Potential increased risk of virus transmission due to exclusion of older donors because of concern over Creutzfeldt-Jakob disease. The National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study

BACKGROUND: Concern over the theoretical possibility of disease transmission via blood from donors who develop Creutzfeldt-Jakob disease has led to proposals to exclude older individuals from donating plasma for further manufacture into pooled plasma donations. The impact of extending this age-deferral policy to blood donors was examined with respect to the risk for known transmissible viruses. STUDY DESIGN AND METHODS: Demographic characteristics and confirmed prevalence rates (/10(5) first-time donations) and incidence rates (/10(5) person-years for repeat donors) for viral markers were compared for donors < 50 years old (n = 1,259,805 [85%]) and > or = 50 years old (n = 219,856 [15%]) and for donors < 60 years old (n = 1,409,176 [95%]) and > or = 60 years old (n = 70,485 [5%]). Incidence rates were combined with infectious window-period estimates for each virus, to calculate the risk of virus transmission per 10(6) donations. RESULTS: Unadjusted prevalence rates were significantly greater for younger than for older donor groups for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) (p < or = 0.05). Incidence rates (and transmission risk estimates) for HBsAg were significantly higher in the < 50 donor group than in the > or = 50 group (p < or = 0.05), and those for HIV, human T-lymphotropic virus, and HCV were not significantly higher (p > 0.05). Blanket removal of donors over the age of 50 would potentially lead to the following significant increases in the risk of infected units: HIV, 12 percent; HCV, 21 percent; and hepatitis B virus (HBsAg), 22 percent. CONCLUSION: Removal of donors over the age of 60 would not significantly affect the risk of infected units. Deferral of donors > or = 50 years of age from whole-blood donations for unfounded concerns about Creutzfeldt-Jakob disease could have adverse effects on both blood availability and safety.     

Inactivation of human immunodeficiency virus by gamma radiation and its effect on plasma and coagulation factors

The inactivation of HIV by gamma-radiation was studied in frozen and liquid plasma; a reduction of the virus titer of 5 to 6 logs was achieved at doses of 5 to 10 Mrad at -80 degrees C and 2.5 Mrad at 15 degrees C. The effect of irradiation on the biologic activity of a number of coagulation factors in plasma and in lyophilized concentrates of factor VIII (FVIII) and prothrombin complex was examined. A recovery of 85 percent of the biologic activity of therapeutic components present in frozen plasma and in lyophilized coagulation factor concentrates was reached at radiation doses as low as 1.5 and 0.5 Mrad, respectively. As derived from the first-order radiation inactivation curves, the radiosensitive target size of HIV was estimated to be 1 to 3 MDa; the target size of FVIII was estimated to be 130 to 160 kDa. Gamma radiation must be disregarded as a method for the sterilization of plasma and plasma-derived products, because of the low reduction of virus infectivity at radiation doses that still give acceptable recovery of biologic activity of plasma components.     

Resolution of infection status of human immunodeficiency virus (HIV)- seroindeterminate donors and high-risk seronegative individuals with polymerase chain reaction and virus culture: absence of persistent silent HIV type 1 infection in a high-prevalence area

To address concerns over the prevalence of silent (antibody-negative) infections among blood donors and high-risk populations, a combination of proviral amplification by polymerase chain reaction (PCR) and viral isolation by co-culture techniques was employed to resolve the human immunodeficiency virus type 1 (HIV-1) infection status of well-characterized groups of suspect blood donors and others identified in the blood bank setting. No silent infections were found in 65 follow-up samples from 26 persistently HIV-1-seroindeterminate blood donors, 16 persistently seronegative heterosexual partners of infected transfusion recipients, and 6 high-risk seronegative homosexual men identified through donor look-back investigations. In contrast, 21 seropositive controls tested positive. These results suggest a low prevalence of persistently silent infections in at-risk populations, even in high HIV prevalence regions. The PCR assay, with a co-detected internal positive control, and appropriate confirmatory algorithms, was found to be a useful direct assay to rule out infection, especially in concert with confirmatory virus isolation.     

Epidemiology and costs of hypertension-related disorders

Epidemiological surveys demonstrate undoubtedly that cardiovascular disorders caused or associated with hypertension are at a high risk of non-fatal or fatal events and occurring with a great rate. Ischaemic heart disease with effort angina and myocardial infarction, often unrecognized myocardial infarction, stroke and transient ischaemic attack may be observed more frequently than other cardiovascular disorders in hypertensive patients. Large-scale trials do not support the hypothesis that effective benefits are reached by current non-pharmacological or pharmacological prevention which need enormous costs to public health. Lowering blood pressure is the main target to reach in an attempt to reduce cardiovascular complications in hypertensive patients. Therefore, the costs-benefit ratio, which estimates public health costs, needs yet marked improvement since the public health expenses are heaviest with results that do not support the economic effort. Statistically, quantitative measures to modify the current regimen need to better evaluate both public health costs and reached benefits.     

Smoking and hypertension: effects on clinical, biochemical and pathological variables due to isolated or combined action on cardiovascular system

Changes in clinical, biochemical and pathological variables characterize cardiovascular damage from smoking and hypertension when it acts independently. However, combined action of these major risk factors increases the rate of cardiovascular events. Ischaemic heart disease with stable effort angina, myocardial infarction and post-infarction arrhythmias may affect cardiovascular system because of smoking exposure. Among cerebrovascular disease, there is evidence that stroke would be related primarily to active smoking. Isolated hypertension plays significantly major action to cause cerebrovascular disease including stroke, recurrent stoke and transient ischaemic attack. Among cardiac events, heart failure is, often, the end-point of hypertensive disease, even if manifestations of ischaemic heart disease similar to those caused by smoking may be increased in rate. Combined action of smoking and hypertension usually increases the rate of cardiovascular complications and leads to a progression of atherosclerosis with narrowing and plaque primarily at the the level of coronary, carotid and cerebrovascular arteries. A pattern specific of both active and passive smoking exposure, but not hypertension, is the thromboangiitis obliterans that dramatically worsens in continuing smokers while it can be improved by stopping smoking.     

Effect of tecarfarin,a novel vitamin K epoxide reductase inhibitor,on coagulation in beagle dogs

Background and purpose:

Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.

Experimental approach:

Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).

Key results:

Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K₁ treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.

Conclusions and implications:

Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients.     

Development of the Manchester framework for the evaluation of emergency department pharmacy services

International Journal of Clinical Pharmacy - Many countries, including the United Kingdom, have established Emergency Department (ED) pharmacy services where some ED pharmacists now work as...