Q&A

BACKGROUND: More than 260,000 cases of pulmonary embolism (PE) are diagnosed each year in the United States. However, the prevalence of PE is estimated to be only 25% to 35% of suspected cases. Commonly used noninvasive diagnostic tools (D-dimer levels, ventilation/perfusion scan, doppler ultrasonography) are inconclusive in a significant number of cases, leading to invasive testing with angiography. Helical computerized tomography (CT) scanning has been suggested by some as a useful test in the diagnosis of PE. This article attempts to address the role of this test in the diagnostic evaluation of those with suspected PE.

POPULATION STUDIED: We studied all adult patients (older than 6 years) presenting to the emergency department of a community teaching hospital in Geneva, Switzerland, over a 25-month period with suspected pulmonary embolism and elevated plasma D-dimer level greater than 500 μg/L. Of the initial 1108 patients enrolled in the study, 35% were excluded on the basis of a normal D-dimer level. Another 38% were excluded on the basis of reasonable criteria (ie, contraindication to CT, declining to participate, taking oral anticoagulants, CT results unavailable or unblinded). There was no clinically significant difference in age, sex, risk factors, clinical presentation, and clinical probability of PE between those included and those excluded.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which 229 patients were evaluated and treated according to the hospital’s current practices. In addition to the usual studies, CT scans were performed on all patients, with results withheld from the treating physician so as to not influence diagnosis and treatment. CT interpretation was performed more than 3 months after acquisition of the films by 3 radiologists who were blinded to all other clinical data and test results. PE was diagnosed if the patient had a positive angiogram, a high-probability lung scan, or DVT and a clinical suspicion of PE. PE was ruled out if the patient had a normal angiogram, a normal or near-normal lung scan, or low clinical suspicion with a nondiagnostic lung scan and no evidence of DVT. Results from the CT were compared with these gold standards. In addition, patients were followed for 3 months for evidence of DVT or PE. It is important to note that the results of the study can only be applied to patients initially presenting as outpatients who were found to have elevated D-dimer levels. The study is well done. The gold standards chosen are reasonable, and the patient population is appropriate; these are the patients for whom the question of whether to proceed to angiography is important.

OUTCOMES MEASURED: Sensitivity and specificity of helical CT in diagnosing PE with and without other diagnostic modalities.

RESULTS: Approximately 40% of the 299 patients with positive D-dimer levels were eventually found to have PE (prevalence = 40%). Of these, the helical CT scan correctly identified 70% (confidence interval [CI], 62%-78%) of patients with embolism and correctly identified as negative 91% (CI, 86%-95%) of patients without embolism (positive likelihood ratio=8.0; negative likelihood ratio=0.3). These results were unchanged by the application of more stringent diagnostic criteria (high-probability scan, low-probability scan, or angiography). The false-negative rate of 30% decreased to 21% in patients who had a positive D-dimer level but negative ultrasound before CT. When used as a fourth-line diagnostic test, after a positive D-dimer, normal ultrasound, and inconclusive pulmonary scan, the false-negative rate decreased to 5% and the false-positive rate decreased to 7%.

BACKGROUND: More than 260,000 cases of pulmonary embolism (PE) are diagnosed each year in the United States. However, the prevalence of PE is estimated to be only 25% to 35% of suspected cases. Commonly used noninvasive diagnostic tools (D-dimer levels, ventilation/perfusion scan, doppler ultrasonography) are inconclusive in a significant number of cases, leading to invasive testing with angiography. Helical computerized tomography (CT) scanning has been suggested by some as a useful test in the diagnosis of PE. This article attempts to address the role of this test in the diagnostic evaluation of those with suspected PE.

POPULATION STUDIED: We studied all adult patients (older than 6 years) presenting to the emergency department of a community teaching hospital in Geneva, Switzerland, over a 25-month period with suspected pulmonary embolism and elevated plasma D-dimer level greater than 500 μg/L. Of the initial 1108 patients enrolled in the study, 35% were excluded on the basis of a normal D-dimer level. Another 38% were excluded on the basis of reasonable criteria (ie, contraindication to CT, declining to participate, taking oral anticoagulants, CT results unavailable or unblinded). There was no clinically significant difference in age, sex, risk factors, clinical presentation, and clinical probability of PE between those included and those excluded.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which 229 patients were evaluated and treated according to the hospital’s current practices. In addition to the usual studies, CT scans were performed on all patients, with results withheld from the treating physician so as to not influence diagnosis and treatment. CT interpretation was performed more than 3 months after acquisition of the films by 3 radiologists who were blinded to all other clinical data and test results. PE was diagnosed if the patient had a positive angiogram, a high-probability lung scan, or DVT and a clinical suspicion of PE. PE was ruled out if the patient had a normal angiogram, a normal or near-normal lung scan, or low clinical suspicion with a nondiagnostic lung scan and no evidence of DVT. Results from the CT were compared with these gold standards. In addition, patients were followed for 3 months for evidence of DVT or PE. It is important to note that the results of the study can only be applied to patients initially presenting as outpatients who were found to have elevated D-dimer levels. The study is well done. The gold standards chosen are reasonable, and the patient population is appropriate; these are the patients for whom the question of whether to proceed to angiography is important.

OUTCOMES MEASURED: Sensitivity and specificity of helical CT in diagnosing PE with and without other diagnostic modalities.

RESULTS: Approximately 40% of the 299 patients with positive D-dimer levels were eventually found to have PE (prevalence = 40%). Of these, the helical CT scan correctly identified 70% (confidence interval [CI], 62%-78%) of patients with embolism and correctly identified as negative 91% (CI, 86%-95%) of patients without embolism (positive likelihood ratio=8.0; negative likelihood ratio=0.3). These results were unchanged by the application of more stringent diagnostic criteria (high-probability scan, low-probability scan, or angiography). The false-negative rate of 30% decreased to 21% in patients who had a positive D-dimer level but negative ultrasound before CT. When used as a fourth-line diagnostic test, after a positive D-dimer, normal ultrasound, and inconclusive pulmonary scan, the false-negative rate decreased to 5% and the false-positive rate decreased to 7%.

BACKGROUND: More than 260,000 cases of pulmonary embolism (PE) are diagnosed each year in the United States. However, the prevalence of PE is estimated to be only 25% to 35% of suspected cases. Commonly used noninvasive diagnostic tools (D-dimer levels, ventilation/perfusion scan, doppler ultrasonography) are inconclusive in a significant number of cases, leading to invasive testing with angiography. Helical computerized tomography (CT) scanning has been suggested by some as a useful test in the diagnosis of PE. This article attempts to address the role of this test in the diagnostic evaluation of those with suspected PE.

POPULATION STUDIED: We studied all adult patients (older than 6 years) presenting to the emergency department of a community teaching hospital in Geneva, Switzerland, over a 25-month period with suspected pulmonary embolism and elevated plasma D-dimer level greater than 500 μg/L. Of the initial 1108 patients enrolled in the study, 35% were excluded on the basis of a normal D-dimer level. Another 38% were excluded on the basis of reasonable criteria (ie, contraindication to CT, declining to participate, taking oral anticoagulants, CT results unavailable or unblinded). There was no clinically significant difference in age, sex, risk factors, clinical presentation, and clinical probability of PE between those included and those excluded.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which 229 patients were evaluated and treated according to the hospital’s current practices. In addition to the usual studies, CT scans were performed on all patients, with results withheld from the treating physician so as to not influence diagnosis and treatment. CT interpretation was performed more than 3 months after acquisition of the films by 3 radiologists who were blinded to all other clinical data and test results. PE was diagnosed if the patient had a positive angiogram, a high-probability lung scan, or DVT and a clinical suspicion of PE. PE was ruled out if the patient had a normal angiogram, a normal or near-normal lung scan, or low clinical suspicion with a nondiagnostic lung scan and no evidence of DVT. Results from the CT were compared with these gold standards. In addition, patients were followed for 3 months for evidence of DVT or PE. It is important to note that the results of the study can only be applied to patients initially presenting as outpatients who were found to have elevated D-dimer levels. The study is well done. The gold standards chosen are reasonable, and the patient population is appropriate; these are the patients for whom the question of whether to proceed to angiography is important.

OUTCOMES MEASURED: Sensitivity and specificity of helical CT in diagnosing PE with and without other diagnostic modalities.

RESULTS: Approximately 40% of the 299 patients with positive D-dimer levels were eventually found to have PE (prevalence = 40%). Of these, the helical CT scan correctly identified 70% (confidence interval [CI], 62%-78%) of patients with embolism and correctly identified as negative 91% (CI, 86%-95%) of patients without embolism (positive likelihood ratio=8.0; negative likelihood ratio=0.3). These results were unchanged by the application of more stringent diagnostic criteria (high-probability scan, low-probability scan, or angiography). The false-negative rate of 30% decreased to 21% in patients who had a positive D-dimer level but negative ultrasound before CT. When used as a fourth-line diagnostic test, after a positive D-dimer, normal ultrasound, and inconclusive pulmonary scan, the false-negative rate decreased to 5% and the false-positive rate decreased to 7%.

