Q&A

BACKGROUND: PPROM is the leading cause of preterm birth, occurring in up to 3.5% of all pregnancies. A recent Cochrane review of several smaller studies was unable to show a statistically significant benefit of antibiotic use for PPROM in improving neonatal mortality or morbidity.¹ Another study by these researchers found these antibiotics had no significant effect on outcomes in preterm labor without prelabor rupture of membranes.² The ORACLE Collaborative Group conducted this large multicenter trial to better address the issue.

POPULATION STUDIED: This was a multicenter international study (though it did not include sites in the United States) intended to be reflective of clinical practice. This researchers recruited 4826 pregnant women with PPROM who were at less than 37 weeks’ gestation. Women were excluded if they were previously taking antibiotics, had a known infection requiring antibiotics, or had a contraindication to the study medications. Approximately half of the patients were beyond 32 weeks’ gestation. There were no significant differences between the study groups after randomization in terms of maternal age, gestational age, cervical dilatation, or other medication use.

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded placebo-controlled study. The women were assigned to 1 of 4 treatment groups: erythromycin 250 mg, amoxicillin/clavulanate 250/125 mg, both antibiotics, or placebo. The medications were taken orally 4 times daily for 10 days or until delivery. The strengths of this study include a large sample size, adequate allocation concealment, multiple checks to ensure validity in data collection and treatment assignment, and high follow-up rate (>99.6%). Data were analyzed by intention to treat. This was an overall very well-designed study, though one weakness is its use of a definition of “chronic lung disease” that is simply a neonate’s requirement of oxygen beyond a 36 weeks’ gestational age.

OUTCOMES MEASURED: The composite primary outcome included the overall rate of neonatal death, chronic lung disease, or major cerebral abnormality by ultrasound examination before discharge. Secondary outcomes included delivery within 48 hours, delivery within 7 days, mode of delivery, neonatal infection, number of days in the hospital, and the development of suspected or proven necrotizing enterocolitis.

RESULTS: For the composite primary outcome, there was no statistically significant difference among any of the treatments or placebo. However, there was a nonsignificant trend toward benefit for this outcome in the erythromycin-only group. This outcome may reach statistical significance with a larger sample size. No benefit was found with amoxicillin/clavulanate. In a subgroup analysis of only singleton pregnancies, the researchers found a statistically significant reduction in the composite primary outcome in the erythromycin-only group versus placebo (11.2% vs 14.4%, number needed to treat [NNT]=33).

The important secondary outcomes measured that were of statistical significance included a delay in delivery by at least 7 days (63.3% vs 57.7%, NNT=18) for women taking any antibiotic, as well as reductions in some disease-oriented short-term pulmonary outcomes with erythromycin. However, infants of women receiving amoxicillin/clavulanate were more likely to develop necrotizing enterocolitis (1.8% vs 0.7%, number needed to harm=91), without receiving any benefit from the treatment.

BACKGROUND: PPROM is the leading cause of preterm birth, occurring in up to 3.5% of all pregnancies. A recent Cochrane review of several smaller studies was unable to show a statistically significant benefit of antibiotic use for PPROM in improving neonatal mortality or morbidity.¹ Another study by these researchers found these antibiotics had no significant effect on outcomes in preterm labor without prelabor rupture of membranes.² The ORACLE Collaborative Group conducted this large multicenter trial to better address the issue.

POPULATION STUDIED: This was a multicenter international study (though it did not include sites in the United States) intended to be reflective of clinical practice. This researchers recruited 4826 pregnant women with PPROM who were at less than 37 weeks’ gestation. Women were excluded if they were previously taking antibiotics, had a known infection requiring antibiotics, or had a contraindication to the study medications. Approximately half of the patients were beyond 32 weeks’ gestation. There were no significant differences between the study groups after randomization in terms of maternal age, gestational age, cervical dilatation, or other medication use.

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded placebo-controlled study. The women were assigned to 1 of 4 treatment groups: erythromycin 250 mg, amoxicillin/clavulanate 250/125 mg, both antibiotics, or placebo. The medications were taken orally 4 times daily for 10 days or until delivery. The strengths of this study include a large sample size, adequate allocation concealment, multiple checks to ensure validity in data collection and treatment assignment, and high follow-up rate (>99.6%). Data were analyzed by intention to treat. This was an overall very well-designed study, though one weakness is its use of a definition of “chronic lung disease” that is simply a neonate’s requirement of oxygen beyond a 36 weeks’ gestational age.

OUTCOMES MEASURED: The composite primary outcome included the overall rate of neonatal death, chronic lung disease, or major cerebral abnormality by ultrasound examination before discharge. Secondary outcomes included delivery within 48 hours, delivery within 7 days, mode of delivery, neonatal infection, number of days in the hospital, and the development of suspected or proven necrotizing enterocolitis.

RESULTS: For the composite primary outcome, there was no statistically significant difference among any of the treatments or placebo. However, there was a nonsignificant trend toward benefit for this outcome in the erythromycin-only group. This outcome may reach statistical significance with a larger sample size. No benefit was found with amoxicillin/clavulanate. In a subgroup analysis of only singleton pregnancies, the researchers found a statistically significant reduction in the composite primary outcome in the erythromycin-only group versus placebo (11.2% vs 14.4%, number needed to treat [NNT]=33).

The important secondary outcomes measured that were of statistical significance included a delay in delivery by at least 7 days (63.3% vs 57.7%, NNT=18) for women taking any antibiotic, as well as reductions in some disease-oriented short-term pulmonary outcomes with erythromycin. However, infants of women receiving amoxicillin/clavulanate were more likely to develop necrotizing enterocolitis (1.8% vs 0.7%, number needed to harm=91), without receiving any benefit from the treatment.

BACKGROUND: PPROM is the leading cause of preterm birth, occurring in up to 3.5% of all pregnancies. A recent Cochrane review of several smaller studies was unable to show a statistically significant benefit of antibiotic use for PPROM in improving neonatal mortality or morbidity.¹ Another study by these researchers found these antibiotics had no significant effect on outcomes in preterm labor without prelabor rupture of membranes.² The ORACLE Collaborative Group conducted this large multicenter trial to better address the issue.

POPULATION STUDIED: This was a multicenter international study (though it did not include sites in the United States) intended to be reflective of clinical practice. This researchers recruited 4826 pregnant women with PPROM who were at less than 37 weeks’ gestation. Women were excluded if they were previously taking antibiotics, had a known infection requiring antibiotics, or had a contraindication to the study medications. Approximately half of the patients were beyond 32 weeks’ gestation. There were no significant differences between the study groups after randomization in terms of maternal age, gestational age, cervical dilatation, or other medication use.

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded placebo-controlled study. The women were assigned to 1 of 4 treatment groups: erythromycin 250 mg, amoxicillin/clavulanate 250/125 mg, both antibiotics, or placebo. The medications were taken orally 4 times daily for 10 days or until delivery. The strengths of this study include a large sample size, adequate allocation concealment, multiple checks to ensure validity in data collection and treatment assignment, and high follow-up rate (>99.6%). Data were analyzed by intention to treat. This was an overall very well-designed study, though one weakness is its use of a definition of “chronic lung disease” that is simply a neonate’s requirement of oxygen beyond a 36 weeks’ gestational age.

OUTCOMES MEASURED: The composite primary outcome included the overall rate of neonatal death, chronic lung disease, or major cerebral abnormality by ultrasound examination before discharge. Secondary outcomes included delivery within 48 hours, delivery within 7 days, mode of delivery, neonatal infection, number of days in the hospital, and the development of suspected or proven necrotizing enterocolitis.

RESULTS: For the composite primary outcome, there was no statistically significant difference among any of the treatments or placebo. However, there was a nonsignificant trend toward benefit for this outcome in the erythromycin-only group. This outcome may reach statistical significance with a larger sample size. No benefit was found with amoxicillin/clavulanate. In a subgroup analysis of only singleton pregnancies, the researchers found a statistically significant reduction in the composite primary outcome in the erythromycin-only group versus placebo (11.2% vs 14.4%, number needed to treat [NNT]=33).

The important secondary outcomes measured that were of statistical significance included a delay in delivery by at least 7 days (63.3% vs 57.7%, NNT=18) for women taking any antibiotic, as well as reductions in some disease-oriented short-term pulmonary outcomes with erythromycin. However, infants of women receiving amoxicillin/clavulanate were more likely to develop necrotizing enterocolitis (1.8% vs 0.7%, number needed to harm=91), without receiving any benefit from the treatment.

BACKGROUND: A meta-analysis of 23 randomized trials published in 1996 found St. John’s wort (SJW) to be effective for treating depressive disorders. However, the trials have been criticized for such flaws as lack of standard diagnostic criteria, short duration, wide dose variation, failure to blind, lack of placebo use, and suboptimal doses of comparison antidepressants. This trial aimed to address those concerns.

POPULATION STUDIED: Patients with major depressive disorder according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition were recruited from 11 academic medical centers’ psychiatry outpatient clinics, and 200 met criteria for randomization. Treatment and control groups were similar, with a mean age of 41.4 years, 64% women, and 85% white. This was the first episode of major depression for 35% of the sample. Patients were excluded for risk of suicide, psychotropic medicine use, history of treatment-resistant depression, or recent enrollment in psychotherapy. Other conditions that led to exclusion were cognitive disorders, posttraumatic stress disorder, eating disorders, substance use disorder, panic disorder, bipolar or psychotic disorders, and borderline, antisocial, or schizotypal personality disorders.

STUDY DESIGN AND VALIDITY: This study was a multisite placebo-controlled trial. Allocation of assignment was concealed. The taste and smell of SJW were masked by using an odorless SJW extract. All patients received placebo for 1 week, and 16 patients were excluded either because they experienced a 25% improvement on the Hamilton Rating Scale for Depression (HAM-D) while taking placebo or had very low HAM-D scores after 1 week. Patients were then randomized to receive either 300 mg of SJW extract or an identical placebo tablet 3 times daily. At 4 weeks the dose increased to 4 times daily if no improvement occurred. The subjects were followed up for 8 weeks. The researchers addressed many of the concerns about previous studies by using standard diagnostic techniques and a standardized drug dose. The use of a placebo run-in period decreases the overall response rate of both groups. Therefore, it should not affect statistical significance in comparing the 2 groups, but the response rate may appear lower than the results seen in clinical practice. This study had the power to detect a 17.5% difference in response between SJW and placebo. Smaller differences may exist but may not be clinically meaningful.

