Fresh frozen plasma (FFP) is prepared in blood banks world-wide as a by- product of red blood cell concentrate preparation. Appropriate clinical use is for coagulation factor disorders where appropriate concentrates are unavailable and when multiple coagulation factor deficits occur such as in surgery. Viral safety depends on donor selection and screening; thus, there continues to be a small but defined risk of viral transmission comparable with that exhibited by whole blood. We have prepared a virus sterilized FFP (S/D-FFP) by treatment of FFP with 1% tri(n-butyl)phosphate (TNBP) and 1% Triton X-100 at 30 degrees C for 4 hours. Added reagents are removed by extraction with soybean oil and chromatography on insolubilized C18 resin. Treatment results in the rapid and complete inactivation of greater than or equal to 10(7.5) infectious doses (ID50) of vesicular stomatitis virus (VSV) and greater than or equal to 10(6.9) ID50 of sindbis virus (used as marker viruses), greater than or equal to 10(6.2) ID50 of human immunodeficiency virus (HIV), greater than or equal to 10(6) chimp infectious doses (CID50) of hepatitis B virus (HBV), and greater than or equal to 10(5) CID50 of hepatitis C virus (HCV). Immunization of rabbits with S/D-FFP and subsequent adsorption of elicited antibodies with untreated FFP confirmed the absence of neoimmungen formation. Coagulation factor content was comparable with that found in FFP. Based on these laboratory and animal studies, together with the extensive history of the successful use of S/D-treated coagulation factor concentrates, we conclude that replacement of FFP with S/D-FFP, prepared in a manufacturing facility, will result in improved virus safety and product uniformity with no loss of efficacy.

Fresh frozen plasma (FFP) is prepared in blood banks world-wide as a by- product of red blood cell concentrate preparation. Appropriate clinical use is for coagulation factor disorders where appropriate concentrates are unavailable and when multiple coagulation factor deficits occur such as in surgery. Viral safety depends on donor selection and screening; thus, there continues to be a small but defined risk of viral transmission comparable with that exhibited by whole blood. We have prepared a virus sterilized FFP (S/D-FFP) by treatment of FFP with 1% tri(n-butyl)phosphate (TNBP) and 1% Triton X-100 at 30 degrees C for 4 hours. Added reagents are removed by extraction with soybean oil and chromatography on insolubilized C18 resin. Treatment results in the rapid and complete inactivation of greater than or equal to 10(7.5) infectious doses (ID50) of vesicular stomatitis virus (VSV) and greater than or equal to 10(6.9) ID50 of sindbis virus (used as marker viruses), greater than or equal to 10(6.2) ID50 of human immunodeficiency virus (HIV), greater than or equal to 10(6) chimp infectious doses (CID50) of hepatitis B virus (HBV), and greater than or equal to 10(5) CID50 of hepatitis C virus (HCV). Immunization of rabbits with S/D-FFP and subsequent adsorption of elicited antibodies with untreated FFP confirmed the absence of neoimmungen formation. Coagulation factor content was comparable with that found in FFP. Based on these laboratory and animal studies, together with the extensive history of the successful use of S/D-treated coagulation factor concentrates, we conclude that replacement of FFP with S/D-FFP, prepared in a manufacturing facility, will result in improved virus safety and product uniformity with no loss of efficacy.

To assess the possible efficacy of passive immunization against human immunodeficiency virus (HIV) an immune globulin was prepared from plasma of HIV-seropositive donors selected to be among those having the top 12.5% of virus-neutralizing antibody titers. The immune globulin was treated with pepsin to render it intravenously tolerable. The preparation, which we termed HIVIG, neutralized 100 tissue culture 50% infective doses (TCID50) of HIV at an average dilution of 1:1000 in neutralization tests in vitro. During preparation HIVIG was subjected to virus inactivation and removal procedures that in theory resulted in a reduction in HIV infectivity by a factor of 10(25). At a dose of 9-10 ml/kg of body weight both the virus-inactivated source plasma and the final immunoglobulin preparation were noninfective and without adverse effect in two chimpanzees. Two chimpanzees inoculated intravenously with HIVIG at 1 ml/kg and two inoculated with 10 ml/kg were challenged intravenously 1 day later with 400 TCID50 of the same strain of HIV (HTLV-IIIb) used in neutralization assays in vitro. All animals became infected. Incubation periods to virus isolation (by cocultivation with human mononuclear cells) in HIVIG recipients did not differ significantly from the incubation period seen in a control animal that received a normal anti-HIV-free immunoglobulin. These findings may have implications for understanding the failure of experimental vaccines to protect against HIV challenge in chimpanzee experiments.

BackgroundDelirium is a common condition in hospitalized seniors that nonetheless often goes undetected by nurses or is delayed in being detected which negatively impacts quality of care and outcomes. We sought to develop a new screening tool for delirium, The Sour Seven Questionnaire, a 7-item questionnaire suitable to be completed from informal or untrained caregiver observation. The study aimed to develop the scoring criteria for a positive delirium screen and assess concurrent validity of the questionnaire against a geriatric psychiatrist’s assessment.MethodsA pilot study of 80 hospitalized seniors over age 65 recruited from three units (2 medical, 1 orthopedic). Participants were assessed using the Confusion Assessment Method (CAM) with a brief cognitive screen and the Sour Seven Questionnaire posed to the appointed informal caregiver (family member) or untrained nurse for up-to 7 days. Subjects testing positive on the CAM and a random sample of negatively CAM screened subjects were assessed by the geriatric psychiatrist.ResultsFrom 80 participants, 21 screened positive for delirium on the CAM. 18 of the 21 CAM positive screens were diagnosed to have delirium by the geriatric psychiatrist, and 17 of the 18 randomly assigned negative CAM screens were confirmed as not having delirium. From the questionnaires on these 39 participants, weighted scoring for each of the 7 questions of the Sour Seven Questionnaire was developed based on their relative risks for correctly predicting delirium when compared to the geriatric psychiatrist’s clinical assessment. Total scoring of the questionnaire resulted in the following positive predictive values for delirium: 89 % with a total score of 4 (sensitivity 89.5 %, specificity 90 %), and 100 % with a total score of 9 (sensitivity 63.2 %, specificity 100 %). Comparison between scoring on questionnaires posed to informal caregivers versus untrained nurses showed no differences.ConclusionA weighted score of 4 in the Sour Seven Questionnaire has concurrent validity as a screening tool for delirium and a score of 9 is diagnostic for delirium. The Sour Seven Questionnaire is the first screening tool for delirium shown to be suitable for use by informal caregivers and untrained nurses in hospitalized seniors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12877-016-0217-2) contains supplementary material, which is available to authorized users.