BACKGROUND: Observation studies have suggested that hormone replacement therapy (HRT) prevents osteoporotic fractures; however, few randomized trials have been reported. The influential Heart and Estrogen/progestin Replacement Study (HERS) was a randomized multicenter trial that reported HRT as not effective for secondary prevention of coronary artery disease (CAD) events. The investigators took advantage of data from the HERS trial to further study the relationship between HRT and fracture risk.

POPULATION STUDIED: The study enrolled 2763 postmenopausal women (all younger than 80 years) with an intact uterus and documented coronary artery disease (CAD). Two thirds of the women were 65 years or older. Women were excluded if they had had a coronary event within 6 months, serum triglycerides of 300 mg per dL or greater, hormone use within 3 months, history of deep vein thrombosis, pulmonary embolism, breast or endometrial cancer, uncontrolled hypertension, diabetes, or any other life-threatening disease.

STUDY DESIGN AND VALIDITY: This was a randomized double-blind, placebo-controlled trial. Participants were randomized to either placebo or combined conjugated equine estrogen 0.625 mg and medroxyprogestrone acetate 2.5 mg daily. The average follow-up was 4.1 years with 64% of the women still having HRT at the end of the study period. Allocation to treatment group was concealed, and the study was well designed. The 2 groups did not differ in their baseline characteristics. No attempt was made to assess or augment subjects’ intake of calcium or vitamin D.

OUTCOMES MEASURED: The primary outcome was clinical fractures determined by reviewing interval diagnoses of a fracture. In a subset of 408 women older than 65 years, bone mineral density (BMD) was measured at baseline and on the final visit. Standing height, measured with a height rod or a Harpenden Stadiometer, was assessed at baseline and annually, and served as a validated surrogate for vertebral fractures.

RESULTS: During 10,554 person-years of follow-up, 286 women experienced fractures: 138 in the treatment group, 148 in the placebo group (relative hazard = 0.94; 95% confidence interval [CI], 0.8-1.2), a nonstatistically significant difference. HRT did not prevent fractures at any specific location (wrist, hip, spine, or other). Similarly, the relative risk of experiencing a height loss of 2 cm or greater was 0.8 (0.6 to 1.1) for all women studied, regardless of treatment group. Of women with the lowest hip BMD ( 0.7 g/cmx2), HRT use had a relative risk of fracture of 0.4 (95% CI, 0.2-1.2). Total hip BMD did increase 3.3% in the HRT group, compared with a 2.7% loss in the placebo group.

BACKGROUND: Observation studies have suggested that hormone replacement therapy (HRT) prevents osteoporotic fractures; however, few randomized trials have been reported. The influential Heart and Estrogen/progestin Replacement Study (HERS) was a randomized multicenter trial that reported HRT as not effective for secondary prevention of coronary artery disease (CAD) events. The investigators took advantage of data from the HERS trial to further study the relationship between HRT and fracture risk.

POPULATION STUDIED: The study enrolled 2763 postmenopausal women (all younger than 80 years) with an intact uterus and documented coronary artery disease (CAD). Two thirds of the women were 65 years or older. Women were excluded if they had had a coronary event within 6 months, serum triglycerides of 300 mg per dL or greater, hormone use within 3 months, history of deep vein thrombosis, pulmonary embolism, breast or endometrial cancer, uncontrolled hypertension, diabetes, or any other life-threatening disease.

STUDY DESIGN AND VALIDITY: This was a randomized double-blind, placebo-controlled trial. Participants were randomized to either placebo or combined conjugated equine estrogen 0.625 mg and medroxyprogestrone acetate 2.5 mg daily. The average follow-up was 4.1 years with 64% of the women still having HRT at the end of the study period. Allocation to treatment group was concealed, and the study was well designed. The 2 groups did not differ in their baseline characteristics. No attempt was made to assess or augment subjects’ intake of calcium or vitamin D.

OUTCOMES MEASURED: The primary outcome was clinical fractures determined by reviewing interval diagnoses of a fracture. In a subset of 408 women older than 65 years, bone mineral density (BMD) was measured at baseline and on the final visit. Standing height, measured with a height rod or a Harpenden Stadiometer, was assessed at baseline and annually, and served as a validated surrogate for vertebral fractures.

RESULTS: During 10,554 person-years of follow-up, 286 women experienced fractures: 138 in the treatment group, 148 in the placebo group (relative hazard = 0.94; 95% confidence interval [CI], 0.8-1.2), a nonstatistically significant difference. HRT did not prevent fractures at any specific location (wrist, hip, spine, or other). Similarly, the relative risk of experiencing a height loss of 2 cm or greater was 0.8 (0.6 to 1.1) for all women studied, regardless of treatment group. Of women with the lowest hip BMD ( 0.7 g/cmx2), HRT use had a relative risk of fracture of 0.4 (95% CI, 0.2-1.2). Total hip BMD did increase 3.3% in the HRT group, compared with a 2.7% loss in the placebo group.

BACKGROUND: Observation studies have suggested that hormone replacement therapy (HRT) prevents osteoporotic fractures; however, few randomized trials have been reported. The influential Heart and Estrogen/progestin Replacement Study (HERS) was a randomized multicenter trial that reported HRT as not effective for secondary prevention of coronary artery disease (CAD) events. The investigators took advantage of data from the HERS trial to further study the relationship between HRT and fracture risk.

POPULATION STUDIED: The study enrolled 2763 postmenopausal women (all younger than 80 years) with an intact uterus and documented coronary artery disease (CAD). Two thirds of the women were 65 years or older. Women were excluded if they had had a coronary event within 6 months, serum triglycerides of 300 mg per dL or greater, hormone use within 3 months, history of deep vein thrombosis, pulmonary embolism, breast or endometrial cancer, uncontrolled hypertension, diabetes, or any other life-threatening disease.

STUDY DESIGN AND VALIDITY: This was a randomized double-blind, placebo-controlled trial. Participants were randomized to either placebo or combined conjugated equine estrogen 0.625 mg and medroxyprogestrone acetate 2.5 mg daily. The average follow-up was 4.1 years with 64% of the women still having HRT at the end of the study period. Allocation to treatment group was concealed, and the study was well designed. The 2 groups did not differ in their baseline characteristics. No attempt was made to assess or augment subjects’ intake of calcium or vitamin D.

OUTCOMES MEASURED: The primary outcome was clinical fractures determined by reviewing interval diagnoses of a fracture. In a subset of 408 women older than 65 years, bone mineral density (BMD) was measured at baseline and on the final visit. Standing height, measured with a height rod or a Harpenden Stadiometer, was assessed at baseline and annually, and served as a validated surrogate for vertebral fractures.

RESULTS: During 10,554 person-years of follow-up, 286 women experienced fractures: 138 in the treatment group, 148 in the placebo group (relative hazard = 0.94; 95% confidence interval [CI], 0.8-1.2), a nonstatistically significant difference. HRT did not prevent fractures at any specific location (wrist, hip, spine, or other). Similarly, the relative risk of experiencing a height loss of 2 cm or greater was 0.8 (0.6 to 1.1) for all women studied, regardless of treatment group. Of women with the lowest hip BMD ( 0.7 g/cmx2), HRT use had a relative risk of fracture of 0.4 (95% CI, 0.2-1.2). Total hip BMD did increase 3.3% in the HRT group, compared with a 2.7% loss in the placebo group.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia and is an important contributor to cardiovascular morbidity and mortality. To prevent thromboembolism, physicians conventionally employ anticoagulant therapy for 3 to 4 weeks before an attempted cardioversion. Studies suggest that the duration of AF before cardioversion is a critical determinant of the reestablishment and maintenance of sinus rhythm. This study attempts to determine whether early transesophageal echocardiography (TEE), by ruling out a thrombus, can safely lead to more rapid cardioversion with improved outcomes.

POPULATION STUDIED: The subjects were 539 patients with AF recruited at 2 university hospitals over a 9-year period.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study. Patients were excluded if estimated duration of AF was less than 2 days, if duration of AF was unknown, or if patients received long-term warfarin anticoagulation before admission. At admission, patients were given intravenous heparin and oral warfarin. Once therapeutic partial thromboplastin time was obtained, TEE was performed or supervised by 1 of 15 attending physicians, and all images were reviewed by at least 2 experienced practitioners to reach consensus for diagnosis of atrial thrombus. If no thrombus was detected, patients underwent chemical or direct-current cardioversion. However, if thrombus was demonstrated, cardioversion was deferred until follow-up TEE showed no thrombus after conventional warfarin treatment. For 1 month following cardioversion, patients continued to receive warfarin and were followed up for evidence of clinical thromboembolic events. Patients were followed up for 1 year to determine their health status. There are some methodologic concerns to this study. First, without randomization to a control group (anticoagulation 4 weeks preceding cardioversion), it is difficult to assess whether there is any direct effect of the early TEE strategy on the favorable outcomes reported. Second, the mode of cardioversion and use or choice of post-cardioversion antiarrhythmic medication were left to the discretion of the patient’s attending physician; this provides the opportunity for bias between patient groups. Third, objective surveillance data from 24-hour Holter monitoring was not used; thus, true incidence of AF recurrence was likely underestimated. Finally, though there were no complications attributed to the early cardioversion approach, safety was inferred by comparison with previously published studies rather than directly measured. This method could have underestimated asymptomatic thromboembolic events.

