Q&A

BACKGROUND: Significant morbidity can occur in untreated patients with Lyme disease. Currently the Infectious Disease Society of America (IDSA) recommends treatment only in the presence of erythema migrans or seropositivity with symptoms of systemic disease. Although the IDSA does not recommend antimicrobial prophylaxis to patients with a documented tick bite, it may be possible to prevent Lyme disease by treating patients prophylactically after removing the tick Ixodes scapularis.

POPULATION STUDIED: Study subjects were recruited from Westchester County, New York, an area in which Lyme disease is hyperendemic. Inclusion criteria included age older than 12 years with a history of having removed an Ixodes scapularis tick within 72 hours of enrollment. Subjects whose ticks were later shown to not be Ixodes scapularis were included only in the analysis of safety. Other exclusion criteria included having been vaccinated against Lyme disease, having a rash consistent with erythema migrans, actively taking or having recently completed a course of antibiotics effective against Borrelia burgdorferi, being pregnant or lactating, and not having the tick available for analysis.

STUDY DESIGN AND VALIDITY: The study was a randomized controlled double-blind trial of 506 patients with a documented bite from the Ixodes scapularis tick. The subjects received either a single dose of 200 mg of doxycycline or matched placebo. Ticks were examined by a medical entomologist who confirmed the species type and the life cycle stage as either adult or nymphal. Ticks were also classified as unfed (flat) or partly fed (engorged) on the basis of visual inspection. Observers blind to treatment group assignment evaluated patients at enrollment, 3 weeks, and 6 weeks. Medications were swallowed by direct observation to ensure 100% compliance. The follow-up completion rate of all 3 visits was 89%.

OUTCOMES MEASURED: The primary outcome was the development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at secondary sites and laboratory evidence of Borrelia burgdorferi.

RESULTS: In the doxycycline group, 1 of 235 subjects developed erythema migrans, compared with 8 of 247 in the placebo group (0.4% vs 3.2%, P <.04; number needed to treat = 36). Serologic confirmation of Lyme disease occurred in 8 of the 9 patients with erythema migrans. Objective systemic manifestations of Lyme disease and asymptomatic seroconversions were not observed in any patient. Adverse events were more common in the treatment group (30% vs 11%, P <.001) and were primarily gastrointestinal. A subgroup analysis demonstrated that none of the 116 patients in the placebo group that had unfed (flat) ticks developed erythema migrans. Ticks removed within 72 hours were also very unlikely to transmit disease.

BACKGROUND: Significant morbidity can occur in untreated patients with Lyme disease. Currently the Infectious Disease Society of America (IDSA) recommends treatment only in the presence of erythema migrans or seropositivity with symptoms of systemic disease. Although the IDSA does not recommend antimicrobial prophylaxis to patients with a documented tick bite, it may be possible to prevent Lyme disease by treating patients prophylactically after removing the tick Ixodes scapularis.

POPULATION STUDIED: Study subjects were recruited from Westchester County, New York, an area in which Lyme disease is hyperendemic. Inclusion criteria included age older than 12 years with a history of having removed an Ixodes scapularis tick within 72 hours of enrollment. Subjects whose ticks were later shown to not be Ixodes scapularis were included only in the analysis of safety. Other exclusion criteria included having been vaccinated against Lyme disease, having a rash consistent with erythema migrans, actively taking or having recently completed a course of antibiotics effective against Borrelia burgdorferi, being pregnant or lactating, and not having the tick available for analysis.

STUDY DESIGN AND VALIDITY: The study was a randomized controlled double-blind trial of 506 patients with a documented bite from the Ixodes scapularis tick. The subjects received either a single dose of 200 mg of doxycycline or matched placebo. Ticks were examined by a medical entomologist who confirmed the species type and the life cycle stage as either adult or nymphal. Ticks were also classified as unfed (flat) or partly fed (engorged) on the basis of visual inspection. Observers blind to treatment group assignment evaluated patients at enrollment, 3 weeks, and 6 weeks. Medications were swallowed by direct observation to ensure 100% compliance. The follow-up completion rate of all 3 visits was 89%.

OUTCOMES MEASURED: The primary outcome was the development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at secondary sites and laboratory evidence of Borrelia burgdorferi.

RESULTS: In the doxycycline group, 1 of 235 subjects developed erythema migrans, compared with 8 of 247 in the placebo group (0.4% vs 3.2%, P <.04; number needed to treat = 36). Serologic confirmation of Lyme disease occurred in 8 of the 9 patients with erythema migrans. Objective systemic manifestations of Lyme disease and asymptomatic seroconversions were not observed in any patient. Adverse events were more common in the treatment group (30% vs 11%, P <.001) and were primarily gastrointestinal. A subgroup analysis demonstrated that none of the 116 patients in the placebo group that had unfed (flat) ticks developed erythema migrans. Ticks removed within 72 hours were also very unlikely to transmit disease.

BACKGROUND: Significant morbidity can occur in untreated patients with Lyme disease. Currently the Infectious Disease Society of America (IDSA) recommends treatment only in the presence of erythema migrans or seropositivity with symptoms of systemic disease. Although the IDSA does not recommend antimicrobial prophylaxis to patients with a documented tick bite, it may be possible to prevent Lyme disease by treating patients prophylactically after removing the tick Ixodes scapularis.

POPULATION STUDIED: Study subjects were recruited from Westchester County, New York, an area in which Lyme disease is hyperendemic. Inclusion criteria included age older than 12 years with a history of having removed an Ixodes scapularis tick within 72 hours of enrollment. Subjects whose ticks were later shown to not be Ixodes scapularis were included only in the analysis of safety. Other exclusion criteria included having been vaccinated against Lyme disease, having a rash consistent with erythema migrans, actively taking or having recently completed a course of antibiotics effective against Borrelia burgdorferi, being pregnant or lactating, and not having the tick available for analysis.

STUDY DESIGN AND VALIDITY: The study was a randomized controlled double-blind trial of 506 patients with a documented bite from the Ixodes scapularis tick. The subjects received either a single dose of 200 mg of doxycycline or matched placebo. Ticks were examined by a medical entomologist who confirmed the species type and the life cycle stage as either adult or nymphal. Ticks were also classified as unfed (flat) or partly fed (engorged) on the basis of visual inspection. Observers blind to treatment group assignment evaluated patients at enrollment, 3 weeks, and 6 weeks. Medications were swallowed by direct observation to ensure 100% compliance. The follow-up completion rate of all 3 visits was 89%.

OUTCOMES MEASURED: The primary outcome was the development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at secondary sites and laboratory evidence of Borrelia burgdorferi.

RESULTS: In the doxycycline group, 1 of 235 subjects developed erythema migrans, compared with 8 of 247 in the placebo group (0.4% vs 3.2%, P <.04; number needed to treat = 36). Serologic confirmation of Lyme disease occurred in 8 of the 9 patients with erythema migrans. Objective systemic manifestations of Lyme disease and asymptomatic seroconversions were not observed in any patient. Adverse events were more common in the treatment group (30% vs 11%, P <.001) and were primarily gastrointestinal. A subgroup analysis demonstrated that none of the 116 patients in the placebo group that had unfed (flat) ticks developed erythema migrans. Ticks removed within 72 hours were also very unlikely to transmit disease.

BACKGROUND: Heartburn is the most common symptom of gastroesophageal reflux disease (GERD). This study compared 4 pharmacologic strategies using the proton pump inhibitor (PPI) lansoprazole (Prevacid) and the H2-receptor antagonist ranitidine (Zantac) in the treatment of moderate to severe heartburn.

POPULATION STUDIED: This study included 593 men and women older than 18 years who experienced heartburn on at least 50% of days during a 7- to 10-day screening period, including at least one moderate to severe episode. Patients were excluded if they had coexisting systemic disease affecting the esophagus, active gastrointestinal bleeding, Zollinger-Ellison syndrome, esophageal varices, significant disease of major organs, abnormal laboratory values, current alcohol or illegal drug use, use of a PPI in the previous 3 months, or use of anticholinergic or prokinetic drugs during the screening period.

STUDY DESIGN AND VALIDITY: This was a double-blind controlled multicenter trial in which patients were randomized to 1 of 4 treatment groups. The subjects received one of the following: (1) lansoprazole 30 mg daily for 20 weeks; (2) ranitidine 150 mg twice daily for 20 weeks; (3) step-down therapy consisting of lansoprazole 30 mg daily for 8 weeks followed by ranitidine 150 mg twice a day for 12 weeks; or (4) a step-up approach of ranitidine 150 mg twice daily for 8 weeks followed by lansoprazole 30 mg once daily for 12 weeks.

