Q&A

ABSTRACT

BACKGROUND: B-type natriuretic peptide is released from the cardiac ventricles in response to volume expansion and pressure overload. Levels correlate with severity of congestive heart failure (CHF) and prognosis. A rapid assay for B-type natriuretic peptide might help clinicians’ accuracy in distinguishing CHF from other conditions (eg, chronic obstructive pulmonary disease) as the cause of acute dyspnea in an emergency setting.

POPULATION STUDIED: The investigators enrolled 1586 patients from 7 sites (5 in the United States, 1 in France, 1 in Norway). Eligible subjects (at least 18 years old) presented to the emergency department with shortness of breath for which CHF could not be obviously ruled out (such as in trauma or cardiac tamponade). Patients were not included if they had acute myocardial infarction or renal failure; patients were also not included if they had unstable angina, unless their predominant presenting symptom was dyspnea. Forty-four percent of the subjects were women; 49% were white, 45% were black, and 6% were from other races.

STUDY DESIGN AND VALIDITY: This study evaluated the role B-type natriuretic peptide determinations might play in the diagnosis of CHF by comparing B-type natriuretic peptide levels with clinical diagnosis as the gold standard. Blood was drawn from all included patients for measurement of B-type natriuretic peptide. Emergency room physicians, who were not given the laboratory results, assessed the probability that the patient had CHF. Patients with a history of CHF were classified as having either an exacerbation of CHF or dyspnea from another cause with underlying left ventricular dysfunction.

OUTCOMES MEASURED: Whole blood or plasma levels of B-type natriuretic peptide were measured using a fluorescence immunoassay kit (Triage BNP Test; Biosite Inc, San Diego, CA) and the results were compared with clinical diagnoses to determine the sensitivity, specificity, and accuracy of the test in the diagnosis of CHF. Receiver-operating-characteristic curves were constructed to illustrate various cutoff values of B-type natriuretic peptide. Long-term outcomes of patients with CHF were not measured.

RESULTS: Congestive heart failure was diagnosed in 744 patients (47%), dyspnea due to noncardiac causes in 72 patients with a history of CHF (5%), and no CHF in 770 (48%). The B-type natriuretic peptide level test performed well for diagnosing CHF; the area under the receiver-operating-characteristic curve was 0.91 (where 1.0 indicates a perfect test). A value of 100 pg/mL or more was the single most accurate predictor of the presence of CHF when compared with clinical predictors such as history, physical examination, or chest x-ray. This B-type natriuretic peptide cutoff value of 100 pg/mL was 90% sensitive, 76% specific, and 83% accurate in differentiating CHF from other causes of dyspnea. As such, this cutoff value outperformed the accuracy of 2 commonly used clinical criteria used for diagnosing CHF, the National Health and Nutrition Examination Survey (NHANES) criteria (67%) and Framingham criteria (73%). At this prevalence of 47%, a level of 50 pg/mL was associated with a negative predictive value of 96%. B-type natriuretic peptide values also correlated with CHF severity as determined by the New York Heart Association functional class.

ABSTRACT

BACKGROUND: B-type natriuretic peptide is released from the cardiac ventricles in response to volume expansion and pressure overload. Levels correlate with severity of congestive heart failure (CHF) and prognosis. A rapid assay for B-type natriuretic peptide might help clinicians’ accuracy in distinguishing CHF from other conditions (eg, chronic obstructive pulmonary disease) as the cause of acute dyspnea in an emergency setting.

POPULATION STUDIED: The investigators enrolled 1586 patients from 7 sites (5 in the United States, 1 in France, 1 in Norway). Eligible subjects (at least 18 years old) presented to the emergency department with shortness of breath for which CHF could not be obviously ruled out (such as in trauma or cardiac tamponade). Patients were not included if they had acute myocardial infarction or renal failure; patients were also not included if they had unstable angina, unless their predominant presenting symptom was dyspnea. Forty-four percent of the subjects were women; 49% were white, 45% were black, and 6% were from other races.

STUDY DESIGN AND VALIDITY: This study evaluated the role B-type natriuretic peptide determinations might play in the diagnosis of CHF by comparing B-type natriuretic peptide levels with clinical diagnosis as the gold standard. Blood was drawn from all included patients for measurement of B-type natriuretic peptide. Emergency room physicians, who were not given the laboratory results, assessed the probability that the patient had CHF. Patients with a history of CHF were classified as having either an exacerbation of CHF or dyspnea from another cause with underlying left ventricular dysfunction.

OUTCOMES MEASURED: Whole blood or plasma levels of B-type natriuretic peptide were measured using a fluorescence immunoassay kit (Triage BNP Test; Biosite Inc, San Diego, CA) and the results were compared with clinical diagnoses to determine the sensitivity, specificity, and accuracy of the test in the diagnosis of CHF. Receiver-operating-characteristic curves were constructed to illustrate various cutoff values of B-type natriuretic peptide. Long-term outcomes of patients with CHF were not measured.

RESULTS: Congestive heart failure was diagnosed in 744 patients (47%), dyspnea due to noncardiac causes in 72 patients with a history of CHF (5%), and no CHF in 770 (48%). The B-type natriuretic peptide level test performed well for diagnosing CHF; the area under the receiver-operating-characteristic curve was 0.91 (where 1.0 indicates a perfect test). A value of 100 pg/mL or more was the single most accurate predictor of the presence of CHF when compared with clinical predictors such as history, physical examination, or chest x-ray. This B-type natriuretic peptide cutoff value of 100 pg/mL was 90% sensitive, 76% specific, and 83% accurate in differentiating CHF from other causes of dyspnea. As such, this cutoff value outperformed the accuracy of 2 commonly used clinical criteria used for diagnosing CHF, the National Health and Nutrition Examination Survey (NHANES) criteria (67%) and Framingham criteria (73%). At this prevalence of 47%, a level of 50 pg/mL was associated with a negative predictive value of 96%. B-type natriuretic peptide values also correlated with CHF severity as determined by the New York Heart Association functional class.

ABSTRACT

BACKGROUND: B-type natriuretic peptide is released from the cardiac ventricles in response to volume expansion and pressure overload. Levels correlate with severity of congestive heart failure (CHF) and prognosis. A rapid assay for B-type natriuretic peptide might help clinicians’ accuracy in distinguishing CHF from other conditions (eg, chronic obstructive pulmonary disease) as the cause of acute dyspnea in an emergency setting.

POPULATION STUDIED: The investigators enrolled 1586 patients from 7 sites (5 in the United States, 1 in France, 1 in Norway). Eligible subjects (at least 18 years old) presented to the emergency department with shortness of breath for which CHF could not be obviously ruled out (such as in trauma or cardiac tamponade). Patients were not included if they had acute myocardial infarction or renal failure; patients were also not included if they had unstable angina, unless their predominant presenting symptom was dyspnea. Forty-four percent of the subjects were women; 49% were white, 45% were black, and 6% were from other races.

STUDY DESIGN AND VALIDITY: This study evaluated the role B-type natriuretic peptide determinations might play in the diagnosis of CHF by comparing B-type natriuretic peptide levels with clinical diagnosis as the gold standard. Blood was drawn from all included patients for measurement of B-type natriuretic peptide. Emergency room physicians, who were not given the laboratory results, assessed the probability that the patient had CHF. Patients with a history of CHF were classified as having either an exacerbation of CHF or dyspnea from another cause with underlying left ventricular dysfunction.

OUTCOMES MEASURED: Whole blood or plasma levels of B-type natriuretic peptide were measured using a fluorescence immunoassay kit (Triage BNP Test; Biosite Inc, San Diego, CA) and the results were compared with clinical diagnoses to determine the sensitivity, specificity, and accuracy of the test in the diagnosis of CHF. Receiver-operating-characteristic curves were constructed to illustrate various cutoff values of B-type natriuretic peptide. Long-term outcomes of patients with CHF were not measured.

RESULTS: Congestive heart failure was diagnosed in 744 patients (47%), dyspnea due to noncardiac causes in 72 patients with a history of CHF (5%), and no CHF in 770 (48%). The B-type natriuretic peptide level test performed well for diagnosing CHF; the area under the receiver-operating-characteristic curve was 0.91 (where 1.0 indicates a perfect test). A value of 100 pg/mL or more was the single most accurate predictor of the presence of CHF when compared with clinical predictors such as history, physical examination, or chest x-ray. This B-type natriuretic peptide cutoff value of 100 pg/mL was 90% sensitive, 76% specific, and 83% accurate in differentiating CHF from other causes of dyspnea. As such, this cutoff value outperformed the accuracy of 2 commonly used clinical criteria used for diagnosing CHF, the National Health and Nutrition Examination Survey (NHANES) criteria (67%) and Framingham criteria (73%). At this prevalence of 47%, a level of 50 pg/mL was associated with a negative predictive value of 96%. B-type natriuretic peptide values also correlated with CHF severity as determined by the New York Heart Association functional class.

