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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
PubMed2001

Do blood transfusions improve outcomes related to mechanical ventilation?

BACKGROUND: Correcting the decrease in oxygen delivery from anemia using allogeneic RBC transfusions has been hypothesized to help with increased oxygen demands during weaning from mechanical ventilation. However, it is also possible that transfusions hinder the process because RBCs may not be able to adequately increase oxygen delivery. In this study, we determined whether a liberal RBC transfusion strategy improved outcomes related to mechanical ventilation. METHODS: Seven hundred thirteen patients receiving mechanical ventilation, representing a subgroup of patients from a larger trial, were randomized to either a restrictive transfusion strategy, receiving allogeneic RBC transfusions at a hemoglobin concentration of 7.0 g/dL (and maintained between 7.0 g/dL and to 9.0 g/dL), or to a liberal transfusion strategy, receiving RBCs at 10.0 g/dL (and maintained between 10.0 g/dL and 12.0 g/dL). The larger trial was designed to evaluate transfusion practice rather than weaning per se. RESULTS: Baseline characteristics in the restrictive-strategy group (n = 357) and the liberal-strategy group (n = 356) were comparable. The average durations of mechanical ventilation were 8.3 +/- 8.1 days and 8.3 +/- 8.1 days (95% confidence interval [CI] around difference, - 0.79 to 1.68; p = 0.48), while ventilator-free days were 17.5 +/- 10.9 days and 16.1 +/- 11.4 days (95% CI around difference, - 3.07 to 0.21; p = 0.09) in the restrictive-strategy group vs the liberal-strategy group, respectively. Eighty-two percent of the patients in the restrictive-strategy group were considered successfully weaned and extubated for at least 24 h, compared to 78% for the liberal-strategy group (p = 0.19). The relative risk (RR) of extubation success in the restrictive-strategy group compared to the liberal-strategy group, adjusted for the confounding effects of age, APACHE (acute physiology and chronic health evaluation) II score, and comorbid illness, was 1.07 (95% CI, 0.96 to 1.26; p = 0.43). The adjusted RR of extubation success associated with restrictive transfusion in the 219 patients who received mechanical ventilation for > 7 days was 1.1 (95% CI, 0.84 to 1.45; p = 0.47). CONCLUSION: In this study, there was no evidence that a liberal RBC transfusion strategy decreased the duration of mechanical ventilation in a heterogeneous population of critically ill patients.

APACHE↗
PubMed2001

Trials comparing alternative weaning modes and discontinuation assessments.

We identified 16 randomized controlled trials (RCTs) of methods for weaning patients from mechanical ventilation, 8 of which were trials of discontinuation assessment strategies, 5 of which were trials of stepwise reduction in mechanical ventilatory support, and 3 of which were trials comparing alternative ventilation modes for weaning periods lasting < 48 h. We found that different thresholds for deciding when a patient is ready for a trial of spontaneous breathing, different criteria for a successful trial, and different thresholds for extubation may overwhelm the impact of alternative ventilation strategies. Nevertheless, the results of these studies suggest the possibility that multiple daily T-piece weaning or pressure support may be superior to synchronized intermittent mandatory ventilation. Other RCTs suggest that early extubation with the back-up institution of noninvasive positive-pressure ventilation as needed may be a useful strategy in selected patients.

Evidence-Based Medicine↗
PubMed2001

Mechanical ventilator weaning protocols driven by nonphysician health-care professionals: evidence-based clinical practice guidelines.

Health-care professionals (HCPs) can provide protocol-based care that has a measurable impact on critically ill patients beyond their liberation from mechanical ventilation (MV). Randomized controlled trials have demonstrated that protocols for liberating patients from MV driven by nonphysician HCPs can reduce the duration of MV. The structure and features of protocols should be adapted from published protocols to incorporate patient-specific needs, clinician preferences, and institutional resources. As a general approach, shortly after patients demonstrate that their condition has been stabilized on the ventilator, a spontaneous breathing trial (SBT) is safe to perform and is indicated. Ventilator management strategies for patients who fail a trial of spontaneous breathing include the following: (1) consideration of all remediable factors (such as electrolyte derangements, bronchospasm, malnutrition, patient positioning, and excess secretions) to enhance the prospects of successful liberation from MV; (2) use of a comfortable, safe, and well-monitored mode of MV (such as pressure support ventilation); and (3) repeating a trial of spontaneous breathing on the following day. For patients who pass the SBT, the decision to extubate must be guided by clinical judgment and objective data to minimize the risk of unnecessary reintubations and self-extubations. Protocols should not represent rigid rules but, rather, guides to patient care. Moreover, the protocols may evolve over time as clinical and institutional experience with them increases. Useful protocols aim to safely and efficiently liberate patients from MV, reducing unnecessary or harmful variations in approach.

