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Biomedical subjects

B McClelland

Publications and source records attributed to B McClelland.

18 recordsLinked to original sources

Desmopressin for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Public concerns regarding the safety of transfused blood have prompted re-consideration of the use of allogeneic (from an unrelated donor) red blood cell (RBC) transfusion, and of a range of techniques designed to minimise transfusion requirements. OBJECTIVES: To examine the evidence for the efficacy of desmopressin acetate (1-deamino-8-D-arginine-vasopressin; DDAVP), in reducing perioperative blood loss and the need for red cell transfusion in patients who do not have congenital bleeding disorders. SEARCH STRATEGY: Articles were identified by: computer searches of MEDLINE, EMBASE, Current Contents (to May 2003), and the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 1, 2003). References in the identified trials and review articles were searched and authors contacted to identify additional studies. SELECTION CRITERIA: Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to DDAVP, or to a control group, who did not receive the intervention. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using criteria proposed by Schulz et al. (Schulz 1995) and Jadad et al. (Jadad 1996). Main outcomes measured were: the number of patients exposed to allogeneic red cell transfusion, and the amount of blood transfused. Other outcomes measured were: re-operation for bleeding, blood loss, post-operative complications (thrombosis, infection, non-fatal myocardial infarction), mortality, and length of hospital stay (LOS). MAIN RESULTS: Eighteen trials of DDAVP (n=1295) reported data on the number of patients transfused with allogeneic RBC transfusion. In subjects treated with DDAVP, the pooled relative risk of exposure to perioperative allogeneic RBC transfusion was 0.95 (95%CI = 0.86 to 1.06). The use of DDAVP did not significantly reduce blood loss; weighted mean difference (WMD) = -114.3ml: 95% confidence interval (95%CI) = -258.8 to 30.2ml per patient) or the volume of RBC transfused (WMD = -0.35 units: 95%CI = -0.70 to 0.01 units). In DDAVP-treated patients the relative risk of requiring re-operation due to bleeding was 0.69 (95%CI = 0.26 to 1.83). There was no statistically significant effect overall for mortality and non-fatal myocardial infarction in DDAVP-treated patients compared with control (RR = 1.72: 95%CI = 0.68 to 4.33) and (RR = 1.38: 95%CI = 0.77 to 2.50) respectively. REVIEWER'S CONCLUSIONS: There is no convincing evidence that desmopressin minimises perioperative allogeneic RBC transfusion in patients who do not have congenital bleeding disorders. These data suggest that there is no benefit from using DDAVP as a means of minimising perioperative allogeneic RBC transfusion.

Adult↗

Desmopressin for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Public concerns regarding the safety of transfused blood have prompted re-consideration of the use of allogeneic (from an unrelated donor) red blood cell (RBC) transfusion, and a range of techniques designed to minimise transfusion requirements. OBJECTIVES: To examine the evidence for the efficacy of desmopressin (1-deamino-8-D-arginine-vasopressin), in reducing perioperative blood loss and the need for red cell transfusion in patients who do not have congenital bleeding disorders. SEARCH STRATEGY: Articles were identified by: computer searches of OVID MEDLINE, EMBASE, and Current Contents (to August 2000) and web sites of international health technology assessment agencies (to May 1998). References in the identified trials and review articles were checked and authors contacted to identify additional studies. SELECTION CRITERIA: Randomised controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to DDAVP, or to a control group, who did not receive the intervention. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using criteria proposed by Schulz et al. (1995) and Jadad et al. (1996). The principal outcomes were: the number of patients exposed to red cells, and the amount of blood transfused. Other clinical outcomes are detailed in the review. MAIN RESULTS: Fourteen trials of DDAVP (N=1034) reported data on the proportion of patients exposed to allogeneic RBC transfusion. In subjects treated with DDAVP the relative risk of exposure to peri-operative allogeneic blood transfusion was 0.98 (95%CI: 0.88 to 1.10) compared with control. In DDAVP-treated patients the relative risk of requiring re-operation due to bleeding was 0.56 (95%CI: 0.18 to 1.73). There was no statistically significant effect overall for mortality and non-fatal myocardial infarction in DDAVP-treated patients compared with control (RR=1.53: 95%CI: 0.58 to 4.05) and (RR=1.52: 95%CI: 0.67 to 3.49) respectively. REVIEWER'S CONCLUSIONS: There is no convincing evidence that desmopressin minimises perioperative allogeneic RBC transfusion in patients who do not have congenital bleeding disorders. These data suggest that there is no benefit of using DDAVP as a means of minimising perioperative allogeneic RBC transfusion. This meta-analysis had 90% power to detect a relative risk reduction of at least 17% for receiving a red cell transfusion at alpha = 0.05 (two-sided).

