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Biomedical subjects

R J Cook

Publications and source records attributed to R J Cook.

At least 91 records · Page 5Linked to original sources

Interim monitoring of bivariate responses using repeated confidence intervals.

A method for interim monitoring is described for bivariate response data arising in clinical trials. This procedure centers on a sequence of rectangular joint confidence regions obtained by inverting the hypothesis testing-confidence interval relationship when the testing procedure is governed by a bivariate group sequential design described by Cook and Farewell [4]. The advantage of this type of design over other possible multivariate sequential designs is that the marginal analyses are maintained throughout the trial. This approach proves to be particularly advantageous for active control trials in which a region of therapeutic equivalence is specified for two responses related to efficacy. Two examples illustrate the design and analysis aspects of this approach. The procedure is presented in the context of normally distributed responses; however, adaptations to handle bivariate binary and bivariate failure time data are indicated. Generalizations of this procedure to handle multivariate response data are straightforward.

Administration, Inhalation↗

Prolactinomas in men masquerading as invasive skull base tumours.

Four giant prolactin-secreting tumours invading the skull base are described. All of them occurred in men. The presenting features were sufficiently diverse to be clinically misleading. We advocate the estimation of prolactin levels before embarking on complicated skull base surgery in men where doubt remains regarding the diagnosis after clinical and radiological study.

Adolescent↗

Guidelines for monitoring efficacy and toxicity responses in clinical trials.

There is currently a need for clinical trial methodology that allows formal consideration of toxicity responses. Since a complete evaluation of an experimental therapy addresses both relative efficacy and relative toxicity, general methods for handling bivariate response data are of interest. A procedure for sequentially analysing both efficacy and toxicity data is presented. The procedure is designed to allow early termination due to efficacy results, toxicity results, or both. The method is based on modified marginal sequential analyses, accounting for bivariate correlated responses and multiple analyses over time. The theory is presented in the context of normally distributed responses. Extensions to bivariate failure time data are indicated and an example from a kidney transplant study demonstrates the procedure.

Analysis of Variance↗

Neurologic changes during carotid endarterectomy under cervical block predict a high risk of postoperative stroke.

BACKGROUND: This study was undertaken to confirm a previous report that patients having neurologic changes with carotid artery clamping were at greater risk of developing permanent postoperative neurologic complications after carotid endarterectomy. METHODS: Superficial and deep cervical plexus blocks were performed in 389 patients undergoing carotid endarterectomy. The patients were premedicated and sedated to a level that allowed awake neurologic assessment. Intraoperative neurologic changes were recorded and all patients were examined postoperatively by an independent anesthesiologist to record postoperative neurologic outcome. RESULTS: Trial carotid artery cross clamping resulted in 24% of patients having neurologic changes that usually responded to declamping and shunt insertion. Postoperative permanent neurologic complications occurred in 2.6% of patients, but were more common in patients who had neurologic changes associated with carotid artery cross clamping (6.6% compared to 1.1%, P < 0.01). Thrombosis of the carotid artery was the most common finding in patients who underwent reexploration of the carotid artery after developing postoperative neurologic changes. CONCLUSIONS: This study confirms that patients undergoing carotid endarterectomy under cervical plexus block who have intraoperative neurologic changes have a sixfold increase in the chance of developing a postoperative stroke. This high-risk group may benefit from antithrombotic therapies to improve their outcome.

Aged↗

The Westmead Head Injury Project. Physical and social outcomes following severe head injury.

This study reports the physical outcomes of 181 survivors of severe head injury [Glasgow Coma Score (GCS) 8 or less] following aggressive head injury management which included early triage, evacuation and resuscitation, the use of ventilation in the Intensive Care Unit and intracranial pressure (ICP) measurement and control. At the conclusion of the study period of 2 years after the head injury, 71% had achieved a Glasgow Outcome Score (GOS) of 1, 17% GOS 2, 10% GOS 3 and 2% GOS 4. Physical recovery continued during the 2 years. Locomotor independence was achieved in 93% despite a motor disorder in 59%. About 90% were considered independent for basic life functions, e.g. feeding, bathing, dressing or toileting. Speech disorders were present in 19%. A return to an occupation, either a job or studies, at or below the pre-morbid level was achieved in 68%. Most patients were cared for at home by family or relatives. The majority of patients make a reasonable physical recovery following severe head injury with independence in locomotion and basic life skills. It was our impression that the neuropsychological sequelae of cognitive and behavioural disorders were a major impediment to re-assimilation into society.