OUTCOMES MEASURED: The researchers measured efficacy of treatment using standard assessment tools. The primary measure of efficacy was the difference in the rate of improvement between SJW and placebo on total HAM-D scores over 8 weeks. The researchers also looked for differences in response (50% improvement in HAM-D scores) and remission (a HAM-D score of ≤7 and a clinical global impression score of 1-2), and they did a subgroup analysis of patients with mild depression (HAM-D scores <23).

RESULTS: Of the 98 patients completing the placebo run-in and randomized to SJW, 80 completed the trial compared with 87 of 100 placebo-assigned patients. Both intention-to-treat and completer analysis were performed for all measures of effect. The rate of improvement over time was not significantly different between SJW and placebo (P=.58). The 26.5% clinical response for SJW was not significantly better at 8 weeks than the 18.6% response for placebo (P=.15). Remission rates were significantly higher for SJW compared with placebo in the intention-to-treat analysis (14.3%; 95% confidence interval [CI], 8.6%-22.8% vs 4.9%; 95% CI, 2.0%-11.3%, P=.02; number needed to treat=11). The only significant adverse outcome was headache, which occurred in 41% of patients taking SJW (number needed to harm=7).

BACKGROUND: A meta-analysis of 23 randomized trials published in 1996 found St. John’s wort (SJW) to be effective for treating depressive disorders. However, the trials have been criticized for such flaws as lack of standard diagnostic criteria, short duration, wide dose variation, failure to blind, lack of placebo use, and suboptimal doses of comparison antidepressants. This trial aimed to address those concerns.

POPULATION STUDIED: Patients with major depressive disorder according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition were recruited from 11 academic medical centers’ psychiatry outpatient clinics, and 200 met criteria for randomization. Treatment and control groups were similar, with a mean age of 41.4 years, 64% women, and 85% white. This was the first episode of major depression for 35% of the sample. Patients were excluded for risk of suicide, psychotropic medicine use, history of treatment-resistant depression, or recent enrollment in psychotherapy. Other conditions that led to exclusion were cognitive disorders, posttraumatic stress disorder, eating disorders, substance use disorder, panic disorder, bipolar or psychotic disorders, and borderline, antisocial, or schizotypal personality disorders.

STUDY DESIGN AND VALIDITY: This study was a multisite placebo-controlled trial. Allocation of assignment was concealed. The taste and smell of SJW were masked by using an odorless SJW extract. All patients received placebo for 1 week, and 16 patients were excluded either because they experienced a 25% improvement on the Hamilton Rating Scale for Depression (HAM-D) while taking placebo or had very low HAM-D scores after 1 week. Patients were then randomized to receive either 300 mg of SJW extract or an identical placebo tablet 3 times daily. At 4 weeks the dose increased to 4 times daily if no improvement occurred. The subjects were followed up for 8 weeks. The researchers addressed many of the concerns about previous studies by using standard diagnostic techniques and a standardized drug dose. The use of a placebo run-in period decreases the overall response rate of both groups. Therefore, it should not affect statistical significance in comparing the 2 groups, but the response rate may appear lower than the results seen in clinical practice. This study had the power to detect a 17.5% difference in response between SJW and placebo. Smaller differences may exist but may not be clinically meaningful.

OUTCOMES MEASURED: The researchers measured efficacy of treatment using standard assessment tools. The primary measure of efficacy was the difference in the rate of improvement between SJW and placebo on total HAM-D scores over 8 weeks. The researchers also looked for differences in response (50% improvement in HAM-D scores) and remission (a HAM-D score of ≤7 and a clinical global impression score of 1-2), and they did a subgroup analysis of patients with mild depression (HAM-D scores <23).

RESULTS: Of the 98 patients completing the placebo run-in and randomized to SJW, 80 completed the trial compared with 87 of 100 placebo-assigned patients. Both intention-to-treat and completer analysis were performed for all measures of effect. The rate of improvement over time was not significantly different between SJW and placebo (P=.58). The 26.5% clinical response for SJW was not significantly better at 8 weeks than the 18.6% response for placebo (P=.15). Remission rates were significantly higher for SJW compared with placebo in the intention-to-treat analysis (14.3%; 95% confidence interval [CI], 8.6%-22.8% vs 4.9%; 95% CI, 2.0%-11.3%, P=.02; number needed to treat=11). The only significant adverse outcome was headache, which occurred in 41% of patients taking SJW (number needed to harm=7).

BACKGROUND: A meta-analysis of 23 randomized trials published in 1996 found St. John’s wort (SJW) to be effective for treating depressive disorders. However, the trials have been criticized for such flaws as lack of standard diagnostic criteria, short duration, wide dose variation, failure to blind, lack of placebo use, and suboptimal doses of comparison antidepressants. This trial aimed to address those concerns.

POPULATION STUDIED: Patients with major depressive disorder according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition were recruited from 11 academic medical centers’ psychiatry outpatient clinics, and 200 met criteria for randomization. Treatment and control groups were similar, with a mean age of 41.4 years, 64% women, and 85% white. This was the first episode of major depression for 35% of the sample. Patients were excluded for risk of suicide, psychotropic medicine use, history of treatment-resistant depression, or recent enrollment in psychotherapy. Other conditions that led to exclusion were cognitive disorders, posttraumatic stress disorder, eating disorders, substance use disorder, panic disorder, bipolar or psychotic disorders, and borderline, antisocial, or schizotypal personality disorders.

STUDY DESIGN AND VALIDITY: This study was a multisite placebo-controlled trial. Allocation of assignment was concealed. The taste and smell of SJW were masked by using an odorless SJW extract. All patients received placebo for 1 week, and 16 patients were excluded either because they experienced a 25% improvement on the Hamilton Rating Scale for Depression (HAM-D) while taking placebo or had very low HAM-D scores after 1 week. Patients were then randomized to receive either 300 mg of SJW extract or an identical placebo tablet 3 times daily. At 4 weeks the dose increased to 4 times daily if no improvement occurred. The subjects were followed up for 8 weeks. The researchers addressed many of the concerns about previous studies by using standard diagnostic techniques and a standardized drug dose. The use of a placebo run-in period decreases the overall response rate of both groups. Therefore, it should not affect statistical significance in comparing the 2 groups, but the response rate may appear lower than the results seen in clinical practice. This study had the power to detect a 17.5% difference in response between SJW and placebo. Smaller differences may exist but may not be clinically meaningful.

OUTCOMES MEASURED: The researchers measured efficacy of treatment using standard assessment tools. The primary measure of efficacy was the difference in the rate of improvement between SJW and placebo on total HAM-D scores over 8 weeks. The researchers also looked for differences in response (50% improvement in HAM-D scores) and remission (a HAM-D score of ≤7 and a clinical global impression score of 1-2), and they did a subgroup analysis of patients with mild depression (HAM-D scores <23).

RESULTS: Of the 98 patients completing the placebo run-in and randomized to SJW, 80 completed the trial compared with 87 of 100 placebo-assigned patients. Both intention-to-treat and completer analysis were performed for all measures of effect. The rate of improvement over time was not significantly different between SJW and placebo (P=.58). The 26.5% clinical response for SJW was not significantly better at 8 weeks than the 18.6% response for placebo (P=.15). Remission rates were significantly higher for SJW compared with placebo in the intention-to-treat analysis (14.3%; 95% confidence interval [CI], 8.6%-22.8% vs 4.9%; 95% CI, 2.0%-11.3%, P=.02; number needed to treat=11). The only significant adverse outcome was headache, which occurred in 41% of patients taking SJW (number needed to harm=7).

BACKGROUND: Guidelines for management of patients after acute myocardial infarction (AMI) recommend daily aspirin therapy.¹ Although ticlopidine reduces the incidence of vascular death, MI, and stroke among people with atherosclerotic disease,² it has not been compared directly with aspirin in the post-AMI period. This study compares the efficacy and safety of aspirin and ticlopidine in survivors of AMI treated with a thrombolytic agent.

POPULATION STUDIED: This multicenter trial enrolled 1470 patients recruited at the time of discharge from the hospital after receiving successful treatment for AMI with a thrombolytic agent. Patients were not included if they required anticoagulation with warfarin, were scheduled for major surgery, had uncontrolled hypertension, or had severe comorbidity likely to limit their life expectancy. The 2 groups were similar with regard to major coronary artery disease risk factors (eg, hypertension, diabetes, smoking) as well as characteristics and management of the incident MI (eg, infarct location, ejection fraction, medications at discharge).

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded multicenter trial. The patients were randomized at hospital discharge to receive either aspirin (80 mg twice daily) or ticlopidine (250 mg twice daily). Clinical follow-up was at 45 days, 3 months, and 6 months after enrollment. During these visits, compliance was assessed and information was collected on outcome endpoints, adverse reactions, and concomitant medications. An intention-to-treat analysis was performed, and patients were followed up for 6 months regardless of whether they were still taking the study drug. The study was large enough to detect a 5% difference in primary endpoints with 95% power. The main limitations in this study were the short follow-up period (6 months) and the relatively low event rate (10%). Compliance and follow-up appear to be good.

OUTCOMES MEASURED: The primary endpoint was the first occurrence of any of the following during the 6 month follow-up: fatal and nonfatal MI, fatal and nonfatal stroke, angina with objective evidence of myocardial ischemia, vascular death, or death due to any cause. The study was not large enough to detect differences for specific endpoints, only in the total frequency of endpoints.