OUTCOMES MEASURED: The study compared the incidence of recurrent AF and prevalence of sinus rhythm at 1 year in those patients with clinically estimated initial AF of less than 3 weeks’ duration with those with initial AF greater than 3 weeks’ duration.

RESULTS: No significant differences were noted between the 2 studied groups on the basis of age, sex, left ventricular dysfunction, left atrial dimension, left/right atrial spontaneous echocardiographic contrast, or severity of mitral regurgitation. Patients who underwent cardioversion less than 3 weeks after the onset of AF had a lower likelihood of recurrence over the following year than did patients with more than 3 weeks of AF (41.1% vs 57.9%; P <.01). For every 6 patients who underwent cardioversion immediately rather than after 3 to 4 weeks of anticoagulation, there would be 1 less patient with recurrence of AF during the following year (number needed to treat [NNT]=6). At 1 year, the prevalence of sinus rhythm was also higher in the patients who received earlier cardioversion (65.8% vs 51.3%, P <.03; NNT=7). There were no complications attributed to early cardioversion.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia and is an important contributor to cardiovascular morbidity and mortality. To prevent thromboembolism, physicians conventionally employ anticoagulant therapy for 3 to 4 weeks before an attempted cardioversion. Studies suggest that the duration of AF before cardioversion is a critical determinant of the reestablishment and maintenance of sinus rhythm. This study attempts to determine whether early transesophageal echocardiography (TEE), by ruling out a thrombus, can safely lead to more rapid cardioversion with improved outcomes.

POPULATION STUDIED: The subjects were 539 patients with AF recruited at 2 university hospitals over a 9-year period.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study. Patients were excluded if estimated duration of AF was less than 2 days, if duration of AF was unknown, or if patients received long-term warfarin anticoagulation before admission. At admission, patients were given intravenous heparin and oral warfarin. Once therapeutic partial thromboplastin time was obtained, TEE was performed or supervised by 1 of 15 attending physicians, and all images were reviewed by at least 2 experienced practitioners to reach consensus for diagnosis of atrial thrombus. If no thrombus was detected, patients underwent chemical or direct-current cardioversion. However, if thrombus was demonstrated, cardioversion was deferred until follow-up TEE showed no thrombus after conventional warfarin treatment. For 1 month following cardioversion, patients continued to receive warfarin and were followed up for evidence of clinical thromboembolic events. Patients were followed up for 1 year to determine their health status. There are some methodologic concerns to this study. First, without randomization to a control group (anticoagulation 4 weeks preceding cardioversion), it is difficult to assess whether there is any direct effect of the early TEE strategy on the favorable outcomes reported. Second, the mode of cardioversion and use or choice of post-cardioversion antiarrhythmic medication were left to the discretion of the patient’s attending physician; this provides the opportunity for bias between patient groups. Third, objective surveillance data from 24-hour Holter monitoring was not used; thus, true incidence of AF recurrence was likely underestimated. Finally, though there were no complications attributed to the early cardioversion approach, safety was inferred by comparison with previously published studies rather than directly measured. This method could have underestimated asymptomatic thromboembolic events.

OUTCOMES MEASURED: The study compared the incidence of recurrent AF and prevalence of sinus rhythm at 1 year in those patients with clinically estimated initial AF of less than 3 weeks’ duration with those with initial AF greater than 3 weeks’ duration.

RESULTS: No significant differences were noted between the 2 studied groups on the basis of age, sex, left ventricular dysfunction, left atrial dimension, left/right atrial spontaneous echocardiographic contrast, or severity of mitral regurgitation. Patients who underwent cardioversion less than 3 weeks after the onset of AF had a lower likelihood of recurrence over the following year than did patients with more than 3 weeks of AF (41.1% vs 57.9%; P <.01). For every 6 patients who underwent cardioversion immediately rather than after 3 to 4 weeks of anticoagulation, there would be 1 less patient with recurrence of AF during the following year (number needed to treat [NNT]=6). At 1 year, the prevalence of sinus rhythm was also higher in the patients who received earlier cardioversion (65.8% vs 51.3%, P <.03; NNT=7). There were no complications attributed to early cardioversion.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia and is an important contributor to cardiovascular morbidity and mortality. To prevent thromboembolism, physicians conventionally employ anticoagulant therapy for 3 to 4 weeks before an attempted cardioversion. Studies suggest that the duration of AF before cardioversion is a critical determinant of the reestablishment and maintenance of sinus rhythm. This study attempts to determine whether early transesophageal echocardiography (TEE), by ruling out a thrombus, can safely lead to more rapid cardioversion with improved outcomes.

POPULATION STUDIED: The subjects were 539 patients with AF recruited at 2 university hospitals over a 9-year period.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study. Patients were excluded if estimated duration of AF was less than 2 days, if duration of AF was unknown, or if patients received long-term warfarin anticoagulation before admission. At admission, patients were given intravenous heparin and oral warfarin. Once therapeutic partial thromboplastin time was obtained, TEE was performed or supervised by 1 of 15 attending physicians, and all images were reviewed by at least 2 experienced practitioners to reach consensus for diagnosis of atrial thrombus. If no thrombus was detected, patients underwent chemical or direct-current cardioversion. However, if thrombus was demonstrated, cardioversion was deferred until follow-up TEE showed no thrombus after conventional warfarin treatment. For 1 month following cardioversion, patients continued to receive warfarin and were followed up for evidence of clinical thromboembolic events. Patients were followed up for 1 year to determine their health status. There are some methodologic concerns to this study. First, without randomization to a control group (anticoagulation 4 weeks preceding cardioversion), it is difficult to assess whether there is any direct effect of the early TEE strategy on the favorable outcomes reported. Second, the mode of cardioversion and use or choice of post-cardioversion antiarrhythmic medication were left to the discretion of the patient’s attending physician; this provides the opportunity for bias between patient groups. Third, objective surveillance data from 24-hour Holter monitoring was not used; thus, true incidence of AF recurrence was likely underestimated. Finally, though there were no complications attributed to the early cardioversion approach, safety was inferred by comparison with previously published studies rather than directly measured. This method could have underestimated asymptomatic thromboembolic events.

OUTCOMES MEASURED: The study compared the incidence of recurrent AF and prevalence of sinus rhythm at 1 year in those patients with clinically estimated initial AF of less than 3 weeks’ duration with those with initial AF greater than 3 weeks’ duration.

RESULTS: No significant differences were noted between the 2 studied groups on the basis of age, sex, left ventricular dysfunction, left atrial dimension, left/right atrial spontaneous echocardiographic contrast, or severity of mitral regurgitation. Patients who underwent cardioversion less than 3 weeks after the onset of AF had a lower likelihood of recurrence over the following year than did patients with more than 3 weeks of AF (41.1% vs 57.9%; P <.01). For every 6 patients who underwent cardioversion immediately rather than after 3 to 4 weeks of anticoagulation, there would be 1 less patient with recurrence of AF during the following year (number needed to treat [NNT]=6). At 1 year, the prevalence of sinus rhythm was also higher in the patients who received earlier cardioversion (65.8% vs 51.3%, P <.03; NNT=7). There were no complications attributed to early cardioversion.

BACKGROUND: Some physicians seem reluctant to treat older patients with statins to lower lipids; they think statins are more effective in high-risk younger patients. This study used existing data from a large study of both older and younger patients to compare the level of benefit in these 2 types of patients.

POPULATION STUDIED: The authors enrolled 9014 patients from 87 centers in Australia and New Zealand who were between the ages of 31 and 75 years. Patients had a history of a myocardial infarction or had been hospitalized for unstable angina. Their baseline total cholesterol was between 155 and 271 mg per dL.

STUDY DESIGN AND VALIDITY: This subgroup analysis of the previously published Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study¹ compared the outcomes of the 3514 patients between the ages of 65 and 75 years with the remaining population younger than 65 years. This double-blind placebo-controlled clinical trial randomized patients to receive either placebo or pravastatin (Pravachol) 40 mg per day for an average of 6.1 years. Other lipid-lowering therapy could be used at the discretion of the patients’ usual physician. Both groups received education on a low cholesterol diet. The randomization method and allocation concealment were not specifically addressed.² The groups were similar at the outset of the trial. Data were analyzed on an intention-to-treat basis. An outcomes assessment committee blinded to treatment group assignment reviewed all deaths, myocardial infarctions, and strokes. Although no difference in the relative risk of outcomes was found between age groups, the study was not powered to detect such differences in outcomes by age.

