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Biomedical subjects

D J Cook

Publications and source records attributed to D J Cook.

At least 127 records · Page 7Linked to original sources

Benefit of heparin in central venous and pulmonary artery catheters: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effect of heparin on thrombus formation and infection associated with use of central venous and pulmonary artery catheters. DATA SOURCES: We used MEDLINE, EMBASE, citation review of relevant primary and review articles, personal files, and contact with expert informants. STUDY SELECTION: Fourteen randomized controlled trials evaluating prophylactic doses of heparin or heparin bonding were included. DATA EXTRACTION: In duplicate, independently, we abstracted data on the population, intervention, outcome, and methodologic quality. DATA SYNTHESIS: Prophylactic heparin decreases catheter-related venous thrombosis (relative risk [RR], 0.43; 95% confidence interval [CI], 0.23, 0.78) and bacterial colonization (RR, 0.18; 95% CI, 0.06, 0.60) of central venous catheters and may decrease catheter-related bacteremia (RR, 0.26; 95% CI, 0.07, 1.03). Heparin bonding decreases the risk of pulmonary artery catheter clot formation within 24 h (RR, 0.08; 95% CI, 0.02, 0.37). CONCLUSIONS: Heparin administration effectively reduces thrombus formation and may reduce catheter-related infections in patients who have central venous and pulmonary artery catheters in place. Cost-effectiveness comparisons of unfractionated heparin, low molecular weight heparin, and warfarin are needed.

Adult↗

The effect of positive pressure airway support on mortality and the need for intubation in cardiogenic pulmonary edema: a systematic review.

OBJECTIVE: To critically appraise and summarize the trials examining the addition of continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NPPV) to standard therapy on hospital mortality, need for endotracheal intubation, and predischarge left ventricular function in patients admitted to the hospital with cardiogenic pulmonary edema with gas exchange abnormalities. DATA SOURCES: We searched MEDLINE (1983 to June 1997) and bibliographies of all selected articles and review articles. We also reviewed the abstracts from the proceedings of relevant meetings from 1985 to 1997. STUDY SELECTION: (1) POPULATION: patients presenting to hospital with cardiogenic pulmonary edema; (2) intervention: one of the following three: (a) the use of CPAP and standard medical therapy vs standard medical therapy alone; (b) the use of NPPV and standard medical therapy vs standard medical therapy alone; and (c) the use of NPPV and standard therapy vs CPAP and standard therapy; (3) outcome: hospital survival, need for endotracheal intubation, or predischarge left ventricular dysfunction; and (4) study design: randomized controlled trial (RCT); if there were fewer than two RCTs, other study designs were included. DATA EXTRACTION: Two authors independently extracted data and evaluated the methodologic quality of the studies. DATA SYNTHESIS: CPAP was associated with a decrease in need for intubation (risk difference, -26%, 95% confidence intervals, -13 to -38%) and a trend to a decrease in hospital mortality (risk difference, -6.6%; +3 to -16%) compared with standard therapy alone. There was insufficient evidence to comment on the effectiveness of NPPV either compared with standard therapy or CPAP and standard therapy. Evidence was also lacking on the potential for either intervention to cause harm. CONCLUSIONS: A modest amount of favorable experimental evidence exists to support the use of CPAP in patients with cardiogenic pulmonary edema. CPAP appears to decrease intubation rates and data suggest a trend toward a decrease in mortality, although the potential for harm has not been excluded. The role of NPPV in this setting requires further study before it can be widely recommended.

Clinical Trials as Topic↗

Flow cytometry crossmatching (FCXM) in the UNOS Kidney Transplant Registry.

1. Among 5,776 transplants reported to the UNOS Scientific Renal Transplant Registry with flow cytometry crossmatch (FCXM) results, 13% had a positive FCXM. The majority (8.8%) had B-cell only reactivity and the remaining 4.2% had T-cell reactivity. 2. Retransplanted patients, females and sensitized patients were more likely to have been FCXM positive than primary transplants, males, or unsensitized patients. 3. A positive FCXM was associated with less than optimal function as evidenced by an increased need for posttransplant dialysis, more grafts that never functioned, longer hospital stays and a higher incidence of rejection. 4. The impact of antibodies detected by FCXM on graft survival was strongest among retransplanted patients (60% 3-year graft survival with a positive FCXM vs 79% with a negative FCXM, p = 0.003), although significant differences were also noted in primary transplants (76% 3-year graft survival with a positive FCXM vs 81% with a negative FCXM, p < 0.001). Class I reactivity generally had a greater impact on survival, although class II antibodies had a deleterious effect as well. 5. Primary transplants across a T+B+ FCXM (n = 187) had a 76% 3-year graft survival rate compared with 74% for 509 T-B+ transplants. Both were significantly lower than the 81% 3-year graft survival rate for 5,017 T-B- FCXM transplants. 6. Retransplants across a T+B+ FCXM (n = 48) had a 60% 3-year regraft survival rate compared with 73% for 118 T-B+ regrafts and 79% when the FCXM was negative when tested against both targets (T-B-, n = 698). 7. Although there is room for improvement in the technique, the FCXM continues to be effective in identifying kidney transplants at risk of early graft failure and of rejection.

