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Biomedical subjects

D J Cook

Publications and source records attributed to D J Cook.

At least 55 records · Page 3Linked to original sources

Vascular rejection post heart transplantation is associated with positive flow cytometric cross-matching.

OBJECTIVE: Use of flow cytometry cross-matching for measurement of donor-specific alloreactivity and monitoring anti-donor antibodies is well established. This study was performed to determine (1) its accuracy as a marker of vascular rejection, (2) its correlation with post-transplant outcome and (3) its ability to monitor highly sensitized patients requiring antibody removal with plasma exchange. METHODS: Serial serum samples from 99 heart transplant recipients were examined for the presence of anti-donor antibodies of the IgG class that were reactive with T and/or B cryopreserved donor lymphocytes. A sub-group of 20 HLA sensitized patients required plasma exchange to remove the anti-HLA antibodies and were monitored with flow cytometry cross-matching to assess the degree of antibody removal. RESULTS: Positive T-cell reactions were observed in 26 patients and positive B-cell reactions in 54. Twenty patients had vascular rejection. A significantly larger number of patients with a positive flow cytometry cross-match had vascular rejection (42% versus 12% for T-cell reactions, and 32% versus 7% for B-cell reactions; P = 0.002 each). Of the patients who had vascular rejection, 11 had a positive T-cell reaction (flow cytometry cross-match sensitivity of 55%), and 17 had a positive B-cell reaction (sensitivity of 85%). Of the 79 patients who did not develop vascular rejection, 64 had a negative T-cell reaction (specificity of 81%), and 42 had a negative B-cell reaction (specificity of 53%). The actuarial 2-year survival estimates were significantly higher in patients with negative T-cell reactions (90% versus 75%; P = 0.04), and B-cell reactions (95% versus 78%; P = 0.02). In the highly sensitized subgroup (n = 20) the effectiveness of plasma exchange to decrease anti-HLA antibody reactivity was a strong predictor of outcome. For patients in whom plasma exchange (PE) reduced anti-donor reactivity, 1-year survival was 87% compared to 25% in those whom PE did not reduce the level of antibody binding as assessed with flow cytometry cross-matching (P < 0.0001). CONCLUSIONS: Flow cytometry cross-matching provides a valuable marker for the detection of vascular rejection after cardiac transplantation. Quantitative measurements may allow evaluation of the efficacy of treatment modalities employed in the management of vascular rejection in an attempt to improve outcome.

Actuarial Analysis

Normothermic cardiopulmonary bypass increases heparin requirements necessary to maintain anticoagulation.

OBJECTIVE: With the practice of warm cardiopulmonary bypass (CPB) at our institution we have observed an apparent increase in heparin requirements. CPB temperature predictability affects pharmacokinetics and differences in drug metabolism can be expected. We hypothesized that heparin requirements would increase with increasing CPB temperature. METHODS: Following Institutional Review Board approval, we reviewed the charts of 354 patients undergoing primary coronary artery bypass graft surgery. We recorded patient demographic data, CPB duration, heparin requirements, and temperature during CPB. CPB was conducted between 24 degrees C and 37 degrees C. The Spearman's correlation coefficient, Pearson chi-square, and rank-sum tests were used for data analysis. RESULTS: Core temperature during CPB correlated with heparin requirements (r = 0.13, p < 0.02). However, CPB duration was shorter in warm patients than in cold patients (r = -0.455, p < 0.0001). Additional heparin requirements adjusted for duration of CPB (units/minute) were also significantly greater in the warm group (p = 0.018). CONCLUSIONS: Maintenance of adequate heparin anticoagulation during CPB is clinically important. Warm CPB patients required more heparin per minute than those undergoing cold CPB. More frequent assessment of anticoagulation and administration of additional heparin should be considered in patients undergoing warm CPB.

Aged

Development of a questionnaire to measure quality of life in patients with irritable bowel syndrome.

OBJECTIVE: To develop a questionnaire for measuring health-related quality of life (HRQL) in patients with Irritable Bowel Syndrome (IBS). METHODS: We surveyed the existing literature, and interviewed patients and clinicians, to develop a list of 182 potential problems for IBS patients. One hundred patients with IBS completed a questionnaire in which they told us whether each of the 182 items was a problem for them, and if so the magnitude of their importance in their lives. RESULTS: Patients identified four major problem areas: bowel symptoms, fatigue, activity limitations, and emotional dysfunction. On the basis of these findings, we constructed a 26-item questionnaire which, in pre-testing, 16 patients found clear and easy to complete. CONCLUSION: We have developed a questionnaire that measures HRQL in IBS patients and is suitable for use as an outcome measure in clinical trials in IBS.