OUTCOMES MEASURED: Two outcome measurements were reported, including the median severity of heartburn using a scale of 0 (no heartburn), 1 (mild heartburn), 2 (moderate heartburn), or 3 (severe heartburn) and the percentage of 24-hour heartburn-free days. Outcomes measurements were based on self-report in daily diaries. Antacid use was also reported.

RESULTS: All patients, regardless of treatment, reported a marked clinically relevant decline in the intensity of their heartburn symptoms. The median heartburn severity decreased from 1.88 to 0.46 in the ranitidine group, from 1.75 to 0.25 in the lansoprazole group, from 1.75 to 0.35 in the step-up group, and from 1.70 to 0.44 in the step-down group (P <.05 for lansoprazole vs the other groups). The lansoprazole group also had a significantly higher percentage of 24-hour heartburn-free days (median=81.4%; P <.01) than the ranitidine (66.6%), step-up (66.9%), and step-down (73.6%) groups. In the step-up and step-down groups, heartburn was less severe, and percentages of 24-hour heartburn-free days were higher during lansoprazole treatment regardless of treatment sequence (P <.001). Over the 20 weeks of treatment, antacid use was required on a significantly higher percentage of days in the ranitidine (median=18.7%; P <.001), step-up (12.3%; P <.05), and step-down (18.5%; P <.001) groups than in the lansoprazole group (8.6%).

BACKGROUND: Heartburn is the most common symptom of gastroesophageal reflux disease (GERD). This study compared 4 pharmacologic strategies using the proton pump inhibitor (PPI) lansoprazole (Prevacid) and the H2-receptor antagonist ranitidine (Zantac) in the treatment of moderate to severe heartburn.

POPULATION STUDIED: This study included 593 men and women older than 18 years who experienced heartburn on at least 50% of days during a 7- to 10-day screening period, including at least one moderate to severe episode. Patients were excluded if they had coexisting systemic disease affecting the esophagus, active gastrointestinal bleeding, Zollinger-Ellison syndrome, esophageal varices, significant disease of major organs, abnormal laboratory values, current alcohol or illegal drug use, use of a PPI in the previous 3 months, or use of anticholinergic or prokinetic drugs during the screening period.

STUDY DESIGN AND VALIDITY: This was a double-blind controlled multicenter trial in which patients were randomized to 1 of 4 treatment groups. The subjects received one of the following: (1) lansoprazole 30 mg daily for 20 weeks; (2) ranitidine 150 mg twice daily for 20 weeks; (3) step-down therapy consisting of lansoprazole 30 mg daily for 8 weeks followed by ranitidine 150 mg twice a day for 12 weeks; or (4) a step-up approach of ranitidine 150 mg twice daily for 8 weeks followed by lansoprazole 30 mg once daily for 12 weeks.

OUTCOMES MEASURED: Two outcome measurements were reported, including the median severity of heartburn using a scale of 0 (no heartburn), 1 (mild heartburn), 2 (moderate heartburn), or 3 (severe heartburn) and the percentage of 24-hour heartburn-free days. Outcomes measurements were based on self-report in daily diaries. Antacid use was also reported.

RESULTS: All patients, regardless of treatment, reported a marked clinically relevant decline in the intensity of their heartburn symptoms. The median heartburn severity decreased from 1.88 to 0.46 in the ranitidine group, from 1.75 to 0.25 in the lansoprazole group, from 1.75 to 0.35 in the step-up group, and from 1.70 to 0.44 in the step-down group (P <.05 for lansoprazole vs the other groups). The lansoprazole group also had a significantly higher percentage of 24-hour heartburn-free days (median=81.4%; P <.01) than the ranitidine (66.6%), step-up (66.9%), and step-down (73.6%) groups. In the step-up and step-down groups, heartburn was less severe, and percentages of 24-hour heartburn-free days were higher during lansoprazole treatment regardless of treatment sequence (P <.001). Over the 20 weeks of treatment, antacid use was required on a significantly higher percentage of days in the ranitidine (median=18.7%; P <.001), step-up (12.3%; P <.05), and step-down (18.5%; P <.001) groups than in the lansoprazole group (8.6%).

BACKGROUND: Heartburn is the most common symptom of gastroesophageal reflux disease (GERD). This study compared 4 pharmacologic strategies using the proton pump inhibitor (PPI) lansoprazole (Prevacid) and the H2-receptor antagonist ranitidine (Zantac) in the treatment of moderate to severe heartburn.

POPULATION STUDIED: This study included 593 men and women older than 18 years who experienced heartburn on at least 50% of days during a 7- to 10-day screening period, including at least one moderate to severe episode. Patients were excluded if they had coexisting systemic disease affecting the esophagus, active gastrointestinal bleeding, Zollinger-Ellison syndrome, esophageal varices, significant disease of major organs, abnormal laboratory values, current alcohol or illegal drug use, use of a PPI in the previous 3 months, or use of anticholinergic or prokinetic drugs during the screening period.

STUDY DESIGN AND VALIDITY: This was a double-blind controlled multicenter trial in which patients were randomized to 1 of 4 treatment groups. The subjects received one of the following: (1) lansoprazole 30 mg daily for 20 weeks; (2) ranitidine 150 mg twice daily for 20 weeks; (3) step-down therapy consisting of lansoprazole 30 mg daily for 8 weeks followed by ranitidine 150 mg twice a day for 12 weeks; or (4) a step-up approach of ranitidine 150 mg twice daily for 8 weeks followed by lansoprazole 30 mg once daily for 12 weeks.

OUTCOMES MEASURED: Two outcome measurements were reported, including the median severity of heartburn using a scale of 0 (no heartburn), 1 (mild heartburn), 2 (moderate heartburn), or 3 (severe heartburn) and the percentage of 24-hour heartburn-free days. Outcomes measurements were based on self-report in daily diaries. Antacid use was also reported.

RESULTS: All patients, regardless of treatment, reported a marked clinically relevant decline in the intensity of their heartburn symptoms. The median heartburn severity decreased from 1.88 to 0.46 in the ranitidine group, from 1.75 to 0.25 in the lansoprazole group, from 1.75 to 0.35 in the step-up group, and from 1.70 to 0.44 in the step-down group (P <.05 for lansoprazole vs the other groups). The lansoprazole group also had a significantly higher percentage of 24-hour heartburn-free days (median=81.4%; P <.01) than the ranitidine (66.6%), step-up (66.9%), and step-down (73.6%) groups. In the step-up and step-down groups, heartburn was less severe, and percentages of 24-hour heartburn-free days were higher during lansoprazole treatment regardless of treatment sequence (P <.001). Over the 20 weeks of treatment, antacid use was required on a significantly higher percentage of days in the ranitidine (median=18.7%; P <.001), step-up (12.3%; P <.05), and step-down (18.5%; P <.001) groups than in the lansoprazole group (8.6%).

BACKGROUND: Women older than 40 years using OCs for birth control often experience perimenopausal symptoms, such as hot flashes, vaginal dryness, or emotional disturbances, especially during the hormone-free days of an OC cycle. The authors of this study conducted a randomized controlled trial to assess whether the addition of estrogen to the hormone-free days during OC use can reduce perimenopausal symptomatology.

POPULATION STUDIED: The study population included 60 healthy Chilean women aged 40 to 49 years presenting to various outpatient clinics with mood disorders or hot flashes who were already taking OCs. Women taking concurrent psychiatric medications were excluded.

STUDY DESIGN AND VALIDITY: This was a randomized controlled double-blind study during 3 cycles of OC use. A total of 26 women received an OC containing 20 μg of ethinyl estradiol and 150 μg desogestrel for 21 days followed by 7 placebo tablets; the other group of 34 women received the same OC combination, followed by 2 placebo tablets and then 5 identical-appearing ethinyl estradiol tablets (10 μg). Three women from the placebo group and 1 woman from the estrogen group did not complete the study. The patients were evaluated at baseline and the end of 3 cycles using the Greene scale. This scale, a questionnaire tool used to analyze 21 perimenopausal symptoms in the categories of vasomotor, somatic, psychologic, and sexual function, is intended to standardize climacteric complaints for comparative purposes.