B-Lymphocytes↗

Evidence-based disease management.

Disease management is an approach to patient care that emphasizes coordinated, comprehensive care along the continuum of disease and across health care delivery systems. Evidence-based medicine is an approach to practice and teaching that integrates pathophysiological rationale, caregiver experience, and patient preferences with valid and current clinical research evidence. Using diabetes mellitus as an example, we describe the importance of evidence-based medicine to the development of disease management programs. We present a method for developing and implementing evidence-based clinical guidelines, clinical pathways, and algorithms and describe the creation of systems to measure and report processes and outcomes that could drive quality improvement in diabetes care. Multidisciplinary teams are ideally suited to develop, lead, and implement evidence-based disease management programs, since they play an essential role in the preventive, diagnostic, and therapeutic decisions for patients with diabetes throughout the course of their disease.

Algorithms↗

Minimum hematocrit for normothermic cardiopulmonary bypass in dogs.

BACKGROUND: The purpose of this study was to determine the minimum hematocrit supporting cerebral oxygenation during normothermic cardiopulmonary bypass (CPB) in dogs. The effect of hemodilution on cerebral blood flow (CBF), cerebral metabolic rate (CMRO2), and cerebral oxygen delivery (CDO2) was determined over a range of hematocrits. METHODS AND RESULTS: Measurements were obtained during 37.5 degrees C CPB with progressive normovolemic hemodilution (hematocrit 0.39 to 0.9) in eight anesthetized animals. Dextran 70 (6%) was used as a diluent. CBF was measured using the sagittal sinus outflow technique. CMRO2 and CDO2 were calculated using standard formula. Hemodilution was associated with a reciprocal rise in CBF. CBF at a hematocrit of 0.09 was 240% of the CBF when the hematocrit was 0.39. Increases in CBF compensated for decreased arterial oxygen content and CDO2 was maintained to a mean hematocrit of 0.14+/-0.02. At a hematocrit of 0.09+/-0.02, CDO2 and CMRO2 declined. Intracranial pressure remained stable throughout. Thus, the critical hematocrit for brain (the hematocrit at which metabolism becomes delivery-dependent) was between 0.09 and 0.14 during normothermic CPB in dogs. CONCLUSIONS: This is the first systematic attempt to determine the critical hematocrit supporting cerebral oxygenation during warm CPB. The curve describing the relationship between hematocrit and cerebral oxygen balance has a broad plateau and a genu near a hematocrit value of 0.15. While we do not advocate hemodilution to a hematocrit of 15% during "warm" CPB, these data provide a physiological foundation for our hemodilution practice and offer an explanation why low hematocrits are tolerated in certain patient populations.

Animals↗

The relation between systematic reviews and practice guidelines.

Clinical practice guidelines have been developed to improve the process and outcomes of health care and to optimize resource utilization. By addressing such issues as prevention, diagnosis, and treatment, they can aid in health care decision making at many levels. Several other decision aids are cast in the guideline lexicon, regardless of their focus, formulation, or format; this can foster misunderstanding of the term "guideline." Whether created or adapted locally or nationally, most guidelines are an amalgam of clinical experience, expert opinion, and research evidence. Approaches to practice guideline development vary widely. Given the resources required to identify all relevant primary studies, many guidelines rely on systematic reviews that were either previously published or created de novo by guideline developers. Systematic reviews can aid in guideline development because they involve searching for, selecting, critically appraising, and summarizing the results of primary research. The more rigorous the review methods used and the higher the quality of the primary research that is synthesized, the more evidence-based the practice guideline is likely to be. Summaries of relevant research incorporated into guideline documents can help to keep practitioners up to date with the literature. Systematic reviews have also been published on the dissemination and implementation strategies most likely to change clinician behavior and improve patient outcomes. These can be useful in more effectively translating research evidence into practice.

Evidence-Based Medicine↗

Multicenter evaluation of the flow cytometry T-cell crossmatch: results from the American Society of Histocompatibility and Immunogenetics-College of American Pathologists proficiency testing program.

