James J. Stevermer, MD, MSPH

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: The American Academy of Pediatrics recommends that pediatric sinusitis be a clinical diagnosis, based on persistent rhinosinusitis and cough for more than 10 to 14 days. Limited-spectrum antibiotics are recommended when antibiotic treatment is felt necessary. However, these recommendations are based on limited clinical research. Recent European studies have suggested that antibiotics may only be minimally effective for children with otitis media and adults with sinusitis.

POPULATION STUDIED: The authors enrolled 188 patients between the ages of 1 and 18 years from 3 primary care pediatric practices in suburban St. Louis, Missouri. The children had persistent cough and rhinosinusitis symptoms for 10 to 28 days, the criteria for clinical diagnosis of acute sinusitis. Patients were excluded if they had fulminant sinusitis including a fever of 39° C or higher, facial swelling, and headache/facial pain. The study also excluded patients with minimal symptoms, chronic sinusitis (>28 days), cystic fibrosis, and other valid reasons.

STUDY DESIGN AND VALIDITY: Patients were stratified by age (older or younger than 7 years) and symptom severity. They were randomly assigned to either a 14-day treatment course of amoxicillin (40 mg/kg up to 500 mg 3 times daily), amoxicillin-clavulanate (45 mg/kg/day of amoxicillin component up to 875 mg twice daily), or placebo. Nineteen patients were later excluded because they failed to meet eligibility criteria. However, 97% of all follow-up interviews were completed. Physicians could recommend ancillary nonantimicrobial therapies (such as decongestants) to any patient. There were no major differences in these treatments in the 3 groups. This study was well designed, used concealed allocation, had good follow-up, and the analysis appeared appropriate.

OUTCOMES MEASURED: The main outcome was a severity of symptom score, assessed by using the S5 score (a validated combination score of 5 items, including nasal obstruction, nighttime coughing, daytime coughing, headache/facial pain, and colored nasal mucous) with symptom score ranging from 0 to 3. Outcomes were assessed by telephone interview at 3, 7, 10, 14, 21, 28, and 60 days. Secondary outcomes included patient/parent satisfaction, adverse drug effects, illness days, and functional status.

RESULTS: Patient outcomes did not differ in any of the groups at any date. The 2-week improvement rate was 79% for the placebo and amoxicillin groups and 81% for the amoxicillin-clavulanate group (P=.97). Average symptom scores dropped from around 2.0 to 0.6 (of a possible 3.0). Secondary outcomes such as patient satisfaction and side effects did not differ significantly in the groups except for a higher incidence of side effects in the amoxicillin group (19% in the amoxicillin group vs 11% in the amoxicillin-clavulanate group and 10% in the placebo group, P=.017).

BACKGROUND: The American Academy of Pediatrics recommends that pediatric sinusitis be a clinical diagnosis, based on persistent rhinosinusitis and cough for more than 10 to 14 days. Limited-spectrum antibiotics are recommended when antibiotic treatment is felt necessary. However, these recommendations are based on limited clinical research. Recent European studies have suggested that antibiotics may only be minimally effective for children with otitis media and adults with sinusitis.

POPULATION STUDIED: The authors enrolled 188 patients between the ages of 1 and 18 years from 3 primary care pediatric practices in suburban St. Louis, Missouri. The children had persistent cough and rhinosinusitis symptoms for 10 to 28 days, the criteria for clinical diagnosis of acute sinusitis. Patients were excluded if they had fulminant sinusitis including a fever of 39° C or higher, facial swelling, and headache/facial pain. The study also excluded patients with minimal symptoms, chronic sinusitis (>28 days), cystic fibrosis, and other valid reasons.

STUDY DESIGN AND VALIDITY: Patients were stratified by age (older or younger than 7 years) and symptom severity. They were randomly assigned to either a 14-day treatment course of amoxicillin (40 mg/kg up to 500 mg 3 times daily), amoxicillin-clavulanate (45 mg/kg/day of amoxicillin component up to 875 mg twice daily), or placebo. Nineteen patients were later excluded because they failed to meet eligibility criteria. However, 97% of all follow-up interviews were completed. Physicians could recommend ancillary nonantimicrobial therapies (such as decongestants) to any patient. There were no major differences in these treatments in the 3 groups. This study was well designed, used concealed allocation, had good follow-up, and the analysis appeared appropriate.

OUTCOMES MEASURED: The main outcome was a severity of symptom score, assessed by using the S5 score (a validated combination score of 5 items, including nasal obstruction, nighttime coughing, daytime coughing, headache/facial pain, and colored nasal mucous) with symptom score ranging from 0 to 3. Outcomes were assessed by telephone interview at 3, 7, 10, 14, 21, 28, and 60 days. Secondary outcomes included patient/parent satisfaction, adverse drug effects, illness days, and functional status.

RESULTS: Patient outcomes did not differ in any of the groups at any date. The 2-week improvement rate was 79% for the placebo and amoxicillin groups and 81% for the amoxicillin-clavulanate group (P=.97). Average symptom scores dropped from around 2.0 to 0.6 (of a possible 3.0). Secondary outcomes such as patient satisfaction and side effects did not differ significantly in the groups except for a higher incidence of side effects in the amoxicillin group (19% in the amoxicillin group vs 11% in the amoxicillin-clavulanate group and 10% in the placebo group, P=.017).

BACKGROUND: The American Academy of Pediatrics recommends that pediatric sinusitis be a clinical diagnosis, based on persistent rhinosinusitis and cough for more than 10 to 14 days. Limited-spectrum antibiotics are recommended when antibiotic treatment is felt necessary. However, these recommendations are based on limited clinical research. Recent European studies have suggested that antibiotics may only be minimally effective for children with otitis media and adults with sinusitis.

POPULATION STUDIED: The authors enrolled 188 patients between the ages of 1 and 18 years from 3 primary care pediatric practices in suburban St. Louis, Missouri. The children had persistent cough and rhinosinusitis symptoms for 10 to 28 days, the criteria for clinical diagnosis of acute sinusitis. Patients were excluded if they had fulminant sinusitis including a fever of 39° C or higher, facial swelling, and headache/facial pain. The study also excluded patients with minimal symptoms, chronic sinusitis (>28 days), cystic fibrosis, and other valid reasons.

STUDY DESIGN AND VALIDITY: Patients were stratified by age (older or younger than 7 years) and symptom severity. They were randomly assigned to either a 14-day treatment course of amoxicillin (40 mg/kg up to 500 mg 3 times daily), amoxicillin-clavulanate (45 mg/kg/day of amoxicillin component up to 875 mg twice daily), or placebo. Nineteen patients were later excluded because they failed to meet eligibility criteria. However, 97% of all follow-up interviews were completed. Physicians could recommend ancillary nonantimicrobial therapies (such as decongestants) to any patient. There were no major differences in these treatments in the 3 groups. This study was well designed, used concealed allocation, had good follow-up, and the analysis appeared appropriate.

OUTCOMES MEASURED: The main outcome was a severity of symptom score, assessed by using the S5 score (a validated combination score of 5 items, including nasal obstruction, nighttime coughing, daytime coughing, headache/facial pain, and colored nasal mucous) with symptom score ranging from 0 to 3. Outcomes were assessed by telephone interview at 3, 7, 10, 14, 21, 28, and 60 days. Secondary outcomes included patient/parent satisfaction, adverse drug effects, illness days, and functional status.