OUTCOMES MEASURED: The main outcome measure was death resulting from coronary heart disease. Secondary end points included nonfatal myocardial infarction (MI), stroke, coronary revascularization, death of any cause including cardiovascular, and duration of hospital stay.

RESULTS: As would be expected, the death rate was higher during the 6 years of study in the group 65 years and older (20.6%) than in the group aged 34 to 64 (9.8%). The risk of MI, unstable angina, and stroke was also significantly higher, though not as marked. In patients older than 65 years, pravastatin decreased overall mortality 21% (95% confidence interval [CI], 7%-32%) and heart disease-related death by 24% (95% CI, 7%-38%), as well as decreasing the rate of MI or stroke. Although the relative risk reduction was similar in older and younger groups, the absolute risk reduction and number needed to treat (NNT) were approximately twice that seen in younger patients. Among older patients, 22 patients would have to be treated for 6 years to prevent 1 of them from dying during this period (NNT=22; 95% CI, 17-36), and 35 to prevent 1 heart disease–related death (NNT=35; 95% CI, 24-67). This benefit was due to the fact that the rate of adverse outcomes (eg, heart disease–related death) was greater in the older age group. There were no differences in the relative risk of the secondary end points by age. The rates of adverse events were not significantly different by age groups.

BACKGROUND: Some physicians seem reluctant to treat older patients with statins to lower lipids; they think statins are more effective in high-risk younger patients. This study used existing data from a large study of both older and younger patients to compare the level of benefit in these 2 types of patients.

POPULATION STUDIED: The authors enrolled 9014 patients from 87 centers in Australia and New Zealand who were between the ages of 31 and 75 years. Patients had a history of a myocardial infarction or had been hospitalized for unstable angina. Their baseline total cholesterol was between 155 and 271 mg per dL.

STUDY DESIGN AND VALIDITY: This subgroup analysis of the previously published Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study¹ compared the outcomes of the 3514 patients between the ages of 65 and 75 years with the remaining population younger than 65 years. This double-blind placebo-controlled clinical trial randomized patients to receive either placebo or pravastatin (Pravachol) 40 mg per day for an average of 6.1 years. Other lipid-lowering therapy could be used at the discretion of the patients’ usual physician. Both groups received education on a low cholesterol diet. The randomization method and allocation concealment were not specifically addressed.² The groups were similar at the outset of the trial. Data were analyzed on an intention-to-treat basis. An outcomes assessment committee blinded to treatment group assignment reviewed all deaths, myocardial infarctions, and strokes. Although no difference in the relative risk of outcomes was found between age groups, the study was not powered to detect such differences in outcomes by age.

OUTCOMES MEASURED: The main outcome measure was death resulting from coronary heart disease. Secondary end points included nonfatal myocardial infarction (MI), stroke, coronary revascularization, death of any cause including cardiovascular, and duration of hospital stay.

RESULTS: As would be expected, the death rate was higher during the 6 years of study in the group 65 years and older (20.6%) than in the group aged 34 to 64 (9.8%). The risk of MI, unstable angina, and stroke was also significantly higher, though not as marked. In patients older than 65 years, pravastatin decreased overall mortality 21% (95% confidence interval [CI], 7%-32%) and heart disease-related death by 24% (95% CI, 7%-38%), as well as decreasing the rate of MI or stroke. Although the relative risk reduction was similar in older and younger groups, the absolute risk reduction and number needed to treat (NNT) were approximately twice that seen in younger patients. Among older patients, 22 patients would have to be treated for 6 years to prevent 1 of them from dying during this period (NNT=22; 95% CI, 17-36), and 35 to prevent 1 heart disease–related death (NNT=35; 95% CI, 24-67). This benefit was due to the fact that the rate of adverse outcomes (eg, heart disease–related death) was greater in the older age group. There were no differences in the relative risk of the secondary end points by age. The rates of adverse events were not significantly different by age groups.

BACKGROUND: Some physicians seem reluctant to treat older patients with statins to lower lipids; they think statins are more effective in high-risk younger patients. This study used existing data from a large study of both older and younger patients to compare the level of benefit in these 2 types of patients.

POPULATION STUDIED: The authors enrolled 9014 patients from 87 centers in Australia and New Zealand who were between the ages of 31 and 75 years. Patients had a history of a myocardial infarction or had been hospitalized for unstable angina. Their baseline total cholesterol was between 155 and 271 mg per dL.

STUDY DESIGN AND VALIDITY: This subgroup analysis of the previously published Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study¹ compared the outcomes of the 3514 patients between the ages of 65 and 75 years with the remaining population younger than 65 years. This double-blind placebo-controlled clinical trial randomized patients to receive either placebo or pravastatin (Pravachol) 40 mg per day for an average of 6.1 years. Other lipid-lowering therapy could be used at the discretion of the patients’ usual physician. Both groups received education on a low cholesterol diet. The randomization method and allocation concealment were not specifically addressed.² The groups were similar at the outset of the trial. Data were analyzed on an intention-to-treat basis. An outcomes assessment committee blinded to treatment group assignment reviewed all deaths, myocardial infarctions, and strokes. Although no difference in the relative risk of outcomes was found between age groups, the study was not powered to detect such differences in outcomes by age.

OUTCOMES MEASURED: The main outcome measure was death resulting from coronary heart disease. Secondary end points included nonfatal myocardial infarction (MI), stroke, coronary revascularization, death of any cause including cardiovascular, and duration of hospital stay.

RESULTS: As would be expected, the death rate was higher during the 6 years of study in the group 65 years and older (20.6%) than in the group aged 34 to 64 (9.8%). The risk of MI, unstable angina, and stroke was also significantly higher, though not as marked. In patients older than 65 years, pravastatin decreased overall mortality 21% (95% confidence interval [CI], 7%-32%) and heart disease-related death by 24% (95% CI, 7%-38%), as well as decreasing the rate of MI or stroke. Although the relative risk reduction was similar in older and younger groups, the absolute risk reduction and number needed to treat (NNT) were approximately twice that seen in younger patients. Among older patients, 22 patients would have to be treated for 6 years to prevent 1 of them from dying during this period (NNT=22; 95% CI, 17-36), and 35 to prevent 1 heart disease–related death (NNT=35; 95% CI, 24-67). This benefit was due to the fact that the rate of adverse outcomes (eg, heart disease–related death) was greater in the older age group. There were no differences in the relative risk of the secondary end points by age. The rates of adverse events were not significantly different by age groups.

BACKGROUND: Sildenafil has been proved an effective oral pill for erectile dysfunction in men. Synthesis and releases of nitric oxide may also regulate clitoral corpus cavernousum smooth muscle tone. Thus, the same mechanism that regulates male erections may play a role in female sexual arousal disorder. Sexual arousal disorder is the persistent or recurrent inability to attain or maintain sufficient sexual excitement, expressed as a lack of genital lubrication or swelling response.

POPULATION STUDIED: Study subjects included 53 volunteer women ages 22 to 38 years seen in a sexual arousal disorders clinic in Italy for an inability to attain orgasm. Eligible women were healthy, with a subjectively normal sexual desire, not taking any known medications that could effect sexual arousal, had not experienced any clitoral and vaginal sensation or were slow to respond, and had not lubricated for a minimum of 6 months; they were all in stable, satisfying heterosexual relationships.

STUDY DESIGN AND VALIDITY: Subjects were randomized in a double-blind, 3 crossover periods fashion (allocation assignment concealed) to each of 6 possible sequences, each consisting of 3 medication series: (1) sildenafil 25 mg; (2) sildenafil 50 mg; and (3) placebo. Each participant took either dose of sidenafil or placebo 1 hour before planned intercourse. Each drug was used for a 4-week period, with a 1-week washout period between treatment periods. Patients were followed monthly for a total of 3 months. Since the study subjects were those seen in a tertiary care center they may not reflect similar patients seen by family physicians.

OUTCOMES MEASURED: The authors used a 5-point Likert Personal Experience Questionnaire to detect changes in sexual behavior, measuring scores at baseline and at the conclusion of each 4-week period. No documentation was given regarding reproducibility and internal validity of the findings. The primary outcome measured was arousal score. Secondary outcomes included an ability to achieve an orgasm, sexual enjoyment, frequency of intercourse, and the number of sexual fantasies.