OUTCOMES MEASURED: The outcomes measured were changes in vasomotor symptoms, symptoms of depression, somatic symptoms (headaches, musculoskeletal pain, and dizziness) and sexual dysfunction between the 2 study groups.

RESULTS: There were no significant differences at baseline between the treatment groups regarding age, height, weight, or parity. Symptom scores at the end of the study (3 months later) were improved in both the estrogen and placebo groups; however, there was statistically significant greater improvement in the estrogen group. Depression scores fell 61% in the estrogen group versus 24% in the placebo group (P <.004). Likewise, somatic scores fell 59% versus 32% (P <.04); vasomotor scores fell 76% versus 48% (P <.03); and sexual dysfunction scores fell 75% versus 33% (P <.002) in the estrogen and placebo groups. Anxiety scores did not differ between the groups. Interestingly, headache scores were reduced with estrogen but not with placebo.

BACKGROUND: Women older than 40 years using OCs for birth control often experience perimenopausal symptoms, such as hot flashes, vaginal dryness, or emotional disturbances, especially during the hormone-free days of an OC cycle. The authors of this study conducted a randomized controlled trial to assess whether the addition of estrogen to the hormone-free days during OC use can reduce perimenopausal symptomatology.

POPULATION STUDIED: The study population included 60 healthy Chilean women aged 40 to 49 years presenting to various outpatient clinics with mood disorders or hot flashes who were already taking OCs. Women taking concurrent psychiatric medications were excluded.

STUDY DESIGN AND VALIDITY: This was a randomized controlled double-blind study during 3 cycles of OC use. A total of 26 women received an OC containing 20 μg of ethinyl estradiol and 150 μg desogestrel for 21 days followed by 7 placebo tablets; the other group of 34 women received the same OC combination, followed by 2 placebo tablets and then 5 identical-appearing ethinyl estradiol tablets (10 μg). Three women from the placebo group and 1 woman from the estrogen group did not complete the study. The patients were evaluated at baseline and the end of 3 cycles using the Greene scale. This scale, a questionnaire tool used to analyze 21 perimenopausal symptoms in the categories of vasomotor, somatic, psychologic, and sexual function, is intended to standardize climacteric complaints for comparative purposes.

OUTCOMES MEASURED: The outcomes measured were changes in vasomotor symptoms, symptoms of depression, somatic symptoms (headaches, musculoskeletal pain, and dizziness) and sexual dysfunction between the 2 study groups.

RESULTS: There were no significant differences at baseline between the treatment groups regarding age, height, weight, or parity. Symptom scores at the end of the study (3 months later) were improved in both the estrogen and placebo groups; however, there was statistically significant greater improvement in the estrogen group. Depression scores fell 61% in the estrogen group versus 24% in the placebo group (P <.004). Likewise, somatic scores fell 59% versus 32% (P <.04); vasomotor scores fell 76% versus 48% (P <.03); and sexual dysfunction scores fell 75% versus 33% (P <.002) in the estrogen and placebo groups. Anxiety scores did not differ between the groups. Interestingly, headache scores were reduced with estrogen but not with placebo.

BACKGROUND: Women older than 40 years using OCs for birth control often experience perimenopausal symptoms, such as hot flashes, vaginal dryness, or emotional disturbances, especially during the hormone-free days of an OC cycle. The authors of this study conducted a randomized controlled trial to assess whether the addition of estrogen to the hormone-free days during OC use can reduce perimenopausal symptomatology.

POPULATION STUDIED: The study population included 60 healthy Chilean women aged 40 to 49 years presenting to various outpatient clinics with mood disorders or hot flashes who were already taking OCs. Women taking concurrent psychiatric medications were excluded.

STUDY DESIGN AND VALIDITY: This was a randomized controlled double-blind study during 3 cycles of OC use. A total of 26 women received an OC containing 20 μg of ethinyl estradiol and 150 μg desogestrel for 21 days followed by 7 placebo tablets; the other group of 34 women received the same OC combination, followed by 2 placebo tablets and then 5 identical-appearing ethinyl estradiol tablets (10 μg). Three women from the placebo group and 1 woman from the estrogen group did not complete the study. The patients were evaluated at baseline and the end of 3 cycles using the Greene scale. This scale, a questionnaire tool used to analyze 21 perimenopausal symptoms in the categories of vasomotor, somatic, psychologic, and sexual function, is intended to standardize climacteric complaints for comparative purposes.

OUTCOMES MEASURED: The outcomes measured were changes in vasomotor symptoms, symptoms of depression, somatic symptoms (headaches, musculoskeletal pain, and dizziness) and sexual dysfunction between the 2 study groups.

RESULTS: There were no significant differences at baseline between the treatment groups regarding age, height, weight, or parity. Symptom scores at the end of the study (3 months later) were improved in both the estrogen and placebo groups; however, there was statistically significant greater improvement in the estrogen group. Depression scores fell 61% in the estrogen group versus 24% in the placebo group (P <.004). Likewise, somatic scores fell 59% versus 32% (P <.04); vasomotor scores fell 76% versus 48% (P <.03); and sexual dysfunction scores fell 75% versus 33% (P <.002) in the estrogen and placebo groups. Anxiety scores did not differ between the groups. Interestingly, headache scores were reduced with estrogen but not with placebo.

BACKGROUND: Acute conjunctivitis (pinkeye) accounts for 1% to 4% of primary care office visits. Although often viral, common bacterial pathogens include Streptococcus pneumoniae, Haemophilus influenza, and Staphylococcus aureus. Antibiotics are commonly prescribed in the belief that they hasten recovery and reduce complications, although little data are available to support this assertion.

POPULATION STUDIED: The authors of this meta-analysis performed a comprehensive search of MEDLINE, The Cochrane Library, the Cochrane Eyes and Vision Group Register, Science Citation Index, the bibliographies of retrieved reports, and inquiry to authors and pharmaceutical companies producing relevant ophthalmic preparations. They identified 5 randomized controlled trials comparing topical antibiotics with placebo for the treatment of bacterial conjunctivitis. Two trials were excluded because of incomplete blinding or deficient reporting of data. The remaining 3 trials involved 527 patients of various ages (1 studied children only, 1 did not specify, and 1 studied adults) treated with: (1) polymyxin and bacitracin, (2) ciprofloxacin or tobramycin, or (3) norfloxacin.

STUDY DESIGN AND VALIDITY: Two authors determined whether studies met inclusion criteria and graded eligible studies for quality. Relative benefit (relative risk of clinical or microbial remission) was calculated using Review Manager software (Cochrane Collaboration).The 3 included studies were not homogeneous in their populations studied (children vs adults), the method of diagnosis (culture vs clinical assessment), and the outcomes measured (clinical vs microbiologic resolution, time to resolution measured). However, the results of the 3 studies were statistically homogenous, supporting the combination of the results by meta-analysis. The criteria used to make clinical assessments for inclusion or for evaluating outcomes are not discussed, making it difficult to assess their validity. In 1 study, data were combined from of 2 trials, 1 comparing the use of ciprofloxacin with placebo, and the other comparing ciprofloxacin with tobramycin. Details about the nature of the allocation process for this study are lacking, but exclusion of this study does not significantly change the results. The greatest limitation of this study is its applicability to the primary care setting. The majority of the patients come from hospital-based clinics, and 2 of the 3 studies used subjects with culture-confirmed bacterial conjunctivitis, while most patients in primary care are treated empirically without culture confirmation.

OUTCOMES MEASURED: Outcomes included clinical cure (not otherwise described) or microbiologic cure (by culture) at 2 time frames: early (2-5 days) and late (6-10 days). One of the 3 studies measured microbiologic remission only at day 3. results By clinical cure, conjunctivitis was resolved by day 2 to 5 in 64% of patients using placebo and in 83% of those using topical antibiotics (relative risk [RR]=1.31; 95% confidence interval [CI], 1.11-1.55; number needed to treat [NNT]=5.3). This relative benefit was not statistically significant after 5 days (RR=1.27; 95% CI, 1.00-1.61) in the 1 study providing evaluation at this time. The relative benefit was also smaller in the study that used clinical assessment to diagnose bacterial infection (RR=1.31; 95% CI, 1.11-1.55; NNT=6.25). Microbiologic remission was also more often attained in the patients receiving antibiotics than in those on placebo, with a relative benefit of 1.71 (95% CI, 1.32-2.21), which remained stable at 6 to 10 days as well. No serious adverse reactions were reported in either the treatment groups or the placebo groups.

