Q&A

BACKGROUND: An effective pneumococcal vaccine could reduce the incidence of otitis media caused by the most common bacterial pathogen, Streptococcus pneumoniae.

POPULATION STUDIED: Researchers from the Finnish Otitis Media Vaccine Trial recruited infants from prenatal and child health centers in 3 communities in Finland. The 2497 infants enrolled in the study from December 1995 through April 1997 represented 55% of the eligible children in the study communities and were therefore similar to a primary care population. This analysis studied 1662 of the enrolled children; 831 infants were assigned to receive the pneumococcal vaccine and another 831 to receive the hepatitis B vaccine as a control. Totals of 786 (94.6%) in the pneumococcal vaccine group and 794 (95.5%) in the control vaccine group completed the study. The remaining 835 were assigned to receive a different pneumococcal vaccine and were not included in this analysis.

STUDY DESIGN AND VALIDITY: The study was a prospective randomized double-blind cohort study. Allocation concealment was not specified. Infants were randomized to receive either the heptavalent pneumococcal-CRM197 conjugate vaccine or the control hepatitis B vaccine at the age of 2, 4, 6, and 12 months. They were also given a combined diphtheria-tetanus-pertussis and Haemophilus influenzae type b (DTP-Hib) vaccine at 2, 4, and 6 months, inactivated polio vaccine at 7 and 12 months, and measles-mumps-rubella vaccine at 18 months. Subjects were monitored until they were aged 2 years, and their parents were urged to record adverse reactions and bring their children to the study clinics for symptoms suggestive of respiratory infection or otitis media. Acute otitis media (AOM) was diagnosed according to predefined clinical criteria and confirmed by culture of middle ear fluid obtained by myringotomy with identification of specific bacterial serotypes.

OUTCOMES MEASURED: Researchers measured adverse reactions to the vaccines and episodes of AOM in several overlapping categories: all episodes meeting clinical criteria; culture-confirmed pathogen-specific episodes; episodes due to serotypes included in the vaccine, serotypes which cross-react with those serotypes, and other pneumococcal serotypes and groups; episodes due to H influenzae; and episodes due to Moraxella catarrhalis. They followed strict definitions for separate episodes in the same study subject and for recurrent otitis media.

RESULTS: Among the 1662 subjects, there were 2596 episodes of clinical AOM during the follow-up. The vaccine did not reduce the overall number of episodes of AOM. The vaccine reduced the number of all culture-confirmed pneumococcal episodes by 34% (95% confidence interval [CI], 21%-45%; number needed to treat=6). It reduced episodes due to serotypes contained in the vaccine and to serotypes that cross-react with those in the vaccine by 57% and 51%, respectively. Because 95% of enrolled subjects completed the study, intention-to-treat analysis produced similar results.

BACKGROUND: An effective pneumococcal vaccine could reduce the incidence of otitis media caused by the most common bacterial pathogen, Streptococcus pneumoniae.

POPULATION STUDIED: Researchers from the Finnish Otitis Media Vaccine Trial recruited infants from prenatal and child health centers in 3 communities in Finland. The 2497 infants enrolled in the study from December 1995 through April 1997 represented 55% of the eligible children in the study communities and were therefore similar to a primary care population. This analysis studied 1662 of the enrolled children; 831 infants were assigned to receive the pneumococcal vaccine and another 831 to receive the hepatitis B vaccine as a control. Totals of 786 (94.6%) in the pneumococcal vaccine group and 794 (95.5%) in the control vaccine group completed the study. The remaining 835 were assigned to receive a different pneumococcal vaccine and were not included in this analysis.

STUDY DESIGN AND VALIDITY: The study was a prospective randomized double-blind cohort study. Allocation concealment was not specified. Infants were randomized to receive either the heptavalent pneumococcal-CRM197 conjugate vaccine or the control hepatitis B vaccine at the age of 2, 4, 6, and 12 months. They were also given a combined diphtheria-tetanus-pertussis and Haemophilus influenzae type b (DTP-Hib) vaccine at 2, 4, and 6 months, inactivated polio vaccine at 7 and 12 months, and measles-mumps-rubella vaccine at 18 months. Subjects were monitored until they were aged 2 years, and their parents were urged to record adverse reactions and bring their children to the study clinics for symptoms suggestive of respiratory infection or otitis media. Acute otitis media (AOM) was diagnosed according to predefined clinical criteria and confirmed by culture of middle ear fluid obtained by myringotomy with identification of specific bacterial serotypes.

OUTCOMES MEASURED: Researchers measured adverse reactions to the vaccines and episodes of AOM in several overlapping categories: all episodes meeting clinical criteria; culture-confirmed pathogen-specific episodes; episodes due to serotypes included in the vaccine, serotypes which cross-react with those serotypes, and other pneumococcal serotypes and groups; episodes due to H influenzae; and episodes due to Moraxella catarrhalis. They followed strict definitions for separate episodes in the same study subject and for recurrent otitis media.

RESULTS: Among the 1662 subjects, there were 2596 episodes of clinical AOM during the follow-up. The vaccine did not reduce the overall number of episodes of AOM. The vaccine reduced the number of all culture-confirmed pneumococcal episodes by 34% (95% confidence interval [CI], 21%-45%; number needed to treat=6). It reduced episodes due to serotypes contained in the vaccine and to serotypes that cross-react with those in the vaccine by 57% and 51%, respectively. Because 95% of enrolled subjects completed the study, intention-to-treat analysis produced similar results.

BACKGROUND: An effective pneumococcal vaccine could reduce the incidence of otitis media caused by the most common bacterial pathogen, Streptococcus pneumoniae.

POPULATION STUDIED: Researchers from the Finnish Otitis Media Vaccine Trial recruited infants from prenatal and child health centers in 3 communities in Finland. The 2497 infants enrolled in the study from December 1995 through April 1997 represented 55% of the eligible children in the study communities and were therefore similar to a primary care population. This analysis studied 1662 of the enrolled children; 831 infants were assigned to receive the pneumococcal vaccine and another 831 to receive the hepatitis B vaccine as a control. Totals of 786 (94.6%) in the pneumococcal vaccine group and 794 (95.5%) in the control vaccine group completed the study. The remaining 835 were assigned to receive a different pneumococcal vaccine and were not included in this analysis.

STUDY DESIGN AND VALIDITY: The study was a prospective randomized double-blind cohort study. Allocation concealment was not specified. Infants were randomized to receive either the heptavalent pneumococcal-CRM197 conjugate vaccine or the control hepatitis B vaccine at the age of 2, 4, 6, and 12 months. They were also given a combined diphtheria-tetanus-pertussis and Haemophilus influenzae type b (DTP-Hib) vaccine at 2, 4, and 6 months, inactivated polio vaccine at 7 and 12 months, and measles-mumps-rubella vaccine at 18 months. Subjects were monitored until they were aged 2 years, and their parents were urged to record adverse reactions and bring their children to the study clinics for symptoms suggestive of respiratory infection or otitis media. Acute otitis media (AOM) was diagnosed according to predefined clinical criteria and confirmed by culture of middle ear fluid obtained by myringotomy with identification of specific bacterial serotypes.

OUTCOMES MEASURED: Researchers measured adverse reactions to the vaccines and episodes of AOM in several overlapping categories: all episodes meeting clinical criteria; culture-confirmed pathogen-specific episodes; episodes due to serotypes included in the vaccine, serotypes which cross-react with those serotypes, and other pneumococcal serotypes and groups; episodes due to H influenzae; and episodes due to Moraxella catarrhalis. They followed strict definitions for separate episodes in the same study subject and for recurrent otitis media.

RESULTS: Among the 1662 subjects, there were 2596 episodes of clinical AOM during the follow-up. The vaccine did not reduce the overall number of episodes of AOM. The vaccine reduced the number of all culture-confirmed pneumococcal episodes by 34% (95% confidence interval [CI], 21%-45%; number needed to treat=6). It reduced episodes due to serotypes contained in the vaccine and to serotypes that cross-react with those in the vaccine by 57% and 51%, respectively. Because 95% of enrolled subjects completed the study, intention-to-treat analysis produced similar results.

BACKGROUND: Traditional treatments for osteoarthritis, including acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids all have potentially serious side effects and do not affect the progression of the disease. Glucosamine sulfate shows promising short-term positive effects on symptoms and quality of life, but the long-term effects on the progression of osteoatrhritis are unknown.

