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Biomedical subjects

D J Cook

Publications and source records attributed to D J Cook.

At least 19 recordsLinked to original sources

Early and late rejection and HLA sensitization at the time of heart transplantation in patients bridged with left ventricular assist devices.

Over the years, the frequency of heart transplant candidates with HLA sensitization has increased as a result of the number of patients bridged to transplant using left ventricular assist devices (LVAD). Here we have examined 119 patients who were bridged to transplant with LVAD for a relationship between HLA antibodies and early (30 days) and late (2 years or more) rejection, as evidenced by endomyocardial biopsies. Both cytotoxic panel-reactive antibody reactions against a panel of T lymphocytes (T-PRA) and the percentage of transplants that occurred across a positive class I flow cross-match were examined. Biopsies were scored using ISHLT criteria. At 30 days, patients who had a biopsy grade of 0 had a mean T-PRA at transplant of 2.2%, while the mean PRAs of the other biopsy grades were significantly higher (P < .001). A similar pattern was seen with the highest biopsy results at 2 years or later (P < .001). None of the patients who had a grade 0 biopsy at 30 days posttransplant had a positive flow cytometry class I cross-match (P = .02), although the same pattern did not occur later due to a small number of patients (n = 3) who had negative biopsies. Thus, when biopsy results were examined early or late posttransplant, patients with negative biopsy results tended to have less HLA sensitization. While the methods of HLA sensitization involve humoral responses, more aggressive immunosuppression might be warranted to attempt to reduce cellular rejection posttransplant if HLA class I antibodies are present at the time of transplant.

Flow Cytometry↗

Survival beyond 10 years following heart transplantation: The Cleveland Clinic Foundation experience.

BACKGROUND: Long-term survival after heart transplantation is a desirable although challenging goal. METHODS: We analyzed clinical outcomes in the cohort of 170 patients who have undergone heart transplantation at The Cleveland Clinic Foundation and survived >10 years. RESULTS: We found 10-year and 15-year survival rates of 54% and 41%, respectively, in these patients, but there was also a high incidence of complications, such as hypertension, renal dysfunction, transplant vasculopathy, and malignancy. CONCLUSIONS: Long-term survival following cardiac transplantation is possible although complications are frequent. Beyond 10 years, malignancy is a major cause of death.

Adult↗

Agreement of aspiration tests using barium videofluoroscopy, salivagram, and milk scan in children with cerebral palsy.

To study the agreement between three tests for aspiration, barium videofluoroscopy, salivagram, and milk scan we studied 63 children with severe non-ambulant spastic quadriplegic cerebral palsy (CP) aged 14 months to 16 years (32 males, 31 females). The salivagram was most frequently positive (56%, 95% confidence interval 43 to 68%); the next most frequently positive was barium videofluoroscopy when aspiration was defined as the presence of either laryngeal penetration of material or frank aspiration (39%, 95% confidence interval 26 to 53%). The milk scan was rarely positive (6%, 95% confidence interval 2 to 16%). Agreement between the tests of aspiration was poor. The maximum agreement (kappa=0.20) was between aspiration as diagnosed with the salivagram and by barium videofluoroscopy. Positive tests for aspiration are frequent in children with severe CP. Frequency varies widely depending on the investigation used. There is poor agreement between tests used for the diagnosis of aspiration. This information is of importance in assessing the significance of test results.

Adolescent↗

Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for CNI and steroid-free kidney transplant immunosuppression.

We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1, none thereafter), mycophenolate mofetil (MMF) maintenance (500 mg b.i.d) and sirolimus (concentration controlled 8-12 ng/mL). With a mean follow-up of 15.9 months, patient survival is (21/22) 96% and graft survival (19/22) 87%. Acute rejections occurred in (8) 36.3% (two humoral). Of 19 surviving grafts, 18 (95%) remain steroid and 15 (79%) CNI-free. At 1 year, mean creatinine was 1.43 mg/dL. Overall infection rates were low, but 2 patients developed severe acute respiratory distress syndrome (ARDS) at month 3 and 7, respectively, resulting in mortality in one and a graft loss in the other. No cancer or PTLD was observed. Leukopenia was common and MMF dose was reduced or eliminated in 6/22 (27%) patients. The reported higher than expected rate of acute rejection, leukopenia and possible pulmonary toxicity suggests excessive morbidity. Modifications such as an initial period of CNI use should be considered.