Activities of Daily Living

Telekid Care: bringing health care into schools.

BACKGROUND: Telekid Care is a project that attempts to overcome the health and educational barriers faced by children in urban Kansas City, Kansas. Telemedicine units were placed in school nurses' offices and linked to physicians at the University of Kansas Medical Center (KUMC). This paper describes the development of this project, presents utilization data, and discuss the lessons learned from the application of telemedicine in a school setting. RESULTS: Project developers spent 11 months designing the protocol and procedures for a pilot test. Four elementary schools participated, and 187 consultations were conducted. The most common reason for consultation was ear, nose, and throat (ENT) problems, making up 28% of all consults. Mandatory school physical examinations and dermatology problems combined to make up an additional 40% of the consults. The average time that elapsed between the request for a consult and confirmation of an appointment was 23 minutes. When immediate service was requested, 85% of the consults occurred the day of the request. These results strongly demonstrate telemedicine's ability to offer immediate service to children in need. CONCLUSION: Telemedicine enabled underserved inner-city children to gain access to health services. This service was most effective when it was integrated into the delivery system. Furthermore, community groups strongly favored the project, positively influencing its acceptance as an innovative health care delivery system.

Appointments and Schedules

Confidence in life-support decisions in the intensive care unit: a survey of healthcare workers. Canadian Critical Care Trials Group.

OBJECTIVE: To examine the relationship between intensive care unit (ICU) healthcare workers' confidence and their decision to withdraw life support. DESIGN: Cross-sectional survey of Canadian intensivists, ICU housestaff, and bedside nurses. Respondents chose the level of care (from comfort measures only to full aggressive care) for 12 patients described in clinical scenarios, and rated their confidence in their decisions. SETTING: Thirty-seven Canadian university-affiliated hospitals. PATIENTS: None. INTERVENTIONS: We used discrete data analysis models to examine the association between the chosen level of care, confidence in the decisions, the clinical scenario, and healthcare worker group. MEASUREMENTS AND MAIN RESULTS: The response rate was 1,361 (76%)/1,795; for this analysis, we used data from 1,306 respondents with completed questionnaires. Responses for each scenario varied widely among respondents. The level of care chosen was dependent on the scenario, the healthcare worker group, and the confidence with which the decisions were made (p < .001 for each). Intensivists were less aggressive than the ICU nurses, who were less aggressive than the housestaff, but the magnitude of effect was small. Overall, respondents were very confident about their decisions 34% of the time. After adjustment for clinical scenario and chosen level of care, intensivists were more confident than nurses, who were more confident than housestaff (40% of intensivists, 29% of nurses, and 23% of housestaff were very confident). In general, healthcare workers tended to be more confident when they chose extreme levels of care than when they chose intermediate levels of care. Considerable variability in responses to scenarios remained even when we considered only those responses made with the highest level of confidence. CONCLUSIONS: While confidence in decisions about withdrawal of life support increases with seniority and authority, consistency of decisions may not. When given standard information, healthcare workers can make contradictory decisions yet still be very confident about the level of care they would administer.

Aged

Frequency and methodologic rigor of quality-of-life assessments in the critical care literature.

OBJECTIVES: To present a framework for describing/measuring quality of life (QOL) and health-related quality of life (HRQL), and to assess the frequency and methodologic rigor of QOL studies in the adult critical care literature. DATA SOURCES: Computerized bibliographic search of published research, manual search of key intensive care unit (ICU) journals, and citation review of relevant articles. STUDY SELECTION: We manually searched Critical Care Medicine, American Journal of Respiratory and Critical Care Medicine, and Intensive Care Medicine for the period January 1992 to July 1995 to assess the frequency of published QOL studies. Combined with a computerized bibliographic search, we found 64 studies that met our criteria that reported on patient-related outcomes (other than mortality) after hospital discharge. DATA EXTRACTION: We abstracted data on the nature of each study, the instruments used to measure QOL, and the methodologic rigor of the QOL assessments. We evaluated each study using criteria we developed to assess the validity of HRQL measurements. MEASUREMENTS AND MAIN RESULTS: In our manual search, we found 1,073 articles relevant to the practice of adult critical care. Of these, 19 (1.7%)/1073 included QOL measurements. Combined with our comprehensive search strategy, we found 64 papers that evaluated QOL in ICU patients. These papers dealt primarily with issues of: prognosis (32 [50%]), resource allocation (23 [36%]), and clinical prediction (9 [14%]). We found no randomized trials that included post-ICU QOL as an outcome. With respect to the validity of the HRQL assessments, 63/64 (98%) studies evaluated aspects of patients' lives that we considered important. Thirty-three (52%) studies were limited in scope to specific aspects of HRQL, and 31 (48%) studies covered broad areas of HRQL. In these 64 studies, there were 108 different instruments used. The reliability and validity of the instruments used were reported in 7 (6%) and 15 (14%) cases, respectively. For 81 (75%) instruments, the investigators either explained the results or used informative, qualitative descriptors whose interpretation was self-evident. Overall, three (5%) of the included studies met all four methodologic criteria to assess the validity of HRQL assessments. CONCLUSIONS: QOL assessments occur infrequently in the ICU literature and are of limited methodologic quality. More studies using valid and reliable instruments are necessary to document the long-term QOL of critically ill patients, especially those at risk of a "poor" outcome.