POPULATION STUDIED: The investigators in Belgium enrolled 212 patients older than 50 years with established mild to moderate osteoarthritis of the medial tibiofemoral compartment of the knee and similar mild to moderate symptom severity. Patients were not enrolled if they had other rheumatologic diseases, severe articular inflammation, traumatic knee lesions, a body mass index greater than 30, or if they received corticosteroids in the 3 months preceding enrollment. The demographics of both groups were similar at the start and the end of the study and reflect patients commonly seen in a primary care setting.

STUDY DESIGN AND VALIDITY: Patients in this study were randomized to receive either placebo or 1500 mg glucosamine sulfate daily for 3 years. Rescue analgesia (acetaminophen or NSAIDs) was allowed in both groups. Weight-bearing antero-posterior radiographs of each knee were taken at baseline and 1 and 3 years after the start of the study. The mean joint-space width of the medial and lateral compartments of the tibiofemoral joint was measured by a single independent blinded reader. A visual analog scale version of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index was used to assess the severity of joint pain, stiffness, and limitation of physical function. Results for patients who dropped out of the study were calculated by either extrapolating their data forward or by assigning values for the average joint-space change of the placebo group who did finish (worst-case scenario).

OUTCOMES MEASURED: The primary outcome was the mean joint-space change of the medial compartment of the tibiofemoral joint and change in the total WOMAC index of pain, stiffness, and functional mobility after 3 years. Secondary outcomes included use of rescue medications, withdrawal rates, and adverse effects.

RESULTS: Of the 355 patients screened, 212 were enrolled and randomly assigned to receive glucosamine sulfate or placebo. Withdrawals were similar in both groups, and patients in both groups showed more than 70% compliance with study treatment. The mean joint-space change was -0.31 mm narrowing in the placebo group and 0.07 mm improvement in the glucosamine sulfate group (0.38 mm difference; 95% confidence interval, 0.02-0.73 mm). Compared with baseline WOMAC index values, symptoms worsened in the placebo group and improved in the glucosamine sulfate group (9.8% decline vs 24.3%, improvement; P=.016). The most significant changes were in pain and function. Change in stiffness was similar in both groups. However, symptom improvement did not correlate with joint-space change, with some patients in the glucosamine sulfate group showing an improvement of symptoms and worsened joint-space narrowing. Use of rescue analgesia, adverse events, and withdrawal from the study were similar in both groups.

BACKGROUND: Traditional treatments for osteoarthritis, including acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids all have potentially serious side effects and do not affect the progression of the disease. Glucosamine sulfate shows promising short-term positive effects on symptoms and quality of life, but the long-term effects on the progression of osteoatrhritis are unknown.

POPULATION STUDIED: The investigators in Belgium enrolled 212 patients older than 50 years with established mild to moderate osteoarthritis of the medial tibiofemoral compartment of the knee and similar mild to moderate symptom severity. Patients were not enrolled if they had other rheumatologic diseases, severe articular inflammation, traumatic knee lesions, a body mass index greater than 30, or if they received corticosteroids in the 3 months preceding enrollment. The demographics of both groups were similar at the start and the end of the study and reflect patients commonly seen in a primary care setting.

STUDY DESIGN AND VALIDITY: Patients in this study were randomized to receive either placebo or 1500 mg glucosamine sulfate daily for 3 years. Rescue analgesia (acetaminophen or NSAIDs) was allowed in both groups. Weight-bearing antero-posterior radiographs of each knee were taken at baseline and 1 and 3 years after the start of the study. The mean joint-space width of the medial and lateral compartments of the tibiofemoral joint was measured by a single independent blinded reader. A visual analog scale version of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index was used to assess the severity of joint pain, stiffness, and limitation of physical function. Results for patients who dropped out of the study were calculated by either extrapolating their data forward or by assigning values for the average joint-space change of the placebo group who did finish (worst-case scenario).

OUTCOMES MEASURED: The primary outcome was the mean joint-space change of the medial compartment of the tibiofemoral joint and change in the total WOMAC index of pain, stiffness, and functional mobility after 3 years. Secondary outcomes included use of rescue medications, withdrawal rates, and adverse effects.

RESULTS: Of the 355 patients screened, 212 were enrolled and randomly assigned to receive glucosamine sulfate or placebo. Withdrawals were similar in both groups, and patients in both groups showed more than 70% compliance with study treatment. The mean joint-space change was -0.31 mm narrowing in the placebo group and 0.07 mm improvement in the glucosamine sulfate group (0.38 mm difference; 95% confidence interval, 0.02-0.73 mm). Compared with baseline WOMAC index values, symptoms worsened in the placebo group and improved in the glucosamine sulfate group (9.8% decline vs 24.3%, improvement; P=.016). The most significant changes were in pain and function. Change in stiffness was similar in both groups. However, symptom improvement did not correlate with joint-space change, with some patients in the glucosamine sulfate group showing an improvement of symptoms and worsened joint-space narrowing. Use of rescue analgesia, adverse events, and withdrawal from the study were similar in both groups.

BACKGROUND: Traditional treatments for osteoarthritis, including acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids all have potentially serious side effects and do not affect the progression of the disease. Glucosamine sulfate shows promising short-term positive effects on symptoms and quality of life, but the long-term effects on the progression of osteoatrhritis are unknown.

POPULATION STUDIED: The investigators in Belgium enrolled 212 patients older than 50 years with established mild to moderate osteoarthritis of the medial tibiofemoral compartment of the knee and similar mild to moderate symptom severity. Patients were not enrolled if they had other rheumatologic diseases, severe articular inflammation, traumatic knee lesions, a body mass index greater than 30, or if they received corticosteroids in the 3 months preceding enrollment. The demographics of both groups were similar at the start and the end of the study and reflect patients commonly seen in a primary care setting.

STUDY DESIGN AND VALIDITY: Patients in this study were randomized to receive either placebo or 1500 mg glucosamine sulfate daily for 3 years. Rescue analgesia (acetaminophen or NSAIDs) was allowed in both groups. Weight-bearing antero-posterior radiographs of each knee were taken at baseline and 1 and 3 years after the start of the study. The mean joint-space width of the medial and lateral compartments of the tibiofemoral joint was measured by a single independent blinded reader. A visual analog scale version of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index was used to assess the severity of joint pain, stiffness, and limitation of physical function. Results for patients who dropped out of the study were calculated by either extrapolating their data forward or by assigning values for the average joint-space change of the placebo group who did finish (worst-case scenario).

OUTCOMES MEASURED: The primary outcome was the mean joint-space change of the medial compartment of the tibiofemoral joint and change in the total WOMAC index of pain, stiffness, and functional mobility after 3 years. Secondary outcomes included use of rescue medications, withdrawal rates, and adverse effects.

RESULTS: Of the 355 patients screened, 212 were enrolled and randomly assigned to receive glucosamine sulfate or placebo. Withdrawals were similar in both groups, and patients in both groups showed more than 70% compliance with study treatment. The mean joint-space change was -0.31 mm narrowing in the placebo group and 0.07 mm improvement in the glucosamine sulfate group (0.38 mm difference; 95% confidence interval, 0.02-0.73 mm). Compared with baseline WOMAC index values, symptoms worsened in the placebo group and improved in the glucosamine sulfate group (9.8% decline vs 24.3%, improvement; P=.016). The most significant changes were in pain and function. Change in stiffness was similar in both groups. However, symptom improvement did not correlate with joint-space change, with some patients in the glucosamine sulfate group showing an improvement of symptoms and worsened joint-space narrowing. Use of rescue analgesia, adverse events, and withdrawal from the study were similar in both groups.

BACKGROUND: The upper respiratory tract is usually colonized by nonpathogenic bacteria that provide a protective effect against the organisms that cause otitis media and pharyngotonsillitis. Alpha-streptococci isolated from normal pharyngeal flora inhibit the growth of Group A b-hemolytic streptococcus (GAS) in vitro and prevent recurrence of GAS pharyngitis. Similarly, healthy children have higher levels of inhibitory a-streptococci compared with children prone to otitis media. This investigation sought to determine whether recolonization of the nasopharynx with a nasal spray of a-streptococci prevents the recurrence of otitis media in children.

POPULATION STUDIED: Three ear, nose, and throat (ENT) physicians enrolled 132 children with recurrent otitis media aged between 6 months and 6 years at an outpatient specialty clinic in Sweden. Each child had at least 2 episodes of otitis media in the previous 6 months or 5 episodes in the last year. When such children presented with acute otitis media, they were enrolled in the study and began a 10-day course of antibiotics. Children were excluded from the study if they had penicillin allergy, pressure equalizing tubes, chronic otitis media, serious underlying disease, or major oral lesions.

