Users' guides to the medical literature. IX. A method for grading health care recommendations. Evidence-Based Medicine Working Group.
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Biomedical subjects
Publications and source records attributed to D J Cook.
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OBJECTIVES: To explore the importance of and satisfaction with clinical responsibilities, teaching, research and interpersonal issues among general internists; to understand the barriers to satisfaction in these domains and the usefulness of potential solutions to these problems. DESIGN: Cross-sectional survey conducted from November 1992 to June 1994. SETTING: Ontario. PARTICIPANTS: General internists who were fellows of the Royal College of Physicians and Surgeons of Canada and members of the Ontario Medical Association. Of 1192 physicians, 1007 (84.5%) returned a completed questionnaire; only the 199 who devoted at least 50% of their time to the practice of general internal medicine were included in this analysis. RESULTS: The respondents were satisfied with their primary role as clinicians dealing with complex, undifferentiated problems caring for the total patient and providing consultation. Guidelines for the referral of patients to general internists, computerization of test results, recruitment of general internal medicine fellows and more confidence in the future of general internal medicine were some of the solutions considered likely to increase professional satisfaction. The respondents involved in teaching suggested additional solutions, such as an opportunity to improve their teaching and evidence-based medicine skills and a greater recognition for their teaching efforts. Few of the general internists conducted research, barriers included lack of personal and project funding, and pressure to generate clinical earnings. In the domain of professional interpersonal issues, women were significantly more likely than men to rate having a mentor, peer support groups, ongoing career counselling, promotion and tenure guidelines for parental leave, availability of on-site day care, addressing gender discrimination and adoption of gender-neutral language as likely to improve the work environment. CONCLUSIONS: The primary role of general internists is that of patient-centred clinician. Our findings suggest that general internists want to take responsibility for revitalizing this discipline. The potential solutions generated in this survey may help to promote action that will improve professional satisfaction in the area of clinical responsibilities, teaching, research and interpersonal issues.
To determine the adequacy of initial anticoagulation by intravenous heparin for patients who have deep venous thrombosis (DVT), and the factors that influence delayed anticoagulation, independent, duplicate chart review of 63 consecutive patients who had venography-proven DVT was conducted. Adequate heparinization (AH) was defined as an activated partial thromboplastin time (PTT) of more than 1.5 times the normal laboratory control. The proportions of patients achieving AH within 24 hours and 48 hours of initial heparin bolus were 46% and 62%, respectively. Patients who weighed more were less likely to achieve AH (p < 0.05), while patients receiving care from the thromboembolism service were more likely to achieve AH (p < 0.05). Low initial infusion rate was strongly but not significantly predictive of inadequate anticoagulation (p = 0.06). The mean heparin bolus and initial infusion rates were significantly lower than those suggested in the literature (p < 0.01). The AH rates were comparable to historical controls but suboptimal compared with the rates of 66% at 24 hours and 81% at 48 hours reported in association with heparin nomogram use (p < 0.05). A heparin nomogram is likely to achieve consistently higher rates of adequate heparinization.
OBJECTIVE: To determine the effect of corticosteroid therapy on morbidity and mortality in patients with sepsis. DATA SOURCES: We searched for published and unpublished research using MEDLINE, EMBASE, and the Science Citation Index, manual searching of Index Medicus, citation review of relevant primary and review articles, personal files, and contact with primary investigators. STUDY SELECTION: From a pool of 124 potentially relevant articles, duplicate independent review identified nine relevant, randomized, controlled trials of corticosteroid therapy in sepsis and septic shock among critically ill adults. DATA EXTRACTION: In duplicate, independently, we abstracted key data on population, intervention, outcome, and methodologic quality of the randomized controlled trials. DATA SYNTHESIS: Corticosteroids appear to increase mortality in patients with overwhelming infection (relative risk 1.13, 95% confidence interval 0.99 to 1.29), and have no beneficial effect in the subgroup of patients with septic shock (relative risk 1.07, 95% confidence interval 0.91 to 1.26). Studies with the highest methodologic quality scores also suggest a trend toward increased mortality overall (relative risk 1.10, 95% confidence interval 0.94 to 1.29). A similar trend was observed for patients with septic shock (relative risk 1.12, 95% confidence interval 0.95 to 1.32). No difference in secondary infection rates was demonstrated in corticosteroid-treated patients with sepsis or septic shock. However, there was a trend toward increased mortality from secondary infections in patients receiving corticosteroids (relative risk 1.70, 95% confidence interval 0.70 to 4.12). The occurrence rate of gastrointestinal bleeding was increased slightly in the treatment group (relative risk 1.17, 95% confidence interval 0.79 to 1.73). CONCLUSIONS: Current evidence provides no support for the use of corticosteroids in patients with sepsis or septic shock, and suggests that their use may be harmful. These trials underscore the need for future methodologically rigorous trials evaluating new immune-modulating therapies in well-defined critically ill patients with overwhelming infection.