ABSTRACT

BACKGROUND: Despite mortality benefits, β-blockers are often underused, possibly because of concerns of developing side effects. The authors systematically reviewed trials with patients receiving β-blockers for myocardial infarction, heart failure, or hypertension that assessed for symptoms of depression, fatigue, and sexual dysfunction.

POPULATION STUDIED: Researchers identified controlled trials completed before December 2001 using a MEDLINE search. Reference lists of published trials were reviewed for additional studies. The authors identified 475 articles that matched keyword searches and found 15 randomized placebo-controlled trials meeting inclusion criteria of enrollment of at least 100 patients with a minimum 6-month follow-up. This evaluation included 6 post-myocardial infarction, 3 heart failure, and 6 hypertension trials totaling more than 35,000 patients.

STUDY DESIGN AND VALIDITY: The authors compared β-blockers with placebo in relation to patient-reported depression, fatigue, and sexual dysfunction, and withdrawal due to these agents. Propranolol and timolol were classified as early-generation drugs and the remaining tested β-blockers classified as late-generation agents. Bucindolol, carvedilol, and propranolol were categorized as highly lipid soluble agents, with the rest as low-to-moderately lipid soluble.

OUTCOMES MEASURED: The main outcomes measured were number of patient-reported symptoms and withdrawal of therapy related to each of the evaluated side effects—depression, fatigue, or sexual dysfunction—compared with placebo.

RESULTS: Seven of the 15 trials evaluated the overall frequency of reported depressive symptoms. Combining the result of these 7 trials identified no difference compared with placebo. Withdrawal of medication attributed to depression was assessed in 4 trials (N = 5800) with an average follow-up of 14 months. No difference was noted between b-blocker therapy and placebo for risk of withdrawal due to depression (relative risk [RR] = 0.94; 95% confidence interval [CI], 0.44–2.01). Early-generation and highly lipid soluble b-blockers were studied in 3 and 5 trials, respectively, with an average follow-up of 16 months. The comparisons for generation and solubility revealed no difference in the incidence of depression.

ABSTRACT

BACKGROUND: Despite mortality benefits, β-blockers are often underused, possibly because of concerns of developing side effects. The authors systematically reviewed trials with patients receiving β-blockers for myocardial infarction, heart failure, or hypertension that assessed for symptoms of depression, fatigue, and sexual dysfunction.

POPULATION STUDIED: Researchers identified controlled trials completed before December 2001 using a MEDLINE search. Reference lists of published trials were reviewed for additional studies. The authors identified 475 articles that matched keyword searches and found 15 randomized placebo-controlled trials meeting inclusion criteria of enrollment of at least 100 patients with a minimum 6-month follow-up. This evaluation included 6 post-myocardial infarction, 3 heart failure, and 6 hypertension trials totaling more than 35,000 patients.

STUDY DESIGN AND VALIDITY: The authors compared β-blockers with placebo in relation to patient-reported depression, fatigue, and sexual dysfunction, and withdrawal due to these agents. Propranolol and timolol were classified as early-generation drugs and the remaining tested β-blockers classified as late-generation agents. Bucindolol, carvedilol, and propranolol were categorized as highly lipid soluble agents, with the rest as low-to-moderately lipid soluble.

OUTCOMES MEASURED: The main outcomes measured were number of patient-reported symptoms and withdrawal of therapy related to each of the evaluated side effects—depression, fatigue, or sexual dysfunction—compared with placebo.

RESULTS: Seven of the 15 trials evaluated the overall frequency of reported depressive symptoms. Combining the result of these 7 trials identified no difference compared with placebo. Withdrawal of medication attributed to depression was assessed in 4 trials (N = 5800) with an average follow-up of 14 months. No difference was noted between b-blocker therapy and placebo for risk of withdrawal due to depression (relative risk [RR] = 0.94; 95% confidence interval [CI], 0.44–2.01). Early-generation and highly lipid soluble b-blockers were studied in 3 and 5 trials, respectively, with an average follow-up of 16 months. The comparisons for generation and solubility revealed no difference in the incidence of depression.

ABSTRACT

BACKGROUND: Despite mortality benefits, β-blockers are often underused, possibly because of concerns of developing side effects. The authors systematically reviewed trials with patients receiving β-blockers for myocardial infarction, heart failure, or hypertension that assessed for symptoms of depression, fatigue, and sexual dysfunction.

POPULATION STUDIED: Researchers identified controlled trials completed before December 2001 using a MEDLINE search. Reference lists of published trials were reviewed for additional studies. The authors identified 475 articles that matched keyword searches and found 15 randomized placebo-controlled trials meeting inclusion criteria of enrollment of at least 100 patients with a minimum 6-month follow-up. This evaluation included 6 post-myocardial infarction, 3 heart failure, and 6 hypertension trials totaling more than 35,000 patients.

STUDY DESIGN AND VALIDITY: The authors compared β-blockers with placebo in relation to patient-reported depression, fatigue, and sexual dysfunction, and withdrawal due to these agents. Propranolol and timolol were classified as early-generation drugs and the remaining tested β-blockers classified as late-generation agents. Bucindolol, carvedilol, and propranolol were categorized as highly lipid soluble agents, with the rest as low-to-moderately lipid soluble.

OUTCOMES MEASURED: The main outcomes measured were number of patient-reported symptoms and withdrawal of therapy related to each of the evaluated side effects—depression, fatigue, or sexual dysfunction—compared with placebo.

RESULTS: Seven of the 15 trials evaluated the overall frequency of reported depressive symptoms. Combining the result of these 7 trials identified no difference compared with placebo. Withdrawal of medication attributed to depression was assessed in 4 trials (N = 5800) with an average follow-up of 14 months. No difference was noted between b-blocker therapy and placebo for risk of withdrawal due to depression (relative risk [RR] = 0.94; 95% confidence interval [CI], 0.44–2.01). Early-generation and highly lipid soluble b-blockers were studied in 3 and 5 trials, respectively, with an average follow-up of 16 months. The comparisons for generation and solubility revealed no difference in the incidence of depression.

ABSTRACT

BACKGROUND: Several nonrandomized, observational studies have suggested that antioxidant vitamins decrease vascular disease, cancer, and mortality. However, large randomized trials are needed to counter biases such as the “healthy user effect” often seen in observational studies.

POPULATION STUDIED: The investigators studied 20,536 adults (mostly men from the United Kingdom) aged 40 to 80 years with diabetes, peripheral artery disease, or coronary artery disease. Patients were included if their total cholesterol concentration was above 3.5 mmol/L (135 mg/dL) and they were at a “substantial risk” for more than 5 years of death from coronary disease due to the presence of known cardiovascular disease (coronary artery disease, peripheral artery disease, cerebrovascular disease), diabetes, or hypertension. Patients were excluded if they had other life-threatening illnesses, diagnosed cancer, or were already taking high-dose vitamin E supplements.

STUDY DESIGN AND VALIDITY: Patients in this impressive placebo-controlled, double-blind randomized (masked allocation via central telephone system) trial received antioxidant supplementation (vitamin E 600 mg, vitamin C 250 mg, and beta-carotene 20 mg daily) or matching placebo. This study was part of the MRC/BHF study on simvastatin. All patients in the vitamin treatment group also received simvastatin. In an 8- to 10-week “prerandomization run-in” phase eligibility and compliance with the 5-year study protocol was assessed. Patients were seen at 4, 8, and 12 months, and then every 6 months during a 5-year period.

OUTCOMES MEASURED: The primary outcomes measured were “major coronary events” (nonfatal myocardial infarction or death from coronary disease) and fatal coronary heart disease. Secondary outcomes measured were effects on major coronary events and major vascular events and nonfatal or fatal stroke. Other outcomes included site-specific cancer, cerebral hemorrhage, vascular procedures, and hospitalization for various causes.