STUDY DESIGN AND VALIDITY: After completing the 10-day course of penicillin V or amoxicillin clavulanic acid, the children were randomized to receive either a nasal spray made with 5 strains of a-streptococci or a placebo spray. Parents gave their children 3 puffs of spray in each nostril twice daily for 10 days. At day 60, a second course of spray was administered. Subjects were followed up for 3 months. Of 132 children enrolled, 108 (82%) were eligible for analysis of efficacy (using at least 50% of their sprays). The authors used concealed allocation; their randomization worked well; and the follow-up was satisfactory.

OUTCOMES MEASURED: Each subject had 5 scheduled visits to the ENT specialist during the course of the investigation. At each visit a detailed inspection of the tympanic membrane was performed using otomicroscopy. The clinical response to treatment was classified as cured, improved, secretory (serous) otitis media, or recurrent (acute otitis media). The main outcome measures were recurrence of otitis media and presence of a normal tympanic membrane at the last visit.

RESULTS: Children who received the a-streptococcal spray had a significant reduction in recurrence of otitis media compared with those receiving placebo. During the investigation, 42% of the subjects who received the a-streptococcal spray experienced no acute otitis media and had normal tympanic membranes at the last visit compared with 22% of the placebo group (adjusted relative risk [ARR]=20%; 95% confidence interval [CI], 2.8%-37%; number needed to treat [NNT]=5). There were fewer children in the treated group with secretory otitis media at the last visit (ARR=9%; 95% CI, 6.5%-28.5%; NNT=11). Side effects were roughly the same in both groups; the only patients who dropped out because of adverse effects were in the placebo group.

BACKGROUND: The upper respiratory tract is usually colonized by nonpathogenic bacteria that provide a protective effect against the organisms that cause otitis media and pharyngotonsillitis. Alpha-streptococci isolated from normal pharyngeal flora inhibit the growth of Group A b-hemolytic streptococcus (GAS) in vitro and prevent recurrence of GAS pharyngitis. Similarly, healthy children have higher levels of inhibitory a-streptococci compared with children prone to otitis media. This investigation sought to determine whether recolonization of the nasopharynx with a nasal spray of a-streptococci prevents the recurrence of otitis media in children.

POPULATION STUDIED: Three ear, nose, and throat (ENT) physicians enrolled 132 children with recurrent otitis media aged between 6 months and 6 years at an outpatient specialty clinic in Sweden. Each child had at least 2 episodes of otitis media in the previous 6 months or 5 episodes in the last year. When such children presented with acute otitis media, they were enrolled in the study and began a 10-day course of antibiotics. Children were excluded from the study if they had penicillin allergy, pressure equalizing tubes, chronic otitis media, serious underlying disease, or major oral lesions.

STUDY DESIGN AND VALIDITY: After completing the 10-day course of penicillin V or amoxicillin clavulanic acid, the children were randomized to receive either a nasal spray made with 5 strains of a-streptococci or a placebo spray. Parents gave their children 3 puffs of spray in each nostril twice daily for 10 days. At day 60, a second course of spray was administered. Subjects were followed up for 3 months. Of 132 children enrolled, 108 (82%) were eligible for analysis of efficacy (using at least 50% of their sprays). The authors used concealed allocation; their randomization worked well; and the follow-up was satisfactory.

OUTCOMES MEASURED: Each subject had 5 scheduled visits to the ENT specialist during the course of the investigation. At each visit a detailed inspection of the tympanic membrane was performed using otomicroscopy. The clinical response to treatment was classified as cured, improved, secretory (serous) otitis media, or recurrent (acute otitis media). The main outcome measures were recurrence of otitis media and presence of a normal tympanic membrane at the last visit.

RESULTS: Children who received the a-streptococcal spray had a significant reduction in recurrence of otitis media compared with those receiving placebo. During the investigation, 42% of the subjects who received the a-streptococcal spray experienced no acute otitis media and had normal tympanic membranes at the last visit compared with 22% of the placebo group (adjusted relative risk [ARR]=20%; 95% confidence interval [CI], 2.8%-37%; number needed to treat [NNT]=5). There were fewer children in the treated group with secretory otitis media at the last visit (ARR=9%; 95% CI, 6.5%-28.5%; NNT=11). Side effects were roughly the same in both groups; the only patients who dropped out because of adverse effects were in the placebo group.

BACKGROUND: The upper respiratory tract is usually colonized by nonpathogenic bacteria that provide a protective effect against the organisms that cause otitis media and pharyngotonsillitis. Alpha-streptococci isolated from normal pharyngeal flora inhibit the growth of Group A b-hemolytic streptococcus (GAS) in vitro and prevent recurrence of GAS pharyngitis. Similarly, healthy children have higher levels of inhibitory a-streptococci compared with children prone to otitis media. This investigation sought to determine whether recolonization of the nasopharynx with a nasal spray of a-streptococci prevents the recurrence of otitis media in children.

POPULATION STUDIED: Three ear, nose, and throat (ENT) physicians enrolled 132 children with recurrent otitis media aged between 6 months and 6 years at an outpatient specialty clinic in Sweden. Each child had at least 2 episodes of otitis media in the previous 6 months or 5 episodes in the last year. When such children presented with acute otitis media, they were enrolled in the study and began a 10-day course of antibiotics. Children were excluded from the study if they had penicillin allergy, pressure equalizing tubes, chronic otitis media, serious underlying disease, or major oral lesions.

STUDY DESIGN AND VALIDITY: After completing the 10-day course of penicillin V or amoxicillin clavulanic acid, the children were randomized to receive either a nasal spray made with 5 strains of a-streptococci or a placebo spray. Parents gave their children 3 puffs of spray in each nostril twice daily for 10 days. At day 60, a second course of spray was administered. Subjects were followed up for 3 months. Of 132 children enrolled, 108 (82%) were eligible for analysis of efficacy (using at least 50% of their sprays). The authors used concealed allocation; their randomization worked well; and the follow-up was satisfactory.

OUTCOMES MEASURED: Each subject had 5 scheduled visits to the ENT specialist during the course of the investigation. At each visit a detailed inspection of the tympanic membrane was performed using otomicroscopy. The clinical response to treatment was classified as cured, improved, secretory (serous) otitis media, or recurrent (acute otitis media). The main outcome measures were recurrence of otitis media and presence of a normal tympanic membrane at the last visit.

RESULTS: Children who received the a-streptococcal spray had a significant reduction in recurrence of otitis media compared with those receiving placebo. During the investigation, 42% of the subjects who received the a-streptococcal spray experienced no acute otitis media and had normal tympanic membranes at the last visit compared with 22% of the placebo group (adjusted relative risk [ARR]=20%; 95% confidence interval [CI], 2.8%-37%; number needed to treat [NNT]=5). There were fewer children in the treated group with secretory otitis media at the last visit (ARR=9%; 95% CI, 6.5%-28.5%; NNT=11). Side effects were roughly the same in both groups; the only patients who dropped out because of adverse effects were in the placebo group.

BACKGROUND: There is no consensus concerning the frequency of screening Pap tests in postmenopausal women. High false-positive rates for abnormal test results in this group increase cost, risk, and discomfort of invasive procedures, and anxiety. In postmenopausal women, the majority of abnormal Pap test results are composed of atyptical squamous cells of uncertain significance (ASCUS) and data conflict as to whether hormone replacement therapy (HRT) has any effect on its development.

POPULATION STUDIED: From 20 outpatient clinical centers, 2561 postmenopausal women were recruited from screening interviews of 68,561 women. The criteria for entering the study were age younger than 80 years, an intact uterus, and a normal Pap test result at baseline. The mean age was 66.7 years, and all had coronary artery disease.

STUDY DESIGN AND VALIDITY: This is a 2-part study using a prospective cohort design to calculate the incidence of cytologic abnormalities and a randomized double-blinded placebo-controlled design to evaluate the effect of HRT. Cervical tests were performed annually in participating clinics, with all tests evaluated at the same central pathology laboratory. Abnormal Pap test results were managed in the conventional manner. For each cytologic abnormality the final histologic diagnosis was considered normal only if all follow-up tests were normal or proved negative by colposcopy. In a second aspect of the study, the participants were randomly assigned to receive placebo or the combination of oral conjugated equine estrogens 0.625 mg plus medroxy- progesterone acetate 2.5 mg daily.

