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Biomedical subjects

R Jaeschke

Publications and source records attributed to R Jaeschke.

At least 19 recordsLinked to original sources

Digitalis for treatment of congestive heart failure in patients in sinus rhythm.

BACKGROUND: Digitalis glycosides have been in clinical use in the treatment of congestive heart failure (CHF) for more than 200 years. In recent years several trials have been conducted to address concerns about efficacy and toxicity. Although a systematic review of the literature was published in 1990, an update is required to include more current trials. OBJECTIVES: To examine the effectiveness of digitalis glycosides in treating CHF in patients with normal sinus rhythm. To examine the effect of digitalis in patients taking diuretics, angiotensin converting enzyme inhibitors, and beta-blockers; patients with varying severity and duration of disease; patients with prior exposure to digitalis vs. no prior exposure; and patients with "CHF due to systolic dysfunction" vs. "CHF with preserved systolic function." SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) 2003 Issue 4, MEDLINE (1966 to December 2003) and EMBASE (1990 to December 2003) were searched. Dissertation Abstracts and annual meeting abstracts of the American Heart Association, American College of Cardiology, and European Society of Cardiology were also searched from 1996-2003. In addition, reference lists provided by the pharmaceutical industry (Glaxo Wellcome Inc.) were searched. SELECTION CRITERIA: Included were randomized placebo-controlled trials of 20 or more adult patients of either sex with symptomatic CHF who were studied for seven weeks or more. Excluded were trials in which the prevalence of atrial fibrillation was 2% or greater, or in which any arrhythmia that might compromise cardiac function or any potentially reversible cause of CHF such as acute ischemic heart disease or myocarditis was present. DATA COLLECTION AND ANALYSIS: Articles selected from the searches described above were evaluated as a joint effort of the coauthors. The staff of the Cochrane Heart Group ran searches on the Cochrane Central Register of Controlled Trials. MAIN RESULTS: Thirteen articles meeting the defined criteria were identified, and major endpoints of mortality, hospitalization, and clinical status, based respectively upon 8, 4, and 12 of these selected studies, were recorded and analyzed. The data show that there is no evidence of a difference in mortality between treatment and control groups, whereas digitalis therapy is associated with a lower rate of hospitalization and of clinical deterioration. REVIEWERS' CONCLUSIONS: The literature indicates that digitalis has a useful role in the treatment of patients with CHF who are in normal sinus rhythm.

Cardiotonic Agents↗

Digitalis for treatment of congestive heart failure in patients in sinus rhythm.

BACKGROUND: Digitalis glycosides have been in clinical use in the treatment of congestive heart failure for more than 200 years. In recent years several trials have been conducted to address concerns about efficacy and toxicity. Although a systematic review of the literature was recently published, an update is required to include more current trials. OBJECTIVES: To examine the effectiveness of digitalis glycosides in treating congestive heart failure in patients with normal sinus rhythm. To examine the effect of digitalis in patients taking diuretics, ACE inhibitors, and beta blockers; patients with varying severity and duration of disease; patients with prior exposure to digitalis vs. no prior exposure; and patients with diastolic vs. systolic dysfunction. SEARCH STRATEGY: Electronic databases were searched between 1966 and 2000. Dissertation Abstracts and annual meeting abstracts of the American Heart Association, American College of Cardiology, and European Society of Cardiology were searched from 1996-2000. In addition, reference lists provided by the pharmaceutical industry (Glaxo Wellcome Inc.) were searched. SELECTION CRITERIA: Included were randomized placebo-controlled trials of 20 or more adult patients of either sex with symptomatic congestive heart failure who were studied for seven weeks or more. Excluded were trials in which the prevalence of atrial fibrillation was 2% or greater, or in which any arrhythmia that might compromise cardiac function or any potentially reversible cause of heart failure such as acute ischemic heart disease or myocarditis was present. DATA COLLECTION AND ANALYSIS: Articles selected from the searches described above were reviewed by one of the coauthors, and validated by staff from the central office of the Heart Collaborative Review Group in Bristol, UK. MAIN RESULTS: Eleven articles meeting the defined criteria were identified, and major endpoints of mortality, hospitalization, and clinical status, based respectively upon on 8, 4, and 10 of these selected studies, were recorded and analyzed. The data show that there is no difference in mortality between treatment and control groups, whereas digitalis therapy is associated with a lower rate of hospitalization and of clinical deterioration. REVIEWER'S CONCLUSIONS: The literature indicates that digitalis has a useful role in the treatment of patients with congestive heart failure who are in normal sinus rhythm.