Adult↗

Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Concerns regarding the safety of transfused blood have prompted re-consideration of the use of allogeneic (blood from an unrelated donor) blood transfusion. OBJECTIVES: To assess the effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid, and epsilon aminocaproic acid, on peri-operative red blood cell (RBC) transfusion. SEARCH STRATEGY: We searched MEDLINE (to May 1998), EMBASE (to December 1997), web sites of international health technology assessment agencies (to May 1998). References in identified trials and review articles were checked and authors contacted to identify any additional studies. SELECTION CRITERIA: Randomised controlled trials of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: We found 61 trials of aprotinin (7027 participants). Aprotinin reduced the rate of RBC transfusion by a relative 30% (RR=0.70: 95%CI: 0.64 to 0.76). The average absolute risk reduction (ARR) was 20.4% (95%CI: 15.6% to 25.3%). On average, aprotinin use saved 1.1 units of RBC (95%CI: 0.69 to 1.47) in those requiring transfusion. Aprotinin also significantly reduced the need for re-operation due to bleeding (RR=0.40: 95%CI: 0.25 to 0.66). We found 18 trials of tranexamic acid (TXA) (1,342 participants). TXA reduced the rate of RBC transfusion by a relative 34% (RR=0.66: 95%CI: 0.54 to 0.81). This represented an ARR of 17.2% (95%CI: 8.7% to 25.7%). TXA use resulted in a saving of 1.03 units of RBC (95%CI: 0.67 to 1.39) in those requiring transfusion. We found four trials of epsilon aminocaproic acid (EACA) (208 participants). EACA use resulted in a statistically non-significant reduction in RBC transfusion (RR=0.48: 95%CI: 0.19 to 1.19). Comparisons between agents Eight trials made 'head-to-head' comparisons between TXA and aprotinin. There was no significant difference between the two drugs in the rate of RBC transfusion: RR=1.21 (95%CI: 0.83 to 1.76) for TXA compared to aprotinin. Adverse Effects Aprotinin did not seem to be associated with an excess risk of adverse effects, including thrombo-embolic events (thrombosis RR=0.64: 95%CI: 0.31 to 1.31) and renal failure (RR=1.19: 95%CI: 0.79 to 1.79). Fewer data were available for TXA and EACA. REVIEWER'S CONCLUSIONS: From this review it appears that aprotinin reduces the need for red cell transfusion, and the need for re-operation due to bleeding, without serious adverse effects. However, there was significant heterogeneity in trial outcomes, and some evidence of publication bias. Similar trends were seen with TXA and EACA, although the data were rather sparse. The poor evaluation of these latter drugs is unfortunate as results suggest they may be equally as effective as aprotinin, but are significantly cheaper. The evidence reviewed here supports the use of aprotinin in cardiac surgery. Further small trials of this drug are not warranted. Future trials should be large enough to compare the efficacy and cost-effectiveness of aprotinin with that of TXA and EACA.

Aminocaproic Acid↗

Technologies to minimize blood transfusion in cardiac and orthopedic surgery. Results of a practice variation survey in nine countries. International Study of Peri-operative Transfusion (ISPOT) Investigators.