BACKGROUND: The performance characteristics and interlaboratory comparisons of the T-cell flow cytometry crossmatch remain largely unknown. METHODS: This study was performed using data from the ASHI-CAP proficiency testing program. Four unknown sera and two unknown cells were sent to participating laboratories twice a year for 4 years. RESULTS: In one survey in which different crossmatch techniques were compared, flow cytometry was slightly more sensitive than the antiglobulin method and considerably more sensitive than direct cytotoxicity. However, the proportion of participants in any given survey detecting antibodies in all sera expected to be positive was 50-60% and has not changed over the years. Failure to detect antibodies correlated with low antibody concentration, diluting the unknown serum by the testing laboratory, and with the instrument used. False positive results with normal sera were infrequent. Fluorescence intensity values were not standardized and were highly variable, but when fluorescence units reported by individual laboratories were divided by their own positive-negative cutoff values, results from different centers were more comparable. In general, fluorescence-to-cutoff ratios >5 correlated with complement binding activity, whereas values <5 denoted concentrations below those required to fix complement. CONCLUSIONS: Flow cytometry, as used by most centers, is highly sensitive and allows relative antibody quantitation. Furthermore, the data define objective parameters that may help to standardize the test and improve its predictive value in clinical transplantation.

Antibodies↗

A guide to interpreting discordant systematic reviews.

Systematic reviews are becoming prominent tools to guide health care decisions. As the number of published systematic reviews increases, it is common to find more than 1 systematic review addressing the same or a very similar therapeutic question. Despite the promise for systematic reviews to resolve conflicting results of primary studies, conflicts among reviews are now emerging. Such conflicts produce difficulties for decision-makers (including clinicians, policy-makers, researchers and patients) who rely on these reviews to help them make choices among alternative interventions when experts and the results of trials disagree. The authors provide an adjunct decision tool--a decision algorithm--to help decision-makers select from among discordant reviews.

Algorithms↗

Attitudes toward the use of gender-inclusive language among residency trainees. The McMaster Residency Training Program Directors.

OBJECTIVE: To explore postgraduate medical trainees' attitudes toward the use of gender-inclusive language. DESIGN: Self-administered questionnaire. SETTING: Seven residency training programs at McMaster University, Hamilton, Ont., from July 1993 to June 1994. PARTICIPANTS: Of 225 residents in the programs, 186 responded to the survey, for a response rate of 82.7%. Men and women were equally represented among the respondents. OUTCOME MEASURES: Categorization of attitudes about the use of language as gender-inclusive or gender-exclusive; characteristics predicting a gender-inclusive attitude. RESULTS: Factor analysis and Cronbach's alpha (0.90) supported the existence of a construct related to attitudes about language use, the poles of which were categorized as gender-inclusive and gender-exclusive. The authors classified residents with respect to their attitudes to language use from their responses to the questionnaire. In univariate analyses, sex, residency program and country of graduation significantly predicted a gender-inclusive attitude (p < 0.01). Only the first 2 variables were significant in a multivariate model; residency program explained 18% of the variance and sex 3%. Residents in obstetrics and gynecology and psychiatry had the most gender-inclusive attitudes, whereas residents in surgery and anesthesia had the most gender-exclusive attitudes. CONCLUSIONS: Residents' values are reflected in the language they choose to use. Language use may provide an index of underlying attitudes that may create hostile environments for female trainees.

Adult↗

Systematic reviews: synthesis of best evidence for clinical decisions.

Systematic reviews can help practitioners keep abreast of the medical literature by summarizing large bodies of evidence and helping to explain differences among studies on the same question. A systematic review involves the application of scientific strategies, in ways that limit bias, to the assembly, critical appraisal, and synthesis of all relevant studies that address a specific clinical question. A meta-analysis is a type of systematic review that uses statistical methods to combine and summarize the results of several primary studies. Because the review process itself (like any other type of research) is subject to bias, a useful review requires clear reporting of information obtained using rigorous methods. Used increasingly to inform medical decision making, plan future research agendas, and establish clinical policy, systematic reviews may strengthen the link between best research evidence and optimal health care.

Decision Making↗

Nitrous oxide method of measuring cerebral blood flow during hypothermic cardiopulmonary bypass.

BACKGROUND: Determination of cerebral blood flow and oxygenation is a means of evaluating our cardiopulmonary bypass (CPB) practice. Because much of CPB is hypothermic, our measurement technique must be valid over a range of temperatures. In this study we evaluate the validity of N2O washin for measurement of cerebral blood flow and oxygenation at three temperatures. METHODS: Cerebral blood flow and oxygenation were measured in 7 dogs undergoing CPB at 37 degrees, 32 degrees, and 27 degrees C using simultaneous direct (sagittal sinus outflow) and indirect (nitrous oxide washin) techniques. Animals underwent CPB with a whole blood prime and alpha-stat pH management. RESULTS: In the absence of hemodilution, cerebral blood flow and oxygenation were reduced by approximately 38% and 55% at 32 degrees C and 27 degrees C, respectively, by both techniques. Direct and indirect methods showed an excellent correlation (R = 0.87) during CPB between 27.5 degrees C and 37.8 degrees C (21 paired measurements). CONCLUSIONS: This investigation demonstrates that the correlation between a direct measure of global cerebral blood flow and that obtained by the N2O saturation method is excellent during CPB over the range of common CPB temperatures.