Acute Disease↗

Safety Climate Survey: reliability of results from a multicenter ICU survey.

BACKGROUND: It is important to understand the clinical properties of instruments used to measure patient safety before they are used in the setting of an intensive care unit (ICU). METHODS: The Safety Climate Survey (SCSu), an instrument endorsed by the Institute for Healthcare Improvement, the Safety Culture Scale (SCSc), and the Safety Climate Mean (SCM), a subset of seven items from the SCSu, were administered in four Canadian university affiliated ICUs. All staff including nurses, allied healthcare professionals, non-clinical staff, intensivists, and managers were invited to participate in the cross sectional survey. RESULTS: The response rate was 74% (313/426). The internal consistency of the SCSu and SCSc was 0.86 and 0.80, respectively, while the SCM performed poorly at 0.51. Because of poor internal consistency, no further analysis of the SCM was therefore performed. Test-retest reliability of the SCSu and SCSc was 0.92. Out of a maximum score of 5, the mean (SD) scores of the SCSu and SCSc were 3.4 (0.6) and 3.4 (0.7), respectively. No differences were noted between the three medical-surgical and one cardiovascular ICU. Managers perceived a significantly more positive safety climate than other staff, as measured by the SCSu and SCSc. These results need to be interpreted cautiously because of the small number of management participants. CONCLUSIONS: Of the three instruments, the SCSu and SCSc appear to be measuring one construct and are sufficiently reliable. Future research should examine the properties of patient safety instruments in other ICUs, including responsiveness to change, to ensure that they are valid outcome measures for patient safety initiatives.

Canada↗

Neither baseline tests of molecular hypercoagulability nor D-dimer levels predict deep venous thrombosis in critically ill medical-surgical patients.

OBJECTIVE: Predicting patients who are harboring asymptomatic deep venous thrombosis (DVT), or who are at particular risk of developing DVT, is a desirable clinical goal since prevention or early treatment of DVT might reduce the risk of fatal pulmonary embolism. Thus validation of simple laboratory tests that reliably predict venous thromboembolism (VTE) would be clinically very important. Tests that might be useful for these applications include markers of hypercoagulability (predicting patients at risk of DVT) and D-dimer (predicting which patients may have acute DVT). METHODS: In a prospective cohort study we measured a panel of hypercoagulability markers at the time of ICU admission, and six commercial D-dimer assays were performed serially during the ICU stay in medical-surgical ICU patients who were screened for DVT with biweekly lower limb compression ultrasonography. Ultrasonography was also performed at the time of any clinically suspected DVT events. We matched cases with DVT with controls without DVT for length of stay in the ICU to generate receiver operating characteristics (ROC) curves. RESULTS: One hundred ninety-seven patients were enrolled. Blood was collected on a total of 763 occasions (median number of occasions per patient: 3, range 1-21). None of the assays predicted DVT, as indicated by the areas under the ROC curves, that did not differ significantly from 50%. CONCLUSION: In critically ill patients, neither tests of hypercoagulability nor D-dimer levels predict patients at risk of DVT and thus they should not be used to guide diagnostic testing for DVT.

Aged↗

Improving patients' safety locally: changing clinician behaviour.

Safety initiatives in hospitals should focus on common health care interventions that when used appropriately can improve important health outcomes, and when used inappropriately or not at all, result in substantial harm. We suggest that errors of omission should be a safety priority. We focus on preventive health care interventions, and describe five steps that can improve patients' safety by changing clinician behaviour. The steps are to: do an environmental scan; understand current behaviour, target behaviour for change (why, what, when, where, and who); adopt effective strategies to change behaviour; and synergise.