Adult

How to use practice guidelines in the intensive care unit: Diagnosis and management of unstable angina.

OBJECTIVE: Practice guidelines are often based on expert opinion, and are sometimes based on research evidence, but are usually a mix of both. The goal of this article is to aid in the evaluation of the validity of practice guidelines. DATA SYNTHESIS: The Agency for Health Care Policy and Research Practice Guideline on Management of Unstable Angina and other relevant primary and synthetic research. METHODS: Critical appraisal of guidelines requires understanding how guideline developers identified, appraised, and summarized the evidence, and how they chose the values reflected in their recommendations. To determine whether guidelines are applicable in our practice, we look for clear and concise recommendations about specific populations, describing common options linked to clinically important outcomes. Guidelines must be considered in light of local skills, culture, and resources, and need to be individualized to different patients and settings. CONCLUSIONS: As better evidence and new clinical insights emerge, guidelines require updating. The ultimate value of a guideline is determined by evaluating its effect on process of care, resource utilization, and most importantly, patient outcomes.

Angina, Unstable

How to use a review article: prophylactic endoscopic sclerotherapy for esophageal varices. Evidence Based Critical Care Medicine Group.

OBJECTIVE: To assess the validity of a meta-analysis about sclerotherapy for the primary prevention of bleeding from esophageal varices, to interpret the results, and discuss whether they apply in practice. DATA SOURCES: Critical appraisal techniques for systematic reviews. DATA EXTRACTION: Systematic reviews are distinct from narrative reviews in that they answer specific clinical questions, and have explicit and reproducible methods for searching, selecting, and appraising the primary studies, to create the most valid synthesis of the evidence. DATA SYNTHESIS: Meta-analyses are systematic reviews containing a critical appraisal and statistical summary of individual study results and their confidence limits, whereas qualitative systematic reviews provide a narrative executive summary of study results. CONCLUSIONS: High-quality systematic reviews are being used increasingly to guide practice, strengthening the link between research results and improved health outcomes. Understanding their strengths and limitations helps us to use them appropriately in practice.

Critical Care

Tunneling short-term central venous catheters to prevent catheter-related infection: a meta-analysis of randomized, controlled trials.

OBJECTIVE: To evaluate the efficacy of tunneling short-term central venous catheters to prevent catheter-related infections. DATA SOURCES: MEDLINE, EMBASE, conference proceedings, citation review of relevant primary and review articles, personal files, and contact with expert informants. STUDY SELECTION: From a pool of 225 randomized, controlled trials of venous and arterial catheter management, we identified 12 relevant trials and included seven of these trials in the analysis. DATA EXTRACTION: In duplicate, independently, we abstracted data on the population, intervention, outcomes, and methodologic quality. DATA SYNTHESIS: Tunneling decreased bacterial colonization of the catheter by 39% (relative risk of 0.61; 95% confidence interval [CI] of 0.39 to 0.95) and decreased catheter-related sepsis with bacteriologic confirmation by 44% (relative risk of 0.56; 95% CI of 0.31 to 1) in comparison with standard placement. The majority of the benefit in the decreased rate of catheter-sepsis came from one trial at the internal jugular site (relative risk of 0.30, 95% CI of 0.10 to 0.89) and the reduction in risk was not significant when the data from five subclavian catheter trials were pooled (relative risk of 0.71, 95% CI of 0.36 to 1.43). Tunneling was not associated with increased risk of mechanical complications from placement or technical difficulties during placement. However, this outcome was not rigorously evaluated. CONCLUSIONS: Tunneling decreases central venous catheter-related infections. However, current evidence does not support routine tunneling until its efficacy is evaluated at different placement sites and relative to other interventions.

Bacteremia

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

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