RESULTS: Patients taking vitamins had significantly higher levels of these vitamins in their blood. Despite this increase no difference was noted in all-cause mortality or deaths due to vascular or nonvascular causes. There were no differences in nonfatal myocardial infarctions, coronary death, nonfatal or fatal stroke, or coronary or noncoronary revascularization. No differences were noted in cancer incidence or hospitalization for any other nonvascular cause.

ABSTRACT

BACKGROUND: Several nonrandomized, observational studies have suggested that antioxidant vitamins decrease vascular disease, cancer, and mortality. However, large randomized trials are needed to counter biases such as the “healthy user effect” often seen in observational studies.

POPULATION STUDIED: The investigators studied 20,536 adults (mostly men from the United Kingdom) aged 40 to 80 years with diabetes, peripheral artery disease, or coronary artery disease. Patients were included if their total cholesterol concentration was above 3.5 mmol/L (135 mg/dL) and they were at a “substantial risk” for more than 5 years of death from coronary disease due to the presence of known cardiovascular disease (coronary artery disease, peripheral artery disease, cerebrovascular disease), diabetes, or hypertension. Patients were excluded if they had other life-threatening illnesses, diagnosed cancer, or were already taking high-dose vitamin E supplements.

STUDY DESIGN AND VALIDITY: Patients in this impressive placebo-controlled, double-blind randomized (masked allocation via central telephone system) trial received antioxidant supplementation (vitamin E 600 mg, vitamin C 250 mg, and beta-carotene 20 mg daily) or matching placebo. This study was part of the MRC/BHF study on simvastatin. All patients in the vitamin treatment group also received simvastatin. In an 8- to 10-week “prerandomization run-in” phase eligibility and compliance with the 5-year study protocol was assessed. Patients were seen at 4, 8, and 12 months, and then every 6 months during a 5-year period.

OUTCOMES MEASURED: The primary outcomes measured were “major coronary events” (nonfatal myocardial infarction or death from coronary disease) and fatal coronary heart disease. Secondary outcomes measured were effects on major coronary events and major vascular events and nonfatal or fatal stroke. Other outcomes included site-specific cancer, cerebral hemorrhage, vascular procedures, and hospitalization for various causes.

RESULTS: Patients taking vitamins had significantly higher levels of these vitamins in their blood. Despite this increase no difference was noted in all-cause mortality or deaths due to vascular or nonvascular causes. There were no differences in nonfatal myocardial infarctions, coronary death, nonfatal or fatal stroke, or coronary or noncoronary revascularization. No differences were noted in cancer incidence or hospitalization for any other nonvascular cause.

ABSTRACT

BACKGROUND: Several nonrandomized, observational studies have suggested that antioxidant vitamins decrease vascular disease, cancer, and mortality. However, large randomized trials are needed to counter biases such as the “healthy user effect” often seen in observational studies.

POPULATION STUDIED: The investigators studied 20,536 adults (mostly men from the United Kingdom) aged 40 to 80 years with diabetes, peripheral artery disease, or coronary artery disease. Patients were included if their total cholesterol concentration was above 3.5 mmol/L (135 mg/dL) and they were at a “substantial risk” for more than 5 years of death from coronary disease due to the presence of known cardiovascular disease (coronary artery disease, peripheral artery disease, cerebrovascular disease), diabetes, or hypertension. Patients were excluded if they had other life-threatening illnesses, diagnosed cancer, or were already taking high-dose vitamin E supplements.

STUDY DESIGN AND VALIDITY: Patients in this impressive placebo-controlled, double-blind randomized (masked allocation via central telephone system) trial received antioxidant supplementation (vitamin E 600 mg, vitamin C 250 mg, and beta-carotene 20 mg daily) or matching placebo. This study was part of the MRC/BHF study on simvastatin. All patients in the vitamin treatment group also received simvastatin. In an 8- to 10-week “prerandomization run-in” phase eligibility and compliance with the 5-year study protocol was assessed. Patients were seen at 4, 8, and 12 months, and then every 6 months during a 5-year period.

OUTCOMES MEASURED: The primary outcomes measured were “major coronary events” (nonfatal myocardial infarction or death from coronary disease) and fatal coronary heart disease. Secondary outcomes measured were effects on major coronary events and major vascular events and nonfatal or fatal stroke. Other outcomes included site-specific cancer, cerebral hemorrhage, vascular procedures, and hospitalization for various causes.

RESULTS: Patients taking vitamins had significantly higher levels of these vitamins in their blood. Despite this increase no difference was noted in all-cause mortality or deaths due to vascular or nonvascular causes. There were no differences in nonfatal myocardial infarctions, coronary death, nonfatal or fatal stroke, or coronary or noncoronary revascularization. No differences were noted in cancer incidence or hospitalization for any other nonvascular cause.

ABSTRACT

BACKGROUND: Although Candida is often isolated from nails afflicted with chronic paronychia, the benefit of treating chronic paronychia with antifungal agents has never been proved. More recently, chronic paronychia is thought to be an eczematous condition better treated with corticosteroids.

POPULATION STUDIED: A total of 45 patients, 22 to 69 years of age, presenting to a dermatology clinic in Italy with chronic paronychia were enrolled. The diagnosis of chronic paronychia was established by the following criteria: absence of the cuticle with swelling and erythema of the proximal nail fold. Exclusion criteria included hypersensitivity to imidazoles or terbinafine, use of drugs interfering with itraconazole or terbinafine metabolism, pregnancy, liver or renal dysfunction, history of contact dermatitis from steroids, onychomycosis, psoriasis, lichen planus, and self-induced or manicure-related nail abnormalities. Disease duration before the study ranged from 1 month to 40 years (mean 2.3 years).

STUDY DESIGN AND VALIDITY: Patients were randomized in a double blind fashion to receive either itraconazole 200 mg daily; terbinafine 250 mg daily; or topical methylprednisolone aceponate cream 0.1%, 5 mg daily. Treatment duration was 3 weeks and patients were followed for an additional 6 weeks. Mycological samples were obtained and a clinical examination performed at baseline, the end of treatment, and the end of follow-up. Nail abnormalities were rated as cured (regrowth of cuticle with normal proximal nail fold), improved (proximal nail fold not inflamed, absence of cuticle, nail plate growing normally), stable (proximal nail fold still inflamed), or worsened (acute flare with purulent inflammation of the proximal nail fold).

OUTCOMES MEASURED: The primary outcomes measured were the presence of Candida in the proximal nail fold and the clinical status of nails and patients at the end of the follow-up period. No measure of patient satisfaction was determined.

RESULTS: The 3 groups were similar at baseline in terms of sex, age, and number of fingernails affected by chronic paronychia. A total of 42 patients (93%) completed 6 weeks of follow-up. The presence of Candida was not linked to disease activity; mycological examination before treatment revealed the presence of Candida in the proximal nail fold of only 18 of 45 patients. Only 2 of these patients had simultaneous eradication of Candida and clinical cure by the end of the study, both of whom were in the topical steroid group. Clinical improvement or cure of total nails at the end of follow-up was superior with topical steroids compared with either terbinafine or itraconazole (85% vs 53% vs 45%; P < .01; NNT = 3 and 2.5, respectively). Improvement or cure was observed in 60% of patients treated with topical steroids compared with 33% treated with itraconazole and 20% treated with terbinafine.

ABSTRACT

BACKGROUND: Although Candida is often isolated from nails afflicted with chronic paronychia, the benefit of treating chronic paronychia with antifungal agents has never been proved. More recently, chronic paronychia is thought to be an eczematous condition better treated with corticosteroids.

POPULATION STUDIED: A total of 45 patients, 22 to 69 years of age, presenting to a dermatology clinic in Italy with chronic paronychia were enrolled. The diagnosis of chronic paronychia was established by the following criteria: absence of the cuticle with swelling and erythema of the proximal nail fold. Exclusion criteria included hypersensitivity to imidazoles or terbinafine, use of drugs interfering with itraconazole or terbinafine metabolism, pregnancy, liver or renal dysfunction, history of contact dermatitis from steroids, onychomycosis, psoriasis, lichen planus, and self-induced or manicure-related nail abnormalities. Disease duration before the study ranged from 1 month to 40 years (mean 2.3 years).