OBJECTIVES: Due to the discovery in the 1980s that blood transfusion can transmit HIV, there has been increased interest in technologies that reduce the amount of allogeneic blood used during and after surgery. These technologies include drugs (aprotinin, tranexamic acid, epsilon-aminocaproic acid, erythropoietin), devices (cell salvage), and techniques (acute hemodilution, predeposited autologous donation). The purpose of this study was to ascertain the degree of practice variation, if any, that exists for eight technologies in nine countries in orthopedic and cardiac surgery. METHODS: In each country, either all hospitals or a random sample of hospitals with medical/surgical beds were surveyed between 1995 and 1997. Two instruments were used. The first instrument was a postcard that asked recipients whether the technologies were currently being used in their hospital for orthopedic and/or cardiac surgery to reduce perioperative allogeneic transfusion. The second questionnaire elicited information regarding the degree of use both in qualitative and quantitative terms. Data were collected, entered, and analyzed in each country, with summary results submitted to the Canadian coordinating center on a standardized data collection form. RESULTS: Pharmaceuticals were generally used in a much smaller proportion of hospitals in orthopedic than in cardiac surgery. Aprotinin and tranexamic acid were the drugs most frequently used in cardiac surgery. Nonpharmacological technologies were used to a greater degree than drugs in orthopedic surgery, although there was wide variation among technologies and countries. Acute hemodilution and cell salvage were used in a greater proportion of hospitals for cardiac surgery than orthopedic surgery. CONCLUSIONS: The results of this survey indicate that there is considerable practice variation in the use of technologies to minimize exposure to perioperative allogeneic transfusion within and between countries.

Antifibrinolytic Agents↗

A pilot randomized trial comparing symptomatic vs. hemoglobin-level-driven red blood cell transfusions following hip fracture.

BACKGROUND: The indications for transfusion have never been evaluated in an adequately sized clinical trial. A pilot study was conducted to plan larger clinical trials. STUDY DESIGN AND METHODS: Hip fracture patients undergoing surgical repair who had postoperative hemoglobin levels less than 10 g per dL were randomly assigned to receive 1) symptomatic transfusion: that is, transfusion for symptoms of anemia or for a hemoglobin level that dropped below 8 g per dL or 2) threshold transfusion: that is, patients receive 1 unit of packed RBCs at the time of random assignment and as much blood as necessary to keep the hemoglobin level above 10 g per dL. Outcomes were 60-day mortality, morbidity, functional status, and place of residence. RESULTS: Among 84 eligible patients enrolled, mean (+/- SD) prerandomization hemoglobin was 9.1 (+/- 0.6) g/ dL. The median number of units transfused in the threshold transfusion group was 2 (interquartile range, = 1-2), and that in the symptomatic transfusion group was 0 (6; interquartile range, = 0-2) (p < 0.001). Mean hemoglobin levels were approximately 1 g per dL higher in the threshold group than in the symptomatic group: for example, on Day 2, 10.3 (+/- 0.9) g per dL versus 9.3 (+/- 1.2) g per dL, respectively (p < 0.001). At 60 days, death or inability to walk across the room without assistance occurred in 16 (39.0%) of the symptomatic transfusion group and 19 (45.2%) of the threshold transfusion group. Death occurred by 60 days in 5 (11.9%) of the symptomatic transfusion group and 2 (4.8%) in the threshold transfusion group (relative risk = 2.5; 95% CI, 0.5-12.2). Other outcomes were similar for the two groups. CONCLUSIONS: Symptomatic transfusion may be an effective blood-sparing protocol associated with the transfusion of appreciably fewer units of RBCs and lower mean hemoglobin levels than are associated with the threshold transfusion policy. However, it is unknown whether these two clinical strategies have comparable mortality, morbidity, or functional status. A definitive trial is needed.

Adult↗

Perioperative red cell transfusion: evidence, guidelines and practice.

Although we still do not know enough about the influence of anaemia and transfusion on outcomes for the surgical patient, it is possible to develop a general consensus about many aspects of management. A quality programme to improve consistency of practice in these consensus areas is feasible. (Table 6) This should be linked with further randomised trials to evaluate the clinical effectiveness of alternative regimes.

Adult↗

Potential of epoetin alfa in patients in autologous blood donation programs for orthopedic surgery.