RESULTS: Of the 53 women who initiated treatment, complete follow-up information was available on 51. Sexual arousal scores (sexual enjoyment, feeling of satisfaction, and frequency of sexual fantasies) improved with both doses of sildenafil, compared with placebo: Average score of 4.2 from a maximum of 5 for either dose versus 2.6 for placebo, compared with 1.5 at baseline (P <.001). The frequency of orgasm also improved significantly with both doses of sildenafil compared with placebo: average score of 3.8 for sildenafil and 2.4 for placebo compared with 1.0 at baseline (P <.001). There were no statistically significant differences between the 2 doses of sildenafil in any of the outcomes measured and the order in which the treatments were allocated did not show any effect. Four women (7.8%) stopped taking sildenafil 50 mg, 2 women (3.9%) stopped taking sildenafil 25 mg, and 2 women (3.9%) stopped taking placebo. Reasons given for discontinuing treatment included vision problems, headache and fear of adverse reactions.

BACKGROUND: Sildenafil has been proved an effective oral pill for erectile dysfunction in men. Synthesis and releases of nitric oxide may also regulate clitoral corpus cavernousum smooth muscle tone. Thus, the same mechanism that regulates male erections may play a role in female sexual arousal disorder. Sexual arousal disorder is the persistent or recurrent inability to attain or maintain sufficient sexual excitement, expressed as a lack of genital lubrication or swelling response.

POPULATION STUDIED: Study subjects included 53 volunteer women ages 22 to 38 years seen in a sexual arousal disorders clinic in Italy for an inability to attain orgasm. Eligible women were healthy, with a subjectively normal sexual desire, not taking any known medications that could effect sexual arousal, had not experienced any clitoral and vaginal sensation or were slow to respond, and had not lubricated for a minimum of 6 months; they were all in stable, satisfying heterosexual relationships.

STUDY DESIGN AND VALIDITY: Subjects were randomized in a double-blind, 3 crossover periods fashion (allocation assignment concealed) to each of 6 possible sequences, each consisting of 3 medication series: (1) sildenafil 25 mg; (2) sildenafil 50 mg; and (3) placebo. Each participant took either dose of sidenafil or placebo 1 hour before planned intercourse. Each drug was used for a 4-week period, with a 1-week washout period between treatment periods. Patients were followed monthly for a total of 3 months. Since the study subjects were those seen in a tertiary care center they may not reflect similar patients seen by family physicians.

OUTCOMES MEASURED: The authors used a 5-point Likert Personal Experience Questionnaire to detect changes in sexual behavior, measuring scores at baseline and at the conclusion of each 4-week period. No documentation was given regarding reproducibility and internal validity of the findings. The primary outcome measured was arousal score. Secondary outcomes included an ability to achieve an orgasm, sexual enjoyment, frequency of intercourse, and the number of sexual fantasies.

RESULTS: Of the 53 women who initiated treatment, complete follow-up information was available on 51. Sexual arousal scores (sexual enjoyment, feeling of satisfaction, and frequency of sexual fantasies) improved with both doses of sildenafil, compared with placebo: Average score of 4.2 from a maximum of 5 for either dose versus 2.6 for placebo, compared with 1.5 at baseline (P <.001). The frequency of orgasm also improved significantly with both doses of sildenafil compared with placebo: average score of 3.8 for sildenafil and 2.4 for placebo compared with 1.0 at baseline (P <.001). There were no statistically significant differences between the 2 doses of sildenafil in any of the outcomes measured and the order in which the treatments were allocated did not show any effect. Four women (7.8%) stopped taking sildenafil 50 mg, 2 women (3.9%) stopped taking sildenafil 25 mg, and 2 women (3.9%) stopped taking placebo. Reasons given for discontinuing treatment included vision problems, headache and fear of adverse reactions.

BACKGROUND: Sildenafil has been proved an effective oral pill for erectile dysfunction in men. Synthesis and releases of nitric oxide may also regulate clitoral corpus cavernousum smooth muscle tone. Thus, the same mechanism that regulates male erections may play a role in female sexual arousal disorder. Sexual arousal disorder is the persistent or recurrent inability to attain or maintain sufficient sexual excitement, expressed as a lack of genital lubrication or swelling response.

POPULATION STUDIED: Study subjects included 53 volunteer women ages 22 to 38 years seen in a sexual arousal disorders clinic in Italy for an inability to attain orgasm. Eligible women were healthy, with a subjectively normal sexual desire, not taking any known medications that could effect sexual arousal, had not experienced any clitoral and vaginal sensation or were slow to respond, and had not lubricated for a minimum of 6 months; they were all in stable, satisfying heterosexual relationships.

STUDY DESIGN AND VALIDITY: Subjects were randomized in a double-blind, 3 crossover periods fashion (allocation assignment concealed) to each of 6 possible sequences, each consisting of 3 medication series: (1) sildenafil 25 mg; (2) sildenafil 50 mg; and (3) placebo. Each participant took either dose of sidenafil or placebo 1 hour before planned intercourse. Each drug was used for a 4-week period, with a 1-week washout period between treatment periods. Patients were followed monthly for a total of 3 months. Since the study subjects were those seen in a tertiary care center they may not reflect similar patients seen by family physicians.

OUTCOMES MEASURED: The authors used a 5-point Likert Personal Experience Questionnaire to detect changes in sexual behavior, measuring scores at baseline and at the conclusion of each 4-week period. No documentation was given regarding reproducibility and internal validity of the findings. The primary outcome measured was arousal score. Secondary outcomes included an ability to achieve an orgasm, sexual enjoyment, frequency of intercourse, and the number of sexual fantasies.

RESULTS: Of the 53 women who initiated treatment, complete follow-up information was available on 51. Sexual arousal scores (sexual enjoyment, feeling of satisfaction, and frequency of sexual fantasies) improved with both doses of sildenafil, compared with placebo: Average score of 4.2 from a maximum of 5 for either dose versus 2.6 for placebo, compared with 1.5 at baseline (P <.001). The frequency of orgasm also improved significantly with both doses of sildenafil compared with placebo: average score of 3.8 for sildenafil and 2.4 for placebo compared with 1.0 at baseline (P <.001). There were no statistically significant differences between the 2 doses of sildenafil in any of the outcomes measured and the order in which the treatments were allocated did not show any effect. Four women (7.8%) stopped taking sildenafil 50 mg, 2 women (3.9%) stopped taking sildenafil 25 mg, and 2 women (3.9%) stopped taking placebo. Reasons given for discontinuing treatment included vision problems, headache and fear of adverse reactions.

BACKGROUND: Recent public and legislative focus on pain management practices has led to scrutiny of guidelines for the role of opioids in pain therapy. A survey by the World Health Organization in 1998 revealed that 22% of patients seeing primary care physicians reported persistent pain. Better, more acceptable methods of pain control are needed. This study compared 2 methods of administering potent opioids to patients to determine which method produced better results.

POPULATION STUDIED: A panel of 256 adult patients (age range = 26-82 years) was drawn from specialist pain clinics in Europe, Canada, and South Africa. Many of these patients (70%) had previous therapy with opioids for chronic non-cancer pain. Patients (N=24) were excluded who had previous exposure to morphine and had rated it “bad” or “very bad.” Sixty patients withdrew, leaving 196 patients to complete the study. Duration of pain ranged from less than 1 year to 50 years, with a mean duration of 9 years.

STUDY DESIGN AND VALIDITY: The researchers of this randomized multicenter open label crossover trial enrolled patients with nociceptive and/or neuropathic pain. As the method of administration of the 2 drugs is different, patients were aware of the change in therapy. Patients received doses of opioid equivalent to their pre-study requirements. The study compared fentanyl patch (25, 50, 75, or 100 μg/hr) and sustained-release oral morphine (10-, 30-, 60-, 100-, or 200-mg tablets). One group received 4 weeks of fentanyl followed by 4 weeks of morphine; the other received the drugs in reverse sequence. Medication dosage was fixed and not titrated to achieve pain control. This is perhaps the most important study limitation, because empiric dosage conversions are based on opioid equivalents determined in populations and often do not predict individual response.

OUTCOMES MEASURED: Overall, patient preference was assessed, as well as feelings regarding convenience, adverse events, and pain relief. Pain control was evaluated through intensity of pain (scale of 0-100) and need for a rescue drug. Quality of life was evaluated using the Medical Outcomes Study 36-item short form quality-of-life instrument. Safety-related outcomes included the rate of nausea, constipation (using a bowel function questionnaire), and hypoventilation.

RESULTS: A preference for one product over another could not be assessed in 39 patients (15%). The 212 remaining patients (65%) either “preferred” or “very much preferred” transdermal fentanyl, compared with 28% preferring sustained-release oral morphine (P <.001.) Seven percent expressed no preference. Patients in the fentanyl group had lower pain intensity with a mean rating of 57.8 mm (range=33.1-82.5 mm), compared with a mean rating of 62.9 mm (range = 41.2-84.6 mm; P <.001). Pain control was rated “good” or “very good” by 35% of the patients while receiving fentanyl, but only by 23% of the patients while taking morphine (P=.002.) They also reported higher quality-of-life scores during fentanyl therapy than during sustained-release oral morphine use, with scores in the categories of bodily pain, vitality, social functioning, and mental health being significantly different. The incidence and proportion of adverse events was similar; fentanyl, however, produced higher rates of nausea (26% vs 18%) but less constipation (16% vs 22%).