Cardiotonic Agents↗

Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease.

Regular short-acting inhaled beta-agonist therapy is of uncertain benefit in patients with chronic obstructive pulmonary disease (COPD). We conducted a randomized, concealed, double-blind, placebo-controlled crossover trial in two periods, each of 3-mo duration, involving 53 patients with a smoking history of > 20 pack-years, an FEV1 of < 70% predicted, and an FEV1/VC ratio of < 0.7 after inhalation of 200 microg albuterol. All patients received regular ipratropium bromide at 20 microg per puff in 2 puffs four times daily, beclomethasone at 250 microg per puff or equivalent corticosteroid in 2 puffs twice daily, and open-label inhaled albuterol as needed. Interventional therapy consisted of regular inhaled albuterol (100 microg per puff, in 2 puffs four times daily) versus placebo. Patients used twice as much active albuterol in the regular use period (mean: 8.07 puffs of coded and 4.68 puffs of open-label medication; total: 12.75 puffs daily) than during the as-needed period (mean: 6.34 puffs of open-label albuterol daily). Despite greater beta-agonist use, patients showed similar results during treatment and control periods for all outcomes. Differences between active and placebo periods were: FEV1: -0.04 L (95% confidence interval [CI]: -0.09 to 0.01 L); slow vital capacity: 0.04 L (95% CI: -0.12 to 0.20 L); 6-min walk test distance: -3.1 m (95% CI: -16.8 to 10.5 m); and Chronic Respiratory Questionnaire scores for dyspnea: 0.02 (95% CI: -0.13 to 0.16); fatigue: -0.02 (95% CI: -0.25 to 0.20); mastery: 0.01 (95% CI: -0.20 to 0.24); and emotional function: 0.02 (95% CI: -0.20 to 0.24). We found that in patients with COPD, use of regular short-acting inhaled beta-agonists resulted in twice as much beta-agonist use without physiologic or clinical benefit as did use on an as-needed basis.

Administration, Inhalation↗

Grades of recommendation for antithrombotic agents.

The strength of any recommendation depends on two factors: the trade-off between benefits and risks, and the strength of the methodology that leads us to estimates of the treatment effect. The framework that we used for this conference captures these factors. We grade the trade-off between benefits and risks in two categories: (1) the trade-off is clear enough that most patients, despite differences in values, would make the same choice; and (2) the trade-off is less clear, and each patient's values will likely lead to different choices. We grade methodologic strength in three categories: (1) randomized trials, ideally summarized in a meta-analysis, that show consistent results; (2) randomized trials with inconsistent results; and (3)observational studies. The framework summarized in Table 1 therefore generates recommendations from the very strong (1A: benefit/risk clear, methods strong) to the very weak (2C: benefit/risk questionable, methods weak). Whatever the grade of recommendation, clinicians must bring their judgment considering local and individual patient circumstances, and patient values, to bear in making individual decisions. In general, however, they should place progressively greater weight on expert recommendations as they move from 2C to 1A.

Fibrinolytic Agents↗

The clinical utility of invasive diagnostic techniques in the setting of ventilator-associated pneumonia. Canadian Critical Care Trials Group.

OBJECTIVE: To evaluate the clinical utility of bronchoscopy with protected brush catheter (PBC) and BAL for patients with ventilator-associated pneumonia (VAP). DESIGN: Prospective cohort study. SETTING: Ten tertiary care ICUs in Canada. PATIENTS: Ninety-two mechanically ventilated patients with a clinical suspicion of VAP who underwent bronchoscopy were compared with 49 patients with a clinical suspicion of pneumonia who did not. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We compared antibiotic use, duration of mechanical ventilation, ICU stay, and mortality. In addition, for patients who received bronchoscopy, we administered a questionnaire (before and after bronchoscopy) to evaluate the effect of PBC or BAL on (1) physician perception of the probability of VAP, (2) physician confidence in the diagnosis of VAP, and (3) changes to antibiotic management. After bronchoscopy results became available, from the physician's perspective, the diagnosis of VAP was deemed much less likely (p < 0.001), confidence in the diagnosis increased (p = 0.03), and level of comfort with the management plan increased (p = 0.02). Following the results of invasive diagnostic tests, in the group that underwent bronchoscopy, patients were receiving fewer antibiotics (31/92 vs 9/49, p = 0.05) and more patients had treatment with all their antibiotics discontinued (18/92 vs 3/49, p = 0.04) compared with the group that did not undergo bronchoscopy. Duration of mechanical ventilation and ICU stay were similar between the two groups, but mortality was lower in the group that underwent bronchoscopy with PBC or BAL (18.5% vs 34.7%, p = 0.03). CONCLUSIONS: Invasive diagnostic testing may increase physician confidence in the diagnosis and management of VAP and allows for greater ability to limit or discontinue antibiotic treatment. Whether performing PBC or BAL affects clinically important outcomes requires further study.

