A risk assessment model for transfusion transmission of dengue.

Dengue virus (DENV) is a disease-causing agent normally transmitted from person to person through the bite of an infected mosquito. In addition to mosquito-borne cases of dengue, there are instances of transmission of dengue after receipt of blood products or donor organs or tissue. To improve blood safety, we developed a quantitative risk assessment model to estimate the dengue risk of transmission to blood transfusion recipients from preclinical and subclinical blood donors. We derived predictive coefficients from model simulations for predicting the risk outcomes such as monthly infectious blood units and transfusion-transmitted DENV cases based on the rate of reported clinical cases. The model was validated with a previous study where donor blood samples from the 2012 dengue transmission season in Rio de Janeiro, Brazil were tested for DENV RNA by a transcription-mediated amplification (TMA) assay. In that study, about 69·4% of donations were tested by the TMA assay and 78 samples were found positive, indicating that 112 DENV RNA-positive donations would have been detected if testing screening had been performed on all donations. Our model estimated a mean of 93 (2.5-97.5th%ile: 47-186) infected units among the donations, which was consistent with the reported numbers.

Comparison of hemagglutination inhibition and hemagglutinin pseudovirus neutralization titres in relation to protection against influenza in a mouse model.

The hemagglutination inhibition (HI) test has long been used as a standard measure of antibody response for inactivated influenza vaccines. However, the HI test has limitations, such as insensitivity when using some H3N2 virus strains and failure to detect neutralizing antibodies that target regions distant from the receptor binding site. We therefore examined a hemagglutinin pseudovirus neutralization (PVN) test as a possible supplement or alternative to the HI test. We evaluated the association of HI or PVN titres with protection against influenza infection in mice based on morbidity (where the illness was defined as 25% body weight loss). We assessed this relationship using dose-response models incorporating HI or PVN titres as a variable. The morbidity was correlated with the pre-exposure titres, and such a correlation was well described by a modified dose-response model. The mathematical modelling suggests that PVN titres consistently show a stronger association with in vivo protection as compared to HI titres in mice. Given our findings, the PVN test warrants further investigation as a tool for evaluating antibody responses to influenza vaccines containing hemagglutinin. The resulting models may also be useful for analyzing human clinical data to identify potentially protective antibody titres against influenza illness.

A modified dose-response model that describes the relationship between haemagglutination inhibition titre and protection against influenza infection.

AIMS: Develop a model for quantifying the risk of an adverse human response to influenza virus infection as a function of exposure dose and pre-exposure antibody titre level. METHODS AND RESULTS: We evaluated the relationship between haemagglutination inhibition (HI) titre (as a measure of specific antibody response) and protection against influenza infection and modelled this relationship by incorporating HI titre as a variable into dose-response models. Using a maximum likelihood estimation approach, the resulting model was capable of providing statistically acceptable fits to most available data. CONCLUSIONS: The incorporated HI titre dependency in the model quantifies the protective effect of antibody titre. The modelling can be used to predict the protection effectiveness associated with elevated HI titre levels post vaccination to different levels of exposures. SIGNIFICANCE AND IMPACT OF THE STUDY: The study incorporates HI titre level as a variable into a dose-response model for influenza infection. The approaches developed in this study could be used to evaluate other factors associated with the predictability of HI titre or other surrogate endpoints for influenza vaccines.

Predicting dose sparing benefit and bleeding risk of pharmacokinetic-based personalized prophylactic dosing of factor VIII products.

BACKGROUND: Previously published factor VIII (FVIII) pharmacokinetic (PK)-based dosing approaches employ fixed infusion interval with a wide dose range that may lead to increased risk of bleeding, excessive doses or decreased health-related quality of life. AIM: The objectives of the study includes (i) personalizing infusion interval in lieu of fixed infusion, (ii) constraining dose within the range of 10-50 IU/kg and (iii) characterizing bleeding risk of PK-based dosing in comparison with empiric standard doses. METHODS: Patient demographics and PK parameters for conventional FVIII products were obtained from published literatures. Subject-specific PK parameters were derived from FVIII activities vs time data generated through simulation. RESULTS: Our data indicated approximately 4%, 38%, 37% and 20% of the subjects can be dosed with infusion interval of every 24, 48, 72 and 96 hours, respectively, for maintaining a target 1 IU/dL FVIII level within the dose range of 10-50 IU/kg. Maintaining an alternative trough value of 3 or 5 IU/dL requires more frequent infusion. The predicted median probability of bleeding risk per year was 35.7% (range, 11%-49%) for PK-based dosing maintaining 1 IU/dL. Predicted median bleeding risk was 37.9% (0%-74%), 32.8% (0%-72%) and 26.7% (0%-70%) for standard dosing of 20, 30 and 50 IU/kg, respectively. PK-based dosing resulted in a dose sparing benefit compared to standard dose of 30 or 50 IU/kg three times per week. CONCLUSION: The results of the study demonstrate the feasibility of individualizing infusion interval, restricting FVIII dose, trough and peak concentration within an acceptable range.