RESULTS: At the end of the 6-month follow-up, equal numbers of patients experienced at least 1 primary endpoint (8.0% in each group). Fewer patients taking ticlopidine suffered a repeat nonfatal MI: 8 in the ticlopidine group versus 18 in the aspirin group (1.1% vs 2.4%; P=.049). There were no differences between the groups in frequencies of cardiovascular death, nonvascular death, nonfatal stroke, and documented angina. Seventy-two patients taking aspirin and 90 patients taking ticlopidine reported at least 1 drug-related adverse effect (9.8% vs 12.3%). Serious adverse effects occurred in 11 patients taking aspirin and 18 taking ticlopidine (1.5% vs 2.4%). Thirty-five patients in the aspirin group and 53 in the ticlopidine group stopped treatment because of adverse events. Gastrointestinal symptoms were the most common adverse reactions in both study groups.

BACKGROUND: Guidelines for management of patients after acute myocardial infarction (AMI) recommend daily aspirin therapy.¹ Although ticlopidine reduces the incidence of vascular death, MI, and stroke among people with atherosclerotic disease,² it has not been compared directly with aspirin in the post-AMI period. This study compares the efficacy and safety of aspirin and ticlopidine in survivors of AMI treated with a thrombolytic agent.

POPULATION STUDIED: This multicenter trial enrolled 1470 patients recruited at the time of discharge from the hospital after receiving successful treatment for AMI with a thrombolytic agent. Patients were not included if they required anticoagulation with warfarin, were scheduled for major surgery, had uncontrolled hypertension, or had severe comorbidity likely to limit their life expectancy. The 2 groups were similar with regard to major coronary artery disease risk factors (eg, hypertension, diabetes, smoking) as well as characteristics and management of the incident MI (eg, infarct location, ejection fraction, medications at discharge).

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded multicenter trial. The patients were randomized at hospital discharge to receive either aspirin (80 mg twice daily) or ticlopidine (250 mg twice daily). Clinical follow-up was at 45 days, 3 months, and 6 months after enrollment. During these visits, compliance was assessed and information was collected on outcome endpoints, adverse reactions, and concomitant medications. An intention-to-treat analysis was performed, and patients were followed up for 6 months regardless of whether they were still taking the study drug. The study was large enough to detect a 5% difference in primary endpoints with 95% power. The main limitations in this study were the short follow-up period (6 months) and the relatively low event rate (10%). Compliance and follow-up appear to be good.

OUTCOMES MEASURED: The primary endpoint was the first occurrence of any of the following during the 6 month follow-up: fatal and nonfatal MI, fatal and nonfatal stroke, angina with objective evidence of myocardial ischemia, vascular death, or death due to any cause. The study was not large enough to detect differences for specific endpoints, only in the total frequency of endpoints.

RESULTS: At the end of the 6-month follow-up, equal numbers of patients experienced at least 1 primary endpoint (8.0% in each group). Fewer patients taking ticlopidine suffered a repeat nonfatal MI: 8 in the ticlopidine group versus 18 in the aspirin group (1.1% vs 2.4%; P=.049). There were no differences between the groups in frequencies of cardiovascular death, nonvascular death, nonfatal stroke, and documented angina. Seventy-two patients taking aspirin and 90 patients taking ticlopidine reported at least 1 drug-related adverse effect (9.8% vs 12.3%). Serious adverse effects occurred in 11 patients taking aspirin and 18 taking ticlopidine (1.5% vs 2.4%). Thirty-five patients in the aspirin group and 53 in the ticlopidine group stopped treatment because of adverse events. Gastrointestinal symptoms were the most common adverse reactions in both study groups.

BACKGROUND: Guidelines for management of patients after acute myocardial infarction (AMI) recommend daily aspirin therapy.¹ Although ticlopidine reduces the incidence of vascular death, MI, and stroke among people with atherosclerotic disease,² it has not been compared directly with aspirin in the post-AMI period. This study compares the efficacy and safety of aspirin and ticlopidine in survivors of AMI treated with a thrombolytic agent.

POPULATION STUDIED: This multicenter trial enrolled 1470 patients recruited at the time of discharge from the hospital after receiving successful treatment for AMI with a thrombolytic agent. Patients were not included if they required anticoagulation with warfarin, were scheduled for major surgery, had uncontrolled hypertension, or had severe comorbidity likely to limit their life expectancy. The 2 groups were similar with regard to major coronary artery disease risk factors (eg, hypertension, diabetes, smoking) as well as characteristics and management of the incident MI (eg, infarct location, ejection fraction, medications at discharge).

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded multicenter trial. The patients were randomized at hospital discharge to receive either aspirin (80 mg twice daily) or ticlopidine (250 mg twice daily). Clinical follow-up was at 45 days, 3 months, and 6 months after enrollment. During these visits, compliance was assessed and information was collected on outcome endpoints, adverse reactions, and concomitant medications. An intention-to-treat analysis was performed, and patients were followed up for 6 months regardless of whether they were still taking the study drug. The study was large enough to detect a 5% difference in primary endpoints with 95% power. The main limitations in this study were the short follow-up period (6 months) and the relatively low event rate (10%). Compliance and follow-up appear to be good.

OUTCOMES MEASURED: The primary endpoint was the first occurrence of any of the following during the 6 month follow-up: fatal and nonfatal MI, fatal and nonfatal stroke, angina with objective evidence of myocardial ischemia, vascular death, or death due to any cause. The study was not large enough to detect differences for specific endpoints, only in the total frequency of endpoints.

RESULTS: At the end of the 6-month follow-up, equal numbers of patients experienced at least 1 primary endpoint (8.0% in each group). Fewer patients taking ticlopidine suffered a repeat nonfatal MI: 8 in the ticlopidine group versus 18 in the aspirin group (1.1% vs 2.4%; P=.049). There were no differences between the groups in frequencies of cardiovascular death, nonvascular death, nonfatal stroke, and documented angina. Seventy-two patients taking aspirin and 90 patients taking ticlopidine reported at least 1 drug-related adverse effect (9.8% vs 12.3%). Serious adverse effects occurred in 11 patients taking aspirin and 18 taking ticlopidine (1.5% vs 2.4%). Thirty-five patients in the aspirin group and 53 in the ticlopidine group stopped treatment because of adverse events. Gastrointestinal symptoms were the most common adverse reactions in both study groups.

BACKGROUND: Patients experience the highest rate of death and recurrent ischemia in the early period after the onset of acute coronary syndrome (ACS). The authors of this study hoped to determine whether treatment with a statin soon after an ACS could reduce the reoccurrence of these events.

POPULATION STUDIED: The population studied included 3086 adults 18 years or older with unstable angina or non–Q-wave acute myocardial infarction (AMI). The intervention and control groups were similar in baseline characteristics. Patients were not included if they had experienced a Q-wave AMI, had a recent or planned coronary revascularization procedure, had severe heart failure, or had left bundle branch block. Those with a contraindication to atorvastatin or who were taking high doses of vitamin E were also excluded.

STUDY DESIGN AND VALIDITY: Using a double-blind study design with concealed allocation assignment, patients received either atorvastatin 80 mg per day or matching placebo, beginning 24 and 96 hours after hospital admission. Lipid analysis was measured at baseline, 6 weeks, and 16 weeks. All patients received counseling to promote compliance with a National Cholesterol Education Project Step I diet. The patients were evaluated at 2, 6, and 16 weeks following enrollment. They were analyzed in the groups to which they were assigned (intention-to-treat analysis). Follow-up was available for 99.6% of the subjects. This study was well designed. The main limitations were not including a group with the most typical dose of atorvastatin (10 mg) and a relatively short follow-up period (16 weeks). Short follow-up may lead to either an underestimation or overestimation of the effect of atorvastatin.

OUTCOMES MEASURED: Primary endpoints included death, nonfatal acute MI, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. Secondary endpoints included nonfatal stroke, recurrent angina without objective evidence of ischemia, and coronary revascularization procedures. Subsets of the individual endpoints were also analyzed.

RESULTS: Death or recurrent ischemia or infarction occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (P=.048; number needed to treat [NNT]=38). Analyzing subgroups of this primary endpoint, the atorvastatin group had a lower incidence symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; P=.02; NNT=46). There were no significant differences in the remaining individual primary endpoints. Fewer patients in the atorvastatin group experienced a stroke (12 vs 24 events; P=.045; NNT=1600). No other secondary outcomes were affected by active therapy. In the atorvastatin group, mean low-density lipoprotein cholesterol level declined 40% (124 mg/dL to 72 mg/dL), while the placebo group actually increased 12% (124 mg/dL to 135 mg/dL). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P=.001; number needed to harm=52).

BACKGROUND: Patients experience the highest rate of death and recurrent ischemia in the early period after the onset of acute coronary syndrome (ACS). The authors of this study hoped to determine whether treatment with a statin soon after an ACS could reduce the reoccurrence of these events.

POPULATION STUDIED: The population studied included 3086 adults 18 years or older with unstable angina or non–Q-wave acute myocardial infarction (AMI). The intervention and control groups were similar in baseline characteristics. Patients were not included if they had experienced a Q-wave AMI, had a recent or planned coronary revascularization procedure, had severe heart failure, or had left bundle branch block. Those with a contraindication to atorvastatin or who were taking high doses of vitamin E were also excluded.

STUDY DESIGN AND VALIDITY: Using a double-blind study design with concealed allocation assignment, patients received either atorvastatin 80 mg per day or matching placebo, beginning 24 and 96 hours after hospital admission. Lipid analysis was measured at baseline, 6 weeks, and 16 weeks. All patients received counseling to promote compliance with a National Cholesterol Education Project Step I diet. The patients were evaluated at 2, 6, and 16 weeks following enrollment. They were analyzed in the groups to which they were assigned (intention-to-treat analysis). Follow-up was available for 99.6% of the subjects. This study was well designed. The main limitations were not including a group with the most typical dose of atorvastatin (10 mg) and a relatively short follow-up period (16 weeks). Short follow-up may lead to either an underestimation or overestimation of the effect of atorvastatin.

OUTCOMES MEASURED: Primary endpoints included death, nonfatal acute MI, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. Secondary endpoints included nonfatal stroke, recurrent angina without objective evidence of ischemia, and coronary revascularization procedures. Subsets of the individual endpoints were also analyzed.