RESULTS: Patient outcomes did not differ in any of the groups at any date. The 2-week improvement rate was 79% for the placebo and amoxicillin groups and 81% for the amoxicillin-clavulanate group (P=.97). Average symptom scores dropped from around 2.0 to 0.6 (of a possible 3.0). Secondary outcomes such as patient satisfaction and side effects did not differ significantly in the groups except for a higher incidence of side effects in the amoxicillin group (19% in the amoxicillin group vs 11% in the amoxicillin-clavulanate group and 10% in the placebo group, P=.017).

Recommendations from others

Evidence summary

Vaginal cuff screening is common. Of women with a hysterectomy attending teaching hospital clinics in San Francisco,⁵ 51% had a Pap test in the previous 3 years. In a Wisconsin survey,⁶ 55% of women with a hysterectomy had a Pap test in the previous 3 years. The annual risk of vaginal cancer is low (0.7 cases per 100,000 women). It is estimated that approximately 250 women will die of vaginal cancer annually in the United States.⁷ As with cervical disease, the rationale for vaginal cuff tests is to detect precancerous changes before cancer develops. Vaginal intraepithelial neoplasia (VAIN) is graded from VAIN 1 for a low-grade lesion to VAIN 3, which includes carcinoma-in-situ and highly dysplastic lesions. The natural history of VAIN is not well delineated. Although VAIN may be a common precursor to vaginal cancer, it will also resolve without treatment. In one study,8 23 women with VAIN were followed from 3 to 15 years. While the diseases of 2 women progressed (9%), the overall regression rate was 78%.

The accuracy of the Pap test for detecting VAIN has not been well documented. The estimated sensitivity of the Pap test is 50%9 to 83%.¹⁰ Fetters and colleagues⁷ estimated that the positive predictive value of an abnormal vaginal Pap test result was 0.05%; only 1 in 2000 women with abnormal test results would have cancer.

In the largest cohort study,¹¹ 9610 vaginal cuff Pap tests from 5682 women who had had a hysterectomy for benign disease were reviewed. The authors found 104 test results (from 79 women) were abnormal. Of these, 52 showed atypical squamous cells of undetermined significance, 44 were low-grade squamous intraepithelial lesions, 6 were high-grade squamous intraepithelial lesions, and 2 were read as carcinoma. Of the 79 women 27 were referred for colposcopy. Colposcopy results showed that 19 had normal mucosa, and 8 had VAIN 1 or 2. Six of these cases resolved without further treatment. Two were lost to follow-up, and no cancers were diagnosed. One of the women with a Pap-based diagnosis of cancer was lost to follow-up; the other had VAIN 1. No confirmed cases of carcinoma were found. The positive predictive value (the probability that an abnormal test result meant the patient had cancer) was 0% (95% confidence interval, 0.0%-33.0%).

There are multiple suggested treatments for VAIN, all based on case series. No randomized controlled trials were found comparing any of these treatments either to each other or to watchful waiting.

In summary, the overall risk of mortality and morbidity due to primary vaginal cancer is low. The natural history of the purported precursor lesion (VAIN) is not well understood, and it can regress without treatment. There are no trials showing that treatments of VAIN are more effective than placebo. The Pap test of the vaginal cuff is almost certain to miss some abnormalities. In addition, the extremely low prevalence means that almost all abnormal test results will be false positives. Given these data, it is unlikely that Pap test screening for vaginal cancer is clinically effective, and it is almost certain to be cost-prohibitive.

Recommendations from others

Evidence summary

Vaginal cuff screening is common. Of women with a hysterectomy attending teaching hospital clinics in San Francisco,⁵ 51% had a Pap test in the previous 3 years. In a Wisconsin survey,⁶ 55% of women with a hysterectomy had a Pap test in the previous 3 years. The annual risk of vaginal cancer is low (0.7 cases per 100,000 women). It is estimated that approximately 250 women will die of vaginal cancer annually in the United States.⁷ As with cervical disease, the rationale for vaginal cuff tests is to detect precancerous changes before cancer develops. Vaginal intraepithelial neoplasia (VAIN) is graded from VAIN 1 for a low-grade lesion to VAIN 3, which includes carcinoma-in-situ and highly dysplastic lesions. The natural history of VAIN is not well delineated. Although VAIN may be a common precursor to vaginal cancer, it will also resolve without treatment. In one study,8 23 women with VAIN were followed from 3 to 15 years. While the diseases of 2 women progressed (9%), the overall regression rate was 78%.

The accuracy of the Pap test for detecting VAIN has not been well documented. The estimated sensitivity of the Pap test is 50%9 to 83%.¹⁰ Fetters and colleagues⁷ estimated that the positive predictive value of an abnormal vaginal Pap test result was 0.05%; only 1 in 2000 women with abnormal test results would have cancer.

In the largest cohort study,¹¹ 9610 vaginal cuff Pap tests from 5682 women who had had a hysterectomy for benign disease were reviewed. The authors found 104 test results (from 79 women) were abnormal. Of these, 52 showed atypical squamous cells of undetermined significance, 44 were low-grade squamous intraepithelial lesions, 6 were high-grade squamous intraepithelial lesions, and 2 were read as carcinoma. Of the 79 women 27 were referred for colposcopy. Colposcopy results showed that 19 had normal mucosa, and 8 had VAIN 1 or 2. Six of these cases resolved without further treatment. Two were lost to follow-up, and no cancers were diagnosed. One of the women with a Pap-based diagnosis of cancer was lost to follow-up; the other had VAIN 1. No confirmed cases of carcinoma were found. The positive predictive value (the probability that an abnormal test result meant the patient had cancer) was 0% (95% confidence interval, 0.0%-33.0%).

There are multiple suggested treatments for VAIN, all based on case series. No randomized controlled trials were found comparing any of these treatments either to each other or to watchful waiting.

In summary, the overall risk of mortality and morbidity due to primary vaginal cancer is low. The natural history of the purported precursor lesion (VAIN) is not well understood, and it can regress without treatment. There are no trials showing that treatments of VAIN are more effective than placebo. The Pap test of the vaginal cuff is almost certain to miss some abnormalities. In addition, the extremely low prevalence means that almost all abnormal test results will be false positives. Given these data, it is unlikely that Pap test screening for vaginal cancer is clinically effective, and it is almost certain to be cost-prohibitive.

Recommendations from others

Evidence summary

Vaginal cuff screening is common. Of women with a hysterectomy attending teaching hospital clinics in San Francisco,⁵ 51% had a Pap test in the previous 3 years. In a Wisconsin survey,⁶ 55% of women with a hysterectomy had a Pap test in the previous 3 years. The annual risk of vaginal cancer is low (0.7 cases per 100,000 women). It is estimated that approximately 250 women will die of vaginal cancer annually in the United States.⁷ As with cervical disease, the rationale for vaginal cuff tests is to detect precancerous changes before cancer develops. Vaginal intraepithelial neoplasia (VAIN) is graded from VAIN 1 for a low-grade lesion to VAIN 3, which includes carcinoma-in-situ and highly dysplastic lesions. The natural history of VAIN is not well delineated. Although VAIN may be a common precursor to vaginal cancer, it will also resolve without treatment. In one study,8 23 women with VAIN were followed from 3 to 15 years. While the diseases of 2 women progressed (9%), the overall regression rate was 78%.

The accuracy of the Pap test for detecting VAIN has not been well documented. The estimated sensitivity of the Pap test is 50%9 to 83%.¹⁰ Fetters and colleagues⁷ estimated that the positive predictive value of an abnormal vaginal Pap test result was 0.05%; only 1 in 2000 women with abnormal test results would have cancer.