Activities of Daily Living↗

The Westmead Head Injury Project outcome in severe head injury. A comparative analysis of pre-hospital, clinical and CT variables.

A prospective study of 315 consecutive patients with a severe head injury was undertaken to study factors contributing to mortality and morbidity, both in the pre-hospital and hospital phases. Entry criteria were a Glasgow Coma Scale (GCS) score of 8 or less after non-surgical resuscitation within 6 h of the injury, or a deterioration to that level within 48 h. Patients with gunshot wounds or who were dead on arrival were excluded. End points of the study were either death or at 6 months after the injury. Predictors of mortality were increasing age, the presence of hypotension, a low GCS, abnormal motor responses and pupillary non-reactivity. In the 167 patients in whom intracranial pressure (ICP) was measured, raised ICP and failure to respond to treatment for raised ICP also predicted mortality. Three CT predictors of mortality were the presence of cerebral oedema, intraventricular blood and the degree of midline shift. When analysed using logistic regression, the most accurate model (accuracy 84.4%) included increasing age, abnormal motor responses and the three CT indicators. Analysis of the data for 'good' (Glasgow Outcome Score (GOS) 1 and 2) vs 'poor' (GOS 3 and 4) survival at 6 months was also performed using logistic regression. The model which provided the most accurate prediction of poor outcome included age, hypotension and three different CT characteristics, subarachnoid blood, intracerebral haematoma or intracerebral contusion (accuracy 72.5%).

Adolescent↗

The natural history of asymptomatic urolithiasis.

An inception cohort of 107 patients was reviewed to establish the natural history of asymptomatic urolithiasis. With an over-all mean followup of 31.6 months, 73 patients (68.2%) remained asymptomatic and were censored at the time of the last clinical visit. A symptomatic event developed in 34 patients (31.8%). Spontaneous passage occurred in 16 patients (15.0%), endoureteral removal was done in 6 (5.6%), percutaneous nephrostolithotomy was done in 3 (2.8%) and 9 (8.4%) were referred for therapeutic lithotripsy. Cumulative 5-year probability of a symptomatic event developing was 48.5%. A linear association was identified between the development of a symptomatic event and the number of previous stones as well as the number of asymptomatic stones at identification. A significant burden of illness is associated with an expectant strategy as an approach to asymptomatic urolithiasis. Of the patients who had a symptomatic event 47% had spontaneous stone passage, while 26.5% required urological intervention and 26.5% were referred for therapeutic lithotripsy. Prophylactic extracorporeal shock wave lithotripsy, although often advocated, has associated risks and is not always a benign procedure. A randomized controlled trial is required to evaluate properly the role of prophylactic lithotripsy versus an expectant strategy.

Adult↗

Canadian Hemodialysis Morbidity Study.

The objective of this study was to determine the probabilities of specific morbid events or death among patients with end-stage renal disease (ESRD) treated by hemodialysis. A prospective cohort study was performed between March 1988 and September 1989 in 18 hemodialysis centers in 13 Canadian cities, representing about one third of the hemodialysis population in Canada. The inception cohort consisted of 496 patients entering hemodialysis who had survived 1 month. The few new hemodialysis patients who received erythropoietin (EPO) in the last 3 months of the study were excluded. Survival curves were compared using the Cox proportional hazards regression model. Older age and history of cardiovascular disease were independently associated with a greater probability of death. Age and history of cardiovascular disease were also associated with a greater probability of nonfatal circulatory events (myocardial infarction, angina requiring hospitalization, or stroke), while a serum albumin level less than or equal to 30 g/L (3.0 g dL) was associated with an increased probability of pulmonary edema. The probability of surviving 12 months without receiving a blood transfusion was 47.2% for males and 27.5% for females. The incidence of non-A, non-B hepatitis, as estimated by unexplained elevations in serum aspartate aminotransferase (AST) values, was not different between patients receiving and not receiving blood transfusions. The probability of hospitalization for any cause was greater for patients with grafts for vascular access than for those with fistulae, for those with a history of cardiovascular disease, for those with a serum albumin level less than or equal to 30 g/L, and for those with renal disease due to diabetes or vascular disease. Hospitalization due to circulatory disease was more likely among those with a history of cardiovascular disease and among those with a lower serum albumin level. Hospitalization for infectious disease was more likely among those with a lower serum albumin level and less likely among those with a fistula for vascular access. Among all patients receiving hemodialysis treatment for more than 6 months, there were 14.8 hospital days per year.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Contribution of phenazine antibiotic biosynthesis to the ecological competence of fluorescent pseudomonads in soil habitats.