RESULTS: Death or recurrent ischemia or infarction occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (P=.048; number needed to treat [NNT]=38). Analyzing subgroups of this primary endpoint, the atorvastatin group had a lower incidence symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; P=.02; NNT=46). There were no significant differences in the remaining individual primary endpoints. Fewer patients in the atorvastatin group experienced a stroke (12 vs 24 events; P=.045; NNT=1600). No other secondary outcomes were affected by active therapy. In the atorvastatin group, mean low-density lipoprotein cholesterol level declined 40% (124 mg/dL to 72 mg/dL), while the placebo group actually increased 12% (124 mg/dL to 135 mg/dL). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P=.001; number needed to harm=52).

BACKGROUND: Patients experience the highest rate of death and recurrent ischemia in the early period after the onset of acute coronary syndrome (ACS). The authors of this study hoped to determine whether treatment with a statin soon after an ACS could reduce the reoccurrence of these events.

POPULATION STUDIED: The population studied included 3086 adults 18 years or older with unstable angina or non–Q-wave acute myocardial infarction (AMI). The intervention and control groups were similar in baseline characteristics. Patients were not included if they had experienced a Q-wave AMI, had a recent or planned coronary revascularization procedure, had severe heart failure, or had left bundle branch block. Those with a contraindication to atorvastatin or who were taking high doses of vitamin E were also excluded.

STUDY DESIGN AND VALIDITY: Using a double-blind study design with concealed allocation assignment, patients received either atorvastatin 80 mg per day or matching placebo, beginning 24 and 96 hours after hospital admission. Lipid analysis was measured at baseline, 6 weeks, and 16 weeks. All patients received counseling to promote compliance with a National Cholesterol Education Project Step I diet. The patients were evaluated at 2, 6, and 16 weeks following enrollment. They were analyzed in the groups to which they were assigned (intention-to-treat analysis). Follow-up was available for 99.6% of the subjects. This study was well designed. The main limitations were not including a group with the most typical dose of atorvastatin (10 mg) and a relatively short follow-up period (16 weeks). Short follow-up may lead to either an underestimation or overestimation of the effect of atorvastatin.

OUTCOMES MEASURED: Primary endpoints included death, nonfatal acute MI, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. Secondary endpoints included nonfatal stroke, recurrent angina without objective evidence of ischemia, and coronary revascularization procedures. Subsets of the individual endpoints were also analyzed.

RESULTS: Death or recurrent ischemia or infarction occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (P=.048; number needed to treat [NNT]=38). Analyzing subgroups of this primary endpoint, the atorvastatin group had a lower incidence symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; P=.02; NNT=46). There were no significant differences in the remaining individual primary endpoints. Fewer patients in the atorvastatin group experienced a stroke (12 vs 24 events; P=.045; NNT=1600). No other secondary outcomes were affected by active therapy. In the atorvastatin group, mean low-density lipoprotein cholesterol level declined 40% (124 mg/dL to 72 mg/dL), while the placebo group actually increased 12% (124 mg/dL to 135 mg/dL). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P=.001; number needed to harm=52).

BACKGROUND: Anticholinergic medications are the mainstay of pharmacologic therapy for an overactive bladder (defined as urge incontinence, urgency, or frequency). Immediate-release oxybutynin and tolterodine (the most popular options) are equally effective, but tolterodine has a better side effect profile. The efficacy and tolerability of the newly developed extended-release oxybutynin is compared with tolterodine in this study.

POPULATION STUDIED: The investigators enrolled 378 mostly white (87%), mostly women (83%) participants aged 21 to 87 years (mean=59 years); 88% of the participants completed the study. The patients were required to experience between 7 and 50 episodes of urge incontinence per week and 10 or more voids in a 24-hour period. The study was conducted in 37 specialty outpatient-based practices across the United States. Previous exposure or response to therapy did not preclude participation. Patients were excluded if they had uncontrolled medical conditions, significant risk for urinary retention, or incontinence related to prostatitis, interstitial cystitis, urinary tract obstruction, urethral diverticulum, bladder tumor, bladder stone, prostate cancer, or urinary tract infection. Other exclusions included pelvic organ prolapse, pregnancy, and potential poor adherence to therapy.

STUDY DESIGN AND VALIDITY: This was a prospective randomized controlled trial (RCT) sponsored by the makers of oxybutynin. The study participants were treated for 12 weeks with either oxybutynin 10 mg per day or tolterodine 2 mg twice daily. Stratified randomization insured equal representation of mild incontinence (≤21 episodes weekly) and moderate to severe incontinence (>21 episodes weekly) within each treatment group. Study visits occurred at weeks 2, 4, 8, and 12. Each subject kept a 24-hour urinary diary documenting micturition frequency and the number and nature of incontinence episodes during the 7-day period before each study visit. The participants were asked at each visit about adverse events or unusual symptoms. This study was well designed, avoiding bias with a double-blind double-dummy stratified randomization approach. Dropout rates were similar for the 2 groups. Formal intention-to-treat analysis was not possible, but the authors stated that analysis of partial data from dropouts was not different from reported results. The study may not be generalizable to most primary care populations, since patients were recruited exclusively from specialty practices. The authors adjusted for the nonsignificant baseline differences in incontinence frequency; this is statistically valid but not necessary in an randomized controlled trial. Without this adjustment, outcome differences between the 2 medications were substantially smaller and no longer statistically significant.

OUTCOMES MEASURED: The primary outcome measured was baseline versus end of study (week 12) episodes of urge incontinence. Total episodes of incontinence, micturition frequency, and medication side effects were secondary outcomes.

RESULTS: Both treatment groups showed a substantial reduction in urge incontinence, total incontinence, and micturition frequency. Urge incontinence decreased 76% in the oxybutynin-treated group and 68% in the tolterodine-treated group (P=.03). Total incontinence episodes in the oxybutynin-treated group dropped 75% from 28.6 to 7.1 episodes per week, while decreasing 66% from 27.0 to 9.3 episodes per week in the tolterodine-treated group. The net difference between the groups was 3.8 (P=.02) or 2.1 (P=NS) fewer episodes of incontinence per week with extended-release oxybutynin, adjusting or not adjusting for the baseline difference between the groups. Weekly bathroom trips declined by 27% in the oxybutynin-treated group versus 22% in the tolterodine-treated group (P=.02). Rates of side effects were similar for oxybutynin compared with tolterodine.

BACKGROUND: Anticholinergic medications are the mainstay of pharmacologic therapy for an overactive bladder (defined as urge incontinence, urgency, or frequency). Immediate-release oxybutynin and tolterodine (the most popular options) are equally effective, but tolterodine has a better side effect profile. The efficacy and tolerability of the newly developed extended-release oxybutynin is compared with tolterodine in this study.

POPULATION STUDIED: The investigators enrolled 378 mostly white (87%), mostly women (83%) participants aged 21 to 87 years (mean=59 years); 88% of the participants completed the study. The patients were required to experience between 7 and 50 episodes of urge incontinence per week and 10 or more voids in a 24-hour period. The study was conducted in 37 specialty outpatient-based practices across the United States. Previous exposure or response to therapy did not preclude participation. Patients were excluded if they had uncontrolled medical conditions, significant risk for urinary retention, or incontinence related to prostatitis, interstitial cystitis, urinary tract obstruction, urethral diverticulum, bladder tumor, bladder stone, prostate cancer, or urinary tract infection. Other exclusions included pelvic organ prolapse, pregnancy, and potential poor adherence to therapy.

STUDY DESIGN AND VALIDITY: This was a prospective randomized controlled trial (RCT) sponsored by the makers of oxybutynin. The study participants were treated for 12 weeks with either oxybutynin 10 mg per day or tolterodine 2 mg twice daily. Stratified randomization insured equal representation of mild incontinence (≤21 episodes weekly) and moderate to severe incontinence (>21 episodes weekly) within each treatment group. Study visits occurred at weeks 2, 4, 8, and 12. Each subject kept a 24-hour urinary diary documenting micturition frequency and the number and nature of incontinence episodes during the 7-day period before each study visit. The participants were asked at each visit about adverse events or unusual symptoms. This study was well designed, avoiding bias with a double-blind double-dummy stratified randomization approach. Dropout rates were similar for the 2 groups. Formal intention-to-treat analysis was not possible, but the authors stated that analysis of partial data from dropouts was not different from reported results. The study may not be generalizable to most primary care populations, since patients were recruited exclusively from specialty practices. The authors adjusted for the nonsignificant baseline differences in incontinence frequency; this is statistically valid but not necessary in an randomized controlled trial. Without this adjustment, outcome differences between the 2 medications were substantially smaller and no longer statistically significant.

OUTCOMES MEASURED: The primary outcome measured was baseline versus end of study (week 12) episodes of urge incontinence. Total episodes of incontinence, micturition frequency, and medication side effects were secondary outcomes.

RESULTS: Both treatment groups showed a substantial reduction in urge incontinence, total incontinence, and micturition frequency. Urge incontinence decreased 76% in the oxybutynin-treated group and 68% in the tolterodine-treated group (P=.03). Total incontinence episodes in the oxybutynin-treated group dropped 75% from 28.6 to 7.1 episodes per week, while decreasing 66% from 27.0 to 9.3 episodes per week in the tolterodine-treated group. The net difference between the groups was 3.8 (P=.02) or 2.1 (P=NS) fewer episodes of incontinence per week with extended-release oxybutynin, adjusting or not adjusting for the baseline difference between the groups. Weekly bathroom trips declined by 27% in the oxybutynin-treated group versus 22% in the tolterodine-treated group (P=.02). Rates of side effects were similar for oxybutynin compared with tolterodine.

BACKGROUND: Anticholinergic medications are the mainstay of pharmacologic therapy for an overactive bladder (defined as urge incontinence, urgency, or frequency). Immediate-release oxybutynin and tolterodine (the most popular options) are equally effective, but tolterodine has a better side effect profile. The efficacy and tolerability of the newly developed extended-release oxybutynin is compared with tolterodine in this study.