In the largest cohort study,¹¹ 9610 vaginal cuff Pap tests from 5682 women who had had a hysterectomy for benign disease were reviewed. The authors found 104 test results (from 79 women) were abnormal. Of these, 52 showed atypical squamous cells of undetermined significance, 44 were low-grade squamous intraepithelial lesions, 6 were high-grade squamous intraepithelial lesions, and 2 were read as carcinoma. Of the 79 women 27 were referred for colposcopy. Colposcopy results showed that 19 had normal mucosa, and 8 had VAIN 1 or 2. Six of these cases resolved without further treatment. Two were lost to follow-up, and no cancers were diagnosed. One of the women with a Pap-based diagnosis of cancer was lost to follow-up; the other had VAIN 1. No confirmed cases of carcinoma were found. The positive predictive value (the probability that an abnormal test result meant the patient had cancer) was 0% (95% confidence interval, 0.0%-33.0%).

There are multiple suggested treatments for VAIN, all based on case series. No randomized controlled trials were found comparing any of these treatments either to each other or to watchful waiting.

In summary, the overall risk of mortality and morbidity due to primary vaginal cancer is low. The natural history of the purported precursor lesion (VAIN) is not well understood, and it can regress without treatment. There are no trials showing that treatments of VAIN are more effective than placebo. The Pap test of the vaginal cuff is almost certain to miss some abnormalities. In addition, the extremely low prevalence means that almost all abnormal test results will be false positives. Given these data, it is unlikely that Pap test screening for vaginal cancer is clinically effective, and it is almost certain to be cost-prohibitive.

BACKGROUND: Injudicious use of antibiotics in the management of sore throat contributes to the proliferation of resistant organisms and exposes patients to adverse effects of unnecessary medication. A clinical decision-making tool that better identifies patients with streptococcal infection would decrease unnecessary testing and antibiotic therapy. The authors of this study evaluated the validity of such a clinical rule in a primary care setting.

POPULATION STUDIED: Family physicians in Ontario, Canada, enrolled 621 patients, all of whom presented with a sore throat and an upper respiratory infection. Of these, two thirds were women and one fourth were aged younger than 15 years. Exclusion criteria included age younger than 3 years, recent treatment with antibiotics, or an alternate diagnosis that explains the symptoms (eg, otitis media, pneumonia).

STUDY DESIGN AND VALIDITY: The authors compared the results of a clinical rule with the independent clinical decisions of the treating physician. Physicians evaluated and treated patients per their usual routine and recorded their findings and interventions on an assessment form. Throat cultures were obtained for all patients. The physicians also recorded the “strep” score for each patient. This rule assigns 1 point for each of the following symptoms: temperature greater than 38°C, absence of cough, tender anterior cervical adenopathy, tonsillar swelling or exudate, and age younger than 15 years. One point is subtracted for age older than 45 years. A score of 1 or less was considered negative, and neither throat culture nor antibiotic therapy was recommended. A score of 2 or 3 was considered indeterminate, and a throat culture was recommended with antibiotic therapy based on culture results. A score of 4 or greater was considered positive, and antibiotic therapy or throat culture was recommended. Comparison of the number of antibiotic prescriptions and throat cultures was made between the physicians’ plan and the clinical rule.

OUTCOMES MEASURED: The primary outcomes were the sensitivity and specificity of the clinical rule. Concordance of antibiotic treatment and throat culture results was evaluated.

RESULTS: Physicians prescribed antibiotics to 27.9% of patients. Of these, only 37% had group A streptococcus (GAS) on culture. Cultures were positive for GAS in 17% of all patients. The clinical rule was 85% sensitive for identifying GAS infection (95% confidence interval [CI], 76.5%-91.4%) and 92.1% specific (95% CI, 89.3%-94.3%). Few patients with a clinical rule score of 1 or less had GAS pharyngitis (4.7%). The prevalence of GAS was 17% for a score of 2, 35% for a score of 3, and 51% for a score of 4 or more. Use of the clinical rule would have reduced antibiotic use by 52.3% and throat culture by 35.8% in all patients. Although this effect was more notable in adult patients, even in children the score was more sensitive than the clinical assessment and would have reduced unnecessary testing.

BACKGROUND: Injudicious use of antibiotics in the management of sore throat contributes to the proliferation of resistant organisms and exposes patients to adverse effects of unnecessary medication. A clinical decision-making tool that better identifies patients with streptococcal infection would decrease unnecessary testing and antibiotic therapy. The authors of this study evaluated the validity of such a clinical rule in a primary care setting.

POPULATION STUDIED: Family physicians in Ontario, Canada, enrolled 621 patients, all of whom presented with a sore throat and an upper respiratory infection. Of these, two thirds were women and one fourth were aged younger than 15 years. Exclusion criteria included age younger than 3 years, recent treatment with antibiotics, or an alternate diagnosis that explains the symptoms (eg, otitis media, pneumonia).

STUDY DESIGN AND VALIDITY: The authors compared the results of a clinical rule with the independent clinical decisions of the treating physician. Physicians evaluated and treated patients per their usual routine and recorded their findings and interventions on an assessment form. Throat cultures were obtained for all patients. The physicians also recorded the “strep” score for each patient. This rule assigns 1 point for each of the following symptoms: temperature greater than 38°C, absence of cough, tender anterior cervical adenopathy, tonsillar swelling or exudate, and age younger than 15 years. One point is subtracted for age older than 45 years. A score of 1 or less was considered negative, and neither throat culture nor antibiotic therapy was recommended. A score of 2 or 3 was considered indeterminate, and a throat culture was recommended with antibiotic therapy based on culture results. A score of 4 or greater was considered positive, and antibiotic therapy or throat culture was recommended. Comparison of the number of antibiotic prescriptions and throat cultures was made between the physicians’ plan and the clinical rule.

OUTCOMES MEASURED: The primary outcomes were the sensitivity and specificity of the clinical rule. Concordance of antibiotic treatment and throat culture results was evaluated.

RESULTS: Physicians prescribed antibiotics to 27.9% of patients. Of these, only 37% had group A streptococcus (GAS) on culture. Cultures were positive for GAS in 17% of all patients. The clinical rule was 85% sensitive for identifying GAS infection (95% confidence interval [CI], 76.5%-91.4%) and 92.1% specific (95% CI, 89.3%-94.3%). Few patients with a clinical rule score of 1 or less had GAS pharyngitis (4.7%). The prevalence of GAS was 17% for a score of 2, 35% for a score of 3, and 51% for a score of 4 or more. Use of the clinical rule would have reduced antibiotic use by 52.3% and throat culture by 35.8% in all patients. Although this effect was more notable in adult patients, even in children the score was more sensitive than the clinical assessment and would have reduced unnecessary testing.

BACKGROUND: Injudicious use of antibiotics in the management of sore throat contributes to the proliferation of resistant organisms and exposes patients to adverse effects of unnecessary medication. A clinical decision-making tool that better identifies patients with streptococcal infection would decrease unnecessary testing and antibiotic therapy. The authors of this study evaluated the validity of such a clinical rule in a primary care setting.

POPULATION STUDIED: Family physicians in Ontario, Canada, enrolled 621 patients, all of whom presented with a sore throat and an upper respiratory infection. Of these, two thirds were women and one fourth were aged younger than 15 years. Exclusion criteria included age younger than 3 years, recent treatment with antibiotics, or an alternate diagnosis that explains the symptoms (eg, otitis media, pneumonia).