The ability of epoetin alfa to increase hematopoiesis in a dose-dependent manner when administered by the intravenous (i.v.) or subcutaneous (s.c.) route has been demonstrated in pharmacokinetic studies in healthy volunteers. Epoetin alfa may therefore be a useful adjunct to autologous blood (AB) donation. By facilitating AB donation, the use of allogeneic blood could be reduced. In patients scheduled to undergo orthopedic surgery, i.v. administration of epoetin alfa 600 IU/kg twice weekly for 3 weeks prior to surgery (in conjunction with oral iron supplementation) significantly increased the number of AB units and total red blood cell (RBC) volume donated and increased the number of patients able to donate > or = 4 AB units. However, there was no difference between epoetin alfa and placebo groups with respect to allogeneic blood exposure.

Anemia↗

Evaluation of monoclonal antibodies to blood group A.

Balb/c mice were immunized with human blood-group A2 active cyst fluid glycoprotein. Fusion of spleen cells with NS-1 myeloma cell line produced a total of 11 blood group antibody secreting hybridomas of which seven were apparently specific for blood-group A and were subjected to further evaluation. Of these 2 were IgM class and 5 IgG class. Two anti-A supernatants showed a significant decrease in avidity time against A2B cells when ionic strength was increased to 0.25. Tube titres of all anti-A supernatants were unaffected by ionic strength. pH had no effect on the avidity time or tube titre of any of the antibodies tested. The supernatant from one hybrid (ES-9) was selected for further evaluation as a blood grouping reagent. This supernatant had a tube titre of 1:128 and was used without concentration for comparison of its serological reactivity with two examples of commercial monoclonal anti-A and one example of human anti-A. Monoclonal anti-A (ES-9) was found to be a potentially useful red cell grouping reagent.

ABO Blood-Group System↗

A monoclonal antibody to human blood group B. Performance, evaluation and optimisation.

A monoclonal anti-B antibody (ES-4) was obtained by fusing spleen cells from a mouse immunized with soluble human blood group B substance with mouse myeloma cell line NS-1. The antibody was shown to agglutinate optimally group B cells at pH 7.2 and 0.15 ionic strength. Increasing the ionic strength to 0.24 gave optimal reactivity over a wider pH range. Culture supernatant containing anti-B (ES-4), after pH and ionic strength adjustment could be used in unconcentrated form as a red cell typing reagent. Anti-B (ES-4) agglutinated five examples of cells of the Bweak (Bw) phenotype and one example of acquired B phenotype. In contrast three of the Bw cells and the acquired B phenotype were not agglutinated by a commercial monoclonal anti-B by a tube technique. The data suggested that the equilibrium constant of the monoclonal anti-B (ES-4) was higher than that of the commercial reagent.

ABO Blood-Group System↗

A modified radio-immune antiglobulin test for the screening of anti-red blood cell antibodies in hybridoma supernatants.

A radio-immune antiglobulin test was developed using mouse monoclonal anti-human A red blood cell (RBC) antibodies, and applied to the screening and study of hybridoma supernatants containing anti-human RBC antibodies. The latter antibodies were provided either as known monoclonal antibodies from culture supernatants and ascitic fluids, or as culture supernatants to be screened. The technical feasibility of the test was greatly facilitated by the use of remova-well disposable polystyrene plates, multichannel pipettes, and multiple-plate centrifuge holders. The sensitivity of the test and its relevance for the screening of hybridoma anti-human RBC antibodies is discussed.

Animals↗

How government policy decisions affect seniors' quality of life: findings from a participatory policy study carried out in Toronto, Canada.

Toronto seniors explored how government policy decisions were influencing their health and well-being. In this participatory policy study, emphasis was upon the lay and critical knowledge of highly informed seniors. Focus groups and interviews revealed that all three levels of governments were seen as not listening to seniors' voices. In nine key policy areas identified as influencing seniors' quality of life--hearing seniors' voices, housing, acute illness care, long-term care, income supports, transportation and mobility, promoting healthy lifestyles, access to information, and hearing voices from cultural communities--many concerns were raised. The gap between government rhetoric and government action on seniors' issues merits public health attention.

Aged↗