POPULATION STUDIED: The investigators enrolled 378 mostly white (87%), mostly women (83%) participants aged 21 to 87 years (mean=59 years); 88% of the participants completed the study. The patients were required to experience between 7 and 50 episodes of urge incontinence per week and 10 or more voids in a 24-hour period. The study was conducted in 37 specialty outpatient-based practices across the United States. Previous exposure or response to therapy did not preclude participation. Patients were excluded if they had uncontrolled medical conditions, significant risk for urinary retention, or incontinence related to prostatitis, interstitial cystitis, urinary tract obstruction, urethral diverticulum, bladder tumor, bladder stone, prostate cancer, or urinary tract infection. Other exclusions included pelvic organ prolapse, pregnancy, and potential poor adherence to therapy.

STUDY DESIGN AND VALIDITY: This was a prospective randomized controlled trial (RCT) sponsored by the makers of oxybutynin. The study participants were treated for 12 weeks with either oxybutynin 10 mg per day or tolterodine 2 mg twice daily. Stratified randomization insured equal representation of mild incontinence (≤21 episodes weekly) and moderate to severe incontinence (>21 episodes weekly) within each treatment group. Study visits occurred at weeks 2, 4, 8, and 12. Each subject kept a 24-hour urinary diary documenting micturition frequency and the number and nature of incontinence episodes during the 7-day period before each study visit. The participants were asked at each visit about adverse events or unusual symptoms. This study was well designed, avoiding bias with a double-blind double-dummy stratified randomization approach. Dropout rates were similar for the 2 groups. Formal intention-to-treat analysis was not possible, but the authors stated that analysis of partial data from dropouts was not different from reported results. The study may not be generalizable to most primary care populations, since patients were recruited exclusively from specialty practices. The authors adjusted for the nonsignificant baseline differences in incontinence frequency; this is statistically valid but not necessary in an randomized controlled trial. Without this adjustment, outcome differences between the 2 medications were substantially smaller and no longer statistically significant.

OUTCOMES MEASURED: The primary outcome measured was baseline versus end of study (week 12) episodes of urge incontinence. Total episodes of incontinence, micturition frequency, and medication side effects were secondary outcomes.

RESULTS: Both treatment groups showed a substantial reduction in urge incontinence, total incontinence, and micturition frequency. Urge incontinence decreased 76% in the oxybutynin-treated group and 68% in the tolterodine-treated group (P=.03). Total incontinence episodes in the oxybutynin-treated group dropped 75% from 28.6 to 7.1 episodes per week, while decreasing 66% from 27.0 to 9.3 episodes per week in the tolterodine-treated group. The net difference between the groups was 3.8 (P=.02) or 2.1 (P=NS) fewer episodes of incontinence per week with extended-release oxybutynin, adjusting or not adjusting for the baseline difference between the groups. Weekly bathroom trips declined by 27% in the oxybutynin-treated group versus 22% in the tolterodine-treated group (P=.02). Rates of side effects were similar for oxybutynin compared with tolterodine.

BACKGROUND: Ectopic pregnancy is a major cause of morbidity and mortality in women of reproductive age, but uncertainty remains about the best strategy for early diagnosis.

POPULATION STUDIED: This study used a hypothetical cohort of 10,000 women with first trimester pregnancies (positive pregnancy test result) who presented to an inner-city emergency department with abdominal pain or bleeding. Patients with any evidence of intra-abdominal hemorrhage were excluded. Their assumed prevalences of ectopic, intrauterine, and nonviable pregnancies were 9.4%, 61.1%, and 29.9%, respectively, based on a weighted average of 3 studies from inner-city teaching hospitals. The availability of 24-hour endovaginal ultrasound and human chorionic gonadotropin (HCG) testing was assumed. The results derived from this population are likely to be similar to those seen by family physicians, but caution should be exercised in generalizing this information to settings such as office practices or rural emergency departments.

STUDY DESIGN AND VALIDITY: The decision analysis defined 6 diagnostic algorithms: (1) transvaginal ultrasound (US) followed by quantitative HCG; (2) quantitative HCG followed by US; (3) progesterone followed by US and quantitative HCG; (4) progesterone followed by quantitative HCG and US; (5) US followed by repeat US; and (6) clinical examination. In practice, ultrasound and HCG are often done simultaneously, but otherwise the descriptions are appropriate. Strategies involving transabdominal US, serial HCGs, and methotrexate were not included. It was assumed that dilatation and curettage (D&C) and laparoscopy were 100% diagnostic and that US does not mistake intrauterine pregnancy for ectopic pregnancy. One- and two-way sensitivity analysis of test characteristics were performed using values obtained from the literature; prevalence of disease and performance of clinical examination were not included in the analysis.The methodologic strength of this study was fair. This clinical question is well suited to decision analysis; the different options are described well; and the analysis addresses appropriate outcomes, including unnecessarily interrupted pregnancies. The major weakness is a lack of information about the literature search and sensitivity analysis that makes it difficult to assess whether the authors’ underlying assumptions are valid. In addition, the authors assume that the highest priority is to avoid missed ectopic pregnancies. Although this is reasonable, no effort was made to query the literature, other professionals, or patients about what their preferred priorities would be, especially when the large majority of ectopic pregnancies are being detected by most of the strategies.

OUTCOMES MEASURED: The primary outcome was the number of missed ectopic pregnancies per 10,000 women. Secondary outcomes included the number of interrupted intrauterine pregnancies; the number of D&Cs, laparoscopies, USs, blood collections, and admissions; the days until diagnosis; and the hospital charges.

RESULTS: No ectopic pregnancies were missed with strategies that involved only US and HCG. Of those 2 strategies, US as the first step led to the fewest interrupted intrauterine pregnancies (70 vs 122). The progesterone algorithms missed more women with ectopic pregnancies (24) and required more surgeries but had the fewest number of interrupted pregnancies (25 and 39). US followed by US missed no ectopic pregnancies and had the shortest time until diagnosis but had the highest hospital charges. Clinical examination alone missed all ectopic pregnancies (940). Sensitivity analysis confirmed that the strategy of HCG followed by US was the most favorable, provided the sensitivity of the US for diagnosing intrauterine pregnancy was above 93%.

BACKGROUND: Ectopic pregnancy is a major cause of morbidity and mortality in women of reproductive age, but uncertainty remains about the best strategy for early diagnosis.

POPULATION STUDIED: This study used a hypothetical cohort of 10,000 women with first trimester pregnancies (positive pregnancy test result) who presented to an inner-city emergency department with abdominal pain or bleeding. Patients with any evidence of intra-abdominal hemorrhage were excluded. Their assumed prevalences of ectopic, intrauterine, and nonviable pregnancies were 9.4%, 61.1%, and 29.9%, respectively, based on a weighted average of 3 studies from inner-city teaching hospitals. The availability of 24-hour endovaginal ultrasound and human chorionic gonadotropin (HCG) testing was assumed. The results derived from this population are likely to be similar to those seen by family physicians, but caution should be exercised in generalizing this information to settings such as office practices or rural emergency departments.

STUDY DESIGN AND VALIDITY: The decision analysis defined 6 diagnostic algorithms: (1) transvaginal ultrasound (US) followed by quantitative HCG; (2) quantitative HCG followed by US; (3) progesterone followed by US and quantitative HCG; (4) progesterone followed by quantitative HCG and US; (5) US followed by repeat US; and (6) clinical examination. In practice, ultrasound and HCG are often done simultaneously, but otherwise the descriptions are appropriate. Strategies involving transabdominal US, serial HCGs, and methotrexate were not included. It was assumed that dilatation and curettage (D&C) and laparoscopy were 100% diagnostic and that US does not mistake intrauterine pregnancy for ectopic pregnancy. One- and two-way sensitivity analysis of test characteristics were performed using values obtained from the literature; prevalence of disease and performance of clinical examination were not included in the analysis.The methodologic strength of this study was fair. This clinical question is well suited to decision analysis; the different options are described well; and the analysis addresses appropriate outcomes, including unnecessarily interrupted pregnancies. The major weakness is a lack of information about the literature search and sensitivity analysis that makes it difficult to assess whether the authors’ underlying assumptions are valid. In addition, the authors assume that the highest priority is to avoid missed ectopic pregnancies. Although this is reasonable, no effort was made to query the literature, other professionals, or patients about what their preferred priorities would be, especially when the large majority of ectopic pregnancies are being detected by most of the strategies.

OUTCOMES MEASURED: The primary outcome was the number of missed ectopic pregnancies per 10,000 women. Secondary outcomes included the number of interrupted intrauterine pregnancies; the number of D&Cs, laparoscopies, USs, blood collections, and admissions; the days until diagnosis; and the hospital charges.

RESULTS: No ectopic pregnancies were missed with strategies that involved only US and HCG. Of those 2 strategies, US as the first step led to the fewest interrupted intrauterine pregnancies (70 vs 122). The progesterone algorithms missed more women with ectopic pregnancies (24) and required more surgeries but had the fewest number of interrupted pregnancies (25 and 39). US followed by US missed no ectopic pregnancies and had the shortest time until diagnosis but had the highest hospital charges. Clinical examination alone missed all ectopic pregnancies (940). Sensitivity analysis confirmed that the strategy of HCG followed by US was the most favorable, provided the sensitivity of the US for diagnosing intrauterine pregnancy was above 93%.

BACKGROUND: Ectopic pregnancy is a major cause of morbidity and mortality in women of reproductive age, but uncertainty remains about the best strategy for early diagnosis.

POPULATION STUDIED: This study used a hypothetical cohort of 10,000 women with first trimester pregnancies (positive pregnancy test result) who presented to an inner-city emergency department with abdominal pain or bleeding. Patients with any evidence of intra-abdominal hemorrhage were excluded. Their assumed prevalences of ectopic, intrauterine, and nonviable pregnancies were 9.4%, 61.1%, and 29.9%, respectively, based on a weighted average of 3 studies from inner-city teaching hospitals. The availability of 24-hour endovaginal ultrasound and human chorionic gonadotropin (HCG) testing was assumed. The results derived from this population are likely to be similar to those seen by family physicians, but caution should be exercised in generalizing this information to settings such as office practices or rural emergency departments.