STUDY DESIGN AND VALIDITY: Patients were randomized in a double blind fashion to receive either itraconazole 200 mg daily; terbinafine 250 mg daily; or topical methylprednisolone aceponate cream 0.1%, 5 mg daily. Treatment duration was 3 weeks and patients were followed for an additional 6 weeks. Mycological samples were obtained and a clinical examination performed at baseline, the end of treatment, and the end of follow-up. Nail abnormalities were rated as cured (regrowth of cuticle with normal proximal nail fold), improved (proximal nail fold not inflamed, absence of cuticle, nail plate growing normally), stable (proximal nail fold still inflamed), or worsened (acute flare with purulent inflammation of the proximal nail fold).

OUTCOMES MEASURED: The primary outcomes measured were the presence of Candida in the proximal nail fold and the clinical status of nails and patients at the end of the follow-up period. No measure of patient satisfaction was determined.

RESULTS: The 3 groups were similar at baseline in terms of sex, age, and number of fingernails affected by chronic paronychia. A total of 42 patients (93%) completed 6 weeks of follow-up. The presence of Candida was not linked to disease activity; mycological examination before treatment revealed the presence of Candida in the proximal nail fold of only 18 of 45 patients. Only 2 of these patients had simultaneous eradication of Candida and clinical cure by the end of the study, both of whom were in the topical steroid group. Clinical improvement or cure of total nails at the end of follow-up was superior with topical steroids compared with either terbinafine or itraconazole (85% vs 53% vs 45%; P < .01; NNT = 3 and 2.5, respectively). Improvement or cure was observed in 60% of patients treated with topical steroids compared with 33% treated with itraconazole and 20% treated with terbinafine.

ABSTRACT

BACKGROUND: Although Candida is often isolated from nails afflicted with chronic paronychia, the benefit of treating chronic paronychia with antifungal agents has never been proved. More recently, chronic paronychia is thought to be an eczematous condition better treated with corticosteroids.

POPULATION STUDIED: A total of 45 patients, 22 to 69 years of age, presenting to a dermatology clinic in Italy with chronic paronychia were enrolled. The diagnosis of chronic paronychia was established by the following criteria: absence of the cuticle with swelling and erythema of the proximal nail fold. Exclusion criteria included hypersensitivity to imidazoles or terbinafine, use of drugs interfering with itraconazole or terbinafine metabolism, pregnancy, liver or renal dysfunction, history of contact dermatitis from steroids, onychomycosis, psoriasis, lichen planus, and self-induced or manicure-related nail abnormalities. Disease duration before the study ranged from 1 month to 40 years (mean 2.3 years).

STUDY DESIGN AND VALIDITY: Patients were randomized in a double blind fashion to receive either itraconazole 200 mg daily; terbinafine 250 mg daily; or topical methylprednisolone aceponate cream 0.1%, 5 mg daily. Treatment duration was 3 weeks and patients were followed for an additional 6 weeks. Mycological samples were obtained and a clinical examination performed at baseline, the end of treatment, and the end of follow-up. Nail abnormalities were rated as cured (regrowth of cuticle with normal proximal nail fold), improved (proximal nail fold not inflamed, absence of cuticle, nail plate growing normally), stable (proximal nail fold still inflamed), or worsened (acute flare with purulent inflammation of the proximal nail fold).

OUTCOMES MEASURED: The primary outcomes measured were the presence of Candida in the proximal nail fold and the clinical status of nails and patients at the end of the follow-up period. No measure of patient satisfaction was determined.

RESULTS: The 3 groups were similar at baseline in terms of sex, age, and number of fingernails affected by chronic paronychia. A total of 42 patients (93%) completed 6 weeks of follow-up. The presence of Candida was not linked to disease activity; mycological examination before treatment revealed the presence of Candida in the proximal nail fold of only 18 of 45 patients. Only 2 of these patients had simultaneous eradication of Candida and clinical cure by the end of the study, both of whom were in the topical steroid group. Clinical improvement or cure of total nails at the end of follow-up was superior with topical steroids compared with either terbinafine or itraconazole (85% vs 53% vs 45%; P < .01; NNT = 3 and 2.5, respectively). Improvement or cure was observed in 60% of patients treated with topical steroids compared with 33% treated with itraconazole and 20% treated with terbinafine.

ABSTRACT

BACKGROUND: The search for optimal protection against mosquitoes is particularly timely, with West Nile virus infection becoming more of a threat in the United States. Internationally, malaria is the primary infectious disease transmitted by mosquito. Mosquito-transmitted diseases are responsible for 1 in 17 deaths worldwide. New repellents have come out on the market, but their relative effectiveness has not been delineated.

POPULATION STUDIED: The researchers recruited 15 volunteers from the staff of the Medical Entomology Laboratory at the University of Florida (10 were women). Age, ethnicity, and medical histories were not reported.

STUDY DESIGN AND VALIDITY: The goal of the researchers was to compare the effectiveness of 16 products containing 7 botanical repellents. The products included those containing 4 different concentrations of DEET (N, N-diethyl-3-methylbenzamide), 2% soybean oil, 5 different formulations of citronella, and IR3535; in addition, 3 repellentimpregnated wristbands were tested. All products are nationally available in the United States. The study used an “arm-in-cage” design; volunteers inserted their repellent-treated bare arms into a cage with 10 hungry, disease-free female mosquitoes. This low mosquito density environment was considered to be similar to typical exposures. The order of tests was randomized and the volunteers were blinded to the repellent used. Hours of light and dark, humidity, and temperature were constant. Each repellent was tested 3 times on each subject. No more than 1 repellent was tested per day. The repellents were applied according to the instructions on the product’s label. Subjects inserted an arm into the cage for 1 minute every 5 minutes. If they were not bitten after 20 minutes, the insertion interval was changed to every 15 minutes. The test was stopped with the first bite. The study was funded by the State of Florida.

OUTCOMES MEASURED: Time to the first mosquito bite using different repellents in a controlled situation.

RESULTS: DEET was the clear winner in these tests, especially in the highest concentration. The highest DEET concentration (23.8%) protected for an average of 301.5 ± 37.6 minutes. This concentration, which was alcohol based, protected significantly longer than the 20% controlled-release formulation (245.5 ± 31.8 minutes). Only DEET-containing repellents protected longer than 1.5 hours. The soybean oil repellent protected similar to the lowest concentration of DEET (94.6 vs 88 minutes, respectively). The wristbands were essentially not effective. Citronella-based lotions worked for only 10.3 ± 7.9 minutes at best.

ABSTRACT

BACKGROUND: The search for optimal protection against mosquitoes is particularly timely, with West Nile virus infection becoming more of a threat in the United States. Internationally, malaria is the primary infectious disease transmitted by mosquito. Mosquito-transmitted diseases are responsible for 1 in 17 deaths worldwide. New repellents have come out on the market, but their relative effectiveness has not been delineated.

POPULATION STUDIED: The researchers recruited 15 volunteers from the staff of the Medical Entomology Laboratory at the University of Florida (10 were women). Age, ethnicity, and medical histories were not reported.

STUDY DESIGN AND VALIDITY: The goal of the researchers was to compare the effectiveness of 16 products containing 7 botanical repellents. The products included those containing 4 different concentrations of DEET (N, N-diethyl-3-methylbenzamide), 2% soybean oil, 5 different formulations of citronella, and IR3535; in addition, 3 repellentimpregnated wristbands were tested. All products are nationally available in the United States. The study used an “arm-in-cage” design; volunteers inserted their repellent-treated bare arms into a cage with 10 hungry, disease-free female mosquitoes. This low mosquito density environment was considered to be similar to typical exposures. The order of tests was randomized and the volunteers were blinded to the repellent used. Hours of light and dark, humidity, and temperature were constant. Each repellent was tested 3 times on each subject. No more than 1 repellent was tested per day. The repellents were applied according to the instructions on the product’s label. Subjects inserted an arm into the cage for 1 minute every 5 minutes. If they were not bitten after 20 minutes, the insertion interval was changed to every 15 minutes. The test was stopped with the first bite. The study was funded by the State of Florida.

OUTCOMES MEASURED: Time to the first mosquito bite using different repellents in a controlled situation.

RESULTS: DEET was the clear winner in these tests, especially in the highest concentration. The highest DEET concentration (23.8%) protected for an average of 301.5 ± 37.6 minutes. This concentration, which was alcohol based, protected significantly longer than the 20% controlled-release formulation (245.5 ± 31.8 minutes). Only DEET-containing repellents protected longer than 1.5 hours. The soybean oil repellent protected similar to the lowest concentration of DEET (94.6 vs 88 minutes, respectively). The wristbands were essentially not effective. Citronella-based lotions worked for only 10.3 ± 7.9 minutes at best.