OUTCOMES MEASURED: The primary outcomes were the incidence over 2 years of new cervical cytologic abnormalities (ASCUS, atypical glandular cells of undetermined significance [AGCUS], low-grade squamous intraepithelial lesion [LGSIL], and high-grade squamous intraepithelial lesion [HGSIL]), and final histologic diagnoses, with the main outcome being the actual diagnosis of cervical cancer.

RESULTS: The incidence of new cytologic abnormalities in the first year was 78 women (3%), and in the second year there were an additional 32 women (1.4%). The total incidence of abnormal Pap results for the 2 years following a normal test was 110, or 2.3%. Most of Pap abnormalities were reported as ASCUS (67.3%) or AGCUS (21%); 10.9% were LGSIL; and 0.9% were HGSIL. More important, no women in the first year were found to have high-grade cervical intraepithelial neoplasia (CIN). In the second year, one patient had a CIN grade 1 or 2 lesion. Therefore, the positive predictive value of any abnormal test identified 1 year after an initial normal test was 0% (95% confidence interval [CI], 0%-5%) and within 2 years was 0.9% (95% CI, 0%-3%). Hormone therapy did not show any significant effect on the incidence of cervical cytologic abnormalities.

BACKGROUND: There is no consensus concerning the frequency of screening Pap tests in postmenopausal women. High false-positive rates for abnormal test results in this group increase cost, risk, and discomfort of invasive procedures, and anxiety. In postmenopausal women, the majority of abnormal Pap test results are composed of atyptical squamous cells of uncertain significance (ASCUS) and data conflict as to whether hormone replacement therapy (HRT) has any effect on its development.

POPULATION STUDIED: From 20 outpatient clinical centers, 2561 postmenopausal women were recruited from screening interviews of 68,561 women. The criteria for entering the study were age younger than 80 years, an intact uterus, and a normal Pap test result at baseline. The mean age was 66.7 years, and all had coronary artery disease.

STUDY DESIGN AND VALIDITY: This is a 2-part study using a prospective cohort design to calculate the incidence of cytologic abnormalities and a randomized double-blinded placebo-controlled design to evaluate the effect of HRT. Cervical tests were performed annually in participating clinics, with all tests evaluated at the same central pathology laboratory. Abnormal Pap test results were managed in the conventional manner. For each cytologic abnormality the final histologic diagnosis was considered normal only if all follow-up tests were normal or proved negative by colposcopy. In a second aspect of the study, the participants were randomly assigned to receive placebo or the combination of oral conjugated equine estrogens 0.625 mg plus medroxy- progesterone acetate 2.5 mg daily.

OUTCOMES MEASURED: The primary outcomes were the incidence over 2 years of new cervical cytologic abnormalities (ASCUS, atypical glandular cells of undetermined significance [AGCUS], low-grade squamous intraepithelial lesion [LGSIL], and high-grade squamous intraepithelial lesion [HGSIL]), and final histologic diagnoses, with the main outcome being the actual diagnosis of cervical cancer.

RESULTS: The incidence of new cytologic abnormalities in the first year was 78 women (3%), and in the second year there were an additional 32 women (1.4%). The total incidence of abnormal Pap results for the 2 years following a normal test was 110, or 2.3%. Most of Pap abnormalities were reported as ASCUS (67.3%) or AGCUS (21%); 10.9% were LGSIL; and 0.9% were HGSIL. More important, no women in the first year were found to have high-grade cervical intraepithelial neoplasia (CIN). In the second year, one patient had a CIN grade 1 or 2 lesion. Therefore, the positive predictive value of any abnormal test identified 1 year after an initial normal test was 0% (95% confidence interval [CI], 0%-5%) and within 2 years was 0.9% (95% CI, 0%-3%). Hormone therapy did not show any significant effect on the incidence of cervical cytologic abnormalities.

BACKGROUND: There is no consensus concerning the frequency of screening Pap tests in postmenopausal women. High false-positive rates for abnormal test results in this group increase cost, risk, and discomfort of invasive procedures, and anxiety. In postmenopausal women, the majority of abnormal Pap test results are composed of atyptical squamous cells of uncertain significance (ASCUS) and data conflict as to whether hormone replacement therapy (HRT) has any effect on its development.

POPULATION STUDIED: From 20 outpatient clinical centers, 2561 postmenopausal women were recruited from screening interviews of 68,561 women. The criteria for entering the study were age younger than 80 years, an intact uterus, and a normal Pap test result at baseline. The mean age was 66.7 years, and all had coronary artery disease.

STUDY DESIGN AND VALIDITY: This is a 2-part study using a prospective cohort design to calculate the incidence of cytologic abnormalities and a randomized double-blinded placebo-controlled design to evaluate the effect of HRT. Cervical tests were performed annually in participating clinics, with all tests evaluated at the same central pathology laboratory. Abnormal Pap test results were managed in the conventional manner. For each cytologic abnormality the final histologic diagnosis was considered normal only if all follow-up tests were normal or proved negative by colposcopy. In a second aspect of the study, the participants were randomly assigned to receive placebo or the combination of oral conjugated equine estrogens 0.625 mg plus medroxy- progesterone acetate 2.5 mg daily.

OUTCOMES MEASURED: The primary outcomes were the incidence over 2 years of new cervical cytologic abnormalities (ASCUS, atypical glandular cells of undetermined significance [AGCUS], low-grade squamous intraepithelial lesion [LGSIL], and high-grade squamous intraepithelial lesion [HGSIL]), and final histologic diagnoses, with the main outcome being the actual diagnosis of cervical cancer.

RESULTS: The incidence of new cytologic abnormalities in the first year was 78 women (3%), and in the second year there were an additional 32 women (1.4%). The total incidence of abnormal Pap results for the 2 years following a normal test was 110, or 2.3%. Most of Pap abnormalities were reported as ASCUS (67.3%) or AGCUS (21%); 10.9% were LGSIL; and 0.9% were HGSIL. More important, no women in the first year were found to have high-grade cervical intraepithelial neoplasia (CIN). In the second year, one patient had a CIN grade 1 or 2 lesion. Therefore, the positive predictive value of any abnormal test identified 1 year after an initial normal test was 0% (95% confidence interval [CI], 0%-5%) and within 2 years was 0.9% (95% CI, 0%-3%). Hormone therapy did not show any significant effect on the incidence of cervical cytologic abnormalities.

BACKGROUND: Bilateral prophylactic mastectomy can significantly reduce the risk of breast cancer in women at increased risk, but little is known about the psychological impact of this surgery. The authors of this study designed a prospective analysis of the psychosocial implications of prophylactic surgery for breast cancer.

POPULATION STUDIED: Women at increased risk for developing breast cancer who had been offered bilateral prophylactic mastectomy were referred to the researchers from 20 centers throughout the United Kingdom. A total of 168 women were referred after meeting the eligibility criteria consisting of family history of breast cancer or high risk of developing breast cancer. The researchers did not know the risk level used by the referring clinicians to select patients. More than 73% of both groups were employed, and more than 75% had children. Ethnicity and education level were not reported.

STUDY DESIGN AND VALIDITY: The authors conducted a prospective nonrandomized controlled trial using 6 validated questionnaires to assess the psychological morbidity, anxiety state, sexual activity, coping strategies, risk perception, and body image of the study participants. Women accepting surgery were interviewed at the time of referral and at 6 and 18 months postoperatively. Those declining surgery were interviewed at referral and 18 months later. Of the 168 women, 11 were lost to contact before completing the assessment. Of the 154 remaining participants, 79 (51%) chose surgery; 64 (42%) declined; and 11 (7%) chose to defer their decision making and were not included in the analysis.

OUTCOMES MEASURED: This study involved a comparison of the psychological and sexual morbidity in women having prophylactic mastectomy with those who were offered the surgery but declined.

RESULTS: Psychological morbidity decreased significantly (P <.001) over time in the group accepting surgery, as measured by the “General health questionnaire 30,” a tool used to determine psychiatric morbidity in outpatients. Those who declined showed no change in psychiatric morbidity over the 18 months. Anxiety scores declined significantly over this time period for those who accepted (P=.001) but remained unchanged for those who declined. A significantly higher proportion of those who declined had high baseline anxiety (P=.006), and their anxiety levels remained high at the 18-month follow-up. Those who accepted tended to use a problem-focused approach to coping, while those who declined tended to use a detached style of coping. Sexual activity and sexual discomfort did not change significantly over time in either group, and it did not differ between the groups. Body image was not different in either group (most women who had surgery had immediate breast reconstruction). A risk perception questionnaire revealed that those who accepted had a significantly higher (32% vs 10%, P=.001) belief that it was inevitable that they would develop breast cancer. More than half of those who accepted felt they had at least a 50-50 chance of developing cancer (their actual likelihood was much lower).