STUDY DESIGN AND VALIDITY: The authors compared the results of a clinical rule with the independent clinical decisions of the treating physician. Physicians evaluated and treated patients per their usual routine and recorded their findings and interventions on an assessment form. Throat cultures were obtained for all patients. The physicians also recorded the “strep” score for each patient. This rule assigns 1 point for each of the following symptoms: temperature greater than 38°C, absence of cough, tender anterior cervical adenopathy, tonsillar swelling or exudate, and age younger than 15 years. One point is subtracted for age older than 45 years. A score of 1 or less was considered negative, and neither throat culture nor antibiotic therapy was recommended. A score of 2 or 3 was considered indeterminate, and a throat culture was recommended with antibiotic therapy based on culture results. A score of 4 or greater was considered positive, and antibiotic therapy or throat culture was recommended. Comparison of the number of antibiotic prescriptions and throat cultures was made between the physicians’ plan and the clinical rule.

OUTCOMES MEASURED: The primary outcomes were the sensitivity and specificity of the clinical rule. Concordance of antibiotic treatment and throat culture results was evaluated.

RESULTS: Physicians prescribed antibiotics to 27.9% of patients. Of these, only 37% had group A streptococcus (GAS) on culture. Cultures were positive for GAS in 17% of all patients. The clinical rule was 85% sensitive for identifying GAS infection (95% confidence interval [CI], 76.5%-91.4%) and 92.1% specific (95% CI, 89.3%-94.3%). Few patients with a clinical rule score of 1 or less had GAS pharyngitis (4.7%). The prevalence of GAS was 17% for a score of 2, 35% for a score of 3, and 51% for a score of 4 or more. Use of the clinical rule would have reduced antibiotic use by 52.3% and throat culture by 35.8% in all patients. Although this effect was more notable in adult patients, even in children the score was more sensitive than the clinical assessment and would have reduced unnecessary testing.

BACKGROUND: Annual screening mammography is universally accepted as the standard of care in the United States for woman 50 years and older. Although evidence supports screening as effective in reducing breast cancer mortality, it is not known whether mammography plus a clinical breast examination (CBE) is more effective at reducing cancer mortality than a thorough CBE alone.

POPULATION STUDIED: A total of 39,459 Canadian women 50 to 59 years were recruited through general publicity, mailings, and physician referral. These women had not received a mammogram in the previous year and did not have a history of breast cancer.

STUDY DESIGN AND VALIDITY: The women were randomized to receive either 5 annual CBEs with mammography or a CBE alone annually for 5 years. Well-trained nurses using a visual inspection component and palpation in a radial pattern performed most of the breast examinations. Physicians performed the others. The examinations were very thorough and took approximately 10 minutes. Patients were also taught breast self-examination. Two-view mammograms were used and independently reviewed. Patients with abnormal findings were referred to the Canadian National Breast Screening Study (CNBSS) clinic for further evaluation by a surgeon. Breast cancers were identified through the CNBSS centers and the National Cancer Registry during the 13-year follow-up. The cause of death was identified through the participant’s family members, physicians, and the Canadian Mortality Data Base. Overall the study appeared valid. The 2 randomized groups seemed equal for breast cancer risk factors and other demographics. There was excellent follow-up and good compliance within each group. Randomization was not concealed. Previous scrutiny of this study centered on a change in mammography technique during the screening. Further analysis showed high sensitivity and expected cancer detection rates despite this change. The article does not mention what types of screening the participants underwent after the initial 5-year study period. This could potentially have an effect on the mortality numbers, if women decided to stop their screening after the study period ended. This study did not address differences in quality of life, such as discomfort from mammograms and additional procedures from false-positive screenings.

OUTCOMES MEASURED: Breast cancer mortality was the primary outcome. The tumor size and number of lymph node–positive cancers were also reported.

RESULTS: Only 54 of the original participants were excluded from the analysis. At the 13-year follow-up there were 107 breast cancer deaths in the combined mammography plus CBE group and 105 deaths in the CBE-only group (rate ratio=1.02; 95% confidence interval, 0.78-1.33). A total of 622 invasive and 71 in situ cancers were found in the combined group and 610 invasive and 16 in situ cancers were identified in the CBE-only group. Mammography was able to detect a cancer 2.1 years earlier than CBE alone. However, this lead time did not appear to improve survival. Overall, the tumors identified by mammography were smaller. There was no significant difference between the 2 groups in the number of lymph node–positive cancers detected by the end of the study. As expected, there were approximately 3 times as many biopsies and more diagnostic tests performed in the mammogram group.

BACKGROUND: Annual screening mammography is universally accepted as the standard of care in the United States for woman 50 years and older. Although evidence supports screening as effective in reducing breast cancer mortality, it is not known whether mammography plus a clinical breast examination (CBE) is more effective at reducing cancer mortality than a thorough CBE alone.

POPULATION STUDIED: A total of 39,459 Canadian women 50 to 59 years were recruited through general publicity, mailings, and physician referral. These women had not received a mammogram in the previous year and did not have a history of breast cancer.

STUDY DESIGN AND VALIDITY: The women were randomized to receive either 5 annual CBEs with mammography or a CBE alone annually for 5 years. Well-trained nurses using a visual inspection component and palpation in a radial pattern performed most of the breast examinations. Physicians performed the others. The examinations were very thorough and took approximately 10 minutes. Patients were also taught breast self-examination. Two-view mammograms were used and independently reviewed. Patients with abnormal findings were referred to the Canadian National Breast Screening Study (CNBSS) clinic for further evaluation by a surgeon. Breast cancers were identified through the CNBSS centers and the National Cancer Registry during the 13-year follow-up. The cause of death was identified through the participant’s family members, physicians, and the Canadian Mortality Data Base. Overall the study appeared valid. The 2 randomized groups seemed equal for breast cancer risk factors and other demographics. There was excellent follow-up and good compliance within each group. Randomization was not concealed. Previous scrutiny of this study centered on a change in mammography technique during the screening. Further analysis showed high sensitivity and expected cancer detection rates despite this change. The article does not mention what types of screening the participants underwent after the initial 5-year study period. This could potentially have an effect on the mortality numbers, if women decided to stop their screening after the study period ended. This study did not address differences in quality of life, such as discomfort from mammograms and additional procedures from false-positive screenings.

OUTCOMES MEASURED: Breast cancer mortality was the primary outcome. The tumor size and number of lymph node–positive cancers were also reported.

RESULTS: Only 54 of the original participants were excluded from the analysis. At the 13-year follow-up there were 107 breast cancer deaths in the combined mammography plus CBE group and 105 deaths in the CBE-only group (rate ratio=1.02; 95% confidence interval, 0.78-1.33). A total of 622 invasive and 71 in situ cancers were found in the combined group and 610 invasive and 16 in situ cancers were identified in the CBE-only group. Mammography was able to detect a cancer 2.1 years earlier than CBE alone. However, this lead time did not appear to improve survival. Overall, the tumors identified by mammography were smaller. There was no significant difference between the 2 groups in the number of lymph node–positive cancers detected by the end of the study. As expected, there were approximately 3 times as many biopsies and more diagnostic tests performed in the mammogram group.

BACKGROUND: Annual screening mammography is universally accepted as the standard of care in the United States for woman 50 years and older. Although evidence supports screening as effective in reducing breast cancer mortality, it is not known whether mammography plus a clinical breast examination (CBE) is more effective at reducing cancer mortality than a thorough CBE alone.

POPULATION STUDIED: A total of 39,459 Canadian women 50 to 59 years were recruited through general publicity, mailings, and physician referral. These women had not received a mammogram in the previous year and did not have a history of breast cancer.