OBJECTIVE: To develop an objective scale to measure the severity of the multiple organ dysfunction syndrome as an outcome in critical illness. DESIGN: Systematic literature review; prospective cohort study. SETTING: Surgical intensive care unit (ICU) of a tertiary-level teaching hospital. PATIENTS: All patients (n = 692) admitted for > 24 hrs between May 1988 and March 1990. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Computerized database review of MEDLINE identified clinical studies of multiple organ failure that were published between 1969 and 1993. Variables from these studies were evaluated for construct and content validity to identify optimal descriptors of organ dysfunction. Clinical and laboratory data were collected daily to evaluate the performance of these variables individually and in aggregate as an organ dysfunction score. Seven systems defined the multiple organ dysfunction syndrome in more than half of the 30 published reports reviewed. Descriptors meeting criteria for construct and content validity could be identified for five of these seven systems: a) the respiratory system (Po2/FIO2 ratio); b) the renal system (serum creatinine concentration); c) the hepatic system (serum bilirubin concentration); d) the hematologic system (platelet count); and e) the central nervous system (Glasgow Coma Scale). In the absence of an adequate descriptor of cardiovascular dysfunction, we developed a new variable, the pressure-adjusted heart rate, which is calculated as the product of the heart rate and the ratio of central venous pressure to mean arterial pressure. These candidate descriptors of organ dysfunction were then evaluated for criterion validity (ICU mortality rate) using the clinical database. From the first half of the database (the development set), intervals for the most abnormal value of each variable were constructed on a scale from 0 to 4 so that a value of 0 represented essentially normal function and was associated with an ICU mortality rate of < 5%, whereas a value of 4 represented marked functional derangement and an ICU mortality rate of > or = 50%. These intervals were then tested on the second half of the data set (the validation set). Maximal scores for each variable were summed to yield a Multiple Organ Dysfunction Score (maximum of 24). This score correlated in a graded fashion with the ICU mortality rate, both when applied on the first day of ICU admission as a prognostic indicator and when calculated over the ICU stay as an outcome measure. For the latter, ICU mortality was approximately 25% at 9 to 12 points, 50% at 13 to 16 points, 75% at 17 to 20 points, and 100% at levels of > 20 points. The score showed excellent discrimination, as reflected in areas under the receiver operating characteristic curve of 0.936 in the development set and 0.928 in the validation set. The incremental increase in scores over the course of the ICU stay (calculated as the difference between maximal scores and those scores obtained on the first day [i.e., the delta Multiple Organ Dysfunction Score]) also demonstrated a strong correlation with the ICU mortality rate. In a logistic regression model, this incremental increase in scores accounted for more of the explanatory power than admission severity indices. CONCLUSIONS: This multiple organ dysfunction score, constructed using simple physiologic measures of dysfunction in six organ systems, mirrors organ dysfunction as the intensivist sees it and correlates strongly with the ultimate risk of ICU mortality and hospital mortality. The variable, delta Multiple Organ Dysfunction Score, reflects organ dysfunction developing during the ICU stay, which therefore is potentially amenable to therapeutic manipulation. (ABSTRACT TRUNCATED)