Clinical Protocols↗
PubMed2001

Trials of corticosteroids to prevent postextubation airway complications.

We identified three randomized controlled trials (RCTs) that addressed whether preextubation steroid administration reduces postextubation complications in children. The pooled analysis of primary extubation in children demonstrated significantly less stridor (relative risk [RR], 0.57; 95% confidence interval [CI], 0.40 to 0.81) and a trend toward less reintubation (RR, 0.50; 95% CI, 0.02 to 13.87) with corticosteroids. One non-RCT in children who had failed extubation the first time found a significant reduction in duration of prolonged reintubation (> or = 6 days) and in failed reextubations. The four RCTs in adults reported very low reintubation rates, and no conclusions can be drawn. Only one RCT assessed postextubation stridor and found little difference. Overall, we found that corticosteroids decreased the risk of postextubation stridor in children by about 40%. However, the effect of corticosteroids in children and adults to reduce postextubation complications such as reintubation is uncertain.

Adrenal Cortex Hormones↗
PubMed2001

Qualitative studies on the patient's experience of weaning from mechanical ventilation.

In contrast to primarily deductive quantitative research, qualitative research aims to interpret data to develop theoretical insights that describe and explain phenomena such as interactions, experiences, roles, perspectives, and organizations. In this review, we summarize qualitative studies that used primarily in-depth personal interviews as a data collection method and a grounded theory analytic approach. The liberal use of illustrative excerpts and interpretive descriptions offer clinicians vicarious accounts of patient experiences of weaning from mechanical ventilation. Important experiences of patients during their weaning from mechanical ventilation included frustration, uncertainty, hopelessness, fear, and lack of mastery. The extent to which, in at least some patients, these experiences were determinants of weaning failure, consequences of weaning failure, or both, was difficult to establish. An assumption of this genre of research is that if clinicians understand the lived experiences of patients, they can better appreciate patient needs during the weaning process, and by inference, their role as clinicians during weaning from mechanical ventilation.

Data Collection↗
PubMed2001

Deriving robust operating rules for the interim control of the Kirazdere reservoir.

A methodology is developed for deriving robust operating rules for the interim control of a multipurpose reservoir. The methodology includes the generation of policies using optimisation models, the derivation of robust operating rules using artificial neural networks and the evaluation of the identified policies through simulation. The approach developed is demonstrated through an application to the Kirazdere Reservoir located on the Kiraz River in Turkey.

Conservation of Natural Resources↗
PubMed2001

Weaning from mechanical ventilation: the evidence from clinical research.

Mechanical ventilation incurs substantial morbidity, mortality, and costs. Both premature extubation and delayed extubation can cause harm. Therefore, weaning that is both expeditious and safe is highly desirable. The purpose of this review is to summarize the literature related to weaning modes, spontaneous breathing trials, weaning predictors, weaning with noninvasive positive pressure ventilation, and weaning protocols. We used 5 computerized databases and a duplicate independent review process to select articles for this review. We included randomized clinical trials evaluating any weaning interventions and nonrandomized trials of weaning predictors, with a focus on studies reporting clinically important outcomes. We abstracted quantitative data using several metrics and pooled results across studies only when our assessment of the patients, interventions, and outcomes indicated that pooling was legitimate. The available clinical research evidence suggests that, for progressive weaning of the level of mechanical support, it may be best to choose modes other than synchronized intermittent mandatory ventilation and it is unreasonable to be dogmatic about the use of other modes. There may also be substantial benefits to early extubation with back-up institution of noninvasive positive pressure ventilation, as needed, though this remains an experimental approach. For trials of spontaneous breathing, low levels of pressure support may hasten extubation. We did not uncover any consistently powerful weaning predictors, suggesting that formal use of predictors in patients being considered for reduction or discontinuation of mechanical support is unlikely to improve patient care. The likely explanation is that clinicians already fully consider information from weaning predictors in choosing patients for trials of reduction or discontinuation of mechanical ventilation. Finally, implementation of respiratory therapist- or nurse-driven protocols may be useful for all phases of weaning, and clinicians should adopt daily assessment for a trial of unassisted breathing as a safe method to reduce the duration of mechanical ventilation.