BACKGROUND: Recent public and legislative focus on pain management practices has led to scrutiny of guidelines for the role of opioids in pain therapy. A survey by the World Health Organization in 1998 revealed that 22% of patients seeing primary care physicians reported persistent pain. Better, more acceptable methods of pain control are needed. This study compared 2 methods of administering potent opioids to patients to determine which method produced better results.

POPULATION STUDIED: A panel of 256 adult patients (age range = 26-82 years) was drawn from specialist pain clinics in Europe, Canada, and South Africa. Many of these patients (70%) had previous therapy with opioids for chronic non-cancer pain. Patients (N=24) were excluded who had previous exposure to morphine and had rated it “bad” or “very bad.” Sixty patients withdrew, leaving 196 patients to complete the study. Duration of pain ranged from less than 1 year to 50 years, with a mean duration of 9 years.

STUDY DESIGN AND VALIDITY: The researchers of this randomized multicenter open label crossover trial enrolled patients with nociceptive and/or neuropathic pain. As the method of administration of the 2 drugs is different, patients were aware of the change in therapy. Patients received doses of opioid equivalent to their pre-study requirements. The study compared fentanyl patch (25, 50, 75, or 100 μg/hr) and sustained-release oral morphine (10-, 30-, 60-, 100-, or 200-mg tablets). One group received 4 weeks of fentanyl followed by 4 weeks of morphine; the other received the drugs in reverse sequence. Medication dosage was fixed and not titrated to achieve pain control. This is perhaps the most important study limitation, because empiric dosage conversions are based on opioid equivalents determined in populations and often do not predict individual response.

OUTCOMES MEASURED: Overall, patient preference was assessed, as well as feelings regarding convenience, adverse events, and pain relief. Pain control was evaluated through intensity of pain (scale of 0-100) and need for a rescue drug. Quality of life was evaluated using the Medical Outcomes Study 36-item short form quality-of-life instrument. Safety-related outcomes included the rate of nausea, constipation (using a bowel function questionnaire), and hypoventilation.

RESULTS: A preference for one product over another could not be assessed in 39 patients (15%). The 212 remaining patients (65%) either “preferred” or “very much preferred” transdermal fentanyl, compared with 28% preferring sustained-release oral morphine (P <.001.) Seven percent expressed no preference. Patients in the fentanyl group had lower pain intensity with a mean rating of 57.8 mm (range=33.1-82.5 mm), compared with a mean rating of 62.9 mm (range = 41.2-84.6 mm; P <.001). Pain control was rated “good” or “very good” by 35% of the patients while receiving fentanyl, but only by 23% of the patients while taking morphine (P=.002.) They also reported higher quality-of-life scores during fentanyl therapy than during sustained-release oral morphine use, with scores in the categories of bodily pain, vitality, social functioning, and mental health being significantly different. The incidence and proportion of adverse events was similar; fentanyl, however, produced higher rates of nausea (26% vs 18%) but less constipation (16% vs 22%).

BACKGROUND: Recent public and legislative focus on pain management practices has led to scrutiny of guidelines for the role of opioids in pain therapy. A survey by the World Health Organization in 1998 revealed that 22% of patients seeing primary care physicians reported persistent pain. Better, more acceptable methods of pain control are needed. This study compared 2 methods of administering potent opioids to patients to determine which method produced better results.

POPULATION STUDIED: A panel of 256 adult patients (age range = 26-82 years) was drawn from specialist pain clinics in Europe, Canada, and South Africa. Many of these patients (70%) had previous therapy with opioids for chronic non-cancer pain. Patients (N=24) were excluded who had previous exposure to morphine and had rated it “bad” or “very bad.” Sixty patients withdrew, leaving 196 patients to complete the study. Duration of pain ranged from less than 1 year to 50 years, with a mean duration of 9 years.

STUDY DESIGN AND VALIDITY: The researchers of this randomized multicenter open label crossover trial enrolled patients with nociceptive and/or neuropathic pain. As the method of administration of the 2 drugs is different, patients were aware of the change in therapy. Patients received doses of opioid equivalent to their pre-study requirements. The study compared fentanyl patch (25, 50, 75, or 100 μg/hr) and sustained-release oral morphine (10-, 30-, 60-, 100-, or 200-mg tablets). One group received 4 weeks of fentanyl followed by 4 weeks of morphine; the other received the drugs in reverse sequence. Medication dosage was fixed and not titrated to achieve pain control. This is perhaps the most important study limitation, because empiric dosage conversions are based on opioid equivalents determined in populations and often do not predict individual response.

OUTCOMES MEASURED: Overall, patient preference was assessed, as well as feelings regarding convenience, adverse events, and pain relief. Pain control was evaluated through intensity of pain (scale of 0-100) and need for a rescue drug. Quality of life was evaluated using the Medical Outcomes Study 36-item short form quality-of-life instrument. Safety-related outcomes included the rate of nausea, constipation (using a bowel function questionnaire), and hypoventilation.

RESULTS: A preference for one product over another could not be assessed in 39 patients (15%). The 212 remaining patients (65%) either “preferred” or “very much preferred” transdermal fentanyl, compared with 28% preferring sustained-release oral morphine (P <.001.) Seven percent expressed no preference. Patients in the fentanyl group had lower pain intensity with a mean rating of 57.8 mm (range=33.1-82.5 mm), compared with a mean rating of 62.9 mm (range = 41.2-84.6 mm; P <.001). Pain control was rated “good” or “very good” by 35% of the patients while receiving fentanyl, but only by 23% of the patients while taking morphine (P=.002.) They also reported higher quality-of-life scores during fentanyl therapy than during sustained-release oral morphine use, with scores in the categories of bodily pain, vitality, social functioning, and mental health being significantly different. The incidence and proportion of adverse events was similar; fentanyl, however, produced higher rates of nausea (26% vs 18%) but less constipation (16% vs 22%).

BACKGROUND: Two smaller randomized controlled trials failed to show a statistically significant difference between acetaminophen and the non steroidal anti-inflammatory drugs (NSAIDs) ibuprofen and naproxen in the treatment of osteoarthritis (OA). However, survey data showing a benefit with NSAIDs and a meta-analysis suggesting their superiority led the researchers to conduct this larger clinical trial.

POPULATION STUDIED: A total of 227 patients were recruited in 12 ambulatory sites either directly or by advertising. The study was not conducted in a primary care setting. Eighty percent of the patients had already seen a rheumatologist before recruitment in the study. Patients were older than 40 years, had Kellgren-Lawrence radiographic scale grade 2 to 4 OA of the hip or knee, and a visual analog pain scale score of 30 mm or greater (range=0-100). Patients with severe comorbidities and hypersensitivity to the medications were excluded.

STUDY DESIGN AND VALIDITY: This was a double-blind crossover trial with all patients receiving both therapies. The study consisted of 2 treatment periods of 6 weeks each, separated by a 3- to 7-day washout period. In period 1, half the patients took diclofenac 75 mg plus 200 μg misoprostol twice daily, and the other group of patients took acetaminophen 1000 mg 4 times daily. Both groups took a placebo of the other medication. In period 2, the therapies for the 2 groups were reversed.

OUTCOMES MEASURED: There were 2 primary outcome measures. The first was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) directed to the primary involved joint. The second was the Multidimensional Health Assessment Questionnaire (MDHAQ) visual analog pain scale. These pain, stiffness, and functional status scoring systems are the best, although imperfect, measurement tools for OA. Since the scores are derived from patient self-reporting, they are reasonable surrogates for patient-oriented outcomes. Other outcomes measured included gastrointestinal distress, global patient status, a general bodily pain score, and the investigator’s estimate of patient status.

RESULTS: For the first 6-week treatment period, the WOMAC index improved by 12.2 points (on a 100-point scale) for the diclofenac-treated patients and by 6.6 points for the acetaminophen-treated patients. For the second period, the improvement was 12.9 points and 2.1 points, again favoring diclofenac. Likewise, the MDHAQ pain scale improved more with diclofenac plus misoprostol in both treatment periods, 20.8 points (also a 100-point scale) compared with 13.1 for acetaminophen in period 1, and 24.6 points versus 0.4 points for acetaminophen in period 2.

BACKGROUND: Two smaller randomized controlled trials failed to show a statistically significant difference between acetaminophen and the non steroidal anti-inflammatory drugs (NSAIDs) ibuprofen and naproxen in the treatment of osteoarthritis (OA). However, survey data showing a benefit with NSAIDs and a meta-analysis suggesting their superiority led the researchers to conduct this larger clinical trial.