Clotting factor product administration and same-day occurrence of thrombotic events, as recorded in a large healthcare database during 2008-2013.

BACKGROUND: Thrombotic events (TEs) are serious adverse events that can occur following administration of clotting factors (CFs). OBJECTIVES: To evaluate occurrence of same-day TEs for different CF products and potential risk factors. METHODS: A retrospective cohort study of individuals exposed to CF products during 2008-2013 was conducted using a large commercial insurance database. CF products were identified by procedure codes, and TEs were ascertained via diagnosis codes. Crude same-day TE rates (per 1000 persons exposed) were estimated overall and by congenital factor deficiency (CFD) status, CF products, age and gender. Multivariable logistic regression analyses were used to control for confounding. Laboratory analysis was used to compare the procoagulant activities of FIX products. RESULTS: Of 3801 individuals exposed to CFs, 117 (30.8 per 1000) had same-day TEs recorded. The crude same-day TE rate was higher for CF users without CFD, 70.2 (102 of 1452), as compared with those with CFD, 6.4 (15 of 2349) (RR, 11.0; 95% CI, 6.4-18.9). For individuals without CFD, a significantly increased same-day TE risk was identified for factor IX complex (OR, 6.92; 95% CI, 3.11-15.40), factor VIIa (OR, 9.42; 95% CI, 4.99-17.78) and other products when compared with fibrin sealant. An increased risk of a TE was found with older age (≥ 45 years), history of TEs and underlying health conditions. The laboratory identified elevated procoagulant activity in Profilnine(®) and Benefix(®) . CONCLUSIONS: The study shows an increased same-day TE risk for CF users without CFD and suggests substantial off-label CF use. The study findings also show elevated same-day TE rates for different CF products and suggest the importance of product properties and patient factors.

Febrile non-haemolytic transfusion reaction occurrence and potential risk factors among the U.S. elderly transfused in the inpatient setting, as recorded in Medicare databases during 2011-2012.

BACKGROUND AND OBJECTIVES: Febrile non-haemolytic transfusion reaction (FNHTR) is an acute transfusion complication resulting in fever, chills and/or rigours. Study's objective was to assess FNHTR occurrence and potential risk factors among inpatient U.S. elderly Medicare beneficiaries, ages 65 and older, during 2011-2012. MATERIALS AND METHODS: Our retrospective claims-based study utilized large Medicare administrative databases. FNHTR was ascertained via ICD-9-CM diagnosis code, and transfusions were identified by recorded procedure and revenue centre codes. The study ascertained FNHTR rates among the inpatient elderly overall and by age, gender, race, blood components and units transfused. Multivariate logistic regression analyses were used to assess potential risk factors. RESULTS: Among 4 336 338 inpatient transfusion stays for elderly during 2011-2012, 2517 had FNHTR diagnosis recorded, an overall rate of 58.0 per 100,000 stays. FNHTR rates (per 100,000 stays) varied by age, gender, number of units and blood components transfused. FNHTR rates were substantially higher for RBCs- and platelets-containing transfusions as compared to plasma only. Significantly higher odds of FNHTR were identified with greater number of units transfused (P < 0.01), for females vs. males (OR = 1.15, 95% CI 1.04-1.27), and with 1-year histories of transfusion (OR = 1.25, 95% CI 1.10-1.42), lymphoma (OR = 1.22, 95% CI 1.02-1.46), leukaemia (OR = 1.90, 95% CI 1.56-2.31) and other diseases. CONCLUSIONS: Our study shows increased FNHTR occurrence among elderly with greater number of units and with RBCs- and platelets-containing transfusions, suggesting need to evaluate effectiveness of prestorage leucoreduction in elderly. The study also suggests importance of prior recipient alloimmunization and underlying health conditions in the development of FNHTR.

