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Biomedical subjects

D J Cook

Publications and source records attributed to D J Cook.

At least 145 records · Page 8Linked to original sources
PubMed1997

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

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

Confidence Intervals↗
PubMed1997

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

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

Cause of Death↗
PubMed1997

Documenting life-support preferences in hospitalized patients.

PURPOSE: The purpose of this article was to determine the extent to which patients at high risk of hospital death who undergo cardiopulmonary resuscitation (CPR) have previously had their life support preferences addressed and documented. MATERIALS AND METHODS: We conducted a retrospective chart review of all patients older than 18 years of age hospitalized for more than 24 hours who sustained a cardiac arrest with attempted CPR at our tertiary care university teaching hospital during 1994 (n = 71). We searched all hospital charts specifying ICD-9 codes: Cardiac arrest, ventricular fibrillation, ventricular tachycardia, asystole, electromechanical dissociation, defibrillation, or CPR. Patients were selected if (1) they had a true cardiac arrest (abrupt cessation of spontaneous circulation) and (2) had attempted CPR or defibrillation. Patients were classified as "high risk" if they satisfied at least one of the following: modified prearrest morbidity index > or = 7, moderate/severe dementia, day 1 APACHE II score > 24 or > or = 4 dysfunctional organ systems. RESULTS: We searched 147 charts; of 71 patients meeting inclusion criteria, 53 were high risk. Of patients at high risk of sustaining a cardiopulmonary arrest during the index hospital admission, 3 (6%) had preferences addressed within the first 24 hours of hospitalization, 7 (13%) had delayed discussion of preferences before arrest, 23 (43%) had preferences addressed post arrest, and 20 (38%) had no documented discussions. Of the 23 high-risk patients initially surviving cardiac arrest, all were subsequently given "do not resuscitate" orders. Univariate analysis of factors associated with life-support discussion before cardiac arrest were previous cardiac arrest (OR, 5.9) and APACHE II score > 24 (OR, 1.1), although neither reached statistical significance. None of the 32 patients with a modified PAM index > or = 7 (32 of 71) survived hospitalization. Only 3 patients survived to hospital discharge. CONCLUSIONS: Early communication regarding life-support preferences is important in high-risk patients so that inappropriate or unwanted treatment is not implemented. Given that optimal care includes addressing and documenting life-support preferences in high-risk patients early in their hospitalization, this standard was infrequently met.

APACHE↗
PubMed1997

Effect of pump flow rate on cerebral blood flow during hypothermic cardiopulmonary bypass in adults.

OBJECTIVE: The purpose of this study was to examine the effect of cardiopulmonary bypass flow rate on cerebral blood flow and cerebral metabolic rate for oxygen during hypothermic (27 degrees C) cardiopulmonary bypass. DESIGN, SETTING, AND PARTICIPANTS: The investigation was a prospective, randomized study in a tertiary care hospital setting. The 30 participants were volunteer adult cardiac surgical patients at a single institution. INTERVENTIONS: The N2O saturation method of Kety and Schmidt was used to determine global cerebral blood flow and metabolic rate during four periods: prebypass, cardiopulmonary bypass (CPB) (27 degrees C) flow rates of 2.3 and 1.2 L/min/m2, and 30 minutes post-CPB. Anesthesia consisted of fentanyl and midazolam; pH management was alpha-stat, and mean arterial pressure was maintained at 50 to 70 mmHg throughout CPB. MEASUREMENTS AND MAIN RESULTS: In the context of an unchanged mean arterial pressure, the pump flow did not affect cerebral blood flow or metabolic rate during hypothermic CPB. Systemic venous oxygen saturation was also maintained during reduced flow at 27 degrees C. Hemodilution during hypothermic CPB maintained cerebral blood flow at prebypass levels. In the postbypass period, persistent hemodilution resulted in an elevated cerebral blood flow. CONCLUSIONS: Brain oxygenation is well maintained at lower than conventional pump flow levels during CPB. There may be practical advantages to reduced flows during hypothermia, and flow reductions do not appear to adversely affect cerebral blood flow or metabolism.

Adult↗
PubMed1997

The effects of pulsatile cardiopulmonary bypass on cerebral and renal blood flow in dogs.