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OBJECTIVE: Failure of a kidney to grow satisfactorily in childhood is evidence of renal disease. Because kidneys may enlarge during an episode of acute pyelonephritis, concomitant renal length measurements cannot be used as baselines for growth assessment. This study was designed to determine the degree of renal enlargement in children with acute pyelonephritis and the time the enlargement takes to resolve after treatment is started to find the optimum time for obtaining baseline measurements. SUBJECTS AND METHODS: In a cohort study, 180 children younger than 5 years old with their first proven acute urinary tract infection, with or without pyelonephritis, had renal scintigraphy and sonography within 15 days of starting treatment. The presence of cortical defects on scintigrams indicated pyelonephritis. The lengths of kidneys with and without scintigraphic defects (i.e., with and without pyelonephritis) were compared, adjusting for age and sex, and the length of kidneys with defects was related to time elapsed between the start of treatment and sonography. RESULTS: Ninety-nine kidneys (28%) in 77 children (43%) had scintigraphic defects. Kidneys with defects were an average of 3.2 mm longer than kidneys without defects. Length and time interval between treatment and sonography in kidneys with defects correlated negatively, with mean length approaching that of kidneys without defects by 10-11 days. CONCLUSION: Kidneys with acute pyelonephritis initially increase in length but return to normal on average by the 11th day of treatment. If poor renal growth is used as an indication of renal disease, sonography should be delayed or repeated at least 2 weeks after the start of treatment to determine the length of the uninflamed kidney.
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Endoscopic hemostatic therapy for upper gastrointestinal bleeding is gaining widespread acceptance despite often conflicting results of randomized controlled trials. To examine the effect of endoscopic therapy in acute nonvariceal upper gastrointestinal hemorrhage, a meta-analysis was performed using a computerized search of the English-language literature and a bibliographic review. The methodology, population, intervention, and outcomes of each relevant trial were evaluated by duplicate independent review. Thirty randomized controlled trials evaluating hemostatic endoscopic treatment were identified. Endoscopic therapy significantly reduced rates of further bleeding (odds ratio, 0.38; 95% confidence interval, 0.32-0.45), surgery (odds ratio, 0.36; 95% confidence interval, 0.28-0.45), and mortality (odds ratio, 0.55; 95% confidence interval, 0.40-0.76). When analyzed separately, thermal-contact devices (monopolar and bipolar electrocoagulation and heater probe), laser treatment, and injection therapy all significantly decreased further bleeding and surgery rates. The reductions in mortality were comparable for all three forms of therapy, but the decrease reached statistical significance only for laser therapy. Further examination of subgroups indicated that endoscopic treatment decreased rates of further bleeding, surgery, and mortality in patients with high-risk endoscopic features of active bleeding or nonbleeding visible vessels. Rebleeding was not reduced by endoscopic therapy in patients with ulcers containing flat pigmented spots or adherent clots. Endoscopic hemostatic therapy provides a clinically important reduction in morbidity and mortality in patients with acute nonvariceal upper gastrointestinal hemorrhage.
Tricuspid valve stenosis in the setting of endocarditis is associated with a high morbidity. Diagnostic approaches incorporate a high clinical index of suspicion, echocardiographic evidence, and inferences about hemodynamic data derived from pulmonary artery catheterization. As demonstrated by the case presented herein, inadequate initial evaluation of right-sided pressures delayed the diagnosis and treatment of prosthetic tricuspid valve stenosis.