STUDY DESIGN AND VALIDITY: The decision analysis defined 6 diagnostic algorithms: (1) transvaginal ultrasound (US) followed by quantitative HCG; (2) quantitative HCG followed by US; (3) progesterone followed by US and quantitative HCG; (4) progesterone followed by quantitative HCG and US; (5) US followed by repeat US; and (6) clinical examination. In practice, ultrasound and HCG are often done simultaneously, but otherwise the descriptions are appropriate. Strategies involving transabdominal US, serial HCGs, and methotrexate were not included. It was assumed that dilatation and curettage (D&C) and laparoscopy were 100% diagnostic and that US does not mistake intrauterine pregnancy for ectopic pregnancy. One- and two-way sensitivity analysis of test characteristics were performed using values obtained from the literature; prevalence of disease and performance of clinical examination were not included in the analysis.The methodologic strength of this study was fair. This clinical question is well suited to decision analysis; the different options are described well; and the analysis addresses appropriate outcomes, including unnecessarily interrupted pregnancies. The major weakness is a lack of information about the literature search and sensitivity analysis that makes it difficult to assess whether the authors’ underlying assumptions are valid. In addition, the authors assume that the highest priority is to avoid missed ectopic pregnancies. Although this is reasonable, no effort was made to query the literature, other professionals, or patients about what their preferred priorities would be, especially when the large majority of ectopic pregnancies are being detected by most of the strategies.

OUTCOMES MEASURED: The primary outcome was the number of missed ectopic pregnancies per 10,000 women. Secondary outcomes included the number of interrupted intrauterine pregnancies; the number of D&Cs, laparoscopies, USs, blood collections, and admissions; the days until diagnosis; and the hospital charges.

RESULTS: No ectopic pregnancies were missed with strategies that involved only US and HCG. Of those 2 strategies, US as the first step led to the fewest interrupted intrauterine pregnancies (70 vs 122). The progesterone algorithms missed more women with ectopic pregnancies (24) and required more surgeries but had the fewest number of interrupted pregnancies (25 and 39). US followed by US missed no ectopic pregnancies and had the shortest time until diagnosis but had the highest hospital charges. Clinical examination alone missed all ectopic pregnancies (940). Sensitivity analysis confirmed that the strategy of HCG followed by US was the most favorable, provided the sensitivity of the US for diagnosing intrauterine pregnancy was above 93%.

BACKGROUND: Persistent primary insomnia is common (affecting up to 5% of the general population) and predicts both depression and increased health care use. Common treatments include sedative hypnotics and antidepressants, both of which have numerous side effects and often lead to a relapse once they are stopped. Behavioral treatments have shown more durable improvements but only address sleep onset problems. It is not known whether CBT, by addressing both sleep onset and sleep maintenance problems, can provide a better outcome.

POPULATION STUDIED: The study included 75 adults (aged 40-80 years) with a mean duration of symptoms of 14 years who were recruited by a single academic medical center primarily through newspaper ads. Multiple exclusion criteria included anyone meeting criteria for an Axis I psychiatric disorder (including major depression).

STUDY DESIGN AND VALIDITY: Patients were randomly assigned (uncertain allocation concealment) to a therapist offering CBT, relaxation training (RT), or placebo treatment (PT) on a weekly basis for 6 weeks (3-6 hours of total contact). Those in the CBT arm were educated to misconceptions about sleep requirements and the effects of aging, circadian rhythms, and sleep loss on sleep/wake functioning, followed by instructions to: (1) establish a standard wake-up time; (2) get out of bed during extended awakenings; (3) avoid sleep-incompatible behaviors in bed; and (4) eliminate daytime napping. They also received sleep prescriptions with weekly adjustments based on sleep efficiency. RT recipients received progressive muscle relaxation training and were encouraged to use these skills to help return to sleep on awakening. PT recipients received “quasi-desensitization treatment” involving imagined scenes of neutral activities to eliminate conditioned arousals. The subjects completed pretreatment assessment, 6 weeks of therapy, 2 weeks of post-treatment assessment, and a 6-month follow-up assessment.

OUTCOME MEASURED: The outcomes measured included objective (polysomnography) and subjective (sleep logs) evaluations of total sleep time, wake time after sleep onset (WASO), and sleep efficiency. Questionnaires were used to assess subjective insomnia symptoms, changes in perceived control over sleep, and mood disturbances.

RESULTS: Overall, CBT was superior to both RT and PT in treating chronic insomnia. CBT recipients reported a 54% reduction in WASO compared with 16% and 12% for RT and PT patients, respectively (P=.02). CBT also produced greater improvements in sleep efficiency and improved subjective insomnia symptoms. An objective increase in total sleep time measured by polysomnography in the CBT group (approximately 12 minutes) persisted through the 6-month follow-up period. The PT group showed a decrease in objective sleep time (approximately 9 minutes). Objective (polysomnographic) differences were less dramatic than those derived from the sleep log, although both favored CBT.

BACKGROUND: Persistent primary insomnia is common (affecting up to 5% of the general population) and predicts both depression and increased health care use. Common treatments include sedative hypnotics and antidepressants, both of which have numerous side effects and often lead to a relapse once they are stopped. Behavioral treatments have shown more durable improvements but only address sleep onset problems. It is not known whether CBT, by addressing both sleep onset and sleep maintenance problems, can provide a better outcome.

POPULATION STUDIED: The study included 75 adults (aged 40-80 years) with a mean duration of symptoms of 14 years who were recruited by a single academic medical center primarily through newspaper ads. Multiple exclusion criteria included anyone meeting criteria for an Axis I psychiatric disorder (including major depression).

STUDY DESIGN AND VALIDITY: Patients were randomly assigned (uncertain allocation concealment) to a therapist offering CBT, relaxation training (RT), or placebo treatment (PT) on a weekly basis for 6 weeks (3-6 hours of total contact). Those in the CBT arm were educated to misconceptions about sleep requirements and the effects of aging, circadian rhythms, and sleep loss on sleep/wake functioning, followed by instructions to: (1) establish a standard wake-up time; (2) get out of bed during extended awakenings; (3) avoid sleep-incompatible behaviors in bed; and (4) eliminate daytime napping. They also received sleep prescriptions with weekly adjustments based on sleep efficiency. RT recipients received progressive muscle relaxation training and were encouraged to use these skills to help return to sleep on awakening. PT recipients received “quasi-desensitization treatment” involving imagined scenes of neutral activities to eliminate conditioned arousals. The subjects completed pretreatment assessment, 6 weeks of therapy, 2 weeks of post-treatment assessment, and a 6-month follow-up assessment.

OUTCOME MEASURED: The outcomes measured included objective (polysomnography) and subjective (sleep logs) evaluations of total sleep time, wake time after sleep onset (WASO), and sleep efficiency. Questionnaires were used to assess subjective insomnia symptoms, changes in perceived control over sleep, and mood disturbances.

RESULTS: Overall, CBT was superior to both RT and PT in treating chronic insomnia. CBT recipients reported a 54% reduction in WASO compared with 16% and 12% for RT and PT patients, respectively (P=.02). CBT also produced greater improvements in sleep efficiency and improved subjective insomnia symptoms. An objective increase in total sleep time measured by polysomnography in the CBT group (approximately 12 minutes) persisted through the 6-month follow-up period. The PT group showed a decrease in objective sleep time (approximately 9 minutes). Objective (polysomnographic) differences were less dramatic than those derived from the sleep log, although both favored CBT.

BACKGROUND: Persistent primary insomnia is common (affecting up to 5% of the general population) and predicts both depression and increased health care use. Common treatments include sedative hypnotics and antidepressants, both of which have numerous side effects and often lead to a relapse once they are stopped. Behavioral treatments have shown more durable improvements but only address sleep onset problems. It is not known whether CBT, by addressing both sleep onset and sleep maintenance problems, can provide a better outcome.

POPULATION STUDIED: The study included 75 adults (aged 40-80 years) with a mean duration of symptoms of 14 years who were recruited by a single academic medical center primarily through newspaper ads. Multiple exclusion criteria included anyone meeting criteria for an Axis I psychiatric disorder (including major depression).

STUDY DESIGN AND VALIDITY: Patients were randomly assigned (uncertain allocation concealment) to a therapist offering CBT, relaxation training (RT), or placebo treatment (PT) on a weekly basis for 6 weeks (3-6 hours of total contact). Those in the CBT arm were educated to misconceptions about sleep requirements and the effects of aging, circadian rhythms, and sleep loss on sleep/wake functioning, followed by instructions to: (1) establish a standard wake-up time; (2) get out of bed during extended awakenings; (3) avoid sleep-incompatible behaviors in bed; and (4) eliminate daytime napping. They also received sleep prescriptions with weekly adjustments based on sleep efficiency. RT recipients received progressive muscle relaxation training and were encouraged to use these skills to help return to sleep on awakening. PT recipients received “quasi-desensitization treatment” involving imagined scenes of neutral activities to eliminate conditioned arousals. The subjects completed pretreatment assessment, 6 weeks of therapy, 2 weeks of post-treatment assessment, and a 6-month follow-up assessment.

OUTCOME MEASURED: The outcomes measured included objective (polysomnography) and subjective (sleep logs) evaluations of total sleep time, wake time after sleep onset (WASO), and sleep efficiency. Questionnaires were used to assess subjective insomnia symptoms, changes in perceived control over sleep, and mood disturbances.

RESULTS: Overall, CBT was superior to both RT and PT in treating chronic insomnia. CBT recipients reported a 54% reduction in WASO compared with 16% and 12% for RT and PT patients, respectively (P=.02). CBT also produced greater improvements in sleep efficiency and improved subjective insomnia symptoms. An objective increase in total sleep time measured by polysomnography in the CBT group (approximately 12 minutes) persisted through the 6-month follow-up period. The PT group showed a decrease in objective sleep time (approximately 9 minutes). Objective (polysomnographic) differences were less dramatic than those derived from the sleep log, although both favored CBT.

BACKGROUND: Currently, most screening questions in the primary care setting address only alcohol abuse, but it is also important to screen for other substance abuse. The authors of this study examined the validity of a 2-question screening test for alcohol and other substances.

POPULATION STUDIED: The participants were 1252 patients randomly selected from 3 University of Wisconsin primary care clinics. They ranged in age from 18 to 59 years; 68% were women; and the population was racially diverse. Sixty-nine percent had private insurance. The prevalence of substance disorders in this study population was high (23%).