ABSTRACT

BACKGROUND: The search for optimal protection against mosquitoes is particularly timely, with West Nile virus infection becoming more of a threat in the United States. Internationally, malaria is the primary infectious disease transmitted by mosquito. Mosquito-transmitted diseases are responsible for 1 in 17 deaths worldwide. New repellents have come out on the market, but their relative effectiveness has not been delineated.

POPULATION STUDIED: The researchers recruited 15 volunteers from the staff of the Medical Entomology Laboratory at the University of Florida (10 were women). Age, ethnicity, and medical histories were not reported.

STUDY DESIGN AND VALIDITY: The goal of the researchers was to compare the effectiveness of 16 products containing 7 botanical repellents. The products included those containing 4 different concentrations of DEET (N, N-diethyl-3-methylbenzamide), 2% soybean oil, 5 different formulations of citronella, and IR3535; in addition, 3 repellentimpregnated wristbands were tested. All products are nationally available in the United States. The study used an “arm-in-cage” design; volunteers inserted their repellent-treated bare arms into a cage with 10 hungry, disease-free female mosquitoes. This low mosquito density environment was considered to be similar to typical exposures. The order of tests was randomized and the volunteers were blinded to the repellent used. Hours of light and dark, humidity, and temperature were constant. Each repellent was tested 3 times on each subject. No more than 1 repellent was tested per day. The repellents were applied according to the instructions on the product’s label. Subjects inserted an arm into the cage for 1 minute every 5 minutes. If they were not bitten after 20 minutes, the insertion interval was changed to every 15 minutes. The test was stopped with the first bite. The study was funded by the State of Florida.

OUTCOMES MEASURED: Time to the first mosquito bite using different repellents in a controlled situation.

RESULTS: DEET was the clear winner in these tests, especially in the highest concentration. The highest DEET concentration (23.8%) protected for an average of 301.5 ± 37.6 minutes. This concentration, which was alcohol based, protected significantly longer than the 20% controlled-release formulation (245.5 ± 31.8 minutes). Only DEET-containing repellents protected longer than 1.5 hours. The soybean oil repellent protected similar to the lowest concentration of DEET (94.6 vs 88 minutes, respectively). The wristbands were essentially not effective. Citronella-based lotions worked for only 10.3 ± 7.9 minutes at best.

ABSTRACT

BACKGROUND: More than 650,000 arthroscopic procedures are performed each year when medical therapy fails in the treatment of osteoarthritis (OA) of the knee. Uncontrolled studies have shown that up to half of patients receive pain relief from this procedure; however, the exact reason is unclear. There is no evidence that arthroscopic surgery contributes to the cure or arrest in the natural course of OA.

POPULATION STUDIED: The investigators enrolled patients (mean age 52.3 ± 11.3 years) recruited from the Houston Veterans Administration Medical Center who had OA of the knee, as defined by the American College of Rheumatology. The patients reported at least moderate knee pain on average (at least a 4 on a 10-point visual analogue scale) despite at least 6 months of medical treatment. These patients had not undergone arthroscopy in the past 2 years. Patients were excluded for severe pain, severe deformity, and serious medical problems.

STUDY DESIGN AND VALIDITY: This double-blind, randomized controlled trial evaluated 3 treatments: arthroscopic lavage alone, arthroscopic debridement along with lavage, or placebo (“sham”) procedure. Allocation to these groups was appropriately concealed. One orthopedist performed all the operations. The lavage-only group had the joint lavaged with 10 L of fluid and no general debridement was performed. “Bucket-handle” tears to a meniscus or mechanically important deficits were repaired as in the debridement group. The debridement group underwent arthroscopy and joint lavage with 10 L of fluid, shaving of any rough articular surface, removal of debris, and repair of any torn menisci to form a smooth, firm, and fixed rim. Patients in these 2 groups received general anesthesia and were intubated. The placebo procedure simulated debridement by placing three 1-cm incisions in the skin and the surgeon asking for all of the instruments and manipulating the knee as if arthroscopy was being performed. These patients received a short-acting intravenous tranquilizer and an opioid and spontaneously breathed oxygen-enriched air but were not fully anesthetized.

OUTCOMES MEASURED: The primary end point was pain in the study knee 2 years after the intervention, as assessed by a 12-item self-reported Knee-Specific Pain Scale created for this study. The scale ranged from 0 to 100 with higher scores indicating more pain. Five secondary end points were assessed using 2 measures of pain and 3 measures of function.

RESULTS: Mean pain scores for all groups did not differ at any of the recorded time intervals (mean Knee-Specific Pain Scale scores in all 3 groups were 51–54 out of 100). The improvement in pain occurred within the first 2 weeks for all groups (6-to 12-point improvement) and then increased slightly for the remaining 2 years.

ABSTRACT

BACKGROUND: More than 650,000 arthroscopic procedures are performed each year when medical therapy fails in the treatment of osteoarthritis (OA) of the knee. Uncontrolled studies have shown that up to half of patients receive pain relief from this procedure; however, the exact reason is unclear. There is no evidence that arthroscopic surgery contributes to the cure or arrest in the natural course of OA.

POPULATION STUDIED: The investigators enrolled patients (mean age 52.3 ± 11.3 years) recruited from the Houston Veterans Administration Medical Center who had OA of the knee, as defined by the American College of Rheumatology. The patients reported at least moderate knee pain on average (at least a 4 on a 10-point visual analogue scale) despite at least 6 months of medical treatment. These patients had not undergone arthroscopy in the past 2 years. Patients were excluded for severe pain, severe deformity, and serious medical problems.

STUDY DESIGN AND VALIDITY: This double-blind, randomized controlled trial evaluated 3 treatments: arthroscopic lavage alone, arthroscopic debridement along with lavage, or placebo (“sham”) procedure. Allocation to these groups was appropriately concealed. One orthopedist performed all the operations. The lavage-only group had the joint lavaged with 10 L of fluid and no general debridement was performed. “Bucket-handle” tears to a meniscus or mechanically important deficits were repaired as in the debridement group. The debridement group underwent arthroscopy and joint lavage with 10 L of fluid, shaving of any rough articular surface, removal of debris, and repair of any torn menisci to form a smooth, firm, and fixed rim. Patients in these 2 groups received general anesthesia and were intubated. The placebo procedure simulated debridement by placing three 1-cm incisions in the skin and the surgeon asking for all of the instruments and manipulating the knee as if arthroscopy was being performed. These patients received a short-acting intravenous tranquilizer and an opioid and spontaneously breathed oxygen-enriched air but were not fully anesthetized.

OUTCOMES MEASURED: The primary end point was pain in the study knee 2 years after the intervention, as assessed by a 12-item self-reported Knee-Specific Pain Scale created for this study. The scale ranged from 0 to 100 with higher scores indicating more pain. Five secondary end points were assessed using 2 measures of pain and 3 measures of function.

RESULTS: Mean pain scores for all groups did not differ at any of the recorded time intervals (mean Knee-Specific Pain Scale scores in all 3 groups were 51–54 out of 100). The improvement in pain occurred within the first 2 weeks for all groups (6-to 12-point improvement) and then increased slightly for the remaining 2 years.

ABSTRACT

BACKGROUND: More than 650,000 arthroscopic procedures are performed each year when medical therapy fails in the treatment of osteoarthritis (OA) of the knee. Uncontrolled studies have shown that up to half of patients receive pain relief from this procedure; however, the exact reason is unclear. There is no evidence that arthroscopic surgery contributes to the cure or arrest in the natural course of OA.

POPULATION STUDIED: The investigators enrolled patients (mean age 52.3 ± 11.3 years) recruited from the Houston Veterans Administration Medical Center who had OA of the knee, as defined by the American College of Rheumatology. The patients reported at least moderate knee pain on average (at least a 4 on a 10-point visual analogue scale) despite at least 6 months of medical treatment. These patients had not undergone arthroscopy in the past 2 years. Patients were excluded for severe pain, severe deformity, and serious medical problems.