STUDY DESIGN AND VALIDITY: The women were randomized to receive either 5 annual CBEs with mammography or a CBE alone annually for 5 years. Well-trained nurses using a visual inspection component and palpation in a radial pattern performed most of the breast examinations. Physicians performed the others. The examinations were very thorough and took approximately 10 minutes. Patients were also taught breast self-examination. Two-view mammograms were used and independently reviewed. Patients with abnormal findings were referred to the Canadian National Breast Screening Study (CNBSS) clinic for further evaluation by a surgeon. Breast cancers were identified through the CNBSS centers and the National Cancer Registry during the 13-year follow-up. The cause of death was identified through the participant’s family members, physicians, and the Canadian Mortality Data Base. Overall the study appeared valid. The 2 randomized groups seemed equal for breast cancer risk factors and other demographics. There was excellent follow-up and good compliance within each group. Randomization was not concealed. Previous scrutiny of this study centered on a change in mammography technique during the screening. Further analysis showed high sensitivity and expected cancer detection rates despite this change. The article does not mention what types of screening the participants underwent after the initial 5-year study period. This could potentially have an effect on the mortality numbers, if women decided to stop their screening after the study period ended. This study did not address differences in quality of life, such as discomfort from mammograms and additional procedures from false-positive screenings.

OUTCOMES MEASURED: Breast cancer mortality was the primary outcome. The tumor size and number of lymph node–positive cancers were also reported.

RESULTS: Only 54 of the original participants were excluded from the analysis. At the 13-year follow-up there were 107 breast cancer deaths in the combined mammography plus CBE group and 105 deaths in the CBE-only group (rate ratio=1.02; 95% confidence interval, 0.78-1.33). A total of 622 invasive and 71 in situ cancers were found in the combined group and 610 invasive and 16 in situ cancers were identified in the CBE-only group. Mammography was able to detect a cancer 2.1 years earlier than CBE alone. However, this lead time did not appear to improve survival. Overall, the tumors identified by mammography were smaller. There was no significant difference between the 2 groups in the number of lymph node–positive cancers detected by the end of the study. As expected, there were approximately 3 times as many biopsies and more diagnostic tests performed in the mammogram group.

BACKGROUND: Limb compression bandages, such as Unna boots, successfully treat 30% to 60% of venous leg ulcers. The authors of this study attempted to create a simple model to predict which patients’ ulcers will heal using this therapy.

POPULATION STUDIED: All patients were drawn from a dermatology skin ulcer clinic. A training group of 260 consecutive patients with chronic venous leg ulcers was used to develop predictive models. Venous ulcers were defined as wounds in the “gaiter area” of the limb from the mid-calf to 1 inch below the malleolus. All patients had lower leg edema and cutaneous evidence of venous disease. second group of 219 patients enrolled in the control arm of 2 randomized controlled trials testing skin allograft versus compression was used to validate the rule. Ulcers in this study were at least 4 weeks old and between 0.5 and 200 cm2 in area.

STUDY DESIGN AND VALIDITY: This was a cohort study for developing and validating a clinical decision rule. Prognostic models were created with 10 risk factors and statistically analyzed for their ability to correctly predict wound healing. The models were simplified by dropping prognostic factors one by one from the model, as long as the ability to predict healing was not affected. All of the models were evaluated by measuring the area under the receiver-operating characteristic (ROC) curve. By definition, an area closer to 1 indicates a better ability to distinguish which ulcers will heal. An area of 0.5 indicates a worthless test or rule. The most accurate model from the training group was evaluated using the validation group.

OUTCOMES MEASURED: The primary outcome measure was the ability of a model to predict wound healing within 24 weeks as measured by the area under the ROC curve.

RESULTS: Overall, 65% of ulcers from the training group and 56% of ulcers from the validation group healed by 24 weeks. All of the candidate models had areas under the ROC curve greater than 0.80, meaning that the model discriminated between ulcers that did and did not heal more than 80% of the time. The simplest model, which gave a score of 1 point for a wound area greater than 5 cm2 (measured by a template) and 1 point for wound age greater than 6 months, correctly predicted healing 87% of the time. Ulcers with a score of 0 healed in 95% of the validation group, while ulcers with a score of 1 healed in 73% of the validation group.

BACKGROUND: Limb compression bandages, such as Unna boots, successfully treat 30% to 60% of venous leg ulcers. The authors of this study attempted to create a simple model to predict which patients’ ulcers will heal using this therapy.

POPULATION STUDIED: All patients were drawn from a dermatology skin ulcer clinic. A training group of 260 consecutive patients with chronic venous leg ulcers was used to develop predictive models. Venous ulcers were defined as wounds in the “gaiter area” of the limb from the mid-calf to 1 inch below the malleolus. All patients had lower leg edema and cutaneous evidence of venous disease. second group of 219 patients enrolled in the control arm of 2 randomized controlled trials testing skin allograft versus compression was used to validate the rule. Ulcers in this study were at least 4 weeks old and between 0.5 and 200 cm2 in area.

STUDY DESIGN AND VALIDITY: This was a cohort study for developing and validating a clinical decision rule. Prognostic models were created with 10 risk factors and statistically analyzed for their ability to correctly predict wound healing. The models were simplified by dropping prognostic factors one by one from the model, as long as the ability to predict healing was not affected. All of the models were evaluated by measuring the area under the receiver-operating characteristic (ROC) curve. By definition, an area closer to 1 indicates a better ability to distinguish which ulcers will heal. An area of 0.5 indicates a worthless test or rule. The most accurate model from the training group was evaluated using the validation group.

OUTCOMES MEASURED: The primary outcome measure was the ability of a model to predict wound healing within 24 weeks as measured by the area under the ROC curve.

RESULTS: Overall, 65% of ulcers from the training group and 56% of ulcers from the validation group healed by 24 weeks. All of the candidate models had areas under the ROC curve greater than 0.80, meaning that the model discriminated between ulcers that did and did not heal more than 80% of the time. The simplest model, which gave a score of 1 point for a wound area greater than 5 cm2 (measured by a template) and 1 point for wound age greater than 6 months, correctly predicted healing 87% of the time. Ulcers with a score of 0 healed in 95% of the validation group, while ulcers with a score of 1 healed in 73% of the validation group.

BACKGROUND: Limb compression bandages, such as Unna boots, successfully treat 30% to 60% of venous leg ulcers. The authors of this study attempted to create a simple model to predict which patients’ ulcers will heal using this therapy.

POPULATION STUDIED: All patients were drawn from a dermatology skin ulcer clinic. A training group of 260 consecutive patients with chronic venous leg ulcers was used to develop predictive models. Venous ulcers were defined as wounds in the “gaiter area” of the limb from the mid-calf to 1 inch below the malleolus. All patients had lower leg edema and cutaneous evidence of venous disease. second group of 219 patients enrolled in the control arm of 2 randomized controlled trials testing skin allograft versus compression was used to validate the rule. Ulcers in this study were at least 4 weeks old and between 0.5 and 200 cm2 in area.

STUDY DESIGN AND VALIDITY: This was a cohort study for developing and validating a clinical decision rule. Prognostic models were created with 10 risk factors and statistically analyzed for their ability to correctly predict wound healing. The models were simplified by dropping prognostic factors one by one from the model, as long as the ability to predict healing was not affected. All of the models were evaluated by measuring the area under the receiver-operating characteristic (ROC) curve. By definition, an area closer to 1 indicates a better ability to distinguish which ulcers will heal. An area of 0.5 indicates a worthless test or rule. The most accurate model from the training group was evaluated using the validation group.