BACKGROUND: Bilateral prophylactic mastectomy can significantly reduce the risk of breast cancer in women at increased risk, but little is known about the psychological impact of this surgery. The authors of this study designed a prospective analysis of the psychosocial implications of prophylactic surgery for breast cancer.

POPULATION STUDIED: Women at increased risk for developing breast cancer who had been offered bilateral prophylactic mastectomy were referred to the researchers from 20 centers throughout the United Kingdom. A total of 168 women were referred after meeting the eligibility criteria consisting of family history of breast cancer or high risk of developing breast cancer. The researchers did not know the risk level used by the referring clinicians to select patients. More than 73% of both groups were employed, and more than 75% had children. Ethnicity and education level were not reported.

STUDY DESIGN AND VALIDITY: The authors conducted a prospective nonrandomized controlled trial using 6 validated questionnaires to assess the psychological morbidity, anxiety state, sexual activity, coping strategies, risk perception, and body image of the study participants. Women accepting surgery were interviewed at the time of referral and at 6 and 18 months postoperatively. Those declining surgery were interviewed at referral and 18 months later. Of the 168 women, 11 were lost to contact before completing the assessment. Of the 154 remaining participants, 79 (51%) chose surgery; 64 (42%) declined; and 11 (7%) chose to defer their decision making and were not included in the analysis.

OUTCOMES MEASURED: This study involved a comparison of the psychological and sexual morbidity in women having prophylactic mastectomy with those who were offered the surgery but declined.

RESULTS: Psychological morbidity decreased significantly (P <.001) over time in the group accepting surgery, as measured by the “General health questionnaire 30,” a tool used to determine psychiatric morbidity in outpatients. Those who declined showed no change in psychiatric morbidity over the 18 months. Anxiety scores declined significantly over this time period for those who accepted (P=.001) but remained unchanged for those who declined. A significantly higher proportion of those who declined had high baseline anxiety (P=.006), and their anxiety levels remained high at the 18-month follow-up. Those who accepted tended to use a problem-focused approach to coping, while those who declined tended to use a detached style of coping. Sexual activity and sexual discomfort did not change significantly over time in either group, and it did not differ between the groups. Body image was not different in either group (most women who had surgery had immediate breast reconstruction). A risk perception questionnaire revealed that those who accepted had a significantly higher (32% vs 10%, P=.001) belief that it was inevitable that they would develop breast cancer. More than half of those who accepted felt they had at least a 50-50 chance of developing cancer (their actual likelihood was much lower).

BACKGROUND: Bilateral prophylactic mastectomy can significantly reduce the risk of breast cancer in women at increased risk, but little is known about the psychological impact of this surgery. The authors of this study designed a prospective analysis of the psychosocial implications of prophylactic surgery for breast cancer.

POPULATION STUDIED: Women at increased risk for developing breast cancer who had been offered bilateral prophylactic mastectomy were referred to the researchers from 20 centers throughout the United Kingdom. A total of 168 women were referred after meeting the eligibility criteria consisting of family history of breast cancer or high risk of developing breast cancer. The researchers did not know the risk level used by the referring clinicians to select patients. More than 73% of both groups were employed, and more than 75% had children. Ethnicity and education level were not reported.

STUDY DESIGN AND VALIDITY: The authors conducted a prospective nonrandomized controlled trial using 6 validated questionnaires to assess the psychological morbidity, anxiety state, sexual activity, coping strategies, risk perception, and body image of the study participants. Women accepting surgery were interviewed at the time of referral and at 6 and 18 months postoperatively. Those declining surgery were interviewed at referral and 18 months later. Of the 168 women, 11 were lost to contact before completing the assessment. Of the 154 remaining participants, 79 (51%) chose surgery; 64 (42%) declined; and 11 (7%) chose to defer their decision making and were not included in the analysis.

OUTCOMES MEASURED: This study involved a comparison of the psychological and sexual morbidity in women having prophylactic mastectomy with those who were offered the surgery but declined.

RESULTS: Psychological morbidity decreased significantly (P <.001) over time in the group accepting surgery, as measured by the “General health questionnaire 30,” a tool used to determine psychiatric morbidity in outpatients. Those who declined showed no change in psychiatric morbidity over the 18 months. Anxiety scores declined significantly over this time period for those who accepted (P=.001) but remained unchanged for those who declined. A significantly higher proportion of those who declined had high baseline anxiety (P=.006), and their anxiety levels remained high at the 18-month follow-up. Those who accepted tended to use a problem-focused approach to coping, while those who declined tended to use a detached style of coping. Sexual activity and sexual discomfort did not change significantly over time in either group, and it did not differ between the groups. Body image was not different in either group (most women who had surgery had immediate breast reconstruction). A risk perception questionnaire revealed that those who accepted had a significantly higher (32% vs 10%, P=.001) belief that it was inevitable that they would develop breast cancer. More than half of those who accepted felt they had at least a 50-50 chance of developing cancer (their actual likelihood was much lower).

BACKGROUND: Dyspepsia is a common primary care problem, but optimal management remains unclear. In the past decade, attempts have been made to distinguish subtypes of ulcer-like (nighttime epigastric pain), reflux-like (heartburn, regurgitation), and dysmotility-like (bloating, distention, flatulence, nausea) dyspepsia, but there is overlap among the categories. Also, 50% to 60% of dyspeptic patients fit no single pattern. The authors of this study attempted to define characteristics of patients with dyspepsia who responded to omeprazole.

POPULATION STUDIED: A total of 471 Danish primary care patients aged 18 to 65 years with ulcer-or gastroesophageal reflux (GERD)-like dyspepsia were enrolled. The protocol excluded patients with dysmotility and untypeable dyspepsia, patients with dysmotility and other types of dyspepsia, and those with a history of peptic ulcer disease, reflux esophagitis, alarm symptoms (weight loss, dysphagia, bloody or black stools, anemia, jaundice), or current nonsteroidal anti-inflammatory drug use. The average age was 42 years, with the patients evenly split by sex and smoking status. Approximately half (45%) had experienced symptoms for less than 1 month. On average the patients were slightly overweight, with an average body mass index of 24.6. Thirty-nine percent had used H2-blockers or antacids in the past month, and none had undergone endoscopy or laboratory investigations. Thus, though the clinical characteristics seem similar to patients presenting to family physicians in the United States, generalizations to all patients with dyspepsia should be cautious.

STUDY DESIGN AND VALIDITY: This study is a re-analysis of data from a randomized controlled trial of omeprazole for dyspepsia to determine a clinical prediction rule regarding which patients with dyspepsia will respond to therapy with omeprazole. Patients received omeprazole 20 mg or placebo daily for 2 weeks and were randomly divided into samples used to develop the decision rule (N=236) and to test the rule (n= 235). Logistic regression was used to identify the relationship between specific symptoms and complete response of symptoms to omeprazole. The authors then developed a rule for predicting which dyspeptic patients respond to omeprazole and validated it in the test sample.

OUTCOMES MEASURED: The major outcome was a list of symptoms associated with therapeutic response; these symptoms were used to develop a clinical decision rule to predict response to omeprazole. Patient satisfaction, adverse effects, and cost were not addressed.

RESULTS: High body mass index, nighttime pain, and recent antacid or H2-blocker use predicted a good response to omeprazole, while nausea predicted a poor response. The prediction rule incorporating these variables identified patients likely to respond to omeprazole (number needed to treat=2.6). Validity testing confirmed these findings.

BACKGROUND: Dyspepsia is a common primary care problem, but optimal management remains unclear. In the past decade, attempts have been made to distinguish subtypes of ulcer-like (nighttime epigastric pain), reflux-like (heartburn, regurgitation), and dysmotility-like (bloating, distention, flatulence, nausea) dyspepsia, but there is overlap among the categories. Also, 50% to 60% of dyspeptic patients fit no single pattern. The authors of this study attempted to define characteristics of patients with dyspepsia who responded to omeprazole.