Transfusion-associated circulatory overload (TACO) and potential risk factors among the inpatient US elderly as recorded in Medicare administrative databases during 2011.

BACKGROUND AND OBJECTIVES: Transfusion-associated circulatory overload (TACO) is a serious transfusion complication resulting in respiratory distress. The study's objective was to assess TACO occurrence and potential risk factors among elderly Medicare beneficiaries (ages 65 and older) in the inpatient setting during 2011. MATERIALS AND METHODS: This retrospective claims-based study utilized Medicare administrative databases in coordination with Centers for Medicare & Medicaid Services. Transfusions were identified by recorded procedure and revenue centre codes, while TACO was ascertained via ICD-9-CM diagnosis code. We evaluated TACO diagnosis code rates overall and by age, gender, race, number of units and blood components transfused. Multivariate logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 2,147,038 inpatient transfusion stays for elderly in 2011, 1340 had TACO diagnosis code, overall rate of 62·4 per 100,000 stays. TACO rates increased significantly with age and units transfused (P < 0·0001). After adjustment for confounding, significantly higher odds of TACO were found for women vs. men (OR = 1·40, 95% CI 1·26-1·60), White people vs. non-White people (OR = 1·38, 95% CI 1·20-1·62) and persons with congestive heart failure (OR = 1·61, 95% CI 1·44-1·88), chronic pulmonary disease (OR = 1·19, 95% CI 1·08-1·32) and different anaemias. CONCLUSION: Our study identified largest number of potential TACO cases to date and showed a substantial increase in TACO occurrence with age and number of units transfused. The study suggested increased TACO risk in elderly with congestive heart failure, chronic pulmonary disease and anaemias. Overall, study shows importance of large administrative databases as an additional epidemiological tool.

Evaluation of the association of demographics and beverage consumption with dental caries.

There is much speculation about the role of carbonated soft drinks in the development of dental caries. We examine the relationships between certain demographic variables, beverage consumption, and professional dental care and their contribution to the number of decayed, missing, and filled surfaces (DMFS). The National Health and Nutrition Examination Survey III (NHANES III) conducted by the National Center for Health Statistics was used to examine DMFS among four age groups: 17-24 yr, 25-40 yr, 41-60 yr, and over 60 yr. Age has a strong, positive relationship with DMFS. About 15% of young adults aged 17-24 yr have no DMFS, and the average DMFS is only 10.4 in this age group. Less than 1% of adults over age 40 have a DMFS score of 0, and nearly one in five has the maximum of 128 DMFS. Controlling for other factors, whites have more DMFS than do blacks and Hispanics. Beverages have a weak, but statistically significant, relationship with DMFS among the older age groups only. Regular professional dental care was associated with lower DMFS among the older age groups. Age and ethnicity are the strongest predictors of DMFS. Young adults have fewer DMFS regardless of dietary factors. This study suggests that carbonated soft drinks are not associated with poor dental health. Useful strategies to reduce dental caries involve good personal dental hygiene, regular use of fluoridated toothpastes and mouthwashes, and regular care by dental professionals.

The role of added sugars in the diet quality of children and adolescents.

OBJECTIVE: The associations between added sugars intake and consumption of vitamins, minerals and servings of foods in the USDA Food Guide Pyramid were examined. METHODS: Data from the USDA 1994-96 Continuing Survey of Food Intakes by Individuals were used in multivariate regression analyses to assess the statistical and practical significance of added sugars intake for diet and nutrient adequacy. RESULTS: The association of added sugars with consumption of vitamins, minerals and servings of foods in the USDA Food Guide Pyramid was usually statistically significant. For the model of all individuals over two years of age, individuals who consume more added sugars are predicted to consume more grains, lean meat and iron and to consume fewer vegetables and fruits and less dairy, vitamin A, calcium and folates. Children who consume more added sugars are predicted to consume more grains, vitamin C, iron and folates and to consume less dairy. Adolescents who consume more added sugars are predicted to consume more grains, vitamin C and iron and less fruit. CONCLUSION: The associations, whether positive or negative, however, were always small from either a practical perspective or in comparison to the associations of other sources of energy.