OUTCOMES MEASURED: The primary outcome measure was the ability of a model to predict wound healing within 24 weeks as measured by the area under the ROC curve.

RESULTS: Overall, 65% of ulcers from the training group and 56% of ulcers from the validation group healed by 24 weeks. All of the candidate models had areas under the ROC curve greater than 0.80, meaning that the model discriminated between ulcers that did and did not heal more than 80% of the time. The simplest model, which gave a score of 1 point for a wound area greater than 5 cm2 (measured by a template) and 1 point for wound age greater than 6 months, correctly predicted healing 87% of the time. Ulcers with a score of 0 healed in 95% of the validation group, while ulcers with a score of 1 healed in 73% of the validation group.

BACKGROUND: Cardiopulmonary resuscitation (CPR) initiated at the scene of a cardiac arrest may increase survival by up to 50%. In some locations 911 dispatchers provide instructions for CPR to untrained bystanders. Bystanders who witness a cardiac arrest often do not perform CPR because of fears of contamination and contagion. A pilot study performed in King County, Washington, showed a 3.5% increase in survival with chest compressions alone when compared with chest compressions with mouth-to-mouth ventilation.

POPULATION STUDIED: The study was performed in the Seattle, Washington, area with a fire department-based emergency medical care system. Patients were enrolled if they had a cardiac arrest diagnosed over the telephone by the dispatcher and there was a bystander willing to be instructed. A total of 1296 patients were included in the trial. Of these, 776 were excluded on the basis of a subsequent paramedic report of drug or alcohol overdose, carbon monoxide poisoning, trauma, or absence of cardiac arrest. The 520 remaining patients had an average age of 68 years, 64% were men, 58% had a witnessed cardiac arrest, and 88% occurred in a home.

STUDY DESIGN AND VALIDITY: After receiving a 911 call the emergency medical services (EMS) dispatcher would determine if the patient was eligible for this study. On the basis of computer randomization, the dispatcher provided instructions for traditional CPR or chest compressions alone. A total of 1296 patients were randomized; after exclusions 520 were analyzed. Of these, 241 were assigned to receive chest compressions alone and 279 to receive the traditional method of CPR. The study design was reasonable given the limitations of performing a trial under these circumstances.

OUTCOMES MEASURED: The primary outcome measured was survival to hospital discharge. Secondary outcomes included admission to the hospital, neurologic status of the survivors, duration of instructions, and bystander opinions.

RESULTS: Of the 520 patients included in the study, 64 survived to hospital discharge. Twenty-nine patients (10.4%) survived in the CPR with mouth-to-mouth ventilation group, and 35 patients (14.6%) survived in the chest compressions only group. There was no statistically significant difference in survival to discharge between the 2 groups (P=.18). A similar nonsignificant trend was noted for hospitalizations, with 34.1% of patients in the CPR group admitted to the hospital and 40.2% of the patients in the chest compressions-only group admitted (P=.15). There was no difference found in neurologic morbidity after a mean follow-up time of 2.4 years. Fewer bystanders refused the instructions in the compressions-only group (7.2% vs 2.9%), and instruction time was much shorter (1 minute vs 2.4 minutes). Compliance of the EMS dispatchers with the written protocol was excellent.

BACKGROUND: Cardiopulmonary resuscitation (CPR) initiated at the scene of a cardiac arrest may increase survival by up to 50%. In some locations 911 dispatchers provide instructions for CPR to untrained bystanders. Bystanders who witness a cardiac arrest often do not perform CPR because of fears of contamination and contagion. A pilot study performed in King County, Washington, showed a 3.5% increase in survival with chest compressions alone when compared with chest compressions with mouth-to-mouth ventilation.

POPULATION STUDIED: The study was performed in the Seattle, Washington, area with a fire department-based emergency medical care system. Patients were enrolled if they had a cardiac arrest diagnosed over the telephone by the dispatcher and there was a bystander willing to be instructed. A total of 1296 patients were included in the trial. Of these, 776 were excluded on the basis of a subsequent paramedic report of drug or alcohol overdose, carbon monoxide poisoning, trauma, or absence of cardiac arrest. The 520 remaining patients had an average age of 68 years, 64% were men, 58% had a witnessed cardiac arrest, and 88% occurred in a home.

STUDY DESIGN AND VALIDITY: After receiving a 911 call the emergency medical services (EMS) dispatcher would determine if the patient was eligible for this study. On the basis of computer randomization, the dispatcher provided instructions for traditional CPR or chest compressions alone. A total of 1296 patients were randomized; after exclusions 520 were analyzed. Of these, 241 were assigned to receive chest compressions alone and 279 to receive the traditional method of CPR. The study design was reasonable given the limitations of performing a trial under these circumstances.

OUTCOMES MEASURED: The primary outcome measured was survival to hospital discharge. Secondary outcomes included admission to the hospital, neurologic status of the survivors, duration of instructions, and bystander opinions.

RESULTS: Of the 520 patients included in the study, 64 survived to hospital discharge. Twenty-nine patients (10.4%) survived in the CPR with mouth-to-mouth ventilation group, and 35 patients (14.6%) survived in the chest compressions only group. There was no statistically significant difference in survival to discharge between the 2 groups (P=.18). A similar nonsignificant trend was noted for hospitalizations, with 34.1% of patients in the CPR group admitted to the hospital and 40.2% of the patients in the chest compressions-only group admitted (P=.15). There was no difference found in neurologic morbidity after a mean follow-up time of 2.4 years. Fewer bystanders refused the instructions in the compressions-only group (7.2% vs 2.9%), and instruction time was much shorter (1 minute vs 2.4 minutes). Compliance of the EMS dispatchers with the written protocol was excellent.

BACKGROUND: Cardiopulmonary resuscitation (CPR) initiated at the scene of a cardiac arrest may increase survival by up to 50%. In some locations 911 dispatchers provide instructions for CPR to untrained bystanders. Bystanders who witness a cardiac arrest often do not perform CPR because of fears of contamination and contagion. A pilot study performed in King County, Washington, showed a 3.5% increase in survival with chest compressions alone when compared with chest compressions with mouth-to-mouth ventilation.

POPULATION STUDIED: The study was performed in the Seattle, Washington, area with a fire department-based emergency medical care system. Patients were enrolled if they had a cardiac arrest diagnosed over the telephone by the dispatcher and there was a bystander willing to be instructed. A total of 1296 patients were included in the trial. Of these, 776 were excluded on the basis of a subsequent paramedic report of drug or alcohol overdose, carbon monoxide poisoning, trauma, or absence of cardiac arrest. The 520 remaining patients had an average age of 68 years, 64% were men, 58% had a witnessed cardiac arrest, and 88% occurred in a home.

STUDY DESIGN AND VALIDITY: After receiving a 911 call the emergency medical services (EMS) dispatcher would determine if the patient was eligible for this study. On the basis of computer randomization, the dispatcher provided instructions for traditional CPR or chest compressions alone. A total of 1296 patients were randomized; after exclusions 520 were analyzed. Of these, 241 were assigned to receive chest compressions alone and 279 to receive the traditional method of CPR. The study design was reasonable given the limitations of performing a trial under these circumstances.

OUTCOMES MEASURED: The primary outcome measured was survival to hospital discharge. Secondary outcomes included admission to the hospital, neurologic status of the survivors, duration of instructions, and bystander opinions.