POPULATION STUDIED: A total of 471 Danish primary care patients aged 18 to 65 years with ulcer-or gastroesophageal reflux (GERD)-like dyspepsia were enrolled. The protocol excluded patients with dysmotility and untypeable dyspepsia, patients with dysmotility and other types of dyspepsia, and those with a history of peptic ulcer disease, reflux esophagitis, alarm symptoms (weight loss, dysphagia, bloody or black stools, anemia, jaundice), or current nonsteroidal anti-inflammatory drug use. The average age was 42 years, with the patients evenly split by sex and smoking status. Approximately half (45%) had experienced symptoms for less than 1 month. On average the patients were slightly overweight, with an average body mass index of 24.6. Thirty-nine percent had used H2-blockers or antacids in the past month, and none had undergone endoscopy or laboratory investigations. Thus, though the clinical characteristics seem similar to patients presenting to family physicians in the United States, generalizations to all patients with dyspepsia should be cautious.

STUDY DESIGN AND VALIDITY: This study is a re-analysis of data from a randomized controlled trial of omeprazole for dyspepsia to determine a clinical prediction rule regarding which patients with dyspepsia will respond to therapy with omeprazole. Patients received omeprazole 20 mg or placebo daily for 2 weeks and were randomly divided into samples used to develop the decision rule (N=236) and to test the rule (n= 235). Logistic regression was used to identify the relationship between specific symptoms and complete response of symptoms to omeprazole. The authors then developed a rule for predicting which dyspeptic patients respond to omeprazole and validated it in the test sample.

OUTCOMES MEASURED: The major outcome was a list of symptoms associated with therapeutic response; these symptoms were used to develop a clinical decision rule to predict response to omeprazole. Patient satisfaction, adverse effects, and cost were not addressed.

RESULTS: High body mass index, nighttime pain, and recent antacid or H2-blocker use predicted a good response to omeprazole, while nausea predicted a poor response. The prediction rule incorporating these variables identified patients likely to respond to omeprazole (number needed to treat=2.6). Validity testing confirmed these findings.

BACKGROUND: Dyspepsia is a common primary care problem, but optimal management remains unclear. In the past decade, attempts have been made to distinguish subtypes of ulcer-like (nighttime epigastric pain), reflux-like (heartburn, regurgitation), and dysmotility-like (bloating, distention, flatulence, nausea) dyspepsia, but there is overlap among the categories. Also, 50% to 60% of dyspeptic patients fit no single pattern. The authors of this study attempted to define characteristics of patients with dyspepsia who responded to omeprazole.

POPULATION STUDIED: A total of 471 Danish primary care patients aged 18 to 65 years with ulcer-or gastroesophageal reflux (GERD)-like dyspepsia were enrolled. The protocol excluded patients with dysmotility and untypeable dyspepsia, patients with dysmotility and other types of dyspepsia, and those with a history of peptic ulcer disease, reflux esophagitis, alarm symptoms (weight loss, dysphagia, bloody or black stools, anemia, jaundice), or current nonsteroidal anti-inflammatory drug use. The average age was 42 years, with the patients evenly split by sex and smoking status. Approximately half (45%) had experienced symptoms for less than 1 month. On average the patients were slightly overweight, with an average body mass index of 24.6. Thirty-nine percent had used H2-blockers or antacids in the past month, and none had undergone endoscopy or laboratory investigations. Thus, though the clinical characteristics seem similar to patients presenting to family physicians in the United States, generalizations to all patients with dyspepsia should be cautious.

STUDY DESIGN AND VALIDITY: This study is a re-analysis of data from a randomized controlled trial of omeprazole for dyspepsia to determine a clinical prediction rule regarding which patients with dyspepsia will respond to therapy with omeprazole. Patients received omeprazole 20 mg or placebo daily for 2 weeks and were randomly divided into samples used to develop the decision rule (N=236) and to test the rule (n= 235). Logistic regression was used to identify the relationship between specific symptoms and complete response of symptoms to omeprazole. The authors then developed a rule for predicting which dyspeptic patients respond to omeprazole and validated it in the test sample.

OUTCOMES MEASURED: The major outcome was a list of symptoms associated with therapeutic response; these symptoms were used to develop a clinical decision rule to predict response to omeprazole. Patient satisfaction, adverse effects, and cost were not addressed.

RESULTS: High body mass index, nighttime pain, and recent antacid or H2-blocker use predicted a good response to omeprazole, while nausea predicted a poor response. The prediction rule incorporating these variables identified patients likely to respond to omeprazole (number needed to treat=2.6). Validity testing confirmed these findings.

BACKGROUND: The yield for positive stool cultures with non–C-diff species in hospitalized patients with diarrhea is very low (2.6%-6.4%) and is even lower after 3 days (0.6%). Thus, many hospital laboratories will not accept or will discard samples obtained 72 hours after admission (the 3-day rule).

POPULATION STUDIED: Derivation of the guideline was made on the data obtained from adults 18 years or older admitted to a tertiary-care hospital in Germany. The validation portions of the study were conducted with adults in secondary and tertiary health centers in Switzerland, Spain, and England.

STUDY DESIGN AND VALIDITY: Five phases looking both retrospectively and prospectively at 10 cohorts of patients made up the study. Hospital laboratories analyzed stool samples for the following organisms and species: Salmonella, Shigella, Campylobacter, Yersinia, Vibrio, Clostridium difficile, and Escherichia coli. To establish a baseline prevalence of infection, patient charts were initially reviewed retrospectively over 1 year, during which 2391 stool cultures were ordered on 1182 patients. In phase II, patient charts were surveyed prospectively over 7 months to identify characteristics that predicted positive cultures. Specifically, recent family history of diarrhea or travel outside Europe, nausea/vomiting, 8 or more bowel movements per day, temperature higher than 38° C, and presence of abdominal pain were evaluated.

OUTCOMES MEASURED: The investigators sought to identify and validate criteria predictive of which patients with non–C-diff diarrhea were most likely to have positive stool cultures after 3 days in the hospital. Monetary costs and technician time were also measured.

RESULTS: A total of 3416 stool cultures were obtained from 1735 patients in phases I and II. Of these, only 34 (1%) were found to have a bacterial pathogen other than C-diff. Most of these (29) were detected on the first sample obtained from a patient, and 20 were positive in the first 72 hours after admission. Analysis of the risk factors gathered in phase II showed a significant association between a positive culture and a recent family history of diarrhea or travel outside Europe. Criteria identified during phase III predictive of positive cultures obtained from patients with diarrhea 72 hours or more after admission included: age 65 years or older with preexisting comorbidity, human immunodeficency virus (HIV) infection or neutropenia, suspected nosocomial outbreak, and nondiarrheal manifestations of enteric infections (eg, acalculous cholecystitis, fever of unknown origin, polyarthritis). Applying these guidelines to the patients in phase II would have resulted in missing only 1.2% of the positive samples sent after 72 hours. Calculated savings were $10,300 annually as well as 356 technician hours. Prospective testing of the guidelines in one cohort with 65 positive cultures resulted in missing only 2 positive cultures from patients who did not need treatment. Validation in a separate cohort of 330 cultures found that 42% of the cultures could have been avoided while missing only one positive culture.

BACKGROUND: The yield for positive stool cultures with non–C-diff species in hospitalized patients with diarrhea is very low (2.6%-6.4%) and is even lower after 3 days (0.6%). Thus, many hospital laboratories will not accept or will discard samples obtained 72 hours after admission (the 3-day rule).

POPULATION STUDIED: Derivation of the guideline was made on the data obtained from adults 18 years or older admitted to a tertiary-care hospital in Germany. The validation portions of the study were conducted with adults in secondary and tertiary health centers in Switzerland, Spain, and England.

STUDY DESIGN AND VALIDITY: Five phases looking both retrospectively and prospectively at 10 cohorts of patients made up the study. Hospital laboratories analyzed stool samples for the following organisms and species: Salmonella, Shigella, Campylobacter, Yersinia, Vibrio, Clostridium difficile, and Escherichia coli. To establish a baseline prevalence of infection, patient charts were initially reviewed retrospectively over 1 year, during which 2391 stool cultures were ordered on 1182 patients. In phase II, patient charts were surveyed prospectively over 7 months to identify characteristics that predicted positive cultures. Specifically, recent family history of diarrhea or travel outside Europe, nausea/vomiting, 8 or more bowel movements per day, temperature higher than 38° C, and presence of abdominal pain were evaluated.

OUTCOMES MEASURED: The investigators sought to identify and validate criteria predictive of which patients with non–C-diff diarrhea were most likely to have positive stool cultures after 3 days in the hospital. Monetary costs and technician time were also measured.