POPULATION STUDIED: A total of 227 patients were recruited in 12 ambulatory sites either directly or by advertising. The study was not conducted in a primary care setting. Eighty percent of the patients had already seen a rheumatologist before recruitment in the study. Patients were older than 40 years, had Kellgren-Lawrence radiographic scale grade 2 to 4 OA of the hip or knee, and a visual analog pain scale score of 30 mm or greater (range=0-100). Patients with severe comorbidities and hypersensitivity to the medications were excluded.

STUDY DESIGN AND VALIDITY: This was a double-blind crossover trial with all patients receiving both therapies. The study consisted of 2 treatment periods of 6 weeks each, separated by a 3- to 7-day washout period. In period 1, half the patients took diclofenac 75 mg plus 200 μg misoprostol twice daily, and the other group of patients took acetaminophen 1000 mg 4 times daily. Both groups took a placebo of the other medication. In period 2, the therapies for the 2 groups were reversed.

OUTCOMES MEASURED: There were 2 primary outcome measures. The first was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) directed to the primary involved joint. The second was the Multidimensional Health Assessment Questionnaire (MDHAQ) visual analog pain scale. These pain, stiffness, and functional status scoring systems are the best, although imperfect, measurement tools for OA. Since the scores are derived from patient self-reporting, they are reasonable surrogates for patient-oriented outcomes. Other outcomes measured included gastrointestinal distress, global patient status, a general bodily pain score, and the investigator’s estimate of patient status.

RESULTS: For the first 6-week treatment period, the WOMAC index improved by 12.2 points (on a 100-point scale) for the diclofenac-treated patients and by 6.6 points for the acetaminophen-treated patients. For the second period, the improvement was 12.9 points and 2.1 points, again favoring diclofenac. Likewise, the MDHAQ pain scale improved more with diclofenac plus misoprostol in both treatment periods, 20.8 points (also a 100-point scale) compared with 13.1 for acetaminophen in period 1, and 24.6 points versus 0.4 points for acetaminophen in period 2.

BACKGROUND: Two smaller randomized controlled trials failed to show a statistically significant difference between acetaminophen and the non steroidal anti-inflammatory drugs (NSAIDs) ibuprofen and naproxen in the treatment of osteoarthritis (OA). However, survey data showing a benefit with NSAIDs and a meta-analysis suggesting their superiority led the researchers to conduct this larger clinical trial.

POPULATION STUDIED: A total of 227 patients were recruited in 12 ambulatory sites either directly or by advertising. The study was not conducted in a primary care setting. Eighty percent of the patients had already seen a rheumatologist before recruitment in the study. Patients were older than 40 years, had Kellgren-Lawrence radiographic scale grade 2 to 4 OA of the hip or knee, and a visual analog pain scale score of 30 mm or greater (range=0-100). Patients with severe comorbidities and hypersensitivity to the medications were excluded.

STUDY DESIGN AND VALIDITY: This was a double-blind crossover trial with all patients receiving both therapies. The study consisted of 2 treatment periods of 6 weeks each, separated by a 3- to 7-day washout period. In period 1, half the patients took diclofenac 75 mg plus 200 μg misoprostol twice daily, and the other group of patients took acetaminophen 1000 mg 4 times daily. Both groups took a placebo of the other medication. In period 2, the therapies for the 2 groups were reversed.

OUTCOMES MEASURED: There were 2 primary outcome measures. The first was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) directed to the primary involved joint. The second was the Multidimensional Health Assessment Questionnaire (MDHAQ) visual analog pain scale. These pain, stiffness, and functional status scoring systems are the best, although imperfect, measurement tools for OA. Since the scores are derived from patient self-reporting, they are reasonable surrogates for patient-oriented outcomes. Other outcomes measured included gastrointestinal distress, global patient status, a general bodily pain score, and the investigator’s estimate of patient status.

RESULTS: For the first 6-week treatment period, the WOMAC index improved by 12.2 points (on a 100-point scale) for the diclofenac-treated patients and by 6.6 points for the acetaminophen-treated patients. For the second period, the improvement was 12.9 points and 2.1 points, again favoring diclofenac. Likewise, the MDHAQ pain scale improved more with diclofenac plus misoprostol in both treatment periods, 20.8 points (also a 100-point scale) compared with 13.1 for acetaminophen in period 1, and 24.6 points versus 0.4 points for acetaminophen in period 2.

BACKGROUND: In the middle of the last decade several studies suggested an increased risk of thromboembolic events in women using the newer generation of oral contraceptives (OCs). These pills contain the newer progestins desogestrel, gestodene, and norgestimate. The authors of this meta-analysis attempted to address possible confounders and biases in these past studies and quantify the strength of the association.

POPULATION STUDIED: The meta-analysis included 9 case-control studies involving 3417 cases of thromboembolic disease with 9600 controls, as well as 3 cohort studies of more than 1 million women. Reported ages ranged from 15 to 49 years. All but one study (with 471 cases and 1772 controls) reported exclusion of women with a previous history of thromboembolism. Settings included hospitals, primary care offices and specialty clinics, primarily in Europe. Only studies comparing third-generation OCs to second-generation OCs were included in the final analyses.

STUDY DESIGN AND VALIDITY: The selected cohort or case-control articles were required to define cases as women with venous thrombosis or thromboembolism, and they had to contain sufficient information to determine relative risk and confidence intervals. The data were all obtained before November 1995. The study addressed possible heterogeneity among studies by stratified analysis of the results.

OUTCOMES MEASURED: The main outcome was the onset of venous embolism, comparing third-generation OC users to second-generation OC users. Because no randomized trial data were available, the investigators used odds ratios as an approximation of relative risk.

RESULTS: The study arrived at an overall adjusted odds ratio of 1.7 (95% confidence interval [CI], 1.4-2.0), a 70% higher association with thromboembolism for third-generation OCs compared with second-generation OCs. The highest odds ratio, 3.1 (95% CI, 2.0-4.6), was among first-time users. For short-term users (less than 1 year) the odds ratio was 2.5 (95% CI, 1.6-4.1), compared with 2.0 (95% CI, 1.4-2.7) for use longer than 1 year. Studies funded by the pharmaceutical industry had an odds ratio of 1.3 (95% CI, 1.0-1.7), while independent studies had an odds ratio of 2.3 (95% CI, 1.7-3.2). Age and confirmation of thromboembolism by vascular studies did not affect the odds ratios. These numbers translate to 1.5 additional incidents of thromboembolic disease per 10,000 woman years, approximately 4 additional deaths per 1,000,000 woman years. In other words, 25,000 women have to be treated over 10 years with third-generation OCs instead of second-generation OCs to expect one additional death.

BACKGROUND: In the middle of the last decade several studies suggested an increased risk of thromboembolic events in women using the newer generation of oral contraceptives (OCs). These pills contain the newer progestins desogestrel, gestodene, and norgestimate. The authors of this meta-analysis attempted to address possible confounders and biases in these past studies and quantify the strength of the association.

POPULATION STUDIED: The meta-analysis included 9 case-control studies involving 3417 cases of thromboembolic disease with 9600 controls, as well as 3 cohort studies of more than 1 million women. Reported ages ranged from 15 to 49 years. All but one study (with 471 cases and 1772 controls) reported exclusion of women with a previous history of thromboembolism. Settings included hospitals, primary care offices and specialty clinics, primarily in Europe. Only studies comparing third-generation OCs to second-generation OCs were included in the final analyses.

STUDY DESIGN AND VALIDITY: The selected cohort or case-control articles were required to define cases as women with venous thrombosis or thromboembolism, and they had to contain sufficient information to determine relative risk and confidence intervals. The data were all obtained before November 1995. The study addressed possible heterogeneity among studies by stratified analysis of the results.

OUTCOMES MEASURED: The main outcome was the onset of venous embolism, comparing third-generation OC users to second-generation OC users. Because no randomized trial data were available, the investigators used odds ratios as an approximation of relative risk.

RESULTS: The study arrived at an overall adjusted odds ratio of 1.7 (95% confidence interval [CI], 1.4-2.0), a 70% higher association with thromboembolism for third-generation OCs compared with second-generation OCs. The highest odds ratio, 3.1 (95% CI, 2.0-4.6), was among first-time users. For short-term users (less than 1 year) the odds ratio was 2.5 (95% CI, 1.6-4.1), compared with 2.0 (95% CI, 1.4-2.7) for use longer than 1 year. Studies funded by the pharmaceutical industry had an odds ratio of 1.3 (95% CI, 1.0-1.7), while independent studies had an odds ratio of 2.3 (95% CI, 1.7-3.2). Age and confirmation of thromboembolism by vascular studies did not affect the odds ratios. These numbers translate to 1.5 additional incidents of thromboembolic disease per 10,000 woman years, approximately 4 additional deaths per 1,000,000 woman years. In other words, 25,000 women have to be treated over 10 years with third-generation OCs instead of second-generation OCs to expect one additional death.