OBJECTIVE: The purpose of this study was to determine the effects of pulsatility on cerebral blood flow, cerebral metabolism, and renal blood flow over a range of cardiopulmonary bypass temperature and flow conditions. DESIGN/SETTING: The investigation was prospective, randomized, and performed in a canine physiology laboratory at the Mayo Foundation. PARTICIPANTS AND INTERVENTIONS: Anesthetized dogs were studied during pulsatile (n = 9) or nonpulsatile (n = 10) cardiopulmonary bypass at two flow rates (2.4 and 1.2 L/min/m2) at each of three temperatures (37 degrees, 32 degrees, and 27 degrees C). Pulsatility was achieved by use of a pediatric intraaortic balloon pump. Cerebral blood flow and metabolic rate were determined using the sagittal sinus outflow method. Renal blood flow was determined by a periarterial ultrasonic flow probe. MEASUREMENTS AND MAIN RESULTS: In the pulsatile group, a pulse pressure of 29 mmHg had no effect on cerebral blood flow or metabolism at any temperature under either flow condition. Renal blood flow was also unaffected by pulsatility, but decreased with hypothermia and reduced pump flow. Pulsatility also did not attenuate the systemic effects of normothermic hypoperfusion. CONCLUSIONS: Pulsatility has no significant effect on cerebral or renal perfusion over a broad range of cardiopulmonary bypass temperature and flow conditions. Cerebral blood flow and metabolism were functions of temperature but not pulsatility or flow rate. Renal blood flow was affected by both temperature and cardiopulmonary bypass flow rate but not by pulsatility. Finally, central nervous system perfusion may be preserved under low-flow cardiopulmonary bypass conditions by shunting of perfusion from splanchnic vascular beds.

Animals↗
PubMed1997

Single daily dosing of aminoglycosides in immunocompromised adults: a systematic review.

We examined the efficacy and toxicity of single daily dosing (SDD) of aminoglycosides for febrile, immunocompromised adults by systematically reviewing four randomized, controlled trials of SDD vs. standard dosing regimens. We assessed the methodological quality of each study and extracted data pertaining to efficacy and toxicity outcomes. Pooled risk ratios for the efficacy outcomes were bacteriologic cure, 1.00 (95% confidence interval [CI], 0.86-1.16); clinical cure, 0.97 (95% CI, 0.91-1.05); and mortality, 0.93 (95% CI, 0.62-1.41). The pooled nephrotoxicity risk ratio was 0.78 (95% CI, 0.31-1.94). Only one study assessed ototoxicity. Although our study was limited by the small number of trials available for review, the results suggest that SDD of aminoglycosides may be efficacious for febrile, immunocompromised patients. Additional studies are necessary for more precise quantification of the mortality and toxicity risk ratios.

Adult↗
PubMed1997

How to use an article on therapy or prevention: pneumonia prevention using subglottic secretion drainage.

Evidence based critical care medicine involves integrating clinical experience, expertise, and patient preferences with explicit, systematic, and judicious use of current best evidence in making medical decisions. Published evidence has many sources: research from the basic sciences of medicine, and from patient-centered clinical research on the accuracy of diagnostic tests, the power of prognostic markers, and the effectiveness and safety of preventive, therapeutic, rehabilitative, and palliative interventions. When critically appraising a clinical article for potential use in intensive care unit (ICU) practice, the first question we ask ourselves is: Is this study valid? If examination of the study methods reveals that the design is rigorous, we can turn to the two other key questions: What are the results? and, Will the results help me care for my patients? This approach may aid in the interpretation of an article on therapy or prevention; in it we discuss a strategy designed to prevent ventilator associated pneumonia in critically ill patients.

Critical Care↗
PubMed1997

How to use diagnostic test articles in the intensive care unit: diagnosing weanability using f/Vt.

Medical diagnosis involves generating a set of hypotheses and obtaining information that modifies these hypotheses. Sources of this information include the history, physical examination, and laboratory investigations, all of which function as diagnostic tests. Studies of diagnostic tests are useful when a) the population under study is representative of those to whom we would like to apply the results; b) when an independent, blind comparison is made of the test results with a reference standard; and c) when the reference standard is performed on all patients, rather than restricted to those patients with particular test results. Clinicians can use the data from such high quality studies in the form of sensitivity and specificity, as well as likelihood ratios, which indicate the direction and magnitude of the change in probability of a target condition from pretest to posttest. Study results will be more easily applicable to practice when the performance and interpretation of the test is similar in study and clinical settings. We conduct diagnostic tests primarily to improve the process of patient care and patient outcome, and test ordering behavior ideally reflects these goals.