Behavior↗

The influence of donor gender on allograft vasculopathy: evidence from intravascular ultrasound.

BACKGROUND: Allograft vasculopathy is a major risk factor for mortality following cardiac transplantation. Several immune and nonimmune factors have been evaluated as risk factors for the development of coronary vasculopathy. OBJECTIVE: We evaluated the influence of donor gender on the progression of coronary vasculopathy in heart transplant recipients. METHODS: Eighty-nine heart transplant recipients (67 men, 22 women of mean age: 56 +/- 12 years) underwent serial volumetric intravascular ultrasound analysis (IVUS) at baseline (within 1 month) and at 1 year after transplantation. Patients were divided into four groups in relation to the donor-recipient gender status: female-female, n=17; female-male, n=28; male-female, n=5; male-male, n=39. Ultrasound images were recorded during an automated pullback and with an equal number of slices (average=22 per coronary vessel). The measured IVUS indices for the left anterior descending artery were: change in maximal intimal thickness, average intimal area, total plaque volume, and intimal index. RESULTS: Patients were similar in baseline characteristics. At 1 year after transplantation, IVUS indices of coronary vasculopathy were significantly increased among recipients of female allografts (P <.05). CONCLUSION: Heart transplant recipients of female allografts display increased coronary vasculopathy progression.

Adult↗

Donor intracranial bleeding is associated with advanced transplant coronary vasculopathy: evidence from intravascular ultrasound.

OBJECTIVES: We evaluated the impact of spontaneous intracranial bleeding (ICB) in the donor on transplant coronary vasculopathy using serial intravascular ultrasound examinations. MATERIALS AND METHODS: Between January 1995 and December 2000, 72 recipients underwent cardiac transplantation from donors who had experienced spontaneous ICB (ICB group). Their findings using serial intravascular ultrasound analysis at baseline (within 1 month) and 1 year after transplantation were compared with 90 recipients who had undergone transplantation from trauma donors (trauma group). RESULTS: Compared with the Trauma group, the ICB group showed increased coronary intimal thickness (0.55 +/- 0.33 vs 0.39 +/- 0.3 mm; P = .034), plaque volume (3.84 +/- 2.5 vs 2.28 +/- 1.65 mm(3); P = .015) and plaque burden (7.4 vs 2%) at 1 year after transplantation. CONCLUSIONS: Donor spontaneous ICB is associated with significantly increased coronary vasculopathy.

Adult↗

Characterization of a new HLA-C allele: Cw*0719.

We describe a new human leukocyte antigen (HLA)-Cw*07 allele that differs from Cw*0718 by a single-coding nucleotide. DNA-based genotyping identified a clinical sample from a Black African-American patient that differed from known Cw alleles. The allele was amplified independently with a haplo-specific primer and sequenced in its entirety.

Exons↗

Guidelines in the intensive care unit.

The recent movement toward standardization of critical care practice is associated with a growth in the use of guidelines and protocols. Although complex, the process of guideline development, implementation, evaluation, and maintenance can be systematic. Guideline implementation can improve the processes and outcomes of care; however, guideline adherence represents a major challenge to their success. The quality of the growing number of practice guidelines in critical care is important to assess and several useful instruments are available for this purpose.

Decision Making↗

Effectiveness of the Cobra aortic catheter for dual-temperature management during adult cardiac surgery.