STUDY DESIGN AND VALIDITY: This double-blind, randomized controlled trial evaluated 3 treatments: arthroscopic lavage alone, arthroscopic debridement along with lavage, or placebo (“sham”) procedure. Allocation to these groups was appropriately concealed. One orthopedist performed all the operations. The lavage-only group had the joint lavaged with 10 L of fluid and no general debridement was performed. “Bucket-handle” tears to a meniscus or mechanically important deficits were repaired as in the debridement group. The debridement group underwent arthroscopy and joint lavage with 10 L of fluid, shaving of any rough articular surface, removal of debris, and repair of any torn menisci to form a smooth, firm, and fixed rim. Patients in these 2 groups received general anesthesia and were intubated. The placebo procedure simulated debridement by placing three 1-cm incisions in the skin and the surgeon asking for all of the instruments and manipulating the knee as if arthroscopy was being performed. These patients received a short-acting intravenous tranquilizer and an opioid and spontaneously breathed oxygen-enriched air but were not fully anesthetized.

OUTCOMES MEASURED: The primary end point was pain in the study knee 2 years after the intervention, as assessed by a 12-item self-reported Knee-Specific Pain Scale created for this study. The scale ranged from 0 to 100 with higher scores indicating more pain. Five secondary end points were assessed using 2 measures of pain and 3 measures of function.

RESULTS: Mean pain scores for all groups did not differ at any of the recorded time intervals (mean Knee-Specific Pain Scale scores in all 3 groups were 51–54 out of 100). The improvement in pain occurred within the first 2 weeks for all groups (6-to 12-point improvement) and then increased slightly for the remaining 2 years.

ABSTRACT

BACKGROUND: High-altitude pulmonary edema (HAPE) is a life-threatening manifestation of high-altitude illness. Although conventional medications such as acetazolamide and dexamethasone can prevent acute mountain sickness (a more common and less severe stage of high-altitude illness). Dexamethasone is known to be ineffective and acetazolamide has not been studied specifically for HAPE.¹ Beta-agonists may decrease HAPE by promoting the clearance of alveolar fluid and thus relieving pulmonary edema and alveolar hypoxia. This study investigated the use of salmeterol to prevent HAPE in climbers at high risk for this condition.
POPULATION STUDIED: The investigators studied 37 mountaineers who had a history of HAPE (average of 2 previous episodes per subject). Most subjects were men, and the average age was 48 years. Baseline demographics were similar between groups. The population was appropriate for the condition being studied, although these men were at much higher risk for HAPE than the average recreational mountain climber.
STUDY DESIGN AND VALIDITY: This study was double-blind, randomized, and placebo controlled. Starting the day before ascent, the climbers inhaled either salmeterol 125 μg (about 3 times the normal asthma dosage) or placebo every 12 hours via metered-dose inhaler with spacer. They ascended (via cable car and mountaineering) from 1130 m to a high-altitude (4559 m) research laboratory in Italy over a period of 22 hours. Investigators then observed the subjects over a period of 2 days and nights for clinical and laboratory signs of HAPE and acute mountain sickness. Participants who developed symptoms of HAPE were evacuated to low altitude.
OUTCOMES MEASURED: The major patient-oriented end point was clinical and radiographic evidence of pulmonary edema. Investigators recorded Lake Louise Acute Mountain Sickness scores, arterial oxygen saturations, and carbon dioxide and oxygen arterial partial pressures. They also compared chest radiographs obtained at the high-altitude laboratory.
RESULTS: The incidence of pulmonary edema was less in the salmeterol group than with placebo (74% vs 33%; P=.02; numbers needed to treat=2.5). Lake Louise Acute Mountain Sickness scores were significantly better in the salmeterol group than in the placebo group (5.8 vs 11.5 out of a possible 24; P < .001). Chest radiographs, arterial oxygen saturations, and oxygen arterial partial pressures were also significantly improved with salmeterol.

ABSTRACT

BACKGROUND: High-altitude pulmonary edema (HAPE) is a life-threatening manifestation of high-altitude illness. Although conventional medications such as acetazolamide and dexamethasone can prevent acute mountain sickness (a more common and less severe stage of high-altitude illness). Dexamethasone is known to be ineffective and acetazolamide has not been studied specifically for HAPE.¹ Beta-agonists may decrease HAPE by promoting the clearance of alveolar fluid and thus relieving pulmonary edema and alveolar hypoxia. This study investigated the use of salmeterol to prevent HAPE in climbers at high risk for this condition.
POPULATION STUDIED: The investigators studied 37 mountaineers who had a history of HAPE (average of 2 previous episodes per subject). Most subjects were men, and the average age was 48 years. Baseline demographics were similar between groups. The population was appropriate for the condition being studied, although these men were at much higher risk for HAPE than the average recreational mountain climber.
STUDY DESIGN AND VALIDITY: This study was double-blind, randomized, and placebo controlled. Starting the day before ascent, the climbers inhaled either salmeterol 125 μg (about 3 times the normal asthma dosage) or placebo every 12 hours via metered-dose inhaler with spacer. They ascended (via cable car and mountaineering) from 1130 m to a high-altitude (4559 m) research laboratory in Italy over a period of 22 hours. Investigators then observed the subjects over a period of 2 days and nights for clinical and laboratory signs of HAPE and acute mountain sickness. Participants who developed symptoms of HAPE were evacuated to low altitude.
OUTCOMES MEASURED: The major patient-oriented end point was clinical and radiographic evidence of pulmonary edema. Investigators recorded Lake Louise Acute Mountain Sickness scores, arterial oxygen saturations, and carbon dioxide and oxygen arterial partial pressures. They also compared chest radiographs obtained at the high-altitude laboratory.
RESULTS: The incidence of pulmonary edema was less in the salmeterol group than with placebo (74% vs 33%; P=.02; numbers needed to treat=2.5). Lake Louise Acute Mountain Sickness scores were significantly better in the salmeterol group than in the placebo group (5.8 vs 11.5 out of a possible 24; P < .001). Chest radiographs, arterial oxygen saturations, and oxygen arterial partial pressures were also significantly improved with salmeterol.

ABSTRACT

BACKGROUND: High-altitude pulmonary edema (HAPE) is a life-threatening manifestation of high-altitude illness. Although conventional medications such as acetazolamide and dexamethasone can prevent acute mountain sickness (a more common and less severe stage of high-altitude illness). Dexamethasone is known to be ineffective and acetazolamide has not been studied specifically for HAPE.¹ Beta-agonists may decrease HAPE by promoting the clearance of alveolar fluid and thus relieving pulmonary edema and alveolar hypoxia. This study investigated the use of salmeterol to prevent HAPE in climbers at high risk for this condition.
POPULATION STUDIED: The investigators studied 37 mountaineers who had a history of HAPE (average of 2 previous episodes per subject). Most subjects were men, and the average age was 48 years. Baseline demographics were similar between groups. The population was appropriate for the condition being studied, although these men were at much higher risk for HAPE than the average recreational mountain climber.
STUDY DESIGN AND VALIDITY: This study was double-blind, randomized, and placebo controlled. Starting the day before ascent, the climbers inhaled either salmeterol 125 μg (about 3 times the normal asthma dosage) or placebo every 12 hours via metered-dose inhaler with spacer. They ascended (via cable car and mountaineering) from 1130 m to a high-altitude (4559 m) research laboratory in Italy over a period of 22 hours. Investigators then observed the subjects over a period of 2 days and nights for clinical and laboratory signs of HAPE and acute mountain sickness. Participants who developed symptoms of HAPE were evacuated to low altitude.
OUTCOMES MEASURED: The major patient-oriented end point was clinical and radiographic evidence of pulmonary edema. Investigators recorded Lake Louise Acute Mountain Sickness scores, arterial oxygen saturations, and carbon dioxide and oxygen arterial partial pressures. They also compared chest radiographs obtained at the high-altitude laboratory.
RESULTS: The incidence of pulmonary edema was less in the salmeterol group than with placebo (74% vs 33%; P=.02; numbers needed to treat=2.5). Lake Louise Acute Mountain Sickness scores were significantly better in the salmeterol group than in the placebo group (5.8 vs 11.5 out of a possible 24; P < .001). Chest radiographs, arterial oxygen saturations, and oxygen arterial partial pressures were also significantly improved with salmeterol.