Critical Care↗
PubMed1997

Effect of noninvasive positive pressure ventilation on mortality in patients admitted with acute respiratory failure: a meta-analysis.

OBJECTIVE: To critically appraise and summarize the trials examining the addition of noninvasive positive pressure ventilation to standard therapy on hospital mortality and need for endotracheal intubation in patients admitted with acute respiratory failure. DATA SOURCES: We searched MEDLINE (1966 to September 1995) and key references were searched forward using the Scientific Citation Index (SCISEARCH). Bibliographies of all selected articles and review articles were examined. Authors of all selected and review articles were contacted by letter to identify unpublished work. STUDY SELECTION: a) POPULATION: patients with acute respiratory failure; b) intervention: noninvasive positive pressure ventilation; c) outcome: mortality and/or endotracheal intubation; and d) design: randomized, controlled study. Two of us independently selected the articles for inclusion; disagreements were settled by consensus. Seven (three unpublished) of 212 initially identified studies were selected. DATA EXTRACTION: Two authors independently extracted data and evaluated methodologic quality of the studies. DATA SYNTHESIS: Noninvasive positive pressure ventilation was associated with decreased mortality (odds ratio = 0.29; 95% confidence interval 0.15 to 0.59) and a decreased need for endotracheal intubation (odds ratio = 0.20; 95% confidence interval 0.11 to 0.36). Sensitivity analysis suggested a greater benefit of noninvasive positive pressure ventilation in patients with chronic obstructive pulmonary disease (COPD). The inclusion/exclusion of unpublished trials did not influence these results. CONCLUSIONS: The addition of noninvasive positive pressure ventilation to standard therapy in patients with acute respiratory failure improves survival and decreases the need for endotracheal intubation. However, this effect is restricted to patients whose cause of acute respiratory failure is an exacerbation of COPD. Further research is warranted to determine whether noninvasive positive pressure ventilation confers benefit in patients without COPD who have acute respiratory failure.

Acute Disease↗
PubMed1997

How to use articles about harm: the relationship between high tidal volumes, ventilating pressures, and ventilator-induced lung injury.

BACKGROUND: Intensivists commonly encounter patients who may be inadvertently harmed by critical care interventions. This article is designed to guide clinicians in the evaluations of an individual article assessing a question of harm, as well as the sum of multiple pieces of evidence. OBJECTIVES: To assess the vaidity of a group of articles about the relationship between high tidal volumes and ventilating pressures on ventilator-induced lung injury; to interpret the results of these studies; and to consider whether they apply in practice. DATA SOURCES: Issues of harm are sometimes measured in randomized trials, but are evaluated more often in myriad observational studies. DATA EXTRACTION: We use critical appraisal guides for experimental studies (e.g., randomized trials) and observational studies (e.g., cohort studies, case-control studies and case series) that evaluate the potentially harmful exposure of high tidal volumes and ventilating pressures. This involves assessing the validity of the research, then determining the strength of association between the putative harmful exposure and adverse outcomes. These study designs and their interpretation using relative risks and odds ratios are reviewed. Finally, the relevance of this information (or lack thereof) to clinical practice needs to be determined. DATA SYNTHESIS: Examining these studies individually and in totality, there appears to be a relationship between high tidal volumes and ventilating pressures, although the strength of inference from this research is limited by design issues and sample sizes. CONCLUSIONS: Critically appraising a body of literature is more challenging than evaluating a single study, but often gives a broader view of the available evidence. Future large, rigorous, randomized trials of different approaches to mechanical ventilation will help to advance our understanding and to better inform our practice.

Clinical Trials as Topic↗
PubMed1997

Lectins for drug delivery within the oral cavity--investigation of lectin binding to oral mucosa.