RESULTS: Of the 520 patients included in the study, 64 survived to hospital discharge. Twenty-nine patients (10.4%) survived in the CPR with mouth-to-mouth ventilation group, and 35 patients (14.6%) survived in the chest compressions only group. There was no statistically significant difference in survival to discharge between the 2 groups (P=.18). A similar nonsignificant trend was noted for hospitalizations, with 34.1% of patients in the CPR group admitted to the hospital and 40.2% of the patients in the chest compressions-only group admitted (P=.15). There was no difference found in neurologic morbidity after a mean follow-up time of 2.4 years. Fewer bystanders refused the instructions in the compressions-only group (7.2% vs 2.9%), and instruction time was much shorter (1 minute vs 2.4 minutes). Compliance of the EMS dispatchers with the written protocol was excellent.

BACKGROUND: Intermittent claudication is a painful symptom of peripheral arterial disease. Nonsurgical treatment consists of modification of lifestyle risk factors (quit smoking, lower cholesterol levels), regular physical exercise, and a variety of medications. The clinical effectiveness of these interventions has usually been modest. Gingko biloba, a commonly used medicinal herb, has active ingredients that inhibit platelets and potentially decrease red blood cell aggregation. Because of these actions, it has been tested for intermittent claudication. Although some controlled studies have suggested benefit, the results have been inconclusive. The authors performed a meta-analysis to better summarize the current evidence.

POPULATION STUDIED: A total of 415 patients were included in this analysis. Their demographic information was not provided.

STUDY DESIGN AND VALIDITY: This was a meta-analysis of the existing literature. Manuscripts were identified for inclusion through a systematic search of 6 appropriate databases, contacting manufacturers of the product for published and unpublished literature, and contacting authors for additional data. Eight randomized controlled trials (RCTs) were identified that compared gingko with placebo and included an assessment of walking distance. Two researchers independently reviewed each study, grading them on quality (randomization strategy, description of withdrawals and dropouts, blinding protocol) and extracting information on pain-free walking distance. Appropriate statistical tools were used to find the pooled difference in pain-free walking distance between gingko and placebo.

OUTCOMES MEASURED: The primary outcome studied was pain-free walking distance. Seven of the 8 studies also reported maximal walking distance at baseline and after randomization to gingko or placebo. Three of the 8 studies used the same standardized assessment of treadmill walking that included ergometer speed of 3 km per hour on a grade of 12%.

RESULTS: Six of the 8 RCTs had a quality score of at least 4 on a scale of 1 to 5. Seven of the studies showed that gingko was more effective than placebo; however, only 4 of those studies were statistically significant. When all 8 studies were pooled, gingko increased pain-free walking distance by 34 meters (95% confidence interval, 26-43 m) more than placebo. When the authors pooled different subsets of articles, similar results were found. Side effects of gingko were not reported in 3 of the studies. In the remaining 5 studies, the primary side effects were abdominal complaints, nausea, and dyspepsia, although the rates were not given.

BACKGROUND: Intermittent claudication is a painful symptom of peripheral arterial disease. Nonsurgical treatment consists of modification of lifestyle risk factors (quit smoking, lower cholesterol levels), regular physical exercise, and a variety of medications. The clinical effectiveness of these interventions has usually been modest. Gingko biloba, a commonly used medicinal herb, has active ingredients that inhibit platelets and potentially decrease red blood cell aggregation. Because of these actions, it has been tested for intermittent claudication. Although some controlled studies have suggested benefit, the results have been inconclusive. The authors performed a meta-analysis to better summarize the current evidence.

POPULATION STUDIED: A total of 415 patients were included in this analysis. Their demographic information was not provided.

STUDY DESIGN AND VALIDITY: This was a meta-analysis of the existing literature. Manuscripts were identified for inclusion through a systematic search of 6 appropriate databases, contacting manufacturers of the product for published and unpublished literature, and contacting authors for additional data. Eight randomized controlled trials (RCTs) were identified that compared gingko with placebo and included an assessment of walking distance. Two researchers independently reviewed each study, grading them on quality (randomization strategy, description of withdrawals and dropouts, blinding protocol) and extracting information on pain-free walking distance. Appropriate statistical tools were used to find the pooled difference in pain-free walking distance between gingko and placebo.

OUTCOMES MEASURED: The primary outcome studied was pain-free walking distance. Seven of the 8 studies also reported maximal walking distance at baseline and after randomization to gingko or placebo. Three of the 8 studies used the same standardized assessment of treadmill walking that included ergometer speed of 3 km per hour on a grade of 12%.

RESULTS: Six of the 8 RCTs had a quality score of at least 4 on a scale of 1 to 5. Seven of the studies showed that gingko was more effective than placebo; however, only 4 of those studies were statistically significant. When all 8 studies were pooled, gingko increased pain-free walking distance by 34 meters (95% confidence interval, 26-43 m) more than placebo. When the authors pooled different subsets of articles, similar results were found. Side effects of gingko were not reported in 3 of the studies. In the remaining 5 studies, the primary side effects were abdominal complaints, nausea, and dyspepsia, although the rates were not given.

BACKGROUND: Intermittent claudication is a painful symptom of peripheral arterial disease. Nonsurgical treatment consists of modification of lifestyle risk factors (quit smoking, lower cholesterol levels), regular physical exercise, and a variety of medications. The clinical effectiveness of these interventions has usually been modest. Gingko biloba, a commonly used medicinal herb, has active ingredients that inhibit platelets and potentially decrease red blood cell aggregation. Because of these actions, it has been tested for intermittent claudication. Although some controlled studies have suggested benefit, the results have been inconclusive. The authors performed a meta-analysis to better summarize the current evidence.

POPULATION STUDIED: A total of 415 patients were included in this analysis. Their demographic information was not provided.

STUDY DESIGN AND VALIDITY: This was a meta-analysis of the existing literature. Manuscripts were identified for inclusion through a systematic search of 6 appropriate databases, contacting manufacturers of the product for published and unpublished literature, and contacting authors for additional data. Eight randomized controlled trials (RCTs) were identified that compared gingko with placebo and included an assessment of walking distance. Two researchers independently reviewed each study, grading them on quality (randomization strategy, description of withdrawals and dropouts, blinding protocol) and extracting information on pain-free walking distance. Appropriate statistical tools were used to find the pooled difference in pain-free walking distance between gingko and placebo.

OUTCOMES MEASURED: The primary outcome studied was pain-free walking distance. Seven of the 8 studies also reported maximal walking distance at baseline and after randomization to gingko or placebo. Three of the 8 studies used the same standardized assessment of treadmill walking that included ergometer speed of 3 km per hour on a grade of 12%.

RESULTS: Six of the 8 RCTs had a quality score of at least 4 on a scale of 1 to 5. Seven of the studies showed that gingko was more effective than placebo; however, only 4 of those studies were statistically significant. When all 8 studies were pooled, gingko increased pain-free walking distance by 34 meters (95% confidence interval, 26-43 m) more than placebo. When the authors pooled different subsets of articles, similar results were found. Side effects of gingko were not reported in 3 of the studies. In the remaining 5 studies, the primary side effects were abdominal complaints, nausea, and dyspepsia, although the rates were not given.

CLINICAL QUESTION: Does vitamin E supplementation play a role in the secondary prevention of cardiovascular events in high-risk patients?

BACKGROUND: The role of the antioxidant vitamin E in primary and secondary prevention of cardiovascular disease is unclear. Observational studies suggest that vitamin E may slow the development and progression of atherosclerosis. Four published randomized controlled trials reached differing conclusions that may be partly attributed to different study designs. This investigation, as part of the Heart Outcomes Prevention Evaluation (HOPE) study, evaluates the utility of vitamin E in secondary prevention in high-risk cardiovascular patients.