BACKGROUND: Acute conjunctivitis (pinkeye) accounts for 1% to 4% of primary care office visits. Although often viral, common bacterial pathogens include Streptococcus pneumoniae, Haemophilus influenza, and Staphylococcus aureus. Antibiotics are commonly prescribed in the belief that they hasten recovery and reduce complications, although little data are available to support this assertion.

POPULATION STUDIED: The authors of this meta-analysis performed a comprehensive search of MEDLINE, The Cochrane Library, the Cochrane Eyes and Vision Group Register, Science Citation Index, the bibliographies of retrieved reports, and inquiry to authors and pharmaceutical companies producing relevant ophthalmic preparations. They identified 5 randomized controlled trials comparing topical antibiotics with placebo for the treatment of bacterial conjunctivitis. Two trials were excluded because of incomplete blinding or deficient reporting of data. The remaining 3 trials involved 527 patients of various ages (1 studied children only, 1 did not specify, and 1 studied adults) treated with: (1) polymyxin and bacitracin, (2) ciprofloxacin or tobramycin, or (3) norfloxacin.

STUDY DESIGN AND VALIDITY: Two authors determined whether studies met inclusion criteria and graded eligible studies for quality. Relative benefit (relative risk of clinical or microbial remission) was calculated using Review Manager software (Cochrane Collaboration).The 3 included studies were not homogeneous in their populations studied (children vs adults), the method of diagnosis (culture vs clinical assessment), and the outcomes measured (clinical vs microbiologic resolution, time to resolution measured). However, the results of the 3 studies were statistically homogenous, supporting the combination of the results by meta-analysis. The criteria used to make clinical assessments for inclusion or for evaluating outcomes are not discussed, making it difficult to assess their validity. In 1 study, data were combined from of 2 trials, 1 comparing the use of ciprofloxacin with placebo, and the other comparing ciprofloxacin with tobramycin. Details about the nature of the allocation process for this study are lacking, but exclusion of this study does not significantly change the results. The greatest limitation of this study is its applicability to the primary care setting. The majority of the patients come from hospital-based clinics, and 2 of the 3 studies used subjects with culture-confirmed bacterial conjunctivitis, while most patients in primary care are treated empirically without culture confirmation.

OUTCOMES MEASURED: Outcomes included clinical cure (not otherwise described) or microbiologic cure (by culture) at 2 time frames: early (2-5 days) and late (6-10 days). One of the 3 studies measured microbiologic remission only at day 3. results By clinical cure, conjunctivitis was resolved by day 2 to 5 in 64% of patients using placebo and in 83% of those using topical antibiotics (relative risk [RR]=1.31; 95% confidence interval [CI], 1.11-1.55; number needed to treat [NNT]=5.3). This relative benefit was not statistically significant after 5 days (RR=1.27; 95% CI, 1.00-1.61) in the 1 study providing evaluation at this time. The relative benefit was also smaller in the study that used clinical assessment to diagnose bacterial infection (RR=1.31; 95% CI, 1.11-1.55; NNT=6.25). Microbiologic remission was also more often attained in the patients receiving antibiotics than in those on placebo, with a relative benefit of 1.71 (95% CI, 1.32-2.21), which remained stable at 6 to 10 days as well. No serious adverse reactions were reported in either the treatment groups or the placebo groups.

BACKGROUND: Acute conjunctivitis (pinkeye) accounts for 1% to 4% of primary care office visits. Although often viral, common bacterial pathogens include Streptococcus pneumoniae, Haemophilus influenza, and Staphylococcus aureus. Antibiotics are commonly prescribed in the belief that they hasten recovery and reduce complications, although little data are available to support this assertion.

POPULATION STUDIED: The authors of this meta-analysis performed a comprehensive search of MEDLINE, The Cochrane Library, the Cochrane Eyes and Vision Group Register, Science Citation Index, the bibliographies of retrieved reports, and inquiry to authors and pharmaceutical companies producing relevant ophthalmic preparations. They identified 5 randomized controlled trials comparing topical antibiotics with placebo for the treatment of bacterial conjunctivitis. Two trials were excluded because of incomplete blinding or deficient reporting of data. The remaining 3 trials involved 527 patients of various ages (1 studied children only, 1 did not specify, and 1 studied adults) treated with: (1) polymyxin and bacitracin, (2) ciprofloxacin or tobramycin, or (3) norfloxacin.

STUDY DESIGN AND VALIDITY: Two authors determined whether studies met inclusion criteria and graded eligible studies for quality. Relative benefit (relative risk of clinical or microbial remission) was calculated using Review Manager software (Cochrane Collaboration).The 3 included studies were not homogeneous in their populations studied (children vs adults), the method of diagnosis (culture vs clinical assessment), and the outcomes measured (clinical vs microbiologic resolution, time to resolution measured). However, the results of the 3 studies were statistically homogenous, supporting the combination of the results by meta-analysis. The criteria used to make clinical assessments for inclusion or for evaluating outcomes are not discussed, making it difficult to assess their validity. In 1 study, data were combined from of 2 trials, 1 comparing the use of ciprofloxacin with placebo, and the other comparing ciprofloxacin with tobramycin. Details about the nature of the allocation process for this study are lacking, but exclusion of this study does not significantly change the results. The greatest limitation of this study is its applicability to the primary care setting. The majority of the patients come from hospital-based clinics, and 2 of the 3 studies used subjects with culture-confirmed bacterial conjunctivitis, while most patients in primary care are treated empirically without culture confirmation.

OUTCOMES MEASURED: Outcomes included clinical cure (not otherwise described) or microbiologic cure (by culture) at 2 time frames: early (2-5 days) and late (6-10 days). One of the 3 studies measured microbiologic remission only at day 3. results By clinical cure, conjunctivitis was resolved by day 2 to 5 in 64% of patients using placebo and in 83% of those using topical antibiotics (relative risk [RR]=1.31; 95% confidence interval [CI], 1.11-1.55; number needed to treat [NNT]=5.3). This relative benefit was not statistically significant after 5 days (RR=1.27; 95% CI, 1.00-1.61) in the 1 study providing evaluation at this time. The relative benefit was also smaller in the study that used clinical assessment to diagnose bacterial infection (RR=1.31; 95% CI, 1.11-1.55; NNT=6.25). Microbiologic remission was also more often attained in the patients receiving antibiotics than in those on placebo, with a relative benefit of 1.71 (95% CI, 1.32-2.21), which remained stable at 6 to 10 days as well. No serious adverse reactions were reported in either the treatment groups or the placebo groups.

BACKGROUND: Emergency departments triage more than 5 million patients with chest pain each year. Cardiac blood tests are used to identify patients at higher risk for MI or death. The bedside instrument in this study is a new approach to the immediate risk stratification of patients with symptoms suggestive of myocardial ischemia.

POPULATION STUDIED: The investigators enrolled 1005 patients older than 18 years with possible myocardial ischemia who presented to the emergency room of 6 US hospitals. Patients were excluded if electrocardiography showed ST-segment elevation or left bundle branch block. The average patient age was 51years; 51% were women; 14% had a previous MI; 21% had diabetes; 53% had hypertension; and 38% were current cigarette smokers. The researchers were able to provide complete results for 95% of the patients.

STUDY DESIGN AND VALIDITY: This was a prospective study looking at the prognostic value of a bedside instrument measuring cardiac enzymes at the point of care. Blood samples were obtained from patients at baseline and at 3 and 6 hours. If the patient was hospitalized, samples were obtained at 9, 12, and 16 to 24 hours. These were analyzed by the Dade-Behring Stratus CS STAT near-patient instrument, which assays myoglobin; creatine kinase, myocardial bound (CK-MB); and troponin I (cTnI) from a blood sample in 15 to 20 minutes. Two multimarker strategies (MMS) were defined: MMS-1 included all 3 markers, and MMS-2 included only CK-MB and cTnI. A strategy was considered positive if any of the markers was positive. The CS STAT assay was compared with the CK-MB result of the local hospital laboratory. All patients underwent both local laboratory testing and bedside testing, but treating physicians used only local CK-MB results in making management decisions. This study was well designed for comparing the prognostic value of the CS STAT values with conventional CK-MB values. However, a more useful outcome would be the utility of this bedside instrument in the diagnosis of MI. Also, whether such an instrument would lead to clinically significant changes in prognosis outside of special chest pain units is unclear.

