Detection of hepatitis C virus and human immunodeficiency virus-1 antibody-negative donations: Canadian Blood Services' experience with nucleic acid testing.
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Biomedical subjects
Publications and source records attributed to E C Vamvakas.
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BACKGROUND AND OBJECTIVES: An association of white blood cell (WBC) reduction with decreased mortality was reported by one observational, before-and-after study. A meta-analysis was undertaken to examine whether this finding is supported by all the evidence currently available from before-and-after studies, and whether these studies support an association of WBC reduction with a decreased risk of postoperative infection. MATERIALS AND METHODS: Observational, before-and-after studies were retrieved that reported on postoperative infection and/or mortality between January 1997 and June 2003. Six studies met the criteria for meta-analysis. Unadjusted summary odds ratios (ORs) of postoperative infection or mortality in patients transfused after (compared with before) WBC reduction were calculated across the studies if the hypothesis of homogeneity was not rejected. Adjusted summary ORs were calculated across three studies that had reported multivariate analyses. RESULTS: There was an unadjusted association of WBC reduction with a decreased risk of postoperative infection [summary OR = 0.93; 95% confidence interval (95% CI), 0.88-0.99; P < 0.01] that did not persist following adjustment for confounding factors (summary OR = 0.94; 95% CI, 0.85-1.04; P > 0.05). There was neither an unadjusted nor an adjusted association of WBC reduction with decreased mortality (summary OR = 0.94; 95% CI, 0.71-1.23; P > 0.05; and OR = 0.92; 95% CI, 0.80-1.05; P > 0.05, respectively). CONCLUSIONS: An association of WBC reduction with decreased mortality was not detected across the results available from all before-and-after studies. An unadjusted association of WBC reduction with a decreased risk of postoperative infection exists, but this was not detected across the three studies that reported multivariate analyses.
BACKGROUND AND OBJECTIVES: In patients undergoing open-heart surgery, allogeneic blood transfusion (ABT) may be related to an enhanced inflammatory response and impaired pulmonary function, resulting in a need for prolonged mechanical ventilation. Transfused red blood cell (RBC) supernatant, platelet supernatant or plasma components, may exercise varying effects on pulmonary function, because these fluids differ in their content of soluble biological-response modifiers. MATERIALS AND METHODS: The records of 416 patients undergoing coronary artery bypass graft operations at the Massachusetts General Hospital were reviewed. Possible predictors and the number of days of postoperative ventilation, as well as the number of all transfused blood components, were recorded. The association between mechanical ventilation past the day of operation and the volume of transfused RBC supernatant, platelet supernatant, or plasma components, was calculated by logistic regression analyses. RESULTS: The volume of each transfused fluid differed (P < 0.0001) among patients ventilated for 0, 1, 2, 3, or > or = 4 days after the day of the operation. After adjusting for the effects of confounding factors, the volume of administered RBC supernatant was associated (P = 0.0312) with the likelihood of postoperative ventilation past the day of operation, but the volume of platelet supernatant, plasma components, or total transfused fluid was not (P = 0.1528, P = 0.1847, and P = 0.0504, respectively). CONCLUSIONS: These results are congruent with the hypotheses that ABT may impair postoperative pulmonary function and that any such adverse effect of ABT is probably mediated by the supernatant fluid of stored RBCs. Both hypotheses should be examined further, in future studies of the outcomes of ABT.