Clinical Trials as Topic↗
PubMed2000

Users' Guides to the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users' Guides to patient care. Evidence-Based Medicine Working Group.

This series provides clinicians with strategies and tools to interpret and integrate evidence from published research in their care of patients. The 2 key principles for applying all the articles in this series to patient care relate to the value-laden nature of clinical decisions and to the hierarchy of evidence postulated by evidence-based medicine. Clinicians need to be able to distinguish high from low quality in primary studies, systematic reviews, practice guidelines, and other integrative research focused on management recommendations. An evidence-based practitioner must also understand the patient's circumstances or predicament; identify knowledge gaps and frame questions to fill those gaps; conduct an efficient literature search; critically appraise the research evidence; and apply that evidence to patient care. However, treatment judgments often reflect clinician or societal values concerning whether intervention benefits are worth the cost. Many unanswered questions concerning how to elicit preferences and how to incorporate them in clinical encounters constitute an enormously challenging frontier for evidence-based medicine. Time limitation remains the biggest obstacle to evidence-based practice but clinicians should seek evidence from as high in the appropriate hierarchy of evidence as possible, and every clinical decision should be geared toward the particular circumstances of the patient.

Clinical Competence↗
PubMed2000

Association between a positive flow cytometry crossmatch and the development of chronic rejection in primary renal transplantation.

OBJECTIVES: With the current repertoire of immunosuppressants available, the results of organ transplantation are now very good in the short term. However, many grafts continue to be lost in the long term because of chronic rejection. This study examined the effect of kidney transplantation against a positive flow cytometry crossmatch (FCXM) on the subsequent development of chronic rejection and graft failure. METHODS: We examined 187 primary renal transplantations performed at our institution between 1993 and 1996. All of these patients had a negative cytotoxicity crossmatch. All had a pretransplant FCXM, and patients were divided according to the results of the FCXM into three categories: FCXM negative, FCXM class I positive, and FCXM class II positive. RESULTS: We found that a positive FCXM at the time of transplantation was strongly associated with the ultimate development of chronic rejection. In FCXM-negative individuals, 16.9% developed chronic rejection compared with 80% of those with an HLA class I (T and B-cell) reaction and 40.9% of those with a class II (B-cell-only) reaction (P <0.001). The 3-year graft survival rate was 93% for FCXM-negative patients compared with 86% for FCXM class II positive and 80% for FCXM class I positive patients (P = 0.001). CONCLUSIONS: A strong association between a positive FCXM and subsequent development of chronic rejection was identified. This finding raises the possibility that more aggressive treatment of patients with a positive FCXM might ultimately result in a lower incidence of chronic rejection and improve overall graft survival.

Acute Disease↗
PubMed2000

Users' guides to the medical literature: XXIII. Qualitative research in health care B. What are the results and how do they help me care for my patients? Evidence-Based Medicine Working Group.

The second part of this 2-part series on how to interpret qualitative research addresses, "what are the results," and, "how do they help me care for my patients?" Qualitative analysis is a process of summarizing and interpreting data to develop theoretical insights that describe and explain social phenomena such as interactions, experiences, roles, perspectives, symbols, and organizations. Key results are often illustrated with excerpts from interview transcripts, field notes, or documents. The results of a qualitative research report are best understood as an empirically based contribution to ongoing dialogue and exploration. Empirically based theory evolves from a process of exploration, discovery, analysis, and synthesis. Each concept should be defined carefully in a way that is meaningful to the reader. Concepts should be adequately developed and illustrated when theoretical conclusions are drawn. Arguments should be explained and justified. The qualitative research report ideally should address how the findings relate to other theories in the field. The qualitative study can provide a useful road map for understanding and navigating similar social settings interactions, or relationships. JAMA. 2000;284:478-482

Advance Directives↗
PubMed2000

Users' guides to the medical literature: XXIII. Qualitative research in health care A. Are the results of the study valid? Evidence-Based Medicine Working Group.