Phenazine antibiotics produced by Pseudomonas fluorescens 2-79 and Pseudomonas aureofaciens 30-84, previously shown to be the principal factors enabling these bacteria to suppress take-all of wheat caused by Gaeumannomyces graminis var. tritici, also contribute to the ecological competence of these strains in soil and in the rhizosphere of wheat. Strains 2-79 and 30-84, their Tn5 mutants defective in phenazine production (Phz-), or the mutant strains genetically restored for phenazine production (Phz+) were introduced into Thatuna silt loam (TSL) or TSL amended with G. graminis var. tritici. Soils were planted with three or five successive 20-day plant-harvest cycles of wheat. Population sizes of Phz- derivatives declined more rapidly than did population sizes of the corresponding parental or restored Phz+ strains. Antibiotic biosynthesis was particularly critical to survival of these strains during the fourth and fifth cycles of wheat in the presence of G. graminis var. tritici and during all five cycles of wheat in the absence of take-all. In pasteurized TSL, a Phz- derivative of strain 30-84 colonized the rhizosphere of wheat to the same extent that the parental strain did. The results indicate that production of phenazine antibiotics by strains 2-79 and 30-84 can contribute to the ecological competence of these strains and that the reduced survival of the Phz- strains is due to a diminished ability to compete with the resident microflora.

Anti-Bacterial Agents↗

Prevention of tachycardia with atenolol pretreatment for carotid endarterectomy under cervical plexus blockade.

A double-blind, randomised, controlled trial of forty patients was carried out to determine if oral atenolol pretreatment would reduce the incidence of tachycardia during carotid endarterectomy performed under cervical plexus block. Twenty patients received a placebo and twenty patients 50 mg of atenolol two hours prior to surgery. The superficial and deep cervical blocks were performed with 1.5% lignocaine containing 1:200,000 adrenaline. The patients were monitored with the V5 lead of the electrocardiogram and intra-arterial blood pressure. These measurements were recorded on a correctly calibrated paper recorder. Tachycardia (heart rate greater than 90 beats per minute for more than three minutes) occurred in thirteen patients in the placebo group and two patients in the atenolol group (P less than 0.01). There was no difference in the occurrence of bradycardia, hypotension or hypertension between the two groups. It is concluded that atenolol pretreatment is an effective method of reducing the incidence of tachycardia during carotid endarterectomy performed under cervical plexus blockade.

Aged↗

Isolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase.

We have isolated and characterized cDNA clones encoding rat liver cytosol 10-formyltetrahydrofolate dehydrogenase (EC 1.5.1.6). An open reading frame of 2706 base pairs encodes for 902 amino acids of Mr 99,015. The deduced amino acid sequence contains exact matches to the NH2-terminal sequence (28 residues) and the sequences of five peptides derived from cyanogen bromide cleavage of the purified protein. The amino acid sequence of 10-formyltetrahydrofolate dehydrogenase has three putative domains. The NH2-terminal sequence (residues 1-203) is 24-30% identical to phosphoribosylglycinamide formyltransferase (EC 2.1.2.2) from Bacillus subtilis (30%), Escherichia coli (24%), Drosophila melanogaster (24%), and human hepatoma HepG2 (27%). Residues 204-416 show no extensive homology to any known protein sequence. Sequence 417-900 is 46% (mean) identical to the sequences of a series of aldehyde dehydrogenase (NADP+) (EC 1.2.1.3). Intact 10-formyltetrahydrofolate dehydrogenase exhibits NADP-dependent aldehyde dehydrogenase activity. The sequence identity to phosphoribosylglycinamide formyltransferase is discussed, and a binding region for 10-formyltetrahydrofolate is proposed.

Amino Acid Sequence↗

Stress ulcer prophylaxis in the critically ill: a meta-analysis.