Anti-Bacterial Agents↗

Confidence in life-support decisions in the intensive care unit: a survey of healthcare workers. Canadian Critical Care Trials Group.

OBJECTIVE: To examine the relationship between intensive care unit (ICU) healthcare workers' confidence and their decision to withdraw life support. DESIGN: Cross-sectional survey of Canadian intensivists, ICU housestaff, and bedside nurses. Respondents chose the level of care (from comfort measures only to full aggressive care) for 12 patients described in clinical scenarios, and rated their confidence in their decisions. SETTING: Thirty-seven Canadian university-affiliated hospitals. PATIENTS: None. INTERVENTIONS: We used discrete data analysis models to examine the association between the chosen level of care, confidence in the decisions, the clinical scenario, and healthcare worker group. MEASUREMENTS AND MAIN RESULTS: The response rate was 1,361 (76%)/1,795; for this analysis, we used data from 1,306 respondents with completed questionnaires. Responses for each scenario varied widely among respondents. The level of care chosen was dependent on the scenario, the healthcare worker group, and the confidence with which the decisions were made (p < .001 for each). Intensivists were less aggressive than the ICU nurses, who were less aggressive than the housestaff, but the magnitude of effect was small. Overall, respondents were very confident about their decisions 34% of the time. After adjustment for clinical scenario and chosen level of care, intensivists were more confident than nurses, who were more confident than housestaff (40% of intensivists, 29% of nurses, and 23% of housestaff were very confident). In general, healthcare workers tended to be more confident when they chose extreme levels of care than when they chose intermediate levels of care. Considerable variability in responses to scenarios remained even when we considered only those responses made with the highest level of confidence. CONCLUSIONS: While confidence in decisions about withdrawal of life support increases with seniority and authority, consistency of decisions may not. When given standard information, healthcare workers can make contradictory decisions yet still be very confident about the level of care they would administer.

Aged↗

Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?

OBJECTIVE: To determine if health-related quality of life (HRQL) in patients of middle age and older with elevated thyroid-stimulating hormone (TSH) and normal total thyroid hormone levels-subclinical hypothyroidism-improves with L-thyroxine replacement therapy. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinic. PATIENTS: Thirty-seven patients with subclinical hypothyroidism, most with symptoms consistent with hypothyroidism, over 55 years of age. INTERVENTIONS: Placebo or L-thyroxine replacement therapy to achieve normal TSH level. MEASUREMENTS AND MAIN RESULTS: Disease-specific and general HRQL, cognitive function, bone mineral density, lipid levels. The mean daily dose of L-thyroxine replacement in the active group was 68 +/- 21 micrograms. TSH decreased by 8.6 mIU/L (95% confidence interval [CI] 4.1 to 13.1) and T4 increased by 27.9 nmol/L (95% CI 14.8 to 41.2). There was a statistically significant improvement in a composite psychometric memory score in treated versus control patients; all other outcomes showed similar findings in the two groups. Although confidence intervals for most measures did not exclude an important improvement in HRQL with thyroid replacement, no measure of symptoms or HRQL either showed clinically important trends in favor of treatment, or approached conventional levels of statistical significance. CONCLUSIONS: In middle-aged and older patients with elevated TSH and normal T4, it may not be harmful to follow biochemical and clinical status even in the presence of nonspecific symptoms potentially associated with hypothyroidism.

Aged↗

Determinants in Canadian health care workers of the decision to withdraw life support from the critically ill. Canadian Critical Care Trials Group.

OBJECTIVE: To examine the attitudes of health care workers regarding the withdrawal of life support. DESIGN: Cross-sectional survey. PARTICIPANTS: Attending staff, house staff, and intensive care unit (ICU) nurses in 37 Canadian university-affiliated hospitals. MAIN OUTCOME MEASURES: Health care workers' ratings of the importance of 17 factors considered in the decision to withdraw life support, and their ratings of five levels of care ranging from comfort measures to intensive care in two of 12 different clinical scenarios. RESULTS: We surveyed 1361 respondents (149 of 167 potentially eligible ICU attending staff, 142 of 173 ICU house staff, and 1070 of 1455 ICU nurses, with response rates of 89%, 82% and 74%, respectively). The most important factors were likelihood of surviving the current episode, likelihood of long-term survival, premorbid cognitive function, and age of the patient. In choosing the level of care for the patient scenarios, the same option was chosen by more than 50% of respondents in only one of 12 scenarios; opposite extremes of care were chosen by more than 10% of the respondents in eight of 12 scenarios. Respondent characteristics affecting choices included the number of years since graduation, the city and province in which they worked, the number of beds in their ICU, and their assessment of the likelihood that they would withdraw life support in comparison with their colleagues (P < .001 for all comparisons). CONCLUSIONS: While ICU health care workers consistently identify a number of patient factors as important in decisions to withdraw care, there is extreme variability, which may be explained in part by the values of individual health care providers.