RESULTS: A total of 3416 stool cultures were obtained from 1735 patients in phases I and II. Of these, only 34 (1%) were found to have a bacterial pathogen other than C-diff. Most of these (29) were detected on the first sample obtained from a patient, and 20 were positive in the first 72 hours after admission. Analysis of the risk factors gathered in phase II showed a significant association between a positive culture and a recent family history of diarrhea or travel outside Europe. Criteria identified during phase III predictive of positive cultures obtained from patients with diarrhea 72 hours or more after admission included: age 65 years or older with preexisting comorbidity, human immunodeficency virus (HIV) infection or neutropenia, suspected nosocomial outbreak, and nondiarrheal manifestations of enteric infections (eg, acalculous cholecystitis, fever of unknown origin, polyarthritis). Applying these guidelines to the patients in phase II would have resulted in missing only 1.2% of the positive samples sent after 72 hours. Calculated savings were $10,300 annually as well as 356 technician hours. Prospective testing of the guidelines in one cohort with 65 positive cultures resulted in missing only 2 positive cultures from patients who did not need treatment. Validation in a separate cohort of 330 cultures found that 42% of the cultures could have been avoided while missing only one positive culture.

BACKGROUND: The yield for positive stool cultures with non–C-diff species in hospitalized patients with diarrhea is very low (2.6%-6.4%) and is even lower after 3 days (0.6%). Thus, many hospital laboratories will not accept or will discard samples obtained 72 hours after admission (the 3-day rule).

POPULATION STUDIED: Derivation of the guideline was made on the data obtained from adults 18 years or older admitted to a tertiary-care hospital in Germany. The validation portions of the study were conducted with adults in secondary and tertiary health centers in Switzerland, Spain, and England.

STUDY DESIGN AND VALIDITY: Five phases looking both retrospectively and prospectively at 10 cohorts of patients made up the study. Hospital laboratories analyzed stool samples for the following organisms and species: Salmonella, Shigella, Campylobacter, Yersinia, Vibrio, Clostridium difficile, and Escherichia coli. To establish a baseline prevalence of infection, patient charts were initially reviewed retrospectively over 1 year, during which 2391 stool cultures were ordered on 1182 patients. In phase II, patient charts were surveyed prospectively over 7 months to identify characteristics that predicted positive cultures. Specifically, recent family history of diarrhea or travel outside Europe, nausea/vomiting, 8 or more bowel movements per day, temperature higher than 38° C, and presence of abdominal pain were evaluated.

OUTCOMES MEASURED: The investigators sought to identify and validate criteria predictive of which patients with non–C-diff diarrhea were most likely to have positive stool cultures after 3 days in the hospital. Monetary costs and technician time were also measured.

RESULTS: A total of 3416 stool cultures were obtained from 1735 patients in phases I and II. Of these, only 34 (1%) were found to have a bacterial pathogen other than C-diff. Most of these (29) were detected on the first sample obtained from a patient, and 20 were positive in the first 72 hours after admission. Analysis of the risk factors gathered in phase II showed a significant association between a positive culture and a recent family history of diarrhea or travel outside Europe. Criteria identified during phase III predictive of positive cultures obtained from patients with diarrhea 72 hours or more after admission included: age 65 years or older with preexisting comorbidity, human immunodeficency virus (HIV) infection or neutropenia, suspected nosocomial outbreak, and nondiarrheal manifestations of enteric infections (eg, acalculous cholecystitis, fever of unknown origin, polyarthritis). Applying these guidelines to the patients in phase II would have resulted in missing only 1.2% of the positive samples sent after 72 hours. Calculated savings were $10,300 annually as well as 356 technician hours. Prospective testing of the guidelines in one cohort with 65 positive cultures resulted in missing only 2 positive cultures from patients who did not need treatment. Validation in a separate cohort of 330 cultures found that 42% of the cultures could have been avoided while missing only one positive culture.

BACKGROUND: A group of neurologists noted a significant improvement in migraine frequency after one of their patients began taking lisinopril for hypertension. ACE inhibitors’ effects on sympathetic activity, decreased free radicals, and increased prostacyclin may explain its role in decreasing migraine headache. Additionally, recent genetic studies have found that migraine without aura is more common in people with a certain genotype for ACE.

POPULATION STUDIED: Sixty adult patients with migraine headache occurring 2 to 6 times per month were recruited from an outpatient neurology clinic and with advertisements. The study presents complete data for 38 women (mean age=41 years) and 9 men (mean age=43 years). Standard criteria for the definition of migraine were used. Patients were excluded if they had nonmigraine headaches that could not be distinguished from migraine, used other prophylactic medications, were pregnant or unable to use contraceptives, had impaired hepatic or renal function, or had a history of hypersensitivity to ACE inhibitors. The study cohort likely represents migraine sufferers at the more severe end of the spectrum seen by primary care physicians.

STUDY DESIGN AND VALIDITY: The participants entered a double-blind placebo-controlled crossover study. There was a 12-week treatment period: The dose of lisinopril was 10 mg for 1 week, then 20 mg for the remaining 11 weeks. After this initial period, patients receiving lisinopril were switched to placebo for 12 weeks and vice versa. The participants kept a daily diary of headache symptoms, medication use, sick leave use, and quality-of-life measures.

OUTCOMES MEASURED: The primary outcome measures were the number of hours and days with headache and the number of days with migraine. The secondary outcomes were the headache severity index, use of medications for symptomatic relief, quality of life, number of sick-leave days taken, and the acceptability of treatment.

RESULTS: Sixty patients were randomized, and 55 were included in an intention-to-treat analysis (including 8 patients who did not comply properly with the protocol). Hours with headache decreased from 162 to 138 in the lisinopril group, with a mean reduction of 15% (95% confidence interval [CI], 0-30). Days with headache and days with migraine were also reduced by 16% (95% CI, 5-27) and 22% (95% CI, 11-33), respectively. Fourteen participants (25%) had a 50% decrease in the number of days with headache.

BACKGROUND: A group of neurologists noted a significant improvement in migraine frequency after one of their patients began taking lisinopril for hypertension. ACE inhibitors’ effects on sympathetic activity, decreased free radicals, and increased prostacyclin may explain its role in decreasing migraine headache. Additionally, recent genetic studies have found that migraine without aura is more common in people with a certain genotype for ACE.

POPULATION STUDIED: Sixty adult patients with migraine headache occurring 2 to 6 times per month were recruited from an outpatient neurology clinic and with advertisements. The study presents complete data for 38 women (mean age=41 years) and 9 men (mean age=43 years). Standard criteria for the definition of migraine were used. Patients were excluded if they had nonmigraine headaches that could not be distinguished from migraine, used other prophylactic medications, were pregnant or unable to use contraceptives, had impaired hepatic or renal function, or had a history of hypersensitivity to ACE inhibitors. The study cohort likely represents migraine sufferers at the more severe end of the spectrum seen by primary care physicians.

STUDY DESIGN AND VALIDITY: The participants entered a double-blind placebo-controlled crossover study. There was a 12-week treatment period: The dose of lisinopril was 10 mg for 1 week, then 20 mg for the remaining 11 weeks. After this initial period, patients receiving lisinopril were switched to placebo for 12 weeks and vice versa. The participants kept a daily diary of headache symptoms, medication use, sick leave use, and quality-of-life measures.

OUTCOMES MEASURED: The primary outcome measures were the number of hours and days with headache and the number of days with migraine. The secondary outcomes were the headache severity index, use of medications for symptomatic relief, quality of life, number of sick-leave days taken, and the acceptability of treatment.

RESULTS: Sixty patients were randomized, and 55 were included in an intention-to-treat analysis (including 8 patients who did not comply properly with the protocol). Hours with headache decreased from 162 to 138 in the lisinopril group, with a mean reduction of 15% (95% confidence interval [CI], 0-30). Days with headache and days with migraine were also reduced by 16% (95% CI, 5-27) and 22% (95% CI, 11-33), respectively. Fourteen participants (25%) had a 50% decrease in the number of days with headache.

BACKGROUND: A group of neurologists noted a significant improvement in migraine frequency after one of their patients began taking lisinopril for hypertension. ACE inhibitors’ effects on sympathetic activity, decreased free radicals, and increased prostacyclin may explain its role in decreasing migraine headache. Additionally, recent genetic studies have found that migraine without aura is more common in people with a certain genotype for ACE.