ABSTRACT

BACKGROUND: Clopidogrel is a platelet aggregation inhibitor that is slightly more effective than aspirin in reducing the risk of cardiovascular events in individuals with preexisting cardiovascular disease (0.51% annual absolute risk reduction; Lancet 1996; 348:1329–39). However, clopidogrel is currently 80 times more expensive than aspirin. The authors looked at the risks, benefits, and costs of long-term use of various therapeutic strategies involving these 2 medications.
POPULATION STUDIED: A computer simulation, known as the Coronary Heart Disease Policy Model, was used to predict the number of patients in the United States (35–84 years) who would develop coronary disease before or during the next 25 years, as well as the number of subsequent cardiovascular events and deaths these individuals would experience. Only patients predicted to survive their first month after a cardiac event were included in the therapeutic intervention analysis. Parameters for the model were based on cohort studies and clinical trials found in the medical literature.
STUDY DESIGN AND VALIDITY: Beginning with their estimated number of Americans with coronary disease and cardiovascular events, the authors predicted the reduction in events using aspirin, clopidogrel, or both. The 4 possible treatment strategies were (1) aspirin 325 mg/day for all eligible patients; (2) aspirin for all eligible patients or clopidogrel 75 mg/day for the remaining 5.7% ineligible for aspirin; (3) clopidogrel 75 mg/day for all patients; or (4) a combination of clopidogrel for all patients plus aspirin for all eligible patients. They also considered costs of various interventions, including hospitalizations, rehabilitation services, outpatient and home services, and treatment for adverse drug effects such as gastrointestinal bleeding. To carry out the cost-effectiveness analysis over such a long time period, the authors discounted costs at a rate of 3% per year (a typical amount) and converted all values to year-2000 US dollars. Sensitivity analysis used upper and lower bounds of reductions from past trial data to give a reasonable range of values. As with all hypothetical cost-effectiveness studies, this study only represents the authors’ best estimates of costs and benefits, not actual results from a therapeutic trial or cohort. Issues such as the safety of combination therapy over this prolonged time period have not been well established.
OUTCOMES MEASURED: The main outcome was the cost per quality-adjusted life year (QALY) gained, that is, the cost of an additional year of optimal health.
RESULTS: Aspirin alone in all eligible patients (strategy #1) resulted in an estimated $11,000 per QALY gained. Giving clopidogrel to the 5.7% of patients ineligible for aspirin (strategy #2) would prevent some subsequent events at an increased cost, resulting in a total estimate of $31,000 per QALY gained compared with the first strategy. Using clopidogrel alone for everyone (strategy #3) led to a very high estimated cost of $250,000 per QALY gained compared with strategy #2. Combination therapy of clopidogrel for everyone plus aspirin for the 96.3% of eligible patients (strategy #4) resulted in an estimated cost of $130,000 per QALY gained compared with strategy #2. However, in patients with annual risks 3 times as high as that of the average patient with coronary disease, this ratio fell below $64,000 per QALY gained.

ABSTRACT

BACKGROUND: Clopidogrel is a platelet aggregation inhibitor that is slightly more effective than aspirin in reducing the risk of cardiovascular events in individuals with preexisting cardiovascular disease (0.51% annual absolute risk reduction; Lancet 1996; 348:1329–39). However, clopidogrel is currently 80 times more expensive than aspirin. The authors looked at the risks, benefits, and costs of long-term use of various therapeutic strategies involving these 2 medications.
POPULATION STUDIED: A computer simulation, known as the Coronary Heart Disease Policy Model, was used to predict the number of patients in the United States (35–84 years) who would develop coronary disease before or during the next 25 years, as well as the number of subsequent cardiovascular events and deaths these individuals would experience. Only patients predicted to survive their first month after a cardiac event were included in the therapeutic intervention analysis. Parameters for the model were based on cohort studies and clinical trials found in the medical literature.
STUDY DESIGN AND VALIDITY: Beginning with their estimated number of Americans with coronary disease and cardiovascular events, the authors predicted the reduction in events using aspirin, clopidogrel, or both. The 4 possible treatment strategies were (1) aspirin 325 mg/day for all eligible patients; (2) aspirin for all eligible patients or clopidogrel 75 mg/day for the remaining 5.7% ineligible for aspirin; (3) clopidogrel 75 mg/day for all patients; or (4) a combination of clopidogrel for all patients plus aspirin for all eligible patients. They also considered costs of various interventions, including hospitalizations, rehabilitation services, outpatient and home services, and treatment for adverse drug effects such as gastrointestinal bleeding. To carry out the cost-effectiveness analysis over such a long time period, the authors discounted costs at a rate of 3% per year (a typical amount) and converted all values to year-2000 US dollars. Sensitivity analysis used upper and lower bounds of reductions from past trial data to give a reasonable range of values. As with all hypothetical cost-effectiveness studies, this study only represents the authors’ best estimates of costs and benefits, not actual results from a therapeutic trial or cohort. Issues such as the safety of combination therapy over this prolonged time period have not been well established.
OUTCOMES MEASURED: The main outcome was the cost per quality-adjusted life year (QALY) gained, that is, the cost of an additional year of optimal health.
RESULTS: Aspirin alone in all eligible patients (strategy #1) resulted in an estimated $11,000 per QALY gained. Giving clopidogrel to the 5.7% of patients ineligible for aspirin (strategy #2) would prevent some subsequent events at an increased cost, resulting in a total estimate of $31,000 per QALY gained compared with the first strategy. Using clopidogrel alone for everyone (strategy #3) led to a very high estimated cost of $250,000 per QALY gained compared with strategy #2. Combination therapy of clopidogrel for everyone plus aspirin for the 96.3% of eligible patients (strategy #4) resulted in an estimated cost of $130,000 per QALY gained compared with strategy #2. However, in patients with annual risks 3 times as high as that of the average patient with coronary disease, this ratio fell below $64,000 per QALY gained.

ABSTRACT

BACKGROUND: Clopidogrel is a platelet aggregation inhibitor that is slightly more effective than aspirin in reducing the risk of cardiovascular events in individuals with preexisting cardiovascular disease (0.51% annual absolute risk reduction; Lancet 1996; 348:1329–39). However, clopidogrel is currently 80 times more expensive than aspirin. The authors looked at the risks, benefits, and costs of long-term use of various therapeutic strategies involving these 2 medications.
POPULATION STUDIED: A computer simulation, known as the Coronary Heart Disease Policy Model, was used to predict the number of patients in the United States (35–84 years) who would develop coronary disease before or during the next 25 years, as well as the number of subsequent cardiovascular events and deaths these individuals would experience. Only patients predicted to survive their first month after a cardiac event were included in the therapeutic intervention analysis. Parameters for the model were based on cohort studies and clinical trials found in the medical literature.
STUDY DESIGN AND VALIDITY: Beginning with their estimated number of Americans with coronary disease and cardiovascular events, the authors predicted the reduction in events using aspirin, clopidogrel, or both. The 4 possible treatment strategies were (1) aspirin 325 mg/day for all eligible patients; (2) aspirin for all eligible patients or clopidogrel 75 mg/day for the remaining 5.7% ineligible for aspirin; (3) clopidogrel 75 mg/day for all patients; or (4) a combination of clopidogrel for all patients plus aspirin for all eligible patients. They also considered costs of various interventions, including hospitalizations, rehabilitation services, outpatient and home services, and treatment for adverse drug effects such as gastrointestinal bleeding. To carry out the cost-effectiveness analysis over such a long time period, the authors discounted costs at a rate of 3% per year (a typical amount) and converted all values to year-2000 US dollars. Sensitivity analysis used upper and lower bounds of reductions from past trial data to give a reasonable range of values. As with all hypothetical cost-effectiveness studies, this study only represents the authors’ best estimates of costs and benefits, not actual results from a therapeutic trial or cohort. Issues such as the safety of combination therapy over this prolonged time period have not been well established.
OUTCOMES MEASURED: The main outcome was the cost per quality-adjusted life year (QALY) gained, that is, the cost of an additional year of optimal health.
RESULTS: Aspirin alone in all eligible patients (strategy #1) resulted in an estimated $11,000 per QALY gained. Giving clopidogrel to the 5.7% of patients ineligible for aspirin (strategy #2) would prevent some subsequent events at an increased cost, resulting in a total estimate of $31,000 per QALY gained compared with the first strategy. Using clopidogrel alone for everyone (strategy #3) led to a very high estimated cost of $250,000 per QALY gained compared with strategy #2. Combination therapy of clopidogrel for everyone plus aspirin for the 96.3% of eligible patients (strategy #4) resulted in an estimated cost of $130,000 per QALY gained compared with strategy #2. However, in patients with annual risks 3 times as high as that of the average patient with coronary disease, this ratio fell below $64,000 per QALY gained.