OBJECTIVES: In animals the Cardeon Cobra catheter (Cardeon Corp, Cupertino, Calif) allows independent control of aortic arch and descending aortic temperatures and profoundly reduces cerebral embolization during bypass. This investigation describes the first clinical use of the device during adult cardiac surgery. The purpose of the study was to confirm that the Cobra catheter delivers adequate cerebral and systemic perfusion while providing simultaneous cerebral hypothermia and systemic normothermia during cardiopulmonary bypass. METHODS: In a prospective multicenter study the Cobra aortic catheter was placed in 20 adults undergoing cardiopulmonary bypass. Arch and corporeal temperatures, bypass flows, and arterial blood pressures were recorded intraoperatively. Jugular bulb and mixed venous oxygen saturation was used to assess the adequacy of cerebral and systemic perfusion. RESULTS: Surgeons at 3 institutions placed the Cobra catheter in patients undergoing coronary artery bypass grafting (n = 13), valve (n = 3), and combined valve-bypass (n = 4) operations. Mean total bypass flows of 2.1 +/- 0.2 L x min(-1) x m(-2) maintained mean arterial pressures in arch and descending aortic circulations of greater than 55 mm Hg. A mean differential of 4.3 degrees C between arch and descending aortic temperatures was established before crossclamp application, and a mean maximum temperature differential of 7 degrees C was established during bypass. A 2.4 degrees C temperature differential was maintained at crossclamp removal. Cerebral and systemic venous oxygen saturation remained greater than 65% during bypass. CONCLUSIONS: The Cobra device met all expectations for an arterial cannula with adequate perfusion to the arch and corporeal circulations. Dual perfusion with the Cobra catheter allows for independent temperature control during cardiopulmonary bypass with simultaneous cerebral hypothermia and systemic normothermia.

Adult↗

Evaluation of the ThinkFirst Canada, Smart Hockey, brain and spinal cord injury prevention video.

OBJECTIVE: The ThinkFirst Canada Smart Hockey program is an educational injury prevention video that teaches the mechanisms, consequences, and prevention of brain and spinal cord injury in ice hockey. This study evaluates knowledge transfer and behavioural outcomes in 11-12 year old hockey players who viewed the video. DESIGN: Randomized controlled design. SETTING: Greater Toronto Minor Hockey League, Toronto Ontario. SUBJECTS: Minor, competitive 11-12 year old male ice hockey players and hockey team coaches. INTERVENTIONS: The Smart Hockey video was shown to experimental teams at mid-season. An interview was conducted with coaches to understand reasons to accept or refuse the injury prevention video. MAIN OUTCOME MEASURES: A test of concussion knowledge was administered before, immediately after, and three months after exposure to the video. The incidence of aggressive penalties was measured before and after viewing the video. RESULTS: The number of causes and mechanisms of concussion named by players increased from 1.13 to 2.47 and from 0.67 to 1.22 respectively. This effect was maintained at three months. There was no significant change in control teams. There was no significant change in total penalties after video exposure; however, specific body checking related penalties were significantly reduced in the experimental group. CONCLUSION: This study showed some improvements in knowledge and behaviours after a single viewing of a video; however, these findings require confirmation with a larger sample to understand the sociobehavioural aspects of sport that determine the effectiveness and acceptance of injury prevention interventions.

Attitude to Health↗

Clinical estimation of trunk position among mechanically ventilated patients.

OBJECTIVES: Trunk position at 45 degrees from the horizontal is associated with a decreased risk of gastroesophageal aspiration. The objectives of this study were to determine the accuracy of trunk flexion estimates compared to a reference standard measurement, and to determine agreement about trunk flexion among ICU clinicians. DESIGN: Prospective observational study. SETTING: Two university-affiliated medical-surgical ICUs. PATIENTS AND PARTICIPANTS: Thirty-three mechanically ventilated ICU patients, seven residents, two fellows, three intensivists, and twenty-eight bedside nurses. INTERVENTIONS: Prospectively, concurrently, and independently during rounds, one bedside nurse, one resident, one fellow, and one intensivist clinically estimated the trunk flexion of mechanically ventilated patients. To record the reference standard, a trained investigator measured trunk position in the vertical plane using a goniometer. MEASUREMENTS AND RESULTS: We made 438 clinical assessments on 33 patients aged 57.2+/-19.4 (SD) years with an APACHE II score of 27.3+/-9.4. Mean trunk flexion estimates were: nurses 24.3+/-12.3 degrees from the horizontal, residents 20.2+/-13.7, fellows 20.3+/-10.8, and intensivists 21.1+/-13.1 compared to the reference standard measurement 16.2+/-9.0 degrees. The accuracy of trunk flexion estimates was fair to moderate [intraclass correlation for reference standard versus nurses (ICC 0.42), residents (ICC 0.52), fellows (ICC 0.36), and intensivists (ICC 0.55)]. The agreement among different groups of clinicians was moderate. CONCLUSIONS: In mechanically ventilated patients, we found that clinical estimates of trunk position were moderately good, agreement amongst caregivers was moderately good, but that all clinicians tended to overestimate the angle of semirecumbency.