Quantitative research is designed to test well-specified hypotheses, determine whether an intervention did more harm than good, and find out how much a risk factor predisposes persons to disease. Equally important, qualitative research offers insight into emotional and experiential phenomena in health care to determine what, how, and why. There are 4 essential aspects of qualitative analysis. First, the participant selection must be well reasoned and their inclusion must be relevant to the research question. Second, the data collection methods must be appropriate for the research objectives and setting. Third, the data collection process, which includes field observation, interviews, and document analysis, must be comprehensive enough to support rich and robust descriptions of the observed events. Fourth, the data must be appropriately analyzed and the findings adequately corroborated by using multiple sources of information, more than 1 investigator to collect and analyze the raw data, member checking to establish whether the participants' viewpoints were adequately interpreted, or by comparison with existing social science theories. Qualitative studies offer an alternative when insight into the research is not well established or when conventional theories seem inadequate. JAMA. 2000;284:357-362

Data Collection↗
PubMed2000

The impact of HLA sensitization and donor cause of death in heart transplantation.

Current expansion of the recipient population and increased utilization of left ventricular assist devices as a bridge-to-transplantation have resulted in HLA sensitization becoming an increasingly important clinical problem in cardiac transplantation. We evaluated the impact of HLA sensitization and donor cause of death on survival in 500 cardiac transplant recipients. Donor cause of death was grouped into two categories, trauma and nontrauma. Panel reactive antibodies at the time of transplant were assayed and used as a marker for sensitization if more than 10%. Sensitized recipients had a poorer 1-year survival than those not sensitized (76 vs. 89%, respectively, P=0.2). Donor cause of death had an overall significant impact on survival with 1-year survival for recipients of trauma organs of 92 and 82% for recipients of nontrauma hearts (P=0.02). Trauma hearts transplanted into sensitized recipients yielded a survival of 93% at 1 year whereas if nontrauma donor hearts were transplanted into these recipients, survival was only 52% at 1 year, P<0.001. These intriguing results suggest that graft survival in HLA-sensitized recipients could be significantly improved through the use of hearts from trauma death donors.

Adolescent↗
PubMed2000

A randomized prospective trial of low-dose OKT3 induction therapy to prevent rejection and minimize side effects in recipients of kidney transplants.

BACKGROUND: We attempted to minimize the undesired side effects and maximize the benefit of OKT3 induction therapy in renal transplantation. METHODS: One hundred and one recipients of kidney-only transplants were randomized to three groups. Each received low-dose 2.5-mg OKT3 induction for 7-14 days, but different premedication on days 0, 1, and 2. Group I was given 250 mg i.v. methylprednisolone at 1 and 6 hr, and group II received another 500 mg at 1 hr before initial OKT3. Group III received Atgam 15 mg/kg on day 0 and began OKT3 on day 1. A CD3+ T-cell cut-off of 50/mm3 was used to guide therapy. Maintenance therapy included cyclosporine and steroids for each patient. However, groups I and II were also given mycophenolate mofetil, and group III received azathioprine as a third agent. All rejections were biopsy confirmed and Banff scored. RESULTS: No differences in demographic or transplant characteristics were noted between groups I, II, and III, and mean follow-up was 25.7 (1-38) months. There was no significant difference in actuarial patient (90%, 91%, 94%) or graft survival (83%, 88%, 84%) at 3 years between the respective groups. Mean creatinine values and infectious complications were similar for each group. No patient experienced acute rejection during induction, and eight patients required dose escalation to sustain suppression of CD3 counts. The incidence of acute rejection at 6 and 12 months was significantly (P=0.004) greater in group III (38.2, 44.1%) than in either group I (15.1, 18.1%) or group II (14.7, 17.6%); relative risk 1.988 (95% CI 1.012-3.906). Formation of anti-OKT3 antibody was significantly (P=0.006) greater in group III (26.5%) than in group I (6%) or group II (2.9%). Group I recipients enjoyed significantly (P=0.001) fewer (2.17) OKT3 side effects on days 0, 1, and 2 than group II (3.03) or group III (2.49), and contained the largest number (61%) of recipients who experienced no side effects. Group I also exhibited the most suppressed profile of OKT3-induced release of tumor necrosis factor-alpha (P=0.006), interferon-gamma (P=NS), and interleukin-6 (P=0.01) on days 0 and 1. CONCLUSIONS: Low-dose 2.5-mg OKT3 with pretreatment of split-dose steroids on days 0, 1, and 2 provides the most effective method for OKT3 induction, which minimizes side effects for most patients. Subsequent maintenance therapy with cyclosporine, mycophenolate mofetil, and steroids provides effective rejection prophylaxis without increased complications for up to 3 years. Predepletion of T cells before exposure to OKT3 does not prevent cytokine release.