STUDY DESIGN AND VALIDITY: This prospective cohort study sought to identify 2 questions that could accurately screen for substance abuse. Screening questions were developed through a literature search and a series of focus groups. The interviewers asked patients the screening questions and then administered the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM), a series of questions based on the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised used for identifying substance use disorders. The sensitivity of the screening questions was defined as the proportion of patients with a current substance abuse problem, as detected by CIDI-SAM, who had positive screening results. The high prevalence of substance abuse in this study will improve the positive predictive value of the screening test.This study was well designed and had a high response rate. Although the interviewers were not blinded while administering the screening questions and the CIDI-SAM, they were monitored closely, and a random subset of patients underwent urine drug testing. The authors also tested the validity of the screening questions with questions about patient comfort and truthfulness.

OUTCOMES MEASURED: The primary outcome measured was identification of either alcohol or drug abuse.

RESULTS: Among 1136 participants (91%), a positive response to either of 2 questions was 80% sensitive and specific for current alcohol or drug abuse. With the high prevalence of substance use in this sample, the positive predictive value of the 2 questions was 52% and the negative predictive value was 93%. Comfort with the interviewer was reported by 84% of the participants, and withholding any information by only 11%. Random urine substance screening of 231 patients revealed 14 positive test results in patients with a negative CIDI-SAM, but these results did not change the performance of the screening test.

BACKGROUND: Currently, most screening questions in the primary care setting address only alcohol abuse, but it is also important to screen for other substance abuse. The authors of this study examined the validity of a 2-question screening test for alcohol and other substances.

POPULATION STUDIED: The participants were 1252 patients randomly selected from 3 University of Wisconsin primary care clinics. They ranged in age from 18 to 59 years; 68% were women; and the population was racially diverse. Sixty-nine percent had private insurance. The prevalence of substance disorders in this study population was high (23%).

STUDY DESIGN AND VALIDITY: This prospective cohort study sought to identify 2 questions that could accurately screen for substance abuse. Screening questions were developed through a literature search and a series of focus groups. The interviewers asked patients the screening questions and then administered the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM), a series of questions based on the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised used for identifying substance use disorders. The sensitivity of the screening questions was defined as the proportion of patients with a current substance abuse problem, as detected by CIDI-SAM, who had positive screening results. The high prevalence of substance abuse in this study will improve the positive predictive value of the screening test.This study was well designed and had a high response rate. Although the interviewers were not blinded while administering the screening questions and the CIDI-SAM, they were monitored closely, and a random subset of patients underwent urine drug testing. The authors also tested the validity of the screening questions with questions about patient comfort and truthfulness.

OUTCOMES MEASURED: The primary outcome measured was identification of either alcohol or drug abuse.

RESULTS: Among 1136 participants (91%), a positive response to either of 2 questions was 80% sensitive and specific for current alcohol or drug abuse. With the high prevalence of substance use in this sample, the positive predictive value of the 2 questions was 52% and the negative predictive value was 93%. Comfort with the interviewer was reported by 84% of the participants, and withholding any information by only 11%. Random urine substance screening of 231 patients revealed 14 positive test results in patients with a negative CIDI-SAM, but these results did not change the performance of the screening test.

BACKGROUND: Currently, most screening questions in the primary care setting address only alcohol abuse, but it is also important to screen for other substance abuse. The authors of this study examined the validity of a 2-question screening test for alcohol and other substances.

POPULATION STUDIED: The participants were 1252 patients randomly selected from 3 University of Wisconsin primary care clinics. They ranged in age from 18 to 59 years; 68% were women; and the population was racially diverse. Sixty-nine percent had private insurance. The prevalence of substance disorders in this study population was high (23%).

STUDY DESIGN AND VALIDITY: This prospective cohort study sought to identify 2 questions that could accurately screen for substance abuse. Screening questions were developed through a literature search and a series of focus groups. The interviewers asked patients the screening questions and then administered the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM), a series of questions based on the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised used for identifying substance use disorders. The sensitivity of the screening questions was defined as the proportion of patients with a current substance abuse problem, as detected by CIDI-SAM, who had positive screening results. The high prevalence of substance abuse in this study will improve the positive predictive value of the screening test.This study was well designed and had a high response rate. Although the interviewers were not blinded while administering the screening questions and the CIDI-SAM, they were monitored closely, and a random subset of patients underwent urine drug testing. The authors also tested the validity of the screening questions with questions about patient comfort and truthfulness.

OUTCOMES MEASURED: The primary outcome measured was identification of either alcohol or drug abuse.

RESULTS: Among 1136 participants (91%), a positive response to either of 2 questions was 80% sensitive and specific for current alcohol or drug abuse. With the high prevalence of substance use in this sample, the positive predictive value of the 2 questions was 52% and the negative predictive value was 93%. Comfort with the interviewer was reported by 84% of the participants, and withholding any information by only 11%. Random urine substance screening of 231 patients revealed 14 positive test results in patients with a negative CIDI-SAM, but these results did not change the performance of the screening test.

BACKGROUND: One of the more contentious clinical issues in the use of postmenopausal hormone replacement is the association between HRT, cognitive function, and dementia. The authors of this study examined published literature that assesses the relationship between estrogens and cognition by pooling the results of individual trials.

POPULATION STUDIED: The effects of HRT were examined in postmenopausal women. The individual studies varied significantly in the types of women they included. The women ranged in age from 29 to 80 years and had both surgical and natural menopause. The degree of menopausal symptoms they experienced also differed greatly.

STUDY DESIGN AND VALIDITY: English language research articles were identified using MEDLINE, HealthSTAR, PsychINFO, and The Cochrane Library databases. Twenty-nine studies that met inclusion criteria were rated for scientific rigor by 2 independent researchers. For the outcome of dementia, only retrospective cohort and case-control studies were available. Randomized controlled trials (RCTs) and cohort studies focusing on HRT and cognitive decline were included. Three of the RCTs used a crossover design. Ultimately, only 9 RCTs and 8 cohort studies were reviewed in the final analysis. The greatest limitations of this meta-analysis stem from the relatively poor and variable study design of the original articles. As a result, the conclusions of this meta-analysis, although based on the best available evidence, should be viewed with suspicion. Of the 17 included trials, the quality of 2 of the RCTs was rated as 2 out of 5 points. Two of the cohort studies were rated poor, and 1 was rated good. Although the duration of estrogen use in the RCTs was very short (21 days to 6 months), the retrospective trials ranged from 1.5 to 15 years. Only 7 of the 40 different cognitive tests were used in more than 2 studies. There were insufficient data to make conclusions regarding differences in outcomes between estrogen type, method of administration, dose, or use with or without progestins.

OUTCOMES MEASURED: Each study measured different outcomes. Most focused on aspects of memory, attention, concept formation and reasoning, motor speed, mental status, and verbal functions and language. Patient-oriented outcomes were not assessed, such as the ability to perform activities of daily living or the ability to live independently. The development of clinically diagnosed Alzheimer disease was the main outcome of the dementia trials. Only 1 study assessed the risk of vascular dementia.

RESULTS: Overall, women with preexisting menopausal symptoms appeared to receive more cognitive benefit than those without symptoms. Estrogen exposure was associated with slightly improved verbal memory, vigilance, reasoning, and motor speed, but not with other cognitive functions. The retrospective data suggests HRT use reduces the risk of dementia by approximately one third (summary odds ratio [OR]= 0.66; 95% confidence interval [CI], 0.53-0.82). HRT did not reduce the risk of vascular dementia (OR=0.50; 95% CI, 0.20-1.2).

BACKGROUND: One of the more contentious clinical issues in the use of postmenopausal hormone replacement is the association between HRT, cognitive function, and dementia. The authors of this study examined published literature that assesses the relationship between estrogens and cognition by pooling the results of individual trials.

POPULATION STUDIED: The effects of HRT were examined in postmenopausal women. The individual studies varied significantly in the types of women they included. The women ranged in age from 29 to 80 years and had both surgical and natural menopause. The degree of menopausal symptoms they experienced also differed greatly.

STUDY DESIGN AND VALIDITY: English language research articles were identified using MEDLINE, HealthSTAR, PsychINFO, and The Cochrane Library databases. Twenty-nine studies that met inclusion criteria were rated for scientific rigor by 2 independent researchers. For the outcome of dementia, only retrospective cohort and case-control studies were available. Randomized controlled trials (RCTs) and cohort studies focusing on HRT and cognitive decline were included. Three of the RCTs used a crossover design. Ultimately, only 9 RCTs and 8 cohort studies were reviewed in the final analysis. The greatest limitations of this meta-analysis stem from the relatively poor and variable study design of the original articles. As a result, the conclusions of this meta-analysis, although based on the best available evidence, should be viewed with suspicion. Of the 17 included trials, the quality of 2 of the RCTs was rated as 2 out of 5 points. Two of the cohort studies were rated poor, and 1 was rated good. Although the duration of estrogen use in the RCTs was very short (21 days to 6 months), the retrospective trials ranged from 1.5 to 15 years. Only 7 of the 40 different cognitive tests were used in more than 2 studies. There were insufficient data to make conclusions regarding differences in outcomes between estrogen type, method of administration, dose, or use with or without progestins.

OUTCOMES MEASURED: Each study measured different outcomes. Most focused on aspects of memory, attention, concept formation and reasoning, motor speed, mental status, and verbal functions and language. Patient-oriented outcomes were not assessed, such as the ability to perform activities of daily living or the ability to live independently. The development of clinically diagnosed Alzheimer disease was the main outcome of the dementia trials. Only 1 study assessed the risk of vascular dementia.

RESULTS: Overall, women with preexisting menopausal symptoms appeared to receive more cognitive benefit than those without symptoms. Estrogen exposure was associated with slightly improved verbal memory, vigilance, reasoning, and motor speed, but not with other cognitive functions. The retrospective data suggests HRT use reduces the risk of dementia by approximately one third (summary odds ratio [OR]= 0.66; 95% confidence interval [CI], 0.53-0.82). HRT did not reduce the risk of vascular dementia (OR=0.50; 95% CI, 0.20-1.2).