The aim of this study was to identify receptors present on the buccal mucosa in order to select appropriate lectins that will allow the retention of a dosage form within the oral cavity. Studies using human buccal cells, the avidin-biotin-complex/diaminobenzidine method for identifying lectin binding and a microdensitometer to allow a semi-quantitative analysis of stain intensity, showed a wide diversity of lectin receptors. Kinetic studies of lectin binding to buccal cells revealed significant binding after 20 s, particularly for lectins from Pisum sativum and Arachis hypogaea. A significant reduction in lectin binding was observed after exposing buccal cells to a series of lectin solutions pre-treated with a large excess of secretor or non-secretor saliva. However when bound to the buccal cells, there was little displacement of lectins on exposure to either saliva types. Further studies on rat oral tissue suggested that the lectins appeared to bind to varying degrees on whole oral epithelial surfaces although differences in binding between this and the human buccal cell model were evident. It was concluded that a wide range of possible target receptors for lectins are present on rat oral epithelium and human buccal cells. Lectin binding to these receptors can be affected by the exposure time and the presence of saliva.

Administration, Oral↗
PubMed1997

Health professional decision-making in the ICU: a review of the evidence.

End-of-life decisions in the ICU are often complex and emotionally charged. Intensivists can correct the physiologic abnormalities of acute and chronic illness with drugs and technology, and prolong life in many situations. Understanding and attending to the psychological and emotional needs of not only patients but also their families are part of the delivery of compassionate critical care. The process of communicating and decision-making on the ICU team and in family units has been a domain of active research over the past decade. Studies on do-not-resuscitate orders, and advanced and delayed directives comprise a portion of this work. This article contains a brief summary of selected research evidence on these difficult end-of-life issues.

Advance Directives↗
PubMed1996

Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease.

BACKGROUND: Respiratory rehabilitation is increasingly recognised as an important part of the management of patients with chronic obstructive pulmonary disease (COPD). The widespread application of such programmes should be preceded by evidence of directly attributable improvements in function. We assessed the effect of respiratory rehabilitation on exercise capacity and health-related quality of life (HRQL) in patients with COPD. METHODS: We carried out a meta-analysis of randomised controlled trials of respiratory rehabilitation in patients with COPD that assessed functional or maximal exercise capacity, HRQL, or both. Respiratory rehabilitation was defined as exercise training (for at least 4 weeks) with or without education, psychological support, or both. The most commonly used measure for HRQL was the chronic respiratory questionnaire, in which responses were presented on a 7-point scale. The control groups received no rehabilitation. Within each trial and for each outcome an effect size was calculated; the effect sizes were then pooled by a random-effects model. The overall effect of treatment was compared with its minimum clinically important difference (MCID)--defined as the smallest difference perceived as important by the average patient. FINDINGS: We included 14 trials. Significant improvements were found for all the outcomes. For two important features of HRQL, dyspnoea and mastery, the overall treatment effect was larger than the MCID: 1.0 (95% CI 0.6-1.5) and 0.8 (0.5-1.2), respectively, compared with an MCID of 0.5. For functional exercise capacity (6-min walk test), the overall effect was 55.7 m (27.8-92.8), and for maximum exercise capacity (incremental cycle ergometer test), 8.3 W (2.8-16.5). Functional exercise capacity showed heterogeneity that could not be explained by the sensitivity analyses. INTERPRETATION: Respiratory rehabilitation relieves dyspnoea and improves the control over COPD. These improvements are clinically important. The value of the improvement in exercise capacity is not clear. Respiratory rehabilitation is an effective part of care in patients with COPD.

Exercise Therapy↗
PubMed1996

Recognizing and investigating iron-deficiency anemia in hospitalized elderly people.

OBJECTIVE: To determine whether anemia is documented and appropriately investigated for iron deficiency in hospitalized elderly people. DESIGN: Retrospective chart review. SETTING: Medical clinical teaching unit (CTU) in secondary care hospital in Hamilton, Ont. PARTICIPANTS: Consecutive patients 65 years of age or older admitted between April 1992 and March 1993. OUTCOME MEASURES: Proportion of anemic patients for whom documentation was adequate (included in problem list in patient chart) and for whom adequate investigations were performed (measurement of serum ferritin level in anemic patients in whom iron deficiency was suspected, bone-marrow aspiration for those with intermediate probability of iron deficiency after determination of serum ferritin level, and endoscopy of upper or lower gastrointestinal tract, or both, in patients with iron deficiency). RESULTS: Of 183 eligible patients admitted to the CTU 66 (36%) had anemia, in 47 cases (71%) the anemia was documented by house staff or attending physicians. Of the 66 anemic patients 49 had a non-macrocytic anemia of unknown cause: 26 had their serum ferritin level measured, 5 underwent bone-marrow aspiration, and 21 were referred for gastrointestinal endoscopy. Six of eight patients with probable iron deficiency (i.e., a serum ferritin level that was diagnostic [less than 18 micrograms/L] or suggestive [18 to 45 micrograms/L]) underwent endoscopy, two were found to have cancer of the stomach or cecum. Only 26 of the 49 patients had adequate investigation. CONCLUSIONS: Anemia is common among elderly patients in hospital. However, iron deficiency is underrecognized and underinvestigated.

