Platelet-rich plasmapheresis in cardiac surgery: a meta-analysis of the effect on transfusion requirements.

OBJECTIVE: Our purpose was to determine whether intraoperative platelet-rich plasmapheresis in cardiac surgery is effective in reducing the proportion of patients exposed to allogeneic red cell transfusions. METHODS: A systematic search for prospective, randomized trials of platelet-rich plasmapheresis in cardiac surgery, using MEDLINE, HEALTHSTAR, Current Contents, "Biological Abstracts," and EMBASE/Excerpta Medica up to August 1997, was completed. Trials were included if they reported either the proportion of patients exposed to allogeneic red cells or the units of allogeneic red cells transfused. Trials were abstracted by 2 independent investigators and the quality of trial design was assessed with the use of a validated scale. RESULTS: Seventeen references met the inclusion criteria (1369 patients [675 control: 694 platelet-rich plasmapheresis]). Platelet-rich plasmapheresis reduced the likelihood of exposure to allogeneic red cells in cardiac surgery (odds ratio 0.44; 95% confidence interval 0.27, 0.72, P = .001). Platelet-rich plasmapheresis had a small but statistically significant effect on both the volume of blood lost in the first 24 hours (weighted mean difference -102 mL; 95% confidence interval -148, -55 mL, P < .0001) and the mean units transfused (weighted mean difference -0.33 units; 95% confidence interval -0.43, -0.23, P < .0001). However, platelet-rich plasmapheresis was only marginally effective (odds ratio 0.83, 95% confidence interval 0.34, 2.01, P = .68) for "good" quality trials, whereas it appeared very effective in trials with poor methodologic quality (odds ratio 0.33, 95% confidence interval 0.17, 0.62, P = .0007). CONCLUSIONS: Although platelet-rich plasmapheresis appeared effective in decreasing the proportion of patients receiving transfusions after cardiac operations, the quality of most of the supporting trials was low and the benefit was small in trials of good quality. Further clinical trials should be completed.

Are therapeutic decisions supported by evidence from health care research?

BACKGROUND: One of the most common decisions physicians face is deciding which therapeutic intervention is the most appropriate for their patients. In recent years much emphasis has been placed on making clinical decisions that are based on evidence from the medical literature. Despite the emphasis on incorporation of evidence-based medicine into the undergraduate curriculum and postgraduate medical training programs, there has been controversy regarding the proportion of interventions that are supported by health care research. OBJECTIVE: To investigate the proportion of major therapeutic interventions at our institution that are justified by published evidence. METHODS: One hundred fifty charts from the internal medicine department were reviewed retrospectively. The main diagnosis, therapy provided, and patient profile were identified and a literature search using MEDLINE was performed. A standardized search strategy was developed with high sensitivity and specificity for identifying publication quality. The level of evidence to support each clinical decision was ranked according to a predetermined classification. In this system there were 6 distinct levels, which are explained in the study. RESULTS: Of the decisions studied, 20.9% could be supported by placebo-controlled randomized trials and 43.9% by head-to-head trials. Half of these were shown to be significantly superior to the treatment against which it was being compared. For 10 of the 150 clinical decisions, evidence was found demonstrating alternative therapies as being more effective than that selected. CONCLUSIONS: Most primary therapeutic clinical decisions in 3 general medicine services are supported by evidence from randomized controlled trials. This should be reassuring to those who are concerned about the extent to which clinical medicine is based on empirical evidence. This finding has potential for quality assurance, as exemplified by the discovery that a literature search could have potentially improved these decisions in some cases.

The introduction of evidence-based medicine as a component of daily practice.

Evidence-based medicine is an increasingly important concept in continuing medical education and medical school curricula. To cope with the rapid evolution of medicine, physicians need to remain abreast of the many new therapies and diagnostic tools that affect their practices. Unfortunately, along with the many changes there is also a surplus of relevant written material. Physicians are unable to read all of this information due to time constraints. Instead, they must choose information efficiently. Tools are needed to facilitate this process. Over a two-month period, a demonstration model was carried out at the Ottawa General Hospital to encourage faculty, residents, and students to incorporate evidence-based medicine into their daily practice. A study was conducted to investigate the level and type of information required by these individuals in a clinical setting. A literature searching service was introduced six months after the formal introduction of evidence-based medicine in the Department of Medicine. The logistics of and recommendations for providing such a service are presented in this paper.

Immunochemical analysis of Pseudomonas aeruginosa exotoxin A. Analysis of the His426 determinant.

This study describes a combined immunochemical and genetic approach defining a site on Pseudomonas aeruginosa exotoxin A (ETA) which is critical to the ADP-ribosyltransferase (ADPRT) activity of the toxin. The sequential epitope of a monoclonal antibody (TO-1) which binds to domain III (residues 405-613), containing the ADPRT activity of ETA, has been defined using a series of synthetic peptides. This epitope spans residues 422-432 which composes the major alpha-helical segment of domain III and includes His426 which has previously been shown to be essential for ADPRT activity (Wozniak, D.J., Hsu, L.-Y., and Galloway, D. R. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 8880-8884). The critical His426 residue which projects into a major cleft becomes exposed when the ETA protein is in an ADPRT-active configuration. Since the TC-1 mAb does not block the binding of NAD+, it is possible that the alpha-helix site containing the TC-1 epitope and the His426 residue is associated with the interaction between ETA and its elongation factor 2 substrate.

Biochemical analysis of CRM 66. A nonfunctional Pseudomonas aeruginosa exotoxin A.

Pseudomonas aeruginosa exotoxin A (ETA) is an ADP-ribosyltransferase which inactivates protein synthesis by covalently attaching the ADP-ribose portion of NAD+ onto eucaryotic elongation factor 2 (EF-2). A direct biochemical comparison has been made between ETA and a nonenzymatically active mutant toxin (CRM 66) using highly purified preparations of each protein. The loss of ADP-ribosyltransferase activity and subsequent cytotoxicity have been correlated with the presence of a tyrosine residue in place of a histidine at position 426 in CRM 66. In the native conformation, CRM 66 demonstrated a limited ability (by a factor or at least 100,000) to modify EF-2 covalently and lacked in vitro and in vivo cytotoxicity, yet CRM 66 appeared to be normal with respect to NAD+ binding. Upon activation with urea and dithiothreitol, CRM 66 lost ADP-ribosyltransferase activity entirely yet CRM 66 retained the ability to bind NAD+. Replacement of Tyr-426 with histidine in CRM 66 completely restored cytotoxicity and ADP-ribosyltransferase activity. These results support previous findings from this laboratory (Wozniak, D. J., Hsu, L.-Y., and Galloway, D. R. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 8880-8884) which suggest that the His-426 residue of ETA is not involved in NAD+ binding but appears to be associated with the interaction between ETA and EF-2.