Animals↗

Factors influencing HLA sensitization in implantable LVAD recipients.

BACKGROUND: Patients bridged to transplantation (TX) with the implantable left ventricular assist device (LVAD) may be at increased risk for the development of panel-reactive antibodies (PRA) during support. METHODS: To investigate that, we evaluated 60 patients who received the HeartMate LVAD at our institution, of whom 53 had PRA results available for analysis. T lymphocyte PRA levels were examined before LVAD, at the peak PRA level during LVAD support (PEAK), and just before TX. A PRA level more than 10% was considered indicative of sensitization against HLA antigens. RESULTS: The only factor that had a significant effect on PRA levels before LVAD was patient's sex (1.3% for men versus 7.4% for women; p = 0.005). During LVAD support, peak PRA levels increased significantly and the sex-associated differences were no longer evident (33.3% men, 34.3% women; not significant). At the time of TX, PRAs decreased to 10.9% (men) and 7.0% (women) (not significant). We examined the influence of blood products received before TX on PRA levels. Patients who received less than the median number of total units ( median). When examined by the type of blood product, only the number of platelet transfusions significantly increased the peak PRA ( median: 46.9%; p = 0.03). Patients who received blood that was leukocyte-depleted tended to have lower TX PRA levels (2.9%) compared with those who did not (13.9%, p = 0.18). Forty-two patients were successfully bridged to TX, with three early and two late deaths after TX. Whereas 39 patients received transplants without intervention, 3 were treated by plasmapheresis with a 77% reduction in their HLA antibody levels at TX as measured by flow cytometry. CONCLUSIONS: Patients with the implantable LVAD are at significant risk for the development of anti-HLA antibodies during support. Although this sensitization is often transient, intervention using plasmapheresis may be useful for some patients.

Adult↗

Benefit-risk ratios in the assessment of the clinical evidence of a new therapy.

All therapeutic decisions involve some trade-off between therapeutic benefits and risks; a new therapy may be associated with greater efficacy but also a greater risk of adverse effects. In making treatment decisions clinicians must examine the clinical evidence regarding the magnitudes of benefit and risk and the precision with which they have been estimated. Ideally this requires a systemic assessment of the quality of the research and the strength of the evidence. We examine how the concept of number needed to treat can be used to improve the current presentation of clinical trials data of efficacy and side-effects to give clinicians a more clinically meaningful and quantitative measure of benefit-risk trade-offs. We propose a benefit-risk ratio that quantifies for a new therapy how many therapeutic (efficacy) events will be achieved for each adverse event incurred. We show how data from a clinical trial with a single binary measure of efficacy and a single adverse event of concern can be used to provide point estimates and confidence intervals for the benefit-risk ratio. The approach is illustrated using data from the GUSTO trial comparing tissue plasminogen activator and streptokinase in the management of patients with acute myocardial infarction.

Confidence Intervals↗

Outcome assessment for clinical trials: how many adjudicators do we need? Canadian Lung Oncology Group.

Considerable effort is often expended to adjudicate outcomes in clinical trials, but little has been written on the administration of the adjudication process and its possible impact on study results. As a case study, we describe the function and performance of an adjudication committee in a large randomized trial of two diagnostic approaches to potentially operable lung cancer. Up to five independent adjudicators independently determined two primary outcomes: tumor status at death or at final follow-up and the cause of death. Patients for whom there was any disagreement were discussed in committee until a consensus was achieved. We describe the pattern of agreement among the adjudicators and with the final consensus result. Additionally, we model the adjudication process and predict the results if a smaller committee had been used. We found that reducing the number of adjudicators from five to two or three would probably have changed the consensus outcome in less than 10% of cases. Correspondingly, the effect on the final study results (comparing primary outcomes in both randomized arms) would have been altered very little. Even using a single adjudicator would not have affected the results substantially. About 90 minutes of person-time per patient was required for activities directly related to the adjudication process, or approximately 6 months of full time work for the entire study. This level of effort could be substantially reduced by using fewer adjudicators with little impact on the results. Thus, we suggest that when high observer agreement is demonstrated or anticipated, adjudication committees should consist of no more than three members. Further work is needed to evaluate if smaller committees are adequate to detect small but important treatment effects or if they compromise validity when the level of adjudicator agreement is lower.

Cause of Death↗