ABSTRACT

BACKGROUND: Epidural analgesia effectively relieves labor pain, but questions persist about possible adverse effects of epidurals on labor, the mother, and the neonate. This meta-analysis compared the impact of epidural analgesia with parenteral opioids on birth outcomes.
POPULATION STUDIED: A total of 4721 women from 16 studies were identified. The participants were nulliparous and multiparous women with uneventful pregnancies undergoing spontaneous and induced labor. Thus, the subjects are likely to be similar to those seen by many family physicians, although more detail about race, gestational age, and other obstetric risk factors would have been useful.
STUDY DESIGN AND VALIDITY: The authors searched MEDLINE, EMBASE, the Cochrane Library, and meeting abstracts and references of review articles for randomized controlled trials comparing epidural analgesia with parenteral opioids during labor. Prospective cohorts were used only if no randomized controlled trial was available for a particular outcome and articles met criteria for quality. The authors assessed methodological quality with the Jadad scale. Heterogeneity was assessed with a chi-square test; Cochrane software was used to combine the results using a random effects model on an intent-to-treat basis.
OUTCOMES MEASURED: Maternal outcomes included maternal pain; satisfaction with pain control; labor duration; oxytocin use; temperature of >38°C; incidence of cesarean and instrumental delivery, and incidence of postpartum urinary incontinence and low back pain. Neonatal outcomes included 1- and 5-minute Apgar scores, fetal heart rate abnormalities, umbilical artery pH, and lactation success. Spinal headaches, neonatal jaundice, and hypoglycemia as well as treatment costs were not addressed.
RESULTS: Available trials were of low to moderate quality, with none having blinded assessment of outcomes. The rate of cesarean delivery was similar for patients receiving epidural and parenteral opioid analgesia; analyzing only higher quality trials did not change this result. Compared with women receiving parenteral opioids, patients receiving epidural analgesia had significantly lower pain scores (mean weighted difference = –40 on 100-mm scale; 95% confidence interval [CI], –42 to –38) and greater satisfaction with pain relief (odds ratio [OR] = 0.27; 95% CI, 0.19–0.38; number needed to treat [NNT] = 5). Women receiving epidural analgesia also had a 15-minute longer second stage and more oxytocin use (OR = 2.80; 95% CI, 1.89–4.16; NNT = 5), fever (OR = 5.6; 95% CI, 4.0–7.8; NNT = 5), and instrumental delivery (18.9% vs 12.2%; OR = 2.08; 95% CI, 1.48–2.93; NNT = 14). The rate of instrument use for shoulder dystocia was similar. For patients given parenteral opioid analgesics, naloxone was used most frequently. No differences were noted in incidence of low umbilical pH, low 5-minute Apgar scores, or fetal heart rate abnormalities. Randomized controlled trials were unavailable for lactation and incontinence outcomes; 1 prospective cohort study for each outcome found no differences.

ABSTRACT

BACKGROUND: Epidural analgesia effectively relieves labor pain, but questions persist about possible adverse effects of epidurals on labor, the mother, and the neonate. This meta-analysis compared the impact of epidural analgesia with parenteral opioids on birth outcomes.
POPULATION STUDIED: A total of 4721 women from 16 studies were identified. The participants were nulliparous and multiparous women with uneventful pregnancies undergoing spontaneous and induced labor. Thus, the subjects are likely to be similar to those seen by many family physicians, although more detail about race, gestational age, and other obstetric risk factors would have been useful.
STUDY DESIGN AND VALIDITY: The authors searched MEDLINE, EMBASE, the Cochrane Library, and meeting abstracts and references of review articles for randomized controlled trials comparing epidural analgesia with parenteral opioids during labor. Prospective cohorts were used only if no randomized controlled trial was available for a particular outcome and articles met criteria for quality. The authors assessed methodological quality with the Jadad scale. Heterogeneity was assessed with a chi-square test; Cochrane software was used to combine the results using a random effects model on an intent-to-treat basis.
OUTCOMES MEASURED: Maternal outcomes included maternal pain; satisfaction with pain control; labor duration; oxytocin use; temperature of >38°C; incidence of cesarean and instrumental delivery, and incidence of postpartum urinary incontinence and low back pain. Neonatal outcomes included 1- and 5-minute Apgar scores, fetal heart rate abnormalities, umbilical artery pH, and lactation success. Spinal headaches, neonatal jaundice, and hypoglycemia as well as treatment costs were not addressed.
RESULTS: Available trials were of low to moderate quality, with none having blinded assessment of outcomes. The rate of cesarean delivery was similar for patients receiving epidural and parenteral opioid analgesia; analyzing only higher quality trials did not change this result. Compared with women receiving parenteral opioids, patients receiving epidural analgesia had significantly lower pain scores (mean weighted difference = –40 on 100-mm scale; 95% confidence interval [CI], –42 to –38) and greater satisfaction with pain relief (odds ratio [OR] = 0.27; 95% CI, 0.19–0.38; number needed to treat [NNT] = 5). Women receiving epidural analgesia also had a 15-minute longer second stage and more oxytocin use (OR = 2.80; 95% CI, 1.89–4.16; NNT = 5), fever (OR = 5.6; 95% CI, 4.0–7.8; NNT = 5), and instrumental delivery (18.9% vs 12.2%; OR = 2.08; 95% CI, 1.48–2.93; NNT = 14). The rate of instrument use for shoulder dystocia was similar. For patients given parenteral opioid analgesics, naloxone was used most frequently. No differences were noted in incidence of low umbilical pH, low 5-minute Apgar scores, or fetal heart rate abnormalities. Randomized controlled trials were unavailable for lactation and incontinence outcomes; 1 prospective cohort study for each outcome found no differences.

ABSTRACT

BACKGROUND: Epidural analgesia effectively relieves labor pain, but questions persist about possible adverse effects of epidurals on labor, the mother, and the neonate. This meta-analysis compared the impact of epidural analgesia with parenteral opioids on birth outcomes.
POPULATION STUDIED: A total of 4721 women from 16 studies were identified. The participants were nulliparous and multiparous women with uneventful pregnancies undergoing spontaneous and induced labor. Thus, the subjects are likely to be similar to those seen by many family physicians, although more detail about race, gestational age, and other obstetric risk factors would have been useful.
STUDY DESIGN AND VALIDITY: The authors searched MEDLINE, EMBASE, the Cochrane Library, and meeting abstracts and references of review articles for randomized controlled trials comparing epidural analgesia with parenteral opioids during labor. Prospective cohorts were used only if no randomized controlled trial was available for a particular outcome and articles met criteria for quality. The authors assessed methodological quality with the Jadad scale. Heterogeneity was assessed with a chi-square test; Cochrane software was used to combine the results using a random effects model on an intent-to-treat basis.
OUTCOMES MEASURED: Maternal outcomes included maternal pain; satisfaction with pain control; labor duration; oxytocin use; temperature of >38°C; incidence of cesarean and instrumental delivery, and incidence of postpartum urinary incontinence and low back pain. Neonatal outcomes included 1- and 5-minute Apgar scores, fetal heart rate abnormalities, umbilical artery pH, and lactation success. Spinal headaches, neonatal jaundice, and hypoglycemia as well as treatment costs were not addressed.
RESULTS: Available trials were of low to moderate quality, with none having blinded assessment of outcomes. The rate of cesarean delivery was similar for patients receiving epidural and parenteral opioid analgesia; analyzing only higher quality trials did not change this result. Compared with women receiving parenteral opioids, patients receiving epidural analgesia had significantly lower pain scores (mean weighted difference = –40 on 100-mm scale; 95% confidence interval [CI], –42 to –38) and greater satisfaction with pain relief (odds ratio [OR] = 0.27; 95% CI, 0.19–0.38; number needed to treat [NNT] = 5). Women receiving epidural analgesia also had a 15-minute longer second stage and more oxytocin use (OR = 2.80; 95% CI, 1.89–4.16; NNT = 5), fever (OR = 5.6; 95% CI, 4.0–7.8; NNT = 5), and instrumental delivery (18.9% vs 12.2%; OR = 2.08; 95% CI, 1.48–2.93; NNT = 14). The rate of instrument use for shoulder dystocia was similar. For patients given parenteral opioid analgesics, naloxone was used most frequently. No differences were noted in incidence of low umbilical pH, low 5-minute Apgar scores, or fetal heart rate abnormalities. Randomized controlled trials were unavailable for lactation and incontinence outcomes; 1 prospective cohort study for each outcome found no differences.