PURPOSE: To examine the differential effect of stress ulcer prophylaxis on overt bleeding, clinically important bleeding, and mortality in critically ill patients. DATA IDENTIFICATION: Computerized bibliographic search of published and unpublished research. STUDY SELECTION: Independent review of 168 articles identified 42 relevant randomized trials for inclusion. DATA ABSTRACTION: The validity, population, intervention, and outcomes of each trial were evaluated. RESULTS: Stress ulcer prophylaxis with antacids (odds ratio 0.40 [95% confidence interval (CI) 0.20 to 0.79]) or histamine-2-receptor antagonists (odds ratio 0.29 [95% CI 0.17 to 0.45]) decreases the incidence of overt gastrointestinal bleeding. Histamine-2-receptor antagonists are more effective than antacids at reducing overt hemorrhage (odds ratio 0.56 [95% CI 0.33 to 0.97]). A significant reduction in clinically important gastrointestinal hemorrhage is evident only with histamine-2-receptor antagonist therapy. There is a trend favoring antacids over sucralfate in the outcome of clinically important bleeding (odds ratio 0.65 [95% CI 0.16 to 2.49]); however, there are insufficient data to evaluate histamine-2-receptor antagonists versus sucralfate. No difference in mortality between treated and untreated patients was found. CONCLUSIONS: Overt gastrointestinal bleeding in critically ill patients is reduced by prophylaxis with antacids or histamine-2-receptor antagonists. Histamine-2-receptor antagonists are more effective than antacids at decreasing overt bleeding and are more effective than no treatment at reducing the incidence of clinically important bleeding. Mortality rates in the intensive care unit are not decreased by stress ulcer prophylaxis.

Critical Care↗

Response of the oral mucosa to denture wearing.

This paper reviews both past and current knowledge concerning the controversial subject of mucosal responses associated with denture wearing. The subject has been considered in terms of both gross clinical and histopathological changes arising from daily prosthesis use. Displacement of basal seat tissues during function has been discussed, along with denture-induced alterations of the local microfloral ecosystems. The influences of common drugs and therapeutic regimens such as ionizing radiation treatments have been considered, and as with all the fields discussed, have been related to clinical use and success of prostheses.

Dentures↗

Does combined epidural lignocaine and fentanyl provide better anaesthesia for ESWL than lignocaine alone?

The efficacy of epidural fentanyl combined with lignocaine 1.5% with adrenaline 1:200,000 was studied in a randomised, double-blind, controlled trial of two hundred patients undergoing extracorporeal shock wave lithotripsy with or without ancillary procedures. The quality of anaesthesia was assessed using linear analogue pain scores, the patient's impression, and the rate of intra-operative intervention by the anaesthetist. Postoperative symptomatology was also recorded. The only significant difference lay postoperatively in that the fentanyl-ancillary procedure sub-group had less pain approximately one hour postoperatively (P = 0.01). In the context of this study and in the presence of an adequate autonomic and somatic local anaesthetic blockade, the addition of epidural fentanyl does not appear to confer any significant advantage other than to enhance postoperative analgesia.

Anesthesia, Epidural↗

A comparison of several point estimators of the odds ratio in a single 2 x 2 contingency table.

The relative performance of the unconditioned maximum likelihood estimators (UMLEs), conditional MLEs (CMLEs), and Jewell-type estimators of the odds ratio (OR) and its logarithm were investigated in sets of single 2 x 2 contingency tables. The tables were generated by complete enumeration of all possible cell frequencies consistent with a single fixed margin. The bias, mean squared error (MSE), and average absolute error (AAE) were computed for all estimators using the individual table probabilities as weights. The results showed that, for the OR, Jewell's estimator usually had smaller bias, MSE, and AAE than either of the MLEs. While the differences were often slight for MSE and AAE, for bias it was sometimes substantial. For the log(OR), the UMLE usually had the lowest bias, and its MSE and AAE were only slightly greater than those for the other estimators. Overall, we recommend estimation on the log scale using the UMLE. If OR is to be estimated, Jewell's method had strong merit, although it is nonsymmetric with respect to the table orientation. In view of this, the UMLE may again be favoured in some situations.

Bias↗

The estimation of sensitivity and specificity in colorectal cancer screening methods.

The sensitivity and specificity of three screening tests for colorectal cancer were evaluated using latent class analysis. This type of analysis is useful in situations where screening tests are performed on each person and follow-up diagnostic test results are not available for individuals with negative test results. Traditional methods of evaluation, which assume these individuals to be disease free, may be biased under these circumstances. In addition to providing the parameter estimates, the latent class technique gives standard errors and permits significance tests for differences in sensitivity and specificity. It was found that the radial immunodiffusion technique was significantly more sensitive (p less than 0.001) than either the rehydrated or nonrehydrated Hemoccult II tests for detecting occult blood in patients with cancer or adenoma. While comparable to the rehydrated Hemoccult II test in terms of specificity, the radial immunodiffusion technique was significantly less specific (p less than 0.01) than the nonrehydrated Hemoccult test. Similar results were observed when restricting the analysis to cancer only.

Canada↗