BACKGROUND: One of the more contentious clinical issues in the use of postmenopausal hormone replacement is the association between HRT, cognitive function, and dementia. The authors of this study examined published literature that assesses the relationship between estrogens and cognition by pooling the results of individual trials.

POPULATION STUDIED: The effects of HRT were examined in postmenopausal women. The individual studies varied significantly in the types of women they included. The women ranged in age from 29 to 80 years and had both surgical and natural menopause. The degree of menopausal symptoms they experienced also differed greatly.

STUDY DESIGN AND VALIDITY: English language research articles were identified using MEDLINE, HealthSTAR, PsychINFO, and The Cochrane Library databases. Twenty-nine studies that met inclusion criteria were rated for scientific rigor by 2 independent researchers. For the outcome of dementia, only retrospective cohort and case-control studies were available. Randomized controlled trials (RCTs) and cohort studies focusing on HRT and cognitive decline were included. Three of the RCTs used a crossover design. Ultimately, only 9 RCTs and 8 cohort studies were reviewed in the final analysis. The greatest limitations of this meta-analysis stem from the relatively poor and variable study design of the original articles. As a result, the conclusions of this meta-analysis, although based on the best available evidence, should be viewed with suspicion. Of the 17 included trials, the quality of 2 of the RCTs was rated as 2 out of 5 points. Two of the cohort studies were rated poor, and 1 was rated good. Although the duration of estrogen use in the RCTs was very short (21 days to 6 months), the retrospective trials ranged from 1.5 to 15 years. Only 7 of the 40 different cognitive tests were used in more than 2 studies. There were insufficient data to make conclusions regarding differences in outcomes between estrogen type, method of administration, dose, or use with or without progestins.

OUTCOMES MEASURED: Each study measured different outcomes. Most focused on aspects of memory, attention, concept formation and reasoning, motor speed, mental status, and verbal functions and language. Patient-oriented outcomes were not assessed, such as the ability to perform activities of daily living or the ability to live independently. The development of clinically diagnosed Alzheimer disease was the main outcome of the dementia trials. Only 1 study assessed the risk of vascular dementia.

RESULTS: Overall, women with preexisting menopausal symptoms appeared to receive more cognitive benefit than those without symptoms. Estrogen exposure was associated with slightly improved verbal memory, vigilance, reasoning, and motor speed, but not with other cognitive functions. The retrospective data suggests HRT use reduces the risk of dementia by approximately one third (summary odds ratio [OR]= 0.66; 95% confidence interval [CI], 0.53-0.82). HRT did not reduce the risk of vascular dementia (OR=0.50; 95% CI, 0.20-1.2).

BACKGROUND: The authors previously derived a simple clinical decision aid (CDA) to be used at the bedside for determining the prognosis of inpatients after resuscitation. The CDA was derived from data obtained from a population of 1077 inpatients who underwent resuscitation at 5 teaching hospitals. The authors observed that all resuscitated patients discharged from the hospital had a witnessed arrest, an initial cardiac rhythm of ventricular tachycardia or ventricular fibrillation, or a pulse within 10 minutes of chest compressions. They proposed that resuscitative efforts may be safely withdrawn if the patient does not meet at least 1 criterion. They noted that 100% of patients not meeting the CDA criteria died in the hospital. However, the 95% confidence interval for this figure ranged as low as 97.1%. The purpose of this study was to apply the CDA using data from a second set of patients to determine its usefulness.

POPULATION STUDIED: This validation study used a registry of data from 3960 attempted resuscitations at a 550-bed community teaching hospital. The investigators included 2181 arrests of inpatients 16 years and older who were pulseless at the start of resuscitation. They excluded patients who arrested in the operating room or neonatal intensive care unit; those who had an initial rhythm other than ventricular tachycardia, ventricular fibrillation, pulseless electrical activity, or asystole; those whose time to initial chest compressions exceeded 15 minutes; and those who received no chest compressions at all. Nearly 300 patients were also excluded because information needed to apply the CDA was missing.

STUDY DESIGN AND VALIDITY: The research team reviewed code sheets and records with hospital charges including cardioversion, defibrillation, or administration of epinephrine. Witnessed arrests were classified as those observed directly or on cardiac monitoring. They compared actual discharge status to that predicted by the CDA. Only 460 (21%) of the 2181 arrests were considered unwitnessed. No further details are given about the 7% who did not have adequate information to include in the study.

OUTCOMES MEASURED: The primary outcome was survival to discharge.

RESULTS: Fifteen percent (N=327) of the 2181 attempted resuscitations resulted in eventual discharge from the hospital. Of those 327 events, all but 3 were correctly predicted by the CDA (sensitivity=99.1%). Those 3 patients were among the 269 patients predicted by the CDA to have no chance of discharge (negative predictive value=98.9%). Because of the generally low success rate of attempted resuscitations, the specificity and positive predictive value of the CDA were low (14.4% and 17.0%, respectively). The negative likelihood ratio of this CDA was 0.064; this would lower the probability of surviving to discharge from 15% to 1.1% if the patient did not satisfy the CDA criteria. Of the 3 surviving patients predicted to have no chance of discharge, 2 were transferred to a nursing home, and 1 died 2 months after discharge.

BACKGROUND: The authors previously derived a simple clinical decision aid (CDA) to be used at the bedside for determining the prognosis of inpatients after resuscitation. The CDA was derived from data obtained from a population of 1077 inpatients who underwent resuscitation at 5 teaching hospitals. The authors observed that all resuscitated patients discharged from the hospital had a witnessed arrest, an initial cardiac rhythm of ventricular tachycardia or ventricular fibrillation, or a pulse within 10 minutes of chest compressions. They proposed that resuscitative efforts may be safely withdrawn if the patient does not meet at least 1 criterion. They noted that 100% of patients not meeting the CDA criteria died in the hospital. However, the 95% confidence interval for this figure ranged as low as 97.1%. The purpose of this study was to apply the CDA using data from a second set of patients to determine its usefulness.

POPULATION STUDIED: This validation study used a registry of data from 3960 attempted resuscitations at a 550-bed community teaching hospital. The investigators included 2181 arrests of inpatients 16 years and older who were pulseless at the start of resuscitation. They excluded patients who arrested in the operating room or neonatal intensive care unit; those who had an initial rhythm other than ventricular tachycardia, ventricular fibrillation, pulseless electrical activity, or asystole; those whose time to initial chest compressions exceeded 15 minutes; and those who received no chest compressions at all. Nearly 300 patients were also excluded because information needed to apply the CDA was missing.

STUDY DESIGN AND VALIDITY: The research team reviewed code sheets and records with hospital charges including cardioversion, defibrillation, or administration of epinephrine. Witnessed arrests were classified as those observed directly or on cardiac monitoring. They compared actual discharge status to that predicted by the CDA. Only 460 (21%) of the 2181 arrests were considered unwitnessed. No further details are given about the 7% who did not have adequate information to include in the study.

OUTCOMES MEASURED: The primary outcome was survival to discharge.

RESULTS: Fifteen percent (N=327) of the 2181 attempted resuscitations resulted in eventual discharge from the hospital. Of those 327 events, all but 3 were correctly predicted by the CDA (sensitivity=99.1%). Those 3 patients were among the 269 patients predicted by the CDA to have no chance of discharge (negative predictive value=98.9%). Because of the generally low success rate of attempted resuscitations, the specificity and positive predictive value of the CDA were low (14.4% and 17.0%, respectively). The negative likelihood ratio of this CDA was 0.064; this would lower the probability of surviving to discharge from 15% to 1.1% if the patient did not satisfy the CDA criteria. Of the 3 surviving patients predicted to have no chance of discharge, 2 were transferred to a nursing home, and 1 died 2 months after discharge.

BACKGROUND: The authors previously derived a simple clinical decision aid (CDA) to be used at the bedside for determining the prognosis of inpatients after resuscitation. The CDA was derived from data obtained from a population of 1077 inpatients who underwent resuscitation at 5 teaching hospitals. The authors observed that all resuscitated patients discharged from the hospital had a witnessed arrest, an initial cardiac rhythm of ventricular tachycardia or ventricular fibrillation, or a pulse within 10 minutes of chest compressions. They proposed that resuscitative efforts may be safely withdrawn if the patient does not meet at least 1 criterion. They noted that 100% of patients not meeting the CDA criteria died in the hospital. However, the 95% confidence interval for this figure ranged as low as 97.1%. The purpose of this study was to apply the CDA using data from a second set of patients to determine its usefulness.

POPULATION STUDIED: This validation study used a registry of data from 3960 attempted resuscitations at a 550-bed community teaching hospital. The investigators included 2181 arrests of inpatients 16 years and older who were pulseless at the start of resuscitation. They excluded patients who arrested in the operating room or neonatal intensive care unit; those who had an initial rhythm other than ventricular tachycardia, ventricular fibrillation, pulseless electrical activity, or asystole; those whose time to initial chest compressions exceeded 15 minutes; and those who received no chest compressions at all. Nearly 300 patients were also excluded because information needed to apply the CDA was missing.

STUDY DESIGN AND VALIDITY: The research team reviewed code sheets and records with hospital charges including cardioversion, defibrillation, or administration of epinephrine. Witnessed arrests were classified as those observed directly or on cardiac monitoring. They compared actual discharge status to that predicted by the CDA. Only 460 (21%) of the 2181 arrests were considered unwitnessed. No further details are given about the 7% who did not have adequate information to include in the study.

OUTCOMES MEASURED: The primary outcome was survival to discharge.

RESULTS: Fifteen percent (N=327) of the 2181 attempted resuscitations resulted in eventual discharge from the hospital. Of those 327 events, all but 3 were correctly predicted by the CDA (sensitivity=99.1%). Those 3 patients were among the 269 patients predicted by the CDA to have no chance of discharge (negative predictive value=98.9%). Because of the generally low success rate of attempted resuscitations, the specificity and positive predictive value of the CDA were low (14.4% and 17.0%, respectively). The negative likelihood ratio of this CDA was 0.064; this would lower the probability of surviving to discharge from 15% to 1.1% if the patient did not satisfy the CDA criteria. Of the 3 surviving patients predicted to have no chance of discharge, 2 were transferred to a nursing home, and 1 died 2 months after discharge.