POPULATION STUDIED: This study enrolled 10,576 individuals aged 55 years and older from more than 200 outpatient centers on 3 continents. Enrolled patients had known coronary artery disease, stroke, or peripheral vascular disease. Patients were also enrolled if they had diabetes and one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, tobacco use, or microalbuminuria. Exclusion criteria included a known ejection fraction of less than 40%, currently taking an angiotensin-converting enzyme (ACE) inhibitor or vitamin E, having uncontrolled hypertension or overt nephropathy, or a history of myocardial infarction or stroke within 4 weeks of enrollment. Approximately 25% of the patients were women.

STUDY DESIGN AND VALIDITY: This study was designed to test the effect of vitamin E and ramipril on cardiovascular events in high-risk patients. The authors of this study report only the RESULTS: for vitamin E. Before randomization an initial run-in period with a low dose of ramipril eliminated more than 1000 participants because of noncompliance, medication side effects, or abnormal serum creatinine or potassium levels. In an adequately concealed fashion, 9541 patients were randomized in a double-blinded fashion to either 400 IU of vitamin E from natural sources or placebo. They were followed for a mean of 4.5 years with evaluation every 6 months. The vitamin E group had 89% compliance at 5 years. The study was discontinued early because of the significant benefit demonstrated in the ramipril arm (see next POEM). The study had adequate power to detect a clinically relevant reduction in the primary outcome. The diverse population characteristics of enrollees will tend to make this study’s findings applicable to many primary care patients.

OUTCOMES MEASURED: The primary outcome was the combined end point of myocardial infarction, stroke, or cardiovascular death while secondary outcomes were death from any cause, worsening congestive heart failure, unstable angina, complications associated with diabetes, or any of the individual primary end points.

RESULTS: There were no significant differences in primary or secondary outcomes between the vitamin E group and the placebo group. No differences in primary and secondary outcomes were revealed when analyzing patient subgroups defined by sex, age, previous cardiovascular disease, medication use, diabetes, tobacco use, or ramipril versus placebo use. There was also no increase in the rate of adverse effects with the vitamin E group, in particular with respect to hemorrhagic stroke.

CLINICAL QUESTION: Does vitamin E supplementation play a role in the secondary prevention of cardiovascular events in high-risk patients?

BACKGROUND: The role of the antioxidant vitamin E in primary and secondary prevention of cardiovascular disease is unclear. Observational studies suggest that vitamin E may slow the development and progression of atherosclerosis. Four published randomized controlled trials reached differing conclusions that may be partly attributed to different study designs. This investigation, as part of the Heart Outcomes Prevention Evaluation (HOPE) study, evaluates the utility of vitamin E in secondary prevention in high-risk cardiovascular patients.

POPULATION STUDIED: This study enrolled 10,576 individuals aged 55 years and older from more than 200 outpatient centers on 3 continents. Enrolled patients had known coronary artery disease, stroke, or peripheral vascular disease. Patients were also enrolled if they had diabetes and one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, tobacco use, or microalbuminuria. Exclusion criteria included a known ejection fraction of less than 40%, currently taking an angiotensin-converting enzyme (ACE) inhibitor or vitamin E, having uncontrolled hypertension or overt nephropathy, or a history of myocardial infarction or stroke within 4 weeks of enrollment. Approximately 25% of the patients were women.

STUDY DESIGN AND VALIDITY: This study was designed to test the effect of vitamin E and ramipril on cardiovascular events in high-risk patients. The authors of this study report only the RESULTS: for vitamin E. Before randomization an initial run-in period with a low dose of ramipril eliminated more than 1000 participants because of noncompliance, medication side effects, or abnormal serum creatinine or potassium levels. In an adequately concealed fashion, 9541 patients were randomized in a double-blinded fashion to either 400 IU of vitamin E from natural sources or placebo. They were followed for a mean of 4.5 years with evaluation every 6 months. The vitamin E group had 89% compliance at 5 years. The study was discontinued early because of the significant benefit demonstrated in the ramipril arm (see next POEM). The study had adequate power to detect a clinically relevant reduction in the primary outcome. The diverse population characteristics of enrollees will tend to make this study’s findings applicable to many primary care patients.

OUTCOMES MEASURED: The primary outcome was the combined end point of myocardial infarction, stroke, or cardiovascular death while secondary outcomes were death from any cause, worsening congestive heart failure, unstable angina, complications associated with diabetes, or any of the individual primary end points.

RESULTS: There were no significant differences in primary or secondary outcomes between the vitamin E group and the placebo group. No differences in primary and secondary outcomes were revealed when analyzing patient subgroups defined by sex, age, previous cardiovascular disease, medication use, diabetes, tobacco use, or ramipril versus placebo use. There was also no increase in the rate of adverse effects with the vitamin E group, in particular with respect to hemorrhagic stroke.

CLINICAL QUESTION: Does vitamin E supplementation play a role in the secondary prevention of cardiovascular events in high-risk patients?

BACKGROUND: The role of the antioxidant vitamin E in primary and secondary prevention of cardiovascular disease is unclear. Observational studies suggest that vitamin E may slow the development and progression of atherosclerosis. Four published randomized controlled trials reached differing conclusions that may be partly attributed to different study designs. This investigation, as part of the Heart Outcomes Prevention Evaluation (HOPE) study, evaluates the utility of vitamin E in secondary prevention in high-risk cardiovascular patients.

POPULATION STUDIED: This study enrolled 10,576 individuals aged 55 years and older from more than 200 outpatient centers on 3 continents. Enrolled patients had known coronary artery disease, stroke, or peripheral vascular disease. Patients were also enrolled if they had diabetes and one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, tobacco use, or microalbuminuria. Exclusion criteria included a known ejection fraction of less than 40%, currently taking an angiotensin-converting enzyme (ACE) inhibitor or vitamin E, having uncontrolled hypertension or overt nephropathy, or a history of myocardial infarction or stroke within 4 weeks of enrollment. Approximately 25% of the patients were women.

STUDY DESIGN AND VALIDITY: This study was designed to test the effect of vitamin E and ramipril on cardiovascular events in high-risk patients. The authors of this study report only the RESULTS: for vitamin E. Before randomization an initial run-in period with a low dose of ramipril eliminated more than 1000 participants because of noncompliance, medication side effects, or abnormal serum creatinine or potassium levels. In an adequately concealed fashion, 9541 patients were randomized in a double-blinded fashion to either 400 IU of vitamin E from natural sources or placebo. They were followed for a mean of 4.5 years with evaluation every 6 months. The vitamin E group had 89% compliance at 5 years. The study was discontinued early because of the significant benefit demonstrated in the ramipril arm (see next POEM). The study had adequate power to detect a clinically relevant reduction in the primary outcome. The diverse population characteristics of enrollees will tend to make this study’s findings applicable to many primary care patients.

OUTCOMES MEASURED: The primary outcome was the combined end point of myocardial infarction, stroke, or cardiovascular death while secondary outcomes were death from any cause, worsening congestive heart failure, unstable angina, complications associated with diabetes, or any of the individual primary end points.

RESULTS: There were no significant differences in primary or secondary outcomes between the vitamin E group and the placebo group. No differences in primary and secondary outcomes were revealed when analyzing patient subgroups defined by sex, age, previous cardiovascular disease, medication use, diabetes, tobacco use, or ramipril versus placebo use. There was also no increase in the rate of adverse effects with the vitamin E group, in particular with respect to hemorrhagic stroke.