BACKGROUND: In the middle of the last decade several studies suggested an increased risk of thromboembolic events in women using the newer generation of oral contraceptives (OCs). These pills contain the newer progestins desogestrel, gestodene, and norgestimate. The authors of this meta-analysis attempted to address possible confounders and biases in these past studies and quantify the strength of the association.

POPULATION STUDIED: The meta-analysis included 9 case-control studies involving 3417 cases of thromboembolic disease with 9600 controls, as well as 3 cohort studies of more than 1 million women. Reported ages ranged from 15 to 49 years. All but one study (with 471 cases and 1772 controls) reported exclusion of women with a previous history of thromboembolism. Settings included hospitals, primary care offices and specialty clinics, primarily in Europe. Only studies comparing third-generation OCs to second-generation OCs were included in the final analyses.

STUDY DESIGN AND VALIDITY: The selected cohort or case-control articles were required to define cases as women with venous thrombosis or thromboembolism, and they had to contain sufficient information to determine relative risk and confidence intervals. The data were all obtained before November 1995. The study addressed possible heterogeneity among studies by stratified analysis of the results.

OUTCOMES MEASURED: The main outcome was the onset of venous embolism, comparing third-generation OC users to second-generation OC users. Because no randomized trial data were available, the investigators used odds ratios as an approximation of relative risk.

RESULTS: The study arrived at an overall adjusted odds ratio of 1.7 (95% confidence interval [CI], 1.4-2.0), a 70% higher association with thromboembolism for third-generation OCs compared with second-generation OCs. The highest odds ratio, 3.1 (95% CI, 2.0-4.6), was among first-time users. For short-term users (less than 1 year) the odds ratio was 2.5 (95% CI, 1.6-4.1), compared with 2.0 (95% CI, 1.4-2.7) for use longer than 1 year. Studies funded by the pharmaceutical industry had an odds ratio of 1.3 (95% CI, 1.0-1.7), while independent studies had an odds ratio of 2.3 (95% CI, 1.7-3.2). Age and confirmation of thromboembolism by vascular studies did not affect the odds ratios. These numbers translate to 1.5 additional incidents of thromboembolic disease per 10,000 woman years, approximately 4 additional deaths per 1,000,000 woman years. In other words, 25,000 women have to be treated over 10 years with third-generation OCs instead of second-generation OCs to expect one additional death.

BACKGROUND: UTIs are common in adult women, and many will have recurrences of UTI. The effectiveness of cranberry juice or Lactobacillus in preventing such recurrences is not known.

POPULATION STUDIED: The authors recruited women with culture-confirmed Escherichia coli UTI from university students and staff of a university hospital in Finland (n=149). Participants had an average age of 30 years and averaged 6 previous UTIs. Only 5 patients were older than 55 years. The study groups were similar; however, the cranberry juice group had a slightly higher previous use of antibiotics. The population studied would likely fit the practices of many family physicians. Eighty-five percent of the women had taken antimicrobials for a UTI in the year before enrollment. All were treated for their index episode of UTI with 5 days of standard drug therapy (communication with authors). Most (78%) used birth control during the study; none used a diaphragm or spermicides. Five women became pregnant during the 1-year follow-up.

STUDY DESIGN AND VALIDITY: Patients were randomized to 1 of 3 groups, with study personnel unaware of patients’ treatment assignments until after they were enrolled (concealed allocation; communication with authors). Fifty patients received daily oral concentrate (50 mL) of cranberry-lingonberry juice for 6 months. They were to dilute the concentrate with 200 mL of water. This product is no longer commercially available, even in Finland. In the second group, 49 patients took a Lactobacillus drink 5 days a week for 12 months. The 100-mL drink contained 4 × 1010 cfu of Lactobacillus. There were 50 untreated control patients. Treating physicians and patients were not blinded to the treatment assignment. Each recurrence was treated with nitrofurantoin for 5 days (communication with authors).

OUTCOMES MEASURED: The primary outcome measured was recurrence of UTI within 1 year. Patient symptoms were confirmed with culture to diagnose each recurrence.

RESULTS: Daily cranberry juice significantly decreased the incidence of UTI. Lactobacillus ingestion did not change the recurrence rate. Eight patients in the cranberry group had at least one recurrent UTI, compared with 19 in the Lactobacillus group and 18 in the control group (P=.023; number needed to treat [NNT]=5; 95% confidence interval [CI], 3-34). At 12 months, 12 patients in the cranberry group had a recurrent UTI, compared with 21 in the Lactobacillus group and 19 in the control group (P=.048; NNT=7). Most (80%) of the recurrences were due to E coli.

BACKGROUND: UTIs are common in adult women, and many will have recurrences of UTI. The effectiveness of cranberry juice or Lactobacillus in preventing such recurrences is not known.

POPULATION STUDIED: The authors recruited women with culture-confirmed Escherichia coli UTI from university students and staff of a university hospital in Finland (n=149). Participants had an average age of 30 years and averaged 6 previous UTIs. Only 5 patients were older than 55 years. The study groups were similar; however, the cranberry juice group had a slightly higher previous use of antibiotics. The population studied would likely fit the practices of many family physicians. Eighty-five percent of the women had taken antimicrobials for a UTI in the year before enrollment. All were treated for their index episode of UTI with 5 days of standard drug therapy (communication with authors). Most (78%) used birth control during the study; none used a diaphragm or spermicides. Five women became pregnant during the 1-year follow-up.

STUDY DESIGN AND VALIDITY: Patients were randomized to 1 of 3 groups, with study personnel unaware of patients’ treatment assignments until after they were enrolled (concealed allocation; communication with authors). Fifty patients received daily oral concentrate (50 mL) of cranberry-lingonberry juice for 6 months. They were to dilute the concentrate with 200 mL of water. This product is no longer commercially available, even in Finland. In the second group, 49 patients took a Lactobacillus drink 5 days a week for 12 months. The 100-mL drink contained 4 × 1010 cfu of Lactobacillus. There were 50 untreated control patients. Treating physicians and patients were not blinded to the treatment assignment. Each recurrence was treated with nitrofurantoin for 5 days (communication with authors).

OUTCOMES MEASURED: The primary outcome measured was recurrence of UTI within 1 year. Patient symptoms were confirmed with culture to diagnose each recurrence.

RESULTS: Daily cranberry juice significantly decreased the incidence of UTI. Lactobacillus ingestion did not change the recurrence rate. Eight patients in the cranberry group had at least one recurrent UTI, compared with 19 in the Lactobacillus group and 18 in the control group (P=.023; number needed to treat [NNT]=5; 95% confidence interval [CI], 3-34). At 12 months, 12 patients in the cranberry group had a recurrent UTI, compared with 21 in the Lactobacillus group and 19 in the control group (P=.048; NNT=7). Most (80%) of the recurrences were due to E coli.

BACKGROUND: UTIs are common in adult women, and many will have recurrences of UTI. The effectiveness of cranberry juice or Lactobacillus in preventing such recurrences is not known.

POPULATION STUDIED: The authors recruited women with culture-confirmed Escherichia coli UTI from university students and staff of a university hospital in Finland (n=149). Participants had an average age of 30 years and averaged 6 previous UTIs. Only 5 patients were older than 55 years. The study groups were similar; however, the cranberry juice group had a slightly higher previous use of antibiotics. The population studied would likely fit the practices of many family physicians. Eighty-five percent of the women had taken antimicrobials for a UTI in the year before enrollment. All were treated for their index episode of UTI with 5 days of standard drug therapy (communication with authors). Most (78%) used birth control during the study; none used a diaphragm or spermicides. Five women became pregnant during the 1-year follow-up.

STUDY DESIGN AND VALIDITY: Patients were randomized to 1 of 3 groups, with study personnel unaware of patients’ treatment assignments until after they were enrolled (concealed allocation; communication with authors). Fifty patients received daily oral concentrate (50 mL) of cranberry-lingonberry juice for 6 months. They were to dilute the concentrate with 200 mL of water. This product is no longer commercially available, even in Finland. In the second group, 49 patients took a Lactobacillus drink 5 days a week for 12 months. The 100-mL drink contained 4 × 1010 cfu of Lactobacillus. There were 50 untreated control patients. Treating physicians and patients were not blinded to the treatment assignment. Each recurrence was treated with nitrofurantoin for 5 days (communication with authors).

OUTCOMES MEASURED: The primary outcome measured was recurrence of UTI within 1 year. Patient symptoms were confirmed with culture to diagnose each recurrence.

RESULTS: Daily cranberry juice significantly decreased the incidence of UTI. Lactobacillus ingestion did not change the recurrence rate. Eight patients in the cranberry group had at least one recurrent UTI, compared with 19 in the Lactobacillus group and 18 in the control group (P=.023; number needed to treat [NNT]=5; 95% confidence interval [CI], 3-34). At 12 months, 12 patients in the cranberry group had a recurrent UTI, compared with 21 in the Lactobacillus group and 19 in the control group (P=.048; NNT=7). Most (80%) of the recurrences were due to E coli.