OUTCOMES MEASURED: The rate of MI or death at 30 days was determined for patients with either a positive or negative MMS or CK-MB test result. Additional assessments included time from arrival to a positive test result and the relation of MMS status to the rates of MI, death, and revascularization at 30 days.

RESULTS: Testing at baseline (on initial evaluation in the emergency department) predicted death or MI within 30 days in 19% of patients with a positive MMS-1, 22% with a positive MMS-2, and 13% with a positive CK-MB result. Conversely, only 3% with a negative MMS-1 or MMS-2 and 6% with a negative CK-MB result died or had a MI at 30 days. With serial testing 55% of persons with an abnormal CK-MB result had a MI at 30 days, while serial MMS testing did not discriminate any better than the single test. The bedside 3-marker strategy was superior in predicting 30-day mortality; all 3 patients who died had a positive MMS-1 at baseline, while only 1 of 3 had an abnormal CK-MB on serial testing. An abnormal CK-MB result predicted revascularization within 30-days better than bedside testing using both single and serial measurements. After emergency department arrival, positive test results were obtained more quickly using the bedside instrument (MMS-1=2.5 hours, MMS-2=2.8 hours, LL=3.4 hours; P=.0001).

BACKGROUND: Emergency departments triage more than 5 million patients with chest pain each year. Cardiac blood tests are used to identify patients at higher risk for MI or death. The bedside instrument in this study is a new approach to the immediate risk stratification of patients with symptoms suggestive of myocardial ischemia.

POPULATION STUDIED: The investigators enrolled 1005 patients older than 18 years with possible myocardial ischemia who presented to the emergency room of 6 US hospitals. Patients were excluded if electrocardiography showed ST-segment elevation or left bundle branch block. The average patient age was 51years; 51% were women; 14% had a previous MI; 21% had diabetes; 53% had hypertension; and 38% were current cigarette smokers. The researchers were able to provide complete results for 95% of the patients.

STUDY DESIGN AND VALIDITY: This was a prospective study looking at the prognostic value of a bedside instrument measuring cardiac enzymes at the point of care. Blood samples were obtained from patients at baseline and at 3 and 6 hours. If the patient was hospitalized, samples were obtained at 9, 12, and 16 to 24 hours. These were analyzed by the Dade-Behring Stratus CS STAT near-patient instrument, which assays myoglobin; creatine kinase, myocardial bound (CK-MB); and troponin I (cTnI) from a blood sample in 15 to 20 minutes. Two multimarker strategies (MMS) were defined: MMS-1 included all 3 markers, and MMS-2 included only CK-MB and cTnI. A strategy was considered positive if any of the markers was positive. The CS STAT assay was compared with the CK-MB result of the local hospital laboratory. All patients underwent both local laboratory testing and bedside testing, but treating physicians used only local CK-MB results in making management decisions. This study was well designed for comparing the prognostic value of the CS STAT values with conventional CK-MB values. However, a more useful outcome would be the utility of this bedside instrument in the diagnosis of MI. Also, whether such an instrument would lead to clinically significant changes in prognosis outside of special chest pain units is unclear.

OUTCOMES MEASURED: The rate of MI or death at 30 days was determined for patients with either a positive or negative MMS or CK-MB test result. Additional assessments included time from arrival to a positive test result and the relation of MMS status to the rates of MI, death, and revascularization at 30 days.

RESULTS: Testing at baseline (on initial evaluation in the emergency department) predicted death or MI within 30 days in 19% of patients with a positive MMS-1, 22% with a positive MMS-2, and 13% with a positive CK-MB result. Conversely, only 3% with a negative MMS-1 or MMS-2 and 6% with a negative CK-MB result died or had a MI at 30 days. With serial testing 55% of persons with an abnormal CK-MB result had a MI at 30 days, while serial MMS testing did not discriminate any better than the single test. The bedside 3-marker strategy was superior in predicting 30-day mortality; all 3 patients who died had a positive MMS-1 at baseline, while only 1 of 3 had an abnormal CK-MB on serial testing. An abnormal CK-MB result predicted revascularization within 30-days better than bedside testing using both single and serial measurements. After emergency department arrival, positive test results were obtained more quickly using the bedside instrument (MMS-1=2.5 hours, MMS-2=2.8 hours, LL=3.4 hours; P=.0001).

BACKGROUND: Emergency departments triage more than 5 million patients with chest pain each year. Cardiac blood tests are used to identify patients at higher risk for MI or death. The bedside instrument in this study is a new approach to the immediate risk stratification of patients with symptoms suggestive of myocardial ischemia.

POPULATION STUDIED: The investigators enrolled 1005 patients older than 18 years with possible myocardial ischemia who presented to the emergency room of 6 US hospitals. Patients were excluded if electrocardiography showed ST-segment elevation or left bundle branch block. The average patient age was 51years; 51% were women; 14% had a previous MI; 21% had diabetes; 53% had hypertension; and 38% were current cigarette smokers. The researchers were able to provide complete results for 95% of the patients.

STUDY DESIGN AND VALIDITY: This was a prospective study looking at the prognostic value of a bedside instrument measuring cardiac enzymes at the point of care. Blood samples were obtained from patients at baseline and at 3 and 6 hours. If the patient was hospitalized, samples were obtained at 9, 12, and 16 to 24 hours. These were analyzed by the Dade-Behring Stratus CS STAT near-patient instrument, which assays myoglobin; creatine kinase, myocardial bound (CK-MB); and troponin I (cTnI) from a blood sample in 15 to 20 minutes. Two multimarker strategies (MMS) were defined: MMS-1 included all 3 markers, and MMS-2 included only CK-MB and cTnI. A strategy was considered positive if any of the markers was positive. The CS STAT assay was compared with the CK-MB result of the local hospital laboratory. All patients underwent both local laboratory testing and bedside testing, but treating physicians used only local CK-MB results in making management decisions. This study was well designed for comparing the prognostic value of the CS STAT values with conventional CK-MB values. However, a more useful outcome would be the utility of this bedside instrument in the diagnosis of MI. Also, whether such an instrument would lead to clinically significant changes in prognosis outside of special chest pain units is unclear.

OUTCOMES MEASURED: The rate of MI or death at 30 days was determined for patients with either a positive or negative MMS or CK-MB test result. Additional assessments included time from arrival to a positive test result and the relation of MMS status to the rates of MI, death, and revascularization at 30 days.

RESULTS: Testing at baseline (on initial evaluation in the emergency department) predicted death or MI within 30 days in 19% of patients with a positive MMS-1, 22% with a positive MMS-2, and 13% with a positive CK-MB result. Conversely, only 3% with a negative MMS-1 or MMS-2 and 6% with a negative CK-MB result died or had a MI at 30 days. With serial testing 55% of persons with an abnormal CK-MB result had a MI at 30 days, while serial MMS testing did not discriminate any better than the single test. The bedside 3-marker strategy was superior in predicting 30-day mortality; all 3 patients who died had a positive MMS-1 at baseline, while only 1 of 3 had an abnormal CK-MB on serial testing. An abnormal CK-MB result predicted revascularization within 30-days better than bedside testing using both single and serial measurements. After emergency department arrival, positive test results were obtained more quickly using the bedside instrument (MMS-1=2.5 hours, MMS-2=2.8 hours, LL=3.4 hours; P=.0001).

BACKGROUND: Back problems are among the most prevalent conditions afflicting Americans, and complementary and alternative medical therapies are frequently sought for treatment. This randomized trial compares acupuncture, massage, and self-care education in the treatment of persistent back pain.

POPULATION STUDIED: Individuals aged 20 to 70 years who visited a primary care physician for low back pain were identified, and those who were interested were contacted. The typical study subject was aged 45 years, white, well educated, and employed. Exclusion criteria included sciatica, pregnancy, involvement with litigation or compensation claims for back pain, severe or progressive neurologic deficits, lumbar surgery within the past 3 years, serious comorbid conditions, and bothersomeness of back pain rated as less than 4 on a scale from 0 to 10.