APACHE↗

An in-vitro evaluation of lectin cytotoxicity using cell lines derived from the ocular surface.

Lectins are proteins or glycoproteins of non-immune origin capable of binding to one or more specific sugar residues. The potential for using lectins as a means of locating and "anchoring" a drug delivery system to a target site on a mucosal surface in order to promote controlled drug delivery and enhanced absorption has been described in previous work. Toxicity is evident for many lectins, and this study has investigated the cytotoxicity of lectins to cells derived from the cornea and conjunctiva. Cultures of transformed cell lines from the conjunctiva and cornea were exposed to solution of lectins, and the viability of these cells assessed by their ability to take up an MTT stain relative to the control. Clear evidence of lectin cytotoxicity was apparent for all of the lectins tested in this study, particularly at higher concentrations and over the longer (48 h) time period. This would raise issues with their potential use in targeted drug delivery systems. The lectins from Lycopersicon esculentum and Helix pomatia appeared to show the least cytotoxic activity and so could be considered the most promising. The lectins from Solanum tuberosum and Triticum vulgaris showed significant cytotoxicity, which contrasts with previous in-vivo studies. However, they might be considered for investigation as targeted therapeutic agents in the treatment of malignant diseases.

Antineoplastic Agents↗

Cardiopulmonary resuscitation directives on admission to intensive-care unit: an international observational study.

BACKGROUND: Resuscitation directives should be a sign of patient's preference. Our objective was to ascertain prevalence, predictors, and procurement pattern of cardiopulmonary resuscitation directives within 24 h of admission to the intensive-care unit (ICU). METHODS: We enrolled 2916 patients aged 18 years and older from 15 ICUs in four countries, and recorded whether, when, and by whom their cardiopulmonary resuscitation directives were established. By polychotomous logistic regression we identified factors associated with a resuscitate or do-not-resuscitate directive. FINDINGS: Of 2916 patients, 318 (11%; 95% CI 9.8-12.1) had an explicit resuscitation directive. In 159 (50%; 44.4-55.6) patients, the directive was do-not-resuscitate. Directives were established by residents for 145 (46%; 40.0-51.3) patients. Age strongly predicted do-not-resuscitate directives: for 50-64, 65-74, and 75 years and older, odds ratios were 3.4 (95% CI 1.6-7.3), 4.4 (2.2-9.2), and 8.8 (4.4-17.8), respectively. APACHE II scores greater than 20 predicted resuscitate and do-not-resuscitate directives in a similar way. An explicit directive was likely for patients admitted at night (odds ratio 1.4 [1.0-1.9] and 1.6 [1.2-2.3] for resuscitate and do-not-resuscitate, respectively) and during weekends (1.9 [1.3-2.7] and 2.2 [1.5-3.2], respectively). Inability to make a decision raised the likelihood of a do-not-resuscitate (3.7 [2.6-5.4]) than a resuscitate (1.7 [1.2-2.3]) directive (p=0.0005). Within Canada and the USA, cities differed strikingly, as did centres within cities. INTERPRETATION: Cardiopulmonary resuscitation directives established within 24 h of admission to ICU are uncommon. As well as clinical factors, timing and location of admission might determine rate and nature of resuscitation directives.

APACHE↗