Aged↗
PubMed1996

Multidisciplinary education for oxygen prescription. A continuous quality improvement study.

OBJECTIVES: To examine the oxygen-prescribing habits and monitoring patterns on a medical teaching ward and to review the literature in this area. DESIGN: A continuous quality improvement study. SETTING: A 29-bed medical clinical teaching unit in a 453-bed university-affiliated tertiary care hospital. PATIENTS: We studied 50 consecutive patients who required 79 oxygen treatments. METHODS: We recorded the indication, prescriber, documentation of prior hypoxemia, method and mode of delivery, oxygenation assessment after initiation, and duration of therapy. RESULTS: Patients received oxygen for a mean (+/- SD) of 4.7 +/- 4.5 days. Oxygen therapy was ordered on a continuous basis 60.3% of the time. It was ordered by house staff in 54 cases (68%); nurses initiated oxygen therapy in 14 cases (18%) but discontinued it more often than any other health care workers. The most common indications for starting oxygen therapy were dyspnea and tachypnea. In 15 patients (30%), none of the American College of Chest Physicians and National Heart, Lung, and Blood Institute criteria for starting oxygen therapy were fulfilled. For 16 patients (32%), arterial blood gas values were measured within 1 hour of oxygen administration; for 29 patients, oximetry was performed. For 9 patients (18%), no testing of adequate oxygenation was performed within 24 hours. Oxygenation status was assessed daily for 23 patients (46%). CONCLUSIONS: Oxygen prescribing and monitoring practices were suboptimal on our busy medical teaching ward. Practice guidelines based on best available evidence are needed to increase the efficiency of oxygen use. A physiologic, multidisciplinary educational focus on the benefits and hazards of supplemental oxygen is necessary, and randomized trials of such educational interventions should be conducted.

Aged↗
PubMed1996

Residents' experiences of abuse, discrimination and sexual harassment during residency training. McMaster University Residency Training Programs.

OBJECTIVE: To assess the prevalence of psychological abuse, physical assault, and discrimination on the basis of gender and sexual orientation, and to examine the prevalence and impact of sexual harassment in residency training programs. DESIGN: Self-administered questionnaire. SETTING: McMaster University, Hamilton, Ont. PARTICIPANTS: Residents in seven residency training programs during the academic year from July 1993 to June 1994. Of 225 residents 186 (82.7%) returned a completed questionnaire, and 50% of the respondents were women. OUTCOME MEASURES: Prevalence of psychological abuse, physical assault and discrimination on the basis of gender and sexual orientation experienced by residents during medical training, prevalence and residents' perceived frequency of sexual harassment. RESULTS: Psychological abuse was reported by 50% of the residents. Some of the respondents reported physical assault, mostly by patients and their family members (14.7% reported assaults by male patients and family members, 9.8% reported assaults by female patients and family members), 5.4% of the female respondents reported assault by male supervising physicians. Discrimination on the basis of gender was reported to be common and was experienced significantly more often by female residents than by male residents (p < 0.01). Ten respondents, all female, reported having experienced discrimination on the basis of their sexual orientation. Most of the respondents experienced sexual harassment, especially in the form of sexist jokes, flirtation and unwanted compliments on their dress or figure. On average, 40% of the respondents, especially women (p < 0.01), reported experiencing offensive body language and receiving sexist teaching material and unwanted compliments on their dress. Significantly more female respondents than male respondents stated that they had reported events of sexual harassment to someone (p < 0.001). The most frequent emotional reactions to sexual harassment were embarassment (reported by 24.0%), anger (by 23.4%) and frustration (20.8%). CONCLUSION: Psychological abuse, discrimination on the basis of gender and sexual harassment are commonly experienced by residents in training programs. A direct, progressive, multidisciplinary approach is needed to label and address these problems.

Adult↗