STUDY DESIGN AND VALIDITY: A total of 262 study participants were randomly allocated to receive traditional Chinese medical acupuncture, massage therapy that focused on the manipulation of soft tissue, or self care. The authors did not state whether the investigators knew to which group the patients would be assigned before enrolling them in the study. Study acupuncturists, massage therapists, and consultants established treatment protocols that were considered clinically reasonable.The acupuncturists and massage therapists were allowed to schedule up to 10 visits over 10 weeks. The patients allocated to self care received high-quality and relatively inexpensive unpublished educational materials designed for people with chronic back pain. Interviewers who were masked to treatment group performed follow-up by telephone. Randomization was successful and follow-up personnel were blinded. There were no significant differences among the groups at baseline. The study was designed to have 80% power to detect a 2.5-point difference on the Roland Disability Scale and a 1.5-point difference on the symptom bothersomeness scale for the comparison of acupuncture and massage. Many of the acupuncturists felt some level of restraint in treatment options because of study protocols.

OUTCOMES MEASURED: The primary outcomes of interest were symptoms and dysfunction. Patients measured how bothersome symptoms of back pain, leg pain, numbness, and tingling had been during the preceding week on a scale of 0 to 10. Dysfunction was measured on a modified Roland Disability Scale. Secondary outcomes included disability, utilization, cost, satisfaction with overall care for the back problem, use of medications, the 12-item Medical Outcomes Study short form (SF-12) physical and mental health summary scales, and numbers of days of aerobic exercise and back exercise performed. results At 10 weeks, the massage group had less severe symptoms than the self-care group (P=.01) and less dysfunction than the self-care group (P <.001) and the acupuncture group (P=.01). At 1 year, massage was superior to acupuncture in its effect on symptoms (P=.002) and function (P=.051). At 10 weeks, the massage group and the acupuncture group did not differ from each other in medication use, but did use significantly less medication than the self-care group (P <.05.) Use of medications at 1-year was lower in the massage group than in the other groups (P <.05.) There was no difference in the SF-12 mental health score at 10 weeks, though the SF-12 physical health scores showed massage to be superior to self care (P=.004). At 1 year there were no differences in the SF-12 physical or mental health scores. At the end of the treatment period there was no difference among the groups in number of days exercised.

BACKGROUND: Back problems are among the most prevalent conditions afflicting Americans, and complementary and alternative medical therapies are frequently sought for treatment. This randomized trial compares acupuncture, massage, and self-care education in the treatment of persistent back pain.

POPULATION STUDIED: Individuals aged 20 to 70 years who visited a primary care physician for low back pain were identified, and those who were interested were contacted. The typical study subject was aged 45 years, white, well educated, and employed. Exclusion criteria included sciatica, pregnancy, involvement with litigation or compensation claims for back pain, severe or progressive neurologic deficits, lumbar surgery within the past 3 years, serious comorbid conditions, and bothersomeness of back pain rated as less than 4 on a scale from 0 to 10.

STUDY DESIGN AND VALIDITY: A total of 262 study participants were randomly allocated to receive traditional Chinese medical acupuncture, massage therapy that focused on the manipulation of soft tissue, or self care. The authors did not state whether the investigators knew to which group the patients would be assigned before enrolling them in the study. Study acupuncturists, massage therapists, and consultants established treatment protocols that were considered clinically reasonable.The acupuncturists and massage therapists were allowed to schedule up to 10 visits over 10 weeks. The patients allocated to self care received high-quality and relatively inexpensive unpublished educational materials designed for people with chronic back pain. Interviewers who were masked to treatment group performed follow-up by telephone. Randomization was successful and follow-up personnel were blinded. There were no significant differences among the groups at baseline. The study was designed to have 80% power to detect a 2.5-point difference on the Roland Disability Scale and a 1.5-point difference on the symptom bothersomeness scale for the comparison of acupuncture and massage. Many of the acupuncturists felt some level of restraint in treatment options because of study protocols.

OUTCOMES MEASURED: The primary outcomes of interest were symptoms and dysfunction. Patients measured how bothersome symptoms of back pain, leg pain, numbness, and tingling had been during the preceding week on a scale of 0 to 10. Dysfunction was measured on a modified Roland Disability Scale. Secondary outcomes included disability, utilization, cost, satisfaction with overall care for the back problem, use of medications, the 12-item Medical Outcomes Study short form (SF-12) physical and mental health summary scales, and numbers of days of aerobic exercise and back exercise performed. results At 10 weeks, the massage group had less severe symptoms than the self-care group (P=.01) and less dysfunction than the self-care group (P <.001) and the acupuncture group (P=.01). At 1 year, massage was superior to acupuncture in its effect on symptoms (P=.002) and function (P=.051). At 10 weeks, the massage group and the acupuncture group did not differ from each other in medication use, but did use significantly less medication than the self-care group (P <.05.) Use of medications at 1-year was lower in the massage group than in the other groups (P <.05.) There was no difference in the SF-12 mental health score at 10 weeks, though the SF-12 physical health scores showed massage to be superior to self care (P=.004). At 1 year there were no differences in the SF-12 physical or mental health scores. At the end of the treatment period there was no difference among the groups in number of days exercised.

BACKGROUND: Back problems are among the most prevalent conditions afflicting Americans, and complementary and alternative medical therapies are frequently sought for treatment. This randomized trial compares acupuncture, massage, and self-care education in the treatment of persistent back pain.

POPULATION STUDIED: Individuals aged 20 to 70 years who visited a primary care physician for low back pain were identified, and those who were interested were contacted. The typical study subject was aged 45 years, white, well educated, and employed. Exclusion criteria included sciatica, pregnancy, involvement with litigation or compensation claims for back pain, severe or progressive neurologic deficits, lumbar surgery within the past 3 years, serious comorbid conditions, and bothersomeness of back pain rated as less than 4 on a scale from 0 to 10.

STUDY DESIGN AND VALIDITY: A total of 262 study participants were randomly allocated to receive traditional Chinese medical acupuncture, massage therapy that focused on the manipulation of soft tissue, or self care. The authors did not state whether the investigators knew to which group the patients would be assigned before enrolling them in the study. Study acupuncturists, massage therapists, and consultants established treatment protocols that were considered clinically reasonable.The acupuncturists and massage therapists were allowed to schedule up to 10 visits over 10 weeks. The patients allocated to self care received high-quality and relatively inexpensive unpublished educational materials designed for people with chronic back pain. Interviewers who were masked to treatment group performed follow-up by telephone. Randomization was successful and follow-up personnel were blinded. There were no significant differences among the groups at baseline. The study was designed to have 80% power to detect a 2.5-point difference on the Roland Disability Scale and a 1.5-point difference on the symptom bothersomeness scale for the comparison of acupuncture and massage. Many of the acupuncturists felt some level of restraint in treatment options because of study protocols.

OUTCOMES MEASURED: The primary outcomes of interest were symptoms and dysfunction. Patients measured how bothersome symptoms of back pain, leg pain, numbness, and tingling had been during the preceding week on a scale of 0 to 10. Dysfunction was measured on a modified Roland Disability Scale. Secondary outcomes included disability, utilization, cost, satisfaction with overall care for the back problem, use of medications, the 12-item Medical Outcomes Study short form (SF-12) physical and mental health summary scales, and numbers of days of aerobic exercise and back exercise performed. results At 10 weeks, the massage group had less severe symptoms than the self-care group (P=.01) and less dysfunction than the self-care group (P <.001) and the acupuncture group (P=.01). At 1 year, massage was superior to acupuncture in its effect on symptoms (P=.002) and function (P=.051). At 10 weeks, the massage group and the acupuncture group did not differ from each other in medication use, but did use significantly less medication than the self-care group (P <.05.) Use of medications at 1-year was lower in the massage group than in the other groups (P <.05.) There was no difference in the SF-12 mental health score at 10 weeks, though the SF-12 physical health scores showed massage to be superior to self care (P=.004). At 1 year there were no differences in the SF-12 physical or mental health scores. At the end of the treatment period there was no difference among the groups in number of days exercised.

BACKGROUND: HRT relieves vasomotor symptoms in postmenopausal women but is associated with adverse side effects. Low-dose HRT has been shown to reduce side effects, but its effectiveness for the relief of vasomotor symptoms is uncertain.

POPULATION STUDIED: A total of 241 predominantly white (88%) women who reported at least 7 daily moderate-to-severe baseline hot flushes or at least 50 total hot flushes per week were evaluated. The subjects were chosen from 2673 healthy postmenopausal women who were aged 40 to 65 years, had intact uteruses, and were within 20% of normal body weight. Exclusion criteria included use of hormones or medicines known to affect vasomotor symptoms. This population is similar to the healthy postmenopausal patients of many family physicians.