BACKGROUND AND OBJECTIVES: A previous meta-analysis of randomized controlled trials (RCTs), comparing the risk of postoperative infection between recipients of allogeneic blood or autologous blood obtained by preoperative autologous blood donation (PABD), did not detect an immunomodulatory (TRIM) effect of allogeneic blood transfusion (ABT). If such a TRIM effect was mediated by white blood cell (WBC)-derived soluble mediators accumulating during storage, however, stored autologous blood obtained by PABD would not prevent the TRIM effect, whereas unstored autologous blood obtained by acute normovolemic haemodilution (ANH), intraoperative blood recovery (IBR), or postoperative blood recovery (PBR), would abrogate the TRIM effect. MATERIALS AND METHODS: RCTs reported through January 2002 were retrieved, and five studies met the criteria for meta-analysis. Summary odds ratios (ORs) of postoperative infection in recipients of allogeneic vs. autologous blood were calculated across studies. RESULTS: No difference in the risk of infection between the comparison arms was detected across all five RCTs [summary OR = 1.22, 95% confidence interval (95% CI): 0.75-1.98], or when the results of studies using PABD or ANH/IBR/PBR were integrated separately (summary OR = 1.35; 95% CI: 0.45-4.08; and summary OR = 1.49; 95% CI: 0.69-3.22, respectively). CONCLUSIONS: The finding of no TRIM effect of ABT across RCTs using ANH/IBR/PBR to obtain autologous blood does not support the hypothesis that a TRIM effect of ABT is mediated by WBC-derived soluble mediators accumulating during storage. The null finding of the overall meta-analysis also does not support a TRIM effect of ABT mediated by other blood constituents.
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BACKGROUND: Recombinant human EPO (rHuEPO) has not gained broad acceptance in the treatment of the anemia of prematurity, because its efficacy in diminishing RBC transfusions is questionable. Meta-analysis was used to investigate the extent and reasons for variation in the results of published clinical trials. STUDY DESIGN AND METHODS: Prospective controlled trials published from 1990 through 1999 were retrieved; 21 met the criteria for meta-analysis. Calculated across these studies were the summary OR of RBC transfusion in treated neonates as compared with controls and the summary mean difference between controls and treated neonates in the volume of RBCs transfused and the number of RBC transfusions per infant. Twelve study descriptors were examined as possible reasons for the variation in results. RESULTS: Results of 21 eligible studies varied widely (p<0.001 for the Q test statistic), and this variation persisted in most analyses when studies were stratified by individual study descriptors. When the difference in volume of RBCs transfused was the outcome measure, variation was modest across the four studies with highly desired characteristics (i.e., high blindness and design quality scores, "conservative" transfusion criteria, and the majority of neonates weighing <1 kg at birth), and treatment with rHuEPO reduced RBC transfusions by an average of 11.0 mL per kg (p<0.001). CONCLUSION: Benefit from rHuEPO is detected across high-quality studies using conservative RBC transfusion criteria. However, there is extreme variation overall in the findings of available trials, and-until this variation is accounted for-it is premature to recommend rHuEPO as standard treatment for the anemia of prematurity.
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BACKGROUND: In patients having open heart surgery, allogeneic blood transfusion (ABT) may be related to an enhanced inflammatory response and impaired pulmonary function, resulting in the need for prolonged mechanical ventilation. STUDY DESIGN AND METHODS: The records of 416 consecutive patients undergoing coronary artery bypass graft surgery at Massachusetts General Hospital were reviewed. Possible predictors and the number of days of postoperative ventilation, as well as the number of RBC units transfused and the length of their storage, were recorded. The association between mechanical ventilation after the day of operation and the number of RBC units transfused was calculated by logistic regression analysis. RESULTS: The number of RBC units transfused, but not the length of their storage, differed (p<0.0001) among patients ventilated for 0, 1, 2, 3, or 4 or more days after the day of operation. Patients taken off ventilation on the day of operation received (mean +/- SE) 2.01 +/- 0.14 RBC units; patients kept on ventilation for 4 or more days received 9.45 +/- 1.83 units. After adjusting for the effects of 18 confounding factors, the number of RBC units transfused was not a significant predictor of ventilation past the day of operation. There was, however, a trend suggesting that the likelihood of such ventilation might increase by 26 percent per RBC unit transfused (p = 0.0628). CONCLUSIONS: Future studies of the outcomes of ABT should examine further the possibility of a relationship between the number of transfused RBCs and the likelihood of postoperative ventilation after the day of operation.