Acute Disease↗
PubMed2000

Isoniazid for preventing tuberculosis in non-HIV infected persons.

BACKGROUND: Although isoniazid (INH) is commonly used for treating tuberculosis (TB), it is also effective as preventive therapy. OBJECTIVES: The objective of this review was to estimate the effect of 6 and 12 month courses of INH for preventing TB in HIV-negative people at increased risk of developing active TB. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles. We hand-searched Science Citation Index and Index Medicus. SELECTION CRITERIA: Randomised trials of INH preventive therapy for 6 months or more compared with placebo. Follow-up for a minimum of 2 years. Trials enrolling patients with current or previously treated active TB, or with known HIV infection, were excluded. Criteria were applied by two reviewers independently. DATA COLLECTION AND ANALYSIS: Trial quality was assessed by two reviewers independently, and data extracted by one reviewer using a standardized extraction form. MAIN RESULTS: Eleven trials involving 73,375 patients were included. Trials were generally of high quality. Treatment with INH resulted in a relative risk (RR) of developing active TB of 0.40, (95% confidence interval ¿CI¿ 0.31 to 0.52), over two years or longer. There was no significant difference between 6 and 12 month courses (RR of 0.44, 95% CI 0.27 to 0.73 for six months, and 0.38, 95% CI 0.28 to 0.50 for 12 months). Preventive therapy reduced deaths from TB, but this effect was not seen for all cause mortality. INH was associated with hepatotoxicity in 0.36% of people on 6 months treatment and in 0.52% of people treated for 12 months. REVIEWER'S CONCLUSIONS: Isoniazid is effective for the prevention of active TB in diverse at-risk patients, and six and 12 month regimens have a similar effect.

Antitubercular Agents↗
PubMed2000

Differential perfusion: a new technique for isolated brain cooling during cardiopulmonary bypass.

BACKGROUND: The purpose of this study was to determine the feasibility of differential perfusion of the aortic arch and descending aorta during cardiopulmonary bypass using a cannula designed for aortic segmentation. METHODS: Pigs weighing 57 kg (n = 8), underwent cardiopulmonary bypass using the dual lumen aortic cannula. An inflatable balloon separated proximal (aortic arch) and distal (descending aorta) ports. During differential perfusion, the aorta was segmented and the arch and descending aorta perfused differentially using parallel heat exchangers. Ability to independently control brain and body temperature, cardiopulmonary bypass flow rate and mean arterial blood pressure was determined. RESULTS: During differential perfusion cerebral hypothermia (27 degrees C) with systemic normothermia (38 degrees C) was established in 23 minutes. Independent control of arch and descending aortic flow and mean arterial blood pressure was possible. Analysis of internal jugular venous O2 saturation data indicated an increase in the ratio of cerebral O2 supply to demand during differential perfusion. CONCLUSIONS: A cannulation system segmenting the aorta allows independent control of cerebral and systemic perfusion. This device could provide significant cerebral protection while maintaining the advantages of warm systemic cardiopulmonary bypass temperatures.

Animals↗