STUDY DESIGN AND VALIDITY: The participants were randomized in a double-blind manner (concealed allocation assignment) to 1 of 8 treatment groups including combinations of either placebo or conjugated equine estrogens (CEE) with or without medroxyprogesterone (MPA) for 1 year (13 cycles of 28 days each). Daily dosing regimens were: CEE 0.625 mg, CEE 0.625 mg and MPA 2.5 mg, CEE 0.45 mg, CEE 0.45 mg and MPA 2.5 mg, CEE 0.45 mg and MPA 1.5 mg, CEE 0.3 mg, CEE 0.3 mg and MPA 1.5 mg, or placebo. The patients recorded the number and severity of hot flushes on daily diary cards that were collected at office visits scheduled for cycle 3, 6, 9, and 13. The mean daily number and the mean daily severity of hot flushes were calculated and compared using paired t tests. Vaginal atrophy was assessed by a vaginal maturation index (VMI) that was performed twice. This analysis was done in an intention-to-treat population.Unfortunately, data presentation was ambiguous: No numerical data or confidence intervals were given, making it difficult to both quantify the decrease in number and severity of hot flushes in the treatment groups and to assess clinical significance of the results. The lack of correlation between VMI and symptoms of vaginal atrophy make this information clinically meaningless. Finally, the withdrawal rate of the evaluable population was not given.

OUTCOME MEASURED: The number and severity of hot flushes experienced and the change of the VMIs over the 13 cycles were measured. Cost, quality-of-life improvement, and symptoms of vaginal atrophy were not addressed.

RESULTS: The baseline characteristics of the women in the various groups were similar. All active treatment groups experienced a decrease in the mean number of daily hot flushes when compared with the placebo group (P <.05), and there was no difference observed between the standard dose of HRT therapy (CEE 0.625 mg/MPA 2.5 mg) and low-dose HRT. The CEE 0.625 mg group reported fewer hot flushes than the other lower estrogen-only groups (P <.05). Results were similar for the mean daily severity of hot flushes. All active treatment groups experienced a decrease in severity of hot flushes compared with placebo (P <.05), and there was no significant difference between the standard dose and the lower dose combinations. The CEE 0.625 mg group experienced less severe hot flushes than the other lower estrogen-only treated groups by cycle 3 (P <.05). All active treatment groups reported a significant increase in VMI at cycle 6 and 13 when compared with placebo (P <.001).

BACKGROUND: HRT relieves vasomotor symptoms in postmenopausal women but is associated with adverse side effects. Low-dose HRT has been shown to reduce side effects, but its effectiveness for the relief of vasomotor symptoms is uncertain.

POPULATION STUDIED: A total of 241 predominantly white (88%) women who reported at least 7 daily moderate-to-severe baseline hot flushes or at least 50 total hot flushes per week were evaluated. The subjects were chosen from 2673 healthy postmenopausal women who were aged 40 to 65 years, had intact uteruses, and were within 20% of normal body weight. Exclusion criteria included use of hormones or medicines known to affect vasomotor symptoms. This population is similar to the healthy postmenopausal patients of many family physicians.

STUDY DESIGN AND VALIDITY: The participants were randomized in a double-blind manner (concealed allocation assignment) to 1 of 8 treatment groups including combinations of either placebo or conjugated equine estrogens (CEE) with or without medroxyprogesterone (MPA) for 1 year (13 cycles of 28 days each). Daily dosing regimens were: CEE 0.625 mg, CEE 0.625 mg and MPA 2.5 mg, CEE 0.45 mg, CEE 0.45 mg and MPA 2.5 mg, CEE 0.45 mg and MPA 1.5 mg, CEE 0.3 mg, CEE 0.3 mg and MPA 1.5 mg, or placebo. The patients recorded the number and severity of hot flushes on daily diary cards that were collected at office visits scheduled for cycle 3, 6, 9, and 13. The mean daily number and the mean daily severity of hot flushes were calculated and compared using paired t tests. Vaginal atrophy was assessed by a vaginal maturation index (VMI) that was performed twice. This analysis was done in an intention-to-treat population.Unfortunately, data presentation was ambiguous: No numerical data or confidence intervals were given, making it difficult to both quantify the decrease in number and severity of hot flushes in the treatment groups and to assess clinical significance of the results. The lack of correlation between VMI and symptoms of vaginal atrophy make this information clinically meaningless. Finally, the withdrawal rate of the evaluable population was not given.

OUTCOME MEASURED: The number and severity of hot flushes experienced and the change of the VMIs over the 13 cycles were measured. Cost, quality-of-life improvement, and symptoms of vaginal atrophy were not addressed.

RESULTS: The baseline characteristics of the women in the various groups were similar. All active treatment groups experienced a decrease in the mean number of daily hot flushes when compared with the placebo group (P <.05), and there was no difference observed between the standard dose of HRT therapy (CEE 0.625 mg/MPA 2.5 mg) and low-dose HRT. The CEE 0.625 mg group reported fewer hot flushes than the other lower estrogen-only groups (P <.05). Results were similar for the mean daily severity of hot flushes. All active treatment groups experienced a decrease in severity of hot flushes compared with placebo (P <.05), and there was no significant difference between the standard dose and the lower dose combinations. The CEE 0.625 mg group experienced less severe hot flushes than the other lower estrogen-only treated groups by cycle 3 (P <.05). All active treatment groups reported a significant increase in VMI at cycle 6 and 13 when compared with placebo (P <.001).

BACKGROUND: HRT relieves vasomotor symptoms in postmenopausal women but is associated with adverse side effects. Low-dose HRT has been shown to reduce side effects, but its effectiveness for the relief of vasomotor symptoms is uncertain.

POPULATION STUDIED: A total of 241 predominantly white (88%) women who reported at least 7 daily moderate-to-severe baseline hot flushes or at least 50 total hot flushes per week were evaluated. The subjects were chosen from 2673 healthy postmenopausal women who were aged 40 to 65 years, had intact uteruses, and were within 20% of normal body weight. Exclusion criteria included use of hormones or medicines known to affect vasomotor symptoms. This population is similar to the healthy postmenopausal patients of many family physicians.

STUDY DESIGN AND VALIDITY: The participants were randomized in a double-blind manner (concealed allocation assignment) to 1 of 8 treatment groups including combinations of either placebo or conjugated equine estrogens (CEE) with or without medroxyprogesterone (MPA) for 1 year (13 cycles of 28 days each). Daily dosing regimens were: CEE 0.625 mg, CEE 0.625 mg and MPA 2.5 mg, CEE 0.45 mg, CEE 0.45 mg and MPA 2.5 mg, CEE 0.45 mg and MPA 1.5 mg, CEE 0.3 mg, CEE 0.3 mg and MPA 1.5 mg, or placebo. The patients recorded the number and severity of hot flushes on daily diary cards that were collected at office visits scheduled for cycle 3, 6, 9, and 13. The mean daily number and the mean daily severity of hot flushes were calculated and compared using paired t tests. Vaginal atrophy was assessed by a vaginal maturation index (VMI) that was performed twice. This analysis was done in an intention-to-treat population.Unfortunately, data presentation was ambiguous: No numerical data or confidence intervals were given, making it difficult to both quantify the decrease in number and severity of hot flushes in the treatment groups and to assess clinical significance of the results. The lack of correlation between VMI and symptoms of vaginal atrophy make this information clinically meaningless. Finally, the withdrawal rate of the evaluable population was not given.

OUTCOME MEASURED: The number and severity of hot flushes experienced and the change of the VMIs over the 13 cycles were measured. Cost, quality-of-life improvement, and symptoms of vaginal atrophy were not addressed.

RESULTS: The baseline characteristics of the women in the various groups were similar. All active treatment groups experienced a decrease in the mean number of daily hot flushes when compared with the placebo group (P <.05), and there was no difference observed between the standard dose of HRT therapy (CEE 0.625 mg/MPA 2.5 mg) and low-dose HRT. The CEE 0.625 mg group reported fewer hot flushes than the other lower estrogen-only groups (P <.05). Results were similar for the mean daily severity of hot flushes. All active treatment groups experienced a decrease in severity of hot flushes compared with placebo (P <.05), and there was no significant difference between the standard dose and the lower dose combinations. The CEE 0.625 mg group experienced less severe hot flushes than the other lower estrogen-only treated groups by cycle 3 (P <.05). All active treatment groups reported a significant increase in VMI at cycle 6 and 13 when compared with placebo (P <.001).