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BACKGROUND: While RBC antigen frequencies for whites of Northern European ancestry are known, the relative frequencies of RBC antibodies within this population have not been determined. The distribution of RBC alloantibodies by sex and age was studied, as were the immunogenicity of RBC antigens and the occurrence of RBC alloantibody clusters in a geographically defined population. STUDY DESIGN AND METHODS: RBC alloimmunization among patients and donors in Olmsted County, MN, was determined for the period from 1975 to 1995. Alloantibody frequencies were used to calculate the potency of each antigen relative to K. Cluster analysis was applied to the data to identify natural groupings of antibodies. RESULTS: The frequency and potency of 33 alloantibodies from 1345 alloimmunized subjects were estimated. The most frequent alloantibodies were E (20.8%), Le(a) (18.6%), K (14.7%), D (12.9%), Le(b) (9.4%), M (7.2%), P(1) (6.7%), Fy(a) (6.3%), C (6.8%), and c (3.5%). The most potent antigens were Wr(a) (0.363), C(w) (0.078), Le(a) (0.03), E (0.028), V (0.025), Js(a) (0.023), Kp(b) (0.023), Go(a) (0.023), JMH (0.023), and Rd (0.023). Greater frequency of overall alloimmunization (M:F = 1:2.7), anti-D (p<0.0001), and anti-Le(a) (p = 0.003) was seen among females. Warm autoantibodies were more frequent among males with positive antibody screens (p<0.0001). No other gender differences were observed. Alloimmunization increased with age for K, Kp(a), Fy(a), D, C, E, and warm autoantibodies. Frequencies of alloimmunization to Le(a), Le(b), M, and P(1) decreased with age. The cluster analysis showed grouping of the antibodies to C and D as well as to Le(a) and Le(b), but the other RBC alloantibodies did not form clusters. CONCLUSION: Less than 1 percent of residents tested had positive antibody screens. Anti-E and anti-Le(a) were more common than anti-K. Wr(a) and C(w) were more potent antigens than K. Most antibodies showed an increase in frequency with increasing age. Except for anti-C and -D and anti-Le(a) and -Le(b), RBC alloantibodies did not occur in clusters.
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Meta-analysis is the structured and systematic integration of information from different studies of a given problem. It has been widely used to integrate findings of randomized controlled trials (RCTs) investigating the efficacy of therapeutic interventions, but its use in pathology has lagged behind its use in clinical medicine. The purpose of this review is to present pathologists with the necessary background for reading and evaluating published reports of metaanalyses. The concepts and methods of meta-analyses of RCTs are presented, followed by a discussion of how these concepts and methods potentially can be applied to studies of diagnostic test accuracy. Three differences between RCTs and studies of diagnostic test accuracy are identified, and 4 possible obstacles to the use of meta-analysis in pathology are discussed. Despite these specific difficulties in the meta-analysis of diagnostic test data, meta-analysis can (and should) be used to produce valid summary estimates of the diagnostic accuracy of laboratory tests across all available studies.
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BACKGROUND: The transfusion of old red cells (RBCs) may be associated with reduced delivery of oxygen to tissues and an increased risk of transfusion complications. The association of postoperative morbidity with the length of storage of perioperatively transfused RBCs was studied in 268 consecutive patients receiving a blood transfusion for coronary artery bypass graft surgery. STUDY DESIGN AND METHODS: The postoperative length of hospitalization, the postoperative length of stay in the intensive care unit, and the length of endotracheal intubation after the day of the operation were used as surrogate measures of global postoperative morbidity. The length of storage of the oldest transfused RBC unit, the mean length of storage of the oldest and second oldest RBC units, and the mean length of storage of all RBC units transfused to each patient were tested for association with the three outcome variables. Multiple linear regression analysis and Cox proportional-hazard analysis were used to adjust for the effects of confounding factors that pertained to each patient's severity of illness and the difficulty of each operation. RESULTS: There were no significant associations after adjustment for the effects of confounding factors. CONCLUSION: This study did not corroborate the previously reported association between transfusion of old RBCs and increased morbidity. However, there is surprisingly little research on the clinical outcomes of the transfusions of old RBCs, and this hypothesis should be investigated further.