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Our objective was to determine the extent to which Intensive Care Unit (ICU) physicians are aware of charges for commonly used blood tests. We also wished to ascertain ICU physicians' perception of their motivation for, and appropriateness of, test ordering. Attending physicians and Internal Medicine residents in four university-affiliated ICUs in Hamilton were surveyed using a self-administered questionnaire. The response rate for the questionnaire was 91%. Physicians varied widely in their estimates of charges for ten laboratory tests. On average, residents tended to underestimate charges, while attending physicians sometimes underestimated, and sometimes overestimated. When all ten tests were considered, the mean estimates of the housestaff were lower than the ICU attending physicians (p < 0.001). Overall, attending estimates were 29.5% higher. Over 85% of physicians felt that too many blood tests were being performed. Physicians perceived that they pay insufficient attention to the risk of anemia and to issue of cost. Their feeling that test ordering in the ICU is excessive suggests that they may be open to modifying their practice. Given the large proportion of hospital resources allocated to the intensive care unit, interventions to decrease test ordering are warranted.
The purpose of this study was to determine if ketamine altered the release or disposition of norepinephrine at adrenergic nerve terminals in isolated ferret myocardium. In superfused right ventricular strips, the effect of ketamine on norepinephrine release and uptake was determined. Dihydroxyphenylglycol, the intraneuronally derived metabolite of norepinephrine, served as an index of neuronal uptake and was also measured in superfusate. Pharmacological manipulation of selective aspects of adrenergic transmission with corticosterone, yohimbine, clorgyline and desmethylimipramine allowed the primary site of action of ketamine to be established. Quantitation of tissue norepinephrine content after the experiments provided another means to evaluate ketamine's effect on norepinephrine release as well as to estimate the density of adrenergic innervation in ferret myocardium. Norepinephrine and dihydroxyphenylglycol were quantitated by high-pressure liquid chromatography with electrochemical detection. Ketamine increased norepinephrine overflow and decreased the efflux of dihydroxyphenylglycol in isolated myocardium. Studies in the presence of the clorgyline suggest that ketamine does not increase norepinephrine overflow by means of monoamine oxidase inhibition, and studies in the presence of desmethylimipramine and corticosterone indicate that ketamine does not augment norepinephrine release. Quantitation of tissue norepinephrine content demonstrates that ketamine does not cause depletion of myocardial catecholamines. The ketamine-induced increase in norepinephrine overflow and the observed decrease in dihydroxyphenylglycol production suggest that inhibition of the neuronal uptake of norepinephrine is the primary mechanism of ketamine's effect in isolated myocardium.
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.
Sequestration of neutrophils (PMNs) in the pulmonary microvasculature and associated neutropenia are characteristic features of experimental models of septic lung injury. The etiology of altered PMN kinetics during septic lung injury is uncertain, but may be partially due to increased adhesiveness of activated PMNs to pulmonary endothelium. This study examines the relationship between the expression of PMN CD18 adhesion receptors, the evolving neutropenia, and plasma tumor necrosis factor (TNF) activity in a porcine model of septic lung injury. Acute lung injury was induced by infusion of live Pseudomonas aeruginosa (5 x 10(8) CFU/ml at 0.3 ml/20 kg/min) for 60 min (Group Ps, n = 6). Control animals (Group C, n = 3) received a 60-min infusion of sterile 0.9% saline. CD18 expression of circulating PMNs was measured by quantitative immunofluorescent flow cytometry. Plasma TNF activity was measured by L929 fibroblast cytolytic assay. Group Ps developed a significant neutropenia by 30 min (14.9 +/- 2.5 vs 23.4 +/- 3.3 x 10(3) cells/microliter at baseline, P less than 0.05, ANOVA) with circulating neutrophils exhibiting significantly increased CD18 expression by 60 min (6.34 +/- 0.72 vs 5.01 +/- 0.52 equivalent soluble fluorescence molecules (ESFM) x 10(3) at baseline, P less than 0.05, ANOVA). Group Ps demonstrated a significant increase in plasma TNF activity by 30 min (2.5 +/- 0.9 vs 0.7 +/- 0.3 U/ml at baseline). There was no significant change in PMN count, PMN CD18 expression, or plasma TNF activity in Group C. In complimentary in vitro studies, porcine PMNs stimulated with recombinant human TNF-alpha (n = 5) demonstrated a time- and dose-dependent increase in CD18 expression.(ABSTRACT TRUNCATED AT 250 WORDS)