)1.25] (both p < 0.001). Simulations showed how gentamicin exposure changes across the weight range with currently used dosing algorithms and illustrated that using a nomogram based on a ‘dose weight’ [70 × (TBW/70)0.73] will lead to similar exposure across the entire population. Conclusions In this study in morbidly obese and non-obese individuals ranging from 53 to 221 kg we identifed body weight as an important determinant for both gentamicin CL and Vc. Using a body weight-based dosing algorithm, optimized exposure across the entire p

Cost-effectiveness of HIV screening of blood donations in Accra (Ghana)

AbstractObjectivesAreas 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.MethodsThe 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.ResultsThe 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.ConclusionsAdding p24 antigen, MP-NAT, or ID-NAT to the current antibody screening cannot be regarded as a cost-effective health-care intervention for Ghana

Hepatitis C virus in hemophilia:Health-related quality of life after successful treatment in the sixth Hemophilia in the Netherlands study

INTRODUCTION: Persons with hemophilia and hepatitis C virus (HCV) infection have a lower health‐related quality of life (HRQoL) than those never HCV infected. However, it is unknown whether HRQoL after HCV eradication is comparable to individuals never HCV infected. We aimed to compare HRQoL between HCV‐cured and never chronically HCV‐infected persons with hemophilia. METHODS: All persons with hemophilia in the Netherlands were invited for a nationwide study conducted in 2018–2019. For the current analysis, participants born before 1992 with data on HRQoL and HCV status were included. HCV status was collected from medical records. HRQoL was measured by RAND‐36 questionnaire, with a minimally important difference set at 4.0 points. Multivariable linear regression was used to adjust for age, hemophilia severity, HIV status, and self‐reported joint impairment. RESULTS: In total, 486 persons were eligible; 180 were HCV cured and 306 never chronically HCV infected. Compared with those never HCV infected, HCV‐cured individuals were older (57 vs. 53 years), more often had severe hemophilia (67% vs. 21%), and reported more impaired joints (median 3 vs. 0). Compared with those never HCV infected, adjusted RAND‐36 domain scores of HCV‐cured individuals cured were lower on all RAND‐36 domains except Pain, ranging from a difference of 4.5 (95% CI, −8.8 to −0.3) for Physical functioning to 11.3 (95% CI, −19.4 to −3.1) for Role limitations due to physical problems. CONCLUSION: Despite effective HCV treatment, HRQoL of HCV‐cured persons with hemophilia is still lower than HRQoL of those never chronically HCV‐infected on all RAND‐36 domains. This implies that careful psychosocial follow‐up and support are indicated

Socioeconomic participation of persons with hemophilia:Results from the sixth hemophilia in the Netherlands study

Background and objectives Treatment availability and comprehensive care have resulted in improved clinical outcomes for persons with hemophilia. Recent data on socioeconomic participation in the Netherlands are lacking. This study assessed participation in education, in the labor market, and social participation for persons with hemophilia compared with the general male population. Methods Dutch adults and children (5-75 years) of all hemophilia severities (n = 1009) participated in a questionnaire study that included sociodemographic, occupational, and educational variables. Clinical characteristics were extracted from electronic medical records. General population data were extracted from Statistics Netherlands. Social participation was assessed with the PROMIS Ability to Participate in Social Roles and Activities short form, with a minimal important difference set at 1.0. Results Data from 906 adults and children were analyzed. Participation in education of 20 to 24 year olds was 68% (general male population: 53%). Educational attainment was higher compared with Dutch males, especially for severe hemophilia. Absenteeism from school was more common than in the general population. The employment-to-population ratio and occupational disability were worse for severe hemophilia than in the general population (64.3% vs. 73.2% and 14.7% vs. 4.8%, respectively), but similar for nonsevere hemophilia. Unemployment was 5.4% (general male population: 3.4%). Absenteeism from work was less common (38% vs. 45.2%). Mean PROMIS score was similar to or higher than in the general population (54.2; SD 8.9 vs. 50; SD 10). Conclusion Socioeconomic participation of persons with nonsevere hemophilia was similar to the general male population. Some participation outcomes for persons with severe hemophilia were reduced

Desmopressin in nonsevere hemophilia A:patient perspectives on use and efficacy

Background: Desmopressin increases plasma factor VIII and von Willebrand factor levels in persons with nonsevere hemophilia A. Patients’ perspectives on desmopressin are relevant to increase and optimize its suboptimal use. However, patients’ views on desmopressin are not reported. Objectives: To evaluate the perspectives of persons with nonsevere hemophilia A on desmopressin use, barriers for its use, side effects, and their knowledge about desmopressin's efficacy and side effects. Methods: Persons with nonsevere hemophilia A were included in a cross-sectional, national, multicenter study. Questionnaires were filled out by adult patients and children aged ≥12 years themselves. Caretakers filled out questionnaires for children aged &lt;12 years. Results: In total, 706 persons with nonsevere hemophilia A were included (544 mild, 162 moderate, [age range, 0–88 years]). Of 508 patients, 234 (50%) patients reported previous desmopressin use. Desmopressin was considered as at least moderately effective in 171 of 187 (90%) patients. Intranasal administration was the modality of choice for 138 of 182 (76%) patients. Flushing was the most reported side effect in 54 of 206 (26%) adults and 7 of 22 (32%) children. The most frequently reported advantage and disadvantage were the convenience of intranasal, out-of-hospital administration by 56% (126/227) and side effects in 18% (41/227), respectively. Patients’ self-perceived knowledge was unsatisfactory or unknown in 28% (63/225). Conclusion: Overall, desmopressin was most often used intranasally and considered effective, with flushing as the most common side effect. The most mentioned advantage was the convenience of intranasal administration and disadvantage was side effects. More information and education on desmopressin could answer unmet needs in patients with current or future desmopressin treatment.</p

Validation of PROMIS Profile-29 in adults with hemophilia in the Netherlands

Background The Patient-Reported Outcomes Measurement Information System (PROMIS) Profile-29 questionnaire is widely used worldwide, but it has not yet been validated in the Netherlands, nor in persons with hemophilia. Objective To validate the Dutch-Flemish version of the PROMIS-29 Profile v2.01 in adults with hemophilia. Methods Dutch males with hemophilia (all severities) completed questionnaires that contained sociodemographic and clinical characteristics, the PROMIS-29, RAND-36, and the Hemophilia Activities List (HAL). Structural validity of each subscale was assessed with confirmatory factor analysis (CFA). Internal consistency was calculated for each subscale with sufficient model fit in CFA. Construct validity was assessed by testing hypotheses about (1) correlations of each PROMIS-29 subscale with corresponding scales of RAND-36 and domains of HAL, and (2) mean differences in T-scores between subgroups with different hemophilia severities, self-reported joint impairment, and HIV infection status. We considered &gt;= 75% of data in accordance with the hypotheses evidence for construct validity. Results In total, 770 persons with hemophilia participated in this cross-sectional study. CFA revealed sufficient structural validity for five subscales: Physical Function, Depression, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. Internal consistency was high and Cronbach's alpha ranged from 0.79 for Sleep Disturbance to 0.96 for Pain Interference. Differences between clinical subgroups were in the expected direction. Construct validity was confirmed for Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, and Pain Intensity. Conclusion This study revealed sufficient evidence for structural validity, internal consistency, and construct validity for most PROMIS Profile-29 subscales among people with hemophilia in the Netherlands.</p