BACKGROUND: Previous studies have not shown that routine catheterization and appropriate revascularization offers better outcomes than more conservative approaches in patients with unstable angina or myocardial infarction (MI) without ST-segment elevation. The authors hypothesized that the effectiveness of glycoprotein IIb/IIIa inhibitors and coronary stenting in patients treated with percutaneous coronary revascularization (PCR) would lead to better outcomes in patients with unstable coronary syndromes who are treated with an early invasive strategy.

POPULATION STUDIED: The investigators enrolled 2220 patients presenting with prolonged or recurrent angina at rest or with minimal effort, or with an accelerating pattern of angina. Patients also had to have 1 or more of the following: (1) electrocardiographic evidence of ischemia, (2) abnormal cardiac enzymes, or (3) documented coronary artery disease. Patients were excluded if they had persistent ST-segment elevation, secondary angina, PCR or coronary artery bypass surgery (CABG) within 6 months, left bundle branch block or a paced rhythm, factors associated with increased bleeding risk, severe congestive heart failure or cardiogenic shock, serious systemic disease, serum creatinine higher than 2.5 mg per dL, or recent treatment with ticlopidine, clopidogrel, or warfarin.

STUDY DESIGN AND VALIDITY: This was a randomized controlled trial. Investigators used a central center to randomize patients to immediate (within 48 hours) cardiac angiography with appropriate revascularization or to conservative therapy. Patients receiving conservative therapy had angiography if they met criteria for recurrent ischemia, infarction, hemodynamic instability, ischemia on exercise testing, or readmission. All conservatively managed patients without recurrent ischemia had a treadmill before discharge. All patients received intravenous heparin, aspirin, a b-blocker, nitrates, and tirofiban, a glycoprotein IIb/IIIa inhibitor. Patients were followed up for up to 6 months. The study is methodologically sound. Only 27 patients (1.2 %) were lost to follow-up at 6 months. A weakness of this study is that fewer patients in the conservative strategy group undergoing PCR received tirofiban (59%, vs 95% in the invasive strategy group). An appropriate stratified analysis of this unplanned treatment difference showed no difference in the results.

OUTCOMES MEASURED: The primary outcome was the combined incidence of death, nonfatal MI, and rehospitalization for an acute coronary syndrome at 6 months.

RESULTS: In the invasive strategy arm, 97% of patients received angiography within a median of 22 hours of randomization, and 60% underwent PCR or CABG. An additional 1% required revascularization by 6 months. Among conservatively managed patients, 51% had angiography, and 36% had revascularization during or soon after their initial hospitalization. An additional 8% had revascularization within 6 months. CABG and PCR rates were similar among patients in the 2 groups who underwent catheterization. Most patients (80%) in each group undergoing PCR received stenting.

BACKGROUND: Previous studies have not shown that routine catheterization and appropriate revascularization offers better outcomes than more conservative approaches in patients with unstable angina or myocardial infarction (MI) without ST-segment elevation. The authors hypothesized that the effectiveness of glycoprotein IIb/IIIa inhibitors and coronary stenting in patients treated with percutaneous coronary revascularization (PCR) would lead to better outcomes in patients with unstable coronary syndromes who are treated with an early invasive strategy.

POPULATION STUDIED: The investigators enrolled 2220 patients presenting with prolonged or recurrent angina at rest or with minimal effort, or with an accelerating pattern of angina. Patients also had to have 1 or more of the following: (1) electrocardiographic evidence of ischemia, (2) abnormal cardiac enzymes, or (3) documented coronary artery disease. Patients were excluded if they had persistent ST-segment elevation, secondary angina, PCR or coronary artery bypass surgery (CABG) within 6 months, left bundle branch block or a paced rhythm, factors associated with increased bleeding risk, severe congestive heart failure or cardiogenic shock, serious systemic disease, serum creatinine higher than 2.5 mg per dL, or recent treatment with ticlopidine, clopidogrel, or warfarin.

STUDY DESIGN AND VALIDITY: This was a randomized controlled trial. Investigators used a central center to randomize patients to immediate (within 48 hours) cardiac angiography with appropriate revascularization or to conservative therapy. Patients receiving conservative therapy had angiography if they met criteria for recurrent ischemia, infarction, hemodynamic instability, ischemia on exercise testing, or readmission. All conservatively managed patients without recurrent ischemia had a treadmill before discharge. All patients received intravenous heparin, aspirin, a b-blocker, nitrates, and tirofiban, a glycoprotein IIb/IIIa inhibitor. Patients were followed up for up to 6 months. The study is methodologically sound. Only 27 patients (1.2 %) were lost to follow-up at 6 months. A weakness of this study is that fewer patients in the conservative strategy group undergoing PCR received tirofiban (59%, vs 95% in the invasive strategy group). An appropriate stratified analysis of this unplanned treatment difference showed no difference in the results.

OUTCOMES MEASURED: The primary outcome was the combined incidence of death, nonfatal MI, and rehospitalization for an acute coronary syndrome at 6 months.

RESULTS: In the invasive strategy arm, 97% of patients received angiography within a median of 22 hours of randomization, and 60% underwent PCR or CABG. An additional 1% required revascularization by 6 months. Among conservatively managed patients, 51% had angiography, and 36% had revascularization during or soon after their initial hospitalization. An additional 8% had revascularization within 6 months. CABG and PCR rates were similar among patients in the 2 groups who underwent catheterization. Most patients (80%) in each group undergoing PCR received stenting.

BACKGROUND: Previous studies have not shown that routine catheterization and appropriate revascularization offers better outcomes than more conservative approaches in patients with unstable angina or myocardial infarction (MI) without ST-segment elevation. The authors hypothesized that the effectiveness of glycoprotein IIb/IIIa inhibitors and coronary stenting in patients treated with percutaneous coronary revascularization (PCR) would lead to better outcomes in patients with unstable coronary syndromes who are treated with an early invasive strategy.

POPULATION STUDIED: The investigators enrolled 2220 patients presenting with prolonged or recurrent angina at rest or with minimal effort, or with an accelerating pattern of angina. Patients also had to have 1 or more of the following: (1) electrocardiographic evidence of ischemia, (2) abnormal cardiac enzymes, or (3) documented coronary artery disease. Patients were excluded if they had persistent ST-segment elevation, secondary angina, PCR or coronary artery bypass surgery (CABG) within 6 months, left bundle branch block or a paced rhythm, factors associated with increased bleeding risk, severe congestive heart failure or cardiogenic shock, serious systemic disease, serum creatinine higher than 2.5 mg per dL, or recent treatment with ticlopidine, clopidogrel, or warfarin.

STUDY DESIGN AND VALIDITY: This was a randomized controlled trial. Investigators used a central center to randomize patients to immediate (within 48 hours) cardiac angiography with appropriate revascularization or to conservative therapy. Patients receiving conservative therapy had angiography if they met criteria for recurrent ischemia, infarction, hemodynamic instability, ischemia on exercise testing, or readmission. All conservatively managed patients without recurrent ischemia had a treadmill before discharge. All patients received intravenous heparin, aspirin, a b-blocker, nitrates, and tirofiban, a glycoprotein IIb/IIIa inhibitor. Patients were followed up for up to 6 months. The study is methodologically sound. Only 27 patients (1.2 %) were lost to follow-up at 6 months. A weakness of this study is that fewer patients in the conservative strategy group undergoing PCR received tirofiban (59%, vs 95% in the invasive strategy group). An appropriate stratified analysis of this unplanned treatment difference showed no difference in the results.

OUTCOMES MEASURED: The primary outcome was the combined incidence of death, nonfatal MI, and rehospitalization for an acute coronary syndrome at 6 months.

RESULTS: In the invasive strategy arm, 97% of patients received angiography within a median of 22 hours of randomization, and 60% underwent PCR or CABG. An additional 1% required revascularization by 6 months. Among conservatively managed patients, 51% had angiography, and 36% had revascularization during or soon after their initial hospitalization. An additional 8% had revascularization within 6 months. CABG and PCR rates were similar among patients in the 2 groups who underwent catheterization. Most patients (80%) in each group undergoing PCR received stenting.