Adult↗

Basic statistics for clinicians: 4. Correlation and regression.

Correlation and regression help us to understand the relation between variables and to predict patients' status in regard to a particular variable of interest. Correlation examines the strength of the relation between two variables, neither of which is considered the variable one is trying to predict (the target variable). Regression analysis examines the ability of one or more factors, called independent variables, to predict a patient's status in regard to the target or dependent variable. Independent and dependent variables may be continuous (taking a wide range of values) or binary (dichotomous, yielding yes-or-no results). Regression models can be used to construct clinical prediction rules that help to guide clinical decisions. In considering regression and correlation, clinicians should pay more attention to the magnitude of the correlation or the predictive power of the regression than to whether the relation is statistically significant.

Data Interpretation, Statistical↗

Basic statistics for clinicians: 3. Assessing the effects of treatment: measures of association.

In the third of a series of four articles the authors show the calculation of measures of association and discuss their usefulness in clinical decision making. From the rates of death or other "events" in experimental and control groups in a clinical trial, we can calculate the relative risk (RR) of the event after the experimental treatment, expressed as a percentage of the risk without such treatment. The absolute risk reduction (ARR) is the difference in the risk of an event between the groups. The relative risk reduction is the percentage of the baseline risk (the risk of an event in the control patients) removed as a result of therapy. The odds ratio (OR), which is the measure of choice in case-control studies, gives the ratio of the odds of an event in the experimental group to those in the control group. The OR and the RR provide limited information in reporting the results of prospective trials because they do not reflect changes in the baseline risk. The ARR and the number needed to treat, which tells the clinician how many patients need to be treated to prevent one event, reflect both the baseline risk and the relative risk reduction. If the timing of events is important--to determine whether treatment extends life, for example--survival curves are used to show when events occur over time.

Case-Control Studies↗

Basic statistics for clinicians: 2. Interpreting study results: confidence intervals.

In the second of four articles, the authors discuss the "estimation" approach to interpreting study results. Whereas, in hypothesis testing, study results lead the reader to reject or accept a null hypothesis, in estimation the reader can assess whether a result is strong or weak, definitive or not. A confidence interval, based on the observed result and the size of the sample, is calculated. It provides a range of probabilities within which the true probability would lie 95% or 90% of the time, depending on the precision desired. It also provides a way of determining whether the sample is large enough to make the trial definitive. If the lower boundary of a confidence interval is above the threshold considered clinically significant, then the trial is positive and definitive, if the lower boundary is somewhat below the threshold, the trial is positive, but studies with larger samples are needed. Similarly, if the upper boundary of a confidence interval is below the threshold considered significant, the trial is negative and definitive. However, a negative result with a confidence interval that crosses the threshold means that trials with larger samples are needed to make a definitive determination of clinical importance.

Clinical Trials as Topic↗

Basic statistics for clinicians: 1. Hypothesis testing.

In the first of a series of four articles the authors explain the statistical concepts of hypothesis testing and p values. In many clinical trials investigators test a null hypothesis that there is no difference between a new treatment and a placebo or between two treatments. The result of a single experiment will almost always show some difference between the experimental and the control groups. Is the difference due to chance, or is it large enough to reject the null hypothesis and conclude that there is a true difference in treatment effects? Statistical tests yield a p value: the probability that the experiment would show a difference as great or greater than that observed if the null hypothesis were true. By convention, p values of less than 0.05 are considered statistically significant, and investigators conclude that there is a real difference. However, the smaller the sample size, the greater the chance of erroneously concluding that the experimental treatment does not differ from the control--in statistical terms, the power of the test may be inadequate. Tests of several outcomes from one set of data may lead to an erroneous conclusion that an outcome is significant if the joint probability of the outcomes is not taken into account. Hypothesis testing has limitations, which will be discussed in the next article in the series.

Clinical Trials as Topic↗