POPULATION STUDIED: Sixty adult patients with migraine headache occurring 2 to 6 times per month were recruited from an outpatient neurology clinic and with advertisements. The study presents complete data for 38 women (mean age=41 years) and 9 men (mean age=43 years). Standard criteria for the definition of migraine were used. Patients were excluded if they had nonmigraine headaches that could not be distinguished from migraine, used other prophylactic medications, were pregnant or unable to use contraceptives, had impaired hepatic or renal function, or had a history of hypersensitivity to ACE inhibitors. The study cohort likely represents migraine sufferers at the more severe end of the spectrum seen by primary care physicians.

STUDY DESIGN AND VALIDITY: The participants entered a double-blind placebo-controlled crossover study. There was a 12-week treatment period: The dose of lisinopril was 10 mg for 1 week, then 20 mg for the remaining 11 weeks. After this initial period, patients receiving lisinopril were switched to placebo for 12 weeks and vice versa. The participants kept a daily diary of headache symptoms, medication use, sick leave use, and quality-of-life measures.

OUTCOMES MEASURED: The primary outcome measures were the number of hours and days with headache and the number of days with migraine. The secondary outcomes were the headache severity index, use of medications for symptomatic relief, quality of life, number of sick-leave days taken, and the acceptability of treatment.

RESULTS: Sixty patients were randomized, and 55 were included in an intention-to-treat analysis (including 8 patients who did not comply properly with the protocol). Hours with headache decreased from 162 to 138 in the lisinopril group, with a mean reduction of 15% (95% confidence interval [CI], 0-30). Days with headache and days with migraine were also reduced by 16% (95% CI, 5-27) and 22% (95% CI, 11-33), respectively. Fourteen participants (25%) had a 50% decrease in the number of days with headache.

BACKGROUND: PMS is both common and troublesome, and there is no consensus on the most tolerable and effective therapy. Chasteberry fruit is commonly used in Europe for this condition. Given the strong placebo response noted with PMS¹ and the increasing popularity and availability of herbal formulations in the United States, carefully controlled trials are needed to assess these new treatment options.

POPULATION STUDIED: Six general medicine outpatient clinics in Germany recruited 178 women aged 18 years or older with PMS as defined by the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised. Exclusion criteria included psychotherapy, any serious medical condition, pregnancy, breast-feeding, inadequate contraception, alcohol or drug dependence, hypersensitivity to chasteberry, fever, pituitary disease, or use of sex hormones other than oral contraceptives. The treatment groups did not differ significantly in terms of age (mean=36 years), weight, cycle characteristics, or initial assessments of severity.

STUDY DESIGN AND VALIDITY: In this prospective randomized double-blind placebo-controlled trial, participants received either a chasteberry (ZE 440) 20-mg tablet standardized for casticin (one of the presumed active principles) or matching placebo once daily. The authors assessed efficacy by comparing validated self-assessment scales at baseline (beginning of first menstrual cycle) and at the end of the third cycle. Tolerability was assessed using side effects reported at the last study visit, rather than by recording in a daily diary.

OUTCOMES MEASURED: The primary outcome was the change from baseline to end point in a combined score of 6 self-assessment items rated on a visual analog scale (irritability, mood alteration, anger, headache, other menstrual symptoms including bloating, and breast fullness). The secondary outcomes included each of the 6 items independently, 3 global assessment items (corroborated by physicians), and the responder rate, defined as 50% or more reduction in self-assessed symptoms from baseline.

RESULTS: Compared with placebo, patients who received chasteberry had a significant improvement in the combined symptom score (P <.001). In 5 of the 6 self-assessment items (irritability, mood alteration, anger, headache, and breast fullness), chasteberry was more effective than placebo (P <.01), with “other symptoms including bloating” being unaffected by treatment. All 3 global assessment items significantly favored the treated group, as did the responder rate (52% vs 24%, no statistical analysis presented). These results remained unchanged by subgroup analyses that excluded women taking oral contraceptives and included the 8 women initially screened but without postbaseline values who were removed from the initial intention-to-treat population. Side effect rates were similar in the 2 groups; all were mild, and none led to discontinuation.

BACKGROUND: PMS is both common and troublesome, and there is no consensus on the most tolerable and effective therapy. Chasteberry fruit is commonly used in Europe for this condition. Given the strong placebo response noted with PMS¹ and the increasing popularity and availability of herbal formulations in the United States, carefully controlled trials are needed to assess these new treatment options.

POPULATION STUDIED: Six general medicine outpatient clinics in Germany recruited 178 women aged 18 years or older with PMS as defined by the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised. Exclusion criteria included psychotherapy, any serious medical condition, pregnancy, breast-feeding, inadequate contraception, alcohol or drug dependence, hypersensitivity to chasteberry, fever, pituitary disease, or use of sex hormones other than oral contraceptives. The treatment groups did not differ significantly in terms of age (mean=36 years), weight, cycle characteristics, or initial assessments of severity.

STUDY DESIGN AND VALIDITY: In this prospective randomized double-blind placebo-controlled trial, participants received either a chasteberry (ZE 440) 20-mg tablet standardized for casticin (one of the presumed active principles) or matching placebo once daily. The authors assessed efficacy by comparing validated self-assessment scales at baseline (beginning of first menstrual cycle) and at the end of the third cycle. Tolerability was assessed using side effects reported at the last study visit, rather than by recording in a daily diary.

OUTCOMES MEASURED: The primary outcome was the change from baseline to end point in a combined score of 6 self-assessment items rated on a visual analog scale (irritability, mood alteration, anger, headache, other menstrual symptoms including bloating, and breast fullness). The secondary outcomes included each of the 6 items independently, 3 global assessment items (corroborated by physicians), and the responder rate, defined as 50% or more reduction in self-assessed symptoms from baseline.

RESULTS: Compared with placebo, patients who received chasteberry had a significant improvement in the combined symptom score (P <.001). In 5 of the 6 self-assessment items (irritability, mood alteration, anger, headache, and breast fullness), chasteberry was more effective than placebo (P <.01), with “other symptoms including bloating” being unaffected by treatment. All 3 global assessment items significantly favored the treated group, as did the responder rate (52% vs 24%, no statistical analysis presented). These results remained unchanged by subgroup analyses that excluded women taking oral contraceptives and included the 8 women initially screened but without postbaseline values who were removed from the initial intention-to-treat population. Side effect rates were similar in the 2 groups; all were mild, and none led to discontinuation.

BACKGROUND: PMS is both common and troublesome, and there is no consensus on the most tolerable and effective therapy. Chasteberry fruit is commonly used in Europe for this condition. Given the strong placebo response noted with PMS¹ and the increasing popularity and availability of herbal formulations in the United States, carefully controlled trials are needed to assess these new treatment options.

POPULATION STUDIED: Six general medicine outpatient clinics in Germany recruited 178 women aged 18 years or older with PMS as defined by the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised. Exclusion criteria included psychotherapy, any serious medical condition, pregnancy, breast-feeding, inadequate contraception, alcohol or drug dependence, hypersensitivity to chasteberry, fever, pituitary disease, or use of sex hormones other than oral contraceptives. The treatment groups did not differ significantly in terms of age (mean=36 years), weight, cycle characteristics, or initial assessments of severity.

STUDY DESIGN AND VALIDITY: In this prospective randomized double-blind placebo-controlled trial, participants received either a chasteberry (ZE 440) 20-mg tablet standardized for casticin (one of the presumed active principles) or matching placebo once daily. The authors assessed efficacy by comparing validated self-assessment scales at baseline (beginning of first menstrual cycle) and at the end of the third cycle. Tolerability was assessed using side effects reported at the last study visit, rather than by recording in a daily diary.

OUTCOMES MEASURED: The primary outcome was the change from baseline to end point in a combined score of 6 self-assessment items rated on a visual analog scale (irritability, mood alteration, anger, headache, other menstrual symptoms including bloating, and breast fullness). The secondary outcomes included each of the 6 items independently, 3 global assessment items (corroborated by physicians), and the responder rate, defined as 50% or more reduction in self-assessed symptoms from baseline.

RESULTS: Compared with placebo, patients who received chasteberry had a significant improvement in the combined symptom score (P <.001). In 5 of the 6 self-assessment items (irritability, mood alteration, anger, headache, and breast fullness), chasteberry was more effective than placebo (P <.01), with “other symptoms including bloating” being unaffected by treatment. All 3 global assessment items significantly favored the treated group, as did the responder rate (52% vs 24%, no statistical analysis presented). These results remained unchanged by subgroup analyses that excluded women taking oral contraceptives and included the 8 women initially screened but without postbaseline values who were removed from the initial intention-to-treat population. Side effect rates were similar in the 2 groups; all were mild, and none led to discontinuation.